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In vivo real-time monitoring delayed administration of M2 macrophages to enhance healing of tendon by NIR-II fluorescence imaging

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Nano Research 2024年第5期17卷 4379-4390页

作者： yuzhou Chen Mo Chen Chengxuan yu Huizhu li liman Sai Nguyen T.K.Thanh yueming Wang Yan Wo Jian Zhang Xing Yang Evgenii L.Guryev Andrei V.Zvyagin Hao De Min Tang Shiyi Chen yunxia li yuefeng Hao Sijia Feng Jun Chen Sports Medicine institute of {1. University Department of Sports MedicineHuashan HospitalFudan UniversityShanghai 200040China Department of Orthopedic Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Bone and Joint Surgery Department of OrthopedicsRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200001China Department of Physics Shanghai Normal UniversityShanghai 200234China Biophysics Group Department of Physics and AstronomyUniversity College LondonLondon WC1E 6BTUK UCL Healthcare Biomagnetic and Nanomaterials Laboratories London W1S 4BSUK Department of Anatomy and Physiology School of MedicineShanghai Jiao Tong UniversityShanghai 200025China Department of Orthopedics Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou 215500China institute of Biology and Biomedicine Lobachevsky State University of Nizhny NovgorodNizhny Novgorod 603950Russia Mathematical institute University of OxfordOxford OX26GGUK institute of Natural Sciences School of MathematicsShanghai Jiao Tong UniversityShanghai 200240China

The administration time is a critical but long-neglected point in cell therapy based on macrophages because the incorrect time of macrophage administration could result in diverse outcomes regarding the same macrophage *** this work,the second near-infrared(NIR-II)fluorescence imaging in vivo tracking of M2 macrophages during a pro-healing therapy in the mice model of rotator cuff injury revealed that the behavior of administrated macrophages was influenced by the timing of their *** delayed cell therapy(DCT)group had a longer retention time of injected M2 macrophages in the repairing tissue than that in the immediate cell therapy(ICT)*** Keller-Segel model and histological analysis further demonstrated that DCT altered the chemotaxis of M2 macrophages and improved the healing outcome of the repaired structure in comparison with *** results offer a possible explanation of previous conflicting results on reparative cell therapy and provoke reconsideration of the timing of these therapies.

关键词： macrophage cell therapy NIR-II in vivo imaging delayed therapy tendon healing

Heat Shock Transcription Factor 1.Protects Heart after Pressure Overload through Promoting Myocardial Angiogenesis

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Heat Shock Transcription Factor 1 Protects Heart after Press...

Cloning and characterization of a mouse liver-specific gene mfrep-1. up-regulated in liver regeneration

第八届海峡两岸心血管科学研讨会

作者： Ji-ming li,Hong MA,Hong JIANG,Jie yuAN,Hui GONG, Yan-yan liANG,Ai-li GUAN,Jian WU,Lei li,Ning ZHOU,yu-hong NIU, Ai-jun SUN,yun-zeng ZOU (1.shanghai institute of Cardiovascular Diseases,Zhongshan Hospital,fudan University,shanghai 200032,china 2.institutes of Biomedical Science,fudan University,shanghai 200032,china)

＜正＞Background Heat shock transcription factor 1.HSFl） plays an important role in excise - in- duced cardiac ***,its role in pressure overload - induced cardiac hypertrophy is not completely *** here elucidate whether and how HSF1.protects heart against chronic pressure overload. Methods and Results A sustained constriction of transverse aorta（TAC） was imposed to HSF1.transgenic （TG）,knockout（KO） and their littermate wild type（WT） mice to induce a pressure *** weeks later,adaptive responses to TAC,such as cardiac hypertrophy,contractility and angiogenesis evaluated by echocardiography,catheterization and immunohistochemistry,were well preserved in the TG but less in the KO compared to those in the WT *** angiogenesis inhibitor TNP - 470 abrogated all these adaptive responses in the TG mice,while cardiac transfection of VEGF with angiopoietin - 1.repaired the maladaptive heart in the KO *** response to TAC,p53 was downregulated and hypoxia - inducing transcription factor - 1.HIF - 1.） was upregulated not only in heart tissues but also in cultured cardiac endothelial cells（EC） of the TG mice compared to WT mice whereas these changes became opposite in the KO mice.A small interfere RNA（siRNA） of HIF - 1.but not ap53 gene impaired the adaptive responses of the heart and EC in TG mice,and a siRNA of p53 but not a HIF - 1.gene significantly reversed the heart and EC disorders in the KO mice after pressure *** We conclude that HSF1.promotes cardiac angiogenesis through suppression of p53 and subsequent upregulation of HIF - 1.in endothelial cells during chronic pressure overload,leading to the maintenance of cardiac adaptation.

关键词： angiogenesis cardiac hypertrophy endothelial cell HSF1 pressure verload

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Cell Research 2002年第Z2期 353-361页

作者： JUN VAN, HAD YING, FBI GU, JIN HE, yu li li, Hm MIN liU, YONG HUA XU Laboratory of Molecular and Cellular Oncology, {1. of Biochemistry and Cell Biology, shanghai {1.s for Biological Sciences, Chinese Academy of Sciences, 320 yueyang Road, shanghai 200031. china Department of Surgery, Huashan Hospital, fudan University, shanghai 200031. china Department of Pathology, Changzheng Hospital, Second Military Medical University, shanghai 200003, china

Human fibrinogen-related protein-1.liver fibrinogen-related protein-1.(HFREP-l/LFIRE-1., a liver-specific protein, is a member of fibrinogen superfamily that exerts various biological activities. However, the function of HFREP-l/LFIRE-1.in liver remains unknown. Here we isolated its mouse ortholog gene-mouse fibrinogen-related protein-1.(mfrep-1., which encoded 31. amino acids, exhibiting 80.4% similarity to HFREP-l/LFIRE-1. Northern blot analysis revealed that 1.2-kb mfrep-1.mRNA was detected selectively in mouse liver. To explore the function of MFREP-1. we examined the levels of mfrep-1.mRNA during regeneration after 70% partial hepatectomy (PHx) in mice, mfrep-1.mRNA increased in the regenerating liver and reached the first shoulder peak at 2-4 h after PHx. Cycloheximide pretreatment could suppress the induction of mfrep-1. indicating the up-regulation of this gene need de novo protein synthesis. Its mRNA continued to elevate at 6 h thereafter and reached the second peak at 24 h. The enhanced express

关键词： mfrep-1 in silico cloning liver regeneration liver-specific expression.

1.B-doped MCP detector developed for neutron resonance imaging at Back-n white neutron source

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Nuclear Science and Techniques 2024年第8期35卷 58-68页

作者： Qiang li li‑Jiao Wang Jing‑yu Tang Xiang‑Biao Qiu Zhen Chen Mao‑yuan Zhao Chang‑Jun Ning Kai Pan Wei Xu Tao li Su‑Peng Lu Han Yi Rui‑Rui Fan Chang‑Qing Feng Rong Zhang Xiao‑Yang Sun Qi An Hao‑Fan Bai Jiang‑Bo Bai Jie Bao Ping Cao Qi‑Ping Chen Yong‑Hao Chen Zeng‑Qi Cui An‑Chuan Fan Fan‑Zhen Feng Min‑Hao Gu Chang‑Cai Han Zi‑Jie Han Guo‑Zhu He Yong‑Cheng He Yang Hong Yi‑Wei Hu Han‑Xiong Huang Wei Jiang Zhi‑Jie Jiang Zheng‑Yao Jin ling Kang Bo li Gong li Xiao li Yang li Jie liu Rong liu Shu‑Bin liu Yi‑Na liu Guang‑yuan Luan Jie Ren Zhi‑Zhou Ren Xi‑Chao Ruan Zhao‑Hui Song Kang Sun Zhi‑Xin Tan Sheng‑Da Tang Jin‑Cheng Wang Peng‑Cheng Wang Zhao‑Hui Wang Zhong‑Wei Wen Xiao‑Guang Wu Xuan Wu Cong Xia Yong‑Ji yu Guo‑Hui Zhang Hang‑Chang Zhang lin‑Hao Zhang Qi‑Wei Zhang Xian‑Peng Zhang yu‑liang Zhang yue Zhang Zhi‑Yong Zhang Zhi‑Hao Zhou Ke‑Jun Zhu Chong Zou institute of High Energy Physics Chinese Academy of Sciences(CAS)Beijing 100049China Spallation Neutron Source Science Center Dongguan 523803China State Key Laboratory of Particle Detection and Electronics Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China Dongguan Songshan Lake Future School Dongguan 523808China School of Nuclear Science and Technology University of Science and Technology of ChinaHefei 230027China State Key Laboratory of Particle Detection and Electronics University of Science and Technology of ChinaHefei 230026China North Night Vision Science and Technology(Nanjing)Research institute Co.Ltd Nanjing 211106China Department of Modern Physics University of Science and Technology of ChinaHefei 230026China State Key Laboratory of Nuclear Physics and Technology School of PhysicsPeking UniversityBeijing 100871China institute of Modern Physics Fudan UniversityShanghai 200433China Key Laboratory of Nuclear Data China Institute of Atomic EnergyBeijing 102413China china Academy of Engineering Physics Institute of Nuclear Physics and ChemistryMianyang 621900China USTC archaeometry lab University of Science and Technology of ChinaHefei 230026China Northwest institute of Nuclear Technology Xi’an 710024China University of Chinese Academy of Sciences Beijing 100049China china Shipbuilding Trading Co. LtdBeijing 100044China

Neutron resonance imaging(NRI)has recently emerged as an appealing technique for neutron *** complexity surpasses that of conventional transmission imaging,as it requires a high demand for both a neutron source and ***,the progression of NRI technology has been sluggish since its inception in the 1.80s,particularly considering the limited studies analyzing the neutron energy range above *** white neutron source(Back-n)at the china Spallation Neutron Source(CSNS)provides favorable beam conditions for the development of the NRI technique over a wide neutron energy range from eV to ***-sensitive microchannel plates(MCP)have emerged as a cutting-edge tool in the field of neutron detection owing to their high temporal and spatial resolutions,high detection efficiency,and low *** this study,we report the development of a 1.B-doped MCP detector,along with its associated electronics,data processing system,and NRI experiments at the *** heavy elements such as gold,silver,tungsten,and indium can be easily identified in the transmission images by their characteristic resonance peaks in the 1.1.0 eV energy range;the more difficult medium-weight elements such as iron,copper,and aluminum with resonance peaks in the 1.1.0 keV energy range can also be *** particular,results in the neutron energy range of dozens of keV(Aluminum)are reported here for the first time.

关键词： Neutron resonance imaging 1.B doped MCP detector White neutron source Sample nuclide identification

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Synthesis, structure and characterization of binuclear copper(Ⅱ) complexes

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Chinese Journal of Chemistry 1997年第1期15卷 76-83页

作者： YANG, Rui-Na XUE, Bao-yu WANG, Dong-Mei JIN, Dou-Man Henan {1. of Chemistry, Zhengzhou, Henan 450003, chinaCHEN, Jun li, Ming-Xing Department of Chemistry, fudan University, shanghai 2.0433, china

At room temperature, dibenzoyl peroxide undergoes oxidative addition reaction with metallic copper powder and pyridine N-oxide (triphenylphosphine oxide or 2,9-dimethyl-4,7-diphenyl-1.1.-phenanthrolin) which affords the last products as binuclear copper(II) complexes, [Cu(C5H5NO)-(C6H5COO)2]2(1., [Cu(OPPh3)(C6H5COO)2]2(2) and [Cu(C6H5COO)(C26H2oN2)](3, C26H2oN2 is 2,9-dimethyl-4,7-diphenyl-1.1.-phenanthrolin). The structure of the complexes were characterized by elemental analyses, IR spectra, TG-DTA and magnetic property. Crystals(1. are triclinic, space group P1.a=0.9261.(36),b=1.06973(1.), c=1.0881.(29) nm, a=59.60(2)°, β=74.83(3)°,γ=72.80(2)°, V=0.880 nm3, Dc=1.520 g/cm3, Z=1. R=0.044, Rw=0.048, Mr=805.78, 3477 reflections with I > 3σ(I). Each copper(Ⅱ) ion is coordinated by two bridging bidentate benzoate ligands and one pyridine N-oxide or triphenylphosphine oxide to form dimeric binuclear molecules. The structure of the compound(1. shows a clear centre of symmetry.

关键词： Copper binuclear complex oxidative addition

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Real-world effectiveness of early insulin therapy on the incidence of cardiovascular events in newly diagnosed type 2 diabetes

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2953-2959页

作者： Sihui Luo Xueying Zheng Wei Bao Sheng Nie yu Ding Tong yue Yilun Zhou Ying Hu Hua li Qiongqiong Yang Qijun Wan Bicheng liu Hong Xu Guisen li Gang Xu Chunbo Chen Huafeng liu Yongjun Shi Yan Zha Yaozhong Kong Guobin Su Ying Tang Mengchun Gong linong Ji Fan Fan Hou Jianping Weng Department of Endocrinology First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHeifeiChina institute of Public Health Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina Division of Nephrology National Clinical Research Center for Kidney DiseaseState Key Laboratory of Organ Failure ResearchNanfang HospitalSouthern Medical UniversityGuangzhouChina Department of Nephrology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina The Second Affiliated Hospital of Zhejiang University School of Medicine HangzhouChina Sir Run Run Shaw Hospital Zhejiang University School of MedicineHangzhouChina Department of Nephrology Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouChina The Second People’s Hospital of Shenzhen Shenzhen UniversityShenzhenChina institute of Nephrology Zhongda HospitalSoutheast University School of MedicineNanjingChina Children’s Hospital of fudan University ShanghaiChina Renal Department and institute of Nephrology Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaSichuan Clinical Research Center for Kidney DiseasesChengduChina Division of Nephrology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Critical Care Medicine Maoming People’s HospitalMaomingChina Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City Institute of NephrologyAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina Huizhou Central People’s Hospital Sun Yat-Sen UniversityHuizhouChina Guizhou Provincial People’s Hospital Guizhou UniversityGuiyangChina Department of Nephrology the First People’s Hospital of FoshanFoshanChina Department of Nephrology Guangdong Provincial Hospital of Chinese Medicinethe Second Affiliated Hospitalthe Second Clinical CollegeGuangzhou University of Chinese Medicin

Early insulin therapy is capable to achieve glycemic control and restoreβ-cell function in newly diagnosed type 2 diabetes(T2D),but its effect on cardiovascular outcomes in these patients remains *** this nationwide real-world study,we analyzed electronic health record data from 1. medical centers across china between 1.January 2000,and 26 May *** included 5424 eligible patients(mean age 56 years,21.6 women/3248 men)who were diagnosed T2D within six months and did not have prior cardiovascular *** Cox regression models were used to estimate the associations of early insulin therapy(defined as the first-line therapy for at least two weeks in newly diagnosed T2D patients)with the incidence of major cardiovascular events including coronary heart disease(CHD),stroke,and hospitalization for heart failure(HF).During 1.,1.8 persons years of observation,we documented 834 incident CHD cases,71. stroke cases,and 230 hospitalized cases for *** diagnosed T2D patients who received early insulin therapy,compared with those who did not receive such treatment,had 31.lower risk of incident stroke,and 28%lower risk of hospitalization for *** significant difference in the risk of CHD was *** found similar results when repeating the aforesaid analysis in a propensity-score matched population of 4578 patients and with inverse probability of treatment weighting *** findings suggest that early insulin therapy in newly diagnosed T2D may have cardiovascular benefits by reducing the risk of incident stroke and hospitalization for HF.

关键词： cardiovascular treatment nationwide

DEAD-box helicase 1.(DDX1.)protects cardiac function by promoting mitochondrial homeostasis in heart failure

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2774-2790页

作者： Mingjing Yan Junpeng Gao Ming Lan Que Wang yuan Cao yuxuan Zheng Yao Yang Wenlin li Xiaoxue yu Xiuqing Huang lin Dou Bing liu Junmeng liu Hongqiang Cheng Kunfu Ouyang Kun Xu Shenghui Sun Jin liu Weiqing Tang Xiyue Zhang Yong Man liang Sun Jianping Cai Qing He Fuchou Tang Jian li Tao Shen The Key Laboratory of Geriatrics Beijing Institute of GeriatricsInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing Hospital/National Center of Gerontology of National Health CommissionBeijing 100730China Peking University Fifth School of Clinical Medicine Beijing 100730China Department of Laboratory Medicine Huashan HospitalShanghai Medical CollegeFudan UniversityShanghai 200040China Biomedical Pioneering Innovation Center School of Life SciencesPeking UniversityBeijing 100871China Emergency Center Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Cardiology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Graduate School of Peking Union Medical College Beijing 100730China Department of Health Care Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Peking-Tsinghua Center for life Sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100871China Department of Pathology and Pathophysiology and Department of Cardiology at Sir Run Run Shaw Hospital Zhejiang University School of MedicineHangzhou 310058China Department of Cardiovascular Surgery Peking University Shenzhen HospitalShenzhen 518036China Experimental Technology Center for life Sciences at Beijing Normal University Beijing 100875China

DEAD-box helicase 1.(DDX1.)is a typical member of the DEAD-box family with transcriptional cofactor *** DDX1. is abundantly expressed in the myocardium,its role in heart is not fully *** generated cardiomyocyte-specific Ddx1.-knockout mice(Ddx1.-cKO),cardiomyocyte-specific Ddx1. transgenic mice(Ddx1.-Tg),and various models of cardiomyocyte injury and heart failure(HF).DDX1. is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte ***-specific knockout of Ddx1. promotes autophagic flux blockage and cardiomyocyte apoptosis,leading to progressive cardiac dysfunction,maladaptive remodeling and progression to heart *** of DDX1. expression in cardiomyocytes protects cardiac function under pathological *** studies showed that DDX1. can bind to the transcriptional repressor B-cell lymphoma 6(BCL6)and inhibit the expression of dynamin-related protein 1.DRP1..When DDX1. expression is reduced,transcriptional repression of BCL6 is attenuated,leading to increased DRP1.expression and mitochondrial fission,which in turn leads to impaired mitochondrial homeostasis and heart *** also investigated the correlation of DDX1. expression with cardiac function and DRP1.expression in myocardial biopsy samples from patients with heart *** findings suggest that DDX1. protects cardiac function by promoting mitochondrial homeostasis through the BCL6-DRP1.pathway in heart failure.

关键词： DDX1. homeostasis cardiac

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 1. 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,1.6 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],0.1.-0.56;P1.and cEFR(29.0 vs.8.3 months;HR=0.26;95%CI,0.1.-0.57;P1..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

TEA domain transcription factor 1.TEAD1.induces cardiac fibroblasts cells remodeling through BRD4/Wnt4 pathway

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1209-1220页

作者： Shuai Song Xiaokai Zhang Zihang Huang Yongchao Zhao Shuyang Lu linqi Zeng Fengze Cai Tongyao Wang Zhiqiang Pei Xinyu Weng Wei Luo Hao Lu Zilun Wei Jian Wu Peng yu li Shen Xiaochun Zhang Aijun Sun Junbo Ge Department of Cardiology Zhongshan HospitalFudan UniversityShanghai Institute of Cardiovascular DiseasesShanghaiChina State Key Laboratory of Cardiology Zhongshan HospitalFudan UniversityShanghaiChina Key Laboratory of Viral Heart Diseases National Health CommissionShanghaiChina Key Laboratory of Viral Heart Diseases Chinese Academy of Medical SciencesShanghaiChina National Clinical Research Center for Interventional Medicine ShanghaiChina Department of cardiac surgery Zhongshan HospitalFudan UniversityShanghaiChina institutes of Biomedical Sciences Fudan UniversityShanghaiChina shanghai {1. of Hypertension Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Cardiac fibroblasts(CFs)are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure(HF).TEAD1.has been shown to be essential for heart development and ***,fibroblast endogenous TEAD1.in cardiac remodeling remains incompletely *** analyses revealed consistently upregulated cardiac TEAD1.expression in mice 4 weeks after transverse aortic constriction(TAC)and Ang-l *** investigation revealed that CFs were the primary cell type expressing elevated TEAD1.levels in response to pressure *** TEAD1.knockout was achieved by crossing TEAD1.floxed mice with CFs-and myofibroblasts-specific Cre *** and histological analyses demonstrated that CFs-and myofibroblasts-specific TEAD1.deficiency and treatment with TEAD1.inhibitor,VT1.3,ameliorated TAC-induced cardiac ***,RNA-seq and ChiP-seq analysis identified Wnt4 as a novel TEAD1.***1.has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway,and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1.***,coimmunoprecipitation combined with mass spectrometry,chromatin immunoprecipitation,and luciferase assays demonstrated interaction between TEAD1.and BET protein BRD4,leading to the binding and activation of the Wnt4 *** conclusion,TEAD1.is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signallingpathway.

关键词： TEAD1 expression Wnt4