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Elevated peripheral levels of receptor-interacting protein kinase 1(RIPK1)and IL-8 as biomarkers of human amyotrophic lateral sclerosis

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Signal Transduction and Targeted Therapy 2024年第1期9卷 271-278页

作者： Jun Wei Min Li Zhi Ye Xinqian Hu xiaoyan he Jia Wang Gaofeng Chen Chengyu Zou Daichao Xu Hongbing Zhang Junying Yuan Yunhong Zha Institute of Neural Regeneration and Repair and Department of Neurology The First College of Clinical Medical ScienceYichang Central HospitalCollege of Basic Medical ScienceChina Three Gorges UniversityHubei Province Clinical Medical Research Center for Rare Diseases of Nervous SystemYichang 443000China Interdisciplinary Research Center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai Key Laboratory of Aging StudiesShanghai 201210China State Key Laboratory of Common Mechanism Research for Major Diseases Haihe Laboratory of Cell EcosystemDepartment of PhysiologyInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Amyotrophic lateral sclerosis(ALS)is a devastating fatal neurodegenerative disease with no cure.Receptor-interacting protein kinase 1(RIPK1)has been proposed to mediate pathogenesis of ALS.Primidone has been identified as an old drug that can also inhibit RIPK1 kinase.We conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1G93A mice and ALS patients.SOD1G93A mice treated with primidone showed significant delay of symptomatic onset and improved motor performance.One-hundred-sixty-two ALS participants dosed daily with primidone(62.5 mg)completed 24-week follow-up.A significant reduction was showed in serum levels of RIPK1 and IL-8,which were significantly higher in ALS patients than that of healthy controls(Phe severity of bulbar symptoms(Pheral can be used as clinical biomarkers for the activation of RIPK1 in central nervous system in human ALS patients.Repurposing primidone may provide a promising therapeutic strategy for ALS.The effect of primidone for the treatment of other inflammatory diseases may also be considered,since the activation of RIPK1 has been implicated in mediating a variety of inflammatory diseases including COVID-19-associated cytokine release syndrome(CRS).(ChiCTR2200060149).

关键词： RIPK1 diseases Serum

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Stable oral lubrication enhancer obtained from thiolated polyethylene glycol and mucin

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Friction 2023年第4期11卷 617-634页

作者： xiaoyan he Pravin SMART Mohamad TAUFIQURRAKHMAN Chun WANG Michael BRYANT Institute of Functional Surfaces School of Mechanical EngineeringUniversity of LeedsLeeds LS29JTUnited Kingdom Reliability Engineering Institute National Engineering Research Center for Water Transport SafetyWuhan University of TechnologyWuhan 430063China

Mucins are vital components contributing to the unique lubrication properties of human whole saliva.For patients receiving medication and or treatment such as diabetes or radiotherapy,xerostomia(dry mouth)is a common with numerous and deleterious side effects.Although products exist on the market to relive the symptoms of Xerostomia there remains a drive to formulate a biocompatible lubricant that replicate the functionality offered by the natural biological environment.herein,a combination of mucin and thiolated polyethylene glycol(PEG-SH)was proposed as a new saliva substitute.Mucin and PEG-SH molecules could form hydrated layers immediately by chemisorption.Meanwhile,the chemical interactions between mucin and PEG-SH molecules also promoted the formation of a mixed layer.All the pre-formed layers could decrease friction and had the potential to decrease wear,especially mucin and PEG-SH mixed layer when compared to mucin only solutions.Further investigations of tribological mechanism implied that the excellent lubrication performance of mixed layer with long effectiveness was contributed to the frictionreducing effect of PEG/mucin molecules and the mucoadhesive property of mucin.The study provides a guide for using mucin as a mucoadhesive agent to stable lubricative polymers with low molecular weight as novel salivary substitutes for lubrication.

关键词： lubrication mucin polyethylene glycol mucoadhesive chemisorption

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Advances in the functional study of glutamine synthetase in plant abiotic stress tolerance response

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The Crop Journal 2022年第4期10卷 917-923页

作者： Huayan Yin Fan Yang xiaoyan he Xuye Du Ping Mu Wujun Ma College of Agronomy Qingdao Agricultural UniversityQingdao 266109ShandongChina Food Futures Institute and College of Science HealthEngineering and EducationMurdoch UniversityPerthWA 6150A ustralia School of Life Sciences Guizhou Normal UniversityGuiyang 550001GuizhouChina

Plant glutamine synthetase(GS,EC6.***.1.2)catalyzes the synthesis of glutamine from glutamate and ammonium ions and acts as a key enzyme in the nitrogen metabolic pathway in organisms.Nitrogen is an essential element for plant growth and development and plays an important role in crop yield and quality formation.Therefore,GS is crucial in many physiological processes in plants.Currently,nitrogen regulation by GS in plants is well-studied in terms of its effect on plant growth and development.This article reviews the regulatory role of plant GS and its molecular mechanism in mitigating stress injury,such as low or high temperature,salinity,drought and oxidation.The function of plant GS in stress tolerance response is focused.The review aims to provide a reference for the utilization of plant GS in crop stress tolerance breeding.

关键词： Glutamine synthetase Plant Abiotic stress Nitrogen metabolism

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A step-by-step multiple stimuli-responsive metal-phenolic network prodrug nanoparticles for chemotherapy

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Nano Research 2022年第2期15卷 1205-1212页

作者： Xiaoqing Yi Weijia Zeng Cui Wang Ying Chen Liangyuan Zheng Xinlin Zhu Yuqiu Ke xiaoyan he Ying Kuang Qitong Huang Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases Ministry of EducationKey Laboratory of Biomaterials and Biofabrication in Tissue Engineering of Jiangxi ProvinceGannan Medical UniversityGanzhou 341000China Faculty of Materials Metallurgy and Chemistry Jiangxi University of Science and TechnologyGanzhou 341000China School of Life Sciences Anhui Medical UniversityHefei 230032China

Currently,chemotherapy is the main clinical therapy of tumors.Depressingly,most chemotherapeutic drugs such as doxorubicin and paclitaxel(PTX)have poor water solubility,leading to low bioavailability and serious side effects.Till now,although a variety of nanoparticulate drug delivery systems have been designed to ameliorate the above disadvantage of chemotherapy drugs,their application is still severely limited due to the complex preparation,poor stability,low drug loading,and premature drug release.herein,a metal phenolic network-based drug delivery system with superior stability,satisfactory drug loading capacity,good biocompatibility,reduced undesired premature release,and excellent anti-tumor ability has been established for achieving step-by-step multiple stimuli-responsive drug delivery.Firstly,the redox-responsive dimeric paclitaxel(diPTX)prodrug was synthesized.Then diPTX@Fe&tannic acid(diPTX@Fe&TA)complex nanoparticles with satisfactory PTX loading capacity were obtained by deposition of Fe&TA network complex on the nanocore of diPTX rapidly with a simple method.The diPTX@Fe&TA nanoparticles have a hydrodynamic diameter of 152.6±1.2 nm,long-term colloidal stability,and high PTX loading content of 24.7%.Besides,diPTX@Fe&TA could expose to the acidic lysosomal environment and the reduction cytoplasmic environment continuously,resulting in the sequential release of diPTX and PTX when it was phagocytosed by tumor cells.Meanwhile,PTX showed almost no release under physiological condition(pH 7.4),which effectively inhibited the undesirable premature release of PTX.More importantly,diPTX@Fe&TA could suppress the growth of tumor effectively in vivo,along with negligible toxicity for organs.This work developed a simple and novel approach for the construction of a stepwise multiple stimuli-responsive drug delivery system with superior stability and satisfactory drug loading capacity to inhibit tumor growth effectively.

关键词： drug delivery step-by-step multiple stimuli-responsive metal-phenolic network superior stability

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Hypo-toxicity and prominent passivation characteristics of 316 L stainless steel fabricated by direct metal laser sintering in a simulated inflammation environment

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Journal of Materials Science & Technology 2021年第34期93卷 205-220页

作者： Xiaoqi Yue Lei Zhang xiaoyan he Decheng Kong Yong Hua Corrosion and Protection Centre University of Science and Technology BeijingBeijing 100083China Shunde Graduate School University of Science and Technology BeijingFoshan 528399China Reliability Engineering Institute National Engineering Research Center for Water Transport SafetyWuhan University of Technology.Wuhan 430063China Institute of Functional Surfaces School of Mechanical Engineering.University of LeedsLeeds LS29JTUnited Kingdom

3D-printing is an emerging technology that challenged wrought counterparts by one-step manufacturing for complicated biological devices.However,the material properties and surface features due to manufacturing parameters play an important role on the corrosion behaviour and influence the toxicity of the material as an implant.In this paper,the improvement of pitting potential was observed by electrochemical experiments as the result of grain refinement of DMLS 316 L at 200 W laser power.The ICP results verified the supressed release of toxic cations after the formation of the passive film with enhanced characteristics.However,the pores from DMLS 316 L have the potential to develop into pits when polarised above pitting potential,promoting the risk of using 3D-printed 316 L as implant materials.

关键词： Inflammation 3D-printing implant Passive film Hypo-toxicity porosity

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科研成果转化的探索性本科药剂学实验教学研究

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实验室研究与探索 2024年第5期43卷 159-162,205页

作者：张继芬何小燕西南大学药学院重庆400715

为实现药学专业本科人才培养目标,把药物纳米晶自稳定皮克林乳液及其设计思路引入本科药剂学实验教学,并转化为一种兼具探索性、创新性和设计性的本科实验项目。介绍了该实验项目的实施方案,包括实验设计、实验操作、实验总结、成绩评... 详细信息

为实现药学专业本科人才培养目标,把药物纳米晶自稳定皮克林乳液及其设计思路引入本科药剂学实验教学,并转化为一种兼具探索性、创新性和设计性的本科实验项目。介绍了该实验项目的实施方案,包括实验设计、实验操作、实验总结、成绩评价等各环节;总结了线上-线下结合的实验教学管理经验。实践表明,该探索性实验项目激发了学生学习的主观能动性,提升了学生综合运用知识分析和解决问题的能力,促进了学生的创新实践能力和团结协作精神。

关键词：药剂学本科学生实验教学科研教学融合

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碳钢和不锈钢在海洋SRB、IRB和IOB下的点蚀研究现状

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表面技术 2024年第2期53卷 15-27,70页

作者：陈杨嵋贺小燕黄谦熊汉桢白秀琴武汉理工大学船海与能源动力工程学院武汉430063 武汉理工大学国家水运安全工程技术研究中心可靠性工程研究所武汉430063 武汉理工大学水路交通控制全国重点实验室武汉430063

微生物腐蚀(Microbiological Induced Corrosion,MIC)带来的危害占海洋腐蚀危害的20%。微生物腐蚀是指由于微生物的生命活动及其代谢产物与金属材料相互作用,影响腐蚀反应的阴极和阳极过程所引发的腐蚀现象,已成为海运业面临的重大技术... 详细信息

微生物腐蚀(Microbiological Induced Corrosion,MIC)带来的危害占海洋腐蚀危害的20%。微生物腐蚀是指由于微生物的生命活动及其代谢产物与金属材料相互作用,影响腐蚀反应的阴极和阳极过程所引发的腐蚀现象,已成为海运业面临的重大技术难题,研究海洋微生物腐蚀对推进我国海洋事业的发展有重要意义。金属材料微生物腐蚀包括全面腐蚀和局部腐蚀,局部腐蚀的危害更大,而点蚀被认为是危害最大的局部腐蚀形式。海洋微生物种类繁多,本文聚焦于硫元素的参与者硫酸盐还原菌(Sulfate-reducing Bacteria,SRB)、铁元素的参与者铁还原细菌(Iron-reducing Bacteria,IRB)和铁氧化细菌(Iron-oxidizing Bacteria,IOB)所引发的微生物点蚀问题,包括由细菌不均匀的生物膜与腐蚀产物膜以及细菌本身的特性引起的点蚀。以广泛应用于海洋平台和船舶的碳钢和不锈钢为对象,分析其在海洋SRB、IRB和IOB下的点蚀状况,从腐蚀形貌和腐蚀产物两方面对比了碳钢、不锈钢在不同细菌体系中的腐蚀差异,腐蚀形貌分析包括腐蚀产物形貌和去除腐蚀产物后金属表面形貌的分析,腐蚀产物分析主要聚焦于金属材料表面不同成分与含量的变化。从代谢产物理论、氧浓差电池作用理论阐释了碳钢和不锈钢的点蚀机理,指出微生物点蚀研究需要综合考虑多种因素,包括多菌种的相互作用和多种环境因素对金属材料的点蚀影响,以及微生物对耐蚀金属材料的点蚀影响等。

关键词：微生物点蚀碳钢不锈钢腐蚀形貌点蚀机理

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Gene signatures associated with genomic aberrations predict prognosis in neuroblastoma

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Cancer Communications 2020年第2期40卷 105-118页

作者： xiaoyan he Chao Qin Yanding Zhao Lin Zou Hui Zhao Chao Cheng Center for Clinical Molecular Medicine Ministry of Education Key Laboratory of Child Development and DisordersNational Clinical Research Center for Child Health and DisordersChina International Science and Technology Cooperation Base of Child Development and Critical DisordersChongqing Key Laboratory of PediatricsChildren’s Hospital of Chongqing Medical UniversityChongqing 400014P.R.China Beijing Key Lab of Traffic Data Analysis and Mining School of Computer and Information TechnologyBeijing Jiaotong UniversityBeijing 100044P.R.China Department of Biomedical Data Science Geisel School of Medicine at DartmouthLebanonNH 03766USA School of Biomedical Sciences Faculty of MedicineThe Chinese University of Hong KongHong Kong 999077P.R.China Department of Medicine Baylor College of MedicineHoustonTX 77030USA Institute for Clinical and Translational Research Baylor College of MedicineHoustonTX 77030USA

Background:Neuroblastoma(NB)is a heterogeneous disease with respect to genomic abnormalities and clinical behaviors.Despite recent advances in our understanding of the association between the genetic aberrations and clinical features,it remains one of the major challenges to predict prognosis and stratify patients for determining personalized therapy in this disease.The aim of this study was to develop an effective prognosis prediction model for NB patients.Methods:We integrated diverse computational analyses to define gene signatures that reflect MYCN activity and chromosomal aberrations including deletion of chromosome 1p(Chr1p_del)and chromosome 11q(Chr11q_del)as well as chromosome 11q whole loss(Chr11q_wls).We evaluated the prognostic and predictive values of these signatures in seven NB gene expression datasets(the number of samples ranges from 94 to 498,with a total of 2120)generated from both RNA sequencing and microarray platforms.Results:MYCN signature was a more effective prognostic marker than MYCN amplification status and MYCN expression.Similarly,the Chr1p_del score was more prognostic than Chr1p status.The activity scores of MYCN,Chr1p_del and Chr11q_del were associated with poor prognosis,while the Chr11q_wls score was linked to good outcome.We integrated the activity scores of MYCN,Chr1p_del,Chr11q_del,and Chr11q_wls and clinical variables into an integrative prognostic model,which displayed significant performance over the clinical variables or each genomic aberration alone.Conclusions:Our integrative gene signature model shows a significantly improved forecast performance with prognostic and predictive information,and thereby can be served as a biomarker to stratify NB patients for prognosis evaluation and surveillance programs.

关键词： chromosome aberration gene expression profile MYCN gene neuroblastoma prognosis survival analysis

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Highly efficient and genotype-independent barley gene editing based on anther culture

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Plant Communications 2021年第2期2卷 89-101页

作者： Yong Han Sue Broughton Li Liu Xiao-Qi Zhang Jianbin Zeng xiaoyan he Chengdao Li Western Barley Genetics Alliance College of ScienceHealthEngineering and EducationMurdoch UniversityMurdochWA 6150Australia Department of Primary Industries and Regional Development 3 Baron-Hay CourtSouth PerthWA 6151Australia Western Australian State Agricultural Biotechnology Centre Murdoch UniversityMurdochWA 6150Australia College of Agronomy Qingdao Agricultural UniversityQingdaoShandong 266109China

Recalcitrance to tissue culture and genetic transformation is the major bottleneck for gene manipulation in crops.In barley,immature embryos of Golden Promise have typically been used as explants for transformation.However,the genotype dependence of this approach limits the genetic modification of commercial varieties.here,we developed an anther culture-based system that permits the effective creation of transgenic and gene-edited plants from commercial barley varieties.The protocol was tested in Golden Promise and four Australian varieties,which differed in phenology,callus induction,and green plant regeneration responses.Agrobacterium-mediated transformation was performed on microspore-derived callus to target the HvPDS gene,and T0 albinos with targeted mutations were successfully obtained from commercial varieties.Further editing of three targets was achieved with an average mutation rate of 53%in the five varieties.In 51 analyzed T0 individuals,Cas9 induced a large proportion(69%)of single-base indels and two-base deletions in the target sites,with variable mutation rates among targets and varieties.Both ontarget and off-target activities were detected in T1 progenies.Compared with immature embryo protocols,this genotype-independent platformcan deliver a high editing efficiency and more regenerant plants within a similar time frame.It shows promise for functional genomics and the application of CRISPR technologies for the precise improvement of commercial varieties.

关键词： Agrobacterium CRISPR genetic transformation Hordeum vulgare off-target targeted mutation

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数据中心主机房的能效评价方法及提升路径

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上海节能 2024年第1期 153-158页

作者：何晓燕上海市建筑科学研究院有限公司

本研究主要根据数据中心主机房的气流组织和UPS应用的实测结果,分析低负载率工况下气流组织存在的问题和UPS电源质量和运行效率,提出相应的机房能效提升路径,从而降低数据中心PUE值。

关键词：数据中心主机房气流组织 UPS电源质量和运行效率能效提升路径

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