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1.
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2.
  • Beal, Jacob, et al. (författare)
  • Robust estimation of bacterial cell count from optical density
  • 2020
  • Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
  • Tidskriftsartikel (refereegranskat)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. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)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.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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5.
  • Jin, Ying-Hui, et al. (författare)
  • Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19 : An evidence-based clinical practice guideline (updated version)
  • 2020
  • Ingår i: Military Medical Research. - : Springer Science and Business Media LLC. - 2054-9369. ; 7:1
  • Tidskriftsartikel (refereegranskat)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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6.
  • Axfors, Cathrine, et al. (författare)
  • Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
  • 2021
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I-2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
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7.
  • Lin, Wei Ju, et al. (författare)
  • Deterministic Loading of Microwaves onto an Artificial Atom Using a Time-Reversed Waveform
  • 2022
  • Ingår i: Nano Letters. - : American Chemical Society (ACS). - 1530-6992 .- 1530-6984. ; 22:20, s. 8137-8142
  • Tidskriftsartikel (refereegranskat)abstract
    • Loading quantum information deterministically onto a quantum node is an important step toward a quantum network. Here, we demonstrate that coherent-state microwave photons with an optimal temporal waveform can be efficiently loaded onto a single superconducting artificial atom in a semi-infinite one-dimensional (1D) transmission-line waveguide. Using a weak coherent state (the number of photons (N) contained in the pulse ≪1) with an exponentially rising waveform, whose time constant matches the decoherence time of the artificial atom, we demonstrate a loading efficiency of 94.2% ± 0.7% from 1D semifree space to the artificial atom. The high loading efficiency is due to time-reversal symmetry: the overlap between the incoming wave and the time-reversed emitted wave is up to 97.1% ± 0.4%. Our results open up promising applications in realizing quantum networks based on waveguide quantum electrodynamics.
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8.
  • Cheng, Yu Ting, et al. (författare)
  • Tuning atom-field interaction via phase shaping
  • 2024
  • Ingår i: Physical Review A. - 2469-9934 .- 2469-9926. ; 109:2
  • Tidskriftsartikel (refereegranskat)abstract
    • A coherent electromagnetic field can be described by its amplitude, frequency, and phase. All these properties can influence the interaction between the field and an atom. Here we demonstrate the phase shaping of microwaves that are scattered by a superconducting artificial atom coupled to the end of a semi-infinite one-dimensional transmission line. In particular, we input a weak exponentially rising pulse with phase modulation to a transmon qubit. We observe that atom-field interaction can be tuned from a nearly full interaction (interaction efficiency, i.e., amount of the field energy interacting with the atom, of 94.5 %) to effectively no interaction (interaction efficiency of 3.5 %).
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9.
  • Chiu, Pei-Fang, et al. (författare)
  • Design, structure–activity relationships, and enzyme kinetic studies of tricyclic and tetracyclic coumarin–based sulfamates as steroid sulfatase inhibitors
  • 2023
  • Ingår i: Bioorganic chemistry. - : Elsevier BV. - 0045-2068. ; 138, s. 106581-106581
  • Tidskriftsartikel (refereegranskat)abstract
    • Inhibition of steroid sulfatase (STS) decreases estrogen production and thus, suppresses tumor proliferation. Inspired by irosustat, the first STS inhibitor in clinical trials, we explored twenty-one tricyclic and tetra-heterocyclic coumarin–based derivatives. Their STS enzyme kinetic parameters, docking models, and cytotoxicity toward breast cancer and normal cells were evaluated. Tricyclic derivative 9e and tetracyclic derivative 10c were the most promising irreversible inhibitors developed in this study, with KI of 0.05 and 0.4 nM, and kinact/KI ratios of 28.6 and 19.1 nM−1min−1 on human placenta STS, respectively.
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10.
  • Desjardins, Kewin, et al. (författare)
  • Characterization of a back-illuminated CMOS camera for soft x-ray coherent scattering
  • 2019
  • Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
  • Konferensbidrag (refereegranskat)abstract
    • A commercial scientific camera has been adapted and characterized at the SOLEIL Synchrotron with the aim to improve the acquisition capabilities on the soft X-ray coherent scattering experimental station at SEXTANTS beamline. This device is equipped by the last generation of back side illuminated scientific CMOS (BSI-sCMOS) of 2048 by 2048 pixels of 11 μm2 able to acquire low noise images with a frame rate up to 48 Hz. The camera's performance measurements have been done and shows a good level of readout noise, a large full-well capacity, a medium dark current and a good homogeneity, respectively, 1.6 e- rms (in High Gain mode), 80 000 e- (in Low Gain mode),<5 e-/pixel/s and ∼ 1%. The quantum efficiency (QE) measurement has been performed at the soft x-ray branch of the METROLOGIE beamline and gives a relatively good agreement with the expected theoretical values. Finally, the demonstration of the camera's efficiency and of the gain in useful time measurement related to the high frame rate have been performed with a series of Airy patterns images compared with an image recorded using the standard BSI-CDD already in operation at the SEXTANTS beamline.
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11.
  • Griesmayer, E., et al. (författare)
  • Applications of single-crystal CVD diamond XBPM detectors with nanometre x-ray beams
  • 2019
  • Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
  • Konferensbidrag (refereegranskat)abstract
    • Measurements with a Diamond XBPM were carried out at the MAX IV Laboratory, Lund, Sweden, at the NanoMAX beam line. This was the first investigation of a Diamond XBPM detector with nanometre beams. The effect of diffusion, as well as the position resolution at the smallest available beam sizes were studied.
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12.
  • Liao, Shih-Fen, et al. (författare)
  • Immunization of fucose-containing polysaccharides from Reishi mushroom induces antibodies to tumor-associated Globo H-series epitopes.
  • 2013
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:34, s. 13809-13814
  • Tidskriftsartikel (refereegranskat)abstract
    • Carbohydrate-based vaccines have shown therapeutic efficacy for infectious disease and cancer. The mushroom Ganoderma lucidum (Reishi) containing complex polysaccharides has been used as antitumor supplement, but the mechanism of immune response has rarely been studied. Here, we show that the mice immunized with a l-fucose (Fuc)-enriched Reishi polysaccharide fraction (designated as FMS) induce antibodies against murine Lewis lung carcinoma cells, with increased antibody-mediated cytotoxicity and reduced production of tumor-associated inflammatory mediators (in particular, monocyte chemoattractant protein-1). The mice showed a significant increase in the peritoneal B1 B-cell population, suggesting FMS-mediated anti-glycan IgM production. Furthermore, the glycan microarray analysis of FMS-induced antisera displayed a high specificity toward tumor-associated glycans, with the antigenic structure located in the nonreducing termini (i.e., Fucα1-2Galβ1-3GalNAc-R, where Gal, GalNAc, and R represent, respectively, D-galactose, D-N-acetyl galactosamine, and reducing end), typically found in Globo H and related tumor antigens. The composition of FMS contains mainly the backbone of 1,4-mannan and 1,6-α-galactan and through the Fucα1-2Gal, Fucα1-3/4Man, Fucα1-4Xyl, and Fucα1-2Fuc linkages (where Man and Xyl represent d-mannose and d-xylose, respectively), underlying the molecular basis of the FMS-induced IgM antibodies against tumor-specific glycans.
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13.
  • Lin, Yi-Ting, et al. (författare)
  • Differences in the Microbial Composition of Hemodialysis Patients Treated with and without β-Blockers
  • 2021
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • β-blockers are commonly prescribed to treat cardiovascular disease in hemodialysis patients. Beyond the pharmacological effects, β-blockers have potential impacts on gut microbiota, but no study has investigated the effect in hemodialysis patients. Hence, we aim to investigate the gut microbiota composition difference between β-blocker users and nonusers in hemodialysis patients. Fecal samples collected from hemodialysis patients (83 β-blocker users and 110 nonusers) were determined by 16S ribosomal RNA amplification sequencing. Propensity score (PS) matching was performed to control confounders. The microbial composition differences were analyzed by the linear discriminant analysis effect size, random forest, and zero-inflated Gaussian fit model. The α-diversity (Simpson index) was greater in β-blocker users with a distinct β-diversity (Bray–Curtis Index) compared to nonusers in both full and PS-matched cohorts. There was a significant enrichment in the genus Flavonifractor in β-blocker users compared to nonusers in full and PS-matched cohorts. A similar finding was demonstrated in random forest analysis. In conclusion, hemodialysis patients using β-blockers had a different gut microbiota composition compared to nonusers. In particular, the Flavonifractor genus was increased with β-blocker treatment. Our findings highlight the impact of β-blockers on the gut microbiota in hemodialysis patients.
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14.
  • Marcouille, O., et al. (författare)
  • Production of high energy photons with in vacuum wigglers : From SOLEIL wiggler to MAXIV wiggler
  • 2019
  • Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
  • Konferensbidrag (refereegranskat)abstract
    • Small gap wigglers become more and more attractive to produce high photon fluxes in the hard X-ray photon range. They use magnet blocks of high magnetization which resists much better to heating (baking, synchrotron radiation) than in the past, produce high magnetic field with numerous periods and are very compact. They also are a very good alternative to superconducting technology which requires special infrastructure, heavy maintenance and is not running cost free. SOLEIL, operating presently at 2.75 GeV has designed and built an in-vacuum wiggler of 38 periods of 50 mm producing 2.1 T at a minimum gap of 5.5 mm to delivered photon beam between 20 keV and 50 keV. Already in operation, further improvements are presently in progress to push photons towards higher energy, in particular thanks to the operation at lower gap (4.5 mm). MAX IV and SOLEIL, in the frame of collaboration, ave built an upgraded version of the existing SOLEIL wiggler with the target to extend the spectral range at high energy (above 50 keV) but also at low energy (4 keV) with the same insertion device. The design of the existing magnetic system has been modified to reach 2.4 T at a minimum gap of 4.2 mm and includes taper operation to avoid undulator structure in the radiated spectrum at low energy.
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15.
  • Plivelic, Tomás S., et al. (författare)
  • X-ray tracing, design and construction of an optimized optics scheme for CoSAXS, the small angle x-ray scattering beamline at MAX IV laboratory
  • 2019
  • Ingår i: Proceedings of the 13th International Conference on Synchrotron Radiation Instrumentation, SRI 2018. - : Author(s). - 9780735417823 ; 2054
  • Konferensbidrag (refereegranskat)abstract
    • A novel optical design for a flexible SAXS beamline at a modern synchrotron has been implemented for the CoSAXS beamline at the 3GeV ring at the MAX TV Laboratory. The performance of the beamline has been simulated through combined ray tracing and wave propagation with the code xrt taking into account the low emittance and highly coherent beam of MAX TV and the short inter-optics distances of the beamline. The total photon flux is estimated to be 1012-1013 ph/s with the coherent flux portion up to 10 % at 7.1 keV. The inhomogeneities in the X-ray beam arising from use of real (non-idealised) mirror surfaces are also modelled using the measured slope profiles of the mirrors. Strategies to mitigate these inhomogeneities are discussed. The optical components for CoSAXS have been constructed and beamline commissioning will start in 2019.
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16.
  • Wu, Ping-Hsun, et al. (författare)
  • Comparative Gut Microbiome Differences between Ferric Citrate and Calcium Carbonate Phosphate Binders in Patients with End-Stage Kidney Disease
  • 2020
  • Ingår i: Microorganisms. - : MDPI. - 2076-2607. ; 8:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Gut dysbiosis in patients with chronic kidney disease (CKD) may induce chronic inflammation and increase morbidity. Phosphate-binding agents, generally used in patients with CKD, may potentially change the composition of the gut microbiota. This study aimed to compare the microbiota composition in hemodialysis patients treated with ferric citrate or calcium carbonate. The stool microbiota was investigated in hemodialysis patients treated with ferric citrate (n = 8) and calcium carbonate (n = 46) using 16S rRNA gene amplicon sequencing profiling using linear discriminant analysis of effect size. Further predictive functional profiling of microbial communities was obtained with Tax4Fun in R. Hemodialysis patients treated with calcium carbonate had a significantly reduced microbial species diversity (Shannon index and Simpson index) and an increased microbial alteration ratio compared with patients treated with ferric citrate. A distinct microbial community structure was found in patients treated with ferric citrate, with an increased abundance of the Bacteroidetes phylum and a decreased abundance of the phylum Firmicutes. Members of the order Lactobacillales were enriched in patients treated with calcium carbonate, whereas taxa of the genera Ruminococcaceae UCG-004, Flavonifractor, and Cronobacter were enriched in patients treated with ferric citrate phosphate binder. In conclusion, Ferric citrate therapy results in a more diverse microbiome community compared to calcium carbonate therapy in hemodialysis patients with phosphate binder treatment. The gut microbiome reflects the phosphate binder choice in hemodialysis patients, further affecting the physiological environment in the gastrointestinal tract.
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17.
  • Chen, Chao-Ying, et al. (författare)
  • Obesity as a clinical predictor for severe manifestation of dengue : a systematic review and meta-analysis
  • 2023
  • Ingår i: BMC Infectious Diseases. - : BioMed Central (BMC). - 1471-2334. ; 23:1
  • Forskningsöversikt (refereegranskat)abstract
    • BackgroundSevere dengue often leads to poor clinical outcomes and high mortality; as a result, it is of vital importance to find prognostic factors associated with the severe form of dengue. Obesity is known to deteriorate many infectious diseases due to impaired immune responses. Several studies have suggested that obese patients with dengue infection tend to have more severe manifestations with poorer prognosis. However, a firm conclusion could not be drawn due to the varied results of these studies. Here, we aimed to conduct a systematic review and meta-analysis to investigate the association between obesity and dengue severity.MethodsA literature search for relevant studies was conducted in PubMed, Embase, Ovid Medline and Cochrane from inception to September 9, 2022. The two main keywords were “dengue” and “obesity”. Mantel-Haenszel method and random effects model was used to analyze the pooled odds ratio with 95% confidence intervals.ResultsA total of 15 article involving a total of 6,508 patients were included in the meta-analysis. Included patients in most studies were hospitalized pediatric patients. Only one study included adulthood data. Three cohort studies, four case-control studies, and one cross-sectional studies found a significant association between obesity and dengue severity. In contrast, three cohort studies, three case-control studies, and one cross-sectional study reported no significant relationship between obesity and dengue severity. Our analysis results showed that patient with obesity is 50% (OR = 1.50; 95%CI: 1.15–1.97) more likely to develop severe manifestation of dengue.ConclusionThis meta-analysis revealed that overweight could be a clinical predictor for severe disease for pediatric patients with dengue infection.
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18.
  • Chiu, Yu-Yao, et al. (författare)
  • The association of obesity and dengue severity in hospitalized adult patients
  • 2023
  • Ingår i: JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION. - : Elsevier BV. - 1684-1182 .- 1995-9133. ; 56:2, s. 267-273
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Obesity is associated with unfavorable outcomes for infectious diseases. Most researches exploring the association between nutritional status and dengue severity have focused on pediatric populations, with only few studies assessing adult patients.Methods: Adult patients with laboratory-confirmed dengue admitted to a tertiary hospital in southern Taiwan between 2014 and 2015 were enrolled retrospectively. Demographics, comorbidities, clinical presentation, laboratory findings, and outcomes were obtained from caserecord forms. Patients were categorized into obese group and nonobese group. The obese group comprised patients with a body mass index of >= 27.5 kg/m(2).Results: A total of 1417 hospitalized patients with dengue were evaluated. The mean age was 57.9 years (range: 18e92 years). The obese and nonobese groups comprised 333 (23.5%) and 1084 (76.5%) patients, respectively. The obese group included more patients with hypertension (85%, p < 0.001), diabetes mellitus (33%, p < 0.001), and congestive heart failure ( 6.3%, p Z 0.049). Multivariate analysis revealed that the obese group had more petechiae (AOR: 1.353, 95% CI: 1.025e1.786, p Z 0.033), more dyspnea (AOR: 1.380, 95% CI: 1.015e1.876, p Z 0.040), and more severe hepatitis (AOR: 2.061, 95% CI: 1.050e4.048, p Z 0.036). The obese group also had higher peak hematocrit values (44.1%, p < 0.001) and lower nadir platelet count (45.3 x 10(3)/mL, p Z 0.049) than the nonobese group.Conclusion: In adult patients with dengue, obese group had more petechiae, dyspnea, severe hepatitis, lower nadir of platelet count, and higher peak hematocrit level. We observed no difference in severe dengue or mortality between obese and nonobese group.
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19.
  • Hsu, Yu-Cheng, et al. (författare)
  • One-Pot Tandem Photoredox and Cross-Coupling Catalysis with a Single Palladium Carbodicarbene Complex
  • 2018
  • Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 57:17, s. 4622-4626
  • Tidskriftsartikel (refereegranskat)abstract
    • The combination of conventional transition-metal-catalyzed coupling (2e(-) process) and photoredox catalysis (1e(-) process) has emerged as a powerful approach to catalyze difficult cross-coupling reactions under mild reaction conditions. Reported is a palladium carbodicarbene (CDC) complex that mediates both a Suzuki-Miyaura coupling and photoredox catalysis for C-N bond formation upon visible-light irradiation. These two catalytic pathways can be combined to promote both conventional transition-metal-catalyzed coupling and photoredox catalysis to mediate C-H arylation under ambient conditions with a single catalyst in an efficient one-pot process.
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20.
  • Lin, Chun-Yu, et al. (författare)
  • Mono-(2-ethylhexyl) phthalate Promotes Dengue Virus Infection by Decreasing IL-23-Mediated Antiviral Responses
  • 2021
  • Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 12
  • Tidskriftsartikel (refereegranskat)abstract
    • Exposure to environmental hormones such as di(2-ethylhexyl) phthalate (DEHP) has become a critical human health issue globally. This study aimed to investigate the correlations between DEHP/mono-(2-ethylhexyl) phthalate (MEHP) levels and macrophage-associated immune responses and clinical manifestations in dengue virus (DV)-infected patients. Among 89 DV-infected patients, those with DV infection-related gastrointestinal (GI) bleeding (n = 13, 15% of patients) had significantly higher DEHP exposure than those without GI bleeding (n = 76, 85% of patients), which were 114.2 ng/ml versus 52.5 ng/ml ΣDEHP in urine; p = 0.023). In an in vitro study using cultured human monocyte-derived macrophages (MDMs) to investigate the effects of MEHP, treatment increased IL-1β and TNF-α release but decreased IL-23 release, with negative correlations observed between urine ΣDEHP and serum IL-23 levels in patients. MEHP-treated MDMs had lower antiviral Th17 response induction activity in mixed T-cell response tests. The in vitro data showed that MEHP increased DV viral load and decreased IL-23 release dose-dependently, and adding IL-23 to MEHP-exposed MDMs significantly reduced the DV viral load. MEHP also suppressed IL-23 expression via the peroxisome proliferator-activated receptor-gamma (PPAR-γ) pathway. Further, the PPAR-γ antagonist GW9662 significantly reversed MEHP-induced IL-23 suppression and reduced the DV viral load. These study findings help to explain the associations between high MEHP levels and the high global burden of dengue disease.
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21.
  • Tu, Chien Ming, et al. (författare)
  • Helicity-dependent terahertz emission spectroscopy of topological insulator S b2 T e3 thin films
  • 2017
  • Ingår i: Physical Review B. - 2469-9950. ; 96:19
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on helicity-dependent terahertz emissions that originate from the helicity-dependent photocurrents in topological insulator Sb2Te3 thin films due to ultrafast optical excitation. The polarity of the emitted terahertz radiation is controlled by both the incident angle and the helicity of optical pulses. Using an unprecedented decomposition-recombination procedure in the time domain, the signals of the Dirac fermions are fully separated from bulk contributions. These results provide insights into the optical coupling of topological surface states and open up opportunities for applying helicity-dependent terahertz emission spectroscopy in spintronics.
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22.
  • Tu, Chien Ming, et al. (författare)
  • Helicity-dependent terahertz radiation from topological insulator Sb2Te3 thin film by femtosecond optical excitation
  • 2016
  • Ingår i: 41st International Conference on Infrared, Millimeter and Terahertz Waves, IRMMW-THz 2016. - 9781467384858
  • Konferensbidrag (refereegranskat)abstract
    • We report on terahertz radiation from topological insulator (TI) Sb2Te3 thin film under ultrafast optical excitation with different helicity. Polarity-reversals of the emitted THz radiation were observed as the helicity of optical pulses reversed. The observed phenomena are coincident with the characteristics of the helicity-dependent photocurrent on TIs. Our work demonstrates the potential applications of surface photocurrents on TIs for opto-spintronics devices.
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23.
  • Andhikaputra, Gerry, et al. (författare)
  • The impact of temperature and precipitation on all-infectious-, bacterial-, and viral-diarrheal disease in Taiwan
  • 2023
  • Ingår i: Science of the Total Environment. - : Elsevier BV. - 1879-1026 .- 0048-9697. ; 862
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The ongoing climate change will elevate the incidence of diarrheal in 2030-2050 in Asia, including Taiwan. This study investigated associations between meteorological factors (temperature, precipitation) and burden of age-cause-specific diarrheal diseases in six regions of Taiwan using 13 years of (2004-2016) population-based data.METHODS: Weekly cause-specific diarrheal and meteorological data were obtained from 2004 to 2016. We used distributed lag non-linear model to assess age (under five, all age) and cause-specific (viral, bacterial) diarrheal disease burden associated with extreme high (99th percentile) and low (5th percentile) of climate variables up to lag 8 weeks in six regions of Taiwan. Random-effects meta-analysis was used to pool these region-specific estimates.RESULTS: Extreme low temperature (15.30 °C) was associated with risks of all-infectious and viral diarrhea, with the highest risk for all-infectious diarrheal found at lag 8 weeks among all age [Relative Risk (RR): 1.44; 95 % Confidence Interval (95 % CI): 1.24-1.67]. The highest risk of viral diarrheal infection was observed at lag 2 weeks regardless the age. Extreme high temperature (30.18 °C) was associated with risk of bacterial diarrheal among all age (RR: 1.07; 95 % CI: 1.02-1.13) at lag 8 weeks. Likewise, extreme high precipitation (290 mm) was associated with all infectious diarrheal, with the highest risk observed for bacterial diarrheal among population under five years (RR: 2.77; 95 % CI: 1.60-4.79) at lag 8 weeks. Extreme low precipitation (0 mm) was associated with viral diarrheal in all age at lag 1 week (RR: 1.08; 95 % CI: 1.01-1.15)].CONCLUSION: In Taiwan, extreme low temperature is associated with an increased burden of viral diarrheal, while extreme high temperature and precipitation elevated burden of bacterial diarrheal. This distinction in cause-specific and climate-hazard specific diarrheal disease burden underscore the importance of incorporating differences in public health preparedness measures designed to enhance community resilience against climate change.
  •  
24.
  • Chen, Yu-Pin, et al. (författare)
  • Prognostic factors for 1-year functional outcome, quality of life, care demands, and mortality after surgery in Taiwanese geriatric patients with a hip fracture : a prospective cohort study
  • 2021
  • Ingår i: Therapeutic Advances in Musculoskeletal Disease. - : Sage Publications. - 1759-7218 .- 1759-720X. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Hip fractures are a major public health concern among elderly individuals. This study aimed to investigate potential perioperative factors that predict 1-year functional outcome, quality of life (QoL), care demands, and mortality in geriatric patients with a hip fracture.Methods: We prospectively enrolled geriatric patients who had undergone hip fracture surgery in one medical center from December 2017 to December 2019. Basic demographic data, handgrip strength, and responses to questionnaires for QoL and activities of daily living (ADL) before the injury were collected at baseline. QoL, ADL, additional care demands other than family support, and mortality events were monitored at 1 year after the operation.Results: Among 281 patients with a hip fracture, 39 (13.9%) died within 1 year of the index operation. The mean follow-up interval for the survivors was 403.3 (range: 358–480) days. Among the 242 survivors, ADL and QoL considerably decreased at approximately 1 year following hip surgery. Up to 33.9% of the participants became severely dependent and needed additional care at 1-year follow up. Prefracture ADL status was the crucial predictor for functional outcome, QoL, and additional care demand at 1-year follow up. Cox regression models indicated that male sex, low preoperative serum creatinine, handgrip strength, long surgical delay after a falling accident, and high Charlson Comorbidity Index were considerably associated with a high 1-year mortality risk in the geriatric hip fracture population.Conclusion: Hip fracture has long-lasting effects (e.g. functional loss, decline in QoL, increased care demands, and high postoperative mortality rate) on the geriatric population. A robust screening method must be developed for identifying potential prognostic factors, and a stratified care approach must be used that accounts for personalized risks to improve functional outcomes and reduce mortality after hip fracture in geriatric patients, especially in Taiwan.
  •  
25.
  • Jianfeng, Lin, 1994, et al. (författare)
  • Hydrodynamic simulation for evaluating Magnus anti-rolling devices with varying angles of attack
  • 2022
  • Ingår i: Ocean Engineering. - : Elsevier BV. - 0029-8018. ; 260
  • Tidskriftsartikel (refereegranskat)abstract
    • The effective operation of anti-rolling devices is important for ensuring ship safety, comfort, combat capability, and performance. Stabilizers based on the principle of the Magnus effect were investigated in this study. The hydrodynamic performance of a three-dimensional Magnus anti-rolling device at different angles of attack was examined using the improved delayed detached eddy simulation method based on shear stress transport. Subsequently, a convergence analysis was performed to verify the accuracy of the method. Moreover, the effects of the rotational speed, angle of attack, and incoming flow speed on the lift–drag characteristics and wake flow field of the Magnus anti-rolling device were analyzed. The results indicated that the optimal spin ratio maximized the lift–drag ratio. However, in certain cases, the angle of attack and spin ratio significantly influenced the streamwise and crosswise vortex structures in the cylinder wake. These results would be useful for the practical application of Magnus anti-rolling devices.
  •  
26.
  • Juang, Yu-Pu, et al. (författare)
  • Synthesis, distribution analysis and mechanism studies of N-acyl glucosamine-bearing oleanolic saponins
  • 2020
  • Ingår i: Bioorganic chemistry (Print). - : Elsevier. - 0045-2068. ; 99, s. 103835-
  • Tidskriftsartikel (refereegranskat)abstract
    • A series of N-acyl glucosamine-bearingtriterpenoidsaponins has been synthesized with cytotoxic activities evaluated against HL-60, PC-3, HCT-116, and CT-26 tumor cells. Saponins incorporated anoleanolic acid (OA) triterpenoidal core exhibited the highest cytotoxic activity. To study the influence of the lengths of acyl-carbon chain onN-position of glucosamine, cells were treated with28-propargylamides and then reacted with an azido-fluorogenic probe under CuAACclickreactions to visualize the intact distributions of these compounds by confocal microscopy and flow cytometry; it was found that cytotoxic-active compounds (30–32) located in the cytosol and inactivecompounds bearing longer carbon chains (33–35) were impenetrable across cell membranes.Our study demonstrated the defined lipophilic acyl-carbon chain length can precisely regulate thecytotoxic activityof saponins, which is useful for the future development of cytotoxic agents.Furthermore, using quantitative proteomics and immunolabeling,the mechanism ofcytotoxicity induced by the synthetic saponin after membrane penetration could be a result of activation of death receptor pathway and inhibition of PI3K/Akt/mTOR pathway.
  •  
27.
  • Lin, Chun-Yu, et al. (författare)
  • Lipopolysaccharide-Induced Nitric Oxide and Prostaglandin E2 Production Is Inhibited by Tellimagrandin II in Mouse and Human Macrophages
  • 2021
  • Ingår i: Life. - : MDPI. - 2075-1729. ; 11:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Sepsis develops from a serious microbial infection that causes the immune system to go into overdrive. The major microorganisms that induce sepsis are Gram-negative bacteria with lipopolysaccharide (LPS) in their cell walls. Nitric oxide (NO) and cyclooxygenase-2 (COX-2) are the key factors involved in the LPS-induced pro-inflammatory process. This study aimed to evaluate the effects of polyphenol Tellimagrandin II (TGII) on anti-inflammatory activity and its underlying basic mechanism in murine macrophage cell line RAW 264.7 and human monocyte-derived macrophages. Macrophages with more than 90% cell viability were found in the cytotoxicity assay under 50 mu M TGII. Pre- or post-treatment with TGII significantly reduced LPS-induced inducible nitric oxide synthase (NOS2) protein and mRNA expression, reducing LPS-induced COX-2 protein. Downstream of NOS2 and COX-2, NO and prostaglandin E2 (PGE2) were significantly inhibited by TGII. Upstream of NOS2 and COX-2, phospho-p65, c-fos and phospho-c-jun were also reduced after pre-treatment with TGII. Mitogen-activated protein kinases (MAPKs) are also critical to nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) stimulation, and phospho-p38 expression was found to have been blocked by TGII. TGII efficiently reduces LPS-induced NO production and its upstream regulatory factors, suggesting that TGII may be a potential therapeutic agent for sepsis and other inflammatory diseases.
  •  
28.
  • Lu, R.S., et al. (författare)
  • A ring-like accretion structure in M87 connecting its black hole and jet
  • 2023
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 616:7958, s. 686-690
  • Tidskriftsartikel (refereegranskat)abstract
    • The nearby radio galaxy M87 is a prime target for studying black hole accretion and jet formation1,2. Event Horizon Telescope observations of M87 in 2017, at a wavelength of 1.3 mm, revealed a ring-like structure, which was interpreted as gravitationally lensed emission around a central black hole3. Here we report images of M87 obtained in 2018, at a wavelength of 3.5 mm, showing that the compact radio core is spatially resolved. High-resolution imaging shows a ring-like structure of [Formula: see text] Schwarzschild radii in diameter, approximately 50% larger than that seen at 1.3 mm. The outer edge at 3.5 mm is also larger than that at 1.3 mm. This larger and thicker ring indicates a substantial contribution from the accretion flow with absorption effects, in addition to the gravitationally lensed ring-like emission. The images show that the edge-brightened jet connects to the accretion flow of the black hole. Close to the black hole, the emission profile of the jet-launching region is wider than the expected profile of a black-hole-driven jet, suggesting the possible presence of a wind associated with the accretion flow.
  •  
29.
  • Sui, Jiong-Ming, et al. (författare)
  • Isolation and characterization of a stress responsive small GTP-binding protein AhRabG3b in peanut (Arachis hypogaea L.)
  • 2013
  • Ingår i: Euphytica. - : Springer Science and Business Media LLC. - 0014-2336 .- 1573-5060. ; 189:2, s. 161-172
  • Tidskriftsartikel (refereegranskat)abstract
    • Rab7 is a member of small GTP-binding protein family involved in intracellular vesicle trafficking from late endosome to vacuole, some of them are found to be responsive by different environmental stresses. Here we report the isolation of a Rab7 (RabG3b) cDNA from peanut (Arachis hypogaea). Overexpression of the open reading frame (ORF) of Rab7 cDNA encoding 205 amino acids in E. coli conferred the cells tolerance to various abiotic stresses. Transcription of AhRabG3b was differentially up-regulated by different environmental stimuli such as cold, dehydration, NaCl and the plant hormone ABA. Overexpression of the AhRabG3b exhibited enhanced tolerance to drought and salinity stresses in transgenic peanut. These results suggested that the AhRabG3b be a potential candidate gene responsible for both salinity and dehydration tolerance in cultivated peanut.
  •  
30.
  • Wang, Anqi, et al. (författare)
  • Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
  • 2023
  • Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
  • Tidskriftsartikel (refereegranskat)abstract
    • The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
  •  
31.
  • Abbafati, Cristiana, et al. (författare)
  • 2020
  • Tidskriftsartikel (refereegranskat)
  •  
32.
  • Gan, Wensheng, et al. (författare)
  • Utility-Driven Data Analytics on Uncertain Data
  • 2020
  • Ingår i: IEEE Systems Journal. - : IEEE. - 1932-8184 .- 1937-9234. ; 14:3, s. 4442-4453
  • Tidskriftsartikel (refereegranskat)abstract
    • Modern Internet of Things (IoT) applications generate massive amounts of data, much of them in the form of objects/items of readings, events, and log entries. Specifically, most of the objects in these IoT data contain rich embedded information (e.g., frequency and uncertainty) and different levels of importance (e.g., unit risk/utility of items, interestingness, cost, or weight). Many existing approaches in data mining and analytics have limitations, such as only the binary attribute is considered within a transaction, as well as all the objects/items having equal weights or importance. To solve these drawbacks, a novel utility-driven data analytics algorithm named HUPNU is presented in this article. As a general utility-driven uncertain data mining model, HUPNU can extract High-Utility patterns by considering both Positive and Negative unit utilities from Uncertain data. The qualified high-utility patterns can be effectively discovered for intrusion detection, risk prediction, manufacturing management, and decision-making, among others. By using the developed vertical Probability-Utility list with the positive and negative utilities structure, as well as several effective pruning strategies, experiments showed that the developed HUPNU approach with the pruning strategies performed great in mining the qualified patterns efficiently and effectively.
  •  
33.
  • Heldin, Paraskevi, et al. (författare)
  • Involvement of hyaluronan and CD44 in cancer and viral infections
  • 2020
  • Ingår i: Cellular Signalling. - : ELSEVIER SCIENCE INC. - 0898-6568 .- 1873-3913. ; 65
  • Tidskriftsartikel (refereegranskat)abstract
    • Hyaluronan and its major receptor CD44 are ubiquitously distributed. They have important structural as well as signaling roles, regulating tissue homeostasis, and their expression levels are tightly regulated. In addition to signaling initiated by the interaction of the intracellular domain of CD44 with cytoplasmic signaling molecules, CD44 has important roles as a co-receptor for different types of receptors of growth factors and cytokines. Dysregulation of hyaluronan-CD44 interactions is seen in diseases, such as inflammation and cancer. In the present communication, we discuss the mechanism of hyaluronan-induced signaling via CD44, as well as the involvement of hyaluronan-engaged CD44 in malignancies and in viral infections.
  •  
34.
  • Heldin, Paraskevi, et al. (författare)
  • Regulation of hyaluronan biosynthesis and clinical impact of excessive hyaluronan production
  • 2019
  • Ingår i: Matrix Biology. - : ELSEVIER SCIENCE BV. - 0945-053X .- 1569-1802. ; 78-79, s. 100-117
  • Tidskriftsartikel (refereegranskat)abstract
    • The tightly regulated biosynthesis and catabolism of the glycosaminoglycan hyaluronan, as well as its role in organizing tissues and cell signaling, is crucial for the homeostasis of tissues. Overexpression of hyaluronan plays pivotal roles in inflammation and cancer, and markedly high serum and tissue levels of hyaluronan are noted under such pathological conditions. This review focuses on the complexity of the regulation at transcriptional and posttranslational level of hyaluronan synthetic enzymes, and the outcome of their aberrant expression and accumulation of hyaluronan in clinical conditions, such as systemic B-cell cancers, aggressive breast carcinomas, metabolic diseases and virus infection.
  •  
35.
  • Hsu, Ya-Ching, et al. (författare)
  • Methadone concentrations in blood, plasma, and oral fluid determined by isotope-dilution gas chromatography-mass spectrometry
  • 2013
  • Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Verlag (Germany). - 1618-2642 .- 1618-2650. ; 405:12, s. 3921-3928
  • Tidskriftsartikel (refereegranskat)abstract
    • Methadone (MTD) is widely used for detoxification of heroin addicts and also in pain management programs. Information about the distribution of methadone between blood, plasma, and alternative specimens, such as oral fluid (OF), is needed in clinical, forensic, and traffic medicine when analytical results are interpreted. We determined MTD and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) in blood, plasma, blood cells, and OF by gas chromatography-mass spectrometry (GC-MS) after adding deuterium-labeled internal standards. The analytical limits of quantitation for MTD and EDDP by this method were 20 and 3 ng/mL, respectively. The amounts of MTD and EDDP were higher in plasma (80.4 % and 76.5 %) compared with blood cells (19.6 % and 23.5 %) and we found that repeated washing of blood cells with phosphate-buffered saline increased the amounts in plasma (93.6 % and 88.6 %). Mean plasma/blood concentration ratios of MTD and EDDP in spiked samples (N = 5) were 1.27 and 1.21, respectively. In clinical samples from patients (N = 46), the concentrations of MTD in plasma and whole blood were highly correlated (r = 0.92, p andlt; 0.001) and mean (median) plasma/blood distribution ratios were 1.43 (1.41). The correlations between MTD in OF and plasma (r = 0.46) and OF and blood (r = 0.52) were also statistically significant (p andlt; 0.001) and the mean OF/plasma and OF/blood distribution ratios were 0.55 and 0.77, respectively. The MTD concentration in OF decreased as salivary pH increased (more basic). These results will prove useful in clinical and forensic medicine when MTD concentrations in alternative specimens are compared and contrasted.
  •  
36.
  • Huang, Wen-Yi, et al. (författare)
  • Effectiveness of using calligraphic activity to treat people with schizophrenia : a randomized controlled trial in Southern Taiwan
  • 2022
  • Ingår i: THERAPEUTIC ADVANCES IN CHRONIC DISEASE. - : Sage Publications. - 2040-6223 .- 2040-6231. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Prior research has shown preliminary evidence that calligraphy activity improves various body functions and decreases severity of psychotic symptoms in individuals with schizophrenia. However, major limitations of earlier studies include small and heterogeneous samples. The current large-scale randomized controlled trial examined effects of calligraphy activity on cognition (including attention), emotions, psychotic symptoms, quality of life, and mood in people with schizophrenia. Methods: One-hundred-and-fifty patients with schizophrenia were randomly allocated to the treatment group (receiving calligraphy activity) or the control group (receiving general activity), both of which lasted for 24weeks (70 minutes per session; one session per week). Assessments were conducted at pretest, posttest, and three-month follow-up. The Montreal Cognitive Assessment, Chu's Attention Test, Depression, Anxiety, and Stress Scale, Positive and Negative Syndrome Scale, World Health Questionnaire on the Quality of Life-Brief Form, and Visual Analogue Scale were used. Results: Improved cognition and attention were found in both groups, although no group effects were shown. The treatment group appeared to show lower severity of positive symptoms at follow-up than posttest, whereas the control group appeared to show the opposite pattern. Improved mood was found in the treatment group. Conclusion: This study provides evidence regarding effects of calligraphy activity on increasing cognition and potentially decreasing severity of positive symptoms in patients with schizophrenia. Calligraphy activity can be incorporated in clinical occupational therapy and may be provided to supplement medication treatment.
  •  
37.
  • Kolliopoulos, Constantinos, et al. (författare)
  • Has2 natural antisense RNA and Hmga2 promote Has2 expression during TGFβ-induced EMT in breast cancer
  • 2019
  • Ingår i: Matrix Biology. - : Elsevier BV. - 0945-053X .- 1569-1802. ; 80, s. 29-45
  • Tidskriftsartikel (refereegranskat)abstract
    • The glycosaminoglycan hyaluronan has a crucial role in tissue organization and cell signaling. Hyaluronan accumulates in conjunction with rapid tissue remodeling during embryogenesis, as well as in inflammatory conditions and cancer. We report a negative correlation between the expression of genes encoding hyaluronan synthase HAS2, its natural antisense transcript HAS2-AS, the chromatin modulating factor HMGA2 and transforming growth factor-β (TGFβ), and survival of patients with invasive breast carcinomas. In mouse mammary epithelial cells, TGFβ activates Smad and non-Smad signaling pathways, resulting in the transcriptional induction of Has2, Has2as (the mouse ortholog of HAS2-AS) and Hmga2, as well as epithelial-mesenchymal transition (EMT)-promoting transcription factors, such as Snail. Importantly, Has2as abrogation suppressed the TGFβ induction of EMT markers, including Snai1, Hmga2, Fn1, and suppressed the mesenchymal phenotype. TGFβ induction of Hmga2, Has2as and Has2, and synthesis of hyaluronan were accompanied with activation of Akt and Erk1/2 MAP-kinase signaling and were required for breast cancer cell motility. Importantly, the hyaluronan receptor Cd44, but not Hmmr, was required for TGFβ-mediated EMT phenotype. Interestingly, Has2as was found to contribute to the maintenance of stem cell factors and breast cancer stemness. Our findings show that Has2as has a key role in TGFβ- and HAS2-induced breast cancer EMT, migration and acquisition of stemness.
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38.
  • Li, Shenpan, et al. (författare)
  • Hepatic injury and ileitis associated with gut microbiota dysbiosis in mice upon F–53B exposure
  • 2024
  • Ingår i: Environmental Research. - : Elsevier. - 0013-9351 .- 1096-0953. ; 248
  • Tidskriftsartikel (refereegranskat)abstract
    • Chlorinated polyfluorinated ether sulfonate (F–53B), a substitute of perfluorooctane sulfonic acid (PFOS), has attracted significant attention for its link to hepatotoxicity and enterotoxicity. Nevertheless, the underlying mechanisms of F–53B-induced enterohepatic toxicity remain incompletely understood. This study aimed to explore the role of F–53B exposure on enterohepatic injury based on the gut microbiota, pathological and molecular analysis in mice. Here, we exposed C57BL/6 mice to F–53B (0, 4, 40, and 400 μg/L) for 28 days. Our findings revealed a significant accumulation of F–53B in the liver, followed by small intestines, and feces. In addition, F–53B induced pathological collagen fiber deposition and lipoid degeneration, up-regulated the expression of fatty acid β-oxidation-related genes (PPARα and PPARγ, etc), while simultaneously down-regulating pro-inflammatory genes (Nlrp3, IL-1β, and Mcp1) in the liver. Meanwhile, F–53B induced ileal mucosal barrier damage, and an up-regulation of pro-inflammatory genes and mucosal barrier-related genes (Muc1, Muc2, Claudin1, Occludin, Mct1, and ZO-1) in the ileum. Importantly, F–53B distinctly altered gut microbiota compositions by increasing the abundance of Akkermansia and decreasing the abundance of Prevotellaceae_NK3B31_group in the feces. F–53B-altered microbiota compositions were significantly associated with genes related to fatty acid β-oxidation, inflammation, and mucosal barrier. In summary, our results demonstrate that F–53B is capable of inducing hepatic injury, ileitis, and gut microbiota dysbiosis in mice, and the gut microbiota dysbiosis may play an important role in the F–53B-induced enterohepatic toxicity.
  •  
39.
  • Lin, Chun-Yu, et al. (författare)
  • High levels of serum hyaluronan is an early predictor of dengue warning signs and perturbs vascular integrity
  • 2019
  • Ingår i: EBioMedicine. - : ELSEVIER. - 2352-3964. ; 48, s. 425-441
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A main pathological feature of severe dengue virus infection is endothelial hyper-permeability. The dengue virus nonstructural protein 1 (NS1) has been implicated in the vascular leakage that characterizes severe dengue virus infection, however, the molecular mechanisms involved are not known.Methods: A cohort of 250 dengue patients has been followed from the onset of symptoms to the recovery phase. Set urn hyaluronan levels and several other clinical parameters were recorded. The effect of NS1 treatment of cultured fibroblasts and endothelial cells on the expressions of hyaluronan synthetic and catabolic enzymes and the hyaluronan receptor CD44, were determined, as have the effects on the formation of hyaluronan-rich matrices and endothelial permeability.Findings: Elevated serum hyaluronan levels (70 ng/ml) during early infection was found to be an independent predictor for occurrence of warning signs, and thus severe dengue fever. High circulating levels of the viral protein NS1, indicative of disease severity, correlated with high concentrations of serum hyaluronan. NS1 exposure decreased the expression of CD44 in differentiating endothelial cells impairing the integrity of vessel-like structures, and promoted the synthesis of hyaluronan in dermal fibroblasts and endothelial cells in synergy with dengue-induced pro-inflammatory mediators. Deposited hyaluronan-rich matrices around cells cultured in vitro recruited CD44-expressing macrophage-like cells, suggesting a mechanism for enhancement of inflammation. In cultured endothelial cells, perturbed hyaluronan-CD44 interactions enhanced endothelial permeability through modulation of VE-cadherin and cytoskeleton re-organization, and exacerbated the NS1-induced disruption of endothelial integrity.Interpretation: Pharmacological targeting of hyaluronan biosynthesis and/or its CD44-mediated signaling may limit the life-threatening vascular leakiness during moderate-to-severe dengue virus infection. 
  •  
40.
  • Lin, Chun-Yu, et al. (författare)
  • Hyaluronan-Induced CD44-iASPP Interaction Affects Fibroblast Migration and Survival
  • 2023
  • Ingår i: Cancers. - : MDPI. - 2072-6694. ; 15:4
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present study, we show that the inhibitor of the apoptosis-stimulating protein of p53 (iASPP) physically interacts with the hyaluronan receptor CD44 in normal and transformed cells. We noticed that the CD44 standard isoform (CD44s), but not the variant isoform (CD44v), bound to iASPP via the ankyrin-binding domain in CD44s. The formation of iASPP-CD44s complexes was promoted by hyaluronan stimulation in fibroblasts but not in epithelial cells. The cellular level of p53 affected the amount of the iASPP-CD44 complex. iASPP was required for hyaluronan-induced CD44-dependent migration and adhesion of fibroblasts. Of note, CD44 altered the sub-cellular localization of the iASPP-p53 complex; thus, ablation of CD44 promoted translocation of iASPP from the nucleus to the cytoplasm, resulting in increased formation of a cytoplasmic iASPP-p53 complex in fibroblasts. Overexpression of iASPP decreased, but CD44 increased the level of intracellular reactive oxygen species (ROS). Knock-down of CD44s, in the presence of p53, led to increased cell growth and cell density of fibroblasts by suppression of p27 and p53. Our observations suggest that the balance of iASPP-CD44 and iASPP-p53 complexes affect the survival and migration of fibroblasts.
  •  
41.
  • Lin, Chun-Yu, 1976- (författare)
  • The role of hyaluronan and its CD44 receptor in inflammation and cancer
  • 2024
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Hyaluronan, an important extra-cellular matrix molecule, was thought to be interstitial connecting glue decades ago. However, recent evidence has revealed that hyaluronan and its binding proteins also play crucial roles in various pathophysiological conditions in humans, including inflammation and infection.Study I focused on dengue virus infection and found that elevated serum hyaluronan levels during early infection phase was an independent predictor for occurrence of warning signs, and thus severe dengue. High circulating levels of the viral non-structural protein 1 (NS1) correlated with high concentrations of serum hyaluronan. NS1 exposure decreased the expression of CD44 in differentiating endothelial cells impairing the integrity of vessel-like structures and promoted the synthesis of hyaluronan in dermal fibroblasts and endothelial cells in synergy with dengue-induced pro-inflammatory mediators. Perturbed hyaluronan-CD44 interactions enhanced endothelial permeability through modulation of VE-cadherin and cytoskeleton re-organization, and exacerbated the NS1-induced disruption of endothelial integrity. Study II reports a negative correlation between the expression of genes encoding hyaluronan synthase HAS2, its natural antisense transcript HAS2-AS, the chromatin modulating factor HMGA2 and transforming growth factor-β (TGFβ), and survival of patients with invasive breast cancer. TGFβ induction of Hmga2, Has2as and Has2 in mouse mammary epithelial cells, and synthesis of hyaluronan were accompanied with activation of Akt and Erk1/2 MAP-kinase signaling and were required for breast cancer cell motility. Importantly, the hyaluronan receptor Cd44, but not Hmmr, was required for TGFβ-mediated epithelial-mesenchymal transition phenotype. Has2as was found to contribute to the maintenance of stem cell factors and breast cancer stemness. Study III explored the physical interaction between the inhibitor of the apoptosis-stimulating protein of p53 (iASPP) and the hyaluronan receptor CD44. The CD44 standard isoform (CD44s), but not the variant isoform, bound to iASPP via the ankyrin-binding domain in CD44s. iASPP was required for hyaluronan-induced CD44-dependent migration and adhesion of fibroblasts. CD44 altered the sub-cellular localization of the iASPP-p53 complex; thus, ablation of CD44 promoted translocation of iASPP from the nucleus to the cytoplasm, resulting in increased formation of a cytoplasmic iASPP-p53 complex in fibroblasts. Overexpression of iASPP decreased the level of intracellular reactive oxygen species, while overexpression of CD44 increased. Knock-down of CD44s, in the presence of p53, led to increased cell growth and cell density of fibroblasts by suppression of p27 and p53.In summary, we investigated the interaction of hyaluronan and its transmembranous receptor, CD44, as well as the modulation of hyaluronan synthesis, in several different pathophysiological conditions.
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42.
  • Liu, Yu, et al. (författare)
  • Diagnostic Values of METTL1-Related Genes and Immune Characteristics in Systemic Lupus Erythematosus
  • 2023
  • Ingår i: Journal of Inflammation Research. - : Dove Medical Press. - 1178-7031. ; 16, s. 5367-5383
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose: Methyltransferase like 1 (METTL1) regulates epitranscriptomes via the m7G modification in mammalian mRNA and microRNA. Systemic lupus erythematosus (SLE) is caused by abnormal immune reactivity and has diverse clinical manifestations. RNA methylation as a mechanism to regulate gene expression is widely implicated in immune regulation. However, the role of m7G in immune response of SLE has not been extensively studied.Patients and Methods: Expression of METTL1 was identified in the public dataset GSE122459 and validated in an independent cohort of SLE patients. We investigated the association between METTL1-expression and clinical manifestations of SLE. Subsequently, differentially expressed genes (DEG) that were correlated with METTL1-expression in GSE122459 were used for functional enrichment analysis. The correlation between infiltrating immune cells and METTL1, as well as candidate biomarkers identified to be correlated with either METTL1 or immune cell infiltration were assessed by single-sample GSEA. Potential mechanisms were explored with Gene ontology and KEGG pathway enrichment. Diagnostic performances of candidate biomarkers in SLE were analyzed.Results: The mRNA and protein expression of METTL1 in SLE patients were significantly decreased in both datasets. METTL1-coexpressed DEGs were enriched in several key immune-related pathways. Activated CD8 T cells, activated CD4 T cells, memory B cells and type 2 helper T cells were different between patients with high and low METTL1 expression. Further, activated CD8 T-cells, activated CD4 T-cells, memory B-cells were correlated with METTL1. The genes of LAMP3, CD83, PDCD1LG2, IGKVD3D-20, IGKV5-2, IGKV2D-30, IGLV3-19 and IGLV4-60 were identified as candidate targets that were correlated with immune cell proportion. Moreover, LAMP3, CD83, and PDCD1LG2 expression were of diagnostic value in SLE as indicated by ROC analysis.Conclusion: Our findings suggested that METTL1 and its candidate targets LAMP3, CD83, PDCD1LG2 may be used for diagnosing SLE and could be explored for developing targeted molecular therapy for SLE.
  •  
43.
  • Lo, Sheng-Han, et al. (författare)
  • Rapid desolvation-triggered domino lattice rearrangement in a metal-organic framework
  • 2020
  • Ingår i: Nature Chemistry. - : Springer Science and Business Media LLC. - 1755-4330 .- 1755-4349. ; 12:1, s. 90-97
  • Tidskriftsartikel (refereegranskat)abstract
    • Topological transitions between considerably different phases typically require harsh conditions to collectively break chemical bonds and overcome the stress caused to the original structure by altering its correlated bond environment. In this work we present a case system that can achieve rapid rearrangement of the whole lattice of a metal-organic framework through a domino alteration of the bond connectivity under mild conditions. The system transforms from a disordered metal-organic framework with low porosity to a highly porous and crystalline isomer within 40s following activation (solvent exchange and desolvation), resulting in a substantial increase in surface area from 725 to 2,749m(2)g(-1). Spectroscopic measurements show that this counter-intuitive lattice rearrangement involves a metastable intermediate that results from solvent removal on coordinatively unsaturated metal sites. This disordered-crystalline switch between two topological distinct metal-organic frameworks is shown to be reversible over four cycles through activation and reimmersion in polar solvents. A disordered metal-organic framework converts into a more porous, crystalline phase within 40s following solvent exchange and desolvation. The rapid domino rearrangement of the whole lattice, which involves carboxylate migration on coordinatively unsaturated metal sites, is accompanied by a substantial increase in surface area.
  •  
44.
  • Ollila, Hanna M., et al. (författare)
  • Narcolepsy risk loci outline role of T cell autoimmunity and infectious triggers in narcolepsy
  • 2023
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix (R). Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix (R).
  •  
45.
  • van der Heijden, Jaap, et al. (författare)
  • Plasma Hyaluronan Decreases During ICU Stay in COVID-19 Survivors but Not inNon-Survivor : A Retrospective Cohort Study
  • 2021
  • Ingår i: Biomarkers Journal. - 2472-1646. ; 7:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Plasma hyaluronan concentration is associated with disease severity in COVID-19 patients. Hyaluronan is found in secretions and alveolar exudate in COVID-19 patients, and increased perialveolar interstitial hyaluronan has been found in the lungs of COVID-19 patients. This may obstruct alveoli and impair gas exchange and thereby contribute to hypoxemia and respiratory failure. The aim of this study was to describe the dynamics of plasma hyaluronan concentrations and to compare hyaluronan concentrations between non-survivors and survivors in critically ill COVID-19 patients.
  •  
46.
  • Wu, Ping-Hsun, et al. (författare)
  • A Low Ankle-Brachial Index and High Brachial-Ankle Pulse Wave Velocity Are Associated with Poor Cognitive Function in Patients Undergoing Hemodialysis
  • 2019
  • Ingår i: Disease Markers. - : Hindawi Limited. - 0278-0240 .- 1875-8630. ; 2019
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with end-stage renal disease (ESRD) have an increased risk of both impaired cognitive function and peripheral artery disease (PAD) than the general population. The association between PAD and dementia is recognized, but there are limited studies in patients with ESRD. The aim of this study was to evaluate the relationship between ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV) and cognitive impairment in patients receiving hemodialysis (HD). We enrolled 136 prevalent HD patients (mean age 59.3 +/- 10.5 years, 55.9% male). Cognitive performance was measured using the Montreal Cognitive Assessment (MoCA) and Cognitive Abilities Screening Instrument (CASI) by trained psychiatrists. Associations between the cognitive function and ABI and baPWV were assessed using multiple linear regression analysis. Compared with HD patients with ABI >= 0.9, patients with ABI<0.9 had lower MoCA score (p=0.027) and lower CASI score but did not achieve significant level (p=0.056). In the multivariate stepwise linear regression analysis, ABI (per 0.1) was independently positively associated with the MoCA score (beta coefficient=0.62, p=0.011) and the CASI score (beta coefficient=1.43, p=0.026). There is a negative association between baPWV (per 100cm/s) and CASI (beta coefficient=-0.70, p=0.009). In conclusion, a low ABI or high baPWV was associated with a lower cognitive function in HD patients.
  •  
47.
  • Wu, Ping-Hsun, et al. (författare)
  • Association between Circulation Indole-3-Acetic Acid Levels and Stem Cell Factor in Maintenance Hemodialysis Patients : A Cross-Sectional Study
  • 2020
  • Ingår i: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Protein-bound uremic toxin is a cardiovascular (CV) risk factor for patients with end-stage renal disease. Indole-3-acetic acid (IAA) was found to be associated with CV disease but the detailed pathophysiology remains unknown. Moreover, mitogen-activated protein kinase (MAPK) signaling cascades play an important role in the pathogenesis of CV disease. Thus, we explored the association between circulating IAA levels and forty MAPK cascade associated proteins in patients undergoing hemodialysis (HD). Circulating total form IAA was quantified by mass spectrometry and forty MAPK cascade associated proteins by a proximity extension assay in 331 prevalent HD patients. Accounting for multiple testing, and in multivariable-adjusted linear regression models, circulating total form IAA levels were positively associated with stem cell factor (beta coefficient 0.13, 95% confidence interval 0.04 to 0.21, p = 0.004). A bioinformatics approach using the search tool for interactions of chemicals (STITCH) tool provided information that IAA may be involved in the regulation of cell proliferation, hematopoietic cells, and the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. The knowledge gained here can be generalized, thereby impacting the non-traditional CV risk factors in patients with kidney disease. Further in vitro work is necessary to validate the translation of the mechanistic pathways.
  •  
48.
  • Yen, Ying-Tzu, et al. (författare)
  • Prominent Enhancement of Cisplatin Efficacy with Optimized Methoxy Poly(ethylene glycol)-Polycaprolactone Block Copolymeric Nanoparticles
  • 2020
  • Ingår i: Journal of Biomedical Nanotechnology. - : AMER SCIENTIFIC PUBLISHERS. - 1550-7033 .- 1550-7041. ; 16:3, s. 335-343
  • Tidskriftsartikel (refereegranskat)abstract
    • Chemotherapy has been one of the major standard treatments for a variety of cancers. cis-Dichlorodiamminoplatiunum(II) (cisplatin, CDDP), as one of the anticancer agents, demonstrated excellent efficacy against tumor and has been an indispensable component in chemotherapy, chemoradiation, chemo-molecular targeted therapy and chemo-immunotherapy. However, its therapeutic concentration was limited since its inevitable toxicity. Previously, we have constructed CDDP-loaded nanoparticles (NPs) with mixture of poly(ethyleneglycol)-polycaprolactone (PEG-PCL) and polycarprolactone (HO-PCL) by a facile method. The most optimal proportion of the two copolymers was selected through a series of physical, chemical, cytological and histological evaluations. In the present study, we explored the mechanisms of NPs and observed the in vivo antitumor effect after administrating CDDP-loaded PEG-PCL NPs. Positron emission tomography as well as computed tomography (PET/CT) were adopted for detecting tumoral metabolic activity. Images from fluorescence microscope revealed superior cellular uptake of CDDP-loaded NPs with rhodamine B aggregated intracellularly in cancer cells. Similar apoptotic rates between free CDDP group and CDDP-loaded NPs group was measured by flow cytometry. Tumor volumes and murine weights confirmed the superiority of CDDP-loaded NPs in therapeutic efficacy as compared with free CDDP. Blood tests showed milder side effects in CDDP-loaded nanoparticle group. PET/CT images illustrated less uptake intensity of FDG in mice received CDDP-loaded NPs than free CDDP. Our results suggest that PEG-PCL/PCL NPs could be a promising antitumor drug carrier for CDDP delivery with solid efficacy and minor side effects.
  •  
49.
  • Zhang, Qiang, et al. (författare)
  • Spatial and temporal variability of precipitation maxima during 1960-2005 in the Yangtze River basin and possible association with large-scale circulation
  • 2008
  • Ingår i: Journal of Hydrology. - : Elsevier BV. - 0022-1694 .- 1879-2707. ; 353:3-4, s. 215-227
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigated spatial and temporal patterns of trends of the precipitation maxima (defined as the annual./seasonal. maximum precipitation) in the Yangtze River basin for 1960-2005 using Mann-Kendall trend test, and explored association of changing patterns of the precipitation maxima with large-scale circulation using NCEP/NCAR reanalysis data. The research results indicate changes of precipitation maxima from relative stable patterns to the significant increasing/decreasing trend in the middle 1970s. With respect to annual variability, the rainy days are decreasing and precipitation intensity is increasing, and significant increasing trend of precipitation intensity was detected in the middle and lower Yangtze River basin. Number of rain days with daily precipitation exceeding 95th and 99th percentiles and related precipitation intensities are in increasing tendency in summer. Large-scale atmospheric circulation analysis indicates decreasing strength of East Asian summer monsoon during 1975-2005 as compared to that during 1961-1974 and increasing geopotential height in the north China, South China Sea and west Pacific regions, all of which combine to negatively impact the northward propagation of the vapor flux. This circulation pattern will be beneficial for the longer stay of the Meiyu front in the Yangtze River basin, leading to more precipitation in the middle and lower Yangtze River basin in summer months. The significant increasing summer precipitation intensity and changing frequency in the rain/no-rain days in the middle and lower Yangtze River basin have potential to result in higher occurrence probability of flood and drought hazards in the region.
  •  
50.
  • Zheng, Xiaopeng, et al. (författare)
  • Managing grains and interfaces via ligand anchoring enables 22.3%-efficiency inverted perovskite solar cells
  • 2020
  • Ingår i: NATURE ENERGY. - : Nature Publishing Group. - 2058-7546. ; 5, s. 131-140
  • Tidskriftsartikel (refereegranskat)abstract
    • Inverted perovskite solar cells have attracted increasing attention because they have achieved long operating lifetimes. However, they have exhibited significantly inferior power conversion efficiencies compared to regular perovskite solar cells. Here we reduce this efficiency gap using a trace amount of surface-anchoring alkylamine ligands (AALs) with different chain lengths as grain and interface modifiers. We show that long-chain AALs added to the precursor solution suppress nonradiative carrier recombination and improve the optoelectronic properties of mixed-cation mixed-halide perovskite films. The resulting AAL surface-modified films exhibit a prominent (100) orientation and lower trap-state density as well as enhanced carrier mobilities and diffusion lengths. These translate into a certified stabilized power conversion efficiency of 22.3% (23.0% power conversion efficiency for lab-measured champion devices). The devices operate for over 1,000 h at the maximum power point under simulated AM1.5 illumination, without loss of efficiency. While perovskite solar cells with an inverted architecture hold great promise for operation stability, their power conversion efficiency lags behind that of conventional cells. Here, Zheng et al. achieve a certified 22.34% efficiency, exploiting alkylamine ligands as grain and interface modifiers.
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