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Recent progress in co-detection of single-cell transcripts and proteins

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Nano Research 2024年第1期17卷 132-150页

作者： Shanqing Huang Qian Fan Yidi Wang Zhi Huang Weixiong Shi Yanli Gong Ting Yang Jie Wang Lingling Wu Chaoyong Yang Discipline of Intelligent Instrument and Equipment College of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005China institute of Molecular medicine Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China department of General Surgery Xiang’an Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361101China Research Center for Analytical Sciences Department of ChemistryCollege of SciencesNortheastern UniversityShenyang 110819China

Cellular heterogeneity is a universal property of living systems,and the interrogation of single cells facilitates in-depth understanding of distinct cellular states and functions in various biological ***-analysis of transcripts and proteins from the same single cells opens the way to decipher complex RNA regulatory frameworks and phenotypes,facilitating the understanding of cellular fate and function regulations,discovery of novel cell types,and construction of a high-resolution cell ***,we review the state-of-art advances in the development of methodologies for co-analysis of single-cell transcripts and ***,imaging-based methods are summarized with particular emphasis on optical and mass spectrometry ***,sequencing-based approaches for high-throughput and sensitive co-analysis of single-cell transcripts and proteins are described,including droplet-,microwell-,and split-pool-based ***,combined methods with more flexibility and universality are *** methods commonly employ different strategies or reactions to convert transcripts and proteins of single cells into distinct signals simultaneously,which can be detected by different instruments or ***,some perspectives on the future challenges and development trends in this field are presented.

关键词： single cell optical imaging mass spectrometry imaging single-cell RNA sequencing(scRNA-seq) co-detection

The expanded application of CAR-T cell therapy for the treatment of multiple non-tumoral diseases

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Protein & Cell 2024年第9期15卷 633-641页

作者： Zhuoqun Liu Yuchen Xiao Jianjun Lyu Duohui Jing Liu Liu Yanbin Fu Wenxin Niu Lingjing Jin Chao Zhang Fundamental Research Center Shanghai Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center)School of MedicineTongji UniversityShanghai 201619China Hubei Topgene Research institute of Hubei Topgene Biotechnology Co. Ltd.East Lake High-Tech Development ZoneWuhan 430205China shanghai institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China shanghai Yuhui Pharmaceutical Technology(Group)Co. Ltd.and Shanghai Ruishen Technology Development Co.Ltd.Shanghai 201203China shanghai Cancer institute Department of Biliary-Pancreatic SurgeryRenji Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200127China

As a powerful cell-based therapeutic approach,CAR-T therapy was originally designed for treating acquired immunodeficiency syndrome(AIDS)(Baker et al.,2023),but had been strikingly successful in curing hematologic malignancies and multiple solid *** evidence has expanded the medical application of CAR-T therapy for the treatment of many other human diseases beyond *** this article,we discuss the principle of CAR-T and enumerate the current application and limitation in ***,we provide a comprehensive perspective of current advance and future directions of CAR-T in treating multiple non-tumoral diseases.

关键词： diseases expanded treatment

Molecular Engineering of Aptamer to Solubilize Hydrophobic Near-Infrared Photosensitizer for Enhanced Cancer Photodynamic Therapy

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CCS Chemistry 2024年第5期6卷 1240-1254页

作者： Rongjun Zhang Ding-Kun Ji Defan Yao Zeyu Xiao Weihong Tan institute of Molecular medicine(IMM) Renji HospitalState Key Laboratory of Oncogenes and Related GenesShanghai Jiao Tong University School of MedicineShanghai 200240 department of Radiology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200092 department of Pharmacology and Chemical Biology School of MedicineShanghai Jiao Tong UniversityShanghai 200025 Zhejiang Cancer hospital Hangzhou Institute of Medicine(HIM)The Chinese Academy of SciencesHangzhouZhejiang 310022 Molecular Science and Biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of BiologyAptamer Engineering Center of Hunan ProvinceHunan UniversityChangshaHunan 410082

Photodynamic therapy(PDT)is a clinically representative treatment strategy for ***,conventional photosensitizers(PSs)are usually hampered by poor water solubility and low targeting ***,we report the precise molecular engineering of aptamer oligonucleotides to solubilize hydrophobic near-infrared(NIR)PSs for enhanced cancer *** pyropheophorbide A(PA)is precisely conjugated to aptamer oligonucleotides by combing DNA solid-phase synthesis technology and Cu-free click *** coupling of insoluble PA to hydrophilic aptamer oligonucleotides vastly improves its solubility to as high as 750μM in water without any cosolvent,resulting in an enhanced NIR fluorescence property(quantum yield=23%)and ***,the targeting ability of aptamer oligonucleotides is not affected by our molecular engineering *** reactive oxygen species(ROS)are produced intracellularly with 660 nm laser irradiation,eliciting mitochondria damage and cell *** growth is effectively inhibited with a single dose of aptamer-PA conjugates without in vivo *** therapeutic effect is more than 20-fold higher than that of *** with traditional formulation,using aptamer oligonucleotides as functional carriers to solubilize hydrophobic NIR PSs is more precise and *** DNA molecular engineering strategy paves a way for the rational design of molecularly targeted medicine for future clinical cancer therapy.

关键词： aptamer aptamer-drug conjugates photosensitive drugs targeted photodynamic therapy cancer theranostics

A toolbox for genetic manipulation in intestinal Clostridium symbiosum

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Synthetic and Systems Biotechnology 2024年第1期9卷 43-54页

作者： Pengjie Yang Jinzhong Tian Lu Zhang Hui Zhang Gaohua Yang Yimeng Ren Jingyuan Fang Yang Gu Weihong Jiang CAS-Key Laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant SciencesShanghai Institute of Plant Physiology and EcologyChinese Academy of SciencesShanghai200032China university of Chinese Academy of Sciences Beijing100049China Xianghu Laboratory Hangzhou311231China NHC Key Laboratory of digestive diseases Division of Gastroenterology and HepatologyShanghai Institute of Digestive DiseaseRenji HospitalSchool of MedicineShanghai Jiao Tong University145 Middle Shandong RoadShanghai200001China Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen518120China The Wallenberg Laboratory Department of Molecular and Clinical MedicineSahlgrenska AcademyUniversity of GothenburgBruna Straket 16Gothenburg41345Sweden

Gut microbes are closely related with human health,but remain much to *** symbiosum is a conditionally pathogenic human gut bacterium and regarded as a potential biomarker for early diagnosis of intestinal ***,the absence of an efficient toolbox that allows diverse genetic manipulations of this bacterium limits its in-depth ***,we obtained the complete genome sequence of *** ATCC 14940,a representative strain of *** this basis,we further developed a series of genetic manipulation methods for this ***,following the identification of a functional replicon pBP1 in *** ATCC 14940,a highly efficient conjugative DNA transfer method was established,enabling the rapid introduction of exogenous plasmids into ***,we constructed a dual-plasmid CRISPR/Cas12a system for genome editing in this bacterium,reaching over 60% repression for most of the chosen genes as well as efficient deletion(>90%)of three target ***,this toolbox was used for the identification of crucial functional genes,involving growth,synthesis of important metabolites,and virulence of *** ATCC *** work has effectively established and optimized genome editing methods in intestinal ***,thereby providing strong support for further basic and application research in this bacterium.

关键词： Gut Clostridium symbiosum Toolbox Gene overexpression Gene deletion Gene regulation

Aptamer-Based Cell-Surface Profiling with Single-Cell Resolution Enables Precise Cancer Characterization

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CCS Chemistry 2024年第1期6卷 196-207页

作者： Liujun Xu Yawei Feng tong Wang Shenhuan Li Kangli Xu Yue Sun Yi Luo Yishan Ye Yan Miao Yun Dong Zhenzhen Guo Qing Zhang Benshang Li He Huang Xue-Qiang Wang Liping Qiu Weihong Tan Molecular Science and Biomedicine Laboratory State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of BiologyAptamer Engineering Center of Hunan ProvinceHunan UniversityChangshaHunan 410082 The Key Laboratory of Zhejiang Province for Aptamers and Theranostics Zhejiang Cancer HospitalHangzhou Institute of MedicineChinese Academy of SciencesHangzhouZhejiang 310022 institute of Molecular medicine Renji HospitalShanghai Jiao Tong University School of MedicineCollege of Chemistry and Chemical EngineeringShanghai Jiao Tong UniversityShanghai 200240 Bone Marrow Transplantation Center The First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003 institute of Hematology Zhejiang UniversityHangzhou 310003 department of Hematology and Oncology Shanghai Children’s Medical CenterShanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghai 200127

Molecular profiling of cell-surface proteins is a powerful strategy for precise cancer *** mass cytometry(MC)enables synchronous detection of over 40 cellular parameters,its full potential in disease classification is challenged by the limited types of recognition probes currently *** this work,we synthesize a panel of heavy isotopeconjugated aptamers to profile cancer-associated signatures on the surface of hematological malignancy(HM)*** on 15 molecular signatures,we performed cell-surface profiling that allowed the precise classification of 8 HM cell *** with machine-learning technology,this aptamer-based MC platform also achieved multiclass identification of HM subtypes in clinical sampleswith 100%accuracy in the training cohort and 80%accuracy in the test ***,we report an effective and practical strategy for precise cancer classification at the singlecell level,paving the way for its clinical use in the near future.

关键词： molecular profiling cancer diagnosis mass cytometry aptamers machine learning

Injectable thermosensitive microsphere-hydrogel composite system:combined therapy of hepatocellular carcinoma by remodeling tumor immune microenvironment

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Science China Materials 2024年第10期67卷 3379-3391页

作者： Jinghan Liao Zhihua Wu Yijie Qiu Fangqin Xue Ke Gong Yi Duan Chao Xu Bin Liu Jiangtao Lin Yi Dong Ying Sun Yourong Duan State Key Laboratory of Systems medicine for Cancer Shanghai Cancer InstituteRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200032China department of Ultrasound Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China department of Gastrointestinal Surgery Shengli Clinical Medical College of Fujian Medical UniversityFujian Provincial HospitalFuzhou 350001China

Advanced hepatocellular carcinoma(HCC)is one of the most prevalent malignancies,and the clinical treatment outcomes are not *** to the complexity,heterogeneity,and immunosuppressive microenvironment of HCC,monotherapies have limited ***,combined therapy may effectively enhance antitumor treatment by remodeling the tumor immune *** study reports an injectable thermosensitive microsphere-hydrogel composite system for local co-delivery of the targeted drug sorafenib(SOR)and immunomodulatory cytokines for the combined therapy of *** delivery system exhibited superior properties such as dual-drug delivery,sustained and slow release,local injectability,thermosensitivity,and low side ***,it successfully remodeled the immune microenvironment of HCC by increasing the infiltration of CD8^(+)T cells and natural killer cells while decreasing the infiltration of immunosuppressive Treg cells,thereby achieving a potent synergistic effect with *** safe composite delivery system can remodel the tumor microenvironment and enhance anti-tumor treatment,providing a valuable option for the treatment of HCC.

关键词： microspheres thermosensitive hydrogel combined therapy immunomodulation hepatocellular carcinoma

DMF-scMT-seq linking methylome and transcriptome within single cells with digital microfluidics

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Science China Chemistry 2024年第6期67卷 2070-2078页

作者： Xing Xu Xi Zeng Xin Lin Shiyan Lin Shanshan Liang Tian Tian Rui Su Jia Song Chaoyong Yang Collaborative Innovation Center of Chemistry for Energy Materials The MOE Key Laboratory of Spectrochemical Analysis and InstrumentationState Key Laboratory of Physical Chemistry of Solid SurfacesDepartment of Chemical BiologyCollege of Chemistry and Chemical EngineeringThe First Affiliated Hospital of Xiamen UniversityXiamen UniversityXiamen361005China institute of Molecular medicine Renji HospitalShanghai Jiao Tong University School of MedicineShanghai200127China Chemistry and Materials Science College Shanghai Normal UniversityShanghai200234China Chemistry and Biomedicine Innovation Center(ChemBIC) School of Chemistry and Chemical EngineeringNanjing UniversityNanjing210023China

Single-cell joint analysis of methylome and transcriptome reveals how the methylation regulates the transcriptional ***,traditional bench-top protocols for single-cell DNA methylation and RNA transcription co-detection are laborintensive,cost-ineffective and ***,we establish the DMF-sc MT-seq,a highly-efficient and cost-effective method to simultaneously analyze single-cell DNA methylation and transcriptional activity based on digital *** MT-seq automates the workflow of single-cell isolation,cellular hypotonic lysis,nucleic acid separation and methylome/transcriptome library construction in a contactless and addressable *** system ensures high accuracy(R>0.85),high gene detection ability(14,697 genes per cell at 4 million sequencing depth),and high CpG coverage(677,198 CpG sites per cell at 1million sequencing depth).By using DMF-sc MT-seq,the relationship of DNA methylation and RNA transcription under different genomic contexts is *** further apply DMF-sc MT-seq to study the dynamics of transcription regulation with methylation-inhibiting anti-tumor Decitabine,and identify the methylated promoter/gene body driven genes in response to Decitabine ***-sc MT-seq facilitates the construction of the correlation of DNA methylation and transcriptional activity at the single-cell level in a flexible,sensitive and accurate way,which is anticipated to be a powerful tool in studying single-cell biological systems.

关键词： single-cell analysis digital microfluidics methylome sequencing transcriptome sequencing

Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

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Hepatobiliary & Pancreatic diseases International 2024年第3期23卷 241-248页

作者： Chao Sun George Boon-Bee Goh Wan-Cheng Chow Wah-Kheong Chan Grace Lai-Hung Wong Wai-Kay Seto Yi-Hsiang Huang Han-Chieh Lin I-Cheng Lee Hye Won Lee Seung Up Kim Vincent Wai-Sun Wong Jian-Gao Fan Center for Fatty Liver disease Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Lab of Pediatric Gastroenterology and NutritionShanghai 200092China department of gastroenterology&Hepatology Singapore General HospitalSingaporeSingapore gastroenterology and Hepatology Unit Department of MedicineFaculty of MedicineUniversity of MalayaKuala LumpurMalaysia department of medicine and Therapeutics and State Key Laboratory of digestive disease The Chinese University of Hong KongHong KongChina department of medicine The University of Hong KongHong KongChina institute of Clinical medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina Division of gastroenterology and Hepatology Taipei Veterans General HospitalTaipeiTaiwanChina Faculty of medicine National Yang Ming Chiao Tung University School of MedicineTaipeiTaiwanChina department of Internal medicine Yonsei University College of MedicineSeoulKorea

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic ***,the prevalence and risk factors for impaired renal function in patients with NAFLD remain *** objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD ***:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective *** fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 *** renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)***:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,*** multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of *** glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

关键词： Nonalcoholic fatty liver disease Impaired renal function Agile 3+ Agile 4 Metabolic syndrome

Application Analysis of Doctor-Nurse Cooperation Follow-up Model Based on the Internet Platform in Continuation Care of Patients after Urooncology Surgery

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Journal of Clinical and Nursing Research 2024年第7期8卷 310-321页

作者： Yan Guo Hanjing Zhu Sijie You Yeli Cao Liya Ma Xia Yuan Nursing department Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China

Objective:To explore the application effect of a doctor-nurse cooperation follow-up model based on an Internet platform in the continuation of care for patients after uro-oncology ***:A convenient sampling method was used to select patients with urinary system tumors who underwent surgery in the department of Urology in Grade III A general hospital in shanghai from May to August *** who underwent surgery from May to June 2022 were assigned to the control group,and those who underwent surgery from July to August 2022 were assigned to the experimental *** control group received routine post-discharge nursing health education and telephone *** the basis of routine discharge guidance,the experimental group implemented the intervention method based on the Internet platform in continuation *** levels of self-management efficacy,satisfaction,and incidence of unplanned readmission were compared one month after discharge between the two ***:One month after discharge,the self-management efficacy of the experimental group(90.15±7.92)was significantly higher than that of the control group(79.10±7.84),and the patient satisfaction score(97.83±2.32)was significantly higher than that of the control group(90.23±2.58),with statistical significance(P<0.05).Additionally,the incidence of unplanned readmissions within one month after discharge in the experimental group(1.59%)was slightly lower than that in the control group(4.84%).Conclusion:The doctor-nurse cooperation follow-up model based on the Internet platform in continuation care can significantly improve the self-management efficiency of patients after discharge and enhance patient satisfaction,providing a new approach for discharge follow-up of urological tumor patients after surgery.

关键词： Urologic neoplasms Internet platform Doctor-nurse cooperation Continuation care