Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report...Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.展开更多
Metabolic reprogramming reshapes the tumor microenvironment(TME)and facilitates metastasis,but its molecular mechanisms remain incompletely understood.Here,we identified enolase 2(ENO2),a critical glycolytic enzyme,as...Metabolic reprogramming reshapes the tumor microenvironment(TME)and facilitates metastasis,but its molecular mechanisms remain incompletely understood.Here,we identified enolase 2(ENO2),a critical glycolytic enzyme,as being associated with lymphatic metastasis in head and neck squamous cell carci-noma(HNSCC).Mechanistically,phosphoenolpyruvate(PEP),the metabolite secreted by ENO2-expressing HNSCC cells,drove histone H3 lysine 18 lactylation(H3K18la)-mediated M2 polarization in macrophages,which,in turn,enhanced the epithelial-mesenchymal transition(EMT)and invasiveness of HNSCC cells.Pharmacological inhibition of ENO2 with POMHEX effectively reversed M2 macrophage polarization and inhibited HNSCC lymphatic metastasis.Collectively,our findings underscore the prog-nostic significance of ENO2 and highlight its potential as a therapeutic target for metastatic HNSCC.Furthermore,we reveal a previously underappreciated role of PEP in modulating the tumor immune microenvironment and tumor metastasis via epigenetic modification.展开更多
[Objectives]To obtain a novel cultivar of Chuanminshen violaceum with robust growth,high yield,and stable genetic traits.[Methods]A systematic selection method was employed to conduct a multi-point testing and regiona...[Objectives]To obtain a novel cultivar of Chuanminshen violaceum with robust growth,high yield,and stable genetic traits.[Methods]A systematic selection method was employed to conduct a multi-point testing and regional production trial utilizing C.violaceum strain CMS1,which was sourced from a semi-wild population in Langzhong,Sichuan Province,as the experimental material.In contrast,C.violaceum CMS2,derived from a cultivated population in Langzhong,Sichuan Province,along with a mixed population of C.violaceum cultispecies from the same region,served as the control material.Through a comparative analysis of phenological periods,agronomic traits,yield,and quality,a novel cultivar,‘Chengming No.1’,was ultimately selected and developed based on its superior comprehensive evaluation.[Results]In the phenological period survey conducted as part of a two-year comparative study,the CMS1 strain exhibited a shorter growth cycle compared to others.Furthermore,the agronomic characteristics of the CMS1 strain were superior to those of both CMS2 and CK.The average yields of CMS1,CMS2,and CK in the 2019 cultivar comparison test and yield trial were 468.88,448.52,and 422.15 kg/667 m 2,respectively.This resulted in an average yield increase of 11.07%for CMS1 compared to CK and 6.25%for CMS2 compared to CK.The average yields of CMS1,CMS2,and CK in the 2020 cultivar comparison test and yield trial were 482.69,467.54,and 436.82 kg/667 m 2,respectively.CMS1 exhibited an average yield increase of 10.50%compared to CK,while CMS2 demonstrated an average yield increase of 7.03%relative to CK.Furthermore,the average yield of CMS1 per 667 m 2 achieved a statistically significant level compared to CK in both years of the study.In multiple-point comparison and yield trials conducted in 2019 and 2020,the CMS1 strain exhibited a total ash content of 15.30%,an acid-insoluble ash content of 1.30%,a moisture content of 10.80%,and water-soluble extract amounting to 11.40%.All of the indicators conformed to the criteria established by the Sichuan Standards for Chinese Medicinal Materials(2010 Edition).[Conclusions]The CMS1 strain successfully passed the field technical appraisal for the novel cultivar of C.violaceum in 2021.This cultivar is characterized by high yield,excellent quality,and stable traits.In 2022,it received validation from the Sichuan Provincial Committee for the Certification of Non-Staple Crop Varieties and was officially named‘Chengming No.1’(CRY 2022002).This cultivar demonstrates significant potential for widespread cultivation.展开更多
The H9N2 subtype avian influenza virus(AIV)continues to propagate and undergo evolution within China,thereby posing a significant threat to the poultry industry.This study encompassed the collection of 436 samples and...The H9N2 subtype avian influenza virus(AIV)continues to propagate and undergo evolution within China,thereby posing a significant threat to the poultry industry.This study encompassed the collection of 436 samples and swabs in East China over the period spanning 2018 to 2019,from which 31 strains of the H9N2 subtype viruses were isolated and purified.We revealed that the HA and NA genes of the 31 isolates categorized within the Y280 branch,while the PB2 and M genes were associated with the G1 branch,and the remaining genes aligned with the F/98 branch.Despite this alignment,antigenic mapping demonstrated differences between the 2018 and 2019 strains,with the early vaccine strains displaying low serological reactivity toward these isolates.Notably,the CK/SH/49/19 isolate exhibited lethality in mice,characterized by a PB2 E627V mutation and a HA deletion at amino acid position 217.Mechanistically,in vitro studies showed that the influenza virus CK/SH/49/19 carrying PB2627V and HA 217M mutations displayed enhanced replication capacity,attributed to the heightened activity of the polymerase with PB2627V.Moreover,the absence of the amino acid at the HA 217 site obstructed viral adsorption and internalization,resulted in lower activation pH,and impeded the virus budding process.Critically,in vivo experiments revealed that CK/SH/49/19(PB2627V,HA 217Δ)triggered a robust activation of interferon response and interferon-stimulated genes.This study furnished a theoretical foundation for the scientific prevention and control strategies against H9N2 subtype avian influenza.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82171429,81771384a grant from Wuxi Municipal Health Commission,No.1286010241190480(all to YS)。
文摘Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.
基金supported by grants from the National Natural Science Foundation of China(82204428,U24A20815,82304526,82204427,82201001,82430108,82293681(82293680),82273941)the National High-level Personnelof Special Support Program(to Dongmei Zhang and Minfeng Chen)+5 种基金the Natural Science Foundation of Guangdong Province(2023A1515010361 and 2022A1515011813)the Guangdong Basic and Applied Basic Research Foundation(2024B1515020098)the Science and Technology Program of Guangzhou(SL2024A04J00410,SL2024A04J00374,SL2024A04J00280)the Fundamental Research Funds for The Central Universities(21624103)the Science and Technology Projects in Guangzhou(2023A03J1030,202201010173,202102070001)the Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University,China(JNU1AF-CFTP-2022-a01210).
文摘Metabolic reprogramming reshapes the tumor microenvironment(TME)and facilitates metastasis,but its molecular mechanisms remain incompletely understood.Here,we identified enolase 2(ENO2),a critical glycolytic enzyme,as being associated with lymphatic metastasis in head and neck squamous cell carci-noma(HNSCC).Mechanistically,phosphoenolpyruvate(PEP),the metabolite secreted by ENO2-expressing HNSCC cells,drove histone H3 lysine 18 lactylation(H3K18la)-mediated M2 polarization in macrophages,which,in turn,enhanced the epithelial-mesenchymal transition(EMT)and invasiveness of HNSCC cells.Pharmacological inhibition of ENO2 with POMHEX effectively reversed M2 macrophage polarization and inhibited HNSCC lymphatic metastasis.Collectively,our findings underscore the prog-nostic significance of ENO2 and highlight its potential as a therapeutic target for metastatic HNSCC.Furthermore,we reveal a previously underappreciated role of PEP in modulating the tumor immune microenvironment and tumor metastasis via epigenetic modification.
基金Supported by Sichuan Innovation Team Project of China Agricultural Industry Research System(SCCXTD-2023-19)Key R&D Project of Sichuan Provincial Department of Science and Technology(2022YFS0592)Sichuan Provincial Science and Technology Innovation Seedling Project(MZGC20230119,MZGC20230126).
文摘[Objectives]To obtain a novel cultivar of Chuanminshen violaceum with robust growth,high yield,and stable genetic traits.[Methods]A systematic selection method was employed to conduct a multi-point testing and regional production trial utilizing C.violaceum strain CMS1,which was sourced from a semi-wild population in Langzhong,Sichuan Province,as the experimental material.In contrast,C.violaceum CMS2,derived from a cultivated population in Langzhong,Sichuan Province,along with a mixed population of C.violaceum cultispecies from the same region,served as the control material.Through a comparative analysis of phenological periods,agronomic traits,yield,and quality,a novel cultivar,‘Chengming No.1’,was ultimately selected and developed based on its superior comprehensive evaluation.[Results]In the phenological period survey conducted as part of a two-year comparative study,the CMS1 strain exhibited a shorter growth cycle compared to others.Furthermore,the agronomic characteristics of the CMS1 strain were superior to those of both CMS2 and CK.The average yields of CMS1,CMS2,and CK in the 2019 cultivar comparison test and yield trial were 468.88,448.52,and 422.15 kg/667 m 2,respectively.This resulted in an average yield increase of 11.07%for CMS1 compared to CK and 6.25%for CMS2 compared to CK.The average yields of CMS1,CMS2,and CK in the 2020 cultivar comparison test and yield trial were 482.69,467.54,and 436.82 kg/667 m 2,respectively.CMS1 exhibited an average yield increase of 10.50%compared to CK,while CMS2 demonstrated an average yield increase of 7.03%relative to CK.Furthermore,the average yield of CMS1 per 667 m 2 achieved a statistically significant level compared to CK in both years of the study.In multiple-point comparison and yield trials conducted in 2019 and 2020,the CMS1 strain exhibited a total ash content of 15.30%,an acid-insoluble ash content of 1.30%,a moisture content of 10.80%,and water-soluble extract amounting to 11.40%.All of the indicators conformed to the criteria established by the Sichuan Standards for Chinese Medicinal Materials(2010 Edition).[Conclusions]The CMS1 strain successfully passed the field technical appraisal for the novel cultivar of C.violaceum in 2021.This cultivar is characterized by high yield,excellent quality,and stable traits.In 2022,it received validation from the Sichuan Provincial Committee for the Certification of Non-Staple Crop Varieties and was officially named‘Chengming No.1’(CRY 2022002).This cultivar demonstrates significant potential for widespread cultivation.
基金supported by National Natural Science Foundation of China[Grant number:32272992(JP),31772775(JP)]National Key Research and Development Program of China[Grant number:2021YFD1800205(JP)].
文摘The H9N2 subtype avian influenza virus(AIV)continues to propagate and undergo evolution within China,thereby posing a significant threat to the poultry industry.This study encompassed the collection of 436 samples and swabs in East China over the period spanning 2018 to 2019,from which 31 strains of the H9N2 subtype viruses were isolated and purified.We revealed that the HA and NA genes of the 31 isolates categorized within the Y280 branch,while the PB2 and M genes were associated with the G1 branch,and the remaining genes aligned with the F/98 branch.Despite this alignment,antigenic mapping demonstrated differences between the 2018 and 2019 strains,with the early vaccine strains displaying low serological reactivity toward these isolates.Notably,the CK/SH/49/19 isolate exhibited lethality in mice,characterized by a PB2 E627V mutation and a HA deletion at amino acid position 217.Mechanistically,in vitro studies showed that the influenza virus CK/SH/49/19 carrying PB2627V and HA 217M mutations displayed enhanced replication capacity,attributed to the heightened activity of the polymerase with PB2627V.Moreover,the absence of the amino acid at the HA 217 site obstructed viral adsorption and internalization,resulted in lower activation pH,and impeded the virus budding process.Critically,in vivo experiments revealed that CK/SH/49/19(PB2627V,HA 217Δ)triggered a robust activation of interferon response and interferon-stimulated genes.This study furnished a theoretical foundation for the scientific prevention and control strategies against H9N2 subtype avian influenza.
