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ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2–BECN1 interaction

Acta Pharmaceutica Sinica B 2024年第5期14卷 2026-2038页

作者： Shiqiang Xu Qilian Ma Junwen Shen Ningning Li Shan Sun Nana Wang Yang Chen Chunsheng Dong Kin Yip Tam Jochen H.M.Prehn Hongfeng Wang zheng ying Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China MOE Key Laboratory of Geriatric Diseases and Immunology College of Pharmaceutical SciencesSuzhou Medical College of Soochow UniversitySuzhou 215123China Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow UniversitySuzhou 215123China Dept.of Physiology&Medical Physics and FUTURE-NEURO Research Centre Royal College of Surgeons in IrelandDublin D02 YN77Ireland Faculty of Health Sciences University of MacaoTaipaMacao 999078China Insititutes of Biology and Medical Science Soochow UniversitySuzhou 215123China

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis(ALS)and frontotemporal dementia(FTD),two neurodegenerative disorders.The GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72(C9orf72)is the most genetic cause of both ALS and FTD.According to the previous studies,GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation,which produces dipeptide repeat(DPR)proteins.Although there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/FTD,whether these DPRs can affect autophagy remains unclear.In the present study,we find that poly-GR and poly-PR,two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies,strongly inhibit starvation-induced autophagy.Moreover,our data indicate that arginine-rich DPRs enhance the interaction between BCL2 and BECN1/Beclin 1 by inhibiting BCL2 phosphorylation,therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in cells.Importantly,our study not only highlights the role of C9orf72 DPR in autophagy dysfunction,but also provides novel insight that pharmacological intervention of autophagy using SW063058,a small molecule compound that can disrupt the interaction between BECN1 and BCL2,may reduce C9orf72 DPR-induced neurotoxicity.

关键词： Amyotrophic lateral sclerosis Frontotemporal dementia C9orf72 Autophagy BCL2 BECN1/Beclin 1 Dipeptide repeat Neurodegeneration

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Blood pressure targets in patients with chronic kidney disease:Comments and controversies

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Chinese Medical Journal 2024年第3期137卷 270-272页

作者： ying zheng Guangyan Cai Xiangmei Chen Department of Nephrology First Medical Center of Chinese PLA General HospitalNational Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijing 100853China

According to the Global Burden of Disease Study 2017,there are 132 million patients with chronic kidney disease(CKD)in China,^([1])and the prevalence of hypertension in Chinese patients with CKD(67.3%)is significantly higher than that in the general population(23.2%).^([2,3])CKD is both a cause and a consequence of hypertension,and these two conditions form a vicious cycle that leads to the high prevalence rate of hypertension in patients with CKD.Uncontrolled hypertension accelerates the deterioration of renal function,which significantly increases the risk of developing end-stage renal disease(ESRD),as well as cardiovascular and cerebrovascular diseases,leading to poor patient outcomes.

关键词： patients Blood hypertension

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Development of Fixture Layout Optimization for Thin-Walled Parts:A Review

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Chinese Journal of Mechanical Engineering 2024年第1期37卷 15-39页

作者： Changhui Liu Jing Wang Binghai Zhou Jianbo Yu ying zheng Jianfeng Liu School of Mechanical Engineering Tongji UniversityShanghai 201804China Shanghai Jiaotong University Shanghai 200240China Shanghai Waigaoqiao Shipbuilding Co. Ltd.Shanghai 200137China

An increasing number of researchers have researched fixture layout optimization for thin-walled part assembly during the past decades.However,few papers systematically review these researches.By analyzing existing literature,this paper summarizes the process of fixture layout optimization and the methods applied.The process of optimization is made up of optimization objective setting,assembly variation/deformation modeling,and fixture layout optimization.This paper makes a review of the fixture layout for thin-walled parts according to these three steps.First,two different kinds of optimization objectives are introduced.Researchers usually consider in-plane variations or out-of-plane deformations when designing objectives.Then,modeling methods for assembly variation and deformation are divided into two categories:Mechanism-based and data-based methods.Several common methods are discussed respectively.After that,optimization algorithms are reviewed systematically.There are two kinds of optimization algorithms:Traditional nonlinear programming and heuristic algorithms.Finally,discussions on the current situation are provided.The research direction of fixture layout optimization in the future is discussed from three aspects:Objective setting,improving modeling accuracy and optimization algorithms.Also,a new research point for fixture layout optimization is discussed.This paper systematically reviews the research on fixture layout optimization for thin-walled parts,and provides a reference for future research in this field.

关键词： Thin-walled parts Assembly quality Fixture layout optimization Modeling methods Optimization algorithms

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Effect of lens surgery on health-related quality of life in preschool children with congenital ectopia lentis

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 66-72页

作者： Yan-Qiao Huang Qian-Zhong Cao Yi-Yao Wang Yi-Jing Zhou Dan-ying zheng State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangdong Provincial Clinical Research Center for Ocular DiseasesGuangzhou 510060Guangdong ProvinceChina

AIM:To evaluate the effect of lens surgery on health-related quality of life(HRQoL)of preschool children with congenital ectopia lentis(CEL).METHODS:A prospective self-controlled study was conducted in Zhongshan Ophthalmic Center.Children aged from 5 to 7y whom were diagnosed with CEL and underwent phacoemulsification with scleral-fixated posterior chamber intraocular lens implantation and their parents were enrolled in this study.All of them completed the child and proxy(parental)PedsQL™4.0 before and after the surgery.Their preoperative scores were compared to their postoperative ones.Subgroup analyses were performed based on gender and preoperative bilateral presenting visual acuity of the children.RESULTS:Thirty-two children with CEL successfully underwent surgery without any complications,among whom 8 had monocular surgery and 24 had binocular surgery.Preoperative and postoperative questionnaires were completed by 32 child-parent pairs.Surgical intervention could significantly improve the vision of affected children(P<0.001).The medians of physical,psychosocial and total health scores self-reported by the children were 68.75(62.50,81.25),65.00(60.00,80.00)and 67.39(60.87,78.26)preoperatively and were 93.75(87.50,100.00),90.00(83.33,96.67)and 89.13(85.32,95.65)postoperatively.The preoperative scores of the affected children were significantly lower in all scales than age-matched healthy children(P<0.001).All the postoperative scores were significantly higher than the preoperative scores in affected children and their parents(P<0.001).In the physical functioning evaluation,the preoperative score reported by parents of girls was higher than parents of boys(P=0.041),and the postoperative score of girls was higher than that of boys(P=0.036).CONCLUSION:CEL is associated with significantly worse quality of life in preschool children.Surgical intervention can significantly improve the HRQoL in affected children from both personal and family perspective.

关键词： congenital ectopia lentis surgical intervention health-related quality of life preschool children

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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 lacking.Emerging in vivo imaging and labeling methods offer great potential for observing dynamic neural processes in the central nervous system in conditions of health and disease.This 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 SCI.We then summarize and compare the techniques behind these studies and clarify the advantages of in vivo imaging compared with traditional neuroscience examinations.Finally,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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Field experimental study on the effect of thawed depth of frozen alpine meadow soil on rill erosion by snowmelt waterflow

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International Soil and Water Conservation Research 2024年第1期12卷 54-63页

作者： ying zheng Xiaonan Shi Fan Zhang Tingwu Lei Chen Zeng Xiong Xiao Li Wang Guanxing Wang State Key Laboratory of Tibetan Plateau Earth System Resources and Environment(TPESRE)Institute of Tibetan Plateau ResearchChinese Academy of SciencesBeijing100101China University of Chinese Academy of Sciences Beijing100101China State Key Laboratory of Hydrology-Water Resources and Hydraulic Engineering Hohai UniversityNanjing210098China College of Water Resources and Civil Engineering China Agricultural UniversityBeijing100083China College of Geographic Science Hunan Normal UniversityChangsha410081China

Soil erosion by snow or ice melt waterflow is an important type of soil erosion in many high-altitude and high-latitude regions and is further aggravated by climate warming.The snowmelt waterflow erosion process is affected by soil freeze-thaws and is highly dynamically variable.In this study,a methodology was developed to conduct in situ field experiments to investigate the effects of the thawed depth of the frozen soil profile on snowmelt waterflow erosion.The method was implemented on an alpine meadow soil slope at an altitude of 3700 m on the northeastern Tibetan Plateau.The erosion experiments involved five thawed soil depths of 0,10,30(35),50,and 80(100)mm under two snowmelt waterflow rates(3 and 5 L/min).When the topsoil was fully frozen or shallow-thawed(≤10 mm),its hydrothermal and structural properties caused a significant lag in the initiation of runoff and delayed soil erosion in the initial stage.The runoff and sediment concentration curves for fully frozen and shallow-thawed soil showed two-stage patterns characteristic of a sediment supply limited in the early stage and subject to hydrodynamic-controlled processes in the later stage.However,this effect did not exist where the thawed soil depth was greater than 30 mm.The deep-thawed cases(≥30 mm)showed normal hydrograph and sedigraph patterns similar to those of the unfrozen soil.The findings of this study are important for understanding the erosion rates of partially thawed soil and for improving erosion simulations in cold regions.

关键词： Snowmelt waterflow erosion Hillslope erosion process Soil freeze and thaw Runoff generation In situ experimental method

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Mathematical methods for main tenance and operation cost prediction based on transfer learning in State Grid

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Applied Mathematics(A Journal of Chinese Universities) 2022年第4期37卷 598-614页

作者： GUO Yun-peng WANG Dong-fa zheng ying DING Wei-bin State Grid Zhejiang Electric Power Company Jinhua Power Supply Company Jinhua 321000China State Grid Zhejiang Electric Power Company Hangzhou 310018China

The electric power enterprise is an important basic energy industry for national development,and it is also the first basic industry of the national economy.With the continuous expansion of State Grid,the progressively complex operating conditions,and the increasing scope and frequency of data collection,how to make reasonable use of electrical big data,improve utilization,and provide a theoretical basis for the reliability of State Grid operation,has become a new research hot spot.Since electrical data has the characteristics of large volume,multiple types,low-value density,and fast processing speed,it is a challenge to mine and analyze it deeply,extract valuable information efficiently,and serve for the actual problem.According to the features of these data,this paper uses artificial intelligence methods such as time series and support vector regression to establish a data mining network model for standard cost prediction through transfer learning.The experimental results show that the model in this paper obtains better prediction results on a small sample data set,which verifies the feasibility of the deep transfer model.Compared with activity-based costing and the traditional prediction method,the average absolute error of the proposed method is reduced by 10%,which is effective and superior.

关键词： transfer learning LSTM support vector regression activity based costing State Grid

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重构新中国时尚:1955年服装改革运动与民族化设计探析

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艺术设计研究 2024年第2期 5-13页

作者：郑颖上海大学上海美术学院

学界对新中国服装的固有印象一直停留在严肃而刻板的制服文化。本文旨在深入分析1955年的服装改革运动①这一现象,并探究在统一的新中国制服语境中服装改革运动的兴起背后涌现的政治、经济、文化等多重因素。通过审视民众对该运动的态... 详细信息

学界对新中国服装的固有印象一直停留在严肃而刻板的制服文化。本文旨在深入分析1955年的服装改革运动①这一现象,并探究在统一的新中国制服语境中服装改革运动的兴起背后涌现的政治、经济、文化等多重因素。通过审视民众对该运动的态度和相应行为反馈,进一步剖析新中国服装形成单调性的复杂成因。在对服装样式的筛选和讨论中,体现当时社会意识与观念,而围绕服装样式展开的多方讨论则构建了一场自上而下的美学探索。同时,文章将聚焦本土化设计在该改革运动中的体现,通过这些追问试图拓宽学界对新中国服装文化的固有概念和印象,亦提供了一种新中国时期的服装文化解读的新视角。

关键词：服装改革运动新中国民族化设计郁风

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Development and Regeneration Performance of LaNiO_(3)Perovskite Oxides for Dry Reforming of Methane

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热科学学报:英文版 2023年第5期32卷 1935-1944页

作者： CAO Dingshan LUO Cong CAI Guoqiu LUO Tong WU Fan LI Xiaoshan zheng ying ZHANG Liqi State Key Laboratory of Coal Combustion School of Energy and Power EngineeringHuazhong University of Science and TechnologyWuhan 430074China

Dry reforming of methane(DRM)process has attracted much attention in recent years for the direct conversion of CH_4 and CO_(2)into high-value-added syngas.The key for DRM was to develop catalysts with high activity and stability.In this study,LaNiO_(3)was prepared by the sol-gel,co-precipitation,and hydro-thermal methods to explore the influence of preparation methods on the catalyst structure and DRM reaction performance.The regeneration properties of the used LaNiO_(3)catalysts were also investigated under steam,CO_(2),and air atmospheres,respectively.The results showed that LaNiO_(3)prepared by sol-gel method showed the best DRM performance at 750℃.The DRM performance of the samples prepared by hydro-thermal method was inhibited at 750℃due to the residual of Na^(+)ions during the preparation process.The regeneration tests showed that none of the three atmospheres could restore LaNiO_(3)perovskite phase in the samples,but they could eliminate the carbon deposits in the samples during the DRM reaction,so the samples could maintain stable DRM performance at different cycling stages.

关键词： dry reforming of methane perovskite LaNiO_(3) CO_(2)utilization thermal conversion

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Identification of Bulbocodin D and C as novel STAT3 inhibitors and their anticancer activities in lung cancer cells

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Chinese Journal of Natural Medicines 2023年第11期21卷 842-851页

作者： HE Xinyu FU Jiarui LYU Wenyu HUANG Muyang MO Jianshan CHENG Yaxin XU Yulian zheng Lijun ZHANG Xiaolei QI Lu ZHANG Lele zheng ying HUANG Mingqing NI Lin LU Jinjian State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China College of Plant Protection Fujian Agriculture and Forestry UniversityFuzhou 350002China National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation Guangdong Key Laboratory of Chiral Molecule and Drug DiscoverySchool of Pharmaceutical SciencesSun Yat-Sen UniversityGuangzhou 510006China College of Life Sciences China Jiliang UniversityHangzhou 310018China Department of Pharmacy Fujian Medical University Union HospitalFuzhou 350100China Department of Pathology School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China School of Basic Medical Sciences Chengdu UniversityChengdu 610106China College of Pharmacy Fujian University of Traditional Chinese MedicineFuzhou 350003China Department of Pharmaceutical Sciences Faculty of Health SciencesUniversity of MacaoMacao 999078China Guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease Research University of MacaoMacao 999078China

Cancer stands as one of the predominant causes of mortality globally, necessitating ongoing efforts to develop innovative therapeutics. Historically, natural products have been foundational in the quest for anticancer agents. Bulbocodin D (BD) and Bulbocodin C (BC), two bibenzyls derived from Pleione bulbocodioides (Franch.) Rolfe, have demonstrated notable in vitro anticancer activity. In human lung cancer A549 cells, the IC50s for BD and BC were 11.63 and 11.71 μmol·L^(−1), respectively. BD triggered apoptosis, as evidenced by an upsurge in Annexin V-positive cells and elevated protein expression of cleaved-PARP in cancer cells. Furthermore, BD and BC markedly inhibited the migratory and invasive potentials of A549 cells. The altered genes identified through RNA-sequencing analysis were integrated into the CMap dataset, suggesting BD’s role as a potential signal transducer and activator of transcription 3 (STAT3) inhibitor. SwissDock and MOE analyses further revealed that both BD and BC exhibited a commendable binding affinity with STAT3. Additionally, a surface plasmon resonance assay confirmed the direct binding affinity between these compounds and STAT3. Notably, treatment with either BD or BC led to a significant reduction in p-STAT3 (Tyr 705) protein levels, regardless of interleukin-6 stimulation in A549 cells. In addition, the extracellular signal-regulated kinase (ERK) was activated after BD or BC treatment. An enhancement in cancer cell mortality was observed upon combined treatment of BD and U0126, the MEK1/2 inhibitor. In conclusion, BD and BC emerge as promising novel STAT3 inhibitors with potential implications in cancer therapy.

关键词： Cancer Natural products Bulbocodin D Bulbocodin C STAT3 ERK

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