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Targeting proprotein convertase subtilisin/kexin type 9(PCSK9):from bench to bedside

Signal Transduction and Targeted Therapy 2024年第2期9卷 509-557页

作者： Xuhui Bao Yongjun Liang Hanman Chang Tianji Cai Baijie Feng Konstantin Gordon Yuekun Zhu Hailian Shi Yundong He Liyi Xie Institute of Therapeutic Cancer Vaccines Fudan University Pudong Medical CenterShanghaiChina Shanghai Key Laboratory of Regulatory Biology School of Life SciencesEast China Normal UniversityShanghaiChina Department of Oncology Fudan University Pudong Medical CenterShanghaiChina Center for Clinical Research Fudan University Pudong Medical CenterShanghaiChina Clinical Research Center for Cell-based Immunotherapy Fudan UniversityShanghaiChina Department of Pathology Duke University Medical CenterDurhamNCUSA Center for Medical Research and Innovation Fudan University Pudong Medical CenterShanghaiChina Institute for Food Safety and Health Illinois Institute of TechnologyChicagoILUSA Department of Sociology University of MacaoTaipaMacaoChina Medical Institute Peoples’Friendship University of RussiaMoscowRussia A.Tsyb Medical Radiological Research Center ObninskRussia Department of Colorectal Surgery The First Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiangChina Shanghai Key Laboratory of Compound Chinese Medicines Institute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineZhangjiang Hi-tech ParkShanghaiChina Department of Radiation Oncology Fudan University Shanghai Cancer CenterShanghaiChina Department of Oncology Shanghai Medical CollegeFudan UniversityShanghaiChina

Proprotein convertase subtilisin/kexin type 9(PCSK9)has evolved as a pivotal enzyme in lipid metabolism and a revolutionary therapeutic target for hypercholesterolemia and its related cardiovascular diseases(CVD).This comprehensive review delineates the intricate roles and wide-ranging implications of PCSK9,extending beyond CVD to emphasize its significance in diverse physiological and pathological states,including liver diseases,infectious diseases,autoimmune disorders,and notably,*** exploration offers insights into the interaction between PCSK9 and low-density lipoprotein receptors(LDLRs),elucidating its substantial impact on cholesterol homeostasis and cardiovascular *** also details the evolution of PCSK9-targeted therapies,translating foundational bench discoveries into bedside applications for optimized patient *** advent and clinical approval of innovative PCSK9 inhibitory therapies(PCSK9-iTs),including three monoclonal antibodies(Evolocumab,Alirocumab,and Tafolecimab)and one small interfering RNA(siRNA,Inclisiran),have marked a significant breakthrough in cardiovascular *** therapies have demonstrated unparalleled efficacy in mitigating hypercholesterolemia,reducing cardiovascular risks,and have showcased profound value in clinical applications,offering novel therapeutic avenues and a promising future in personalized medicine for cardiovascular ***,emerging research,inclusive of our findings,unveils PCSK9’s potential role as a pivotal indicator for cancer prognosis and its prospective application as a transformative target for cancer *** review also highlights PCSK9’s aberrant expression in various cancer forms,its association with cancer prognosis,and its crucial roles in carcinogenesis and cancer *** conclusion,this synthesized review integrates existing knowledge and novel insights on PCSK9,providing a holistic perspective on its transformative impact in reshaping therapeutic paradigms acr

关键词： PCSK9 metabolism convert

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Vitamin D inhibits COX-2 expression and inflammatory response by targeting thioesterase superfamily member 4

Vitamin D inhibits COX-2 expression and inflammatory respons...

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2013海南省第五届生命科学联合学术会议

作者： Qingsong Wang Yuhu He Yujun Shen Qianqian Zhang Di Chen Jing Qin Junwen Wang Ying Yu Key Laboratory of Food Safety Research Institute for Nutritional SciencesShanghai Institutes for Biological SciencesChinese Academy of Sciences Department of Biochemistry and Molecular Biology Hainan Medical College Centre for Genomic Sciences LKS Faculty of MedicineThe University of Hong Kong Department of Cardiology Ruijin HospitalShanghai Jiao Tong University School of Medicine Department of Biochemistry LKS Faculty of MedicineThe University of Hong Kong Shenzhen Institute of Research and Innovation The University of Hong Kong Shenzhen Institute of Research and Innovation The University of Hong Kong Key Laboratory of Food Safety Risk Assessment Ministry of Health

CAPSULE Background:Vitamin D insufficiency and deficiency has reached epidemic proportions,with more than 50%of the global population at risk,and has been associated with chronic inflammatory diseases such as cardiovascular disease,and even ***,the underlying mechanisms of these associations remain unclear. Results:1,25(OH)D including 1,25(OH)D and 1,25(OH)D,the active hormonal form of itamin D,inhibits COX-2 expression in macrophages and pro-inflammatory cytokines in vitro and in vivo by modulating the Akt/NF-κB signaling pathway via direct up-regulation ofhioesterase superfamily member 4 (THEM4)1,25(OH)D administration inhibits the inflammatory response in mice. Conclusions:Besides maintaining a healthy mineralized skeleton,Vitamin D plays novel roles in anti-inflammation in mice. Significance:Supplemental Vitamin D could protect against chronic inflammatory diseases by targeting THEM4/Akt/NF-κB signaling.

关键词： vitamin D lipopolysaccharide cyclooxygenase-2 macrophage NF-κB pathway VDR

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无钝化制备半透明钙钛矿太阳能模组（英文）

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Science Bulletin 2024年第20期 3197-3200页

作者：冯孟磊秦知校王耀郭嘉豪缪炎峰陈悦天赵一新 school of Environmental Science and Engineering Frontiers Science Center for Transformative MoleculesShanghai Jiao Tong University Shanghai Non-Carbon Energy Conversion and Utilization Institute State Key Laboratory of Metal Matrix Composites Shanghai Jiao Tong University

Semi-transparent perovskite solar cells(ST-PSCs) have attracted great attention not only owing to the numerous optoelectronic merits of metal halide perovskites, but also their extensive applications for building-integrated photovoltaics and tandem solar cells[1]. For practical commercialization, it is essential to transfer the decent photovoltaic performance of small-area ST-PSCs into large-area perovskite solar modules(PSMs). However, the current PSMs still suffer from lower efficiency and poorer reproducibility due to the inhomogeneous perovskite crystallization on the substrate of larger area and insufficient passivation effect post film deposition [2]. Largely due to the hardship on fabricating largearea perovskite film of high quality, semi-transparent perovskite solar minimodule has been rarely reported. Herein, we demonstrate a passivating-step-free strategy, which can simultaneously regulate the growth and surface properties of perovskite. The high-quality, large-area perovskite film is made possible with the incorporation of 2,2'-(ethylenedioxy)bis(ethylammonium) dihydroiodide(EDEADI)(Fig. S1 online) to perovskite precursor.

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Generation of polarized electron beams through self-injection in the interaction of a laser with a pre-polarized plasma

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High Power Laser Science and Engineering 2024年第3期12卷 62-68页

作者： L.R.Yin X.F.Li Y.J.Gu N.Cao Q.Kong M.Büscher S.M.Weng M.Chen Z.M.Sheng Key Laboratory of Nuclear Physics and Ion-beam Application(MoE) Institute of Modern PhysicsDepartment of Nuclear Science and TechnologyFudan UniversityShanghaiChina State Key Laboratory of High Field Laser Physics Shanghai Institute of Optics and Fine MechanicsChinese Academy of SciencesShanghaiChina SANKEN(Institute of Scientific and Industrial Research) Osaka UniversityOsakaJapan Sichuan Research Institute Shanghai Jiao Tong UniversityChengduChina Peter Grünberg Institut(PGI-6) Forschungszentrum JülichJülichGermany Institut für Laser-und Plasmaphysik Heinrich-Heine-Universität DüsseldorfDüsseldorfGermany Key Laboratory for Laser Plasmas(MoE) School of Physics and AstronomyShanghai Jiao Tong UniversityShanghaiChina Collaborative Innovation Center of IFSA Shanghai Jiao Tong UniversityShanghaiChina Tsung-Dao Lee Institute Shanghai Jiao Tong UniversityShanghaiChina

Polarized electron beam production via laser wakefield acceleration in pre-polarized plasma is investigated by particlein-cell *** evolution of the electron beam polarization is studied based on the Thomas±Bargmann±Michel±Telegdi equation for the transverse and longitudinal self-injection,and the depolarization process is found to be influenced by the injection *** the case of transverse self-injection,as found typically in the bubble regime,the spin precession of the accelerated electrons is mainly influenced by the ***,in the case of longitudinal injection in the quasi-1D regime(for example,*** et al.,***.110,135002(2013)),the direction of electron spin oscillates in the laser *** the electrons move around the laser axis,the net influence of the laser field is nearly zero and the contribution of the wakefield can be ***,an ultra-short electron beam with polarization of 99%can be obtained using longitudinal self-injection.

关键词： laser wakefield acceleration longitudinal self-injection particle-in-cell simulation polarized electron beam

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Persistent surface states with diminishing gap in MnBi_(2)Te_(4)/Bi_(2)Te_(3) superlattice antiferromagnetic topological insulator

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Science Bulletin 2020年第24期65卷 2086-2093,M0005页

作者： Lixuan Xu Yuanhao Mao Hongyuan Wang Jiaheng Li Yujie Chen Yunyouyou Xia Yiwei Li Ding Pei Jing Zhang Huijun Zheng Kui Huang Chaofan Zhang Shengtao Cui Aiji Liang Wei Xia Hao Su Sungwon Jung Cephise Cacho Meixiao Wang Gang Li Yong Xu Yanfeng Guo Lexian Yang Zhongkai Liu Yulin Chen Mianheng Jiang Center for Excellence in Superconducting Electronics State Key Laboratory of Functional Material for InformaticsShanghai Institute of Microsystem and Information TechnologyChinese Academy of SciencesShanghai 200050China school of Physical Science and Technology ShanghaiTech University and CAS-Shanghai Science Research CenterShanghai 201210China ShanghaiTech Laboratory for Topological Physics Shanghai 200031China University of Chinese Academy of Sciences Beijing 100049China College of Advanced Interdisciplinary Studies National University of Defense TechnologyChangsha 410073China State Key Laboratory of Low Dimensional Quantum Physics Department of PhysicsTsinghua UniversityBeijing 100084China Department of Physics Clarendon LaboratoryUniversity of OxfordOxford 0X13PUUK Advanced Light Source Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA Diamond Light Source Harwell CampusDidcot 0X11 ODEUK Frontier Science Center for Quantum Information Beijing 100084China RIKEN Center for Emergent Matter Science(CEMS) WakoSaitama 351-0198Japan

Magnetic topological quantum materials(TQMs) provide a fertile ground for the emergence of fascinating topological magneto-electric effects. Recently, the discovery of intrinsic antiferromagnetic(AFM) topological insulator MnBi_(2)Te_(4) that could realize quantized anomalous Hall effect and axion insulator phase ignited intensive study on this family of TQM compounds. Here, we investigated the AFM compound Mn Bi4 Te7 where Bi_(2)Te_(3) and MnBi_(2)Te_(4) layers alternate to form a superlattice. Using spatial-and angleresolved photoemission spectroscopy, we identified ubiquitous(albeit termination dependent) topological electronic structures from both Bi_(2)Te_(3) and MnBi_(2)Te_(4) terminations. Unexpectedly, while the bulk bands show strong temperature dependence correlated with the AFM transition, the topological surface states with a diminishing gap show negligible temperature dependence across the AFM *** with the results of its sister compound MnBi_(2)Te_(4), we illustrate important aspects of electronic structures and the effect of magnetic ordering in this family of magnetic TQMs.

关键词： Spatially resolved angle-resolved photoemission spectroscopy Electronic band structure Quantum anomalous Hall effect Magnetic topological insulator

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Self-healing and shape-shifting polymers controlled by dynamic bonds

Smart Molecules

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Smart Molecules 2023年第2期1卷 1-15页

作者： Shang-Wu Zhou Chengyuan Yu Meng Chen Chen-Yu Shi Ruirui Gu Da-Hui Qu Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Feringa Nobel Prize Scientist Joint Research CenterFrontiers Science Center for Materiobiology and Dynamic ChemistryInstitute of Fine ChemicalsSchool of Chemistry and Molecular EngineeringEast China University of Science and TechnologyShanghaiChina

Dynamic chemistry refers to a type of fundamental science that involves precise construction or regulation of reactional,motional,or constitutional dynamics of chemical *** the meticulous design of chemists,the nanoscopic dynamics,either molecular or supramolecular,are managed to scale up to macroscopic dynamic *** example,the stimuli-induced conformational or configurational changes of polymer skeletons result in unexpected functions of polymers,such as self-healing and shape-shifting *** review focuses on how the microscopic dynamics of these molecular components initiate the reversible macroscopic deformation of the corresponding polymer materials upon external *** self-healing and shape-shifting materials are discussed in terms of the subtle molecular design,dynamic reversible mechanisms,and critical roles of the dynamic components in building these ***,this review puts forward the challenges and opportunities for the field of dynamic polymers in both aspects of fundamental chemistry and material *** hope this review can provide new inspiration for the development of this particular research field.

关键词： dynamers dynamic bonds self-healing shape-shifting supramolecular chemistry

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E8粒子的自旋动力学研究（英文）

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Science Bulletin 2024年第19期 2974-2977页

作者：王骁 Konrad Puzniak Karin Schmalzl Christian Balz Masaaki Matsuda Akira Okutani Masayuki Hagiwara 马杰吴建达 Bella Lake Tsung-Dao Lee Institute Shanghai Jiao Tong University Helmholtz-Zentrum Berlin für Materialien und Energie GmbH Institut für Festk?rperphysik Technische Universit?t Berlin Jülich Centre for Neutron Science JCNS Forschungszentrum Jülich GmbH ISIS Neutron and Muon Source STFC Rutherford Appleton Laboratory Neutron Scattering Division Oak Ridge National Laboratory Center for Advanced High Magnetic Field Science Graduate School of ScienceOsaka University school of Physics&Astronomy Shanghai Jiao Tong University Collaborative Innovation Center of Advanced Microstructures Nanjing University Shanghai Branch Hefei National Laboratory

Unlike the classical phase transition driven by thermal fluctuations,the quantum phase transition arises at zero temperature when the system is tuned by a non-thermal parameter[1].For a continuous quantum phase transition,novel physics with higher symmetry may emerge at the quantum critical point (QCP).As the system is driven away from the QCP with a relevant perturbation,exotic physics may further emerge due to the strong renormalization of the almost infinite low-lying excitations[2].The transverse-field Ising chain (TFIC) is a paradigmatic model[1–3]:when an Ising chain is tuned to its QCP by a magnetic field applied transverse to its Ising anisotropy,

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Central nervous system efficacy of aumolertinib versus gefitinib in patients with untreated,EGFR-mutated,advanced non-small cell lung cancer:data froma randomized phase III trial(AENEAS)

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Cancer Communications 2024年第9期44卷 1005-1017页

作者： Shun Lu Xiaorong Dong Hong Jian Jianhua Chen Gongyan Chen Yuping Sun Yinghua Ji ZipingWang Jianhua Shi Junguo Lu Shaoshui Chen Dongqing Lv Guojun Zhang Chunling Liu Juan Li Xinmin Yu Zhong Lin Zhuang Yu ZhehaiWang Jiuwei Cui Xingxiang Xu Jian Fang Jifeng Feng Zhi Xu RuiMa Jie Hu Nong Yang Xiangdong Zhou XiaohongWu Chengping Hu Zhihong Zhang You Lu Yanping Hu Liyan Jiang Qiming wang Renhua Guo Jianying Zhou Baolan Li Chunhong Hu Wancheng Tong Helong Zhang LinMa Yuan Chen Zhijun Jie Yu Yao Longzhen Zhang JieWeng Weidong Li Jianping Xiong Xianwei Ye Jianchun Duan Haihua Yang Meili Sun HongyingWei JiaweiWei Zheyu Zhang QiongWu Department of Medical Oncology Shanghai Chest Hospital Shanghai JiaoTong UniversityShanghaiP.R.China Cancer Center Union Hospital Tongji Medical College Huazhong University of Science and TechnologyWuhanHubeiP.R.China Department of Medical Oncology-Chest Hunan Cancer Hospital&The Affiliated Cancer Hospital of Central South University Xiangya School of MedicineChangshaHunanP.R.China Thoracic OncologyMedicine HarbinMedical University Cancer HospitalHarbinHeilongjiangP.R.China Department of Oncology Jinan Central HospitalJinanShandongP.R.China Department of Oncology First Affiliated Hospital of Xinxiang Medical UniversityXinxiangHenanP.R.China Department of Chest Medicine Beijing Cancer HospitalBeijingP.R.China Department of Internal Medicine Linyi Cancer HospitalLinyiShandongP.R.China Department of Respiratory Medicine Nantong Tumor HospitalNantongJiangsuP.R.China Department of Oncology Binzhou Medical University HospitalBinzhouShandongP.R.China Breath Internal Medicine Taizhou Hospital of Zhejiang ProvinceLinhaiZhejiangP.R.China Department of Respiration The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanP.R.China Department of Lung Internal Medicine Affiliated Tumor Hospital of Xinjiang Medical UniversityUrumqiXinjiangP.R.China Department of Thoracic Oncology Sichuan Cancer HospitalChengduSichuanP.R.China Thoracic Medical Oncology Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)HangzhouZhejiangP.R.China Department of Thoracic Oncology The Fifth Subsidiary Sun Yat-sen University HospitalZhuhaiGuangdongP.R.China Department of Oncology The Affiliated Hospital of QingdaoUniversityQingdaoShandongP.R.China Department of Oncology Shandong Cancer HospitalJinanShandongP.R.China Department of Oncology The First BethuneHospital of Jilin UniversityChangchunJilinP.R.China Department of Respiration Northern Jiangsu People’s Hospital Affiliated to Yangzhou UniversityYangzhouJiangsuP.R.China Department of Internal

Background:The initial randomized,double-blinded,actively controlled,phase III ANEAS study(NCT03849768)demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor(EGFR)-mutated advanced non-small cell lung cancer(NSCLC).Metastatic disease in the central nervous system(CNS)remains a challenge in the management of *** study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS ***:Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded *** with asymptomatic,stable CNS metastases were ***-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months,then every *** responsewas assessed by a neuroradiological blinded,independent central review(neuroradiological-BICR).The primary endpoint for this subgroup analysis was CNS progression-free survival(PFS).Results:Of the 429 patients enrolled and randomized in the ANEAS study,106 patients were found to have CNS metastases(CNS Full Analysis Set,cFAS)at baseline by neuroradiological-BICR,and 60 of them had CNS target lesions(CNS Evaluable for Response,cEFR).Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS(29.0 vs.8.3 months;hazard ratio[HR]=0.31;95%confidence interval[CI],0.17-0.56;P<0.001)and cEFR(29.0 vs.8.3 months;HR=0.26;95%CI,0.11-0.57;P<0.001).The confirmed CNS overall response rate in cEFRwas 85.7%and 75.0%in patients treated with aumolertinib and gefitinib,*** risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNSmetastases at *** new safety findings were ***:The

关键词： aumolertinib brain metastasis non-small cell lung cancer third-generation EGFR-TKI

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Measurement of the integrated luminosity of the Phase 2 data of the Belle Ⅱ experiment

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Chinese Physics C 2020年第2期44卷 1-12页

作者： F.Abudinén I.Adachi P.Ahlburg H.Aihara N.Akopov A.Aloisio F.Ameli L.Andricek N.Anh Ky D.M.Asner H.Atmacan T.Aushev V.Aushev T.Aziz K.Azmi V.Babu S.Baehr S.Bahinipati A.M.Bakich P.Bambade Sw.Banerjee S.Bansal V.Bansal M.Barrett J.Baudot A.Beaulieu J.Becker P.K.Behera J.V.Bennett E.Bernieri F.U.Bernlochner M.Bertemes M.Bessner S.Bettarini V.Bhardwaj F.Bianchi T.Bilka S.Bilokin D.Biswas G.Bonvicini A.Bozek M.Bračko P.Branchini N.Braun T.E.Browder A.Budano S.Bussino M.Campajola L.Cao G.Casarosa C.Cecchi D.Červenkov M.-C.Chang P.Chang R.Cheaib V.Chekelian Y.Q.Chen Y.-T.Chen B.G.Cheon K.Chilikin H.-E.Cho K.Cho S.Cho S.-K.Choi S.Choudhury D.Cinabro L.Corona L.M.Cremaldi S.Cunliffe T.Czank F.Dattola E.De La Cruz-Burelo G.De Nardo M.De Nuccio G.De Pietro R.de Sangro M.Destefanis S.Dey A.De Yta-Hernandez F.Di Capua S.Di Carlo J.Dingfelder Z.Doležal I.Domínguez Jiménez T.V.Dong K.Dort S.Dubey S.Duell S.Eidelman M.Eliachevitch T.Ferber D.Ferlewicz G.Finocchiaro S.Fiore A.Fodor F.Forti A.Frey B.G.Fulsom M.Gabriel E.Ganiev M.Garcia-Hernandez R.Garg A.Garmash V.Gaur A.Gaz U.Gebauer A.Gellrich J.Gemmler T.Geßler R.Giordano A.Giri B.Gobbo R.Godang P.Goldenzweig B.Golob P.Gomis P.Grace W.Gradl E.Graziani D.Greenwald C.Hadjivasiliou S.Halder K.Hara T.Hara O.Hartbrich K.Hayasaka H.Hayashii C.Hearty M.T.Hedges I.Heredia de la Cruz M.Hernández Villanueva A.Hershenhorn T.Higuchi E.C.Hill H.Hirata M.Hoek S.Hollitt T.Hotta C.-L.Hsu Y.Hu K.Huang T.Iijima K.Inami G.Inguglia J.Irakkathil Jabbar A.Ishikawa R.Itoh M.Iwasaki Y.Iwasaki S.Iwata P.Jackson W.W.Jacobs D.E.Jaffe E.-J.Jang H.B.Jeon S.Jia Y.Jin C.Joo J.Kahn H.Kakuno A.B.Kaliyar G.Karyan Y.Kato T.Kawasaki H.Kichimi C.Kiesling B.H.Kim C.-H.Kim D.Y.Kim S.-H.Kim Y.K.Kim Y.Kim T.D.Kimmel K.Kinoshita C.Kleinwort B.Knysh P.Kodyš T.Koga I.Komarov T.Konno S.Korpar D.Kotchetkov N.Kovalchuk T.M.G.Kraetzschmar P.Križan R.Kroeger J.F.Krohn P.Krokovny W.Kuehn T.Kuhr M.Kumar R.Kumar K.Kumara S.Kurz A.Kuzmin Y.-J.Kwon S.Lacaprara Y.-T.Lai C.La Licata K.Lalwani L.Lanceri J.S.Lange K.Lautenbach I.-S.Le Beihang University Beijing 100191 Brookhaven National Laboratory UptonNew York 11973 Budker Institute of Nuclear Physics SB RAS Novosibirsk 630090 Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional Mexico City 07360 Faculty of Mathematics and Physics Charles University12116 Prague Chiba University Chiba 263-8522 Consejo Nacional de Ciencia y Tecnología Mexico City 03940 Deutsches Elektronen–Synchrotron 22607 Hamburg Duke University DurhamNorth Carolina 27708 Earthquake Research Institute University of TokyoTokyo 113-0032 Forschungszentrum Jülich 52425 Jülich Department of Physics Fu Jen Catholic UniversityTaipei 24205 Key Laboratory of Nuclear Physics and Ion-beam Application(MOE)and Institute of Modern Physics Fudan UniversityShanghai 200443 II.Physikalisches Institut Georg-August-Universität Göttingen37073 Göttingen Gifu University Gifu 501-1193 The Graduate University for Advanced Studies(SOKENDAI) Hayama 240-0193 Gyeongsang National University Jinju 52828 Department of Physics and Institute of Natural Sciences Hanyang UniversitySeoul 04763 High Energy Accelerator Research Organization(KEK) Tsukuba 305-0801 J-PARC Branch KEK Theory CenterHigh Energy Accelerator Research Organization(KEK)Tsukuba 305-0801 Indian Institute of Science Education and Research Mohali SAS Nagar140306 Indian Institute of Technology Bhubaneswar Satya Nagar 751007 Indian Institute of Technology Hyderabad Telangana 502285 Indian Institute of Technology Madras Chennai 600036 Indiana University BloomingtonIndiana 47408 Institute for High Energy Physics Protvino 142281 Institute of High Energy Physics Vienna 1050 Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049 Institute of Particle Physics(Canada) VictoriaBritish Columbia V8W 2Y2 Institute of Physics Hanoi Instituto de Fisica Corpuscular Paterna 46980 INFN Laboratori Nazionali di Frascati I-00044 Frascati INFN Sezione di Napoli I-80126 Napoli INFN Sezione di Padova I-35131 Padova INFN Sezione di Perugia I-06123 Perugia

From April to July 2018,a data sample at the peak energy of the T(4 S) resonance was collected with the Belle Ⅱ detector at the SuperKEKB electron-positron *** is the first data sample of the Belle Ⅱ *** Bhabha and digamma events,we measure the integrated luminosity of the data sample to be(496.3±0.3±3.0) pb-1,where the first uncertainty is statistical and the second is *** work provides a basis for future luminosity measurements at Belle Ⅱ.

关键词： luminosity Bhabha digamma Belle II

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Multiplexed imaging of tumor immune microenvironmental markers in locally advanced or metastatic non-small-cell lung cancer characterizes the features of response to PD-1 blockade plus chemotherapy

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Cancer Communications 2022年第12期42卷 1331-1346页

作者： Fengying Wu Tao Jiang Gongyan Chen Yunchao Huang Jianying Zhou Lizhu Lin Jifeng Feng Zhehai Wang Yongqian Shu Jianhua Shi Yi Hu Qiming Wang Ying Cheng Jianhua Chen Xiaoyan Lin Yongsheng Wang Jianan Huang Jiuwei Cui Lejie Cao Yunpeng Liu Yiping Zhang Yueyin Pan Jun Zhao LiPing Wang Jianhua Chang Qun Chen Xiubao Ren Wei Zhang Yun Fan Zhiyong He Jian Fang Kangsheng Gu Xiaorong Dong Tao Zhang Wei Shi Jianjun Zou Xuejuan Bai Shengxiang Ren Caicun Zhou Department of Thoracic Medical Oncology Shanghai Pulmonary HospitalTongji University School of MedicineShanghai 200433P.R.China Department of Respiratory Medicine Harbin Medical University Cancer HospitalHarbinHeilongjiang 150000P.R.China Department of Thoracic Surgery Oncology Yunnan Cancer Hospital&The Third Affiliated Hospital of Kunming Medical University&Yunnan Cancer CenterKunmingYunnan 650118P.R.China Department of Respiratory Medicine The First Affiliated Hospital of Zhejiang UniversityHangzhouZhejiang 310009P.R.China Department of Oncology Center The First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhouGuangdong 510405P.R.China Department of Thoracic Medical Oncology Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research&The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjingJiangsu 210009P.R.China Department of Respiratory Shandong Cancer Hospital&InstituteJinanShandong 250117P.R.China Department of Oncology Jiangsu Province HospitalNanjingJiangsu 210000P.R.China Department of Medical Oncology Linyi Cancer HospitalLinyiShandong 276000P.R.China Department of Oncology Chinese PLA General HospitalBeijing 100853P.R.China Department of Respiratory Medicine Henan Cancer HospitalZhengzhouHenan 450000P.R.China Department of Thoracic Oncology Jilin Cancer HospitalChangchunJilin 130012P.R.China Department of Medical Oncology-Chest Hunan Cancer HospitalChangshaHunan 410006P.R.China Department of Oncology Fujian Medical University Union HospitalFuzhouFujian 350001P.R.China Department of Thoracic Medical Oncology West China HospitalSichuan UniversityChengduSichuan 610000P.R.China Department of Respiration First Affiliated Hospital of Suzhou UniversitySuzhouJiangsu 215002P.R.China Department of Medical Oncology The First Bethune Hospital of Jilin UniversityChangchunJilin 130021P.R.China Pulmonary and Critical Care Medicine The First Affiliated Hospital University of Science Technology of ChinaHefeiAnhui 230036P.R.China De

Background:Although programmed cell death 1(PD-1)blockade plus chemotherapy can significantly prolong the progression-free survival(PFS)and overall survival(OS)in first-line settings in patients with driver-negative advanced non-small-cell lung cancer(NSCLC),the predictive biomarkers remain ***,we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus ***:Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy *** immune microenvironmental markers,including PD-1 ligand(PDL1),CD8,CD68,CD4 and forkhead box P3,were assessed using multiplex immunofluorescence(mIF)***-Meier curveswere used to determine treatment outcome differences according to their expression *** profiles were compared between tumors with distinct expression levels of these markers and their ***:Responders had significantly higher CD8/PD-L1(P=0.015)or CD68/PD-L1 co-expression levels(P=0.021)than non-responders in the camrelizumab plus chemotherapy group,while no difference was observed in the chemotherapy *** with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS(P=0.002,P=0.024;respectively)and OS(P=0.006,P=0.026;respectively)than those with low co-expression in camrelizumab plus chemotherapy *** comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification,significantly better PFS(P=0.003)and OS(P=0.032)were observed in high co-expression *** predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological *** the prevalence of TP53 or KRAS mutations was similar bet

关键词： Non-small-cell lung cancer PD-1 CD8 CD68 tumor immune microenvironment

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