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Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK

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International Journal of Oral Science 2024年第3期16卷 471-485页

作者： Dexuan Zhuang Shuangshuang Wang Huiting Deng Yuxin shi Chang Liu Xue Leng Qun Zhang Fuxiang Bai Bin Zheng jing Guo Xunwei Wu School and Hospital of Stomatology Cheeloo College of MedicineShandong University&Shandong Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration&Shandong Provincial Clinical Research Center for Oral DiseasesJinanChina Engineering Laboratory for Biomaterials and Tissue Regeneration Ningbo Stomatology HospitalSavaid Stomatology SchoolHangzhou Medical CollegeNingboChina Cedars-Sinai Cancer Institute Department of Biomedical SciencesCedars-Sinai Medical CenterLos AngelesCAUSA

The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new *** has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC *** found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in ***-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC ***,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC ***,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of *** summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell *** study supports the potential clinical utility of phenformin for OSCC treatment in the future.

关键词： drugs treatment AMPK DDI

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Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

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Neural Regeneration Research 2024年第6期19卷 1325-1335页

作者： Li Sun Zhaoyan Zhao jing Guo Yuan Qin Qian Yu Xiaolong shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao Qian Yang Department of Experimental Surgery The Second Affiliated Hospital of Air Force Medical UniversityXi’anShaanxi ProvinceChina Department of Anesthesiology The Second Affiliated Hospital of Air Force Medical UniversityXi’anShaanxi ProvinceChina

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion *** mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion ***,transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic *** explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke,in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ).Animal behavior tests,immunofluorescence staining,2,3,5-triphenyltetrazolium chloride(TTC)staining,mRNA-seq,and western blotting were used to assess mouse anxiety and memory,cortical infarct area,pyroptosis,and neurogenesis,*** bioinformatics analysis,western blotting,co-immunoprecipitation,and mass spectroscopy,we identified S100 calcium binding protein A9(S100A9)as a potential regulator of mitochondrial function and determined its possible interacting *** between exogenous and endogenous mitochondria,as well as the effect of exogenous mitochondria on recipient microglia,were assessed in *** data showed that:(1)mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function,as well as reducing infarct area,inhibiting pyroptosis,and promoting cortical neurogenesis;(2)microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3)in vitro,exogenous mitochondria enhanced mitochondrial function,reduced redox stress,and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria;and(4)S100A9 promoted internalization of exogenous mitochondria by the microglia,thereby amplifying their pro-proliferation and anti-inflammatory ***

关键词： ischemic stroke microglia mitochondria transplantation neurogenesis pyroptosis

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A new study on formation mechanism of ordered porous anodized metal oxides

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Rare Metals 2024年第10期43卷 5410-5418页

作者： Xi-Di Sun Xin Guo Jia-Han Zhang jing Wu Yi shi Hui-Yuan Sun Cao-Feng Pan Li-Jia Pan Collaborative Innovation Center of Advanced Microstructures School of Electronic Science and EngineeringNanjing University College of Physics and Hebei Advanced Thin Film Laboratory Hebei Normal University Institute of Atomic Manufacturing Beihang University

The preparation of ordered porous metal oxide films by anodic oxidation is an efficient and simple preparation ***,there has been no unified explanation about the formation mechanism of the porous structure for many *** this paper,the relationship between the crystal structure of metals and the morphology of ordered porous metal oxide films is *** influence of the crystal structures of different metals on the optimal morphology of porous films is discussed.

关键词： Anodic oxidation

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CCDC181 is required for sperm flagellum biogenesis and male fertility in mice

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Zoological Research 2024年第5期45卷 1061-1072页

作者： Xiang-Jun Zhang Xiao-Ning Hou Jian-Teng Zhou Bao-Lu shi jing-Wei Ye Meng-Lei Yang Xiao-Hua Jiang Bo Xu Li-Min Wu Qing-Hua shi Division of Reproduction and Genetics First Affiliated Hospital of University of Science and Technology of China(USTC)Hefei National Laboratory for Physical Sciences at MicroscaleSchool of Basic Medical SciencesDivision of Life Sciences and MedicineBiomedical Sciences and Health Laboratory of Anhui ProvinceInstitute of Health and MedicineHefei Comprehensive National Science CenterUniversity of Science and Technology of ChinaHefeiAnhui 230001China

The structural integrity of the sperm flagellum is essential for proper sperm *** defects can result in male infertility,yet the precise mechanisms underlying this relationship are not fully ***181,a coiled-coil domain-containing protein,is known to localize on sperm flagella and at the basal regions of motile *** this knowledge,the specific functions of CCDC181 in flagellum biogenesis remain *** this study,Ccdc181 knockout mice were *** absence of CCDC181 led to defective sperm head shaping and flagellum ***,the Ccdc181 knockout mice exhibited extremely low sperm counts,grossly aberrant sperm morphologies,markedly diminished sperm motility,and typical multiple morphological abnormalities of the flagella(MMAF).Additionally,an interaction between CCDC181 and the MMAF-related protein LRRC46 was identified,with CCDC181 regulating the localization of LRRC46 within sperm *** findings suggest that CCDC181 plays a crucial role in both manchette formation and sperm flagellum biogenesis.

关键词： Male infertility CCDC181 MMAF Spermiogenesis Flagellum biogenesis

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Therapeutic Effectiveness of Leukocyte-and Platelet-rich Fibrin for Diabetic Foot Ulcers:A Retrospective Study

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Current Medical Science 2024年第3期44卷 568-577页

作者： Fen WANG Xiao-ling ZHANG jing ZHANG Song GONG jing TAO Hui XIANG Xiao-qing FU Xu-na BIAN Xue-feng YU An-hui XU Cheng-la YI shi-ying SHAO Department of Endocrinology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Branch of National Clinical Research Center for Metabolic Diseases Wuhan430030China Department of Radiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Trauma Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective Diabetic foot ulcer(DFU)is one of the most serious complications of ***-and platelet-rich fibrin(L-PRF)is a second-generation autologous platelet-rich *** study aims to investigate the clinical effects of L-PRF in patients with diabetes in real clinical *** Patients with DFU who received L-PRF treatment and standard of care(SOC)from 2018 to 2019 in Tongji Hospital were *** clinical information including patient characteristics,wound evaluation(area,severity,infection,blood supply),SOC of DFU,and images of ulcers was retrospectively extracted and analyzed.L-PRF treatment was performed every 7±2 days until the ulcer exhibited complete epithelialization or an overall percent volume reduction(PVR)greater than 80%.Therapeutic effectiveness,including overall PVR and the overall and weekly healing rates,was *** Totally,26 patients with DFU were enrolled,and they had an ulcer duration of 47.0(35.0,72.3)*** severity and infection of ulcers varied,as indicated by the Site,Ischemia,Neuropathy,Bacterial Infection,and Depth(SINBAD)scores of 2–6,Wagner grades of 1–4,and the Perfusion,Extent,Depth,Infection and Sensation(PEDIS)scores of 2–*** initial ulcer volume before L-PRF treatment was 4.94(1.50,13.83)cm3,and the final ulcer volume was 0.35(0.03,1.76)*** median number of L-PRF doses was 3(2,5).A total of 11 patients achieved complete epithelialization after the fifth week of treatment,and 19 patients achieved at least an 80%volume reduction after the seventh *** overall wound-healing rate was 1.47(0.63,3.29)cm3/week,and the healing rate was faster in the first 2 weeks than in the remaining *** treatment did not change the percentage of complete epithelialization or healing *** Adding L-PRF to SOC significantly improved wound healing in patients with DFU independent of the ankle brachial index,SINBAD score,or Wagner grade,indicating that this method is appropriate for D

关键词： diabetic foot ulcer autologous platelet-rich plasma leukocyte-and platelet-rich fibrin standard of care percentage volume reduction

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Magnetic Field Assisted Oxygen Evolution Reaction:Beyond Spin Effects

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Renewables 2024年第4期2卷 264-269页

作者： shi-Yi Lin jing Fu School of Materials Science and Engineering Tongji UniversityShanghai 201804

The sluggish kinetics of oxygen evolution reaction(OER)have seriously obstructed the industrial application of water electrolysis and rechargeable metal-air *** by the molecular orbital bonding of O2 in a spin triplet state,magnetic field-assisted strategies are widely explored to boost OER electroctalytic activities such as magnetohydrodynamic(MHD)effect,magnetoresistance effect,magnetothermal effect,and spin ***,we investigated the impact of magnetic fields on ferromagnetic catalysts,demonstrating that magnetic fields enhance OER activity by aligning spins and improving mass transfer;then we proposed reasonable verification methods for spin ***,the possibilities of both mass diffusion and surface conditions besides the spin effect were analyzed ***,we highlighted the importance of distinguishing spin effects from MHD influences.

关键词： oxygen evolution reaction magnetic field spin alignment magnetohydrodynamic effect electrocatalysis

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Metallaphotoredox-Catalyzed Three-Component Couplings for Practical Synthesis of Ureas and Carbamates

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Chinese Journal of Chemistry 2024年第3期42卷 264-270页

作者： Ernest Koranteng Zhen-Cao Shu Yi-Yin Liu Qian Yang Bin shi Qiang-Xian Wu Fen Tan Liang-Qiu Lu Wen-jing Xiao Engineering Research Center of Photoenergy Utilization for Pollution Control and Carbon Reduction Ministry of EducationCollege of ChemistryCentral China Normal University152 Luoyu RoadWuhanHubei430079 China Wuhan Youji Industries Co. LtdNo.1 2nd Chemical Rd.WuhanHubei430082 China Hubei Key Laboratory of purification and Application of Plant Anti-cancer Active Ingredients School of Chemistry and Life SciencesHubei University of EducationWuhanHubei430205 China State Key Laboratory for Oxo Synthesis and Selective Oxidation Lanzhou Institute of Chemical PhysicsChinese Academy of SciencesLanzhouGansu730000 China School of Chemistry and Chemical Engineering Henan Normal UniversityXinxiangHenan453007 China Wuhan Institute of Photochemistry and Technology WuhanHubei430082 China State Key Laboratory of Organometallic Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai200032 China

Ureas are widely used in drugs,materials and catalysts because of their diamide structure,which can form strong hydrogen ***,it is of great scientific significance to develop efficient and green methods for the synthesis of urea compounds,especially unsymmetrical ***,we have disclosed novel and highly efficient three-component coupling reactions of organic halides,sodium cyanate and amines enabled by nickel/photoredox dual catalysis for the preparation of unsymmetrical *** reaction features simple and safe operations,broad substrate scopes,and product *** allows the facile synthesis of N-aryl/vinyl ureas from readily available,user-friendly feedstocks under mild conditions(27 examples,36%—98%yields).In addition,this method is further derived to alcohols as nucleophiles to synthesize a series of carbamates(15 examples,40%—95%yields).The mechanism experiment shows that the isocyanate produced by the coupling of halide and sodium cyanate may be the key intermediate in this reaction.

关键词： Cross-coupling Nickel Photoredox catalysis Three-component reaction Ureas Carbamates

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Omics data analysis reveals the system-level constraint on cellular amino acid composition

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Synthetic and Systems Biotechnology 2024年第2期9卷 304-311页

作者： Yuanyuan Huang Zhitao Mao Yue Zhang Jianxiao Zhao Xiaodi Luan Ke Wu Lili Yun jing Yu Zhenkun shi Xiaoping Liao Hongwu Ma College of Biotechnology Tianjin University of Science and TechnologyTianjin300457China Haihe Laboratory of Synthetic Biology Tianjin300308China Biodesign Center Key Laboratory of Engineering Biology for Low-carbon ManufacturingTianjin Institute of Industrial BiotechnologyChinese Academy of SciencesTianjin300308China National Center of Technology Innovation for Synthetic Biology Tianjin300308China Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering(Ministry of Education) Tianjin UniversityTianjin300072China Tianjin Medical Laboratory BGI-TianjinBGI-ShenzhenTianjin300308China

Proteins play a pivotal role in coordinating the functions of organisms,essentially governing their traits,as the dynamic arrangement of diverse amino acids leads to a multitude of folded configurations within peptide *** dynamic changes in amino acid composition of an individual protein(referred to as AAP)and great variance in protein expression levels under different conditions,our study,utilizing transcriptomics data from four model organisms uncovers surprising stability in the overall amino acid composition of the total cellular proteins(referred to as AACell).Although this value may vary between different species,we observed no significant differences among distinct strains of the same *** indicates that organisms enforce system-level constraints to maintain a consistent AACell,even amid fluctuations in AAP and protein *** exploration of this phenomenon promises insights into the intricate mechanisms orchestrating cellular protein expression and adaptation to varying environmental challenges.

关键词： Omics data System-level constraint Amino acid composition

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Sporophytic control of tapetal development and pollen fertility by a mitogen-activated protein kinase cascade in rice

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Journal of Integrative Plant Biology 2024年第7期66卷 1500-1516页

作者： Jianguo Zeng Manman Duan Yiqing Wang Guangtao Li Yujing You Jie shi Changhao Liu Jinyang Zhang Juan Xu Shuqun Zhang jing Zhao Department of Plant Pathology Nanjing Agricultural UniversityNanjing 210095China State Key Laboratory of Plant Physiology and Biochemistry College of Life SciencesZhejiang UniversityHangzhou 310058China Division of Biochemistry University of MissouriColumbia65211MOUSA

Tapetum,the innermost layer of the anther wall,provides essential nutrients and materials for pollen *** degradation of anther tapetal cells is a prerequisite for normal pollen development in flowering *** cells facilitate male gametogenesis by providing cellular contents after highly coordinated programmed cell death(PCD).Tapetal development is regulated by a transcriptional ***,the signaling pathway(s)involved in this process are poorly *** this study,we report that a mitogen-activated protein kinase(MAPK)cascade composed of OsYDA1/OsYDA2-OsMKK4-OsMPK6 plays an important role in tapetal development and male gametophyte *** of function of this MAPK cascade leads to anther indehiscence,enlarged tapetum,and aborted pollen *** cells in osmkk4 and osmpk6 mutants exhibit an increased presence of lipid body-like structures within the cytoplasm,which is accompanied by a delayed occurrence of *** of a constitutively active version of OsMPK6(CA-OsMPK6)can rescue the pollen defects in osmkk4 mutants,confirming that OsMPK6 functions downstream of OsMKK4 in this *** crosses also demonstrated that the MAPK cascade sporophyticly regulates pollen *** study reveals a novel function of rice MAPK cascade in plant male reproductive biology.

关键词： degradation MAPK cascade pollen fertility rice tapetum

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Synergistic induction of mitotic pyroptosis and tumor remission by inhibiting proteasome and WEE family kinases

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3467-3482页

作者： Zhan-Li Chen Chen Xie Wei Zeng Rui-Qi Huang Jin-E Yang Jin-Yu Liu Ya-jing Chen shi-Mei Zhuang MOE Key Laboratory of Gene Function and Regulation Guangdong Province Key Laboratory of Pharmaceutical Functional GenesSchool of Life SciencesState Key Laboratory of Oncology in Southern ChinaSun Yat-sen UniversityGuangzhouPR China Key Laboratory of Liver Disease of Guangdong Province The Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630PR China

Mitotic catastrophe(MC),which occurs under dysregulated mitosis,represents a fascinating tactic to specifically eradicate tumor *** pyroptosis can be a death form of MC remains ***-mediated protein degradation is crucial for ***(BTZ),which inhibits the 20S catalytic particle of proteasome,is approved to treat multiple myeloma and mantle cell lymphoma,but not solid tumors due to primary *** date,whether and how proteasome inhibitor affected the fates of cells in M-phase remains ***,we show that BTZ treatment,or silencing of PSMC5,a subunit of 19S regulatory particle of proteasome,causes G2-and M-phase arrest,multi-polar spindle formation,and consequent caspase-3/GSDME-mediated pyroptosis in M-phase(designated as mitotic pyroptosis).Further investigations reveal that inhibitor of WEE1/PKMYT1(PD0166285),but not inhibitor of ATR,CHK1 or CHK2,abrogates the BTZ-induced G2-phase arrest,thus exacerbates the BTZ-induced mitotic arrest and *** BTZ and PD0166285 treatment(named BP-Combo)selectively kills various types of solid tumor cells,and significantly lessens the IC50 of both BTZ and PD0166285 compared to BTZ or PD0166285 *** using various mouse models show that BP-Combo has much stronger inhibition on tumor growth and metastasis than BTZ or PD0166285 monotreatment,and no obvious toxicity is observed in BP-Combo-treated *** findings disclose the effect of proteasome inhibitors in inducing pyroptosis in M-phase,characterize pyroptosis as a new death form of mitotic catastrophe,and identify dual inhibition of proteasome and WEE family kinases as a promising anti-cancer strategy to selectively kill solid tumor cells.

关键词： proteasome inhibiting catastrophe

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