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1.
  • Beal, Jacob, et al. (author)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Journal article (peer-reviewed)abstract
    • Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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3.
  • Klionsky, Daniel J., et al. (author)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Research review (peer-reviewed)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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4.
  • Aad, G, et al. (author)
  • 2015
  • swepub:Mat__t
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5.
  • Kristan, Matej, et al. (author)
  • The Visual Object Tracking VOT2015 challenge results
  • 2015
  • In: Proceedings 2015 IEEE International Conference on Computer Vision Workshops ICCVW 2015. - : IEEE. - 9780769557205 ; , s. 564-586
  • Conference paper (peer-reviewed)abstract
    • The Visual Object Tracking challenge 2015, VOT2015, aims at comparing short-term single-object visual trackers that do not apply pre-learned models of object appearance. Results of 62 trackers are presented. The number of tested trackers makes VOT 2015 the largest benchmark on short-term tracking to date. For each participating tracker, a short description is provided in the appendix. Features of the VOT2015 challenge that go beyond its VOT2014 predecessor are: (i) a new VOT2015 dataset twice as large as in VOT2014 with full annotation of targets by rotated bounding boxes and per-frame attribute, (ii) extensions of the VOT2014 evaluation methodology by introduction of a new performance measure. The dataset, the evaluation kit as well as the results are publicly available at the challenge website(1).
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6.
  • Jin, Ying-Hui, et al. (author)
  • Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
  • 2020
  • In: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
  • Journal article (peer-reviewed)abstract
    • The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.
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7.
  • Abgrall, N., et al. (author)
  • The large enriched germanium experiment for neutrinoless double beta decay (LEGEND)
  • 2017
  • In: AIP Conference Proceedings. - : Author(s). - 1551-7616 .- 0094-243X. ; 1894
  • Conference paper (peer-reviewed)abstract
    • The observation of neutrinoless double-beta decay (0νββ) would show that lepton number is violated, reveal that neu-trinos are Majorana particles, and provide information on neutrino mass. A discovery-capable experiment covering the inverted ordering region, with effective Majorana neutrino masses of 15 - 50 meV, will require a tonne-scale experiment with excellent energy resolution and extremely low backgrounds, at the level of ∼0.1 count /(FWHM·t·yr) in the region of the signal. The current generation 76Ge experiments GERDA and the Majorana Demonstrator, utilizing high purity Germanium detectors with an intrinsic energy resolution of 0.12%, have achieved the lowest backgrounds by over an order of magnitude in the 0νββ signal region of all 0νββ experiments. Building on this success, the LEGEND collaboration has been formed to pursue a tonne-scale 76Ge experiment. The collaboration aims to develop a phased 0νββ experimental program with discovery potential at a half-life approaching or at 1028 years, using existing resources as appropriate to expedite physics results.
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8.
  • Liu, Y., et al. (author)
  • Recent enhancement of central Pacific El Nino variability relative to last eight centuries
  • 2017
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Journal article (peer-reviewed)abstract
    • The far-reaching impacts of central Pacific El Nino events on global climate differ appreciably from those associated with eastern Pacific El Nino events. Central Pacific El Nino events may become more frequent in coming decades as atmospheric greenhouse gas concentrations rise, but the instrumental record of central Pacific sea-surface temperatures is too short to detect potential trends. Here we present an annually resolved reconstruction of NINO4 sea-surface temperature, located in the central equatorial Pacific, based on oxygen isotopic time series from Taiwan tree cellulose that span from 1190 AD to 2007 AD. Our reconstruction indicates that relatively warm Nino4 sea-surface temperature values over the late twentieth century are accompanied by higher levels of interannual variability than observed in other intervals of the 818-year-long reconstruction. Our results imply that anthropogenic greenhouse forcing may be driving an increase in central Pacific El Nino-Southern Oscillation variability and/or its hydrological impacts, consistent with recent modelling studies.
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9.
  • Nie, Huizhen, et al. (author)
  • The short isoform of PRLR suppresses the pentose phosphate pathway and nucleotide synthesis through the NEK9-Hippo axis in pancreatic cancer
  • 2021
  • In: Theranostics. - : Ivyspring International Publisher. - 1838-7640. ; 11:8, s. 3898-3915
  • Journal article (peer-reviewed)abstract
    • Prolactin binding to the prolactin receptor exerts pleiotropic biological effects in vertebrates. The prolactin receptor (PRLR) has multiple isoforms due to alternative splicing. The biological roles and related signaling of the long isoform (PRLR-LF) have been fully elucidated. However, little is known about the short isoform (PRLR-SF), particularly in cancer development and metabolic reprogramming, a core hallmark of cancer. Here, we reveal the role and underlying mechanism of PRLR-SF in pancreatic ductal adenocarcinoma (PDAC). Methods: A human PDAC tissue array was used to investigate the clinical relevance of PRLR in PDAC. The in vivo implications of PRLR-SF in PDAC were examined in a subcutaneous xenograft model and an orthotopic xenograft model. Immunohistochemistry was performed on tumor tissue obtained from genetically engineered KPC (KrasG12D/+; Trp53R172H/+; Pdx1-Cre) mice with spontaneous tumors. 13C-labeled metabolite measures, LC-MS, EdU incorporation assays and seahorse analyses were used to identify the effects of PRLR-SF on the pentose phosphate pathway and glycolysis. We identified the molecular mechanisms by immunofluorescence, coimmunoprecipitation, proximity ligation assays, chromatin immunoprecipitation and promoter luciferase activity. Public databases (TCGA, GEO and GTEx) were used to analyze the expression and survival correlations of the related genes. Results: We demonstrated that PRLR-SF is predominantly expressed in spontaneously forming pancreatic tumors of genetically engineered KPC mice and human PDAC cell lines. PRLR-SF inhibits the proliferation of PDAC cells (AsPC-1 and BxPC-3) in vitro and tumor growth in vivo. We showed that PRLR-SF reduces the expression of genes in the pentose phosphate pathway (PPP) and nucleotide biosynthesis by activating Hippo signaling. TEAD1, a downstream transcription factor of Hippo signaling, directly regulates the expression of G6PD and TKT, which are PPP rate-limiting enzymes. Moreover, NEK9 directly interacts with PRLR-SF and is the intermediator between PRLR and the Hippo pathway. The PRLR expression level is negatively correlated with overall survival and TNM stage in PDAC patients. Additionally, pregnancy and lactation increase the ratio of PRLR-SF:PRLR-LF in the pancreas of wild-type mice and subcutaneous PDAC xenograft tumors. Conclusion: Our characterization of the relationship between PRLR-SF signaling, the NEK9-Hippo pathway, PPP and nucleotide synthesis explains a mechanism for the correlation between PRLR-SF and metabolic reprogramming in PDAC progression. Strategies to alter this pathway might be developed for the treatment or prevention of pancreatic cancer.
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10.
  • Schuettpelz, Eric, et al. (author)
  • A community-derived classification for extant lycophytes and ferns
  • 2016
  • In: Journal of Systematics and Evolution. - : Wiley. - 1674-4918 .- 1759-6831. ; 54:6, s. 563-603
  • Journal article (peer-reviewed)abstract
    • Phylogeny has long informed pteridophyte classification. As our ability to infer evolutionary trees has improved, classifications aimed at recognizing natural groups have become increasingly predictive and stable. Here, we provide a modern, comprehensive classification for lycophytes and ferns, down to the genus level, utilizing a community-based approach. We use monophyly as the primary criterion for the recognition of taxa, but also aim to preserve existing taxa and circumscriptions that are both widely accepted and consistent with our understanding of pteridophyte phylogeny. In total, this classification treats an estimated 11 916 species in 337 genera, 51 families, 14 orders, and two classes. This classification is not intended as the final word on lycophyte and fern taxonomy, but rather a summary statement of current hypotheses, derived from the best available data and shaped by those most familiar with the plants in question. We hope that it will serve as a resource for those wanting references to the recent literature on pteridophyte phylogeny and classification, a framework for guiding future investigations, and a stimulus to further discourse.
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12.
  • Bai, Ru, et al. (author)
  • Clinical characteristics and phylogenetic analysis of human enteric adenovirus type 41 (HAdV-F41) from children with gastroenteritis during SARS-CoV-2 pandemic
  • 2024
  • In: Infection, Genetics and Evolution. - : Elsevier. - 1567-1348 .- 1567-7257. ; 123
  • Journal article (peer-reviewed)abstract
    • Human adenovirus type 41 (HAdV-F41) usually causes pediatrics gastroenteritis. However, it was reported to be associated with the outbreaks of severe acute hepatitis of unknown aetiology (SAHUA) in pediatrics during COVID-19 pandemic. In this study, we investigated the prevalence of enteric HAdV-F41 in 37,920 paediatric gastroenteritis cases from 2017 to 2022 in Guangzhou, China. All children presented were tested negative for SARS-CoV-2 during the “zero-COVID” period. The main clinical symptom of the children was diarrhea (96.5%). No fatalities nor liver abnormal symptoms was found. In 2021, one year since the pandemic of COVID-19, the prevalence of HAdV-F41 abruptly increased from 3.71% to 8.64% (P < 0.001). All of HAdV-F41 circulating worldwide were classified into eight different subtypes (G1-G8) based on the phylogenetic clustering permutation of the four capsid genes of HAdV-F41. G3 was the predominant subtype (56.2%; 77/137). CRV5 isolates from SAHUA cases belong to this subtype, in which N312D and H335D mutations in the short fiber knob were identified in both Guangzhou and CRV5 isolates, presumably changing the virus tropism by directly interacting with the heparin sulfate (HS) receptor. Additionally, a novel recombinant G6 subtype, which is unique and only circulating in China was first identified in this study. This is the first study highlighting the prevalence of HAdV-F41 in paediatric cases of gastroenteritis during COVID-19 pandemic in China. The clinical and viral evolution finding of HAdV-F41 provide insight into the clinical characteristics of children with HAdV-F41 infections as well as the uncertain role of HAdV-F41 in the cause of SAHUA.
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13.
  • Clark, DW, et al. (author)
  • Associations of autozygosity with a broad range of human phenotypes
  • 2019
  • In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4957-
  • Journal article (peer-reviewed)abstract
    • In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding.
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14.
  • Li, Yingkui, et al. (author)
  • Timing and extent of Quaternary glaciations in the Tianger Range, eastern Tian Shan, China, investigated using Be-10 surface exposure dating
  • 2014
  • In: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 98, s. 7-23
  • Journal article (peer-reviewed)abstract
    • Reconstructing glacial chronologies with consistent methods is critical for efforts to examine the timing and pattern of past climate change. Cosmogenic Be-10 surface exposure dating has been widely used to constrain the timing of glacial events on the Tibetan Plateau and in Central Asia. However, few such studies have been conducted in the Chinese Tian Shan and available Be-10 ages from this region have only provided evidence for glacial events during the global Last Glacial Maximum (gLGM) and Lateglacial. Here, we present 45 Be-10 surface exposure ages from glacial landforms in the Ala and Daxi valleys, two formerly glaciated valleys draining the Tianger Range, eastern Tian Shan. Combined with previously published Be-10 surface exposure ages from the Daxi Valley in the source area of the Urumqi River, the new ages record five major glacial events during Marine Oxygen Isotope Stages (MIS) 6 or older, 4, 3, 2, and 1 (during the Little Ice Age, LIA). Landforms from glacial events since MIS 2 are found on the northern slope of the Tianger Range (Daxi Valley), whereas evidence for the older glacial events is only preserved on its southern slope (Ala Valley). This disparity may be caused by different preservation- and micro-climatic conditions on the northern and southern slopes of this mountain range, due to differences in gradient and aspect. The LIA glacial advances are apparently the only Holocene glacial event recorded in this area. Earlier Holocene glacial events were probably so restricted in extent that they were destroyed by subsequent LIA advances.
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15.
  • Liu, Kui, et al. (author)
  • Kallikrein genes are associated with lupus and glomerular basement membrane-specific antibody-induced nephritis in mice and humans
  • 2009
  • In: Journal of Clinical Investigation. - 0021-9738 .- 1558-8238. ; 119:4, s. 911-923
  • Journal article (peer-reviewed)abstract
    • Immune-mediated nephritis contributes to disease in systemic lupus erythematosus, Goodpasture syndrome (caused by antibodies specific for glomerular basement membrane [anti-GBM antibodies]), and spontaneous lupus nephritis. Inbred mouse strains differ in susceptibility to anti-GBM antibody-induced and spontaneous lupus nephritis. This study sought to clarify the genetic and molecular factors that maybe responsible for enhanced immune-mediated renal disease in these models. When the kidneys of 3 mouse strains sensitive to anti-GBM antibody-induced nephritis were compared with those of 2 control strains using microarray analysis, one-fifth of the underexpressed genes belonged to the kallikrein gene family,which encodes serine esterases. Mouse strains that upregulated renal and urinary kallikreins exhibited less evidence of disease. Antagonizing the kallikrein pathway augmented disease, while agonists dampened the severity of anti-GBM antibody-induced nephritis. In addition, nephritis-sensitive mouse strains had kallikrein haplotypes that were distinct from those of control strains, including several regulatory polymorphisms,some of which were associated with functional consequences. Indeed, increased susceptibility to anti-GBM antibody-induced nephritis and spontaneous lupus nephritis was achieved by breeding mice with a genetic interval harboring the kallikrein genes onto a disease-resistant background. Finally, both human SLE and spontaneous lupus nephritis were found to be associated with kallikrein genes, particularly KLK1 and the KLK3 promoter, when DNA SNPs from independent cohorts of SLE patients and controls were compared. Collectively, these studies suggest that kallikreins are protective disease-associated genes in anti-GBM antibody-induced nephritis and lupus.
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16.
  • Lozano, Rafael, et al. (author)
  • Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017
  • 2018
  • In: The Lancet. - : Elsevier. - 1474-547X .- 0140-6736. ; 392:10159, s. 2091-2138
  • Journal article (peer-reviewed)abstract
    • Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030.
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18.
  • Senanayake, Indunil C., et al. (author)
  • Fungal diversity notes 1611–1716: taxonomic and phylogenetic contributions on fungal genera and species emphasis in south China
  • 2023
  • In: Fungal Diversity. - 1560-2745 .- 1878-9129. ; 122, s. 161-403
  • Journal article (peer-reviewed)abstract
    • This article is the 15th contribution in the Fungal Diversity Notes series, wherein 115 taxa from three phyla, nine classes, 28 orders, 48 families, and 64 genera are treated. Fungal taxa described and illustrated in the present study include a new family, five new genera, 61 new species, five new combinations, one synonym, one new variety and 31 records on new hosts or new geographical distributions. Ageratinicolaceae fam. nov. is introduced and accommodated in Pleosporales. The new genera introduced in this study are Ageratinicola, Kevinia, Pseudomultiseptospora (Parabambusicolaceae), Marasmiellomycena, and Vizzinia (Porotheleaceae). Newly described species are Abrothallus altoandinus, Ageratinicola kunmingensis, Allocryptovalsa aceris, Allophoma yuccae, Apiospora cannae, A. elliptica, A. pallidesporae, Boeremia wisteriae, Calycina papaeana, Clypeococcum lichenostigmoides, Coniochaeta riskali-shoyakubovii, Cryphonectria kunmingensis, Diaporthe angustiapiculata, D. campylandrae, D. longipapillata, Diatrypella guangdongense, Dothiorella franceschinii, Endocalyx phoenicis, Epicoccum terminosporum, Fulvifomes karaiensis, F. pannaensis, Ganoderma ghatensis, Hysterobrevium baoshanense, Inocybe avellaneorosea, I. lucida, Jahnula oblonga, Kevinia lignicola, Kirschsteiniothelia guangdongensis, Laboulbenia caprina, L. clavulata, L. cobiae, L. cosmodisci, L. nilotica, L. omalii, L. robusta, L. similis, L. stigmatophora, Laccaria rubriporus, Lasiodiplodia morindae, Lyophyllum agnijum, Marasmiellomycena pseudoomphaliiformis, Melomastia beihaiensis, Nemania guangdongensis, Nigrograna thailandica, Nigrospora ficuum, Oxydothis chinensis, O. yunnanensis, Petriella thailandica, Phaeoacremonium chinensis, Phialocephala chinensis, Phytophthora debattistii, Polyplosphaeria nigrospora, Pronectria loweniae, Seriascoma acutispora, Setoseptoria bambusae, Stictis anomianthi, Tarzetta tibetensis, Tarzetta urceolata, Tetraploa obpyriformis, Trichoglossum beninense, and Tricoderma pyrrosiae. We provide an emendation for Urnula ailaoshanensis Agaricus duplocingulatoides var. brevisporus introduced as a new variety based on morphology and phylogeny.
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19.
  • Zhou, Xuming, et al. (author)
  • Research on Gob-Side Entry Retaining Mining of Fully Mechanized Working Face in Steeply Inclined Coal Seam: A Case in Xinqiang Coal Mine
  • 2022
  • In: Sustainability. - : MDPI. - 2071-1050. ; 14:16
  • Journal article (peer-reviewed)abstract
    • As a kind of non-coal pillar roadway support technique, gob-side entry retaining is of great significance to improve the production efficiency of a fully mechanized working face. However, the construction of the roadway is often subject to the surrounding rock conditions, the application is mainly concentrated in the nearly horizontal and gently inclined coal seam conditions, and the application in the steeply inclined coal seam conditions is relatively less. This paper is based on the gob-side entry retaining roadway construction of the 58# upper right 3# working face in the fifth district of Xinqiang Coal Mine, and describes the investigation in which we measured the advanced abutment stress, mining stress, and roof stress and analyzed the moving rule of roof. On this basis, in this work, we determined the filling parameters and process and investigated the filling effect from the perspective of the deformation of the filling body and the surrounding rock. The results show that the influence range of the advanced abutment stress in the working face is about 20~25 m, the stress in the upper part is intense, and stress in the middle and lower parts are relaxed. The setting load, the cycle-end resistance, and the time-weighted mean resistance at the upper end of working face along the direction of length are the largest, followed by the middle part, and the lower end is the minimum. When exploiting the steep inclined coal seam, the upper part of the working face is more active than the lower part, and the damaging range of overlaying strata is mainly in the upper part of the goaf. With this research, we established the filling mining process in steeply inclined coal seams and determined the relevant parameters. The gangue cement mortar filling can ensure the deformation of the filling body, the surrounding rock of the roadway is small in the process of roadway retention, and the stress of the filling body is also small, which ensure the successful retention of the roadway. This study verifies the possibility of repair-less exploitation and provides a reference for the popularization and application of the gob-side entry retaining technique in steep inclined coal seam. 
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20.
  • Ade, Peter, et al. (author)
  • The Simons Observatory : science goals and forecasts
  • 2019
  • In: Journal of Cosmology and Astroparticle Physics. - : IOP Publishing. - 1475-7516. ; :2
  • Journal article (peer-reviewed)abstract
    • The Simons Observatory (SO) is a new cosmic microwave background experiment being built on Cerro Toco in Chile, due to begin observations in the early 2020s. We describe the scientific goals of the experiment, motivate the design, and forecast its performance. SO will measure the temperature and polarization anisotropy of the cosmic microwave background in six frequency bands centered at: 27, 39, 93, 145, 225 and 280 GHz. The initial con figuration of SO will have three small-aperture 0.5-m telescopes and one large-aperture 6-m telescope, with a total of 60,000 cryogenic bolometers. Our key science goals are to characterize the primordial perturbations, measure the number of relativistic species and the mass of neutrinos, test for deviations from a cosmological constant, improve our understanding of galaxy evolution, and constrain the duration of reionization. The small aperture telescopes will target the largest angular scales observable from Chile, mapping approximate to 10% of the sky to a white noise level of 2 mu K-arcmin in combined 93 and 145 GHz bands, to measure the primordial tensor-to-scalar ratio, r, at a target level of sigma(r) = 0.003. The large aperture telescope will map approximate to 40% of the sky at arcminute angular resolution to an expected white noise level of 6 mu K-arcmin in combined 93 and 145 GHz bands, overlapping with the majority of the Large Synoptic Survey Telescope sky region and partially with the Dark Energy Spectroscopic Instrument. With up to an order of magnitude lower polarization noise than maps from the Planck satellite, the high-resolution sky maps will constrain cosmological parameters derived from the damping tail, gravitational lensing of the microwave background, the primordial bispectrum, and the thermal and kinematic Sunyaev-Zel'dovich effects, and will aid in delensing the large-angle polarization signal to measure the tensor-to-scalar ratio. The survey will also provide a legacy catalog of 16,000 galaxy clusters and more than 20,000 extragalactic sources.
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21.
  • Cheng, Shi-Ping, et al. (author)
  • Haplotype-resolved genome assembly and allele-specific gene expression in cultivated ginger
  • 2021
  • In: Horticulture Research. - : Springer Nature. - 2052-7276. ; 8:1
  • Journal article (peer-reviewed)abstract
    • Ginger (Zingiber officinale) is one of the most valued spice plants worldwide; it is prized for its culinary and folk medicinal applications and is therefore of high economic and cultural importance. Here, we present a haplotype-resolved, chromosome-scale assembly for diploid ginger anchored to 11 pseudochromosome pairs with a total length of 3.1 Gb. Remarkable structural variation was identified between haplotypes, and two inversions larger than 15 Mb on chromosome 4 may be associated with ginger infertility. We performed a comprehensive, spatiotemporal, genome-wide analysis of allelic expression patterns, revealing that most alleles are coordinately expressed. The alleles that exhibited the largest differences in expression showed closer proximity to transposable elements, greater coding sequence divergence, more relaxed selection pressure, and more transcription factor binding site differences. We also predicted the transcription factors potentially regulating 6-gingerol biosynthesis. Our allele-aware assembly provides a powerful platform for future functional genomics, molecular breeding, and genome editing in ginger.
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22.
  • Docherty, Anna R, et al. (author)
  • GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
  • 2023
  • In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
  • Journal article (peer-reviewed)abstract
    • Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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23.
  • Estrada, Karol, et al. (author)
  • Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
  • 2012
  • In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
  • Journal article (peer-reviewed)abstract
    • Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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24.
  • Gu, Peng, et al. (author)
  • A metabolite from commensal Candida albicans enhances the bactericidal activity of macrophages and protects against sepsis
  • 2023
  • In: Cellular & Molecular Immunology. - London : Nature Publishing Group. - 1672-7681 .- 2042-0226. ; 20:10, s. 1156-1170
  • Journal article (peer-reviewed)abstract
    • The gut microbiome is recognized as a key modulator of sepsis development. However, the contribution of the gut mycobiome to sepsis development is still not fully understood. Here, we demonstrated that the level of Candida albicans was markedly decreased in patients with bacterial sepsis, and the supernatant of Candida albicans culture significantly decreased the bacterial load and improved sepsis symptoms in both cecum ligation and puncture (CLP)-challenged mice and Escherichia coli-challenged pigs. Integrative metabolomics and the genetic engineering of fungi revealed that Candida albicans-derived phenylpyruvate (PPA) enhanced the bactericidal activity of macrophages and reduced organ damage during sepsis. Mechanistically, PPA directly binds to sirtuin 2 (SIRT2) and increases reactive oxygen species (ROS) production for eventual bacterial clearance. Importantly, PPA enhanced the bacterial clearance capacity of macrophages in sepsis patients and was inversely correlated with the severity of sepsis in patients. Our findings highlight the crucial contribution of commensal fungi to bacterial disease modulation and expand our understanding of the host-mycobiome interaction during sepsis development. © 2023, The Author(s), under exclusive licence to CSI and USTC.
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25.
  • Jiang, Qiyun, et al. (author)
  • Development and Validation of a Risk Score Screening Tool to Identify People at Risk for Hypertension in Shanghai, China.
  • 2022
  • In: Risk management and healthcare policy. - 1179-1594. ; 15, s. 553-562
  • Journal article (peer-reviewed)abstract
    • This study aimed to develop a screening tool based on a risk scoring approach that could identify individuals at high risk for hypertension in Shanghai, China.A total of 3147 respondents from the 2013 Shanghai Chronic Disease and Risk Factor Surveillance were randomly divided into the derivation group and validation group. The coefficients obtained from multivariable logistic regression were used to assign a score to each variable category. The receiver operating characteristic (ROC) curve was used to find the optimal cut-off point and to evaluate the screening performance.Age, family history of hypertension, having diabetes, having dyslipidemia, body mass index, and having abdominal obesity contributed to the risk score. The area under the ROC curve was 0.817 (95% CI: 0.797-0.836). The optimal cut-off value of 20 had a sensitivity of 83.4%, and a specificity of 64.3%, demonstrating good performance.We developed a simple and valid screening tool to identify individuals at risk for hypertension. Early detection could be beneficial for high-risk groups to better manage their conditions and delay the progression of hypertension and related complications.
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26.
  • Kristan, Matej, et al. (author)
  • The Visual Object Tracking VOT2013 challenge results
  • 2013
  • In: 2013 IEEE INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW). - : IEEE. - 9781479930227 ; , s. 98-111
  • Conference paper (peer-reviewed)abstract
    • Visual tracking has attracted a significant attention in the last few decades. The recent surge in the number of publications on tracking-related problems have made it almost impossible to follow the developments in the field. One of the reasons is that there is a lack of commonly accepted annotated data-sets and standardized evaluation protocols that would allow objective comparison of different tracking methods. To address this issue, the Visual Object Tracking (VOT) workshop was organized in conjunction with ICCV2013. Researchers from academia as well as industry were invited to participate in the first VOT2013 challenge which aimed at single-object visual trackers that do not apply pre-learned models of object appearance (model-free). Presented here is the VOT2013 benchmark dataset for evaluation of single-object visual trackers as well as the results obtained by the trackers competing in the challenge. In contrast to related attempts in tracker benchmarking, the dataset is labeled per-frame by visual attributes that indicate occlusion, illumination change, motion change, size change and camera motion, offering a more systematic comparison of the trackers. Furthermore, we have designed an automated system for performing and evaluating the experiments. We present the evaluation protocol of the VOT2013 challenge and the results of a comparison of 27 trackers on the benchmark dataset. The dataset, the evaluation tools and the tracker rankings are publicly available from the challenge website(1).
  •  
27.
  • Li, Dianxiang, et al. (author)
  • Expression of the Shrimp wap gene in Drosophila elicits defense responses and protease inhibitory activity
  • 2018
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8
  • Journal article (peer-reviewed)abstract
    • The wap gene encodes a single whey acidic protein (WAP) domain-containing peptide from Chinese white shrimp (Fenneropenaeus chinensis), which shows broad-spectrum antimicrobial activities and proteinase inhibitory activities in vitro. To explore the medical applications of the WAP peptide, a wap gene transgenic Drosophila melanogaster was constructed. In wap-expressing flies, high expression levels of wap gene (> 100 times) were achieved, in contrast to those of control flies, by qRT-PCR analysis. The wap gene expression was associated with increased resistance to microbial infection and decreased bacterial numbers in the flies. In addition, the WAP protein extract from wap-expressing flies, compared with control protein extract from control flies, showed improved antimicrobial activities against broad Gram-positive and Gram-negative bacteria, including the clinical drug resistant bacterium of methicillin-resistant S. aureus (MRSA), improved protease inhibitor activities against crude proteinases and commercial proteinases, including elastase, subtilis proteinase A, and proteinase K in vitro, and improved growth rate and microbial resistance, as well as wound-healing in loach and mouse models. These results suggest that wap-expressing flies could be used as a food additive in aquaculture to prevent infections and a potential antibacterial for fighting drug-resistant bacteria.
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28.
  • Li, Fei, et al. (author)
  • Iron(III) complexes with a tripodal N3O ligand containing an internal base as a model for catechol intradiol-cleaving dioxygenases
  • 2007
  • In: Inorganic Chemistry. - : American Chemical Society (ACS). - 0020-1669 .- 1520-510X. ; 46:22, s. 9364-9371
  • Journal article (peer-reviewed)abstract
    • A bis(mu-alkoxo)-bridged dinuclear iron(III) complex [Fe(L)(NO3)](2)(NO3)(2) [1; HL = NN-bis(2-pyridylmethyl)-N-(2hydroxyethyl)amine] of the tripodal N3O ligand was prepared as a biomimetic model for the intradiol-cleaving dioxygenase enzymes. The reaction of 1 and catechol in the presence of excess triethylamine gave the catecholate (CAT) chelate b is(u -al koxo) -bridged dinuclear iron(Ill) complex [Fe(L)(CAT)12 (2). The molecular structures of complexes 1 and 2 were determined by X-ray crystallography. Diiron complexes 1 and 2 contain the same bis(u-alkoxo)diiron diamond core. All heteroatoms (N3O) of the ligand are coordinated to the iron center in complex 1 with two pyridine nitrogen atoms on the axial bonds, while one of the pyridyl arms of the ligand is left uncoordinated in complex 2. The interaction of the diiron complex 1 and 3,5-di-tert-butylcatechol (H2DBC) was investigated by electronic and mass spectroscopy. Complex 1 displays the intradiol-cleaving dioxygenase activity, and the coordinate ethoxyl arm of the ligand is capable of accepting the proton from catechol, which mimics the function of Tyr447 in the. protocatechuate 3,4-dioxygenase as an internal base. The spectrop h oto metric titration experiment indicates the relatively low demand of the external base (0.8 equiv based on Fe3+) for attaining the highest dioxygenase activity of complex 1. The reaction rate of the reactive intermediate [Fe(HL)(DBC)](+) with dioxygen is 0.38 M-1 s(-1) determined by kinetic studies.
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29.
  • Li, Fang-Yi, et al. (author)
  • Inhibition of K-Ras4B-plasma membrane association with a membrane microdomain-targeting peptide
  • 2020
  • In: Chemical Science. - : Royal Society of Chemistry. - 2041-6520 .- 2041-6539. ; 11:3, s. 826-832
  • Journal article (peer-reviewed)abstract
    • The association of K-Ras4B protein with plasma membrane (PM) is required for its signaling activity. Thus, direct inhibition of K-Ras4B-PM interaction could be a potential anti-Ras therapeutic strategy. However, it remains challenging to modulate such protein-PM interaction. Based on Ras isoform-specific PM microdomain localization patterns, we have developed a potent and isoform-selective peptide inhibitor, Memrasin, for detachment of K-Ras4B from the PM. Memrasin is one of the first direct inhibitors of K-Ras4B-PM interaction, and consists of a membrane l(d) region-binding sequence derived from the C-terminal region of K-Ras4B and an endosome-escape enhancing motif that can aggregate on membrane. It forms peptide-enriched domains in the l(d) region, abrogates the tethering of K-Ras4B to the PM and accordingly impairs Ras signaling activity, thereby efficiently decreasing the viability of several human lung cancer cells in a dose-responsive and K-Ras dependent manner. Memrasin provides a useful tool for exploring the biological function of K-Ras4B on or off the PM and a potential starting point for further development into anti-Ras therapeutics.
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30.
  • Li, Hanbing, et al. (author)
  • Dual Function of PI(4,5)P2 in Insulin-Regulated Exocytic Trafficking of GLUT4 in Adipocytes
  • 2020
  • In: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 432:16, s. 4341-4357
  • Journal article (peer-reviewed)abstract
    • Phosphoinositides are important signaling molecules involved in the regulation of vesicular trafficking. It has been implicated that phosphatidylinositol 4,5-bisphosphate [PI(4,5)P-2] is involved in insulin-regulated GLUT4 translocation in adipocytes. However, it remains unclear where and how PI(4,5)P-2 regulates discrete steps of GLUT4 vesicle translocation in adipocytes, especially on the exocytic arm of regulation. Here, we employed optogenetic tools to acutely control the PI(4,5)P-2 metabolism in living cells. By combination of TIRFM imaging, we were able to monitor the temporal-spatial-dependent PI(4,5)P-2 regulation on discrete steps of GLUT4 translocation in adipocytes. We found that the plasma membrane localized PI(4,5)P-2 is crucial for proper insulin signaling propagation and for insulin-stimulated GLUT4 vesicle translocation in 3T3-L1 adipocytes. Global depletion of PI(4,5)P-2 on the cell surface blunted insulin-stimulated Akt phosphorylation and abolished insulin effects in promotion of the docking and fusion of GLUT4 vesicle with the plasma membrane. Furthermore, by development of a novel optogenetic module to selectively modulate PI(4,5)P-2 levels on the GLUT4 vesicle docking site, we identified an important regulatory role of PI(4,5)P-2 in controlling of vesicle docking process. Local depletion of PI(4,5)P-2 at the vesicle docking site promoted GLUT4 vesicle undocking, diminished insulin-stimulated GLUT4 vesicle docking and fusion, but without perturbation of insulin signaling propagation in adipocytes. Our results provide strong evidence that cell surface PI(4,5)P-2 plays two distinct functions on regulation of the exocytic trafficking of GLUT4 in adipocytes. PI(4,5)P-2 not only regulates the proper activation of insulin signaling in general but also controls GLUT4 vesicle docking process at the vesicle-membrane contact sites.
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31.
  • Li, Kai, et al. (author)
  • Metal thermopile infrared detector with vertical graphene
  • 2023
  • In: Wuli Xuebao/Acta Physica Sinica. - : Acta Physica Sinica, Chinese Physical Society and Institute of Physics, Chinese Academy of Sciences. - 1000-3290. ; 72:3
  • Journal article (peer-reviewed)abstract
    • Thermopile infrared detector is a kind of detector device mainly composed of thermocouple as the basic unit. Because of its simple principle, no need of cooling equipment, and other advantages, it has been widely used in various fields of production and life. However, the absorption rates of the materials in conventional thermopile devices are poor, and the majority of them are incompatible with microfabrication methods. In this work, a metal thermopile infrared detector with vertical graphene (VG) is designed and fabricated. The VG is grown via plasma enhanced chemical vapor deposition, and retained at the device’s thermal ends to provide the thermopile IR detector’s wideband and high response characteristics. The detector achieves a room temperature responsivity reaching a value as high as 1.53 V/W at 792 nm, which can increase the response results about 28 times and reduce the response time to 0.8 ms compared with the thermopile detector without VG. After systematically measuring the response results, it is finally found that there are three main mechanisms responsible for the response on the composite device. The first one is the response generated by the metal thermopile itself alone. The second one is the response increased eventually by the contribution of VG covered at the metal thermal junction that expands the temperature difference. The last one is the response generated by the temperature gradient existing inside the VG on the surface of the device after the absorption of heat. The portion of each partial response mechanism in the total response is also analyzed, providing a new reference direction for analyzing the response generation mechanism of thermopile detectors with other absorbing materials. The process is compatible with the microfabrication, while the device performance is enhanced and suitable for mass production. Furthermore, by utilizing the surface plasmon resonance to combine VG with metal nanoparticles, the material’ s light absorption is found to be enhanced significantly under the same conditions, and the resulting thermal voltage can be increased to 6 times. The results indicate that VG promises to possess practical applications, in many fields such as photoelectric sensing and power production devices. This technology provides a new method to manufacture high-performance thermopile infrared detectors and other sensor devices.
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32.
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33.
  • Li, Ming, et al. (author)
  • Potency increase of spiroketal analogs of membrane inserting indolyl mannich base antimycobacterials is due to acquisition of MmpL3 inhibition
  • 2020
  • In: ACS - Infectious Diseases. - : American Chemical Society (ACS). - 2373-8227. ; 6:7, s. 1882-1893
  • Journal article (peer-reviewed)abstract
    • Chemistry campaigns identified amphiphilic indolyl Mannich bases as novel membrane-permeabilizing antimycobacterials. Spiroketal analogs of this series showed increased potency, and the lead compound 1 displayed efficacy in a mouse model of tuberculosis. Yet the mechanism by which the spiroketal moiety accomplished the potency “jump” remained unknown. Consistent with its membrane-permeabilizing mechanism, no resistant mutants could be isolated against indolyl Mannich base 2 lacking the spiroketal moiety. In contrast, mutations resistant against spiroketal analog 1 were obtained in mycobacterial membrane protein large 3 (MmpL3), a proton motive force (PMF)-dependent mycolate transporter. Thus, we hypothesized that the potency jump observed for 1 may be due to MmpL3 inhibition acquired by the addition of the spiroketal moiety. Here we showed that 1 inhibited MmpL3 flippase activity without loss of the PMF, colocalized with MmpL3tb–GFP in intact organisms, and yielded a consistent docking pose within the “common inhibitor binding pocket” of MmpL3. The presence of the spiroketal motif in 1 ostensibly augmented its interaction with MmpL3, an outcome not observed in the nonspiroketal analog 2, which displayed no cross-resistance to mmpL3 mutants, dissipated the PMF, and docked poorly in the MmpL3 binding pocket. Surprisingly, 2 inhibited MmpL3 flippase activity, which may be an epiphenomenon arising from its wider membrane disruptive effects. Hence, we conclude that the potency increase associated with the spiroketal analog 1 is linked to the acquisition of a second mechanism, MmpL3 inhibition. In contrast, the nonspiroketal analog 2 acts pleiotropically, affecting several cell membrane-embedded targets, including MmpL3, through its membrane permeabilizing and depolarizing effects.
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34.
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35.
  • Mei, J, et al. (author)
  • Development and external validation of a COVID-19 mortality risk prediction algorithm: a multicentre retrospective cohort study
  • 2020
  • In: BMJ open. - : BMJ. - 2044-6055. ; 10:12, s. e044028-
  • Journal article (peer-reviewed)abstract
    • This study aimed to develop and externally validate a COVID-19 mortality risk prediction algorithm.DesignRetrospective cohort study.SettingFive designated tertiary hospitals for COVID-19 in Hubei province, China.ParticipantsWe routinely collected medical data of 1364 confirmed adult patients with COVID-19 between 8 January and 19 March 2020. Among them, 1088 patients from two designated hospitals in Wuhan were used to develop the prognostic model, and 276 patients from three hospitals outside Wuhan were used for external validation. All patients were followed up for a maximal of 60 days after the diagnosis of COVID-19.MethodsThe model discrimination was assessed by the area under the receiver operating characteristic curve (AUC) and Somers’ D test, and calibration was examined by the calibration plot. Decision curve analysis was conducted.Main outcome measuresThe primary outcome was all-cause mortality within 60 days after the diagnosis of COVID-19.ResultsThe full model included seven predictors of age, respiratory failure, white cell count, lymphocytes, platelets, D-dimer and lactate dehydrogenase. The simple model contained five indicators of age, respiratory failure, coronary heart disease, renal failure and heart failure. After cross-validation, the AUC statistics based on derivation cohort were 0.96 (95% CI, 0.96 to 0.97) for the full model and 0.92 (95% CI, 0.89 to 0.95) for the simple model. The AUC statistics based on the external validation cohort were 0.97 (95% CI, 0.96 to 0.98) for the full model and 0.88 (95% CI, 0.80 to 0.96) for the simple model. Good calibration accuracy of these two models was found in the derivation and validation cohort.ConclusionThe prediction models showed good model performance in identifying patients with COVID-19 with a high risk of death in 60 days. It may be useful for acute risk classification.
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36.
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37.
  • Mullins, Niamh, et al. (author)
  • Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
  • 2022
  • In: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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38.
  • Pan, Xiong-Fei, et al. (author)
  • Circulating fatty acids and risk of gestational diabetes mellitus : prospective analyses in China
  • 2021
  • In: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 185:1, s. 87-97
  • Journal article (peer-reviewed)abstract
    • Objective: We aimed to examine prospective associations between circulating fatty acids in early pregnancy and incident gestational diabetes mellitus (GDM) among Chinese pregnant women.Methods: Analyses were based on two prospective nested case-control studies conducted in western China (336 GDM cases and 672 matched controls) and central China (305 cases and 305 matched controls). Fasting plasma fatty acids in early pregnancy (gestational age at enrollment: 10.4 weeks(s.d., 2.0)) and 13.2 weeks (1.0), respectively) were determined by gas chromatography-mass spectrometry, and GDM was diagnosed based on the International Association of Diabetes in Pregnancy Study Groups criteria during 24-28 weeks of gestation. Multiple metabolic biomarkers (HOMA-IR (homeostatic model assessment for insulin resistance), HbA1c, c-peptide, high-sensitivity C-reactive protein, adiponectin, leptin, and blood lipids) were additionally measured among 672 non-GDM controls at enrollment.Results: Higher levels of saturated fatty acids (SFAs) 14:0 (pooled odds ratio, 1.41 for each 1-s.d. increase; 95% CI: 1.25, 1.59) and 16:0 (1.19; 1.05, 1.35) were associated with higher odds of GDM. Higher levels of n-6 polyunsaturated fatty acid (PUFA) 18:2n-6 were strongly associated with lower odds of GDM (0.69; 0.60, 0.80). In non-GDM pregnant women, higher SFAs 14:0 and 16:0 but lower n-6 PUFA 18:2n-6 were generally correlated with unfavorable metabolic profiles.Conclusions: We documented adverse associations of 14:0 and 16:0 but a protective association of 18:2n-6 with GDM among Chinese pregnant women. Our findings highlight the distinct roles of specific fatty acids in the onset of GDM.
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39.
  • Shi, Tian-Le, et al. (author)
  • High-quality genome assembly enables prediction of allele-specific gene expression in hybrid poplar
  • 2024
  • In: Plant Physiology. - : Oxford University Press. - 0032-0889 .- 1532-2548. ; 195:1, s. 652-670
  • Journal article (peer-reviewed)abstract
    • Poplar (Populus) is a well-established model system for tree genomics and molecular breeding, and hybrid poplar is widely used in forest plantations. However, distinguishing its diploid homologous chromosomes is difficult, complicating advanced functional studies on specific alleles. In this study, we applied a trio-binning design and PacBio high-fidelity long-read sequencing to obtain haplotype-phased telomere-to-telomere genome assemblies for the 2 parents of the well-studied F1 hybrid “84K” (Populus alba × Populus tremula var. glandulosa). Almost all chromosomes, including the telomeres and centromeres, were completely assembled for each haplotype subgenome apart from 2 small gaps on one chromosome. By incorporating information from these haplotype assemblies and extensive RNA-seq data, we analyzed gene expression patterns between the 2 subgenomes and alleles. Transcription bias at the subgenome level was not uncovered, but extensive-expression differences were detected between alleles. We developed machine-learning (ML) models to predict allele-specific expression (ASE) with high accuracy and identified underlying genome features most highly influencing ASE. One of our models with 15 predictor variables achieved 77% accuracy on the training set and 74% accuracy on the testing set. ML models identified gene body CHG methylation, sequence divergence, and transposon occupancy both upstream and downstream of alleles as important factors for ASE. Our haplotype-phased genome assemblies and ML strategy highlight an avenue for functional studies in Populus and provide additional tools for studying ASE and heterosis in hybrids.
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40.
  • Sun, Hongfei, et al. (author)
  • Synthesis and structure of a mu-oxo diiron(III) complex with an N-pyridylmethyl-N,N-bis(4-methylbenzimidazol-2-yl)amine ligand and its catalytic property for hydrocarbon oxidation
  • 2008
  • In: Applied organometallic chemistry. - : Wiley. - 0268-2605 .- 1099-0739. ; 22:10, s. 573-576
  • Journal article (peer-reviewed)abstract
    • A mu-oxo diiron(III) complex [{Fe(pbba)Cl}(2)(mu-O)]Cl-2 (1, pbba = N-pyridylmethyl-N,N-bis(4-methylbenzimidazol-2-yl)amine) bearing multi-imidazolyl motifs was synthesized and characterized by X-ray crystallography to closely mimic the structural features of methane monooxygenase. As shown by its X-ray crystal structure, complex 1 is a centrosymmetric dimer with an Fe-O-Fe angle of 180 degrees, and pseudo-octahedral around each iron(III) center. The catalytic ability of title compound in the oxidation of alkane and alkene is investigated by employing tert-butylhydroperoxide and m-chloroperbenzoic acid as oxidants under mild conditions. The catalytic oxidation results showed that radical intermediate dominates the oxidation process.
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41.
  • Sun, S., et al. (author)
  • Inhibition of the Activation and Recruitment of Microglia-Like Cells Protects Against Neomycin-Induced Ototoxicity
  • 2015
  • In: Molecular Neurobiology. - : Springer Science and Business Media LLC. - 0893-7648 .- 1559-1182. ; 51:1, s. 252-267
  • Journal article (peer-reviewed)abstract
    • One of the most unfortunate side effects of aminoglycoside (AG) antibiotics such as neomycin is that they target sensory hair cells (HCs) and can cause permanent hearing impairment. We have observed HC loss and microglia-like cell (MLC) activation in the inner ear (cochlea) following neomycin administration. We focused on CX3CL1, a membrane-bound glycoprotein expressed on neurons and endothelial cells, as a way to understand how the MLCs are activated and the role these cells play in HC loss. CX3CL1 is the exclusive ligand for CX3CR1, which is a chemokine receptor expressed on the surface of macrophages and MLCs. In vitro experiments showed that the expression levels of CX3CL1 and CX3CR1 increased in the cochlea upon neomycin treatment, and CX3CL1 was expressed on HCs, while CX3CR1 was expressed on MLCs. When cultured with 1 mu g/mL exogenous CX3CL1, MLCs were activated by CX3CL1, and the cytokine level was increased in the cochleae leading to apoptosis in the HCs. In CX3CR1 knockout mice, a significantly greater number of cochlear HCs survived than in wild-type mice when the cochlear explants were cultured with neomycin in vitro. Furthermore, inhibiting the activation of MLCs with minocycline reduced the neomycin-induced HC loss and improved the hearing function in neomycin-treated mice in vivo. Our results demonstrate that CX3CL1-induced MLC activation plays an important role in the induction of HC death and provide evidence for CX3CL1 and CX3CR1 as promising new therapeutic targets for the prevention of hearing loss.
  •  
42.
  • Wei, Jiang, et al. (author)
  • 17β-estradiol regulates the expression of apolipoprotein M through estrogen receptor α-specific binding motif in its promoter
  • 2017
  • In: Lipids in Health and Disease. - : Springer Science and Business Media LLC. - 1476-511X. ; 16:1, s. 1-8
  • Journal article (peer-reviewed)abstract
    • Background: We have previously demonstrated that estrogen could significantly enhance expression of apolipoprotein M (apoM), whereas the molecular basis of its mechanism is not fully elucidated yet. To further investigate the mechanism behind the estrogen induced up-regulation of apoM expression. Results: Our results demonstrated either free 17β-estradiol (E2) or membrane-impermeable bovine serum albumin-conjugated E2 (E2-BSA) could modulate human apoM gene expression via the estrogen receptor alpha (ER-α) pathway in the HepG2 cells. Moreover, experiments with the luciferase activity analysis of truncated apoM promoters could demonstrate that a regulatory region (from-1580 to −1575 bp (−GGTCA-)) upstream of the transcriptional start site of apoM gene was essential for the basal transcriptional activity that regulated by the ER-α. With the applications of an electrophoresis mobility shift assay and a chromatin immunoprecipitation assay, we could successfully identify a specific ER-α binding element in the apoM promoter region. Conculsion: In summary, the present study indicates that 17β-estradiol induced up-regulation of apoM in HepG2 cells is through an ER-α-dependent pathway involving ER-α binding element in the promoter of the apoM gene.
  •  
43.
  • Xue, Ru, et al. (author)
  • Variations of methane fluxes and methane microbial community composition with soil depth in the riparian buffer zone of a sponge city park
  • 2023
  • In: Journal of Environmental Management. - : Elsevier. - 0301-4797 .- 1095-8630. ; 339
  • Journal article (peer-reviewed)abstract
    • Riparian buffers benefit both natural and man-made ecosystems by preventing soil erosion, retaining soil nu-trients, and filtering pollutants. Nevertheless, the relationship between vertical methane fluxes, soil carbon, and methane microbial communities in riparian buffers remains unclear. This study examined vertical methane fluxes, soil carbon, and methane microbial communities in three different soil depths (0-5 cm, 5-10 cm, and 10-15 cm) within a riparian buffer of a Sponge City Park for one year. Structural equation model (SEM) results demonstrated that vertical methane fluxes varied with soil depths (lambda =-0.37) and were primarily regulated by methanogenic community structure (lambda = 0.78). Notably, mathematical regression results proposed that mcrA/ pmoA ratio (R2 = 0.8) and methanogenic alpha diversity/methanotrophic alpha diversity ratio (R2 = 0.8) could serve as valid predictors of vertical variation in methane fluxes in the riparian buffer of urban river. These findings suggest that vertical variation of methane fluxes in riparian buffer soils is mainly influenced by carbon inputs and methane microbial abundance and community diversity. The study's results quantitatively the relationship between methane fluxes in riparian buffer soils and abiotic and biotic factors in the vertical di-rection, therefore contributing to the further development of mathematical models of soil methane emissions.
  •  
44.
  • Yao, Xiangyu, et al. (author)
  • A highly sensitive bead-based flow cytometric competitive binding assay to detect SARS-CoV-2 neutralizing antibody activity
  • 2022
  • In: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
  • Journal article (peer-reviewed)abstract
    • Accurate detection of SARS-CoV-2 neutralizing antibody (nAb) is critical for assessing the immunity levels after virus infection or vaccination. As fast, cost-effective alternatives to viral infection-based assays, competitive binding (CB) assays were developed to quantitate nAb by monitoring the ability of sera to inhibit the binding of viral spike (S) protein to the angiotensin converting enzyme 2 (ACE2) receptor. Herein, we established a bead-based flow cytometric CB assay and tested the detection performance of six combination models, i.e. immobilized ACE2 and soluble Fc-tagged S1 subunit of S protein (iACE2/S1-Fc), immobilized ACE2 and soluble Fc-tagged receptor binding domain (RBD) of S protein (iACE2/RBD-Fc), immobilized S1 and soluble Fc-tagged ACE2 (iS1/ACE2-Fc), immobilized S1 and soluble His-tagged ACE2 (iS1/ACE2-His), immobilized RBD and soluble Fc-tagged ACE2 (iRBD/ACE2-Fc), and immobilized RBD and soluble His-tagged ACE2 (iRBD/ACE2-His). Using SARS-CoV-2 monoclonal antibodies and sera of convalescent COVID-19 patients and vaccinated subjects, the combination models iACE2/RBD-Fc, iACE2/S1-Fc and iS1/ACE2-His were identified to be able to specifically detect SARS-CoV-2 nAb, among which iACE2/RBD-Fc model showed the highest sensitivity, superior to a commercial SARS-CoV-2 surrogate virus neutralization test (sVNT) ELISA kit. Further studies demonstrated that the sensitivity and specificity of CB assays were affected by the tag of ACE2, type of spike and method of measuring binding rate between ACE2 and spike. Moreover, the iACE2/RBD-Fc model showed good performance in detecting kinetic development of nAb against both the prototype SARS-CoV-2 strain and an omicron variant of SARS-CoV-2 in people immunized by an inactivated SARS-CoV-2 vaccine, and the results of iACE2/RBD-Fc model are correlated well with those of live virus-based and pseudovirus-based neutralization tests, demonstrating the potential to be developed into a highly sensitive, specific, versatile and high-throughput method for detecting SARS-CoV-2 nAb in clinical practice.
  •  
45.
  • Yuan-Biao, Qiao, et al. (author)
  • Antifungal resistance-modifying multiplexing action of Momordica charantia protein and phosphorylated derivatives on the basis of growth-dependent gene coregulation in Candida albicans
  • 2021
  • In: Medical Mycology. - : Oxford University Press. - 1369-3786 .- 1460-2709. ; 59:6, s. 515-527
  • Journal article (peer-reviewed)abstract
    • Fungal growth-dependent gene coregulation is strongly implicated in alteration of gene-encoding target proteases ruling with an antifungal resistance niche and biology of resistant mutants. On the basis of multialterative processes in this platform, the resistance-modifying strategy is designed in ketoconazole resistant Candida albicans and evaluated with less selective Momordica charantia protein and allosterically phosphorylated derivatives at the Thr102, Thr24 and Thr255 sites, respectively. We demonstrate absolutely chemosensitizing efficacy regarding stepwise-modifying resistance in sensitivity, by a load of only 26.23-40.00 mu g/l agents in Sabouraud's dextrose broth. Five successive modifying-steps realize the decreasing of ketoconazole E-test MIC50 from 11.10 to a lower level than 0.10 mg/l. With the ketoconazole resistance-modifying, colony undergoes a high-frequency morphological switch between high ploidy (opaque) and small budding haploid (white). A cellular event in the first modifying-step associates with relatively slow exponential growth (ie, a 4-h delay)-dependent action, mediated by agents adsorption. Moreover, multiple molecular roles are coupled with intracellularly and extracellularly binding to ATP-dependent RNA helicase dbp6; the 0.08-2.45 fold upregulation of TATA-box-binding protein, rRNA-processing protein and translation initiation factor 5A; and the 7.52-55.33% decrease of cytochrome P450 lanosterol 14 alpha-demethylase, glucan 1, 3-beta glucosidase, candidapepsin-1 and 1-acylglycerol-3-phosphate O-acyltransferase. Spatial and temporal gene coregulation, in the transcription and translation initiation stages with rRNA-processing, is a new coprocessing platform enabling target protease attenuations for resistance-impairing. An updated resistance-modifying measure of these agents in the low-dose antifungal strategic design may provide opportunities to a virtually safe therapy that is in high dose-dependency.
  •  
46.
  • Zhang, Li, et al. (author)
  • Characterization of anti-BCG benz[α]anthraquinones and new siderophores from a Xinjiang desert-isolated rare actinomycete Nocardia sp. XJ31
  • 2020
  • In: Applied Microbiology and Biotechnology. - : Springer Science and Business Media LLC. - 0175-7598 .- 1432-0614. ; 104:19, s. 8267-8278
  • Journal article (peer-reviewed)abstract
    • The current global demand for novel anti-TB drugs has drawn urgent attention on the discovery of natural product compounds with anti-TB activity. Lots of efforts have emphasized on environmental samples from unexplored or underexplored natural habits and identified numerous rare actinomycete taxa producing structurally diverse bioactive natural products. Herein, we report a survey of the rare actinobacteria diversity in Xinjiang region together with the discovery of anti-TB active natural products from these strains. We have collected 17 soil samples at different sites with different environmental conditions, from which 39 rare actinobacteria were identified by using a selective isolation strategy with 5 media variations. Among those isolated strains, XJ31 was identified as a new Nocardia sp. based on 16S rRNA gene analysis. Through one strain-many compounds (OSMAC) strategy combined with anti-Bacillus Calmette-Guérin bioassay-guided isolation, two groups of compounds were identified. They were twelve siderophores (nocardimicins, 1-12) and two anthraquinones (brasiliquinones, 13 and 14) and ten of them were identified as new compounds. The structures of the purified compounds were elucidated using HR-ESI-MS, 1D NMR, and 2D NMR techniques. The anti-TB bioassays revealed that the two benz[α]anthraquinones have potent activity against BCG (MICs = 25 μM), which can be used as a promising start point for further anti-TB drug development.
  •  
47.
  • Zhang, Pan, et al. (author)
  • Photochemical H-2 production with noble-metal-free molecular devices comprising a porphyrin photosensitizer and a cobaloxime catalyst
  • 2010
  • In: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; 46:46, s. 8806-8808
  • Journal article (peer-reviewed)abstract
    • Among three noble-metal-free molecular devices (1-3) containing a porphyrin photosensitizer and a cobaloxime catalyst, the one with a zinc porphyrin unit displayed apparently higher efficiency for photoinduced H-2 production than complex 2 with a magnesium porphyrin and 3 with a free-base porphyrin, possibly due to the formation of a TEA center dot center dot center dot ZnPor-Co triad in solution.
  •  
48.
  • Zhang, Ting-Ting, et al. (author)
  • Protophilicity, electrochemical property, and desulfurization of diiron dithiolate complexes containing a functionalized C-2 bridge with two vicinal basic sites
  • 2009
  • In: Polyhedron. - : Elsevier BV. - 0277-5387 .- 1873-3719. ; 28:6, s. 1138-1144
  • Journal article (peer-reviewed)abstract
    • Two chiron dithiolate complexes [{mu-SC(NBn)CH(NHBn)S-mu)Fe-2(CO)(5)L] (L = PPh3, 2; P(Pyr)(3), 3) containing a functionlized C-2 bridge with two vicinal basic sites were prepared and characterized as models of the FeFe-hydrogenase active site. The molecular structures of 2 and its N-protonated form [(2H(N))(OTf)] were determined by X-ray analyses of single crystals. In the solid state of [(2HN)(OTf)]. Each asymmetric unit contains a molecule of [(2H(N))(OTf)] and a molecule of water. The molecule of water is close to the iron atom of the [Fe(CO)(3)] unit (Fe center dot center dot center dot O(H2O), 4J 99 angstrom). The complexes 2 and 3 are relatively protophilic. P-31 NMR spectra and cyclic voltammograms show that they can be protonated by the mild acids CCl3COOH and CF3COOH. Electrochemical studies show that the first reduction peak of 3 at - 1.51 V versus Fc(+)/Fc is 110 mV more positive than that (-1.62V) found for the analogous diiron azadithiolate complex [{(mu-SCH2)N(CH2C6H5)}Fe-2(CO)(5)P(Pyr)(3)] (7). Protonation of 2 and 3 leads to the anodic shifts of 610-650 mV for the (FeFe1)-Fe-1/(FeFe0)-Fe-1 reduction potentials. The shifts are apparently larger than that (450 mV) for protonation of 7. The reaction of the all-carbonyl complex [{(mu-SC(NBn)CH(NHBn)S-mu}Fe-2(CO)(5)L] with two equivalents of bis(diphenylphosphino)methane (dppm) in refluxing toluene affords a desulfurized complex 1(mu-S)(mu-dppm)(2)Fe-2(CO)(4)] (6). The reaction process was studied. A dppm mono-dentate intermediate [{mu-SC(NBn)CH(NHBn)S-mu)Fe-2(CO)(5)(kappa(1)-dppm)] (4) and a dppm mu-bridging species [{mu-SC(NBn)CH(NHBn)S-mu)Fe-2(CO)(4)(mu-dppm)] (5) have been isolated and spectroscopically characterized.
  •  
49.
  • Zhao, Li-Juan, et al. (author)
  • Lysine demethylase LSD1 delivered via small extracellular vesicles promotes gastric cancer cell stemness
  • 2021
  • In: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 22:8
  • Journal article (peer-reviewed)abstract
    • Several studies have examined the functions of nucleic acids in small extracellular vesicles (sEVs). However, much less is known about the protein cargos of sEVs and their functions in recipient cells. This study demonstrates the presence of lysine-specific demethylase 1 (LSD1), which is the first identified histone demethylase, in the culture medium of gastric cancer cells. We show that sEVs derived from gastric cancer cells and the plasma of patients with gastric cancer harbor LSD1. The shuttling of LSD1-containing sEVs from donor cells to recipient gastric cancer cells promotes cancer cell stemness by positively regulating the expression of Nanog, OCT4, SOX2, and CD44. Additionally, sEV-delivered LSD1 suppresses oxaliplatin response of recipient cells in vitro and in vivo, whereas LSD1-depleted sEVs do not. Taken together, we demonstrate that LSD1-loaded sEVs can promote stemness and chemoresistance to oxaliplatin. These findings suggest that the LSD1 content of sEV could serve as a biomarker to predict oxaliplatin response in gastric cancer patients.
  •  
50.
  • Abbafati, Cristiana, et al. (author)
  • 2020
  • Journal article (peer-reviewed)
  •  
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