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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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Morphological and biochemical characteristics associated with autophagy in gastrointestinal diseases

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World Journal of Gastroenterology 2024年第11期30卷 1524-1532页

作者： Yi-Fan Chang jia-Jing Li tao Liu Chong-Qing Wei Li-Wei Ma Vladimir N Nikolenko Wei-Long Chang Department of Gastrointestinal Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Department of Pathology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Department of Clinical Laboratory The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Department of Human Anatomy and Histology I.M.Sechenov First Moscow State Medical University(Sechenov University)Moscow 119991Russia

Autophagy is a cellular catabolic process characterized by the formation of double-membrane *** electron microscopy is the most rigorous method to clearly visualize autophagic engulfment and degradation.A large number of studies have shown that autophagy is closely related to the digestion,secretion,and regeneration of gastrointestinal(GI)***,the role of autophagy in GI diseases remains *** article focuses on the morphological and biochemical characteristics of autophagy in GI diseases,in order to provide new ideas for their diagnosis and treatment.

关键词： Autophagy Morphological study Biochemical characteristics Subcellular structure Transmission electron microscopy Gastrointestinal diseases

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Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function:implication of miRNAs and microvesicles

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Military Medical Research 2024年第1期11卷 1-18页

作者： Zi-Sen Zhang Yi-Yan Liu Shuang-Shuang He Dai-Qin Bao Hong-Chen Wang Jie Zhang Xiao-Yong Peng jia-tao Zang Yu Zhu Yue Wu Qing-Hui Li tao Li Liang-Ming Liu State Key Laboratory of Trauma Burns and Combined InjuryDepartment of Shock and TransfusionResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqing 400042China

Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon *** hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and *** We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)*** a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive *** pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic *** effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also *** CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin *** Pericytes are protective a

关键词： Pericyte Vascular reactivity Vascular permeability Cx43 Microvesicle

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The Uptake and Distribution Evidence of Nano-and Microplastics in vivo after a Single High Dose of Oral Exposure

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Biomedical and Environmental Sciences 2024年第1期37卷 31-41页

作者： HONG tao SUN Wei DENG Yuan LYU jian Da JIN Cui Hong BAI Ying Long NA jun ZHANG Rui GAO Yuan PAN Guo Wei YANG Zuo Sen YAN Ling jun Research Center for Universal Health School of Public HealthChina Medical UniversityShenyang 110122LiaoningChina Department of Pain Management Shengjing Hospital of China Medical UniversityShenyang 110004LiaoningChina Department of Toxicology School of Public HealthChina Medical UniversityShenyang 110122LiaoningChina Department of Maternal and Child Health School of Public HealthChina Medical UniversityShenyang 110122LiaoningChina Institute of Preventive Medicine China Medical UniversityShenyang 110122LiaoningChina Institute of Chronic Diseases Liaoning Provincial Center for Disease Control and PreventionShenyang 110000LiaoningChina

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in *** Fluorescent microspheres(100 nm,3μm,and 10μm)were given once at a dose of 200 mg/(kg∙body weight).The fluorescence intensity(FI)in observed organs was measured using the IVIS Spectrum at 0.5,1,2,and 4 h after *** was performed to corroborate these *** In the 100 nm group,the FI of the stomach and small intestine were highest at 0.5 h,and the FI of the large intestine,excrement,lung,kidney,liver,and skeletal muscles were highest at 4 h compared with the control group(P<0.05).In the 3μm group,the FI only increased in the lung at 2 h(P<0.05).In the 10μm group,the FI increased in the large intestine and excrement at 2 h,and in the kidney at 4 h(P<0.05).The presence of nano-/microplastics in tissues was further verified by *** peak time of nanoplastic absorption in blood was *** Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however,only small amounts of MPs could penetrate the organs.

关键词： Microplastics Nanoplastics IVIS Spectrum small-animal imaging system Tissue distribution Blood

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Work-function-induced interfacial electron redistribution of MoO_(2)/WO_(2) heterostructures for high-efficiency electrocatalytic hydrogen evolution reaction

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Rare Metals 2024年第2期43卷 489-499页

作者： Tong-Fei Li Jing Li Lu-Ping Zhang jia-Wei Ke Meng-Xing Fan Li-Fang Zhang Cheng-Wei Deng Yi Sun tao Qian Cheng-Lin Yan School of Chemistry and Chemical Engineering Nantong UniversityNantong226019China jiangsu Key Laboratory of New Power Batteries Jiangsu Collaborative Innovation Centre of Biomedical Functional MaterialsSchool of Chemistry and Materials ScienceNanjing Normal UniversityNanjing210023China Aerospace Hydrogen Energy Technology(Shanghai)Co.Ltd. Shanghai201800China Key Laboratory of Core Technology of High Specific Energy Battery and Key Materials for Petroleum and Chemical Industry College of EnergySoochow UniversitySuzhou215006China Light Industry Institute of Electrochemical Power Sources Suzhou215006China

The engineering of the electronic configurations of active sites,together with the production of more accessible active sites through heterostructure design,has been established as a forceful methodology for boosting water electrolysis ***,a facile approach is developed to fabricate well-dispersed MoO_(2) and WO_(2) nanoparticles with abundant heterointerfaces entrapped in N,P-doped carbon nanofibers(referred to as MoO_(2)/WO_(2)@N,P-CNFs hereafter)as hydrogen evolution reaction(HER)electrocatalysts in alkaline and acidic *** spectroscopic analyses and theoretical findings manifest that the heterointerface formed by the work function modulation of MoO_(2)/WO_(2) triggers the spontaneous electron redistribution from MoO_(2)to WO_(2) and a built-in electric field,which is essential to promote water adsorption,optimize the H-intermediate adsorption energy,result in the enhanced charge transfer efficiency,and ultimately increase the intrinsic HER ***,the intimate confinement of MoO_(2)/WO_(2) heterostructures in the porous carbon substrate can restrain the active sites from unfavorable coarsening and detachment,thus ensuring facilitated HER kinetics and outstanding structural *** a result,MoO_(2)/WO_(2)@N,P-CNFs exhibit superior catalytic HER performance in acidic and basic solutions,requiring 118 and 95 mV overpotentials to achieve 10 mA·cm^(−2),respectively,surpassing a number of reported non-noble metal-based *** work provides guidelines for the rational design and construction of special metallic heterocomponents with optimized interfacial electronic structure for various electrochemical technologies.

关键词： Electrospinning MoO_(2)/WO_(2) heterostructure Work function Hydrogen evolution reaction

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Role of deubiquitinase JOSD2 in the pathogenesis of esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2024年第6期30卷 565-578页

作者： Wen-Peng Wang Dan Shi Duo Yun jun Hu Jie-Fu Wang jia Liu Yan-Peng Yang Ming-Rui Li jun-FengWang Da-Lu Kong Department of Colorectal Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China Department of Gastrointestinal Surgery Tianjin Nan Kai HospitalTianjin Medical UniversityTianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM RepairInstitute of Integrative Medicine for Acute Abdominal DiseasesTianjin 300100China Department of Oncology The First Hospital of HohhotHohhot 010000Inner Mongolia Autonomous RegionChina Department of Endocrinology Dazhou Central HospitalDazhou 635000Sichuan ProvinceChina

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment ***(DUBs)have been confirmed to play a crucial role in the development of malignant ***2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in *** To investigate the impact of JOSD2 on the progression of *** Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in *** transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor *** analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal ***2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ***,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these *** vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ***,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling *** spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and *** JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.

关键词： Esophageal squamous cell carcinoma JOSD2 Ubiquitination Biomarker Targeted therapy Drug resistance

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Highly Sensitive Ammonia Gas Sensors at Room Temperature Based on the Catalytic Mechanism of N,C Coordinated Ni Single-Atom Active Center

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Nano-Micro Letters 2024年第12期16卷 515-531页

作者： Wenjing Quan jia Shi Min Zeng Wen Lv Xiyu Chen Chao Fan Yongwei Zhang Zhou Liu Xiaolu Huang jianhua Yang Nantao Hu tao Wang Zhi Yang National Key Laboratory of Advanced Micro and Nano Manufacture Technology Shanghai Jiao Tong UniversityShanghai 200240People’s Republic of China Department of Micro/Nano Electronics School of Electronic Information and Electrical EngineeringShanghai Jiao Tong UniversityShanghai 200240People’s Republic of China Shanghai Key Laboratory of Intelligent Sensing and Detection Technology School of Mechanical and Power EngineeringEast China University of Science and TechnologyShanghai 200237People’s Republic of China

Significant challenges are posed by the limitations of gas sensing mechanisms for trace-level detection of ammonia(NH3).In this study,we propose to exploit single-atom catalytic activation and targeted adsorption properties to achieve highly sensitive and selective NH3 gas ***,Ni singleatom active sites based on N,C coordination(Ni-N-C)were interfacially confined on the surface of two-dimensional(2D)MXene nanosheets(Ni-N-C/Ti_(3)C_(2)Tx),and a fully flexible gas sensor(MNPE-Ni-N-C/Ti_(3)C_(2)Tx)was *** sensor demonstrates a remarkable response value to 5 ppm NH3(27.3%),excellent selectivity for NH3,and a low theoretical detection limit of 12.1 *** analysis by density functional calculation reveals that the Ni single-atom center with N,C coordination exhibits specific targeted adsorption properties for ***,its catalytic activation effect effectively reduces the Gibbs free energy of the sensing elemental reaction,while its electronic structure promotes the spill-over effect of reactive oxygen species at the gas-solid *** sensor has a dual-channel sensing mechanism of both chemical and electronic sensitization,which facilitates efficient electron transfer to the 2D MXene conductive network,resulting in the formation of the NH3 gas molecule sensing ***,the passivation of MXene edge defects by a conjugated hydrogen bond network enhances the long-term stability of MXene-based electrodes under high humidity *** work achieves highly sensitive room-temperature NH3 gas detection based on the catalytic mechanism of Ni single-atom active center with N,C coordination,which provides a novel gas sensing mechanism for room-temperature trace gas detection research.

关键词： Gas sensor Single atom Catalytic activation Targeted adsorption End-sealing passivation

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Clinical risk factors for preterm birth and evaluating maternal psychology in the postpartum period

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World Journal of Psychiatry 2024年第5期14卷 661-669页

作者： jia-jun Chen Xue-Jin Chen Qiu-Min She Jie-Xi Li Qiu-Hong Luo Department of Clinical Laboratory Shenzhen Bao’an District Songgang People’s HospitalShenzhen 518000Guangdong ProvinceChina Department of Otolaryngology Head and Neck Surgery Outpatient Shenzhen Children’s HospitalShenzhen 518000Guangdong ProvinceChina Department of Prevention and Health Care Shenzhen Bao’an District Songgang People’s HospitalShenzhen 518000Guangdong ProvinceChina Department of Obstetrics Shenzhen Bao’an District Songgang People’s HospitalShenzhen 518000Guangdong ProvinceChina

BACKGROUND Although the specific pathogenesis of preterm birth(PTB)has not been thoroughly clarified,it is known to be related to various factors,such as pregnancy complications,maternal socioeconomic factors,lifestyle habits,reproductive history,environmental and psychological factors,prenatal care,and nutritional *** has serious implications for newborns and families and is associated with high mortality and ***,the prediction of PTB risk can facilitate early intervention and reduce its resultant adverse *** To analyze the risk factors for PTB to establish a PTB risk prediction model and to assess postpartum anxiety and depression in *** A retrospective analysis of 648 consecutive parturients who delivered at Shenzhen Bao’an District Songgang People’s Hospital between January 2019 and January 2022 was *** to the diagnostic criteria for premature infants,the parturients were divided into a PTB group(n=60)and a full-term(FT)group(n=588).Puerperae were assessed by the Self-rating Anxiety Scale(SAS)and Self rating Depression Scale(SDS),based on which the mothers with anxiety and depression symptoms were screened for further *** factors affecting PTB were analyzed by univariate analysis,and the related risk factors were identified by logistic *** According to univariate analysis,the PTB group was older than the FT group,with a smaller weight change and greater proportions of women who underwent artificial insemination and had gestational diabetes mellitus(P<0.05).In addition,greater proportions of women with reproductive tract infections and greater white blood cell(WBC)counts(P<0.05),shorter cervical lengths in the second trimester and lower neutrophil percentages(P<0.001)were detected in the PTB group than in the FT *** PTB group exhibited higher postpartum SAS and SDS scores than did the FT group(P<0.0001),with a higher number of mothers experiencing anxiety and depress

关键词： Preterm birth Risk factors Postpartum psychological state Risk model Prediction

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No Incidence of Liver Cancer Was Observed in A Retrospective Studyof Patients with Aristolochic Acid Nephropathy

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Chinese Journal of Integrative Medicine 2024年第2期30卷 99-106页

作者： SU tao FANG Zhi-e GUO Yu-ming WANG Chun-yu WANG jia-bo JI Dong BAI Zhao-fang YANG Li XiAO Xiao-he Renal Division Department of MedicinePeking University First HospitalBeijing(100034)China Department of Pharmacy Chongqing Hospital of Traditional Chinese MedicineChongqing(400021)China Department of Hepatology Fifth Medical Center of Chinese PLA General HospitalBeijing(100039)China China Military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing(100039)China Phase I Clinical Trials Unit Department of Medicine for Infectious DiseasesFifth Medical Center of Chinese PLA General HospitalBeijing(100039)China Department of Pharmacy Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinan(250000)China National Key Laboratory of Kidney Diseases Beijing(100039)China

Objective:To assess the risk of aristolochic acid(AA)-associated cancer in patients with AA nephropathy(AAN).Methods:A retrospective study was conducted on patients diagnosed with AAN at Peking University First Hospital from January 1997 to December ***-term surveillance and follow-up data were analyzed to investigate the influence of different factors on the prevalence of *** primary endpoint was the incidence of liver cancer,and the secondary endpoint was the incidence of urinary cancer during 1 year after taking AA-containing medication to ***:A total of 337 patients diagnosed with AAN were included in this *** the initiation of taking AA to the termination of follow-up,39 patients were diagnosed with *** cases of liver cancer were observed throughout the entire follow-up period,with urinary cancer being the predominant type(34/39,87.17%).Logistic regression analysis showed that age,follow-up period,and diabetes were potential risk factors,however,the dosage of the drug was not significantly associated with urinary ***:No cases of liver cancer were observed at the end of ***,a high prevalence of urinary cancer was observed in AAN *** a direct causality between AA and HCC is challenging.

关键词： aristolochic acid hepatocellular carcinoma urinary cancer drug safety retrospective study

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哈尔滨东宾县凹陷白垩纪地层层序及其与松辽盆地的对比

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地质通报 2006年第9期25卷 1143-1151页

作者：贾军涛王璞珺张斌万晓樵吉林大学地球科学学院吉林长春130061 中国地质大学地球科学与资源学院北京100083

根据实测剖面并结合前人研究成果厘定了宾县凹陷白垩纪地层层序:下白垩统板子房组、宁远村组、淘淇河组、泉头组和上白垩统青山口组、姚家组。综合运用岩性地层、生物地层、地质事件和同位素年龄的方法将宾县凹陷白垩系与松辽盆地进行... 详细信息

根据实测剖面并结合前人研究成果厘定了宾县凹陷白垩纪地层层序:下白垩统板子房组、宁远村组、淘淇河组、泉头组和上白垩统青山口组、姚家组。综合运用岩性地层、生物地层、地质事件和同位素年龄的方法将宾县凹陷白垩系与松辽盆地进行了对比。根据同位素年龄对比,板子房组相当于沙河子组上部和营城组下部,宁远村组相当于营城组中上部。根据植物化石组合分析,淘淇河组可与营城组顶部、登娄库组和泉头组底部对比。“鸟河组”下部红层作为区域性气候事件的产物可与泉头组下部对比;该组以Triangulicypristorsuosus和***繁盛为特征的介形类化石组合与青山口组相似,轮藻类化石Atopocharatrivolvis、Aclistocharasongliaoensis和Obtusocharaniaoheensis在泉头组至嫩江组均有发现;因此将“鸟河组”分解为泉头组、青山口组、姚家组和嫩江组。

关键词：松辽盆地宾县凹陷白垩系地层对比

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