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Copper-Free Click Chemistry-Mediated Assembly of Single Quantum Dot Nanosensor for Accurately Monitoring Locus-Specific m^(6)A in Cancer Cells

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Chinese Journal of Chemistry 2024年第5期42卷 499-504页

作者： Yue-Ying Li Ning-Ning Zhao Yi-Xuan Geng Qian Han Jian-Ge Qiu Bing-Hua Jiang Zi-Yue Wang Chun-Yang Zhang Translational Medicine Center The First Affiliated Hospital of Zhengzhou UniversityThe Academy of Medical SciencesHenan Institute of Medical and Pharmaceutical Sciences BGI CollegeZhengzhou UniversityZhengzhouHenan450052 China college of Chemistry Chemical Engineering and Materials ScienceShandong Normal UniversityJinanShandong250014 China School of Chemistry and Chemical Engineering Southeast UniversityNanjingJiangsu211189 China

N6-methyladenosine(m^(6)A)plays an important role in embryogenesis,nuclear export,transcription splicing,and protein translation ***,we demonstrate a copper-free click chemistry-mediated assembly of single quantum dot(QD)nanosensor for accurately monitoring locus-specific m^(6)A in cancer *** m^(6)A-sensitive endoribonuclease MazF can digest the unmethylated A-RNA,and the intact m^(6)A-RNA then hybridizes with DNA probes a and b to produce a sandwich hybrid,initiating the click chemistry to generate probe a–b ligation product via first tandem ligation detection reaction(LDR)***,DNA probes c and d can hybridize with the probe a–b ligation product to generate the probe c–d ligation product via second LDR *** LDR cycles can be repeated through denaturation and annealing reaction to generate abundant biotin-/fluorophore-modified probe c–d ligation products that can easily assemble on the QD surface to induce distinct fluorescence resonance energy transfer(FRET)between QD and *** assay can be homogenously performed without the involvement of copper catalyst,m^(6)A-specific antibody,radioactive labeling,ligase enzyme,enzymatic reverse transcription,and next-generation ***,it can discriminate even 0.01% m^(6)A level in complex samples and accurately measure cellular m^(6)A-RNA expression,providing a promising avenue for clinical diagnostics and biomedical research.

关键词： RNA methylation Click chemistry Förster resonance energy transfer Biosensor Cancer

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An innovative indirect competitive immunosorbent approach for precise detetion aflatoxin Bbased on high-affinity IgG coupled CuO-anchored FeOnanozymes

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Food Science and Human Wellness 2024年

作者： Xueqin Wang Chuan Liu Haizhen Tao Xuanping Zhao Mengna Wan Junyan Liu Na Li college of Bioengineering， henan University of Technology henan institute of medical and pharmaceutical sciences， Zhengzhou University henan Provincial Key Laboratory of Ultrasound Imaging and Artificial Intelligence， henan Provincial People's Hospital， Zhengzhou University People's Hospital， Zhengzhou University

Aflatoxin B1(AFB1) is a carcinogenic toxin naturally produced in most food crops that severely threaten human health， and effective methods are urgent to improve the detection accuracy. Herein an indirect competitive immunosorbent approach was elaborately developed based on high-affinity immunoglobulin G (IgG) coupled CuO-anchored Fe3O4nanozymes for precise and ultrasensitive detection of AFB1in food crops including peanut， corn and wheat. The high-affinity nanozymes were fabricated by the assembly of inner core Fe3O4nanoparticles (Fe3O4NPs) and mesoporous silica capping layer， CuO further situated within large aperture of the coating layer via in-situ growth， and then conjugated with ligand rabbit anti-mouse IgG， which can specifically bind with AFB1. The results showed the hybrid high-affinity nanozymes displayed enhanced peroxidase (POD)-mimic activities and catalytic performances， achieving a linear range of 0.06-61.93 ng/mL and a detection limit of 0.0037 ng/mL， 30 times better than that of the conventional ELISA method. The constructed nanozymes were successfully applied to the detection of AFB1in food products with an average spiked recovery of 96.53% and relative standard deviations (RSDs) less than 2.8%. Therefore， the accurate hybrid nanozymes may serve for AFB1detection in various foods in future.

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Rapid identification of full-length genome and tracing variations of monkeypox virus in clinical specimens based on mNGS and amplicon sequencing

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Virologica Sinica 2024年第1期39卷 134-143页

作者： Changcheng Wu Ruhan A Sheng Ye Fei Ye Weibang Huo Roujian Lu Yue Tang Jianwei Yang Xuehong Meng Yun Tang Shuang Chen Li Zhao Baoying Huang Zhongxian Zhang Yuda Chen Dongfang Li Wenling Wang Ke-jia Shan Jian Lu Wenjie Tan NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing100052China Chongqing Municipal Key Laboratory for High Pathogenic Microbes Chongqing Center for Disease Control and PreventionChongqing400042China MGI BGI-ShenzhenShenzhen518083China Thermo Fisher Scientific Beijing100013China School of Public Health Baotou Medical CollegeBaotou014030China bgi PathoGenesis pharmaceutical Technology Shenzhen518000China State Key Laboratory of Protein and Plant Gene Research Center for BioinformaticsSchool of Life SciencesPeking UniversityBeijing100871China college of Life sciences University of Chinese Academy of SciencesBeijing100049China

The monkeypox virus(MPXV)has triggered a current outbreak *** sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and *** is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads,as it is one of the DNA viruses with the largest genome and the most AT-biased,and has a significant number of tandem *** we evaluated the performance of metagenomic and amplicon sequencing techniques,and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese *** rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical *** sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV ***-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published ***,several intra-host single nucleotide variations were identified in the first imported mpox *** study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical *** findings of this study will significantly enhance the surveillance of MPXV.

关键词： Monkeypox virus(MPXV) Metagenomic Next generation sequencing Amplicon Third-generation sequencing

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Strategies that regulate LSD1 for novel therapeutics

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1494-1507页

作者： Meng Li Mengge Dai Bing Cheng Shaotong Li Enhui Guo Junwei Fu Ting Ma Bin Yu School of pharmaceutical sciences&Key Laboratory of Advanced Drug Preparation Technologies Ministry of EducationZhengzhou UniversityZhengzhou 450001China college of Chemistry Zhengzhou UniversityZhengzhou 450001China Tianjian Laboratory of Advanced Biomedical sciences Institute of Advanced Biomedical SciencesZhengzhou UniversityZhengzhou 450000China Pingyuan Laboratory State Key Laboratory of Antiviral DrugsHenan Normal UniversityXinxiang 453007China State Key Laboratory of pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Histone methylation plays crucial roles in regulating chromatin structure and gene transcrip-tion in epigenetic ***-specific demethylase 1(LSD1),the first identified histone de-methylase,is universally overexpressed in various ***1 dysregulation is closely associated with cancer,viral infections,and neurodegenerative diseases,etc.,making it a promising therapeutic *** LSD1 inhibitors and two small-molecule degraders(UM171 and BEA-17)have entered the clinical ***1 can remove methyl groups from histone 3 at lysine 4 or lysine 9(H3K4 or H3K9),resulting in either transcription repression or *** the roles of LSD1 in transcrip-tional regulation are well-established,studies have revealed that LSDl can also be dynamically regulated by other *** example,the expression or activity of LSD1 can be regulated by many proteins that form transcriptional corepressor complexes with ***,some post-transcriptional modifica-tions and cellular metabolites can also regulate LSD1 expression or its demethylase ***,in this review,we will systematically summarize how proteins involved in the transcriptional corepressor complex,various post-translational modifications,and metabolites act as regulatory factors for LSD1 ac-tivity.

关键词： LSD1 regulation Transcription repression Transcription activation the Corepressor complex Post-transcriptional modifications Metabolites

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β-Carboline alkaloids from the roots of Peganum harmala L.

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Chinese Journal of Natural Medicines 2024年第2期22卷 171-177页

作者： LI Shengge ZHANG Qin WANG Yuetong LIN Bin LI Dahong HUA Huiming HU Xu henan Key Laboratory of Zhang Zhongjing Formulate and Herbs for Immunoregulation Zhang Zhongjing Traditional School of Chinese MedicineNanyang Institute of TechnologyNanyang 473004China Key Laboratory of Structure-Based Drug Design&Discovery Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China Wuya college of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China School of pharmaceutical Engineering Shenyang Pharmaceutical UniversityShenyang 110016China

This study reports the isolation of four newβ-carboline alkaloids(1−4)and six previously identified alkaloids(5−10)from the roots of Peganum harmala *** these compounds,1 and 2 were characterized as rareβ-carboline-quinazoline dimers exhibiting axial *** 3 possessed a unique 6/5/6/7 tetracyclic ring system with an azepine ring,and compound 4 was a novel annomontineβ-*** structures of these compounds were elucidated by spectroscopic data and quantum mechanical *** biosynthetic pathways of 1−3 were ***,the cytotoxicity of some isolates against four cancer cell lines(HL-60,A549,MDA-MB-231,and DU145)was ***,compound 4 exhibited significant cytotoxicity against HL-60,A549,and DU145 cells with IC_(50) values of 12.39,12.80,and 30.65μmol·L^(−1),***,compound 2 demonstrated selective cytotoxicity against HL-60 cells with an IC_(50) value of 17.32μmol·L^(−1).

关键词： β-Carboline alkaloids Peganum harmala Structure elucidation Cytotoxic activity

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Consensus of Chinese experts on glioma multidisciplinary team management(2nd edition)

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Chinese medical Journal 2024年第11期137卷 1267-1270页

作者： Jinsong Wu Zhirui Zhou Zanyi Wu Zhiwei Tang Ming Li Siyuan Yin Xufei Luo Ling Wang Yaolong Chen Guoguang Zhao Tao Jiang Ying Mao The National Glioma MDT Alliance of National Center for Neurological Diseases Department of Neurosurgery Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200040China Department of Radiation Oncology Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200040China Department of Neurosurgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350005China Neurosurgery Department The First Affiliated Hospital of Kunming Medical UniversityKunmingYunnan 650032China Department of Neurosurgery Henan Provincial People’s HospitalPeople’s Hospital of Zhengzhou UniversityZhengzhouHenan 463599China State Key Laboratory of pharmaceutical Biotechnology Institute for Brain SciencesAdvanced Institute for Life SciencesSchool of Life SciencesNanjing UniversityNanjingJiangsu 210023China Evidence-Based Medicine Center School of Basic Medical SciencesLanzhou UniversityLanzhouGansu 730000China School of Public Health Lanzhou UniversityLanzhouGansu 730000China Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijing 100053China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China 不详

To increase the consistency of glioma multidisciplinary team(MDT)management across different regions and hospitals at varying levels,we have updated the Expert Consensus on MDT of Glioma in China based on the currently available *** version has revised and updated the process-management rules and quality-control standards for a glioma MDT,providing reference and guidance for relevant clinical disciplines and *** members of the Consensus Expert Group,abstract,background,and prospects can be seen in supplementaryle,http://***/CM9/B999.

关键词： glioma MDT Expert

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Discovery of TK-642 as a highly potent,selective,orally bioavailable pyrazolopyrazine-based allosteric SHP2 inhibitor

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3624-3642页

作者： Kai Tang Shu Wang Siqi Feng Xinyu Yang Yueyang Guo Xiangli Ren Linyue Bai Bin Yu Hong-Min Liu Yihui Song School of pharmaceutical sciences&Key Laboratory of Advanced Drug Preparation Technologies Ministry of EducationZhengzhou UniversityZhengzhou 450001China college of Chemistry Pingyuan LaboratoryState Key Laboratory of Antiviral DrugsZhengzhou UniversityZhengzhou 450001China Tianjian Laboratory of Advanced Biomedical sciences Institute of Advanced Biomedical SciencesZhengzhou UniversityZhengzhou 450000China State Key Laboratory of pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Src homology-2-containing protein tyrosine phosphatase 2(SHP2)is a promising therapeutic target for cancer *** this work,we presented the structure-guided design of 5,6-fused bicyclic allosteric SHP2 inhibitors,leading to the identification of pyrazolopyrazine-based TK-642 as a highly potent,selective,orally bioavailable allosteric SHP2 inhibitor(SHP2WT IC_(50)=2.7 nmol/L)with favorable pharmacokinetic profiles(F=42.5%;t_(1/2)=2.47 h).Both dual inhibition biochemical assay and docking analysis indicated that TK-642 likely bound to the“tunnel”allosteric site of ***-642 could effectively suppress cell proliferation(KYSE-520 cells IC_(50)=5.73μmol/L)and induce apoptosis in esophageal cancer cells by targeting the SHP2-mediated AKT and ERK signaling ***,oral administration of TK-642 also demonstrated effective anti-tumor effects in the KYSE-520 xenograft mouse model,with a T/C value of 83.69%.Collectively,TK-642 may warrant further investigation as a promising lead compound for the treatment of esophageal cancer.

关键词： Protein tyrosine phosphatase Pyrazolopyrazine SHP2 inhibitor Esophageal cancer

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CGG repeat expansion in LOC642361/NUTM2B-AS1 typically presents as oculopharyngodistal myopathy

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Journal of Genetics and Genomics 2024年第2期51卷 184-196页

作者： Yan Shi Chunyan Cao Yiheng Zeng Yuanliang Ding Long Chen Fuze Zheng Xuejiao Chen Fanggui Zhou Xiefeng Yang Jinjing Li Liuqing Xu Guorong Xu Minting Lin Hiroyuki Ishiura Shoji Tsuji Ning Wang Zhiqiang Wang Wan-Jin Chen Kang Yang Department of Neurology and institute of Neurology of First Affiliated Hospital Institute of NeuroscienceFujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian 350005China Department of Neurology National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouFujian 350212China The First Affiliated Hospital College of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan 471000China Department of Neurology Zhangzhou Municipal Hospital of Fujian Province and Zhangzhou Affiliated Hospital of Fujian Medical UniversityZhangzhouFujian 363000China Department of Neurology Jian'ou Municipal Hospital of Fujian ProvinceJian'ouFujian 353100China Department of Radiology First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350005China Department of Neurology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Department of Neurology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 700-8558Japan institute of medical Genomics International University of Health and WelfareChiba 286-0048Japan

CGG repeat expansions in LOC642361/NUTM2B-AS1 have recently been identified as a cause of oculopharyngeal myopathy with ***,since only three patients from a single family were reported,it remains unknown whether their clinicopathological features are typical for CGG repeat expansions in LOC642361/***,using repeat-primed-polymerase chain reaction and long-read sequencing,we identify 12 individuals from 3 unrelated families with CGG repeat expansions in LOC642361/NUTM2B-AS1,typically presenting with oculopharyngodistal *** CGG repeat expansions range from 161 to 669 repeat *** of the patients present with ptosis,restricted eye movements,dysphagia,dysarthria,and diffuse limb muscle *** one patient shows T2-weighted hyperintensity in the cerebellar white matter surrounding the deep cerebellar nuclei on brain magnetic resonance *** biopsies from three patients show a myopathic pattern and rimmed *** of muscle biopsies suggest that CGG repeat expansions in LOC642361/NUTM2B-AS1 may deleteriously affect aggrephagic capacity,suggesting that RNA toxicity and mitochondrial dysfunction may contribute to *** study thus expands the phenotypic spectrum for the CGG repeat expansion of LOC642361/NUTM2B-AS1 and indicates that this genetic variant typically manifests as oculopharyngodistal myopathy with chronic myopathic changes with rimmed vacuoles and filamentous intranuclear inclusions in muscle fibers.

关键词： Oculopharyngeal myopathy with leukoencephalopathy Oculopharyngodistal myopathy CGG repeat expansion Rimmed vacuoles

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Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia:randomized trials and multiomics analysis

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Military medical Research 2024年第1期11卷 19-33页

作者： Liang-Kun Guo Yi Su Yu-Ya-Nan Zhang Hao Yu Zhe Lu Wen-Qiang Li Yong-Feng Yang Xiao Xiao Hao Yan Tian-Lan Lu Jun Li Yun-Dan Liao Zhe-Wei Kang Li-Fang Wang Yue Li Ming Li Bing Liu Hai-Liang Huang Lu-Xian Lv Yin Yao Yun-Long Tan Gerome Breen Ian Everall Hong-Xing Wang Zhuo Huang Dai Zhang Wei-Hua Yue institute of Mental Health Peking University Sixth HospitalBeijing 100191China National Clinical Research Center for Mental Disorders Peking University Sixth HospitalBeijing 100191China NHC Key Laboratory of Mental Health and Research Unit of Diagnosis and Treatment of Mood Cognitive Disorder(2018RU006) Chinese Academy of Medical SciencesBeijing 100191China Peking University Huilongguan Clinical medical School Beijing Huilongguan HospitalBeijing 100096China Department of Psychiatry Jining Medical UniversityJining 272067ShandongChina henan Key Lab of Biological Psychiatry the Second Affiliated Hospital of Xinxiang Medical UniversityXinxiang 435001HenanChina Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China institute of Psychiatry Psychology and NeuroscienceKing’s College LondonLondon WC2R 2LSUK State Key Laboratory of Cognitive Neuroscience and Learning Beijing Normal UniversityBeijing 100875China Analytic and Translational Genetics Unit Massachusetts General HospitalBostonMA 02114USA Stanley Center for Psychiatric Research the Broad Institute of MIT and HarvardCambridgeMA 02141USA Department of Medicine Harvard Medical SchoolBostonMA 02115USA Department of Biostatistics and Computational Biology School of Life SciencesFudan UniversityShanghai 200438China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Natural and Biomimetic Drugs Key Laboratory for Neuroscience for Ministry of EducationSchool of Pharmaceutical SciencesPeking University Health Science CenterBeijing 100191China PKU-IDG/McGovern institute for Brain Research Peking UniversityBeijing 100871China Chinese institute for Brain Research Beijing 102206China

Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective *** studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been ***,further research is imperative to enhance precision medicine in SCZ ***:Participants with SCZ were recruited from two randomized *** discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)*** external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole ***,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic *** genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,*** study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin *** learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve ***:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment *** developed and externally validated predictio

关键词： Schizophrenia Antipsychotic drug Treatment response Prediction model Genetics Epigenetics

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Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy

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Journal of pharmaceutical Analysis 2024年第3期14卷 321-334页

作者： Rangrang Fan Linrui Cai Hao Liu Hongxu Chen Caili Chen Gang Guo Jianguo Xu Department of Neurosurgery and institute of Neurosurgery Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China NMPA Key Laboratory for Technical Research on Drug Products in Vitro and in Vivo Correlation Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOENational Drug Clinical-Trial InstitutionWest China Second HospitalSichuan UniversityChengdu610041China Department of Immunology School of Basic Medical SciencesXinxiang Medical UniversityXinxiangHenan453000China

Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in *** the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in ***,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was *** coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton ***–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its ***,this pH-responsive nanoplatform presents controllable drug release *** in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free *** in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their *** triple-combination therapy approach is promising for efficient and targeted cancer treatment.

关键词： Metformin Glucose oxidase Metabolism disruption Tumor starvation Combination cancer therapy

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