Publications by authors named "Yiting Wang"

233 Publications

Association between Serum Uric Acid and Renal Outcome in Patients with Biopsy-confirmed Diabetic Nephropathy.

Endocr Connect 2021 Sep 1. Epub 2021 Sep 1.

F Liu, Division of Nephrology, Sichuan University West China Hospital, Chengdu, China.

Objective: To investigate the relationship between serum uric acid (SUA) level and renal outcome in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy(DN).

Methods: A total of 393 Chinese patients with T2DM and biopsy-proven DN and followed at least one year were enrolled in this study. Patients were stratified by the quartiles of baseline level of SUA: Q1 group286.02± 46.66 μmol/L (n=98); Q2 group: 358.23±14.03μmol/L (n=99); Q3 group: 405.50±14.59μmol/L (n=98) and Q4 group: 499.14±56.97μmol/L (n=98).Renal outcome was defined by progression to end stage renal disease (ESRD). Kaplan-Meier survival analysis and Cox proportional hazards model were used to analyze the association between SUA quartiles and the renal outcomes.

Results: During the median 3-year follow-up period, there were 173 ESRD outcome events (44.02%) during follow-up. No significant difference among SUA level the risk of progression of DN (P=0.747) was shown in the Kaplan-Meier survival analysis. In multivariable-adjusted model, HRs for developing ESRD were 1.364(0.621-2.992; p=0.439), 1.518(0.768-3.002; p=0.230) and 1.411(0.706-2.821; p=0.330) for the Q2, Q3 and Q4, respectively, in comparison with the Q1 (P=0.652).

Conclusions: No significant association between SUA level and renal outcome of ESRD in Chinese patients with T2DM and DN was found in our study. Besides, the role of uric acid-lowering therapy in delaying DN progression and improve ESRD outcome had not yet been proven. Further study was needed to clarify the renal benefit of the uric acid-lowering therapy in the treatment of DN.
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http://dx.doi.org/10.1530/EC-21-0307DOI Listing
September 2021

Radiosensitivity-specific proteomic and signaling pathway network of non-small cell lung cancer.

Int J Radiat Oncol Biol Phys 2021 Sep 7. Epub 2021 Sep 7.

Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, China. Electronic address:

Purpose: An unmet clinical need in non-small cell lung cancer (NSCLC) management is the accurate prediction of radiation response in patients receiving radical radiotherapy. We explored the intrinsic radiosensitivity of NSCLC from the proteomic profiles of NSCLC cell lines and paraffin-embedded human samples.

Experimental Design: To uncover radiosensitivity-specific proteomic and signaling pathways, we performed quantitative proteomics by data-independent acquisition mass spectrometry assay on 29 human NSCLC cell lines and 13 paraffin-embedded human NSCLC samples. Closely interacting radioresistant proteins were validated by western blotting, immunofluorescence, real-time quantitative PCR in NSCLC cell lines, and immunohistochemistry in paraffin-embedded human samples. The functions of three key hub proteins were validated by lentivirus transfection, clonogenic survival assay, and flow cytometry.

Results: The proteomic profiling of NSCLC showed that the intrinsic radiosensitivity of NSCLC is mainly modulated by signaling pathways of proteoglycans in cancer, focal adhesion, and regulation of the actin cytoskeleton. We identified 71 differentially expressed proteins, and eight closely interacting proteins were validated as radioresistant proteins of NSCLC. Moreover, we also validated the functionality of integrin-linked protein kinase, p21-activated kinase 1, and Ras GTPase-activating-like protein IQGAP1 in the radiation response of NSCLC cell lines. Finally, with the NSCLC radiosensitivity-specific proteins, we delineated the atlas network of NSCLC radiosensitivity-related signaling pathways.

Conclusion: Radiosensitivity-specific proteins have the potential to guide individualized radiotherapy in clinical practice by predicting the radiation response of patients with NSCLC. Moreover, the NSCLC radiosensitivity-related signaling pathway atlas could guide further exploration of the underlying mechanism.
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http://dx.doi.org/10.1016/j.ijrobp.2021.08.041DOI Listing
September 2021

The Amino Acid-mTORC1 Pathway Mediates APEC TW-XM-Induced Inflammation in bEnd.3 Cells.

Int J Mol Sci 2021 Aug 26;22(17). Epub 2021 Aug 26.

College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.

The blood-brain barrier (BBB) is key to establishing and maintaining homeostasis in the central nervous system (CNS); meningitis bacterial infection can disrupt the integrity of BBB by inducing an inflammatory response. The changes in the cerebral uptake of amino acids may contribute to inflammatory response during infection and were accompanied by high expression of amino acid transporters leading to increased amino acid uptake. However, it is unclear whether amino acid uptake is changed and how to affect inflammatory responses in mouse brain microvascular endothelial (bEnd.3) cells in response to Avian Pathogenic TW-XM (APEC XM) infection. Here, we firstly found that APEC XM infection could induce serine (Ser) and glutamate (Glu) transport from extracellular into intracellular in bEnd.3 cells. Meanwhile, we also shown that the expression sodium-dependent neutral amino acid transporter 2 (SNAT2) for Ser and excitatory amino acid transporter 4 (EAAT4) for Glu was also significantly elevated during infection. Then, in amino acid deficiency or supplementation medium, we found that Ser or Glu transport were involving in increasing SNAT2 or EAAT4 expression, mTORC1 (mechanistic target of rapamycin complex 1) activation and inflammation, respectively. Of note, Ser or Glu transport were inhibited after SNAT2 silencing or EAAT4 silencing, resulting in inhibition of mTORC1 pathway activation, and inflammation compared with the APEC XM infection group. Moreover, pEGFP-SNAT2 overexpression and pEGFP-EAAT4 overexpression in bEnd.3 cells all could promote amino acid uptake, activation of the mTORC1 pathway and inflammation during infection. We further found mTORC1 silencing could inhibit inflammation, the expression of SNAT2 and EAAT4, and amino acid uptake. Taken together, our results demonstrated that APEC TW-XM infection can induce Ser or Glu uptake depending on amino acid transporters transportation, and then activate amino acid-mTORC1 pathway to induce inflammation in bEnd.3 cells.
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http://dx.doi.org/10.3390/ijms22179245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8431488PMC
August 2021

Sociodemographic Inequalities in Health Insurance Ownership among Women in Selected Francophone Countries in Sub-Saharan Africa.

Biomed Res Int 2021 17;2021:6516202. Epub 2021 Aug 17.

School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

In sub-Saharan Africa, improving equitable access to healthcare remains a major challenge for public health systems. Health policymakers encourage the adoption of health insurance schemes to promote universal healthcare. Nonetheless, progress towards this goal remains suboptimal due to inequalities health insurance ownership especially among women. In this study, we aimed to explore the sociodemographic factors contributing to health insurance ownership among women in selected francophone countries in sub-Saharan Africa. . This study is based on cross-sectional data obtained from Demographic and Health Surveys on five countries including Benin ( = 13,407), Madagascar ( = 12,448), Mali ( = 10,326), Niger ( = 12,558), and Togo ( = 6,979). The explanatory factors included participant age, marital status, type of residency, education, household wealth quantile, employment stats, and access to electronic media. Associations between health insurance ownership and the explanatory factors were analyzed using multivariate regression analysis, and effect sizes were reported in terms in average marginal effects (AMEs). . The highest percentage of insurance ownership was observed for Togo (3.31%), followed by Madagascar (2.23%) and Mali (2.2%). After stratifying by place of residency, the percentages were found to be significantly lower in the rural areas for all countries, with the most noticeable difference observed for Niger (7.73% in urban vs. 0.54% in rural women). Higher levels of education and wealth quantile were positively associated with insurance ownership in all five countries. In the pooled sample, women in the higher education category had higher likelihood of having an insurance: Benin (AME = 1.18; 95% CI = 1.10, 1.27), Madagascar (AME = 1.10; 95% CI = 1.05, 1.15), Mali (AME = 1.14; 95% CI = 1.04, 1.24), Niger (AME = 1.13; 95% CI = 1.07, 1.21), and Togo (AME = 1.17; 95% CI = 1.09, 1.26). Regarding wealth status, women from the households in the highest wealth quantile had 4% higher likelihood of having insurance in Benin and Mali and 6% higher likelihood in Madagascar and Togo. . Percentage of women who reported having health insurance was noticeably low in all five countries. As indicated by the multivariate analyses, the actual situation is likely to be even worse due to significant socioeconomic inequalities in the distribution of women having an insurance plan. Increasing women's access to healthcare is an urgent priority for population health promotion in these countries, and therefore, addressing the entrenched sociodemographic disparities should be given urgent policy attention in an effort to strengthen universal healthcare-related goals.
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http://dx.doi.org/10.1155/2021/6516202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387175PMC
August 2021

Circular RNA circBCBM1 promotes breast cancer brain metastasis by modulating miR-125a/BRD4 axis.

Int J Biol Sci 2021 22;17(12):3104-3117. Epub 2021 Jul 22.

Department of Clinical Laboratory, Liaocheng People's Hospital, Medical College of Liaocheng University, Liaocheng, P.R. China.

Circular RNAs (circRNAs) play critical roles in tumorigenesis and the progression of various cancers. We previously identified a novel upregulated circRNA, circBCBM1 (hsa_circ_0001944), in the context of breast cancer brain metastasis. However, the potential biological function and molecular mechanism of circBCBM1 in breast cancer brain metastasis remain largely unknown. In this study, we confirmed that circBCBM1 was a stable and cytoplasmic circRNA. Functionally, circBCBM1 promoted the proliferation and migration of 231-BR cells and growth and brain metastasis . Mechanistically, circBCBM1 acted as an endogenous miR-125a sponge to inhibit miR-125a activity, resulting in the upregulation of BRD4 (bromodomain containing 4) and subsequent upregulation of MMP9 (matrix metallopeptidase 9) through Sonic hedgehog (SHH) signaling pathway. Importantly, circBCBM1 was markedly upregulated in the breast cancer brain metastasis cells and clinical tissue and plasma samples; besides, circBCBM1 overexpression in primary cancerous tissues was associated with shorter brain metastasis-free survival (BMFS) of breast cancer patients. These findings indicate that circBCBM1 is involved in breast cancer brain metastasis via circBCBM1/miR-125a/BRD4 axis. CircBCBM1 may serve as a novel diagnostic and prognostic biomarker and potential therapeutic target for breast cancer brain metastasis.
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http://dx.doi.org/10.7150/ijbs.58916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375234PMC
July 2021

Sex Differences in Biopsy-Confirmed Diabetic Kidney Disease.

Front Endocrinol (Lausanne) 2021 29;12:670674. Epub 2021 Jul 29.

Division of Nephrology, West China Hospital of Sichuan University, Chengdu, China.

Background: To investigate the association between sex differences and end-stage kidney disease (ESKD) in patients with biopsy-confirmed diabetic kidney disease (DKD).

Method: We performed a retrospective cohort study. A total of 336 patients with biopsy-confirmed DKD who were followed up for at least 12 months were enrolled. Baseline clinical and pathological data at the time of biopsy were collected. ESKD was defined by an estimated glomerular filtration rate of <15 ml/min/1.73 m or initiation of renal replacement therapy. The association between sex differences and ESKD was assessed using the log-rank test and Cox regression.

Result: There were 239 (71%) male and 97 (29%) female patients in our cohort. Female patients had higher systolic blood pressure, total cholesterol and low-density lipoprotein cholesterol levels compared with male. There were a lower proportion of female patients in the very high risk grade according to the chronic kidney disease categories (37% of female vs. 44% of male). During a median follow-up time of 20 months, 101 (57.7%) male and 43 (44.3%) female entered into ESKD, with no significant difference by the log-rank test (0.05). Univariate [male: hazard ratio (HR) [95% confidence interval (CI)], 1.005, (0.702-1.439)] and multivariable ([male: HR (95%CI), 1.164, (0.675-2.007)]. Cox regression further showed that sex difference was not significantly associated with ESKD.

Conclusion: Female patients had the higher systolic blood pressure, total cholesterol, LDL-C, compared with male patients. However, there was no significant association observed between sex difference and ESKD in our study.
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http://dx.doi.org/10.3389/fendo.2021.670674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360678PMC
July 2021

Changes in the pathogenic spectrum of acute respiratory tract infections during the COVID-19 epidemic in Beijing, China: A large-scale active surveillance study.

J Infect 2021 Aug 11. Epub 2021 Aug 11.

Institute for immunization and prevention, Beijing Center for Disease Control and Prevention, Beijing Research Center for Preventive Medicine, No.16 Hepingli Middle Street, Dongcheng District, Beijing, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2021.08.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8354886PMC
August 2021

Krüppel-like factor 9 upregulates E-cadherin transcription and represses breast cancer invasion and metastasis.

Am J Cancer Res 2021 15;11(7):3660-3673. Epub 2021 Jul 15.

Medical College, Dalian University Dalian, China.

Aberrant expression of Krüppel-like factor 9 (KLF9) is frequently found in some types of cancer and is implicated in cancer initiation and progression. However, the effects of KLF9 on cancer metastases and the underlying mechanisms still need to be understood. Here, we found that KLF9 evidently inhibited the capabilities of migration and invasion of breast cancer cells. The expression of KLF9 was markedly decreased in breast cancer patients compared with benign tumors, and was positively correlated with the expression of E-cadherin in the tissues of breast cancer patients. Mechanistically, chromatin immunoprecipitation combined with site-directed mutagenesis-luciferase assay revealed that KLF9 activated the promoter by binding to GT-box elements located +84 bp and -143 bp from the in the promoter, leading to elevated expression of E-cadherin mRNA and protein. experiments confirmed that KLF9 strongly inhibited the lung metastasis of breast cancer and increased mouse E-cadherin expression in 4T1 mouse breast cancer cells. Taken together, our findings demonstrated that KLF9 could suppress breast cancer invasion and metastasis by upregulating E-cadherin, which provided new insight into aggressive treatment of breast cancer by targeting the KLF9/E-cadherin axis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8332869PMC
July 2021

QSOX2 Is an E2F1 Target Gene and a Novel Serum Biomarker for Monitoring Tumor Growth and Predicting Survival in Advanced NSCLC.

Front Cell Dev Biol 2021 19;9:688798. Epub 2021 Jul 19.

Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Background: Quiescin Q6 sulfhydryl oxidase 2 (QSOX2), an enzyme that can be directly secreted into the extracellular space, is known to be associated with oxidative protein folding. However, whether is abnormally expressed in non-small cell lung cancer (NSCLC) and its role in tumor growth remains unclear.

Methods: Real-time quantitative PCR (qPCR), immunohistochemistry (IHC), bioinformatics analyses were applied to analyze the expression pattern and prognostic significance of QSOX2 in NSCLC. Xenografts model, enzyme-linked immunosorbent assays (ELISA), western blot analysis (WB), and IHC were preformed to examine tumor suppression and intracellular and extracellular expression of QSOX2. Flow cytometry, WB and qPCR analyses were used to elucidate the role of QSOX2 in cell cycle regulation. Chromatin immunoprecipitation assay (ChIP) assay and Dual-Luciferase reporter assay were employed to investigate transcriptional regulation of by E2F Transcription Factor 1 ().

Results: Quiescin sulfhydryl oxidase 2 was significantly overexpressed in NSCLC and associated with poor survival in advanced-stage patients. The intracellular and extracellular expression of QSOX2 by tumor cells markedly decreased after anti-cancer therapy , and in the clinic. Moreover, silencing in NSCLC cell lines resulted in inhibition of cancer cell proliferation, induction of apoptosis, and decreased expression of cell division-related genes (CENPF and NUSAP1) and Wnt pathway activators (PRRX2 and Nuc-β-catenin). Mechanistically, QSOX2 was expressed periodically during cell cycle and directly regulated by E2F1.

Conclusions: Our findings demonstrate that QSOX2 is directly regulated by E2F1 in the cell cycle, which is essential for the proliferation of NSCLC cells. Furthermore, QSOX2 is a prognostic indicator for NSCLC and may be developed into a biomarker for monitoring tumor burden and therapeutic progress.
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http://dx.doi.org/10.3389/fcell.2021.688798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326667PMC
July 2021

Genetic source tracking of human plague cases in Inner Mongolia-Beijing, 2019.

PLoS Negl Trop Dis 2021 Aug 3;15(8):e0009558. Epub 2021 Aug 3.

National Institute for Communicable Disease Control and Prevention (ICDC), China CDC, Changping, Beijing, China.

On 12 November 2019, one couple from the Sonid Left Qi (County) in the Inner Mongolia Autonomous Region was diagnosed with pneumonic plague in Beijing. The wife acquired the infection from her husband. Thereafter, two bubonic plague cases were identified in Inner Mongolia on November 16th and 24th. In this study, genome-wide single nucleotide polymorphism (SNP) analysis was used to identify the phylogenetic relationship of Yersinia pestis strains isolated in Inner Mongolia. Strains isolated from reservoirs in 2018 and 2019 in Inner Mongolia, together with the strain isolated from Patient C, were further clustered into 2.MED3m, and two novel lineages (2.MED3q, 2.MED3r) in the 2.MED3 population. According to the analysis of PCR-based molecular subtyping methods, such as the MLVA 14 scheme and seven SNP allele sequencing, Patients A/B and D were classified as 2.MED3m. In addition, strains from rodents living near the patients' residences were clustered into the same lineage as patients. Such observations indicated that human plague cases originated from local reservoirs. Corresponding phylogenetic analysis also indicated that rodent plague strains in different areas in Inner Mongolia belong to different epizootics rather than being caused by spreading from the same epizootic in Meriones unguiculatus in 2019.
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http://dx.doi.org/10.1371/journal.pntd.0009558DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8362994PMC
August 2021

A topological switch in CFTR modulates channel activity and sensitivity to unfolding.

Nat Chem Biol 2021 09 2;17(9):989-997. Epub 2021 Aug 2.

SFMB, Université Libre de Bruxelles, Brussels, Belgium.

The cystic fibrosis transmembrane conductance regulator (CFTR) anion channel is essential to maintain fluid homeostasis in key organs. Functional impairment of CFTR due to mutations in the cftr gene leads to cystic fibrosis. Here, we show that the first nucleotide-binding domain (NBD1) of CFTR can spontaneously adopt an alternate conformation that departs from the canonical NBD fold previously observed. Crystallography reveals that this conformation involves a topological reorganization of NBD1. Single-molecule fluorescence resonance energy transfer microscopy shows that the equilibrium between the conformations is regulated by adenosine triphosphate binding. However, under destabilizing conditions, such as the disease-causing mutation F508del, this conformational flexibility enables unfolding of the β-subdomain. Our data indicate that, in wild-type CFTR, this conformational transition of NBD1 regulates channel function, but, in the presence of the F508del mutation, it allows domain misfolding and subsequent protein degradation. Our work provides a framework to design conformation-specific therapeutics to prevent noxious transitions.
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http://dx.doi.org/10.1038/s41589-021-00844-0DOI Listing
September 2021

Unraveling synonymous and deep intronic variants causing aberrant splicing in two genetically undiagnosed epilepsy families.

BMC Med Genomics 2021 Jun 9;14(1):152. Epub 2021 Jun 9.

Cipher Gene, Ltd., Beijing, 100080, China.

Background: Variants identified through parent-child trio-WES yield up to 28-55% positive diagnostic rate across a variety of Mendelian disorders, there remain numerous patients who do not receive a genetic diagnosis. Studies showed that some aberrant splicing variants, which are either not readily detectable by WES or could be miss-interpreted by regular detecting pipelines, are highly relevant to human diseases.

Methods: We retrospectively investigated the negative molecular diagnostics through trio-WES for 15 genetically undiagnosed patients whose clinical manifestations were highly suspected to be genetic disorders with well-established genotype-phenotype relationships. We scrutinized the synonymous variants from WES data and Sanger sequenced the suspected intronic region for deep intronic variants. The functional consequences of variants were analyzed by in vitro minigene experiments.

Results: Here, we report two abnormal splicing events, one of which caused exon truncating due to the activation of cryptic splicing site by a synonymous variant; the other caused partial intron retention due to the generation of splicing sites by a deep intronic variant.

Conclusions: We suggest that, despite initial negative genetic test results in clinically highly suspected genetic diseases, the combination of predictive bioinformatics and functional analysis should be considered to unveil the genetic etiology of undiagnosed rare diseases.
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http://dx.doi.org/10.1186/s12920-021-01008-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188693PMC
June 2021

A Novel Virus of Associated with Sexual Precocity in .

mSystems 2021 Jun 8;6(3):e0000321. Epub 2021 Jun 8.

Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Laboratory for Marine Fisheries Science and Food Production Processes, Pilot National Laboratory for Marine Science and Technology (Qingdao), Key Laboratory of Maricultural Organism Disease Control, Ministry of Agriculture and Rural Affairs, Qingdao Key Laboratory of Mariculture Epidemiology and Biosecurity, Qingdao, China.

Since 2010, sexual precocity, a typical sign of the iron prawn syndrome (IPS), resulting in the reduced size of farmed giant freshwater prawns , has caused substantial production losses. However, the cause of IPS was not clear. We ran tests for eight major shrimp pathogens, but none were detected from IPS-affected prawns. We performed the histopathological examination of tissues and identified an eosinophilic inclusion in the perinuclear cytoplasm of cells in various tissues associated with nervous and endocrinal functions in the compound eyes. A subsequent bioassay with viral extracts of IPS-affected samples reproduced the gross signs of IPS. Metatranscriptomic sequencing identified a novel virus of in all IPS-affected prawns, which was not found in samples without IPS. This virus contains a positive-sense, single-stranded RNA genome of 12,630 nucleotides (nt). Phylogenetic analysis of the conserved RdRp and NS3 domains showed that it may belong to a new genus between Jingmenvirus and . Under transmission electron microscopy (TEM), putative virus particles showed as spherical with a diameter of 40 to 60 nm. hybridization found hybridization signals consistent with the histopathology in the compound eyes from IPS-affected . We provisionally name this virus infectious precocity virus (IPV) and propose the binominal Latin name gen. nov., sp. nov. We developed a nested reverse transcription-PCR diagnostic assay and confirmed that all IPS-affected prawns tested IPV positive but normal prawns tested negative. Collectively, our study revealed a novel virus of associated with sexual precocity in . The iron prawn syndrome (IPS), also described as sexual precocity, results in the reduced size of farmed prawns at harvest and significant economic losses. IPS has been frequently reported in populations of farmed since 2010, but the cause was heretofore unknown. Here, we reported a novel virus identified from prawns with IPS using infection experiments, metatranscriptomic sequencing, and transmission electron microscopy and provisionally named it infectious precocity virus (IPV). Phylogenetic analysis showed that IPV represents a new genus, proposed as gen. nov., in the family . This study provides novel insight that a viral infection may cause pathological change and sexual maturation and subsequently affect crustacean growth. Therefore, we call for quarantine inspection of IPV in transboundary trade of live and enhanced surveillance of IPV in aquaculture in the region and globally.
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http://dx.doi.org/10.1128/mSystems.00003-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269200PMC
June 2021

Modelling the oil spill transport in inland waterways based on experimental study.

Environ Pollut 2021 Sep 28;284:117473. Epub 2021 May 28.

School of River and Ocean Engineering, Chongqing Jiaotong University, Chongqing, 400074, China; National Engineering Research Center for Inland Waterway Regulation, Chongqing, 400074, China.

Oil spills occurring either in oceans or inland waterways may cause serious economic losses and ecological damage. Previous studies pertaining to oil spills and their consequences are primarily based on marine environments, whereas few have focused on oil spills occurring in inland waterways characterised by pronounced flow advection transport effects, which differ from the marine environment. A generalised flume experiment is performed to investigate the spread and transport of oil spills, and the relationships between the area and thickness of oil slick over time are analysed parametrically. An oil spill model combined with a depth-integrated two-dimensional non-uniform flow model, which is suitable for modelling inland waterways based on the Lagrangian method, is established; it is calibrated and verified using measured data from the flume experiment. The model is applied to three scenarios on the Luoqi reach of the Yangtze River, and spilled oil drifting trajectory maps are obtained and analysed considering the field wind parameters. The results show that the drift distance of the oil slick in the inland waterway is primarily controlled by the flow velocity with effects of advection transport; however, the oil spill trajectory spreads toward the wind direction when the flow velocity is relatively small compared with the wind speed. The results of this study serve as a reference for predicting the spread and transport of oil spills in inland waterways.
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http://dx.doi.org/10.1016/j.envpol.2021.117473DOI Listing
September 2021

MicroRNA-342 Promotes the Malignant-Like Phenotype of Endometrial Stromal Cells via Regulation of Annexin A2.

Anal Cell Pathol (Amst) 2021 15;2021:1328682. Epub 2021 May 15.

Department of Gynecology, Heilongjiang Provincial Hospital, Harbin, 150036 Heilongjiang, China.

The relevance of miRNA- (miR-) 342 to endometriosis has been highlighted, while its function in regulating the malignant-like phenotype of endometrial stromal cells which demonstrate epigenetic abnormalities that alter expression of transcription factors, remains unclear. Therefore, we sought to characterize the effects of miR-342 in endometrial stromal cell proliferation by regulating Annexin A2 (ANXA2). We first characterized the levels of miR-342 and ANXA2 in 31 cases of normal endometrium from patients with grade II-III cervical intraepithelial neoplasia or patients with hysterectomy versus ectopic endometrial tissues of 42 patients with endometriosis. miR-342 was upregulated, while ANXA2 was downregulated in ectopic endometrial tissues. Bioinformatics website and dual-luciferase reporter assay revealed that miR-342 negatively modulated ANXA2 expression. Following loss- and gain-of-function approaches, CCK-8, Transwell, and flow cytometry demonstrated that overexpression of miR-342 markedly increased cell proliferation, migration, and invasion but inhibited cell apoptotic ratio of endometrial stromal cells, which was reversed by ANXA2 elevation. Further, overexpressed miR-342 activated the PI3K/AKT/mTOR signaling pathway, as evidenced by upregulated levels of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. Taken together, miR-342 targets ANXA2 to activate the PI3K/AKT/mTOR signaling pathway, thereby promoting the malignant-like phenotype of endometrial stromal cells, highlighting miR-342 inhibition as a promising approach for the treatment of endometriosis.
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http://dx.doi.org/10.1155/2021/1328682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143883PMC
May 2021

Extracellular phosphate enhances the function of F508del-CFTR rescued by CFTR correctors.

J Cyst Fibros 2021 May 18. Epub 2021 May 18.

Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom. Electronic address:

Background: The clinical response to cystic fibrosis transmembrane conductance regulator (CFTR) modulators varies between people with cystic fibrosis (CF) of the same genotype, in part through the action of solute carriers encoded by modifier genes. Here, we investigate whether phosphate transport by SLC34A2 modulates the function of F508del-CFTR after its rescue by CFTR correctors.

Methods: With Fischer rat thyroid (FRT) cells heterologously expressing wild-type and F508del-CFTR and fully-differentiated CF and non-CF human airway epithelial cells, we studied SLC34A2 expression and the effects of phosphate on CFTR-mediated transepithelial ion transport. F508del-CFTR was trafficked to the plasma membrane by incubation with different CFTR correctors (alone or in combination) or by low temperature.

Results: Quantitative RT-PCR demonstrated that both FRT and primary airway epithelial cells express SLC34A2 mRNA and no differences were found between cells expressing wild-type and F508del-CFTR. For both heterologously expressed and native F508del-CFTR rescued by either VX-809 or C18, the magnitude of CFTR-mediated Cl currents was dependent on the presence of extracellular phosphate. However, this effect of phosphate was not detected with wild-type and low temperature-rescued F508del-CFTR Cl currents. Importantly, the modulatory effect of phosphate was observed in native CF airway cells exposed to VX-445, VX-661 and VX-770 (Trikafta) and was dependent on the presence of both sodium and phosphate.

Conclusions: Extracellular phosphate modulates the magnitude of CFTR-mediated Cl currents after F508del-CFTR rescue by clinically-approved CFTR correctors. This effect likely involves electrogenic phosphate transport by SLC34A2. It might contribute to inter-individual variability in the clinical response to CFTR correctors.
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http://dx.doi.org/10.1016/j.jcf.2021.04.013DOI Listing
May 2021

Ultrasonic diagnosis of asymptomatic rupture of uterine in second trimester of pregnancy after laparoscopic surgery for interstitial pregnancy: a case report.

BMC Pregnancy Childbirth 2021 May 14;21(1):375. Epub 2021 May 14.

Department of Obstetrics and Gynecology, Peking University Third Hospital, 49 North Garden Rd, Haidian District, Beijing, 100191, China.

Background: Uterine rupture is a rare, life-threatening event in obstetrics that may be fatal for the mother and fetus. Therefore, obstetricians need to pay attention to and should consider the antenatal diagnosis of uterine rupture in women having its risk factors. Successful conservative management for asymptomatic uterine rupture due to previous laparoscopic surgery for interstitial pregnancy has already been reported but remains understudied.

Case Presentation: A 39-year-old woman was diagnosed asymptomatic uterine rupture at 22 weeks gestation by a routine second-trimester ultrasound scan. She had a history of laparoscopic salpingectomy with cornual wedge resection for interstitial pregnancy 10 months before this pregnancy. Refusing doctor's twice advice of terminating the pregnancy, the patient insisted carrying on the pregnancy, and followed up by ultrasound and magnetic resonance imaging. Fetal growth was appropriate, fetal movements were good and the patient had no symptoms, without uterine contraction or amniotic fluid loss throughout follow-up period. Caesarean section was carried out at 34 + 1 weeks with a good maternal and neonatal outcome.

Conclusions: A previous history of laparoscopic salpingectomy with cornual wedge resection could be a risk factor for uterine rupture in pregnant women. Sonographers should be alert to this potential risk in pregnant women with a history of laparoscopic salpingectomy with cornual wedge resection even in asymptomatic patients.
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http://dx.doi.org/10.1186/s12884-021-03845-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120851PMC
May 2021

Population genomics provides insights into the evolution and adaptation to humans of the waterborne pathogen Mycobacterium kansasii.

Nat Commun 2021 05 3;12(1):2491. Epub 2021 May 3.

Shanghai Institute of Infectious Disease and Biosecurity, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), Shanghai Medical College and School of Basic Medical Sciences, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

Mycobacterium kansasii can cause serious pulmonary disease. It belongs to a group of closely-related species of non-tuberculous mycobacteria known as the M. kansasii complex (MKC). Here, we report a population genomics analysis of 358 MKC isolates from worldwide water and clinical sources. We find that recombination, likely mediated by distributive conjugative transfer, has contributed to speciation and on-going diversification of the MKC. Our analyses support municipal water as a main source of MKC infections. Furthermore, nearly 80% of the MKC infections are due to closely-related M. kansasii strains, forming a main cluster that apparently originated in the 1900s and subsequently expanded globally. Bioinformatic analyses indicate that several genes involved in metabolism (e.g., maintenance of the methylcitrate cycle), ESX-I secretion, metal ion homeostasis and cell surface remodelling may have contributed to M. kansasii's success and its ongoing adaptation to the human host.
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http://dx.doi.org/10.1038/s41467-021-22760-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093194PMC
May 2021

A novel mechanism of streptomycin resistance in Yersinia pestis: Mutation in the rpsL gene.

PLoS Negl Trop Dis 2021 04 22;15(4):e0009324. Epub 2021 Apr 22.

National Institute for Communicable Disease Control and Prevention, China CDC, Changping, Beijing, China.

Streptomycin is considered to be one of the effective antibiotics for the treatment of plague. In order to investigate the streptomycin resistance of Y. pestis in China, we evaluated streptomycin susceptibility of 536 Y. pestis strains in China in vitro using the minimal inhibitory concentration (MIC) and screened streptomycin resistance-associated genes (strA and strB) by PCR method. A clinical Y. pestis isolate (S19960127) exhibited high-level resistance to streptomycin (the MIC was 4,096 mg/L). The strain (biovar antiqua) was isolated from a pneumonic plague outbreak in 1996 in Tibet Autonomous Region, China, belonging to the Marmota himalayana Qinghai-Tibet Plateau plague focus. In contrast to previously reported streptomycin resistance mediated by conjugative plasmids, the genome sequencing and allelic replacement experiments demonstrated that an rpsL gene (ribosomal protein S12) mutation with substitution of amino-acid 43 (K43R) was responsible for the high-level resistance to streptomycin in strain S19960127, which is consistent with the mutation reported in some streptomycin-resistant Mycobacterium tuberculosis strains. Streptomycin is used as the first-line treatment against plague in many countries. The emergence of streptomycin resistance in Y. pestis represents a critical public health problem. So streptomycin susceptibility monitoring of Y. pestis isolates should not only include plasmid-mediated resistance but also include the ribosomal protein S12 gene (rpsL) mutation, especially when treatment failure is suspected due to antibiotic resistance.
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http://dx.doi.org/10.1371/journal.pntd.0009324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096067PMC
April 2021

The Potentials of Melatonin in the Prevention and Treatment of Bacterial Meningitis Disease.

Molecules 2021 Mar 5;26(5). Epub 2021 Mar 5.

College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.

Bacterial meningitis (BM) is an acute infectious central nervous system (CNS) disease worldwide, occurring with 50% of the survivors left with a long-term serious sequela. Acute bacterial meningitis is more prevalent in resource-poor than resource-rich areas. The pathogenesis of BM involves complex mechanisms that are related to bacterial survival and multiplication in the bloodstream, increased permeability of blood-brain barrier (BBB), oxidative stress, and excessive inflammatory response in CNS. Considering drug-resistant bacteria increases the difficulty of meningitis treatment and the vaccine also has been limited to several serotypes, and the morbidity rate of BM still is very high. With recent development in neurology, there is promising progress for drug supplements of effectively preventing and treating BM. Several in vivo and in vitro studies have elaborated on understanding the significant mechanism of melatonin on BM. Melatonin is mainly secreted in the pineal gland and can cross the BBB. Melatonin and its metabolite have been reported as effective antioxidants and anti-inflammation, which are potentially useful as prevention and treatment therapy of BM. In bacterial meningitis, melatonin can play multiple protection effects in BM through various mechanisms, including immune response, antibacterial ability, the protection of BBB integrity, free radical scavenging, anti-inflammation, signaling pathways, and gut microbiome. This manuscript summarizes the major neuroprotective mechanisms of melatonin and explores the potential prevention and treatment approaches aimed at reducing morbidity and alleviating nerve injury of BM.
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http://dx.doi.org/10.3390/molecules26051419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7961363PMC
March 2021

A Photopolymerized Semi-Interpenetrating Polymer Networks-Based Hydrogel Incorporated with Nanoparticle for Local Chemotherapy of Tumors.

Pharm Res 2021 Apr 1;38(4):669-680. Epub 2021 Apr 1.

Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, 3663 North Zhong-shan Road, Shanghai, 200062, People's Republic of China.

Purpose: To address the issue of local drug delivery in tumor treatment, a novel nanoparticle-hydrogel superstructure, namely semi-interpenetrating polymer networks (semi-IPNs) hydrogel composed of poly (ethylene glycol) diacrylate (PEGDA) and hyaluronic acid (HA) and incorporated with paclitaxel (PTX) loaded PLGA nanoparticles (PEGDA-HA/PLGA-PTX), was prepared by in situ UV photopolymerization for the use of local drug delivery.

Methods: Using the gelation time, swelling rate and degradation rate as indicators, the optimal proportion of Irgacure 2959 initiator and the concentration of HA was screened and obtained for preparing hydrogels. Next, paclitaxel (PTX) loaded PLGA nanoparticles (PLGA-PTX NPs) were prepared by the emulsion solvent evaporation method.

Results: The mass ratio of the initiator was 1%, and the best concentration of HA was 5 mg/mL in PEGDA-HA hydrogel. In vitro experiments showed that PLGA-PTX NPs had similar cytotoxicity to free PTX, and the cell uptake ratio on NCI-H460 cells was up to 96% by laser confocal microscopy and flow cytometry. The drug release of the PEGDA-HA/PLGA-PTX hydrogel local drug delivery system could last for 13 days. In vivo experiments proved that PEGDAHA/PLGA-PTX hydrogel could effectively inhibit the tumor growth without causing toxic effects in mice.

Conclusions: This study demonstrated that the PEGDA-HA/PLGA-PTX hydrogel is a promising local drug delivery system in future clinical applications for tumor therapy. A photopolymerized semi-interpenetrating polymer networks-based hydrogel incorporated with paclitaxel-loaded nanoparticles was fabricated by in situ UV photopolymerization, providing a promised nanoplatform for local chemotherapy of tumors.
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http://dx.doi.org/10.1007/s11095-021-03029-5DOI Listing
April 2021

A Clip-with-Line Traction Suture Method for Closing Mucosal Defects after Endoscopic Submucosal Dissection.

Gastroenterol Res Pract 2021 2;2021:8817726. Epub 2021 Mar 2.

Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Jiangxi, China.

Endoscopic submucosal dissection (ESD) is a technically difficult endoscopic procedure for treating gastrointestinal diseases. Procedure time is longer, and complications such as mucosal defects, intraoperative perforation, and bleeding occur frequently. Here, to solve these problems, we described the clip-with-line traction suture method that applied and performed for closing mucosal defects after ESD in three representative cases.
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http://dx.doi.org/10.1155/2021/8817726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946448PMC
March 2021

Deletion of FaeG alleviated Enterotoxigenic Escherichia coli F4ac-induced apoptosis in the intestine.

AMB Express 2021 Mar 18;11(1):44. Epub 2021 Mar 18.

College of Veterinary Medicine (Institute of Comparative Medicine), Yangzhou University, Yangzhou 12th East Wenhui Road, Yangzhou, 225009, China.

Enterotoxigenic Escherichia coli (ETEC) F4ac is a major constraint to the development of the pig industry, which is causing newborn and post-weaning piglets diarrhea. Previous studies proved that FaeG is the major fimbrial subunit of F4ac E. coli and efficient for bacterial adherence and receptor recognition. Here we show that the faeG deletion attenuates both the clinical symptoms of F4ac infection and the F4ac-induced intestinal mucosal damage in piglets. Antibody microarray analysis and the detection of mRNA expression using porcine neonatal jejunal IPEC-J2 cells also determined that the absence of FaeG subunit alleviated the F4ac promoted apoptosis in the intestinal epithelial cells. Thus, targeted depletion of FaeG is still beneficial for the prevention or treatment of F4ac infection.
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http://dx.doi.org/10.1186/s13568-021-01201-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973317PMC
March 2021

Understanding patient journey in ulcerative colitis prior to biologic initiation: a 5-year exploration.

BMC Gastroenterol 2021 Mar 17;21(1):121. Epub 2021 Mar 17.

Janssen Global Services, LLC, Raritan, 08869, NJ, USA.

Background: There has been a more pronounced shift toward earlier, more aggressive therapies in Crohn's disease than in ulcerative colitis (UC). The aim of this study was to describe the pre-biologic treatment and health care experience, including co-morbidities and overall health care utilization, for UC patients who initiated biologic therapies, in the 5 years prior to the initiation of the first biologic agent.

Methods: UC patients who initiated a biologic agent approved for UC between 9/15/2005 and 1/30/2018 were identified from the IBM® MarketScan® Commercial Database, a large US database. The date of the first recorded UC biologic exposure was defined as the index date, and ≥ 5 years of pre-index records were required to evaluate patients' treatment, disease progression and overall health care utilization prior to initiating biologic agents.

Results: Among the 1891 eligible patients, treatment with oral corticosteroids, 5-aminosalicylates, and other non-biologic immunomodulators, all increased progressively across the 5 years prior to the index. From within year-five to within year-one prior to the index, the median duration of oral corticosteroid treatment increased from 34 to 88 days per year and the proportion of patients who experienced more extensive/pancolitis disease increased from 16 to 59%. Overall, the frequency of all-cause health care visits also increased.

Conclusions: Patients with UC experienced increasing morbidity and treatment burden in the 5 years prior to initiating biologic therapy. To achieve reduced corticosteroids in UC management, better risk stratification is needed to help identify patients for more timely biologic treatment.
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http://dx.doi.org/10.1186/s12876-021-01708-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967955PMC
March 2021

Early-onset of type 2 diabetes mellitus is a risk factor for diabetic nephropathy progression: a biopsy-based study.

Aging (Albany NY) 2021 03 3;13(6):8146-8154. Epub 2021 Mar 3.

Division of Nephrology, West China Hospital of Sichuan University, Chengdu, Sichuan, China.

Several studies show that patients with early-onset diabetes have higher risk of diabetic complications than those diagnosed in middle age. However, whether early-onset of type 2 diabetes mellitus (T2DM) is a risk factor for diabetic nephropathy (DN) progression remains unclear, especially a lack of data in biopsy-confirmed cohort. In This study, we enrolled 257 patients with T2DM and biopsy-confirmed DN to investigate the role of early-onset T2DM in DN progression. Participants were divided into two groups according to the age of T2DM diagnosis: early-onset group (less than 40 years) and later-onset group (40 years or older). We found that patients with early-onset T2DM had higher glomerular grades and arteriolar hyalinosis scores than those in later-onset group. After adjusted for confounding factors, early-onset of T2DM remained an independent predictor of end-stage renal disease (ESRD) for patients with DN. In conclusion, although with the comparable renal function and proteinuria, patients with early-onset T2DM and DN had worse renal pathological changes than those with later-onset. Early-onset of T2DM might be an important predictor of ESRD for patients with DN, which called more attention to early supervision and prevention for patients with early-onset T2DM and DN.
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http://dx.doi.org/10.18632/aging.202624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034912PMC
March 2021

Association between atherosclerotic cardiovascular diseases risk and renal outcome in patients with type 2 diabetes mellitus.

Ren Fail 2021 Dec;43(1):477-487

Division of Nephrology, West China Hospital of Sichuan University, Chengdu, China.

Aims: Chronic kidney disease (CKD) and diabetes mellitus increase atherosclerotic cardiovascular diseases (ASCVD) risk. However, the association between renal outcome of diabetic kidney disease (DKD) and ASCVD risk is unclear.

Methods: This retrospective study enrolled 218 type 2 diabetic patients with biopsy-proven DKD, and without known cardiovascular diseases. Baseline characteristics were obtained and the 10-year ASCVD risk score was calculated using the Pooled Cohort Equation (PCE). Renal outcome was defined as progression to end-stage renal disease (ESRD). The association between ASCVD risk and renal function and outcome was analyzed with logistic regression and Cox analysis.

Results: Among all patients, the median 10-year ASCVD risk score was 14.1%. The median of ASCVD risk score in CKD stage 1, 2, 3, and 4 was 10.9%, 12.3%, 16.5%, and 14.8%, respectively ( = 0.268). Compared with patients with lower ASCVD risk (<14.1%), those with higher ASCVD risk had lower eGFR, higher systolic blood pressure, and more severe renal interstitial inflammation. High ASCVD risk (>14.1%) was an independent indicator of renal dysfunction in multivariable-adjusted logistic analysis (OR, 3.997; 95%CI, 1.385-11.530;  = 0.010), though failed to be an independent risk factor for ESRD in patients with DKD in univariate and multivariate Cox analysis.

Conclusions: DKD patients even in CKD stage 1 had comparable ASCVD risk score to patients in CKD stage 2, 3, and 4. Higher ASCVD risk indicated severe renal insufficiency, while no prognostic value of ASVCD risk for renal outcome was observed, which implied macroangiopathy and microangiopathy in patients with DKD were related, but relatively independent.
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http://dx.doi.org/10.1080/0886022X.2021.1893186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946063PMC
December 2021

The Long Noncoding RNA Hepatocyte Nuclear Factor 4 Antisense RNA 1 Negatively Regulates Cytochrome P450 Enzymes in Huh7 Cells via Histone Modifications.

Drug Metab Dispos 2021 May 5;49(5):361-368. Epub 2021 Mar 5.

Department of Pharmacology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, China (P.W., S.C., Y.W., X.W., K.Y., S.H., L.Z.); Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China (L.Y.); and Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut (X.-b.Z.)

The maintenance of homeostasis of cytochromes P450 enzymes (P450s) under both physiologic and xenobiotic exposure conditions is ensured by the action of positive and negative regulators. In the current study, the hepatocyte nuclear factor 4 (HNF4A) antisense RNA 1 (HNF4A-AS1), an antisense long noncoding RNA of , was found to be a negative regulator of the basal and rifampicin (RIF)-induced expression of nuclear receptors and downstream P450s. In Huh7 cells, knockdown of HNF4A-AS1 resulted in elevated expression of HNF4A, pregnane X receptor (PXR), and P450s (including CYP3A4) under both basal and RIF-induced conditions. Conversely, overexpression of HNF4A-AS1 led to decreased basal expression of constitutive androstane receptor, aryl hydrocarbon receptor, PXR, and all studied P450s. Of note, significantly diminished induction levels of PXR and CYP1A2, 2C8, 2C19, and 3A4 by RIF were also observed in HNF4A-AS1 plasmid-transfected Huh7 cells. Moreover, the negative feedback of HNF4A on HNF4A-AS1-mediated gene expression was validated using a loss-of-function experiment in this study. Strikingly, our data showed that increased enrichment levels of histone 3 lysine 4 trimethylation and HNF4A in the promoter contribute to the elevated CYP3A4 expression after HNF4A-AS1 knockdown. Overall, the current study reveals that histone modifications contribute to the negative regulation of nuclear receptors and P450s by HNF4A-AS1 in basal and drug-induced levels. SIGNIFICANCE STATEMENT: Utilizing loss-of-function and gain-of-function experiments, the current study systematically investigated the negative regulation of HNF4A-AS1 on the expression of nuclear receptors (including HNF4A, constitutive androstane receptor, aryl hydrocarbon receptor, and pregnane X receptor) and P450s (including CYP1A2, 2E1, 2B6, 2D6, 2C8, 2C9, 2C19, and 3A4) in both basal and rifampicin-induced levels in Huh7 cells. Notably, this study is the first to reveal the contribution of histone modification to the HNF4A-AS1-mediated expression of CYP3A4 in Huh7 cells.
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http://dx.doi.org/10.1124/dmd.120.000316DOI Listing
May 2021

Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes.

Sci Rep 2021 Feb 25;11(1):4658. Epub 2021 Feb 25.

Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia.

Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) for ESRD. Single glomerular proteomics and immunohistochemistry were used to identify differentially expressed proteins and enriched pathways in glomeruli. During the median follow-up period of 24 months, 144 (45%) patients progressed to ESRD. In multivariable models, the Renal Pathology Society classification failed to predict ESRD, although the solidified glomerulosclerosis (score 1: HR 1.65, 95% confidence interval [CI] 1.04-2.60; score 2: HR 2.48, 95% CI 1.40-4.37) and extracapillary hypercellularity (HR 2.68, 95% CI 1.55-4.62) were identified as independent risk factors. Additionally, single glomerular proteomics, combined with immunohistochemistry, revealed that complement C9 and apolipoprotein E were highly expressed in solidified glomerulosclerosis. Therefore, solidified glomerulosclerosis and extracapillary hypercellularity predict diabetic ESRD in Chinese patients. Single glomerular proteomics identified solidified glomerulosclerosis as a unique pathological change that may be associated with complement overactivation and abnormal lipid metabolism.
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http://dx.doi.org/10.1038/s41598-021-83856-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907371PMC
February 2021

Comb-like structural modification stabilizes polyvinylidene fluoride membranes to realize thermal-regulated sustainable transportation efficiency.

J Colloid Interface Sci 2021 Jun 4;591:173-183. Epub 2021 Feb 4.

College of Materials Science& Engineering, Zhejiang University of Technology, Hangzhou 310014, PR China. Electronic address:

Hydrophobic micro-porous membrane such as polyvinylidene fluoride (PVDF) with excellent thermal-/chemical-stability and low surface energy has received extensive attention in industrial water treatment and sustainable energy conversion. However, undesirable contaminants caused by inevitable proteins or microorganisms adhesion may lead to a rapid loss of separation efficiency, which significantly deteriorate their porous structures and eventually limit their practical performance. Herein, we present a scalable approach for fabricating comb-like copolymer modified PVDF membranes ([email protected]) that prevent bacteria from proliferating on the surface and temperature-controlled release of adhered contaminants. Comb-like structured copolymers were imparted to a polydopamine (PDA)-treated PVDF membrane by Michael addition reaction, which enabled a covalent binding of comb-like structured copolymers to the membrane. Such unique structural design of grafted copolymer, containing hydrophilic side chain and temperature-responsive chain backbone, stably prevents bacteria adhesion and provides reversible surface wettability. Therefore, the resultant membranes were evaluated to prevent bacterial adhesion, high touch-killing efficiency and temperature-controlled contaminants release (~99% of protein and ~75% of bacteria). Moreover, with the collapse and stretch of grafted copolymer chain backbone, the synthetic membrane further reversibly adjusted inner micro-porous structure and surface wettability, which eventually helped to achieve variable water fluid transport efficiency. This study not only provides a feasible structural design for stably coping with the challenging of antifouling and subsequent contamination adhesion of PVDF membrane, but also potentially answers the significant gap between lab research advances and practical application, particularly in the industrial membrane field.
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http://dx.doi.org/10.1016/j.jcis.2021.01.091DOI Listing
June 2021

Comparison of the analgesic effect of quadratus lumborum block and epidural block in open uterine surgery: a randomized controlled trial.

Minerva Anestesiol 2021 04 16;87(4):414-422. Epub 2021 Feb 16.

Department of Anesthesiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China -

Background: Effective regional analgesia during open surgery could reduce opioid consumption and enhance early recovery. We compared the effects of the newly developed quadratus lumborum block (QLB) and the traditional epidural block (EB) in open uterine surgery.

Methods: In this randomized controlled trial, we included patients scheduled for elective open uterine surgery during May - September 30, 2019. Patients received QLB or EB for perioperative pain relief before general anesthesia. Perioperative opioid consumption, and numeric rating scale (NRS: 0-10) pain scores after surgery, heart rate (HR), mean arterial pressure (MAP), ephedrine and urapidil use during surgery, lower limb muscle strength, timing of first flatus and defecation, nausea, vomiting, and other complications within 24 h post-surgery, were the primary and secondary outcomes, respectively.

Results: Data of 72 (86%; 36/group) of 83 eligible patients were analyzed. Remifentanil consumption during surgery was higher in the QLB than in the EB group, while cumulative sufentanil consumption within 24 h post-surgery was similar between both groups. NRS pain scores at rest and during activity were higher at 1 h post-surgery, and MAP was higher at 5-, 15-, and 30-min postincision in the QLB than in the EB group; HR was similar between groups. Lower ephedrine requirements, higher lower limb muscle strength at 1 h post-surgery, and lower nausea incidence were observed in the QLB group.

Conclusions: QLB produces a less intense but longer block and fewer side effects in the first 24 h after open uterine surgery than those produced by EB.
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http://dx.doi.org/10.23736/S0375-9393.21.14800-XDOI Listing
April 2021
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