Numerous studies have characterized the critical role of circular RNAs(circRNAs)as regulatory factors in the progression of multiple cancers.However,the biological functions of circRNAs and their underlying molecular ...Numerous studies have characterized the critical role of circular RNAs(circRNAs)as regulatory factors in the progression of multiple cancers.However,the biological functions of circRNAs and their underlying molecular mechanisms in the progression of uveal melanoma(UM)remain enigmatic.In this study,we identified a novel circRNA,circ_0053943,through re-analysis of UM microarray data and quantitative RT-PCR.Circ_0053943 was found to be upregulated in UM and to promote the proliferation and metastatic ability of UM cells in both in vitro and in vivo settings.Mechanistically,circ_0053943 was observed to bind to the KH1 and KH2 domains of insulin-like growth factor 2 mRNA-binding protein 3(IGF2BP3),thereby enhancing the function of IGF2BP3 by stabilizing its target mRNA.RNA sequencing assays identified epidermal growth factor receptor(EGFR)as a target gene of circ_0053943 and IGF2BP3 at the transcriptional level.Rescue assays demonstrated that circ_0053943 exerts its biological function by stabilizing EGFR mRNA and regulating the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK)signaling pathway.Collectively,circ_0053943 may promote UM progression by stabilizing EGFR mRNA and activating the MAPK/ERK signaling pathway through the formation of a circ_0053943/IGF2BP3/EGFR RNA-protein ternary complex,thus providing a potential biomarker and therapeutic target for UM.展开更多
Extracting the amplitude and time information from the shaped pulse is an important step in nuclear physics experiments.For this purpose,a neural network can be an alternative in off-line data processing.For processin...Extracting the amplitude and time information from the shaped pulse is an important step in nuclear physics experiments.For this purpose,a neural network can be an alternative in off-line data processing.For processing the data in real time and reducing the off-line data storage required in a trigger event,we designed a customized neural network accelerator on a field programmable gate array platform to implement specific layers in a convolutional neural network.The latter is then used in the front-end electronics of the detector.With fully reconfigurable hardware,a tested neural network structure was used for accurate timing of shaped pulses common in front-end electronics.This design can handle up to four channels of pulse signals at once.The peak performance of each channel is 1.665 Giga operations per second at a working frequency of 25 MHz.展开更多
Oestrogen is essential for maintaining bone mass, and it has been demonstrated to induce osteoblast proliferation and bone formation.In this study, complementary DNA(cDNA) microarrays were used to identify and study...Oestrogen is essential for maintaining bone mass, and it has been demonstrated to induce osteoblast proliferation and bone formation.In this study, complementary DNA(cDNA) microarrays were used to identify and study the expression of novel genes that may be involved in MC3T3-E1 cells’ response to 17-b estradiol. MC3T3-E1 cells were inoculated in minimum essential media alpha(a-MEM)cell culture supplemented with 17-b estradiol at different concentrations and for different time periods. MC3T3-E1 cells treated with1028mol?L2117-b estradiol for 5 days exhibited the highest proliferation and alkaline phosphatase(ALP) activity; thus, this group was chosen for microarray analysis. The harvested RNA was used for microarray hybridisation and subsequent real-time reverse transcription polymerase chain reaction(RT-PCR) to validate the expression levels for selected genes. The microarray results were analysed using both functional and pathway analysis. In this study, microarray analysis detected 5 403 differentially expressed genes,of which 1 996 genes were upregulated and 3 407 genes were downregulated, 1 553 different functional classifications were identified by gene ontology(GO) analysis and 53 different pathways were involved based on pathway analysis. Among the differentially expressed genes, a portion not previously reported to be associated with the osteoblast response to oestrogen was identified. These findings clearly demonstrate that the expression of genes related to osteoblast proliferation, cell differentiation, collagens and transforming growth factor beta(TGF-b)-related cytokines increases, while the expression of genes related to apoptosis and osteoclast differentiation decreases, following the exposure of MC3T3-E1 cells to a-MEM supplemented with 17-b estradiol. Microarray analysis with functional gene classification is critical for a complete understanding of complementary intracellular processes. This microarray analysis provides large-scale gene expression data that require further confirmatory studies.展开更多
Taking Haotang Village in Xinyang City of Henan Province as an example,this paper analyzed experience of this village in development of new socialist countryside construction. The new socialist countryside planning an...Taking Haotang Village in Xinyang City of Henan Province as an example,this paper analyzed experience of this village in development of new socialist countryside construction. The new socialist countryside planning and construction should attach importance to research on original spatial pattern of villages,really respect and bring into play subject function of farmers,and deeply explore rural financial services. It is expected to provide reference for future new socialist countryside planning and construction.展开更多
Ischemic stroke is a severe disorder resulting from acute cerebral thrombosis.Here we demonstrated that post-ischemic treatment with ciclopirox olamine(CPX),a potent antifungal clinical drug,alleviated brain infarctio...Ischemic stroke is a severe disorder resulting from acute cerebral thrombosis.Here we demonstrated that post-ischemic treatment with ciclopirox olamine(CPX),a potent antifungal clinical drug,alleviated brain infarction,neurological deficits and brain edema in a classic rat model of ischemic stroke.Single dose post-ischemic administration of CPX provided a long-lasting neuroprotective effect,which can be further enhanced by multiple doses administration of CPX.CPX also effectively reversed ischemia-induced neuronal loss,glial activation as well as blood-brain barrier(BBB)damage.Employing quantitative phosphoproteomic analysis,130 phosphosites in 122 proteins were identified to be significantly regulated by CPX treatment in oxygen glucose deprivation(OGD)-exposed SH-SY5 Y cells,which revealed that phosphokinases and cell cycle-related phosphoproteins were largely influenced.Subsequently,we demonstrated that CPX markedly enhanced the AKT(protein kinase B,PKB/AKT)and GSK3β(glycogen synthase kinase 3β)phosphorylation in OGD-exposed SH-SY5 Y cells,and regulated the cell cycle progression and nitric oxide(NO)release in lipopolysaccharide(LPS)-induced B V-2 cells,which may contribute to its ameliorative effects against ischemia-associated neuronal death and microglial inflammation.Our study suggests that CPX could be a promising compound to reduce multiple ischemic injuries;however,further studies will be needed to clarify the molecular mechanisms involved.展开更多
Rapid and efficient isolation of unknown flanking DNA sequences adjacent to known regions is important for molecular biology research.For this purpose,several PCR-based methods have been reported,including inverse PCR...Rapid and efficient isolation of unknown flanking DNA sequences adjacent to known regions is important for molecular biology research.For this purpose,several PCR-based methods have been reported,including inverse PCR(Uchiyama and Watanabe,2006),ligation-mediated PCR(Yan et al.,2003;Ballester et al.,2005;Wang et al.,2007;Trinh et al.,2012)and randomly primed PCR(Liu and Whittier,1995;Liu et al.,1995;Antal et al.展开更多
Semiparametric transformation models provide a class of flexible models for regression analysis of failure time data. Several authors have discussed them under different situations when covariates are time- independe...Semiparametric transformation models provide a class of flexible models for regression analysis of failure time data. Several authors have discussed them under different situations when covariates are time- independent (Chen et al., 2002; Cheng et al., 1995; Fine et al., 1998). In this paper, we consider fitting these models to right-censored data when covariates are time-dependent longitudinal variables and, furthermore, may suffer measurement errors. For estimation, we investigate the maximum likelihood approach, and an EM algorithm is developed. Simulation results show that the proposed method is appropriate for practical application, and an illustrative example is provided.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82273159 and 82171838)the Jiangsu Province’s Science and Technology Project(No.BE2020722).
文摘Numerous studies have characterized the critical role of circular RNAs(circRNAs)as regulatory factors in the progression of multiple cancers.However,the biological functions of circRNAs and their underlying molecular mechanisms in the progression of uveal melanoma(UM)remain enigmatic.In this study,we identified a novel circRNA,circ_0053943,through re-analysis of UM microarray data and quantitative RT-PCR.Circ_0053943 was found to be upregulated in UM and to promote the proliferation and metastatic ability of UM cells in both in vitro and in vivo settings.Mechanistically,circ_0053943 was observed to bind to the KH1 and KH2 domains of insulin-like growth factor 2 mRNA-binding protein 3(IGF2BP3),thereby enhancing the function of IGF2BP3 by stabilizing its target mRNA.RNA sequencing assays identified epidermal growth factor receptor(EGFR)as a target gene of circ_0053943 and IGF2BP3 at the transcriptional level.Rescue assays demonstrated that circ_0053943 exerts its biological function by stabilizing EGFR mRNA and regulating the downstream mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK)signaling pathway.Collectively,circ_0053943 may promote UM progression by stabilizing EGFR mRNA and activating the MAPK/ERK signaling pathway through the formation of a circ_0053943/IGF2BP3/EGFR RNA-protein ternary complex,thus providing a potential biomarker and therapeutic target for UM.
基金supported by the National Natural Science Foundation of China(Nos.11875146 and 11505074)National Key Research and Development Program of China(No.2016YFE0100900).
文摘Extracting the amplitude and time information from the shaped pulse is an important step in nuclear physics experiments.For this purpose,a neural network can be an alternative in off-line data processing.For processing the data in real time and reducing the off-line data storage required in a trigger event,we designed a customized neural network accelerator on a field programmable gate array platform to implement specific layers in a convolutional neural network.The latter is then used in the front-end electronics of the detector.With fully reconfigurable hardware,a tested neural network structure was used for accurate timing of shaped pulses common in front-end electronics.This design can handle up to four channels of pulse signals at once.The peak performance of each channel is 1.665 Giga operations per second at a working frequency of 25 MHz.
基金supported by grants from the Natural Science Fund (ZR2010HM035) of Shandong Provincethe Shandong Provincial Health Development Project Fund (2011WSB19002) in China
文摘Oestrogen is essential for maintaining bone mass, and it has been demonstrated to induce osteoblast proliferation and bone formation.In this study, complementary DNA(cDNA) microarrays were used to identify and study the expression of novel genes that may be involved in MC3T3-E1 cells’ response to 17-b estradiol. MC3T3-E1 cells were inoculated in minimum essential media alpha(a-MEM)cell culture supplemented with 17-b estradiol at different concentrations and for different time periods. MC3T3-E1 cells treated with1028mol?L2117-b estradiol for 5 days exhibited the highest proliferation and alkaline phosphatase(ALP) activity; thus, this group was chosen for microarray analysis. The harvested RNA was used for microarray hybridisation and subsequent real-time reverse transcription polymerase chain reaction(RT-PCR) to validate the expression levels for selected genes. The microarray results were analysed using both functional and pathway analysis. In this study, microarray analysis detected 5 403 differentially expressed genes,of which 1 996 genes were upregulated and 3 407 genes were downregulated, 1 553 different functional classifications were identified by gene ontology(GO) analysis and 53 different pathways were involved based on pathway analysis. Among the differentially expressed genes, a portion not previously reported to be associated with the osteoblast response to oestrogen was identified. These findings clearly demonstrate that the expression of genes related to osteoblast proliferation, cell differentiation, collagens and transforming growth factor beta(TGF-b)-related cytokines increases, while the expression of genes related to apoptosis and osteoclast differentiation decreases, following the exposure of MC3T3-E1 cells to a-MEM supplemented with 17-b estradiol. Microarray analysis with functional gene classification is critical for a complete understanding of complementary intracellular processes. This microarray analysis provides large-scale gene expression data that require further confirmatory studies.
文摘Taking Haotang Village in Xinyang City of Henan Province as an example,this paper analyzed experience of this village in development of new socialist countryside construction. The new socialist countryside planning and construction should attach importance to research on original spatial pattern of villages,really respect and bring into play subject function of farmers,and deeply explore rural financial services. It is expected to provide reference for future new socialist countryside planning and construction.
基金supported by the National Natural Science Foundation of China(Nos.81872859,81661148046,81522045,and 81703507)the National Special Fund for State Key Laboratory of Bioreactor Engineering(No.2060204,China)+1 种基金the National R&D Projects for major research instruments(ZDYZ2013-1,China)the Institutional Technology Service Center of Shanghai Institute of Materia Medica,Chinese Academy of Sciences for technical support.
文摘Ischemic stroke is a severe disorder resulting from acute cerebral thrombosis.Here we demonstrated that post-ischemic treatment with ciclopirox olamine(CPX),a potent antifungal clinical drug,alleviated brain infarction,neurological deficits and brain edema in a classic rat model of ischemic stroke.Single dose post-ischemic administration of CPX provided a long-lasting neuroprotective effect,which can be further enhanced by multiple doses administration of CPX.CPX also effectively reversed ischemia-induced neuronal loss,glial activation as well as blood-brain barrier(BBB)damage.Employing quantitative phosphoproteomic analysis,130 phosphosites in 122 proteins were identified to be significantly regulated by CPX treatment in oxygen glucose deprivation(OGD)-exposed SH-SY5 Y cells,which revealed that phosphokinases and cell cycle-related phosphoproteins were largely influenced.Subsequently,we demonstrated that CPX markedly enhanced the AKT(protein kinase B,PKB/AKT)and GSK3β(glycogen synthase kinase 3β)phosphorylation in OGD-exposed SH-SY5 Y cells,and regulated the cell cycle progression and nitric oxide(NO)release in lipopolysaccharide(LPS)-induced B V-2 cells,which may contribute to its ameliorative effects against ischemia-associated neuronal death and microglial inflammation.Our study suggests that CPX could be a promising compound to reduce multiple ischemic injuries;however,further studies will be needed to clarify the molecular mechanisms involved.
基金supported by grants from the Ministry of Agriculture of China (2016ZX08010001)the National Natural Science Foundation of China (31771740)
文摘Rapid and efficient isolation of unknown flanking DNA sequences adjacent to known regions is important for molecular biology research.For this purpose,several PCR-based methods have been reported,including inverse PCR(Uchiyama and Watanabe,2006),ligation-mediated PCR(Yan et al.,2003;Ballester et al.,2005;Wang et al.,2007;Trinh et al.,2012)and randomly primed PCR(Liu and Whittier,1995;Liu et al.,1995;Antal et al.
文摘Semiparametric transformation models provide a class of flexible models for regression analysis of failure time data. Several authors have discussed them under different situations when covariates are time- independent (Chen et al., 2002; Cheng et al., 1995; Fine et al., 1998). In this paper, we consider fitting these models to right-censored data when covariates are time-dependent longitudinal variables and, furthermore, may suffer measurement errors. For estimation, we investigate the maximum likelihood approach, and an EM algorithm is developed. Simulation results show that the proposed method is appropriate for practical application, and an illustrative example is provided.