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Inducing mitochondriopathy-like damages by transformable nucleopeptide nanoparticles for targeted therapy of bladder cancer

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National Science Review 2024年第4期11卷 216-227页

作者： Da-Yong Hou Ni-yuan Zhang Lu Wang Mei-yu Lv Xiang-Peng Li Peng Zhang yue-Ze Wang Lei Shen xiu-Hai Wu Bo Fu Peng-yu Guo Zi-qi Wang Dong-Bing Cheng Hao Wang Wanhai Xu NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics Heilongjiang Key Laboratory of Scientific Research in Urology Harbin Medical University department of Urology Harbin Medical University Cancer Hospital CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology(NCNST) School of Chemistry Chemical Engineering & Life Science Hubei Key Laboratory of Nanomedicine for Neurodegenerative Diseases Wuhan University of Technology

Mitochondriopathy inspired adenosine triphosphate(ATP) depletions have been recognized as a powerful way for controlling tumor growth. Nevertheless, selective sequestration or exhaustion of ATP under complex biological environments remains a prodigious challenge. Harnessing the advantages of in vivo self-assembled nanomaterials, we designed an Intracellular ATP Sequestration(IAS) system to specifically construct nanofibrous nanostructures on the surface of tumor nuclei with exposed ATP binding sites,leading to highly efficient suppression of bladder cancer by induction of mitochondriopathy-like ***, the reported transformable nucleopeptide(NLS-FF-T) self-assembled into nuclear-targeted nanoparticles with ATP binding sites encapsulated inside under aqueous conditions. By interaction with KPNA2, the NLS-FF-T transformed into a nanofibrous-based ATP trapper on the surface of tumor nuclei,which prevented the production of intracellular energy. As a result, multiple bladder tumor cell lines(T24,EJ and RT-112) revealed that the half-maximal inhibitory concentration(IC50) of NLS-FF-T was reduced by approximately 4-fold when compared to NLS-T. Following intravenous administration, NLS-FF-T was found to be dose-dependently accumulated at the tumor site of T24 xenograft mice. More significantly, this IAS system exhibited an extremely antitumor efficacy according to the deterioration of T24 tumors and simultaneously prolonged the overall survival of T24 orthotopic xenograft mice. Together, our findings clearly demonstrated the therapeutic advantages of intracellular ATP sequestration-induced mitochondriopathy-like damages, which provides a potential treatment strategy for malignancies.

关键词： self-assembly nucleopeptide nanomaterial bladder cancer mitochondriopathy

Application of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy in curative surgery for esophageal cancer:A metaanalysis

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 214-233页

作者： Mao-xiu yuan qi-Gui Cai Zhen-Yang Zhang Jian-Zhong Zhou Cai-yun Lan Jiang-Bo Lin The Graduate School Fujian Medical UniversityFuzhou 350000Fujian ProvinceChina department of Thoracic Surgery Affiliated Hospital of Jinggangshan UniversityJi’an 343000Jiangxi ProvinceChina department of Thoracic Surgery Fujian Medical University Union HospitalFuzhou 350000Fujian ProvinceChina

BACKGROUND The effectiveness of neoadjuvant therapy in esophageal cancer(EC)treatment is still a subject of *** To compare the clinical efficacy and toxic side effects between neoadjuvant chemoradiotherapy(nCRT)and neoadjuvant chemotherapy(nCT)for locally advanced EC(LAEC).METHODS A comprehensive search was conducted using multiple databases,including PubMed,EMBASE,MEDLINE,Science Direct,The Cochrane Library,china National Knowledge Infrastructure,Wanfang Database,Chinese Science and Technology Journal Database,and Chinese Biomedical Literature Database *** up to December 2022 comparing nCRT and nCT in patients with EC were *** The analysis revealed significant differences between nCRT and nCT in terms of disease-free *** results indicated that nCRT provided better outcomes in terms of the 3-year overall survival rate(OSR)[odds ratio(OR)=0.95],complete response rate(OR=3.15),and R0 clearance rate(CR)(OR=2.25).However,nCT demonstrated a better 5-year OSR(OR=1.02)than ***,when compared to nCRT,nCT showed reduced risks of cardiac complications(OR=1.15)and pulmonary complications(OR=1.30).CONCLUSION Overall,both nCRT and nCT were effective in terms of survival outcomes for ***,nCT exhibited better performance in terms of postoperative complications.

关键词： Esophageal cancer Neoadjuvant chemoradiotherapy Radical resection for esophageal cancer Neoadjuvant chemotherapy Meta-analysis

Unveiling the secrets of gastrointestinal mucous adenocarcinoma survival after surgery with artificial intelligence:A population-based study

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2404-2418页

作者： Jie Song Xiang-xiu Yan Fang-Liang Zhang Yong-Yi Lei Zi-Yin Ke Fang Li Kai Zhang yu-qi He Wei Li Chao Li yuan-Ming Pan department of Gastroenterology Dongying People’s HospitalDongying Hospital of Shandong Provincial Hospital GroupDongying 257000Shandong ProvinceChina Gastrointestinal Surgery department Suining Central HospitalSuining 629000Sichuan ProvinceChina Obstetrical department Suining Central HospitalSuining 629000Sichuan ProvinceChina School of Medicine Shenzhen Campus of Sun Yat-sen UniversityShenzhen 518107Guangdong ProvinceChina department of Pathology Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijing 100049China General department Beijing Chest HospitalCapital Medical University/Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149China department of Gastroenterology Beijing Chest HospitalCapital Medical University/Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149China department of Thoracic Surgery Sichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072Sichuan ProvinceChina department of Gastroenterology Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijing 100049China Cancer Research Center Beijing Chest HospitalCapital Medical University/Beijing Tuberculosis and Thoracic Tumor Research InstituteBeijing 101149China

BACKGROUND Research on gastrointestinal mucosal adenocarcinoma(GMA)is limited and controversial,and there is no reference tool for predicting postoperative *** To investigate the prognosis of GMA and develop predictive *** From the Surveillance,Epidemiology,and End Results database,we collected clinical information on patients with *** random sampling,the patients were divided into the discovery(70%of the total,for model training),validation(20%,for model evaluation),and completely blind test cohorts(10%,for further model evaluation).The main assessment metric was the area under the receiver operating characteristic curve(AUC).All collected clinical features were used for Cox proportional hazard regression analysis to determine factors influencing GMA’s *** This model had an AUC of 0.7433[95% confidence intervals(95%CI):0.7424-0.7442]in the discovery cohort,0.7244(GMA:0.7234-0.7254)in the validation cohort,and 0.7388(95%CI:0.7378-0.7398)in the test *** packaged it into Windows software for doctors’use and uploaded *** gastric adenocarcinoma had the worst prognosis,and these were protective factors of GMA:Regional nodes examined[hazard ratio(HR):0.98,95%CI:0.97-0.98,P1]and chemotherapy(HR:0.62,95%CI:0.58-0.66,P1).CONCLUSION The deep learning-based tool developed can accurately predict the overall survival of patients with GMA *** surgery,chemotherapy,and adequate lymph node dissection during surgery can improve patient outcomes.

关键词： Deep learning Gastrointestinal mucous adenocarcinoma Overall survival Surgery Clinical tool

The clinical features and potential mechanisms of cognitive disorders in peripheral autoimmune and inflammatory diseases

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Fundamental Research 2024年第2期4卷 226-236页

作者： Ke-qi Fan Tao Huang Jian-shuai yu Yi-yuan Li Jin Jin MOE Laboratory of Biosystem Homeostasis and Protection and Life Sciences InstituteZhejiang UniversityHangzhou 310058China department of Gastroenterology Sir Run Shaw HospitalCollege of Medicine Zhejiang UniversityHangzhou 310016China Key Laboratory for Developmental Genes and Human Disease Ministry of EducationInstitute of Life SciencesJiangsu Province High-Tech Key Laboratory for Bio-Medical ResearchSoutheast UniversityNanjing 210096China

According to a study from World Health Organization’s Global Burden of Disease,mental and neurological disorders have accounted for 13%of global diseases in recent years and are on the *** conditions or neuroinflammatory disorders are linked by the presence of an exaggerated immune response both peripherally and in the central nervous system(CNS).Cognitive dysfunction(CD)encompasses a complex group of diseases and has frequently been described in the field of autoimmune diseases,especially in multiple non-CNS-related autoimmune *** studies have provided various hypotheses regarding the occurrence of cognitive impairment in autoimmune diseases,including that abnormally activated immune cells can disrupt the integrity of the blood-brain barrier(BBB)to trigger a central neuroinflammatory *** the BBB is intact,autoantibodies and pro-inflammatory molecules in peripheral circulation can enter the brain to activate microglia,inducing CNS inflammation and ***,the mechanisms explaining the association between the immune system and neural function and their contribution to diseases are *** this review,we used clinical statistics to illustrate the correlation between CD and autoimmune diseases that do not directly affect the CNS,summarized the clinical features and mechanisms by which autoimmune diseases trigger cognitive impairment,and explored existing knowledge regarding the link between CD and autoimmune diseases from the perspective of the field of neuroimmunology.

关键词： Autoimmune diseases Neuroinflammation Central nervous system dysfunction Autoantibodies Inflammatory cytokines

Transcriptomic Landscape Analysis Reveals a Persistent DNA Damage Response in Metabolic Dysfunction-associated Steatohepatitis Post-dietary Intervention

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Journal of Clinical and Translational Hepatology 2024年第9期12卷 765-779页

作者： Zi-yuan Zou Tian-Yi Ren Jia-qi Li Ting-Ying Jiao Meng-yu Wang Lei-Jie Huang Shuang-Zhe Lin yuan-Yang Wang Xiao-Zhen Guo Ye-yu Song Rui-Xu Yang Cen xie Jian-Gao Fan Center for Fatty Liver Department of GastroenterologyXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina university of Chinese Academy of Sciences BeijingChina Human Phenome Institute School of Life SciencesFudan UniversityShanghaiChina department of Gastroenterology Ningbo No.2 HospitalNingboZhejiangChina Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition ShanghaiChina

Background and Aims:Metabolic dysfunction-associated steatotic liver disease(MASLD)and its more advanced form,metabolic dysfunction-associated steatohepatitis,have emerged as the most prevalent liver diseases ***,lifestyle modification is the foremost guidelinerecommended management strategy for ***,it remains unclear which detrimental signals persist in MASLD even after disease ***,we aimed to examine the persistent changes in liver transcriptomic profiles following this ***:Male C57BL/6J mice were divided into three groups:Western diet(WD)feeding,chow diet(CD)feeding,or diet reversal from WD to *** 16 weeks of feeding,RNA sequencing was performed on the mice’s livers to identify persistent alterations characteristic of ***,RNA sequencing databases containing high-fat diet-fed P53-knockout mice and human MASLD samples were ***:WD-induced MASLD triggered persistent activation of the DNA damage response(DDR)and its primary transcription factor,P53,long after the resolution of the hepatic phenotype through dietary *** levels of P53 might promote apoptosis,thereby exacerbating metabolic dysfunction-associated steatohepatitis,as they strongly correlated with hepatocyte ballooning,an indicator of apoptosis ***,P53 knockout in mice led to downregulated expression of apoptosis signaling in the ***,P53 may regulate apoptosis by transcriptionally activating the expression of apoptosis-enhancing nuclease(AEN).Consistently,P53,AEN,and the apoptosis process all exhibited persistently elevated expression and showed a strong inter-correlation in the liver following dietary ***:The liver demonstrated upregulation of DDR signaling and the P53-AEN-apoptosis axis both during and after exposure to *** findings provide new insights into the mechanisms of MASLD relapse,highlighting DDR signaling as a promising target to prevent MASLD recu

关键词： Apoptosis DNA Damage Metabolic dysfunction-associated steatotic liver disease RNA-Seq Tumor suppressor protein P53 Western Diets

Chemico-biological conversion of carbon dioxide

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Journal of Energy Chemistry 2024年第2期89卷 371-387,I0009页

作者： Liangwei Hu Junzhu Yang qi Xia Jin Zhang Hongxin Zhao yuan Lu zhejiang Province Key Laboratory of Plant Secondary Metabolism and Regulation College of Life Sciences and MedicineZhejiang Sci-Tech UniversityHangzhou 310018ZhejiangChina Key Laboratory of Industrial Biocatalysis Ministry of EducationTsinghua UniversityBeijing 100084China department of Chemical Engineering Tsinghua UniversityBeijing 100084China College of Biological and Chemical Engineering Jiaxing UniversityJiaxing 314000ZhejiangChina

The unabated carbon dioxide(CO_(2))emission into the atmosphere has exacerbated global climate change,resulting in extreme weather events,biodiversity loss,and an intensified greenhouse *** address these challenges and work toward carbon(C)neutrality and reduced CO_(2)emissions,the capture and utilization of CO_(2)have become imperative in both scientific research and *** cutting-edge approach to achieving efficient catalytic performance involves integrating green bioconversion and chemical *** innovative strategy offers several advantages,including environmental friendliness,high efficiency,and *** study provides a comprehensive review of existing technical routes for carbon sequestration(CS)and introduces two novel CS pathways:the electrochemicalbiological hybrid and artificial photosynthesis *** also thoroughly examines the synthesis of valuable Cnproducts from the two CS systems employing different catalysts and *** both systems heavily rely on electron transfer,direct and mediated electron transfer has been discussed and summarized in ***,this study explores the conditions suitable for different catalysts and assesses the strengths and weaknesses of *** also explored the biocompatibility of the electrode materials and developed novel *** materials were specifically engineered to combine with enzymes or microbial cells to solve the biocompatibility problem,while improving the electron transfer efficiency of ***,this review summarizes the relevant systems developed in recent years for manufacturing different products,along with their respective production efficiencies,providing a solid database for development in this *** novel chemical-biological combination proposed herein holds great promise for the future conversion of CO_(2)into advanced organic ***,it offers exciting prospects for utilizing CO_(2)in synthesizing

关键词： Carbon dioxide Bioelectric synthesis Artificial photosynthesis Synthetic product

Association of CASP9,CASP10 gene polymorphisms and tea drinking with colorectal cancer risk in the Han Chinese population

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Journal of zhejiang university-Science B(Biomedicine & Biotechnology) 2013年第1期14卷 47-57页

作者： He LIU Ming-wu ZHANG Yi-feng PAN yun-xian yu Shan-chun ZHANG Xin-yuan MA qi-long LI Kun CHEN department of Epidemiology and Health Statistics School of Medicine Zhejiang University Hangzhou 310058 China Institute of Cancer Research and Prevention of Jiashan County Jiashan 314100 China

The initiators caspase-9 （CASP9） and caspase-10 （CASPIO） are two key controllers of apoptosis and play important roles in carcinogenesis. This study aims to explore the association between CASPs gene polymorphisms and colorectal cancer （CRC） susceptibility in a population-based study. A two-stage designed population-based case-control study was carried out, including a testing set with 300 cases and 296 controls and a validation set with 206 cases and 845 controls. A total of eight tag selected single nucleotide polymorphisms （SNPs） in CASP9 and CASPIO were chosen based on HapMap and the National Center of Biotechnology Information （NCBI） datasets and genotyped by restriction fragment length polymorphism （RFLP） assay. Multivariate logistic regression models were applied to evaluate the association of SNPs with CRC risk. In the first stage, from eight tag SNPs, three polymorphisms rs4646077 （odds ratio （OR）AA＋AG： 0.654, 95% confidence interval （CI）： 0.406-1.055; P=0.082）, rs4233532 （ORcc： 1.667, 95% CI： 0.967-2.876; Oacm： 1.435, 95% CI： 0.998-2.063; P=0.077）, and rs2881930 （ORcc： 0.263, 95% CI： 0.095-0.728, P=0.036） showed possible association with CRC risk. However, none of the three SNPs, rs4646077 （ORAA＋AG： 1.233, 95% CI： 0.903-1.683）, rs4233532 （ORcc： 0.892, 95% CI： 0.640-1.243; ORcT： 1.134, 95% CI： 0.897-1.433）, and rs2881930 （ORcc： 1.096, 95% CI： 0.620-1.938; ORcT： 1.009, 95% CI： 0.801-1.271）, remained significant with CRC risk in the validation set, even after stratification for different tumor locations （colon or rectum）. In addition, never tea drinking was associated with a significantly increased risk of CRC in testing set together with validation set （OR： 1.755, 95% CI： 1.319-2.334）. Our results found that polymorphisms of CASP9 and CASPIO genes may not contribute to CRC risk in Chinese population and thereby the large-scale case-control studies might be in consideration. In addition, tea drinking was a protective factor for CRC.

关键词： CASP9 CASPIO Colorectal cancer Single nucleotide polymorphisms Susceptibility to cancer Tea drinking

Enhanced homing of mesenchymal stem cells for in situ niche remodeling and bone regeneration

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Nano Research 2024年第8期17卷 7449-7460页

作者： Yin yuan Lijun Chen Jing Yang Sining Zhou Yangxin Fang qi Zhang Ning Zhang Yifei Li Li yuan Fan Jia Shuo Ni Charlie Xiang State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China department of Biology The David H.Koch Institute for Integrative Cancer Research at MITMassachusetts Institute of TechnologyCambridgeMA 02139USA Research Units of Infectious disease and Microecology Chinese Academy of Medical SciencesHangzhou 310003China Innovative Precision Medicine(IPM)Group Hangzhou 311215China MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of zhejiang Province Department of CardiologySir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China department of Cancer Immunology and Virology Dana-Farber Cancer InstituteBostonMA 02215USADepartment of ImmunologyHarvard Medical SchoolBoston MA 02115USA department of Orthopedic Surgery and Shanghai Institute of Microsurgery on Extremities Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiaotong University School of MedicineShanghai 200233China

Mesenchymal stem cells(MSCs)transplantation is a promising strategy for osteoporosis ***,limited sources and poor tissue-homing efficiency limit their clinical *** this study,we isolated a kind of MSCs from women’s menstrual blood(MenSCs)noninvasively and established a novel MSCs bone marrow-targeted delivery system by utilizing waterin-oil-in-water droplet *** were encapsulated withinβ-cyclodextrin-functionalized alginate microcapsules loaded with zoledronates,which has a high affinity for *** this delivery system,MenSCs could be preferentially delivered to the bone marrow tissues via intravenous infusion,and restored bone mass by remodeling the bone marrow niche in situ in ovariectomized mouse ***,scRNA-seq analysis demonstrated that those MenSCs homed to the bone marrow recruited CD4^(+)FOXP3^(+)natural regulatory T(nT_(reg))cells by secreting *** recruited nTreg promoted CD8^(+)T cells to secret Wnt family member 10B(WNT10B),activating the Wnt signaling in osteoblasts and thus promoting bone formation in situ in the bone *** study reveals a promising application of MenSCs in postmenopausal osteoporosis treatment and highlights the clinical value of MenSCs by encouraging women to reserve autologous MenSCs before menopause to prevent and alleviate postmenopausal osteoporosis.

关键词： mesenchymal stem cells microfluidics bone marrow homing stem cell niche postmenopausal osteoporosis

Considerable impact of major air pollutants on hypertension in Guizhou province,southwest china

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Chinese Medical Journal 2024年第4期137卷 496-498页

作者： Ping yuan Guojia qi xiu Dai Xiangyuan Chu Zhijun Liu Guoqin Liu xiuquan Shi department of Epidemiology and Health Statistics School of Public HealthZunyi Medical UniversityZunyiGuizhou 563006China School of Management Zunyi Medical UniversityZunyiGuizhou 563006China Center for Injury Research and Policy&Center for Pediatric Trauma Research The Research Institute at Nationwide Children’s HospitalThe Ohio State University College of MedicineColumbusOH 43210USA

To the Editor:Air pollution can lead to respiratory and cardiovascular diseases(CVDs),and its impact on human health is very *** particles less than 0.1µm can pass through the blood brain barrier,reach the brain,and enter the central nervous system,causing physiological and pathological changes.A study shows that long-term exposure to fine particulate matter(PM_(2.5))will increase the risk of CVDs among Chinese residents.^([1])Another study found that a short time exposure to low concentrations of air pollutants may also lead to the onset of acute coronary syndrome within one hour.^([2])A meta-analysis based on seven databases showed that environmental air pollution was positively correlated with elevated blood pressure and hypertension.^([3])Mounting evidence indicates that air pollution can cause cardiovascular and cerebrovascular diseases and affect human health furtherly.

关键词： pollution impact Guizhou