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Development of a new cerebral ischemia reperfusion model of Mongolian gerbils and standardized evaluation system

Animal Models and Experimental Medicine 2024年第1期7卷 48-55页

作者： Ying Wu Caijiao Hu Zhihui Li Feiyang Li Jianyi Lv Meng Guo Xin Liu Changlong Li Xueyun Huo Zhenwen Chen Lifeng Yang Xiaoyan Du School of Basic Medical sciences Capital Medical UniversityBeijingChina Laboratory for clinical Medicine Capital Medical UniversityBeijingChina College of veterinary Medicine China Agricultural UniversityBeijingChina

Background:The Mongolian gerbil is an excellent laboratory animal for preparing the cerebral ischemia model due to its inherent deficiency in the circle of Willis.However,the low incidence and unpredictability of symptoms are caused by numerous complex variant types of the circle.Additionally,the lack of an evaluation system for the cer-ebral ischemia/reperfusion(I/R)model of gerbils has shackled the application of this model.Methods:We created a symptom-oriented principle and detailed neurobehavioral scoring criteria.At different time points of reperfusion,we analyzed the alteration in locomotion by rotarod test and grip force score,infarct volume by triphenyltetrazo-lium chloride(TTC)staining,neuron loss using Nissl staining,and histological charac-teristics using hematoxylin-eosin(H&E)straining.Results:With a successful model rate of 56%,32 of the 57 gerbils operated by our method harbored typical features of cerebral I/R injury,and the mortality rate in the male gerbils was significantly higher than that in the female gerbils.The suc-cessfully prepared I/R gerbils demonstrated a significant reduction in motility and grip strength at 1 day after reperfusion;formed obvious infarction;exhibited typi-cal pathological features,such as tissue edema,neuronal atrophy and death,and vacuolated structures;and were partially recovered with the extension of reperfu-sion time.Conclusion:This study developed a new method for the unilateral common carotid artery ligation I/R model of gerbil and established a standardized evaluation system for this model,which could provide a new cerebral I/R model of gerbils with more practical applications.

关键词： ischemia/reperfusion Mongolian gerbil standardized model system unilateral carotid occlusion

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Sleep-based neuronal oscillations as a physiological biomarker for Alzheimer's disease:is night time the right time?

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Neural Regeneration Research 2024年第7期19卷 1417-1418页

作者： Jonathan Witton Erica S.Brady Michael T.Craig Department of clinical and Biomedical sciences Faculty of Health and Life SciencesUniversity of ExeterExeterEnglandUK Gladstone Institute for Neurological Disease San FranciscoCAUSA School of Psychology and Neuroscience College of MedicalVeterinary and Life SciencesUniversity of GlasgowGlasgowScotlandUK

Dementia is a devastating syndrome characterized by memory problems,confusion,and behavior changes that prevent people from performing everyday activities.It is the leading cause of dependency and disability amongst older people,resulting in a global economic cost of ~$1.3 trillion.Around 58 million people are currently afflicted by dementia worldwide,with Alzheimer s disease(AD) causing most(60-70%) of these cases.

关键词： Alzheimer everyday performing

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Additively manufactured Ti–Ta–Cu alloys for the next-generation load-bearing implants

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International Journal of Extreme Manufacturing 2024年第1期6卷 353-374页

作者： Amit Bandyopadhyay Indranath Mitra Sushant Ciliveri Jose D Avila William Dernell Stuart B Goodman Susmita Bose W.M.Keck Biomedical Materials Research Laboratory School of Mechanical and Materials EngineeringWashington State UniversityPullmanWA 99164United States of America veterinary clinical sciences College of Veterinary MedicineWashington State UniversityPullmanWA 99164United States of America Department of Orthopedic Surgery Stanford University Medical CenterRedwood CityCA 94063United States of America

Bacterial colonization of orthopedic implants is one of the leading causes of failure and clinical complexities for load-bearing metallic implants. Topical or systemic administration of antibiotics may not offer the most efficient defense against colonization, especially in the case of secondary infection, leading to surgical removal of implants and in some cases even limbs. In this study, laser powder bed fusion was implemented to fabricate Ti3Al2V alloy by a 1:1 weight mixture of CpTi and Ti6Al4V powders. Ti-Tantalum(Ta)–Copper(Cu) alloys were further analyzed by the addition of Ta and Cu into the Ti3Al2V custom alloy. The biological,mechanical, and tribo-biocorrosion properties of Ti3Al2V alloy were evaluated. A 10 wt.% Ta(10Ta) and 3 wt.% Cu(3Cu) were added to the Ti3Al2V alloy to enhance biocompatibility and impart inherent bacterial resistance. Additively manufactured implants were investigated for resistance against Pseudomonas aeruginosa and Staphylococcus aureus strains of bacteria for up to 48 h. A 3 wt.% Cu addition to Ti3Al2V displayed improved antibacterial efficacy, i.e.78%–86% with respect to CpTi. Mechanical properties for Ti3Al2V–10Ta–3Cu alloy were evaluated, demonstrating excellent fatigue resistance, exceptional shear strength, and improved tribological and tribo-biocorrosion characteristics when compared to Ti6Al4V. In vivo studies using a rat distal femur model revealed improved early-stage osseointegration for alloys with10 wt.% Ta addition compared to CpTi and Ti6Al4V. The 3 wt.% Cu-added compositions displayed biocompatibility and no adverse infammatory response in vivo. Our results establish the Ti3Al2V–10Ta–3Cu alloy’s synergistic effect on improving both in vivo biocompatibility and microbial resistance for the next generation of load-bearing metallic implants.

关键词： Ti6Al4V load-bearing implants additive manufacturing 3D printing antibacterial performance

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Changes in structural plasticity of hippocampal neurons in an animal model of multiple sclerosis

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Zoological Research 2024年第2期45卷 398-414页

作者： Poornima D.E.Weerasinghe-Mudiyanselage Sohi Kang Joong-Sun Kim Sung-Ho Kim Hongbing Wang Taekyun Shin Changjong Moon Department of veterinary Anatomy and Animal Behavior College of Veterinary Medicine and BK21 FOUR ProgramChonnam National UniversityGwangju 61186Republic of Korea Department of Anatomy and Convergence Medical Science Institute of Health SciencesCollege of MedicineGyeongsang National UniversityJinju 52727Republic of Korea Department of Physiology and Neuroscience Program Michigan State UniversityEast LansingMI 48824USA Department of veterinary Anatomy College of Veterinary Medicine and Veterinary Medical Research InstituteJeju National UniversityJeju 63243Republic of Korea

Structural plasticity is critical for the functional diversity of neurons in the brain.Experimental autoimmune encephalomyelitis(EAE)is the most commonly used model for multiple sclerosis(MS),successfully mimicking its key pathological features(inflammation,demyelination,axonal loss,and gliosis)and clinical symptoms(motor and non-motordysfunctions).Recentstudieshave demonstrated the importance of synaptic plasticity in EAE pathogenesis.In the present study,we investigated the features of behavioral alteration and hippocampal structural plasticity in EAE-affected mice in the early phase(11 days post-immunization,DPI)and chronic phase(28DPI).EAE-affected mice exhibited hippocampus-related behavioral dysfunction in the open field test during both early and chronic phases.Dendritic complexity was largely affected in the cornu ammonis 1(CA1)and CA3 apical and dentate gyrus(DG)subregions of the hippocampus during the chronic phase,while this effect was only noted in the CA1 apical subregion in the early phase.Moreover,dendritic spine density was reduced in the hippocampal CA1 and CA3 apical/basal and DG subregions in the early phase of EAE,but only reduced in the DG subregion during the chronic phase.Furthermore,mRNA levels of proinflammatory cytokines(Il1β,Tnfα,and Ifnγ)and glial cell markers(Gfap and Cd68)were significantly increased,whereas the expression of activity-regulated cytoskeletonassociated protein(ARC)was reduced during the chronic phase.Similarly,exposure to the aforementioned cytokines in primary cultures of hippocampal neurons reduced dendritic complexity and ARC expression.Primary cultures of hippocampal neurons also showed significantly reduced extracellular signal-regulated kinase(ERK)phosphorylation upon treatment with proinflammatory cytokines.Collectively,these results suggest that autoimmune neuroinflammation alters structural plasticity in the hippocampus,possibly through the ERK-ARC pathway,indicating that this alteration may be associated with hippocampal dysfunctions in EAE.

关键词： Activity-regulated cytoskeleton-associated protein Anxiety-like behavior Experimental autoimmune encephalomyelitis Hippocampal dysfunction Neuroinflammation

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High-throughput computational screening and in vitro evaluation identifies 5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl)phenyl]-1H-isoindole-1,3(2H)-dione(C3),as a novel EGFR—HER2 dual inhibitor in gastric tumors

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Oncology Research 2024年第2期32卷 251-259页

作者： MESFER AL SHAHRANI REEM GAHTANI MOHAMMAD ABOHASSAN MOHAMMAD ALSHAHRANI YASSER ALRAEY AYED DERA MOHAMMAD RAJEH ASIRI PRASANNA RAJAGOPALAN Department of clinical Laboratory sciences College of Applied Medical SciencesKing Khalid UniversityAbhaSaudi Arabia

Gastric cancers are caused primarily due to the activation and amplification of the EGFR or HER2 kinases resulting in cell proliferation,adhesion,angiogenesis,and metastasis.Conventional therapies are ineffective due to the intra-tumoral heterogeneity and concomitant genetic mutations.Hence,dual inhibition strategies are recommended to increase potency and reduce cytotoxicity.In this study,we have conducted computational high-throughput screening of the ChemBridge library followed by in vitro assays and identified novel selective inhibitors that have a dual impediment of EGFR/HER2 kinase activities.Diversity-based High-throughput Virtual Screening(D-HTVS)was used to screen the whole ChemBridge small molecular library against EGFR and HER2.The atomistic molecular dynamic simulation was conducted to understand the dynamics and stability of the protein-ligand complexes.EGFR/HER2 kinase enzymes,KATOIII,and Snu-5 cells were used for in vitro validations.The atomistic Molecular Dynamics simulations followed by solvent-based Gibbs binding free energy calculation of top molecules,identified compound C3(5-(4-oxo-4H-3,1-benzoxazin-2-yl)-2-[3-(4-oxo-4H-3,1-benzoxazin-2-yl)phenyl]-1H-isoindole-1,3(2H)-dione)to have a good affinity for both EGFR and HER2.The predicted compound,C3,was promising with better binding energy,good binding pose,and optimum interactions with the EGFR and HER2 residues.C3 inhibited EGFR and HER2 kinases with IC50 values of 37.24 and 45.83 nM,respectively.The GI50 values of C3 to inhibit KATOIII and Snu-5 cells were 84.76 and 48.26 nM,respectively.Based on these findings,we conclude that the identified compound C3 showed a conceivable dual inhibitory activity on EGFR/HER2 kinase,and therefore can be considered as a plausible lead-like molecule for treating gastric cancers with minimal side effects,though testing in higher models with pharmacokinetic approach is required.

关键词： Dual inhibitor Drug discovery EGFR/HER2 kinase Gastric cancer High-throughput screening

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Gram-negative bacterial diversity and evidence of international clones of multidrug-resistant strains in zoo animals

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Integrative Zoology 2024年第3期19卷 417-423页

作者： João Pedro Rueda FURLAN Micaela Santana RAMOS Fábio Parra SELLERA Irys Hany Lima GONZALEZ Patrícia Locosque RAMOS Eliana Guedes STEHLING Department of clinical Analyses Toxicology and Food ScienceSchool of Pharmaceutical Sciences of Ribeirão PretoUniversity of São PauloRibeirão PretoBrazil Department of Internal Medicine School of Veterinary Medicine and Animal ScienceUniversity of São PauloSão PauloBrazil School of veterinary Medicine Metropolitan University of SantosSantosBrazil Coordination of Wild Fauna Secretary of EnvironmentInfrastructure and LogisticsSão PauloBrazil

Antimicrobial resistance(AMR)is a growing phenomenon that poses a major public health challenge worldwide(Dhingra et al.2020;Antimicrobial Resistance Collaborators 2022).The selective pressure exerted in clinical settings has contributed to the longlasting successful dissemination of multidrug-resistant(MDR)Gram-negative bacteria in these environments(Chia et al.2020).

关键词： multidrug clinical

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Comprehensive characterization of cell disulfidptosis in human cancers:An integrated pan-cancer analysis

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Genes & Diseases 2024年第4期11卷 5-8页

作者： Guo Zhao Yale Jiang Yuning Wang Shuhang Wang Ning Li clinical Trial Center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Excessive accumulation of disulfide molecules,like cystine,can induce disulfide stress and high toxicity in cells,but the reduced form of nicotinamide adenine dinucleotide phosphate can reverse this process and mitiga... 详细信息

关键词： disulfide cancer characterization

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Outcomes of long-acting injectable antipsychotics use in pregnancy:A literature review

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World Journal of Psychiatry 2024年第4期14卷 582-599页

作者： Ana V Pejčić Srdjan M Stefanović MilošN Milosavljević Vladimir S Janjić Marko M Folić Nevena D Folić Jovana Z Milosavljević Department of Pharmacology and Toxicology Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Department of Pharmacy Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Department of clinical Pharmacology University Clinical Center KragujevacKragujevac 34000Serbia Department of Psychiatry Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Clinic for Psychiatry University Clinical Center KragujevacKragujevac 34000Serbia Center for Pharmaceutical and Pharmacological Research Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Department of Pediatrics Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia Pediatric Clinic University Clinical Center KragujevacKragujevac 34000Serbia Department of Anatomy Faculty of Medical SciencesUniversity of KragujevacKragujevac 34000Serbia

BACKGROUND Women with a history of serious psychotic disorders are at increased risk of disease relapse during pregnancy.Long-acting injectable(LAI)antipsychotics have been widely used to improve adherence and prevent relapse in patients with various severe psychotic disorders,but there is a lack of high-quality data from previous research on the safety of LAI antipsychotics during pregnancy.AIM To summarize relevant data on maternal,pregnancy,neonatal,and developmental outcomes from published cases of LAI antipsychotic use in pregnancy.METHODS A literature search was performed through November 11,2023,using three online databases:PubMed/MEDLINE,Scopus,and Web of Science.Case reports or case series that reported information about the outcomes of pregnancy in women who used LAI antipsychotics at any point in pregnancy,with available full texts,were included.Descriptive statistics,narrative summation,and tabulation of the extracted data were performed.RESULTS A total of 19 publications satisfied the inclusion criteria:3 case series,15 case reports,and 1 conference abstract.They reported the outcomes of LAI antipsychotic use in 74 women and 77 pregnancies.The use of secondgeneration LAI antipsychotics was reported in the majority(n=47;61.0%)of pregnancies.First-generation LAI antipsychotics were administered during 30 pregnancies(39.0%).Most of the women(approximately 64%)had either satisfactory control of symptoms or no information about relapse,while approximately 12%of them had developed gestational diabetes mellitus.A minority of cases reported adverse outcomes such as stillbirth,spontaneous abortion,preterm birth,low birth weight,congenital anomalies,and neurological manifestations in newborns.However,there were no reports of negative long-term developmental outcomes.CONCLUSION Currently available data seem reassuring,but further well-designed studies are required to properly evaluate the risks and benefits of LAI antipsychotic use during pregnancy.

关键词： Antipsychotic agents Long-acting injectable Pregnancy Outcome Review

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18F-prostate specific membrane antigen positron emission tomography/computerized tomography for lymph node staging in medium/high risk prostate cancer: A systematic review and meta-analysis

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中华医学杂志(英文版) 2024年第8期137卷 949-958页

作者： Lv Zhengtong Song Liuqi Wang Miao Hou Huimin Li Haodong Wang Xuan Wang Jianye Wang Jianlong Liu Ming Beijing 100029 Department of Urology Beijing Hospital National Center of Gerontology Institute of Geriatric Medicine Chinese Academy of Medical sciences Beijing 100730 China Peking University Fifth School of clinical Medicine Peking University China-Japan Friendship School of clinical Medicine

Background: Lymph node staging of prostate cancer (PCa) is important for planning and monitoring of treatment.18F-prostate specific membrane antigen positron emission tomography/computerized tomography (18F-PSMA PET/CT) has several advantages over68Ga-PSMA PET/CT, but its diagnostic value requires further investigation. This meta-analysis focused on establishing the diagnostic utility of18F-PSMA PET/CT for lymph node staging in medium/high-risk PCa.Methods: We searched the EMBASE, PubMed, Cochrane library, and Web of Science databases from inception to October 1, 2022. Prostate cancer,18F, lymph node, PSMA, and PET/CT were used as search terms and the language was limited to English. We additionally performed a manual search using the reference lists of key articles. Patients and study characteristics were extracted and the QUADAS-2 tool was employed to evaluate the quality of included studies. Sensitivity, specificity, the positive and negative likelihood ratio (PLR and NLR), diagnostic odds ratio (DOR), area under the curve (AUC), and 95% confidence interval (CI) were used to evaluate the diagnostic value of18F-PSMA PET/CT. Stata 17 software was employed for calculation and statistical analyses.Results: A total of eight diagnostic tests including 734 individual samples and 6346 lymph nodes were included in this meta-analysis. At the patient level, the results of each consolidated summary were as follows: sensitivity of 0.57 (95% CI 0.39-0.73), specificity of 0.95 (95% CI 0.92-0.97), PLR of 11.2 (95% CI 6.6-19.0), NLR of 0.46 (95% CI 0.31-0.68), DOR of 25 (95% CI 11-54), and AUC of 0.94 (95% CI 0.92-0.96). At the lesion level, the results of each consolidated summary were as follows: sensitivity of 0.40 (95% CI 0.21-0.62), specificity of 0.99 (95% CI 0.95-1.00), PLR of 40.0 (95% CI 9.1-176.3), NLR of 0.61 (95% CI 0.42-0.87), DOR of 66 (95% CI 14-311), and AUC of 0.86 (95% CI 0.83-0.89).Conclusions: 18F-PSMA PET/CT showed moderate sensitivity but high specificity in lymph node staging of medium/high-risk PCa. The

关键词： 18F-PSMA PET/CT Diagnostic test Lymph node Meta-analysis Prostate cancer

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RNA modifications in cellular metabolism:implications for metabolism-targeted therapy and immunotherapy

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1565-1594页

作者： Wei-Wei Liu Si-Qing Zheng Tian Li Yun-Fei Fei Chen Wang Shuang Zhang Fei Wang Guan-Min Jiang Hao Wang Department of Laboratory Medicine The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina School of clinical Medicine Shandong UniversityJinanChina Core Unit of National clinical Research Center for Laboratory Medicine HefeiChina Neurosurgical Department The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina Department of clinical Laboratory The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhaiChina

Cellular metabolism is an intricate network satisfying bioenergetic and biosynthesis requirements of cells.Relevant studies have been constantly making inroads in our understanding of pathophysiology,and inspiring development of therapeutics.As a crucial component of epigenetics at post-transcription level,RNA modification significantly determines RNA fates,further affecting various biological processes and cellular phenotypes.To be noted,immunometabolism defines the metabolic alterations occur on immune cells in different stages and immunological contexts.In this review,we characterize the distribution features,modifying mechanisms and biological functions of 8 RNA modifications,including N6-methyladenosine(m6A),N6,2'-O-dimethyladenosine(m6Am),N1-methyladenosine(m1A),5-methylcytosine(m5C),N4-acetylcytosine(ac4C),N7-methylguanosine(m7G),Pseudouridine(V),adenosine-to-inosine(A-to-l)editing,which are relatively the most studied types.Then regulatory roles of these RNA modification on metabolism in diverse health and disease contexts are comprehensively described,categorized as glucose,lipid,amino acid,and mitochondrial metabolism.And we highlight the regulation of RNA modifications on immunometabolism,further influencing immune responses.Above all,we provide a thorough discussion about clinical implications of RNA modification in metabolism-targeted therapy and immunotherapy,progression of RNA modification-targeted agents,and its potential in RNAtargeted therapeutics.Eventually,we give legitimate perspectives for future researches in this field from methodological requirements,mechanistic insights,to therapeutic applications.

关键词： metabolism targeted alterations

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