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Small-molecule agents for cancer immunotherapy

Acta Pharmaceutica Sinica B 2024年第3期14卷 905-952页

作者： Fang Wang Kai Fu Yujue Wang Can pan Xueping Wang Zeyu Liu Chuan Yang Ying Zheng Xiaopeng Li Yu Lu Kenneth Kin Wah To Chenglai Xia Jianye Zhang Zhi Shi Zeping Hu Min Huang Liwu Fu State Key Laboratory of Oncology in South china Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical sciences Tsinghua-Peking Center for Life SciencesBeijing Frontier Research Center for Biological StructureTsinghua UniversityBeijing 100084China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacology NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Pharmacy The Chinese University of Hong KongHong Kong 999077China Affiliated Foshan Maternity and Child Healthcare Hospital Southern Medical UniversityFoshan 528000China

Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer *** induce long-term tumor regression and overall survival benefit in many types of *** the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for *** molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively *** of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor ***,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

关键词： Cancer immunotherapy Small-molecule agents Immune checkpoints Oncogenic signaling Metabolic pathways Cytokine/chemokine signaling Antitumor immunity Tumor immune microenvironment

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MiR-106a targets ATG7 to inhibit autophagy and angiogenesis after myocardial infarction

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Animal Models and Experimental Medicine 2024年第4期7卷 408-418页

作者： Guofeng Bai Jinghao Yang Weili Liao Xiaofeng Zhou Yingting He Nian Li Liuhong Zhang Yifei Wang Xiaoli Dong Hao Zhang Jinchun pan Liangxue Lai Xiaolong Yuan Xilong Wang Guangdong Provincial Key Laboratory of Laboratory Animals Guangdong Laboratory Animals Monitoring InstituteGuangzhouChina Guangdong Laboratory of Lingnan Modern Agriculture National Engineering Research Center for Breeding Swine IndustryState Key Laboratory of Swine and Poultry Breeding IndustryGuangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular BreedingCollege of Animal ScienceSouth China Agricultural UniversityGuangzhouGuangdongChina Huidong County Animal Quarantine and Inspection Institute HuizhouGuangdongChina department of Cardiology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHainan Clinical Medicine Research InstitutionHaikouPeople's Republic of China Key Laboratory of Regenerative Biology Guangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdongChina

Background:Myocardial infarction(MI)is an acute condition in which the heart mus-cle dies due to the lack of blood *** research has suggested that au-tophagy and angiogenesis play vital roles in the prevention of heart failure after MI,and miR-106a is considered to be an important regulatory factor in *** the specific mechanism remains *** this study,using cultured venous endothelial cells and a rat model of MI,we aimed to identify the potential target genes of miR-106a and discover the mechanisms of inhibiting autophagy and ***:We first explored the biological functions of miR-106a on autophagy and angiogenesis on endothelial *** we identified ATG7,which was the down-stream target gene of *** expression of miR-106a and ATG7 was investi-gated in the rat model of ***:We found that miR-106a inhibits the proliferation,cell cycle,autophagy and angiogenesis,but promoted the apoptosis of vein endothelial ***,ATG7 was identified as the target of miR-106a,and ATG7 rescued the inhibition of autophagy and angiogenesis by *** expression of miR-106a in the rat model of MI was decreased but the expression of ATG7 was increased in the infarction ***:Our results indicate that miR-106a may inhibit autophagy and angiogenesis by targeting *** mechanism may be a potential therapeutic treatment for MI.

关键词： angiogenesis ATG7 autophagy miR-106a miRNAs myocardial infarction

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Genomic investigation and nationwide tracking of pediatric invasive nontyphoidal Salmonella in china

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mLife 2024年第1期3卷 156-160页

作者： Yefang Ke Lin Teng Zhe Zhu Wenbo Lu Wenyuan Liu Haiyang Zhou Qi Yu Lina Ye pan Zhu Guoping Zhao Min Yue Deparment of Clinical Laboratory Ningbo Women and Children's HospitalNingboChina department of Veterinary Medicine Zhejiang University Cllege of Animal SciencesHangzhouChina department of Blood Transfusion Ningbo No.2 HospitalNingboChina Office of Screening Ningbo Women and Children's HospitalNingboChina Neonatal Intensive Care Unit Ningbo Women and Children's HospitalNingboChina School of Life Science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouChina CAS Key Laboratory of Synthetic Biology Institute of Plant Physiology and EcologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina department of Microbiology and Microbial Engineering School of Life SciencesFudan UniversityShanghaiChina State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouChina Hainan Institute of Zhejiang university SanyaChina

Impact Statement。Invasive nontyphoidal Salmonella(iNTS)causes significant concern with~15%morbidity,affecting populations mainly in African countries.

关键词： pediatric nationwide morbidity

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Recent advances in chemical protein synthesis:method developments and biological applications

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Science china Chemistry 2024年第4期67卷 1060-1096页

作者： Suwei Dong Ji-Shen Zheng Yiming Li Huan Wang Gong Chen Yongxiang Chen Gemin Fang Jun Guo Chunmao He Honggang Hu Xuechen Li Yanmei Li Zigang Li Man pan Shan Tang Changlin Tian Ping Wang Bian Wu Chuanliu Wu Junfeng Zhao Lei Liu State Key Laboratory of Natural and Biomimetic Drugs and School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Division of Life sciences and Medicine University of Science and Technology of ChinaHefei 230027China School of Food and biological Engineering Engineering Research Center of Bio-processMinistry of EducationHefei University of TechnologyHefei 230009China School of Chemistry and Chemical Engineering Nanjing UniversityNanjing 210023China State Key Laboratory of Elemento-Organic Chemistry Nankai UniversityTianjin 300071China department of Chemistry Tsinghua UniversityBeijing 100084China Institute of Health sciences Anhui UniversityHefei 230601China College of Chemistry Central China Normal UniversityWuhan 430079China School of Chemistry and Chemical Engineering South China University of TechnologyGuangzhou 510640China School of Medicine or Institute of Translational Medicine Shanghai UniversityShanghai 200444China department of Chemistry The University of Hong KongHong Kong 999077China Shenzhen Graduate School Peking UniversityShenzhen 518055China School of Chemistry and Chemical Engineering Shanghai Jiao Tong UniversityShanghai 200240China School of Life sciences University of Science and Technology of ChinaHefei 230026China department of Chemical Biology Shanghai Jiao Tong UniversityShanghai 200240China Institute of Microbiology Chinese Academy of SciencesBeijing 100101China department of Chemistry Xiamen UniversityXiamen 361005China School of Pharmaceutical Science Guangzhou Medical UniversityGuangzhou 511436China

The central dogma of modern biology underscores the pivotal roles proteins play in diverse biological processes,the study of which necessitates advanced methods to produce proteins with precision and *** protein synthesis,a powerful approach utilizing chemical reactions for the de novo construction of structurally accurate proteins,has emerged as a transformative tool for studying proteins and generating protein derivatives/mimics inaccessible by natural biological machinery,including post-translationally modified proteins,proteins comprised of unnatural amino acids,as well as mirror-image *** review summarizes recent strides in synthetic method developments for chemical protein synthesis,including innovative techniques in solid-phase peptide synthesis,the challenges presented by difficult sequences in either synthesis or folding and the exploration of novel ligation reactions using both chemical and enzymatic ***,the review also delves into newly developed protocols for site-selective protein modifications and the generation of stapled or macrocyclized peptides/miniproteins,highlighting the power of chemical methods to make structurally diverse *** applications of synthetic proteins in investigating post-translational modifications(phosphorylation,lipidation,glycosylation,ubiquitination,etc.),mirror-image biological processes and drug development are further ***,these topics provide a comprehensive overview of the current landscape of chemical protein synthesis.

关键词： chemical protein synthesis solid-phase peptide synthesis ligation reactions post-translational modifications mirror-image proteins peptide drugs

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Andrographolide Attenuates Noise-Induced Hearing Loss by Ameliorating Cochlear Inflammation

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World Journal of Traditional Chinese Medicine 2024年第2期10卷 204-212页

作者： Meng-Hua Li Wan-Qi Wang Li-Ting Zheng Meng Bing Chen Yang Chu Miao Qiao Zuo-Li Zhang Konduru Naveena Yong pan Yun-Shi Zhang He Sun Xiao-Hui Ma Xi Shi Artificial Auditory Laboratory of Jiangsu Province Xuzhou Medical UniversityXuzhouChina Key Laboratory of Tropical biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouChina department of ENT Beijing Friendship HospitalCapital Medical UniversityBeijingChina National Key Laboratory of Chinese Medicine Modernization Tasly AcademyTasly Pharmaceutical Group Co.Ltd.TianjinChina Endoscopy Center Ankang People's HospitalAnkangChina department of Respiratory Medicine Xuzhou Infectious Diseases HospitalAffiliated Hospital of Xuzhou Medical UniversityXuzhouChina department of ENT The People's Hospital of Rongchang DistrictChongqingChina

Objective:This study aimed to explore andrographolide's mechanism of action and its protective effect on noise-induced hearing loss(NIHL).Materials and Methods:A mice animal model for NIHL was established through exposure to broadband noise at 12. d B sound pressure level for 4 *** analysis and pharmacodynamic experiments were carried ***:Andrographolide enters the inner ear and effectively prevents hearing damage following noise exposure in the mice model for permanent hearing ***,treatment with andrographolide inhibited the excessive activation of inflammatory factors in the cochleae of noise-exposed ***:Andrographolide might be a promising candidate for auditory protective drug investigation.

关键词： Andrographolide anti-inflammatory auditory protection noise-induced hearing loss traditional Chinese medicine compound

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Genetic variation in a heat shock transcription factor modulates cold tolerance in maize

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Molecular Plant 2024年第9期17卷 1423-1438页

作者： Lei Gao Lingling pan Yiting Shi Rong Zeng Minze Li Zhuoyang Li Xuan Zhang Xiaoming Zhao Xinru Gong Wei Huang Xiaohong Yang Jinsheng Lai Jianru Zuo Zhizhong Gong Xiqing Wang Weiwei Jin Zhaobin Dong Shuhua Yang State Key Laboratory of Plant Environmental Resilience Frontiers Science Center for Molecular Design BreedingCollege of Biological SciencesCenter for Crop Functional Genomics and Molecular BreedingChina Agricultural UniversityBeijing 100193China State Key Laboratory of Maize Bio-breeding National Maize Improvement CenterFrontiers Science Center for Molecular Design BreedingDepartment of Plant Geneticsand BreedingChinaAgricultural UniversityBeijingChina State Key Laboratory of Plant Genomics and National Plant Gene Research Center Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing100101China

Understanding how maize(Zea mays)responds to cold stress is crucial for facilitating breeding programs of cold-tolerant *** extensive utilization of the genome-wide association study(GWAs)approach for exploring favorable natural alleles associated with maize cold tolerance,few studies have successfully identified candidate genes that contribute to maize cold *** this study,we used a diverse panel of inbred maize lines collected from different germplasm sources to perform a GWAS on var-iations in the relative injured area of maize true leaves during cold stress-a trait very closely correlated with maize cold *** identified HsF2.,which encodes a B-class heat shock transcription factor(HSF)that positively regulates cold tolerance at both the seedling and germination *** varia-tions in the promoter of the cold-tolerant HSF2.Hap1 allele led to increased HSF2. expression under cold stress by inhibiting binding of the basic leucine zipper bziP68 transcription factor,a negative regulator of cold *** integrating transcriptome deep sequencing,DNA affinity purification sequencing,and targeted lipidomic analysis,we revealed the function of HsF2. in regulating lipid metabolism homeo-stasis to modulate cold tolerance in *** addition,we found that HsF2. confers maize cold tolerance without incurring yield ***,this study establishes HsF2. as a key regulator that en-hances cold tolerance in maize,providing valuable genetic resources for breeding of cold-tolerant maize varieties.

关键词： heat shock factor HSF2. cold tolerance natural variation bZiP68 lipid metabolism maize

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Tripchlorolide protects against 1-methy1-4-phenyl-1,2.3,6-tetrahydropyridine（MPTP）-induced neurotoxicity in C57BL/6 mice

Tripchlorolide protects against 1-methy1-4-phenyl-1,2,3,6-te...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Zhen HONG,~1 Gang WANG,~1 Jing GU,~3 Jing pan~1,Li BAT~1,Shi ZHANG~1,Sheng-Di CHEN~(1,2.) 1 department of Neurology and Institute of Neurology,Ruijin Hospital affiliated to Shanghai Jiaotong {2. School of Medicine,Shanghai,2.002.{2. 2.Institute of Health Science,Shanghai Institutes of biological sciences(SIBS),Chinese Academy of sciences(CAS) & Shanghai Jiaotong {2. School of Medicine,Shanghai,2.002.{2. 3 National Key Laboratory of Medical Neurobiology,Medical Center of Fudan {2.,Shanghai,2.0032.3}.

＜正＞Many current theories of Parkinson’s disease（PD） suggest that inflammation is involved in the neurodegenerative ***（TW397）,a traditional Chinese herbal compound with anti-inflammatory and immunosuppressive properties,has been shown to protect and restore dopaminergic neurons against the neurotoxicity induced by 1-methyl- 4-phenylpyridinium ion in *** study was designed to investigate TW397’s effect in vivo in the PD model of 1- methyl-4-phenyl-1,2.3,6-tetrahydropyridine（MPTP） lesioned C57BL/6 *** the present study,the neurotoxin MPTP reduced the survival ratio of tyrosine hydroxylase-immunoreactive（TH-IR） neurons in the substantia nigra pars compacta and TH-IR fibers in striatum to 65%and 12.of the normal control,***,treatment with TW397 of 1μg/kg for 16 days once per day dramatically improved the survival rate of TH-IR neurons in the substantia nigra pars compacta and TH-IR fibers in striatum to 82.and 38%of the control,meanwhile,significantly improved the level of dopamine in the substantia nigra and striatum to 157%and 191%of the vehicle-treated group,*** addition,the Rota-Rod performance of the animals treated with 0.5μg/kg or 1μg/kg TW397 were significantly improved for about 2.or 3 fold relative to vehicle-treated animals,*** data demonstrate a neuroprotective action of TW397 in vivo against MPTP toxicity,which has important implications for the treatment of PD.

关键词： Tripchlorolide neurotrophic Parkinson’s disease immunosuppressant 1-methyl-4-phenyl-1,2.3,6-tetrahydropyridine(MPTP) Tripterygium wilfordii Hook F.

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Proteomic difference between spinal cord stem cells and motor neurons

Proteomic difference between spinal cord stem cells and moto...

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中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Peng-Fei LI,Chun-Fang WANG~*,Fei WANG,Hong-En WEI department of biotechnology,Shanxi Medical {2.,Taiyuan 030001,china

＜正＞Objective Motor neuron damage always occurs in amyotrophic lateral sclerosis and spinal cord *** research offers hope that neural stem cells（NSCs） may be donors to replace lost motor *** vitro,we proved that NSCs can differentiate into cholinergic neurons（motor neuron is a type of cholinergic neuron） in a special condition. Others have shown that some factors could induce mouse embryonic stem（ES） cells to differentiate into motor neurons. Since proteomic approaches are most appropriate to determine protein content,stability and subcellular localization,many people used the 2.DE comparative proteome analysis to study the differentiation process of *** some learned details of the differentiation process,questions that whether these differentiated cells are really the ones which we want remain ***,before inducing NSCs into motor neurons,we should find the difference between *** this paper,we used the proteomic analysis to gain more insight into molecular mechanisms of the difference between NSCs and motor *** cord stem cells（SCSCs） are a subclass of NSCs and as such are restricted to generating neural tissues,which is a notable advantage over embryonic stem cells,and have the further advantage of being regionally specified to produce spinal cord *** SCSCs and motor neurons obtained from the same 16-day-old rat fetus spinal cord,this can make our result have more obviously biological statistical ***,we employed the method of difference gel electrophoresis（DIGE）,which allows protein differences between two samples to be analyzed on the same *** the transiently expressed p75-NGFR was chosen for motor neuron isolation from embryonic day 15 to postnatal day 15 rat spinal cords,we used CELLection pan Mouse IgG Kit to separate motor neurons,and we used the rest spinal cord after motor neurons separation to SCSCs *** cell lysate preparation,we did 2. gel analysis according

关键词： neural stem cells motor neurons proteome

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ATP-dependent retrograde axonal transport of P2.3 receptor in primary sensory neurons

ATP-dependent retrograde axonal transport of P2X3 receptor i...

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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： Bin WANG~1,Xu-Qiao CHEN~1,Cheng-Biao WU~2.Jin pan~1,Bo YUAN~3,Yuan-Yuan SU~1,Xing-Yu JIANG~3, Xu ZHANG~4,Lan BAO~(1,*) 1 Laboratory of Molecular Cell Biology,Institute of Biochemistry and Cell Biology,Shanghai Institutes for biological {2.,Chinese Academy of {2.,Shanghai 2.0031,china 2.department of Neuro{2.,School of Medicine,university of California,San Diego,La Jolla,California 92.93- 0662.USA 3 National Center for Nanoscience and Technology,Beijing 100080,china 4 Institute of Neuroscience and State Key Laboratory of Neuroscience,Institutes for biological {2.,Chinese Academy of {2.,Shanghai 2.0031,china

Objective P2. receptors are ATP-gated cation channels and play variable roles in pathophysiological *** P2. receptors,P2.

关键词： primary sensory neuron P2.3 receptor axonal retrograde transport

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Lipid rafts mediates ATP-induced endocytosis,signal transduction and retrograde transport of P2.3 receptor

Lipid rafts mediates ATP-induced endocytosis,signal transduc...

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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： Xu-Qiao CHEN~(1,#),Bin WANG~(1,#),Chengbiao WU~2.Jin pan~1,Bo YUAN~3,Yuan-Yuan SU~1,Xing-Yu JIANG~3,Xu ZHANG~4 Lan BAO~(1,*) 1 Laboratory of Molecular Cell Biology,Institute of Biochemistry and Cell Biology,Shanghai Institutes for biological {2.,Chinese Academy of {2.,Shanghai 2.0031,china 2.department of Neuro{2.,School of Medicine,university of California,San Diego,La Jolla,California,USA 3National Center of Nanoscience and Technology,Beijing 100190,china 4 Institute of Neuroscience and State Key Laboratory of Neuroscience,Shanghai Institutes for biological {2., Chinese Academy of {2.,Shanghai 2.0031,china

P2. receptors are a family of cation channels expressed in neurons and nonneuronal *** play a variety of roles including synaptic transmission,muscle contraction,neuronal secretion and inflammation response. Among P2. receptors,the P2. subtype is selectively expressed in dorsal root ganglion *** raft is a specialized membrane microdomain and participate many signal transduction *** report showed that P2. receptor is localized in the lipid rafts of DRG *** have found P2. receptor engaged in retrograde transport in the form of signaling *** we investigated the role of lipid rafts in a,B-MeATP-dependent endocytosis and signal transduction,and retrograde transport of P2. *** of lipid raft with MBCD or nystatin abolished ATP-dependent endocytosis of P2. receptor and ATP-induced ERK activation in P2. receptor-expressing HEK2.3 *** vivo sucrose gradient fractionation with vesicular pellets prepared from sciatic nerve axoplasm showed that abundant P2. receptor was localized in lipid raft *** transported P2. receptors were colocalized with the lipid raft marker caveolinla in sciatic *** terminal treatment with MPCD attenuated retrograde transport of P2. receptor in axon of dorsal root ganglion ***,lipid raft mediates ATP-induced endocytosis,signal transduction and retrograde transport of P2. receptor.

关键词： P2.3 receptor lipid raft endocytosis ERK retrograde transport

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