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Signal Transduction and Targeted Therapy 2021年第3期6卷 593-595页

作者： Yao Sun Yongqing Guo Xuejian Feng Lu Fu Yayuan Zheng Yue Dong Yong Zhang Xianghui Yu' Wei Kong Hui Wu National Engineering Laboratory for AIDS Vaccine School of Life SciencesJilin UniversityChangchun 130012China Laboratory of Pathogenic Microbiology and Immunology College of Life ScienceJilin Agricultural UniversityChangchun 130012China Key Laboratory for Molecular Enzymology and Engineering the Ministry of EducationSchool of Life SciencesJilin UniversityChangchun 130012China

Dear Editor,Currently,there are no FDA-approved disease-modifying therapies that can prevent,halt,or reverse Alzheimer's disease(AD).As the unsatisfactory of amyloid-p-targeted treatment in recent years,development of Tau-targeted active immunotherapy takes much concern.1 Tau protein,a major microtubule-associated protein in the nervous system,was found to be abnormally hyperphosphorylated at six epitopes:Ser396/404,Ser202,Thr205,Ser238,and Ser262 in AD patients.2 Hence,immunotherapy targeting more highly-expressed phosphorylated Tau(pTau)species may induce a sufficient pool of pTau antibodies to eliminate pathological tau and elicit cognitive improvement.

关键词： tau markedly Alzheimer

The Functional Redundancy of Neddylation E2s and E3s in Modulating the Fitness of Regulatory T Cells

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Research 2024年第2期2023卷 373-387页

作者： Di Wu Yi Sun Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China Cancer Center of Zhejiang University Hangzhou 310029China Zhejang Provincial Clinical Research Center for Cancer Zhejang ProvinceChina Key Laboratory of Molecular Biology in Medical Sciences Zhejang ProvinceChina Research Center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China

Neddylation is necessary for activation of Cullin-RING ligases(CRLs),which degrade various immune regulatory *** recent study showed that while depletion of neddylation E2-E3 pair Ube2f-Sag in regulatory T(T_(reg))cells had no obvious phenotype,the same depletion of either Ube2m or Rbx1 caused inflammation disorders with different *** these E2s or E3s compensate each other in functional regulations of T_(reg)cells is,however,previously *** this report,we generated Foxp3^(Cre);Ube2m^(fl/fl);Ube2f^(fl/fl)or Foxp3^(Cre);Rbx1^(fl/fl);Sag^(fl/fl)double-null mice by simultaneous deletion of both neddylation E2s or E3s in T_(reg)cells,***,Ube2m&Ube2f double-null mice developed much severe autoimmune phenotypes than did Ube2m-null mice,indicating that Ube2m markedly compensates Ube2f in T_(reg)*** minor worsened autoimmune phenotypes seen at the very early stage in Rbx1&Sag double-null than Rbx1-null mice is likely due to already severe phenotypes of the later,indicating a minor compensation of Rbx1 for *** RNA profiling-based analyses revealed that up-and down-regulations of few signaling pathways in T_(reg)cells are associated with the severity of autoimmune ***,severer inflammation phenotypes seen in mice with double E3-null than with double E2-null T_(reg)cells indicate a neddylation-independent mechanism of 2 E3s,also known to serve as the RING component of CRLs in regulation of T_(reg)cell fitness.

关键词： Foxp3 inflammation markedly

Neurokinin-2 receptor antagonist SR48968 induced necroptosis of myeloid leukemia cells by calcium overload-driven reactive oxygen species accumulation

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Genes & Diseases 2024年第5期11卷 33-35页

作者： Zhibin Yan Xiangyu Hong Qihao Lin Leijie Wang Gang Shao Chentao Ge Ruilong Xia Caiyun Fu Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine College of Life Sciences and MedicineZhejiang Sci-Tech UniversityHangzhouZhejiang 310018China College of Life Sciences China Jiliang UniversityHangzhouZhejiang 310018China

Increasing evidence highlight tachykinin receptors as a prominent player in hematological *** previously revealed the proto-oncogenic role of neurokinin-1 receptor(NK-1R)in acute myeloid leukemia(AML),1 whereas the role of neurokinin-2 receptor(NK-2R)has not been ***,we found NK-2R was significantly up-regulated in AML patients in The Cancer Genome Atlas *** result was further confirmed in blood from AML patients and a range of human leukemia ***,we verified that blocking NK-2R by SR48968 markedly promoted cell death in human myeloid leukemia without cytotoxicity to normal ***,we uncovered that SR48968 induced cytotoxicity through necroptosis mediated by calcium overload-driven reactive oxygen species(ROS)*** summary,our results propose that NK-2R antagonist SR48968 may be used as a new therapeutic approach for myeloid leukemia.

关键词： myeloid antagonist markedly

Targeting BCL9/BCL9L enhances antigen presentation by promoting conventional type 1 dendritic cell(cDC1)activation and tumor infiltration

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2804-2818页

作者： Fenglian He Zhongen Wu Chenglong Liu Yuanyuan Zhu Yan Zhou Enming Tian Rina Rosin-Arbesfeld Dehua Yang Ming-Wei Wang Di Zhu Department of Pharmacology Minhang Hospitaland Key Laboratory of Smart Drug DeliveryShanghai Engineering Research Center of Immune TherapySchool of PharmacyFudan UniversityShanghai 201203China The National Center for Drug Screening and the CAS Key Laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of Sciences(CAS)Shanghai 201203China Department of Microbiology and Immunology Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael Department of Pharmacology School of Basic Medical SciencesFudan UniversityShanghai 200032China Research Center for Deepsea Bioresources SanyaChina Department of Chemistry School of ScienceThe University of TokyoTokyoJapan Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education School of PharmacyHainan Medical UniversityHaikouChina Shandong Academy of Pharmaceutical Science JinanChina

Conventional type 1 dendritic cells(cDC1)are the essential antigen-presenting DC subset in antitumor *** B-cell lymphoma 9 and B-cell lymphoma 9-like(BCL9/BCL9L)inhibits tumor growth and boosts immune responses against ***,whether oncogenic BCL9/BCL9L impairs antigen presentation in tumors is still not completely ***,we show that targeting BCL9/BCL9L enhanced antigen presentation by stimulating cDC1 activation and infiltration into *** inhibition of BCL9/BCL9L with a novel inhibitor hsBCL9z96 or Bcl9/Bcl9l knockout mice markedly delayed tumor growth and promoted antitumor CD8^(+)T cell ***,targeting BCL9/BCL9L promoted antigen presentation in *** is due to the increase of cDC1 activation and tumor infiltration by the XCL1-XCR1 ***,using single-cell transcriptomics analysis,we found that Bcl9/Bcl9l deficient cDC1 were superior to wild-type(WT)cDC1 at activation and antigen presentation via NF-κB/IRF1 ***,we demonstrate that targeting BCL9/BCL9L plays a crucial role in cDC1-modulated antigen presentation of tumor-derived antigens,as well as CD8^(+)T cell activation and tumor *** BCL9/BCL9L to regulate cDC1 function and directly orchestrate a positive feedback loop necessary for optimal antitumor immunity could serve as a potential strategy to counter immune suppression and enhance cancer immunotherapy.

关键词： immunity Targeting markedly

Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development

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Bone Research 2024年第1期12卷 199-214页

作者： Laura J.Brylka Assil-Ramin Alimy Miriam E.A.Tschaffon-Müller Shan Jiang Tobias Malte Ballhause Anke Baranowsky Simon von Kroge Julian Delsmann Eva Pawlus Kian Eghbalian Klaus Püschel Astrid Schoppa Melanie Haffner-Luntzer David J.Beech Frank Timo Beil Michael Amling Johannes Keller Anita Ignatius Timur A.Yorgan Tim Rolvien Thorsten Schinke Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf20246 HamburgGermany Department of Trauma and Orthopedic Surgery University Medical Center Hamburg-Eppendorf20246 HamburgGermany Institute of Orthopedic Research and Biomechanics University Medical Center UlmBadenWürttemberg89081 UlmGermany Department Legal Medicine University Medical Center Hamburg-Eppendorf20246 HamburgGermany Leeds Institute of Cardiovascular and Metabolic Medicine School of MedicineUniversity of LeedsLS29JT LeedsUK

Piezo proteins are mechanically activated ion channels,which are required for mechanosensing functions in a variety of cell *** we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for boneanabolic processes,there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in *** we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis(OA)*** with chondrocyte-specific inactivation of Piezo1(Piezo1^(Col2a1Cre)),but not of Piezo2,developed a near absence of trabecular bone below the chondrogenic growth plate ***,all Piezo1^(Col2a1Cre) animals displayed multiple fractures of rib bones at 7 days of age,which were located close to the growth *** skeletal growth was only mildly affected in these mice,OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of ***,when OA was induced by anterior cruciate ligament transection,only the chondrocyte inactivation of Piezo1,not of Piezo2,resulted in attenuated articular cartilage ***,osteophyte formation and maturation were also reduced in Piezo1^(Col2a1Cre) *** further observed increased Piezo1 protein abundance in cartilaginous zones of human ***,we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in ***,our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes,but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

关键词： Piezo1 markedly ossification

CD147 Facilitates the Pathogenesis of Psoriasis through Glycolysis and H3K9me3 Modification in Keratinocytes

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Research 2024年第1期2023卷 509-523页

作者： Chao Chen Xiaoqing Yi Panpan Liu Jie Li Bei Yan Detian Zhang Lei Zhu Pian Yu Lei Li Jiaxiong Zhang Yehong Kuang Shuang Zhao Wu Zhu Cong Peng Xiang Chen Department of Dermatology Xiangya HospitalCentral South UniversityChangshaHunanChina National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology ChangshaHunanChina Furong Laboratory ChangshaHunanChina Hunan Key Laboratory of Skin Cancer and Psoriasis Hunan Engineering Research Center of Skin Health and DiseaseXiangya HospitalCentral South UniversityChangshaHunanChina National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunanChina

Psoriasis is a chronic inflammatory skin disease featuring rapid proliferation of epidermal *** elevated glycolysis flux has been reported in psoriasis,the molecular mechanisms underlying its pathogenesis remain *** investigated the role of the integral membrane protein CD147 in psoriasis pathogenesis,observing its high expression in psoriatic skin lesions of humans and imiquimod(IMQ)-induced mouse *** mouse models,genomic deletion of epidermal CD147 markedly attenuated IMQ-induced psoriatic *** found that CD147 interacted with glucose transporter 1(Glut1).Depletion of CD147 in the epidermis blocked glucose uptake and glycolysis in vitro and in *** CD147-knockout mice and keratinocytes,oxidative phosphorylation was increased in the epidermis,indicating CD147's pivotal role in glycolysis reprogramming during pathogenesis of *** non-targeted and targeted metabolic techniques,we found that epidermal deletion of CD147 significantly increased the production of carnitine and α-ketoglutaric acid(α-KG).

关键词： CD147 pathogenesis markedly

YKL40 potentially via activating the P38 pathway in decreasing atherosclerotic plaque stability

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Chinese Medical Journal 2024年第8期137卷 1003-1005页

作者： Chao Wang Yandong Liu Wei Huan Jianjin Wu Jie Jin Sili Zou Yu Chen Lefeng Qu Department of Vascular and Endovascular Surgery Changzheng Hospital Affiliated to the Naval Medical UniversityShanghai 200003China Department of Emergency Navy 905th HospitalShanghai 200050China Clinical Research Institute of Integrative Medicine Yueyang HospitalShanghai University of Traditional Chinese MedicineShanghai 200437China

To the Editor:Atherosclerosis is the main pathological feature of ischemic stroke,which remains a major cause of disability and death worldwide.[1]Vulnerable plaque,was characterized by ulceration,platelet activation,and thrombosis,potentially leading to emboli detachment and stroke.[2]Vascular smooth muscle cells(VSMCs),a major cellular component within lesions,can display pleiotropic phenotypes,including osteogenic or inammatory phenotypes,which may be harmful in maintaining advanced atherosclerotic plaque stability.[3]The modulation of the function of VSMCs,including proliferation,migration,and synthesizing the extracellular matrix(ECM)and matrix metalloproteinase(MMP),is thought to markedly affect plaque formation and vulnerability.[4]Therefore,it is of considerable signicance to drive harmful VSMCs toward VSMCs having benecial properties to strengthen plaque stability and retard plaque development.

关键词： YKL40 markedly stability

The single-cell landscape reveals unique tumor subsets and microenvironments associated with poor clinical outcomes in primary testicular diffuse large B-cell lymphoma

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Genes & Diseases 2024年第1期11卷 80-83页

作者： Zhouliang Bian Benhong Gu Guohai Shi Jiahui Guo Dong Li Hanlin Zengg Bin Jiang Daliu Min Hengchuan Su Yanjie Zhang Department of Oncology Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghai 201900China Shanghai Institute of Precision Medicine Ninth People's HospitalShanghai Jiao Tong University School of MedicineShanghai 200125China Department of Urology Tongren HospitalShanghai Jiao Tong University School of MedicineShanghai 200336China Department of Urology Fudan University Shanghai Cancer CenterShanghai200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Department of Oncology Shanghai Jiao Tong University Affiliated Sixth People's HospitalShanghai 200233China

Diffuse large B cell lymphoma(DLBCL)is one of the most prevalent lymphoid *** current standard of care can cure about two-thirds of DLBCL patients.1 Primary testicular diffuse large B-cell lymphoma(PT-DLBCL)is a rare but highly aggressive form of mature B-cell lymphoma that accounts for approximately 1%-9%of testicular *** from nodal DLBCL,PT-DLBCL has a markedly worse prognosis because of inferior response to the current treatment regimens and significant extranodal tropism.2 Three main questions remained unresolved in the field of PT-DLBCL research.

关键词： lymphoma markedly prognosis

Leukocyte-Specific Morrbid Promotes Leukocyte Differentiation and Atherogenesis

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Research 2024年第2期2023卷 123-137页

作者： Di Xiang Lei Jiang Qiong Yuan Yang Yu Ruiming Liu Meiting Chen Zheng Kuai Wendy Zhang Fan Yang Tingting Wu Zhiyu He Zuhui Ke Wanzi Hong Pengcheng He Ning Tan Yeying Sun Zhen Shi Xuebiao Wei Jianfang Luo Xiaoqiu Tan Yuqing Huo Gangjian Qin Chunxiang Zhang Department of Cardiology Key Laboratory of Medical ElectrophysiologyMinistry of EducationInstitute of Cardiovascular ResearchThe Affiliated Hospital of Southwest Medical UniversitySouthwest Medical UniversityLuzhouSichuan 646000China Department of Biomedical Engineering School of Medicine The University of Alabama at BirminghamBirminghamAL 35233USA Department of Cardiology.Guangdong Cardiovascular Institute Guangdong Provincial Key Laboratory of Coronary Heart Disease PreventionGuangdong Provincial Institute of Geriatric MedicineGuangdong General HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdong 510100China Vascular Biology Center Medical College of GeorgiaAugusta UniversityAugustaGA 30912USA

Monocyte-to-M0/M1 macrophage differentiation with unclear molecular mechanisms is a pivotal cellular event in many cardiovascular diseases including *** non-coding RNAs(lncRNAs)are a group of protein expression regulators;however,the roles of monocyte-lncRNAs in macrophage differentiation and its related vascular diseases are still *** study aims to investigate whether the novel leukocyte-specific lncRNA Morrbid could regulate macrophage differentiation and *** identified that Morrbid was increased in monocytes and arterial walls from atherosclerotic mouse and from patients with *** cultured monocytes,Morrbid expression was markedly increased during monocyte to M0 macrophage differentiation with an additional increase during M0 macrophage-to-M1 macrophage *** differentiation stimuli-induced monocyte-macrophage differentiation and the macrophage activity were inhibited by Morrbid ***,overexpression of Morrbid alone was sufficient to elicit the monocyte-macrophage *** role of Morrbid in monocyte-macrophage differentiation was also identified in vivo in atherosclerotic mice and was verified in Morrbid knockout *** identified that PI3-kinase/Akt was involved in the up-regulation of Morrbid expression,whereas s100a10 was involved in Morrbid-mediated effect on macrophage *** provide a proof of concept of Morrbid in pathogenesis of monocyte/macrophage-related vascular disease,we applied an acute atherosclerosis model in *** results revealed that overexpression of Morrbid enhanced but monocyte/macrophage-specific Morrbid knockout inhibited the monocytes/macrophages recruitment and atherosclerotic lesion formation in *** results suggest that Morrbid is a novel biomarker and a modulator of monocyte-macrophage phenotypes,which is involved in atherogenesis.

关键词： inhibited Mor markedly

Post-Marketing Surveillance of Adverse Events Following Immunization with Haemophilus Influenzae Type b Conjugate Vaccine — China, 2010–2021

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China CDC weekly 2024年第33期6卷 834-840页

作者： Minrui Ren Keli Li Yan Li Chunxiang Fan Yuyang Xu Lina Zhang Yuan Li Lei Cao Wenzhou Yu Zundong Yin National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases(NITFID) National Immunization ProgrammeChinese Center for Disease Control and PreventionBeijingChina Department of Expanded Programme on Immunization Hangzhou Center for Disease Control and PreventionHangzhou CityZhejiang ProvinceChina

Introduction The Haemophilus influenzae type b(Hib)conjugate vaccine is widely administered in *** We extracted data on Hib vaccine doses administered and adverse events following immunization(AEFI)reported between 2010 and 2021 from the Chinese National Immunization Information System(CNIIS).A descriptive analysis was conducted to examine the characteristics and incidence rates of AEFI with the Hib *** In China,between 2010 and 2021,a total of 52,910 AEFIs with the Hib vaccine were reported,resulting in an overall AEFI reporting rate of 38.10 per 100,000 ***(typically minor)and rare(potentially serious)vaccine reactions occurred at rates of 34.71 and 2.78 per 100,000 doses,*** the common vaccine reactions,the incidences of fever(axillary temperature≥38.6℃),injection site redness and swelling(>2.5 cm in diameter),and injection site induration(>2.5 cm in diameter)were 11.93,9.69,and 3.38 per 100,000 doses,*** vaccine reactions included anaphylactic rash,angioedema,and febrile convulsion with reported incidences of 2.42,0.10,and 0.05 per 100,000 doses,*** incidence of serious rare vaccine reactions was 0.16 per 100,000 *** The reported incidence of AEFI with the Hib vaccine was low,with the occurrence of serious rare adverse reactions also being markedly low throughout the period 2010–2021 in China.

关键词： doses markedly injection