Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study...Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study,bulk RNA sequencing data(GSE47681 and GSE5296)and single-cell RNA sequencing data(GSE162610)were acquired from gene expression databases.We then conducted differential analysis and immune infiltration analysis.Atf3 and Piezo1 were identified as key ferroptosis genes through random forest and least absolute shrinkage and selection operator algorithms.Further analysis of single-cell RNA sequencing data revealed a close relationship between ferroptosis and cell types such as macrophages/microglia and their intrinsic state transition processes.Differences in transcription factor regulation and intercellular communication networks were found in ferroptosis-related cells,confirming the high expression of Atf3 and Piezo1 in these cells.Molecular docking analysis confirmed that the proteins encoded by these genes can bind cycloheximide.In a mouse model of T8 spinal cord injury,low-dose cycloheximide treatment was found to improve neurological function,decrease levels of the pro-inflammatory cytokine inducible nitric oxide synthase,and increase levels of the anti-inflammatory cytokine arginase 1.Correspondingly,the expression of the ferroptosis-related gene Gpx4 increased in macrophages/microglia,while the expression of Acsl4 decreased.Our findings reveal the important role of ferroptosis in the treatment of spinal cord injury,identify the key cell types and genes involved in ferroptosis after spinal cord injury,and validate the efficacy of potential drug therapies,pointing to new directions in the treatment of spinal cord injury.展开更多
Traumatic spinal cord injury(SCI)is a debilitating condition characterized by the impairment of neural circuits,leading to the loss of motor and sensory functions and accompanied by severe complications.Substantial re...Traumatic spinal cord injury(SCI)is a debilitating condition characterized by the impairment of neural circuits,leading to the loss of motor and sensory functions and accompanied by severe complications.Substantial research has reported the therapeutic potential of Omega-3 fatty acids for the central nervous system,particularly after traumatic SCI.Omega-3 fatty acids may contribute to improving SCI recovery through their anti-inflammatory,anti-oxidative,neurotrophic,and membrane integrity-preserving properties.These functions of Omega-3 fatty acids are primarily mediated via the activation of G protein-coupled receptor 120(GPR120),commonly known as the fish oil-specific receptor.Advancements in understanding of the molecular mechanisms of GPR120’s recognition of Omega-3 fatty acids and its downstream signaling mechanisms has significantly promoted research on the pharmacological potential of Omega-3 fatty acids and the development of highly selective and high-affinity alternatives.This review aims to provide in-depth analysis of the comprehensive therapeutic potential of Omega-3 fatty acids for SCI and its accompanying complications,and the prospects for developing novel drugs based on the recognition of Omega-3 fatty acids by GPR120.展开更多
Microbial communities play indispensable roles in the biogeochemical cycling of river ecosystems.However,the response patterns of microbial community diversity,niche breadth,and assembly to rainfall disturbances in co...Microbial communities play indispensable roles in the biogeochemical cycling of river ecosystems.However,the response patterns of microbial community diversity,niche breadth,and assembly to rainfall disturbances in complex mountainous riverine reservoirs remain inadequately understood.We employed high-throughput sequencing of 16S and 18S ribosomal RNA genes,along with multivariate statistical methods to systematically investigate prokaryotic and eukaryotic microorganisms in the riverine Zhaoshandu Reservoir,Wenzhou,Zhejiang,East China.Results show significant temporal heterogeneity in both prokaryotic and eukaryotic microbial communities,with eukaryotic microbes showing more pronounced temporal variation.Canonical correspondence analysis revealed that rainfall and water temperature were the key drivers shaping microbial communities.Additionally,eukaryotic microorganisms exhibited a more pronounced response to rainfall and water temperature compared to prokaryotes.Modified stochasticity ratio model indicated that deterministic processes predominantly governed microbial community assembly,with stronger deterministic processes in eukaryotic compared to prokaryotic microorganisms.Rainfall has significantly altered water quality,notably increasing phosphorus concentration in the water column.Total phosphorus and total nitrogen showed significant correlations with the niche breadth of prokaryotic and eukaryotic microorganisms,and phosphorus nutrients served as keystones and playing indispensable roles in their co-occurrence networks.A structural equation model confirmed the notable impacts of rainfall and water temperature on microbial community diversity,further revealing that rainfall indirectly influenced the niche breadth and co-occurrence relationships of microbial communities by altering phosphorus concentrations.The findings underscore the influence of rainfall and water temperature on microbial distribution,highlighting the sensitivity of riverine reservoir ecosystems to climate change.展开更多
基金supported by the National Natural Science Foundation of China,No.81972073(to HZ)a grant from the Taishan Scholars Program ofShandong Province-Young Taishan Scholars,No.tsqn201909197(to HZ)+1 种基金a grant from Tianjin Key Medical Discipline(Specialty)Construct Project,No.TJYXZDXK-027A(to SF)a grant from Academic Expert International Innovation Summit,No.22JRRCRC00010(to SF).
文摘Ferroptosis,a type of cell death that mainly involves iron metabolism imbalance and lipid peroxidation,is strongly correlated with the phagocytic response caused by bleeding after spinal cord injury.Thus,in this study,bulk RNA sequencing data(GSE47681 and GSE5296)and single-cell RNA sequencing data(GSE162610)were acquired from gene expression databases.We then conducted differential analysis and immune infiltration analysis.Atf3 and Piezo1 were identified as key ferroptosis genes through random forest and least absolute shrinkage and selection operator algorithms.Further analysis of single-cell RNA sequencing data revealed a close relationship between ferroptosis and cell types such as macrophages/microglia and their intrinsic state transition processes.Differences in transcription factor regulation and intercellular communication networks were found in ferroptosis-related cells,confirming the high expression of Atf3 and Piezo1 in these cells.Molecular docking analysis confirmed that the proteins encoded by these genes can bind cycloheximide.In a mouse model of T8 spinal cord injury,low-dose cycloheximide treatment was found to improve neurological function,decrease levels of the pro-inflammatory cytokine inducible nitric oxide synthase,and increase levels of the anti-inflammatory cytokine arginase 1.Correspondingly,the expression of the ferroptosis-related gene Gpx4 increased in macrophages/microglia,while the expression of Acsl4 decreased.Our findings reveal the important role of ferroptosis in the treatment of spinal cord injury,identify the key cell types and genes involved in ferroptosis after spinal cord injury,and validate the efficacy of potential drug therapies,pointing to new directions in the treatment of spinal cord injury.
基金supported by the National Key Research and Development Project of Stem Cell and Transformation Research(2019YFA0112100)Taishan Scholars Programof Shandong Province-Young Taishan Scholars(tsqn201909197)+1 种基金Cutting Edge Development Fund of Advanced Medical Research Institute(Shandong University)National Natural Science Foundation of China(82220108005)。
文摘Traumatic spinal cord injury(SCI)is a debilitating condition characterized by the impairment of neural circuits,leading to the loss of motor and sensory functions and accompanied by severe complications.Substantial research has reported the therapeutic potential of Omega-3 fatty acids for the central nervous system,particularly after traumatic SCI.Omega-3 fatty acids may contribute to improving SCI recovery through their anti-inflammatory,anti-oxidative,neurotrophic,and membrane integrity-preserving properties.These functions of Omega-3 fatty acids are primarily mediated via the activation of G protein-coupled receptor 120(GPR120),commonly known as the fish oil-specific receptor.Advancements in understanding of the molecular mechanisms of GPR120’s recognition of Omega-3 fatty acids and its downstream signaling mechanisms has significantly promoted research on the pharmacological potential of Omega-3 fatty acids and the development of highly selective and high-affinity alternatives.This review aims to provide in-depth analysis of the comprehensive therapeutic potential of Omega-3 fatty acids for SCI and its accompanying complications,and the prospects for developing novel drugs based on the recognition of Omega-3 fatty acids by GPR120.
基金Supported by the Zhejiang Provincial Natural Science Foundation of China(No.LD21C030001)the Key Research and Development Program of National Natural Science Foundation of China(No.2021YFE0112000)+1 种基金the National Natural Science Foundation of China(Nos.32371634,31970219)the Scientific Research Project of the Shanghai Municipal Bureau of Ecology and Environment(No.202409)。
文摘Microbial communities play indispensable roles in the biogeochemical cycling of river ecosystems.However,the response patterns of microbial community diversity,niche breadth,and assembly to rainfall disturbances in complex mountainous riverine reservoirs remain inadequately understood.We employed high-throughput sequencing of 16S and 18S ribosomal RNA genes,along with multivariate statistical methods to systematically investigate prokaryotic and eukaryotic microorganisms in the riverine Zhaoshandu Reservoir,Wenzhou,Zhejiang,East China.Results show significant temporal heterogeneity in both prokaryotic and eukaryotic microbial communities,with eukaryotic microbes showing more pronounced temporal variation.Canonical correspondence analysis revealed that rainfall and water temperature were the key drivers shaping microbial communities.Additionally,eukaryotic microorganisms exhibited a more pronounced response to rainfall and water temperature compared to prokaryotes.Modified stochasticity ratio model indicated that deterministic processes predominantly governed microbial community assembly,with stronger deterministic processes in eukaryotic compared to prokaryotic microorganisms.Rainfall has significantly altered water quality,notably increasing phosphorus concentration in the water column.Total phosphorus and total nitrogen showed significant correlations with the niche breadth of prokaryotic and eukaryotic microorganisms,and phosphorus nutrients served as keystones and playing indispensable roles in their co-occurrence networks.A structural equation model confirmed the notable impacts of rainfall and water temperature on microbial community diversity,further revealing that rainfall indirectly influenced the niche breadth and co-occurrence relationships of microbial communities by altering phosphorus concentrations.The findings underscore the influence of rainfall and water temperature on microbial distribution,highlighting the sensitivity of riverine reservoir ecosystems to climate change.
