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TDP-43 is a key molecule accelerating development of Alzheimer’s disease following traumatic brain injury

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Neural Regeneration Research 2024年第5期19卷 955-956页

作者： Chu Chen department of cellular and Integrative Physiology Long School of MedicineUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA

Currently,more than 55 million people have dementia worldwide and Alzheimer’s disease(AD)is one of the most common causes of dementia in ***,no effective therapies are currently available for the prevention and treatment of *** is largely due to our limited understanding of the mechanisms underlying the neuropathogenesis of *** has widely been recognized that AD is heterogeneous and that multi-factors are contributing to the pathogenesis of *** evidence suggests that traumatic brain injury(TBI)is an important risk factor for the development of AD and dementia later in life(Guo et al.,2000;Johnson et al.,2010).However,the precise mechanism by which TBI contributes to developing AD has yet to be elucidated.

关键词： Alzheimer traumatic

Promising use of metformin in treating neurological disorders:biomarker-guided therapies

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Neural Regeneration Research 2024年第5期19卷 1045-1055页

作者： Allison Loan Charvi Syal Margarita Lui Ling He Jing Wang Regenerative medicine Program Ottawa Hospital Research InstituteOttawaONCanada department of Biology Faculty of ScienceUniversity of OttawaOttawaONCanada department of Pediatrics and medicine Johns Hopkins Medical SchoolBaltimoreMDUSA department of cellular and Molecular medicine Faculty of MedicineUniversity of OttawaOttawaONCanada University of Ottawa Brain and Mind Research Institute OttawaONCanada

Neurological disorders are a diverse group of conditions that affect the nervous system and include neurodegenerative diseases(Alzheimer’s disease,multiple sclerosis,Parkinson’s disease,Huntington’s disease),cerebrovascular conditions(stroke),and neurodevelopmental disorders(autism spectrum disorder).Although they affect millions of individuals around the world,only a limited number of effective treatment options are available *** most neurological disorders express mitochondria-related metabolic perturbations,metformin,a biguanide type II antidiabetic drug,has attracted a lot of attention to be repurposed to treat neurological disorders by correcting their perturbed energy ***,controversial research emerges regarding the beneficial/detrimental effects of metformin on these neurological *** that most neurological disorders have complex etiology in their pathophysiology and are influenced by various risk factors such as aging,lifestyle,genetics,and environment,it is important to identify perturbed molecular functions that can be targeted by metformin in these neurological *** molecules can then be used as biomarkers to stratify subpopulations of patients who show distinct molecular/pathological properties and can respond to metformin treatment,ultimately developing targeted *** this review,we will discuss mitochondria-related metabolic perturbations and impaired molecular pathways in these neurological disorders and how these can be used as biomarkers to guide metformin-responsive treatment for the targeted therapy to treat neurological disorders.

关键词： Alzheimer’s disease Huntington’s disease metformin mitochondrial perturbation multiple sclerosis neural degenerative diseases Parkinson’s disease stroke targeted therapy

STING agonist-conjugated metal-organic framework induces artificial leukocytoid structures and immune hotspots for systemic antitumor responses

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National Science Review 2024年第7期11卷 189-204页

作者： Taokun Luo Xiaomin Jiang Yingjie Fan Eric Yuan Jinhong Li Langston Tillman Wenbin Lin department of Chemistry University of Chicago department of Radiation and cellular Oncology and the Ludwig Center for Metastasis Research University of Chicago

Radiotherapy is widely used for cancer treatment, but its clinical utility is limited by radioresistance and its inability to target metastases. Nanoscale metal-organic frameworks(MOFs) have shown promise as high-Z nanoradiosensitizers to enhance radiotherapy and induce immunostimulatory regulation of the tumor microenvironment. We hypothesized that MOFs could deliver small-molecule therapeutics to synergize with radiotherapy for enhanced antitumor efficacy. Herein, we develop a robust nanoradiosensitizer,GA-MOF, by conjugating a STING agonist, 2,3-cyclic guanosine monophosphate–adenosine monophosphate(GA), on MOFs for synergistic radiosensitization and STING activation. GA-MOF demonstrated strong anticancer efficacy by forming immune-cell-rich nodules(artificial leukocytoid structures) and transforming them into immunostimulatory hotspots with radiotherapy. Further combination with an immune checkpoint blockade suppressed distant tumors through systemic immune activation. Our work not only demonstrates the potent radiosensitization of GA-MOF, but also provides detailed mechanisms regarding MOF distribution, immune regulatory pathways and long-term immune effects.

关键词： metal-organic framework radiosensitization STING agonist artificial leukocytoid structures immune hotspots immunotherapy nanomedicine

Black phosphorus quantum dots induce myocardial inflammatory responses and metabolic disorders in mice

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Journal of Environmental Sciences 2024年第3期137卷 53-64页

作者： Chao Shen Xiaoyan Ding Jinpeng Ruan Fengkai Ruan Weiping Hu Jiyi Huang Chengyong He Yi Yu Zhenghong Zuo department of Nephrology State Key Laboratory of Cellular Stress BiologySchool of Life SciencesFaculty of Medicine and Life SciencesFujian Clinical Research Center for Chronic Glomerular DiseaseThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamen 361102China

As an ultrasmall derivative of black phosphorus(BP)sheets,BP quantum dots(BP-QDs)have been effectively used in many ***,information on the cardiotoxicity induced by BP-QDs remains *** aimed to evaluate BP-QD-induced cardiac toxicity in *** examination of heart tissue sections was *** sequencing,real-time quantitative PCR(RT–qPCR),western blotting,and enzyme-linked immunosorbent assay(ELISA)assays were used to detect the m RNA and/or protein expression of proinfammatory cytokines,nuclear factor kappa B(NF-κB),phosphatidylinositol3 kinase-protein kinase B(PI3K-AKT),peroxisome proliferator-activated receptor gamma(PPARγ),and glucose/lipid metabolism pathway-related *** found that heart weight and heart/body weight index(HBI)were significantly reduced in mice after intragastric administration of 0.1 or 1 mg/kg BP-QDs for 28 *** addition,obvious infammatory cell infiltration and increased cardiomyocyte diameter were observed in the BP-QD-treated *** expression of proinfammatory cytokines and genes related to the NF-κB signaling pathway further confirmed that BP-QD exposure induced infammatory *** addition,BP-QD treatment also affected the PI3K-AKT,PPARγ,thermogenesis,oxidative phosphorylation,and cardiac muscle contraction signaling *** expression of genes related to glucose/lipid metabolism signaling pathways was dramatically affected by BP-QD exposure,and the effect was primarily mediated by the PPAR signaling *** study provides new insights into the toxicity of BP-QDs to human health.

关键词： BP-QDs Cardiac toxicity Infammatory responses NF-κB signaling pathway PPARγsignaling pathway Glucose/lipid metabolism

Enhancement of endogenous midbrain neurogenesis by microneurotrophin BNN-20 after neural progenitor grafting in a mouse model of nigral degeneration

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Neural Regeneration Research 2024年第6期19卷 1318-1324页

作者： Theodora Mourtzi Nasia Antoniou Christina Dimitriou Panagiotis Gkaravelas Georgia Athanasopoulou Panagiota Nti Kostantzo Olga Stathi Efthymia Theodorou Maria Anesti Rebecca Matsas Fevronia Angelatou Georgia Kouroupi Ilias Kazanis Laboratory of Developmental Biology Department of BiologyUniversity of PatrasPatrasGreece Laboratory of cellular and Molecular Neurobiology-Stem Cells Hellenic Pasteur InstituteAthensGreece department of Physiology School of MedicineUniversity of PatrasPatrasGreece

We have previously shown the neuroprotective and pro-neurogenic activity of microneurotrophin BNN-20 in the substantia nigra of the“weaver”mouse,a model of progressive nigrostriatal ***,we extended our investigation in two clinically-relevant ***,we assessed the effects of BNN-20 on human induced pluripotent stem cell-derived neural progenitor cells and neurons derived from healthy and parkinsonian ***,we assessed if BNN-20 can boost the outcome of mouse neural progenitor cell intranigral transplantations in weaver mice,at late stages of *** found that BNN-20 has limited direct effects on cultured human induced pluripotent stem cell-derived neural progenitor cells,marginally enhancing their differentiation towards neurons and partially reversing the pathological phenotype of dopaminergic neurons generated from parkinsonian *** agreement,we found no effects of BNN-20 on the mouse neural progenitor cells grafted in the substantia nigra of weaver ***,the graft strongly induced an endogenous neurogenic response throughout the midbrain,which was significantly enhanced by the administration of microneurotrophin *** results provide straightforward evidence of the existence of an endogenous midbrain neurogenic system that can be specifically strengthened by ***,the lack of major similar activity on cultured human induced pluripotent stem cell-derived neural progenitors and their progeny reveals the in vivo specificity of the aforementioned pro-neurogenic effect.

关键词： adult neurogenesis BNN-20 brain-derived neurotrophic factor cell replacement induced pluripotent stem cells(iPSCs) neurotrophic factors Parkinson's disease substantia

Anoctamin 4 defines glucose-inhibited neurons in the ventromedial hypothalamus

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Neural Regeneration Research 2024年第6期19卷 1177-1178页

作者： Longlong Tu Yanlin He Yong Xu Children’s Nutrition Research Center Department of PediatricsBaylor College of MedicineOne Baylor PlazaHoustonTXUSA Brain Glycemic and Metabolism Control department Pennington Biomedical Research CenterLouisiana State UniversityBaton RougeLAUSA department of Molecular and cellular Biology Section of EndocrinologyDiabetes and MetabolismDepartment of MedicineBaylor College of MedicineHoustonTXUSA

Glucose is the primary fuel source of the brain,and therefore glucose levels need to be tightly regulated and maintained within a small physiological ***,the body necessitates a stable supply of energy mainly provided by glucose for various bodily *** or low blood glucose levels would impair the physiological functions of various organs of the body.

关键词： inhibited medial organs

Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G

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Virologica Sinica 2024年第2期39卷 218-227页

作者： Zigui Chen Rita Way Yin Ng Grace Lui Lowell Ling Agnes S.Y.Leung Chit Chow Siaw Shi Boon Wendy C.S.Ho Maggie Haitian Wang Renee Wan Yi Chan Albert Martin Li David Shu Cheong Hui Paul Kay Sheung Chan department of Microbiology Faculty of MedicineThe Chinese University of Hong KongHong KongChina department of medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong KongChina department of Anaesthesia and Intensive Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina department of Paediatrics Faculty of MedicineThe Chinese University of Hong KongHong KongChina department of Anatomical and cellular Pathology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Jockey Club School of Public Health and Primary Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Stanley Ho Centre for Emerging Infectious Diseases Faculty of MedicineThe Chinese University of Hong KongHong KongChina

The SARS-CoV-2 Omicron variants are notorious for their transmissibility,but little is known about their subgenomic RNA(sgRNA)*** study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern(non-VOC)-D614G.A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOCD614G regardless of host gender,age and presence of ***,such profile was lost in samples with low viral load,suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point.A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and *** presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load(AUC¼0.91,95%CI 0.88–0.94),and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual *** potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

关键词： Coronavirus SARS-CoV-2 Omicron BA.2 Non-VOC-D614G RNA-seq Subgenomic RNA(sgRNA)

DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

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Genes & Diseases 2024年第4期11卷 368-380页

作者： Dafei Chai Xu Wang Praveen Neeli Shan Zhou Xingfang Yu Kanaga Sabapathy Yong Li department of medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA Division of cellular&Molecular Research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense ***,there are currently no approved targeted therapies or immunotherapies against mutant ***,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in *** then delivered DNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic *** results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells,with no cross-reactivity with wild-type *** cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular *** made a recombinant MC38 mouse cell line(MC38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 *** vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in *** administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-PD-1 *** results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 PD-1 R175H

Androgens exert multifaceted functions in sex differences analyzed through single-cell transcriptome

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Science China Life Sciences 2024年第11期67卷 2530-2531页

作者： Xinxin Tang Yinkun Fu Zhihui Zou Yue Li Ming He Key Laboratory of Cell Differentiation and Apoptosis of Ministry of Education Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases Department of Pathophysiology School of Medicine Shanghai Jiao Tong University department of Pathology The Affiliated Hospital of Youjiang Medical University for Nationalities

Sex differences are ubiquitous in human development, aging and disease. For example, the overwhelming majority of non-reproductive system cancers are more common in males(Mauvais-Jarvis et al., 2020), while autoimmune diseases are more common in females. Hormones,especially androgens and oestrogens, contribute to sex-biased phenotypes(Khramtsova et al., 2019).

关键词： PROSTATE CASTRATION