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Enzymatic self-assembly/disassembly turns “ON”/“OFF” the mimetic hydrolytic activity of histidine nanofibers

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Science China Chemistry 2024年第2期67卷 517-522页

作者： Xianbao Sun Manli Wang Xiaoyang Liu Wenjun Zhan Guangqiong Xu Qiaochu Jiang Hai-Dong Xu Fuqiang Wang Gaolin Liang State Key Laboratory of Digital medical Engineering School of Biological Science and Medical EngineeringSoutheast UniversityNanjing210096China Analysis Center Nanjing Medical UniversityNanjing210029China

Mimetic enzymes are devised as alternates or supplements of natural enzymes in broad fields but regulating their activities in a switchable manner remains ***,we proposed an enzymatic self-assembly/disassembly strategy to address this issue.A peptide molecule Nap FFEYIH(YH) was rationally designed which,after self-assembling into nanofibers,lined up the histidine moieties to form active hydrolysis centers for mimicking hydrolase *** dephosphorylation of Nap FFEYp IH(Yp H) by alkaline phosphatase to yield YH also turned “ON” the hydrolase *** turn,phosphorylation of YH by phosphokinase epidermal growth factor receptor to yield Yp H disassembled the nanofibers and thus turned the activity “OFF”.As such,the “ON”/“OFF” of the mimetic hydrolase activities could be regulated under physiological conditions through ALP/EGFR-mediated self-assembly/disassembly of histidine *** work provides a feasible strategy for the on-demand fabrication of artificial enzymes with controllable and superior activities.

关键词： disassembly hydrolytic activity mimetic enzyme phosphorylation self-assembly

The emerging tumor microbe microenvironment: From delineation to multidisciplinary approach-based interventions

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1560-1591页

作者： Yu Fu Jia Li Wenyun Cai Yulan Huang Xinlong Liu Zhongyi Ma Zhongjie Tang Xufei Bian Ji Zheng Jiayun Jiang Chong Li medical Research Institute College of Pharmaceutical SciencesSouthwest UniversityChongqing 400715China Institute of Hepatobiliary Surgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Department of Urology Urologic Surgery CenterXinqiao HospitalThird Military Medical University(Army Medical University)Chongqing 400037China

Intratumoral microbiota has become research hotspots,and emerges as a non-negligent new component of tumor microenvironments(TME),due to its powerful infuence on tumor initiation,metas-tasis,immunosurveillance and prognosis despite in *** accumulations of microbes,and their related components and metabolites within tumor tissues,endow TME with additional pluralistic features which are distinct from the conventional ***,it's definitely necessary to comprehen-sively delineate the sophisticated landscapes of tumor microbe microenvironment,as well as their func-tions and related underlying ***,in this review,we focused on the fields of tumor microbe microenvironment,including the heterogeneity of intratumor microbiota in different types of tu-mors,the controversial roles of intratumoral microbiota,the basic features of tumor microbe microenvi-ronment(i.e.,pathogen-associated molecular patterns(PAMPs),typical microbial metabolites,autophagy,infammation,multi-faceted immunomodulation and chemoresistance),as well as the multi-disciplinary approach-based intervention of tumor microbiome for cancer therapy by applying wild-type or engineered live microbes,microbiota metabolites,antibiotics,synthetic biology and rationally de-signed *** hope our work will provide valuable insight to deeply understand the interplay of cancer-immune-microbial,and facilitate the development of microbes-based tumor-specific treatments.

关键词： Tumor microbe microenvironment Microbiota metabolites Immunomodulation Chemoresistance Multidisciplinary approach Genetically engineered microbiota Autophagy Outer membrane vesicles

New clinical trial design in precision medicine:discovery,development and direction

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1293-1321页

作者： Xiao-Peng Duan Bao-Dong Qin Xiao-Dong Jiao Ke Liu Zhan Wang Yuan-Sheng Zang Department of medical Oncology Changzheng HospitalNaval Medical UniversityShanghaiChina

In the era of precision medicine,it has been increasingly recognized that individuals with a certain disease are complex and different from each *** to the underestimation of the significant heterogeneity across participants in traditional"one-sizefits-all"trials,patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket,umbrella,and platform trial designs under the master protocol *** recent years,the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous *** the rapid increase in the number of basket,umbrella,and platform trials,the current clinical and research understanding of these new trial designs,as compared with traditional trial designs,remains *** majority of the research focuses on methodologies,and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial ***,we provide this comprehensive review of the discovery and development of basket,umbrella,and platform trials and their underlying logic from the perspective of precision ***,we discuss future directions on the potential development of these new clinical design in view of the"Precision Pro","Dynamic Precision",and"Intelligent Precision".This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic,which be essential to accelerate the progression of precision medicine.

关键词： clinical approval successive

Predictive value of preoperative routine examination for the prognosis of patients with pT2N0M0 or pT3N0M0 colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2429-2438页

作者： Peng-Fei Jing Jin Chen En-Da Yu Chao-Yu Miao Department of Colorectal Surgery Changhai HospitalSecond Military Medical University/Naval Medical UniversityShanghai 200433China Department of Endocrinology and Metabolism Changhai HospitalSecond Military Medical University/Naval Medical UniversityShanghai 200433China Department of Pharmacology Second Military Medical University/Naval Medical UniversityShanghai 200433China

BACKGROUND In recent years,the incidence of colorectal cancer(CRC)has been *** the popularization of endoscopic technology,a number of early CRC has been ***,despite current treatment methods,some patients with early CRC still experience postoperative recurrence and *** To search for indicators associated with early CRC recurrence and metastasis to identify high-risk *** A total of 513 patients with pT2N0M0 or pT3N0M0 CRC were retrospectively enrolled in this *** of blood routine test,liver and kidney function tests and tumor markers were collected before *** were followed up through disease-specific database and telephone *** recurrence,metastasis or death were used as the end point of study to find the risk factors and predictive value related to early CRC recurrence and *** We comprehensively compared the predictive value of preoperative blood routine,blood biochemistry and tumor markers for disease-free survival(DFS)and overall survival(OS)of *** multivariate analysis demonstrated that low platelet count was significantly associated with poor DFS[hazard ratio(HR)=0.995,95% confidence interval(CI):0.991-0.999,P=0.015],while serum carcinoembryonic antigen(CEA)level(HR=1.008,95%CI:1.001-1.016,P=0.027)and serum total cholesterol level(HR=1.538,95%CI:1.026-2.305,P=0.037)were independent risk factors for *** cutoff value of serum CEA level for predicting OS was 2.74 ng/*** the OS of CRC patients with serum CEA higher than the cutoff value was worse than those with lower CEA level,the difference between the two groups was not statistically significant(P=0.075).CONCLUSION For patients with T2N0M0 or T3N0M0 CRC,preoperative platelet count was a protective factor for DFS,while serum CEA level was an independent risk factor for *** that these measures are easier to detect and more acceptable to patients,they may have broader applications.

关键词： Colorectal cancer Platelet count Serum carcinoembryonic antigen Total cholesterol level Overall survival Disease-free survival

Zinc finger protein 831 promotes apoptosis and enhances chemosensitivity in breast cancer by acting as a novel transcriptional repressor targeting the STAT3/Bcl2 signaling pathway

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Genes & Diseases 2024年第1期11卷 430-448页

作者： Jun Fan Zhe Zhang Hongqiang Chen Dongjiao Chen Wenbo Yuan Jingzhi Li Yong Zeng Shimeng Zhou Shu Zhang Gang Zhang Jiashen Xiong Lu Zhou Jing Xu Wenbin Liu Yan Xu Department of Breast and Thyroid Surgery Daping HospitalArmy Medical University(Third Military Medical University)Chongqing 400042China Institute of Toxicology College of Preventive MedicineArmy Medical University(Third Military Medical University)Chongqing 400038China Department of Environmental Health College of Preventive MedicineArmy Medical University(Third Military Medical University)Chongqing 400038China Anesthesia and Intensive Care Chinese University of Hong KongHong Kong SAR 999077China School of Public Health Xinxiang Medical UniversityXinxiangHenan 453003China School of Public Health China Medical UniversityShenyangLiaoning 110122China

Emerging evidence suggested that zinc finger protein 831(ZNF831)was associated with immune activity and stem cell regulation in breast ***,the roles and molec-ular mechanisms of ZNF831 in oncogenesis remain ***831 expression was significantly diminished in breast cancer which was associated with promoter CpG methylation but not *** over-expression of ZNF831 suppressed breast cancer cell proliferation and col-ony formation and promoted apoptosis in vitro,while knockdown of ZNF831 resulted in an opposite ***-proliferation effect of ZNF831 was verified in *** analysis of public databases and transcriptome sequencing both showed that ZNF831 could enhance apoptosis through transcriptional regulation of the JAK/STAT *** and luciferase report assays demonstrated that ZNF831 could directly bind to one specific region of STAT3 promoter and induce the transcriptional inhibition of *** a result,the attenuation of STAT3 led to a restraint of the transcription of Bcl2 and thus accelerated the apoptotic *** of STAT3 diminished the apoptosis-promoting effect of ZNF831 in breast cancer cell ***,ZNF831 could ameliorate the anti-proliferation effect of capecitabine and gemcitabine in breast cancer cell *** findings demonstrate for the first time that ZNF831 is a novel transcriptional suppressor through inhibiting the expression of STAT3/Bcl2 and promoting the apoptosis process in breast cancer,suggesting ZNF831 as a novel biomarker and potential therapeutic target for breast cancer patients.

关键词： Apoptosis Breast cancer Chemosensitivity STAT3 ZNF831

Multifunctional high-performance pressure/proximity/temperature sensors enabled by hybrid resistive-supercapacitive response

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Nano Research 2024年第6期17卷 5604-5613页

作者： Huijun Kong Zhongqian Song Meichun Ding Changxiang Shao Jiahui Yu Baolei Wang Weiyan Li Chenwei Li Li Niu School of Chemistry and Pharmaceutical Engineering Shandong First Medical University and Shandong Academy of Medical SciencesJinan 250117China College of Artificial Intelligence and Big Data for medical Sciences Shandong First Medical University and Shandong Academy of Medical SciencesJinan 250117China School of Chemical Engineering and Technology Sun Yat-sen UniversityZhuhai 519082China

The issue of sensitivity attenuation in high-pressure region has been a persistent concern for pressure-sensitive electronic *** order to tackle such trade-off between sensitivity and linear range,herein,a hybrid piezoresistive-supercapacitive(HRSC)strategy is proposed via introducing a piezoresistive porous aerogel layer between the charge collecting electrodes and iontronic films of the pressure ***,the HRSC-induced impedance regulation and supercapacitive behavior contribute to significant mitigation in sensitivity attenuation,achieving high sensitivity across wide linear range(44.58 kPa^(−1)from 0 to 3 kPa and 23.6 kPa^(−1)from 3 to 12 kPa).The HRSC pressure sensor exhibits a low detection limit of 1 Pa,fast responsiveness(~130 ms),and excellent cycling stability,allowing to detect tiny pressure of air flow,finger bending,and human ***,the HRSC sensor exhibits exceptional perception capabilities for proximity and temperature,broadening its application scenarios in prosthetic perception and electronic *** proposed HRSC strategy may boost the ongoing research on structural design of high-performance and multimodal electronic sensors.

关键词： multimodal sensor pressure sensor high sensitivity MXene/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)(PEDOT:PSS)aerogel structural design

IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53

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Genes & Diseases 2024年第1期11卷 495-508页

作者： Baoyu He Jing Liang Qianqian Qin Yuqin Zhang Shuo Shi Jinghe Cao Zhixin Zhang Qingli Bie Rou Zhao Li Wei Baogui Zhang Bin Zhang Department of Laboratory Medicine Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Postdoctoral Mobile Station of Shandong university of Traditional Chinese Medicine JinanShandong 250355China Department of Reproductive Medicine Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Department of Gastrointestinal Surgery Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Institute of Forensic Medicine and Laboratory Medicine Jining Medical UniversityJiningShandong 272067China

Cancer stem cells(CSCs)are considered tumor-initiating cells and the main drivers of disease *** these rare cancer cells,however,remains challenging with respect to therapeutic ***,we report the up-regulation of IL-13RA2 expression in colorectal cancer(CRC)tissues and spheroid *** expression of IL-13RA2 was positively correlated with canonical stemness markers in *** further demonstrated that the level of IL-13 was up-regulated in the serum of CRC ***,recombinant IL-13(rIL13)stimulation promoted the sphere formation,proliferation,and migration of CRC cells in vitro and enhanced tumorigenesis in *** phenotype could be reversed by knocking down ***,IL-13 activated autophagy by inducing LC3I/LC3II transformation in CRC-CSCs,which was crucial for the biological functions of *** further demonstrated that IL-13RA2 acted as a modular link of the E3 ligase UBE3C and the substrate p53 protein,enhancing the interaction of UBE3C and p53,thereby inducing the K48-linked ubiquitination of *** conclusion,the IL-13/IL-13RA2 signaling cascade promotes CRC-CSC self-renewal and tumorigenesis by inducing p53 ubiquitination,adding an important layer to the connection between IL-13 and p53,which can be translated into novel targeted therapies.

关键词： Autophagy Colorectal cancer stem cells IL-13/IL-13RA2 signaling p53

The role of lipid metabolism in osteoporosis:Clinical implication and cellular mechanism

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Genes & Diseases 2024年第4期11卷 220-233页

作者： Jing Zhang Wenhui Hu Zhi Zou Yuheng Li Fei Kang Jianmei Li Shiwu Dong College of Bioengineering Chongqing UniversityChongqing 400044China Department of Biomedical Materials Science College of Biomedical EngineeringArmy Medical University(Third Military Medical University)Chongqing 400038China State Key Laboratory of Trauma and Chemical Poisoning Army Medical University(Third Military Medical University)Chongqing 400038China

In recent years,researchers have become focused on the relationship between lipids and bone metabolism ***,many diseases related to lipid metabolism dis-orders,such as nonalcoholic fatty liver disease,atherosclerosis,obesity,and menopause,are associated with osteoporotic *** has been clinically observed in humans that these lipid metabolism disorders promote changes in osteoporosis-related indicators bone mineral density and bone ***,similar osteoporotic phenotype changes were observed in high-fat and high-cholesterol-induced animal *** lipid metabolism(such as increased oxidized lipids and elevated plasma cholesterol)affects bone microenvironment ho-meostasis via cross-organ communication,promoting differentiation of mesenchymal stem cells to adipocytes,and inhibiting commitment towards ***,disturbances in lipid metabolism affect the bone metabolism balance by promoting the secretion of cyto-kines such as receptor activator of nuclear factor-kappa B ligand by osteoblasts and stimulating the differentiation of ***,this review addresses the possible link be-tween lipid metabolism disorders and osteoporosis and elucidates the potential modulatory mechanisms and signaling pathways by which lipid metabolism affects bone metabolism *** also summarize the possible approaches and prospects of intervening lipid meta-bolismforosteoporosistreatment.

关键词： Bone homeostasis Cross-organ communication Lipid metabolism Osteoclast Osteoporosis

TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells via Targeting Wnt/β-catenin Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 322-329页

作者： QIN Jing-jing NIU Meng-da CHA Zhe GENG Qing-hua LI Yu-lin REN Chun-guang David P.Molloy YU Hua-rong Research Center of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Laboratory of Developmental Biology Department of Cell Biology and GeneticsSchool of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Department of Biochemistry and Molecular Biology School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China

Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma *** Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,*** reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was *** Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(P<0.01).TCCT up-regulated the expression of GSK-3β and down-regulated the expression of β-catenin and its associated proteins(P<0.05 or P<0.01),including c-Myc,Cyclin-D1,and matrix metalloproteinase(MMP)-*** addition,LiCl,an activator of the Wnt signaling pathway,restored the inhibitory effects of TCCT on the expression of β-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(P<0.05 or P<0.01).Conclusions Celastrol and TRAIL can synergistically suppress glioblastoma cell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin *** underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

关键词： celastrol Chinese medicine tumor necrosis factor-related apoptosis-induced ligand glioblastoma β-catenin Tripterygium wilfordii