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

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

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Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

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Neural Regeneration Research 2025年第1期20卷 93-106页

作者： Yujie Yang Xinyi Li Jiaying Lu Jingjie Ge Mingjia Chen Ruixin Yao Mei Tian Jian Wang Fengtao Liu Chuantao Zuo Key Laboratory of Arrhythmias Ministry of EducationDepartment of Medical GeneticsShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina department of Neurology National Research Center for Aging and MedicineNational Center for Neurological Disordersand State Key Laboratory of Medical NeurobiologyHuashan HospitalFudan UniversityShanghaiChina department of Nuclear Medicine&PET Center National Center for Neurological Disordersand National Clinical Research Center for Aging and MedicineHuashan HospitalFudan UniversityShanghaiChina International Human Phenome Institutes(shanghai) ShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of *** review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest *** conducted a thorough literature search using reputable databases such as PubMed and Web of *** criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical *** findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting ***,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo *** validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic *** summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

关键词： aromatic amino acid decarboxylase brain imaging dopamine transporter Parkinson’s disease parkinsonism positron emission tomography presynaptic dopaminergic function vesicle monoamine transporter type 2

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AZD1775 synergizes with sLC7A11 inhibition to promote ferroptosis

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science China Life sciences 2025年第1期 204-218页

作者： Chen Xiong Hong Ling Yingdan Huang Hanzhi Dong Bangxiang Xie Qian Hao Xiang Zhou fudan university shanghai Cancer Center and Institutes of Biomedical sciences Fudan University department of Oncology Shanghai Medical CollegeFudan University department of Breast surgery Fudan University Shanghai Cancer CenterFudan University department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer Key Laboratory of Breast Cancer in shanghai Fudan University Shanghai Cancer CenterFudan University shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

Tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of sLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the sLC7A11 promoter by repressing the expression of the histone methyltransferase sETDB1, thereby enhancing NRF2-mediated sLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited sLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of sLC7A11 through the WEE1-sETDB1 cascade and NRF2-induced transcription, and inhibition of sLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

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Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

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Neural Regeneration Research 2025年第9期20卷 2727-2736页

作者： Yujia Liu Xue Han Yan su Yiming Zhou Minhui Xu Jiyan Xu Zhengliang Ma Xiaoping Gu Tianjiao Xia department of Anesthesiology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina Medical school Nanjing UniversityNanjingJiangsu ProvinceChina Jiangsu Key Laboratory of Molecular Medicine Nanjing UniversityNanjingJiangsu ProvinceChina state Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjingJiangsu ProvinceChina department of Anesthesiology Zhongshan HospitalFudan UniversityShanghaiChina

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of *** date,there are no viable treatment options for postoperative cognitive *** identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future *** identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GsE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial *** dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub ***,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re *** were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning *** addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western *** with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expr

关键词： Chil1 hippocampus learning and memory M2 microglia neuroinflammation postoperative cognitive dysfunction(POCD) recombinant CHI3L1

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Resting-state brain network remodeling after different nerve reconstruction surgeries:a functional magnetic resonance imaging study in brachial plexus injury rats

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Neural Regeneration Research 2025年第5期20卷 1495-1504页

作者： Yunting Xiang Xiangxin Xing Xuyun Hua Yuwen Zhang Xin Xue Jiajia Wu Mouxiong Zheng He Wang Jianguang Xu school of Rehabilitation science Shanghai University of Traditional Chinese MedicineShanghaiChina Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation Ministry of EducationShanghaiChina department of Rehabilitation Medicine Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina department of Traumatology and Orthopedics Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghaiChina Institute of science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghaiChina Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence(fudan university) Ministry of EducationShanghaiChina Human Phenome Institute Fudan UniversityShanghaiChina

Distinct brain remodeling has been found after different nerve reconstruction strategies,including motor representation of the affected ***,differences among reconstruction strategies at the brain network level have not been *** study aimed to explore intranetwork changes related to altered peripheral neural pathways after different nerve reconstruction surgeries,including nerve repair,endto-end nerve transfer,and end-to-side nerve ***–Dawley rats underwent complete left brachial plexus transection and were divided into four equal groups of eight:no nerve repair,grafted nerve repair,phrenic nerve end-to-end transfer,and end-to-side transfer with a graft sutured to the anterior upper ***-state brain functional magnetic resonance imaging was obtained 7 months after *** independent component analysis algorithm was utilized to identify group-level network components of interest and extract resting-state functional connectivity values of each voxel within the *** in intra-network resting-state functional connectivity were compared among the *** muscle reinnervation was assessed by behavioral observation(elbow flexion)and *** results showed that alterations in the sensorimotor and interoception networks were mostly related to changes in the peripheral neural *** repair was related to enhanced connectivity within the sensorimotor network,while end-to-side nerve transfer might be more beneficial for restoring control over the affected limb by the original motor *** thalamic-cortical pathway was enhanced within the interoception network after nerve repair and end-to-end nerve *** areas related to cognition and emotion were enhanced after end-to-side nerve *** study revealed important brain networks related to different nerve *** networks may be potential targets for enhancing motor recovery.

关键词： brain functional networks end-to-end nerve transfer end-to-side nerve transfer independent component analysis nerve repair peripheral plexus injury resting-state functional connectivity

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Role of the globus pallidus in motor and non-motor symptoms of Parkinson's disease

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Neural Regeneration Research 2025年第6期20卷 1628-1643页

作者： Yimiao Jiang Zengxin Qi Huixian Zhu Kangli shen Ruiqi Liu Chenxin Fang Weiwei Lou Yifan Jiang Wangrui Yuan Xin Cao Liang Chen Qianxing Zhuang department of Physiology School of MedicineNantong UniversityNantongJiangsu ProvinceChina department of Neurosurgery Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiChina National Center for Neurological Disorders ShanghaiChina shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration ShanghaiChina state Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain science Institute of Brain ScienceFudan UniversityShanghaiChina

The globus pallidus plays a pivotal role in the basal ganglia circuit. Parkinson's disease is characterized by degeneration of dopamine-producing cells in the substantia nigra, which leads to dopamine deficiency in the brain that subsequently manifests as various motor and non-motor symptoms. This review aims to summarize the involvement of the globus pallidus in both motor and non-motor manifestations of Parkinson's disease. The firing activities of parvalbumin neurons in the medial globus pallidus, including both the firing rate and pattern, exhibit strong correlations with the bradykinesia and rigidity associated with Parkinson's disease. Increased beta oscillations, which are highly correlated with bradykinesia and rigidity, are regulated by the lateral globus pallidus. Furthermore,bradykinesia and rigidity are strongly linked to the loss of dopaminergic projections within the cortical-basal ganglia-thalamocortical loop. Resting tremors are attributed to the transmission of pathological signals from the basal ganglia through the motor cortex to the cerebellum-ventral intermediate nucleus circuit. The cortico–striato–pallidal loop is responsible for mediating pallidi-associated sleep disorders. Medication and deep brain stimulation are the primary therapeutic strategies addressing the globus pallidus in Parkinson's disease. Medication is the primary treatment for motor symptoms in the early stages of Parkinson's disease, while deep brain stimulation has been clinically proven to be effective in alleviating symptoms in patients with advanced Parkinson's disease,particularly for the movement disorders caused by levodopa. Deep brain stimulation targeting the globus pallidus internus can improve motor function in patients with tremordominant and non-tremor-dominant Parkinson's disease, while deep brain stimulation targeting the globus pallidus externus can alter the temporal pattern of neural activity throughout the basal ganglia–thalamus network. Therefore, the comp

关键词： anxiety basal ganglia bradykinesia deep brain stimulation depression globus pallidus externus globus pallidus internus lateral globus pallidus medial globus pallidus neural circuit Parkinson's disease

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Group B streptococcus causes severe sepsis in term neonates:8 years experience of a major Chinese neonatal unit

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World Journal of Pediatrics 2017年第4期13卷 314-320页

作者： Ying Dong si-Yuan Jiang Qi Zhou Yun Cao department of neonatology Children's Hospital of Fudan UniversityShanghaiChina

Background:In contrast to industrialized countries,the clinical characteristics of neonatal sepsis caused by Group B streptococcus (GBs) are largely unexplored in ***:A retrospective case series study was performed at a high-capacity neonatal unit in shanghai,China from January 2008 to December *** characteristics of neonates with culture-proven GBs sepsis and antibiotic susceptibility of isolated strains were ***:Forty-three term neonates were included during the study *** majority (74.4%) had early-onset sepsis with symptoms of respiratory *** was significantly more common in lateonset sepsis than in early-onset sepsis (81.5% vs.18.8%,Ps (n=16)developed severe sepsis,defined as sepsis with organ dysfunctions,and respiratory dysfunction/failure was the most common (32.6%).The in-hospital mortality rate of GBs sepsis was 4.7%.Neonates who progressed to severe sepsis had significantly lower pH level at the onset of symptoms than those who did not (7.26±0.12 vs.7.39±0.05,P=-0.006).Treatment of severe GBs sepsis required lots of medical resources including extracorporeal membrane *** tested GBs strains were susceptible to penicillin,but the rate of resistance to clindamycin (84.0%) and erythromycin (88.0%) was ***:GBs as a pathogen for neonatal sepsis has been receiving little attention in *** data demonstrated that GBs sepsis was likely to be *** recognition followed by antibiotics and adequate supportive therapies was critical for successful *** clinicians should be aware of GBs infection when treating neonatal sepsis,especially in the absence of universal maternal GBs screening.

关键词： drug resistance neonate sepsis streptococcus agalactiae

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Factors relating caesarean section to persistent pulmonary hypertension of the newborn

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World Journal of Pediatrics 2017年第6期13卷 517-527页

作者： Niralee Babooa Wen-Jing shi Chao Chen department of neonatology Children Hospital of Fudan UniversityShanghaiChina

Background:several studies have clearly demonstrated a significantly higher incidence of persistent pulmonary hypertension of the newborn (PPHN) in neonates delivered by caesarean section (Cs) compared to those delivered *** pathophysiological factors underlying the link between Cs and PPHN are still poorly *** this review,we describe the mechanisms that could explain the association between Cs delivery and subsequent PPHN,as well as potential preventive *** sources:A literature search was conducted by electronic scanning of databases such as PubMed and Web of science using the key words 'persistent pulmonary hypertension of the newborn','caesarean section','iatrogenic prematarity','oxidative stress','late preterm','labor' and 'vasoaetive agents'.Results:Iatrogenic prematurity,higher rates of late preterm delivery and lack of physiological changes of labor play an important role in the association between Cs and *** delivery also results in limited endogenous pulmonary vasodilator synthesis and lower levels of protective anti-oxidants in the *** addition,Cs delivery exposes infants to a higher risk of respiratory distress syndrome and its concomitant increase in endothelin-1 levels,which might indirectly lead to a higher risk of developing *** believe that neonates delivered by Cs are exposed to a combination of these pathophysiological events,culminating in an endpoint of respiratory distress,hypoxia,acidosis,and delayed transition and thereby increased risks of *** use of antenatal corticosteroids prior to elective Cs in late preterm deliveries,promoting accurate informed-consent process,delaying elective Cs to 39 weeks of gestation or beyond and antenatal maternal anti-oxidant supplementation could potentially mitigate the effects of Cs delivery and minimize Cs-related ***:The link between Cs delivery and PPHN is *** view of the rising rates of Cs worldwide,there is an urgent need to further e

关键词： caesarean section iatrogenic prematurity oxidative stress persistent pulmonary hypertension of the newborn vasoactive agents

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secondary genomic findings in the 2020 China Neonatal Genomes Project participants

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World Journal of Pediatrics 2022年第10期18卷 687-694页

作者： Hui Xiao Jian-Tao Zhang Xin-Ran Dong Yu-Lan Lu Bing-Bing Wu Hui-Jun Wang Zheng-Yan Zhao Lin Yang Wen-Hao Zhou department of neonatology Children’s Hospital of Fudan UniversityShanghaiChina Center for Molecular Medicine Children’s Hospital of Fudan UniversityShanghaiChina department of Child Health Care Children’s HospitalZhejiang University School of MedicineHangzhouChina department of Pediatric Endocrinology and Inherited Metabolic Diseases Children’s Hospital of Fudan UniversityShanghaiChina

Background During next generation sequencing(NGs)data interpretation in critically ill newborns,there is a potential for recognizing and reporting secondary findings(sFs).Early awareness of sFs may provide clues for disease *** this study,we assessed the frequency of sFs in the China Neonatal Genomes Project(CNGP)*** A total of 2020 clinical exome sequencing(CEs)datasets were screened for variants from a list of 59 genes recommended by the American College of Medical Genetics and Genomics(ACMG)for secondary findings reporting v2.0(ACMG sF v2.0).Identified variants were classified according to the evidence-based guidelines reached by a joint consensus of the ACMG and the Association for Molecular Pathology(AMP).Results Among the 2020 CEs datasets,we identified 23 ACMG-reportable genes in 61 individuals,resulting in an overall frequency of sFs at 3.02%.A total of 53 unique variants were identified,including 35 pathogenic and 18 likely pathogenic *** common disease categories of sFs associated were cardiovascular and cancer *** sF results affected the medical management and follow-up strategy in 49(80.3%)*** We presented the frequency of sFs and their impact on clinical management strategies in CNGP *** study demonstrated that sFs have important practical value in disease prevention and intervention at an early stage.

关键词： Genetics secondary findings Neonate Next generation sequencing

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What can we learn from neonates with COVID-19?

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World Journal of Pediatrics 2020年第3期16卷 280-283页

作者： Tian-Tian Xiao Kai Yan Lai-shuan Wang Wen-Hao Zhou National Clinical Research Center for children's hospital of fudan university ShanghaiChina department of neonatology Children's Hospital of Fudan University399 Wanyuan RoadShanghai 201102China

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (sARs-CoV-2) has become a global *** on epidemiological and clinical characteristics of patients with COVID-19 have indicated that children are susceptible to sARs-CoV-2 [1-3].To date,the largest study in China reported that over 90% of 2143 children with COVID-19 were asymptomatic,or had mild or moderate illness,and that 5.8% presented critical illness [3].Although the data of neonates are limited and only six neonates with COVID-19 have been reported thus far,several important points should be addressed from these neonatal cases.

关键词： acute respiratory nates

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