Meiosis is a highly complex process significantly influenced by transcriptional regulation.However,studies on the mechanisms that govern transcriptomic changes during meiosis,especially in prophase I,are limited.Here,...Meiosis is a highly complex process significantly influenced by transcriptional regulation.However,studies on the mechanisms that govern transcriptomic changes during meiosis,especially in prophase I,are limited.Here,we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene spermatocytes.This event,conserved in mice,involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional onset.Furthermore,we identified 282 transcriptional regulators(TRs)that underwent activation or deactivation subsequent to this process.Evidence suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes,while secreted ENHO signals may alter metabolic patterns in these cells.Our results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia(NOA).This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.展开更多
Objective:To explore the function and mechanism of microRNA-155 to regulate the angiogenesis after the cerebral infarction of rats through the angiotensin Ⅱ receptor 1(AT1R)/vascular endothelial growth factor(VEGF) s...Objective:To explore the function and mechanism of microRNA-155 to regulate the angiogenesis after the cerebral infarction of rats through the angiotensin Ⅱ receptor 1(AT1R)/vascular endothelial growth factor(VEGF) signaling pathway.Methods:Female SD rats were chosen for the construction of cerebral infarction model of rats using the modified right middle cerebral artery occlusion.The real-time PCR(RT-PCR) method was employed to detect the expression of microRNA-155 in each group at different time points after the cerebral infarction(1 h,I d,3 d and 7 d).SD rats were randomly divided into four groups(n=20 rats):sham operation group(Sham group),MACO group,MACO+microRNA-155 mimic group,and MACO+microRNA-155 inhibitor group.Sham group was given the free graft,while MACO+microRNA-155 mimic group and MACO+microRNA-155 inhibitor group were treated with microRNA-155 mimic and microRNA-155 inhibitor respectively.The Zea Longa5-point scale was used to score the neurologic impairment of rats in each group;2,3,5-triphenyl tetrazolium chloride staining to evaluate the volume of cerebral infarction of rats in each group;the immunohistochemistry to detect the expression of CD31;Western blot and RT-PCR to detect the expression of AT1 R and VEGF receptor 2(VEGFR2).Results:The expression of microRNA-155 was increased in the cerebral ischemia tissue after the cerebral infarction.It was significantly increased at 1 d of ischemia and maintained at the high level for a long time.Rats in the Sham group had no symptom of neurologic impairment while rats in the MACO group had the obvious neurologic impairment.After being treated with microRNA-155 inhibitor,the neural function of MACO rats had been improved,with the decreased area of cerebral infarction.But after being treated with microRNA-155 mimic,the neural function was further worsened,with the increased area of cerebral infarction.Results of immunohistoehemical assay indicated that microRNA-155 inhibitor could up-regulate the expression of CD31,while microRNA-155 mimic could down-regulate the expression of CD31.The RT-PCR found that,after being treated with microRNA-155 inhibitor,MACO rats had the increased expression of ATIR and VEGFR2 messenger RNA(mRNA);but after being treated with microRNA-155 mimic,the expression of ATIR and VEGFR2 mRNA was decreased.Results of Western blot showed that,after being treated with microRNA-155 inhibitor,MACO rats had the increased expression of ATIR and VEGFR2 mRNA;but after being treated with microRNA-155 mimic,the expression of ATIR and VEGFR2 mRNA was decreased.Conclusions:The inhibition of microRNA-155 can improve the neurologic impairment of rats with the cerebral infarction,reduce the volume of cerebral infarction and effectively promote the angiogenesis in the region of ischemia,which may be mediated through AT1R/VEGFR2 pathway.展开更多
To solve the problem that the existing acoustic emission(AE) source location algorithms cannot always obtain accurate results for multilayer cylindrical media,a new acoustic emission source location method considering...To solve the problem that the existing acoustic emission(AE) source location algorithms cannot always obtain accurate results for multilayer cylindrical media,a new acoustic emission source location method considering refraction was proposed.AE source coordinates were solved by the complex method.Pencil-lead-break experiments were used to verify this method.The absolute distance errors of location results are less than 3 mm,much less than those by the traditional method.The numerical experiments were used to further analyze factors that affect location accuracy.The results of numerical experiments show that the location accuracy of the proposed method is not affected by the ratio of wave velocities but affected by the measurement accuracy of wave velocity.These results show that new method can obtain accurate AE source location in the two-layered cylindrical surface media such as the triaxial compression test.展开更多
BACKGROUND Pancreatic ductal cancer(PDAC)has high malignancy and poor prognosis.Long noncoding RNAs(lncRNAs)are associated with high levels of malignancy,including PDAC.However,the biological and clinical significance...BACKGROUND Pancreatic ductal cancer(PDAC)has high malignancy and poor prognosis.Long noncoding RNAs(lncRNAs)are associated with high levels of malignancy,including PDAC.However,the biological and clinical significance of negative regulator of antiviral response(NRAV)in PDAC is unclear.AIM To study the regulatory role of lncRNA NRAV in PDAC.METHODS GEPIA analyzed lncRNA NRAV and miRNA(miR-299-3p)expression levels in PDAC tissues and measured them in PDAC cells by quantitative measurements in real time.The specific role of NRAV and miR-299-3p in cell proliferation and transfer potential was evaluated by cell formation analysis,Cell Counting Kit-8 and Transwell analysis.The relationship between NRAV and miR-299-3p was studied by predictive bioinformatics,RNA immunoassay,and fluorescence enzyme analysis.In vivo experiments included transplantation of simulated tumor cells under naked mice.RESULTS The expression level of lncRNA NRAV was higher in both tumor tissues and cell lines of PDAC and was negatively associated with the clinical survival of PDAC patients.Functionally,overexpression of NRAV promoted cell proliferation and metastasis of PDAC cells,while knockdown of NRAV reversed these effects.Finally,NRAV was performed as a molecular sponge of miR-299-3p.Moreover,overexpression of miR-299-3p could reverse the promoting effects of NRAV on cell proliferation and metastasis of PDAC cells.CONCLUSION NRAV facilitates progression of PDAC as a molecular sponge of miR-299-3p and may be a potential molecular marker for diagnosis and treatment of PDAC.展开更多
The divergence and continuous evolution of plants and animals contribute to ecological diversity.Promoters and transcription factors(TFs) are key determinants of gene regulation and transcription throughoutlife.Howeve...The divergence and continuous evolution of plants and animals contribute to ecological diversity.Promoters and transcription factors(TFs) are key determinants of gene regulation and transcription throughoutlife.However,theevolutionary trajectories and relationships of promoters and TFs are still poorly understood. Here, we conducted extensive analysis of large-scale multi-omics sequences in 420 animal species and 223 plant species spanning nearly a billion years of evolutionary history. Results showed that promoter GC-contentandTFisoelectricpoints,as features/signatures that accompany long biological evolution, exhibited increasing growth in animal cells but a decreasing trend in plant cells. Furthermore, the evolutionary trajectories of promoter and TF signatures in the animal kingdom provided further evidence that Mammalia as well as Aves evolved directly from the ancestor Reptilia. The strong correlation between promoter and TF signatures indicates that promoters and TFs formed antagonistic coevolution in the animal kingdom, but mutualistic coevolution in the plant kingdom. The distinct coevolutionary patterns potentially drive the plant-animal divergence, divergent evolution and ecological diversity.展开更多
Adverse nutritional conditions during the perinatal stage are related to early menopause in adulthood;however,the underlying mechanism is still unclear.Herein,we revealed that colostrum-activated ketone body elevation...Adverse nutritional conditions during the perinatal stage are related to early menopause in adulthood;however,the underlying mechanism is still unclear.Herein,we revealed that colostrum-activated ketone body elevation during the postnatal stage regulated primordial follicle reservoir size and then affected ovarian ageing.We found that the expression of the ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2(Hmgcs2)was largely enhanced during primordial follicle pool formation after birth and might be activated in the ovaries by colostrum.Reactive oxygen species(ROS)elevation in the ovaries leads to follicle apoptosis to deplete damaged follicles,while Hmgcs2 deficiency enhances follicle apoptosis and thus decreases the size of the primordial follicle pool and leads to premature ovarian ageing(POA),which might be related to the activation of cellular endogenous antioxidant system.All these defects could be rescued by ketone body administration,which suppressed ROS-activated follicle apoptosis.Our results suggest that the internal metabolic homeostasis of newborn mice is critical for the primordial reservoir and that any intrauterine and perinatal undernutrition could result in POA.展开更多
Dystocia is a serious problem for pregnant women, and it increases the cesarean section rate. Although uterine dysfunction has an unknown etiology, it is responsible for cesarean delivery and clinical dystocia, result...Dystocia is a serious problem for pregnant women, and it increases the cesarean section rate. Although uterine dysfunction has an unknown etiology, it is responsible for cesarean delivery and clinical dystocia, resulting in neonatal morbidity and mortality;thus, there is an urgent need for novel therapeutic agents. Previous studies indicated that statins, which inhibit the mevalonate (MVA) pathway of cholesterol synthesis, can reduce the incidence of preterm birth, but the safety of statins for pregnant women has not been thoroughly evaluated. Therefore, to unambiguously examine the function of the MVA pathway in pregnancy and delivery, we employed a genetic approach by using myometrial cell-specific deletion of geranylgeranyl pyrophosphate synthase (Ggps1) mice. We found that Ggps1 deficiency in myometrial cells caused impaired uterine contractions, resulting in disrupted embryonic placing and dystocia. Studies of the underlying mechanism suggested that Ggps1 is required for uterine contractions to ensure successful parturition by regulating RhoA prenylation to activate the RhoA/Rock2/p-MLC pathway. Our work indicates that perturbing the MVA pathway might result in problems during delivery for pregnant females, but modifying protein prenylation with supplementary farnesyl pyrophosphate or geranylgeranyl pyrophosphate might be a strategy to avoid side effects.展开更多
基金supported by the National Natural Science Foundation of China(82271645)National Key Research and Development Program of China(2021YFC2700200 to F.S.)。
文摘Meiosis is a highly complex process significantly influenced by transcriptional regulation.However,studies on the mechanisms that govern transcriptomic changes during meiosis,especially in prophase I,are limited.Here,we performed single-cell ATAC-seq of human testis tissues and observed reprogramming during the transition from zygotene to pachytene spermatocytes.This event,conserved in mice,involved the deactivation of genes associated with meiosis after reprogramming and the activation of those related to spermatogenesis before their functional onset.Furthermore,we identified 282 transcriptional regulators(TRs)that underwent activation or deactivation subsequent to this process.Evidence suggested that physical contact signals from Sertoli cells may regulate these TRs in spermatocytes,while secreted ENHO signals may alter metabolic patterns in these cells.Our results further indicated that defective transcriptional reprogramming may be associated with non-obstructive azoospermia(NOA).This study revealed the importance of both physical contact and secreted signals between Sertoli cells and germ cells in meiotic progression.
基金supported by Shandong Key Scientific and Technological Project Fund(No.2013YD 18021)
文摘Objective:To explore the function and mechanism of microRNA-155 to regulate the angiogenesis after the cerebral infarction of rats through the angiotensin Ⅱ receptor 1(AT1R)/vascular endothelial growth factor(VEGF) signaling pathway.Methods:Female SD rats were chosen for the construction of cerebral infarction model of rats using the modified right middle cerebral artery occlusion.The real-time PCR(RT-PCR) method was employed to detect the expression of microRNA-155 in each group at different time points after the cerebral infarction(1 h,I d,3 d and 7 d).SD rats were randomly divided into four groups(n=20 rats):sham operation group(Sham group),MACO group,MACO+microRNA-155 mimic group,and MACO+microRNA-155 inhibitor group.Sham group was given the free graft,while MACO+microRNA-155 mimic group and MACO+microRNA-155 inhibitor group were treated with microRNA-155 mimic and microRNA-155 inhibitor respectively.The Zea Longa5-point scale was used to score the neurologic impairment of rats in each group;2,3,5-triphenyl tetrazolium chloride staining to evaluate the volume of cerebral infarction of rats in each group;the immunohistochemistry to detect the expression of CD31;Western blot and RT-PCR to detect the expression of AT1 R and VEGF receptor 2(VEGFR2).Results:The expression of microRNA-155 was increased in the cerebral ischemia tissue after the cerebral infarction.It was significantly increased at 1 d of ischemia and maintained at the high level for a long time.Rats in the Sham group had no symptom of neurologic impairment while rats in the MACO group had the obvious neurologic impairment.After being treated with microRNA-155 inhibitor,the neural function of MACO rats had been improved,with the decreased area of cerebral infarction.But after being treated with microRNA-155 mimic,the neural function was further worsened,with the increased area of cerebral infarction.Results of immunohistoehemical assay indicated that microRNA-155 inhibitor could up-regulate the expression of CD31,while microRNA-155 mimic could down-regulate the expression of CD31.The RT-PCR found that,after being treated with microRNA-155 inhibitor,MACO rats had the increased expression of ATIR and VEGFR2 messenger RNA(mRNA);but after being treated with microRNA-155 mimic,the expression of ATIR and VEGFR2 mRNA was decreased.Results of Western blot showed that,after being treated with microRNA-155 inhibitor,MACO rats had the increased expression of ATIR and VEGFR2 mRNA;but after being treated with microRNA-155 mimic,the expression of ATIR and VEGFR2 mRNA was decreased.Conclusions:The inhibition of microRNA-155 can improve the neurologic impairment of rats with the cerebral infarction,reduce the volume of cerebral infarction and effectively promote the angiogenesis in the region of ischemia,which may be mediated through AT1R/VEGFR2 pathway.
基金Project(2015CB060200)supported by the National Basic Research Program of ChinaProject(41772313)supported by the National Natural Science Foundation of China+1 种基金Project(MDPC201803)supported by the Open Fund Research Program of State Key Laboratory of Mining Disaster Prevention and Control Co-founded by Shandong Province and the Ministry of Science and Technology,ChinaProject(2019zzts308)supported by the Fundamental Research Fund for the Central Universities of Central South University,China
文摘To solve the problem that the existing acoustic emission(AE) source location algorithms cannot always obtain accurate results for multilayer cylindrical media,a new acoustic emission source location method considering refraction was proposed.AE source coordinates were solved by the complex method.Pencil-lead-break experiments were used to verify this method.The absolute distance errors of location results are less than 3 mm,much less than those by the traditional method.The numerical experiments were used to further analyze factors that affect location accuracy.The results of numerical experiments show that the location accuracy of the proposed method is not affected by the ratio of wave velocities but affected by the measurement accuracy of wave velocity.These results show that new method can obtain accurate AE source location in the two-layered cylindrical surface media such as the triaxial compression test.
基金Supported by the National Natural Science Foundation of China,No.81974372
文摘BACKGROUND Pancreatic ductal cancer(PDAC)has high malignancy and poor prognosis.Long noncoding RNAs(lncRNAs)are associated with high levels of malignancy,including PDAC.However,the biological and clinical significance of negative regulator of antiviral response(NRAV)in PDAC is unclear.AIM To study the regulatory role of lncRNA NRAV in PDAC.METHODS GEPIA analyzed lncRNA NRAV and miRNA(miR-299-3p)expression levels in PDAC tissues and measured them in PDAC cells by quantitative measurements in real time.The specific role of NRAV and miR-299-3p in cell proliferation and transfer potential was evaluated by cell formation analysis,Cell Counting Kit-8 and Transwell analysis.The relationship between NRAV and miR-299-3p was studied by predictive bioinformatics,RNA immunoassay,and fluorescence enzyme analysis.In vivo experiments included transplantation of simulated tumor cells under naked mice.RESULTS The expression level of lncRNA NRAV was higher in both tumor tissues and cell lines of PDAC and was negatively associated with the clinical survival of PDAC patients.Functionally,overexpression of NRAV promoted cell proliferation and metastasis of PDAC cells,while knockdown of NRAV reversed these effects.Finally,NRAV was performed as a molecular sponge of miR-299-3p.Moreover,overexpression of miR-299-3p could reverse the promoting effects of NRAV on cell proliferation and metastasis of PDAC cells.CONCLUSION NRAV facilitates progression of PDAC as a molecular sponge of miR-299-3p and may be a potential molecular marker for diagnosis and treatment of PDAC.
基金supported by the National Key Research and Development Program of China (2017YFA0505500 to L.N.C., 2017YFC0909502 to J.S.Z.)Strategic Priority Research Program of the Chinese Academy of Sciences (XDB38040400 to L.N.C., XDB13000000 to W.W.)+3 种基金National Science Foundation of China (12131020 and 31930022 to L.N.C, 61602460 to J.S.Z.)Major Key Project of PCL (PCL2021A12 to L.N.C.)Special Fund for Science and Technology Innovation Strategy of Guangdong Province(2021B0909050004 and 2021B0909060002 to L.N.C.)Fundamental Research Funds for the Central Universities(3102019JC007 to W.W.)。
文摘The divergence and continuous evolution of plants and animals contribute to ecological diversity.Promoters and transcription factors(TFs) are key determinants of gene regulation and transcription throughoutlife.However,theevolutionary trajectories and relationships of promoters and TFs are still poorly understood. Here, we conducted extensive analysis of large-scale multi-omics sequences in 420 animal species and 223 plant species spanning nearly a billion years of evolutionary history. Results showed that promoter GC-contentandTFisoelectricpoints,as features/signatures that accompany long biological evolution, exhibited increasing growth in animal cells but a decreasing trend in plant cells. Furthermore, the evolutionary trajectories of promoter and TF signatures in the animal kingdom provided further evidence that Mammalia as well as Aves evolved directly from the ancestor Reptilia. The strong correlation between promoter and TF signatures indicates that promoters and TFs formed antagonistic coevolution in the animal kingdom, but mutualistic coevolution in the plant kingdom. The distinct coevolutionary patterns potentially drive the plant-animal divergence, divergent evolution and ecological diversity.
基金supported by the National Key Research and Development Program of China(2018YFC1004703).
文摘Adverse nutritional conditions during the perinatal stage are related to early menopause in adulthood;however,the underlying mechanism is still unclear.Herein,we revealed that colostrum-activated ketone body elevation during the postnatal stage regulated primordial follicle reservoir size and then affected ovarian ageing.We found that the expression of the ketogenesis rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA synthase 2(Hmgcs2)was largely enhanced during primordial follicle pool formation after birth and might be activated in the ovaries by colostrum.Reactive oxygen species(ROS)elevation in the ovaries leads to follicle apoptosis to deplete damaged follicles,while Hmgcs2 deficiency enhances follicle apoptosis and thus decreases the size of the primordial follicle pool and leads to premature ovarian ageing(POA),which might be related to the activation of cellular endogenous antioxidant system.All these defects could be rescued by ketone body administration,which suppressed ROS-activated follicle apoptosis.Our results suggest that the internal metabolic homeostasis of newborn mice is critical for the primordial reservoir and that any intrauterine and perinatal undernutrition could result in POA.
基金This work was supported by the National Natural Science Foundation of China(31530046)the National Science and Technology Major Project(SQ2018YFC100242).
文摘Dystocia is a serious problem for pregnant women, and it increases the cesarean section rate. Although uterine dysfunction has an unknown etiology, it is responsible for cesarean delivery and clinical dystocia, resulting in neonatal morbidity and mortality;thus, there is an urgent need for novel therapeutic agents. Previous studies indicated that statins, which inhibit the mevalonate (MVA) pathway of cholesterol synthesis, can reduce the incidence of preterm birth, but the safety of statins for pregnant women has not been thoroughly evaluated. Therefore, to unambiguously examine the function of the MVA pathway in pregnancy and delivery, we employed a genetic approach by using myometrial cell-specific deletion of geranylgeranyl pyrophosphate synthase (Ggps1) mice. We found that Ggps1 deficiency in myometrial cells caused impaired uterine contractions, resulting in disrupted embryonic placing and dystocia. Studies of the underlying mechanism suggested that Ggps1 is required for uterine contractions to ensure successful parturition by regulating RhoA prenylation to activate the RhoA/Rock2/p-MLC pathway. Our work indicates that perturbing the MVA pathway might result in problems during delivery for pregnant females, but modifying protein prenylation with supplementary farnesyl pyrophosphate or geranylgeranyl pyrophosphate might be a strategy to avoid side effects.
