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Ochratoxin A induces mitochondrial apoptosis and ferroptosis by inhibiting Sigma-1 receptor to disrupt redox and cholesterol homeostasis

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Food Science and Human Wellness 2024年

作者： Song yao Wenying Chen Hongwei Wang Ruiran Yang yao Zhou Shuangchao Liu xiaoli Shen School of Public Health， Zunyi Medical University Key Laboratory of Maternal & Child Health and Exposure Science of Guizhou Higher Education Institutes

Ochratoxin A (OTA)， a secondary fungal metabolite known for its nephrotoxic effects， is widespread in various foods and animal feeds. Our recent investigation suggests a correlation between OTA-induced nephrotoxicity and Sigma-1 receptor (Sig-1R)-mediated mitochondrial apoptosis in human proximal tubule epithelial-originated kidney-2 (HK-2) cells. However， the involvement of Sig-1R in OTA-induced nephrotoxicity， encompassing other forms of regulated cell death like ferroptosis， remains unexplored. In this research， cell viability， apoptotic rate， cholesterol levels， mitochondrial glutathione (mGSH) levels， reactive oxygen species (ROS) levels， and protein expressions in HK-2 cells treated with OTA and/or blarcamesine hydrochloride (Anavex 2-73) were evaluated. The results suggest that OTA induces mitochondrial apoptosis and ferroptosis by inhibiting Sig-1R， subsequently promoting sterol regulatory element-binding protein 2 (SREBP2)， 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)， GRAM domain-containing protein 1B (GRAMD1B)， steroidogenic acute regulatory protein， mitochondrial (StARD1)， 78 kDa glucose-regulated protein (GRP78)， CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP)， cyclophilin D (CypD)， Cleaved-Caspase-3， B-cell lymphoma-2-associated X protein (BAX)， and long-chain fatty acid-CoA ligase 4 (ACSL4)， inhibiting tumor necrosis factor receptor-associated protein 1 (TRAP1)， mitochondrial 2-oxoglutarate/malate carrier protein (SLC25A11)， B-cell lymphoma-2-like protein 1 (BCL-XL)， and glutathione peroxidase 4 (GPX4)， reducing mGSH levels， and increasing total cholesterol， mitochondrial cholesterol， and ROS levels. In conclusion， OTA induces mitochondrial apoptosis and ferroptosis by inhibiting Sig-1R， thereby disrupting redox and cholesterol homeostasis in vitro. The regulation of cholesterol homeostasis by Sig-1R and its involvement in OTA-induced mitochondrial apoptosis and ferroptosis are reported here for the first time.

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一种高气压金属卤化物气体放电灯用新型电源的原理研究

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西安交通大学学报 2001年第6期35卷 568-572页

作者：王汝文姚晓莉姚建军西安交通大学电气工程学院西安710049

提出一种用于高气压金属卤化物气体放电灯供电电源的新型主电路拓扑 .不需设置专门提供起燃脉冲的高压脉冲发生器 ,只须改变电路工作频率 ,即能满足这类灯在起燃、负阻运行、稳态运行各阶段对电源不同输出特性的要求 .电路结构简单 ,装... 详细信息

提出一种用于高气压金属卤化物气体放电灯供电电源的新型主电路拓扑 .不需设置专门提供起燃脉冲的高压脉冲发生器 ,只须改变电路工作频率 ,即能满足这类灯在起燃、负阻运行、稳态运行各阶段对电源不同输出特性的要求 .电路结构简单 ,装置体积小 .在负载稳定运行后 ,电源输出特性近似电流源 ,开关器件电流幅值较低 ,并可实现零电流换相 .讨论了这种电源的工作原理和系统结构 ,并给出了模拟负载的PSPICE仿真和实验室试验结果 ,表明其完全符合电路的工作原理和设计思想 .

关键词：谐振逆变器电流源零电流换相高气压金属卤化物气体放电灯

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Investigating the Genetic Bases of Growth Regulation by E2F3 in Dwarf Surf Clams Mulinia lateralis

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Journal of Ocean University of China 2024年第5期23卷 1347-1358页

作者： yao Ruixing WANG Chen KONG Lingling WANG Yujue BAO Zhenmin HU xiaoli MOE Key Laboratory of Marine Genetics and Breeding College of Marine Life Sciences Ocean University of China Laboratory for Marine Fisheries Science and Food Production Processes Qingdao Marine Science and TechnologyCenter Key Laboratory of Tropical Aquatic Germplasm of Hainan Province Sanya Oceanographic Institution Ocean University of China

Bivalve aquaculture plays a crucial role in the aquaculture industry due to the economic value of many bivalve species. Understanding the underlying genetic basis of bivalve growth regulation is essential for enhancing germplasm innovation and ensuring sustainable development of the industry. Though numerous candidate genes have been identified, their functional validation remains challenging. Fortunately, the dwarf surf clam(Mulinia lateralis) serves as a promising model organism for investigating genetic mechanisms underlying growth regulation in bivalves. The GWAS study in the Yesso scallop(Patinopecten yessoensis) has pinpointed the E2F3 gene as a key regulator of growth-related traits. However, the specific role of E2F3 in bivalve growth remains unclear. This study aimed to further confirm the regulatory function of the E2F3 gene in the dwarf surf clam through RNA interference experiments. Our results revealed several genes are associated with individual growth and development, including CTS7, HSP70B2, and PGLYRP3, as well as genes involved in lipid metabolism such as FABP2 and FASN. Functional enrichment analysis indicated that E2F3 primarily modulates critical processes like amino acid and lipid metabolism. These findings suggest that E2F3 likely regulates growth in the dwarf surf clam by influencing amino acid and lipid metabolism. Overall, this study advances our understanding on the function of E2F3 gene in growth regulation in bivalves, providing valuable insights for future research in this field.

关键词： bivalve dwarf surf clam Mulinia lateralis E2F3 growth regulation RNA interference experiment transcriptomic analysis

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Alcohol exposure impairs brain paravascular functions

Alcohol exposure impairs brain paravascular functions

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中国神经科学学会第十二届全国学术会议

作者： Qiang Liu xiaoli yao Zhong Pei Huanxing Su State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau Department of Neurology National Key Clinical Department and Key Discipline of Neurology The First Affiliated Hospital Sun Yat-Sen University

Alcoholism is a risk factor for the development of cognitive decline and dementia. Here we demonstrated that the paravascular function in the brain was impaired by ethanol in a dose-dependent manner. Acute moderate and heavy ethanol administration substantially retarded and reduced the entry of subarachnoid cerebrospinal fluid（CSF） via the paravascular space into the cerebral parenchyma, thus impaired CSFinterstitial fluid（ISF） exchange and parenchymal amyloid β（Aβ） peptide clearance. The elevated release of β-endorphin and reduced cerebrovascular pulsatility after acute ethanol administration could account for the impairment of the paravascular function. Chronic ethanol consumption led to a global activation of astrocytes and a widespread loss of perivascular AQP4 polarization in the brain, which results in an irreversible impairment of the paravascular function and parenchymal Aβ clearance. Therefore, we propose that impaired paravascular functions and reduced parenchymal Aβ clearance found in both acute and chronic ethanol-treated animals may contribute to the development of cognitive decline and dementia in alcoholism.

关键词： Alcoholism AQP4 polarization Aβ clearance CSF-ISF exchange

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Efficacy and safety of modified medium-chain triglyceride ketogenic diet in patients with drug-resistant epilepsy

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Acta Epileptologica 2024年第1期7卷 44-52页

作者： Hua Li yao Wang Jing Guo Peiqi Zhang Zheng Xu Kai Peng xiaoli Dong Liming Zhao Department of Neurology Guangdong Sanjiu Brain HospitalGuangzhou510510China

Background Medium-chain triglyceride ketogenic diet(MCTKD)is previously less commonly used in *** study was aimed to assess the efficacy and safety of the modified MCTKD in the treatment of drug-resistant epilepsy in Chinese *** Patients with drug-resistant epilepsy were enrolled to receive treatment with modified MCTKD in Guangdong Sanjiu Brain Hospital during December 2020 and September *** modified MCTKD contained fat that provided 50–70%of the total energy,as well as proteins and carbohydrates that provided 20–30%and 20%of energy,*** fat component was composed of 20–30%medium-chain triglycerides(MCTs)and 30–40%long-chain *** efficacy and safety of the diet were assessed at 1,3 and 6 *** A total of 123 patients aged 2.5 to 65 years,were included in this *** response rates at 1,3 and 6 months were 49.6%,43.1%,and 30.9%,*** seizure freedom rates at 1,3 and 6 months were 12.2%,10.6%,and 6.5%,*** retention rates at 1,3 and 6 months were 98.4%,65.0%and 33.3%*** effects occurred in 21.14%of patients,which were predominantly gastrointestinal symptoms such as abdominal pain,diarrhea,vomiting,and constipation,and most of them resolved after dietary adjustments.A total of 82 patients(66.7%)discontinued the treatment with the reason of refusing to eat(8.1%),poor efficacy(35.0%),poor compliance(4.9%),and inability to follow-up(9.8%).Only 4 patients(3.3%)withdrew the diet due to side *** The modified MCTKD with MCTs providing 20–30%of energy has a good safety in patients with drug-resistant epilepsy,but its effectiveness needs to be *** modifications of MCTKD with an optimal energy ratio are required to achieve a better efficacy and safety.

关键词： Medium-chain triglyceride ketogenic diet Ketogenic diet Drug-resistant epilepsy Efficacy Safety

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Researching for affection facts of CBM production in Linfen block based on the method of gray co-connection

Researching for affection facts of CBM production in Linfen ...

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2015年全国沉积学大会

作者： Wang Dan Zhao Fenghua yao xiaoli Wu Xiaolei Li Xiufang College of Geoscience and Surveying Engineering China University of Mining and Technology(Beijing) Linfen Branch Pet-rochina Coalbed Methane Company Limited

Linfen Block locates in the south of Erdos Basin. It is a large west-east monocline structure. A NE-SW pressure fault lays through whole block and make it complex and form interphase col-pump structure. Maincoal beds developed in the block and coal body structure is protogenetic structure coal and fragment coal. In the vicinity of faults, crumpled coal and mylonitic coal developed. Two different hydrology units exist in the block from east to west. The watershed between the two units is Xueguan reverse fault which penetrates through the block. The hydrology unit in the east includes water supplying area, radial-flow area and water escaping area. In the west of the fault,it is not obvious for the character of water supplying. Researching the drilling,completion,and seismic data of 76 exploration wells, to make a choice with single parameter. It eliminated those wells with low production potential, which is: buried depth deeper than 1400 m,the thickness of coal bed thinner than 1m,gas content per ton less than 4m3,locating in water supplying and radial-flowing area. 14 wells are got rid of. Then to evaluate the the left 62 wells with the method of gray correlation and choose 7 main factors, it made out related coefficient of compared sequence and reference sequence to get the average, that is the degree of association. It recognized that the main static factors of the degree of association for productivity from big to small is: coal body structure, hydrology geology, thickness of coal bed, resolution pressure gradient, CBM content, reservoir bed pressure gradient. In the last, to optimize the most potential block for developing CBM based on the sequence of correction data of 62 wells. It worked out the potential block is Xiaohuigong-yaoqu-Caojing and Puxian-MIngzhu-Sange. The secondary block locates in the surrounding area of the north and south area.

关键词： Linfen Block CBM Gray Co-connection the Potential Block

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碳四烃的综合利用研究

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石油化工 2009年第11期38卷 1245-1252页

作者：李涛柏基业姚小利中国石化扬子石油化工有限公司研究院江苏南京210048

分析了C_4烃的来源、组成、分离技术和加工利用途径,探讨了目前国内C_4烃的加工利用流程,针对炼化装置副产的异丁烷和催化裂化C_4烃,提出建设直接烷基化油装置加以利用;对裂解C_4抽余液的加工利用问题进行了多方案对比,提出建设甲基叔... 详细信息

分析了C_4烃的来源、组成、分离技术和加工利用途径,探讨了目前国内C_4烃的加工利用流程,针对炼化装置副产的异丁烷和催化裂化C_4烃,提出建设直接烷基化油装置加以利用;对裂解C_4抽余液的加工利用问题进行了多方案对比,提出建设甲基叔丁基醚(MTBE)裂解制纯异丁烯装置,发展以纯异丁烯为主的下游产品;或将原有MTBE装置进行部分改造,增加加氢单元,采用间接烷基化工艺改产高辛烷值的异辛烷烷基化油。

关键词：碳四烃异丁烯异丁烷裂解C_4抽余液综合利用

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神经遗传病治疗的新希望

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中华神经科杂志 2022年第7期55卷 671-681页

作者：何若洁姚晓黎中山大学附属第一医院神经科广东省重大神经疾病诊治研究重点实验室国家临床重点专科和国家重点学科广州510080

神经遗传病是一组主要累及神经系统,包括中枢神经、周围神经、肌肉的遗传性疾病,临床表现复杂多样,治疗难度较大。近年来,随着对神经遗传性疾病病因和发病机制的深入研究,针对突变基因研发的基因治疗方法如反义寡核苷酸、RNA干扰、腺相... 详细信息

神经遗传病是一组主要累及神经系统,包括中枢神经、周围神经、肌肉的遗传性疾病,临床表现复杂多样,治疗难度较大。近年来,随着对神经遗传性疾病病因和发病机制的深入研究,针对突变基因研发的基因治疗方法如反义寡核苷酸、RNA干扰、腺相关病毒介导的基因转导、具有基因修饰作用的小分子化合物和规律间隔成簇短回文重复序列/Cas9基因编辑等以及针对致病机制关键靶点研发的具有潜在疗效的药物逐步向临床应用转化,为神经遗传病患者的治疗带来新的希望。

关键词：遗传学,医学神经系统疾病临床试验,Ⅰ期临床试验,Ⅱ期临床试验,Ⅲ期基因治疗

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前上纵隔异位甲状旁腺腺瘤致原发性甲状旁腺功能亢进症1例

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中华胸心血管外科杂志 2020年第7期36卷 428-429页

作者：高楚淇姚孝礼刘娟西安交通大学第一附属医院内分泌科 710061

44岁女性患者,因间断腰背痛8年入院,院外多次治疗泌尿系统结石,血液检查证实有高钙、低磷和高甲状旁腺激素血症,影像学检查证实前上纵隔瘤性占位。术前限钙摄入和补液利尿后,在全麻下行胸腔镜经剑突下纵隔肿瘤切除术。术后病理诊断为前... 详细信息

44岁女性患者,因间断腰背痛8年入院,院外多次治疗泌尿系统结石,血液检查证实有高钙、低磷和高甲状旁腺激素血症,影像学检查证实前上纵隔瘤性占位。术前限钙摄入和补液利尿后,在全麻下行胸腔镜经剑突下纵隔肿瘤切除术。术后病理诊断为前上纵隔异位甲状旁腺腺瘤,术后钙、磷水平恢复正常。

关键词：前上纵隔原发性甲状旁腺功能亢进症纵隔肿瘤切除术腰背痛甲状旁腺激素泌尿系统结石胸腔镜血液检查

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运动神经元病的鉴别诊断

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中华神经科杂志 2019年第10期52卷 841-846页

作者：廉羚姚晓黎中山大学附属第一医院神经科(广东省重大神经疾病诊治研究重点实验室) 广州510080

运动神经元病(MND)是一类累及上、下运动神经元的慢性进行性神经系统变性疾病,主要包括肌萎缩侧索硬化、进行性延髓麻痹、原发性侧索硬化、进行性肌萎缩、脊髓性肌萎缩症几种类型。不同类型的运动神经元病有各自不同的特点,诊断主要依... 详细信息

运动神经元病(MND)是一类累及上、下运动神经元的慢性进行性神经系统变性疾病,主要包括肌萎缩侧索硬化、进行性延髓麻痹、原发性侧索硬化、进行性肌萎缩、脊髓性肌萎缩症几种类型。不同类型的运动神经元病有各自不同的特点,诊断主要依赖临床表现、体格检查及电生理检查,并排除其他诊断。对于不典型病例,临床上有时难与上、下运动神经元受累的其他疾病相鉴别。本文按照运动神经元病受累部位对各类型MND及其鉴别诊断进行介绍。

关键词：运动神经元病肌萎缩侧索硬化上运动神经元下运动神经元鉴别诊断

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