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Ghrelin inhibits autophagy mediated by AKT/mTOR pathway to ameliorate retinal angiogenesis induced by high glucose stress

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 785-793页

作者： jiang-Li fan Rong Li Min Zhang Chao Chen Guo-Min Yao Ling-xiao Zhou Department of Ophthalmology Gongshu District People’s Hospital of Integrated Traditional Chinese and Western MedicineHangzhou 310004Zhejiang ProvinceChina Department of Ophthalmology the First Affiliated Hospital of Xi’an Medical UniversityXi’an 710077Shaanxi ProvinceChina Department of Endocrinology the First Affiliated Hospital of Xi’an Medical UniversityXi’an 710077Shaanxi ProvinceChina Department of General Surgery the First Affiliated Hospital of Xi’an Medical UniversityXi’an 710077Shaanxi ProvinceChina

AIM:To observe the effect of ghrelin,a growth hormonereleasing peptide,on retinal angiogenesis in vitro under high glucose(HG)stress and to explore the possible mechanism of autophagy.METHODS:Human retinal microvascular endothelial cells(HRMECs)were treated with high concentration of glucose alone or in combination with ghrelin.The cell migration,tube formation and the expression of the autophagy-related proteins LC3-II/I,Beclin-1,p62,phosphorylated AKT(p-AKT)/AKT and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR were detected.Then,to clarify the correlation between ghrelin effect and autophagy,AKT inhibitor VIII was adopted to treat HRMECs,and cell migration,tube formation as well as the protein expressions of LC3-II/I,Beclin-1 and p62 were observed.RESULTS:Under HG stress,ghrelin inhibited migration and tube formation of HRMECs.Ghrelin inhibited the increases in the protein levels of LC3-II/I,Beclin-1 and the decreases in the protein levels of p62,p-AKT/AKT and p-mTOR/mTOR induced by HG stress.Moreover,under the action of AKT/mTOR pathway inhibitors,the effects of ghrelin on migration and tube formation were both reduced.In addition,the expression of LC3-II/I and Beclin-1 were significantly up-regulated and the expression of p62 was down-regulated.CONCLUSION:Retinal angiogenesis under in vitro HG stress can be inhibited by ghrelin through activating AKT/mTOR pathway to inhibit autophagy.

关键词： ghrelin retinal endothelial cell angiogenesis autophagy stress

Revolutionizing tumor immunotherapy:unleashing the power of progenitor exhausted T cells

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Cancer Biology & Medicine 2024年第6期21卷 499-512页

作者： Zhang fang Xinyi Ding Hao Huang Hongwei jiang Jingting jiang xiao Zheng Department of Tumor Biological Treatment The Third Affiliated Hospital of Soochow University jiangsu Engineering Research Center for Tumor Immunotherapy The Third Affiliated Hospital of Soochow University Institute for Cell Therapy of Soochow University The Third Affiliated Hospital of Soochow University

In exploring persistent infections and malignancies, a distinctive subgroup of CD8+T cells, progenitor exhausted CD8+T（Tpex） cells, has been identified. These Tpex cells are notable for their remarkable self-renewal and rapid proliferation abilities. Recent strides in immunotherapy have demonstrated that Tpex cells expand and differentiate into responsive exhausted CD8+T cells, thus underscoring their critical role in the immunotherapeutic retort. Clinical examinations have further clarified a robust positive correlation between the proportional abundance of Tpex cells and enhanced clinical prognosis. Tpex cells have found noteworthy applications in the formulation of inventive immunotherapeutic approaches against tumors. This review describes the functions of Tpex cells in the tumor milieu, particularly their potential utility in tumor immunotherapy. Precisely directing Tpex cells may be essential to achieving successful outcomes in immunotherapy against tumors.

关键词： Progenitor exhausted CD8 T cells TCF-1 cellular crosstalk immunotherapy tumor microenvironment

A booming field of large animal model research

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Zoological Research 2024年第2期45卷 311-313页

作者： xiao-jiang Li Liangxue Lai Guangdong Key Laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)GHM Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong 510632China State Key Laboratory of Bioactive Molecules and Druggability Assessment Jinan UniversityGuangzhouGuangdong 510632China CAS Key Laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China

Animal models are integral to the study of fundamental biological processes and the etiology of human diseases.Small animal models,especially those involving mice,have yielded abundant and significant insights,greatly... 详细信息

关键词： mechanisms insight field

A Robust Framework for Multimodal Sentiment Analysis with Noisy Labels Generated from Distributed Data Annotation

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Computer Modeling in Engineering & Sciences 2024年第6期139卷 2965-2984页

作者： Kai jiang Bin Cao Jing fan School of Computer Science and Technology Zhejiang University of TechnologyHangzhou310023China

Multimodal sentiment analysis utilizes multimodal data such as text,facial expressions and voice to detect people’s attitudes.With the advent of distributed data collection and annotation,we can easily obtain and share such multimodal data.However,due to professional discrepancies among annotators and lax quality control,noisy labels might be introduced.Recent research suggests that deep neural networks(DNNs)will overfit noisy labels,leading to the poor performance of the DNNs.To address this challenging problem,we present a Multimodal Robust Meta Learning framework(MRML)for multimodal sentiment analysis to resist noisy labels and correlate distinct modalities simultaneously.Specifically,we propose a two-layer fusion net to deeply fuse different modalities and improve the quality of the multimodal data features for label correction and network training.Besides,a multiple meta-learner(label corrector)strategy is proposed to enhance the label correction approach and prevent models from overfitting to noisy labels.We conducted experiments on three popular multimodal datasets to verify the superiority of ourmethod by comparing it with four baselines.

关键词： Distributed data collection multimodal sentiment analysis meta learning learn with noisy labels

Fast spreading of surface ozone in both temporal and spatial scale in Pearl River Delta

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Journal of Environmental Sciences 2024年第3期137卷 540-552页

作者： Tianhui Cao Haichao Wang Lei Li xiao Lu Yiming Liu Shaojia fan School of Atmospheric Sciences Sun Yat-sen University and Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)Zhuhai 519082China Guangdong Provincial Observation and Research Station for Climate Environment and Air Quality Change in the Pearl River Estuary Key Laboratory of Tropical Atmosphere-Ocean SystemMinistry of EducationZhuhai 519082China

Surface ozone(O_(3))is a major air pollutant and draw increasing attention in the Pearl River Delta(PRD),China.Here,we characterize the spatial-temporal variability of ozone based on a dataset obtained from 57 national monitoring sites during 2013-2019.Our results show that:(1)the seasonal difference of ozone distribution in the inland and coastal areas was significant,which was largely affected by the wind pattern reversals related to the East Asian monsoon,and local ozone production and destruction;(2)the daily maximum 8hr average(MDA8 O_(3))showed an overall upward trend by 1.11 ppbv/year.While the trends in the nine cities varied differently by ranging from-0.12 to 2.51 ppbv/year.The hot spots of ozone were spreading to southwestern areas from the central areas since 2016.And ozone is becoming a year-round air pollution problem with the pollution season extending to winter and spring in PRD region.(3)at the central and southwestern PRD cities,the percentage of exceedance days from the continuous type(defined as≥3 days)was increasing.Furthermore,the ozone concentration of continuous type was much higher than that of scattered exceedance type(<3 days).In addition,although the occurrence of continuous type starts to decline since2017,the total number of exceedance days during the continuous type is increasing.These results indicate that it is more difficult to eliminate the continuous exceedance than the scatter pollution days and highlight the great challenge in mitigation of O_(3)pollution in these cities.

关键词： Surface ozone pollution Ozone trend Spatial and temporal variability Pearl River Delta Pollution mitigation

Assembly of peptide nanostructures with controllable sizes

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Nano Research 2024年第1期17卷 151-161页

作者： Dan Cheng fan Jia Yun-Bao jiang Vincent P.Conticello Tao jiang The MOE Key Laboratory of Spectrochemical Analysis and Instrumentation Department of ChemistryCollege of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005China Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(IKKEM) Xiamen 361005China Department of Chemistry Emory UniversityAtlanta 30033USA

Controlled peptide assembly offers significant promise to develop synthetic supramolecular nanostructures to display material and biological properties that mimic protein assemblies in nature.Despite the progress in forming peptide nanostructures of various morphology,there exists a distinct gap between natural and synthetic assembly systems in terms of size control.Constructing nanostructures with a narrow size distribution that can be tuned over a wide range of length-scales is essential for applications that require precise spacing between objects.This approach provides the opportunity to correlate materials and biological properties of interest with assembly size.In this review,we discuss representative endeavors over the past two decades for design of size-controllable peptide nanostructures using tunable building blocks.Other mechanisms for size control,e.g.,molecular frustration,template-directed peptide assembly,and multi-component peptide co-assembly,will also be discussed.We also demonstrate the applicable scopes of these strategies and suggest potential future avenues for scientific advances in this field.

关键词： peptide assembly controllable size template multi-component

Bioinspired metal-organic framework nanozyme reinforced with thermosensitive hydrogel for regulating inflammatory responses in Parkinson’s disease

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Nano Research 2024年第2期17卷 858-865页

作者： xiaowan fan Tao Zhang Xin Ding Yushuo Gu Qing Li Wei jiang Kelong fan Nanozyme Medical Center Academy of Medical ScienceZhengzhou UniversityZhengzhou 450001China Department Central-China Branch of National Center for Cardiovascular DiseasesHean Cardiovascular Disease CenterFuwai Central-China HospitalCentral China Fuwai Hospital of Zhengzhou UniversityZhengzhou 450046China Application Center for Precision Medicine the Second Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China CAS Engineering Laboratory for Nanozyme Key Laboratory of Protein and Peptide PharmaceuticalsInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 101408China Department of General Surgery Strategic Support Force Medical CenterBeijing 100101China Department of Anesthesiology Pain and Perioperative MedicineThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Parkinson’s disease(PD)is a prevalent neurodegenerative disorder accompanied by movement disorders and neuroinflammatory injury.Anti-inflammatory intervention to regulate oxidative stress in the brain is beneficial for managing PD.However,traditional natural antioxidants have failed to meet the clinical treatment demands due to insufficient activity and sustainability.Herein,Cu-doping zeolite imidazolate framework-8(ZIF-8)nanozyme is designed to simulate Cu/Zn superoxide dismutase(SOD)by biomimetic mineralization.The nanozyme composite is then integrated into thermosensitive hydrogel(poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid)(PLGA-PEG-PLGA))to form an effective antioxidant system(Cu-ZIF@Hydrogel).The thermosensitive hydrogel incorporating nanozymes demonstrate distinct viscoelastic properties aimed at enhancing local nanozyme adhesion,prolonging nanozyme retention time,and modulating antioxidant activity,thus significantly improving the bioavailability of nanozymes.At the cellular and animal levels of PD,we find that Cu-ZIF@Hydrogel bypass the blood-brain barrier and efficiently accumulate in the nerve cells.Moreover,the Cu-ZIF@Hydrogel significantly alleviate the PD’s behavioral and pathological symptoms by reducing the neuroinflammatory levels in the lesion site.Therefore,the hydrogel-incorporating nanozyme system holds great potential as a simple and reliable avenue for managing PD.

关键词： bioinspired nanozyme thermosensitive hydrogel Parkinson’s disease oxidative stress neuroinflammatory

Targeting the adenosine A2A receptor for neuroprotection and cognitive improvement in traumatic brain injury and Parkinson's disease

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Chinese Journal of Traumatology 2024年第3期27卷 125-133页

作者： Yan Zhao Yuan-Guo Zhou jiang-fan Chen Department of Army Occupational Disease State Key Laboratory of TraumaBurns and Combined InjuryResearch Institute of SurgeryDaping HospitalArmy Medical University.Chongqing400042China The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center The State Key Laboratory of OphthalmologyOptometry and Vision ScienceWenzhou Medical UniversityWenzhou325035Zhejiang ProvinceChina Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou325035Zhejiang ProvinceChina

Adenosine exerts its dual functions of homeostasis and neuromodulation in the brain by acting at mainly 2 G-protein coupled receptors,called A1 and A2A receptors.The adenosine A2A receptor(A2AR)antagonists have been clinically pursued for the last 2 decades,leading to final approval of the istradefylline,an A2AR antagonist,for the treatment of OFF-Parkinson's disease(PD)patients.The approval paves the way to develop novel therapeutic methods for A2AR antagonists to address 2 major unmet medical needs in PD and traumatic brain injury(TBI),namely neuroprotection or improving cognition.In this review,we first consider the evidence for aberrantly increased adenosine signaling in PD and TBI and the sufficiency of the increased A2AR signaling to trigger neurotoxicity and cognitive impairment.We further discuss the increasing preclinical data on the reversal of cognitive deficits in PD and TBI by A2AR antagonists through control of degenerative proteins and synaptotoxicity,and on protection against TBI and PD pathologies by A2AR antagonists through control of neuroinflammation.Moreover,we provide the supporting evidence from multiple human prospective epidemiological studies which revealed an inverse relation between the consumption of caffeine and the risk of developing PD and cognitive decline in aging population and Alzheimer's disease patients.Collectively,the convergence of clinical,epidemiological and experimental evidence supports the validity of A2AR as a new therapeutic target and facilitates the design of A2AR antagonists in clinical trials for disease-modifying and cognitive benefit in PD and TBI patients.

关键词： Receptor,Adenosine A2A Adenosine A2 receptor antagonists Parkinson's disease Brain injuries,traumatic

Comparison of the hygrothermal performance of two light-framed timber structure buildings under different operation modes

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2024年第1期25卷 18-35页

作者： Wanqing XU Yucong XUE jiang LU Yifan fan xiaoyu LUO College of Civil Engineering and Architecture Zhejiang UniversityHangzhou310058China International Research Center for Green Building and Low-Carbon City International CampusZhejiang UniversityJiaxing314400China School of Civil Engineering and Architecture Zhejiang University of Science and TechnologyHangzhou310023China

Light-framed timber structure(LTS)buildings have been highly valued in recent years due to their low-carbon characteristics.However,the applicability of the building envelope is closely related to indoor and outdoor conditions.The hot summer and cold winter(HSCW)climate zone in China has high humidity and great temperature variation throughout the year,resulting in distinct outdoor environments in different seasons.The indoor environment is greatly affected by energy-consumption patterns and window-opening habits,which largely depend upon the regulation operations of occupants.All these interrelated factors lead to extremely complex boundary conditions on each side of the building envelope.Whether the structures of LTS buildings are applicable in this climate zone,therefore,needs to be carefully considered.In this study,two LTS buildings with different envelopes were established in Haining,China,situated in the HSCW climate zone,and selected as the study objects.Different operation modes were adopted to create a variety of indoor environments.Under each condition,the processes of heat and moisture transfer within the building envelopes and the indoor environment were monitored and compared.The comparison indicated that the building envelope with high moisture storage and insulation ability maintained a relatively stable indoor environment,especially when the environment changed abruptly.Conversely,if the outdoor environment was equable(e.g.,relative humidity within the range of 30%–60%)or intermittent energy consumption modes were adopted,the building envelope with a low thermal inertia index and weak moisture-buffering ability performed better because it enabled a faster response of the indoor environment to air conditioning.Moreover,a high risk of moisture accumulation between the thermal insulation layer and other materials with a large water vapour transfer resistance factor was also identified,suggesting a higher requirement for the vapour insulation of the envelopes of LTS buildings.

关键词： Light-framed timber structure(LTS)buildings In-situ experiment Typical operation mode Indoor environment Heatand moisture transfer