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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3585-3599页

作者： De-Gang Li Jia-Peng Jiang fan-ye chen Wei Wu Jun Fu Gong-He Wang Yu-Bo Li Department of Gastrointestinal and Anorectal Surgery The First Affiliated Hospital of Guangxi University of Chinese MedicineNanning 530023Guangxi Zhuang Autonomous RegionChina

BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract *** is the first-line therapy for GIST *** resistance limits the long-term effectiveness of *** regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse *** To further investigate the mechanism of IGF2 specific to *** IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)*** IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry *** used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated *** injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of *** Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug *** cells with high expression of IGF2 had increased proliferation and migration,invasiveness and *** of IGF2 significantly inhibited those *** addition,OEIGF2 promoted GIST metastasis in vivo in nude ***2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver *** cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib ***,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in *** IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.

关键词： Insulin-like growth factor 2 Gastrointestinal stromal tumors IGF1R Glycolysis Imatinib resistance

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Quantitative Trait Loci for Yield Traits Located Between Hd3a and Hd1 on Short Arm of Chromosome 6 in Rice

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Rice science 2011年第4期18卷 257-264页

作者： ye-yang fan chen chen Ji-rong WU Shi-hua chenG Jie-yun ZHUANG Chinese National Center for Rice Improvement / State Key Laboratory of Rice Biology China National Rice Research Institute Hangzhou 310006 China

QTLs for heading date located in the regions of Hd3a and Hd1 were detected using an F2:3 population developed from a residual heterozygous line(RHL) identified from the recombinant inbred lines of the indica rice cross Zhenshan 97B /Milyang *** in coupling phase between the QTLs for heading date and yield traits detected in a previous study was *** more F2:3 populations were each developed from an RHL that was homozygous at Hd3a and Hd1 but heterozygous in a portion of the intervals flanked by Hd3a and *** for grain yield per plant,number of panicles per plant,number of grains per panicle and 1000-grain weight were detected in the heterozygous *** sets of near-isogenic lines(NILs) with overlapping heterogenous segments covering the interval RM6119-RM6779 were developed and used to validate and delimitate the QTLs.A QTL conferring a consistent effect for the number of grains per panicle was located within the interval RM19615-RM19652 that corresponded to a 514.4-kb region on chromosome *** same region might have pleiotropic effects on the other three yield-related traits analyzed,but the effects varied greatly among different populations and across different *** study suggests that it is possible to develop a population with little variation on heading date and to identify QTLs for yield traits that might not be associated with heading date by using the information of physical positions of DNA markers and cloned genes.

关键词： rice yield trait heading date quantitative trait locus residual heterozygous line

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Avoidance of Linkage Drag Between Blast Resistance Gene and the QTL Conditioning Spikelet Fertility Based on Genotype Selection Against Heading Date in Rice

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Rice science 2009年第1期16卷 21-26页

作者： LIU Wen-qiang fan ye-yang chen Jie SHI Yong-feng Wu Jian-li Chinese National Center for Rice Improvement/State Key Laboratory for Rice Biology China National Rice Research Institute Hangzhou 310006 China

Previous study showed that a linkage drag between a blast resistance gene Pi25（t） and QTLs conditioning spikelet fertility （qSF-6） and number of filled grains per panicle （qNFGP-6） was detected on the short arm of chromosome 6. A larger population was used for further verification, and the results confirmed the linkage drag between the blast resistance gene and QTL conditioning spikelet fertility, other than QTL conditioning number of filled grains per panicle. Breakdown or avoidance of the linkage drag could be achieved by selection against the genotype background of a heading-date gene （qHD-7） that resided in the region between RM2 and RM214 on chromosome 7. For further validation, two lines with almost identical genotypes on all chromosomal regions except the Pi25（t） region on chromosome 6 were chosen to develop a new population The results showed that qSF-6 could be further subdivided into qSF-6-1 and qSF-6-2. When the genotype of the region between RM2 and RM214 was from rice variety Zhong 156, the linkage drag between Pi25（t） and qSF-6-2 was detected and the allele of qSF-6-2 from rice variety Gumei 2 reduced the spikelet fertility. When the genotype of the region between RM2 and RM214 was from Gumei 2, no linkage drag was detected. This indicates that the linkage drag between the blast resistance gene and the QTL conditioning spikelet fertility could be broken down or avoided under a certain background genotype selection against heading-date and provides a marker aided solution for high level of blast resistance and yield breeding in rice and other crops as well.

关键词： rice (Oryza sativa) linkage drag blast resistance quantitative trait locus spikelet fertility heading date

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The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration Research 2025年第5期20卷 1505-1512页

作者： Jieying Wu Shan ye Xiangyi Liu Yingsheng Xu Dongsheng fan Department of Neurology Peking University Third HospitalBeijingChina Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative Diseases BeijingChina Key Laboratory for Neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor *** bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to ***,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is *** address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral *** used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis *** factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb *** results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis *** findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

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Netrin-1 signaling pathway mechanisms in neurodegenerative diseases

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Neural Regeneration Research 2025年第4期20卷 960-972页

作者： Kedong Zhu Hualong Wang Keqiang ye Guiqin chen Zhaohui Zhang Department of Neurology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina Department of Neurology The First Hospital of Hebei Medical UniversityBrain Aging and Cognitive Neuroscience Laboratory of Heibei ProvinceShijiazhuangHebei ProvinceChina Faculty of Life and Health Sciences Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal *** profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic *** amounts of evidence highlight several key points:(1)Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer’s disease and Parkinson’s disease,and potentially,similar alterations occur in humans.(2)Genetic mutations of Netrin-1 receptors increase an individuals’susceptibility to neurodegenerative disorders.(3)Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function.(4)Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of *** findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative *** a comprehensive review of Netrin-1 signaling pathways,our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.

关键词： Alzheimer’s disease axon guidance colorectal cancer Netrin-1 receptors Netrin-1 signaling pathways Netrin-1 neurodegenerative diseases neuron survival Parkinson’s disease UNC5C

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Coordinated Control Strategy of New Energy Power Generation System with Hybrid Energy Storage Unit

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Energy Engineering 2025年第1期122卷 167-184页

作者： Yun Zhang ZifenHan Biao Tian Ning chen Yi fan School of Mechano-Electronic Engineering Xidian UniversityXi’an710071China Electric Power Control Center State Grid Gansu Electric Power CompanyLanzhou730030China Electric Power Control Center State Grid Gansu Electric Power Company Zhangye Power Supply BranchZhangye734000China

The new energy power generation is becoming increasingly important in the power *** as photovoltaic power generation has become a research hotspot,however,due to the characteristics of light radiation changes,photovoltaic power generation is unstable and random,resulting in a low utilization rate and directly affecting the stability of the power *** solve this problem,this paper proposes a coordinated control strategy for a newenergy power generation system with a hybrid energy storage unit based on the lithium iron phosphate-supercapacitor hybrid energy storage ***,the variational mode decomposition algorithm is used to separate the high and low frequencies of the power signal,which is conducive to the rapid and accurate suppression of the power fluctuation of the energy storage ***,the fuzzy control algorithm is introduced to balance the power between energy *** this paper,the actual data is used for simulation,and the simulation results show that the strategy realizes the effective suppression of the bus voltage fluctuation and the accurate control of the internal state of the energy storage unit,effectively avoiding problems such as overshoot and over-discharge,and can significantly improve the stability of the photovoltaic power generation systemand the stability of the Direct Current *** is of great significance to promote the development of collaborative control technology for photovoltaic hybrid energy storage units.

关键词： Photovoltaic power suppression hybrid energy storage unit variationalmodal decomposition fuzzy control power distribution control

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Dynamic behaviors of graphene platelets-reinforced metal foam piezoelectric beams with velocity feedback control

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Applied Mathematics and Mechanics(English Edition) 2025年第1期46卷 63-80页

作者： Jie chen Xinyue ZHANG Mingyang fan School of Mathematics Statistics and Mechanics Beijing University of Technology College of Mechanical & Energy Engineering Beijing University of Technology

Graphene platelets(GPLs)-reinforced metal foam structures enhance the mechanical properties while maintaining the lightweight characteristics of metal foams. Further bonding piezoelectric actuator and sensor layers on the surfaces of GPLs-reinforced metal foam beams enables active vibration control, greatly expanding their applications in the aerospace industry. For the first time, this paper investigates the vibration characteristics and active vibration control of GPLs-reinforced metal foam beams with surfacebonded piezoelectric layers. The constant velocity feedback scheme is used to design the closed-loop controller including piezoelectric actuators and sensors. The effects of the GPLs on the linear and nonlinear free vibrations of the beams are numerically *** Newmark-β method combined with Newton's iteration technique is used to calculate the nonlinear responses of the beams under different load forms including harmonic loads,impact loads, and moving loads. Additionally, special attention is given to the vibration reduction performance of the velocity feedback control on the responses of the beam.

关键词： Piezoelectric actuators

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Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

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Neural Regeneration Research 2025年第6期20卷 1541-1554页

作者： Jinmei ye Cong Duan Jiaxin Han Jinrong chen Ning Sun Yuan Li Tifei Yuan Daihui Peng Division of Mood Disorder Shanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Department of Psychiatry First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Shanghai Key Laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina Co-Innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

关键词： biomarker cytokine exosomes inflammasome major depressive disorder microglia mitochondrial DNA mitochondrial dysfunction neuroinflammation Toll-like receptor

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Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model

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Neural Regeneration Research 2025年第3期20卷 858-872页

作者： Xintian Ding Chun chen Heng Zhao Bin Dai Lei ye Tao Song Shuai Huang Jia Wang Tao You Department of Orthopedics The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Orthopedics Provincial Hospital Affiliated to Anhui Medical UniversityHefeiAnhui ProvinceChina

Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2(SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

关键词： apoptosis glycolysis inflammatory response microglia neurons polarization spinal cord injury Src homology 2-containing protein tyrosine phosphatase 2

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Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke

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Neural Regeneration Research 2025年第2期20卷 491-502页

作者： Shuai Feng Juanji Li Tingting Liu Shiqi Huang Xiangliang chen Shen Liu Junshan Zhou Hongdong Zhao ye Hong Department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Neurology Nanjing Jinling HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina

Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion ***-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s ***,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic *** address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke ***,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting *** observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/***,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated ***-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective ***,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte *** findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.

关键词： inflammation ischemia/reperfusion injury ischemic stroke low-density lipoprotein receptor neuroprotective astrocytes neurotoxic astrocytes NLRP3 inflammasome polarization

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