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NLRP3/1-mediated pyroptosis:beneficial clues for the development of novel therapies for Alzheimer’s disease

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Neural Regeneration Research 2024年第11期19卷 2400-2410页

作者： Bo Hu Jiaping Zhang Jie Huang Bairu Luo Xiansi Zeng Jinjing Jia Department of Pathology and Municipal Key-Innovative Discipline of Molecular Diagnostics Jiaxing Hospital of Traditional Chinese MedicineJiaxing UniversityJiaxingZhejiang ProvinceChina Research center of Neuroscience Jiaxing University Medical CollegeJiaxingZhejiang ProvinceChina Department of Clinical Pathology Jiaxing University Master Degree Cultivation BaseZhejiang Chinese Medical UniversityJiaxingZhejiang ProvinceChina

The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell death.There is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s disease.In this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on neuroinflammation.We also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s disease.Finally,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.

关键词： Alzheimer’s disease caspase-1 GSDMD inflammasome neuroinflammation NLRP1 NLRP3 pyroptosis therapeutic strategies

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A prognostic four-gene signature and a therapeutic strategy for hepatocellular carcinoma:Construction and analysis of a circRNA-mediated competing endogenous RNA network

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 272-287页

作者： Hai-Yan Zhang Jia-Jie Zhu Zong-Ming Liu Yu-Xuan Zhang Jia-Jia Chen Ke-Da Chen zhejiang Chinese Medical university Hangzhou 310053China Shulan International Medical College Zhejiang Shuren UniversityHangzhou 310015China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

Background:Hepatocellular carcinoma(HCC)has a poor long-term prognosis.The competition of circular RNAs(circRNAs)with endogenous RNA is a novel tool for predicting HCC prognosis.Based on the alterations of circRNA regulatory networks,the analysis of gene modules related to HCC is feasible.Methods:Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC.Gene function,pathway,and protein interaction analyses were performed for the differentially expressed genes(DEGs)in this regulatory network.In the proteinprotein interaction network,hub genes were identified and subjected to regression analysis,producing an optimized four-gene signature for prognostic risk stratification in HCC patients.Anti-HCC drugs were excavated by assessing the DEGs between the low-and high-risk groups.A circRNA-microRNA-hub gene subnetwork was constructed,in which three hallmark genes,KIF4A,CCNA2,and PBK,were subjected to functional enrichment analysis.Results:A four-gene signature(KIF4A,CCNA2,PBK,and ZWINT)that effectively estimated the overall survival and aided in prognostic risk assessment in the The cancer Genome Atlas(TCGA)cohort and International cancer Genome Consortium(ICGC)cohort was developed.CDK inhibitors,PI3K inhibitors,HDAC inhibitors,and EGFR inhibitors were predicted as four potential mechanisms of drug action(MOA)in high-risk HCC patients.Subsequent analysis has revealed that PBK,CCNA2,and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion,regulating microsatellite instability(MSI),and exerting an impact on HCC progression.Conclusions:The present study highlights the role of the circRNA-related regulatory network,identifies a four-gene prognostic signature and biomarkers,and further identifies novel therapy for HCC.

关键词： Hepatocellular carcinoma circRNA-related ceRNA network Biomarker Least absolute shrinkage and selection operator Bioinformatics

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Construction and properties of venlafaxine hydrochloride sustained release system based on hollow mesoporous silica microspheres

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Particuology 2024年第3期86卷 205-210页

作者： Chenjing Liang Lingling Shi Zhengguo Chen Lan Zhou Zhaoxia Zhang Guoqing Zhang School of Materials Science and Engineering Zhejiang Sci-tech UniversityHangzhouChina College of Textile Science and Engineering Zhejiang Sci-tech UniversityHangzhouChina zhejiang Provincial Innovation center of Advanced Textile Technology ShaoxingChina

The aim of this work is to develop a venlafaxine hydrochloride sustained release system based on hollow mesoporous silica microspheres(HMSMs).HMSMs were innovatively prepared with tetraethyl silicate(TEOS)as the precursor and volatile n-heptane as a soft template.The obtained HMSMs show a well-defined hollow structure with an average size of 967 nm and pore volume of 0.85 cm^(3)/g,implying it is a potential drug carrier.Subsequently,venlafaxine hydrochloride(VF)was absorbed in the HMSMs with a content of 37.67% or so.The sustained release effect is further measured by the dissolution in-strument at 37℃ and 50 rpm in ultrapure water.The results showed that the HMSMs/VF system shows good sustained release properties compared with sustained release tablets with hydroxypropyl meth-ylcellulose as the main component.This HMSMs sustained release system appears to be a promising candidate for a sustained drug release.

关键词： Hollowmesoporous silica microspheres(HMSMs) Venlafaxine hydrochloride Drug loading Sustained release

Intranasal boosting with RBD-HR protein vaccine elicits robust mucosal and systemic immune responses

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Genes & Diseases 2024年第4期11卷 327-339页

作者： Li Chen Wenyan Ren Hong Lei Jiayu Wang Haiying Que Dandan Wan Aqu Alu Dandan Peng Minyang Fu Weiqi Hong Yuhe Huang Xiangrong Song Guangwen Lu Xiawei Wei Laboratory of Aging Research and cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China

The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants has decreased the efficacy of SARs-CoV-2 vaccines in containing coronavirus disease 2019(CoVID-19)over time,and booster vaccination strategies are urgently necessitated to achieve sufficient protection.Intranasal immunization can improvemucosal immunity,offer-ing protection against the infection and sustaining the spread of SARS-CoV-2.In this study,an intranasal booster of the RBD-HR vaccine after two doses of the mRNA vaccine significantly increased the levels of specific binding antibodies in serum,nasal lavage fluid,and bronchoal-veolar lavage fluid compared with only two doses of mRNA vaccine.After intranasal boosting with the RBD-HR vaccine,the levels of serum neutralizing antibodies against prototype and variant strains of SARS-Cov-2 pseudoviruses weremarkedly higher than those in mice receiving mRNA vaccine alone,and intranasal boosting with the RBD-HR vaccine also inhibited the bind-ing of RBD to hACE2 receptors.Furthermore,the heterologous intranasal immunization regimen promoted extensive memory T cell responses and activated CD103+dendritic cells in the respiratory mucosa,and potently enhanced the formation of T follicular helper cells and germinal center B cells in vital immune organs,including mediastinal lymph nodes,inguinal lymph nodes,and spleen.Collectively,these data infer that heterologous intranasal boosting with the RBD-HR vaccine elicited broad protective immunity against SARS-CoV-2 both locallyandsystemically.

关键词： Heterologous immunization Intranasal immunization mRNA vaccine SARS-CoV-2 Subunitprotein vaccine

A retrospective analysis of mature T-and NK-cell lymphomas

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cancer Biology & Medicine 2024年第3期21卷 223-229页

作者： Junlei Jia Xiaohui Wang Zheng Song Shen Meng Yue Fei Jingwei Yu Xia Liu Xue Han Lanfang Li Lihua Qiu Zhengzi Qian Shiyong Zhou Wenchen Gong Bin Meng Xiubao Ren Xianhuo Wang Huilai Zhang National Key Laboratory of Druggability Evaluation and Systematic Translational Medicine and Department of LymphomaTianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinThe Sino-US Center for Lymphoma and Leukemia ResearchTianjin 300060China Department of Radiation Oncology Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinan 250117China Department of Pathology Department of Immunology/Biotherapy Tianjin Medical University Cancer Institute&HospitalNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin 300060China

Mature T-and natural killer(NK)-cell lymphomas are heterogeneous groups of malignant lymphoid neoplasms arising from T and NK cells. The incidence of mature T-and NK-cell lymphomas is 2.1 per 100,000 people, according... 详细信息

关键词： lymphoma neoplasms killer

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Advance in reversible Zn anodes promoted by 2D materials

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Rare Metals 2024年第4期43卷 1350-1369页

作者： Shu-Yuan Lei Jin-Xiu Feng Yu-Chao Chen Dong Zheng Wen-Xian Liu Wen-Hui Shi Fang-Fang Wu Xie-Hong Cao School of Materials Science and Engineering Zhejiang University of Technology center for Membrane Separation and Water Science and Technology College of Chemical EngineeringZhejiang University of Technology

With the growing energy demand associated with high safety and low-cost requirement,aqueous zinc-ion batteries(AZIBs) have been considered as one of the most promising next-generation batteries.However,some key issues,such as uncontrollable dendrites growth,severe corrosion,hydrogen evolution and side reactions of Zn anodes during charge/discharge process,have hindered its pragmatic applications.Two-dimensional(2D) materials hold advantages of unique physical and chemical properties,large surface areas and abundant active sites,which have been successfully used to overcome the above shortcomings of Zn anodes in recent years.In this review,the issues and challenges of Zn anodes are outlined.Then,the state-of-the-art progress on Zn anodes modification based on 2D materials such as graphene,2D metal carbides and nitrides(MXenes),2D metal-organic frameworks(MOFs),2D covalent organic frameworks(COFs),2D transition metal compounds and other 2D materials is discussed in detail.Finally,the perspectives of employing 2D materials in highly reversible Zn anodes are summarized and discussed.

关键词： 2D materials Aqueous zinc-ion battery Zn anodes Dendrites growth

Calcification-associated molecular traits and therapeutic strategies in hormone receptor-positive HER2-negative breast cancer

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cancer Biology & Medicine 2024年第5期21卷 400-415页

作者： Yuwei Li Yuzheng Xu Caijin Lin Xi Jin Ding Ma Zhiming Shao Department of Breast Surgery Fudan University Shanghai Cancer Center Key Laboratory of Breast cancer in Shanghai Fudan University Shanghai Cancer Center Department of Oncology Shanghai Medical College Fudan University

Objective: Mammographic calcifications are a common feature of breast cancer, but their molecular characteristics and treatment implications in hormone receptor-positive(HR+)/human epidermal growth factor receptor 2-negative(HER2-) breast cancer remain unclear.Methods: We retrospectively collected mammography records of an HR+/HER2-breast cancer cohort(n = 316) with matched clinicopathological, genomic, transcriptomic, and metabolomic data. On the basis of mammographic images, we grouped tumors by calcification status into calcification-negative tumors, tumors with probably benign calcifications, tumors with calcification of lowmoderate suspicion for maligancy and tumors with calcification of high suspicion for maligancy. We then explored the molecular characteristics associated with each calcification status across multiple dimensions.Results: Among the different statuses, tumors with probably benign calcifications exhibited elevated hormone receptor immunohistochemical staining scores, estrogen receptor(ER) pathway activation, lipid metabolism, and sensitivity to endocrine therapy. Tumors with calcifications of high suspicion for malignancy had relatively larger tumor sizes, elevated lymph node metastasis incidence, Ki-67 staining scores, genomic instability, cell cycle pathway activation, and may benefit from cyclin-dependent kinase 4 and 6(CDK4/6) inhibitors.Conclusions: Our research established links between tumor calcifications and molecular features, thus proposing potential precision treatment strategies for HR+/HER2-breast cancer.

关键词： HR+/HER2-breast cancer mammographic calcifications molecular features precision treatment ENDOCRINE THERAPY SENSITIVITY REPAIR

A spaceborne advanced storage system for remote sensing microsatellites

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Frontiers of Information Technology & Electronic Engineering 2024年第4期25卷 600-615页

作者： Shilei TU Huiquan WANG Yue HUANG Zhonghe JIN Micro-Satellite Research center Zhejiang UniversityHangzhou 310027China Key Laboratory of Micro-Nano Satellite Research Zhejiang ProvinceHangzhou 310027China

With the development of satellite miniaturization and remote sensing,the establishment of microsatellite constellations is an inevitable trend.Due to their limited size,weight,and power,spaceborne storage systems with excellent scalability,performance,and reliability are still one of the technical bottlenecks of remote sensing microsatellites.Based on the commercial off-the-shelf field-programmable gate array and memory devices,a spaceborne advanced storage system(SASS)is proposed in this paper.This work provides a dynamic programming,queue scheduling multiple-input multiple-output cache technique and a high-speed,high-reliability NAND flash controller for multiple microsatellite payload data.Experimental results show that SASS has outstanding scalability with a maximum write rate of 2429 Mb/s and preserves at least 78.53%of the performance when a single NAND flash fails.The scheduling technique effectively shortens the data scheduling time,and the data remapping method of the NAND flash controller can reduce the retention error by at least 50.73%and the program disturbance error by at least 37.80%.

关键词： Microsatellite Spaceborne advanced storage system(SASS) Scalability Performance Reliability

New role of platelets in schizophrenia:predicting drug response

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General Psychiatry 2024年第2期37卷 197-206页

作者： Yamin Zhang Yanghao Zheng Peiyan Ni Sugai Liang Xiaojing Li Hua Yu Wei Wei Xueyu Qi Xueli Yu Rui Xue Liansheng Zhao Wei Deng Qiang Wang Wanjun Guo Tao Li Department of Neurobiology Zhejiang University School of Medicine Affiliated Mental Health Centre&Hangzhou Seventh People's HospitalHangzhouZhejiangChina Liangzhu Laboratory Zhejiang University MOE Frontier Science Center for Brain Science and Brain Machine IntegrationHangzhouZhejiangChina Mental Health center and Psychiatric Laboratory West China Hospital of Sichuan UniversityChengduSichuanChina

Background Elevated platelet count(PLTc)is associated with first-episode schizophrenia and adverse outcomes in individuals with precursory psychosis.However,the impact of antipsychotic medications on PLTc and its association with symptom improvement remain unclear.Aims We aimed to investigate changes in PLTc levels following antipsychotic treatment and assess whether PLTc can predict antipsychotic responses and metabolic changes after accounting for other related variables.Methods A total of 2985 patients with schizophrenia were randomised into seven groups.Each group received one of seven antipsychotic treatments and was assessed at 2,4 and 6 weeks.Clinical symptoms were evaluated using the positive and negative syndrome scale(PANSS).Additionally,we measured blood cell counts and metabolic parameters,such as blood lipids.Repeated measures analysis of variance was used to examine the effect of antipsychotics on PLTc changes,while structural equation modelling was used to assess the predictive value of PLTc on PANSS changes.Results PLTc significantly increased in patients treated with aripiprazole(F=6.00,p=0.003),ziprasidone(F=7.10,p<0.001)and haloperidol(F=3.59,p=0.029).It exhibited a positive association with white blood cell count and metabolic indicators.Higher baseline PLTc was observed in non-responders,particularly in those defined by the PANSS-negative subscale.In the structural equation model,PLTc,white blood cell count and a latent metabolic variable predicted the rate of change in the PANSS-negative subscale scores.Moreover,higher baseline PLTc was observed in individuals with less metabolic change,although this association was no longer significant after accounting for baseline metabolic values.Conclusions Platelet parameters,specifically PLTc,are influenced by antipsychotic treatment and could potentially elevate the risk of venous thromboembolism in patients with schizophrenia.Elevated PLTc levels and associated factors may impede symptom improvement by promoting inflammation.Given PLTc’s easy measur

关键词： schizophrenia assessed treatment