In 2022,four earthquakes with M_(S)≥6.0 including the Menyuan M_(S)6.9 and Luding M_(S)6.8 earthquakes occurred in the North-South Seismic Zone(NSSZ),which demonstrated high and strong seismicity.Pattern Informatics(...In 2022,four earthquakes with M_(S)≥6.0 including the Menyuan M_(S)6.9 and Luding M_(S)6.8 earthquakes occurred in the North-South Seismic Zone(NSSZ),which demonstrated high and strong seismicity.Pattern Informatics(PI)method,as an effective long and medium term earthquake forecasting method,has been applied to the strong earthquake forecasting in Chinese mainland and results have shown the positive performance.The earthquake catalog with magnitude above M_(S)3.0 since 1970 provided by China Earthquake Networks Center was employed in this study and the Receiver Operating Characteristic(ROC)method was applied to test the forecasting efficiency of the PI method in each selected region related to the North-South Seismic Zone systematically.Based on this,we selected the area with the best ROC testing result and analyzed the evolution process of the PI hotspot map reflecting the small seismic activity pattern prior to the Menyuan M_(S)6.9 and Luding M_(S)6.8 earthquakes.A“forward”forecast for the area was carried out to assess seismic risk.The study shows the following.1)PI forecasting has higher forecasting efficiency in the selected study region where the difference of seismicity in any place of the region is smaller.2)In areas with smaller differences of seismicity,the activity pattern of small earthquakes prior to the Menyuan M_(S)6.9 and Luding M_(S)6.8 earthquakes can be obtained by analyzing the spatio-temporal evolution process of the PI hotspot map.3)The hotspot evolution in and around the southern Tazang fault in the study area is similar to that prior to the strong earthquakes,which suggests the possible seismic hazard in the future.This study could provide some ideas to the seismic hazard assessment in other regions with high seismicity,such as Japan,Californi,Turkey,and Indonesia.展开更多
目的探讨NOTCH3基因第5外显子C260S位点突变导致的伴有皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)家系的临床和影像学...目的探讨NOTCH3基因第5外显子C260S位点突变导致的伴有皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)家系的临床和影像学特征。方法选取2021年12月首都医科大学附属北京同仁医院来自同一家庭的CADASIL患者,对所有患者进行NOTCH3基因测序,回顾性分析患者的临床表现和头颅影像学特征。复习既往文献报道的导致同一位置氨基酸改变的其他突变类型的临床及影像学特征。结果4名家庭成员中,包括先证者(46岁,女)及其两个姐姐(分别为48岁和50岁)和女儿(18岁)。先证者及其父亲、两个姐姐都有偏头痛病史,其中大姐有记忆力减退;先证者患有脑梗死及伴有视觉先兆的偏头痛;先证者女儿体健;先证者父亲因脑梗死去世。4名家庭成员均存在C260S位点的NOTCH3基因突变。既往文献无此位点突变的报道,先证者头颅MRI示右侧脑桥亚急性梗死,颞叶、脑室周围及脑干异常高信号改变,其大姐脑桥可见腔隙性梗死灶。结论NOTCH3基因第5外显子c.778T>A(p.C260S)的罕见突变导致的CADASIL发病时间早,早期会出现认知障碍。合并偏头痛的脑干梗死患者,需警惕CADASIL的可能。展开更多
Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosi...Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.展开更多
基金the National Natural Science Foundation of China Study on the Theory and Methods of Deterministic-Probabilistic(No.U2039207)the National Key Research and Development Program of China‘CSEP China in the Context of China Seismic Experimental Site’(No.2018YFE0109700).
文摘In 2022,four earthquakes with M_(S)≥6.0 including the Menyuan M_(S)6.9 and Luding M_(S)6.8 earthquakes occurred in the North-South Seismic Zone(NSSZ),which demonstrated high and strong seismicity.Pattern Informatics(PI)method,as an effective long and medium term earthquake forecasting method,has been applied to the strong earthquake forecasting in Chinese mainland and results have shown the positive performance.The earthquake catalog with magnitude above M_(S)3.0 since 1970 provided by China Earthquake Networks Center was employed in this study and the Receiver Operating Characteristic(ROC)method was applied to test the forecasting efficiency of the PI method in each selected region related to the North-South Seismic Zone systematically.Based on this,we selected the area with the best ROC testing result and analyzed the evolution process of the PI hotspot map reflecting the small seismic activity pattern prior to the Menyuan M_(S)6.9 and Luding M_(S)6.8 earthquakes.A“forward”forecast for the area was carried out to assess seismic risk.The study shows the following.1)PI forecasting has higher forecasting efficiency in the selected study region where the difference of seismicity in any place of the region is smaller.2)In areas with smaller differences of seismicity,the activity pattern of small earthquakes prior to the Menyuan M_(S)6.9 and Luding M_(S)6.8 earthquakes can be obtained by analyzing the spatio-temporal evolution process of the PI hotspot map.3)The hotspot evolution in and around the southern Tazang fault in the study area is similar to that prior to the strong earthquakes,which suggests the possible seismic hazard in the future.This study could provide some ideas to the seismic hazard assessment in other regions with high seismicity,such as Japan,Californi,Turkey,and Indonesia.
文摘目的探讨NOTCH3基因第5外显子C260S位点突变导致的伴有皮层下梗死和白质脑病的常染色体显性遗传性脑动脉病(cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy,CADASIL)家系的临床和影像学特征。方法选取2021年12月首都医科大学附属北京同仁医院来自同一家庭的CADASIL患者,对所有患者进行NOTCH3基因测序,回顾性分析患者的临床表现和头颅影像学特征。复习既往文献报道的导致同一位置氨基酸改变的其他突变类型的临床及影像学特征。结果4名家庭成员中,包括先证者(46岁,女)及其两个姐姐(分别为48岁和50岁)和女儿(18岁)。先证者及其父亲、两个姐姐都有偏头痛病史,其中大姐有记忆力减退;先证者患有脑梗死及伴有视觉先兆的偏头痛;先证者女儿体健;先证者父亲因脑梗死去世。4名家庭成员均存在C260S位点的NOTCH3基因突变。既往文献无此位点突变的报道,先证者头颅MRI示右侧脑桥亚急性梗死,颞叶、脑室周围及脑干异常高信号改变,其大姐脑桥可见腔隙性梗死灶。结论NOTCH3基因第5外显子c.778T>A(p.C260S)的罕见突变导致的CADASIL发病时间早,早期会出现认知障碍。合并偏头痛的脑干梗死患者,需警惕CADASIL的可能。
基金supported by Jiangsu Provincial Medical Key Discipline,No.ZDXK202217(to CFL)Jiangsu Planned Projects for Postdoctoral Research Funds,No.1601056C(to SL).
文摘Parkinson’s disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction.Gastrointestinal dysfunction can precede the onset of motor symptoms by several years.Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson’s disease,whether it plays a causal role in motor dysfunction,and the mechanism underlying this potential effect,remain unknown.CCAAT/enhancer binding proteinβ/asparagine endopeptidase(C/EBPβ/AEP)signaling,activated by bacterial endotoxin,can promoteα-synuclein transcription,thereby contributing to Parkinson’s disease pathology.In this study,we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling,α-synuclein-related pathology,and motor symptoms using a rotenone-induced mouse model of Parkinson’s disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation.We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier,as well as activation of the C/EBP/AEP pathway,α-synuclein aggregation,and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits.However,treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics.Importantly,we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits,intestinal inflammation,and endotoxemia.Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits,intestinal inflammation,endotoxemia,and intestinal barrier impairment.These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits,C/EBPβ/AEP signaling activation,andα-synuclein-related pathology in a rotenone-induced mouse model of Parkinson’s disease.Additionally,our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson’s disease.
