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Si-Miao-Yong-An Decoction alleviates thromboangiitis obliterans by regulating miR-548j-5p/IL-17A signaling pathway

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Chinese Journal of Natural Medicines 2024年第6期22卷 541-553页

作者： CHU Chu SUN Shangwen ZHANG Zhen WU Qi LI Haoyang LIANG Gang MIAO Xiuming JIANG Haiqiang GAO Yan ZHANG Yunhong WANG Bin LI Xia Innovative Institute of Chinese Medicine and Pharmacy Shandong University of Traditional Chinese MedicineJinan 250355China National Key Laboratory for Innovation and Transformation of Luobing Theory The Key Laboratory of Cardiovascular Remod-eling and Function ResearchChinese Ministry of EducationChinese National Health Commission and Chinese Academy of Medical SciencesDepartment of CardiologyQilu Hospital of Shandong UniversityJinan 250012China school of Clinical and Basic medical Sciences Shandong First Medical University&Shandong Academy of Medical SciencesJinan 271016China Affiliated Hospital of Shandong university of Traditional Chinese Medicine Jinan 250014China international Business school Tianjin Foreign Studies UniversityTianjin 300204China Institute of Pharmaceutical Research Shandong University of Traditional Chinese MedicineJinan 250355China

Thromboangiitis obliterans(TAO)is a rare,chronic,progressive,and segmental inflammatory disease characterized by a high rate of amputation,significantly compromising the quality of life of ***-Miao-Yong-An decoction(SMYA),a tradition-al prescription,exhibits anti-inflammatory,anti-thrombotic,and various other pharmacological ***,it was fully proved to be effective for TAO therapy,but the specific therapeutic effect of SMYA on TAO has been ***,deep unveiling the mechanism of SMYA in TAO for identifying clinical therapeutic targets is extremely *** this study,we observed elev-ated levels of IL-17A in the peripheral blood mononuclear cells(PBMCs)of TAO patients,whereas the expression of miR-548j-5p was significantly decreased.A negative correlation between the levels of miR-548j-5p and IL-17A was also *** vitro ex-periments showed that overexpression of miR-548j-5p led to a decrease in IL-17A levels,whereas downregulation of miR-548j-5p showed the opposite *** a dual luciferase assay,we confirmed that miR-548j-5p directly targets ***,serum containing SMYA effectively decreased IL-17A levels by increasing the expression of *** importantly,the results of in vivo tests indicated that SMYA mitigated the development of TAO by inhibiting IL-17A through the upregulation of miR-548j-5p in vascular *** conclusion,SMYA significantly enhances the expression of miR-548j-5p,thereby reducing the levels of the target gene IL-17A and alleviating *** research not only identifies novel targets and pathways for the clinical diagnosis and treatment of TAO but also advances the innovation in traditional Chinese medicine through the elucidation of the SMYA/miR-548j-5p/IL-17A regulatory axis in the pathogenesis of TAO.

关键词： Thromboangiitis obliterans IL-17A Inflammation miR-548j-5p Si-Miao-Yong-An Decoction

Beyond 1,4-addition of in-situ generated(aza-)quinone methides and indole imine methides

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Chinese Chemical Letters 2024年第7期35卷 35-53页

作者： Yan-Li Li Zhi-Ming Li Kai-Kai Wang Xiao-Long He medical College Xinxiang UniversityXinxiang 453000China school of Pharmacy Xinxiang UniversityXinxiang 453000China school of Food and Bioengineering Xihua UniversityChengdu 610039China

The conjugate addition of in-situ generated(aza-)quinone methides(QMs)and indole imine methides(IIMs)emerged as a powerful protocol to access densely functionalized benzenes and *** alcohols,aminobenzhydryl alcohols,and varied indolylmethanols served as most effective precursors for the in-situ generation of such reactive species under acid *** relevant propargylic alcohol has proven to be an elegant precursor to generate the propargylic-QMs and-IIMs via the acid promoted dehydration process,thus enabling diverse challenging remote activation to proceed conjugate1,6-and 1,***,the heteroarene has proven to be workable to transfer the LUMO of the p-QMs and 2-IIMs,thus inducing the remote nucleophilic dearomative *** conjugate additions of(aza-)p-QMs and varied IIMs has made significant contribution in the field of remote activation chemistry in past *** review summarizes the latest advances of the remote conjugate additions of the in-situ generated QMs and IIMs.

关键词： Conjugate addition QMs IIMs LUMO Remote activation Dearomative addition

Moderate Fields, Maximum Potential: Achieving High Records with Temperature‑Stable Energy Storage in Lead‑Free BNT‑Based Ceramics

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Nano-Micro Letters 2024年第5期16卷 184-200页

作者： Wenjing Shi Leiyang Zhang Ruiyi Jing Yunyao Huang Fukang Chen Vladimir Shur Xiaoyong Wei Gang Liu Hongliang Du Li Jin Electronic Materials Research Laboratory Key Laboratory of the Ministry of EducationSchool of Electronic Science and EngineeringXi’an Jiaotong UniversityXi’an 710049People’s Republic of China school of Materials and Energy Southwest UniversityChongqing 400715People’s Republic of China school of Natural Sciences and Mathematics Ural Federal UniversityEkaterinburg 620000Russia Multifunctional Electronic Ceramics Laboratory College of EngineeringXi’an International UniversityXi’an 710077People’s Republic of China

The increasing awareness of environmental concerns has prompted a surge in the exploration of leadfree,high-power ceramic *** efforts to develop leadfree dielectric ceramics with exceptional energystorage performance(ESP)have predominantly relied on multicomponent composite strategies,often accomplished under ultrahigh electric ***,this approach poses challenges in insulation and system downsizing due to the necessary working voltage under such *** extensive study,bulk ceramics of(Bi_(0.5)Na_(0.5))TiO_(3)(BNT),a prominent lead-free dielectric ceramic family,have seldom achieved a recoverable energy-storage(ES)density(Wrec)exceeding 7 J cm^(−3).This study introduces a novel approach to attain ceramic capacitors with high ESP under moderate electric fields by regulating permittivity based on a linear dielectric model,enhancing insulation quality,and engineering domain structures through chemical formula *** incorporation of SrTiO_(3)(ST)into the BNT matrix is revealed to reduce the dielectric constant,while the addition of Bi(Mg_(2/3)Nb_(1/3))O_(3)(BMN)aids in maintaining ***,the study elucidates the methodology to achieve high ESP at moderate electric fields ranging from 300 to 500 kV cm^(−1).In our optimized composition,0.5(Bi_(0.5)Na_(0.4)K_(0.1))TiO_(3)–0.5(2/3ST-1/3BMN)(B-0.5SB)ceramics,we achieved a Wrec of 7.19 J cm^(−3) with an efficiency of 93.8%at 460 kV cm^(−1).Impressively,the B-0.5SB ceramics exhibit remarkable thermal stability between 30 and 140℃ under 365 kV cm^(−1),maintaining a Wrec exceeding 5 J cm^(−3).This study not only establishes the B-0.5SB ceramics as promising candidates for ES materials but also demonstrates the feasibility of optimizing ESP by modifying the dielectric constant under specific electric field ***,it provides valuable insights for the future design of ceramic capacitors with high ESP under constraints of limited electric field.

关键词： BNT Energy storage Lead-free Relaxor ferroelectrics Capacitors

LonP1 Links Mitochondria–ER Interaction to Regulate Heart Function

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Research 2024年第1期2023卷 595-609页

作者： Yujie Li Dawei Huang Lianqun Jia Fugen Shangguan Shiwei Gong Linhua Lan Zhiyin Song Juan Xu Chaojun Yan Tongke Chen Yin Tan Yongzhang Liu Xingxu Huang Carolyn K.Suzuki Zhongzhou Yang Guanlin Yang Bin Lu The Affiliated Nanhua Hospital and school of Basic medical Sciences Hengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China school of Laboratory Medicine and Life Sciences Wenzhou Medical UniversityWenzhouZhejiang 325035China National Health Commission Key Laboratory of Birth Defect Research and Prevention Hunan Provincial Maternal and Child Health Care HospitalChangshaHunan 410008China Key Laboratory of Ministry of education for TCM Viscera-State Theory and Applications Ministry of Education of ChinaLiaoning University of Traditional Chinese MedicineShenyangLiaoning 110847China Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina Hubei Key Laboratory of Cell Homeostasis College of Life SciencesWuhan UniversityWuhanHubei 430072China Nanjing Maternity and Child Health Care Hospital Obstetrics and Gynecology Hospital Affiliated to Nanjing Medical UniversityNanjing 210004China Animal Center Wenzhou Medical UniversityWenzhouZhejiang 325035China Department of Cardiology The First Affiliated Hospital of University of South ChinaHengyangHunanChina school of Life Science and Technology Shanghai Tech UniversityShanghai 201210China Department of Microbiology Biochemistry and Molecular GeneticsNew Jersey Medical School-RutgersThe State University of New JerseyNewarkNJUSA State Key Laboratory of Pharmaceutical Biotechnology Department of CardiologyNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical School and MOE Key Laboratory of Model Animal for Disease StudyModel Animal Research CenterNanjing UniversityNanjing 210061China

Interorganelle contacts and communications are increasingly recognized to play a vital role in cellular function and *** particular,the mitochondria–endoplasmic reticulum(ER)membrane contact site(MAM)is known to regulate ion and lipid transfer,as well as signaling and organelle ***,the regulatory mechanisms of MAM formation and their function are still ***,we identify mitochondrial Lon protease(LonP1),a highly conserved mitochondrial matrix protease,as a new MAM tethering *** removal of LonP1 substantially reduces MAM formation and causes mitochondrial ***,deletion of LonP1 in the cardiomyocytes of mouse heart impairs MAM integrity and mitochondrial fusion and activates the unfolded protein response within the ER(UPR^(ER)).Consequently,cardiac-specific LonP1 deficiency causes aberrant metabolic reprogramming and pathological heart *** findings demonstrate that LonP1 is a novel MAM-localized protein orchestrating MAM integrity,mitochondrial dynamics,and UPR^(ER),offering exciting new insights into the potential therapeutic strategy for heart failure.

关键词： offering programming insight

Allosteric modulation of G protein-coupled receptors as a novel therapeutic strategy in neuropathic pain

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Acta Pharmaceutica Sinica B 2024年第1期14卷 67-86页

作者： Chunhao Zhu Xiaobing Lan Zhiqiang Wei Jianqiang Yu Jian Zhang school of Pharmacy Ningxia Medical UniversityYinchuan 750004China Medicinal Chemistry and Bioinformatics Center Shanghai Jiao Tong University School of MedicineShanghai 200025China school of Basic medical Science Ningxia Medical UniversityYinchuan 750004China Medicinal Chemistry and Bioinformatics Center Ocean University of ChinaQingdao 266100China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical ***,current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful adverse *** G protein-coupled receptors(GPCRs)are widely distributed throughout the body,including the pain transmission pathway and descending inhibition pathway,the development of novel neuropathic pain treatments based on GPCRs allosteric modulation theory is gaining *** research has shown that allosteric modulators targeting GPCRs on the pain pathway can effectively alleviate symptoms of neuropathic pain while reducing or eliminating adverse *** review aims to provide a comprehensive summary of the progress made in GPCRs allosteric modulators in the treatment of neuropathic pain,and discuss the potential benefits and adverse factors of this *** will also concentrate on the development of biased agonists of GPCRs,and based on important examples of biased agonist development in recent years,we will describe universal strategies for designing structure-based biased *** is foreseeable that,with the continuous improvement of GPCRs allosteric modulation and biased agonist theory,effective GPCRs allosteric drugs will eventually be available for the treatment of neuropathic pain with acceptable safety.

关键词： Neuropathic pain Allosteric modulators G protein-coupled receptors Analgesia

lncRNA Gm20257 alleviates pathological cardiac hypertrophy by modulating the PGC-1α–mitochondrial complexⅣaxis

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Frontiers of Medicine 2024年第4期18卷 664-677页

作者： Tong Yu Qiang Gao Guofang Zhang Tianyu Li Xiaoshan Liu Chao Li Lan Zheng Xiang Sun Jianbo Wu Huiying Cao Fangfang Bi Ruifeng Wang Haihai Liang Xuelian Li Yuhong Zhou Lifang Lv Hongli Shan Department of Physiology School of Basic MedicineHarbin Medical UniversityHarbin150081China State Key Laboratory of Frigid Zone Cardiovascular Disease Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China Key Laboratory of Cardiovascular Research Ministry of Education)College of PharmacyHarbin Medical UniversityHarbin150081China The Center of Functional Experiment Teaching School of Basic MedicineHarbin Medical UniversityHarbin150081China

Pathological cardiac hypertrophy,a major contributor to heart failure,is closely linked to mitochondrial *** roles of long noncoding RNAs(lncRNAs),which regulate mitochondrial function,remain largely unexplored in this ***,a previously unknown lncRNA,Gm20257,was *** markedly increased under hypertrophic stress in vivo and in *** suppression of Gm20257 by using small interfering RNAs significantly induced cardiomyocyte ***,the overexpression of Gm20257 through plasmid transfection or adeno-associated viral vector-9 mitigated angiotensinⅡ-induced hypertrophic phenotypes in neonatal mouse ventricular cells or alleviated cardiac hypertrophy in a mouse TAC model respectively,thus restoring cardiac ***,Gm20257 restored mitochondrial complexⅣlevel and enhanced mitochondrial *** prediction showed that Gm20257 had a high binding score with peroxisome proliferator–activated receptor coactivator-1(PGC-1α),which could increase mitochondrial complex ***,Western blot analysis results revealed that Gm20257 substantially affected the expression of PGC-1α.Further analyses through RNA immunoprecipitation and immunoblotting following RNA pull-down indicated that PGC-1αwas a direct downstream target of *** interaction was demonstrated to rescue the reduction of mitochondrial complex IV induced by hypertrophic stress and promote the generation of mitochondrial *** findings suggest that Gm20257 improves mitochondrial function through the PGC-1α-mitochondrial complexⅣaxis,offering a novel approach for attenuating pathological cardiac hypertrophy.

关键词： lncRNA Gm20257 cardiac hypertrophy PGC-1α mitochondrial complexⅣ ATP

Emerging role of lncRNAs as mechanical signaling molecules in mechanotransduction and their association with Hippo-YAP signaling:a review

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 280-292页

作者： Siyi LIN Xinyu HE Ying WANG Yu CHEN Aifu LIN College of Medicine Zhejiang UniversityHangzhou 310058China College of Life Sciences Zhejiang UniversityHangzhou 310058China Cancer Center Zhejiang UniversityHangzhou 310058China Key Laboratory for Cell and Gene Engineering of Zhejiang Province Hangzhou 310058China international school of Medicine International Institutes of Medicinethe Fourth Affiliated Hospital of Zhejiang University School of MedicineYiwu 322000China Key Laboratory of Cancer Prevention and Intervention China National Ministry of EducationHangzhou 310058China Future Health Laboratory Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxing 314100China

Cells within tissues are subject to various mechanical forces,including hydrostatic pressure,shear stress,compression,and *** mechanical stimuli can be converted into biochemical signals through mechanoreceptors or cytoskeleton-dependent response processes,shaping the microenvironment and maintaining cellular physiological *** studies have demonstrated the roles of Yes-associated protein(YAP)and its homolog transcriptional coactivator with PDZ-binding motif(TAZ)as mechanotransducers,exerting dynamic influence on cellular phenotypes including differentiation and disease *** regulatory function entails the involvement of the cytoskeleton,nucleoskeleton,integrin,focal adhesions(FAs),and the integration of multiple signaling pathways,including extracellular signal-regulated kinase(ERK),wingless/integrated(WNT),and Hippo ***,emerging evidence substantiates the implication of long non-coding RNAs(lncRNAs)as mechanosensitive molecules in cellular *** this review,we discuss the mechanisms through which YAP/TAZ and lncRNAs serve as effectors in responding to mechanical ***,we summarize and elaborate on the crucial signal molecules involved in mechanotransduction.

关键词： YAP/TAZ Long non-coding RNA(lncRNA) Mechanotransduction F-actin

Establishment of NaLuF_(4):15%Tb-based low dose X-PDT agent and its application on efficient antitumor therapy

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international Journal of Minerals,Metallurgy and Materials 2024年第3期31卷 599-610页

作者： Yi Tian Zhiguang Fu Xiaosheng Zhu Chunjing Zhan Jinwei Hu Li Fan Chaojun Song Qian Yang Yu Wang Mei Shi Department of Radiation Oncology Xijing HospitalThe Fourth Military Medical UniversityXi’an 710032China Department of Oncology Air Force Medical CenterPLAThe Fourth Military Medical UniversityBeijing 100142China Department of Tumor Radiotherapy Air Force Medical CenterPLAThe Fourth Military Medical UniversityBeijing 100142China Department of Gastroenterology Air Force Hospital of Southern Theater CommandGuangzhou 510062China Department of Pharmaceutical Chemistry and Analysis School of PharmacyThe Fourth Military Medical UniversityXi’an 710032China school of Life Sciences Northwestern Polytechnical UniversityXi’an 710072China Institue of Materia Medica School of PharmacyThe Fourth Military Medical UniversityXi’an 710032China

X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration ***,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT *** address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet *** system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after *** immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were *** the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor ***-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,*** by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,***,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.

关键词： X-ray excited photodynamic therapy singlet oxygen low dose X-Ray irradiation efficient antitumor therapy anti-tumor immunity

Utilization of 3D printing technology in hepatopancreatobiliary surgery

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2024年第2期25卷 123-134页

作者： Wujiang SHI Jiangang WANG Jianjun GAO Xinlei ZOU Qingfu DONG Ziyue HUANG Jialin SHENG Canghai GUAN Yi XU Yunfu CUI Xiangyu ZHONG Department of Hepatopancreatobiliary Surgery the Second Affiliated Hospital of Harbin Medical UniversityHarbin150086China Department of General Surgery Tangdu HospitalAir Force Medical UniversityXi’an710032China Key Laboratory of Basic Pharmacology of Ministry of education Zunyi Medical UniversityZunyi563006China Key Laboratory of Functional and Clinical Translational Medicine Fujian Province UniversityXiamen Medical CollegeXiamen361000China Department of Pathology Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina Jiangsu Province Engineering Research Center of Tumor Targeted Nano Diagnostic and Therapeutic Materials Yancheng Teachers UniversityYancheng224007China Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang Province Hangzhou310053China Key Laboratory of Gastrointestinal Cancer(Fujian medical university) Ministry of EducationSchool of Basic Medical SciencesFujian Medical UniversityFuzhou350122China Key Laboratory of Myocardial Ischemia Harbin Medical UniversityMinistry of EducationHarbin150086China

The technology of three-dimensional(3D)printing emerged in the late 1970s and has since undergone considerable development to find numerous applications in mechanical engineering,industrial design,and *** biomedical science,several studies have initially found that 3D printing technology can play an important role in the treatment of diseases in hepatopancreatobiliary *** example,3D printing technology has been applied to create detailed anatomical models of disease organs for preoperative personalized surgical strategies,surgical simulation,intraoperative navigation,medical training,and patient ***,cancer models have been created using 3D printing technology for the research and selection of chemotherapy *** the aim to clarify the development and application of 3D printing technology in hepatopancreatobiliary surgery,we introduce seven common types of 3D printing technology and review the status of research and application of 3D printing technology in the field of hepatopancreatobiliary surgery.

关键词： 3D printing Hepatopancreatobiliary surgery Organ model Cancer model