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Resident immune responses to spinal cord injury:role of astrocytes and microglia

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Neural Regeneration Research 2024年第8期19卷 1678-1685页

作者： Sydney Brockie Cindy Zhou Michael G.Fehlings Division of Genetics and Development Krembil Research InstituteUniversity Health NetworkTorontoONCanada Institute of medical Science University of TorontoTorontoONCanada Division of Neurosurgery and Spine Program Department of SurgeryUniversity of TorontoTorontoONCanada

Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our *** r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal *** makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative *** these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory *** review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after ***,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural *** the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous *** advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are *** key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

关键词： astrocytes glial signaling microglia spinal cord injury synaptic transmission

Prolonged intermittent theta burst stimulation restores the balance between A_(2A)R-and A_(1)R-mediated adenosine signaling in the 6-hydroxidopamine model of Parkinson's disease

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Neural Regeneration Research 2025年第7期20卷 2053-2067页

作者： Milica Zeljkovic Jovanovic Jelena Stanojevic Ivana Stevanovic Milica Ninkovic Tihomir V.Ilic Nadezda Nedeljkovic Milorad Dragic Laboratory for Neurobiology Department of General Physiology and BiophysicsFaculty of BiologyUniversity of BelgradeBelgradeSerbia medical Faculty of Military medical Academy University of DefenceBelgradeSerbia

An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's *** therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in *** transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's ***,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain *** purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated *** with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod ***,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate *** intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate *** with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor *** treatment with prolonged intermittent theta burst stimulation,complete motor recovery was *** improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst *** results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)***

关键词： A_(1)R A_(2A)R adenosine receptors adenosine ecto-5′-nucleotidase intermittent theta burst stimulation non-invasive brain stimulation Parkinson's disease purinergic signalling

Efficient adsorption separation of methane from C_(2)-C_(3) hydrocarbons in a Co(Ⅱ)-nodes metal-organic framework

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Chinese Journal of Chemical Engineering 2024年第5期69卷 192-198页

作者： Jie Zhang Xingzhe Guo Bing Lin Guangzu Xiong Hanshuang Wang Min Zhang Liwen Fan Bingwen Li Shuisheng Chen department of Chemistry and Chemical Engineering Taiyuan Institute of TechnologyTaiyuan 030008China Engineering Research Center of Oligosaccharides Fuyang Normal UniversityFuyang 236041China Shandong Key Laboratory of biophysics Institute of BiophysicsDezhou UniversityDezhou 253023China

Methane(CH_(4))as a substitute for other mineral fuels plays a crucial role in reducing energy consumption and preventing environmental *** present study employs a solvothermal method to fabricate a porous framework Co-metal-organic framework(Co-MOF)containing two distinct secondary building units(SBUs):an anionic[Co_(2)(μ_(2)-OH)(COO)_(4)(H_(2)O)]and a neutral[CoN_(2)(COO)_(2)].Notably,within the anionic SBUs,the coordinated water molecules induce the generation of divergent unsaturated Co(Ⅱ)centers in the unidirectional porous channels,thereby creating open metal *** adsorption performance of Co-MOF towards pure component gases was systematically *** results demonstrated that Co-MOF exhibits superior adsorption capacity for C_(2)-C_(3) hydrocarbons compared to CH_(4),which offers the potential for efficient adsorption and separation of CH_(4) from C_(2)-C_(3) *** gas selectivity separation ratios of Co-MOF for C_(2)H_(6)/CH_(4) and C_(3)H_8/CH_(4) were calculated using the ideal adsorbed solution theory method at 273/298 K and 0.1 *** results revealed that Co-MOF achieved remarkable equilibrium separation selectivity for CH_(4) and C_(2)-C_(3) hydrocarbon gases among non-modified MOFs,signifying the potential of the synthesized Co-MOF for efficient recovery and purification of CH_(4) from C_(2)-C_(3) *** experiments further demonstrate the ability of Co-MOF to purify methane from C_(2)-C_(3) hydrocarbons in practical gas separation ***,molecular simulation calculations further substantiate the propensity of anionic SBUs to interact with C_(2)-C_(3) hydrocarbon *** study provides a novel paradigm for the development of porous MOF materials in the application of gas mixture separation.

关键词： Co-MOF Separation hydrocarbons Dynamic breakthrough curves Molecular simulations adsorbent Monte Carlo simulation

High-yield and rapid isolation of extracellular vesicles by flocculation via orbital acoustic trapping:FLOAT

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Microsystems & Nanoengineering 2024年第1期10卷 313-323页

作者： Joseph Rufo Peiran Zhang Zeyu Wang Yuyang Gu Kaichun Yang Joseph Rich Chuyi Chen Ruoyu Zhong Ke Jin Ye He Jianping Xia Ke Li Jiarong Wu Yingshi Ouyang Yoel Sadovsky Luke P.Lee Tony Jun Huang department of Mechanical Engineering and Materials Science Duke UniversityDurhamNCUSA department of Biomedical Engineering Duke UniversityDurhamNCUSA department of Obstetrics Gynecologyand Reproductive SciencesMagee-Womens Research InstituteUniversity of PittsburghPittsburghPAUSA department of Microbiology and Molecular Genetics School of MedicineUniversity of PittsburghPittsburghPAUSA Renal Division and Division of Engineering in Medicine Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMAUSA department of Bioengineering Department of Electrical Engineering and Computer ScienceUniversity of CaliforniaBerkeleyBerkeleyCAUSA department of biophysics Institute of Quantum BiophysicsSungkyunkwan UniversitySuwonKorea

Extracellular vesicles(EVs)have been identified as promising biomarkers for the noninvasive diagnosis of various ***,challenges in separating EVs from soluble proteins have resulted in variable EV recovery rates and low ***,we report a high-yield(>90%)and rapid(<10 min)EV isolation method called FLocculation via Orbital Acoustic Trapping(FLOAT).The FLOAT approach utilizes an acoustofluidic droplet centrifuge to rotate and controllably heat liquid *** adding a thermoresponsive polymer flocculant,nanoparticles as small as 20 nm can be rapidly and selectively concentrated at the center of the *** demonstrate the ability of FLOAT to separate urinary EVs from the highly abundant Tamm-Horsfall protein,addressing a significant obstacle in the development of EV-based liquid *** to its high-yield nature,FLOAT reduces biofluid starting volume requirements by a factor of 100(from 20 mL to 200µL),demonstrating its promising potential in point-of-care diagnostics.

关键词： trapping utilize separating

Establishment of a cholangiocarcinoma risk evaluation model based on mucin expression levels

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1344-1360页

作者： Chun-Yuan Yang Li-Mei Guo Yang Li Guang-Xi Wang Xiao-Wei Tang Qiu-Lu Zhang Ling-Fu Zhang Jian-Yuan Luo department of Pathology Institute of Systems BiomedicineSchool of Basic Medical Sciences Peking UniversityPeking University Third HospitalPeking University Health Science CenterBeijing 100191China department of General Surgery Peking University Third HospitalBeijing 100191China department of medical Genetics Department of Biochemistry and BiophysicsSchool of Basic Medical Sciences Peking UniversityPeking University Health Science CenterBeijing 100191China

BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant cancer,characterized by frequent mucin ***1 has been identified as a critical oncogene in the progression of ***,the comprehensive understanding of how the mucin family influences CCA progression and prognosis is still *** To investigate the functions of mucins on the progression of CCA and to establish a risk evaluation formula for stratifying CCA *** Single-cell RNA sequencing data from 14 CCA samples were employed for elucidating the roles of mucins,complemented by bioinformatic ***-quent validations were conducted through spatial transcriptomics and *** construction of a risk evaluation model utilized the least absolute shrinkage and selection operator regression algorithm,which was further confirmed by independent cohorts and diverse data *** CCA tumor cells with elevated levels of MUC1 and MUC4 showed activated nucleotide metabolic pathways and increased ***5AC-high cells were found to promote CCA progression through WNT ***5B-high cells exhibited robust cellular oxidation activities,leading to resistance against antitumoral ***13-high cells were observed to secret chemokines,recruiting and transforming macrophages into the M2-polarized state,thereby suppressing antitumor ***16-high cells were found to promote tumor progression through interleukin-1/nuclear factor kappa-light-chain-enhancer of activated B cells signaling upon interaction with *** the expression levels of these mucins,a risk factor evaluation formula for CCA was developed and validated across multiple *** samples with higher risk factors exhibited stronger metastatic potential,chemotherapy resistance,and poorer *** Our study elucidates the functional mechanisms through which mucins contribute to CCA development,and provides tools for risk stratification in CCA.

关键词： Mucin Cholangiocarcinoma Single-cell RNA sequencing Spatial transcriptomics Prognosis

Effects of Lycium barbarum polysaccharide on cytokines in adolescents with subthreshold depression:a randomized controlled study

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Neural Regeneration Research 2024年第9期19卷 2036-2040页

作者： Xiaoyue Li Tao Liu Xuan Mo Runhua Wang Xueyan Kong Robin Shao Roger S.Mclntyre Kwok-Fai So Kangguang Lin department of Affective Disorders The Affiliated Brain Hospital of Guangzhou Medical University(Guangzhou Huiai Hospital)GuangzhouGuangdong ProvinceChina Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina department of Psychiatry The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina Mood Disorders Psychopharmacology Unit Poul Hansen Family Centre for DepressionUniversity Health NetworkTorontoONCanada department of Psychiatry University of TorontoTorontoONCanada Brain and Cognition Discovery Foundation TorontoCanada Ministry of Education Joint International Research Laboratory of CNS Regeneration Jinan UniversityGuangzhouGuangdong ProvinceChina Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation SciencesQingdaoShandong ProvinceChina

Strong evidence has accumulated to show a correlation between depression symptoms and inflammatory ***,anti-inflammatory treatment has shown partial effectiveness in alleviating depression *** barbarum polysaccharide(LBP),derived from Goji berries,exhibits notable antioxidative and anti-inflammatory *** our recent double-blinded randomized placebo-controlled trial,we found that LBP significantly reduced depressive symptoms in adolescents with subthreshold *** is presumed that the antidepressant effect of LBP may be associated with its influence on inflammatory *** the double-blinded randomized controlled trial,we enrolled 29 adolescents with subthreshold depression and randomly divided them into an LBP group and a placebo *** the LBP group,adolescents were given 300 mg/d LBP.A 6-week follow up was completed by 24 adolescents,comprising 14 adolescents from the LBP group(15.36±2.06 years,3 men and 11 women)and 10 adolescents from the placebo group(14.9±1.6 years,2 men and 8 women).Our results showed that after 6 weeks of treatment,the interleukin-17A level in the LBP group was lower than that in the placebo *** analysis showed that LBP reduced the correlations and connectivity between inflammatory factors,which were associated with the improvement in depressive *** findings suggest that 6-week administration of LBP suppresses the immune response by reducing interleukin-17A level,thereby exerting an antidepressant effect.

关键词： adolescents cytokines efficacy Goji berry inflammatory responses interleukin-17A Lycium barbarum polysaccharide randomized controlled study subthreshold depression

Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors

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The Innovation 2024年第3期5卷 129-137页

作者： Balázs Gyorffy department of biophysics Medical SchoolUniversity of Pecs7624 PecsHungary department of Bioinformatics Semmelweis University1094 BudapestHungary Cancer Biomarker Research Group Institute of Molecular Life SciencesHUN-REN Research Centre for Natural Sciences1117 BudapestHungary

Identifying genes with prognostic significance that can act as biomarkers in solid tumors can help stratify patients and uncover novel therapy ***,our goal was to expand our previous ranking analysis of survival-associated genes in various solid tumors to include colon cancer specimens with available transcriptomic and clinical data.A Gene Expression Omnibus search was performed to identify available datasets with clinical data and raw gene expression measurements.A combined database was set up and integrated into our Kaplan-Meier plotter,making it possible to identify genes with expression changes linked to altered *** a demonstration of the utility of the platform,the most powerful genes linked to overall survival in colon cancer were identified using uni-and multivariate Cox regression *** combined colon cancer database includes 2,137 tumor samples from 17 independent *** most significant genes associated with relapse-free survival with a false discovery rate below 1%in colon cancer carcinoma were RBPMS(hazard rate[HR]=2.52),TIMP1(HR=2.44),and COL4A2(HR=2.36).The three strongest genes associated with shorter survival in stage II colon cancer include CSF1R(HR=2.86),FLNA(HR=2.88),and TPBG(HR=2.65).In summary,a new integrated database for colon cancer is presented.A colon cancer analysis subsystem was integrated into our Kaplan-Meier plotter that can be used to mine the entire database(https://***).The portal has the potential to be employed for the identification and prioritization of promising biomarkers and therapeutic target candidates in multiple solid tumors including,among others,breast,lung,ovarian,gastric,pancreatic,and colon cancers.

关键词： colon tumors analysis

New clinical trial design in precision medicine:discovery,development and direction

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1293-1321页

作者： Xiao-Peng Duan Bao-Dong Qin Xiao-Dong Jiao Ke Liu Zhan Wang Yuan-Sheng Zang department of medical Oncology Changzheng HospitalNaval Medical UniversityShanghaiChina

In the era of precision medicine,it has been increasingly recognized that individuals with a certain disease are complex and different from each *** to the underestimation of the significant heterogeneity across participants in traditional"one-sizefits-all"trials,patient-centered trials that could provide optimal therapy customization to individuals with specific biomarkers were developed including the basket,umbrella,and platform trial designs under the master protocol *** recent years,the successive FDA approval of indications based on biomarker-guided master protocol designs has demonstrated that these new clinical trials are ushering in tremendous *** the rapid increase in the number of basket,umbrella,and platform trials,the current clinical and research understanding of these new trial designs,as compared with traditional trial designs,remains *** majority of the research focuses on methodologies,and there is a lack of in-depth insight concerning the underlying biological logic of these new clinical trial ***,we provide this comprehensive review of the discovery and development of basket,umbrella,and platform trials and their underlying logic from the perspective of precision ***,we discuss future directions on the potential development of these new clinical design in view of the"Precision Pro","Dynamic Precision",and"Intelligent Precision".This review would assist trial-related researchers to enhance the innovation and feasibility of clinical trial designs by expounding the underlying logic,which be essential to accelerate the progression of precision medicine.

关键词： clinical approval successive

ACSL3 regulates breast cancer progression via lipid metabolism reprogramming and the YES1/YAP axis

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Cancer Biology & Medicine 2024年第7期21卷 606-635页

作者： Shirong Tan Xiangyu Sun Haoran Dong Mozhi Wang Litong Yao Mengshen Wang Ling Xu Yingying Xu department of Breast Surgery The First Affiliated Hospital of China Medical University department of Thyroid and Breast Surgery Affiliated Hospital of Xuzhou Medical University department of medical Oncology The First Hospital of China Medical University

Objective: Mitochondrial fatty acid oxidation is a metabolic pathway whose dysregulation is recognized as a critical factor in various cancers, because it sustains cancer cell survival, proliferation, and metastasis. The acyl-Co A synthetase long-chain(ACSL) family is known to activate long-chain fatty acids, yet the specific role of ACSL3 in breast cancer has not been ***: We assessed the prognostic value of ACSL3 in breast cancer by using data from tumor samples. Gain-of-function and lossof-function assays were also conducted to determine the roles and downstream regulatory mechanisms of ACSL3 in vitro and in ***: ACSL3 expression was notably downregulated in breast cancer tissues compared with normal tissues, and this phenotype correlated with improved survival outcomes. Functional experiments revealed that ACSL3 knockdown in breast cancer cells promoted cell proliferation, migration, and epithelial±mesenchymal transition. Mechanistically, ACSL3 was found to inhibit β-oxidation and the formation of associated byproducts, thereby suppressing malignant behavior in breast cancer. Importantly, ACSL3 was found to interact with YES proto-oncogene 1, a member of the Src family of tyrosine kinases, and to suppress its activation through phosphorylation at Tyr419. The decrease in activated YES1 consequently inhibited YAP1 nuclear colocalization and transcriptional complex formation, and the expression of its downstream genes in breast cancer cell ***: ACSL3 suppresses breast cancer progression by impeding lipid metabolism reprogramming, and inhibiting malignant behaviors through phospho-YES1 mediated inhibition of YAP1 and its downstream pathways. These findings suggest that ACSL3 may serve as a potential biomarker and target for comprehensive therapeutic strategies for breast cancer.

关键词： ACSL3 Breast cancer YAP lipid metabolism metastasis