Let Km,n be a completebipartite graph with two partite sets having m and n vertices,respectively. A Kp,q-factorization of Km,n is a set ofedge-disjoint Kp,q-factors of Km,n which partition theset of edges of Km,n. Whe...Let Km,n be a completebipartite graph with two partite sets having m and n vertices,respectively. A Kp,q-factorization of Km,n is a set ofedge-disjoint Kp,q-factors of Km,n which partition theset of edges of Km,n. When p=1 and q is a prime number,Wang, in his paper 'On K1,k-factorizations of a completebipartite graph' (Discrete Math, 1994, 126: 359-364),investigated the K1,q-factorization of Km,n and gave asufficient condition for such a factorization to exist. In the paper'K1,k-factorizations of complete bipartite graphs' (DiscreteMath, 2002, 259: 301-306), Du and Wang extended Wang's resultto the case that q is any positive integer. In this paper, we give a sufficient condition for Km,n to have aKp,q-factorization. As a special case, it is shown that theMartin's BAC conjecture is true when p:q=k:(k+1) for any positiveinteger k.展开更多
Circular RNA(circRNA)is a novel non-coding endogenous RNAs.Evidence has shown that circRNAs are related to many biological processes and play essential roles in different biological functions.Although increasing numbe...Circular RNA(circRNA)is a novel non-coding endogenous RNAs.Evidence has shown that circRNAs are related to many biological processes and play essential roles in different biological functions.Although increasing numbers of circRNAs are discovered using high-throughput sequencing technologies,these techniques are still time-consuming and costly.In this study,we propose a computational method to predict circRNA-disesae associations which is based on metapath2 vec++and matrix factorization with integrated multiple data(called PCD MVMF).To construct more reliable networks,various aspects are considered.Firstly,circRNA annotation,sequence,and functional similarity networks are established,and disease-related genes and semantics are adopted to construct disease functional and semantic similarity networks.Secondly,metapath2 vec++is applied on an integrated heterogeneous network to learn the embedded features and initial prediction score.Finally,we use matrix factorization,take similarity as a constraint,and optimize it to obtain the final prediction results.Leave-one-out cross-validation,five-fold cross-validation,and f-measure are adopted to evaluate the performance of PCD MVMF.These evaluation metrics verify that PCD MVMF has better prediction performance than other methods.To further illustrate the performance of PCD MVMF,case studies of common diseases are conducted.Therefore,PCD MVMF can be regarded as a reliable and useful circRNA-disease association prediction tool.展开更多
Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is cha...Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.展开更多
目的:探究血清CC趋化因子配体2(CCL2)、血管内皮生长因子(VEGFA)与非酒精性脂肪性肝病(NAFLD)患者肝纤维化和代谢综合征(MS)的关系。方法:选取2022年1月至2024年1月在本院就诊的NAFLD患者116例(NAFLD组)作为研究对象,根据患者否并发MS分...目的:探究血清CC趋化因子配体2(CCL2)、血管内皮生长因子(VEGFA)与非酒精性脂肪性肝病(NAFLD)患者肝纤维化和代谢综合征(MS)的关系。方法:选取2022年1月至2024年1月在本院就诊的NAFLD患者116例(NAFLD组)作为研究对象,根据患者否并发MS分为MS组(42例)和非MS组(74例),另取同期体检健康者66例作为对照组。收集所有受试者的临床资料;采用ELISA法检测血清中CCL2和VEGFA表达量;Pearson法分析血清CCL2、VEGFA水平与肝纤维化及MS相关指标的相关性;Logistic多因素分析影响NAFLD患者并发MS的因素;受试者工作特征曲线分析血清CCL2和VEGFA水平对NAFLD患者并发MS的预测价值。结果:NAFLD患者血清CCL2、VEGFA水平以及肝纤维化指标层黏连蛋白(LN)、透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(ⅣC)均显著高于对照组(P<0.05)。MS组的收缩压、舒张压、空腹血糖(FPG)、餐后2 h血糖(2 h PG)、甘油三椡(TG)、CCL2、VEGFA水平显著高于非MS组,丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平显著低于非MS组(P<0.05)。血清中CCL2和VEGFA水平与LN、HA、PCⅢ、ⅣC、收缩压、舒张压、FPG、2 h PG、TG呈正相关,与ALT、AST呈负相关(P<0.05)。收缩压、舒张压、FPG、2 h PG、TG、CCL2、VEGFA是影响NAFLD患者并发MS的危险因素,ALT、AST是影响NAFLD患者并发MS的保护因素(P<0.05)。血清CCL2和VEGFA水平以及联合预测NAFLD患者并发MS情况的曲线下面积分别为0.842、0.884和0.938,联合预测优于各自单独预测(Z_(联合-CCL2)=2.959、Z_(联合-VEGFA)=2.731,P=0.003、0.006)。结论:NAFLD患者血清CCL2和VEGFA水平升高,且二者与NAFLD患者肝纤维化和MS密切相关,二者联合对NAFLD患者并发MS具有较高的预测价值。展开更多
BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese med...BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.展开更多
Diabetic retinopathy(DR),a common complication of diabetes,is characterized by retinal angiogenesis and inflammation.The role of hepatoma-derived growth factor(HDGF)in mediating inflammation during DR remains unclear....Diabetic retinopathy(DR),a common complication of diabetes,is characterized by retinal angiogenesis and inflammation.The role of hepatoma-derived growth factor(HDGF)in mediating inflammation during DR remains unclear.We measured HDGF levels in the aqueous humor and found that HDGF was increased in DR but decreased after anti-angiogenesis treatment.Using public single-cell RNA sequencing datasets,we found that elevated HDGF in DR was mainly produced by Müller cells and targeted microglia.Additionally,integrin beta 2(Itgb2),a target gene of HDGF that induces microglial activation,was significantly upregulated in DR.To verify these results,we performed enzyme-linked immunosorbent assays,quantitative reverse transcription-PCR,Western blotting,and fluorescence immunostaining in cultured Müller and microglial cells treated with HDGF or anti-HDGF,as well as in DR mice receiving intravitreal injections of HDGF or its antibody.Exogenous HDGF further promoted microglial activation,migration,and secretion of pro-inflammatory cytokines,while neutralization of HDGF suppressed these effects caused by high glucose.Furthermore,the HDGF receptor nucleolin was overexpressed in microglia under high glucose stimulation.Therefore,blocking HDGF from Müller cells in DR reduced the excessive inflammatory response in microglia,highlighting HDGF as a potential therapeutic target.展开更多
基金This work was supported by the National Natural Science Foundation of China(Grant No.10071056).
文摘Let Km,n be a completebipartite graph with two partite sets having m and n vertices,respectively. A Kp,q-factorization of Km,n is a set ofedge-disjoint Kp,q-factors of Km,n which partition theset of edges of Km,n. When p=1 and q is a prime number,Wang, in his paper 'On K1,k-factorizations of a completebipartite graph' (Discrete Math, 1994, 126: 359-364),investigated the K1,q-factorization of Km,n and gave asufficient condition for such a factorization to exist. In the paper'K1,k-factorizations of complete bipartite graphs' (DiscreteMath, 2002, 259: 301-306), Du and Wang extended Wang's resultto the case that q is any positive integer. In this paper, we give a sufficient condition for Km,n to have aKp,q-factorization. As a special case, it is shown that theMartin's BAC conjecture is true when p:q=k:(k+1) for any positiveinteger k.
基金supported by the National Natural Science Foundation of China(Nos.61972451,61672334,and 61902230)the Fundamental Research Funds for the Central Universities,Shaanxi Normal University(Nos.GK201901010 and 2018TS079)
文摘Circular RNA(circRNA)is a novel non-coding endogenous RNAs.Evidence has shown that circRNAs are related to many biological processes and play essential roles in different biological functions.Although increasing numbers of circRNAs are discovered using high-throughput sequencing technologies,these techniques are still time-consuming and costly.In this study,we propose a computational method to predict circRNA-disesae associations which is based on metapath2 vec++and matrix factorization with integrated multiple data(called PCD MVMF).To construct more reliable networks,various aspects are considered.Firstly,circRNA annotation,sequence,and functional similarity networks are established,and disease-related genes and semantics are adopted to construct disease functional and semantic similarity networks.Secondly,metapath2 vec++is applied on an integrated heterogeneous network to learn the embedded features and initial prediction score.Finally,we use matrix factorization,take similarity as a constraint,and optimize it to obtain the final prediction results.Leave-one-out cross-validation,five-fold cross-validation,and f-measure are adopted to evaluate the performance of PCD MVMF.These evaluation metrics verify that PCD MVMF has better prediction performance than other methods.To further illustrate the performance of PCD MVMF,case studies of common diseases are conducted.Therefore,PCD MVMF can be regarded as a reliable and useful circRNA-disease association prediction tool.
基金supported by grants from the Zhejiang Provincial TCM Science and Technology Plan Project,No.2023ZL156(to YH)Ningbo Top Medical and Health Research Program,No.2022020304(to XG)+1 种基金the Natural Science Foundation of Ningbo,No.2023J019(to YH)Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province,No.2022E10026(to YH)。
文摘Strokes include both ischemic stroke,which is mediated by a blockade or reduction in the blood supply to the brain,and hemorrhagic stroke,which comprises intracerebral hemorrhage and subarachnoid hemorrhage and is characterized by bleeding within the brain.Stroke is a lifethreatening cerebrovascular condition characterized by intricate pathophysiological mechanisms,including oxidative stress,inflammation,mitochondrial dysfunction,and neuronal injury.Critical transcription factors,such as nuclear factor erythroid 2-related factor 2 and nuclear factor kappa B,play central roles in the progression of stroke.Nuclear factor erythroid 2-related factor 2 is sensitive to changes in the cellular redox status and is crucial in protecting cells against oxidative damage,inflammatory responses,and cytotoxic agents.It plays a significant role in post-stroke neuroprotection and repair by influencing mitochondrial function,endoplasmic reticulum stress,and lysosomal activity and regulating metabolic pathways and cytokine expression.Conversely,nuclear factor-kappa B is closely associated with mitochondrial dysfunction,the generation of reactive oxygen species,oxidative stress exacerbation,and inflammation.Nuclear factor-kappa B contributes to neuronal injury,apoptosis,and immune responses following stroke by modulating cell adhesion molecules and inflammatory mediators.The interplay between these pathways,potentially involving crosstalk among various organelles,significantly influences stroke pathophysiology.Advancements in single-cell sequencing and spatial transcriptomics have greatly improved our understanding of stroke pathogenesis and offer new opportunities for the development of targeted,individualized,cell typespecific treatments.In this review,we discuss the mechanisms underlying the involvement of nuclear factor erythroid 2-related factor 2 and nuclear factor-kappa B in both ischemic and hemorrhagic stroke,with an emphasis on their roles in oxidative stress,inflammation,and neuroprotection.
文摘目的:探究血清CC趋化因子配体2(CCL2)、血管内皮生长因子(VEGFA)与非酒精性脂肪性肝病(NAFLD)患者肝纤维化和代谢综合征(MS)的关系。方法:选取2022年1月至2024年1月在本院就诊的NAFLD患者116例(NAFLD组)作为研究对象,根据患者否并发MS分为MS组(42例)和非MS组(74例),另取同期体检健康者66例作为对照组。收集所有受试者的临床资料;采用ELISA法检测血清中CCL2和VEGFA表达量;Pearson法分析血清CCL2、VEGFA水平与肝纤维化及MS相关指标的相关性;Logistic多因素分析影响NAFLD患者并发MS的因素;受试者工作特征曲线分析血清CCL2和VEGFA水平对NAFLD患者并发MS的预测价值。结果:NAFLD患者血清CCL2、VEGFA水平以及肝纤维化指标层黏连蛋白(LN)、透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(ⅣC)均显著高于对照组(P<0.05)。MS组的收缩压、舒张压、空腹血糖(FPG)、餐后2 h血糖(2 h PG)、甘油三椡(TG)、CCL2、VEGFA水平显著高于非MS组,丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)水平显著低于非MS组(P<0.05)。血清中CCL2和VEGFA水平与LN、HA、PCⅢ、ⅣC、收缩压、舒张压、FPG、2 h PG、TG呈正相关,与ALT、AST呈负相关(P<0.05)。收缩压、舒张压、FPG、2 h PG、TG、CCL2、VEGFA是影响NAFLD患者并发MS的危险因素,ALT、AST是影响NAFLD患者并发MS的保护因素(P<0.05)。血清CCL2和VEGFA水平以及联合预测NAFLD患者并发MS情况的曲线下面积分别为0.842、0.884和0.938,联合预测优于各自单独预测(Z_(联合-CCL2)=2.959、Z_(联合-VEGFA)=2.731,P=0.003、0.006)。结论:NAFLD患者血清CCL2和VEGFA水平升高,且二者与NAFLD患者肝纤维化和MS密切相关,二者联合对NAFLD患者并发MS具有较高的预测价值。
基金Supported by the Provincial Key Cultivation Laboratory for Digestive Disease Research,No.2021SYS13Shanxi Province’s“Si Ge Yi Pi”Science and Technology Driven Medical Innovation Project,No.2021MX03Shanxi Provincial Basic Research Program,No.202403021222423.
文摘BACKGROUND Ulcerative colitis(UC)is a chronic and treatment-resistant disorder requiring potent therapeutics that are effective and safe.Cedrol(CE)is a bioactive natural product present in many traditional Chinese medicines.It is known for its suppression of inflammation and mitigation of oxidative stress.Its therapeutic efficacy and mechanistic underpinnings in UC remain uncharacterized.AIM To investigate the therapeutic potential and mechanisms of CE in UC.METHODS The anti-inflammatory activity and intestinal barrier-repairing effects of CE were assessed in a dextran sulfate sodium-induced murine colitis model.Network pharmacology was employed to predict potential targets and pathways.Then molecular docking and dynamics simulations were utilized to confirm a stable interaction between CE and the toll-like receptor 4(TLR4)/myeloid differentiation factor 2(MD2)complex.The anti-inflammatory mechanisms were further verified using in vitro assays.Additionally,the gut microbiota composition was analyzed via 16S rRNA gene sequencing.RESULTS CE significantly alleviated colitis symptoms,mitigated histopathological damage,and suppressed inflammation.Moreover,CE restored intestinal barrier integrity by enhancing mucus secretion and upregulating tight junction proteins(zonula occludens 1,occludin,claudin-1).Mechanistically,CE stably bound to MD2,inhibiting lipopolysaccharide-induced TLR4 signaling in RAW264.7 cells.This led to suppression of the downstream mitogen-activated protein kinase and nuclear factor kappa B signaling pathways,downregulating the expression of tumor necrosis factor-alpha,interleukin-1β,and interleukin-6.Gut microbiota analysis revealed that CE reversed dextran sulfate sodium-induced dysbiosis with significant enrichment of butyrogenic Christensenella minuta.CONCLUSION CE acted on MD2 to suppress proinflammatory cascades,promoting mucosal barrier reconstitution and microbiota remodeling and supporting its therapeutic use in UC.
基金supported by National Natural Science Foundation of China(Grant No.81900873 to A.Q.)the Jiangsu Provincial Key Research and Development Programme-social development(Grant No.BE2023777 to W.Z.)+1 种基金the Key Medical Research Project of Jiangsu Commission of Health(Grant No.H2022185 to W.Z.)the Clinical Capacity Enhancement Project of Jiangsu Province Hospital(Grant No.JSPH-MB-2023-18 to W.Z.)。
文摘Diabetic retinopathy(DR),a common complication of diabetes,is characterized by retinal angiogenesis and inflammation.The role of hepatoma-derived growth factor(HDGF)in mediating inflammation during DR remains unclear.We measured HDGF levels in the aqueous humor and found that HDGF was increased in DR but decreased after anti-angiogenesis treatment.Using public single-cell RNA sequencing datasets,we found that elevated HDGF in DR was mainly produced by Müller cells and targeted microglia.Additionally,integrin beta 2(Itgb2),a target gene of HDGF that induces microglial activation,was significantly upregulated in DR.To verify these results,we performed enzyme-linked immunosorbent assays,quantitative reverse transcription-PCR,Western blotting,and fluorescence immunostaining in cultured Müller and microglial cells treated with HDGF or anti-HDGF,as well as in DR mice receiving intravitreal injections of HDGF or its antibody.Exogenous HDGF further promoted microglial activation,migration,and secretion of pro-inflammatory cytokines,while neutralization of HDGF suppressed these effects caused by high glucose.Furthermore,the HDGF receptor nucleolin was overexpressed in microglia under high glucose stimulation.Therefore,blocking HDGF from Müller cells in DR reduced the excessive inflammatory response in microglia,highlighting HDGF as a potential therapeutic target.
