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Remodeling the immune microenvironment for gastric cancer therapy through antagonism of prostaglandin E2 receptor 4

Genes & Diseases 2024年第4期11卷 411-425页

作者： Mengmeng Guo Pan Hu Jiayi Xie Kefu tang Shixiu Hu Jialiang Sun Yundong He jing li Weiqiang Lu Huirong liu Mingyao liu Zhengfang yi Shihong Peng shanghai Key Laboratory of Regulatory Biology School of Life SciencesEast China Normal UniversityShanghai 200241China Prenatal Diagnosis Center Department of Clinical LaboratoryChangning Maternity and Infant Health HospitalEast China Normal UniversityShanghai 200051China Key Laboratory of Acupuncture and Immunological Effects Shanghai University of Traditional Chinese MedicineShanghai 201203China Fengxian Hospital Affiliated to Southern Medical university Shanghai 201400China shanghai Yuyao Biotech Co. Ltd.Shanghai 200241China

Gastric cancer is highly prevalent among digestive tract *** to the intri-cate nature of the gastric cancer immune microenvironment,there is currently no effective treatment available for advanced gastric ***,there is promising potential for immunotherapy targeting the prostaglandin E2 receptor subtype 4(EP4)in gastric *** our previous study,we identified a novel small molecule EP4 receptor antagonist called *** with YY001 alone demonstrated a significant reduction in gastric cancer growth and inhibited tumor metastasis to the lungs in a mouse ***,adminis-tration of YYo01 stimulated a robust immune response within the tumor microenvironment,characterized by increased infiltration of antigen-presenting cells,T cells,and M1 ***,our research revealed that YYo01 exhibited remarkable synergistic ef-fects when combined with the PD-1 antibody and the clinically targeted drug apatinib,rather than *** findings suggest that YYo01 holds great promise as a potential therapeutic strategy for gastric cancer,whether used as a standalone treatment or in combination with other drugs.

关键词： EP4 Immunomodulation Synergy Tumor microenvironment YY001

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Deep learning framework for comprehensive molecular and prognostic stratifications of triple-negative breast cancer

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Fundamental Research 2024年第3期4卷 678-689页

作者： Shen Zhao Chao-Yang Yan Hong Lv jing-Cheng Yang Chao You Zi-Ang li Ding Ma yi Xiao Jia Hu Wen-tao Yang yi-Zhou Jiang Jun Xu Zhi-Ming Shao Key Laboratory of Breast Cancer in shanghai Department of Breast SurgeryFudan University Shanghai Cancer CenterShanghai 200032China Institute for AI in Medicine School of Artificial IntelligenceNanjing University of Information Science and TechnologyNanjing 210044China department of Pathology Fudan University Shanghai Cancer CenterShanghai 200032China Greater Bay Area Institute of Precision Medicine Guangzhou 511466China department of Radiology Fudan University Shanghai Cancer CenterShanghai 200032China

Triple-negative breast cancer(TNBC)is the most challenging breast cancer *** stratification and target therapy bring clinical benefit for TNBC patients,but it is difficult to implement comprehensive molecular testing in clinical ***,using our multi-omics TNBC cohort(N=425),a deep learning-based framework was devised and validated for comprehensive predictions of molecular features,subtypes and prognosis from pathological whole slide *** framework first incorporated a neural network to decompose the tissue on WSIs,followed by a second one which was trained based on certain tissue types for predicting different ***-omics molecular features were analyzed including somatic mutations,copy number alterations,germline mutations,biological pathway activities,metabolomics features and immunotherapy *** was shown that the molecular features with therapeutic implications can be predicted including the somatic PIK3CA mutation,germline BRCA2 mutation and PD-L1 protein expression(area under the curve[AUC]:0.78,0.79 and 0.74 respectively).The molecular subtypes of TNBC can be identified(AUC:0.84,0.85,0.93 and 0.73 for the basal-like immune-suppressed,immunomodulatory,luminal androgen receptor,and mesenchymal-like subtypes respectively)and their distinctive morphological patterns were revealed,which provided novel insights into the heterogeneity of TNBC.A neural network integrating image features and clinical covariates stratified patients into groups with different survival outcomes(log-rank Plidated on the TNBC cases from TCGA(N=143)and appeared robust to the changes in patient *** potential clinical translation,we built a novel online platform,where we modularized and deployed our framework along with the validated *** can realize real-time one-stop prediction for new *** summary,using only pathological WSIs,our proposed framework

关键词： Triple-negative breast cancer Deep learning Digital pathology Patient stratification Online platform

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Penpulimab,an anti-PD-1 antibody,for heavily pretreated metastatic nasopharyngeal carcinoma:a single-arm phase II study

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Signal Transduction and targeted Therapy 2024年第7期9卷 3056-3062页

作者： Xiaozhong Chen Wei Wang Qingfeng Zou Xiaodong Zhu Qin lin yi Jiang Yan Sun liangfang Shen lin Wang Guorong Zou Xiaoyan lin Shaojun lin Minying li ying Wang Ruilian Xu Rui Ao Rensheng Wang Haifeng lin Shuang Huang Tingting Xu Wenting li Mengying Xia Yu Xia Zhongmin Wang Baiyong li jingao li Chaosu Hu department of Radiation Oncology Cancer Hospital of the University of ChineseAcademy of Sciences(Zhejiang Cancer Hospital)HangzhouChina Gastroenterology and Urology department II Hunan Cancer Hospital/the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangshaChina Clinical Research Center for Gastrointestinal Cancer in Hunan Province ChangshaChina department of Medical Oncology Affiliated Cancer Hospital&Institute of Guangzhou Medical UniversityGuangzhouChina department of Radiation Oncology Guangxi Medical University Affiliated Tumor Hospital&Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University)Ministry of Education&Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency TumorGuangxi Medical UniversityNanningChina department of Radiation Oncology Cancer CenterThe First Affiliated Hospital of Xiamen UniversityXiamenChina department of Medical Oncology Cancer Hospital of Shantou University Medical CollegeShantouChina department of Radiation Oncology Peking University Cancer Hospital&InstituteBeijingChina department of Oncology Xiangya Hospital Central South UniversityChangshaChina department of Medical Oncology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikouChina department of Oncology The Affiliated Panyu Central Hospital of Guangzhou Medical UniversityGuangzhouChina department of Medical Oncology Fujian Medical University Union HospitalFuzhouChina department of Radiation Oncology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhouChina department of Radiation Therapy for Thoracic Tumors Zhongshan City People’s HospitalZhongshanChina Tumor Radiotherapy Center Chongqing University Cancer HospitalChongqing Cancer HospitalChongqing Cancer InstituteChongqingChina department of Oncology Shenzhen People’s Hospital(The Second Clinical Medical CollegeJinan UniversityThe First Affiliated HospitalSo

Penpulimab is an anti-programmed cell death-1(PD-1)IgG1 antibody with no Fc gamma receptor(FcγR)binding activity,and thus theoretically reduced immune-related adverse events(irAEs)while maintaining *** single-arm,phase II trial conducted across 20 tertiary care centers in china.enrolled adult patients with metastatic nasopharyngeal carcinoma(NPC)who had failed two or more lines of previous systemic *** received 200-mg penpulimab intravenously every 2 weeks(4 weeks per cycle)until disease progression or intolerable *** primary endpoint was objective response rate(ORR)per RECIST(version 1.1),as assessed by an independent radiological review *** secondary endpoints included progression-free survival(PFS)and overall survival(OS).One hundred thirty patients were enrolled and 125 were efficacy *** the data cutoff date(September 28,2022),1 patient achieved complete response and 34 patients attained partial *** ORR was 28.0%(95%CI 20.3–36.7%).The response was durable,with 66.8%still in response at 9 ***-three patients(26.4%)were still on *** median PFS and OS were 3.6 months(95%CI=1.9–7.3 months)and 22.8 months(95%CI=17.1 months to not reached),***(7.6%)patients experienced grade 3 or higher *** has promising anti-tumor activities and acceptable toxicities in heavily pretreated metastatic NPC patients,supporting further clinical development as third-line treatment of metastatic NPC.

关键词： metastatic nasopharyngeal supporting

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Automated Identification of Ordered Phases for Simulation Studies of Block Copolymers

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Chinese Journal of Polymer Science 2024年第5期42卷 683-692,I0011页

作者： Yu-Chen Zhang Wei-ling Huang yi-Xin liu State Key Laboratory of Molecule Engineering of Polymers Department of Macromolecular ScienceFudan UniversityShanghai200433China

In unit cell simulations,identification of ordered phases in block copolymers(BCPs)is a tedious and time-consuming task,impeding the advancement of more streamlined and potentially automated research *** this study,we propose a scattering-based automated identification strategy(SAIS)for characterization and identification of ordered phases of BCPs based on their computed scattering *** approach leverages the scattering theory of perfect crystals to efficiently compute the scattering patterns of periodic morphologies in a unit *** the first stage of the SAIS,phases are identified by comparing reflection conditions at a sequence of Miller *** confirm or refine the identification results of the first stage,the second stage of the SAIS introduces a tailored residual between the test phase and each of the known candidate ***,our strategy incorporates a variance-like criterion to distinguish background species,enabling its extension to multi-species BCP *** has been demonstrated that our strategy achieves exceptional accuracy and robustness while requiring minimal computational ***,the approach allows for real-time expansion and improvement to the candidate phase library,facilitating the development of automated research workflows for designing specific ordered structures and discovering new ordered phases in BCPs.

关键词： Block copolymer Phase identification Scattering function

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Catalytic Decomposition of CFC-12 over Heteropolyacids

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Chinese Journal of Catalysis 2000年第1期21卷 3-4页

作者： MA Zhen, HUA Weiming, taNG yi, GAO Zi(department of Chemistry, fudan university, shanghai 200433, china. 复旦大学上海 2 0 0 43 3

Chlorine atoms from chlorofluorocarbons (CFCs) deplete stratospheric ozone and CFCs are green-house gases too. Owing to these environmental problems, many kinds of CFCs have been banned since the Montreal Protocol and two kinds of cleaning techniques have been developed. One is the synthesis of CFCs alternatives[1,2] and the other is the decomposition of banned CFCs in existing equipments[3,4].

关键词： environmental catalysis chlorofluorocarbon decomposition heteropolyacid

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Synthesis of Nanometer-sized Mesoporous Oxide Spheres

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Chemical Research in Chinese Universities 2001年第2期17卷 143-147页

作者： LUO Qian, li li, XUE Zhi-yuan and ZHAO Dong-yuan (department of Chemistry Analysis and Measurement Center, fudan university, shanghai 200433, P. R. china. 复旦大学上海 200433

A few hundreds nanometer-sized mesoporous silica and alumina spheres were synthesized in organic solvents. The impacts of ammonia, N, N-dimethylformamide (DMF) and stirring speed were also investigated.

关键词： Nanometer-sized Mesoporous Sphere Silica Alumina

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Tislelizumab in previously treated,locally advanced unresectable/metastatic microsatellite instability-high/mismatch repair-deficient solid tumors

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Chinese Journal of Cancer Research 2024年第3期36卷 257-269页

作者： Jian li Ye Xu Aimin Zang Yunong Gao Quanli Gao Yanqiao Zhang Dong Wang Jianming Xu ying Yuan Haiping Jiang Jieer ying Chunmei Shi Yanhong Deng jing Wang Tianshu liu yi Huang Xiaoping Qian Yueyin Pan ying Cheng Sheng Hu jin Wang Mengyue Shi Ke Wang Han Hu lin Shen State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China department of Oncology Fudan University Shanghai Cancer CenterShanghai 200032China department of Medical Oncology Affiliated Hospital of Hebei UniversityBaoding 071000China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of GynecologyPeking University Cancer Hospital&InstituteBeijing 100142China department of Immunotherapy Henan Cancer HospitalZhengzhou 450001China department of Gastrointestinal Oncology Affiliated Cancer Hospital of Harbin Medical UniversityHarbin 150086China department of Gastrointestinal Oncology Chongqing University Cancer HospitalChongqing 400030China department of Gastrointestinal Oncology the Fifth Medical CenterChinese PLA General HospitalBeijing 100048China department of Medical Oncology the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China department of Medical Oncology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China department of Medical Oncology Cancer Hospital of the University of Chinese Academy of SciencesHangzhou 310022China department of Medical Oncology Fujian Medical University Union HospitalFuzhou 350001China department of Oncology the Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China department of Medical Oncology Hunan Cancer HospitalChangsha 410013China department of Medical Oncology Zhongshan HospitalFudan UniversityShanghai 200032China department of Immunotherapy Hubei Cancer HospitalWuhan 430079China department of Medical Oncology the Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China department of Medical Oncology Anhui Provincial HospitalHefei 230001China department of Medical Oncology Jilin Cancer Hospital

Objective:The open-label,phase II RATIONALE-209 study evaluated tislelizumab(anti-programmed cell death protein 1 antibody)as a tissue-agnostic monotherapy for microsatellite instability-high(MSI-H)/mismatch repair-deficient(dMMR)***:Adults with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR solid tumors were *** received tislelizumab 200 mg intravenously every 3 *** response rate(ORR;primary endpoint),duration of response(DoR),and progression-free survival(PFS)were assessed by independent review committee(Response Evaluation Criteria in Solid Tumors v1.1).Results:Eighty patients were enrolled and treated;75(93.8%)patients had measurable disease at *** had metastatic disease and received at least one prior therapy for advanced/metastatic disease(n=79;98.8%).At primary analysis(data cutoff July 8,2021;median follow-up 15.2 months),overall ORR[46.7%;95%confidence interval(95%CI),35.1−58.6;one-sided Ptal(n=46):39.1%(95%CI,25.1–54.6);gastric/gastroesophageal junction(n=9):55.6%(95%CI,21.2−86.3);others(n=20):60.0%(95%CI,36.1−80.9)]were significantly greater with tislelizumab vs.a prespecified historical control ORR of 10%;five(6.7%)patients had complete *** DoR,PFS,and overall survival were not reached with long-term follow-up(data cutoff December 5,2022;median follow-up 28.9 months).Tislelizumab was well tolerated with no unexpected safety ***-related adverse events(TRAEs)of grade≥3 occurred in 53.8%of patients;7.5%of patients discontinued treatment due to ***:Tislelizumab demonstrated a significant ORR improvement in patients with previously treated,locally advanced unresectable or metastatic MSI-H/dMMR tumors and was generally well tolerated.

关键词： Biomarkers DNA mismatch repair immune checkpoint inhibitors microsatellite instability phase II clinical trials programmed cell death 1 receptor

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Hydrogenation of CO over carbides of tungsten

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Chinese Journal of Chemistry 1992年第1期10卷 5-9页

作者： QIN,Dai-yi GAO,Zi department of Chemistry,fudan university,shanghai 200433 QIU,Yue-Ming DONG,Shu-Zhong department of Modern Physics,fudan university,shanghai 200433 department of Chemistry Fudan University Shanghai 200433 department of Modern Physics Fudan University Shanghai 200433

CO hydrogenation on tungsten carbides has been *** methanation activities of tungsten carbides are comparable to that of supported Group VIII metal ***- programmed thermal desorption spectra of CO on tungsten carbide ... 详细信息

关键词： Hydrogenation of CO over carbides of tungsten CO over

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Preparation and characterization of some surface negatively charged residue mutants of cytochrome b_5

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Chinese Science Bulletin 2001年第7期46卷 555-559页

作者： WANG Yunhua, WANG Wenhu, LU Junxia, REN yi, GU Shaohua, XIE yi & HUANG Zhongxian1. Chemical Biology Lab, department of Chemistry, fudan university, shanghai 200433, china.2. Genetic Institute, School of life, fudan university, shanghai 200433, china Chemical Biology Lab Department of Chemistry Fudan University Shanghai China Genetic Institute School of Life Fudan University Shanghai China

Site-directed mutagenesis was used to obtain seven variants of tryptic fragment of bovine liver cytochrome bs (cyt bs), in which the negatively charged residues around the heme exposed edge of cyt bs were replaced by hydropho-bic amino acid alanine. Double-site mutants, triple-site mutants and even quadruple-site mutants were obtained. DNA sequencing and molecular weight measurements of the mutant proteins both confirmed that these site-directed muta-genesises were successfully performed. Spectroelectrochem-istry of these mutant proteins revealed that the apparent redox potentials of these mutant proteins caused a positive shift of 2-10 mV. The global structure of these mutant proteins did not show much difference from that of the wild type cyt bs, providing a solid base for the further study on the roles of the proteins’ surface charges.

关键词： cytochrome bs site-directed mutagenesis negative charge on the protein surface redox potential.

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Impact of coupling coordination development of port and city environments on urban economic competitiveness:Evidence from the coastal port cities in eastern china

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Ecological Economy 2024年第1期20卷 53-71页

作者： li Zhen-qiang yi ying li Jia-li YOU Xiao-yue ZHOU Qiu-yang School of Economics and Management Hunan Institute of Science and TechnologyYueyang 414006CHINA School of Urban and Regional Science Shanghai University of Finance and EconomicsShanghai 200433CHINA

Promoting the coupling coordination development of port and its hinterland city environments is an important way to improve urban economic *** on relevant data of 13 coastal port cities in eastern china.from 2000 to 2018,this study explores the coupling coordination development of port and city environments and its impact on urban economic competitiveness by constructing the coupling coordination degree model and the panel threshold *** research results show that:(1)In terms of the coupling coordination development of port and city environments,most coastal ports and their hinterland cities are in a state of moderate or serious ***,the degree of coupling coordination of port and city environments needs to be further improved;(2)The coupling coordination degree of port and city environments has a significant impact on urban economic competitiveness,and this effect gradually increases with the development of the ports and the urban *** the variables that impact the urban economic competitiveness,fixed assets investment and foreign trade are significant factors that can enhance urban economic competitiveness.(3)At present,there is a“U-shaped”relationship between the coupling coordination degree of port-city environments and the urban economic *** relationship lies on the right side of the inflection point of the“U-shaped”***,following the concept of assigning priority to ecological development,expanding fixed assets investment and actively developing foreign trade can further enhance the urban economic competitiveness.

关键词： coastal ports city environments coupling coordination degree urban economic competitiveness threshold effect

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