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Large-scale loss-of-function perturbations reveal a comprehensive epigenetic regulatory network in breast cancer
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作者 Yumei Wang Haiyan Wang +7 位作者 Wei Shao Yuhui Chen Yu Gui Chao Hu Xiaohong Yi Lijun Huang Shasha Li Dong Wang 《Cancer Biology & Medicine》 SCIE CAS CSCD 2024年第1期83-103,共21页
Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer... Objective:Epigenetic abnormalities have a critical role in breast cancer by regulating gene expression;however,the intricate interrelationships and key roles of approximately 400 epigenetic regulators in breast cancer remain elusive.It is important to decipher the comprehensive epigenetic regulatory network in breast cancer cells to identify master epigenetic regulators and potential therapeutic targets.Methods:We employed high-throughput sequencing-based high-throughput screening(HTS^(2))to effectively detect changes in the expression of 2,986 genes following the knockdown of 400 epigenetic regulators.Then,bioinformatics analysis tools were used for the resulting gene expression signatures to investigate the epigenetic regulations in breast cancer.Results:Utilizing these gene expression signatures,we classified the epigenetic regulators into five distinct clusters,each characterized by specific functions.We discovered functional similarities between BAZ2B and SETMAR,as well as CLOCK and CBX3.Moreover,we observed that CLOCK functions in a manner opposite to that of HDAC8 in downstream gene regulation.Notably,we constructed an epigenetic regulatory network based on the gene expression signatures,which revealed 8 distinct modules and identified 10 master epigenetic regulators in breast cancer.Conclusions:Our work deciphered the extensive regulation among hundreds of epigenetic regulators.The identification of 10 master epigenetic regulators offers promising therapeutic targets for breast cancer treatment. 展开更多
关键词 Epigenetic regulators breast cancer regulatory network HTS^(2)
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The virulence regulator AbsR in avian pathogenic Escherichia coli has pleiotropic effects on bacterial physiology
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作者 Dongfang Zhao Haobo Zhang +4 位作者 Xinyang Zhang Fengwei Jiang Yijing Li Wentong Cai Ganwu Li 《Journal of Integrative Agriculture》 SCIE CAS CSCD 2024年第2期649-668,共20页
Avian pathogenic Escherichia coli(APEC)belonging to extraintestinal pathogenic E.coli(ExPEC)can cause severe infections in extraintestinal tissues in birds and humans,such as the lungs and blood.MprA(microcin producti... Avian pathogenic Escherichia coli(APEC)belonging to extraintestinal pathogenic E.coli(ExPEC)can cause severe infections in extraintestinal tissues in birds and humans,such as the lungs and blood.MprA(microcin production regulation,locus A,herein renamed AbsR,a blood survival regulator),a member of the MarR(multiple antibiotic resistance regulator)transcriptional regulator family,governs the expression of capsule biosynthetic genes in human ExPEC and represents a promising druggable target for antimicrobials.However,a deep understanding of the AbsR regulatory mechanism as well as its regulon is lacking.In this study,we present a systems-level analysis of the APEC AbsR regulon using ChIP-Seq(chromatin immunoprecipitation sequencing)and RNA-Seq(RNA sequencing)methods.We found that AbsR directly regulates 99 genes and indirectly regulates 667 genes.Furthermore,we showed that:1)AbsR contributes to antiphagocytotic effects by macrophages and virulence in a mouse model for systemic infection by directly activating the capsular gene cluster;2)AbsR positively impacts biofilm formation via direct regulation of the T2SS(type II secretion system)but plays a marginal role in virulence;and 3)AbsR directly upregulates the acid tolerance signaling system EvgAS to withstand acid stress but is dispensable in ExPEC virulence.Finally,our data indicate that the role of AbsR in virulence gene regulation is relatively conserved in ExPEC strains.Altogether,this study provides a comprehensive analysis of the AbsR regulon and regulatory mechanism,and our data suggest that AbsR likely influences virulence primarily through the control of capsule production.Interestingly,we found that AbsR severely represses the expression of the type I-F CRISPR(clustered regularly interspaced short palindromic repeats)-Cas(CRISPR associated)systems,which could have implications in CRISPR biology and application. 展开更多
关键词 avian pathogenic Escherichia coli(ApEC) extraintestinal pathogenic Escherichia coli(ExpEC) AbsR RNA-SEQ CHIp-SEQ gene regulation
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The future of artificial hibernation medicine:protection of nerves and organs after spinal cord injury 被引量:1
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作者 Caiyun Liu Haixin Yu +4 位作者 Zhengchao Li Shulian Chen Xiaoyin Li Xuyi Chen Bo Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第1期22-28,共7页
Spinal cord injury is a serious disease of the central nervous system involving irreversible nerve injury and various organ system injuries.At present,no effective clinical treatment exists.As one of the artificial hi... Spinal cord injury is a serious disease of the central nervous system involving irreversible nerve injury and various organ system injuries.At present,no effective clinical treatment exists.As one of the artificial hibernation techniques,mild hypothermia has preliminarily confirmed its clinical effect on spinal cord injury.However,its technical defects and barriers,along with serious clinical side effects,restrict its clinical application for spinal cord injury.Artificial hibernation is a futureoriented disruptive technology for human life support.It involves endogenous hibernation inducers and hibernation-related central neuromodulation that activate particular neurons,reduce the central constant temperature setting point,disrupt the normal constant body temperature,make the body adapt"to the external cold environment,and reduce the physiological resistance to cold stimulation.Thus,studying the artificial hibernation mechanism may help develop new treatment strategies more suitable for clinical use than the cooling method of mild hypothermia technology.This review introduces artificial hibernation technologies,including mild hypothermia technology,hibernation inducers,and hibernation-related central neuromodulation technology.It summarizes the relevant research on hypothermia and hibernation for organ and nerve protection.These studies show that artificial hibernation technologies have therapeutic significance on nerve injury after spinal co rd injury through inflammatory inhibition,immunosuppression,oxidative defense,and possible central protection.It also promotes the repair and protection of res pirato ry and digestive,cardiovascular,locomoto r,urinary,and endocrine systems.This review provides new insights for the clinical treatment of nerve and multiple organ protection after spinal cord injury thanks to artificial hibernation.At present,artificial hibernation technology is not mature,and research fa ces various challenges.Neve rtheless,the effort is wo rthwhile for the future development of medicine. 展开更多
关键词 artificial hibernation central thermostatic-resista nt regulation HYpOTHERMIA multi-system protection neuroprotection organ protection spinal cord injury synthetic torpor
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Epigenetic control on transcription of vernalization genes and whole-genome gene expression profile induced by vernalization in common wheat
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作者 Yunzhen Li Liujie Jin +4 位作者 Xinyu Liu Chao He Siteng Bi Sulaiman Saeed Wenhao Yan 《Plant Diversity》 SCIE CAS CSCD 2024年第3期386-394,共9页
Vernalization is necessary for winter wheat to flower.However,it is unclear whether vernalization is also required for spring wheat,which is frequently sown in fall,and what molecular mechanisms underlie the vernaliza... Vernalization is necessary for winter wheat to flower.However,it is unclear whether vernalization is also required for spring wheat,which is frequently sown in fall,and what molecular mechanisms underlie the vernalization response in wheat varieties.In this study,we examined the molecular mechanisms that regulate vernalization response in winter and spring wheat varieties.For this purpose,we determined how major vernalization genes(VRN1,VRN2,and VRN3)respond to vernalization in these varieties and whether modifications to histones play a role in changes in gene expression.We also identified genes that are differentially regulated in response to vernalization in winter and spring wheat varieties.We found that in winter wheat,but not in spring wheat,VRN1 expression decreases when returned to warm temperature following vernalization.This finding may be associated with differences between spring and winter wheat in the levels of tri-methylation of lysine 27 on histone H3(H3K27me3)and tri-methylation of lysine 4 on histone H3(H3K4me3)at the VRN1 gene.Analysis of winter wheat transcriptomes before and after vernalization revealed that vernalization influences the expression of several genes,including those involved in leucine catabolism,cysteine biosynthesis,and flavonoid biosynthesis.These findings provide new candidates for further study on the mechanism of vernalization regulation in wheat. 展开更多
关键词 WHEAT VERNALIZATION VRN1 Histone modification Regulate network
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Research Progress of Epigenetics in Liver Cancer
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作者 Shijian Fu Min Guo 《Journal of Cancer Therapy》 2024年第3期71-82,共12页
Epigenetic changes are changes in gene expression by regulating gene transcription and translation without changing the nucleotide sequence of the genome. Although the genome itself changes during the occurrence and d... Epigenetic changes are changes in gene expression by regulating gene transcription and translation without changing the nucleotide sequence of the genome. Although the genome itself changes during the occurrence and development of most malignant tumors, recent studies have found that epigenetic changes also play an important role in the occurrence and development of tumors. Epigenetic modification mainly includes DNA methylation, histone modification and miRNA regulation. This review focuses on the role and mechanism of epigenetic modification in the occurrence, metastasis and invasion of hepatocellular carcinoma (HCC), and summarizes the latest methods for the treatment of HCC by restoring dysregulated epigenetic modification. It provides a theoretical basis for revealing the pathogenesis of liver cancer and developing new methods of diagnosis and treatment. 展开更多
关键词 EpiGENETICS Hepatocellular Carcinoma DNA Methylation Histone Modification miRNA Regulation
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An NMOS output-capacitorless low-dropout regulator with dynamic-strength event-driven charge pump
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作者 Yiling Xie Baochuang Wang +1 位作者 Dihu Chen Jianping Guo 《Journal of Semiconductors》 EI CAS CSCD 2024年第6期23-34,共12页
In this paper,an NMOS output-capacitorless low-dropout regulator(OCL-LDO)featuring dual-loop regulation has been proposed,achieving fast transient response with low power consumption.An event-driven charge pump(CP)loo... In this paper,an NMOS output-capacitorless low-dropout regulator(OCL-LDO)featuring dual-loop regulation has been proposed,achieving fast transient response with low power consumption.An event-driven charge pump(CP)loop with the dynamic strength control(DSC),is proposed in this paper,which overcomes trade-offs inherent in conventional structures.The presented design addresses and resolves the large signal stability issue,which has been previously overlooked in the event-driven charge pump structure.This breakthrough allows for the full exploitation of the charge-pump structure's poten-tial,particularly in enhancing transient recovery.Moreover,a dynamic error amplifier is utilized to attain precise regulation of the steady-state output voltage,leading to favorable static characteristics.A prototype chip has been fabricated in 65 nm CMOS technology.The measurement results show that the proposed OCL-LDO achieves a 410 nA low quiescent current(IQ)and can recover within 30 ns under 200 mA/10 ns loading change. 展开更多
关键词 output-capacitorless low-dropout regulator fast transient low quiescent current event-driven charge pump
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Electronic structure and spin state regulation of vanadium nitride via a sulfur doping strategy toward flexible zinc-air batteries
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作者 Daijie Deng Honghui Zhang +6 位作者 Jianchun Wu Xing Tang Min Ling Sihua Dong Li Xu Henan Li Huaming Li 《Journal of Energy Chemistry》 SCIE EI CAS CSCD 2024年第2期239-249,I0007,共12页
Owing to the distinctive structural characteristics,vanadium nitride(VN)is highly regarded as a catalyst for oxygen reduction reaction(ORR)in zinc-air batteries(ZABs).However,VN exhibits limited intrinsic ORR activity... Owing to the distinctive structural characteristics,vanadium nitride(VN)is highly regarded as a catalyst for oxygen reduction reaction(ORR)in zinc-air batteries(ZABs).However,VN exhibits limited intrinsic ORR activity due to the weak adsorption ability to O-containing species.Here,the S-doped VN anchored on N,S-doped multi-dimensional carbon(S-VN/Co/NS-MC)was constructed using the solvothermal and in-situ doping methods.Incorporating sulfur atoms into VN species alters the electron spin state of vanadium in the S-VN/Co/NS-MC for regulating the adsorption energy of vanadium sites to oxygen molecules.The introduced sulfur atoms polarize the V 3d_(z)^(2) electrons,shifting spin-down electrons closer to the Fermi level in the S-VN/Co/NS-MC.Consequently,the introduction of sulfur atoms into VN species enhances the adsorption energy of vanadium sites for oxygen molecules.The*OOH dissociation transitions from being unspontaneous on the VN surface to a spontaneous state on the S-doped VN surface.Then,the ORR barrier on the S-VN/Co/NS-MC surface is reduced.The S-VN/Co/NS-MC demonstrates a higher half-wave potential and limiting current density compared to the VN/Co/N-MC.The S-VN/Co/NS-MC-based liquid ZABs display a power density of 195.7 m W cm^(-2),a specific capacity of 815.7 m A h g^(-1),and a cycling stability exceeding 250 h.The S-VN/Co/NS-MC-based flexible ZABs are successfully employed to charge both a smart watch and a mobile phone.This approach holds promise for advancing the commercial utilization of VN-based catalysts in ZABs. 展开更多
关键词 S-doped VN Electronic structures Spin state regulation Oxygen reduction reaction Zinc-air batteries
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色瓦绵羊GPIHBP1基因克隆及其组织表达特征分析
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作者 潘君茹 李蕊 +7 位作者 张馨 仁青措姆 孙宇 杨井泉 张贞贞 陈华丽 赵旺生 宋天增 《南方农业学报》 CAS CSCD 北大核心 2024年第1期235-242,共8页
【目的】克隆色瓦绵羊乳腺组织糖基化磷脂酰肌醇锚定高密度脂蛋白结合蛋白1基因(GPIHBP1),明确其生物信息学特性及组织表达分布特征,为揭示GPIHBP1基因影响绵羊产奶性状的作用机制提供参考依据。【方法】克隆色瓦绵羊GPIHBP1基因编码区(... 【目的】克隆色瓦绵羊乳腺组织糖基化磷脂酰肌醇锚定高密度脂蛋白结合蛋白1基因(GPIHBP1),明确其生物信息学特性及组织表达分布特征,为揭示GPIHBP1基因影响绵羊产奶性状的作用机制提供参考依据。【方法】克隆色瓦绵羊GPIHBP1基因编码区(CDS)序列,通过Prot Para、Prot Scale、SOPMA、SWISS-MODEL、TMHMM-2.0等在线软件进行生物信息学分析,并以实时荧光定量PCR检测该基因在色瓦绵羊乳腺、肌肉、心脏、肾脏、肝脏、小肠、瘤胃和卵巢等8个组织中的表达情况。【结果】色瓦绵羊GPIHBP1基因CDS序列长519 bp,共编码172个氨基酸残基,与山羊GPIHBP1氨基酸序列(XM_018058666.1)比对,有4处氨基酸发生突变(^(32)A→P、^(52)V→A、^(130)S→N和^(170)M→V);色瓦绵羊GPIHBP1蛋白分子量为18063.87 Da,理论等电点(p I)为4.29,不存在跨膜螺旋结构,但存在信号肽(位于第20~21位氨基酸处),是一种细胞外的酸性亲水性蛋白。色瓦绵羊GPIHBP1蛋白存在12个磷酸化位点(6个丝氨酸磷酸化位点,5个苏氨酸磷酸化位点,1个酪氨酸磷酸化位点),其二级结构以无规则卷曲状态(占55.07%)为主,其次是α-螺旋(占35.47%),延伸链、β-转角分别占5.81%和4.65%。GPIHBP1基因在色瓦绵羊乳腺、肌肉、心脏、肾脏、肝脏、小肠、瘤胃和卵巢等8个组织中均有表达,以乳腺中的相对表达量最高,其次是心脏和肝脏,均极显著高于肌肉中的相对表达量(P<0.01)。【结论】GPIHBP1基因在色瓦绵羊不同组织中均有表达,且以乳腺中的相对表达量最高,可能与乳脂相关基因表达的增减有关,其中,GPIHBP1基因与LPL基因共同作用而参与绵羊泌乳调控。 展开更多
关键词 色瓦绵羊 GpiHBp1基因 乳腺 产奶性状 泌乳调控
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Alleviating the anisotropic microstructural change and boosting the lithium ions diffusion by grain orientation regulation for Ni-rich cathode materials
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作者 Xinyou He Shilin Su +3 位作者 Bao Zhang Zhiming Xiao Zibo Zhang Xing Ou 《Journal of Energy Chemistry》 SCIE EI CAS CSCD 2024年第1期213-222,I0005,共11页
Generally,layered Ni-rich cathode materials exhibit the morphology of polycrystalline secondary sphere composed of numerous primary particles.While the arrangement of primary particles plays a very important role in t... Generally,layered Ni-rich cathode materials exhibit the morphology of polycrystalline secondary sphere composed of numerous primary particles.While the arrangement of primary particles plays a very important role in the properties of Ni-rich cathodes.The disordered particle arrangement is harmful to the cyclic performance and structural stability,yet the fundamental understanding of disordered structure on the structural degradation behavior is unclarified.Herein,we have designed three kinds of LiNi_(0.83)Co_(0.06)Mn_(0.11)O_(2) cathode materials with different primary particle orientations by regulating the precursor coprecipitation process.Combining finite element simulation and in-situ characterization,the Li^(+)transport and structure evolution behaviors of different materials are unraveled.Specifically,the smooth Li^(+)diffusion minimizes the reaction heterogeneity,homogenizes the phase transition within grains,and mitigates the anisotropic microstructural change,thereby modulating the crack evolution behavior.Meanwhile,the optimized structure evolution ensures radial tight junctions of the primary particles,enabling enhanced Li^(+)diffusion during dynamic processes.Closed-loop bidirectional enhancement mechanism becomes critical for grain orientation regulation to stabilize the cyclic performance.This precursor engineering with particle orientation regulation provides the useful guidance for the structural design and feature enhancement of Ni-rich layered cathodes. 展开更多
关键词 Ni-rich cathode Grain orientation regulation Anisotropic microstructural change precursor engineering Li~%pLUS%-ions diffusion
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基于滑模PI控制的电动汽车集群出力与调频联合优化
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作者 吴二博 梁军 +2 位作者 黄征 王要强 陈天锦 《电力自动化设备》 EI CSCD 北大核心 2024年第2期87-93,共7页
电动汽车(EV)集群在参与电网调频时,持续大量的出力可能会导致系统频率出现超调现象,且会增加系统的调频成本和对EV集群的补偿成本。在保证系统频率稳定的前提下,为了协调EV集群与发电机的出力,提出了基于滑模比例-积分(PI)控制的发电机... 电动汽车(EV)集群在参与电网调频时,持续大量的出力可能会导致系统频率出现超调现象,且会增加系统的调频成本和对EV集群的补偿成本。在保证系统频率稳定的前提下,为了协调EV集群与发电机的出力,提出了基于滑模比例-积分(PI)控制的发电机和EV集群联合优化方法,并以系统调频成本和频率稳定为目标,对EV集群的车辆投入比例进行优化。考虑私家车、公交车、出租车这3种类型EV参与电网辅助调频,建立了EV集群参与微电网调频的单区域系统模型,通过滑模PI对EV集群进行控制,在保证频率稳定的情况下,显著减小EV集群出力;进一步对EV集群车辆投入比例参数进行优化,显著降低系统的调频成本。对发电机容量充足、不足的工况进行仿真,并对比参数优化前、后的结果,验证了所提联合优化方法的有效性和经济性。 展开更多
关键词 电动汽车 集群控制 滑模pi控制 调频 联合优化
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Microglia:a promising therapeutic target in spinal cord injury
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作者 Xiaowei Zha Guoli Zheng +3 位作者 Thomas Skutella Karl Kiening Andreas Unterberg Alexander Younsi 《Neural Regeneration Research》 SCIE CAS 2025年第2期454-463,共10页
Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accou... Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal function.In a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal regeneration.In this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor cells.Despite a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive research.This review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target. 展开更多
关键词 ASTROCYTES CYTOKINES functional recovery immune regulation M1/M2 activation MACROpHAGES MICROGLIA NEUROINFLAMMATION spinal cord injury therapy
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Dynamic plugging regulating strategy of pipeline robot based on reinforcement learning
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作者 Xing-Yuan Miao Hong Zhao 《Petroleum Science》 SCIE EI CAS CSCD 2024年第1期597-608,共12页
Pipeline isolation plugging robot (PIPR) is an important tool in pipeline maintenance operation. During the plugging process, the violent vibration will occur by the flow field, which can cause serious damage to the p... Pipeline isolation plugging robot (PIPR) is an important tool in pipeline maintenance operation. During the plugging process, the violent vibration will occur by the flow field, which can cause serious damage to the pipeline and PIPR. In this paper, we propose a dynamic regulating strategy to reduce the plugging-induced vibration by regulating the spoiler angle and plugging velocity. Firstly, the dynamic plugging simulation and experiment are performed to study the flow field changes during dynamic plugging. And the pressure difference is proposed to evaluate the degree of flow field vibration. Secondly, the mathematical models of pressure difference with plugging states and spoiler angles are established based on the extreme learning machine (ELM) optimized by improved sparrow search algorithm (ISSA). Finally, a modified Q-learning algorithm based on simulated annealing is applied to determine the optimal strategy for the spoiler angle and plugging velocity in real time. The results show that the proposed method can reduce the plugging-induced vibration by 19.9% and 32.7% on average, compared with single-regulating methods. This study can effectively ensure the stability of the plugging process. 展开更多
关键词 pipeline isolation plugging robot plugging-induced vibration Dynamic regulating strategy Extreme learning machine Improved sparrow search algorithm Modified Q-learning algorithm
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Mutations in epigenetic regulator KMT2C detected by liquid biopsy are associated with worse survival in prostate cancer patients 被引量:1
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作者 SHA ZHU NANWEI XU +10 位作者 JIAYU LIANG FENGNIAN ZHAO ZILIN WANG YUCHAO NI JINDONG DAI JINGE ZHAO XINGMING ZHANG JUNRU CHEN GUANGXI SUN PENGFEI SHEN HAO ZENG 《Oncology Research》 SCIE 2023年第4期605-614,共10页
Background:KMT2(lysine methyltransferase)family enzymes are epigenetic regulators that activate gene transcription.KMT2C is mainly involved in enhancer-associated H3K4me1,and is also one of the top mutated genes in ca... Background:KMT2(lysine methyltransferase)family enzymes are epigenetic regulators that activate gene transcription.KMT2C is mainly involved in enhancer-associated H3K4me1,and is also one of the top mutated genes in cancer(6.6%in pan-cancer).Currently,the clinical significance of KMT2C mutations in prostate cancer is understudied.Methods:We included 221 prostate cancer patients diagnosed between 2014 and 2021 in West China Hospital of Sichuan University with cell-free DNA-based liquid biopsy test results in this study.We investigated the association between KMT2C mutations,other mutations,and pathways.Furthermore,we evaluated the prognostic value of KMT2C mutations,measured by overall survival(OS)and castration resistance-free survival(CRFS).Also,we explored the prognostic value of KMT2C mutations in different patient subgroups.Lastly,we investigated the predictive value of KMT2C mutations in individuals receiving conventional combined anti-androgen blockade(CAB)and abiraterone(ABI)as measured by PSA progression-free survival(PSA-PFS).Results:The KMT2C mutation rate in this cohort is 7.24%(16/221).KMT2C-mutated patients showed worse survival than KMT2C-wild type(WT)patients regarding both CRFS and OS(CRFS:mutated:9.9 vs.WT:22.0 months,p=0.015;OS:mutated:71.9 vs.WT 137.4 months,p=0.012).KMT2C mutations were also an independent risk factor in OS[hazard ratio:3.815(1.461,9.96),p=0.006]in multivariate analyses.Additionally,we explored the association of KMT2C mutations with other genes.This showed that KMT2C mutations were associated with Serine/Threonine-Protein Kinase 11(STK11,p=0.004)and Catenin Beta 1(CTNNB1,p=0.008)mutations.In the CAB treatment,KMT2C-mutated patients had a significantly shorter PSA-PFS compared to KMT2C-WT patients.(PSA-PFS:mutated:9.9 vs.WT:17.6 months,p=0.014).Moreover,KMT2C mutations could effectively predict shorter PSA-PFS in 10 out of 23 subgroups and exhibited a strong trend in the remaining subgroups.Conclusions:KMT2C-mutated patients showed worse survival compared to KMT2C-WT patients in terms of both CRFS and OS,and KMT2C mutations were associated with STK11 and CTNNB1 mutations.Furthermore,KMT2C mutations indicated rapid progression during CAB therapy and could serve as a potential biomarker to predict therapeutic response in prostate cancer. 展开更多
关键词 KMT2C Epigenetic regulator Liquid biopsy prostate cancer SURVIVAL Biomarker
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Understanding the molecular crossroads in acute liver failure:A pathway to new therapies
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作者 Chun-Yao Cheng Wen-Rui Hao Tzu-Hurng Cheng 《World Journal of Gastroenterology》 SCIE CAS 2024年第23期2931-2933,共3页
In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ d... In this editorial we comment on the article published in a recent issue of the World Journal of Gastroenterology.Acute liver failure(ALF)is a critical condition characterized by rapid hepatocellular injury and organ dysfunction,and it often necessitates liver transplant to ensure patient survival.Recent research has eluci-dated the involvement of distinct cell death pathways,namely ferroptosis and pyroptosis,in the pathogenesis of ALF.Ferroptosis is driven by iron-dependent lipid peroxidation,whereas pyroptosis is an inflammatory form of cell death;both pathways contribute to hepatocyte death and exacerbate tissue damage.This comprehensive review explores the interplay between ferroptosis and pyroptosis in ALF,highlighting the role of key regulators such as silent information regulator sirtuin 1.Insights from clinical and preclinical studies provide valuable perspectives on the dysregulation of cell death pathways in ALF and the therapeutic potential of targeting these pathways.Collaboration across multiple disciplines is essential for translating the experimental insights into effective treatments for this life-threatening condition. 展开更多
关键词 Silent information regulator sirtuin 1 Ferroptosis pYROpTOSIS p53/glutathione peroxidase 4/gasdermin D Acute liver failure
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Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis
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作者 Xing-Nian Zhou Quan Zhang +6 位作者 Hong Peng Yu-Jie Qin Yu-Hong Liu Lu Wang Ming-Liang Cheng Xin-Hua Luo Hong Li 《World Journal of Gastroenterology》 SCIE CAS 2024年第11期1588-1608,共21页
BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple b... BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and pyroptosis.The silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and inflammation.AIM To investigate the association between ferroptosis and pyroptosis and the upstream regulatory mechanisms.METHODS This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce ALF.Gasdermin D(GSDMD)^(-/-)mice were used as an experimental group.Histological changes in liver tissue were monitored by hematoxylin and eosin staining.ALT,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial kits.Ferroptosis-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain reaction.SIRT1,p53,and GSDMD were assessed by immunofluorescence analysis.RESULTS Serum AST and ALT levels were elevated in patients with ALF.SIRT1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver tissue.In the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was mitigated.In mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were detected.In vitro,knockdown of p53 and overexpression of GPX4 reduced AST and ALT levels,the cytostatic rate,and GSDMD expression,restoring SLC7A11 depletion.Moreover,SIRT1 agonist and overexpression of SIRT1 alleviated acute liver injury and decreased iron deposition compared with results in the model group,accompanied by reduced p53,GSDMD,and ACSL4,and increased SLC7A11 and GPX4.Inactivation of SIRT1 exacerbated ferroptotic and pyroptotic cell death and aggravated liver injury in LPS/D-GalNinduced in vitro and in vivo models.CONCLUSION SIRT1 activation attenuates LPS/D-GalN-induced ferroptosis and pyroptosis by inhibiting the p53/GPX4/GSDMD signaling pathway in ALF. 展开更多
关键词 Silent information regulator sirtuin 1 Ferroptosis pYROpTOSIS p53/glutathione peroxidase 4/gasdermin D Acute liver failure
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基于模糊神经网络的氢液化氦气压力PID控制
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作者 李安琪 秦可欣 +1 位作者 杨思锋 兰玉岐 《低温工程》 CAS CSCD 北大核心 2024年第2期92-98,共7页
为了解决氢液化装置氦气压力调节系统超调量大、响应速度慢、调节时间长、控制参数无法在线整定等问题,针对系统具有非线性和时变性的特点,设计了基于模糊神经网络的PID控制器以及基于双曲正切函数的改进型激活函数。仿真结果表明:相比... 为了解决氢液化装置氦气压力调节系统超调量大、响应速度慢、调节时间长、控制参数无法在线整定等问题,针对系统具有非线性和时变性的特点,设计了基于模糊神经网络的PID控制器以及基于双曲正切函数的改进型激活函数。仿真结果表明:相比传统PID控制或模糊PID控制,采用模糊神经网络PID控制的系统动态性能显著改善,使得氢液化装置的氦气压力调节更加稳定可靠。 展开更多
关键词 氦气压力调节系统 模糊神经网络 piD控制 压力控制
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The Effect of Plant Growth Regulators on Physico-Chemical Properties of Safflower (Carthamus tinctorius L.) Derived Biodiesel
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作者 Charles Mazereku Jerekias Gandure Clever Ketlogetswe 《Open Journal of Applied Sciences》 2024年第4期1052-1069,共18页
Global concerns about the environmental impact of combustion emissions from petroleum fuels influence new research to seek for alternative energy sources. The current study investigates the possibility of using safflo... Global concerns about the environmental impact of combustion emissions from petroleum fuels influence new research to seek for alternative energy sources. The current study investigates the possibility of using safflower (Carthamus tinctorius L.) as an alternative biodiesel raw material. Four plant growth regulators (PGR) were used to boost the production of safflower. Thirteen treatments were constituted from the four plant regulators and applied to the safflower crop arranged in completely randomised design, repeated three times. The results show that the effect of plant growth regulators was not more than that of the control. More studies have to be channelled towards the relationship between safflower and plant growth regulators. 展开更多
关键词 SAFFLOWER Biodiesel plant Growth regulators
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Low Level of Cystic Fibrosis Transmembrane Conductance Regulator Is Associated with Human Sperm Autophagy and Vitality
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作者 Jie Hu Han Liu +4 位作者 Chaoyan Ou Liangzhao Liu Linfeng Mo Xuming Liang Yonghua He 《Advances in Reproductive Sciences》 CAS 2024年第1期23-36,共14页
Low sperm motility is one of the main causes of male infertility. Cystic fibrosis transmembrane conductance regulator (CFTR, an anion channel protein) is related to the progressive motility of sperm. CFTR disruptor CF... Low sperm motility is one of the main causes of male infertility. Cystic fibrosis transmembrane conductance regulator (CFTR, an anion channel protein) is related to the progressive motility of sperm. CFTR disruptor CFTRinh-172 or forskolin (FSK) in this study were used to treat human sperm separately, and the rates of sperm autophagy and progressive motility, mitochondrial membrane potential (MMP) and ATP concentration, and the expression levels of related factors were detected to explore their relationship. It was showed that sperms treated with CFTRinh-172 or FSK reduced the levels of cAMP, CFTR and PKA, but increased sperm autophagy rate, expression levels of AMPK and LC3B. However, reactive oxygen species content had no significant difference. It was indicated that low level of CFTR performed with cAMP and its downstream effectors such as PKA and AMPK to regulate mitochondrial structure and function, leading to increased autophagy rate and reduced vitality of sperm. 展开更多
关键词 Low Level of Cystic Fibrosis Transmembrane Conductance regulator Is Associated with Human Sperm Autophagy and Vitality
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基于继电反馈PID自整定的加热系统
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作者 王晓忠 《科技创新与应用》 2024年第7期128-133,共6页
某工厂对某种液体进行加热控制,针对某液体复杂的反应过程,设计出带自整定功能的PID自动调节加热设备。该设计以意法半导体公司(ST)的STM32F103C8T6为控制器,以PT100为温度采集元件,控制可控硅进行过零功率调节,通过MCGS触摸屏来显示,... 某工厂对某种液体进行加热控制,针对某液体复杂的反应过程,设计出带自整定功能的PID自动调节加热设备。该设计以意法半导体公司(ST)的STM32F103C8T6为控制器,以PT100为温度采集元件,控制可控硅进行过零功率调节,通过MCGS触摸屏来显示,设定有关波形和参数,在控制过程中,可以根据有关加热要求选择多种整定参数,以满足液体的不同动态响应类型。该文主要介绍系统硬件组成原理框图,给出系统主要硬件电路图和自整定算法的工作流程,并对PID程序编制的一些关键点进行说明。实验证明加热系统能满足工厂要求。 展开更多
关键词 STM32F103 继电自整定 piD调节 温控 加热系统
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监管设计、效率变革与福利改善——兼论RPI-X定价模型的监管困境
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作者 于文领 李宏舟 闫明喆 《财经论丛》 北大核心 2024年第1期103-112,F0003,共11页
本文利用随机前沿分析框架测算中国电网公司的效率变革,在此基础上选择反事实分析法,模拟实施新型规制模式的成本效应和福利效应。实证结果表明,效率导向型收入上限规制不是零和博弈,能带来监管改革红利。据此,进一步优化现有输配电价... 本文利用随机前沿分析框架测算中国电网公司的效率变革,在此基础上选择反事实分析法,模拟实施新型规制模式的成本效应和福利效应。实证结果表明,效率导向型收入上限规制不是零和博弈,能带来监管改革红利。据此,进一步优化现有输配电价规制模式,不仅可改革输配电行业中被掩盖的低效率环节,还可将其转化为推动行业高质量发展的重要源泉,实现电网公司的效率变革和社会福利的改善。 展开更多
关键词 监管设计 Rpi-X规制 效率变革 随机前沿模型 福利改善
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