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Hierarchical Self-assembly of Atomically Precise Au nanoclusters with Molecular Rotor-based ligands

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Chemical Research in chinese Universities 2024年第4期40卷 670-674页

作者： WANG Guanzhong LU Hui li Jiang WANG lihua {2. ying SONG Shiping GE Zhilei li Qian CHEN Jing FAN Chunhai Division of Physical biology Shanghai Institute of Applied PhysicsChinese Academy of SciencesShanghai201800P.R.China University of chinese academy of sciences Beijing100049P.R.China Zhangjiang laboratory Shanghai201210P.R.China institute of Materiobiology Department of ChemistryCollege of SciencesShanghai UniversityShanghai200444P.R.China School of Chemistry and Chemical Engineering New Cornerstone Science LaboratoryFrontiers Science Center for Transformative MoleculesZhangjiang Institute for Advanced Study and National Center for Translational MedicineShanghai Jiao Tong UniversityShanghai200240P.R.China

The hierarchical assemblies of precise nanoparticles(NPs)have created materials with emergent properties and ***,the complex assemblies remain unclear at a precise ***,we show the hierarchical self-assembly of atomically precise gold nanoclusters(Au NCs)with molecular rotor-based ligands(MRL),featuring a double-layer *** to two other types of monolayer-protected(MLP)Au NCs,the significantly reduced surface density for MRL Au NCs profoundly influences their assembly behavior within the ***,the long length of rotor-based ligands and the rotational freedom of the phenyl-rings of rotor-based ligands also facilitate the assembly of *** works elucidate the hierarchical assembly on a precise scale,suggesting that the rotor-based ligand’s strategy offers promising potential for designing well-defined and more complex structures in supercrystals.

关键词： Gold nanocluster Molecular rotor Hierarchical assembly Double-layer surface

Enhancing immunotherapy efficacy against MHC-I deficient triple-negative breast cancer using LCL161-loaded macrophage membranedecorated nanoparticles

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3218-3231页

作者： Wen Zhang Yihui Zhai ying Cai Xiang Gong Yunxuan Jiang Rong Rong Chao Zheng Binyu zhu Helen He zhu Hao Wang Yaping li Pengcheng Zhang china State institute of Pharmaceutical Industry Shanghai 201203China State Key laboratory of Drug Research&Center of Pharmaceutics Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Biomedical Engineering&State Key laboratory of Advanced Medical Materials and Devices ShanghaiTech UniversityShanghai 201210China School of chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China Yantai institute of Materia Medica Shandong 264000China State Key laboratory of Oncogenes and Related Genes Renji-Med-X Stem Cell Research CenterDepartment of UrologyRen Ji HospitalSchool of Medicine and School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200127China University of chinese academy of sciences Beijing 100049China

Current cytotoxic T lymphocyte(CTL)activating immunotherapy requires a major histocompatibility complex I(MHC-I)-mediated presentation of tumor-associated antigens,which malfunctions in around half of patients with triple-negative breast cancer(TNBC).Here,we create a LCL161-loaded macrophage membrane decorated nanoparticle(LMN)for immunotherapy of MHC-I-deficient *** on the macrophage membrane helps LMNs recognize CD47-expressing cancer cells for targeted delivery of LCL161,which induces the release of high mobility group protein 1 and proinflammatory cytokines from cancer *** released cytokines and high mobility group protein 1 activate antitumor immunity by increasing the intratumoral density of the phagocytic macrophage subtype by 15 times and elevating the intratumoral concentration of CTL lymphotoxin by 4.6 *** also block CD47-mediated phagocytosis *** inhibit the growth of MHC-I-deficient TNBC tumors,as well as those resistant to combined therapy of anti-PDL1 antibody and albumin-bound paclitaxel,and prolong the survival of animals,during which process CTLs also play important *** macrophage membrane-decorated nanoparticle presents a generalizable platform for increasing macrophagemediated antitumor immunity for effective immunotherapy of MHC-I-deficient cancers.

关键词： MHC-I deficiency Macrophage CD47 Immunotherapy Triple-negative breast cancer Phagocytosis Immune checkpoint Innate immunity

Stability and variability of molecular subtypes: comparative analysis of primary and metastatic triple-negative breast cancer

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Cancer biology & medicine 2024年第9期21卷 784-798页

作者： Xiuzhi zhu Xiaohan ying Yin {2.u Yunyi Wang {2. Chen Zhiming Shao Xi Jin Yizhou Jiang Zhonghua Wang Key laboratory of Breast Cancer in shanghai Shanghai Institute of Infectious Disease and Biosecurity Department of Oncology Shanghai Medical College Fudan University Department of Breast Surgery Fudan University Shanghai Cancer Center

Objective: Triple-negative breast cancer(TNBC) is a heterogeneous and aggressive cancer. Although our previous study classified primary TNBC into four subtypes, comprehensive longitudinal investigations are ***: We assembled a large-scale, real-world cohort comprised of 880 TNBC patients [465 early-stage TNBC(e TNBC) and 415 metastatic TNBC(m TNBC) patients] who were treated at Fudan University shanghai Cancer Center. The longitudinal dynamics of TNBC subtypes during disease progression were elucidated in this patient cohort. Comprehensive analysis was performed to compare primary and metastatic lesions within specific TNBC ***: The recurrence and metastasis rates within 3 years after initial diagnosis in the e TNBC cohort were 10.1%(47/465). The median overall survival(OS) in the m TNBC cohort was 2..2.months [95% confidence interval(CI), 2..4±30.2.months], which indicated a poor prognosis. The prognostic significance of the original molecular subtypes in both e TNBC and m TNBC patients was confirmed. Consistent molecular subtypes were maintained in 77.5% of the patients throughout disease progression with the mesenchymal-like(MES) subtype demonstrating a tendency for subtype transition and brain metastasis. Additionally, a precision treatment strategy based on the metastatic MES subtype of target lesions resulted in improved progression-free survival in the FUTURE ***: Our longitudinal study comprehensively revealed the clinical characteristics and survival of patients with the original TNBC subtypes and validated the consistency of most molecular subtypes throughout disease progression. However, we emphasize the major importance of repeat pathologic confirmation of the MES subtype.

关键词： Triple-negative breast cancer metastasis molecular subtype overall survival primary tumor

Dietary cooking oils and cardiometabolic measurements in an elderly chinese population

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Journal of Geriatric Cardiology 2024年第6期21卷 642-650页

作者： Xin-Yu WANG Chao-ying MIAO Xiao-Fei YE Wen-Yuan-Yue WANG Jia-Bo zhu Yi ZHOU Yan {2. Ji-Guang WANG School of Public Health Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Cardiovascular medicine Centre for Epidemiological Studies and Clinical TrialsThe Shanghai Institute of HypertensionRuijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

OBJECTIVE To investigate three features of dietary cooking oil intake,namely,the consumption,cooking style,and composition of fatty acids in relation to several cardiometabolic measurements in an elderly chinese *** The elderly(≥65 years)participants for this study were recruited from two community health centers in the urban area of {2..A questionnaire was administered to collect information on dietary oil consumption(low,medium and high)and cooking styles(fry or stir-fry ***)and the composition of fatty acids(poly-unsaturated ***-unsaturated).The cardiometabolic measurements included anthropometry,blood pressure,fasting plasma glucose and serum *** The 1186 study participants had a mean age of 70.9±5.4 *** mean dietary oil consumption was 35.0 g/d,being low(2. g/d),medium(2.-49 g/d)and high(≥50 g/d)in 485,467 and 2.4 participants,*** proportion of the fry or stir-fry cooking style and oils rich in mono-unsaturated fatty acids was 30.4%and 2..4%,*** before and after adjustment for sex,age,current smoking and alcohol intake,dietary oil consumption was significantly(P≤0.02.and positively associated with the prevalence of treated hypertension and fasting plasma glucose *** similar adjustments as above and additional adjustment for dietary oil consumption,the fry or stir-fry cooking style was significantly(P≤0.048)and positively associated with body mass index,but inversely with systolic and diastolic blood pressure and serum low-density lipoprotein cholesterol,and the dietary intake of oils rich in mono-unsaturated fat acids was significantly(P≤0.02.and positively associated with diastolic blood pressure,serum triglycerides,total cholesterol and low-density lipoprotein cholesterol,and the prevalence of hypertriglyceridemia and *** This study showed that both the consumption and composition of fatty acids of the dietary oils mattered with regard to sev

关键词： cooking elderly unsaturated

Structure-based development of potent and selective type-II kinase inhibitors of RIPK1

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Acta Pharmaceutica Sinica B 2024年第1期14卷 319-334页

作者： ying Qin Dekang li Chunting Qi Huaijiang Xiang Huyan Meng Jingli liu Shaoqing Zhou Xinyu Gong ying li Guifang Xu Rui Zu Hang Xie Yechun Xu Gang Xu Zheng Zhang Shi Chen lifeng Pan ying li li Tan Interdisciplinary Research Center on biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 201210China University of chinese academy of sciences Beijing 100049China State Key laboratory of Chemical biology Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 200032China School of chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China State Key laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China institute of Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People’s Hospitalthe Second Affiliated HospitalSchool of MedicineSouthern University of Science and TechnologyShenzhen 518112China Department of Burn and Plastic Surgery Shenzhen Institute of Translational MedicineShenzhen University Medical SchoolShenzhen Second People’s Hospitalthe First Affiliated Hospital of Shenzhen UniversityShenzhen 518035China

Receptor-interacting serine/threonine-protein kinase 1(RIPK1)functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases.A number of allosteric RIPK1 inhibitors(RIPK1i)have been developed,and some of them have already advanced into clinical ***,selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to ***,we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical *** also describe the structure-guided lead optimization of a potent,selective,and orally bioavailable RIPK1i,62.which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory ***,62.provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

关键词： RIPK1 Necroptosis Type-II kinase inhibitors Rational design Lead optimization Structure‒activity relationship Anti-inflammation Preclinical drug discovery

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 2. tertiary care centers in china enrolled adult patients with metastatic nasopharyngeal carcinoma(NPC)who had failed two or more lines of previous systemic *** received 2.0-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 12. were efficacy *** the data cutoff date(September 2.,2.2.),1 patient achieved complete response and 34 patients attained partial *** ORR was 2..0%(95%CI 2..3–36.7%).The response was durable,with 66.8%still in response at 9 ***-three patients(2..4%)were still on *** median PFS and OS were 3.6 months(95%CI=1.9–7.3 months)and 2..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

The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions:insights from a single-arm,phase II trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2202-2214页

作者： Bo Cheng Caichen li Jianfu li Longlong Gong Peng liang ying Chen Shuting Zhan Shan Xiong Ran Zhong Hengrui liang Yi Feng Runchen Wang Haixuan Wang Hongbo Zheng Jun liu Chengzhi Zhou Wenlong Shao Yuan Qiu Jiancong Sun Zhanhong Xie zhu liang Chenglin Yang Xiuyu Cai Chunxia Su Wei Wang Jianxing He Wenhua liang Department of Thoracic Surgery and Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Medical Department Genecast Biotechnology Co.LtdWuxiChina Department of Radiation Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Respiratory medicine the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Department of Cardiothoracic Surgery Affiliated Hospital of Guangdong Medical UniversityZhanjiangChina Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenChina Department of VIP Inpatient Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaSun Yat-sen UniversityGuangzhouChina Department of Medical Oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Immune checkpoint inhibitors targeting the programmed cell death-1(PD-1)protein significantly improve survival in patients with advanced non-small-cell lung cancer(NSCLC),but its impact on early-stage ground-glass opacity(GGO)lesions remains *** is a single-arm,phase II trial(NCT0402.841)using Simon’s optimal two-stage design,of which 4 doses of sintilimab(2.0 mg per 3 weeks)were administrated in 36 enrolled multiple primary lung cancer(MPLC)patients with persistent high-risk(Lung-RADS category 4 or had progressed within 6 months)*** primary endpoint was objective response rate(ORR).T/B/NK-cell subpopulations,TCR-seq,cytokines,exosomal RNA,and multiplexed immunohistochemistry(mIHC)were monitored and compared between responders and ***,two intent-to-treat(ITT)lesions(pure-GGO or GGO-predominant)showed responses(ORR:5.6%,2.36),and no patients had progressive disease(PD).No grade 3-5 TRAEs *** total response rate considering two ITT lesions and three non-intent-to-treat(NITT)lesions(pure-solid or solid-predominant)was 13.9%(5/36).The proportion of CD8^(+)T cells,the ratio of CD8^(+)/CD4^(+),and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over ***,the mIHC analysis showed more CD8^(+)T cells infiltrated in ***,responders’cytokine concentrations of EGF and CTLA-4 increased during *** exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among ***,PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety *** effects were associated with specific T-cell re-distribution,EGF/CTLA-4 cytokine compensation,and regulation of metabolism pathways.

关键词： lesions metabolism doses

Beta-asarone inhibits synaptic inputs to airway preganglionic parasympathetic motoneurons

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Beta-asarone inhibits synaptic inputs to airway preganglioni...

The ERF transcription factor LTF1 activates DIR1 to control stereoselective synthesis of antiviral lignans and stress defense in Isatis indigotica roots

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Dong-ying QIU~(1,2.,li-li HOU~(1,2.,Yong-Hua CHEN~1,Xu-Jiao ZHOU~1,Lei zhu~,Ji-Jiang WANG~(1,*) 1 The State Key laboratory of Medical Neurobiology and institute of Brain sciences,Fudan University shanghai Medical College,138 Yi-Xue-Yuan Road,shanghai 2.0032.china 2.Fudan University Zhongshan Hospital,180 Fenglin Road,shanghai 2.0032.china

＜正＞Therapeutic application of Asarum,a herbal medicine that has been used for centuries,reportedly causes acute respiratory *** responsible constituents,the sites of action,and the mechanisms involved in this side effect are *** investigated the effects ofβ-asarone,a volatile constituent of Asarum,on neurotransmission in the medullary respiratory neuronal network using extracellular recording of the rhythmic hypoglossal activity and voltage clamp recordings of the postsynaptic activity of the airway preganglionic parasympathetic motoneurons （APPMs）in vitro,β-asarone caused progressive decreases in the duration and area of the hypoglossal bursts in a concentration-dependent *** frequency and amplitude of the bursts were initially unaltered or temporarily increased,but were then inhibited progressively after prolonged *** with the inhibition of the hypoglossal bursts,the tonic and the phasic excitatory and inhibitory postsynaptic currents in the APPMs were attenuated. These data suggest that the Asarum-caused acute respiratory disturbance involvesβ-asarone-induced inhibition of neurotransmission in the medullary respiratory neuronal network.

关键词： respiration Asarum neurotransmission

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Acta Pharmaceutica Sinica B 2024年第1期14卷 405-420页

作者： Ruibing Chen Jian Yu Luyao Yu liang Xiao ying Xiao Junfeng Chen Shouhong Gao Xianghui Chen Qing li Henan Zhang Wansheng Chen Lei Zhang Department of Pharmaceutical Botany School of PharmacyNaval Medical UniversityShanghai 200433China Research and Development Center of chinese medicine Resources and Biotechnology Shanghai University of Traditional Chinese MedicineShanghai 201203China Department of Pharmacy Shanghai Changzheng HospitalNaval Medical UniversityShanghai 200003China School of medicine Shanghai UniversityShanghai 200433China institute of Edible Fungi Shanghai Academy of Agricultural SciencesNational Engineering Research Center of Edible FungiKey Laboratory of Edible Fungi Resources and Utilization(South)Ministry of AgricultureShanghai 201403China College of life sciences and {2. Key Laboratory of Plant Secondary Metabolism and Regulation of Zhejiang ProvinceZhejiang Sci-Tech UniversityHangzhou 310018China State Key laboratory of Dao-di Herbs Beijing 100700China

lignans are a powerful weapon for plants to resist stresses and have diverse bioactive functions to protect human *** the mechanisms of stereoselective biosynthesis and response to stresses of lignans is important for the guidance of plant ***,we identified the complete pathway to stereoselectively synthesize antiviral(-)-lariciresinol glucosides in Isatis indigotica roots,which consists of three-step sequential stereoselective enzymes DIR1/2.PLR,and ***1 was further identified as the key gene in respoJanuary 2.2.nse to stresses and was able to trigger stress defenses by mediating the elevation in lignan ***,the phytohormone-responsive ERF transcription factor LTF1 colocalized with DIR1 in the cell periphery of the vascular regions in mature roots and helped resist biotic and abiotic stresses by directly regulating the expression of *** systematic results suggest that DIR1 as the first common step of the lignan pathway cooperates with PLR and UGT71B2.to stereoselectively synthesize(-)-lariciresinol derived antiviral lignans in *** roots and is also a part of the LTF1-mediated regulatory network to resist *** conclusion,the LTF1-DIR1 module is an ideal engineering target to improve plant Defenses while increasing the content of valuable lignans in plants.

关键词： lignans Stereoselective synthesis Stress resistance Dirigent protein ERF