Publications by authors named "Bei Wang"

749 Publications

Resistance of SARS-CoV-2 variants to neutralization by convalescent plasma from early COVID-19 outbreak in Singapore.

NPJ Vaccines 2021 Oct 25;6(1):125. Epub 2021 Oct 25.

Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.

The rapid spreading of SARS-CoV-2 variants B.1.1.7 originated from the United Kingdom and B.1.351 from South Africa has contributed to the second wave of COVID-19 cases in the respective countries and also around the world. In this study, we employed advanced biochemical and virological methodologies to evaluate the impact of Spike mutations of these strains on the degree of protection afforded by humoral immune responses following natural infection of the ancestral SARS-CoV-2 strain during the early stages of the outbreak. We found that antibody-mediated neutralization activity was partially reduced for B.1.1.7 variant and significantly attenuated for the B.1.351 strain. We also found that mutations outside the receptor-binding domain (RBD) can strongly influence antibody binding and neutralization, cautioning the use of solely RBD mutations in evaluating vaccine efficacy. These findings highlight an urgent need to develop new SARS-CoV-2 vaccines that are not based exclusively on the ancestral SARS-CoV-2 Spike gene sequence.
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http://dx.doi.org/10.1038/s41541-021-00389-2DOI Listing
October 2021

Genetic Characterizations and Molecular Evolution of the Measles Virus Genotype B3's Hemagglutinin (H) Gene in the Elimination Era.

Viruses 2021 Sep 30;13(10). Epub 2021 Sep 30.

Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing 210009, China.

Measles virus (MeV) genotype B3 is one globally significant circulating genotype. Here, we present a systematic description of long-term evolutionary characterizations of the MeV genotype B3's hemagglutinin (H) gene in the elimination era. Our results show that the B3 H gene can be divided into two main sub-genotypes, and the highest intra-genotypic diversity was observed in 2004. MeV genotype B3's H gene diverged in 1976; its overall nucleotide substitution rate is estimated to be 5.697 × 10 substitutions/site/year, and is slowing down. The amino acid substitution rate of genotype B3's H gene is also decreasing, and the mean effective population size has been in a downward trend since 2000. Selection pressure analysis only recognized a few sites under positive selection, and the number of positive selection sites is getting smaller. All of these observations may reveal that genotype B3's H gene is not under strong selection pressure, and is becoming increasingly conservative. MeV H-gene or whole-genome sequencing should be routine, so as to better elucidate the molecular epidemiology of MeV in the future.
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http://dx.doi.org/10.3390/v13101970DOI Listing
September 2021

Mechanistic insights into enhanced waste activated sludge dewaterability with Cu(II) and Cu(II)/HO treatment: Radical and non-radical pathway.

Chemosphere 2021 Oct 12:132549. Epub 2021 Oct 12.

Chinese Academy of Environmental Planning, Beijing, 100012, PR China. Electronic address:

Without extra adjustment of pH, the effects of cupric ions (Cu(II)) and hydrogen peroxide (HO) alone or in combination on sludge dewatering were studied. It showed good dewatering capability after treated by Cu(II) and Cu(II)/HO, which indicated by the capillary suction times (CST) decreased from 120.8 ± 4.7 s (control) to about 40 s, and the water content (Wc) of sludge cake dropped by about 10%. The results showed that the extracellular polymeric substances (EPS) were destroyed, which characterized by a significant decrease in the biopolymers' concentrations in tightly-bound EPS. Meanwhile, more rough and porous microstructures and higher zeta potentials were obtained after conditioned. Based on the changes of physicochemical properties of sludge, the variations of EPS, and the identification of reactive species, two distinct mechanisms of improved sludge dewatering were postulated. As for Cu(II) treatment, it was mainly due to the surface charge neutralization, strong cytotoxicity of Cu(I) produced by intracellular reduction of Cu(II), and pH decline caused by Cu(II) hydrolysis that improved sludge dewatering performance, which could be noted as a "non-radical pathway". When in combination with HO, hydroxyl radicals (·OH) produced by Cu(II)-catalyzed Fenton-like process played a dominant role in degrading sludge flocs and EPS, which could be regarded as a "radical pathway".
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http://dx.doi.org/10.1016/j.chemosphere.2021.132549DOI Listing
October 2021

Alkaloids exhibit a meaningful function as anticancer agents by restraining cellular signaling pathways.

Mini Rev Med Chem 2021 Oct 7. Epub 2021 Oct 7.

College of Medical Science, China Three Gorges University, Yichang 443002. China.

Alkaloids are nitrogen-containing organic compounds widely found in natural products, which play an essential role in clinical treatment. Cellular signaling pathways in tumors are a series of enzymatic reaction pathways that convert extracellular signals into intracellular signals to produce biological effects. The ordered function of cell signaling pathways is essential for tumor cell proliferation, differentiation, and programmed death. This review describes the antitumor progression mediated by various alkaloids after inhibiting classical signaling pathways; related studies are systematically retrieved and collected through PubMed. We selected the four currently most popular pathways for discussion and introduced the molecular mechanisms mediated by alkaloids in different signaling pathways, including the NF-kB signaling pathway, PI3K/AKT signaling pathway, MAPK signaling pathway, and P53 signaling pathway. The research progress of alkaloids related to tumor signal transduction pathways and the realization of alkaloids as cancer prevention drugs by targeting signal pathways remains.
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http://dx.doi.org/10.2174/1389557521666211007114935DOI Listing
October 2021

Challenges of Sustaining Malaria Community Case Management in 81 Township Hospitals along the China-Myanmar Border Region - Yunnan Province, China, 2020.

China CDC Wkly 2021 Apr;3(17):355-359

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research); NHC Key Laboratory of Parasite and Vector Biology; WHO Collaborating Centre for Tropical Diseases; National Center for International Research on Tropical Diseases, Shanghai, China.

The health workforce at township hospitals in the China-Myanmar border region has played a key role in sustaining Community case management of malaria (CCMm), while few studies have investigated their performance and challenges.



Sustaining CCMm in the region was subject to the following major challenges: insufficient training on malaria diagnosis and testing, lacking necessary and timely treatment for patients, and risks of instability among the malaria workforce.



These challenges called for the national and provincial authorities to provide regular trainings and intensive supervision to strengthen malaria diagnosis and treatment capacity in the region and to set up incentive mechanisms and individual career development paths to sustain the workforce.
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http://dx.doi.org/10.46234/ccdcw2021.097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392891PMC
April 2021

A Case Study on the Disease Burden and Influencing Factors of Imported Malaria Patients in a County-Level Hospital - Guangxi Zhuang Autonomous Region, China, 2016-2019.

China CDC Wkly 2021 Apr;3(17):351-354

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Chinese Center for Tropical Diseases Research; WHO Collaborating Centre for Tropical Diseases; National Center for International Research on Tropical Diseases, Ministry of Science and Technology; Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China.

What Is Already Known On This Topic?: Imported malaria cases endanger people's health and potentially cause local re-transmission, and they may also cause economic loss on patients' families and society as a whole.

What Is Added By This Report?: This is the first report to focus on the disease burden of a case study incurred by the imported malaria. The results indicated that the median direct medical cost was 2,904.4 CNY and the median indirect cost was 242.0 CNY for a patient's hospitalization. The economic cost was related to age, time between onset and diagnosis, and days of stay in hospital.

What Are The Implications For Public Health Practice?: This study analyzed the main causes based on both direct and indirect economic loss of imported malaria cases to provide general information for the evaluation of the disease burden of imported malaria patients and shed light on the rational allocation of medical resources.
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http://dx.doi.org/10.46234/ccdcw2021.096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392892PMC
April 2021

Development and Impacts of the Sierra Leone-China Laboratory for Parasitic Diseases Testing and Surveillance.

China CDC Wkly 2021 Apr;3(15):327-330

National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention; Chinese Center for Tropical Diseases Research; WHO Collaborating Centre for Tropical Diseases; National Center for International Research on Tropical Diseases, Ministry of Science and Technology; Key Laboratory of Parasite and Vector Biology, National Health Commission of China, Shanghai, China.

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http://dx.doi.org/10.46234/ccdcw2021.088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393174PMC
April 2021

OIP5-AS1: A fascinating long noncoding RNA in carcinoma.

Curr Pharm Des 2021 Sep 26. Epub 2021 Sep 26.

College of Medical Science, China Three Gorges University, Yichang 443002. China.

Background: It is substantiated that LncRNAs are associated with carcinoma progression. OIP5-AS1 is a tumor-related carcinoma suppressor lncRNA, previously discovered in zebrafish, which is involved in the progression of a variety of cancers, has a regulatory effect on carcinoma, and interacts with miRNA and other biomolecules to affect the physiological and pathological processes of carcinoma cells. This article will discuss the effect of OIP5-AS1 in various cancers and its regulatory mechanism.

Methods: This paper summarized and analyzed OIP5-AS1, which functions on the germination and progression of carcinoma and its regulatory mechanism. Meanwhile, the related research was retrieved and collected by PubMed system. Result:OIP5-AS1 is overexpressed in various tumors, which regulates and controls tumor growth and participates in tumor progression, including breast carcinoma, ovarian carcinoma, cervical carcinoma, lung carcinoma, and laryngeal squamous cell gastric carcinoma, hepatocellular carcinoma. The research evidence proves that OIP5-AS1 takes part in carcinoma proliferation, growth, migration, invasion, and apoptosis.

Conclusion: OIP5-AS1 probably can be an effective biomarker or a potential therapeutic target in multiple tumors.
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http://dx.doi.org/10.2174/1381612827666210927105558DOI Listing
September 2021

Sustaining a Multidisciplinary, Single-Institution, Postoperative Mobilization Clinical Practice Improvement Program Following Hepatopancreatobiliary Surgery During the COVID-19 Pandemic: Prospective Cohort Study.

JMIR Perioper Med 2021 Oct 6;4(2):e30473. Epub 2021 Oct 6.

Department of General Surgery, Tan Tock Seng Hospital, Singapore, Singapore.

Background: The Enhanced Recovery After Surgery (ERAS) protocol has been recently extended to hepatopancreatobiliary (HPB) surgery, with excellent outcomes reported. Early mobilization is an essential facet of the ERAS protocol, but compliance has been reported to be poor. We recently reported our success in a 6-month clinical practice improvement program (CPIP) for early postoperative mobilization. During the COVID-19 pandemic, we experienced reduced staffing and resource availability, which can make CPIP sustainability difficult.

Objective: We report outcomes at 1 year following the implementation of our CPIP to improve postoperative mobilization in patients undergoing major HPB surgery during the COVID-19 pandemic.

Methods: We divided our study into 4 phases-phase 1: before CPIP implementation (January to April 2019); phase 2: CPIP implementation (May to September 2019); phase 3: post-CPIP implementation but prior to the COVID-19 pandemic (October 2019 to March 2020); and phase 4: post-CPIP implementation and during the pandemic (April 2020 to September 2020). Major HPB surgery was defined as any surgery on the liver, pancreas, and biliary system with a duration of >2 hours and with an anticipated blood loss of ≥500 ml. Study variables included length of hospital stay, distance ambulated on postoperative day (POD) 2, morbidity, balance measures (incidence of fall and accidental dislodgement of drains), and reasons for failure to achieve targets. Successful mobilization was defined as the ability to sit out of bed for >6 hours on POD 1 and ambulate ≥30 m on POD 2. The target mobilization rate was ≥75%.

Results: A total of 114 patients underwent major HPB surgery from phases 2 to 4 of our study, with 33 (29.0%), 45 (39.5%), and 36 (31.6%) patients in phases 2, 3, and 4, respectively. No baseline patient demographic data were collected for phase 1 (pre-CPIP implementation). The majority of the patients were male (n=79, 69.3%) and underwent hepatic surgery (n=92, 80.7%). A total of 76 (66.7%) patients underwent ON-Q PainBuster insertion intraoperatively. The median mobilization rate was 22% for phase 1, 78% for phases 2 and 3 combined, and 79% for phase 4. The mean pain score was 2.7 (SD 1.0) on POD 1 and 1.8 (SD 1.5) on POD 2. The median length of hospitalization was 6 days (IQR 5-11.8). There were no falls or accidental dislodgement of drains. Six patients (5.3%) had pneumonia, and 21 (18.4%) patients failed to ambulate ≥30 m on POD 2 from phases 2 to 4. The most common reason for failure to achieve the ambulation target was pain (6/21, 28.6%) and lethargy or giddiness (5/21, 23.8%).

Conclusions: This follow-up study demonstrates the sustainability of our CPIP in improving early postoperative mobilization rates following major HPB surgery 1 year after implementation, even during the COVID-19 pandemic. Further large-scale, multi-institutional prospective studies should be conducted to assess compliance and determine its sustainability.
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http://dx.doi.org/10.2196/30473DOI Listing
October 2021

TBC1D3 family is a prognostic biomarker and correlates with immune infiltration in kidney renal clear cell carcinoma.

Mol Ther Oncolytics 2021 Sep 10;22:528-538. Epub 2021 Jul 10.

Department of Hematology, the Affiliated Hospital of Jiangnan University, Wuxi 124122, China.

The TBC1D3 family is overexpressed in many cancers, including kidney renal clear cell carcinoma (KIRC), which is associated with tumor-infiltrating lymphocytes. However, the expression and prognosis of TBC1D3 family and tumor-infiltrating lymphocytes in KIRC remain unknown. In the present study, we systematically explored and validated the expression and prognostic value of TBC1D3 family expression in KIRC using multiple public databases. In addition, the function of the TBC1D3 family members and the correlations between TBC1D3 family expression and KIRC immune infiltration levels were investigated. We found that TBC1D3 family members were rarely mutated (less than 5 frequencies). TBC1D3 family was overexpressed in KIRC; high expression of the TBC1D3 family members was correlated with poor prognosis. In addition, TBC1D3D may positively regulate proliferation, and overexpression of TBC1D3 promoted clear cell renal cell carcinoma proliferation . In terms of immune infiltrating levels, TBC1D3 family expression was positively associated with CD4 T cells infiltrating levels. These findings suggest that the TBC1D3 family expression is correlated with prognosis and immune infiltrating levels. Therefore, the TBC1D3 family can be used as a biomarker for KIRC and a prognostic biomarker for determining the prognosis and immune infiltration levels in KIRC.
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http://dx.doi.org/10.1016/j.omto.2021.06.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433061PMC
September 2021

BMSCs-exosomes containing GDF-15 alleviated SH-SY5Y cell injury model of Alzheimer's disease via AKT/GSK-3β/β-catenin.

Brain Res Bull 2021 Sep 16;177:92-102. Epub 2021 Sep 16.

Department of Neurosurgery, Zhongnan Hospital of Wuhan University, No.169, East Lake Road, Wuhan 430071, Hubei Province, PR China. Electronic address:

Background: Mesenchymal stem cells (MSCs) therapy has great potential for Alzheimer's disease (AD) treatment. Here, we investigated the roles of BMSCs-exosomes containing growth differentiation factor-15 (GDF-15) in regulating SH-SY5Y cell injury in AD.

Methods: The SH-SY5Y cell injury model was constructed by treating SH-SY5Y cells with 10 μM Aβ. GDF-15 expression was assessed using qRT-PCR and western blot. CCK8 assay and flow cytometry assay were employed to elevate cell proliferation and apoptosis, respectively. The expression levels of inflammatory factors (IL-6, IL-1β, TNFα and IL-8) and Aβ were detected using ELISA. Besides, the levels of apoptosis-related proteins and AKT pathway-related proteins were determined using western blot.

Results: Our results displayed that BMSCs-EVs treatment elevated cell viability, while suppressed cell apoptosis and inflammation in Aβ-treated SH-SY5Y cells. Exosomes secreted by BMSCs after GDF-15 silence lost the ability to restore Aβ-induced SH-SY5Y cell damage. GDF-15 treatment restored Aβ-induced SH-SY5Y cell damage, while it was eliminated by AKT pathway inhibition. BMSCs-exosomes containing GDF-15 upregulated NEP and IDE via activation of AKT/GSK-3β/β-catenin pathway, thereby degrading Aβ protein to relieve SH-SY5Y cell damage.

Conclusion: BMSCs-exosomes containing GDF-15 alleviated SH-SY5Y cell damage via AKT/GSK-3β/β-catenin. Our work confers a promising therapeutic strategy for AD.
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http://dx.doi.org/10.1016/j.brainresbull.2021.09.008DOI Listing
September 2021

Radix Tetrastigma Extracts Enhance the Chemosensitivity in Triple-Negative Breast Cancer Via Inhibiting PI3K/Akt/mTOR-Mediated Autophagy.

Clin Breast Cancer 2021 Aug 4. Epub 2021 Aug 4.

Department of Breast Surgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, 310006, China. Electronic address:

Objective: Drug resistance in tumors is one of the major factors that leads to chemotherapy failure. This study aims to investigate the effect of Radix Tetrastigma extracts (RTEs) on Taxol-induced autophagy and the chemosensitivity against drug resistance in triple-negative breast cancer (TNBC).

Methods: Taxol-resistant MDA-MB-468 (MDA-MB-468/Taxol) cells were induced and treated with RTEs and/or Taxol. Mice were subcutaneously inoculated with MDA-MB- 468/Taxol cells to establish xenograft models. The associated protein levels were measured by western blotting. Flow cytometry, CCK-8 and EdU assay were performed to detect cell apoptosis, viability, and proliferation, respectively.

Results: In MDA-MB-468/Taxol cells, RTEs & Taxol treatment increased cell apoptosis, reduced cell viability and proliferation, up-regulated anti-autophagy marker LC3I/LC3II ratio, and enhanced mTOR level. With RTEs & Taxol treatment, mTOR silencing downregulated LC3I/LC3II ratio, increased cell viability and proliferation, and reduced cell apoptosis, while mTOR overexpression showed the opposite results. PI3K inhibitor reduced AKT and mTOR levels, and the effects on cell activities were similar to the results of mTOR silencing. After RTEs & Taxol injection, xenograft tumor was smaller, and AKT, mTOR, LC3I/LC3II ratio and apoptotic marker cleaved caspase-3 were increased.

Conclusion: RTEs enhanced the chemosensitivity of resistant TNBC cells to Taxol through inhibiting PI3K/Akt/mTOR-mediated autophagy.

Micro: RTEs exerted anti-tumor effects in various cancers, and this study determined its role in TNBC. Taxol-resistant MDA-MB-468 cells were induced and xenograft models were established. We found that RTEs inhibited autophagy of MDA-MB-468/Taxol cells and reduced tumor growth. Inhibition of PI3K/Akt/mTOR pathway promoted autophagy of MDA-MB-468/Taxol cells. We may provide a new potential strategy for TNBC treatment.
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http://dx.doi.org/10.1016/j.clbc.2021.07.015DOI Listing
August 2021

The effects of insulin therapy on mortality in diabetic patients undergoing percutaneous coronary intervention.

Ann Transl Med 2021 Aug;9(16):1294

Cardiovascular Department, Tianjin Medical University General Hospital, Tianjin, China.

Background: A growing number of studies have reported insulin therapy to be associated with a higher incidence of major adverse cardiac events in diabetic patients with coronary artery disease. However, the relationship between insulin use and the clinical outcomes of patients with diabetes who undergoing percutaneous coronary intervention (PCI) has not been fully clarified.

Methods: A total of 1,069 consecutive patients with diabetes who underwent PCI were enrolled and divided into 2groups: oral hypoglycemic agents (OHA) group (709 patients) and insulin therapy group (360 patients). The primary and secondary endpoints of this study were all-cause death and cardiac death, respectively.

Results: At baseline, the maximum creatine kinase-MB (CK-MB), plasma glucose, hemoglobin A1c, high-sensitivity C-reactive protein (CRP), and creatinine levels were higher, while the left ventricular ejection fraction (LVEF) was lower, in the insulin therapy group than in the OHA group. After propensity score matching of baseline characteristics, for patients treated with insulin, the odds ratios of death from any cause in hospital, within 1 year of surgery, and within 2 years of surgery were 12.03 (95% CI: 1.486-97.33, P=0.020), 10.33 (95% CI: 1.21-88.12, P=0.033), and 2.99 (95% CI: 1.22-7.31, P=0.016), respectively, and the odds ratios of cardiac death were 10.33 (95% CI: 1.21-88.12, P=0.033), 6.49 (95% CI: 1.33-31.59, P=0.021), and 5.27 (95% CI: 1.45-19.13, P=0.011), respectively. Generalized estimating equations analysis showed the odds ratios of all-cause death and cardiac death for insulin-treated patients to be 4.77 (95% CI: 1.76-12.95, P=0.002) and 5.38 (95% CI: 1.29-22.96, P=0.023), respectively.

Conclusions: Compared with OHA, insulin therapy significantly increases the risk of in-hospital all-cause and cardiac death in patients with diabetes undergoing PCI, and the risk remains significantly at least 2 years after surgery.
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http://dx.doi.org/10.21037/atm-21-1911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422120PMC
August 2021

An l-rhamnose-binding lectin from Nile tilapia (Oreochromis niloticus) possesses agglutination activity and regulates inflammation, phagocytosis and respiratory burst of monocytes/macrophages.

Dev Comp Immunol 2022 Jan 11;126:104256. Epub 2021 Sep 11.

Guangdong Provincial Key Laboratory for Healthy and Safe Aquaculture, Guangdong Provincial Engineering Technology Research Center for Environmentally-Friendly Aquaculture, School of Life Sciences, South China Normal University, Guangzhou, 510631, PR China. Electronic address:

Rhamnose-binding lectins (RBLs), a Ca-independent lectin family, are widely present in vertebrates and invertebrates, which involve in the innate immune response. However, the functional characterization and related regulation mechanisms of RBLs remain unclear in teleost fish. In this study, an l-rhamnose-binding lectin-like (OnRBL-L) was identified and functionally characterized from Nile tilapia (Oreochromis niloticus). The open reading frame of OnRBL-L is 678 bp encoding 225 aa. The sequence of OnRBL-L has relatively conservative characteristic peptide motifs, including YGR, DPC, and KYL-motif. Expression analysis showed that OnRBL-L was abundantly distributed in intestine tissue, and widely existed in all detected tissues. Meanwhile, the expression of OnRBL-L increased significantly in vivo (liver, spleen, head kidney, intestine, gills and peripheral blood) and in vitro (monocytes/macrophages) following challenges with two important tilapia pathogenic bacteria Streptococcus agalactiae and Aeromonas hydrophila. In addition, the recombinant OnRBL-L was found to bind and agglutinate S. agalactiae and A. hydrophila. Furthermore, OnRBL-L could participate in non-specific cellular immune defense, including reducing the expression of pro-inflammatory factors (IL-6、IL-8 and TNF-α), and enhancement of the phagocytosis and respiratory burst of MO/MФ. Overall, our results provide new insights into the understanding of RBL as an important pattern recognition molecule and regulator in non-specific cell immunity in an early vertebrate.
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http://dx.doi.org/10.1016/j.dci.2021.104256DOI Listing
January 2022

Hepatitis C virus induces oxidation and degradation of apolipoprotein B to enhance lipid accumulation and promote viral production.

PLoS Pathog 2021 Sep 7;17(9):e1009889. Epub 2021 Sep 7.

NHC Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Hepatitis C virus (HCV) infection induces the degradation and decreases the secretion of apolipoprotein B (ApoB). Impaired production and secretion of ApoB-containing lipoprotein is associated with an increase in hepatic steatosis. Therefore, HCV infection-induced degradation of ApoB may contribute to hepatic steatosis and decreased lipoprotein secretion, but the mechanism of HCV infection-induced ApoB degradation has not been completely elucidated. In this study, we found that the ApoB level in HCV-infected cells was regulated by proteasome-associated degradation but not autophagic degradation. ApoB was degraded by the 20S proteasome in a ubiquitin-independent manner. HCV induced the oxidation of ApoB via oxidative stress, and oxidized ApoB was recognized by the PSMA5 and PSMA6 subunits of the 20S proteasome for degradation. Further study showed that ApoB was degraded at endoplasmic reticulum (ER)-associated lipid droplets (LDs) and that the retrotranslocation and degradation of ApoB required Derlin-1 but not gp78 or p97. Moreover, we found that knockdown of ApoB before infection increased the cellular lipid content and enhanced HCV assembly. Overexpression of ApoB-50 inhibited lipid accumulation and repressed viral assembly in HCV-infected cells. Our study reveals a novel mechanism of ApoB degradation and lipid accumulation during HCV infection and might suggest new therapeutic strategies for hepatic steatosis.
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http://dx.doi.org/10.1371/journal.ppat.1009889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448335PMC
September 2021

Corrigendum: Effect of a Topical Nonsteroidal Anti-Inflammatory Drug (0.1% Pranoprofen) on VEGF and COX-2 Expression in Primary Pterygium.

Front Pharmacol 2021 13;12:743733. Epub 2021 Aug 13.

Department of Ophthalmology, Nanjing Lishui District People's Hospital, Lishui Branch of Southeast University Affifiliated Zhongda Hospital, Nanjing, China.

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http://dx.doi.org/10.3389/fphar.2021.743733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415084PMC
August 2021

Antiviral and virucidal activities of lycorine on duck tembusu virus in vitro by blocking viral internalization and entry.

Poult Sci 2021 Oct 25;100(10):101404. Epub 2021 Jul 25.

College of Animal Science and Technology, Anhui Agricultural University, Hefei 230036, China; Anhui Province Key Laboratory of Veterinary Pathobiology and Disease Control, Hefei 230036, China. Electronic address:

Duck tembusu virus (DTMUV) was firstly identified in 2010 in China; since then, it has caused enormous economic loss to breeding industry. Great efforts have been made to develop drugs and vaccines against DTMUV. However, current available vaccines or anti-DTMUV drugs are consistently inefficient. Hence, various more broadly effective drugs have become important for the treatment of DTMUV infection; among these, lycorine, one of the important sources of active alkaloids, is a promising example. Nevertheless, it is not known whether lycorine has any antiviral activities against DTMUV. Therefore, the purpose of the present study is to investigate the anti-DTMUV abilities of lycorine. The cytotoxicity of lycorine was evaluated on BHK-21 cells by CCK-8 assay, and its antiviral effect against DTMUV was examined by real-time PCR assays, virus titer determination, Western blot and immunofluorescence (IFA) assays, respectively. Furthermore, the underlying mechanisms of the anti-DTMUV effects of lycorine were also investigated. The results indicated that the highest nontoxicity concentration of lycorine on BHK-21 cells was 5 µM. Lycorine possessed the antiviral ability against DTMUV on BHK-21 cells, as demonstrated by the reduction of virus titers and copy numbers in vitro. Western blot and IFA analysis showed the inhibitory effect of lycorine on DTMUV envelope (E) protein expression. Moreover, using time-of-addition assays, we found that lycorine displays its antivirus and virucidal activities through blocking viral internalization and entry in vitro. Taken together, our findings firstly demonstrate the antiviral activities of lycorine against DTMUV, suggesting that lycorine can be a potential drug for the treatment of DTMUV infection.
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http://dx.doi.org/10.1016/j.psj.2021.101404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414183PMC
October 2021

HbA combined with glycated albumin or 1,5-anhydroglucitol improves the efficiency of diabetes screening in a Chinese population.

Diabet Med 2021 Sep 2:e14685. Epub 2021 Sep 2.

Department of Endocrinology, School of Medicine, Zhongda Hospital, Institute of Diabetes, Southeast University, Nanjing, China.

Aims: This study aimed to evaluate the ability of HbA combined with glycated albumin (GA) or 1,5-anhydroglucitol (1,5-AG) to detect diabetes in residents of Jiangsu, China.

Methods: The oral glucose tolerance test (OGTT) was performed on 2184 people in Jiangsu. HbA , GA, 1,5-AG and other serum biochemical parameters were measured. Receiver operating characteristic curves were plotted to determine the optimal thresholds of HbA , GA and 1,5-AG according to the Youden index.

Results: (1) The optimal thresholds of HbA , GA and 1,5-AG for the screening of diabetes were ≥45 mmol/mol (6.3%), ≥13.0% and ≤23.0 μg/ml, respectively. (2) The sensitivities of HbA combined with GA and 1,5-AG were both 85%, higher than that of HbA (70%, p < 0.001).

Conclusions: This study is suitable for cases where plasma glucose is unavailable. Among the residents of Jiangsu, HbA combined with GA or 1,5-AG can improve the sensitivity of diabetes screening, reduce the miss rate and save the use of OGTT. GA and 1,5-AG are superior in individuals with mild glucose metabolism disorder. GA enhances the detection of diabetes in the nonobese, and 1,5-AG enhances the detection in those with hyperuricaemia.
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http://dx.doi.org/10.1111/dme.14685DOI Listing
September 2021

The Regulatory Role of Both MBNL1 and MBNL1-AS1 in Several Common Cancers.

Curr Pharm Des 2021 Aug 29. Epub 2021 Aug 29.

College of Medical Science, China Three Gorges University, Yichang 443002. China.

Background: MBNL1, a protein encoded by q25 gene on chromosome 3, belongs to the tissue-specific RNA metabolic regulation family, which controls RNA splicing.[1]MBNL1 formed in the process of development drive large transcriptomic changes in cell differentiation,[2] it serves as a kind of tumor differentiation inhibitory factor.MBNL1 has a close relationship with cancer, comprehensive analysis, [3]found that breast cancer, leukemia, stomach cancer, esophageal adenocarcinoma, glial cell carcinoma and another common tumor in the cut, and cut in Huntington's disease. But MBNL1 plays a promoting role in cervical cancer, is contradictory in colorectal cancer, It promotes colorectal cancer cell proliferation, On the other hand, it inhibits its metastasis, so it is an important physiological marker in many cancers. When we integrated the role of MBNL1 protein in various tumors, we found that its antisense RNA, MBNL1-AS1, had a good inhibitory effect in several colorectal cancer, non-small cell lung cancer, and gastric cancer.

Objective: To elucidate the expression of MBNL1 and MBNL1-AS1 in various tumors, and to search for their physiological markers.

Methods: It was searched by the PUMUB system and summarized its expression in various cancers.

Results: MBNL1 was down-regulated, leukemia, breast cancer, glioblastoma, gastric cancer, overall survival rate, recurrence, metastasis increased. While the metastasis of colon cancer decreased, proliferation was promoted, and the effect of both was promoted for cervical cancer.MBNL1-AS1 was down-regulated, and the overall survival rate, recurrence, and metastasis of lung cancer, colorectal cancer, and bladder cancer increased.

Conclusion: MBNL1 may be an important regulator of cancer, and MBNL1-AS1 is a better tumor suppressor.
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http://dx.doi.org/10.2174/1381612827666210830110732DOI Listing
August 2021

High-grade endometrial stromal sarcoma of the endocervix: An extremely rare case report.

Int J Gynaecol Obstet 2021 Aug 21. Epub 2021 Aug 21.

Hebei General, Hospital, Shijiazhuang, Hebei, China.

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http://dx.doi.org/10.1002/ijgo.13891DOI Listing
August 2021

BAG2 mediates coelomocyte apoptosis in Vibrio splendidus challenged sea cucumber Apostichopus japonicus.

Int J Biol Macromol 2021 Oct 18;189:34-43. Epub 2021 Aug 18.

Key Laboratory of Applied Marine Biotechnology, Ministry of Education, Ningbo University, Ningbo 315211, China; Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China; Collaborative Innovation Center for Zhejiang Marine High-efficiency and Healthy Aquaculture, Ningbo University, Ningbo 315211, China. Electronic address:

MicroRNAs (miRNAs) are closely related to the occurrence, development, and immune response of diseases. BCL2-associated athanogene 2 (BAG2) is a member of the BAG family that functions in diverse cellular processes, including cell death, differentiation, and cell division. In this study, we cloned the cDNA full-length of sea cucumber (Apostichopus japonicus) BAG2 (AjBAG2) and confirmed it is an anti-apoptotic protein in vitro and in vivo during Vibrio splendidus infection. Moreover, we identified a perfect complementarity between miR-375 and the 3'-untranslated region (UTR) sequence of AjBAG2. The miR-375 expression decreased the luciferase activity dose-dependently when co-transfected with the AjBAG2 3'-UTR-luciferase reporter containing the miR-375 target site in epithelioma papulosum cyprini (EPC) cells. This inhibition was partially recovered by a miR-375 specific inhibitor. The mRNA and protein levels of AjBAG2 were opposite to that of coelomocytes in challenged sea cucumber when treated with miR-375 mimics or inhibitors. Additionally, miR-375 expression induced coelomocytes apoptosis and blocked the anti-apoptotic activity of AjBAG2. Our data demonstrated that AjBAG2 is an anti-apoptotic protein during V. splendidus infection and this function can be inhibited by miR-375 in sea cucumbers.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.08.097DOI Listing
October 2021

The therapeutic value and molecular mechanisms of lncRNA FENDRR in human cancer.

Curr Pharm Des 2021 08 19. Epub 2021 Aug 19.

College of Medical Science, China Three Gorges University, Yichang. China.

Background: Long noncoding RNA (lncRNA) fetal-lethal non-coding developmental regulatory RNA (FENDRR), a newly known lncRNA, has been reported to be abnormally expressed in diverse tumors. This review is focused on clarifying the mechanism of FENDRR to regulate the biological process of tumors, affirming its value as a target for tumor therapy.

Methods: The pathophysiological mechanism of FENDRR acting on tumors has been analyzed and summarized by reviewing PubMed.

Results: The expression of lncRNA FENDRR is abnormally altered in clinical cancers, promoting the malignant transformation of a variety of tumors, including colon cancer, cervical cancer, hepatocellular carcinoma, prostate cancer, Malignant melanoma, lung cancer, osteosarcoma, breast cancer, etc. Cellular processions, including proliferation, invasion, apoptosis and migration affected by FENDRR, have been revealed.

Conclusion: Specific evidences for the involvement of LncRNA FENDRR in cancer regulatory processes suggest that FENDRR has the potential to be a biomarker or clinical therapeutic target for malignant tumors.
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http://dx.doi.org/10.2174/1381612827666210820094702DOI Listing
August 2021

[Endogenous protective effects of arachidonic acid epoxygenase metabolites, epoxyeicosatrienoic acids, in cardiovascular system].

Sheng Li Xue Bao 2021 Aug;73(4):617-630

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

The morbidity and mortality of cardiovascular diseases are increasing annually, which is one of the primary causes of human death. Recent studies have shown that epoxyeicosatrienoic acids (EETs), endogenous metabolites of arachidonic acid (AA) via CYP450 epoxygenase, possess a spectrum of protective properties in cardiovascular system. EETs not only alleviate cardiac remodeling and injury in different pathological models, but also improve subsequent hemodynamic disturbances and cardiac dysfunction. Meanwhile, various studies have demonstrated that EETs, as endothelial-derived hyperpolarizing factors, regulate vascular tone by activating various ion channels on endothelium and smooth muscle, which in turn can lower blood pressure, improve coronary blood flow and regulate pulmonary artery pressure. In addition, EETs are protective in endothelium, including inhibiting inflammation and adhesion of endothelial cells, attenuating platelet aggregation, promoting fibrinolysis and revascularization. EETs can also prevent aortic remodeling, including attenuating atherosclerosis, adventitial remodeling, and aortic calcification. Therefore, it is clinically important to study the physiological and pathophysiological effects of EETs in the cardiovascular system to further elucidate the mechanisms, as well as provide new strategy for the prevention and treatment of cardiovascular diseases. This review summarizes the endogenous cardioprotective effects and mechanisms of EETs in order to provide a new insight for research in this field.
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August 2021

[Identification of mouse lines with HA-tagged prostaglandin receptors].

Sheng Li Xue Bao 2021 Aug;73(4):559-570

Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.

Prostaglandins are a class of poly-unsaturated fatty acids-derived bioactive lipids with important physiological function by binding to specific receptors. Prostaglandin receptors lack specific antibodies, which greatly impedes the research on our understanding of the signaling of prostaglandins. The aim of this study was to identify nine mouse lines with amino terminal (-NH2, -N) HA-tagged prostaglandin receptors by using the combination of artificial sperm and CRISPR-Cas9 technology. The guide RNA expression plasmid and labeled targeting vector plasmids were transferred into "artificial sperm cells". The "artificial sperm cells" containing labeled proteins were selected and injected into mouse oocytes, and implanted into pseudopregnant mice to obtain labeled mice. The genomic DNA of the prostaglandin receptor tagged mice was extracted, and the genotypes of mice were detected by PCR method. We also isolated mouse peritoneal macrophages to verify the protein expression of HA-labeled prostaglandin receptor by Western blot. Specific DNA bands were amplified in prostaglandin receptor labeled mice, and specific HA protein bands were detected in macrophage proteins, which was not detected in wild type mice. In summary, we successfully constructed 9 mouse lines with HA-tagged prostaglandin receptors, providing a powerful tool for further study of the pathophysiological functions of prostaglandin signaling both in vivo and in vitro.
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August 2021

-score of some pulsed-wave Doppler indices of right pulmonary artery segments of normal fetuses in the second and third trimestries.

J Matern Fetal Neonatal Med 2021 Aug 15:1-5. Epub 2021 Aug 15.

Ultrasound and Echocardiography Department, Sir Run Run Shaw Hospital, Zhejiang University College of Medicine, Technical Guidance Center for Fetal Echocardiography of Zhejiang Province and Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou, China.

Objective: To establish the -score equation of right pulmonary artery (RPA) segments for some valuable pulse-wave Doppler parameters (PWD) and estimate their reference ranges in normal fetuses.

Methods: Two hundred and seventy-three normal singleton fetuses at 18-38 weeks were enrolled in this fetal echocardiography of a prospective cross-sectional study. The proximal, middle, and distal segments of RPA of pulsed-wave Doppler parameters, such as peak systolic velocity (PSV) and pulsation index (PI) were obtained by using fetal Doppler echocardiography. The mean and standard deviation (SD) of each parameter and gestational age (GA) were analyzed by regression, and the optimal model of -score was established.

Results: There was a significant correlation between fetal pulmonary artery Doppler parameters and gestational age, during the whole pregnancy, PI showed a downward trend with the progress of gestational week, while PSV showed an upward trend. Whether it was the original data or the data converted for the normal distribution of -score, the model that best described the mean value of parameters was quadratic regression. The SDs for PSV of the middle segment was a linear equation, others were constants. From proximal to distal of RPA, PSV showed a decreasing trend while PI showed an increasing trend.

Conclusion: -score models and reference values for some PWD parameters of three segments of RPA were proposed against GA, which may quantitatively assess the flow dynamics of fetal RPA and quantitatively assess fetal lung circulation development and hemodynamic changes.
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http://dx.doi.org/10.1080/14767058.2021.1960974DOI Listing
August 2021

Critical functions of lncRNA DGCR5 in cancers of the digestive system.

Curr Pharm Des 2021 Aug 12. Epub 2021 Aug 12.

College of Medical Science, China Three Gorges University, Yichang 443002. China.

Background: Long non-coding RNAs (lncRNAs) has no protein-coding potential due to the lack of an apparent open reading frame. There is growing evidence that lncRNA DGCR5 has a vital regulatory role in human illnesses' pathological development, particularly in the digestive system's carcinogenesis and progression. Abnormal DGCR5 expression affects different cellular functions such as proliferation, aggression, and metastasis. This paper aims to probe into the pathophysiological functions and molecular mechanisms of DGCR5 in cancers of the digestive system.

Methods: This review summarizes and analyzes the biological functions and mechanisms of lncRNA DGCR5 in digestive system cancers occurrence. Relevant studies were conducted and reviewed by searching PubMed for articles with lncRNA DGCR5 and digestive system cancer as keywords in recent years.

Results: DCGR5, as a novel tumor-related lncRNA, is recently identified to be abnormally expressed in digestive system cancers, such as pancreatic ductal adenocarcinoma, pancreatic cancer, gastric cancer, gallbladder cancer, colorectal cancer, and hepatocellular carcinoma. The role played by DCGR5 is vital and varies in different digestive cancers. Taken together, aberrant expression of DCGR5 regulates the progression of digestive cancers by affecting cancer cell proliferation, aggression, metastasis, and drug resistance.

Conclusion: LncRNA DGCR5 might be a viable marker or a promising therapeutic target in digestive system cancers.
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http://dx.doi.org/10.2174/1381612827666210812130455DOI Listing
August 2021

Effect of Metabolic Health and Obesity Phenotype on Risk of Diabetes Mellitus: A Population-Based Longitudinal Study.

Diabetes Metab Syndr Obes 2021 5;14:3485-3498. Epub 2021 Aug 5.

Key Laboratory of Environment Medicine Engineering of Ministry of Education, Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing, Jiangsu Province, People's Republic of China.

Background: Epidemiologic evidence on body mass index (BMI)-metabolic status phenotypes and diabetes risk remains controversial, especially for metabolically healthy obesity (MHO). We aimed to examine the effect of metabolic health and obesity phenotype on diabetes risk in the Chinese population.

Methods: A population-based cohort study was carried out. The baseline survey was conducted in 2017, with two follow-up visits in 2018 and 2020. Diabetes was defined based on the criteria of the World Health Organization. Robust generalized estimating equation models with a binary distribution using a log link and exchange structure were applied for the pooled analysis sample.

Results: A total sample of 9623 observations was pooled for the longitudinal data analysis. The average follow-up time was 1.64 years per person and the overall incidence density of diabetes was 6.94% person-years. Decreased diabetes risk was found in metabolically healthy overweight phenotype (RR = 0.65; 95% CI = 0.47-0.90) and no significant associations were detected for the MHO individuals (RR = 0.99; 95% CI = 0.63-1.53) compared with those of metabolically healthy normal weight, in contrast to metabolically unhealthy normal weight (MU-NW) (RR = 1.81; 95% CI = 1.28-2.55), metabolically unhealthy overweight (MU-OW) (RR = 2.02; 95% CI = 1.57-2.61) and metabolically unhealthy obesity (MUO) (RR = 2.48; 95% CI = 1.89-3.26) phenotypes. Significant associations between BMI-metabolic status phenotypes and diabetes were found in both males and females.

Conclusion: The MUO phenotype needs to be accorded much more importance. MU-NW and MU-OW are also important component for targeted prevention. Our findings can be targeted for optimizing preventive strategies to mitigate the obviously increased prevalence of diabetes.
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http://dx.doi.org/10.2147/DMSO.S317739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353171PMC
August 2021

Comparison of synchronization between left bundle branch and his bundle pacing in atrial fibrillation patients: An intra-patient-controlled study.

Pacing Clin Electrophysiol 2021 Sep 24;44(9):1523-1531. Epub 2021 Aug 24.

Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310016, China.

Background: His bundle pacing (HBP) is a physiological pacing strategy to preserve the electrical synchrony of ventricular conduction and left ventricular (LV) function. Left bundle branch pacing (LBBP) has emerged as an alternative physiological pacing technique.

Objective: To evaluate cardiac electrical and mechanical synchrony comparing LBBP and HBP in patients with permanent atrial fibrillation (AF).

Methods: Consecutive patients with symptomatic bradycardia and AF were enrolled from January to June of 2019. The cardiac electrical and mechanical synchrony in different pacing mode were evaluated at baseline and after implantation.

Results: Both HBP and LBBP were performed in 20 patients. LBBP significantly widened the QRS duration compared with the intrinsic conduction (113.2 ± 14.5  vs. 96.5 ± 16.2 ms; p = .01), while HBP did not (104.5 ± 22.3  vs. 96.5 ± 16.2 ms; p = .12). Both LBBP and HBP patients had similar LV myocardial strain measurements for the mechanical synchrony evaluation without significant change compared with baseline. There was no significant difference in right ventricular synchrony measurement between LBBP and HBP. Compared to HBP, LBBP had less interventricular synchrony (IMVD, 14.7 ± 9.2  vs. 3.1 ± 12.7 ms, p < .01; Ts-LV-RV, 37.9 ± 10.7  vs. 18.5 ± 10.8 ms, p < .001).

Conclusions: Although LBBP's a physiological pacing mode can achieve a similar cardiac electrical and mechanical synchronization when compared to HBP, LBBP results in modest delay in RV activation, and the clinical implication remains to be studied.
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http://dx.doi.org/10.1111/pace.14331DOI Listing
September 2021
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