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LncFASA promotes cancer ferroptosis via modulating PRDX1 phase separation

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Science China(Life Sciences) 2024年第3期67卷 488-503页

作者： Xiao Fan Fangzhou Liu Xiang Wang Ying Wang Yu Chen Chengyu Shi Xinwan Su Manman Tan Qingfeng Yan Jinrong Peng Jianzhong Shao Yan Xiong Aifu Lin MOE laboratory of Biosystem Homeostasis and Protection College of Life SciencesZhejiang UniversityHangzhou 310058China Key laboratoryof Cancer Prevention and Intervention China National Ministry of EducationHangzhou 310009China Cancer center Zhejiang UniversityHangzhou 310058China Key laboratory for Cell and Gene Engineering of zhejiang Province Hangzhou 310058China Department of Central laboratory the First People's Hospital of HuzhouHuzhou 313000China Key laboratory of Integrated Oncology and Intelligent Medicine of zhejiang Province Affiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou 310006China MOE Key laboratory for Molecular Animal Nutrition College of Animal SciencesZhejiang UniversityHangzhou 310058China Department of Orthopedic Surgery the Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310000China Breast center of the First Affiliated Hospital School of MedicineZhejiang UniversityHangzhou 310003China International School of Medicine International Institutes of MedicineThe 4th Affiliated Hospital of Zhejiang University School of MedicineYiwu 322000China

Ferroptosis, a unique type of non-apoptotic cell death resulting from iron-dependent lipid peroxidation, has a potential physiological function in tumor suppression, but its underlying mechanisms have not been fully elucidated. Here, we report that the long non-coding RNA(lncRNA) LncFASA increases the susceptibility of triple-negative breast cancer(TNBC) to ferroptosis. As a tumor suppressor, LncFASA drives the formation of droplets containing peroxiredoxin1(PRDX1), a member of the peroxidase family, resulting in the accumulation of lipid peroxidation via the SLC7A11-GPX4 axis. Mechanistically, LncFASA directly binds to the Ahpc-TSA domain of PRDX1, inhibiting its peroxidase activity by driving liquid-liquid phase separation, which disrupts intracellular ROS homeostasis. Notably, high LncFASA expression indicates favorable overall survival in individuals with breast cancer, and LncFASA impairs the growth of breast xenograft tumors by modulating ferroptosis. Together, our findings illustrate the crucial role of this lncRNA in ferroptosis-mediated cancer development and provide new insights into therapeutic strategies for breast cancer.

关键词： long non-coding RNA peroxiredoxin liquid-liquid phase separation ferroptosis breast cancer

The role of inflammasomes in human diseases and their potential as therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第2期9卷 479-508页

作者： Jing Yao Keenan Sterling Zhe Wang Yun Zhang Weihong Song The National Clinical Research center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Key laboratory of Neurodegenerative Diseases Ministry of EducationBeijingP.R.China zhejiang Clinical Research center for Mental Disorders Key Laboratory of Alzheimer’s Disease of Zhejiang ProvinceSchool of Mental Health and The Affiliated Kangning HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325000China Oujiang laboratory(zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325000China

Inflammasomes are large protein complexes that play a major role in sensing inflammatory signals and triggering the innate immune *** inflammasome complex has three major components:an upstream sensor molecule that is connected to a downstream effector protein such as caspase-1 through the adapter protein *** formation typically occurs in response to infectious agents or cellular *** active inflammasome then triggers caspase-1 activation,followed by the secretion of pro-inflammatory cytokines and pyroptotic cell *** inflammasome activation and activity contribute to the development of diabetes,cancer,and several cardiovascular and neurodegenerative *** a result,recent research has increasingly focused on investigating the mechanisms that regulate inflammasome assembly and activation,as well as the potential of targeting inflammasomes to treat various *** clinical trials are currently underway to evaluate the therapeutic potential of several distinct inflammasome-targeting ***,understanding how different inflammasomes contribute to disease pathology may have significant implications for developing novel therapeutic *** this article,we provide a summary of the biological and pathological roles of inflammasomes in health and *** also highlight key evidence that suggests targeting inflammasomes could be a novel strategy for developing new disease-modifying therapies that may be effective in several conditions.

关键词： inflam therapeutic potential

A self-centering and stiffness-controlled MEMS accelerometer

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Microsystems & Nanoengineering 2024年第1期10卷 27-40页

作者： Yiming Jin Zhipeng Ma Ziyi Ye Mingkang Li Xudong Zheng Zhonghe Jin School of Aeronautics and Astronautics Zhejiang UniversityHangzhou 310013China Key laboratory of Micro/Nano-Satellite Research of zhejiang Province Hangzhou 310007PR China

This paper presents a high-performance MEMS accelerometer with a DC/AC electrostatic stiffness tuning capability based on double-sided parallel plates(DSPPs).DC and AC electrostatic tuning enable the adjustment of the effective stiffness and the calibration of the geometric offset of the proof mass,respectively.A dynamical model of the proposed accelerometer was developed considering both DC/AC electrostatic tuning and the temperature *** on the dynamical model,a self-centering closed loop is proposed for pulling the reference position of the forceto-rebalance(FTR)to the geometric center of *** self-centering accelerometer operates at the optimal reference position by eliminating the temperature drift of the readout circuit and nulling the net electrostatic tuning *** stiffness closed-loop is also incorporated to prevent the pull-in instability of the tuned low-stiffness accelerometer under a dramatic temperature ***-time adjustments of the reference position and the DC tuning voltage are utilized to compensate for the residue temperature drift of the proposed *** a result,a novel controlling approach composed of a self-centering closed loop,stiffness-closed loop,and temperature drift compensation is achieved for the accelerometer,realizing a temperature drift coefficient(TDC)of approximately 7μg/℃ and an Allan bias instability of less than 1μg.

关键词： stiffness electrostatic centering

Genetic mapping of plasma proteome on brain structure

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Journal of Genetics and Genomics 2024年第7期51卷 774-777页

作者： Shengyi Ma Fengzhe Xu Yuanqing Fu Ju-Sheng Zheng Fudan University Shanghai 200433China School of Life Sciences Westlake UniversityHangzhouZhejiang 310030China Westlake center for Intelligent Proteomics Westlake Laboratory of Life Sciences and BiomedicineHangzhouZhejiang 310030China

The emergence of high-throughput techniques for proteomics measurement has led to an increasing number of proteogenomic studies that aim to reveal protein quantitative trait loci(pQTL)based on large cohorts(Suhre et a... 详细信息

关键词： mapping structure throughput

Defects evolution in n-type 4H-SiC induced by electron irradiation and annealing

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Journal of Semiconductors 2024年第7期45卷 77-83页

作者： Huifan Xiong Xuesong Lu Xu Gao Yuchao Yan Shuai Liu Lihui Song Deren Yang Xiaodong Pi State Key laboratory of Silicon and Advanced Semiconductor Materials&School of Materials Science and Engineering Zhejiang UniversityHangzhou 310027China Key laboratory of Power Semiconductor Materials and Devices of zhejiang Province&Institute of Advanced Semiconductors ZJU-Hangzhou Global Scientific and Technological Innovation CenterZhejiang UniversityHangzhou 311200China

Radiation damage produced in 4H-SiC by electrons of different doses is presented by using multiple characterization techniques. Raman spectra results indicate that SiC crystal structures are essentially impervious to 10 Me V electron irradiation with doses up to 3000 kGy. However, irradiation indeed leads to the generation of various defects, which are evaluated through photoluminescence(PL) and deep level transient spectroscopy(DLTS). The PL spectra feature a prominent broad band centered at 500 nm, accompanied by several smaller peaks ranging from 660 to 808 nm. The intensity of each PL peak demonstrates a linear correlation with the irradiation dose, indicating a proportional increase in defect concentration during irradiation. The DLTS spectra reveal several thermally unstable and stable defects that exhibit similarities at low irradiation ***, after irradiating at the higher dose of 1000 kGy, a new stable defect labeled as R_(2)(Ec-0.51 eV) appeared after annealing at 800 K. Furthermore, the impact of irradiation-induced defects on SiC junction barrier Schottky diodes is discussed. It is observed that high-dose electron irradiation converts SiC n-epilayers to semi-insulating layers. However, subjecting the samples to a temperature of only 800 K results in a significant reduction in resistance due to the annealing out of unstable defects.

关键词： 4H-SiC deep level transient spectroscopy(DLTS) photoluminescence(PL) defects

Regulating photocatalytic overall water splitting of ferroelectric heterostructures by size effect

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Nano Research 2024年第9期17卷 8000-8006页

作者： Zixing Ye Daifu Yu Ruian Zhang Fei Qin Yiran Sun Jie Huang Zhanqi Zhou He Tian Gaorong Han Zhaohui Ren Gang Liu State Key laboratory of Silicon and Advanced Semiconductor Materials School of Materials Science and EngineeringZhejiang UniversityHangzhou 310027China Shenyang National laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China center of Electron Microscopy School of Materials Science and EngineeringZhejiang UniversityHangzhou 310027China

In the past decade,ferroelectric materials have been intensively explored as promising *** intriguing ability of ferroelectrics is to directly sperate the photogenerated electrons and holes,which is believed to arise from a spontaneous *** how polarization affects the photocatalytic performance is vital to design high-efficiency *** this work,we report a size effect of ferroelectric polarization on regulating the photocatalytic overall water splitting of SrTiO_(3)/PbTiO_(3)nanoplate heterostructures for the first *** was realized hydrothermally by controlling the thickness and thus spontaneous polarization strength of single-crystal and single-domain PbTiO_(3)nanoplates,which served as the substrate for selective heteroepitaxial growth of SrTiO_(3).An enhancement of 22 times in the photocatalytic overall water splitting performance of the heterostructures has been achieved when the average thickness of the nanoplate increases from 30 to 107 nm.A combined experimental investigation revealed that the incompletely compensated depolarization filed is the dominated driving force for the photogenerated carrier separation within heterostructures,and its increase with the thickness of the nanoplates accounts for the enhancement of photocatalytic ***,the concentration of oxygen vacancies for negative polarization compensation has been found to grow as the thickness of the nanoplates increases,which promotes oxygen evolution reaction and reduces the stoichiometric ratio of H_(2)/O_(2).These findings may provide the opportunity to design and develop high-efficiency ferroelectric photocatalysts.

关键词： single-domain nanoplates size effect ferroelectric polarization screening photocatalytic overall water splitting

New role of platelets in schizophrenia:predicting drug response

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General Psychiatry 2024年第2期37卷 197-206页

作者： Yamin Zhang Yanghao Zheng Peiyan Ni Sugai Liang Xiaojing Li Hua Yu Wei Wei Xueyu Qi Xueli Yu Rui Xue Liansheng Zhao Wei Deng Qiang Wang Wanjun Guo Tao Li Department of Neurobiology Zhejiang University School of Medicine Affiliated Mental Health Centre&Hangzhou Seventh People's HospitalHangzhouZhejiangChina Liangzhu laboratory Zhejiang University MOE Frontier Science Center for Brain Science and Brain Machine IntegrationHangzhouZhejiangChina Mental Health center and Psychiatric laboratory West China Hospital of Sichuan UniversityChengduSichuanChina

Background Elevated platelet count(PLTc)is associated with first-episode schizophrenia and adverse outcomes in individuals with precursory ***,the impact of antipsychotic medications on PLTc and its association with symptom improvement remain *** We aimed to investigate changes in PLTc levels following antipsychotic treatment and assess whether PLTc can predict antipsychotic responses and metabolic changes after accounting for other related *** A total of 2985 patients with schizophrenia were randomised into seven *** group received one of seven antipsychotic treatments and was assessed at 2,4 and 6 *** symptoms were evaluated using the positive and negative syndrome scale(PANSS).Additionally,we measured blood cell counts and metabolic parameters,such as blood *** measures analysis of variance was used to examine the effect of antipsychotics on PLTc changes,while structural equation modelling was used to assess the predictive value of PLTc on PANSS *** PLTc significantly increased in patients treated with aripiprazole(F=6.00,p=0.003),ziprasidone(F=7.10,p<0.001)and haloperidol(F=3.59,p=0.029).It exhibited a positive association with white blood cell count and metabolic *** baseline PLTc was observed in non-responders,particularly in those defined by the PANSS-negative *** the structural equation model,PLTc,white blood cell count and a latent metabolic variable predicted the rate of change in the PANSS-negative subscale ***,higher baseline PLTc was observed in individuals with less metabolic change,although this association was no longer significant after accounting for baseline metabolic *** Platelet parameters,specifically PLTc,are influenced by antipsychotic treatment and could potentially elevate the risk of venous thromboembolism in patients with *** PLTc levels and associated factors may impede symptom improvement by

关键词： schizophrenia assessed treatment

Key progresses of MOE key laboratory of macromolecular synthesis and functionalization in 2022

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Chinese Chemical Letters 2024年第3期35卷 114-126页

作者： Xumeng Deng Kaihao Chen Kai Pang Xiaoting Liu Minsong Gao Jie Ren Guanwen Yang Guangpeng Wu Chengjian Zhang Xufeng Ni Peng Zhang Jian Ji Jianzhao Liu Zhengwei Mao Ziliang Wu Zhen Xu Haoke Zhang Hanying Li MOE Key laboratory of Macromolecular Synthesis and Functionalization International Research Center for X PolymersDepartment of Polymer Science and EngineeringZhejiang UniversityHangzhou 310027China

In 2022,The MOE Key laboratory of Macromolecular Synthesis and Functionalization in zhejiang University had achieved several important ***,a series of well-defined dinuclear organoboron catalysts were developed to precisely control the enchainment of ether and carbonate segments during the copolymerization of CO_(2)and ***,polyester had been synthesized through cationic copolymerization of cyclic ***,ring-opening polymerization of carbon dioxide based valerolactone had been achieved,revealing the prospect of 3-ethylidene-6-vinyltetrahydro-2H-pyran-2-one(EVL)in utilizing CO_(2)and synthesizing functional ***,machine learning methods have been applied to biomaterial research,enabling high-throughput screening of functional biomaterial surfaces for implantable devices,and searching for potent antimicrobial peptides in whole combinatorial peptide ***,methods of characterization of biomacromolecule RNA transcription and manipulation of nucleoside modification were ***,artificial enzymes-armed Bifidobacterium Longum probiotics were established to tune down gut ***,three-dimensional(3D)printing technologies were used to engineer tough supramolecular ***,hydroplastic foaming graphene frameworks for acoustic and conductive polymer composites were provided for ***,aggregate photophysics about the nature of through-space interactions(TSIs)and manipulating their strength in small molecules with non-conjugated structure had been ***,the forming mechanism of a newfound nested texture in poly(L-lactic acid)(PLLA)spherulitic films had been ***,the isotropically dyeing mechanism of KDP single crystals grown from hydrogels have been *** related works are reviewed in this paper.

关键词： Polymer Catalyst Biomaterial research mRNA Hydrogel Graphene Crystal

A Single-Cell Landscape of Human Liver Transplantation Reveals a Pathogenic Immune Niche Associated with Early Allograft Dysfunction

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Engineering 2024年第5期36卷 193-208页

作者： Xin Shao Zheng Wang Kai Wang Xiaoyan Lu Ping Zhang Rongfang Guo Jie Liao Penghui Yang Shusen Zheng Xiao Xu Xiaohui Fan Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China National Key laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxing 314103China zhejiang University School of Medicine Hangzhou 310058China NHC Key laboratory of Combined Multi-organ Transplantation Hangzhou 310003China Department of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)Hospital Affiliated to Shulan International Medical CollegeZhejiang Shuren UniversityHangzhou 310000China Engineering Research center of Innovative Anticancer Drugs Ministry of EducationHarbin 150023China

Liver transplantation(LT)is the standard therapy for individuals afflicted with end-stage liver *** notable advancements in LT technology,the incidence of early allograft dysfunction(EAD)remains a critical concern,exacerbating the current organ shortage and detrimentally affecting the prognosis of ***,the perplexing hepatic heterogeneity has impeded characterization of the cellular traits and molecular events that contribute to ***,we constructed a pioneering single-cell transcriptomic landscape of human transplanted livers derived from non-EAD and EAD patients,with 12 liver samples collected from 7 donors during the cold perfusion and portal reperfusion *** of the 75231 cells of non-EAD and EAD patients revealed an EAD-associated immune niche comprising mucosal-associated invariant T cells,granzyme B^(+)(GZMB^(+))granzyme K^(+)(GZMK^(+))natural killer cells,and S100 calcium binding protein A12^(+)(S100A12^(+))***,we verified this immune niche and its association with EAD occurrence in two independent *** findings elucidate the cellular characteristics of transplanted livers and the EAD-associated pathogenic immune niche at the single-cell level,thus,offering valuable insights into EAD onset.

关键词： Human liver transplantation Early allograft dysfunction Pathogenic immune niche Single-cell analysis Cell-cell communication