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FSD1 inhibits glioblastoma diffuse infiltration through restriction of HDAC6-mediated microtubule deacetylation

Science China Life sciences 2025年

作者： Dake Xiao Haowen Ran Lishu Chen Yuanyuan Li Yan Cai Songyang Zhang Qinghui Qi Huiran Wu Cheng Zhang Shuailiang Cao Lanjuan Mi Haohao Huang Ji Qi Qiuying Han Haiqing Tu Huiyan Li Tao Zhou Fangye Li Ailing Li Jianghong Man Nanhu Laboratory National Center of Biomedical Analysis School of Traditional Chinese Medicine Capital Medical University Department of Neurosurgery General Hospital of Central Theater Command of Chinese PLA School of Life and Health sciences Huzhou College Department of Neurosurgery Beijing Fengtai Hospital Department of Neurosurgery First Medical Center of PLA General Hospital

The infiltration of glioblastoma multiforme(GBM) is predominantly characterized by diffuse spread, contributing significantly to therapy resistance and recurrence of GBM. In this study, we reveal that microtubule deacetylation, mediated through the downregulation of fibronectin type III and SPRY domain-containing 1(FSD1), plays a pivotal role in promoting GBM diffuse infiltration. FSD1 directly interacts with histone deacetylase 6(HDAC6) at its second catalytic domain, thereby impeding its deacetylase activity on α-tubulin and preventing microtubule deacetylation and depolymerization. This inhibitory interaction is disrupted upon phosphorylation of FSD1 at its Ser317 and Ser324 residues by activated CDK5, leading to FSD1 dissociation from microtubules and facilitating HDAC6-mediated α-tubulin deacetylation. Furthermore, increased expression of FSD1 or interference with FSD1 phosphorylation reduces microtubule deacetylation, suppresses invasion of GBM stem cells, and ultimately mitigates tumor infiltration in orthotopic GBM xenografts. Importantly, GBM tissues exhibit diminished levels of FSD1 expression, correlating with microtubule deacetylation and unfavorable clinical outcomes in GBM patients. These findings elucidate the mechanistic involvement of microtubule deacetylation in driving GBM cell invasion and offer potential avenues for managing GBM infiltration.

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A novel flexible nerve guidance conduit promotes nerve regeneration while providing excellent mechanical properties

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Neural Regeneration Research 2025年第7期20卷 2084-2094页

作者： Tong Li Quhan Cheng Jingai Zhang Boxin Liu Yu Shi Haoxue Wang Lijie Huang Su Zhang Ruixin Zhang Song Wang Guangxu Lu Peifu Tang Zhongyang Liu Kai Wang Department of Orthopedics the Fourth Medical Center of Chinese PLA General HospitalBeijingChina Department of Training and Sports Medicine Characteristic Medical Center of Chinese People’s Armed Police ForceTianjinChina Medical School of Chinese pla BeijingChina Key Laboratory of Bioactive Materials for the Ministry of Education College of Life SciencesNankai UniversityTianjinChina Department of Orthopedics Tianjin HospitalTianjinChina Department of Rehabilitation Medicine Er Quan Hospital of PAPWuxiJiangsu ProvinceChina

Autografting is the gold standard for surgical repair of nerve defects>5 mm in length;however,autografting is associated with potential complications at the nerve donor *** an alternative,nerve guidance conduits may be *** ideal conduit should be flexible,resistant to kinks and lumen collapse,and provide physical cues to guide nerve *** designed a novel flexible conduit using electrospinning technology to create fibers on the innermost surface of the nerve guidance conduit and employed melt spinning to align ***,we prepared disordered electrospun fibers outside the aligned fibers and helical melt-spun fibers on the outer wall of the electrospun fiber *** presence of aligned fibers on the inner surface can promote the extension of nerve cells along the *** helical melt-spun fibers on the outer surface can enhance resistance to kinking and compression and provide *** novel conduit promoted nerve regeneration and functional recovery in a rat sciatic nerve defect model,suggesting that it has potential for clinical use in human nerve injuries.

关键词： aligned fibers anti-kinking helical fibers nerve guidance conduit nerve regeneration peripheral nerve injury topological guidance

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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POplaR/OAK and CHOICE-01 trial

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Science China Life sciences 2025年第1期 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang Department of Oncology The Fifth Medical Center of Chinese PLA General Hospital Department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMS Key Laboratory of Translational Research on Lung Cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences Department of clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,PinteractionplaR/OAK cohort,nsqNSCLCs with LRP1B-del demonstrated improved PFS benefits from atezolizumab over docetaxel(hazard ratio（HR）=0.70,P=0.046),whereas this benefit was negligible in those without LRP1B-del（HR=1.05,P=0.64）.Conversely,sqNSCLCs without LRP1B-del benefited more from atezolizumab（HR=0.60,P=0.002） than those with LRP1B-del（HR=1.30,P=0.31）.Consistent results were observed in the in-house CHOICE-01 cohort,in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone(Pinteraction=0.008).This multi-cohort study delineates the antithetical impacts of LRP1B-del in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy *** findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

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Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

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Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： Xihang Chen Zhifeng Chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei Xu Chang Lin Xi Shi Wei Chen Shiming Yang Senior Department of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of Hearing and Balance Science BeijingChina National clinical Research center for Otolaryngologic Diseases BeijingChina Key Laboratory of Hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of Hearing Impairment Prevention and Treatment BeijingChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Otolaryngology Head and Neck Surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

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In vivo imaging of the neuronal response to spinal cord injury:a narrative review

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Neural Regeneration Research 2024年第4期19卷 811-817页

作者： Junhao Deng Chang Sun Ying Zheng Jianpeng Gao Xiang Cui Yu Wang Licheng Zhang Peifu Tang Department of Orthopedics The Fourth Medical Center of Chinese PLA General Hospital National clinical Research center for Orthopedics Sports Medicine and Rehabilitation School of Life sciences Tsinghua University Department of Orthopedics Air Force Medical CenterPLA Medical School of Chinese pla Institute of Orthopedics The First Medical CenterChinese PLA General Hospital Key Lab of Regenerative Medicine in Orthopedics Key Laboratory of Musculoskeletal Trauma and War Injuries PLA

Deciphering the neuronal response to injury in the spinal cord is essential for exploring treatment strategies for spinal cord injury(SCI).However,this subject has been neglected in part because appropriate tools are *** in vivo imaging and labeling methods offer great potential for observing dynamic neural processes in the central nervous system in conditions of health and *** review first discusses in vivo imaging of the mouse spinal cord with a focus on the latest imaging techniques,and then analyzes the dynamic biological response of spinal cord sensory and motor neurons to *** then summarize and compare the techniques behind these studies and clarify the advantages of in vivo imaging compared with traditional neuroscience ***,we identify the challenges and possible solutions for spinal cord neuron imaging.

关键词： anterior horn neurons calcium imaging central nervous system dorsal horn neurons dorsal root ganglion in vivo imaging neuronal response spinal cord injury spinal cord two-photon microscopy

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Rapid and sensitive detection of urinary KIM-1 using fully printed photonic crystal microarrays

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Nano Research 2024年第5期17卷 4329-4337页

作者： Yang Liu Xuwei He Zewei Lian Qian Guo Jimei Chi Xiaoxue Lin Liyue Zhang Zheng Liu Yingyuan Liu Meng Su Keyu Wang Qiangguo Ao Qingli Cheng Department of Nephrology The Second Medical Center of Chinese PLA General HospitalNational Clinical Research Centre for Geriatric DiseasesBeijing 100853China Chinese pla Medical School Beijing 100853China Key Laboratory of Green Printing CAS Research/Education Center for Excellence in Molecular SciencesBeijing Engineering Research Center of Nanomaterials for Green Printing TechnologyBeijing National Laboratory for Molecular Sciences(BNLMS)Institute of ChemistryChinese Academy of Sciences(ICCAS)Beijing 100190China Department of Rheumatology and Immunology Peking University International HospitalBeijing 102206China Department of clinical Laboratory The Second Medical Center of Chinese PLA General HospitalNational Clinical Research Centre for Geriatric DiseasesBeijing 100853China

Urinary kidney injury molecule 1(uKIM-1)serves as a reliable marker for the early diagnosis of acute kidney injury(AKI).The rapid and facile detection of changes in uKIM-1 is essential for early AKI diagnosis,ultimately improving the prognosis of *** this study,we developed a fully printed photonic crystal-integrated microarray with photonic crystal-enhanced fluorescence properties,which can detect uKIM-1 levels at the *** confirmed its efficacy in the early diagnosis of AKI using clinical urine *** quantitative detection of uKIM-1 was achieved within 10 *** lowest limit of detection is 8.75 pg·mL^(-1) with an accuracy of 94.2%.The diagnostic efficacy was validated using 86 clinical urine samples,highlighting the high sensitivity and stability of the photonic crystal ***,a facile and reliable immunoassay was designed and prepared for the rapid quantitative detection of uKIM-1,which is crucial for the early identification and convenient detection of AKI in hospital or community ***,convenient,cost-effective,and long-term monitoring of changes in uKIM-1 levels can assist clinicians in making timely adjustments to treatment regimens,preventing the transition from AKI to chronic kidney disease(CKD),improving the quality of life of patients with AKI,and reducing healthcare *** highlights the advantages of utilizing urine samples as a noninvasive and easily accessible medium for early detection and monitoring of kidney-related conditions.

关键词： photonic crystal point-of-care testing urine kidney injury molecule-1(KIM-1) acute kidney injury

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Metformin capped Cu_(2)(OH)_(3)Cl nanosheets for chemodynamic wound disinfection

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Nano Research 2023年第3期16卷 3991-3997页

作者： Xueyu Wang Shaobo Wang Jiao Gao Shuncheng Yao Teng Xu Yunchao Zhao Zeyu Zhang Tian Huang Shu Yan Linlin Li 306th clinical College of pla The Fifth Clinical CollegeAnhui Medical UniversityBeijing 100101China Beijing Institute of Nanoenergy and Nanosystems Chinese Academy of SciencesBeijing 101400China center on Nanoenergy Research School of Physical Science and TechnologyGuangxi UniversityNanning 530004China pla Strategic Support Force Characteristic Medical center Beijing 100101China School of Nanoscience and Technology University of Chinese Academy of SciencesBeijing 100049China

Recently,the development of chemodynamic therapy(CDT)offers a potential approach for fighting bacteria and treating infectious diseases,in which those CDT nanoagents can catalyze the generation of hydroxyl radicals(·OH)to destroy *** this work,to improve the efficiency of CDT,we have designed a new kind of metformin(Met)-capped two-dimensional Cu_(2)(OH)_(3)Cl nanosheets(CuOHCl-Met NSs)with good monodispersity,highly positive charge,and good biocompatibility for improving antibacterial effect and accelerating wound *** the capped Met,CuOHCl-Met NSs can effectively kill bacteria under a low concentration(6μg·mL^(−1))and a short treatment time(in 15 min),showing great advantages over the counterpart without *** vivo results demonstrated that CuOHCl-Met NSs accelerated the tissue regeneration of staphylococcus aureus-infected dermal *** study provides a new pathway for improving efficiency of CDT nanoagent through using old drug.

关键词： chemodynamic therapy metformin antibacterial effect wound healing drug repositioning

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Diagnostic Efficacy of^(18)F-FDG PET/CT in Detecting Bone Marrow Infiltration in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma

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Biomedical and Environmental sciences 2023年第6期36卷 510-516页

作者： GUO Bo QIN Ran GU Zhen Yang LI Yan Fen GAO Lei HUANG Wen Rong Department of Hematology The Second Medical Center&National Clinical Research Center for Geriatric DiseasesChinese PLA General HospitalBeijing 100853China Department of Hematology The Fifth Medical CenterChinese PLA General HospitalBeijing 100071China Department of Medical Engineering Medical Supplies Center of PLA General HospitalBeijing 100039China

Objective Diffuse large B-cell lymphoma(DLBCL)is often associated with bone marrow infiltration,and 2-deoxy-2-(18F)fluorodeoxyglucose positron emission tomography/computed tomography(^(18)F-FDG PET/CT)has potential diagnostic significance for bone marrow infiltration in *** A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were *** marrow biopsy and^(18)F-FDG PET/CT examinations were performed at the time of initial *** tests were used to evaluate the agreement of^(18)F-FDG PET/CT with the gold standard,and the imaging features of DLBCL bone marrow infiltration on PET/CT were *** The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy(P=0.302)or between the two bone marrow biopsies(P=0.826).The sensitivity,specificity,and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923(95%CI,0.759-0.979),0.934(95%CI,0.855-0.972),and 0.857,***^(18)F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow ***/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.

关键词： Diffuse large B-cell lymphoma Bone marrow infiltration Positron emission computed tomography(PET/CT) Bone marrow biopsy Diagnostic efficacy

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Analysis of Factors Influencing Insomnia and Construction of a Prediction Model:A Cross-sectional Survey on Rescuers

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Biomedical and Environmental sciences 2020年第7期33卷 502-509页

作者： SAI Xiao Yong CHEN Qiao LUO Ting Gang SUN Yuan Yuan SONG Yu Jian CHEN Juan Department of Epidemiology and Statistics The Graduate School of the Chinese PLA General HospitalBeijing 100853China Institute of Geriatrics Second Medical Center of Chinese PLA General HospitalNational Clinical Research Center of Geriatric DiseaseBeijing 100853China

Objective To determine the factors influencing insomnia and construct early insomnia warning tools for rescuers to informbest practices for early screening and *** Cluster sampling was used to conduct a cross-sectional survey of 1,133 rescuers from one unit in Beijing,*** regression modeling and R software were used to analyze insomniarelated factors and construct a PRISM model,*** The positive rate of insomnia among rescuers was 2.74%.Accounting for participants’age,education,systolic pressure,smoking,per capita family monthly income,psychological resilience,and cognitive emotion regulation,logistic regression analysis revealed that,compared with families with an average monthly income less than 3,000 yuan,the odds ratio(OR)values and the[95%confidence interval(CI)]for participants of the following categories were as follows:average monthly family income greater than 5,000 yuan:2.998(1.307–6.879),smoking:4.124(1.954–8.706),and psychological resilience:0.960(0.933–0.988).The ROC curve area of the PRISM model(AUC)=0.7650,specificity=0.7169,and sensitivity=*** Insomnia was related to the participants’per capita family monthly income,smoking habits,and psychological resilience on rescue *** PRISM model’s good diagnostic value advises its use to screen rescuer early sleep ***,advisable interventions to optimize sleep quality and battle effectiveness include psychological resilience training and smoking cessation.

关键词： Rescuers Insomnia Influencing factors Cross sectional survey Prediction model

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Exploration of pathogenic microorganism within the small intestine of necrotizing enterocolitis

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World Journal of Pediatrics 2024年第2期20卷 165-172页

作者： Yan Wang Kun Jiang Qiao Xia Xia Kang Shan Wang Ji-Hong Yu Wen-Feng Ni Xiao-Qin Qi Ying-Na Zhang Jin-Bao Han Gang Liu Lei Hou Zhi-Chun Feng Liu-Ming Huang clinical Biobank center Medical Innovation Research Division of ChinesePLA General HospitalBeijingChina Institute of Basic Medical sciences Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Senior Department of Pediatrics The Seventh Medical Center of PLA General HospitalBeijing 100700China Department of Neurology The First Medical CenterChinese PLA General HospitalBeijing 100853China Department of Emergency center National Center for Children's HealthBeijing Children's HospitalCapital Medical UniversityBeijing 100045China

Background Necrotizing enterocolitis(NEC)is the most common severe gastrointestinal emergency in *** designed this study to identify the pathogenic microorganisms of NEC in the microbiota of the small intestine of *** Using the 16S ribosomal DNA(rDNA)sequencing method,we compared and analyzed the structure and diversity of microbiotas in the intestinal feces of different groups of neonates:patients undergoing jejunostomy to treat NEC(NP group),neonates undergoing jejunostomy to treat other conditions(NN group),and neonates with NEC undergoing conservative treatment(NC group).We took intestinal feces and saliva samples from patients at different time *** The beta diversities of the NP,NN,and NC groups were all *** comparing the beta diversities between different time points in the NP group,we found similar beta diversities at time points El to E3 but significant differences between the E2-E3 and E4 time points:the abundances of Klebsiella and Enterococcus(Proteobacteria)were higher at the E1-E3 time points;the abundance of Escherichia-Shigella(Proteobacteria)increased at the E2 time point,and the abundance of Klebsiella decreased significantly,whereas that of Streptococcus increased significantly at the E4 time *** Our results suggest that the pathological changes of intestinal necrosis in the small intestine of infants with NEC are not directly caused by excessive proliferation of pathogenic bacteria in the small *** sources of microbiota in the small intestine of neonates,especially in premature infants,may be affected by multiple factors.

关键词： Microbiota Necrotizing enterocolitis-Small intestine 16S rDNA

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