Background Fatty liver disease causes huge economic losses in the poultry industry due to its high occurrence and lethality rate.Three-dimensional(3D)chromatin architecture takes part in disease processing by regulati...Background Fatty liver disease causes huge economic losses in the poultry industry due to its high occurrence and lethality rate.Three-dimensional(3D)chromatin architecture takes part in disease processing by regulating tran-scriptional reprogramming.The study is carried out to investigate the alterations of hepatic 3D genome and H3K27ac profiling in early fatty liver(FLS)and reveal their effect on hepatic transcriptional reprogramming in laying hens.Results Results show that FLS model is constructed with obvious phenotypes including hepatic visible lipid deposi-tion as well as higher total triglyceride and cholesterol in serum.A/B compartment switching,topologically associat-ing domain(TAD)and chromatin loop changes are identified by high-throughput/resolution chromosome conforma-tion capture(HiC)technology.Targeted genes of these alternations in hepatic 3D genome organization significantly enrich pathways related to lipid metabolism and hepatic damage.H3K27ac differential peaks and differential expres-sion genes(DEGs)identified through RNA-seq analysis are also enriched in these pathways.Notably,certain DEGs are found to correspond with changes in 3D chromatin structure and H3K27ac binding in their promoters.DNA motif analysis reveals that candidate transcription factors are implicated in regulating transcriptional reprogram-ming.Furthermore,disturbed folate metabolism is observed,as evidenced by lower folate levels and altered enzyme expression.Conclusion Our findings establish a link between transcriptional reprogramming changes and 3D chromatin struc-ture variations during early FLS formation,which provides candidate transcription factors and folate as targets for FLS prevention or treatment.展开更多
目的研究24h血乳酸(Lac)清除率联合外周血中性粒细胞与淋巴细胞比值(NLR)、降钙素原(PCT)对重症监护病房(ICU)重症肺炎患者28 d病死风险的预测价值。方法回顾性选取2017年12月—2021年12月安徽皖北煤电集团总医院78例重症肺炎患者作为...目的研究24h血乳酸(Lac)清除率联合外周血中性粒细胞与淋巴细胞比值(NLR)、降钙素原(PCT)对重症监护病房(ICU)重症肺炎患者28 d病死风险的预测价值。方法回顾性选取2017年12月—2021年12月安徽皖北煤电集团总医院78例重症肺炎患者作为研究对象,根据28d临床结局将其分为病死组27例和存活组51例。比较两组的一般资料、24hLac清除率、NLR、PCT,采用多因素一般Logistic回归模型分析28d内病死的影响因素,采用受试者工作特征(ROC)曲线评估24hLac清除率联合NLR、PCT对28d内病死风险的预测价值。结果两组的性别、年龄、吸烟史、基础疾病、氧合指数、体温、平均动脉压、白细胞计数、血小板计数、抗菌药物使用时间比较,差异均无统计学意义(P>0.05);病死组肺炎严重程度评分(PSI)、急性生理学和慢性健康状况评价Ⅱ(APACHEⅡ)评分、机械通气治疗占比均高于存活组(P<0.05);病死组24 h Lac清除率低于存活组,NLR、PCT水平高于存活组(P<0.05);经多因素一般Logistic回归分析,PSI评分[O^R=9.440(95%CI:4.108,21.697)]、APACHEⅡ评分[O^R=3.904(95%CI:1.699,8.972)]、24 h Lac清除率[O^R=5.068(95%CI:2.205,11.648)]、NLR[O^R=8.199(95%CI:3.567,18.843)]、PCT[O^R=5.766(95%CI:2.509,13.252)]均为28 d内病死的影响因素(P<0.05);ROC曲线分析结果显示,24 h Lac清除率、NLR、PCT预测28 d内病死的最佳截断值为26.10%、5.95和11.27μg/L,敏感性为81.48%(95%CI:0.613,0.930)、59.26%(95%CI:0.390,0.770)、66.67%(95%CI:0.460,0.828),特异性为72.55%(95%CI:0.580,0.837)、82.35%(95%CI:0.686,0.911)、90.20%(95%CI:0.778,0.963),AUC值为0.809(95%CI:0.704,0.889)、0.736(95%CI:0.624,0.830)、0.802(95%CI:0.697,0.884),联合预测的敏感性为92.59%(95%CI:0.742,0.987)、特异性为86.27%(95%CI:0.731,0.938)、AUC值为0.946(95%CI:0.871,0.985)。结论ICU重症肺炎28 d内病死患者的24 h Lac清除率、NLR、PCT明显异常变化,其对预后评估具有良好预测价值。展开更多
Our previous studies have shown that long noncoding RNA(lncRNA)H19 is upregulated in injured rat sciatic nerve during the process of Wallerian degeneration,and that it promotes the migration of Schwann cells and slows...Our previous studies have shown that long noncoding RNA(lncRNA)H19 is upregulated in injured rat sciatic nerve during the process of Wallerian degeneration,and that it promotes the migration of Schwann cells and slows down the growth of dorsal root ganglion axons.However,the mechanism by which lncRNA H19 regulates neural repair and regeneration after peripheral nerve injury remains unclear.In this study,we established a Sprague-Dawley rat model of sciatic nerve transection injury.We performed in situ hybridization and found that at 4–7 days after sciatic nerve injury,lncRNA H19 was highly expressed.At 14 days before injury,adeno-associated virus was intrathecally injected into the L4–L5 foramina to disrupt or overexpress lncRNA H19.After overexpression of lncRNA H19,the growth of newly formed axons from the sciatic nerve was inhibited,whereas myelination was enhanced.Then,we performed gait analysis and thermal pain analysis to evaluate rat behavior.We found that lncRNA H19 overexpression delayed the recovery of rat behavior function,whereas interfering with lncRNA H19 expression improved functional recovery.Finally,we examined the expression of lncRNA H19 downstream target SEMA6D,and found that after lncRNA H19 overexpression,the SEMA6D protein level was increased.These findings suggest that lncRNA H19 regulates peripheral nerve degeneration and regeneration through activating SEMA6D in injured nerves.This provides a new clue to understand the role of lncRNA H19 in peripheral nerve degeneration and regeneration.展开更多
Bile acids are the main body of enterohepatic circulation in vivo.They have essential functions such as emulsifying fat,bacteriostasis and regulating multiple metabolic pathways as signal molecules.However,the assignm...Bile acids are the main body of enterohepatic circulation in vivo.They have essential functions such as emulsifying fat,bacteriostasis and regulating multiple metabolic pathways as signal molecules.However,the assignments of NMR signals for some lowconcentration bile acids are still needed.This study combined 1D nuclear magnetic resonance(NMR)and 2D NMR techniques including 1He1H correlation spectroscopy(COSY),1He1H total correlation spectroscopy(TOCSY),1H J-resolved spectroscopy(J-Res),1He13C heteronuclear single quantum coherence spectroscopy(HSQC),and 1He13C heteronuclear multiple bond correlation spectroscopy(HMBC)to assign the 1H and 13C signals of six bile acids in aqueous solution at physiological pH(~7.4)and nine bile acids in methanol.These data are of importance to the NMR-based studies on lipid digestion,absorption,and metabolism.展开更多
基金funded by the National Science Foundation of China (32372910 and 32102567)the Program for Shaanxi Science&Technology (2022KJXX-13, 2023-YBNY-144, K3031223077 and 2022GD-TSLD-46–0302)
文摘Background Fatty liver disease causes huge economic losses in the poultry industry due to its high occurrence and lethality rate.Three-dimensional(3D)chromatin architecture takes part in disease processing by regulating tran-scriptional reprogramming.The study is carried out to investigate the alterations of hepatic 3D genome and H3K27ac profiling in early fatty liver(FLS)and reveal their effect on hepatic transcriptional reprogramming in laying hens.Results Results show that FLS model is constructed with obvious phenotypes including hepatic visible lipid deposi-tion as well as higher total triglyceride and cholesterol in serum.A/B compartment switching,topologically associat-ing domain(TAD)and chromatin loop changes are identified by high-throughput/resolution chromosome conforma-tion capture(HiC)technology.Targeted genes of these alternations in hepatic 3D genome organization significantly enrich pathways related to lipid metabolism and hepatic damage.H3K27ac differential peaks and differential expres-sion genes(DEGs)identified through RNA-seq analysis are also enriched in these pathways.Notably,certain DEGs are found to correspond with changes in 3D chromatin structure and H3K27ac binding in their promoters.DNA motif analysis reveals that candidate transcription factors are implicated in regulating transcriptional reprogram-ming.Furthermore,disturbed folate metabolism is observed,as evidenced by lower folate levels and altered enzyme expression.Conclusion Our findings establish a link between transcriptional reprogramming changes and 3D chromatin struc-ture variations during early FLS formation,which provides candidate transcription factors and folate as targets for FLS prevention or treatment.
文摘目的研究24h血乳酸(Lac)清除率联合外周血中性粒细胞与淋巴细胞比值(NLR)、降钙素原(PCT)对重症监护病房(ICU)重症肺炎患者28 d病死风险的预测价值。方法回顾性选取2017年12月—2021年12月安徽皖北煤电集团总医院78例重症肺炎患者作为研究对象,根据28d临床结局将其分为病死组27例和存活组51例。比较两组的一般资料、24hLac清除率、NLR、PCT,采用多因素一般Logistic回归模型分析28d内病死的影响因素,采用受试者工作特征(ROC)曲线评估24hLac清除率联合NLR、PCT对28d内病死风险的预测价值。结果两组的性别、年龄、吸烟史、基础疾病、氧合指数、体温、平均动脉压、白细胞计数、血小板计数、抗菌药物使用时间比较,差异均无统计学意义(P>0.05);病死组肺炎严重程度评分(PSI)、急性生理学和慢性健康状况评价Ⅱ(APACHEⅡ)评分、机械通气治疗占比均高于存活组(P<0.05);病死组24 h Lac清除率低于存活组,NLR、PCT水平高于存活组(P<0.05);经多因素一般Logistic回归分析,PSI评分[O^R=9.440(95%CI:4.108,21.697)]、APACHEⅡ评分[O^R=3.904(95%CI:1.699,8.972)]、24 h Lac清除率[O^R=5.068(95%CI:2.205,11.648)]、NLR[O^R=8.199(95%CI:3.567,18.843)]、PCT[O^R=5.766(95%CI:2.509,13.252)]均为28 d内病死的影响因素(P<0.05);ROC曲线分析结果显示,24 h Lac清除率、NLR、PCT预测28 d内病死的最佳截断值为26.10%、5.95和11.27μg/L,敏感性为81.48%(95%CI:0.613,0.930)、59.26%(95%CI:0.390,0.770)、66.67%(95%CI:0.460,0.828),特异性为72.55%(95%CI:0.580,0.837)、82.35%(95%CI:0.686,0.911)、90.20%(95%CI:0.778,0.963),AUC值为0.809(95%CI:0.704,0.889)、0.736(95%CI:0.624,0.830)、0.802(95%CI:0.697,0.884),联合预测的敏感性为92.59%(95%CI:0.742,0.987)、特异性为86.27%(95%CI:0.731,0.938)、AUC值为0.946(95%CI:0.871,0.985)。结论ICU重症肺炎28 d内病死患者的24 h Lac清除率、NLR、PCT明显异常变化,其对预后评估具有良好预测价值。
基金supported by the National Natural Science Foundation of China,Nos.31971277(to DBY),31950410551(to DBY)Scientific Research Foundation for Returned Scholars,Ministry of Education of China(to DBY)+2 种基金a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)(to DBY)the Postgraduate Research&Practice Innovation Program of Jiangsu Province of China,No.KYCX 19-2050(to JS)Jiangsu College Students’Innovation and Entrepreneurship Training Program,No.202213993005Y(to YY)。
文摘Our previous studies have shown that long noncoding RNA(lncRNA)H19 is upregulated in injured rat sciatic nerve during the process of Wallerian degeneration,and that it promotes the migration of Schwann cells and slows down the growth of dorsal root ganglion axons.However,the mechanism by which lncRNA H19 regulates neural repair and regeneration after peripheral nerve injury remains unclear.In this study,we established a Sprague-Dawley rat model of sciatic nerve transection injury.We performed in situ hybridization and found that at 4–7 days after sciatic nerve injury,lncRNA H19 was highly expressed.At 14 days before injury,adeno-associated virus was intrathecally injected into the L4–L5 foramina to disrupt or overexpress lncRNA H19.After overexpression of lncRNA H19,the growth of newly formed axons from the sciatic nerve was inhibited,whereas myelination was enhanced.Then,we performed gait analysis and thermal pain analysis to evaluate rat behavior.We found that lncRNA H19 overexpression delayed the recovery of rat behavior function,whereas interfering with lncRNA H19 expression improved functional recovery.Finally,we examined the expression of lncRNA H19 downstream target SEMA6D,and found that after lncRNA H19 overexpression,the SEMA6D protein level was increased.These findings suggest that lncRNA H19 regulates peripheral nerve degeneration and regeneration through activating SEMA6D in injured nerves.This provides a new clue to understand the role of lncRNA H19 in peripheral nerve degeneration and regeneration.
文摘Bile acids are the main body of enterohepatic circulation in vivo.They have essential functions such as emulsifying fat,bacteriostasis and regulating multiple metabolic pathways as signal molecules.However,the assignments of NMR signals for some lowconcentration bile acids are still needed.This study combined 1D nuclear magnetic resonance(NMR)and 2D NMR techniques including 1He1H correlation spectroscopy(COSY),1He1H total correlation spectroscopy(TOCSY),1H J-resolved spectroscopy(J-Res),1He13C heteronuclear single quantum coherence spectroscopy(HSQC),and 1He13C heteronuclear multiple bond correlation spectroscopy(HMBC)to assign the 1H and 13C signals of six bile acids in aqueous solution at physiological pH(~7.4)and nine bile acids in methanol.These data are of importance to the NMR-based studies on lipid digestion,absorption,and metabolism.
