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Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction (STRATEGY): protocol for a multicentre, randomised controlled trial

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Stroke & Vascular Neurology 2024年第1期9卷 75-81,I0047-I0052页

作者： Xiaoling Liao Shuo Feng Yicong Wang Yuesong Pan Weiqi Chen Hui Qu Xingquan Zhao Liping Liu Yongjun Wang Yilong Wang Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical research center for Neurological Diseases Beijing TiantanHospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain research BeijingChina National center for Neurological Diseases BeijingChina Advanced innovation center for Human Brain Protection Capital Medical UniversityBeijingChina Beijing Laboratory of Oral Health Capital Medical UniversityBeijingChina

Background Perforating artery territorial infarction(PAI)caused by branch atheromatous disease(BAD)is prone to recurrence and early progression without an effective and well-documented antiplatelet treatment ***,an adjunctive antiplatelet agent,has shown great potential to treat acute ischaemic ***,whether the combination of tirofiban and aspirin can improve the prognosis of PAI remains *** To explore an effective and safe antiplatelet regimen for reducing the risk of recurrence and early neurological deterioration(END)in PAI caused by BAD by comparing the tirofiban and aspirin combination with placebo and aspirin *** Tirofiban combined with Aspirin in the Treatment of Acute Penetrating Artery Territory Infarction(STRATEGY)trial is an ongoing multicentre,randomised,placebo-controlled trial in *** patients shall be randomly assigned to receive standard aspirin with tirofiban or placebo on the first day and standard aspirin from days 2 to *** primary endpoint is a new stroke or END within 90 *** primary safety endpoint is severe or moderate bleeding within 90 *** The STRATEGY trial will assess whether tirofiban combined with aspirin is effective and safe in preventing recurrence and END in patients with *** registration number NCT05310968.

关键词： Aspirin regimen centre

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Polarization-dependent photoinduced metal–insulator transitions in manganites

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Science Bulletin 2024年第2期69卷 183-189页

作者： Lina Deng Weiye Zhang Hanxuan Lin Lifen Xiang Ying Xu Yadi Wang Qiang Li Yinyan Zhu Xiaodong Zhou Wenbin Wang Lifeng Yin Hangwen Guo Chuanshan Tian Jian Shen State Key Laboratory of Surface Physics Institute for Nanoelectronic Devices and Quantum Computingand Department of PhysicsFudan UniversityShanghai 200433China Shanghai research center for Quantum Sciences Shanghai 201315China Zhangjiang Fudan International innovation center Fudan UniversityShanghai 201210China Collaborative innovation center of Advanced Microstructures Nanjing 210093China Shanghai Branch CAS Center for Excellence and Synergetic Innovation Center in Quantum Information and Quantum PhysicsShanghai 201315China

In correlated oxides,collaborative manipulation on light intensity,wavelength,pulse duration and polarization has yielded many exotic discoveries,such as phase transitions and novel quantum *** view of potential optoelectronic applications,tailoring long-lived static properties by light-induced effects is highly *** far,the polarization state of light has rarely been reported as a control parameter for this ***,we report polarization-dependent metal-to-insulator transition(MIT)in phaseseparated manganite thin films,introducing a new degree of freedom to control static ***,we observed giant photoinduced resistance jumps with striking features:(1)a single resistance jump occurs upon a linearly polarized light incident with a chosen polarization angle,and a second resistance jump occurs when the polarization angle changes;(2)the amplitude of the second resistance jump depends sensitively on the actual change of the polarization *** transmittance measurements reveal that the origin of the above phenomena is closely related to the coexistence of anisotropic *** results represent a first step to utilize light polarization as an active knob to manipulate static phase transitions,pointing towards new pathways for nonvolatile optoelectronic devices and sensors.

关键词： Metal-insulator phase transitions Polarization of light Electronic phase separation Selective domain controllability

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Exploration of pathogenic microorganism within the small intestine of necrotizing enterocolitis

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World Journal of Pediatrics 2024年第2期20卷 165-172页

作者： Yan Wang Kun Jiang Qiao Xia Xia Kang Shan Wang Ji-Hong Yu Wen-Feng Ni Xiao-Qin Qi Ying-Na Zhang Jin-Bao Han Gang Liu Lei Hou Zhi-Chun Feng Liu-Ming Huang Clinical Biobank center Medical Innovation Research Division of ChinesePLA General HospitalBeijingChina Institute of Basic medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Senior Department of Pediatrics The Seventh Medical Center of PLA General HospitalBeijing 100700China Department of Neurology The First Medical CenterChinese PLA General HospitalBeijing 100853China Department of Emergency center National Center for Children's HealthBeijing Children's HospitalCapital Medical UniversityBeijing 100045China

Background Necrotizing enterocolitis(NEC)is the most common severe gastrointestinal emergency in *** designed this study to identify the pathogenic microorganisms of NEC in the microbiota of the small intestine of *** Using the 16S ribosomal DNA(rDNA)sequencing method,we compared and analyzed the structure and diversity of microbiotas in the intestinal feces of different groups of neonates:patients undergoing jejunostomy to treat NEC(NP group),neonates undergoing jejunostomy to treat other conditions(NN group),and neonates with NEC undergoing conservative treatment(NC group).We took intestinal feces and saliva samples from patients at different time *** The beta diversities of the NP,NN,and NC groups were all *** comparing the beta diversities between different time points in the NP group,we found similar beta diversities at time points El to E3 but significant differences between the E2-E3 and E4 time points:the abundances of Klebsiella and Enterococcus(Proteobacteria)were higher at the E1-E3 time points;the abundance of Escherichia-Shigella(Proteobacteria)increased at the E2 time point,and the abundance of Klebsiella decreased significantly,whereas that of Streptococcus increased significantly at the E4 time *** Our results suggest that the pathological changes of intestinal necrosis in the small intestine of infants with NEC are not directly caused by excessive proliferation of pathogenic bacteria in the small *** sources of microbiota in the small intestine of neonates,especially in premature infants,may be affected by multiple factors.

关键词： Microbiota Necrotizing enterocolitis-Small intestine 16S rDNA

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The RNA m^(6)A demethylase ALKBH5 drives emergency granulopoiesis and neutrophil mobilization by upregulating G-CSFR expression

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Cellular & Molecular Immunology 2024年第1期21卷 6-18页

作者： Yang Liu Renjie Song Zhike Lu Lu Zhao Xinyi Zhan Yini Li Xuetao Cao Department of Immunology Center for ImmunotherapyInstitute of Basic Medical SciencesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijingChina Suzhou Institute of Systems Medicine Chinese Academy of Medical SciencesSuzhouChina frontier research center for Cell Response Institute of ImmunologyCollege of Life SciencesNankai UniversityTianjinChina School of Life Sciences Westlake UniversityHangzhouChina

Emergency granulopoiesis and neutrophil mobilization that can be triggered by granulocyte colony-stimulating factor(G-CSF)through its receptor G-CSFR are essential for antibacterial innate ***,the epigenetic modifiers crucial for intrinsically regulating G-CSFR expression and the antibacterial response of neutrophils remain largely unclear.N6-methyladenosine(m^(6)A)RNA modification and the related demethylase alkB homolog 5(ALKBH5)are key epigenetic regulators of immunity and inflammation,but their roles in neutrophil production and mobilization are still *** used cecal ligation and puncture(CLP)-induced polymicrobial sepsis to model systemic bacterial infection,and we report that ALKBH5 is required for emergency granulopoiesis and neutrophil ***5 depletion significantly impaired the production of immature neutrophils in the bone marrow of septic *** addition,Alkbh5-deficient septic mice exhibited higher retention of mature neutrophils in the bone marrow and defective neutrophil release into the circulation,which led to fewer neutrophils at the infection site than in their wild-type *** bacterial infection,ALKBH5 imprinted production-and mobilization-promoting transcriptome signatures in both mouse and human ***,ALKBH5 erased m^(6)A methylation on the CSF3R mRNA to increase the mRNA stability and protein expression of G-CSFR,consequently upregulating cell surface G-CSFR expression and downstream STAT3 signaling in *** RIP-qPCR results confirmed the direct binding of ALKBH5 to the CSF3R mRNA,and the binding strength declined upon bacterial infection,accounting for the decrease in G-CSFR expression on bacteria-infected *** these results collectively,we define a new role of ALKBH5 in intrinsically driving neutrophil production and mobilization through m^(6)A demethylation-dependent posttranscriptional regulation,indicating that m^(6)A RNA modification in neutrop

关键词： Emergency granulopoiesis Neutrophil mobilization ALKBH5 m^(6)A RNA modification G-CSF receptor

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An orally-available monovalent SMAC mimetic compound as a broad-spectrum antiviral

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Protein & Cell 2024年第1期15卷 69-75页

作者： Miao Mei Maria_Antonietta Impagnatiello Jun Jiao Ulrich Reiser Ulrike Tontsch-Grunt Ju Zhang Paul Nicklin Bingke Yu Yu Wang Yuan He Xu Tan Tsinghua-Peking center for Life Sciences Beijing Advanced Innovation Center for Structural BiologyBeijing Frontier Research Center for Biological StructureMOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical BiologySchool of Pharmaceutical SciencesTsinghua UniversityBeijing 100084China Chinese Institutes for medical research Beijing 100069China Boehringer Ingelheim RCV GmbH&Co KG ViennaAustria College of Life Sciences and Oceanography Shenzhen UniversityShenzhen 518060China research Beyond Borders Boehringer IngelheimBiberach an der RissGermany research Beyond Borders Boehringer IngelheimShanghai 200120China

DearEditor,The coronavirus disease 2019(COVID-19)pandemic caused great global morbidity and mortality concurrent with astronomical socioeconomic damages and *** now,the culpable pathogen,SARS-CoV-2,has infected over 6 hundred million people resulting in more than 6 million deaths worldwide(WHO SARSCoV-2 cases).There is an urgent need for rapid development of effective and affordable therapeutics for COVID-19 patients.

关键词： mortality spectrum compound

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ExosomalmicroRNA let-7c-5p enhances cell malignant characteristics by inhibiting TAGLN in oral cancer

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Oncology research 2024年第10期32卷 1623-1635页

作者： YI LI TIANYI WANG HAORAN DING SHIYONG ZHUANG XIAOBO DAI BING YAN State Key Laboratory of Oral Diseases&National center for Stomatology&National Clinical research center for Oral Diseases&Department of Head and Neck Oncology Surgery West China Hospital of StomatologySichuan UniversityChengdu610041China frontier innovation center for Dental Medicine Plus Chengdu610041China

Background:Oral cancer,a malignancy that is prevalent worldwide,is often diagnosed at an advanced ***(miRNAs)in circulating exosomes have emerged as promising cancer *** role of miRNA let-7c-5p in oral cancer remains underexplored,and its potential involvement in tumorigenesis warrants comprehensive ***:Serum samples from 30 patients with oral cancer and 20 healthy controls were used to isolate exosomes and quantify their RNA *** of the exosomes was confirmed through transmission electron *** PCR was used to assess the miRNA *** effects of let-7c-5p and TAGLN overexpression on oral cancer cell viability,migration,and invasion were analyzed via CCK-8 and Transwell ***,we conducted mRNA sequencing of exosomal RNA from exosomes overexpressing let-7c-5p to delineate the gene expression profile and identify potential let-7c-5p target ***:let-7c-5p was upregulated in serumderived exosomes of patients with oral *** of let-7c-5p in the TCA8113 and CAL-27 cell lines enhanced their proliferative,migratory,and invasive capacities,and overexpression of let-7c-5p cell-derived exosomes promoted oral cancer cell *** mRNA sequencing revealed 2,551 differentially expressed genes between control cell-derived exosomes and overexpressed let-7c-5p cell-derived *** further identified TAGLN as a direct target of let-7c-5p,which has been implicated in modulating the oncogenic potential of oral cancer *** of TAGLN reverses the promoting role of let-7c-5p on oral cancer ***:Our findings highlight the role of exosomal let-7c-5p in enhancing oral cancer cell aggressiveness by downregulating TAGLN expression,highlighting its potential as a diagnostic and therapeutic strategy.

关键词： Oral cancer Exosomal microRNA let-7c-5p Tumorigenesis biomarkers Gene expression profiling TAGLN

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Multi-performance evaluation of high-throughput accelerated corrosion test for high-strength low-alloy 921A steel

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Journal of Iron and Steel research International 2024年第5期31卷 1260-1278页

作者： Cong-cong Du Ming-hua Qin Zhan-fang Wu Dong-ling Li Lei Zhao Xiang-yang Li Hai-zhou Wang Beijing Advanced innovation center for Materials Genome Engineering National Center for Materials Service SafetyUniversity of Science and Technology BeijingBeijing100083China China Iron and Steel research Institute Group Co. Ltd.Beijing100081China Beijing Advanced innovation center for Materials Genome Engineering Central Iron and Steel Research InstituteBeijing100081China

The corrosion behavior of high-strength low-alloy 921A steel in a simulated marine atmospheric environment was studied using a high-throughput experimental *** corrosion behavior,corrosion morphology,and corrosion products of 921A steels were analyzed using various techniques,including corrosion mass loss method,polarization curve,white-light interferometry,scanning electron microscopy,energy-dispersive spectrometry,microbeam X-ray fluorescence spectrometry,X-ray diffraction technique,and X-ray photoelectron *** test results indicated that 921A steel exhibits better corrosion resistance than Q450NQR1 steel in simulated harsh atmospheric environments,as evidenced by a lower corrosion mass loss rate throughout the corrosion *** corrosion products of both steels consisted ofα-FeOOH,Fe_(3)O_(4),andγ-FeOOH,withα-FeOOH being more prevalent in the rust layer of 921A steel than in Q450NQR1 *** inner rust layer of 921A steel also exhibited an appositional enrichment region of Cr,Ni,Mo,and V,leading to its superior corrosion resistance compared to that of Q450NQR1 *** efficacy of high-throughput accelerated corrosion experimental methods was highlighted for evaluating the corrosion resistance of steel materials in harsh environmental *** findings suggest that 921A steel exhibits better corrosion resistance compared to Q450NQR1 steel and has the potential to be more suitable in harsh marine atmospheric *** characterization of the rust layer structures and composition reveals the parallel enrichment of certain elements in the inner rust layer of 921A steel,which enhances its corrosion resistance.

关键词： Atmospheric corrosion High-throughput experimental method High-strength low-alloy steel Corrosion characteristics Rust layer Element enrichment

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Notch signaling pathway in cancer:from mechanistic insights to targeted therapies

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2527-2563页

作者： Qingmiao Shi Chen Xue Yifan Zeng Xin Yuan Qingfei Chu Shuwen Jiang Jinzhi Wang Yaqi Zhang Danhua Zhu Lanjuan Li State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Notch signaling,renowned for its role in regulating cell fate,organ development,and tissue homeostasis across metazoans,is highly conserved throughout *** Notch receptor and its ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences,typically necessitating receptor-ligand interaction to initiate classical Notch signaling *** evidence indicates that the Notch signaling pathway serves as both an oncogenic factor and a tumor suppressor in various cancer *** of this pathway promotes epithelial-mesenchymal transition and angiogenesis in malignancies,closely linked to cancer proliferation,invasion,and ***,the Notch signaling pathway contributes to maintaining stem-like properties in cancer cells,thereby enhancing cancer *** regulatory role of the Notch signaling pathway in cancer metabolic reprogramming and the tumor microenvironment suggests its pivotal involvement in balancing oncogenic and tumor suppressive ***,the Notch signaling pathway is implicated in conferring chemoresistance to tumor ***,a comprehensive understanding of these biological processes is crucial for developing innovative therapeutic strategies targeting Notch *** review focuses on the research progress of the Notch signaling pathway in cancers,providing in-depth insights into the potential mechanisms of Notch signaling regulation in the occurrence and progression of ***,the review summarizes pharmaceutical clinical trials targeting Notch signaling for cancer therapy,aiming to offer new insights into therapeutic strategies for human malignancies.

关键词： Notch invasion involvement

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Contact engineering for temperature stability improvement of Bi-contacted MoS2 field effect transistors

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Science China(Information Sciences) 2024年第6期67卷 172-179页

作者： Zizheng LIU Qing ZHANG Xiaohe HUANG Chunsen LIU Peng ZHOU State Key Laboratory of Integrated Chip and Systems School of MicroelectronicsZhangjiang Fudan International Innovation CenterFudan University frontier Institute of Chip and System Shanghai Key Lab for Future Computing Hardware and SystemFudan University Shaoxin Laboratory

Semimetallic bismuth（Bi） is one of the most effective strategies for reducing the contact resistance of two-dimensional transition metal dichalcogenide field effect transistors（FETs）. However, the low melting point of Bi contact（271.5℃） limits its reliable applications. In this study, we demonstrated that the temperature stability of Bi-contacted electrodes could be improved by inserting a high-melting point semimetallic antimony（Sb） between the Bi contacting layer and the gold（Au） capping layer. The proposed Bi/Sb/Au contact electrodes tended to form a metal mixture with a continuous surface during the heating process（Voids appeared on the surface of the Bi/Au contact electrodes after heating at 120℃）. Because of the improved contacting layer formed by the semimetal Bi/Sb alloy, the fabricated Bi/Sb/Au-contacted molybdenum sulfide（MoS2） FETs with different gate lengths demonstrated higher on-state current stability after heating treatment than the Bi/Au contact. Because of the Bi/Sb/Au contact and poly（methyl methacrylate） package, the MoS2FETs demonstrated time stability of at least two months from the almost unchanged transfer characteristics. The electrical stability indicates that the insertion of semimetallic Sb is a promising technology for reliable Bi-based contact.

关键词： temperature stability semimetallic bismuth contact semimetallic antimony contact MoS$_{2}$ FETs time stability

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Identification of TMEM217 as a novel prognostic biomarker and potential therapeutic target in acute myeloid leukemia

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Genes & Diseases 2024年第4期11卷 90-93页

作者： Yunying Yao Zhizhou Xi Min Wu Bo Jiao Jiaming Gao Donghe Li Xi Xie Pengfei Xu Jiaoyang Li Lei Yan Ruibao Ren Ping Liu Shanghai Institute of Hematology State Key Laboratory for Medical GenomicsNational Research Center for Translational MedicineCollaborative Innovation Center of HematologyRuijin Hospital affiliated with Shanghai Jiao Tong University School of MedicineShanghai 200025China International center for Aging and Cancer Hainan Medical UniversityHaikouHainan 570102China

Despite remarkable advances in molecular and cell biology of acute myeloid leukemia(AML),AML patients still frequently relapse and have low 5-year overall survival(OS)rates.1 It is worth noting that a recent study from the registry or clinical trial compilation has reported an improvement in the OS of adult AML patients,especially those under 60 years of age.

关键词： acute myeloid leukemia

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