Piezocatalytic hydrogen peroxide(H_(2)O_(2))generation is a promising synthesis method that has received increasing attention;however,the reaction pathway requires further investigation.Here,Bi_(5)Ti_(3)FeO_(15)nanofi...Piezocatalytic hydrogen peroxide(H_(2)O_(2))generation is a promising synthesis method that has received increasing attention;however,the reaction pathway requires further investigation.Here,Bi_(5)Ti_(3)FeO_(15)nanofibers are used to generate H_(2)O_(2)by harvesting mechanical energy,and the reaction pathways are investigated.The H_(2)O_(2)yield over Bi_(5)Ti_(3)FeO_(15)nanofibers steadily increases from 331μmol g1 h1 in the first cycle to 746μmol g1 h1 in the tenth cycle in pure water without a sacrificial agent.Reliable reaction pathways are revealed by monitoring the pH value changes in the reaction solution during the H_(2)O_(2)generation process.In the H_(2)O_(2)generation process,the water oxidation reaction(WOR)provides a large amount of H+in the reaction solution,which promotes the oxygen reduction reaction(ORR)for H_(2)O_(2)generation.Therefore,an efficient synergistic effect between ORR and WOR achieves dual-pathway H_(2)O_(2)generation,contributing to the excellent piezocatalytic performance of Bi_(5)Ti_(3)FeO_(15)nanofibers.Furthermore,mechanistic studies indicate that the piezocatalytic H_(2)O_(2)generation follows the energy band theory.This work not only demonstrates Bi_(5)Ti_(3)FeO_(15)nanofibers as efficient piezocatalysts for H_(2)O_(2)generation but also provides a simple and effective approach to elucidate reaction pathways.This approach can be applied in photocatalytic,tribocatalytic,and electrocatalytic H_(2)O_(2)generation.展开更多
To develop efficient concerted companion(CC)dyes for fabricating high-performance DSSCs,three organic dyes XL1-XL3 have been designed by varying the position and number of theβ-hexylthiophene(HT)bridges,and these org...To develop efficient concerted companion(CC)dyes for fabricating high-performance DSSCs,three organic dyes XL1-XL3 have been designed by varying the position and number of theβ-hexylthiophene(HT)bridges,and these organic dye units are covalently linked with our previously reported porphyrin dye XW10 to construct the corresponding CC dyes XW74-XW76.Among the organic dyes,XL3 contains twoβ-hexylthiophene units at both the donor and acceptor parts and thus possesses stronger light-harvesting capability in the green light region.Because of the most complementary absorption between XL3 and XW10 as well as the excellent photovoltaic behavior of the individual XL3 dye,the corresponding CC dye XW76 affords the best PCE(10.78%)among all the CC dyes.Upon coadsorption with CDCA,XW76 affords a highest PCE of 11.35%,which outperforms the previous cosensitization system of XW10+WS-5.This work provides an approach for developing efficient DSSCs based on CC dyes composed of an organic dye unit with suitableπspacers inserted at appropriate positions.展开更多
Aiming at the selection of fuzzy AHP and fuzzy DH methods in the previous studies, this paper evaluate the qualitative index system using expert questionnaire, the self-learning BP neural network model to construct th...Aiming at the selection of fuzzy AHP and fuzzy DH methods in the previous studies, this paper evaluate the qualitative index system using expert questionnaire, the self-learning BP neural network model to construct the index of system, and complete the establishment of model, in order to avoid the serious subjectivity, and using statistical and measurement methods test the reliability index, analyze the validity of the evaluation index system and completeness. Finally, the paper validate the practicability of the model.展开更多
This paper explores the persistence of educational inequality in the United States through a structural and policyoriented lens.Based on empirical research,it analyzes how academic disparities are caused by the inters...This paper explores the persistence of educational inequality in the United States through a structural and policyoriented lens.Based on empirical research,it analyzes how academic disparities are caused by the intersection of family economic status,racial bias,inter-district financial disparities,and governance fragmentation.The article combs through the evolution of federal education policies from ESEA to NCLB and ESSA,pointing out that performance-oriented reforms and market-oriented strategies that fail to address structural inequality(e.g.,school choice policies),however,may instead exacerbate the concentration of resources and educational stratification.In response to existing limitations,the study proposes equityoriented policy pathways,including student-weighted grants,federally supported teacher development programs in high-poverty districts,and institutional mechanisms for community engagement.These initiatives aim to embed the concept of“responsiveness to difference”in the entire process of policy design and implementation.The study ultimately concludes that the realization of educational equity requires not only the redistribution of resources,but also the promotion of systemic changes at the level of governance structures and social participation,so that education can truly become an institutional support for social mobility and democratic inclusion.展开更多
Rhizosphere microorganisms,as one of the most important components of the soil microbiota and plant holobiont,play a key role in the medicinal plant-soil ecosystem,which are closely related to the growth,adaptability,...Rhizosphere microorganisms,as one of the most important components of the soil microbiota and plant holobiont,play a key role in the medicinal plant-soil ecosystem,which are closely related to the growth,adaptability,nutrient absorption,stress tolerance and pathogen resistance of host plants.In recent years,with the wide application of molecular biology and omics technologies,the outcomes of rhizosphere microorganisms on the health,biomass production and secondary metabolite biosynthesis of medicinal plants have received extensive attention.However,whether or to what extent rhizosphere microorganisms can contribute to the construction of the quality evaluation system of Chinese medicinal materials is still elusive.Based on the significant role of rhizosphere microbes in the survival and quality formation of medicinal plants,this paper proposed a new concept of rhizosphere microbial markers(micro-markers),expounded the relevant research methods and ideas of applying the new concept,highlighted the importance of micro-markers in the quality evaluation and control system of traditional Chinese medicines(TCMs),and introduced the potential value in soil environmental assessment,plant pest control and quality assessment of TCMs.It provides reference for developing ecological planting of TCMs and ensuring the production of high quality TCMs by regulating rhizosphere microbial communities.展开更多
Background Astrocytes regulate blood-brain barrier(BBB)integrity,whereas subarachnoid haemorrhage(SAH)results in astrocyte dysregulation and BBB disruption.Here,we explored the involvement of tissue inhibitor of matri...Background Astrocytes regulate blood-brain barrier(BBB)integrity,whereas subarachnoid haemorrhage(SAH)results in astrocyte dysregulation and BBB disruption.Here,we explored the involvement of tissue inhibitor of matrix metalloprotease-1(TIMP1)in astrocyte-mediated BBB protection during SAH,along with its underlying mechanisms.Methods C57BL/6J mice were used to establish a model of SAH.The effects of TIMP1 on SAH outcomes were analysed by intraperitoneal injection of recombinant mouse TIMP1 protein(rm-TIMP1;250µg/kg).The roles of TIMP1 and its effectorβ1-integrin on astrocytes were observed by in vivo transduction with astrocyte-targeted adeno-associated virus carrying TIMP1 overexpression plasmid orβ1-integrin RNAi.The molecular mechanisms underlying TIMP1 andβ1-integrin interactions were explored in primary cultured astrocytes stimulated with red blood cells(RBCs).Results TIMP1 was upregulated after SAH.Administration of rm-TIMP1 mitigated SAH-induced early brain injury(EBI)in male and female mice.TIMP1 was primarily expressed in astrocytes;its overexpression in astrocytes led to increasedβ1-integrin expression in astrocytes,along with the preservation of astrocytic endfoot attachment to the endothelium and subsequent recovery of endothelial tight junctions.All of these effects were reversed by the knockdown ofβ1-integrin in astrocytes.Molecular analysis showed that TIMP1 overexpression decreased the RBC-induced ubiquitination ofβ1-integrin;this effect was partially achieved by inhibiting the interaction betweenβ1-integrin and the E3 ubiquitin ligase Trim21.Conclusion TIMP1 inhibits the interaction betweenβ1-integrin and Trim21 in astrocytes,thereby rescuing the ubiquitination of astrocyticβ1-integrin.It subsequently restores interactions between astrocytic endfeet and the endothelium,as well as BBB integrity,eventually mitigating SAH-induced EBI.展开更多
The enantioselective allylic amination of Morita-Baylis-Hillman acetates catalyzed by chiral cyclohexane-based thiourea-phosphine catalysts was investigated. In the presence of 20 mol% rosin-derived thiourea-phosphine...The enantioselective allylic amination of Morita-Baylis-Hillman acetates catalyzed by chiral cyclohexane-based thiourea-phosphine catalysts was investigated. In the presence of 20 mol% rosin-derived thiourea-phosphine 3j, the chiral amines were obtained in up to 88% yield and up to 85% ee.展开更多
Suitable conformations and proper alignment of complex natural macrocycles are essential for achieving their unique properties.However,such artificial macrocycle prototypes are still limited due to synthetic difficult...Suitable conformations and proper alignment of complex natural macrocycles are essential for achieving their unique properties.However,such artificial macrocycle prototypes are still limited due to synthetic difficulties.In this respect,directly linked porphyrin analog dimers display tunable conformations and intriguing properties,and thus,they may be employed as a class of promising platforms.Herein,we report that one-pot oxidative dimerization of thiahydrosapphyrin 1 yields dimers,2anti and 2syn,comprising a transoid-oriented plate-like bipyrrolo[1,2-a]indolylidene.The thiophene-containing tetrapyrrole arching subunits in 2 lie at the opposite(anti)and same(syn)sides of the plate,respectively.Meanwhile,multiply fused cisoid-orientated dimer 3 was also obtained;a polycyclic pyrrolo-bridged bipyrroloindole derivative tethered with fullyπ-conjugated bridges was formed.Notably,the anti-dimer 2anti underwent subsequent oxidative fusion to furnish a further-fused[6.5.5.7.5.5.5.6]-octacyclic compound 4anti.In contrast,the syn-orientated 2syn could not be further fused due to the long distance between the potential reaction sites.This study provides a unique approach to the fused dimeric porphyrin analogs for potential near-infrared optical materials by a simple oxidation reaction.It also reveals the importance of conformation-modulated reactivity for constructing complex porphyrin arrays.展开更多
The direct preparation of a kind of fluorinating reagent 1[F-TEDA-N(SO_(2)Ph)_(2)]was realized in high yield via the complexation of N-fluorobenzenesulfonimide(NFSI)with 1-(chloromethyl)-1,4-diazabicyclo[2.2.2]octan-1...The direct preparation of a kind of fluorinating reagent 1[F-TEDA-N(SO_(2)Ph)_(2)]was realized in high yield via the complexation of N-fluorobenzenesulfonimide(NFSI)with 1-(chloromethyl)-1,4-diazabicyclo[2.2.2]octan-1-ium N',N'-bis-(benzenesulfonylimide)salt.In its fluorination to oxindoles,the fluorinating products 6 were afforded in moderate to high yields.展开更多
Background and aims:Polygonum cuspidatum Sieb.et Zucc.(P.cuspidatum)and its active components have been clinically proven to have anti-hepatocellular carcinoma effects.However,the potential targets of P.cuspidatum for...Background and aims:Polygonum cuspidatum Sieb.et Zucc.(P.cuspidatum)and its active components have been clinically proven to have anti-hepatocellular carcinoma effects.However,the potential targets of P.cuspidatum for these effects have not yet been revealed.Methods:We used network pharmacology and single-cell transcriptomic analysis with molecular docking to elucidate the active components and targets of P.cuspidatum for hepatocellular carcinoma.Results:CDK1,ESR1,HSP90A11,and MAPK1 were shown to be the key targets of P.cuspidatum for hepatocellular carcinoma.P.cuspidatum was found to be likely correlated with the improved abnormal expression of CDK1 and ESR1 and the poor prognosis of HSP90AA1 and MAPK1.CDK1 was identified as the most potential antihepatocellular carcinoma target of P.cuspidatum.Among the active components of P.cuspidatum,physcion diglucoside was found to have the most potential to treat hepatocellular carcinoma by targeting CDK1.Conclusion:Our study provides novel insights into the anti-hepatocellular carcinoma pharmacological effects of P.cuspidatum,which could serve as a scientific basis for its development as a medicinal resource and the targeting of CDK1 for hepatocellular carcinoma treatment.展开更多
Background and aims:To identify biomarkers to predict acute liver failure and investigate the mechanisms and immune-related pathways linked to its onset and progression.Methods:We analyzed gene expression differences ...Background and aims:To identify biomarkers to predict acute liver failure and investigate the mechanisms and immune-related pathways linked to its onset and progression.Methods:We analyzed gene expression differences between patients with acute liver failure(ALF)and controls in the GSE14668 dataset.Clinically relevant modules and key ALF-associated genes were identified using weighted gene co-expression network analysis(WGCNA)in conjunction with differential gene expression(DEG)analysis.Enrichment analysis was carried out and protein–protein interaction networks were constructed to understand the functions and pathways.Six potential diagnostic biomarkers were identified using machine learning algorithms.Diagnostic performance was assessed via column charts and area under the curve calculations.Single-sample gene set enrichment analysis evaluated the relationship between known marker gene sets and potential biomarker expression.We also examined diagnostic biomarker mRNA levels in ALF models in vivo and in vitro.We estimated the relative infiltration levels of 22 immune cell subpopulations in ALF samples,and explored the link between diagnostic biomarkers and infiltrating immune cells.Result:We found 352 DEGs associated with ALF.WGCNA analysis and intersecting DEGs identified 191 significant ALF-related genes.Machine learning identified HORMAD2,WNT10A,ATP6V1E2,CMBL,ARRDC4,and LPIN2 as potential diagnostic biomarkers.Cell experiments and quantitative real-time polymerase chain reaction supported the therapeutic potential of eriodictyol for ALF.Immune infiltration analysis suggested that plasma cells,CD4 memory resting and activated T cells,macrophages,and neutrophils might play roles in the progression of ALF.Conclusion:We identified HORMAD2,WNT10A,ATP6V1E2,CMBL,ARRDC4,and LPIN2,as diagnostic biomarkers for ALF and demonstrated the effectiveness of eriodictyol for treating ALF.Immune cell infiltration may play a significant role in the pathogenesis and progression of ALF.展开更多
文摘Piezocatalytic hydrogen peroxide(H_(2)O_(2))generation is a promising synthesis method that has received increasing attention;however,the reaction pathway requires further investigation.Here,Bi_(5)Ti_(3)FeO_(15)nanofibers are used to generate H_(2)O_(2)by harvesting mechanical energy,and the reaction pathways are investigated.The H_(2)O_(2)yield over Bi_(5)Ti_(3)FeO_(15)nanofibers steadily increases from 331μmol g1 h1 in the first cycle to 746μmol g1 h1 in the tenth cycle in pure water without a sacrificial agent.Reliable reaction pathways are revealed by monitoring the pH value changes in the reaction solution during the H_(2)O_(2)generation process.In the H_(2)O_(2)generation process,the water oxidation reaction(WOR)provides a large amount of H+in the reaction solution,which promotes the oxygen reduction reaction(ORR)for H_(2)O_(2)generation.Therefore,an efficient synergistic effect between ORR and WOR achieves dual-pathway H_(2)O_(2)generation,contributing to the excellent piezocatalytic performance of Bi_(5)Ti_(3)FeO_(15)nanofibers.Furthermore,mechanistic studies indicate that the piezocatalytic H_(2)O_(2)generation follows the energy band theory.This work not only demonstrates Bi_(5)Ti_(3)FeO_(15)nanofibers as efficient piezocatalysts for H_(2)O_(2)generation but also provides a simple and effective approach to elucidate reaction pathways.This approach can be applied in photocatalytic,tribocatalytic,and electrocatalytic H_(2)O_(2)generation.
基金financially supported by the National Natural Science Foundation of China (Nos. 22131005, 21772041, 21971063 and 22075077)the Program of Shanghai Academic Research Leader (No. 20XD1401400)+1 种基金the Natural Science Foundation of Shanghai (No. 20ZR1414100)the Fundamental Research Funds for the Central Universities (No. 222201717003)
文摘To develop efficient concerted companion(CC)dyes for fabricating high-performance DSSCs,three organic dyes XL1-XL3 have been designed by varying the position and number of theβ-hexylthiophene(HT)bridges,and these organic dye units are covalently linked with our previously reported porphyrin dye XW10 to construct the corresponding CC dyes XW74-XW76.Among the organic dyes,XL3 contains twoβ-hexylthiophene units at both the donor and acceptor parts and thus possesses stronger light-harvesting capability in the green light region.Because of the most complementary absorption between XL3 and XW10 as well as the excellent photovoltaic behavior of the individual XL3 dye,the corresponding CC dye XW76 affords the best PCE(10.78%)among all the CC dyes.Upon coadsorption with CDCA,XW76 affords a highest PCE of 11.35%,which outperforms the previous cosensitization system of XW10+WS-5.This work provides an approach for developing efficient DSSCs based on CC dyes composed of an organic dye unit with suitableπspacers inserted at appropriate positions.
文摘Aiming at the selection of fuzzy AHP and fuzzy DH methods in the previous studies, this paper evaluate the qualitative index system using expert questionnaire, the self-learning BP neural network model to construct the index of system, and complete the establishment of model, in order to avoid the serious subjectivity, and using statistical and measurement methods test the reliability index, analyze the validity of the evaluation index system and completeness. Finally, the paper validate the practicability of the model.
文摘This paper explores the persistence of educational inequality in the United States through a structural and policyoriented lens.Based on empirical research,it analyzes how academic disparities are caused by the intersection of family economic status,racial bias,inter-district financial disparities,and governance fragmentation.The article combs through the evolution of federal education policies from ESEA to NCLB and ESSA,pointing out that performance-oriented reforms and market-oriented strategies that fail to address structural inequality(e.g.,school choice policies),however,may instead exacerbate the concentration of resources and educational stratification.In response to existing limitations,the study proposes equityoriented policy pathways,including student-weighted grants,federally supported teacher development programs in high-poverty districts,and institutional mechanisms for community engagement.These initiatives aim to embed the concept of“responsiveness to difference”in the entire process of policy design and implementation.The study ultimately concludes that the realization of educational equity requires not only the redistribution of resources,but also the promotion of systemic changes at the level of governance structures and social participation,so that education can truly become an institutional support for social mobility and democratic inclusion.
基金funded by Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-D-202005)the CAMS Innovation Fund for Medical Sciences(CIFMS)(ID:2021-I2M-1-071 and 2022-I2M-2-001).
文摘Rhizosphere microorganisms,as one of the most important components of the soil microbiota and plant holobiont,play a key role in the medicinal plant-soil ecosystem,which are closely related to the growth,adaptability,nutrient absorption,stress tolerance and pathogen resistance of host plants.In recent years,with the wide application of molecular biology and omics technologies,the outcomes of rhizosphere microorganisms on the health,biomass production and secondary metabolite biosynthesis of medicinal plants have received extensive attention.However,whether or to what extent rhizosphere microorganisms can contribute to the construction of the quality evaluation system of Chinese medicinal materials is still elusive.Based on the significant role of rhizosphere microbes in the survival and quality formation of medicinal plants,this paper proposed a new concept of rhizosphere microbial markers(micro-markers),expounded the relevant research methods and ideas of applying the new concept,highlighted the importance of micro-markers in the quality evaluation and control system of traditional Chinese medicines(TCMs),and introduced the potential value in soil environmental assessment,plant pest control and quality assessment of TCMs.It provides reference for developing ecological planting of TCMs and ensuring the production of high quality TCMs by regulating rhizosphere microbial communities.
文摘Background Astrocytes regulate blood-brain barrier(BBB)integrity,whereas subarachnoid haemorrhage(SAH)results in astrocyte dysregulation and BBB disruption.Here,we explored the involvement of tissue inhibitor of matrix metalloprotease-1(TIMP1)in astrocyte-mediated BBB protection during SAH,along with its underlying mechanisms.Methods C57BL/6J mice were used to establish a model of SAH.The effects of TIMP1 on SAH outcomes were analysed by intraperitoneal injection of recombinant mouse TIMP1 protein(rm-TIMP1;250µg/kg).The roles of TIMP1 and its effectorβ1-integrin on astrocytes were observed by in vivo transduction with astrocyte-targeted adeno-associated virus carrying TIMP1 overexpression plasmid orβ1-integrin RNAi.The molecular mechanisms underlying TIMP1 andβ1-integrin interactions were explored in primary cultured astrocytes stimulated with red blood cells(RBCs).Results TIMP1 was upregulated after SAH.Administration of rm-TIMP1 mitigated SAH-induced early brain injury(EBI)in male and female mice.TIMP1 was primarily expressed in astrocytes;its overexpression in astrocytes led to increasedβ1-integrin expression in astrocytes,along with the preservation of astrocytic endfoot attachment to the endothelium and subsequent recovery of endothelial tight junctions.All of these effects were reversed by the knockdown ofβ1-integrin in astrocytes.Molecular analysis showed that TIMP1 overexpression decreased the RBC-induced ubiquitination ofβ1-integrin;this effect was partially achieved by inhibiting the interaction betweenβ1-integrin and the E3 ubiquitin ligase Trim21.Conclusion TIMP1 inhibits the interaction betweenβ1-integrin and Trim21 in astrocytes,thereby rescuing the ubiquitination of astrocyticβ1-integrin.It subsequently restores interactions between astrocytic endfeet and the endothelium,as well as BBB integrity,eventually mitigating SAH-induced EBI.
基金We are grateful for the financial support from the National Natural Science Foundation of China （Nos. 21242007, 21102043）, Science and Technology Com- mission of Shanghai Municipality （No. 15ZR1409200）, and the Fundamental Research Funds for the Central Universities.
文摘The enantioselective allylic amination of Morita-Baylis-Hillman acetates catalyzed by chiral cyclohexane-based thiourea-phosphine catalysts was investigated. In the presence of 20 mol% rosin-derived thiourea-phosphine 3j, the chiral amines were obtained in up to 88% yield and up to 85% ee.
基金The authors thank the Research Center of Analysis and Test of East China University of Science and Technology for compound characterization.
文摘Suitable conformations and proper alignment of complex natural macrocycles are essential for achieving their unique properties.However,such artificial macrocycle prototypes are still limited due to synthetic difficulties.In this respect,directly linked porphyrin analog dimers display tunable conformations and intriguing properties,and thus,they may be employed as a class of promising platforms.Herein,we report that one-pot oxidative dimerization of thiahydrosapphyrin 1 yields dimers,2anti and 2syn,comprising a transoid-oriented plate-like bipyrrolo[1,2-a]indolylidene.The thiophene-containing tetrapyrrole arching subunits in 2 lie at the opposite(anti)and same(syn)sides of the plate,respectively.Meanwhile,multiply fused cisoid-orientated dimer 3 was also obtained;a polycyclic pyrrolo-bridged bipyrroloindole derivative tethered with fullyπ-conjugated bridges was formed.Notably,the anti-dimer 2anti underwent subsequent oxidative fusion to furnish a further-fused[6.5.5.7.5.5.5.6]-octacyclic compound 4anti.In contrast,the syn-orientated 2syn could not be further fused due to the long distance between the potential reaction sites.This study provides a unique approach to the fused dimeric porphyrin analogs for potential near-infrared optical materials by a simple oxidation reaction.It also reveals the importance of conformation-modulated reactivity for constructing complex porphyrin arrays.
基金the National Natural Science Foundation of China(No.21372077)for their financial supports.
文摘The direct preparation of a kind of fluorinating reagent 1[F-TEDA-N(SO_(2)Ph)_(2)]was realized in high yield via the complexation of N-fluorobenzenesulfonimide(NFSI)with 1-(chloromethyl)-1,4-diazabicyclo[2.2.2]octan-1-ium N',N'-bis-(benzenesulfonylimide)salt.In its fluorination to oxindoles,the fluorinating products 6 were afforded in moderate to high yields.
基金Supported by National Training Program of Innovation and Entrepreneurship for Undergraduates(202410145118).
文摘Background and aims:Polygonum cuspidatum Sieb.et Zucc.(P.cuspidatum)and its active components have been clinically proven to have anti-hepatocellular carcinoma effects.However,the potential targets of P.cuspidatum for these effects have not yet been revealed.Methods:We used network pharmacology and single-cell transcriptomic analysis with molecular docking to elucidate the active components and targets of P.cuspidatum for hepatocellular carcinoma.Results:CDK1,ESR1,HSP90A11,and MAPK1 were shown to be the key targets of P.cuspidatum for hepatocellular carcinoma.P.cuspidatum was found to be likely correlated with the improved abnormal expression of CDK1 and ESR1 and the poor prognosis of HSP90AA1 and MAPK1.CDK1 was identified as the most potential antihepatocellular carcinoma target of P.cuspidatum.Among the active components of P.cuspidatum,physcion diglucoside was found to have the most potential to treat hepatocellular carcinoma by targeting CDK1.Conclusion:Our study provides novel insights into the anti-hepatocellular carcinoma pharmacological effects of P.cuspidatum,which could serve as a scientific basis for its development as a medicinal resource and the targeting of CDK1 for hepatocellular carcinoma treatment.
文摘Background and aims:To identify biomarkers to predict acute liver failure and investigate the mechanisms and immune-related pathways linked to its onset and progression.Methods:We analyzed gene expression differences between patients with acute liver failure(ALF)and controls in the GSE14668 dataset.Clinically relevant modules and key ALF-associated genes were identified using weighted gene co-expression network analysis(WGCNA)in conjunction with differential gene expression(DEG)analysis.Enrichment analysis was carried out and protein–protein interaction networks were constructed to understand the functions and pathways.Six potential diagnostic biomarkers were identified using machine learning algorithms.Diagnostic performance was assessed via column charts and area under the curve calculations.Single-sample gene set enrichment analysis evaluated the relationship between known marker gene sets and potential biomarker expression.We also examined diagnostic biomarker mRNA levels in ALF models in vivo and in vitro.We estimated the relative infiltration levels of 22 immune cell subpopulations in ALF samples,and explored the link between diagnostic biomarkers and infiltrating immune cells.Result:We found 352 DEGs associated with ALF.WGCNA analysis and intersecting DEGs identified 191 significant ALF-related genes.Machine learning identified HORMAD2,WNT10A,ATP6V1E2,CMBL,ARRDC4,and LPIN2 as potential diagnostic biomarkers.Cell experiments and quantitative real-time polymerase chain reaction supported the therapeutic potential of eriodictyol for ALF.Immune infiltration analysis suggested that plasma cells,CD4 memory resting and activated T cells,macrophages,and neutrophils might play roles in the progression of ALF.Conclusion:We identified HORMAD2,WNT10A,ATP6V1E2,CMBL,ARRDC4,and LPIN2,as diagnostic biomarkers for ALF and demonstrated the effectiveness of eriodictyol for treating ALF.Immune cell infiltration may play a significant role in the pathogenesis and progression of ALF.
