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Early and Sensitive Detection of Pathogens for Public Health and Biosafety:An Example of Surveillance and Genotyping of SARS-CoV-2 in Sewage Water by Cas12a-Facilitated Portable Plasmonic Biosensor

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Research 2024年第2期2023卷 259-272页

作者： Tianzhong Li Yuzhi Chen Zhi Chen Yuan Hao Minyi Liang Yingxia Liu Guanyong Ou Huanian Zhang Yuxuan Tang Yabing Hao Swelm Wageh Omar AAl-Hartomy Abul Kalam Bin Zhang Xin Shi Xuejin Li Han Zhang College of Physics and Optoelectronic Engineering Institute of Translational MedicineDepartment of OtolaryngologyShenzhen Second People's HospitalFirst Affiliated Hospital of Shenzhen UniversityHealth Science CenterShenzhen UniversityShenzhen 518060China shenzhen Key laboratory of Sensor Technology Shenzhen 518060China The Sixth Affiliated Hospital of Guangzhou Medical University Qingyuan People's HospitalQingyuan 511518China shenzhen Key laboratory of Pathogen and Immunity National Clinical Research Center for Infectious DiseaseState Key Discipline of Infectious DiseaseShenzhen Third People's HospitalSecond Hospital Affiliated to Southern University of Science and TechnologyShenzhen 518112China School of Medicine Southern University of Science and TechnologyShenzhen 518055China School of Physics and Optoelectronic Engineering Shandong University of TechnologyZibo 255049China Department of Physics Faculty of ScienceKing Abdulaziz University Jeddah 21589Saudi Arabia Research Center for Advanced Materials Science(RCAMS) King Khalid UniversityP.0.Box 9004Abha 61413Saudi Arabia Department of Chemistry College of ScienceKing Khalid UniversityP.0.Box9004Abha 61413 Saudi Arabia Health Sciences Institute China Medical UniversityShenyang 110000China The Chinese University of Hong Kong Shenzhen 518060China

Infectious diseases severely threaten public health and global *** addition to transmission through the air,pathogenic microorganisms have also been detected in environmental liquid samples,such as sewage *** biochemical detection methodologies are time-consuming and cost-ineffective,and their detection limits hinder early *** the present study,ultrafine plasmonic fiber probes with a diameter of 125μm are fabricated for clustered regularly interspaced short palindromic repeats/CRISPR-associated protein(CRISPR/Cas)-12a-mediated sensing of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Single-stranded DNA exposed on the fiber surface is trans-cleaved by the Cas12a enzyme to release gold nanoparticles that are immobilized onto the fiber surface,causing a sharp reduction in the surface plasmon resonance(SPR)*** proposed fiber probe is virus-specific with the limit of detection of~2,300 copies/ml,and genomic copy numbers can be reflected as shifts in wavelengths.A total of 21 sewage water samples have been examined,and the data obtained are consistent with those of quantitative polymerase chain reaction(qPCR).In addition,the Omicron variant and its mutation sites have been fast detected using S gene-specific *** study provides an accurate and convenient approach for the real-time surveillance of microbial contamination in sewage water.

关键词： fiber consuming hinder

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Immune-tumor interaction dictates spatially directed evolution of esophageal squamous cell carcinoma

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National Science Review 2024年第5期11卷 170-185页

作者： Yong Zhou Shanlan Mo Heyang Cui Ruifang Sun Weimin Zhang Xiaofei Zhuang Enwei Xu Hongyi Li Yikun Cheng Yongsheng Meng Meilin Liu Ting Yan Huijuan Liu Ling Zhang Bin Yang Yanfeng Xi Shubin Wang Xiaolong Cheng Shuai Cheng Li Zhihua Liu Qimin Zhan Zheng Hu Yongping Cui Cancer Institute Department of Pathology Peking University Shenzhen Hospital Shenzhen Peking University-the Hong Kong University of Science and Technology(PKU-HKUST) Medical Center Institute of Cancer ResearchShenzhen Bay Laboratory Key laboratory of Cellular Physiology of the Ministry of Education Department of Pathology Shanxi Medical University City University of Hong Kong shenzhen Research Institute CAS Key laboratory of Quantitative Engineering Biology Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of Sciences Department of Surgery Faculty of Medicine The Chinese University of Hong Kong Department of Tumor Biobank Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular Oncology Peking University Cancer Hospital & Institute Research Unit of Molecular Cancer Research Chinese Academy of Medical Sciences Department of Thoracic Surgery Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University Department of Pathology Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University College of Letters & Science University of California Berkeley State Key laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College

Esophageal squamous cell carcinoma（ESCC） is a poor-prognostic cancer type with extensive intra-and inter-patient heterogeneity in both genomic variations and tumor microenvironment（TME）. However, the patterns and drivers of spatial genomic and microenvironmental heterogeneity of ESCC remain largely unknown. Here, we generated a spatial multi-omic atlas by whole-exome, transcriptome, and methylome sequencing of 507 tumor samples from 103 patients. We identified a novel tumor suppressor PREX2,accounting for 22% of ESCCs with frequent somatic mutations or hyper-methylation, which promoted migration and invasion of ESCC cells in vitro. Analysis of the TME and quantification of subclonal expansion indicated that ESCCs undergo spatially directed evolution, where subclones mostly originated from the tumor center but had a biased clonal expansion to the upper direction of the ***, we found upper regions of ESCCs often underwent stronger immunoediting with increased selective fitness, suggesting more stringent immune selection. In addition, distinct TMEs were associated with variable genomic and clinical outcomes. Among them, hot TME was associated with high immune evasion and subclonal heterogeneity. We also found that immunoediting, instead of CD8+T cell abundance, acts as an independent prognostic factor of ESCCs. Importantly, we found significant heterogeneity in previously considered potential therapeutic targets, as well as BRCAness characteristics in a subset of patients, emphasizing the importance of focusing on heterogeneity in ESCC targeted ***, these findings provide novel insights into the mechanisms of the spatial evolution of ESCC and inform precision therapeutic strategies.

关键词： squamous cell carcinoma heterogeneity multi-omics evolution tumor microenvironment

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Recent advances in genome-scale engineering in Escherichia coli and their applications

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Engineering Microbiology 2024年第1期4卷 28-38页

作者： Hui Gao Zhichao Qiu Xuan Wang Xiyuan Zhang Yujia Zhang Junbiao Dai Zhuobin Liang Institute of Molecular Physiology Shenzhen Bay LaboratoryShenzhen 518132China CAS Key laboratory of Quantitative Engineering Biology Guangdong Provincial Key Laboratory of Synthetic Genomics and Shenzhen Key Laboratory of Synthetic Genomics.Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Regenerative Medicine Program Bellvitge Institute for Biomedical Research(IDIBELL)and Program for Clinical Translation of Regenerative Medicine in Catalonia(P-CMRC)L’Hospitalet de LlobregatBarcelona 08908Spain Faculty of Pharmacy and Food Science Barcelona UniversityBarcelona 08028Spain College of Life Sciences Northwest A&F UniversityShaanxi 712100China shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureKey Laboratory of Synthetic BiologyMinistry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518120China

Owing to the rapid advancement of genome engineering technologies,the scale of genome engineering has expanded *** editing has progressed from one genomic alteration at a time that could only be employed in few species,to the simultaneous generation of multiple modifications across many genomic loci in numerous *** development and recent advances in multiplex automated genome engineering(MAGE)-associated technologies and clustered regularly interspaced short palindromic repeats and their associated protein(CRISPR-Cas)-based approaches,together with genome-scale synthesis technologies offer unprecedented opportunities for advancing genome-scale engineering in a broader *** approaches provide new tools to generate strains with desired phenotypes,understand the complexity of biological systems,and directly evolve a genome with novel ***,we review the recent major advances in genome-scale engineering tools developed for Escherichia coli,focusing on their applications in identifying essential genes,genome reduction,recoding,and beyond.

关键词： Genome-scale engineering E.coli Recombineering CRISPR-Cas

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Identification of 3-ketocapnine reductase activity within the human microbiota

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mLife 2024年第2期3卷 307-316页

作者： Xiaotong Wu Lukuan Hou Haili Zhang Yi Ma Jufang Wang Mingwei Cai Xiaoyu Tang School of Biology and Biological Engineering South China University of TechnologyGuangzhouChina Institute of Chemical Biology Shenzhen Bay LaboratoryShenzhenChina College of Chemistry and Pharmacy Northwest A&F UniversityYanglingChina

The microbial synthesis of sulfonolipids within the human body is likely involved in maintaining human health or causing ***,the enzymes responsible for their biosynthesis remain largely *** this study,we identified and verified the role of 3-ketocapnine reductase,the third-step enzyme,in the four-step conversion of L-phosphoserine into sulfobacin B both in vivo and in *** finding builds upon our previous research into sulfonolipid biosynthesis,which focused on the vaginal bacterium Chryseobacterium gleum DSM 16776 and the gut bacterium Alistipes finegoldii DSM *** comprehensive gene mapping,we demonstrate the widespread presence of potential sulfonolipid biosynthetic genes across diverse bacterial species inhabiting various regions of the human *** findings shed light on the prevalence of sulfonolipid-like metabolites within the human microbiota,suggesting a potential role for these lipid molecules in influencing the intricate biointeractions within the complex microbial ecosystem of the human body.

关键词： 3-ketocapnine reductase capnines human microbiota sulfonolipids

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Mechanical Behavior and Failure Mechanism of an As-Extruded Mg-11wt%Y Alloy at Elevated Temperature

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Acta Metallurgica Sinica(English Letters) 2024年第6期37卷 969-981页

作者： Lan Zhang Dao-Kui Xu Bao-Jie Wang Cui-Lan Lu Shuo Wang Xiang-Bo Xu Dong-Liang Wang Xin Lv En-Hou Han School of Materials Science and Engineering University of Science and Technology of ChinaShenyang110016China Key laboratory of Nuclear Materials and Safety Assessment Institute of Metal ResearchChinese Academy of SciencesShenyang110016China School of Environmental and Chemical Engineering Shenyang Ligong UniversityShenyang110159China Key Lab of Electromagnetic Processing of Materials Ministry of EducationNortheastern UniversityShenyang110819China Institute of Corrosion Science and Technology Guangdong510070China

Through carrying out the high-temperature tensile experiments on an as-extruded Mg-11wt%Y alloy at 350℃,400℃,450℃,500℃and 550℃,the mechanical behavior and fracture mechanisms at elevated temperatures are investigated and *** results show that with the increase of temperature,the yield strength and ultimate tensile strength of the alloy increase at first and then decrease,while that the elongation ratio decreases firstly and then *** the sample being tested at 350℃,the values of yield strength,ultimate tensile strength and the elongation ratio are 188 MPa,266 MPa and 11%,*** 400℃,the yield strength and ultimate tensile strength reach the maximum values of,respectively,198 MPa and 277 MPa,but the elongation ratio is the lowest and its value is only 8%.When the applied temperature is increased to 550℃,the values of yield strength and ultimate tensile strength,respectively,decrease to 140 MPa and 192 MPa and the elongation ratio increases to 38%.Failure analysis demonstrates that the fracture surfaces of different samples are mainly composed of plastic dimples and exhibit the typical characteristic of ductile *** observation to the fracture side surfaces indicates that at the temperatures of 350℃and 400℃,microcracks mainly initiate in the interior of Mg_(24)Y_(5)*** the temperatures are 450℃,500℃and 550℃,the cracks preferentially initiate at the Mg_(24)Y_(5)/α-Mg interfaces.

关键词： Mg-Y alloy High-temperature tensile properties Fracture mechanism Failure analysis

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Biomimetic manganese-based theranostic nanoplatform for cancer multimodal imaging and twofold immunotherapy

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Bioactive Materials 2023年第1期19卷 237-250页

作者： Yuyue Zhao Yuanwei Pan Kelong Zou Zhou Lan Guowang Cheng Qiuying Mai Hao Cui Qianfang Meng Tongkai Chen Lang Rao Limin Ma Guangtao Yu Stomatological Hospital Southern Medical UniversityGuangzhou510280China Institute of Biomedical Health Technology and Engineering Shenzhen Bay LaboratoryShenzhen518132China Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and Faculty of EngineeringNational University of SingaporeSingapore119074Singapore Science and Technology Innovation Center Guangzhou University of Chinese MedicineGuangzhou510405China Medical Research Center Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou510080China

The limited clinical response and serious side effect have been challenging in cancer immunotherapy resulting from immunosuppressive tumor microenvironment(TME)and inferior drug ***,an active targeting TME nanoplatform capable of revising the immunosuppressive TME microenvironment is ***,gold nanorods(GNRs)are covered with silica dioxide(SiO_(2))and then coated manganese dioxide(MnO_(2))to obtain GNRs@SiO_(2)@MnO_(2)(GSM).Myeloid-derived suppressor cells(MDSCs)membrane is further camouflaged on the surface of GSM to obtain GNRs@SiO_(2)@MnO_(2)@MDSCs(GSMM).In this system,GSMM inherits active targeting TME capacity of *** localized surface plasmon resonance of GNRs is developed in near-infraredⅡwindow by MnO_(2)layer coating,realizing NIR-Ⅱwindow photothermal imaging and photoacoustic imaging of *** on the release of Mn^(2+)in acidic TME,GSMM can be also used for magnetic resonance *** cancer cells,Mn^(2+)catalyzes H_(2)O_(2)into·OH for(chemodynamic therapy)CDT leading to activate cGAS-STING,but also directly acts on STING inducing secretion of typeⅠinterferons,pro-inflammatory cytokines and ***,photothermal therapy and CDT-mediated immunogenic cell death of tumor cells can further enhance anti-tumor immunity via exposure of CRT,HMGB1 and *** summary,our nanoplatform realizes multimodal cancer imaging and dual immunotherapy.

关键词： Biomimetic Manganese ions The second near-infrared window Cancer imaging Immunotherapy

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Emerging 2D pnictogens for biomedical applications

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Chinese Chemical Letters 2022年第5期33卷 2345-2353页

作者： Ruoyao Li Zhengbao Zha Zhaohua Miao Cheng-Yan Xu School of Food and Biological Engineering Hefei University of TechnologyHefei 230009China Sauvage laboratory for Smart Materials School of Materials Science and EngineeringHarbin Institute of Technology(Shenzhen)Shenzhen 518055China shenzhen bay laboratory Shenzhen 518132China

Two-dimensional(2D)materials composed of single pnictogen element,namely,2D pnictogens(e.g.,black phosphorus,arsenene,antimonene and bismuthine),have recently showed remarkable potential for biomedical applications,especially after the rapid development of black *** unique optical and electronic properties,2D pnictogens are considered as promising nanoagents for biosensors,diagnosis and *** this review,after brief introduction of the structure,properties,synthesis strategies,and biocompatibility of 2D pnictogens,their biomedical applications including anti-tumor,anti-inflammation,anti-bacterial,neurodegenerative treatment and tissue repairing are *** major obstacles and opportunities of 2D pnictogens are also *** review provides a short yet timely summary on the synthesis and biomedical applications of emerging 2D pnictogens.

关键词： 2D materials Biomedical applications Anti-tumor Anti-inflammation Anti-bacterial

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Discovery of a highly potent and orally available importin-β1 inhibitor that overcomes enzalutamide-resistance in advanced prostate cancer

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Acta Pharmaceutica Sinica B 2023年第12期13卷 4934-4944页

作者： Jia-Luo Huang Xue-Long Yan Dong Huang Lu Gan Huahua Gao Run-Zhu Fan Shen Li Fang-Yu Yuan Xinying Zhu Gui-Hua Tang Hong-Wu Chen Junjian Wang Sheng Yin School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China School of Pharmacy Guizhou Medical UniversityGuian New DistrictGuizhou 550025China School of Medicine University of California DavisSacramentoCA 95817USA

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many ***,the lack of druggable inhibitors restricts its therapeutic proof of *** the present work,we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability(>25 folds)and oral ***1-Br inhibited the survival of castration-resistant prostate cancer(CRPC)cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy(0.5 mg/kg)and in enzalutamidecombination *** study revealed that by targeting importin-β1,DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers,particularly AR-V7,a main contributor to enzalutamide resistance,leading to the integral suppression of downstream oncogenic *** study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

关键词： Importin-β1 CRPC Drug discovery Enzalutamide-resistance Natural product Cancer Daphnane diterpenoid Nuclear transporter

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Enhanced plasticity of Fe-based bulk metallic glass by tailoring microstructure

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Transactions of Nonferrous Metals Society of China 2012年第2期22卷 348-353页

作者：郭胜锋王敬丰张红菊谢盛辉西南大学材料科学与工程学院重庆400715 重庆大学国家镁合金材料工程技术研究中心重庆400044 深圳大学深圳市特种功能材料重点实验室深圳518060 深圳大学材料科学与工程学院深圳518060

The room temperature compressive plasticity of Fe75MosP10Cs.3B1.7 bulk metallic glass （BMG） was improved from 0.5% to 1.8% by increasing the sample diameter from 1.5 mm to 2.0 mm. With increasing the sample diameter to 2.0 mm, a heterogeneous microstructure with in-situ formed a-Fe dendrite sparsely distributed in the amorphous matrix can be attained. This heterogeneous mierostructure is conceived to be highly responsible for the enhanced global plasticity in this marginal Fe-based BMG.

关键词： bulk metallic glass composite rapid-solidification mechanical property

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A novel inhibitor of N^(6)-methyladenosine demethylase FTO induces m RNA methylation and shows anti-cancer activities

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Acta Pharmaceutica Sinica B 2022年第2期12卷 853-866页

作者： Guoyou Xie Xu-Nian Wu Yuyi Ling Yalan Rui Deyan Wu Jiawang Zhou Jiexin Li Shuibin Lin Qin Peng Zigang Li Hongsheng Wang Hai-Bin Luo School of Pharmaceutical Sciences Sun Yat-sen UniversityGuangzhou 510006China Key laboratory of Tropical Biological Resources of Ministry of Education School of Life and Pharmaceutical SciencesHainan UniversityHaikou 570228China Center for Translational Medicine the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Institute of Systems and Physical Biology Shenzhen Bay LaboratoryShenzhen 518067China

N^(6)-methyladenosine(m^(6)A)modification is critical for m RNA splicing,nuclear export,stability and *** mass and obesity-associated protein(FTO),the first identified m^(6)A demethylase,is critical for cancer ***,we developed small-molecule inhibitors of FTO by virtual screening,structural optimization,and *** a result,two FTO inhibitors namely 18077 and 18097 were identified,which can selectively inhibit demethylase activity of ***,18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer *** addition,18097 reprogrammed the epi-transcriptome of breast cancer cells,particularly for genes related to P53 pathway.18097 increased the abundance of m^(6)A modification of suppressor of cytokine signaling1(SOCS1)m RNA,which recruited IGF2 BP1 to increase m RNA stability of SOCS1 and subsequently activated the P53 signaling ***,18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma(PPARγ),CCAAT/enhancer-binding protein alpha(C/EBPa),and C/EBPβ.Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer ***,we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.

关键词： m6A FTO inhibitors Cancer cell Lipogenesis SOCS1

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