Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq dat...Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.展开更多
The Asiatic hybrid lily(Lilium spp.)is a horticultural crop with high commercial value and diverse anthocyanin pigmentation patterns.However,the regulatory mechanism underlying lily flower color has been largely unexp...The Asiatic hybrid lily(Lilium spp.)is a horticultural crop with high commercial value and diverse anthocyanin pigmentation patterns.However,the regulatory mechanism underlying lily flower color has been largely unexplored.Here,we identified a WRKY transcription factor from lily tepals,LhWRKY44,whose expression was closely associated with anthocyanin accumulation.Functional verification indicated that LhWRKY44 positively regulated anthocyanin accumulation.LhWRKY44 physically interacted with LhMYBSPLATTER and directly bound to the LhMYBSPLATTER promoter,which enhanced the effect of the LhMYBSPLATTER-LhbHLH2 MBW complex activator on anthocyanin accumulation.Moreover,EMSA and dual-luciferase assays revealed that LhWRKY44 activated and bound to the promoters of gene LhF3H and the intracellular anthocyanin-related glutathione S-transferase gene LhGST.Interestingly,our further results showed that LhWRKY44 participated in light and drought-induced anthocyanin accumulation,and improved the drought tolerance in lily via activating stress-related genes.These results generated a multifaceted regulatory mechanism for the LhWRKY44-meditaed enhancement by the environmental signal pathway of anthocyanin accumulation and expanded our understanding of the WRKY-mediated transcriptional regulatory hierarchy modulating anthocyanin accumulation in Asiatic hybrid lilies.展开更多
Objective:Based on the analysis of a biochemical information database,the“target-pathway”network of anlotinib in the treatment of non-small cell lung cancer was constructed by using network pharmacological methods t...Objective:Based on the analysis of a biochemical information database,the“target-pathway”network of anlotinib in the treatment of non-small cell lung cancer was constructed by using network pharmacological methods to explore the mechanism of multi-target and multi-pathway treatment of non-small cell lung cancer.Methods:The 3D molecular structure formula of anlotinib was obtained by searching the PubChem database,and the target of anlotinib was predicted by using the PharmMapper database;obtain non-small cell lung cancer related targets through the GeneCards database,screen common genes related to drug targets and diseases by Venny 2.1.0,and build the relationship between drugs and diseases.Through the STRING11.5 database,the interaction relationship between action targets was built,the protein-protein interaction network was constructed,and the target degree was analyzed by Cytocsape 3.7.2 software to screen molecular docking objects.The DAVID database was used for Gene Ontology gene enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis to predict its mechanism,and the AutoDock software was used for molecular docking of the main targets.Results:The analysis results showed that there were 76 possible targets involved in the treatment of non-small cell lung cancer with anlotinib,mainly acting on epidermal growth factor receptor,mitogen-activated protein kinase 14,tyrosine-protein phosphatase non-receptor type 11,heat shock protein HSP 90-alpha,tyrosine-protein kinase Lck,cAMP-dependent protein kinase catalytic subunit alpha and other target protein genes,Kyoto Encyclopedia of Genes and Genomes pathway analysis obtained 60 possible pathways related to its treatment of non-small cell lung cancer,mainly involving progesterone-mediated oocyte maturation,prostate cancer,proteoglycans in cancer,FoxO signaling pathway,pathways in cancer,Ras signaling pathway,PI3K-Akt signaling pathway,etc.Conclusion:Anlotinib has the characteristics of multi-targets and multi-pathways in the treatment of non-small cell lung cancer,which provides a scientific basis for the follow-up study on the optimization of its efficacy in the treatment of non-small cell lung cancer and the revelation of the pharmacological effects of anlotinib.展开更多
Cancer is a potentially life-threatening disease characterized by the immortalization of tumor cells in the host. Immunotherapy has recently gained increasing interest among researchers due to its tremendous potential...Cancer is a potentially life-threatening disease characterized by the immortalization of tumor cells in the host. Immunotherapy has recently gained increasing interest among researchers due to its tremendous potential for preventing tumor progression and metastasis. Regulatory T cells (Tregs) are a subgroup of suppressive CD4^+ T cells that play a vital role in the maintenance of host immune homeostasis. Treg deficiency can induce severe autoimmune, hypersensitivity, and auto-inflammatory disorders, among other diseases. Tregs are commonly enriched in a tumor microenvironment, and a greater number of immune-suppressive Tregs often indicates a poorer prognosis;therefore, there is renewed interest in the function of Tregs and in their clinical application in antitumor immunotherapy. Accumulating strategies that focus on the depletion of Tregs have appeared to be effective in antitumor immunity. It is expected that Treg-targeting strategies will provide great opportunities for improving antitumor efficiency in combination with other therapeutics (e.g., chimeric antigen receptor T cell (CAR-T)-based cell therapy or immune checkpoint blockading).展开更多
The pine wood nematode(PWN),Bursaphelenchus xylophilus(Steiner & Buhrer) Nickle,is the pathogen of pine wilt disease(PWD) which can devastate forests.PWN can be of hi gh or low severity and the mechanisms underlyi...The pine wood nematode(PWN),Bursaphelenchus xylophilus(Steiner & Buhrer) Nickle,is the pathogen of pine wilt disease(PWD) which can devastate forests.PWN can be of hi gh or low severity and the mechanisms underlying the differences in virulence are unclear.Therefore,it is necessary to study the relationship between differentiation of PWN severity and its resistance to the main defensive substances of pine species(i.e.,α-pinene and H_(2)O_(2)).The feeding rate and fecundity of PWN was examined at different levels of virulence under conditions of a-pinene and H_(2)O_(2) stress.Moreover,the expression patterns of the main resistance genes of PWN with different virulence were determined under conditions of α-pinene and H_(2)O_(2) stress.The feeding rate and fecundity of the high virulence strain AMA3 were higher than those of the low virulence strain YW4.The expression levels of the autophagy gene BxATG5,cytochrome P450 gene BxCYP33 D3,and glutathione S-transferase genes BxGST1 and BxGST3 in AMA3 increased significantly upon exposure to α-pinene for 2 h,while these genes showed smaller degrees of upregulation in YW4.Under conditions of H_(2)O_(2) stress,the expression levels of BxATG5,catalase genes Bxy-ctl-1 and Bxy-ctl-2,and the 2-cysteine peroxiredoxin gene BxPrx in AMA3 were higher than those in YW4.These findings suggest that high virulence PWN has greater resistance to pine defensive substances α-pinene and H_(2)O_(2) than low virulence PWN,and resistance genes mediate the differential resistance of PWN strains.This study will contribute to the clarification of the mechanism underlying virulence differentiation of PWN and will advance understanding of the pathogenic mechanism of PWD.展开更多
BACKGROUND Esophageal squamous cell carcinoma(ESCC),the predominant type of esophageal cancer,has a 5-year survival rate less than 20%.Although the cause of poor prognosis is the high incidence and mortality of ESCC,t...BACKGROUND Esophageal squamous cell carcinoma(ESCC),the predominant type of esophageal cancer,has a 5-year survival rate less than 20%.Although the cause of poor prognosis is the high incidence and mortality of ESCC,the high rate of metastasis after esophageal cancer surgery is the main cause of death after the surgery.Bromodomain-containing protein 4(BRD4),an epigenetic reader of chromatinacetylated histones in tumorigenesis and development,plays an essential role in regulating oncogene expression.BRD4 inhibition and BRD4 inhibition-based treatment can potentially suppress ESCC growth.However,the effects and mechanisms of action of BRD4 on ESCC cell migration remain unclear.AIM To explore the effect of BRD4 on cell migration of ESCC in vitro and its possible molecular mechanism.METHODS Human ESCC cell lines KYSE-450 and KYSE-150 were used.The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay was performed to examine cell proliferation,and the transwell migration assay was conducted to test ESCC cell migration.JQ1,a BRD4 inhibitor,was applied to cells,and BRD4 siRNA was transfected into ESCC cells to knockdown endogenous BRD4.GFP-RFP-LC3 adenovirus was infected into ESCC cells to evaluate the effect of JQ1 on autophagy.Western blotting was performed to determine the protein levels of BRD4,E-cadherin,vimentin,AMP-activated protein kinase(AMPK),and p-AMPK.RESULTS BRD4 was either downregulated by small interfering RNA or pretreated with JQ1 in ESCC cells,leading to increased tumor migration in ESCC cells in a dose-and time-dependent manner.Inhibition of BRD4 not only significantly suppressed cell proliferation but also strongly increased cell migration by inducing epithelial-mesenchymal transition(EMT).The protein expression of vimentin was increased and E-cadherin decreased in a dose-dependent manner,subsequently promoting autophagy in KYSE-450 and KYSE-150 cells.Pretreatment with JQ1,a BRD4 inhibitor,inhibited BRD4-induced LC3-II activation and upregulated AMPK phosphorylation in a dosedependent manner.Additionally,an increased number of autophagosomes and autolysosomes were observed in JQ1-treated ESCC cells.The autophagy inhibitor 3-methyladenine(3-MA)reversed the effects of BRD4 knockdown on ESCC cell migration and blocked JQ1-induced cell migration.3-MA also downregulated the expression of vimentin and upregulation E-cadherin.CONCLUSION BRD4 inhibition enhances cell migration by inducing EMT and autophagy in ESCC cells via the AMPK-modified pathway.Thus,the facilitating role on ESCC cell migration should be considered for BRD4 inhibitor clinical application to ESCC patients.展开更多
Thermally conductive polymer nanocomposites integrated with lightweight,excellent flexural strength,and high fracture toughness(KIc)would be of great use in many fields.However,achieving all of these properties simult...Thermally conductive polymer nanocomposites integrated with lightweight,excellent flexural strength,and high fracture toughness(KIc)would be of great use in many fields.However,achieving all of these properties simultaneously remains a great challenge.Inspired by natural nacre,here we demonstrate a lightweight,strong,tough,and thermally conductive boron nitride nanosheet/epoxy layered(BNNEL)nanocomposite.Because of the layered structure and enhancing the interfacial interactions through hydrogen bonding and Si–O–B covalent bonding,the resulting nacre-inspired BNNEL nanocomposites show high fracture toughness of~4.22 MPa·m^(1/2),which is 7 folds as high as pure epoxy.Moreover,the BNNEL nanocomposites demonstrate sufficient flexural strength(~168.90 MPa,comparable to epoxy resin),while also being lightweight(~1.23 g/cm^(3)).Additionally,the BNNEL nanocomposites display a thermal conductivity(κ)of~0.47 W/(m·K)at low boron nitride nanosheet loading of 2.08 vol.%,which is 2.7 times higher than that of pure epoxy resin.The developed nacre-inspired strategy of layered structure design and interfacial enhancement provides an avenue for fabricating high mechanical properties and thermally conductive polymer nanocomposites.展开更多
With the rapid development of urban power grids and the large-scale integration of renewable energy, traditional power grid fault diagnosis techniques struggle to address the complexities of diagnosing faults in intri...With the rapid development of urban power grids and the large-scale integration of renewable energy, traditional power grid fault diagnosis techniques struggle to address the complexities of diagnosing faults in intricate power grid systems. Although artificial intelligence technologies offer new solutions for power grid fault diagnosis, the difficulty in acquiring labeled grid data limits the development of AI technologies in this area. In response to these challenges, this study proposes a semi-supervised learning framework with self-supervised and adaptive threshold (SAT-SSL) for fault detection and classification in power grids. Compared to other methods, our method reduces the dependence on labeling data while maintaining high recognition accuracy. First, we utilize frequency domain analysis on power grid data to filter abnormal events, then classify and label these events based on visual features, to creating a power grid dataset. Subsequently, we employ the Yule–Walker algorithm extract features from the power grid data. Then we construct a semi-supervised learning framework, incorporating self-supervised loss and dynamic threshold to enhance information extraction capabilities and adaptability across different scenarios of the model. Finally, the power grid dataset along with two benchmark datasets are used to validate the model’s functionality. The results indicate that our model achieves a low error rate across various scenarios and different amounts of labels. In power grid dataset, When retaining just 5% of the labels, the error rate is only 6.15%, which proves that this method can achieve accurate grid fault detection and classification with a limited amount of labeled data.展开更多
Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum...Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.展开更多
Due to the superiority of machine learning(ML)data processing,it is widely used in research of solid waste(SW).This study analyzed the research and developmental progress of the applications of ML in the life cycle of...Due to the superiority of machine learning(ML)data processing,it is widely used in research of solid waste(SW).This study analyzed the research and developmental progress of the applications of ML in the life cycle of SW.Statistical analyses were undertaken on the literature published between 1985 and 2021 in the Science Citation Index Expanded and Social Sciences Citation Index to provide an overview of the progress.Based on the articles considered,a rapid upward trend from 1985 to 2021 was found and international cooperatives were found to have strengthened.The three topics of ML,namely,SW categories,ML algorithms,and specific applications,as applied to the life cycle of SW were discussed.ML has been applied during the entire SW process,thereby affecting its life cycle.ML was used to predict the generation and characteristics of SW,optimize its collection and transportation,and model the processing of its energy utilization.Finally,the current challenges of applying ML to SW and future perspectives were discussed.The goal is to achieve high economic and environmental benefits and carbon reduction during the life cycle of SW.ML plays an important role in the modernization and intellectualization of SW management.It is hoped that this work would be helpful to provide a constructive overview towards the state-of-the-art development of SW disposal.展开更多
Owing to potential regulation capacities from flexible resources in energy coupling,storage,and consumption links,central energy stations(CESs)can provide additional support to power distribution network(PDN)in case o...Owing to potential regulation capacities from flexible resources in energy coupling,storage,and consumption links,central energy stations(CESs)can provide additional support to power distribution network(PDN)in case of power disruption.However,existing research has not explicitly revealed the emergency response of PDN with leveraging multiple CESs.This paper proposes a decentralized self-healing strategy of PDN to minimize the entire load loss,in which multi-area CESs’potentials including thermal storage and building thermal inertia,as well as the flexible topology of PDN,are reasonably exploited for service recovery.For sake of privacy preservation,the co-optimization of PDN and CESs is realized in a decentralized manner using adaptive alternating direction method of multipliers(ADMM).Furtherly,bilateral risk management with conditional value-at-risk(CVaR)for PDN and risk constraints for CESs is integrated to deal with uncertainties from outage duration.Case studies are conducted on a modified IEEE 33-bus PDN with multiple CESs.Numerical results illustrate that the proposed strategy can fully utilize the potentials of multi-area CESs for coordinated load restoration.The effectiveness of the performance and behaviors’adaptation against random risks is also validated.展开更多
Background Observational studies have indicated a potential link between gut microbiota and sarcopenia.However,the underlying mechanisms and a causal relationship have not been established.Thus,the objective of this s...Background Observational studies have indicated a potential link between gut microbiota and sarcopenia.However,the underlying mechanisms and a causal relationship have not been established.Thus,the objective of this study is to examine the possible causal association between gut microbiota and sarcopenia-related traits,including low hand-grip strength and appendicular lean mass(ALM),to shed light on the gut–muscle axis.Methods To investigate the potential impact of gut microbiota on low hand-grip strength and ALM,we utilized a two-sample Mendelian randomization(MR)approach.Summary statistics were obtained from genome-wide association studies of gut microbiota,low hand-grip strength,and ALM.The primary MR analysis employed the random-effects inverse-variance weighted(IVW)method.To assess the robustness,we conducted sensitivity analyses using the MR pleiotropy residual sum and outlier(MR-PRESSO)test to detect and correct for horizontal pleiotropy,as well as the MR-Egger intercept test and leave-one-out analysis.Results Alcaligenaceae,Family XIII,and Paraprevotella were positively associated with the risk of low hand-grip strength(P-values<0.05).Streptococcaceae were negatively associated with low hand-grip strength(P-values<0.05).Eight bacterial taxa(Actinomycetales,Actinomycetaceae,Bacteroidaceae,Porphyromonadaceae,Prevotellaceae,Bacteroides,Marvinbryantia,and Phascolarctobacterium)were associated with a higher risk of ALM(P-values<0.05).Eubacterium fissicatena group was negatively associated with ALM(P-values<0.05).Conclusion We found several gut microbiota components causally associated with sarcopenia-related traits.Our findings provided insights into novel strategies for the prevention and treatment of sarcopenia through the regulation of the gut microbiota,contributing to a better understanding of the gut–muscle axis.展开更多
基金Liuzhou City's Top Ten Hundred Talents Project,Liuzhou Science and Technology Project(Grant Nos.2021CBC0126 and 2021CBC0123)Guangxi Zhuang Autonomous Region Health and Family Planning Commission Projects(Z20210561,Z20210903)+1 种基金liuzhou Scienceand Technology Plan Projects(2021CBC0121,2021CBC0128).
文摘Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be elucidated.Single cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public databases.HOC single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene annotation.Pseudo temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell dusters.Cellular communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME cell.related subtypes and diferent glycogen subtype cell clusters.SCENIC analysis of transcription factors upstream of TME cell clusters with different glycogen metabolism.In addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 types.Bulk seq analysis showed the prognostic signifcance of glycogen metabolism.mediated TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.
基金supported by the National Natural Science Foundation of China(32172624,32172612,31672196)the Programs for National Key R&D Plan(2019YFD1001002).
文摘The Asiatic hybrid lily(Lilium spp.)is a horticultural crop with high commercial value and diverse anthocyanin pigmentation patterns.However,the regulatory mechanism underlying lily flower color has been largely unexplored.Here,we identified a WRKY transcription factor from lily tepals,LhWRKY44,whose expression was closely associated with anthocyanin accumulation.Functional verification indicated that LhWRKY44 positively regulated anthocyanin accumulation.LhWRKY44 physically interacted with LhMYBSPLATTER and directly bound to the LhMYBSPLATTER promoter,which enhanced the effect of the LhMYBSPLATTER-LhbHLH2 MBW complex activator on anthocyanin accumulation.Moreover,EMSA and dual-luciferase assays revealed that LhWRKY44 activated and bound to the promoters of gene LhF3H and the intracellular anthocyanin-related glutathione S-transferase gene LhGST.Interestingly,our further results showed that LhWRKY44 participated in light and drought-induced anthocyanin accumulation,and improved the drought tolerance in lily via activating stress-related genes.These results generated a multifaceted regulatory mechanism for the LhWRKY44-meditaed enhancement by the environmental signal pathway of anthocyanin accumulation and expanded our understanding of the WRKY-mediated transcriptional regulatory hierarchy modulating anthocyanin accumulation in Asiatic hybrid lilies.
基金This research was supported by Innovation and Entrepreneurship Training Plan for College Students in Jiangsu Province(202112688022Y)Suzhou Science and Technology Bureau Minsheng Science and Technology Medical and Health Application Basic Research Project(SYSD2019082).
文摘Objective:Based on the analysis of a biochemical information database,the“target-pathway”network of anlotinib in the treatment of non-small cell lung cancer was constructed by using network pharmacological methods to explore the mechanism of multi-target and multi-pathway treatment of non-small cell lung cancer.Methods:The 3D molecular structure formula of anlotinib was obtained by searching the PubChem database,and the target of anlotinib was predicted by using the PharmMapper database;obtain non-small cell lung cancer related targets through the GeneCards database,screen common genes related to drug targets and diseases by Venny 2.1.0,and build the relationship between drugs and diseases.Through the STRING11.5 database,the interaction relationship between action targets was built,the protein-protein interaction network was constructed,and the target degree was analyzed by Cytocsape 3.7.2 software to screen molecular docking objects.The DAVID database was used for Gene Ontology gene enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis to predict its mechanism,and the AutoDock software was used for molecular docking of the main targets.Results:The analysis results showed that there were 76 possible targets involved in the treatment of non-small cell lung cancer with anlotinib,mainly acting on epidermal growth factor receptor,mitogen-activated protein kinase 14,tyrosine-protein phosphatase non-receptor type 11,heat shock protein HSP 90-alpha,tyrosine-protein kinase Lck,cAMP-dependent protein kinase catalytic subunit alpha and other target protein genes,Kyoto Encyclopedia of Genes and Genomes pathway analysis obtained 60 possible pathways related to its treatment of non-small cell lung cancer,mainly involving progesterone-mediated oocyte maturation,prostate cancer,proteoglycans in cancer,FoxO signaling pathway,pathways in cancer,Ras signaling pathway,PI3K-Akt signaling pathway,etc.Conclusion:Anlotinib has the characteristics of multi-targets and multi-pathways in the treatment of non-small cell lung cancer,which provides a scientific basis for the follow-up study on the optimization of its efficacy in the treatment of non-small cell lung cancer and the revelation of the pharmacological effects of anlotinib.
文摘Cancer is a potentially life-threatening disease characterized by the immortalization of tumor cells in the host. Immunotherapy has recently gained increasing interest among researchers due to its tremendous potential for preventing tumor progression and metastasis. Regulatory T cells (Tregs) are a subgroup of suppressive CD4^+ T cells that play a vital role in the maintenance of host immune homeostasis. Treg deficiency can induce severe autoimmune, hypersensitivity, and auto-inflammatory disorders, among other diseases. Tregs are commonly enriched in a tumor microenvironment, and a greater number of immune-suppressive Tregs often indicates a poorer prognosis;therefore, there is renewed interest in the function of Tregs and in their clinical application in antitumor immunotherapy. Accumulating strategies that focus on the depletion of Tregs have appeared to be effective in antitumor immunity. It is expected that Treg-targeting strategies will provide great opportunities for improving antitumor efficiency in combination with other therapeutics (e.g., chimeric antigen receptor T cell (CAR-T)-based cell therapy or immune checkpoint blockading).
基金funded partly by the National Key Research and Development Program of China(No.2018YFD0600203)the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)+1 种基金Innovation and Entrepreneurship Training Program for Students of Jiangsu Higher Education Institutions (SPITP)Innovation and Entrepreneurship Training Program for Students of Nanjing Forestry University (No.201710298047Z)。
文摘The pine wood nematode(PWN),Bursaphelenchus xylophilus(Steiner & Buhrer) Nickle,is the pathogen of pine wilt disease(PWD) which can devastate forests.PWN can be of hi gh or low severity and the mechanisms underlying the differences in virulence are unclear.Therefore,it is necessary to study the relationship between differentiation of PWN severity and its resistance to the main defensive substances of pine species(i.e.,α-pinene and H_(2)O_(2)).The feeding rate and fecundity of PWN was examined at different levels of virulence under conditions of a-pinene and H_(2)O_(2) stress.Moreover,the expression patterns of the main resistance genes of PWN with different virulence were determined under conditions of α-pinene and H_(2)O_(2) stress.The feeding rate and fecundity of the high virulence strain AMA3 were higher than those of the low virulence strain YW4.The expression levels of the autophagy gene BxATG5,cytochrome P450 gene BxCYP33 D3,and glutathione S-transferase genes BxGST1 and BxGST3 in AMA3 increased significantly upon exposure to α-pinene for 2 h,while these genes showed smaller degrees of upregulation in YW4.Under conditions of H_(2)O_(2) stress,the expression levels of BxATG5,catalase genes Bxy-ctl-1 and Bxy-ctl-2,and the 2-cysteine peroxiredoxin gene BxPrx in AMA3 were higher than those in YW4.These findings suggest that high virulence PWN has greater resistance to pine defensive substances α-pinene and H_(2)O_(2) than low virulence PWN,and resistance genes mediate the differential resistance of PWN strains.This study will contribute to the clarification of the mechanism underlying virulence differentiation of PWN and will advance understanding of the pathogenic mechanism of PWD.
基金the Key Project of Science and Technology of Xinxiang,No.GG2020027the Health Commission of Henan Province of China,No.SBGJ202102188.
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC),the predominant type of esophageal cancer,has a 5-year survival rate less than 20%.Although the cause of poor prognosis is the high incidence and mortality of ESCC,the high rate of metastasis after esophageal cancer surgery is the main cause of death after the surgery.Bromodomain-containing protein 4(BRD4),an epigenetic reader of chromatinacetylated histones in tumorigenesis and development,plays an essential role in regulating oncogene expression.BRD4 inhibition and BRD4 inhibition-based treatment can potentially suppress ESCC growth.However,the effects and mechanisms of action of BRD4 on ESCC cell migration remain unclear.AIM To explore the effect of BRD4 on cell migration of ESCC in vitro and its possible molecular mechanism.METHODS Human ESCC cell lines KYSE-450 and KYSE-150 were used.The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay was performed to examine cell proliferation,and the transwell migration assay was conducted to test ESCC cell migration.JQ1,a BRD4 inhibitor,was applied to cells,and BRD4 siRNA was transfected into ESCC cells to knockdown endogenous BRD4.GFP-RFP-LC3 adenovirus was infected into ESCC cells to evaluate the effect of JQ1 on autophagy.Western blotting was performed to determine the protein levels of BRD4,E-cadherin,vimentin,AMP-activated protein kinase(AMPK),and p-AMPK.RESULTS BRD4 was either downregulated by small interfering RNA or pretreated with JQ1 in ESCC cells,leading to increased tumor migration in ESCC cells in a dose-and time-dependent manner.Inhibition of BRD4 not only significantly suppressed cell proliferation but also strongly increased cell migration by inducing epithelial-mesenchymal transition(EMT).The protein expression of vimentin was increased and E-cadherin decreased in a dose-dependent manner,subsequently promoting autophagy in KYSE-450 and KYSE-150 cells.Pretreatment with JQ1,a BRD4 inhibitor,inhibited BRD4-induced LC3-II activation and upregulated AMPK phosphorylation in a dosedependent manner.Additionally,an increased number of autophagosomes and autolysosomes were observed in JQ1-treated ESCC cells.The autophagy inhibitor 3-methyladenine(3-MA)reversed the effects of BRD4 knockdown on ESCC cell migration and blocked JQ1-induced cell migration.3-MA also downregulated the expression of vimentin and upregulation E-cadherin.CONCLUSION BRD4 inhibition enhances cell migration by inducing EMT and autophagy in ESCC cells via the AMPK-modified pathway.Thus,the facilitating role on ESCC cell migration should be considered for BRD4 inhibitor clinical application to ESCC patients.
基金supported by the National Key Research and Development Program of China(No.2021YFA0715700)the National Science Fund for Distinguished Young Scholars(No.52125302),National Natural Science Foundation of China(No.22075009)111 Project(No.B14009).
文摘Thermally conductive polymer nanocomposites integrated with lightweight,excellent flexural strength,and high fracture toughness(KIc)would be of great use in many fields.However,achieving all of these properties simultaneously remains a great challenge.Inspired by natural nacre,here we demonstrate a lightweight,strong,tough,and thermally conductive boron nitride nanosheet/epoxy layered(BNNEL)nanocomposite.Because of the layered structure and enhancing the interfacial interactions through hydrogen bonding and Si–O–B covalent bonding,the resulting nacre-inspired BNNEL nanocomposites show high fracture toughness of~4.22 MPa·m^(1/2),which is 7 folds as high as pure epoxy.Moreover,the BNNEL nanocomposites demonstrate sufficient flexural strength(~168.90 MPa,comparable to epoxy resin),while also being lightweight(~1.23 g/cm^(3)).Additionally,the BNNEL nanocomposites display a thermal conductivity(κ)of~0.47 W/(m·K)at low boron nitride nanosheet loading of 2.08 vol.%,which is 2.7 times higher than that of pure epoxy resin.The developed nacre-inspired strategy of layered structure design and interfacial enhancement provides an avenue for fabricating high mechanical properties and thermally conductive polymer nanocomposites.
基金supported by the National Natural Science Foundation China under Grants number 62073232,and the Science and Technology Project of Shenzhen,China(KCXST20221021111402006,JSGG20220831105800002)and the“Nanling Team Project”of Shaoguan city,and the Science and Technology project of Tianjin,China(22YFYSHZ00330)+1 种基金and Shenzhen Excellent Innovative Talents RCYX20221008093036022,Shenzhen-HongKong joint funding project(A)(SGDX20230116092053005)the Shenzhen Undertaking the National Major Science and Technology Program,China(CJGJZD20220517141405012).
文摘With the rapid development of urban power grids and the large-scale integration of renewable energy, traditional power grid fault diagnosis techniques struggle to address the complexities of diagnosing faults in intricate power grid systems. Although artificial intelligence technologies offer new solutions for power grid fault diagnosis, the difficulty in acquiring labeled grid data limits the development of AI technologies in this area. In response to these challenges, this study proposes a semi-supervised learning framework with self-supervised and adaptive threshold (SAT-SSL) for fault detection and classification in power grids. Compared to other methods, our method reduces the dependence on labeling data while maintaining high recognition accuracy. First, we utilize frequency domain analysis on power grid data to filter abnormal events, then classify and label these events based on visual features, to creating a power grid dataset. Subsequently, we employ the Yule–Walker algorithm extract features from the power grid data. Then we construct a semi-supervised learning framework, incorporating self-supervised loss and dynamic threshold to enhance information extraction capabilities and adaptability across different scenarios of the model. Finally, the power grid dataset along with two benchmark datasets are used to validate the model’s functionality. The results indicate that our model achieves a low error rate across various scenarios and different amounts of labels. In power grid dataset, When retaining just 5% of the labels, the error rate is only 6.15%, which proves that this method can achieve accurate grid fault detection and classification with a limited amount of labeled data.
基金supported by the National Natural Science Foundation of China(31730036,31871380,31871382,31930055,31930058,32000500,32022034,32030033,32070730,32130046,3217050247,32150005,32200595,32222024,81730019,81730022,81830014,81921006,81925005,81970426,81971301,81971312,82030041,82061160495,82070805,82071595,82090020,82100841,82120108009,82122024,82125002,82125011,82125012,82130045,82171284,82173061,82173398,82225007,82225015,82225017,82225018,82230047,82230088,82271600,91949106,91949201,92049116,92049302,92049304,92149303,92149306,92157202,92168201,92169102,92249301,92268201)the National Key Research and Development Program of China(2018YFA0800700,2018YFC2000100,2018YFC2000102,2018YFC2002003,2019YFA0110900,2019YFA0801703,2019YFA0801903,2019YFA0802202,2019YFA0904800,2020YFA0113400,2020YFA0803401,2020YFA0804000,2020YFC2002900,2020YFC2008000,2020YFE0202200,2021YFA0804900,2021YFA1100103,2021YFA1100900,2021YFE0114200,2021ZD0202400,2022YFA0806001,2022YFA0806002,2022YFA0806600,2022YFA1103200,2022YFA1103601,2022YFA1103701,2022YFA1103800,2022YFA1103801,2022YFA1104100,2022YFA1104904,2022YFA1303000,2022YFC2009900,2022YFC2502401,2022YFC3602400,2022YFE0118000,2022ZD0213200)+14 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030302,XDB39000000,XDB39030600)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2020085,2021080)CAS Project for Young Scientists in Basic Research(YSBR-076)the Program of the Beijing Natural Science Foundation(JQ20031)Clinical Research Operating Fund of Central High level hospitals(2022-PUMCHE-001)CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-I2M1-004)Talent Program of the Chinese Academy of Medical Science(2022RC310-10)Research Funds from Health@Inno HK Program launched by Innovation Technology Commission of the Hong Kong Special Administrative Region,Guangdong Basic and Applied Basic Research Foundation(2020B1515020044)Guangzhou Planned Project of Science and Technology(202002020039)the Major Technology Innovation of Hubei Province(2019ACA141)the Science and Technology Major Project of Hunan Provincial Science and Technology Department(2021SK1010)Shanghai Municipal Science and Technology Major Project(2017SHZDZX01)the Natural Science Foundation of Sichuan Province(2023NSFSC0003)Yunnan Fundamental Research Project(202201AS070080)the State Key Laboratory of Membrane Biology。
文摘Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.
基金This research was supported by the National Natural Science Foundation of China(No.52100157).
文摘Due to the superiority of machine learning(ML)data processing,it is widely used in research of solid waste(SW).This study analyzed the research and developmental progress of the applications of ML in the life cycle of SW.Statistical analyses were undertaken on the literature published between 1985 and 2021 in the Science Citation Index Expanded and Social Sciences Citation Index to provide an overview of the progress.Based on the articles considered,a rapid upward trend from 1985 to 2021 was found and international cooperatives were found to have strengthened.The three topics of ML,namely,SW categories,ML algorithms,and specific applications,as applied to the life cycle of SW were discussed.ML has been applied during the entire SW process,thereby affecting its life cycle.ML was used to predict the generation and characteristics of SW,optimize its collection and transportation,and model the processing of its energy utilization.Finally,the current challenges of applying ML to SW and future perspectives were discussed.The goal is to achieve high economic and environmental benefits and carbon reduction during the life cycle of SW.ML plays an important role in the modernization and intellectualization of SW management.It is hoped that this work would be helpful to provide a constructive overview towards the state-of-the-art development of SW disposal.
基金financially supported by the Fundamental Research Funds for the Central Universities(No.2021QN1066)。
文摘Owing to potential regulation capacities from flexible resources in energy coupling,storage,and consumption links,central energy stations(CESs)can provide additional support to power distribution network(PDN)in case of power disruption.However,existing research has not explicitly revealed the emergency response of PDN with leveraging multiple CESs.This paper proposes a decentralized self-healing strategy of PDN to minimize the entire load loss,in which multi-area CESs’potentials including thermal storage and building thermal inertia,as well as the flexible topology of PDN,are reasonably exploited for service recovery.For sake of privacy preservation,the co-optimization of PDN and CESs is realized in a decentralized manner using adaptive alternating direction method of multipliers(ADMM).Furtherly,bilateral risk management with conditional value-at-risk(CVaR)for PDN and risk constraints for CESs is integrated to deal with uncertainties from outage duration.Case studies are conducted on a modified IEEE 33-bus PDN with multiple CESs.Numerical results illustrate that the proposed strategy can fully utilize the potentials of multi-area CESs for coordinated load restoration.The effectiveness of the performance and behaviors’adaptation against random risks is also validated.
基金supported by grants from Chinese National Science&Technology Pillar Program(Grant No.2020YFC2005600)Sichuan Science and Technology Program(Grant No.2021YFS0136)+2 种基金1·3·5 project for disciplines of excellence-Clinical Research Incubation Project,West China Hospital,Sichuan University(Grant No.19HXFH012)National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University(Grant No.Z20191003)1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(Grant No.ZYJC21005).
文摘Background Observational studies have indicated a potential link between gut microbiota and sarcopenia.However,the underlying mechanisms and a causal relationship have not been established.Thus,the objective of this study is to examine the possible causal association between gut microbiota and sarcopenia-related traits,including low hand-grip strength and appendicular lean mass(ALM),to shed light on the gut–muscle axis.Methods To investigate the potential impact of gut microbiota on low hand-grip strength and ALM,we utilized a two-sample Mendelian randomization(MR)approach.Summary statistics were obtained from genome-wide association studies of gut microbiota,low hand-grip strength,and ALM.The primary MR analysis employed the random-effects inverse-variance weighted(IVW)method.To assess the robustness,we conducted sensitivity analyses using the MR pleiotropy residual sum and outlier(MR-PRESSO)test to detect and correct for horizontal pleiotropy,as well as the MR-Egger intercept test and leave-one-out analysis.Results Alcaligenaceae,Family XIII,and Paraprevotella were positively associated with the risk of low hand-grip strength(P-values<0.05).Streptococcaceae were negatively associated with low hand-grip strength(P-values<0.05).Eight bacterial taxa(Actinomycetales,Actinomycetaceae,Bacteroidaceae,Porphyromonadaceae,Prevotellaceae,Bacteroides,Marvinbryantia,and Phascolarctobacterium)were associated with a higher risk of ALM(P-values<0.05).Eubacterium fissicatena group was negatively associated with ALM(P-values<0.05).Conclusion We found several gut microbiota components causally associated with sarcopenia-related traits.Our findings provided insights into novel strategies for the prevention and treatment of sarcopenia through the regulation of the gut microbiota,contributing to a better understanding of the gut–muscle axis.
