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Targeting ferroptosis and ferritinophagy:new targets for cardiovascular diseases

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第1期25卷 1-22页

作者： Yi luan yang yang Ying luan Hui LIU Han XING Jinyan PEI Hengdao LIU Bo QIN Kaidi REN Clinical Systems Biology Research Laboratories Translational Medicine Centerthe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China State Key Laboratory for Artificial Microstructures and Mesoscopic Physics School of PhysicsPeking UniversityBeijing100871China School of Laboratory Medicine Xinxiang Medical UniversityXinxiang453003China Quality Management Department Henan No.3 Provincial People’s HospitalZhengzhou450052China Department of Cardiology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Center for Translational Medicine the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Department of Pharmacy the First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Henan Key Laboratory of Precision Clinical Pharmacy Zhengzhou UniversityZhengzhou450052China Henan Engineering Research Center for Application&Translation of Precision Clinical Pharmacy Zhengzhou UniversityZhengzhou450052China

Cardiovascular diseases(CVDs)are a leading factor driving mortality worldwide.Iron,an essential trace mineral,is important in numerous biological processes,and its role in CVDs has raised broad discussion for decades.Iron-mediated cell death,namely ferroptosis,has attracted much attention due to its critical role in cardiomyocyte damage and CVDs.Furthermore,ferritinophagy is the upstream mechanism that induces ferroptosis,and is closely related to CVDs.This review aims to delineate the processes and mechanisms of ferroptosis and ferritinophagy,and the regulatory pathways and molecular targets involved in ferritinophagy,and to determine their roles in CVDs.Furthermore,we discuss the possibility of targeting ferritinophagy-induced ferroptosis modulators for treating CVDs.Collectively,this review offers some new insights into the pathology of CVDs and identifies possible therapeutic targets.

关键词： Cardiovascular disease Iron Ferroptosis Ferritinophagy Therapeutic target

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Metagenomic insights into microorganisms and antibiotic resistance genes of waste antibiotic fermentation residues along production,storage and treatment processes

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Journal of Environmental Sciences 2024年第2期136卷 45-55页

作者： Ziming Han Xiao luan Haodi Feng Yanqin Deng Min yang Yu Zhang State Key Laboratory of Environmental Aquatic Chemistry Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China National Engineering Research Center of Industrial Wastewater Detoxication and Resource Recovery Beijing 100085China Wuhan Agricultural Inspection Center Wuhan 430016China University of Chinese Academy of Sciences Beijing 100049China

Antibiotic fermentation residue(AFR)is nutrient-rich solid waste generated from fermentative antibiotic production process.It is demonstrated that AFR contains high-concentration of remaining antibiotics,and thus may promote antibiotic resistance development in receiving environment or feeding farmed animals.However,the dominate microorganisms and antibiotic resistance genes(ARGs)in AFRs have not been adequately explored,hampering understanding on the potential antibiotic resistance risk development caused by AFRs.Herein,seven kinds of representative AFRs along their production,storage,and treatment processes were collected,and multiple methods including amplicon sequencing,metagenomic sequencing,and bioinformatic approaches were adopted to explore the biological characteristics of AFRs.As expected,antibiotic fermentation producer was found as the predominant species in raw AFRs,which were collected at the outlet of fermentation tanks.However,except for producer species,more environment-derived species persisted in stored AFRs,which were temporarily stored at a semi-open space.Lactobacillus genus,classified as Firmicutes phylum and Bacilli class,became predominant bacterial taxa in stored AFRs,which might attribute to its tolerance to high concentration of antibiotics.Results from metagenomic sequencing together with assembly and binning approaches showed that these newly-colonizing species(e.g.,Lactobacillus genus)tended to carry ARGs conferring resistance to the remaining antibiotic.However,after thermal treatment,remaining antibiotic could be efficiently removed from AFRs,and microorganisms together with DNA could be strongly destroyed.In sum,the main risk from the AFRs was the remaining antibiotic,while environment-derived bacteria which tolerate extreme environment,survived in ARFs with high content antibiotics,and may carry ARGs.Thus,hydrothermal or other harmless treatment technologies are recommended to remove antibiotic content and inactivate bacteria before recycling of AFRs in pharmaceutical industry.

关键词： Pharmaceutical manufacturing Antibiotic mycelia residue Antibiotic resistance bacteria Thermal treatment Solid waste

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Pathophysiological changes of muscle after ischemic stroke:a secondary consequence of stroke injury

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Neural Regeneration Research 2024年第4期19卷 737-746页

作者： Hu Qi Dan Tian Fei luan Ruocong yang Nan Zeng State Key Laboratory of Southwestern Chinese Medicine Resources Chengdu University of Traditional Chinese Medicine School of Pharmacy Chengdu University of Traditional Chinese Medicine Acupuncture and Tuina School Chengdu University of Traditional Chinese Medicine

Sufficient clinical evidence suggests that the damage caused by ischemic stroke to the body occurs not only in the acute phase but also during the recovery period,and that the latter has a greater impact on the long-term prognosis of the patient.However,current stroke studies have typically focused only on lesions in the central nervous system,ignoring secondary damage caused by this disease.Such a phenomenon arises from the slow progress of pathophysiological studies examining the central nervous system.Further,the appropriate therapeutic time window and benefits of thrombolytic therapy are still controversial,leading scholars to explore more pragmatic intervention strategies.As treatment measures targeting limb symptoms can greatly improve a patient’s quality of life,they have become a critical intervention strategy.As the most vital component of the limbs,skeletal muscles have become potential points of concern.Despite this,to the best of our knowledge,there are no comprehensive reviews of pathophysiological changes and potential treatments for post-stroke skeletal muscle.The current review seeks to fill a gap in the current understanding of the pathological processes and mechanisms of muscle wasting atrophy,inflammation,neuroregeneration,mitochondrial changes,and nutritional dysregulation in stroke survivors.In addition,the challenges,as well as the optional solutions for individualized rehabilitation programs for stroke patients based on motor function are discussed.

关键词： inflammation ischemic stroke mitochondria muscle atrophy muscle fiber muscle nutrition quality of life rehabilitation ubiquitin

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Field-based evidence for the enrichment of intrinsic antibiotic resistome stimulated by plant-derived fertilizer in agricultural soil

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Journal of Environmental Sciences 2024年第1期135卷 728-740页

作者： Shihai Liu Ziming Han Dong Zhu Xiao luan Liujie Deng Liping Dong Min yang Yu Zhang State Key Laboratory of Environmental Aquatic Chemistry Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China State Key Laboratory of Urban and Regional Ecology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China State Environmental Protection Engineering Center for Harmless Treatment and Resource Utilization of Antibiotic Residues Khorgos 835007China University of Chinese Academy of Sciences Beijing 100049China

Animal manures have been demonstrated to enhance antibiotic resistance in agricultural soils.However,little is known about the effects of plant-derived fertilizer on soil antibiotic resistome.Herein,metagenomic sequencing was used to investigate the effects of a plantderived fertilizer processed from sugarcane and beet on soil antibiotic resistance genes(ARGs)in a soybean field along crop growth stages.ARG profiles in the soils amended by plant-derived fertilizer were compared with those in the soils amended by chicken manure.The abundance and diversity of total ARGs in the soils amended by plant-derived fertilizer were significantly(P<0.05)elevated at the sprout stage,to a level comparable to that in the manured soils.Whereas,unlike chicken manure mainly introducing manure-borne ARGs to soil,the plant-derived fertilizer was indicated to mainly enrich multidrug resistance genes in soil by nourishing indigenous bacteria.ARGs with abundances in amended soils significantly(P<0.05)higher than in unamended soils at the sprout stage of soybean were considered as enriched ARGs.Decrease in the abundance of the enriched ARGs was observed in both the amended soils from the sprout to the harvest.Network analysis further identified Proteobacteria and Bacteroidetes as the primary bacterial taxa involved in the temporal variation of the enriched ARGs in the soils amended by plant-derived fertilizer,while in manured soils were Firmicutes and Actinobacteria.As revealed by multivariate statistical analyses,variation of the enriched ARGs in the soils amended by plant-derived fertilizer was majorly attributed to the response of co-occurred bacteria to depleting nutrients,which was different from the failed establishment of manure-borne bacteria in the manured soils.Our study provided field-based evidence that plant-derived fertilizer stimulated the intrinsic antibiotic resistome,and proposed attention to the un-perceived risk since some clinically relevant ARGs originate and evolve from natural resistome.

关键词： Organic fertilizer Intrinsic antibiotic resistance Indigenous bacteria Metagenomic sequencing

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Mice with type I interferon signaling deficiency are prone to epilepsy upon HSV-1 infection

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Virologica Sinica 2024年第2期39卷 251-263页

作者： Wei yang Chong-yang Tang Dong-Ying Fan Yi-Song Wang Pei-Gang Wang Jing An Guo-Ming luan Beijing Key Laboratory of Epilepsy Sanbo Brain HospitalCapital Medical UniversityBeijing100093China Beijing Institute for Brain Disorders Capital Medical UniversityBeijing100093China Department of Neurosurgery Epilepsy CenterSanbo Brain HospitalCapital Medical UniversityBeijing100093China Department of Microbiology School of Basic Medical SciencesCapital Medical UniversityBeijing100069China Chinese Institute for Brain Research Beijing102206China

Viral encephalitis continues to be a significant public health concern.In our previous study,we discovered a lower expression of antiviral factors,such as IFN-β,STING and IFI16,in the brain tissues of patients with Rasmussen's encephalitis(RE),a rare chronic neurological disorder often occurred in children,characterized by unihemispheric brain atrophy.Furthermore,a higher cumulative viral score of human herpes viruses(HHVs)was also found to have a significant positive correlation with the unihemispheric atrophy in RE.Type I IFNs(IFN-I)signaling is essential for innate anti-infection response by binding to IFN-α/βreceptor(IFNAR).In this study,we infected WT mice and IFNAR-deficient A6 mice with herpes simplex virus 1(HSV-1)via periocular injection to investigate the relationship between IFN-I signaling and HHVs-induced brain lesions.While all mice exhibited typical viral encephalitis lesions in their brains,HSV-induced epilepsy was only observed in A6 mice.The gene expression matrix,functional enrichment analysis and protein-protein interaction network revealed four gene models that were positively related with HSV-induced epilepsy.Additionally,ten key genes with the highest scores were identified.Taken together,these findings indicate that intact IFN-I signaling can effectively limit HHVs induced neural symptoms and brain lesions,thereby confirming the positive correlation between IFN-I signaling repression and brain atrophy in RE and other HHVs encephalitis.

关键词： IFN-I signaling Human herpes viruses(HHVs) Rasmussen's encephalitis(RE)

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Building a domain-specific compiler for emerging processors with a reusable approach

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Science China(Information Sciences) 2024年第1期67卷 20-38页

作者： Mingzhen LI Yi LIU Bangduo CHEN Hailong yang Zhongzhi luan Depei QIAN State Key Laboratory of Software Development Environment School of Computer Science and Engineering Beihang University

High-performance computing and deep learning domains have been motivating the design of domain-specific processors.Although these processors can provide promising computation capability,they are notorious for exotic programming paradigms.To improve programming productivity and fully exploit the performance potential of these processors,domain-specific compilers(DSCs) have been proposed.However,building DSCs for emerging processors requires tremendous engineering efforts because the commonly used compilation stack is difficult to be reused.Owing to the advent of multilevel intermediate representation(MLIR),DSC developers can leverage reusable infrastructure to extend their customized functionalities without rebuilding the entire compilation stack.In this paper,we further demonstrate the effectiveness of MLIR by extending its reusable infrastructure to embrace a heterogeneous many-core processor(Sunway processor).In particular,we design a new Sunway dialect and corresponding backend for the Sunway processor,fully exploiting its architectural advantage and hiding its programming complexity.To show the ease of building a DSC,we leverage the Sunway dialect and existing MLIR dialects to build a stencil compiler for the Sunway processor.The experimental results show that our stencil compiler,built with a reusable approach,can even perform better than state-of-the-art stencil compilers.

关键词： domain-specific compiler emerging processor reusable dialect performance optimization MLIR

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Esophageal cancer screening,early detection and treatment:Current insights and future directions

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1180-1191页

作者： Hong-Tao Qu qing Li Liang Hao Yan-Jing Ni Wen-Yu luan Zhe yang Xiao-Dong Chen Tong-Tong Zhang Yan-Dong Miao Fang Zhang Department of Emergency Yantai Mountain HospitalYantai 264000Shandong ProvinceChina Cancer Center Yantai Affiliated Hospital of Binzhou Medical UniversityThe 2nd Medical College of Binzhou Medical UniversityYantai 264100Shandong ProvinceChina

Esophageal cancer ranks among the most prevalent malignant tumors globally,primarily due to its highly aggressive nature and poor survival rates.According to the 2020 global cancer statistics,there were approximately 604000 new cases of esophageal cancer,resulting in 544000 deaths.The 5-year survival rate hovers around a mere 15%-25%.Notably,distinct variations exist in the risk factors associated with the two primary histological types,influencing their worldwide incidence and distribution.Squamous cell carcinoma displays a high incidence in specific regions,such as certain areas in China,where it meets the cost-effect-iveness criteria for widespread endoscopy-based early diagnosis within the local population.Conversely,adenocarcinoma(EAC)represents the most common histological subtype of esophageal cancer in Europe and the United States.The role of early diagnosis in cases of EAC originating from Barrett's esophagus(BE)remains a subject of controversy.The effectiveness of early detection for EAC,particularly those arising from BE,continues to be a debated topic.The variations in how early-stage esophageal carcinoma is treated in different regions are largely due to the differing rates of early-stage cancer diagnoses.In areas with higher incidences,such as China and Japan,early diagnosis is more common,which has led to the advancement of endoscopic methods as definitive treatments.These techniques have demonstrated remarkable efficacy with minimal complications while preserving esophageal functionality.Early screening,prompt diagnosis,and timely treatment are key strategies that can significantly lower both the occurrence and death rates associated with esophageal cancer.

关键词： Esophageal cancer Screening Early detection Treatment Endoscopic mucosal resection Endoscopic submucosal dissection

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High-Superelasticity NiTi Shape Memory Alloy by Directed Energy Deposition-Arc and Solution Heat Treatment

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Acta Metallurgica Sinica(English Letters) 2024年第1期37卷 132-144页

作者： Junyi Ma Lin Yu qing yang Jie Liu Lei yang State Key Laboratory of Materials Processing and Die&Mould Technology School of Materials Science and EngineeringHuazhong University of Science and TechnologyWuhan430070China School of Transportation and Logistics Engineering Wuhan University of TechnologyWuhan430074China

Directed energy deposition-arc(DED-Arc)technology has the advantages of simple equipment,low manufacturing cost and high deposition rate,while the use of DED-Arc has problems of microstructure inhomogeneity,position dependence of macroscopic mechanical properties and anisotropy.Therefore,it is necessary to carry out a subsequent heat treatment to improve its microstructure uniformity,mechanical properties and superelasticity.In this investigation,the DED-Arc 15-layer NiTi alloy thin-walled parts with the solution treatment at different process parameters were studied to analyze the effects of solution heat treatment on microstructure,phase composition,phase transformation,microhardness,tensile and superelasticity.The temperature range of solution treatment is 800-1050℃,and the treatment time range is 1-5.5 h.The results show that after solution treatment at 800℃/1 h,the content of precipitated phase decreases,the grain is refined,the microhardness increases,and the mechanical properties in the 0°direction are improved.The strain recovery rate after 10 tensile cycles has increased from 37.13%(as-built)to 49.25%(solid solution treatment).This research provides an effective post treatment method for high-performance DED-Arc NiTi shape memory alloys.

关键词： Directed energy deposition-arc(DED-Arc) Cold metal transfer(CMT) NiTi shape memory alloys Microstructure Phase transformation Solution heat treatment

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Investigation of Quantum Dot Color Filter Micro-LED Display

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Photonic Sensors 2024年第1期14卷 40-47页

作者： Xuhui PENG yang ZENG Sitao HUO Zhenyuan yang Xiaoping HUANG qing ZHAO School of Resources and Environment University of Electronic Science and Technology of ChinaChengdu 611731China yangtze Delta Region Institute(Huzhou) University of Electronic Science and Technology of ChinaHuzhou 313001China Shanghai Tianma Microelectronics Shanghai 201201China

In this work,we present the investigation of the quantum dot color filter(QDCF)micro-light emitting diode(micro-LED)display.Green and red quantum dot photoresist(QDPR)materials are patterned into a pixelated array and precisely bonded with an all-blue micro-light emitting diode(micro-LED)substrate,forming a red,green,and blue(RGB)full color display through color conversion.A few factors that influence the achievable color gamut are further investigated.The resulting 1.1-inch 228-pixels per inch(ppi)display demo shows the good performance.The findings in this paper pave a way to the future industrialization of the micro-LED display.

关键词： Quantum dot color filter(QDCF) color conversion micro-light emitting diode(micro-LED) color gamut

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Composite Converter Combined APFC with Switched-capacitor Converter

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CSEE Journal of Power and Energy Systems 2024年第1期10卷 281-291页

作者： qing Fu Yishan Chen Yixing Su yang Hang School of Physics Sun Yat-Sen UniversityGuangzhou 510275China

To reduce switch numbers and voltage stress in semiconductor devices,this paper proposes a novel single-phase converter combined Active Power Factor Correction(APFC)with switched-capacitor converter.In addition,dynamic voltage regulation and voltage gain are improved by integrating the boost converter and switching capacitor cells.The interstage bulk capacitor is no longer needed.An average current control with redistribution of voltage in cells is proposed to obtain voltage lift ability of the switching capacitor cells and maintain a high-power factor.To study and verify the proposed converter preliminarily,theoretical analysis and simulation are presented in the paper.Furthermore,a 50o W prototype with two different configurations is built for experimental verification.The proposed converter can reach 95.62%of maximum efficiency,0.99 of power factor,and 3.55%of THD with 600 V output voltage,simultaneously.

关键词： AC-DC converter composite conveter power factor correction switched capacitor

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