Publications by authors named "Yuting Chen"

171 Publications

Lung stem cells in regeneration and tumorigenesis.

J Genet Genomics 2021 Mar 17. Epub 2021 Mar 17.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences; University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; Shanghai Pulmonary Hospital, Tongji University, Shanghai 200092, China. Electronic address:

Adult lung is a highly quiescent organ, with extremely low cell turnover frequency. However, emerging evidences support the occurrence of repair and regeneration in pulmonary epithelia in response to various injuries. Lung regeneration mainly depends on the proliferation of regionally distributed pulmonary stem cells that re-enter the cell cycle. Genetic lineage-tracing approaches help to track the lung epithelial differentiation and/or de-differentiation path, and single-cell transcriptomic technique reveals the essential molecular signaling involved in lung regeneration. Dysregulation of the molecular signaling that balances quiescence and self-renewal leads to the transformation of lung stem cells, and thus promotes lung cancer development. Interestingly, different subtypes of lung cancer share common cells of origin and the pathological transition among various subtypes is responsible for drug resistance in the clinic. In this review, we summarize the recent understanding of lung stem cells in regeneration and tumorigenesis as well as related molecular mechanisms, with the hope to provide helpful insights for clinical treatments of respiratory diseases.
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http://dx.doi.org/10.1016/j.jgg.2020.12.004DOI Listing
March 2021

Protein tyrosine phosphatase receptor type D gene promotes radiosensitivity via STAT3 dephosphorylation in nasopharyngeal carcinoma.

Oncogene 2021 Apr 6;40(17):3101-3117. Epub 2021 Apr 6.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Radiotherapy is essential to the treatment of nasopharyngeal carcinoma (NPC) and acquired or innate resistance to this therapeutic modality is a major clinical problem. However, the underlying molecular mechanisms in the radiation resistance in NPC are not fully understood. Here, we reanalyzed the microarray data from public databases and identified the protein tyrosine phosphatase receptor type D (PTPRD) as a candidate gene. We found that PTPRD was downregulated in clinical NPC tissues and NPC cell lines with its promoter hypermethylated. Functional assays revealed that PTPRD overexpression sensitized NPC to radiation in vitro and in vivo. Importantly, miR-454-3p directly targets PTPRD to inhibit its expression and biological effect. Interestingly, mechanistic analyses indicate that PTPRD directly dephosphorylates STAT3 to enhance Autophagy-Related 5 (ATG5) transcription, resulting in triggering radiation-induced autophagy. The immunohistochemical staining of 107 NPC revealed that low PTPRD and high p-STAT3 levels predicted poor clinical outcome. Overall, we showed that PTPRD promotes radiosensitivity by triggering radiation-induced autophagy via the dephosphorylation of STAT3, thus providing a potentially useful predictive biomarker for NPC radiosensitivity and drug target for NPC radiosensitization.
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http://dx.doi.org/10.1038/s41388-021-01768-8DOI Listing
April 2021

Sustainable development of microalgal biotechnology in coastal zone for aquaculture and food.

Sci Total Environ 2021 Mar 10;780:146369. Epub 2021 Mar 10.

State Key Laboratory of Marine Resource Utilization in South China Sea, College of Oceanology, Hainan University, Haikou, Hainan 570228, China. Electronic address:

Region-specific Research and Development (R&D) of microalga-derived product systems are crucial if "biotech's green gold" is to be explored in a rational and economically viable way. Coastal zones, particularly the locations around the equator, are typically considered to be optimum cultivation sites due to stable annual temperature, light, and ready availability of seawater. However, a 'cradle-to-grave' assessment of the development of microalgal biotechnology in these areas, not only under the laboratory conditions, but also in the fields has not yet been demonstrated. In this study, to evaluate the viability of microalga-derived multi-product technology, we showed the development of microalgal biotechnology in coastal zones for aquaculture and food. By creating and screening a (sub)tropical microalgal collection, a Chlorella strain MEM25 with a robust growth in a wide range of salinities, temperatures, and light intensities was identified. Evaluation of the economic viability and performance of different scale cultivation system designs (500 L and 5000 L closed photobioreactors and 60,000 L open race ponds, ORPs) at coastal zones under geographically specific conditions showed the stable and robust characteristics of MEM25 across different production system designs and various spatial and temporal scales. It produces high amounts of proteins and polyunsaturated fatty acids (PUFAs) in various conditions. Feeding experiments reveal the nutritional merits of MEM25 as food additives where PUFAs and essential amino acids are enriched and the algal diet improves consumers' growth. Economic evaluation highlights an appreciable profitability of MEM25 production as human or animal food using ORP systems. Therefore, despite the pros and cons, sound opportunities exist for the development of market-ready multiple-product systems by employing region-specific R&D strategies for microalgal biotechnology.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146369DOI Listing
March 2021

Short-term effects of ambient temperature and pollutants on the mortality of respiratory diseases: A time-series analysis in Hefei, China.

Ecotoxicol Environ Saf 2021 Jun 24;215:112160. Epub 2021 Mar 24.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China. Electronic address:

Background: The air pollution has become an important environmental health problem due to its adverse health effect. The objective of this study was to investigate the effects of ambient temperature and pollutants on mortality of respiratory diseases (RD) in Hefei, China, a typical inland city.

Methods: Nonlinear exposure-response dependencies and delayed effects of urban daily mean temperature (DMT) and pollutants were evaluated by distributed lag non-linear models (DLNM). To further explore this effect, different genders and ages were also examined by stratified analysis.

Results: A total of 12876 deaths from RD were collected from January 1, 2014 to December 31, 2018 in Hefei, China. There was a U-shaped correlation between DMT and RD mortality, and the RD mortality rised by 11.6% (95% CI: 2.2-22.0%) when the DMT was 35.8 °C (reference temperature is 20 °C). The results show that risk of death with short-term exposure to elevated concentrations of PM and SO was not significant. The maximum hysteresis and cumulative relative risk (RR) of RD mortality were 1.012 (95% CI: 1.003 ~ 1.021, lag 0 day) and 1.072 (95% CI: 1.014 ~1.133, lag 10 days) for each 10 μg/m augment in NO; 1.005 (95% CI: 1.001-1.009, lag 0 day) and 1.027 (95% CI: 1.004-1.051, lag 10 days) for each 10 μg/m augment in O a negative association between CO exposure and the cumulative risk of death was observed (RR = 0.964, 95% CI: 0.935-0.993, lag 07 days). Subgroup analysis showed the effect of high temperatures, NO O and CO exposure was still statistically significant for the elderly and male.

Conclusion: The present study found that short-term exposure to high temperature, NO O and CO were significantly associated with the risk of RD mortality and male as well as elderly are more susceptible to these factors.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112160DOI Listing
June 2021

Prediction of Soil Clay Content and Cation Exchange Capacity Using Visible Near-Infrared Spectroscopy, Portable X-ray Fluorescence, and X-ray Diffraction Techniques.

Environ Sci Technol 2021 04 22;55(8):4629-4637. Epub 2021 Mar 22.

School of Life and Environmental Sciences, Faculty of Science, The University of Sydney, Eveleigh, NSW 2015, Australia.

This article investigates a novel data fusion method to predict clay content and cation exchange capacity using visible near-infrared (visNIR) spectroscopy, portable X-ray fluorescence (pXRF), and X-ray diffraction (XRD) techniques. A total of 367 soil samples from two study areas in regional Australia were analyzed and intra- and interarea calibration options were explored. Cubist models were constructed using information from each device independently and in combination. pXRF produced the most accurate predictions of any individual device. Models based on fused data significantly improved the accuracy of predictions compared with those based on individual devices. The combination of pXRF and visNIR had the greatest performance. Overall, the relative increase in Lin's concordance correlation coefficient ranged from 1% to 12% and the corresponding decrease in root-mean-square error (RMSE) ranged from 10% to 46%. Provision of XRD data resulted in a decrease in observed RMSE values, although differences were not significant. Validation metrics were less promising when models were calibrated in one study area and then transferred to the other. Observed RMSE values were ∼2 to 3 times larger under this model transfer scenario and independent use of XRD was found to have the best overall performance.
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http://dx.doi.org/10.1021/acs.est.0c04130DOI Listing
April 2021

Multi-modal magnetic resonance imaging-based grading analysis for gliomas by integrating radiomics and deep features.

Ann Transl Med 2021 Feb;9(4):298

School of Biomedical Engineering, Southern Medical University, Guangzhou, China.

Background: To investigate the feasibility of integrating global radiomics and local deep features based on multi-modal magnetic resonance imaging (MRI) for developing a noninvasive glioma grading model.

Methods: In this study, 567 patients [211 patients with glioblastomas (GBMs) and 356 patients with low-grade gliomas (LGGs)] between May 2006 and September 2018, were enrolled and divided into training (n=186), validation (n=47), and testing cohorts (n=334), respectively. All patients underwent postcontrast enhanced T1-weighted and T2 fluid-attenuated inversion recovery MRI scanning. Radiomics and deep features (trained by 8,510 3D patches) were extracted to quantify the global and local information of gliomas, respectively. A kernel fusion-based support vector machine (SVM) classifier was used to integrate these multi-modal features for grading gliomas. The performance of the grading model was assessed using the area under receiver operating curve (AUC), sensitivity, specificity, Delong test, and -test.

Results: The AUC, sensitivity, and specificity of the model based on combination of radiomics and deep features were 0.94 [95% confidence interval (CI): 0.85, 0.99], 86% (95% CI: 64%, 97%), and 92% (95% CI: 75%, 99%), respectively, for the validation cohort; and 0.88 (95% CI: 0.84, 0.91), 88% (95% CI: 80%, 93%), and 81% (95% CI: 76%, 86%), respectively, for the independent testing cohort from a local hospital. The developed model outperformed the models based only on either radiomics or deep features (Delong test, both of P<0.001), and was also comparable to the clinical radiologists.

Conclusions: This study demonstrated the feasibility of integrating multi-modal MRI radiomics and deep features to develop a promising noninvasive grading model for gliomas.
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http://dx.doi.org/10.21037/atm-20-4076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944310PMC
February 2021

Epstein-Barr virus (EBV) encoded microRNA BART8-3p drives radioresistance-associated metastasis in nasopharyngeal carcinoma.

J Cell Physiol 2021 Mar 10. Epub 2021 Mar 10.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Radiotherapy plays an important role in the treatment of nasopharyngeal carcinoma (NPC), however, 20% of patients with NPC exhibit unusual radioresistance. Patients with radioresistance are at risk of recurrence, so it is imperative to explore the mechanism of resistance to radiotherapy. In the past, studies on the mechanism of radioresistance have been restricted to DNA damage and related cell cycle remodeling or apoptosis. So far, no studies have explored the relationship between radioresistance and metastasis. Through the analysis of clinical samples, we observed that the metastasis rate of recurrent NPC was much higher than that of primary patients. In vitro and in vivo experiments showed that NPC cells with acquired radioresistance exhibited a stronger ability for invasion and metastasis. Mechanistically, we found that the Epstein-Barr virus (EBV)-encoded miRNA BART8-3p was increased in patients with NPC, and its expression was positively correlated with adverse prognostic factors, such as radioresistance. Besides this, miR-BART8-3p promoted the epithelial-mesenchymal transition, invasion, and metastasis of radioresistant NPC cells by targeting and inhibiting their PAG1 host gene. These findings suggested a novel role for EBV-miR-BART8-3p in promoting NPC radioresistance-associated metastasis and highlighted its potential value as a prognostic indicator or therapeutic target.
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http://dx.doi.org/10.1002/jcp.30320DOI Listing
March 2021

Epigenetics of ankylosing spondylitis: Recent developments.

Int J Rheum Dis 2021 Apr 19;24(4):487-493. Epub 2021 Feb 19.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China.

Ankylosing spondylitis (AS) is a chronic inflammatory autoimmune disease which mainly affects the spine, sacroiliac joint and peripheral joints. To date, the exact causes and pathogenesis of AS still remain unknown. It is considered that the pathogenesis of AS is associated with genetic, infection, environment, immunity and other factors. Among them, the role of genetic factors in the pathogenesis of AS has been studied most deeply. However, over the past few years, the function of environmental predisposition and epigenetic modification in the pathogenesis of AS has received extensive attention. This paper summarizes the recent progress in the epigenetics of AS, including abnormal epigenetic modifications at AS-associated genomic loci, such as DNA methylation, histone modification, microRNA, and so on. In summary, the findings of this review attempt to explain the role of epigenetic modification in the occurrence and development of AS. Nevertheless, there are still unknown and complicated aspects worth exploring to deepen our understanding of the pathogenesis of AS.
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http://dx.doi.org/10.1111/1756-185X.14080DOI Listing
April 2021

Role of Forkhead box O3a transcription factor in autoimmune diseases.

Int Immunopharmacol 2021 Mar 4;92:107338. Epub 2021 Jan 4.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China; The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China. Electronic address:

Forkhead box O3a (FOXO3a) transcription factor, the most important member of Forkhead box O family, is closely related to cell proliferation, apoptosis, autophagy, oxidative stress and aging. The downregulation of FOXO3a has been verified to be associated with the poor prognosis, severer malignancy and chemoresistance in several human cancers. The activity of FOXO3a mainly regulated by phosphorylation of protein kinase B. FOXO3a plays a vital role in promoting the apoptosis of immune cells. FOXO3a could also modulate the activation, differentiation and function of T cells, regulate the proliferation and function of B cells, and mediate dendritic cells tolerance and immunity. FOXO3a accommodates the immune response through targeting nuclear factor kappa-B and FOXP3, as well as regulating the expression of cytokines. Besides, FOXO3a participates in intercellular interactions. FOXO3a inhibits dendritic cells from producing interleukin-6, which inhibits B-cell lymphoma-2 (BCL-2) and BCL-XL expression, thereby sparing resting T cells from apoptosis and increasing the survival of antigen-stimulated T cells. Recently, plentiful evidences further illustrated the significance of FOXO3a in the pathogenesis of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, ankylosing spondylitis, myositis, multiple sclerosis, and systemic sclerosis. In this review, we focused on the biological function of FOXO3a and related signaling pathways regarding immune system, and summarized the potential role of FOXO3a in the pathogenesis, progress and therapeutic potential of autoimmune diseases.
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http://dx.doi.org/10.1016/j.intimp.2020.107338DOI Listing
March 2021

PremPS: Predicting the impact of missense mutations on protein stability.

PLoS Comput Biol 2020 12 30;16(12):e1008543. Epub 2020 Dec 30.

Center for Systems Biology, Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China.

Computational methods that predict protein stability changes induced by missense mutations have made a lot of progress over the past decades. Most of the available methods however have very limited accuracy in predicting stabilizing mutations because existing experimental sets are dominated by mutations reducing protein stability. Moreover, few approaches could consistently perform well across different test cases. To address these issues, we developed a new computational method PremPS to more accurately evaluate the effects of missense mutations on protein stability. The PremPS method is composed of only ten evolutionary- and structure-based features and parameterized on a balanced dataset with an equal number of stabilizing and destabilizing mutations. A comprehensive comparison of the predictive performance of PremPS with other available methods on nine benchmark datasets confirms that our approach consistently outperforms other methods and shows considerable improvement in estimating the impacts of stabilizing mutations. A protein could have multiple structures available, and if another structure of the same protein is used, the predicted change in stability for structure-based methods might be different. Thus, we further estimated the impact of using different structures on prediction accuracy, and demonstrate that our method performs well across different types of structures except for low-resolution structures and models built based on templates with low sequence identity. PremPS can be used for finding functionally important variants, revealing the molecular mechanisms of functional influences and protein design. PremPS is freely available at https://lilab.jysw.suda.edu.cn/research/PremPS/, which allows to do large-scale mutational scanning and takes about four minutes to perform calculations for a single mutation per protein with ~ 300 residues and requires ~ 0.4 seconds for each additional mutation.
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http://dx.doi.org/10.1371/journal.pcbi.1008543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802934PMC
December 2020

Anti-CD74 antibodies in spondyloarthritis: A systematic review and meta-analysis.

Semin Arthritis Rheum 2021 Feb 10;51(1):7-14. Epub 2020 Dec 10.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China; The Key Laboratory of Major Autoimmune Diseases, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China. Electronic address:

Objective: There is still an unmet need for a simple and reliable biomarker for the diagnosis of spondyloarthritis. Recent studies indicated that anti-CD74 antibody could act as a biomarker for spondyloarthritis. Therefore, this review aims to evaluate the levels of anti-CD74 IgG and IgA antibodies in spondyloarthritis and the diagnostic value of anti-CD74 antibodies.

Methods: PubMed, Web of Science and Medline were comprehensively searched from inception to August 7th, 2019. The pooled standard mean difference (SMD) with 95% confidence interval (CI) was used to estimate the differences of the levels of anti-CD74 IgG and IgA antibodies between spondyloarthritis patients and controls. Sensitivity, specificity and summary receiver operating characteristics (SROC) curve were used for evaluating the diagnostic value of anti-CD74 antibodies. The use of fixed-effect or random-effects model depended on heterogeneity.

Results: Among 55 searched studies, 9 studies were finally included for analysis. Anti-CD74 IgG and IgA antibodies were both significantly increased in spondyloarthritis patients compared with matched controls (IgG: SMD = 0.88, 95% CI = 0.55 to 1.21; IgA: SMD = 0.98, 95% CI = 0.68 to 1.28). The pooled sensitivity, specificity and area under the SROC curve of anti-CD74 IgG antibodies were 0.61, 0.90 and 0.8881, while these indicators of anti-CD74 IgA antibodies were 0.59, 0.95 and 0.8671, respectively.

Conclusion: Anti-CD74 IgG and IgA antibodies were significantly increased in spondyloarthritis patients and suggest a high diagnostic specificity of spondyloarthritis. Anti-CD74 antibody could potentially be a biomarker for the diagnosis of spondyloarthritis, but many open questions remain.
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http://dx.doi.org/10.1016/j.semarthrit.2020.12.002DOI Listing
February 2021

Analysis and Synthesis of Traffic Scenes from Road Image Sequences.

Sensors (Basel) 2020 Dec 4;20(23). Epub 2020 Dec 4.

School of Software Engineering, Xi'an Jiaotong University, Xi'an 710049, China.

Traffic scene construction and simulation has been a hot topic in the community of intelligent transportation systems. In this paper, we propose a novel framework for the analysis and synthesis of traffic elements from road image sequences. The proposed framework is composed of three stages: traffic elements detection, road scene inpainting, and road scene reconstruction. First, a new bidirectional single shot multi-box detector (BiSSD) method is designed with a global context attention mechanism for traffic elements detection. After the detection of traffic elements, an unsupervised CycleGAN is applied to inpaint the occlusion regions with optical flow. The high-quality inpainting images are then obtained by the proposed image inpainting algorithm. Finally, a traffic scene simulation method is developed by integrating the foreground and background elements of traffic scenes. The extensive experiments and comparisons demonstrate the effectiveness of the proposed framework.
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http://dx.doi.org/10.3390/s20236939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730193PMC
December 2020

Hospital emergency management plan during 2019 novel coronavirus (SARS-CoV-2) pandemic in non-epidemic areas.

Int J Clin Exp Pathol 2020 1;13(11):2753-2757. Epub 2020 Nov 1.

Department of Emergency, Shanghai Changhai Hospital Shanghai 200433, China.

The outbreak of the acute respiratory syndrome coronavirus 2 has spread around the world and poses a challenge to clinical frontline nursing staff. In the early stage of the epidemic, our hospital responded promptly and added pertinent prevention measures on the basis of the existing fever clinic (FC) to ensure zero infection of medical staff and patients. The experience of the fever screening site establishment, epidemiologic investigation procedure amelioration, and integrated fever management will be introduced in the communication.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716120PMC
November 2020

Rapid desalting during electrospray ionization mass spectrometry for investigating protein-ligand interactions in the presence of concentrated salts.

Anal Chim Acta 2021 Jan 22;1141:120-126. Epub 2020 Oct 22.

Hefei National Laboratory for Physical Sciences at the Microscale, School of Chemistry and Materials Science, University of Science and Technology of China, 230026, Hefei, China; National Synchrotron Radiation Laboratory, University of Science and Technology of China, Hefei, Anhui, 230029, PR China. Electronic address:

Investigation of protein-ligand interactions in physiological conditions is crucial for better understanding of biochemistry because the binding stoichiometry and conformations of complexes in biological processes, such as various types of regulation and transportation, could reveal key pathways in organisms. Nanoelectrospray ionization mass spectrometry is widely used in studies of biological processes and systems biology. However, non-volatile salts in biological fluid may adversely interfere with nanoelectrospray ionization mass spectrometry. In this study, the previously developed method of induced nanoelectrospray ionization was used to facilitate in situ desalting of protein in solutions with high concentrations of non-volatile salts, and direct investigation of protein-ligand interactions for the first time. In situ desalting occurred at the tip of emitters within a short period lasting for a few to tens of milliseconds, enabling the maintenance of nativelike conditions compatible with mass spectrometry measurements. Induced nanoelectrospray ionization was driven by pulsed potential and exhibited microelectrophoresis effect in each spray cycle, which is not observed in conventional nanoelectrospray ionization because the continuous spray procedure is driven by direct current. Microelectrophoresis caused desalting through micron-sized spray emitters (1-20 μm), as confirmed experimentally with proteins in 100 mM NaCl solution. The method developed in this study has been further illustrated as a potential option for fast and direct identification of protein-ligand (small molecules or metal ions) interactions in complex samples. The results of this study demonstrate that the newly developed method may represent a reliable approach for investigations of proteins and protein complexes in biological samples.
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http://dx.doi.org/10.1016/j.aca.2020.10.036DOI Listing
January 2021

Bioinspired construction of light-harvesting antenna via hierarchically co-assembling approach.

J Colloid Interface Sci 2021 Apr 7;587:550-560. Epub 2020 Nov 7.

Center for Bioengineering and Biotechnology, China University of Petroleum, Qingdao 266580, China. Electronic address:

Biomimetic construction of artificial photosystem capable of converting light energy to chemical energy is a promising strategy in solving the increasing serious energy and environmental problems. Herein, we present a new strategy to construct light-harvesting antenna via hierarchical co-assembly of short-peptide and porphyrin and subsequent self-metallization process. The hierarchically organized antenna exhibits both excellent photocatalytic performance and remarkable sustainability under strong light irradiation (35000 lx) and extraordinary sensitivity to weak light (700 lx). In such cases, light energy can be converted into chemical energy and stored in the energy-storage molecules (nicotinamide adenine dinucleotide, NADH) even under weak light irradiation. This provides a promising step towards an artificial photosystem that can utilize weak light. Moreover, the structures and properties of the antenna are dependent on the competition of short-peptide self-assembling and co-assembling with porphyrin molecules and can be regulated by their molar ratio. This provides new insights into the design and construction of light-harvesting antennas with integrated functionality via precise control of pigments aggregation and coupling of different functional units.
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http://dx.doi.org/10.1016/j.jcis.2020.11.012DOI Listing
April 2021

Involvement of FATP2-mediated tubular lipid metabolic reprogramming in renal fibrogenesis.

Cell Death Dis 2020 11 20;11(11):994. Epub 2020 Nov 20.

Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Following a chronic insult, renal tubular epithelial cells (TECs) contribute to the development of kidney fibrosis through dysregulated lipid metabolism that lead to lipid accumulation and lipotoxicity. Intracellular lipid metabolism is tightly controlled by fatty acids (FAs) uptake, oxidation, lipogenesis, and lipolysis. Although it is widely accepted that impaired fatty acids oxidation (FAO) play a crucial role in renal fibrosis progression, other lipid metabolic pathways, especially FAs uptake, has not been investigated in fibrotic kidney. In this study, we aim to explore the potential mechanically role of FAs transporter in the pathogenesis of renal fibrosis. In the present study, the unbiased gene expression studies showed that fatty acid transporter 2 (FATP2) was one of the predominant expressed FAs transport in TECs and its expression was tightly associated with the decline of renal function. Treatment of unilateral ureteral obstruction (UUO) kidneys and TGF-β induced TECs with FATP2 inhibitor (FATP2i) lipofermata restored the FAO activities and alleviated fibrotic responses both in vivo and in vitro. Moreover, the expression of profibrotic cytokines including TGF-β, connective tissue growth factor (CTGF), fibroblast growth factor (FGF), and platelet-derived growth factor subunit B (PDGFB) were all decreased in FATP2i-treated UUO kidneys. Mechanically, FATP2i can effectively attenuate cell apoptosis and endoplasmic reticulum (ER) stress induced by TGF-β treatment in cultured TECs. Taking together, these findings reveal that FATP2 elicits a profibrotic response to renal interstitial fibrosis by inducing lipid metabolic reprogramming including abnormal FAs uptake and defective FAO in TECs.
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http://dx.doi.org/10.1038/s41419-020-03199-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7679409PMC
November 2020

CYLD Promotes Apoptosis of Nasopharyngeal Carcinoma Cells by Regulating NDRG1.

Cancer Manag Res 2020 27;12:10639-10649. Epub 2020 Oct 27.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.

Purpose: Nasopharyngeal carcinoma (NPC) is among the most common malignancies derived from the epithelium of the nasopharynx. To date, the regulatory networks involved in NPC have not been fully identified. Previous studies revealed multiple loss-of-function mutations in NPC and specifically in cylindromatosis lysine 63 deubiquitinase (); however, the exact role of CYLD in NPC progression and its potential mechanism remains unclear.

Methods: We performed immunohistochemical (IHC) staining and real-time quantitative polymerase chain reaction (qPCR) to measure expression in NPC tissues, and Western blot was conducted to determine CYLD levels in NPC cell lines. Cell proliferation was detected by CCK8 assay and colony formation analysis, and apoptosis was determined by Annexin V/propidium iodide staining. Potential targets of CYLD were verified by co-immunoprecipitation and mass spectrometry. Xenograft assay was conducted to confirm the role of in vivo.

Results: We found that CYLD levels were significantly decreased in both NPC tissues and cell lines, and that overexpression inhibited NPC cell proliferation and promoted apoptosis. Additionally, we revealed that CYLD bound and upregulated N-Myc downstream regulated 1 (NDRG1), and that silencing abolished the tumor-suppressor effect of CYLD on NPC cells. Furthermore, CYLD suppressed tumor growth in xenograft mice models.

Conclusion: These results suggest CYLD as a tumor suppressor, potential biomarker for diagnosing NPC, and therapeutic target.
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http://dx.doi.org/10.2147/CMAR.S268216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604974PMC
October 2020

Effect of Composition on the Crystallization, Water Absorption, and Biodegradation of Poly(-caprolactam-caprolactone) Copolymers.

Polymers (Basel) 2020 Oct 27;12(11). Epub 2020 Oct 27.

State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomaterials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.

Poly(ester amide)s have aroused extensive research interest due to the combination of the degradability of polyester and the higher mechanical properties of polyamide. In this work, a series of poly(-caprolactam-caprolactone) (P(CLACLO)) copolymers with different compositions were synthesized by anionic copolymerization. The structure, crystallization behavior, water absorption, and biodegradation behavior of these copolymers were investigated by means of nuclear magnetic resonance (NMR), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), wide-angle X-ray diffraction (WAXD), and polarized optical micrographs (POM). The results indicated that the composition of P(CLACLO) copolymers can be adjusted by the molar feed ratio. The PCL blocks decreased the crystallization rate of PA6 blocks but had little effect on the melting behavior of PA6, while the crystallized PA6 acted as a heterogeneous nucleating agent and greatly improved the crystallization rate of PCL. Moreover, the introduction of PCL blocks greatly reduced the water absorption of P(CLACLO) copolymers and endow them a certain degree of degradability.
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http://dx.doi.org/10.3390/polym12112488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692460PMC
October 2020

Small extracellular vesicles containing miR-30a-3p attenuate the migration and invasion of hepatocellular carcinoma by targeting SNAP23 gene.

Oncogene 2021 01 27;40(2):233-245. Epub 2020 Oct 27.

Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, PR China.

Cancer cells under hypoxic, endoplasmic reticulum, and reactive oxygen species stress secrete copious amounts of small extracellular vesicles (sEVs) to promote tumor metastasis. The effects of blocking stress-induced sEV release on tumor metastasis remain unknown. We found that miR-30a-3p was selectively sorted into sEVs by hepatocellular carcinoma (HCC) cells under the influence of multiple stressors. miR-30a-3p removal from cancer cells through sEVs promoted HCC cell migration and invasion, whereas exogenous overexpression of miR-30a-3p could inhibit migration, invasion, and sEV release by directly targeting SNAP23. HCC cells efficiently absorbed hepatic stellate cell (HSC) sEVs, providing an advantage in the treatment of HCC using HSC sEVs. Treatment with HSC sEVs rich in miR-30a-3p cargo effectively attenuated HCC migration, invasion, and metastasis. Overall, sEVs containing miR-30a-3p decreased sEV secretion as well as the migration, invasion, and metastasis of HCC by directly targeting SNAP23, thereby providing an effective strategy to attenuate metastasis of HCC.
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http://dx.doi.org/10.1038/s41388-020-01521-7DOI Listing
January 2021

Fanconi syndrome induced by adefovir dipivoxil: a case report and clinical review.

J Int Med Res 2020 Oct;48(10):300060520954713

Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

More than 150 cases of Fanconi syndrome (FS) or hypophosphatemia osteomalacia induced by low-dose adefovir dipivoxil (ADV) have been reported since 2002, when ADV was introduced for the long-term treatment of hepatitis B virus (HBV) infection. Because the life expectancy of HBV-infected individuals has increased, the adverse effects of long-term treatment with antiviral therapies are increasingly observed, and nephrotoxicity is one of the most severe adverse effects of ADV. Therefore, the number of cases may be far higher than reported. Moreover, ADV-induced FS is often misdiagnosed or diagnosed long after it first develops. ADV-induced FS may seriously decrease patient quality of life and lead to bone fractures and even disability. Although progress has been made in the identification of biomarkers and treatments, few systematic clinical guidelines or clinical reviews for FS induced by ADV have been reported. In this study, we highlighted the recent progress toward understanding of FS induced by ADV, described a clinical case, and summarized the primary characteristics and laboratory findings of this disease.
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http://dx.doi.org/10.1177/0300060520954713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607140PMC
October 2020

Direct monitoring of protease activity using an integrated microchip coated with multilayered fluorogenic nanofilms.

Analyst 2021 Jan;145(24):8050-8058

Department of Critical Care Medicine, People's Hospital of Zhengzhou University (Henan Provincial People's Hospital), Zhengzhou, 450003, China.

Proteases play an essential role in the four sequential but overlapping phases of wound healing: hemostasis, inflammation, proliferation, and remodeling. In chronic wounds, excessive protease secretion damages the newly formed extracellular matrix, thereby delaying or preventing the normal healing process. Peptide-based fluorogenic sensors provide a visual platform to sense and analyze protease activity through changes in the fluorescence intensity. Here, we have developed an integrated microfluidic chip coated with multilayered fluorogenic nanofilms that can directly monitor protease activity. Fluorogenic protease sensors were chemically conjugated to polymer films coated on the surface of parallel microfluidic channels. Capillary flow layer-by-layer (CF-LbL) was used for film assembly and combined with subsequent sensor modification to establish a novel platform sensing technology. The benefits of our platform include facile fabrication and processing, controllable film nanostructure, small sample volume, and high sensitivity. We observed increased fluorescence of the LbL nanofilms when they were exposed to model recombinant proteases, confirming their responsiveness to protease activity. Increases in the nanofilms' fluorescence intensity were also observed during incubation with liquid extracted from murine infected wounds, demonstrating the potential of these films to provide real-time, in situ information about protease activity levels.
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http://dx.doi.org/10.1039/d0an01294gDOI Listing
January 2021

Enzymatic Synthesis of a Polyol Ester from Levulinic Acid and Trimethylolpropane and Its Tribological Behavior as Potential Biolubricant Basestock.

Polymers (Basel) 2020 Oct 1;12(10). Epub 2020 Oct 1.

School of Light Industry Science and Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 300175, China.

In this study, a polyol ester from levulinic acid (LA) and trimethylolpropane (TMP) was synthesized by enzymatic catalysis in a solvent-free system. The total conversion of TMP reached up to 84% on average after lipase recycling for five times. The produced ester showed excellent lubrication properties, such as high viscosities at 40 °C (86.53 mm/s) and 100 °C (8.91 mm/s), a good viscosity index (49), a low pour point (-27 °C), and a high flash point (223 °C). The frictional wear behavior was evaluated on a four-ball test machine (FTM) by adding the ester into a reference mineral oil. The blend with 10% ester showed a smaller wear scar diameter (WSD) (0.62 mm) when compared with that of pure mineral oil (0.78 mm). The results demonstrated that the obtained ester has huge potential as biolubricant basestock.
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http://dx.doi.org/10.3390/polym12102256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600818PMC
October 2020

Reinforcement Learning Based Fast Self-Recalibrating Decoder for Intracortical Brain-Machine Interface.

Sensors (Basel) 2020 Sep 27;20(19). Epub 2020 Sep 27.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China.

Background: For the nonstationarity of neural recordings in intracortical brain-machine interfaces, daily retraining in a supervised manner is always required to maintain the performance of the decoder. This problem can be improved by using a reinforcement learning (RL) based self-recalibrating decoder. However, quickly exploring new knowledge while maintaining a good performance remains a challenge in RL-based decoders.

Methods: To solve this problem, we proposed an attention-gated RL-based algorithm combining transfer learning, mini-batch, and weight updating schemes to accelerate the weight updating and avoid over-fitting. The proposed algorithm was tested on intracortical neural data recorded from two monkeys to decode their reaching positions and grasping gestures.

Results: The decoding results showed that our proposed algorithm achieved an approximate 20% increase in classification accuracy compared to that obtained by the non-retrained classifier and even achieved better classification accuracy than the daily retraining classifier. Moreover, compared with a conventional RL method, our algorithm improved the accuracy by approximately 10% and the online weight updating speed by approximately 70 times.

Conclusions: This paper proposed a self-recalibrating decoder which achieved a good and robust decoding performance with fast weight updating and might facilitate its application in wearable device and clinical practice.
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http://dx.doi.org/10.3390/s20195528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582276PMC
September 2020

PEDF promotes the repair of bone marrow endothelial cell injury and accelerates hematopoietic reconstruction after bone marrow transplantation.

J Biomed Sci 2020 Sep 1;27(1):91. Epub 2020 Sep 1.

Blood Diseases Institute, Xuzhou Medical University, Xuzhou, China.

Background: Preconditioning before bone marrow transplantation such as irradiation causes vascular endothelial cells damage and promoting the repair of damaged endothelial cells is beneficial for hematopoietic reconstitution. Pigment epithelium-derived factor (PEDF) regulates vascular permeability. However, PEDF's role in the repair of damaged endothelial cells during preconditioning remains unclear. The purpose of our study is to investigate PEDF's effect on preconditioning-induced damage of endothelial cells and hematopoietic reconstitution.

Methods: Damaged endothelial cells induced by irradiation was co-cultured with hematopoietic stem cells (HSC) in the absence or presence of PEDF followed by analysis of HSC number, cell cycle, colony formation and differentiation. In addition, PEDF was injected into mice model of bone marrow transplantation followed by analysis of bone marrow injury, HSC number and peripheral hematopoietic reconstitution as well as the secretion of cytokines (SCF, TGF-β, IL-6 and TNF-α). Comparisons between two groups were performed by student t-test and multiple groups by one-way or two-way ANOVA.

Results: Damaged endothelial cells reduced HSC expansion and colony formation, induced HSC cell cycle arrest and apoptosis and promoted HSC differentiation as well as decreased PEDF expression. Addition of PEDF increased CD144 expression in damaged endothelial cells and inhibited the increase of endothelial permeability, which were abolished after addition of PEDF receptor inhibitor Atglistatin. Additionally, PEDF ameliorated the inhibitory effect of damaged endothelial cells on HSC expansion in vitro. Finally, PEDF accelerated hematopoietic reconstitution after bone marrow transplantation in mice and promoted the secretion of SCF, TGF-β and IL-6.

Conclusions: PEDF inhibits the increased endothelial permeability induced by irradiation and reverse the inhibitory effect of injured endothelial cells on hematopoietic stem cells and promote hematopoietic reconstruction.
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http://dx.doi.org/10.1186/s12929-020-00685-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466818PMC
September 2020

Decreased prealbumin level is associated with increased risk for mortality in elderly hospitalized patients with COVID-19.

Nutrition 2020 10 3;78:110930. Epub 2020 Jul 3.

Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:

Objectives: High-risk patients ≥65 y of age with coronavirus disease 2019 (COVID-19) tended to have lower serum prealbumin concentrations. The aim of this study was to investigate the association of prealbumin at baseline on COVID-19-related mortality in elderly patients (≥65 y of age).

Methods: We non-selectively and consecutively collected participants from Tongji Hospital in Wuhan from January 17 to February 17, 2020. Univariate and multivariate logistic regression models were employed to evaluate the correlation between prealbumin and in-hospital outcomes (in-hospital mortality, admission to the intensive care unit [ICU], and mechanical ventilation) in elderly patients with COVID-19. Linear trend was performed by entering the median value of each category of prealbumin tertile as a continuous variable and was visually confirmed by using generalized additive models. Interaction and stratified analyses were conducted as well.

Results: We included 446 elderly patients with COVID-19 in the final analyses. In-hospital mortality was 14.79%. Of the 446 patients, 15.47% were admitted to the ICU and 21.3% required mechanical ventilation. Compared with patients in the highest tertile, the prealbumin of patients in the lowest tertile had a 19.09-fold higher risk for death [odds ratio (OR), 20.09; 95% confidence interval (CI), 3.62-111.64; P = 0.0006], 25.39-fold higher risk for ICU admission (OR, 26.39; 95% CI, 4.04-172.39; P = 0.0006), and 1.8-fold higher risk for mechanical ventilation (OR, 2.8; 95% CI, 1.15-6.78; P = 0.0227) after adjustment for potential confounders. There was a linear trend correlation between serum prealbumin concentration and risk for in-hospital mortality, ICU admission, and mechanical ventilation in elderly patients with COVID-19 infection.

Conclusion: Prealbumin is an independent risk factor of in-hospital mortality for elderly patients with COVID-19. Assessment of prealbumin may help identify high-risk individuals ≥65 y of age with COVID-19.
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http://dx.doi.org/10.1016/j.nut.2020.110930DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7333599PMC
October 2020

Acute Kidney Injury Is Associated With In-hospital Mortality in Older Patients With COVID-19.

J Gerontol A Biol Sci Med Sci 2021 02;76(3):456-462

Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: The epidemic of COVID-19 presents a special threat to older adults. However, information on kidney damage in older patients with COVID-19 is limited. Acute kidney injury (AKI) is common in hospitalized adults and associated with poor prognosis. We sought to explore the association between AKI and mortality in older patients with COVID-19.

Methods: We conducted a retrospective, observational cohort study in a large tertiary care university hospital in Wuhan, China. All consecutive inpatients older than 65 years with COVID-19 were enrolled in this cohort. Demographic data, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between patients with AKI and without AKI. The association between AKI and mortality was analyzed.

Results: Of 1764 in-hospital patients, 882 older adult cases were included in this cohort. The median age was 71 years (interquartile range: 68-77), 440 (49.9%) were men. The most presented comorbidity was cardiovascular diseases (58.2%), followed by diabetes (31.4%). Of 882 older patients, 115 (13%) developed AKI and 128 (14.5%) died. Patients with AKI had higher mortality than those without AKI (68 [59.1%] vs 60 [7.8%]; p < .001). Multivariable Cox regression analysis showed that increasing odds of in-hospital mortality are associated with higher interleukin-6 on admission, myocardial injury, and AKI.

Conclusions: Acute kidney injury is not an uncommon complication in older patients with COVID-19 but is associated with a high risk of death. Physicians should be aware of the risk of AKI in older patients with COVID-19.
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http://dx.doi.org/10.1093/gerona/glaa181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454401PMC
February 2021

PremPRI: Predicting the Effects of Missense Mutations on Protein-RNA Interactions.

Int J Mol Sci 2020 Aug 3;21(15). Epub 2020 Aug 3.

Center for Systems Biology, Department of Bioinformatics, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China.

Protein-RNA interactions are crucial for many cellular processes, such as protein synthesis and regulation of gene expression. Missense mutations that alter protein-RNA interaction may contribute to the pathogenesis of many diseases. Here, we introduce a new computational method PremPRI, which predicts the effects of single mutations occurring in RNA binding proteins on the protein-RNA interactions by calculating the binding affinity changes quantitatively. The multiple linear regression scoring function of PremPRI is composed of three sequence- and eight structure-based features, and is parameterized on 248 mutations from 50 protein-RNA complexes. Our model shows a good agreement between calculated and experimental values of binding affinity changes with a Pearson correlation coefficient of 0.72 and the corresponding root-mean-square error of 0.76 kcal·mol, outperforming three other available methods. PremPRI can be used for finding functionally important variants, understanding the molecular mechanisms, and designing new protein-RNA interaction inhibitors.
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http://dx.doi.org/10.3390/ijms21155560DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432928PMC
August 2020

Interleukin-17 Gene Polymorphism (Rs2275913 G/A, Rs763780 C/T) in Rheumatoid arthritis:Meta-analysis Based on Ethnicity.

Immunol Invest 2020 Jul 1:1-15. Epub 2020 Jul 1.

Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University , Hefei, Anhui, China.

Introduction: The association between interleukin()-17A and F gene polymorphism with rheumatoid arthritis (RA) were inconsistent among previous studies. This meta-analysis aimed to determine the association between A and F gene polymorphism with RA.

Methods: We searched Medline up to February 2020. Meta-analyses were performed for the comparisons of allele and multiple genetic models, including dominant, recessive, heterozygous, and homozygous models using fixed or random effects models. Odds ratios (OR) with 95% confidence intervals (95%CI) were utilized to assess the potential relationship.

Results: A total of 2315 confirmed cases and 2342 controls were included from eligible 10 case-controls studies. Meta analysis suggested that rs2275913 G allele increased the risk of RA in Caucasians (G vs A: OR = 1.14, 95% CI = 1.00-1.29, = .044), but not in Mongolians ( > .05). Pooled analysis suggested that a significant associations between rs763780 C allele with RA susceptibility (C vs T: OR = 1.83, 95% CI = 1.13-2.97, = .014). Subgroup analysis by ethnicity indicated that rs763780 C allele was closely related to RA risk in two races ( < .001). TSA plot revealed that the present study sufficient to draw a conclusion.

Conclusions: This meta-analysis demonstrates A and F genes play a significant role in RA, but its role in Mongolian populations needs further exploration.
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http://dx.doi.org/10.1080/08820139.2020.1786397DOI Listing
July 2020

Identification of bilobetin metabolites, in vivo and in vitro, based on an efficient ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry strategy.

J Sep Sci 2020 Sep 8;43(17):3408-3420. Epub 2020 Jul 8.

Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, 050017, P. R. China.

Bilobetin, a natural compound extracted from Ginkgo biloba, has various pharmacological activities such as antioxidation, anticancer, antibacterial, antifungal, anti-inflammatory, antiviral, and promoting osteoblast differentiation. However, few studies have been conducted and there are no reports on its metabolites owing to its low content in nature. In addition, it has been reported to have potential liver and kidney toxicity. Therefore, this study aimed to identify the metabolites of bilobetin in vitro and in vivo. Bilobetin was incubated with liver microsomes to determine metabolites in vitro, and faeces and urine were collected after oral administration to rats to determine metabolites in vivo. After the samples were processed, they were measured using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. As a result, a total of 21 and 9 metabolites were detected in vivo and in vitro, respectively. Demethylation, demethylation and loss of water, demethylation and hydrogenation, demethylation and glycine conjugation, oxidation, methylation, oxidation and methylation, and hydrogenation were the main metabolic pathways. This study is the first to identify the metabolites of bilobetin and provides a theoretical foundation for the safe use of bilobetin in clinical application and the development of new drugs.
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http://dx.doi.org/10.1002/jssc.202000313DOI Listing
September 2020

Advances in the use of chloroquine and hydroxychloroquine for the treatment of COVID-19.

Postgrad Med 2020 Sep 21;132(7):604-613. Epub 2020 Jun 21.

Department of Infectious Diseases, First Affiliated Hospital of Xi'an Jiaotong University , Xi'an, China.

Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading worldwide. Antiviral therapy is the most important treatment for COVID-19. Among the drugs under investigation, anti-malarials, chloroquine (CQ) and hydroxychloroquine (HCQ), are being repurposed as treatment for COVID-19. CQ/HCQ were shown to prevent receptor recognition by coronaviruses, inhibit endosome acidification, which interferes with membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of studies revealed inhibitory effects of CQ/HCQ on various coronaviruses, including SARS-CoV-2 although conflicting results exist. Several clinical studies showed that CQ/HCQ alone or in combination with a macrolide may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay disease progression, with less serious adverse effects. However, recent studies indicated that the use of CQ/HCQ, alone or in combination with a macrolide, did not show any favorable effect on patients with COVID-19. Adverse effects, including prolonged QT interval after taking CQ/HCQ, may develop in COVID-19 patients. Therefore, current data are not sufficient enough to support the use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken about the application of CQ/HCQ in COVID-19 before conclusive findings are obtained by well-designed, multi-center, randomized, controlled studies.
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http://dx.doi.org/10.1080/00325481.2020.1778982DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441788PMC
September 2020