| 1. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 2. |
- Kristan, Matej, et al.
(författare)
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The first visual object tracking segmentation VOTS2023 challenge results
- 2023
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Ingår i: 2023 IEEE/CVF International conference on computer vision workshops (ICCVW). - : Institute of Electrical and Electronics Engineers Inc.. - 9798350307443 - 9798350307450 ; , s. 1788-1810
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking Segmentation VOTS2023 challenge is the eleventh annual tracker benchmarking activity of the VOT initiative. This challenge is the first to merge short-term and long-term as well as single-target and multiple-target tracking with segmentation masks as the only target location specification. A new dataset was created; the ground truth has been withheld to prevent overfitting. New performance measures and evaluation protocols have been created along with a new toolkit and an evaluation server. Results of the presented 47 trackers indicate that modern tracking frameworks are well-suited to deal with convergence of short-term and long-term tracking and that multiple and single target tracking can be considered a single problem. A leaderboard, with participating trackers details, the source code, the datasets, and the evaluation kit are publicly available at the challenge website1
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| 3. |
- Kristan, Matej, et al.
(författare)
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The Ninth Visual Object Tracking VOT2021 Challenge Results
- 2021
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Ingår i: 2021 IEEE/CVF INTERNATIONAL CONFERENCE ON COMPUTER VISION WORKSHOPS (ICCVW 2021). - : IEEE COMPUTER SOC. - 9781665401913 ; , s. 2711-2738
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Konferensbidrag (refereegranskat)abstract
- The Visual Object Tracking challenge VOT2021 is the ninth annual tracker benchmarking activity organized by the VOT initiative. Results of 71 trackers are presented; many are state-of-the-art trackers published at major computer vision conferences or in journals in recent years. The VOT2021 challenge was composed of four sub-challenges focusing on different tracking domains: (i) VOT-ST2021 challenge focused on short-term tracking in RGB, (ii) VOT-RT2021 challenge focused on "real-time" short-term tracking in RGB, (iii) VOT-LT2021 focused on long-term tracking, namely coping with target disappearance and reappearance and (iv) VOT-RGBD2021 challenge focused on long-term tracking in RGB and depth imagery. The VOT-ST2021 dataset was refreshed, while VOT-RGBD2021 introduces a training dataset and sequestered dataset for winner identification. The source code for most of the trackers, the datasets, the evaluation kit and the results along with the source code for most trackers are publicly available at the challenge website(1).
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| 4. |
- Bai, Ru, et al.
(författare)
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Clinical characteristics and phylogenetic analysis of human enteric adenovirus type 41 (HAdV-F41) from children with gastroenteritis during SARS-CoV-2 pandemic
- 2024
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Ingår i: Infection, Genetics and Evolution. - : Elsevier. - 1567-1348 .- 1567-7257. ; 123
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Chen, Zhishan, et al.
(författare)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 6. |
- Chen, Zhi, et al.
(författare)
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Large-Area Crystalline Zeolitic Imidazolate Framework Thin Films
- 2021
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 60:25, s. 14124-14130
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Tidskriftsartikel (refereegranskat)abstract
- We report that continuous MOF films with highly controlled thickness (from 44 to 5100 nm) can be deposited over length scales greater than 80 centimeters by a facile, fast, and cost-effective spray-coating method. Such success relies on our discovery of unprecedented perfectly dispersed colloidal solutions consisting of amorphous MOF nanoparticles, which we adopted as precursors that readily converted to the crystalline films upon low-temperature in situ heating. The colloidal solutions allow for the fabrication of compact and uniform MOF films on a great deal of substrates such as fluorine-doped tin oxide, glass, SiO2, Al2O3, Si, Cu, and even flexible polycarbonate, widening their technological applications where substrates are essential. Despite the present work focuses on the fabrication of uniform cobalt-(2-methylimidazole)2 and zinc-(2-methylimidazole)2 films, our findings mark a great possibility in producing other high-quality MOF thin films on a large scale.
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| 7. |
- de las Fuentes, Lisa, et al.
(författare)
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Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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| 8. |
- Ding, Haoming, et al.
(författare)
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Progress in Structural Tailoring and Properties of Ternary Layered Ceramics
- 2023
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Ingår i: Journal of Inorganic Materials. - : SCIENCE PRESS. - 1000-324X. ; 38:8, s. 845-884
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Forskningsöversikt (refereegranskat)abstract
- MAX/MAB phases are a series of non-van der Waals ternary layered ceramic materials with a hexagonal structure, rich in elemental composition and crystal structure, and embody physical properties of both ceramics and metals. They exhibit great potential for applications in extreme environments such as high temperature, strong corrosion, and irradiation. In recent years, two-dimensional (2D) materials derived from the MAX/MAB phase (MXene and MBene) have attracted enormous interest in the fields of materials physics and materials chemistry and become a new 2D van der Waals material after graphene and transition metal dichalcogenides. Therefore, structural modulation of MAX/MAB phase materials is essential for understanding the intrinsic properties of this broad class of layered ceramics and for investigating the functional properties of their derived structures. In this paper, we summarize new developments in MAX/MAB phases in recent years in terms of structural modulation, theoretical calculation, and fundamental application research and provide an outlook on the key challenges and prospects for the future development of these layered materials.
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| 9. |
- Feng, Hongliang, et al.
(författare)
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Association between accelerometer-measured amplitude of rest-activity rhythm and future health risk : a prospective cohort study of the UK Biobank
- 2023
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Ingår i: The Lancet Healthy Longevity. - 2666-7568. ; 4:5, s. e200-e210
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The health effects of rest-activity rhythm are of major interest to public health, but its associations with health outcomes remain elusive. We aimed to examine the associations between accelerometer-measured rest-activity rhythm amplitude and health risks among the general UK population.METHODS: We did a prospective cohort analysis of UK Biobank participants aged 43-79 years with valid wrist-worn accelerometer data. Low rest-activity rhythm amplitude was defined as the first quintile of relative amplitude; all other quintiles were classified as high rest-activity rhythm amplitude. Outcomes of interest were defined using International Classification of Diseases 10th Revision codes and consisted of incident cancer and cardiovascular, infectious, respiratory, and digestive diseases, and all-cause and disease-specific (cardiovascular, cancer, and respiratory) mortality. Participants with a current diagnosis of any outcome of interest were excluded. We assessed the associations between decreased rest-activity rhythm amplitude and outcomes using Cox proportional hazards models.FINDINGS: Between June 1, 2013, and Dec 23, 2015, 103 682 participants with available raw accelerometer data were enrolled. 92 614 participants (52 219 [56·4%] women and 40 395 [42·6%] men) with a median age of 64 years (IQR 56-69) were recruited. Median follow-up was 6·4 years (IQR 5·8-6·9). Decreased rest-activity rhythm amplitude was significantly associated with increased incidence of cardiovascular diseases (adjusted hazard ratio 1·11 [95% CI 1·05-1·16]), cancer (1·08 [1·01-1·16]), infectious diseases (1·31 [1·22-1·41]), respiratory diseases (1·26 [1·19-1·34]), and digestive diseases (1·08 [1·03-1·14]), as well as all-cause mortality (1·54 [1·40-1·70]) and disease-specific mortality (1·73 [1·34-2·22] for cardiovascular diseases, 1·32 [1·13-1·55] for cancer, and 1·62 [1·25-2·09] for respiratory diseases). Most of these associations were not modified by age older than 65 years or sex. Among 16 accelerometer-measured rest-activity parameters, low rest-activity rhythm amplitude had the strongest or second- strongest associations with nine health outcomes.INTERPRETATION: Our results suggest that low rest-activity rhythm amplitude might contribute to major health outcomes and provide further evidence to promote risk-modifying strategies associated with rest-activity rhythm to improve health and longevity.
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| 10. |
- Gao, Lingfeng, et al.
(författare)
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A Facile Approach for Elemental-Doped Carbon Quantum Dots and Their Application for Efficient Photodetectors
- 2021
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Ingår i: Small. - : John Wiley & Sons. - 1613-6810 .- 1613-6829. ; 17:52
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Tidskriftsartikel (refereegranskat)abstract
- The present work demonstrates a facile hydrothermal approach to synthesize lanthanide-doped carbon quantum dots (CQDs) with europium and/or gadolinium elements. Taking the advantage of broadband adsorption in the ultraviolet-visible region, the doped QDs are directly used as building blocks for photo-electrochemical (PEC)-type photodetectors (PDs) and their performance is systematically investigated under various conditions. The europium (Eu) and gadolinium (Gd) co-doped (C:EuGd) QDs exhibit better photo-response than the single-elemental doped ones and also show outstanding long-term stability. According to the apparent response to light from 350 to 400 nm, the C:EuGd QDs are demonstrated to hold great potential for narrow-band PDs. This work highlights the practical applications of lanthanide-doped CQDs for PDs, and the results are beneficial for the development of elemental-doped CQDs in general.
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| 11. |
- Gong, Yin, et al.
(författare)
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Insights into evolution of a rift basin : Provenance of the middle Eocene-lower Oligocene strata of the Beibuwan Basin, South China Sea from detrital zircon
- 2021
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Ingår i: Sedimentary Geology. - : Elsevier BV. - 0037-0738 .- 1879-0968. ; 419
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Tidskriftsartikel (refereegranskat)abstract
- Investigating rift basins and their provenance is difficult because their tectonic framework is continuously evolving. The Beibuwan Basin in the South China Sea is a typical rift basin that shares many characteristics of major rift basins worldwide. We present new detrital zircon UPb ages from the Beibuwan basin and, by combining with published data from surrounding drainages, are able to define its potential sources and to investigate its provenance evolution from the middle Eocene-lower Oligocene. Detrital zircon age spectra from distinct structural units and formations of the rift basin reveal spatial-temporal differences in provenance. In the middle-upper Eocene, a similar age pattern with major peaks at 263–253 Ma and 450–416 Ma is preserved across the basin and suggests that sediment was uniformly derived from the Yunkai Massif and Hainan Island. In contrast, during the lower Oligocene the basin displays markedly diverse ages with peaks at 250–243, 416, 756, 967–945, 1096–1084 Ma. The increase of Neoproterozoic zircons in the lower Oligocene stratum suggests that a major change in provenance occurred, most likely associated with the reorganization of the paleo-Pearl River along its central reaches due to a topography reversal associated with the uplift of Tibet and the onset of seafloor spreading in the South China Sea. Our spatial analysis of ages indicates that during the lower Oligocene, the detrital input varied across the basin. Rifting processes in the Beibuwan Basin generated multiple isolated depocenters separated by intra-basinal highs. The basin's architecture greatly affected sediment routing, with structural highs serving as barriers to sediment transport. Sediment provenance in the Beibuwan Basin is primarily controlled by drainage evolution and isolated depocenters associated with an evolving topography, processes which are relevant to the evolution of rift basins globally.
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| 12. |
- Huang, Liping, et al.
(författare)
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Interim effects of salt substitution on urinary electrolytes and blood pressure in the China Salt Substitute and Stroke Study (SSaSS).
- 2020
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 221, s. 136-145
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Tidskriftsartikel (refereegranskat)abstract
- The Salt Substitute and Stroke Study is an ongoing 5-year large-scale cluster randomized trial investigating the effects of potassium-enriched salt substitute compared to usual salt on the risk of stroke. The study involves 600 villages and 20,996 individuals in rural China. Intermediate risk markers were measured in a random subsample of villages every 12 months over 3 years to track progress against key assumptions underlying study design. Measures of 24-hour urinary sodium, 24-hour urinary potassium, blood pressure and participants' use of salt substitute were recorded, with differences between intervention and control groups estimated using generalized linear mixed models. The primary outcome of annual event rate in the two groups combined was determined by dividing confirmed fatal and non-fatal strokes by total follow-up time in the first 2 years. The mean differences (95% CI) were -0.32 g (-0.68 to 0.05) for 24-hour urinary sodium, +0.77 g (+0.60 to +0.93) for 24-hour urinary potassium, -2.65 mmHg (-4.32 to -0.97) for systolic blood pressure and +0.30 mmHg (-0.72 to +1.32) for diastolic blood pressure. Use of salt substitute was reported by 97.5% in the intervention group versus 4.2% in the control group (P<.0001). The overall estimated annual event rate for fatal and non-fatal stroke was 3.2%. The systolic blood pressure difference and the annual stroke rate were both in line with the statistical assumptions underlying study design. The trial should be well placed to address the primary hypothesis at completion of follow-up.
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| 13. |
- Huang, Liping, et al.
(författare)
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The contribution of sodium reduction and potassium increase to the blood pressure lowering observed in the Salt Substitute and Stroke Study
- 2024
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Ingår i: Journal of Human Hypertension. - : Springer Nature. - 0950-9240 .- 1476-5527. ; 38:4, s. 298-306
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Tidskriftsartikel (refereegranskat)abstract
- The Salt Substitute and Stroke Study (SSaSS) demonstrated significant reductions in systolic blood pressure (SBP), and the risk of stroke, major cardiovascular events and total mortality with the use of potassium-enriched salt. The contribution of sodium reduction versus potassium increase to these effects is unknown. We identified four different data sources describing the association between sodium reduction, potassium supplementation and change in SBP. We then fitted a series of models to estimate the SBP reductions expected for the differences in sodium and potassium intake in SSaSS, derived from 24-h urine collections. The proportions of the SBP reduction separately attributable to sodium reduction and potassium supplementation were calculated. The observed SBP reduction in SSaSS was -3.3 mmHg with a corresponding mean 15.2 mmol reduction in 24-h sodium excretion and a mean 20.6 mmol increase in 24-h potassium excretion. Assuming 90% of dietary sodium intake and 70% of dietary potassium intake were excreted through urine, the models projected falls in SBP of between -1.67 (95% confidence interval: -4.06 to +0.73) mmHg and -5.33 (95% confidence interval: -8.58 to -2.08) mmHg. The estimated proportional contribution of sodium reduction to the SBP fall ranged between 12 and 39% for the different models fitted. Sensitivity analyses assuming different proportional urinary excretion of dietary sodium and potassium intake showed similar results. In every model, the majority of the SBP lowering effect in SSaSS was estimated to be attributable to the increase in dietary potassium rather than the fall in dietary sodium.
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| 14. |
- Li, Yuling, et al.
(författare)
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Composite Adaptive Control for Bilateral Teleoperation Systems without Persistency of Excitation
- 2020
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Ingår i: Journal of the Franklin Institute. - : Elsevier BV. - 0016-0032. ; 357:2, s. 773-795
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Tidskriftsartikel (refereegranskat)abstract
- Composite adaptive control schemes, which use both the system tracking error and the prediction error to drive the updating law, have become widespread in achieving an improvement of system performance. However, a strong persistent-excitation (PE) condition is required to guarantee the convergence of the parameter estimation errors. This paper proposes a novel composite adaptive control for nonlinear teleoperation systems with dynamic uncertainties and time-varying communication delays, by which the parameter convergence is achieved without the PE condition. The novelty lies in the construction of the prediction errors by designing lower-bounded gain matrices of the prediction errors. The stability criteria of the closed-loop teleoperation system are given in terms of linear matrix inequalities. Simulation studies are given to show the effectiveness of the proposed method.
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| 15. |
- Li, Zheng, et al.
(författare)
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A Review of Spatter in Laser Powder Bed Fusion Additive Manufacturing: In Situ Detection, Generation, Effects, and Countermeasures
- 2022
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Ingår i: Micromachines. - : MDPI AG. - 2072-666X. ; 13:8
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Forskningsöversikt (refereegranskat)abstract
- Spatter is an inherent, unpreventable, and undesired phenomenon in laser powder bed fusion (L-PBF) additive manufacturing. Spatter behavior has an intrinsic correlation with the forming quality in L-PBF because it leads to metallurgical defects and the degradation of mechanical properties. This impact becomes more severe in the fabrication of large-sized parts during the multi-laser L-PBF process. Therefore, investigations of spatter generation and countermeasures have become more urgent. Although much research has provided insights into the melt pool, microstructure, and mechanical property, reviews of spatter in L-PBF are still limited. This work reviews the literature on the in situ detection, generation, effects, and countermeasures of spatter in L-PBF. It is expected to pave the way towards a novel generation of highly efficient and intelligent L-PBF systems.
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| 16. |
- Liang, Huali, et al.
(författare)
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Highly-ordered microstructure and well performance of LiNi0.6Mn0.2Co0.2O2 cathode material via the continuous microfluidic synthesis
- 2020
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Ingår i: Chemical Engineering Journal. - : Elsevier BV. - 1385-8947 .- 1873-3212. ; 394
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Tidskriftsartikel (refereegranskat)abstract
- Ni-rich layered oxides are potential cathode candidate's materials for Li-ion batteries due to their low cost and high energy density. However, it is difficult to reproducibly prepare uniformly distributed element and wellcontrolled morphology of Ni-rich layered oxide particles. This study develops a continuous microfluidic reaction process to synthesize spherical carbonate precursors (Ni0.6Mn0.2Co0.2CO3). The as-synthesized LiNi0.6Co0.2Mn0.2O2 materials exhibit well-defined microsphere morphology, uniform particles size distribution, better thermal stability and homogeneous transition metal distribution, due to the excellent mixing, well mass and heat transfer rate during the microfluidic reaction. Moreover, the as-prepared LiNi0.6Co0.2Mn0.2O2 materials achieve higher initial capacity, excellent electrochemical reversibility and capacity retention than that of the samples prepared by traditional co-precipitation. Therefore, our results demonstrate that microfluidic reaction is a simple and effective synthesis technology for preparing Ni-rich layered cathode.
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| 17. |
- Lv, Fei, et al.
(författare)
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Ultraviolet-cured polyethylene oxide-based composite electrolyte enabling stable cycling of lithium battery at low temperature
- 2021
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier. - 0021-9797 .- 1095-7103. ; 596, s. 257-266
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Tidskriftsartikel (refereegranskat)abstract
- The room and low-temperature performances of solid-state lithium batteries are crucial to expand their practical application. Polyethylene oxide (PEO) has received great attention as the most representative polymer electrolyte matrix. However, most PEO-based solid-state batteries need to operate at high temperature due to low room temperature ionic conductivity. Improving the ionic conductivity by adding plasticizers or reducing the crystallinity of PEO often compromises its mechanical strength. Here, an amorphous PEO-based composite solid-state electrolyte is obtained by ultraviolet (UV) polymerizing PEO and methacryloyloxypropyltrimethoxy silane (KH570)-modified SiO2 which demonstrates both satisfactory mechanical performance and high ionic conductivity at room (3.37 x 10(-4) S cm(-1)) and low temperatures (1.73 x 10(-4) S cm(-1) at 0 degrees C). In this electrolyte, the crystallinity of PEO is reduced through cross-linking, and therefore provides a fast Li+ ions transfer area. Moreover, the KH570-modified SiO2 inorganic particles promote the dissociation of lithium salts by Lewis acid centers to increase the ionic conductivity. Importantly, this kind of cross-linking networks endows the final electrolyte much higher mechanical strength than the pure PEO polymer electrolyte or PEO-inorganic filler blended systems. The solid-state LiFePO4/Li cell assembled with this electrolyte exhibits excellent cycling performance and high capacity at room and low temperatures.
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| 18. |
- Mahajan, Anubha, et al.
(författare)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Tidskriftsartikel (refereegranskat)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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| 19. |
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| 20. |
- Tian, Ruiyi, et al.
(författare)
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Clonal Hematopoiesis and Risk of Incident Lung Cancer
- 2023
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 0732-183X. ; 41:7, s. 1423-1433
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To prospectively examine the association between clonal hematopoiesis (CH) and subsequent risk of lung cancer. METHODS: Among 200,629 UK Biobank (UKBB) participants with whole-exome sequencing, CH was identified in a nested case-control study of 832 incident lung cancer cases and 3,951 controls (2006-2019) matched on age and year at blood draw, sex, race, and smoking status. A similar nested case-control study (141 cases/652 controls) was conducted among 27,975 participants with whole-exome sequencing in the Mass General Brigham Biobank (MGBB, 2010-2021). In parallel, we compared CH frequency in published data from 5,003 patients with solid tumor (2,279 lung cancer) who had pretreatment blood sequencing performed through Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets. RESULTS: In UKBB, the presence of CH was associated with increased risk of lung cancer (cases: 12.5% v controls: 8.7%; multivariable-adjusted odds ratio [OR], 1.36; 95% CI, 1.06 to 1.74). The association remained robust after excluding participants with chronic obstructive pulmonary disease. No significant interactions with known risk factors, including polygenic risk score and C-reactive protein, were identified. In MGBB, we observed similar enrichment of CH in lung cancer (cases: 15.6% v controls: 12.7%). The meta-analyzed OR (95% CI) of UKBB and MGBB was 1.35 (1.08 to 1.68) for CH overall and 1.61 (1.19 to 2.18) for variant allele frequencies ≥ 10%. In Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets, CH with a variant allele frequency ≥ 10% was enriched in pretreatment lung cancer compared with other tumors after adjusting for age, sex, and smoking (OR for lung v breast cancer: 1.61; 95% CI, 1.03 to 2.53). CONCLUSION: Independent of known risk factors, CH is associated with increased risk of lung cancer.
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| 21. |
- Trung, Hieu Tran, et al.
(författare)
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Anti-inflammatory and Antiphytopathogenic Fungal Activity of 2,3-seco-Tirucallane Triterpenoids Meliadubins A and B from Melia dubia Cav. Barks with ChemGPS-NP and In Silico Prediction
- 2023
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Ingår i: ACS Omega. - : American Chemical Society (ACS). - 2470-1343. ; 8:40, s. 37116-37127
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Tidskriftsartikel (refereegranskat)abstract
- Two new rearranged 2,3-seco-tirucallane triterpenoids, meliadubins A (1) and B (2), along with four known compounds, 3-6, were isolated from the barks of Melia dubia Cav. Compound 2 exhibited a significant inflammatory inhibition effect toward superoxide anion generation in human neutrophils (EC50 at 5.54 +/- 0.36 mu M). It bound to active sites of a human inducible nitric oxide synthase (3E7G) through interactions with the residues of GLU377 and PRO350, which may benefit in reducing the neutrophilic inflammation effect. The ChemGPS-NP interpretation combined with bioactivity assay and in silico prediction results suggested 2 to be an agent for targeting iNOS with different mechanisms as compared to a selected set of current approved drugs. Moreover, compounds 1 and 2 showed remarkable inhibition against the rice pathogenic fungus Magnaporthe oryzae in a dose-dependent manner with IC50 values of 137.20 +/- 9.55 and 182.50 +/- 18.27 mu M, respectively. Both 1 and 2 displayed interactions with the residue of TYR223, a key active site of trihydroxynaphthalene reductase (1YBV). The interpretation of 1 and 2 in the ChemGPS-NP physical-chemical property space indicated that both compounds are quite different compared to all members of a selected set of reference compounds. In light of demonstrated biological activity and in silico prediction experiments, both compounds possibly exhibited activity against phytopathogenic fungi via a novel mode of action.
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| 22. |
- van de Vegte, Yordi, et al.
(författare)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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| 23. |
- Wang, Jie, et al.
(författare)
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Impacts of Summer Monsoons on flood characteristics in the Lancang-Mekong River Basin
- 2022
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Ingår i: Journal of Hydrology. - : Elsevier BV. - 0022-1694. ; 604
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Tidskriftsartikel (refereegranskat)abstract
- The impact of monsoon on rainfall in the Lancang-Mekong River Basin (LMRB) has been well understood, but its impact on flood characteristic across the basin is still unclear. To investigate this impact, the Variable Infiltration Capacity (VIC) hydrological model was used to generate the basin-wide discharge and extract flood characteristics. Indian Summer Monsoon (ISM), Western North Pacific Monsoon (WNPM), and their combined effect (ISWN) were considered and represented by monsoon index. The monsoon impact area was firstly obtained based on the monsoon impact on rainfall, followed by the anomaly analyses of flood characteristics within the impact area to quantify the monsoon impact on floods at local and spatial scales. The results show that the ISM and WNPM (or ISWN) can significantly modulate up to 20% of the rainfall interannual variability in the western and eastern parts of the basin, respectively. The monsoon impact on flood is regionally distributed with impact in tributary larger than mainstream. Over half of the monsoon impact areas show the flood start date averagely advances (delays) 8–12 days, flood volume averagely increases (decreases) by 9%–17.5% and Q10 averagely increases (decreases) by 7.4%–14.4% during the strong (weak) monsoon years. Also, the comparisons between monsoon local and spatial impacts reveal that the trade-off of water from different areas can disturb the monsoon impact on flood, suggesting that more stations should be used when using the observed data to analyze the monsoon impact. More importantly, the ISM tends to cause the severe flood in northern Thailand, while WNPM and ISWN mainly induce the severe flood in the southeastern part of the LMRB. This study could help to increase the knowledge of the impact of climate change on flood and help with the regional flood managements.
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| 24. |
- Wang, Xiaohua, et al.
(författare)
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Tacrolimus Causes Hypertension by Increasing Vascular Contractility via RhoA (Ras Homolog Family Member A)/ROCK (Rho-Associated Protein Kinase) Pathway in Mice
- 2022
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Ingår i: Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0194-911X .- 1524-4563. ; 79:10, s. 2228-2238
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Tidskriftsartikel (refereegranskat)abstract
- Background: To provide tacrolimus is first-line treatment after liver and kidney transplantation. However, hypertension and nephrotoxicity are common tacrolimus side effects that limit its use. Although tacrolimus-related hypertension is well known, the underlying mechanisms are not. Here, we test whether tacrolimus-induced hypertension involves the RhoA (Ras homolog family member A)/ROCK (Rho-associated protein kinase) pathway in male C57Bl/6 mice. methods: Intra-arterial blood pressure was measured under anesthesia. The reactivity of renal afferent arterioles and mesenteric arteries were assessed in vitro using microperfusion and wire myography, respectively. Results: Tacrolimus induced a transient rise in systolic arterial pressure that was blocked by the RhoA/ROCK inhibitor Fasudil (12.0 +/- 0.9 versus 3.2 +/- 0.7; P<0.001). Moreover, tacrolimus reduced the glomerular filtration rate, which was also prevented by Fasudil (187 +/- 20 versus 281 +/- 8.5; P<0.001). Interestingly, tacrolimus enhanced the sensitivity of afferent arterioles and mesenteric arteries to Ang II (angiotensin II), likely due to increased intracellular Ca2+ mobilization and sensitization. Fasudil prevented increased Ang II-sensitivity and blocked Ca2+ mobilization and sensitization. Preincubation of mouse aortic vascular smooth muscle cells with tacrolimus activated the RhoA/ROCK/MYPT-1 (myosin phosphatase targeting subunit 1) pathway. Further, tacrolimus increased cytoplasmic reactive oxygen species generation in afferent arterioles (107 +/- 5.9 versus 163 +/- 6.4; P<0.001) and in cultured mouse aortic vascular smooth muscle cells (100 +/- 7.5 versus 160 +/- 23.2; P<0.01). Finally, the reactive oxygen species scavenger Tempol inhibited tacrolimus-induced Ang II hypersensitivity in afferent arterioles and mesenteric arteries. Conclusions: The RhoA/ROCK pathway may play an important role in tacrolimus-induced hypertension by enhancing Ang II-specific vasoconstriction, and reactive oxygen species may participate in this process by activating the RhoA/ROCK pathway.
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| 25. |
- Wu, Haizhou, 1987, et al.
(författare)
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Impact of lipid composition and muscle microstructure on myoglobin-mediated lipid oxidation in washed cod and pig muscle
- 2021
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Ingår i: Food Chemistry. - : Elsevier BV. - 0308-8146 .- 1873-7072. ; 336
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Tidskriftsartikel (refereegranskat)abstract
- The roles of lipid oxidation substrates and muscle microstructure in lipid oxidation were investigated in two muscle models (cod and pig). Added myoglobin (Mb) promoted lipid oxidation in washed cod muscle (WCM) but not in washed pig muscle (WPM). The differing microstructure of WCM e.g. more exposed fat cells or membrane of muscle cells compared to the “denseness” or “wrapped” structure of WPM, may have contributed to the better ability of Mb to facilitate lipid oxidation in the WCM. Added phospholipids with polyenoic indexes of 282 and 24 activated Mb as an oxidant similarly in WPM while added neutral lipids and added free fatty acids had little effect. It is suggested that muscle microstructure and accessibility of Mb to phospholipids play critical roles in relation to Mb-mediated lipid oxidation while the degree of unsaturation in the phospholipids was less important.
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| 26. |
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| 27. |
- Wu, Haizhou, 1987, et al.
(författare)
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Quercetin as an inhibitor of hemoglobin-mediated lipid oxidation: Mechanisms of action and use of molecular docking
- 2022
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Ingår i: Food Chemistry. - : Elsevier BV. - 0308-8146 .- 1873-7072. ; 384
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Tidskriftsartikel (refereegranskat)abstract
- The antioxidant effect of quercetin on hemoglobin(Hb)-mediated lipid oxidation and the mechanisms involved were investigated. Quercetin strongly inhibited Hb-mediated lipid oxidation in washed muscle. Quercetin showed effective hydroxyl radical scavenging ability similar to butylated hydroxytoluene (BHT). Quercetin reduced metHb resulting in formation of oxyHb. Bound quercetin decreased heme dissociation from metHb. Conversion to oxyHb and decreased heme dissociation represent routes to limit Hb-mediated lipid oxidation. Electrospray ionization mass spectrometry (ESI-MS) indicated one molecule of quercetin was covalently bound to Hb α-chain. Quercetin quinone docked 3.3 Å from the thiol of αCys(H15) but not near any other Cys residues of turkey Hb. At the docking site, hydrogen bonding between quercetin quinone and amino acids of α- and β-chain was demonstrated. This represents a path by which quercetin became covalently bound to α-chain. Molecular docking of heme proteins to polyphenols provides a template to better understand antioxidant interactions in muscle foods.
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| 28. |
- Xue, Xiaoyin, et al.
(författare)
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PEDOT:PSS @Molecular Sieve as Dual-Functional Additive to Enhance Electrochemical Performance and Stability of Ni-Rich NMC Lithium-Ion Batteries
- 2020
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Ingår i: Energy Technology. - : Wiley. - 2194-4288 .- 2194-4296. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- Molecular sieves (MSs) coated with conductive polymer (PEDOT:PSS) are used as water scavengers to modify the nickel‐rich LiNi1–x–yCoxMnyO2 (NMC)‐layered cathode. This strategy proactively captures residual water in the battery system without affecting the transport performance of electrons and Li+ ions. The moisture content and nuclear magnetic resonance (NMR) tests show that MSs after coating still maintain good water absorption characteristics and inhibit the decomposition of the electrolyte. The conductivity of the PEDOT:PSS@MS‐NMC electrode is 1.08 × 10−4 S cm−1, which is improved by 63.9%, compared with the MS‐NMC electrode. Through X‐ray photoelectron spectroscopy, transmission electron microscopy, and scanning electron microscopy measurements, it is also shown that the surface structure stability and particle integrity for PEDOT:PSS@MS‐NMC electrode is well retained. After 500 cycles, the capacity retention of the composite cathode is 71.3%, which is higher than that of the NMC (38.3%) and MS‐NMC cathode (62.4%). This is a novel and effective strategy to suppress side reactions at the electrode interface and improve electrode stability, capacity retention, and cycle performance of the Ni‐rich NMC cathode.
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| 29. |
- Yin, Dong-min, et al.
(författare)
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Upgrading the anaerobic membrane bioreactor treatment of chicken manure by introducing in-situ ammonia stripping and hyper-thermophilic pretreatment
- 2020
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Ingår i: Bioresource Technology. - : Elsevier Ltd. - 0960-8524 .- 1873-2976. ; 310
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Tidskriftsartikel (refereegranskat)abstract
- The slow hydrolysis rate and ammonia inhibition effects significantly limit the performance of anaerobic digestion (AD) of nitrogen rich wastes. An innovative two-stage AD was therefore investigated for chicken manure by combining hyper-thermophilic (70 °C) pretreatment and a anaerobic membrane bioreactor (AnMBR). An in-situ stripping unit was assembled into the AnMBR to remove the ammonium-N, thus alleviating the inhibition effects. Through the 120-day experiment, the hydraulic retention time was optimized at 15 days for AnMBR with a constant retention 4 days for pretreatment. The hydrolysis efficiency and methane yield reached 72.4% and 352 mL-CH4/g-VSin respectively. About 3000 mg/L ammonium-N was removed through stripping, attributing to methane yield increased by 139 mL-CH4/g-VSin and volatile fatty acids decreased by 2683 mg/L compared to the control. No significant fouling was observed for the membrane. Conclusively, the combined two-stage AD process may offer an alternative approach for the treatment of nitrogen rich organic waste.
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| 30. |
- Yin, Jie, et al.
(författare)
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Editorial for the Special Issue on Laser Additive Manufacturing: Design, Processes, Materials and Applications
- 2022
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Ingår i: Micromachines. - : MDPI AG. - 2072-666X. ; 13:12
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Laser-based additive manufacturing (LAM) is a revolutionary advanced digital manufacturing technology developed in recent decades, which is also a key strategic technology for technological innovation and industrial sustainability. This technology unlocks the design and constraints of traditional manufacturing and meets the needs of complex geometry fabrication and high-performance part fabrication. A deeper understanding of the design, materials, processes, structures, properties and applications is desired to produce novel functional devices, as well as defect-free structurally sound and reliable LAM parts. The topics in this Special Issue include macro- and micro-scale additive manufacturing with lasers, such as structure/material design, fabrication, modeling and simulation, in situ characterization of additive manufacturing processes and ex situ materials characterization and performance, with an overview that covers various applications in aerospace, biomedicine, optics and energy.
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| 31. |
- Yin, Linxiang, et al.
(författare)
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Characterization of a membrane binding loop leads to engineering botulinum neurotoxin B with improved therapeutic efficacy
- 2020
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 18:3
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Tidskriftsartikel (refereegranskat)abstract
- Botulinum neurotoxins (BoNTs) are a family of bacterial toxins with seven major serotypes (BoNT/A-G). The ability of these toxins to target and bind to motor nerve terminals is a key factor determining their potency and efficacy. Among these toxins, BoNT/B is one of the two types approved for medical and cosmetic uses. Besides binding to well-established receptors, an extended loop in the C-terminal receptor-binding domain (HC) of BoNT/B (HC/B) has been proposed to also contribute to toxin binding to neurons by interacting with lipid membranes (termed lipid-binding loop [LBL]). Analogous loops exist in the HCs of BoNT/C, D, G, and a chimeric toxin DC. However, it has been challenging to detect and characterize binding of LBLs to lipid membranes. Here, using the nanodisc system and biolayer interferometry assays, we find that HC/DC, C, and G, but not HC/B and HC/D, are capable of binding to receptor-free lipids directly, with HC/DC having the highest level of binding. Mutagenesis studies demonstrate the critical role of consecutive aromatic residues at the tip of the LBL for binding of HC/DC to lipid membranes. Taking advantage of this insight, we then create a "gain-of-function" mutant HC/B by replacing two nonaromatic residues at the tip of its LBL with tryptophan. Cocrystallization studies confirm that these two tryptophan residues do not alter the structure of HC/B or the interactions with its receptors. Such a mutated HC/B gains the ability to bind receptor-free lipid membranes and shows enhanced binding to cultured neurons. Finally, full-length BoNT/B containing two tryptophan mutations in its LBL, together with two additional mutations (E1191M/S1199Y) that increase binding to human receptors, is produced and evaluated in mice in vivo using Digit Abduction Score assays. This mutant toxin shows enhanced efficacy in paralyzing local muscles at the injection site and lower systemic diffusion, thus extending both safety range and duration of paralysis compared with the control BoNT/B. These findings establish a mechanistic understanding of LBL-lipid interactions and create a modified BoNT/B with improved therapeutic efficacy.
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| 32. |
- Yin, Wen, 1993-, et al.
(författare)
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Comparison of HER2-targeted affibody conjugates loaded with auristatin-and maytansine-derived drugs
- 2023
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Ingår i: Journal of Controlled Release. - : Elsevier. - 0168-3659 .- 1873-4995. ; 355, s. 515-527
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with antibody drug conjugates targeting receptors over-expressed on cancer cells is well established for clinical use in several types of cancer, however, resistance often occurs motivating the development of novel drugs. We have recently investigated a drug conjugate consisting of an affibody molecule targeting the human epidermal growth factor receptor 2 (HER2), fused to an albumin-binding domain (ABD) for half-life extension, loaded with the cytotoxic maytansine derivative DM1. In this study, we investigated the impact of the cytotoxic payload on binding properties, cytotoxicity and biodistribution by comparing DM1 with the auristatins MMAE and MMAF, as part of the drug conjugate. All constructs had specific and high affinity binding to HER2, human and mouse albumins with values in the low- to sub-nM range. ZHER2-ABD-mcMMAF demonstrated the most potent cytotoxic effect on several HER2-over-expressing cell lines. In an experimental therapy study, the MMAFbased conjugate provided complete tumor regression in 50% of BALB/c nu/nu mice bearing HER2-overexpressing SKOV3 tumors at a 2.9 mg/kg dose, while the same dose of ZHER2-ABD-mcDM1 provided only a moderate anti-tumor effect. A comparison with the non-targeting ZTaq-ABD-mcMMAF control demonstrated HER2-targeting specificity. In conclusion, a combination of potent cytotoxicity in vitro, with minimal uptake in normal organs in vivo, and efficient delivery to tumors provided a superior anti-tumor effect of ZHER2-ABDmcMMAF, while maintaining a favorable toxicity profile with no observed adverse effects.
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| 33. |
- Yin, Wen, 1993-, et al.
(författare)
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The Influence of Domain Permutations of an Albumin-Binding Domain-Fused HER2-Targeting Affibody-Based Drug Conjugate on Tumor Cell Proliferation and Therapy Efficacy
- 2021
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Ingår i: Pharmaceutics. - : MDPI AG. - 1999-4923. ; 13:11, s. 1974-1974
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Tidskriftsartikel (refereegranskat)abstract
- Human epidermal growth factor receptor 2 (HER2) is a clinically validated target for breast cancer therapy. Previously, a drug-fused HER2-targeting affinity protein construct successfully extended the survival of mice bearing HER2-expressing xenografts. The aim of this study was to evaluate the influence of the number and positioning of the protein domains in the drug conjugate. Seven HER2-targeting affibody-based constructs, including one or two affibody molecules (Z) with or without an albumin-binding domain (ABD), namely Z, Z-ABD, ABD-Z, Z-Z, Z-Z-ABD, Z-ABD-Z, and ABD-Z-Z, were evaluated on their effects on cell growth, in vivo targeting, and biodistribution. The biodistribution study demonstrated that the monomeric constructs had longer blood retention and lower hepatic uptake than the dimeric ones. A dimeric construct, specifically ABD-Z-Z, could stimulate the proliferation of HER2 expressing SKOV-3 cells in vitro and the growth of tumors in vivo, whereas the monomeric construct Z-ABD could not. These two constructs demonstrated a therapeutic effect when coupled to mcDM1; however, the effect was more pronounced for the non-stimulating Z-ABD. The median survival of the mice treated with Z-ABD-mcDM1 was 63 days compared to the 37 days for those treated with ABD-Z-Z-mcDM1 or for the control animals. Domain permutation of an ABD-fused HER2-targeting affibody-based drug conjugate significantly influences tumor cell proliferation and therapy efficacy. The monomeric conjugate Z-ABD is the most promising format for targeted delivery of the cytotoxic drug DM1.
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| 34. |
- Yin, Xuejun, et al.
(författare)
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Effects of salt substitutes on clinical outcomes : a systematic review and meta-analysis
- 2022
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Ingår i: Heart. - : BMJ Publishing Group Ltd. - 1355-6037 .- 1468-201X. ; 108:20, s. 1608-1615
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The Salt Substitute and Stroke Study (SSaSS) recently reported blood pressure-mediated benefits of a potassium-enriched salt substitute on cardiovascular outcomes and death. This study assessed the effects of salt substitutes on a breadth of outcomes to quantify the consistency of the findings and understand the likely generalisability of the SSaSS results.METHODS: We searched PubMed, Embase and the Cochrane Library up to 31 August 2021. Parallel group, step-wedge or cluster randomised controlled trials reporting the effect of salt substitute on blood pressure or clinical outcomes were included. Meta-analyses and metaregressions were used to define the consistency of findings across trials, geographies and patient groups.RESULTS: There were 21 trials and 31 949 participants included, with 19 reporting effects on blood pressure and 5 reporting effects on clinical outcomes. Overall reduction of systolic blood pressure (SBP) was -4.61 mm Hg (95% CI -6.07 to -3.14) and of diastolic blood pressure (DBP) was -1.61 mm Hg (95% CI -2.42 to -0.79). Reductions in blood pressure appeared to be consistent across geographical regions and population subgroups defined by age, sex, history of hypertension, body mass index, baseline blood pressure, baseline 24-hour urinary sodium and baseline 24-hour urinary potassium (all p homogeneity >0.05). Metaregression showed that each 10% lower proportion of sodium choloride in the salt substitute was associated with a -1.53 mm Hg (95% CI -3.02 to -0.03, p=0.045) greater reduction in SBP and a -0.95 mm Hg (95% CI -1.78 to -0.12, p=0.025) greater reduction in DBP. There were clear protective effects of salt substitute on total mortality (risk ratio (RR) 0.89, 95% CI 0.85 to 0.94), cardiovascular mortality (RR 0.87, 95% CI 0. 81 to 0.94) and cardiovascular events (RR 0.89, 95% CI 0.85 to 0.94).CONCLUSIONS: The beneficial effects of salt substitutes on blood pressure across geographies and populations were consistent. Blood pressure-mediated protective effects on clinical outcomes are likely to be generalisable across population subgroups and to countries worldwide.TRIAL REGISTRATION NUMBER: CRD42020161077.
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| 35. |
- Yin, Yue, et al.
(författare)
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In Situ Transforming RNA Nanovaccines from Polyethylenimine Functionalized Graphene Oxide Hydrogel for Durable Cancer Immunotherapy
- 2021
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Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6984 .- 1530-6992. ; 21:5, s. 2224-2231
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Tidskriftsartikel (refereegranskat)abstract
- Messenger RNA (mRNA) vaccine is a promising candidate in cancer immunotherapy as it can encode tumor-associated antigens with an excellent safety profile. Unfortunately, the inherent instability of RNA and translational efficiency are major limitations of RNA vaccine. Here, we report an injectable hydrogel formed with graphene oxide (GO) and polyethylenimine (PEI), which can generate mRNA (ovalbumin, a model antigen) and adjuvants (R848)-laden nanovaccines for at least 30 days after subcutaneous injection. The released nanovaccines can protect the mRNA from degradation and confer targeted delivering capacity to lymph nodes. The data show that this transformable hydrogel can significantly increase the number of antigen-specific CD8+ T cells and subsequently inhibit the tumor growth with only one treatment. Meanwhile, this hydrogel can generate an antigen specific antibody in the serum which in turn prevents the occurrence of metastasis. Collectively, these results demonstrate the potential of the PEI-functionalized GO transformable hydrogel for effective cancer immunotherapy.
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| 36. |
- Yin, Yue, et al.
(författare)
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Separable Microneedle Patch to Protect and Deliver DNA Nanovaccines Against COVID-19
- 2021
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Ingår i: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 15:9, s. 14347-14359
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Tidskriftsartikel (refereegranskat)abstract
- The successful control of coronavirus disease 2019 (COVID-19) pandemic is not only relying on the development of vaccines, but also depending on the storage, transportation, and administration of vaccines. Ideally, nucleic acid vaccine should be directly delivered to proper immune cells or tissue (such as lymph nodes). However, current developed vaccines are normally treated through intramuscular injection, where immune cells do not normally reside. Meanwhile, current nucleic acid vaccines must be stored in a frozen state that may hinder their application in developing countries. Here, we report a separable microneedle (SMN) patch to deliver polymer encapsulated spike (or nucleocapsid) protein encoding DNA vaccines and immune adjuvant for efficient immunization. Compared with intramuscular injection, SMN patch can deliver nanovaccines into intradermal for inducing potent and durable adaptive immunity. IFN-gamma(+)CD4/8(+) and IL-2(+)CD4/8(+) T cells or virus specific IgG are significantly increased after vaccination. Moreover, in vivo results show the SMN patches can be stored at room temperature for at least 30 days without decreases in immune responses. These features of nanovaccines-laden SMN patch are important for developing advanced COVID-19 vaccines with global accessibility.
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| 37. |
- Zhai, Pan, et al.
(författare)
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Ionic Conductive Thermoplastic Polymer Welding Layer for Low Electrode/Solid Electrolyte Interface Resistance
- 2020
-
Ingår i: ACS Applied Energy Materials. - : AMER CHEMICAL SOC. - 2574-0962. ; 3:7, s. 7011-7019
-
Tidskriftsartikel (refereegranskat)abstract
- The application of LAGP ceramic solid electrolytes is circumscribed by the large electrode/electrolyte interfacial resistance because of their rigidity and brittleness. Here, a highly cohesive composite polymer layer consisting of poly(vinylene carbonate)-thermoplastic polyurethanes (PVC-TPU) is coated onto both sides of the Li1.5Al0.5Ge1.5(PO4)(3) pellet to address the interfacial problems with the electrodes. The coated PVC-TPU acts as an ionic conductive welding layer to facilitate the interfacial contact of the LAGP pellet with both electrodes and decreases the interfacial resistance of the LAGP pellet against the cathode (from 1.4 x 10(6) to 3.8 x 10(3) Omega cm(2)) and the Li-metal anode (from 3.3 x 10(4) to 890 Omega cm(2)). The resulting composite solid-state electrolyte (CSSE) presents the synergistic effect of the LAGP ceramic pellet and the PVC-TPU layer in terms of electrochemical stability, ionic transport properties, and stable lithium plating/stripping cycling with a low overpotential for 1000 h. Consequently, the LiFePO4/Li solid-state batteries utilizing this CSSE deliver a high capacity retention of 95.3% after 100 cycles at room temperature with a high Coulombic efficiency exceeding 99.99% per cycle and lithium dendrite inhibition.
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| 38. |
- Zhang, Shao-jie, et al.
(författare)
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Genomic regions under selection in the feralization of the dingoes
- 2020
-
Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Dingoes are wild canids living in Australia, originating from domestic dogs. They have lived isolated from both the wild and the domestic ancestor, making them a unique model for studying feralization. Here, we sequence the genomes of 10 dingoes and 2 New Guinea Singing Dogs. Phylogenetic and demographic analyses show that dingoes originate from dogs in southern East Asia, which migrated via Island Southeast Asia to reach Australia around 8300 years ago, and subsequently diverged into a genetically distinct population. Selection analysis identifies 50 positively selected genes enriched in digestion and metabolism, indicating a diet change during feralization of dingoes. Thirteen of these genes have shifted allele frequencies compared to dogs but not compared to wolves. Functional assays show that an A-to-G mutation in ARHGEF7 decreases the endogenous expression, suggesting behavioral adaptations related to the transitions in environment. Our results indicate that the feralization of the dingo induced positive selection on genomic regions correlated to neurodevelopment, metabolism and reproduction, in adaptation to a wild environment.
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| 39. |
- Zhang, Xiao-Jie, et al.
(författare)
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Auto-suppression of Tet dioxygenases protects the mouse oocyte genome from oxidative demethylation
- 2024
-
Ingår i: Nature Structural & Molecular Biology. - : NATURE PORTFOLIO. - 1545-9993 .- 1545-9985. ; 31:1
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Tidskriftsartikel (refereegranskat)abstract
- DNA cytosine methylation plays a vital role in repressing retrotransposons, and such derepression is linked with developmental failure, tumorigenesis and aging. DNA methylation patterns are formed by precisely regulated actions of DNA methylation writers (DNA methyltransferases) and erasers (TET, ten-eleven translocation dioxygenases). However, the mechanisms underlying target-specific oxidation of 5mC by TET dioxygenases remain largely unexplored. Here we show that a large low-complexity domain (LCD), located in the catalytic part of Tet enzymes, negatively regulates the dioxygenase activity. Recombinant Tet3 lacking LCD is shown to be hyperactive in converting 5mC into oxidized species in vitro. Endogenous expression of the hyperactive Tet3 mutant in mouse oocytes results in genome-wide 5mC oxidation. Notably, the occurrence of aberrant 5mC oxidation correlates with a consequent loss of the repressive histone mark H3K9me3 at ERVK retrotransposons. The erosion of both 5mC and H3K9me3 causes ERVK derepression along with upregulation of their neighboring genes, potentially leading to the impairment of oocyte development. These findings suggest that Tet dioxygenases use an intrinsic auto-regulatory mechanism to tightly regulate their enzymatic activity, thus achieving spatiotemporal specificity of methylome reprogramming, and highlight the importance of methylome integrity for development. Here the authors show that TET dioxygenases, the erasers of DNA methylation, use a self-limiting mechanism via their LCD domain to ensure adaptable methylome status and protect the genome from excessive oxidative methylation.
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| 40. |
- Zhang, Yongchao, et al.
(författare)
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Online Sparse Reconstruction for Scanning Radar Using Beam-Updating q-SPICE
- 2022
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Ingår i: IEEE Geoscience and Remote Sensing Letters. - 1545-598X. ; 19
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Tidskriftsartikel (refereegranskat)abstract
- The generalized sparse iterative covariance-based estimation ( $q$ -SPICE) algorithm was recently introduced for scanning radar applications, resulting in substantial improvements in the angular resolution and quality of the processed images. Regrettably, the computational complexity and storage cost are high and quickly increase with growing data size, limiting the applicability of the estimator. In this letter, we strive to alleviate this problem, deriving a beam-updating $q$ -SPICE algorithm, allowing for efficiently updating of the sparse reconstruction result for each online radar measurement along the scanned beam. The resulting method is a regularized extension of the current online $q$ -SPICE implementation, which not only offers constant computational and storage cost, independent of the data size, but also provides enhanced robustness over the current online $q$ -SPICE. Our experimental assessment, conducted using both simulated and real data, demonstrates the advantage of the beam-updating $q$ -SPICE method in the task of sparse reconstruction for scanning radar.
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