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Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi Chen department of Sport Medicine Huashan HospitalFudan UniversityShanghaiChina department of Orthopedic Surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina department of Basic Medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

Glycolytic dysregulation in Alzheimer's disease:unveiling new avenues for understanding pathogenesis and improving therapy

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Neural Regeneration Research 2025年第8期20卷 2264-2278页

作者： You Wu Lijie Yang Wanrong Jiang Xinyuan Zhang Zhaohui Yao department of Geriatrics Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Alzheimer's disease poses a significant global health challenge owing to the progressive cognitive decline of patients and absence of curative *** current therapeutic strategies,primarily based on cholinesterase inhibitors and N-methyl-Daspartate receptor antagonists,offer limited symptomatic relief without halting disease progression,highlighting an urgent need for novel research directions that address the key mechanisms underlying Alzheimer's *** studies have provided insights into the critical role of glycolysis,a fundamental energy metabolism pathway in the brain,in the pathogenesis of Alzheimer's *** in glycolytic processes within neurons and glial cells,including microglia,astrocytes,and oligodendrocytes,have been identified as significant contributors to the pathological landscape of Alzheimer's *** changes impact neuronal health and function,thus offering promising targets for therapeutic *** purpose of this review is to consolidate current knowledge on the modifications in glycolysis associated with Alzheimer's disease and explore the mechanisms by which these abnormalities contribute to disease onset and *** focus on the pathways through which glycolytic dysfunction influences Alzheimer's disease pathology should provide insights into potential therapeutic targets and strategies that pave the way for groundbreaking treatments,emphasizing the importance of understanding metabolic processes in the quest for clarification and management of Alzheimer's disease.

关键词： Alzheimer’s disease glial cells glycolysis neuronal metabolism pathogenesis therapeutic targets

HBx activates FasL and mediates HepG2 cell apoptosis through MLK3-MKK7-JNKs signal module

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World Journal of Gastroenterology 2012年第13期18卷 1485-1495页

作者： Ren-Xian Tang Fan-Yun Kong Bao-Feng Fan Xiao-Mei Liu Hong-Juan You Peng Zhang Kui-Yang Zheng department of Pathogenic Biology and Lab of infection and Immunology Xuzhou Medical CollegeXuzhou 221002Jiangsu ProvinceChina

AIM： To investigate the possible mechanism by which hepatitis B virus X protein （HBx） mediates apoptosis of HepG2 cells. METHODS： HBx expression vector pcDNA3.1-X was transfected into HepG2 cells to establish an HBx high- expression cellular model as pcDNA3.1-X transfected group. The pcDNA3.1-X and pSilencer3.1-shHBX （HBx antagonist） were cotransfected into HepG2 cells to es- tablish an HBx low-expression model as RNAi group. Untransfected HepG2 cells and HepG2 cells transfected with negative control plasmid were used as controls. Apoptosis rate, the expression of Fas/FasL signaling pathway-related proteins and the phosphorylation lev- els of MLK3, MKK7 and JNKs, which are upstream molecules of death receptor pathways and belong to the family of mitogen-activated protein kinases （MAPKs）,were measured in each group RESULTS： Compared with HepG2 cell group and RNAi group, apoptosis rate, the expression of Fas and FasL proteins, and the activation of MLK3, MKK7 and 3NKs were increased in the pcDNA3.1-X transfected group. The activation of JNKs and expression of FasL protein were inhibited in the pcDNA3.1-X transfected group when treated with a known JNK inhibitor, SP600125. When authors treated pcDNA3.1-X transfected group with K252a, a known MLK3 inhibitor, the activation of MLK3, MKK7 and 3NKs as well as expression of FasL protein was inhibited. Furthermore, cell apoptosis rate was also significantly declined in the presence of K252a in the pcDNA3.1-X transfected group. CONCLUSION： HBx can induce HepG2 cell apoptosis via a novel active MLK3-MKK7-JNKs signaling module to upregulate FasL protein expression.

关键词： Hepatitis B virus X protein MLK3 FasL HepG2cell Apoptosis

Value of ^(18)F-FDG PET/CT and MRI in diagnosing primary endometrial small cell carcinoma

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Chinese Journal of Cancer Research 2014年第5期26卷 627-631页

作者： Qi Wan Qian Jiao Xinchun Li Jiaxuan Zhou Qiao Zou Yingshi Deng department of Radiology The First Affiliated Hospital of Guangzhou Medical University infection department The First Affiliated Hospital of Guangzhou Medical University

Primary small cell carcinoma（SCC） is a group of aggressive neoplasms that mainly arise from the lung and digestive tract. Endometrial small cell carcinoma（ESCC） is extremely rare. To our knowledge, less than 90 cases have been reported, and most of these reports were dedicated to describing the clinicopathologic or immunochemical features of ESCC. Herein, we present a new case of ESCC involving a 51-year-old woman and mainly focus on the magnetic resonance imaging（MRI） and positron emission tomography/computed tomography（PET/CT） findings. MRI showed that the uterus was significantly enlarged（11.6 cm × 11.1 cm × 14.4 cm）, and a giant irregular mass（7.5 cm × 8.4 cm × 8.5 cm） was observed in the uterine cavity. The lesion demonstrated an extremely low apparent diffusion coefficient（ADC） value [（0.553±0.088）×10^–3 mm^2/s] and a high FDG uptake value（22.7）. Multiple metastatic lymph nodes（LNs） were identified at different positions, with diameters ranging from 0.3 to 2.8 cm and a maximum standardized uptake value（SUV max） ranging from 6.9 to 19.3.

关键词： Endometrial small cell carcinoma(ESCC) magnetic resonance imaging(MRI) positron emission tomography/computed tomography(PET/CT)

Movement analysis in the diagnosis and management of Parkinson’s disease

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Neural Regeneration Research 2025年第2期20卷 485-486页

作者： Johannes Burtscher Nicolas Bourdillon Jules MJanssen Daalen Aurélien Patoz Julien FBally Martin Kopp Davide Malatesta Bastiaan RBloem Institute of Sport Sciences University of LausanneLausanneSwitzerland Radboud University Medical Center Department of NeurologyDonders Institute for BrainCognition and BehaviorCenter of Expertise for Parkinson and Movement DisordersNijmegenThe Netherlands Radboud University Medical Center Department of Medical BioSciencesNijmegenThe Netherlands Research and Development department Volodalen Swiss Sport LabAigleSwitzerland Service of Neurology Department of Clinical NeurosciencesLausanne University Hospital(CHUV)and University of Lausanne(UNIL)LausanneSwitzerland department of Sport Science University of InnsbruckInnsbruckAustria

Challenges in the diagnosis and treatment of Parkinson’s disease:Parkinson’s disease(PD)is an increasingly prevalent neurodegenerative disease,at first sight primarily characterized by motor symptoms,although non-motor symptoms also constitute a major part of the overall ***,this disease cannot be diagnosed reliably until a large part of the vulnerable dopaminergic neurons has been irretrievably lost,and the disease progresses *** biological criteria for PD have been proposed recently and might eventually improve early diagnosis,but they require further validation,and their use will initially be restricted to a research environment(Darweesh et al.,2024).

关键词： diagnosis Clinical eventually

Scheduling optimization of task allocation in integrated manufacturing system based on task decomposition

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Journal of Systems Engineering and Electronics 2016年第2期27卷 422-433页

作者： Aijun Liu Michele Pfund John Fowler department of management Engineering School of Economics & Management Xidian University department of Supply Chain management W.P. Carey School of Business Arizona State University

How to deal with the collaboration between task decomposition and task scheduling is the key problem of the integrated manufacturing system for complex products. With the development of manufacturing technology, we can probe a new way to solve this problem. Firstly, a new method for task granularity quantitative analysis is put forward, which can precisely evaluate the task granularity of complex product cooperation workflow in the integrated manufacturing system, on the above basis; this method is used to guide the coarse-grained task decomposition and recombine the subtasks with low cohesion coefficient. Then, a multi-objective optimieation model and an algorithm are set up for the scheduling optimization of task scheduling. Finally, the application feasibility of the model and algorithm is ultimately validated through an application case study.

关键词： integrated manufacturing system optimization task decomposition task scheduling

Frontiers in B-cell immunology

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Cellular & Molecular Immunology 2013年第2期10卷 95-96页

作者： Liwei Lu department of Pathology and Center for infection and Immunology The University of Hong Kong Hong Kong China

During the last several decades, significant progress has been made in understanding the roles of B cells inimmunity and autoimmunity. B-cell development, occurring in the bone marrow, is a complex dynamic process involving immunoglobulin （Ig） gene rearrangement and B-cell receptor （BCR） expression. Early progenitor B （pro-B） cells initiate DNA rearrangement at their Ig heavy chain loci, resulting in the synthesis of μ-chains in the cytoplasm and the assembly of the precursor B-cell receptor （pre-BCR）. Following successful rearrangement of light chain genes, these precursor B （pre-B） cells differentiate into immature B cells when whole IgM mole- cules are expressed as the functional BCR on the cell surface.

关键词： Frontiers B-cell immunology

A MULTI-PERIOD PRICING AND INVENTORY CONTROL MODEL

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Journal of Systems Science & Complexity 2010年第2期23卷 249-260页

作者： Juliang ZHANG Jian CHEN department of Logistics management School of Economics and Management Beijing Jiaotong UniversityBeijing 100044 China. department of management Science and Engineering School of Economics and Management Tsinghua University Beijing 100084 China.

The authors analyze a finite horizon,single product,period review model in which pricingand inventory decisions are made *** in different periods are random variablesthat are independent of each other and their distributions depend on the product *** andordering decisions are made at the beginning of each period and all shortage are *** is a convex function of the amount *** objective is to find an inventory and pricing policymaximizing expected discounted profit over the finite *** authors characterize the structure ofthe optimal combined pricing and inventory strategy for this ***,the authors demonstratehow the profit-to-go function,order up to level,reorder point and optimal price change with respectto state and time.

关键词： Convex cost function planning horizon pricing stochastic inventory management uncertainty.

Landslide Susceptibility Mapping Using RBFN-Based Ensemble Machine Learning Models

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 467-500页

作者： Landslide Susceptibility Mapping Using RBFN-Based Ensemble Machine Learning Models Duc-Dam Nguyen Nguyen Viet Tiep Quynh-Anh Thi Bui Hiep Van Le Indra Prakash Romulus Costache Manish Pandey Binh Thai Pham Faculty of Civil Engineering University of Transport TechnologyThanh XuanHa Noi100000Vietnam Faculty of Hydraulic Engineering Hanoi University of Civil EngineeringHa Noi100000Vietnam DDG(R)Geological Survey of India Gandhinagar382010India Research Institute of the University of Bucharest Bucharest050663Romania National Institute of Hydrology and Water management Bucharest013686Romania department of Civil Engineering Transilvania University of BrasovBrasov500152Romania Danube Delta National Institute for Research and Development Tulcea820112Romania Marwadi University Research Center(MURC) Marwadi UniversityRajkotGujaratBharat360003India department of Civil Engineering Faculty of Engineering&TechnologyMarwadi UniversityRajkotGujaratBharat360003India

This study was aimed to prepare landslide susceptibility maps for the Pithoragarh district in Uttarakhand,India,using advanced ensemble models that combined Radial Basis Function Networks(RBFN)with three ensemble learning techniques:DAGGING(DG),MULTIBOOST(MB),and ADABOOST(AB).This combination resulted in three distinct ensemble models:DG-RBFN,MB-RBFN,and ***,a traditional weighted method,Information Value(IV),and a benchmark machine learning(ML)model,Multilayer Perceptron Neural Network(MLP),were employed for comparison and *** models were developed using ten landslide conditioning factors,which included slope,aspect,elevation,curvature,land cover,geomorphology,overburden depth,lithology,distance to rivers and distance to *** factors were instrumental in predicting the output variable,which was the probability of landslide *** analysis of the models’performance indicated that the DG-RBFN model,with an Area Under ROC Curve(AUC)of 0.931,outperformed the other *** AB-RBFN model achieved an AUC of 0.929,the MB-RBFN model had an AUC of 0.913,and the MLP model recorded an AUC of *** results suggest that the advanced ensemble ML model DG-RBFN was more accurate than traditional statistical model,single MLP model,and other ensemble models in preparing trustworthy landslide susceptibility maps,thereby enhancing land use planning and decision-making.

关键词： Landslide susceptibility map spatial analysis ensemble modelling information values(IV)