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Neoantigens:promising targets for cancer therapy

Signal Transduction and Targeted Therapy 2023年第2期8卷 446-483页

作者： Na Xie guobo shen Wei Gao Zhao Huang Canhua Huang Li Fu State Key Laboratory of Biotherapy and Cancer Center West China Hospitaland West China School of Basic Medical Sciences and Forensic MedicineSichuan Universityand Collaborative Innovation Center for BiotherapyChengdu610041China Clinical Genetics Laboratory Affiliated Hospital&Clinical Medical College of Chengdu UniversityChengdu610081China Guangdong Provincial Key Laboratory of Regional Immunity and Diseases Department of Pharmacology and International Cancer CenterShenzhen University Health Science CenterShenzhen518060GuangdongPeople’s Republic of China

Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies,including cancer vaccines,adoptive cell therapy and antibody-based therapies,especially for solid *** are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations,such as genomic mutation,dysregulated RNA splicing,disordered post-translational modification,and integrated viral open reading *** are recognized as non-self and trigger an immune response that is not subject to central and peripheral *** quick identification and prediction of tumor-specific neoantigens have been made possible by the advanced development of next-generation sequencing and bioinformatic *** to tumor-associated antigens,the highly immunogenic and tumor-specific neoantigens provide emerging targets for personalized cancer immunotherapies,and serve as prospective predictors for tumor survival prognosis and immune checkpoint blockade *** development of cancer therapies will be aided by understanding the mechanism underlying neoantigen-induced anti-tumor immune response and by streamlining the process of neoantigen-based *** review provides an overview on the identification and characterization of neoantigens and outlines the clinical applications of prospective immunotherapeutic strategies based on *** also explore their current status,inherent challenges,and clinical translation potential.

关键词： antigens alterations approval

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Nanotechnology’s frontier in combatting infectious and inflammatory diseases:prevention and treatment

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Signal Transduction and Targeted Therapy 2024年第3期9卷 998-1047页

作者： Yujing Huang Xiaohan Guo Yi Wu Xingyu Chen Lixiang Feng Na Xie guobo shen Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China Hospitaland West China School of Basic Medical Sciences and Forensic MedicineSichuan Universityand Collaborative Innovation Center for BiotherapyChengdu 610041China

Inflammation-associated diseases encompass a range of infectious diseases and non-infectious inflammatory diseases,which continuously pose one of the most serious threats to human health,attributed to factors such as the emergence of new pathogens,increasing drug resistance,changes in living environments and lifestyles,and the aging *** rapid advancements in mechanistic research and drug development for these diseases,current treatments often have limited efficacy and notable side effects,necessitating the development of more effective and targeted anti-inflammatory *** recent years,the rapid development of nanotechnology has provided crucial technological support for the prevention,treatment,and detection of inflammation-associated *** types of nanoparticles(NPs)play significant roles,serving as vaccine vehicles to enhance immunogenicity and as drug carriers to improve targeting and *** can also directly combat pathogens and *** addition,nanotechnology has facilitated the development of biosensors for pathogen detection and imaging techniques for inflammatory *** review categorizes and characterizes different types of NPs,summarizes their applications in the prevention,treatment,and detection of infectious and inflammatory *** also discusses the challenges associated with clinical translation in this field and explores the latest developments and *** conclusion,nanotechnology opens up new possibilities for the comprehensive management of infectious and inflammatory diseases.

关键词： prevention inflammatory treatment

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NAD+metabolism:pathophysiologic mechanisms and therapeutic potential

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Signal Transduction and Targeted Therapy 2020年第1期5卷 596-632页

作者： Na Xie Lu Zhang Wei Gao Canhua Huang Peter Ernst Huber Xiaobo Zhou Changlong Li guobo shen Bingwen Zou State Key Laboratory of Biotherapy and Cancer Center West China Hospitaland West China School of Basic Medical Sciences&Forensic MedicineSichuan Universityand Collaborative Innovation Center for BiotherapyChengdu 610041China State Key Laboratory of Biotherapy and Cancer Center West China Hospitaland Collaborative Innovation Center for BiotherapyChengdu 610041China School of Basic Medical Sciences Chengdu University of Traditional Chinese MedicineChengduSichuan 611137China CCU Molecular and Radiation Oncology German Cancer Research CenterDepartment of Radiation OncologyHeidelberg University HospitalHeidelbergGermany First Department of Medicine Medical Faculty MannheimUniversity of HeidelbergTheodor-Kutzer-Ufer 1-368167 MannheimGermany West China School of Basic Medical Sciences&Forensic Medicine West China HospitalSichuan UniversityChengdu 610041China Department of Thoracic Oncology and Department of Radiation Oncology Cancer CenterWest China HospitalSichuan UniversityChengdu 610041Chin

Nicotinamide adenine dinucleotide(NAD^(+))and its metabolites function as critical regulators to maintain physiologic processes,enabling the plastic cells to adapt to environmental changes including nutrient perturbation,genotoxic factors,circadian disorder,infection,inflammation and *** effects are mainly achieved by the driving effect of NAD^(+)on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction ***,multiple NAD^(+)-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA,RNA and proteins,or releasing second messenger cyclic ADPribose(cADPR)and NAADP^(+).Prolonged disequilibrium of NAD^(+)metabolism disturbs the physiological functions,resulting in diseases including metabolic diseases,cancer,aging and neurodegeneration *** this review,we summarize recent advances in our understanding of the molecular mechanisms of NAD^(+)-regulated physiological responses to stresses,the contribution of NAD^(+)deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention.

关键词： metabolism therapeutic potential

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Spike protein of SARS‐CoV‐2 Omicron(B.1.1.529)variant has a reduced ability to induce the immune response

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Signal Transduction and Targeted Therapy 2022年第5期7卷 1379-1382页

作者： Cai He Xuemei He Jingyun Yang Hong Lei Weiqi Hong Xiangrong Song Li Yang Jiong Li Wei Wang guobo shen Guangwen Lu Xiawei Wei Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan University610041 ChengduChina

Dear Editor,The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variant Omicron(B.1.1.529)has attracted great concerns since its identification in South *** is the fifth variant of concern(VOC)after Alpha(B.1.1.7),Beta(B.1.351),Gamma(P.1)and Delta(B.1.617.2),and set a record with the shortest duration from variants of interest(VOI)to VOC so *** 2 months after its first report,over 80%of global sequenced samples are verified as Omicron according to GISAID(https://***/explore/World/AllSamples/from=2021-12-15&to=2022-01-15/variants?pangoLineage=B.1.1.529*).

关键词： acute respiratory shortest

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低温热缩聚-溶剂热萃取法制备同性沥青基碳纤维

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石油学报（石油加工） 2022年第6期38卷 1271-1280页

作者：沈国波刘东中国石油大学(华东)化学工程学院重质油国家重点实验室山东青岛266400

以加氢预处理后的催化裂化油浆为原料,采用低温热缩聚与溶剂热萃取相结合的方法制备同性沥青,并研究了不同热缩聚温度、不同溶剂、不同体积比的正庚烷-甲苯混合溶液对同性沥青的影响。将同性沥青通过熔融纺丝、预氧化、炭化得到同性沥... 详细信息

以加氢预处理后的催化裂化油浆为原料,采用低温热缩聚与溶剂热萃取相结合的方法制备同性沥青,并研究了不同热缩聚温度、不同溶剂、不同体积比的正庚烷-甲苯混合溶液对同性沥青的影响。将同性沥青通过熔融纺丝、预氧化、炭化得到同性沥青基碳纤维。采用偏光显微镜、XRD、红外光谱、元素分析、热重分析和扫描电子显微镜等手段对同性沥青基碳纤维进行表征。结果表明:在热缩聚过程中,温度小于400℃能有效避免中间相小球的生成;在溶剂热萃取过程中,随着制备聚合沥青的热缩聚温度升高,正庚烷不溶物软化点也相应提高;随着甲苯含量的提高,混合溶液不溶物收率降低,软化点升高;390℃低温热缩聚,以正庚烷为溶剂进行溶剂热萃取制得的同性沥青软化点达到230℃,熔纺性能好。原丝纤维最佳预氧化条件为:先以升温速率1℃/min升温至180℃,然后以0.5℃/min升至270℃维持30 min;炭化后得到的同性沥青基碳纤维碳质量分数达到94%,拉伸强度达到1.113 GPa。

关键词：沥青基碳纤维热缩聚溶剂热萃取预氧化

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Low levels of neutralizing antibodies against XBB Omicron subvariants after BA.5 infection

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Signal Transduction and Targeted Therapy 2023年第7期8卷 3486-3497页

作者： Jingyun Yang Weiqi Hong Hong Lei Cai He Wenwen Lei Yanan Zhou Tingmei Zhao Aqu Alu Xuelei Ma Jiong Li Li Yang Zhenling Wang Wei Wang Guangwen Lu guobo shen Shuaiyao Lu Guizhen Wu Huashan Shi Xiawei Wei Laboratory of Aging Research and Cancer Drug Target Department of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityNo.17Block 3Southern Renmin RoadChengduSichuan 610041People’s Republic of China NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and Prevention(China CDC)Beijing 102206China National Kunming High-level Biosafety Primate Research Center Institute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeKunmingYunnanChina

The COVID-19 response strategies in Chinese mainland were recently adjusted due to the reduced pathogenicity and enhanced infectivity of Omicron *** Chengdu,China,an infection wave was predominantly induced by the BA.... 详细信息

关键词： immunity infection antibodies

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S19W,T27W,and N33OY mutations in ACE2 enhance SARS-CoV-2 S-RBD binding toward both wild-type and antibody-resistant viruses and its molecular basis

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Signal Transduction and Targeted Therapy 2021年第10期6卷 3096-3107页

作者： Fei Ye Xi Lin Zimin Che Fanli Yang sheng Lin Jing Yang Hua Chen Honglu Sun Lingling Wang Ao Wen Xindan Zhang Yushan Dai Yu Cao Jingyun Yang guobo shen Li Yang Jiong Li Zhenling Wang Wei Wang Xiawei Wei Guangwen Lu West China Hospital Emergency Department(WCHED) State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengduSichuanChina Disaster Medicine Center West China HospitalSichuan UniversityChengduSichuanChina Laboratory of Aging Research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuanChina

SARS-CoV-2 recognizes,via its spike receptor-binding domain(S-RBD),human angiotensin-converting enzyme 2(ACE2)to initiate ***-domain protein of ACE2 can therefore function as a *** we show that mutations of S19W,T27W,and N330Y in ACE2 could individually enhance SARS-CoV-2 S-RBD binding.Y330 could be synergistically combined with either W19 or W27,whereas W19 and W27 are mutually *** structures of SARS-CoV-2S-RBD bound to the ACE2 mutants reveal that the enhan ced binding is mainly con tributed by the van der Waals interactio ns mediated by the aromatic side-chai ns from W19,W27,and *** Y330 and W19/W27 are distantly located and devoid of any steric interference,W19 and W27 are shown to orient their side-chains toward each other and to cause steric conflicts,explai ning their in ***,using pseudotyped SARS-CoV-2 viruses,we dem on strate that these residue substitutions are associated with dramatically improved entry-inhibition efficacy toward both wild-type and antibody-resistant *** together,our biochemical and structural data have delineated the basis for the elevated S-RBD binding associated with S19W,T27W,and N330Y mutations in ACE2,paving the way for potential application of these mutants in dinical treatment of COVID-19.

关键词： ACE2 elevated RBD

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Comparisons of three polyethyleneimine-derived nanoparticles as delivery system of gene therapy for renal cell carcinoma

Comparisons of three polyethyleneimine-derived nanoparticles...

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中国生物化学与分子生物学会第十届会员代表大会暨全国学术会议

作者： Zhizhong Xu guobo shen Xiangying Xia Qingfa Guo Shuai Shi Shufang Liang Zhiyong Qian Yuquan Wei State Key Lab of Biotherapy and Cancer Center West China HospitalWest China Medical SchoolSichuan University

The VHL gene is a tumor suppressor gene that usually inactivation or absence in clear cell renal cell carcinoma (CCRCC).CCRCC shows no sensitivity to radiotherapy or chemotherapy,and has a poor ***,a novel therapy strategy against CCRCC needs to be *** gene therapy via novel delivery systems may be a new way to treat CCRCC. Recently,polyethyleneimine(PEI),a cationic polymer, is widely used as a delivery system for gene transfection in *** our studies,three PEI-derived nanoparticles, including poly(E-caprolactone)-pluronic-poly(ε-caprolactone) grafted PEI(PCFC-g-PEI),folic acid-PCFC-isophorone

关键词： clear cell renal cell carcinoma VHL polyethyleneimine-derived nanoparticle gene therapy gene delivery

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Histones released by NETosis enhance the infectivity of SARS-CoV-2 by bridging the spike protein subunit 2 and sialic acid on host cells

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Cellular & Molecular Immunology 2022年第5期19卷 577-587页

作者： Weiqi Hong Jingyun Yang Jun Zou Zhenfei Bi Cai He Hong Lei Xuemei He Xue Li Aqu Alu Wenyan Ren Zeng Wang Xiaohua Jiang Kunhong Zhong Guowen Jia Yun Yang Wenhai Yu Qing Huang Mengli Yang Yanan Zhou Yuan Zhao Dexuan Kuang Junbin Wang Haixuan Wang Siyuan Chen Min Luo Ziqi Zhang Tiangi Lu Li Chen Haiying Que Zhiyao He Qiu Sun Wei Wang guobo shen Guangwen Lu Zhiwei Zhao Li Yang Jinliang Yang Zhenling Wang Jiong Li Xiangrong Song Lunzhi Dai Chong Chen Jia Geng Maling Gou Lu Chen Haohao Dong Yong Peng Canhua Huang Zhiyong Qian Wei Cheng Changfa Fan Yuquan Wei Zhaoming Su Aiping Tong Shuaiyao Lu Xiaozhong Peng Xiawei Wei Laboratory of Aging Research and Cancer Drug Targeting State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityNo.17Block 3Southern Renmin RoadChengduSichuan610041China National Kunming High-level Biosafety Primate Research Center Institute of Medical BiologyChinese Academy of Medical Sciences and Peking Union Medical CollegeYunnanChina Westvac Biopharm Co. Ltd.No.618Fenghuang RoadShuangliu DistrictChengduSichuanChina Division of Animal Model Research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug Control102629BeijingChina State Key Laboratory of Medical Molecular Biology Department of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina

Neutrophil extracellular traps(NETs)can capture and kill viruses,such as influenza viruses,human immunodeficiency virus(HIV),and respiratory syncytial virus(RSV),thus contributing to host *** to our expectation,we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2,as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse *** histone H3 or H4 selectively binds to subunit 2 of the spike(S)protein,as shown by a biochemical binding assay,surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino *** acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S ***,histones enhance cell-cell ***,treatment with an inhibitor of NETosis,histone H3 or H4,or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse *** findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19.

关键词： COVID-19 SARS-CoV-2 neutrophil extracellular traps histones sialic acid

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基于贝叶斯优化的高能质子空间传输精确控制

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强激光与粒子束 2023年第10期35卷 120-126页

作者：申诗雨杨晓虎张国博赵子琦马燕云国防科技大学理学院核科学与技术系长沙410073 国防科技大学前沿交叉学科学院长沙410073

综合考虑地磁场、高能质子的相对论效应以及同步辐射的影响,建立了质子在空间传输的单粒子运动模型。基于该模型,提出利用贝叶斯优化方法,实现给定质子能量下,质子从空间初始点传输到目标点的精确控制方法,获得了出射方向随出射位置的... 详细信息

综合考虑地磁场、高能质子的相对论效应以及同步辐射的影响,建立了质子在空间传输的单粒子运动模型。基于该模型,提出利用贝叶斯优化方法,实现给定质子能量下,质子从空间初始点传输到目标点的精确控制方法,获得了出射方向随出射位置的变化规律,当位置径向角取0°和180°时,位置轴向角的取值不会改变粒子的最优出射方向。研究结果为质子束在空间环境中的长程传输提供理论支撑。

关键词：高能质子传输控制空间传输贝叶斯优化

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