Cardiac fibrosis is characterized by an elevated amount of extracellular matrix(ECM)within the heart.However,the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction...Cardiac fibrosis is characterized by an elevated amount of extracellular matrix(ECM)within the heart.However,the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction.Circular RNAs(circRNAs)are emerging as important regulators of cardiac fibrosis.Here,we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism.Functionally,circ-CELF1 was involved in enhancing fibrosis-related markers'expression and promoting the proliferation of cardiac fibroblasts(CFs),thereby exacerbating cardiac fibrosis.Mechanistically,circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3,leading to an elevation of BRPF3 protein levels.Additionally,BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene.Thus,the transcription of Celf1 was dramatically activated,thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis.Moreover,Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing,thereby establishing a feedback loop for circ-CELF1 production.Consequently,a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established,suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.展开更多
针对攻击代价相等时的有限资源网络毁伤问题,给出了网络毁伤最大化的定义。为了改进近似求解算法求解毁伤最大化问题时复杂度较高的缺陷,提出了基于拓扑势和CELF(cost-effective lazy-forward)的TPCELF(algorithm based on topology pot...针对攻击代价相等时的有限资源网络毁伤问题,给出了网络毁伤最大化的定义。为了改进近似求解算法求解毁伤最大化问题时复杂度较高的缺陷,提出了基于拓扑势和CELF(cost-effective lazy-forward)的TPCELF(algorithm based on topology potential and CELF)算法。利用无标度网络和实测网络进行实验,结果表明,TPCELF算法在计算速度上有较大的提升,网络平均毁伤效果接近于近似求解算法;且优于采用常见重要性度量指标排序算法得到的平均毁伤效果。所提方法可从网络毁伤的角度为复杂网络关键节点挖掘提供参考。展开更多
Streptococcus mutans is a well-known cause of dental caries,due to its acidogenicity,aciduricity,and ability to synthesize exopolysaccharides in dental plaques.Intriguingly,not all children who carry S.mutans manifest...Streptococcus mutans is a well-known cause of dental caries,due to its acidogenicity,aciduricity,and ability to synthesize exopolysaccharides in dental plaques.Intriguingly,not all children who carry S.mutans manifest caries,even with similar characteristics in oral hygiene,diet,and other environmental factors.This phenomenon suggests that host susceptibility potentially plays a role in the development of dental caries;however,the association between host genetics,S.mutans,and dental caries remains unclear.Therefore,this study examined the influence of host gene-by-S.mutans interaction on dental caries.Genome-wide association analyses were conducted in 709 US children (<13 years old),using the dbGap database acquired from the center for oral health research in appalachia (COHRA) and the Iowa Head Start programmes (GEIRS).A generalized estimating equation was used to examine the gene-by-S.mutans interaction effects on the outcomes (decayed and missing/filled primary teeth due to caries).Sequentially,the COHRA and GEIRS data were used to identify potential interactions and replicate the findings.Three loci at the genes interleukin 32 (IL32),galactokinase 2 (GALK2),and CUGBP,Elav-like family member 4 (CELF4) were linked to S.mutans carriage,and there was a severity of caries at a suggestive significance level among COHRA children (P < 9×10?5),and at a nominal significance level among GEIRS children (P = 0.047–0.001).The genetic risk score that combined the three loci also significantly interacted with S.mutans (P < 0.000 1).Functional analyses indicated that the identified genes are involved in the host immune response,galactose carbohydrate metabolism,and food-rewarding system,which could potentially be used to identify children at high risk for caries and to develop personalized caries prevention strategies.展开更多
There exist two or more competing products in viral marketing, and the companies can exploit the social interactions of users to propagate the awareness of products. In this paper, we focus on selecting seeds for maxi...There exist two or more competing products in viral marketing, and the companies can exploit the social interactions of users to propagate the awareness of products. In this paper, we focus on selecting seeds for maximizing the competitive influence spread in social networks. First, we establish the possible graphs based on the propagation probability of edges, and then we use the competitive influence spread model (CISM) to model the competitive spread under the possible graph. Further, we consider the objective function of selecting k seeds of one product under the CISM when the seeds of another product have been known, which is monotone and submodular, and thus we use the CELF (cost-effective lazy forward) algorithm to accelerate the greedy algorithm that can approximate the optimal with 1 ? 1/e. Experimental results verify the feasibility and effectiveness of our method.展开更多
基金supported by research grants from the Noncommunicable Chronic Diseases-National Science and Technology Major Project(Nos.2024ZD0521500 and 2024ZD0521501,China)the National Natural Science Foundation of China(82270246,82070240,82470280 and 82300493)+1 种基金the Natural Science Foundation of Heilongjiang Province of China(JJ2024LH2446)China Postdoctoral Science Foundation(2023MD734169,China).
文摘Cardiac fibrosis is characterized by an elevated amount of extracellular matrix(ECM)within the heart.However,the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction.Circular RNAs(circRNAs)are emerging as important regulators of cardiac fibrosis.Here,we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism.Functionally,circ-CELF1 was involved in enhancing fibrosis-related markers'expression and promoting the proliferation of cardiac fibroblasts(CFs),thereby exacerbating cardiac fibrosis.Mechanistically,circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3,leading to an elevation of BRPF3 protein levels.Additionally,BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene.Thus,the transcription of Celf1 was dramatically activated,thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis.Moreover,Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing,thereby establishing a feedback loop for circ-CELF1 production.Consequently,a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established,suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.
文摘针对攻击代价相等时的有限资源网络毁伤问题,给出了网络毁伤最大化的定义。为了改进近似求解算法求解毁伤最大化问题时复杂度较高的缺陷,提出了基于拓扑势和CELF(cost-effective lazy-forward)的TPCELF(algorithm based on topology potential and CELF)算法。利用无标度网络和实测网络进行实验,结果表明,TPCELF算法在计算速度上有较大的提升,网络平均毁伤效果接近于近似求解算法;且优于采用常见重要性度量指标排序算法得到的平均毁伤效果。所提方法可从网络毁伤的角度为复杂网络关键节点挖掘提供参考。
基金supported by the National Institute of Dental and Craniofacial Research (NIDCR) grant K23DE027412
文摘Streptococcus mutans is a well-known cause of dental caries,due to its acidogenicity,aciduricity,and ability to synthesize exopolysaccharides in dental plaques.Intriguingly,not all children who carry S.mutans manifest caries,even with similar characteristics in oral hygiene,diet,and other environmental factors.This phenomenon suggests that host susceptibility potentially plays a role in the development of dental caries;however,the association between host genetics,S.mutans,and dental caries remains unclear.Therefore,this study examined the influence of host gene-by-S.mutans interaction on dental caries.Genome-wide association analyses were conducted in 709 US children (<13 years old),using the dbGap database acquired from the center for oral health research in appalachia (COHRA) and the Iowa Head Start programmes (GEIRS).A generalized estimating equation was used to examine the gene-by-S.mutans interaction effects on the outcomes (decayed and missing/filled primary teeth due to caries).Sequentially,the COHRA and GEIRS data were used to identify potential interactions and replicate the findings.Three loci at the genes interleukin 32 (IL32),galactokinase 2 (GALK2),and CUGBP,Elav-like family member 4 (CELF4) were linked to S.mutans carriage,and there was a severity of caries at a suggestive significance level among COHRA children (P < 9×10?5),and at a nominal significance level among GEIRS children (P = 0.047–0.001).The genetic risk score that combined the three loci also significantly interacted with S.mutans (P < 0.000 1).Functional analyses indicated that the identified genes are involved in the host immune response,galactose carbohydrate metabolism,and food-rewarding system,which could potentially be used to identify children at high risk for caries and to develop personalized caries prevention strategies.
基金This paper was supported by the National Natural Science Foundation of China (61472345, 61562091), the Natural Science Foundation of Yunnan Province (2014FA023,2013FB010), the Program for Innovative Research Team in Yunnan University (XT412011), the Program for Excellent Young Talents of Yunnan University (XT412003), Yunnan Provincial Foundation for Leaders of Disciplines in Science and Technology (2012HB004), and the Research Foundation of the Educational Department of Yunnan Province (2014C134Y).
文摘There exist two or more competing products in viral marketing, and the companies can exploit the social interactions of users to propagate the awareness of products. In this paper, we focus on selecting seeds for maximizing the competitive influence spread in social networks. First, we establish the possible graphs based on the propagation probability of edges, and then we use the competitive influence spread model (CISM) to model the competitive spread under the possible graph. Further, we consider the objective function of selecting k seeds of one product under the CISM when the seeds of another product have been known, which is monotone and submodular, and thus we use the CELF (cost-effective lazy forward) algorithm to accelerate the greedy algorithm that can approximate the optimal with 1 ? 1/e. Experimental results verify the feasibility and effectiveness of our method.
