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Tumor initiation and early tumorigenesis:molecular mechanisms and interventional targets

Signal Transduction and Targeted Therapy 2024年第7期9卷 2900-2935页

作者： Shaosen Zhang Xinyi Xiao Yonglin Yi Xinyu Wang Lingxuan zhu Yanrong Shen Dongxin Lin chen Wu department of Etiology and Carcinogenesis National Cancer Center/National Clinical Research Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College100021 BeijingChina Key Laboratory of Cancer Genomic Biology Chinese Academy of Medical Sciences and Peking Union Medical College100021 BeijingChina Changping Laboratory 100021 BeijingChina Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China Sun Yat-sen university Cancer Center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China CAMS Oxford Institute Chinese Academy of Medical Sciences100006 BeijingChina

Tumorigenesis is a multistep process,with oncogenic mutations in a normal cell conferring clonal advantage as the initial ***,despite pervasive somatic mutations and clonal expansion in normal tissues,their transformation into cancer remains a rare event,indicating the presence of additional driver events for progression to an irreversible,highly heterogeneous,and invasive ***,researchers are emphasizing the mechanisms of environmental tumor risk factors and epigenetic alterations that are profoundly influencing early clonal expansion and malignant evolution,independently of inducing ***,clonal evolution in tumorigenesis reflects a multifaceted interplay between cell-intrinsic identities and various cell-extrinsic factors that exert selective pressures to either restrain uncontrolled proliferation or allow specific clones to progress into ***,the mechanisms by which driver events induce both intrinsic cellular competency and remodel environmental stress to facilitate malignant transformation are not fully *** this review,we summarize the genetic,epigenetic,and external driver events,and their effects on the co-evolution of the transformed cells and their ecosystem during tumor initiation and early malignant evolution.A deeper understanding of the earliest molecular events holds promise for translational applications,predicting individuals at high-risk of tumor and developing strategies to intercept malignant transformation.

关键词： alterations mechanisms restrain

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Intelligent design and construction of novel APN-based theranostic probe driven by advanced computational methods

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Chinese Chemical Letters 2024年第2期35卷 352-357页

作者： Yingli zhu Jie Qian Kunqian Yu Jing Hou Yeshuo Ma Fei chen Jie Dong Wenbin Zeng Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410083China National Engineering Research Center of Rice and Byproduct Deep Processing School of Food Science and EngineeringCentral South University of Forestry and TechnologyChangsha 410004China State Key Laboratory of Drug Research Drug Discovery and Design CenterShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China department of Geriatrics Third Xiangya HospitalCentral South UniversityChangsha 410013China

Multifunctional molecules with both optical signal and pharmacological activity play an important role in drug development,disease diagnosis,and basic theoretical *** N(APN),as a representative tumor biomarker with anti-tumor potential,still lacks a high-precision theranostic probe specifically targeting *** this study,a novel quaternity design strategy for APN theranostic probe was *** proposed strategy utilizes advanced machine learning and molecular dynamics simulations,and cleverly employs the strategy of conformation-induced fluorescence recovery to achieve multi-objective optimization and integration of functional *** this strategy,a unique“Off-On”theranostic probe,ABTP-DPTB,was ingeniously constructed to light up APN through fluorescence restoration,relying on conformation-induced effects and solvent *** from the common diagnostic probes,the intelligent design with non-substrated linkage makes ABTP-DPTB for long-term in-situ *** fabricated probe was used for detecting and inhibiting APN in various environments,with a better in vitro inhibitory than golden-standard drug bestatin.

关键词： Theranostic probe Artificial intelligence Conformational restriction Fluorescence restoration Design strategy

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Exploring the combination of biochar‐amended soil and automated irrigation technology for water regulation and preservation in green infrastructure

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Deep Underground Science and Engineering 2024年第1期3卷 39-52页

作者： Honghu zhu Yuanxu Huang Haihong Song Jian chen Songlei Han Tanwee Mazumder Ankit Garg School of Earth Sciences and Engineering Nanjing UniversityNanjingChina department of Civil and Smart Engineering Construction Guangdong Engineering Center for Structure Safety and Health MonitoringShantou UniversityShantouChina shanghai Municipal Engineering Design Co. LtdShanghaiChina Indian Institute of Technology Madras ChennaiIndia

Biochar is a carbon sink material with the potential to improve water retention in various ***,for the long‐term maintenance of green infrastructure,there is an additional need to regulate the water contents in the covers to maintain vegetation growth in semiarid *** this study,biochar‐amended soil was combined with subsurface drip irrigation,and the water preservation characteristics of this treatment were investigated through a series of one‐dimensional soil column *** ascertain the best treatment method specific to semiarid climatic conditions,the test soil was amended with 0%,1%,3%,and 5%*** irrigation devices equipped with soil moisture sensors were used to control the subsurface water content with the aim of enhancing vegetation *** soil column test lasted 150 h,during which the volumetric water contents and soil suction data were *** experimental results reveal that the soil specimen amended with 3%biochar is the most water‐saving regardless of the time *** with a higher biochar content(e.g.,5%)consumes a more significant amount of water due to the enhancement of the water‐holding *** on the experimental results,it can be concluded that the appropriate ratio can be determined within 1%–3%,which can reduce not only the amount of irrigated/used water but also the time *** technology can be explored for water content regulation in green infrastructure and the development of barriers for protecting the environment around deep underground waste containment.

关键词： biochar drip irrigation underground water preservation water regulation

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Dielectric polymer grafted electrodes enhanced aqueous supercapacitors

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Nano Research 2024年第3期17卷 1525-1534页

作者： Shian Dong Kunming Shi Jie chen Yingke zhu Hongfei Li Weihang Gao Zhenli Xu Qinglei Liu Xingyi Huang shanghai Key Laboratory of Electrical Insulation and Thermal Aging Department of Polymer Science and EngineeringState Key Laboratory of Metal Matrix CompositesShanghai Jiao Tong UniversityShanghai 200240China School of Mathematical Sciences Institute of Natural Sciences and MOE−LSCShanghai Jiao Tong UniversityShanghai 200240China State Key Laboratory of Metal Matrix Composites Shanghai Jiao Tong UniversityShanghai 200240China

Supercapacitors(SCs)have become increasingly important in electrical energy storage and delivery owing to their high power densities and long *** SCs are promising for large-scale engineering applications because of their low cost and ***,the low operating voltage and low energy density of aqueous SCs severely limit their practical *** this study,a nanoscale dielectric layer is grafted onto a graphene electrode to achieve both a high operating voltage and enhanced *** with an SC without dielectric grafting,a dielectric-enhanced SC(DESC)shows a higher capacitance by 2.00%.The mechanism of the capacitance enhancement can be attributed to three factors:the dielectric polarization,the ions desolvation by the dielectric,and the enhanced quantum capacitance from charge transfer and ion adsorption in the polymer *** addition,a 2.5 V pouch DESC with a 1 M KCl electrolyte is confirmed to cycle up to 50,000 times with a capacitance retention of 87.5%.The DESC presents the optimal electrochemical properties after it is grafted with a 5 nm dielectric *** study provides new insights into the design of high-voltage and high-energy-density aqueous SCs.

关键词： supercapacitors dielectric polymer high voltage capacitance enhancement

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Berberine Enhances Intestinal Mucosal Barrier Function by Promoting Vitamin D Receptor Activity

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Chinese Journal of Integrative Medicine 2024年第2期30卷 143-151页

作者： HUANG Yong-quan LIU Jia-lin chen Geng-xin SHEN Dan-ting zhu Wang chen Xin-lin LIU Feng-bin HOU Qiu-ke Graduate School Guangzhou University of Chinese MedicineGuangzhou(510405)China department of Orthopedics the Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou(510006)China department of Preventive Medicine and Health Statistics Guangzhou University of Chinese MedicineGuangzhou(510006)China department of Gastroenterology the First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou(510405)China

Objective:To evaluate if berberine can act on vitamin D receptors(VDR)and thereby regulate the expression of tight junction proteins(TJPs)in irritable bowel syndrome-diarrhea-predominant(IBS-D)***:The newborn rats were induced into IBS-D rat model via neonatal maternal separation combined with acetic acid chemical *** modeling,the model was evaluated and rats were divided into the control group and berberine treatment groups(0.85,1.7 and 3.4 mg/kg,once a day for 2.weeks).The distal colon was obtained and colonic epithelial cells(CECs)were isolated and cultured after IBS-D model *** vitamin D receptor response element(VDRE)reporter gene was determined in the CECs of IBS-D rats to analyze the effect of berberine on the VDRE *** overexpression or silencing technology was used to analyze whether VDR plays a role in promoting intestinal barrier repair,and to determine which region of VDR plays a role in berberine-regulated intestinal ***:The IBS-D rat model was successfully constructed and the symptoms were improved by berberine in a dose-dependent manner(Pnormal control and basic plasmid groups(all P<0.05).RT-qPCR and Western blot results showed that compared with the blank group,expressions of occludin and zonula occludens-1 were significantly higher in VDR containing groups(all P<0.05).Berberine plus pCMV-Myc-VDR-N group exerted the highest expression levels of occludin and zonula occludens-1(P<0.05).Conclusion:Berberine enhances intestinal mucosal barrier function of IBS-D rats by promoting VDR activity,and the main site of action is the N-terminal region of VDR.

关键词： berberine Chinese medicine irritable bowel syndrome-diarrhea-predominant vitamin D receptors intestinal mucosal barrier tight junction proteins

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Thermodynamic Stability of LiFeO_2.in Molten Carbonate Fuel Cell

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Journal of Materials Science & Technology 2000年第1期16卷 71-72页

作者： Licheng YAN, Wencong LU, Yimin DING, Jianhui MNG and Nianyi chen ({2. of Chemistry, shanghai university, shanghai 2.1800, China) Guangyi CAO and Jianxin zhu (Instate of Fuel Cell Technology, Jiaotong university, shanghai 2.0030, China) department of Chemistry Shanghai University Shanghai 201800 China Institute of Fuel Cell Technology Jiaotong University Shanghai 200030 China

LiFeO_2. as one of candidate cathode materials or additive for molten carbonate fuel cell, has been found to be thermodynamically unstable in CO_2.atmosphere at 650℃ (the condition of molten carbonate fuel cell) both... 详细信息

关键词： Li MCFC

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A justice and innovative way ahead of consumption-based emission accounting approach

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Science China Earth Sciences 2024年第10期67卷 2999-3010页

作者： Qun SHEN Hongbo DUAN Yun TANG Linbing TANG Li SHANG Xinyu DOU Wei WEI Weiqiang chen zhu LIU State Key Laboratory of Low Carbon Catalysis and Carbon Dioxide Utilization CAS Key Laboratory of Low-Carbon Conversion Science&EngineeringShanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210China School of Economics&Management University of Chinese Academy of SciencesBeijing 100190China Key Lab of Urban Environment and Health Institute of Urban EnvironmentChinese Academy of SciencesXiamen 361021China department of Earth System Science Tsinghua UnivesityBeijing 100084China

Carbon emission accounting is an important basis for global climate *** on the consumption-based accounting(CBA)method,the characteristics of carbon flow between national,regional,and product processes could be more clearly ***,CBA is more conducive to clarifying the attribution of responsibilities between producers and consumers,with the principles of fairness and *** accounting for carbon emissions in typical countries from 1990 to 2.19,we found that the CBA emissions are higher than the production-based accounting(PBA)emissions in major developed countries,while the results are reversed for developing *** the past 30 years,the CBA emissions in targeted developed countries generally have shown a downward trend,while in developing countries,they have shown an upward *** emissions in China have shown a continuous growth trend from 1990 to 2.19,but the pace has slowed down significantly over the last ***,the embodied carbon intensity of China’s exports continues to decline,indicating that China is providing more green and low-carbon products to the *** the PV industry as an example,this study further reveals the contribution of specific product industries to the country’s carbon transfer through product carbon footprint *** order to provide a scientific basis for global mitigation and climate governance,it is urgent to innovate a scientific,practical,and standardized CBA technology system.

关键词： Consumption-based accounting Production-based accounting Carbon transfer Carbon footprint

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Sorafenib sensitization in tumor therapy by iron overload and AMPK activation

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Nano Research 2024年第7期17卷 6386-6399页

作者： Jun zhu Shoujie Zhao Yejing zhu Shou{2. Ma Tenghui Han Fenghua Xu Huichen Li Bo Wang Zhixiong Guo Da chen Yongquan Qu Zhimin Tian Junlong Zhao Lei Liu State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers National Clinical Research Center for Digestive DiseasesXijing HospitalFourth Military Medical UniversityXi’an 710032China department of General Surgery The Southern Theater Air Force HospitalGuangzhou 510602China department of General Surgery Tangdu HospitalFourth Military Medical UniversityXi’an 710038China department of Thoracic Surgery Tangdu HospitalFourth Military Medical UniversityXi’an 710038China department of Neurology Airborne Army HospitalWuhan 430012China Key Laboratory of Modern Teaching Technology(Ministry of Education) Shaanxi Normal UniversityXi’an 710062China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Department of Biochemistry and Molecular BiologySchool of Basic MedicineFourth Military Medical UniversityXi’an 710032China Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology School of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi’an 710072China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Department of Medical Genetics and Developmental BiologyFourth Military Medical UniversityXi’an 710032China department of Pediatrics Tangdu HospitalFourth Military Medical UniversityXi’an 710000China

Sorafenib,as a first-line drug for advanced hepatocellular carcinoma(HCC),could trigger ferroptosis by inhibiting cystine/glutamate ***,low-level intracellular iron and insufficient activation of adenosine monophosphate(AMP)-activated protein kinase(AMPK)confer impaired response to *** this study,a unique sorafenib nanocomposite dexterously modified with Fe-Material of Institut Lavoisier(sora@Fe-MIL)was synthesized to escalate intracellular iron level and activate AMPK,further potentiating the ferroptotic effect of ***,this strategic deployment of sora@Fe-MIL triggered an extensive demise of cancer cells,while manifesting negligible deleterious impact on normal *** prominent ferroptosis biomarkers,glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11),underwent pronounced downregulation,underscoring the efficacy of this strategy in inducing ***,the bioactivity of AMPK was considerably elevated,and its downstream targets were conspicuously inhibited by the treatment with sora@*** orthotopic HCC animal models,we observed a substantial suppression of primary in situ tumor growth,and ribonucleic acid(RNA)sequencing elucidated an elevated degree of ferroptosis and AMPK activation with the treatment of sora@*** conclusion,we proposed that the meticulously designed strategy for secure and efficacious iron release and AMPK activation could significantly potentiate the ferroptotic impact of sorafenib,thus resuscitating its therapeutic response in HCC patients.

关键词： anti-tumor ferroptosis Fe-Material of Institut Lavoisier(Fe-MIL) sorafenib adenosine monophosphate(AMP)-activated protein kinase(AMPK)

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Enhancing Li-S battery performance via functional polymer binders for polysulfide inhibition

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Journal of Energy Chemistry 2024年第10期97卷 228-236页

作者： Jinpeng Jian Qian chen Hao Sun Rui Li Yaolin Hou Yulong Liu Jia Liu Haiming Xie Jiefang zhu Nation & Local United Engineering Laboratory for Power Batteries Faculty of Chemistry Northeast Normal University Jilin Province Dongchi New Energy Technology Co. Ltd. department of Chemistry-?ngstr?m Laboratory Uppsala University

The commercialization of lithium-sulfur(Li-S) batteries faces several challenges,including poor conductivity,unexpected volume expansion,and continuous sulfur loss from the cathode due to redox *** this study,we introduce a novel polymer via a simple cross-linking between poly(ether-thioureas)(PETU) and poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate)(PEDOT:PSS) as a bifunctio nal binder for Li-S batteries(devotes as "PPTU").Compared to polyvinylidene fluoride(PVDF),as-prepared PPTU exhibits significantly higher electrical conductivity,facilitating electrochemical ***,PPTU demonstrates effective adsorption of lithium polysulfides,leading to improved cycling stability by suppressing the shuttling *** investigate this behavior by monitoring morphological changes at the cell interface using synchrotron X-ray *** with PPTU binders exhibit remarkable rate performance,desired reversibility,and excellent cycling stability even under stringent bending and twisting *** work represents promising progress in functional polymer binder development for Li-S batteries.

关键词： Li-S batteries Bifunctional binders Electrode conductivity Shuttle effect

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Asialoglycoprotein receptor 1 promotes SARS-CoV-2.infection of human normal hepatocytes

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1199-1208页

作者： Xinyi Yang Xu zheng Yuqi zhu Xiaying Zhao Jun Liu Jiangna Xun Songhua Yuan Jun {2. Hanyu Pan Jinlong Yang Jing Wang Zhimin Liang Xiaoting Shen Yue Liang Qinru Lin Huitong Liang Min Li Fei Peng Daru Lu Jianqing Xu Hongzhou Lu Shibo Jiang Ping Zhao Huanzhang zhu State Key Laboratory of Genetic Engineering and Engineering Research Center of Gene Technology Ministry of EducationInstitute of GeneticsSchool of Life SciencesYiwu Research InstituteFudan UniversityShanghaiChina department of Microbiology Faculty of Naval MedicineNaval Medical UniversityShanghai 200433China Scientific Research Center Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina department of Infectious Diseases and Immunology Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Changzheng Hospital Naval Medical UniversityShanghaiChina Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) Shanghai Institute of Infectious Disease and BiosecuritySchool of Basic Medical SciencesFudan UniversityShanghaiChina department of Infectious Diseases and Nursing Research Institution National Clinical Research Center for Infectious DiseasesThe Third People’s Hospital of ShenzhenShenzhenGuangdongChina

Severe acute respiratory syndrome coronavirus 2.SARS-CoV-2.causes multi-organ damage,which includes hepatic dysfunction,as observed in over 50%of COVID-19 *** I converting enzyme(peptidyl-dipeptidase A)2.ACE2.is the primary receptor for SARS-CoV-2.entry into host cells,and studies have shown the presence of intracellular virus particles in human hepatocytes that express ACE2.but at extremely low ***,we asked if hepatocytes might express receptors other than ACE2.capable of promoting the entry of SARS-CoV-2.into *** address this question,we performed a genome-wide CRISPR-Cas9 activation library screening and found that Asialoglycoprotein receptor 1(ASGR1)promoted SARS-CoV-2.pseudovirus infection of HeLa *** Huh-7 cells,simultaneous knockout of ACE2.and ASGR1 prevented SARS-CoV-2.pseudovirus *** the immortalized THLE-2.hepatocyte cell line and primary hepatic parenchymal cells,both of which barely expressed ACE2.SARSCoV-2.pseudovirus could successfully establish an ***,after treatment with ASGR1 antibody or siRNA targeting ASGR1,the infection rate significantly dropped,suggesting that SARS-CoV-2.pseudovirus infects hepatic parenchymal cells mainly through an ASGR1-dependent *** confirmed that ASGR1 could interact with Spike protein,which depends on receptor binding domain(RBD)and N-terminal domain(NTD).Finally,we also used Immunohistochemistry and electron microscopy to verify that SARS-CoV-2.could infect primary hepatic parenchymal *** inhibiting ASGR1 in primary hepatic parenchymal cells by siRNA,the infection efficiency of the live virus decreased ***,these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2.that promotes infection of hepatic parenchymal cells.

关键词： ACE2 infection glycoprotein

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