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Asian Journal of Andrology 2023年第3期25卷 350-355页

作者： Sobia Dil Asad Khan Ahsanullah Unar Meng-Lei Yang Imtiaz Ali Aurang Zeb Huan Zhang Jian-Teng Zhou Muhammad Zubair Khalid Khan Shun Bai Qing-Hua Shi division of Reproduction and Genetics The First Affiliated Hospital of University of Science and Technology of ChinaSchool of Basic Medical SciencesDivision of Life Sciences and MedicineBiomedical Sciences and Health Laboratory of Anhui ProvinceUniversity of Science and Technology of ChinaHefei 230027China

Multiple morphological abnormalities of the sperm flagella(MMAF)is a severe form of asthenozoospermia categorized by immotile spermatozoa with abnormal flagella in ejaculate.Whole-exome sequencing(WES)is used to detect pathogenic variants in patients with MMAF.In this study,a novel homozygous frameshift variant(c.6158_6159insT)in dynein axonemal heavy chain 8(DNAH8)from two infertile brothers with MMAF in a consanguineous Pakistani family was identified by WES.Reverse transcription-polymerase chain reaction(RT-PCR)confirmed DNAH8 mRNA decay in these patients with the DNAH8 mutation.Hematoxylin–eosin staining and transmission electron microscopy revealed highly divergent morphology and ultrastructure of sperm flagella in these patients.Furthermore,an immunofluorescence assay showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients'spermatozoa.Collectively,our study expands the phenotypic spectrum of patients with DNAH8-related MMAF worldwide.

关键词： DNAH8 gene mutation male infertility multiple morphological abnormalities of the sperm flagella

Microbial sensing in the intestine

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Protein & Cell 2023年第11期14卷 824-860页

作者： Tingting Wan Yalong Wang Kaixin He Shu Zhu division of Life sciences and Medicine The CAS Key Laboratory of Innate Immunity and Chronic DiseaseInstitute of ImmunologySchool of Basic Medical SciencesUniversity of Science and Technology of ChinaHefei 230027China Department of Digestive Disease Division of Life Sciences and MedicineThe First Affiliated Hospital of USTCUniversity of Science and Technology of ChinaHefei 230001China Institute of health and Medicine Hefei Comprehensive National Science CenterHefei 230601China

The gut microbiota plays a key role in host health and disease,particularly through their interactions with the immune system.Intestinal homeostasis is dependent on the symbiotic relationships between the host and the diverse gut microbiota,which is influenced by the highly co-evolved immune-microbiota interactions.The first step of the interaction between the host and the gut microbiota is the sensing of the gut microbes by the host immune system.In this review,we describe the cells of the host immune system and the proteins that sense the components and metabolites of the gut microbes.We further highlight the essential roles of pattern recognition receptors(PRRs),the G protein-coupled receptors(GPCRs),aryl hydrocarbon receptor(AHR)and the nuclear receptors expressed in the intestinal epithelial cells(IECs)and the intestine-resident immune cells.We also discuss the mechanisms by which the disruption of microbial sensing because of genetic or environmental factors causes human diseases such as the inflammatory bowel disease(IBD).

关键词： mucosal immunology pattern recognition receptors protein-coupled receptors intestinal epithelial cells immune cells gut microbiota enteric viruses inflammatory bowel disease

Comparative Analysis of Vaccine Inequity and COVID-19 Transmission Amid the Omicron Variant Among Countries--Six Countries,Asia-Pacific Region,2022

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China CDC weekly 2023年第33期5卷 731-736,I0001-I0006页

作者： Jingli Yang Hannah McClymont David JWarne Liping Wang Wenbiao Hu School of Public health and Social Work Queensland University of TechnologyBrisbaneAustralia College of Earth and Environmental sciences Lanzhou UniversityLanzhou CityGansu ProvinceChina School of Mathematical sciences Queensland University of TechnologyBrisbaneAustralia Centre for Data Science Queensland University of TechnologyBrisbaneAustralia division of Infectious Diseases Chinese Center for Diseases Control and PreventionBeijingChina.

What is already known about this topic?The coronavirus disease 2019(COVID-19)persists as a significant global public health crisis.The predominant strain,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),notably the Omicron variant,continues to undergo mutations.While vaccination is heralded as the paramount solution to cease the pandemic,challenges persist in providing equitable access to COVID-19 vaccines.What is added by this report?The distribution of vaccine coverage exhibited disparities between high-income and middle-income countries,with middle-income countries evidencing lower levels of vaccination.The data further suggested that countries with lesser vaccination levels tended to display a higher case fatality rate.Findings indicated that an increase in population-wide vaccination was effective in mitigating COVID-19 related mortalities.What are the implications for public health practice?The findings of this research underscore the pressing necessity for equitable access to vaccines to effectively mitigate the COVID-19 pandemic within the Asia-Pacific region.

关键词： COV income vaccination

Isolation and identification of an isomeric sildenafil analogue as an adulterant in an instant coffee premix

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Forensic sciences Research 2022年第2期7卷 290-298页

作者： Ahmad Yusri Mohd Yusop Linda Xiao Shanlin Fu Centre for Forensic Science University of Technology SydneyUltimoAustralia Pharmacy Enforcement division Ministry of HealthSelangorMalaysia

The proliferation of adulterated health foods and beverages in the market demands a comprehensive analytical strategy to identify the adulterants,particularly those of isomeric phosphodiesterase 5(PDE5)inhibitors.An instant coffee premix(ICP)purchased from an online retailer was flagged for suspected adulteration through PDE5 inhibition assay.The ICP was then analysed using suspected-target and non-targeted screenings of a liquid chromatography-quadrupole time-of-flight mass spectrometry.Based on these findings,a PDE5 inhibitor initially assigned as compound X was isolated from the ICP by employing a liquid chromatography-diode array detection before its structural elucidation with liquid chromatography-ultraviolet(LC-UV)spectroscopy and nuclear magnetic resonance(NMR)spectroscopy.The suspected-target screening matched the protonated molecule([MþH]þ)precursor ion of compound X at m/z 499.2310 with two suspected analytes that are structural isomers of one another.The fragmentation patterns of compound X were comparable to those analogues in the dithiocarbodenafil group through the non-targeted screening.These findings,complemented by the LC-UV and NMR spectroscopy data,together with the chromatographic separation of related structural isomers,conclude the identity of compound X.To our best knowledge,this is the first study to report the presence of 3,5-dimethylpiperazinyl-dithiodesmethylcarbodenafil in an ICP sample.

关键词： Forensic sciences food adulteration non-targeted screening phosphodiesterase 5 inhibitors structural isomer suspected-target screening

NQO1 Mediates Lenvatinib Resistance by Regulating ROS-induced Apoptosis in Hepatocellular Carcinoma

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Current Medical Science 2024年第1期44卷 168-179页

作者： Wei XUE Ting WANG Wen-jing TIAN Si-qi PANG Hua-feng ZHANG Wei-dong JIA Department of General Surgery The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China Institute of health and Medicine Hefei Comprehensive National Science CenterHefei 230601China The Chinese Academy of sciences Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medical SciencesDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China

Objective Hepatocellular carcinoma(HCC)is the third leading cause of cancer-associated death worldwide.As a first-line drug for advanced HCC treatment,lenvatinib faces a significant hurdle due to the development of both intrinsic and acquired resistance among patients,and the underlying mechanism remains largely unknown.The present study aims to identify the pivotal gene responsible for lenvatinib resistance in HCC,explore the potential molecular mechanism,and propose combinatorial therapeutic targets for HCC management.Methods Cell viability and colony formation assays were conducted to evaluate the sensitivity of cells to lenvatinib and dicoumarol.RNA-Seq was used to determine the differences in transcriptome between parental cells and lenvatinib-resistant(LR)cells.The upregulated genes were analyzed by GO and KEGG analyses.Then,qPCR and Western blotting were employed to determine the relative gene expression levels.Afterwards,the intracellular reactive oxygen species(ROS)and apoptosis were detected by flow cytometry.Results PLC-LR and Hep3B-LR were established.There was a total of 116 significantly upregulated genes common to both LR cell lines.The GO and KEGG analyses indicated that these genes were involved in oxidoreductase and dehydrogenase activities,and reactive oxygen species pathways.Notably,NAD(P)H:quinone oxidoreductase 1(NQO1)was highly expressed in LR cells,and was involved in the lenvatinib resistance.The high expression of NQO1 decreased the production of ROS induced by lenvatinib,and subsequently suppressed the apoptosis.The combination of lenvatinib and NQO1 inhibitor,dicoumarol,reversed the resistance of LR cells.Conclusion The high NQO1 expression in HCC cells impedes the lenvatinib-induced apoptosis by regulating the ROS levels,thereby promoting lenvatinib resistance in HCC cells.

关键词： hepatocellular carcinoma lenvatinib resistance NAD(P)H quinone oxidoreductase 1 reactive oxygen species apoptosis dicoumarol

Lipid-lowering effect of Oroxylum indicum(L.)Kurz extract in hyperlipidemic mice

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Asian Pacific Journal of Tropical Biomedicine 2022年第4期12卷 148-155页

作者： Tanaporn Hengpratom Sajeera Kupittayanant Seekaow Churproong Griangsak Eumkeb division of health and Applied sciences Faculty of SciencePrince of Songkla UniversityThailand School of Preclinical sciences Institute of ScienceSuranaree University of TechnologyNakhon RatchasimaThailand Department of Family Medicine and Community Medicine Institute of MedicineSuranaree University of TechnologyNakhon RatchasimaThailand

Objective:To investigate the effect of Oroxylum indicum fruit extract on high-fat diet-induced hyperlipidemic mice.Methods:The phytochemical composition of Oroxylum indicum fruit extract was determined by liquid chromatographymass spectrometry/mass spectrometry(LC-MS/MS)and gas chromatography-mass spectrometry.Forty-two male mice were used.The mice were divided into six groups:normal control,high-fat diet control,simvastatin treatment(20 mg/kg BW/day),and Oroxylum indicum fruit extract(100,200,300 mg/kg BW/day)treatment groups.Food intake,body weight,serum parameters,lipid profile,and histopathological lesions of the kidney,liver,and epididymal fat were observed.Results:LC-MS/MS results revealed four major components of Oroxylum indicum fruit extract:luteolin,apigenin,baicalein,and oroxylin A.Twenty-seven volatile oils were identified from Oroxylum indicum fruit extract.Daily oral administration of Oroxylum indicum fruit extract at 100 to 300 mg/kg BW/day significantly reduced the body weight,total cholesterol,triglyceride,and low-density lipoprotein cholesterol level(P<0.05),whereas high-density lipoprotein cholesterol was higher than the high-fat diet control group.Treatment with 300 mg/kg BW/day Oroxylum indicum fruit extract reduced the pathological lesion and prevented fat accumulation in the kidney and liver.Conclusions:Oroxylum indicum fruit extract has hypolipidemic effect in hyperlipidemic mice,and the active ingredients of Oroxylum indicum fruit extract,both flavonoids and volatile oils,should be further explored as an antihyperlipidemic agent.

关键词： Oroxylum indicum Hyperlipidemia Lipid-lowering effect Extract Mice Anti-adipogenesis Antihyperlipidemic Flavonoids Volatile oils

Berberine enhances antidiabetic effects and attenuates untoward effects of canagliflozin in streptozotocin-induced diabetic mice

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Chinese Journal of Natural Medicines 2016年第7期14卷 518-526页

作者： TIAN Cai-Ming JIANG Xin OUYANG Xiao-Xi ZHANG Ya-Ou XIE Wei-Dong Department of chemistry Tsinghua University Shenzhen Key Lab of health Science and technology Division of Life Science & Health Graduate School at ShenzhenTsinghua University School of Life sciences Tsinghua University

The present study aimed at determining whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus. Streptozotocin-induced diabetic mice were introduced, and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated. Our results showed that berberine combined with canagliflozin(BC) increased reduction of fasting and postprandial blood glucose, diet, and water intake compared with berberine or canagliflozin alone. Interestingly, BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone. In addition, BC showed increased phosphorylated 5' AMP-activated protein kinase(p AMPK) expression and decreased tumor necrosis factor alpha(TNFα) levels in kidneys, compared with berberine or canagliflozin alone. These results indicated that BC was a stronger antidiabetic than berberine or canagliflozin alone with less negative side effects on the kidneys in the diabetic mice. The antidiabetic effect was likely to be mediated by synergically promoting the expression of p AMPK and reducing the expression of TNFα in kidneys. The present study represented the first report that canagliflozin combined with berberine was a promising treatment for diabetes mellitus. The exact underlying mechanisms of action should be investigated in future studies.

关键词： Canagliflozin Berberine Diabetes mellitus AMP-activated protein kinase Sodium-glucose cotransporter-2

From Bench to the Clinic: The Path to Translation of Nanotechnology-Enabled mRNA SARS-CoV-2 Vaccines

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Nano-Micro Letters 2022年第3期14卷 1-31页

作者： Diana O.Lopez‑Cantu Xichi Wang Hector Carrasco‑Magallanes Samson Afewerki Xingcai Zhang Joseph V.Bonventre Guillermo U.Ruiz‑Esparza division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA Division of Health Sciences and Technology Harvard University-Massachusetts Institute of TechnologyBostonMA 02115USA division of Renal Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA Tecnologico de Monterrey School of Engineering and Sciences64849 MonterreyNLMexico Department of Cardiovascular Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022People’s Republic of China Harvard T.H.Chan School of Public health BostonMA 02115USA Tecnologico de Monterrey School of Medicine and Health Sciences64849 MonterreyNLMexico John A.Paulson School of Engineering and Applied sciences Harvard UniversityCambridgeMA 02138USA School of Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA

During the last decades,the use of nanotechnology in med icine has effectively been translated to the design of drug delivery systems,nanostructured tissues,diagnostic platforms,and novel nanomaterials against several human diseases and infectious pathogens.Nanotechnology-enabled vaccines have been positioned as solutions to mitigate the pandemic outbreak caused by the novel pathogen severe acute respiratory syndrome coronavirus 2.To fast-track the development of vaccines,unprecedented industrial and academic collaborations emerged around the world,resulting in the clinical translation of effective vaccines in less than one year.In this article,we provide an overview of the path to translation from the bench to the clinic of nanotechnology-enabled messenger ribonucleic acid vaccines and examine in detail the types of delivery systems used,their mechanisms of action,obtained results during each phase of their clinical development and their regulatory approval process.We also analyze how nanotechnology is impacting global health and economy during the COVID-19 pandemic and beyond.

关键词： Nanovaccines mRNA Coronavirus SARS-CoV-2 COVID-19

Structural and dynamic properties of the YTH domain in complex with N^(6)-methyladenosine RNA studied by accelerated molecular dynamics simulations

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Quantitative Biology 2023年第1期11卷 72-81页

作者： Mingwei Li Guanglin Chen Zhiyong Zhang MOE Key Laboratory for Membraneless Organelles&Cellular Dynamics National Science Center for Physical Sciences at MicroscaleDivision of Life Sciences and Medicineand Biomedical Sciences and Health Laboratory of Anhui ProvinceUniversity of Science and Technology of ChinaHefei 230026China Department of Physics University of Science and Technology of ChinaHefei 230026China

Background:N^(6)-methyladenosine(m^(6)A)modifications of mRNA and long non-coding RNA(lncRNAs)are known to play a significant role in regulation of gene expression and organismal development.Besides writer and eraser proteins of this dynamic modification,the YT521-B homology(YTH)domain can recognize the modification involved in numerous cellular processes.The function of proteins containing YTH domain and its binding mode with N^(6)-methyladenosine RNA has attracted considerable attention.However,the structural and dynamic characteristics of the YTH domain in complex with m^(6)A RNA is still unknown.Method:This work presents results of accelerated molecular dynamics(aMD)simulations at the timescale of microseconds.Principal component analysis(PCA),molecular mechanics generalized Born surface area(MM/GBSA)calculations,contact analysis and contact-based principal component analysis(conPCA)provide new insights into structure and dynamics of the YTH-RNA complex.Results:The aMD simulations indicate that the recognition loop has a larger movement away from the binding pocket in the YTH-A3 RNA than that in the YTH-m^(6)A3 RNA.In aMD trajectories of the apo YTH,there is a significant close-open transition of the recognition loop,that is to say,the apo YTH can take both the closed and open structure.We have found that the YTH domain binds more favorably to the methylated RNA than the nonmethylated RNA.The per-residue free energy decomposition and conPCA suggest that hydrophobic residues including W380,L383-V385,W431-P434,M437,and M441-L442,may play important roles in favorable binding of the m^(6)A RNA to the YTH domain,which is also supported by aMD simulations of a double mutated system(L383A/M437A).Conclusion:The results are in good agreement with higher structural stability of the YTH-m^(6)A RNA than that of the YTH-A3 RNA.The addition of a methylation group on A3 can enhance its binding to the hydrophobic pocket in the YTH domain.Our simulations support a‘conformational selection’mechanism between the YTH-RNA binding

关键词： RNA methylation YTH-m^(6)A3 RNA principal component analysis(PCA) binding free energy contactbased PCA

Psychological interventions for adherence, metabolic control, and coping with stress in adolescents with type 1 diabetes:a systematic review

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World Journal of Pediatrics 2020年第5期16卷 456-470页

作者： Yousef M.Aljawarneh Nesreen M.Al-Qaissi Hana Y.Ghunaim health sciences division School of NursingHigher Colleges of TechnologyP.O.Box 1626FujairahUnited Arab Emirates Higher Colleges of technology P.O.Box 1626FujairahUnited Arab Emirates Fatima College of health sciences Institute of Applied TechnologyP.O.Box 24162Al AinUnited Arab Emirates

Background The aim of this review was to summarize and identify the variations in the effectiveness of psychological interventions on adherence,metabolic control,and coping with stress in adolescents with type 1 diabetes(T1D).Methods An electronic search of literature was performed using PubMed(NLM),Embase(Ovid),CINAHL Plus(EBSCO-host),PsycINFO(Ovid),and Google Scholar.The search was limited to include articles reported the effect of one of the psychological interventions:cognitive behavioral therapy(CBT),coping skills training(CST),stress management,or psychotherapy intervention.The report included peer-reviewed articles published in English from January 1990 until May 2019in adolescents with T1D,and summarizes the results of 24 studies that met the inclusion criteria.Results Psychological interventions showed differential effects on adherence,metabolic control,and coping with stress in adolescents with T1D.Behavioral interventions using principles of CBT appear to have a superior positive effect on regimen adherence compared with other types of psychological protocols.In contrast,metabolic control was significantly improved with the implementation of CST and some forms of CBT.Stress management and psychotherapy interventions showed significant promises for adolescents to cope with their diabetes-related daily stressors.Conclusions However,the findings may add some promises to diabetes management in adolescents,additional research to understand the effect of these interventions is needed.

关键词： Adherence Adolescents Coping Metabolic control Type 1 diabetes