Purpose:To investigate the effect of apigenin on gap junctional intercellular communication (GJIC) in human Tenon's capsule fibroblasts (HTFs) and its underlying mechanism. Methods:After a 48 h treatment of cultur...Purpose:To investigate the effect of apigenin on gap junctional intercellular communication (GJIC) in human Tenon's capsule fibroblasts (HTFs) and its underlying mechanism. Methods:After a 48 h treatment of cultured HTFs with apigenin.(80 μmol/L),the GJIC was detected by a scrape-loading/dye transfer technique with Lucifer yellow dye and rhodamine (Rh) dextran. The coupling index represents a quantification of GJIC where a high coupling index is associated with a greater number of cells demonstrating cell-cell communication through gap junction channels.The changes in connexin 43 (Cx43) distribution and the expression of Cx43 at the protein and mRNA levels were statistically compared between the two groups by means of immunocytochemistry, western blotting,and real-time polymerase chain reaction (PCR). Results:The functioning of GJIC in the HTFs was significantly enhanced after 48 hours by apigenin treatment when compared with the control cells. In the apigenin group, the intercellular dye transfer grade was above 9, while this value was only grade 3-4 in the control group. The coupling index was significantly increased up to 9.205±0.3621 in the apigenin group,compared with 5.1775 ±0.3177 in the control group (F=279.581, P=0.000). The expression of Cx43 at the protein and mRNA levels was significantly up-regulated in the apigenin group compared with the control group. Conclusion:Apigenin can significantly enhance the function of GJIC in HTFs by up-regulating the expression of Cx43 at both the protein and mRNA levels,suggesting that the enhancement of GJIC in HTFs by apigenin probably acts as an important mechanism underlying the inhibitory effect of apigenin on HTF proliferation.展开更多
The positive-definiteness and sparsity are the most important property of high-dimensional precision matrices. To better achieve those property, this paper uses a sparse lasso penalized D-trace loss under the positive...The positive-definiteness and sparsity are the most important property of high-dimensional precision matrices. To better achieve those property, this paper uses a sparse lasso penalized D-trace loss under the positive-definiteness constraint to estimate high-dimensional precision matrices. This paper derives an efficient accelerated gradient method to solve the challenging optimization problem and establish its converges rate as . The numerical simulations illustrated our method have competitive advantage than other methods.展开更多
The heavy fuel compression ignition engines are widely equipped as aircraft piston engines. The fuel injection system is one of the key technologies that determines the performance of engine. One of the main challenge...The heavy fuel compression ignition engines are widely equipped as aircraft piston engines. The fuel injection system is one of the key technologies that determines the performance of engine. One of the main challenges is to precisely control the injected fuel quantity and flow rate in the presence of pressure fluctuation. This challenge is even more serious for heavy fuel. An original design for electrically controlled high pressure fuel injection system called Multi-Pumppressure-reservoirs fuel injection System(MPS) was demonstrated to reduce the pressure fluctuation and help keep injection stable. MPS was compared with an ordinary high pressure Common Rail fuel injection System(CRS). This work established one-dimensional AMESim and mathematical models for both CRS and MPS to study the effect of different structures and geometric parameters on the pressure fluctuations. The calculations show that the average fuel pressure fluctuation of MPS can be reduced by 57% for the crankshaft speed of 1900 r/min, and the pressure fluctuation before injection reduced by 100%. It is concluded that the pressure performance of MPS is less sensitive to pressure reservoir volume than that of CRS, and there is an opportunity for further volume reduction.展开更多
In order to explore the total-pressure distortion test assessment method for a turbofan engine, a Controlled Variable Double-Baffle Distortion Generator(CVDBDG) with a horizontal symmetry moving form was developed, wh...In order to explore the total-pressure distortion test assessment method for a turbofan engine, a Controlled Variable Double-Baffle Distortion Generator(CVDBDG) with a horizontal symmetry moving form was developed, which can adjust the steady-state and time–variant distortion separately in real time. The inlet total-pressure distortion test was conducted on an afterburner turbofan engine. The distortion parameters of CVDBDG and the instability characteristics of the engine were measured. The experimental data were modeled and analyzed by using back propagation artificial neural networks, and the work envelope of CVDBDG was obtained. Based on the analysis of the data on the engine’s instability, the properties of CVDBDG used for the stability assessment were preliminarily evaluated. The results show that CVDBDG can simulate both steady-state and time–variant distortions simultaneously in a range determined by three envelopes.Under the condition of symmetric double baffles, a critical depth of insertion exists, beyond which the symmetric baffles will generate an asymmetric flow field. In the case of double baffles, compared to a single baffle, the engine exhibited different instability characteristics. Based on CVDBDG, it is expected that more efficient engine stability and durability assessment methods can be developed.展开更多
Using the so-called martingale difference correlation(MDC), we propose a novel censoredconditional-quantile screening approach for ultrahigh-dimensional survival data with heterogeneity(which is often present in such ...Using the so-called martingale difference correlation(MDC), we propose a novel censoredconditional-quantile screening approach for ultrahigh-dimensional survival data with heterogeneity(which is often present in such data). By incorporating a weighting scheme, this method is a natural extension of MDCbased conditional quantile screening, as considered by Shao and Zhang(2014), to handle ultrahigh-dimensional survival data. The proposed screening procedure has a sure-screening property under certain technical conditions and an excellent capability of detecting the nonlinear relationship between independent and censored dependent variables. Both simulation results and an analysis of real data demonstrate the effectiveness of the new censored conditional quantile-screening procedure.展开更多
RNA N^(6)-methyladenosine modification is the most prevalent internal modification of eukaryotic RNAs and has emerged as a novel field of RNA epigenetics,garnering increased attention.To date,m^(6)A modification has b...RNA N^(6)-methyladenosine modification is the most prevalent internal modification of eukaryotic RNAs and has emerged as a novel field of RNA epigenetics,garnering increased attention.To date,m^(6)A modification has been shown to impact multiple RNA metabolic processes and play a vital role in numerous biological processes.Recent evidence suggests that aberrant m^(6)A modification is a hallmark of cancer,and it plays a critical role in cancer development and progression through multiple mechanisms.Here,we review the biological functions of mRNA m^(6)A modification in various types of cancers,with a particular focus on metabolic reprogramming,programmed cell death and tumor metastasis.Furthermore,we discuss the potential of targetingm^(6)Amodification or its regulatory proteins as a novel approach of cancer therapy and the progress of research on m^(6)A modification in tumor immunity and immunotherapy.Finally,we summarize the development of different m^(6)A detection methods and their advantages and disadvantages.展开更多
The proliferation and differentiation of adult stem cells must be tightly controlled in order to maintain resident tissue homeostasis. Dysfunction of stem cells is implicated in many human diseases, including cancer. ...The proliferation and differentiation of adult stem cells must be tightly controlled in order to maintain resident tissue homeostasis. Dysfunction of stem cells is implicated in many human diseases, including cancer. However, the regulation of stem cell proliferation and differentiation is not fully understood. Here we show that the sterile-like 20 kinase, Tao, controls tissue homeostasis by regulating the Hippo pathway in the Drosophila adult midgut. Depletion of Tao in the progenitors leads to rapid intestinal stem cell （ISC） proliferation and midgut homeostasis loss. Meanwhile, we find that the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling activity and cytokine production are significantly increased, resulting in stimulated ISC proliferation. Furthermore, expression of the Hippo pathway downstream targets, Diapl and bantam, is dramatically increased in Tao knockdown intestines. Consistently, we show that the Yorkie （Yki） acts downstream of Tao to regulate ISC proliferation. Together, our results provide insights into our understanding of the mechanisms of stem cell proliferation and tissue homeostasis control.展开更多
Multiple testing has gained much attention in high-dimensional statistical theory and applications,and the problem of variable selection can be regarded as a generalization of the multiple testing.It is aiming to sele...Multiple testing has gained much attention in high-dimensional statistical theory and applications,and the problem of variable selection can be regarded as a generalization of the multiple testing.It is aiming to select the important variables among many variables.Performing variable selection in high-dimensional linear models with measurement errors is challenging.Both the influence of high-dimensional parameters and measurement errors need to be considered to avoid severely biases.We consider the problem of variable selection in error-in-variables and introduce the DCoCoLasso-FDP procedure,a new variable selection method.By constructing the consistent estimator of false discovery proportion(FDP)and false discovery rate(FDR),our method can prioritize the important variables and control FDP and FDR at a specifical level in error-in-variables models.An extensive simulation study is conducted to compare DCoCoLasso-FDP procedure with existing methods in various settings,and numerical results are provided to present the efficiency of our method.展开更多
In this paper,the problem of high-dimensional multivariate analysis of variance is investigated under a low-dimensional factor structure which violates some vital assumptions on covariance matrix in some existing lite...In this paper,the problem of high-dimensional multivariate analysis of variance is investigated under a low-dimensional factor structure which violates some vital assumptions on covariance matrix in some existing literature.We propose a new test and derive that the asymptotic distribution of the test statistic is a weighted distribution of chi-squares of 1 degree of freedom under the null hypothesis and mild conditions.We provide numerical studies on both sizes and powers to illustrate performance of the proposed test.展开更多
Background:Pancreatic duct adenocarcinoma(PDAC)remains a major health problem because conventional can-cer treatments are relatively ineffective against it.Microarray studies have linked many genes to pancreatic cance...Background:Pancreatic duct adenocarcinoma(PDAC)remains a major health problem because conventional can-cer treatments are relatively ineffective against it.Microarray studies have linked many genes to pancreatic cancer,but the available data have not been extensively mined for potential insights into PDAC.This study attempted to identify PDAC-associated genes and signaling pathways based on six microarray-based profiles of gene expression in pancre-atic cancer deposited in the gene expression omnibus database.Methods:Pathway network methods were used to analyze core pathways in six publicly available pancreatic cancer gene(GSE71989,GSE15471,GSE16515,GSE32676,GSE41368 and GSE28735)expression profiles.Genes potentially linked to PDAC were assessed for potential impact on survival time based on data in The Cancer Genome Atlas and International Cancer Genome Consortium databases,and the expression of one candidate gene(CKS2)and its association with survival was examined in 102 patients with PDAC from our hospital.Effects of CKS2 knockdown were explored in the PDAC cell lines BxPC-3 and CFPAC-1.Results:The KEGG signaling pathway called“pathway in cancer”may play an important role in pancreatic cancer development and progression.Five genes(BIRC5,CKS2,ITGA3,ITGA6 and RALA)in this pathway were significantly associated with survival time in patients with PDAC.CKS2 was overexpressed in PDAC samples from our hospital,and higher CKS2 expression in these patients was associated with shorter survival time.CKS2 knockdown substantially inhibited PDAC cell proliferation in vitro.Conclusions:Analysis integrating existing microarray datasets allowed identification of the“pathway in cancer”as an important signaling pathway in PDAC.This integrative approach may be powerful for identifying genes and pathways involved in cancer.展开更多
基金supported by Shandong Provincial Natural Science Foundation Project (No.ZR2010HM015)
文摘Purpose:To investigate the effect of apigenin on gap junctional intercellular communication (GJIC) in human Tenon's capsule fibroblasts (HTFs) and its underlying mechanism. Methods:After a 48 h treatment of cultured HTFs with apigenin.(80 μmol/L),the GJIC was detected by a scrape-loading/dye transfer technique with Lucifer yellow dye and rhodamine (Rh) dextran. The coupling index represents a quantification of GJIC where a high coupling index is associated with a greater number of cells demonstrating cell-cell communication through gap junction channels.The changes in connexin 43 (Cx43) distribution and the expression of Cx43 at the protein and mRNA levels were statistically compared between the two groups by means of immunocytochemistry, western blotting,and real-time polymerase chain reaction (PCR). Results:The functioning of GJIC in the HTFs was significantly enhanced after 48 hours by apigenin treatment when compared with the control cells. In the apigenin group, the intercellular dye transfer grade was above 9, while this value was only grade 3-4 in the control group. The coupling index was significantly increased up to 9.205±0.3621 in the apigenin group,compared with 5.1775 ±0.3177 in the control group (F=279.581, P=0.000). The expression of Cx43 at the protein and mRNA levels was significantly up-regulated in the apigenin group compared with the control group. Conclusion:Apigenin can significantly enhance the function of GJIC in HTFs by up-regulating the expression of Cx43 at both the protein and mRNA levels,suggesting that the enhancement of GJIC in HTFs by apigenin probably acts as an important mechanism underlying the inhibitory effect of apigenin on HTF proliferation.
文摘The positive-definiteness and sparsity are the most important property of high-dimensional precision matrices. To better achieve those property, this paper uses a sparse lasso penalized D-trace loss under the positive-definiteness constraint to estimate high-dimensional precision matrices. This paper derives an efficient accelerated gradient method to solve the challenging optimization problem and establish its converges rate as . The numerical simulations illustrated our method have competitive advantage than other methods.
文摘The heavy fuel compression ignition engines are widely equipped as aircraft piston engines. The fuel injection system is one of the key technologies that determines the performance of engine. One of the main challenges is to precisely control the injected fuel quantity and flow rate in the presence of pressure fluctuation. This challenge is even more serious for heavy fuel. An original design for electrically controlled high pressure fuel injection system called Multi-Pumppressure-reservoirs fuel injection System(MPS) was demonstrated to reduce the pressure fluctuation and help keep injection stable. MPS was compared with an ordinary high pressure Common Rail fuel injection System(CRS). This work established one-dimensional AMESim and mathematical models for both CRS and MPS to study the effect of different structures and geometric parameters on the pressure fluctuations. The calculations show that the average fuel pressure fluctuation of MPS can be reduced by 57% for the crankshaft speed of 1900 r/min, and the pressure fluctuation before injection reduced by 100%. It is concluded that the pressure performance of MPS is less sensitive to pressure reservoir volume than that of CRS, and there is an opportunity for further volume reduction.
基金supported by the Beijing Aeronautical Technology Research Center
文摘In order to explore the total-pressure distortion test assessment method for a turbofan engine, a Controlled Variable Double-Baffle Distortion Generator(CVDBDG) with a horizontal symmetry moving form was developed, which can adjust the steady-state and time–variant distortion separately in real time. The inlet total-pressure distortion test was conducted on an afterburner turbofan engine. The distortion parameters of CVDBDG and the instability characteristics of the engine were measured. The experimental data were modeled and analyzed by using back propagation artificial neural networks, and the work envelope of CVDBDG was obtained. Based on the analysis of the data on the engine’s instability, the properties of CVDBDG used for the stability assessment were preliminarily evaluated. The results show that CVDBDG can simulate both steady-state and time–variant distortions simultaneously in a range determined by three envelopes.Under the condition of symmetric double baffles, a critical depth of insertion exists, beyond which the symmetric baffles will generate an asymmetric flow field. In the case of double baffles, compared to a single baffle, the engine exhibited different instability characteristics. Based on CVDBDG, it is expected that more efficient engine stability and durability assessment methods can be developed.
基金supported by the National Statistical Scientific Research Projects(Grant No.2015LZ54)
文摘Using the so-called martingale difference correlation(MDC), we propose a novel censoredconditional-quantile screening approach for ultrahigh-dimensional survival data with heterogeneity(which is often present in such data). By incorporating a weighting scheme, this method is a natural extension of MDCbased conditional quantile screening, as considered by Shao and Zhang(2014), to handle ultrahigh-dimensional survival data. The proposed screening procedure has a sure-screening property under certain technical conditions and an excellent capability of detecting the nonlinear relationship between independent and censored dependent variables. Both simulation results and an analysis of real data demonstrate the effectiveness of the new censored conditional quantile-screening procedure.
基金supported by the National Key R&D Program of China(2021YFA1302100)Natural Science Foundation of China(82072617 to J.Zheng,82003162 to J.Zhang)+1 种基金Program for Guangdong Introducing Innovative and Entrepreneurial Teams(2017ZT07S096 to D.L.)Sun Yat-sen University Intramural Funds(to D.L.and to J.Zheng).
文摘RNA N^(6)-methyladenosine modification is the most prevalent internal modification of eukaryotic RNAs and has emerged as a novel field of RNA epigenetics,garnering increased attention.To date,m^(6)A modification has been shown to impact multiple RNA metabolic processes and play a vital role in numerous biological processes.Recent evidence suggests that aberrant m^(6)A modification is a hallmark of cancer,and it plays a critical role in cancer development and progression through multiple mechanisms.Here,we review the biological functions of mRNA m^(6)A modification in various types of cancers,with a particular focus on metabolic reprogramming,programmed cell death and tumor metastasis.Furthermore,we discuss the potential of targetingm^(6)Amodification or its regulatory proteins as a novel approach of cancer therapy and the progress of research on m^(6)A modification in tumor immunity and immunotherapy.Finally,we summarize the development of different m^(6)A detection methods and their advantages and disadvantages.
基金supported by the grants from the National Natural Science Foundation of China (Nos. 31271582 and 31030049)Wenzhou Medical University (No. XNK07005)+2 种基金Research Foundation for Advanced Talents of Wenzhou Medical College (No. QTJ08012)the National Basic Research Program of China (Nos. 2011CB943901, 2011 CB943902 and 2011CB943802)Strategic Priority Research Program of the Chinese Academy of Sciences (No.XDA01010101)
文摘The proliferation and differentiation of adult stem cells must be tightly controlled in order to maintain resident tissue homeostasis. Dysfunction of stem cells is implicated in many human diseases, including cancer. However, the regulation of stem cell proliferation and differentiation is not fully understood. Here we show that the sterile-like 20 kinase, Tao, controls tissue homeostasis by regulating the Hippo pathway in the Drosophila adult midgut. Depletion of Tao in the progenitors leads to rapid intestinal stem cell （ISC） proliferation and midgut homeostasis loss. Meanwhile, we find that the Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling activity and cytokine production are significantly increased, resulting in stimulated ISC proliferation. Furthermore, expression of the Hippo pathway downstream targets, Diapl and bantam, is dramatically increased in Tao knockdown intestines. Consistently, we show that the Yorkie （Yki） acts downstream of Tao to regulate ISC proliferation. Together, our results provide insights into our understanding of the mechanisms of stem cell proliferation and tissue homeostasis control.
文摘Multiple testing has gained much attention in high-dimensional statistical theory and applications,and the problem of variable selection can be regarded as a generalization of the multiple testing.It is aiming to select the important variables among many variables.Performing variable selection in high-dimensional linear models with measurement errors is challenging.Both the influence of high-dimensional parameters and measurement errors need to be considered to avoid severely biases.We consider the problem of variable selection in error-in-variables and introduce the DCoCoLasso-FDP procedure,a new variable selection method.By constructing the consistent estimator of false discovery proportion(FDP)and false discovery rate(FDR),our method can prioritize the important variables and control FDP and FDR at a specifical level in error-in-variables models.An extensive simulation study is conducted to compare DCoCoLasso-FDP procedure with existing methods in various settings,and numerical results are provided to present the efficiency of our method.
基金supported by the National Statistical Science Research Program(No.2020LY002)the National Natural Science Foundation of China(Nos.11601008,11526070)+2 种基金Doctor Startup Foundation of Anhui Normal University(No.2016XJJ101)supported by Anhui Provincial Natural Science Foundation(No.2008085MA08)supported by Anhui Provincial Natural Science Foundation(No.1908085MA20).
文摘In this paper,the problem of high-dimensional multivariate analysis of variance is investigated under a low-dimensional factor structure which violates some vital assumptions on covariance matrix in some existing literature.We propose a new test and derive that the asymptotic distribution of the test statistic is a weighted distribution of chi-squares of 1 degree of freedom under the null hypothesis and mild conditions.We provide numerical studies on both sizes and powers to illustrate performance of the proposed test.
基金supported by the National Natural Science Foundation of China(No.81572793,81772586 and 81602461)a Grant(No.2016A030313283)from the Natural Science Foundation of Guangdong Provincethe Peking Union Medical College Doctor Innovation Fund(No.2015-0710-17).
文摘Background:Pancreatic duct adenocarcinoma(PDAC)remains a major health problem because conventional can-cer treatments are relatively ineffective against it.Microarray studies have linked many genes to pancreatic cancer,but the available data have not been extensively mined for potential insights into PDAC.This study attempted to identify PDAC-associated genes and signaling pathways based on six microarray-based profiles of gene expression in pancre-atic cancer deposited in the gene expression omnibus database.Methods:Pathway network methods were used to analyze core pathways in six publicly available pancreatic cancer gene(GSE71989,GSE15471,GSE16515,GSE32676,GSE41368 and GSE28735)expression profiles.Genes potentially linked to PDAC were assessed for potential impact on survival time based on data in The Cancer Genome Atlas and International Cancer Genome Consortium databases,and the expression of one candidate gene(CKS2)and its association with survival was examined in 102 patients with PDAC from our hospital.Effects of CKS2 knockdown were explored in the PDAC cell lines BxPC-3 and CFPAC-1.Results:The KEGG signaling pathway called“pathway in cancer”may play an important role in pancreatic cancer development and progression.Five genes(BIRC5,CKS2,ITGA3,ITGA6 and RALA)in this pathway were significantly associated with survival time in patients with PDAC.CKS2 was overexpressed in PDAC samples from our hospital,and higher CKS2 expression in these patients was associated with shorter survival time.CKS2 knockdown substantially inhibited PDAC cell proliferation in vitro.Conclusions:Analysis integrating existing microarray datasets allowed identification of the“pathway in cancer”as an important signaling pathway in PDAC.This integrative approach may be powerful for identifying genes and pathways involved in cancer.
