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Mesenchymal stem cell-derived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration

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Neural Regeneration Research 2024年第1期19卷 49-54页

作者： Ye Xiong Asim Mahmood michael Chopp Department of Neurosurgery Henry Ford HospitalDetroitMIUSA Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA

Traumatic brain injury is a serious and complex neurological condition that affects millions of people *** significant advancements in the field of medicine,effective treatments for traumatic brain injury remain ***,extracellular vesicles released from mesenchymal stem/stromal cells have emerged as a promising novel therapy for traumatic brain *** vesicles are small membrane-bound vesicles that are naturally released by cells,including those in the brain,and can be engineered to contain therapeutic cargo,such as anti-inflammatory molecules,growth factors,and *** administered intravenously,extra cellular vesicles can cross the blood-brain barrier and deliver their cargos to the site of injury,where they can be taken up by recipient cells and modulate the inflammatory response,promote neuroregeneration,and improve functional *** preclinical studies,extracellular vesicle-based therapies have shown promising results in promoting recove ry after traumatic brain injury,including reducing neuronal damage,improving cognitive function,and enhancing motor *** further research is needed to establish the safety and efficacy of extra cellular vesicle-based therapies in humans,extra cellular vesicles represent a promising novel approach for the treatment of traumatic brain *** this review,we summarize mesenchymal ste m/stromal cell-de rived extracellular vesicles as a cell-free therapy for traumatic brain injury via neuroprotection and neurorestoration and brainderived extracellular vesicles as potential biofluid biomarkers in small and large animal models of traumatic brain injury.

关键词： biomarkers extracellular vesicles functional outcome mesenchymal stem/stromal cells neuroinflammation neuroplasticity neuroprotection traumatic brain injury

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Forcing Tumor Cells to Present Their Own Tumor Antigens to the Immune System: a Necessary Design for an Efficient Tumor Immunotherapy

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Cellular & Molecular Immunology 2004年第3期1卷 180-185页

作者： RobertE.Humphreys GildaG.Hillman EricyonHofe minzhenXu AntigenExpress.Inc..100BarberAvenue.Worcester MA01606.USA departmentsofradiationoncology.barbaraannkarmanoscancerinstituteatwaynestateuniversityschoolofmedicineandharperhospital.detroit.mi48201.usa

The general principle for tumor cells to escape from immune surveillance is to prevent tumor antigens from being recognized by the immune *** methods have been developed to increase the immunogenecity of the tumor *** most efficient methods are able to force tumor cells to present their own tumor antigens to the immune *** Th cells by converting tumor cells into MHC class II+/Ii-antigen presenting cells is one of the most efficient *** antisense methods,we suppress the expression of the Ii protein that normally co-expresses with MHC class II molecules and blocks the antigenic peptide binding site of MHC class II molecules during synthesis in the endoplasmic *** such tumor cells,the “unprotected”MHC class II molecules pick up endogenous tumor antigenic peptides,which have been transported into the ER for binding to MHC class I *** presentation of tumor antigens by both MHC class I and II molecules generates a robust and long-lasting anti-tumor immune *** class II+/Ii-tumor cells are potent tumor cell vaccines and also cure a significant number of animals with renal and prostate *** have developed analogous human gene vectors that are suitable for most patients and *** & Molecular Immunology.2004;1(3):180-185.

关键词： immunotherapy cancer vaccine MHC class Ⅱ Th cell

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Long non-coding RNA BANCR promotes pancreatic cancer lymphangiogenesis and lymphatic metastasis by regulating the HIF-1α/VEGF-C/VEGFR-3 pathway via miR-143-5p

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Genes & Diseases 2024年第4期11卷 57-60页

作者： Shaolong Hao Yu Ji Weixuan Pan Hao Sun Fang Nie Jonathan Ray Warren Yuchuan Ding Wei Han Department of General Surgery Beijing Luhe HospitalCapital Medical UniversityTongzhouBeijing 101149China Department of Central Laboratory Beijing Luhe HospitalCapital Medical UniversityTongzhouBeijing 101149China Department of Neurosurgery Wayne State University School of MedicineJohn D.Dingell VA Medical CenterDetroitMI 48201USA

Pancreatic cancer is one of the most aggressive malignant tumors of the digestive *** node metastasis(LNM),as the main way of invasion and metastasis,can occur in the early stage of pancreatic cancer and be considered... 详细信息

关键词： metastasis cancer invasion

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Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

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Neural Regeneration Research 2025年第1期20卷 224-233页

作者： Yi Zhang Zhongwu Liu michael Chopp michael millman Yanfeng Li Pasquale Cepparulo Amy Kemper Chao Li Li Zhang Zheng Gang Zhang Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA Department of Pathology Henry Ford HospitalDetroitMIUSA Division of Pharmacology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional *** previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic *** the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression *** EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a *** male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or *** array of behavior assays was used to measure neurological *** with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological *** vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal *** analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct *** of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of *** data provide evidence that 27a-sEVs have

关键词： axonal remodeling cerebral endothelial cells exosomes miR-27a mitochondria Semaphorin 6A small extracellular vesicles stroke

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TransCell: In Silico Characterization of Genomic Landscape and Cellular Responses by Deep Transfer Learning

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GENOmiCS PROTEOmiCS & BIOINFORMATICS 2024年第2期22卷 qzad008页

作者： Yeh, Shan-Ju Paithankar, Shreya Chen, Ruoqiao Xing, Jing Sun, Mengying Liu, Ke Zhou, Jiayu Chen, Bin michigan State Univ Dept Pediat & Human Dev Grand Rapids MI 49503 USA michigan State Univ Dept Pharmacol & Toxicol Grand Rapids MI 49503 USA michigan State Univ Dept Comp Sci & Engn E Lansing MI 48824 USA

Gene expression profiling of new or modified cell lines becomes routine today; however, obtaining comprehensive molecular characterization and cellular responses for a variety of cell lines, including those derived from underrepresented groups, is not trivial when resources are minimal. Using gene expression to predict other measurements has been actively explored; however, systematic investigation of its predictive power in various measurements has not been well studied. Here, we evaluated commonly used machine learning methods and presented TransCell, a two-step deep transfer learning framework that utilized the knowledge derived from pan-cancer tumor samples to predict molecular features and responses. Among these models, TransCell had the best performance in predicting metabolite, gene effect score (or genetic dependency), and drug sensitivity, and had comparable performance in predicting mutation, copy number variation, and protein expression. Notably, TransCell improved the performance by over 50% in drug sensitivity prediction and achieved a correlation of 0.7 in gene effect score prediction. Furthermore, predicted drug sensitivities revealed potential repurposing candidates for new 100 pediatric cancer cell lines, and predicted gene effect scores reflected BRAF resistance in melanoma cell lines. Together, we investigated the predictive power of gene expression in six molecular measurement types and developed a web portal (http://***/transcell/) that enables the prediction of 352,000 genomic and cellular response features solely from gene expression profiles.

关键词： Genomics Transcriptomics Cancer dependency Drug repurposing Transfer learning GENE ESSENTIALITY PREDICTION DRUG RESPONSE CANCER DISCOVERY NETWORKS SYNERGY LINES

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Contemporary nationwide trends in major adverse cardiovascular events in young cannabis users without concomitant tobacco,alcohol,cocaine use

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World Journal of Cardiology 2024年第9期16卷 512-521页

作者： Rupak Desai Priyatham Gurram Adil S Mohammed Rishabh B Salian Shanmukh Sai Pavan Lingamsetty Sandeep Guntuku Ravi Venkata Sai Krishna Medarametla Rawnak Jahan Zainab Muslehuddin Paritharsh Ghantasala Department of Outcomes Research Independent ResearcherAtlantaGA 30033United States Department of Internal Medicine Central Michigan University College of MedicineSaginawMI 48602United States Department of Medicine Kasturba Medical CollegeMangalore 575001India Department of Medicine Mamata Medical CollegeKhammam 507002India Department of Medicine Bangladesh Medical CollegeDhaka 110015Bangladesh Department of Internal Medicine Wayne State UniversitySinai Grace HospitalDetroit Medical CenterDetroitMI 48201United States

BACKGROUND Cannabis use has increased among young individuals in recent *** dependent cannabis use disorder(CUD)has been associated with various cardiac events,its effects on young adults without concurrent substance use remain *** To examine trends in hospitalizations for major adverse cardiac and cerebrovascular events(MACCE)in this *** used the National Inpatient Sample(2016-2019)to identify hospitalized young individuals(18-44 years),excluding those with concurrent substance usage(tobacco,alcohol,and cocaine).They were divided into CUD+and CUD-.Using International Classification of Diseases-10 codes,we examined the trends in MACCE hospitalizations,including all-cause mortality(ACM),acute myocardial infarction(Ami),cardiac arrest(CA),and acuteischemic stroke(AIS).RESULTSOf 27.4 million hospitalizations among young adults without concurrent substance abuse,4.2%(1.1 million)hadco-existent *** CUD+group,hospitalization rates for MACCE(1.71%vs 1.35%),Ami(0.86%vs 0.54%),CA(0.27%vs 0.24%),and AIS(0.49%vs 0.35%)were higher than in CUD-group(Pmi hospitalizations,compared to 22%and 36%increases in CUDgroup(P<0.05).The CUD+group had a 13%relative decrease in ACM hospitalizations,compared to a 10%relative rise in CUD-group(P<0.05).However,when adjusted for confounders,MACCE odds among CUD+cohort remain comparable between 2016 and *** CUD+group had higher rates of MACCE,but the rising trends were more apparent in the CUD-group ***,the CUD+group had lower ACM rates than the CUD-group.

关键词： Cannabis Major adverse cardiac and cerebrovascular events Myocardial infarction Cardiac arrest Stroke Allcause mortality Young adults Trends

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Multi-wavelength nanowire micro-LEDs for future high speed optical communication

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Opto-Electronic Advances 2024年第3期7卷 1-3页

作者： Ayush Pandey Zetian mi Department of Electrical Engineering and Computer Science University of MichiganAnn ArborMI 48109USA

The future of optoelectronics is directed towards small-area light sources,foremost being ***,their use has been inhibited so far primarily due to fabrication and integration challenges,which impair efficiency and ***,bottom-up nanostructures grown using selective area epitaxy have garnered attention as a solution to the aforementioned *** Fu *** used this technique to demonstrate uniform p-i-n core-shell InGaAs/InP nanowire array light emitting *** devices are capable of voltage and geometry-controlled multi-wavelength and high-speed *** publication accentuates the wide capabilities of bottom-up nanostructures to resolve the difficulties of nanoscale optoelectronics.

关键词： communication high operations

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Risk-Informed Model-Free Safe Control of Linear Parameter-Varying Systems

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IEEE/CAA Journal of Automatica Sinica 2024年第9期11卷 1918-1932页

作者： Babak Esmaeili Hamidreza Modares Department of Mechanical Engineering Michigan State UniversityEast LansingMI 48863 USA

This paper presents a risk-informed data-driven safe control design approach for a class of stochastic uncertain nonlinear discrete-time *** nonlinear system is modeled using linear parameter-varying(LPV)systems.A model-based probabilistic safe controller is first designed to guarantee probabilisticλ-contractivity(i.e.,stability and invariance)of the LPV system with respect to a given polyhedral safe *** obviate the requirement of knowing the LPV system model and to bypass identifying its open-loop model,its closed-loop data-based representation is provided in terms of state and scheduling data as well as a decision *** is shown that the variance of the closedloop system,as well as the probability of safety satisfaction,depends on the decision variable and the noise covariance.A minimum-variance direct data-driven gain-scheduling safe control design approach is presented next by designing the decision variable such that all possible closed-loop system realizations satisfy safety with the highest confidence *** minimum-variance approach is a control-oriented learning method since it minimizes the variance of the state of the closed-loop system with respect to the safe set,and thus minimizes the risk of safety *** the certainty-equivalent approach that results in a risk-neutral control design,the minimum-variance method leads to a risk-averse control *** is shown that the presented direct risk-averse learning approach requires weaker data richness conditions than existing indirect learning methods based on system identification and can lead to a lower risk of safety *** simulation examples along with an experimental validation on an autonomous vehicle are provided to show the effectiveness of the presented approach.

关键词： Data-driven control linear parameter-varying systems probabilistic control safe control

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The role of N-glycosylation in cancer

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1098-1110页

作者： Yu Lin David M.Lubman Department of Surgery University of Michigan Medical CenterAnn ArborMI 48109USA

Despite advances in understanding the development and progression of cancer in recent years,there remains a lack of comprehensive characterization of the cancer *** play an important role in medicine and are involved in various human disease conditions including ***-moieties participate in fundamental cancer processes like cell signaling,invasion,angiogenesis,and *** N-glycosylation significantly impacts cancer processes and targeted therapies in ***,understanding N-glycosylation in a tumor is essential for comprehending disease progression and discovering anti-cancer targets and biomarkers for therapy monitoring and *** review presents the fundamental process of protein N-glycosylation and summarizes glycosylation changes in tumor cells,including increased terminal sialylation,N-glycan branching,and ***,the role of N-glycosylation in tumor signaling pathways,migration,and metabolism are *** and glycopeptides as potential biomarkers for early detection of cancer based on site specificity have been ***,understanding and exploring the cancer glycoproteome,along with its role in medicine,implication in cancer and other human diseases,highlights the significance of N-glycosylation in tumor processes,necessitating further research for potential anticancer targets and biomarkers.

关键词： N-Glycosylated proteins Cancer signaling Cancer angiogenesis Cancer metabolism Cancer biomarkers

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Quantification of grain boundary effects on the geometrically necessary dislocation density evolution and strain hardening of polycrystalline Mg-4Al using in situ tensile testing in scanning electron microscope and HR-EBSD

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Journal of Magnesium and Alloys 2024年第5期12卷 1815-1829页

作者： Eunji Song Mohsen Taheri Andani Amit misra Department of Materials Science and Engineering University of MichiganAnn ArborMI 48109USA Department of Mechanical Engineering University of MichiganAnn ArborMI 48109USA Department of Mechanical Engineering Texas A&M UniversityCollege StationTX 77843USA

In situ tensile testing in a scanning electron microscope(SEM)in conjunction with high-resolution electron backscatter diffraction(HR-EBSD)under load was used to characterize the evolution of geometrically necessary dislocation(GND)densities at individual grain boundaries as a function of applied strain in a polycrystalline Mg-4Al *** increase in GND density was investigated at plastic strains of 0%,0.6%,2.2%,3.3% from the area including 76 grains and correlated with(i)geometric compatibility between slip systems across grain boundaries,and(ii)plastic *** develop expressions for the grain boundary GND density evolution as a function of plastic strain and plastic incompatibility,from which uniaxial tensile stress-strain response of polycrystalline Mg-4Al are computed and compared with experimental *** findings in this study contribute to understanding the mechanisms governing the strain hardening response of single-phase polycrystalline alloys and more reliable prediction of mechanical behaviors in diverse microstructures.

关键词： Mg-Al alloys Grain boundaries Geometrically necessary dislocations Strain gradient plasticity HR-EBSD

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