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DNA walker induced “signal on” fluorescence aptasensor strategy for rapid and sensitive detection of extracellular vesicles in gastric cancer

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Chinese Chemical Letters 2025年第2期36卷 328-331页

作者： Gaojian Yang Zhiyang Li Rabia Usman Zhu Chen Yuan Liu Song Li Hui Chen Yan Deng Yile Fang Nongyue He State key laboratory of Digital medical Engineering School of Biological Science and Medical Engineering Southeast University Department of Clinical laboratory the Affiliated Drum Tower Hospital of Nanjing University Medical School hunan key laboratory of Biomedical Nanomaterials and Devices Hunan University of Technology Institute of Cytology and genetics School of Basic Medical Sciences Hengyang Medical School University of South China Institute for Future Sciences University of South China

The extracellular vesicles show great potential as a noninvasive biomarker for the early detection of cancer. Hence, there is an urgent requirement to create biosensors that are time-saving, simple, and easily scalable in order to accomplish rapid, sensitive, and quantitative detection of extracellular vesicles. In this study, we present a self-propelled DNA walker powered by endonuclease *** CI, which enables the development of a “signal on” sensing platform for the rapid and highly sensitive detection of extracellular vesicles. The DNA motor employed tracks made of streptavidin magnetic beads, which consisted of substrate strands labeled with fluorescein and motor strands locked by aptamers. The aptamer recognition of the target protein on extracellular vesicles unlocked the motor strand, initiating the DNA motor process. After replacing the optimal buffer solution containing the endonuclease *** I, the motor strands autonomously moved along the streptavidin magnetic beads track, continuously releasing fluorescent molecules and producing detectable fluorescence signals. Under optimal conditions, the detection range was from 2×10～4particles/mL to 2×10～9particles/mL, with a detection limit of 2.9×10～3particles/mL,demonstrating excellent selectivity. This method has demonstrated good selectivity in different tumorderived extracellular vesicles and performs well in complex biological samples. The ability to effectively analyze surface proteins of extracellular vesicles in a short period of time gives our DNA walker a tremendous potential for developing simple and cost-effective clinical diagnostic devices.

关键词： Aptamer Detection Extracellular vesicles Nt.BbvCI Streptavidin magnetic beads

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Activation ofγ-globin expression by a common variant disrupting IKAROS-binding motif inβ-thalassemia

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Journal of genetics and Genomics 2025年第2期52卷 157-167页

作者： Hualei Luo Jueheng Wang Lang Qin Xinhua Zhang Hailiang Liu Chao Niu Mengyang Song Congwen Shao Peng Xu Miao Yu Haokun Zhang Yuhua Ye Xiangmin Xu Innovation Center for Diagnostics and Treatment of Thalassemia Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Department of medical genetics School of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China State key laboratory of Genetic Engineering School of Life SciencesFudan UniversityShanghai 201114China Department of Pediatrics 923rd Hospital of the People's Liberation ArmyNanningGuangxi 530021China Cyrus Tang medical Institute National Clinical Research Centre for Hematologic DiseasesCollaborative Innovation Centre of HematologyState Key Laboratory of Radiation Medicine and ProtectionSoochow University SuzhouSuzhouJiangsu 215031China State key laboratory of Genetic Engineering MOE Engineering Research Center of Gene TechnologySchool of Life SciencesFudan UniversityShanghai 200438China

Programmed silencing ofγ-globin genes in adult erythropoiesis is mediated by several chromatin remodeling complexes,which determine the stage-specific genome architecture in this *** of cis-or trans-acting mutations contributing to the diverse extent of fetal hemoglobin(Hb F)might illustrate the underlying mechanism ofγ-β-globin ***,we recruit a cohort of 1142β-thalassemia patients and dissect the natural variants in the wholeβ-globin gene cluster through a targeted next-generation sequencing panel.A previously unreported SNP rs7948668,predicted to disrupt the binding motif of IKAROS as a key component of chromatin remodeling complexes,is identified to be significantly associated with higher levels of Hb F and age at ***-editing on this SNP leads to the elevation of Hb F in both HUDEP-2 and primary CD34+cells while the extent of elevation is amplified in the context ofβ-thalassemia mutations,indicating epistasis effects of the SNP in the regulation of Hb ***,we perform ChIP-qPCR and 4C assays to prove that this variant disrupts the binding motif of IKAROS,leading to enhanced competitiveness of HBG promoters to locus control *** study highlights the significance of common regulatory SNPs and provides potential targets for treatingβ-hemoglobinopathy.

关键词： β-thalassemia Fetal hemoglobin Single nucleotidepolymorphism IKAROS Locus control region

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Antimicrobial resistance crisis:could artificial intelligence be the solution?

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Military medical Research 2025年第1期12卷 72-95页

作者： Guang-Yu Liu Dan Yu Mei-Mei Fan Xu Zhang Ze-Yu Jin Christoph Tang Xiao-Fen Liu Department of Immunology and Pathogen Biology School of Basic Medical SciencesHangzhou Normal UniversityKey Laboratory of Aging and Cancer Biology of Zhejiang ProvinceKey Laboratory of Inflammation and Immunoregulation of HangzhouHangzhou Normal UniversityHangzhou 311121China National key Discipline of Pediatrics key laboratory of Major Diseases in Children Ministry of Education Laboratory of DermatologyBeijing Pediatric Research InstituteBeijing Children’s HospitalCapital Medical UniversityNational Center for Children’s HealthBeijing 100045China Robert and Arlene Kogod Center on Aging Mayo ClinicRochesterMN 55905USA Department of Biochemistry and Molecular Biology Mayo ClinicRochesterMN 55905USA Department of Molecular and Human genetics Baylor College of MedicineHoustonTX 77030USA Sir William Dunn School of Pathology University of OxfordOxford OX13REUK Institute of Antibiotics Huashan HospitalFudan UniversityKey Laboratory of Clinical Pharmacology of AntibioticsNational Health Commission of the People’s Republic of ChinaNational Clinical Research Centre for Aging and MedicineHuashan HospitalFudan UniversityShanghai 200040China

Antimicrobial resistance is a global public health threat,and the World Health Organization(WHO)has announced a priority list of the most threatening pathogens against which novel antibiotics need to be *** discovery and introduction of novel antibiotics are time-consuming and *** to WHO’s report of antibacterial agents in clinical development,only 18 novel antibiotics have been approved since ***,novel antibiotics are critically *** intelligence(AI)has been rapidly applied to drug development since its recent technical breakthrough and has dramatically improved the efficiency of the discovery of novel ***,we first summarized recently marketed novel antibiotics,and antibiotic candidates in clinical *** addition,we systematically reviewed the involvement of AI in antibacterial drug development and utilization,including small molecules,antimicrobial peptides,phage therapy,essential oils,as well as resistance mechanism prediction,and antibiotic stewardship.

关键词： Antibiotic Artificial intelligence(AI) Clinical development Machine learning(ML) Antimicrobial peptide Phage therapy Antibiotic stewardship

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Longitudinal landscape of immune reconstitution after acute SARS-CoV-2 infection at single-cell resolution

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Science Bulletin 2025年第3期70卷 323-327页

作者： Lili Ren Yiwei Liu Yeming Wang Chao Wu Li Guo Lan Chen Xinming Wang Yan Xiao Lixue Huang Jingchuan Zhong Jiacheng Yao Lu Liu Hui Li Ying Wang Yongchao Ma Yichunzi Zhang Lin Di Tao Dong Julian Knight Jianbin Wang Yanyi Huang Bin Cao Xianwen Ren Jianwei Wang National Health Commission key laboratory of Systems Biology of Pathogens and Christophe Mérieux laboratory National Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 102629China key laboratory of Respiratory Disease Pathogenomics Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China State key laboratory of Respiratory Health and Multimorbidity Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100029China Department of Pulmonary and Critical Care Medicine Institute of Respiratory Medicine of Chinese Academy of Medical ScienceNational Center for Respiratory MedicineCenter of Respiratory MedicineNational Clinical Research Center for Respiratory DiseasesChina-Japan Friendship HospitalBeijing 100029China College of Chemistry and Molecular Engineering Peking UniversityBeijing 100871China Biomedical Pioneering Innovation Center(BIOPIC) Beijing Advanced Innovation Center for Genomics(ICG)College of Chemistryand Peking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China MRC Human Immunology Unit MRC Weatherall Institute of Molecular MedicineRadcliffe Department of MedicineThe University of OxfordOxford OX39DSUK Chinese Academy of medical Science(CAMS)Oxford Institute(COI) University of OxfordOxford OX39DSUK Wellcome centre for Human genetics University of OxfordOxford OX39DSUK School of Life Sciences Tsinghua-Peking Center for Life SciencesTsinghua UniversityBeijing 100084China Beijing Advanced Innovation Center for Structural Biology(ICSB) Tsinghua UniversityBeijing 100084China Chinese Institute for Brain Research(CIBR) Beijing 102206China Institute for Cell Analysis Shenzhen Bay LaboratoryShenzhen 518107China Tsinghua University-Peking University Joint Center for Life Sciences Beijing 100084China Biomedical Pioneering Innovation Center(BIOPIC) Peking UniversityBeijing 100871China Changping laboratory Beijing 102206China

The long-term consequences of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection,known as the post-acute sequelae of COVID-19(PASC),have been a growing concern.A significant proportion of COVID-19 patients experience persistent health issues even six to twelve months after recovering from acute infection[1],[2],[3],[4].Therefore,understanding the immune reconstitution process and identifying the molecular and cellular mechanisms underlying PASC is crucial.

关键词： landscape consequences acute

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Cloning, mapping and mutation analysis of human gene GJB5 encoding gap junction protein β-5

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Science China(Life Sciences) 2001年第1期44卷 92-98页

作者：夏家辉郑多唐冬生戴和平潘乾龙志高廖晓东 1. hunan medical University State Key Laboratory of Medical Genetics 410078 Changsha China

By homologous EST searching and nested PCR a new human gene GJB5 encoding gap junction protein p-5 was identified. GJB5 was genetically mapped to human chromosome 1p33-p35 by FISH. RT-PCR revealed that it was expressed in skin, placenta and fetal skin. DMA sequencing of GJB5 was carried out in 142 patients with sensorineural hearing impairment and probands of 36 families with genetic diseases, including erythrokeratodermia (5 families), Char-cot-Marie-Tooth disease (13), ptosis (4), and retinitis pigmentosa and deafness (14). Two mis-sense mutations (686A→G, H229R; 25C→T, L9F) were detected in two sensorineural hearing impairment families. A heterologous deletion of 18 bp within intron was found in 3 families with heredity hearing impairment, and in one of the 3 families, a missense mutation (R265P) was identified also. But the deletion and missense mutation seemed not segregating with hearing impairment in the family. No abnormal mRNA or mRNA expression was detected in deletion carriers by RT-PCR analysis in skin tissue. Mutation analysis in 199 unaffected individuals revealed that two of them were carriers with the same 18 bp deletion.

关键词： gap junction protein, gene cloning, mapping, mutation analysis, mRNA.

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Isolation of 24 novel cDNA fragments from microdissected human chromosome band

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Cell Research 1998年第2期8卷 135-142页

作者： ZHANG MIN L0NG YU PEI RONG HU AN DINGBI JIA HUI XIA HAN XIANG DENG SHOU YUANZHAO(Institute 0f genetics, Fudan University, Shanghai 2O0j23,China(State key La6omtory of medical genetics, hunan medical Un1versity, Chang8ha J10078, China) State key laboratory of medical genetics Hunan Medical University Changsha 410078 China

The strategy of isolating the band-specific expression fragments from a probe pool generated by humanchromosome microdissection was reported. A cliromosome 14q24.3 band-specific single copy DNA pool was constructed based on this probe pool. Using total DNA of the pool as probe to hybridize the human marrow cDNA library, 68 primary positive clones were selected from 5 ×105 cDNA clones. Among these primary clones, 32 secondary clones were obtained after second-round screening and designed as cFD14-1～32. Finally, 24 band-specific expression fragments were identified from these 32 positive clones by DNA hybridization. Those band-specific clones can hybridize to both 14q24.3 DNA and human genomic DNA but cann't hybridize to 17q11～12 DNA. Partial sequences of 13 fragments of them were sequenced and identified as novel cDNA sequences , and these sequences were proved to have some homology with known genes in NCBI database. Analysis of expression spectrum of cFD14-1 suggested that the cDNA fragments thus obtained should be used to isolate the genes can not been cloned in 14q24.3region.

关键词： Probe pool chromosome 14q24.3 single copy DNA pool expression sequences of genes

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IL-24 armored CAR19-T cells show enhanced antitumor activity and persistence

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Signal Transduction and Targeted Therapy 2021年第2期6卷 232-234页

作者： Qian Hu Yuxuan Zhang Peiyun Wang Miaojin Zhou Zhiqing Hu Cong Liu Mujun Liu Lingqian Wu Xionghao Liu Desheng Liang Center for medical genetics&hunan key laboratory of medical genetics School of Life SciencesCentral South UniversityChangshaHunanChina hunan key laboratory of Basic and Applied Hematology School of Life SciencesCentral South UniversityChangshaHunanChina

Dear Editor,Nowadays,two autologous CAR19-T drugs,Tisagenlecleucel(Kymriah^(TM))and axicabtagene ciloleucel(Yescarta^(TM)),have been approved for the treatment of B cell leukemia and lymphoma and achieved unprecedented ***,about 10-20%of B-ALL patients receiving CAR19-T drugs didn't achieve complete remission(CR),while 30~50%of patients achieved CR would relapse mainly within 1 ***,the high CR rate of CAR19-T therapy for B-ALL can't be recaptured in other B-NHLs,'such as Burkitt's lymphoma(BL).Therefore,there is an urgent need to improve the therapeutic efficacy of CAR19-T cells.3.

关键词： drugs CAR lymphoma

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Integrated analysis and systematic characterization of the regulatory network for human germline development

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Journal of genetics and Genomics 2025年第2期52卷 204-219页

作者： Yashi Gu Jiayao Chen Ziqi Wang Qizhe Shao Zhekai Li Yaxuan Ye Xia Xiao Yitian Xiao Wenyang Liu Sisi Xie Lingling Tong Jin Jiang Xiaoying Xiao Ya Yu Min Jin Yanxing Wei Robert S.Young Lei Hou Di Chen Center for Reproductive Medicine of the Second Affiliated Hospital Center for Regeneration and Cell Therapy of Zhejiang University-University of Edinburgh Institute(ZJU-UoE Institute)Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang 310003China Edinburgh medical School:Biomedical Sciences College of Medicine and Veterinary MedicineThe University of EdinburghEdinburghUK Center for Reproductive Medicine of the Second Affiliated Hospital Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang 310003China Department of Obstetrics and Gynecology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China key laboratory of Functional Proteomics of Guangdong Province School of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China Research centre for Women's and Infants'Health Lunenfeld-Tanenbaum Research InstituteSinai Health SystemTorontoM5T3H7Canada Center for Global Health Research Usher InstituteUniversity of EdinburghTeviot Place5-7 Little France RoadEdinburgh BioQuarter-Gate 3EdinburghEH164UXUK Zhejiang University-University of Edinburgh Institute Zhejiang UniversityHainingZhejiang 314400China Section of Biomedical genetics Department of MedicineBoston University School of MedicineBostonMA 02118United States State key laboratory of Biobased Transportation Fuel Technology HainingZhejiang 314400China

Primordial germ cells(PGCs)are the precursors of germline that are specified at the embryonic *** studies reveal that humans employ different mechanisms for PGC specification compared with model organisms such as ***,the specific regulatory machinery remains largely unexplored,mainly due to the inaccessible nature of this complex biological process in ***,we curate and integrate multi-omics data,including 581 RNA-seq,54 ATAC-seq,45 ChIP-seq,and 69 single-cell RNA-seq samples from different stages of human PGC development to recapitulate the precisely controlled and stepwise process,presenting an atlas in the human PGC database(hPGCdb).With these uniformly processed data and integrated analyses,we characterize the potential key transcription factors and regulatory networks governing human germ cell *** validate the important roles of some of the key factors in germ cell development by CRISPRi *** also identify the soma-germline interaction network and discover the involvement of SDC2 and LAMA4 for PGC development,as well as soma-derived NOTCH2 signaling for germ cell *** together,we have built a database for human PGCs(http://43.***.248.15:6882)and demonstrate that hPGCdb enables the identification of the missing pieces of mechanisms governing germline development,including both intrinsic and extrinsic regulatory programs.

关键词： Primordial germ cells Regulatory network Soma-germ cell interaction Database

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Construction of Chromosome 11q23-qter Band-Specific ProbePool by Microdissection

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Chinese Science Bulletin 1994年第2期39卷 162-164页

作者：何小轩夏家辉李麓芸戴和平朱亚辉潘乾 State key laboratory of medical genetics Hunan Medical University Changsha 410078 PRC

Since Ldecke first successfully introduced the PCR technique into microdissectionon banded chromosomes, direct construction of a bandspecific DNA probe pool bymicrodissection has been widely used in cytogenetic and molecular genetic *** can be used not only for the detection of chromosome abnormalities at chromosomeband level but also for the generation of chromosome band-specific DNA probes andgenetic makers.

关键词： human chromosome microdissection PCR chromosome painting.

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Dysregulated CRMP Mediates Circadian Deficits in a Drosophila Model of Fragile X Syndrome

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Neuroscience Bulletin 2021年第7期37卷 973-984页

作者： Juan Zhao Jin Xue Tengfei Zhu Hua He Huaixing Kang Xuan Jiang Wen Huang Ranhui Duan Center for medical genetics School of Life SciencesCentral South UniversityChangsha 410078China hunan key laboratory of medical genetics Central South UniversityChangsha 410078China hunan key laboratory of Animal Models for Human Diseases Central South UniversityChangsha 410078China

Fragile X syndrome(FXS)is the leading inherited cause of intellectual disability,resulting from the lack of functional fragile X mental retardation protein(FMRP),an mRNA binding protein mainly serving as a translational *** of FMRP leads to dysregulation of target *** Drosophila model of FXS show an abnormal circadian rhythm with disruption of the output pathway downstream of the clock *** the FMRP targets involved in circadian regulation have not been ***,we identified collapsing response mediator protein(CRMP)mRNA as a target of *** of pan-neuronal CRMP expression ameliorated the circadian defects and abnormal axonal structures of clock neurons(ventral lateral neurons)in dfmr1 mutant ***,specific reduction of CRMP in the downstream output insulin-producing cells attenuated the aberrant circadian *** analyses revealed that FMRP binds with CRMP mRNA and negatively regulates its *** results indicate that CRMP is an FMRP target and establish an essential role for CRMP in the circadian output in FXS Drosophila.

关键词： Fragile X syndrome FMRP CRMP Circadian rhythm

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