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Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor

National Science Review 2024年第4期11卷 206-215页

作者： Ziyan Liao Jie Jiang Wei Wu Jiaqi Shi Yanfang Wang Yuejun Yao Tao Sheng Feng Liu Wei Liu Peng Zhao Feifei Lv Jie Sun Hongjun Li Zhen Gu National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang University Liangzhu Laboratory Zhejiang University Bone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology Zhejiang University School of Medicine Department of Medical Oncology The First Affiliated Hospital School of Medicine Zhejiang University Department of Laboratory medicine The First Affiliated Hospital Zhejiang University School of Medicine Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalSchool of MedicineZhejiang University Jinhua Institute of Zhejiang university MOE Key Laboratory of Macromolecular Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang University Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University

The limited infiltration and persistence of chimeric antigen receptor(CAR)-T cells is primarily responsible for their treatment deficits in solid tumors. Here, we present a three-dimensional scaffold, inspired by the physiological process of T-cell proliferation in lymph nodes. This scaffold gathers the function of loading,delivery, activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors. This porous device is made from poly(lactic-co-glycolic acid) by a microfluidic technique with the modification of T-cell stimulatory signals, including anti-CD3, anti-CD28 antibodies, as well as cytokines. This scaffold fosters a 50-fold CAR-T cell expansion in vitro and a 15-fold cell expansion in vivo. Particularly, it maintains long-lasting expansion of CAR-T cells for up to 30 days in a cervical tumor model and significantly inhibits the tumor growth. This biomimetic delivery strategy provides a versatile platform of cell delivery and activation for CAR-T cells in treating solid tumors.

关键词： drug delivery cell therapy bioinspired biomaterials cancer immunotherapy

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Defense and anti-defense mechanisms of bacteria and bacteriophages

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2024年第3期25卷 181-196页

作者： Xiaoqing WANG Sebastian LEPTIHN school of medicine Lishui UniversityLishui 323000China university of Edinburgh Medical school Biomedical SciencesCollege of Medicine&Veterinary MedicineThe University of EdinburghEdinburgh EH89JZUK HMU Health and Medical university Am Anger 64/73-99084 ErfurtGermany

In the post-antibiotic era,the overuse of antimicrobials has led to a massive increase in antimicrobial resistance,leaving medical doctors few or no treatment options to fight infections caused by *** use of bacteriophages is a promising alternative to treat infections,supplementing or possibly even replacing *** phages for therapy is possible,since these bacterial viruses can kill bacteria specifically,causing no harm to the normal ***,bacteria have developed a multitude of sophisticated and complex ways to resist infection by phages,including abortive infection and the clustered regularly interspersed short palindromic repeats(CRISPR)/CRISPR-associated(Cas)*** also can evolve and acquire new anti-defense strategies to continue *** in-depth exploration of both defense and anti-defense mechanisms would contribute to optimizing phage therapy,while we would also gain novel insights into the microbial *** this paper,we summarize recent research on bacterial phage resistance and phage anti-defense mechanisms,as well as collaborative win-win systems involving both virus and host.

关键词： Bacteriophage Phage resistance Abortive infection Phage therapy

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Validity of fatty liver prediction scores for diagnosis of fatty liver by Fibroscan

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 353-360页

作者： Seogsong Jeong Sun Jae Park Seong Kyun Na Sang Min Park Byung-Cheol Song Yun Hwan Oh Department of Biomedical Sciences Seoul National University Graduate SchoolSeoul 03080Korea Department of Biomedical Informatics CHA University School of MedicineCHA UniversitySeongnam 13488Korea Department of Internal medicine Inje University College of MedicineSeoul 50834Korea Department of Family medicine Seoul National University HospitalSeoul National University College of MedicineSeoul 03080Korea Department of Internal medicine Jeju National University HospitalJeju National University College of MedicineJeju 63241Korea Department of Family medicine Jeju National University HospitalJeju National University College of MedicineJeju 63241Korea Department of Family medicine Chung-Ang University Gwangmyeong HospitalChung-Ang University College of MedicineGwangmyeong 14353Korea

Background:The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease(K-NAFLD)score was recently developed with the intent to operationally define nonalcoholic fatty liver disease(NAFLD).However,there remained an external validation that confirmed its diagnostic performance,especially in patients with alcohol consumption or hepatitis virus ***:Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®.Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score,fatty liver index(FLI),and hepatic steatosis index(HSI).Results:K-NAFLD-moderate[adjusted odds ratio(aOR)=2.53,95%confidence interval(CI):1.13-5.65]and K-NAFLD-high(aOR=4.14,95%CI:1.69-10.13)groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics,and FLI-moderate and FLI-high groups revealed aORs of 2.05(95%CI:1.22-3.43)and 1.51(95%CI:0.78-2.90),*** addition,the HSI was less predictive for Fibroscan®-defined fatty *** K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection,and the adjusted area under curve values were comparable between K-NAFLD and ***:Externally validation of the K-NAFLD and FLI showed that these scores may be a useful,noninvasive,and non-imaging modality for the identification of fatty *** addition,these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.

关键词： Nonalcoholic fatty liver disease Fatty liver index Hepatic steatosis index

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Depressive semantic awareness from vlog facial and vocal streams via spatio-temporal transformer

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Digital Communications and Networks 2024年第3期10卷 577-585页

作者： Yongfeng Tao Minqiang Yang Yushan Wu Kevin Lee Adrienne Kline Bin Hu school of Information Science and Engineering Lanzhou UniversityLanzhouChina The school of Accounting Auditing and TaxationBusiness SchoolUNSW SydneyAustralia Department of Preventive medicine Northwestern UniversityChicagoILUnited States

With the rapid growth of information transmission via the Internet,efforts have been made to reduce network load to promote *** such application is semantic computing,which can extract and process semantic *** media has enabled users to share their current emotions,opinions,and life events through their mobile ***,people suffering from mental health problems are more willing to share their feelings on social ***,it is necessary to extract semantic information from social media(vlog data)to identify abnormal emotional states to facilitate early identification and *** studies do not consider spatio-temporal information when fusing multimodal information to identify abnormal emotional states such as *** solve this problem,this paper proposes a spatio-temporal squeeze transformer method for the extraction of semantic features of ***,a module with spatio-temporal data is embedded into the transformer encoder,which is utilized to obtain a representation of spatio-temporal ***,a classifier with a voting mechanism is designed to encourage the model to classify depression and non-depression *** are conducted on the D-Vlog *** results show that the method is effective,and the accuracy rate can reach 70.70%.This work provides scaffolding for future work in the detection of affect recognition in semantic communication based on social media vlog data.

关键词： Emotional computing Semantic awareness Depression recognition Vlog data

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Rebuilding insight into the pathophysiology of Alzheimer’s disease through new blood-brain barrier models

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Neural Regeneration Research 2024年第9期19卷 1954-1960页

作者： Kinya Matsuo Hideaki Nshihara Yamaguchi university Graduate school of medicine YamaguchiJapan Department of Neurotherapeutics Yamaguchi UniversityUbeJapan

The blood-brain barrier is a unique function of the microvasculature in the brain parenchyma that maintains homeostasis in the central nervous ***-brain barrier breakdown is a common pathology in various neurological diseases,such as Alzheimer’s disease,stroke,multiple sclerosis,and Parkinson’s ***,it has been considered a consequence of neuroinflammation or neurodegeneration,but recent advanced imaging techniques and detailed studies in animal models show that blood-brain barrier breakdown occurs early in the disease process and may precede neuronal ***,the blood-brain barrier is attractive as a potential therapeutic target for neurological diseases that lack effective *** elucidate the molecular mechanism underlying blood-brain barrier breakdown and translate them into therapeutic strategies for neurological diseases,there is a growing demand for experimental models of human origin that allow for functional ***,several human induced pluripotent stem cell-derived blood-brain barrier models have been established and various in vitro blood-brain barrier models using microdevices have been *** in the Alzheimer’s disease field,the human evidence for blood-brain barrier dysfunction has been demonstrated and human induced pluripotent stem cell-derived blood-brain barrier models have suggested the putative molecular mechanisms of pathological blood-brain *** this review,we summarize recent evidence of blood-brain barrier dysfunction in Alzheimer’s disease from pathological analyses,imaging studies,animal models,and stem cell ***,we discuss the potential future directions for blood-brain barrier research.

关键词： Alzheimer’s disease blood-brain barrier human induced pluripotent stem cells

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Artificial Intelligence and Network Pharmacology Reveal the Medication Rules of Professor Wang Yu-Ying in the Treatment of Climacteric Syndrome

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World Journal of Traditional Chinese medicine 2024年第2期10卷 180-190页

作者： Meng-Yuan Hu Tian-Xing Yi Qi-Rui Liu Xin-Yu Zhang Ai-Ping Chen Yu-Ying Wang Yi Lu school of Traditional Chinese medicine Beijing University of Chinese MedicineBeijingChina

Objective: The objective of this study was to explore the medication rules and academic ideas of Professor Wang Yu-Ying in the treatment of climacteric syndrome(CLS) and to predict new prescriptions. Materials and Methods: The characteristics of frequency, clustering, four properties, and five flavors were analyzed, and new prescriptions were predicted through an artificial intelligence(AI)-based method. The potential pathways of new prescriptions were explored through network pharmacology-based analysis. Results: The top 16 medicinals used by Professor Wang Yu-Ying in the treatment of CLS included Danggui, Longgu, Muli, Fuling, Chuanxiong, Gancao, Xiangfu, and Tusizi. The AI method was applied to predict the basic prescription for treating CLS: Danggui 15 g, Duanlonggu 30 g, Duanmuli 30 g, Fuling 28 g, Chuanxiong 10 g, Gancao 6 g, Xiangfu 12 g, Tusizi 14 g, etc., Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the pathogenesis of CLS might be related to the estrogen pathway, involving typical steroid responses. Conclusions: This study summarized Professor Wang's medication experience in the treatment of CLS based on the data mining of clinical diagnoses and treatment cases. The AI method was used to predict the new prescription of CLS treatment, which was found to be reasonable by network pharmacology studies on its multi-target and multi-pathway mechanisms.

关键词： Artificial intelligence climacteric syndrome medication rules network pharmacology Professor Wang Yu-Ying

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Glyphosate as a direct or indirect activator of pro-inflammatory signaling and cognitive impairment

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Neural Regeneration Research 2024年第10期19卷 2212-2218页

作者： Yukitoshi Izumi Kazuko A.O'Dell Charles F.Zorumski Department of Psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor Family Institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA

Glyphosate-based herbicides are widely used around the world, making it likely that most humans have significant exposure. Because of habitual exposure, there are concerns about toxicity including neurotoxicity that could result in neurological, psychiatric, or cognitive impairment. We recently found that a single injection of glyphosate inhibits long-term potentiation, a cellular model of learning and memory, in rat hippocampal slices dissected 1 day after injection, indicating that glyphosate-based herbicides can alter cognitive function. Glyphosate-based herbicides could adversely affect cognitive function either indirectly and/or directly. Indirectly, glyphosate could affect gut microbiota, and if dysbiosis results in endotoxemia(leaky gut), infiltrated bacterial by-products such as lipopolysaccharides could activate pro-inflammatory cascades. Glyphosate can also directly trigger pro-inflammatory cascades. Indeed, we observed that acute glyphosate exposure inhibits long-term potentiation in rat hippocampal slices. Interestingly, direct inhibition of long-term potentiation by glyphosate appears to be similar to that of lipopolysaccharides. There are several possible measures to control dysbiosis and neuroinflammation caused by glyphosate. Dietary intake of polyphenols, such as quercetin, which overcome the inhibitory effect of glyphosate on long-term potentiation, could be one effective strategy. The aim of this narrative review is to discuss possible mechanisms underlying neurotoxicity following glyphosate exposure as a means to identify potential treatments.

关键词： cognitive impairment glyphosate microglia neuroinflammation roundup toll-like receptor 4 zinc chelation

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Knockdown of neuronal DAF-15/Raptor promotes healthy aging in ***

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Journal of Genetics and Genomics 2024年第5期51卷 507-516页

作者： Xiao Zang Qi Wang Hanxin Zhang Yiyan Zhang Zi Wang Zixing Wu Di Chen Model Animal Research Center of Medical school Nanjing UniversityNanjingJiangsu 210061China Zhejiang university-university of Edinburgh Institute School of MedicineZhejiang UniversityHainingZhejiang 314400China Department of Colorectal Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310058China

The highly conserved target of rapamycin(TOR)pathway plays an important role in aging across *** studies have established that inhibition of the TOR complex 1(TORC1)significantly extends lifespan in Caenorhabditis ***,it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal ***,we apply the auxin-inducible degradation tool to knock down endogenous DAF-15,the *** ortholog of regulatory associated protein of TOR(Raptor),to characterize its roles in *** or tissue-specific inhibition of DAF-15 during development results in various growth defects,whereas neuron-specific knockdown of DAF-15 during adulthood significantly extends lifespan and *** neuronal DAF-15 deficiency-induced longevity requires the intestinal activities of DAF-16/FOXO and PHA-4/FOXA transcription factors,as well as the AAK-2/AMP-activated protein kinaseαcatalytic *** profiling reveals that the neuronal DAF-15 knockdown promotes the expression of genes involved in *** findings define the tissue-specific roles of TORC1 in healthy aging and highlight the importance of neuronal modulation of aging.

关键词： Aging targetof rapamycin DAF-15 DAF-16 C.elegans

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Liquid metal biomaterials: translational medicines,challenges and perspectives

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National Science Review 2024年第2期11卷 264-284页

作者： Hanchi Xu Jincheng Lu Yikuang Xi Xuelin Wang Jing Liu Department of Biomedical Engineering School of Medicine Tsinghua University Beijing Tsinghua Changgung Hospital School of Clinical Medicine Tsinghua University Shanghai World Foreign Language Academy Beijing Advanced Innovation Center for Biomedical Engineering School of Engineering MedicineBeihang University Beijing Key Lab of Cryo-Biomedical Engineering and Key Lab of Cryogenics Technical Institute of Physics and Chemistry Chinese Academy of Sciences

Until now, significant healthcare challenges and growing urgent clinical requirements remain incompletely addressed by presently available biomedical materials. This is due to their inadequate mechanical compatibility, suboptimal physical and chemical properties, susceptibility to immune rejection, and concerns about long-term biological safety. As an alternative, liquid metal(LM) opens up a promising class of biomaterials with unique advantages like biocompatibility, flexibility, excellent electrical conductivity,and ease of functionalization. However, despite the unique advantages and successful explorations of LM in biomedical fields, widespread clinical translations and applications of LM-based medical products remain limited. This article summarizes the current status and future prospects of LM biomaterials, interprets their applications in healthcare, medical imaging, bone repair, nerve interface, and tumor therapy, *** to translate LM materials into medicine and obstacles encountered in practices are *** that, we outline a blueprint for LM clinics, emphasizing their potential in making new-generation artificial organs. Last, the core challenges of LM biomaterials in clinical translation, including bio-safety,material stability, and ethical concerns are also discussed. Overall, the current progress, translational medicine bottlenecks, and perspectives of LM biomaterials signify their immense potential to drive future medical breakthroughs and thus open up novel avenues for upcoming clinical practices.

关键词： liquid metal biomaterials translational medicine clinical device healthcare therapeutics

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Endoplasmic reticulum stress,autophagy,neuroinflammation,and sigma 1 receptors as contributors to depression and its treatment

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Neural Regeneration Research 2024年第10期19卷 2202-2211页

作者： Chika Fujii Charles F.Zorumski Yukitoshi Izumi Department of Psychiatry Washington University School of MedicineSt.LouisMOUSA Taylor Family Institute for Innovative Psychiatric Research Washington University School of MedicineSt.LouisMOUSA

The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functions in recognizing and resolving cellular stress and are possible targets for the pathophysiology and treatment of psychiatric and neurologic illnesses. An increasing number of studies indicate the involvement of endoplasmic reticulum stress and autophagy in the control of neuroinflammation, a contributing factor to multiple neuropsychiatric illnesses. Initial inflammatory triggers induce endoplasmic reticulum stress, leading to neuroinflammatory responses. Subsequently, induction of autophagy by neurosteroids and other signaling pathways that converge on autophagy induction are thought to participate in resolving neuroinflammation. The aim of this review is to summarize our current understanding of the molecular mechanisms governing the induction of endoplasmic reticulum stress, autophagy, and neuroinflammation in the central nervous system. Studies focused on innate immune factors, including neurosteroids with anti-inflammatory roles will be reviewed. In the context of depression, animal models that led to our current understanding of molecular mechanisms underlying depression will be highlighted, including the roles of sigma 1 receptors and pharmacological agents that dampen endoplasmic reticulum stress and associated neuroinflammation.

关键词： allopregnanolone fluvoxamine ketamine neurosteroids postpartum depression quercetin

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