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Metformin alleviates spinal cord injury by inhibiting nerve cell ferroptosis through upregulation of heme oxygenase-1 expression

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Neural Regeneration Research 2024年第9期19卷 2041-2049页

作者： zhihua wang Wu Zhou Zhixiong Zhang Lulu Zhang Meihua Li Department of Neurosurgery The First Affiliated Hospital of Nanchang UniversityNanchangJiangxi ProvinceChina Postdoctoral Innovation Practice Base The First Affiliated Hospital of Nanchang UniversityNanchangJiangxi ProvinceChina Department of Nephrology Nanchang People’s Hospital Affiliated to Nanchang Medical CollegeNanchangJiangxi ProvinceChina

Previous studies have reported upregulation of heme oxygenase-1 in different central nervous system injury *** oxygenase-1 plays a critical anti-inflammatory role and is essential for regulating cellular redox *** is a classic drug used to treat type 2 diabetes that can inhibit *** studies have shown that,when used to treat cardiovascular and digestive system diseases,metformin can also upregulate heme oxygenase-1 ***,we hypothesized that heme oxygenase-1 plays a significant role in mediating the beneficial effects of metformin on neuronal ferroptosis after spinal cord *** test this,we first performed a bioinformatics analysis based on the GEO database and found that heme oxygenase-1 was upregulated in the lesion of rats with spinal cord ***,we confirmed this finding in a rat model of T9 spinal cord compression injury that exhibited spinal cord nerve cell *** intraperitoneal injection of metformin for 14 days was found to both upregulate heme oxygenase-1 expression and reduce neuronal ferroptosis in rats with spinal cord ***,we used a lentivirus vector to knock down heme oxygenase-1 expression in the spinal cord,and found that this significantly reduced the effect of metformin on ferroptosis after spinal cord *** together,these findings suggest that metformin inhibits neuronal ferroptosis after spinal cord injury,and that this effect is partially dependent on upregulation of heme oxygenase-1.

关键词： acyl-CoA synthetase long-chain family member 4 ferroptosis glutathione peroxidase 4 heme oxygenase-1 inflammation iron lipid peroxidation metformin neuroprotection spinal cord injury

Evaluation of the effects of EPS composite soil replacement on the dynamic performance of caisson structure using shaking table tests

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Earthquake Engineering and Engineering Vibration 2024年第4期23卷 829-843页

作者： Gao, Hongmei Ji, Zhanpeng Zhang, Xinlei Zhang, Shushan wang, zhihua Shen, Guangming Research Center of Urban Underground Space Nanjing Tech University Nanjing China Institute of Geotechnical Engineering Nanjing Tech University Nanjing China

The seismic performance of a caisson structure under two types of models with a saturated sandy foundation (CSS) and an expanded polystyrene (EPS) composite soil foundation (CES) are studied using shaking table tests. The macro phenomena of the two different foundation models are described and analyzed. The effects of the replacement of EPS composite soil on seismic-induced liquefaction of backfill and the dynamic performance of a caisson structure are evaluated in detail. The results show that the excess pore water pressure generation in the CES is significantly slower than that in the CSS during the shaking. The dynamic earth pressure acting on the caisson has a triangular shape. The response of horizontal acceleration, displacement, settlement, and rotation angle of the caisson in the CES is smaller than that in the CSS, which means the caisson in the CES has a better seismic performance. Furthermore, the out-of-phase phenomenon between dynamic earth thrust and inertial force in the CES is more obvious than that in the CSS, which is beneficial to reduce the lateral force and improve the stability of the caisson structure.

关键词： EPS composite soil foundation Caisson-type quay wall shaking table test phase difference rotation angle

A New Discovery of Mineralization as Subseafloor Hydrothermal Replacement in the Duddar Super-Large SEDEX Lead-Zinc Deposit in Pakistan

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Journal of Earth Science 2024年第3期35卷 1075-1078页

作者： Huishan Zhang Yucai Song Jianing Sun Jun Hong Yasir Shaheen Khalil Yanguang Li Haidi Zhang zhihua wang MNR Key Laboratory for the Study of Focused Magmatism and Giant Ore Deposits Xi’an Center of Geological SurveyChina Geological SurveyXi’an 710054China Institute of Geology Chinese Academy of Geological SciencesBeijing 100037China Chengdu Center of Geological Survey China Geological SurveyChengdu 610081China China Huaye Group Co. LtdBeijing 100037China Geological Survey of Pakistan Islamabad 44000Pakistan

0 INTRODUCTION Sedimentary exhalative(SEDEX)lead-zinc deposit was traditionally considered as a result of submarine hydrothermal exhalation,including exhalative plume and brine pool models(Izanloo et al.,2022;Spinks et al.,2021;Maghfouri et al.,2020;Sangster,2020,2018;Huang et al.,2019;Rajabi et al.,2015;Goodfellow and Lydon,2007;Large et al.,2005,2001;Peng et al.,2000;Goodfellow et al.,1993;Figures 1a,1b).However,recognition of mineralization as subseafloor hydrothermal replacement in a few SEDEX deposits has challenged the traditional consideration(Magnall et al.,2023,2021,2020a,b;Hayward et al.,2021;Figure 1c).Researchers come to believe that subseafloor replacement rather than submarine exhalation is a dominant process for SEDEX mineralization,but this needs to be examined through more case studies.

关键词： submarine mineralization seafloor

Evaluation of the effects of EPS composite soil replacement on the dynamic performance of caisson structure using shaking table tests

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Earthquake Engineering and Engineering Vibration 2024年第04期 829-843页

作者： Gao Hongmei Ji Zhanpeng Zhang Xinlei Zhang Shushan wang zhihua Shen Guangming Research Center of Urban Underground Space Nanjing Tech University Institute of Geotechnical Engineering Nanjing Tech University

The seismic performance of a caisson structure under two types of models with a saturated sandy foundation(CSS) and an expanded polystyrene(EPS) composite soil foundation(CES) are studied using shaking table tests. The macro phenomena of the two different foundation models are described and analyzed. The effects of the replacement of EPS composite soil on seismic-induced liquefaction of backfill and the dynamic performance of a caisson structure are evaluated in detail. The results show that the excess pore water pressure generation in the CES is significantly slower than that in the CSS during the shaking. The dynamic earth pressure acting on the caisson has a triangular shape. The response of horizontal acceleration, displacement, settlement, and rotation angle of the caisson in the CES is smaller than that in the CSS, which means the caisson in the CES has a better seismic performance. Furthermore, the out-of-phase phenomenon between dynamic earth thrust and inertial force in the CES is more obvious than that in the CSS, which is beneficial to reduce the lateral force and improve the stability of the caisson structure.

关键词：

Dynamic Resistance and Energy Absorption of Sandwich Beam via a Micro-Topology Optimization

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Chinese Journal of Mechanical Engineering 2024年第4期 159-175页

作者： Shiqiang Li Yuwei Li Xiaomin Ma Jianguang Fang Zhifang Liu zhihua wang Institute of Applied Mechanics Taiyuan University of Technology Shanxi Key Laboratory of Material Strength and Structural Impact Taiyuan University of Technology School of Civil and Environmental Engineering University of Technology Sydney

The current research of sandwich structures under dynamic loading mainly focus on the response characteristic of structure. The micro-topology of core layers would sufficiently influence the property of sandwich ***, the micro deformation and topology mechanism of structural deformation and energy absorption are unclear. In this paper, based on the bi-directional evolutionary structural optimization method and periodic base cell(PBC) technology, a topology optimization frame work is proposed to optimize the core layer of sandwich *** objective of the present optimization problem is to maximize shear stiffness of PBC with a volume *** effects of the volume fraction, filter radius, and initial PBC aspect ratio on the micro-topology of the core were discussed. The dynamic response process, core compression, and energy absorption capacity of the sandwich beams under blast impact loading were analyzed by the finite element method. The results demonstrated that the overpressure action stage was coupled with the core compression stage. Under the same loading and mass per unit area,the sandwich beam with a 20% volume fraction core layer had the best blast resistance. The filter radius has a slight effect on the shear stiffness and blast resistances of the sandwich beams. But increasing the filter radius could slightly improve the bending stiffness. Upon changing the initial PBC aspect ratio, there are three ways for PBC evolution: The first is to change the angle between the adjacent bars, the second is to further form holes in the bars, and the third is to combine the first two ways. However, not all three ways can improve the energy absorption capacity of the structure. Changing the aspect ratio of the PBC arbitrarily may lead to worse results. More studies are necessary for further detailed optimization. This research proposes a new topology sandwich beam structure by micro-topology optimization, which has sufficient shear stiffness. The mi

关键词：

Oncogene goosecoid is transcriptionally regulated by E2F1 and correlates with disease progression in prostate cancer

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中华医学杂志(英文版) 2024年第15期137卷 1844-1856页

作者： Ge Yue Ma Sheng Zhou Qiang Xiong Zezhong wang Yanan Li Le Chao Zheng Zhang Junbiao Li Tengfei Wu Zixi Gao Yuan Qu Guanyu Xi Zirui Liu Bo Wu Xi wang zhihua Department of Urology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China Department of Urology Qinghai University Affiliated Hospital Qinghai University Medical College Xining Qinghai China Department of Oncology Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China Department of Urology First Hospital of Laohekou City Xiangyang Hubei China

Background: Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid (GSC) has been implicated in cancer development. However, the comprehensive biological role ofGSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role ofGSC in PCa ***: We performed a systematic bioinformatics exploration ofGSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression ofGSC and its association with patient prognosis, and identifiedGSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis ofGSC in PCa. To understand the transcriptional regulation ofGSC by E2F transcription factor 1 (E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect ofGSC on the tumor cellular phenotype and sensitivity to ***: GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations ofGSC contribute to the progression of various tumors especially in PCa. Patients with PCa and highGSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further,GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor,E2F1, stimulatesGSC by binding to its promoter region. Detailed experiments further demonstrated thatGSC acted as an oncogene and influenced the response of PCa cells to trametinib ***: GSC was highly overexpressed and strongly correlate

关键词： Goosecoid Prostate cancer Prognosis E2F transcription factor 1 Trametinib

Bioorthogonal microglia-inspired mesenchymal stem cell bioengineering system creates livable niches for enhancing ischemic stroke recovery via the hormesis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1412-1427页

作者： Jianpei Xu Yinzhe Sun Yang You Yuwen Zhang Dan Huang Songlei Zhou Yipu Liu Shiqiang Tong Fenfen Ma Qingxiang Song Chengxiang Dai Suke Li Jigang Lei zhihua wang Xiaoling Gao Jun Chen Shanghai Pudong Hospital&Department of Pharmaceutics School of PharmacyFudan UniversityShanghai 201203China Key Laboratory of Smart Drug Delivery Ministry of EducationSchool of PharmacyFudan UniversityShanghai 201203China Department of Pharmacology and Chemical Biology State Key Laboratory of Oncogenes and Related GenesShanghai Universities Collaborative Innovation Center for Translational MedicineShanghai Jiao Tong University School of MedicineShanghai 200025China Department of Emergency Shanghai Pudong HospitalFudan University Pudong Medical CenterShanghai 201399China Institute of Science and Technology for Brain-Inspired Intelligence&Department of Neurology Fudan UniversityShanghai 201203China Department of Rehabilitation Medicine Huashan HospitalFudan UniversityShanghai 201203China Daxing Research Institute University of Science and Technology BeijingBiomedical Industry BaseZhongguancun Science and Technology ParkBeijing 102600China Cellular Biomedicine Group Inc. Shanghai 201210China

Mesenchymal stem cells(MSCs)experience substantial viability issues in the stroke infarct region,limiting their therapeutic efficacy and clinical *** levels of deadly reactive oxygen radicals(ROS)and proinflammatory cytokines(PC)in the infarct milieu kill transplanted MSCs,whereas low levels of beneficial ROS and PC stimulate and improve engrafted MSCs’*** on the intrinsic hormesis effects in cellular biology,we built a microglia-inspired MSC bioengineering system to transform detrimental high-level ROS and PC into vitality enhancers for strengthening MSC *** system is achieved by bioorthogonally arming metabolic glycoengineered MSCs with microglial membrane-coated nanoparticles and an antioxidative extracellular protective *** this system,extracellular ROSscavenging and PC-absorbing layers effectively buffer the deleterious effects and establish a microlivable niche at the level of a single MSC for ***,the infarct’s inanimate milieu is transformed at the tissue level into a new living niche to facilitate *** engineered MSCs achieved viability five times higher than natural MSCs at seven days after transplantation and exhibited a superior therapeutic effect for stroke recovery up to 28 *** vitality-augmented system demonstrates the potential to accelerate the clinical translation of MSC treatment and boost stroke recovery.

关键词： Ischemic stroke Mesenchymal stem cell Cell engineering Hormesis effect Bioorthogonal chemistry Microglia Reactive oxygen spices Proinflammatory cytokines

基于首次穿越PDF自适应估计的时变可靠性分析方法

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机械工程学报 2024年第5期60卷 264-275页

作者：俞水吴晓郭鹏王志华西南交通大学机械工程学院成都610031 轨道交通运维技术与装备四川省重点实验室成都610031 航空工业成都飞机工业(集团)有限公司成都610091

针对机械产品全寿命周期的时变可靠性问题,提出了自适应首次穿越点(First-crossing time point,FCTP)的概率分布模型,可获得寿命周期内可靠性的演化规律,为机械产品在全寿命周期内可靠性分析和设计提供了工具。对于传统时变可靠性首次... 详细信息

针对机械产品全寿命周期的时变可靠性问题,提出了自适应首次穿越点(First-crossing time point,FCTP)的概率分布模型,可获得寿命周期内可靠性的演化规律,为机械产品在全寿命周期内可靠性分析和设计提供了工具。对于传统时变可靠性首次穿越法中首次穿越率模型估计困难的问题,首先基于支持向量回归提出首次穿越时间点自适应代理模型;其次,采用拉丁化部分分层抽样(Latinized partially stratified sampling,LPSS)估计首次穿越时间点代理模型的四阶原点矩;再次,以距离代理模型一阶矩最近的点为中心,结合均匀分布构建自适应学习函数;然后,以相邻两次迭代的各阶矩最大误差为收敛条件,建立最优的首次穿越时间点的代理模型;最后,基于最优代理模型,利用核密度函数求解首次穿越点的概率密度函数(Probability density function,PDF),获得产品寿命周期内时变可靠性的演化趋势。通过三个算例验证了所提方法的有效性。

关键词：时变可靠性全寿命周期首次穿越时间点自适应代理模型核密度函数

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肾上腺异位脑膜瘤1例

中华病理学杂志 2024年第1期53卷 89-91页

作者：吴润红王志华中国科学技术大学附属第一医院(安徽省立医院)临床病理中心中国科学技术大学智慧病理学研究所合肥230036

从脑膜瘤的起源和部位划分,脑膜瘤可分为3类:(1)原发于神经系统内脑膜瘤;(2)原发于神经系统外脑膜瘤;(3)继发性脑膜瘤。异位脑膜瘤主要是指第二类。肾上腺异位脑膜瘤较为罕见,本文报道1例肾上腺异位脑膜瘤,患者血醛固酮水平升高,行单侧... 详细信息

从脑膜瘤的起源和部位划分,脑膜瘤可分为3类:(1)原发于神经系统内脑膜瘤;(2)原发于神经系统外脑膜瘤;(3)继发性脑膜瘤。异位脑膜瘤主要是指第二类。肾上腺异位脑膜瘤较为罕见,本文报道1例肾上腺异位脑膜瘤,患者血醛固酮水平升高,行单侧肾上腺切除术后,血醛固酮水平恢复正常。

关键词：异位脑膜瘤醛固酮水平肾上腺神经系统单侧肾上腺切除原发继发性