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Structure-based design and optimization lead to the identification of novel dihydrothiopyrano[3,2-d]pyrimidine derivatives as potent HIV-1 inhibitors against drug-resistant variants

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1257-1282页

作者： Zhao Wang Heng Zhang Zhen Gao Zihao Sang Erik De Clercq Christophe Pannecouque Dongwei Kang Peng Zhan Xinyong Liu Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Rega Institute for Medical Research Laboratory of Virology and ChemotherapyK.U.LeuvenLeuven B-3000Belgium China-Belgium Collaborative Research center for Innovative Antiviral Drugs of Shandong Province Jinan 250012China suzhou Research Institute Shandong UniversitySuzhou 215123China

With our continuous endeavors in seeking potent anti-HIV-1 agents,we reported here the discovery,biological characterization,and druggability evaluation of a class of nonnucleoside reverse transcriptase *** fully explore the chemical space of the NNRTI-binding pocket,novel series of dihydrothiopyrano[3,2-d]pyrimidines were developed by employing the structure-based design *** of the derivatives were endowed with prominent antiviral activities against HIV-1 wild-type and resistant strains at nanomolar *** them,compound 23h featuring the aminopiperidine moiety was identified as the most potent inhibitor,with EC50values ranging from 3.43 to 21.4 nmol/***,for the challenging double-mutants F227L+V106A and K103N+Y181C,23h exhibited 2.3-to 14.5-fold more potent activity than the first-line drugs efavirenz and ***,the resistance profiles of 23h achieved remarkable improvement compared to efavirenz and *** binding target of 23h was further confirmed to be HIV-1 reverse *** modeling studies were also performed to elucidate the biological evaluation results and give guidance for the optimization ***,no apparent inhibition of the major CYP450 enzymes and hERG channel was observed for *** importantly,23h was characterized by good pharmacokinetic properties and excellent safety in ***,23h holds great promise as a potential candidate for its effective antiviral efficacy and favorable drug-like profiles.

关键词： HIV-1 Reverse transcriptase Dihydrothiopyrano[3,2-d]pyrimidine Antiviral agent

Identification and characterization of human hematopoietic mesoderm

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Science China(Life Sciences) 2024年第2期67卷 320-331页

作者： Yuqi Wen Jingjing Zhao Runqing Zhang Fan Liu Xiaoyuan Chen Dan Wu Mengge Wang Cuicui Liu Pei Su Panpan Meng Yiyue Zhang Xin Gao Lu Wang Hongtao Wang Jiaxi Zhou State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood DiseasesHaihe Laboratory of Cell EcosystemInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China CAMS center for Stem Cell Medicine PUMC Department of Stem Cell and Regenerative MedicineTianjin 300020China Division of Cell Developmental and Integrative BiologySchool of MedicineSouth China University of TechnologyGuangzhou 510006China

The embryonic mesoderm comprises heterogeneous cell subpopulations with distinct lineage *** is unclear whether a bias for the human hematopoietic lineage emerges at this early developmental *** this study,we integrated single-cell transcriptomic analyses of human mesoderm cells from embryonic stem cells and embryos,enabling us to identify and define the molecular features of human hematopoietic mesoderm(HM)cells biased towards hematopoietic *** discovered that BMP4 plays an essential role in HM specification and can serve as a marker for HM ***,BMP4 acts as a downstream target of HDAC1,which modulates the expression of BMP4 by deacetylating its *** of HDAC significantly enhances HM specification and promotes subsequent hematopoietic cell *** conclusion,our study identifies human HM cells and describes new mechanisms for human hematopoietic development.

关键词： hematopoietic mesoderm human pluripotent stem cells human embryos BMP4 HDAC1

Europium-bearing organic framework with excellent X-ray scintillating luminescence

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Journal of Rare Earths 2024年第2期42卷 251-255,I0001页

作者： Yugang Zhang Lanhua Chen Xia Wang Wei Liu Shu'ao Wang State Key Laboratory of Radiation Medicine and Protection School for Radiological and Interdisciplinary Sciences(RAD-X)and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education InstitutionsSoochow UniversitySuzhou215123China School of Environmental and Materials Engineering Yantai UniversityYantai264005China

Two europium-bearing organic frameworks,termed as EuTPO-1 and EuTPO-2(H_(3)TPO=tris(4-carboxylphenyI)-phosphineoxide),are reported in this work.A series of characterizations of EuTPO-1and EuTPO-2,such as X-ray crystallography and photoluminescence spectroscopy,was performed to expatiate their structure and physicochemical *** of them are constructed by dimers of the europium-oxygen subunit of [Eu_(2)O_(16)] and TPO *** from high X-ray stopping attenuation and excellent luminescence efficiency,they emit sufficient luminescence when irradiated with ***,they possess stable light outputs when exposed to high humidities and strong radiation dose,outperforming the commercial scintillator CsI:*** result paves the way for developing new scintillator and enriches the compound of europium-bearing organic framework with X-ray scintillating luminescence.

关键词： Metal-organic frameworks Scintillating material Luminescence efficiency Rare earths

GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines

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World Journal of Stem Cells 2024年第5期16卷 538-550页

作者： Yang-Zhou Jiang Lan-Yue Hu Mao-Shan Chen Xiao-Jie Wang Cheng-Ning Tan Pei-Pei Xue Teng Yu Xiao-Yan He Li-Xin Xiang Yan-Ni Xiao Xiao-Liang Li Qian Ran Zhong-Jun Li Li Chen Laboratory of Radiation Biology Department of Blood TransfusionLaboratory Medicine CenterThe Second Affiliated HospitalThird Military Medical UniversityChongqing 400037China Hematopoietic Acute Radiation Syndrome Medical and Pharmaceutical Basic Research Innovation center Ministry of Education of the People’s Republic of ChinaChongqing 400037China

BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ***,the positive regulators of ANKRD26 are still *** To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 *** Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family *** to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activi

关键词： Ankyrin repeat domain containing 26 GATA binding protein 2 Thrombocytopenia 2 Transcriptional regulation Myeloid-derived cell lines

Association of creatine kinase with Alzheimer’s disease pathology:A cross-sectional study

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Chinese Medical Journal 2024年第1期137卷 117-119页

作者： Yutong Wang Peiyang Gao Hongman Liu Tingyu Wang Jiaming Fan Tingbo Jiang Alzheimer’s Disease Neuroimaging Initiative(ADNI) Beijing Hospital National Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Department of Cardiology The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215000China Institute for Cardiovascular Science of Soochow University SuzhouJiangsu 215000China Department of Neurology Qingdao Municipal HospitalQingdao UniversityQingdaoShandong 266071China Cardiac Function Department the Affiliated Taian City Central Hospital of Qingdao UniversityTaianShandong 271000China Department of Cardiac Surgery The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215000China 不详

To the Editor:Creatine kinase(CK),also called creatine phosphokinase,is primarily located in the cytoplasm and *** can be used to diagnose cardiac diseases such as myocardial infarction,viral myocarditis,and pericarditis because it is a vital kinase directly related to intracellular energy operation,muscle contraction,and adenosine triphosphate(ATP)*** studies have confirmed in recent years that serum biomarkers such as elevated CK are associated with Alzheimer’s disease(AD)and its related pathological protein.[1]Previous research indicated that systemic conditions,particularly cardiovascular and cerebrovascular diseases,are significant risk factors for cognitive impairment,and dysfunction of peripheral organs may also contribute to cognitive decline and AD.[2]However,the connection between CK and AD remains ***,to investigate the association between CK and cerebrospinal fluid(CSF)AD pathology biomarkers,we analyzed data from the Alzheimer’s Disease Neuroimaging Initiative(ADNI),a global multi-centered database.

关键词： Alzheimer pathology organs

Association of Serum Folate and Vitamin B_(12) Concentrations with Obesity in Chinese Children and Adolescents

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Biomedical and Environmental Sciences 2024年第3期37卷 242-253页

作者： ZHU Qian Rang KOK E Dieuwertje BEKELE Hailu Tesfaye MANUSAMA Koen ZHANG Jing Xian XIE Wei ZONG Wen Qi ZUO Hui ZHANG Jian KAMPMAN Ellen DAI Yue Jiangsu Provincial center for Disease Control and Prevention Nanjing 210009JiangsuChina Division of Human Nutrition and Health Wageningen University&ResearchWageningen 176700 AAThe Netherlands School of Public Health Medical College of Soochow UniversitySuzhou 215123JiangsuChina National Institute for Nutrition and Health Chinese Center for Disease Control and PreventionBeijing 100050China

Objective This study aimed to evaluate the associations of serum folate and/or vitamin B12 concentrations with obesity among Chinese children and *** A cross-sectional study was conducted including 3,079 Chinese children and adolescents,aged 6 to 17 years,from Jiangsu,*** indices,such as,children's body mass index(BMI),BMI z-scores,waist circumference,and waist-to-height ratio were *** linear regression and generalized additive models were used to investigate the associations of serum folate and vitamin B12 levels with anthropometric indices and odds of *** We observed that serum vitamin B12 concentrations were inversely associated with all anthropometric indices and the odds of general obesity[odds ratio(OR)=0.68;95%confidence interval(CI)=0.59,0.78]and abdominal obesity(OR=0.68;95%CI=0.60,0.77).When compared to participants with both serum vitamin levels in the two middle quartiles,those with both serum folate and vitamin B12 levels in the highest quartile were less prone to general(OR=0.31,95%CI=0.19,0.50)or abdominal obesity(OR=0.46,95%CI=0.31,0.67).Conversely,participants with vitamin B12 levels in the lowest quartile alongside folate levels in the highest quartile had higher odds of abdominal obesity(OR=2.06,95%CI=1.09,3.91).Conclusion Higher serum vitamin B12 concentrations,but not serum folate concentrations,were associated with lower odds of childhood *** and adolescents with high levels of vitamin B12 and folate were less likely to be obese.

关键词： Folate Vitamin B12 Childhood obesity Micronutrient

ONE SUPER POWER:PEACE

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Beijing Review 2024年第1期67卷 16-17页

作者： Gao Zhikai Soochow University in suzhou and vice president of the center for China and Globalization in Beijing

In 1977,the resumption of the national college entrance examina-Ltion(or gaokao in Chinese)after the tumultuous era of what is referred to as the"Cultural Revolution"(1966-76)marked a seminal moment in China's *** was against this stirring backdrop that my life as a young,ambitious 15-year-old student was about to undergo a dramatic change.

关键词： stirring college young

Activation of biomass-derived porous carbon for supercapacitors:A review

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Chinese Chemical Letters 2024年第7期35卷 121-138页

作者： Zixuan Guo Xiaoshuai Han Chunmei Zhang Shuijian He Kunming Liu Jiapeng Hu Weisen Yang Shaoju Jian Shaohua Jiang Gaigai Duan Jiangsu Co-Innovation center of Efficient Processing and Utilization of Forest Resources International Innovation Center for Forest Chemicals and MaterialsCollege of Materials Science and EngineeringNanjing Forestry UniversityNanjing 210037China Institute of Materials Science and Devices Suzhou University of Science and TechnologySuzhou 215009China Faculty of Materials Metallurgy and Chemistry Jiangxi University of Science and TechnologyGanzhou 341000China Fujian Provincial Key Laboratory of Eco-Industrial Green Technology Key Laboratory of Green Chemical Technology of Fujian Province UniversityCollege of Ecological and Resources EngineeringWuyi UniversityWuyishan 354300China

Due to the advantages of renewable,low pollution and wide distribution of biomass resources,it is selected as the electrode material for *** carbon-based electrode materials,specific surface area and pore structure have a great *** and summarizing the influence of activation on pore structure will greatly broaden this *** on the activation mechanism of activator,this paper summarizes the latest progress of biomass activation applied to supercapacitors,including traditional physical and chemical activation methods and non-traditional methods such as biological activation method,self-activation method,template assisted activation method and green activator ***,the challenges,strategies and prospects for the future development of biomass-derived carbon material activation are pointed *** summary,this review will help researchers choose appropriate strategies to design biomass-derived carbon electrode materials for supercapacitors,thereby promoting the application of biomass materials.

关键词： Biomass-derived Activation Pore structure Electrochemistry Supercapacitor

Regulation and function of endoplasmic reticulum autophagy in neurodegenerative diseases

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Neural Regeneration Research 2025年第1期20卷 6-20页

作者： Xiu-Yun Zhao De-En Xu Ming-Lei Wu Ji-Chuan Liu Zi-Ling Shi Quan-Hong Ma Department of Neurology and Clinical Research center of Neurological Disease the Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu ProvinceChina Institute of Neuroscience&Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases Soochow UniversitySuzhouJiangsu ProvinceChina Department of Neurology Jiangnan University Medical CenterWuxiJiangsu ProvinceChina

The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular *** reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and *** this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular *** also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative *** summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve *** review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.

关键词： autophagy endoplasmic reticulum endoplasmic reticulum autophagy endoplasmic reticulum quality control system endoplasmic reticulum receptors endoplasmic reticulum-associated degradation neurodegeneration neurodegenerative disease selective autophagy unfolded protein response