Historical desertification of the Mu Us Sandy Land is linked to both environmental changes and anthropogenic activities. This paper reports on an analysis of grain size parameters as indicative of such changes in the ...Historical desertification of the Mu Us Sandy Land is linked to both environmental changes and anthropogenic activities. This paper reports on an analysis of grain size parameters as indicative of such changes in the southwestern area of the Mu Us Sandy Land. Combined with analysis of chronologies and historical records, our results indicate that Beidachi Lake and a nearby season- al river have retreated continuously in history and that sand dunes appeared at approximately the end of the Ming dynasty. This study sheds new light on the understanding of spatial-temporal changes of the interior Mu Us Sandy Land in history and has great significance in revealing environmental changes of the interior region of the Mu Us Sandy Land.展开更多
Brugada syndrome(BrS)is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death.Considering that its heterogeneity in clinical manifestations may result from genetic bac...Brugada syndrome(BrS)is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death.Considering that its heterogeneity in clinical manifestations may result from genetic background,the application of patient-specific induced pluripotent stem cell-derived cardiomyocytes(iPSC-CMs)may help to reveal cell phenotype characteristics underlying different genetic variations.Here,to verify and compare the pathogenicity of mutations(SCN5A c.4213G>A and SCN1B c.590C>T)identified from two BrS patients,we generated two novel BrS iPS cell lines that carried missense mutations in SCN5A or SCN1B,compared their structures and electrophysiology,and evaluated the safety of quinidine in patient-specific iPSC-derived CMs.Compared to the control group,BrS-CMs showed a significant reduction in sodium current,prolonged action potential duration,and varying degrees of decreased Vmax,but no structural difference.After applying different concentrations of quinidine,drug-induced cardiotoxicity was not observed within 3-fold unbound effective therapeutic plasma concentration(ETPC).The data presented proved that iPSC-CMs with variants in SCN5A c.4213G>A or SCN1B c.590C>T are able to recapitulate single-cell phenotype features of BrS and respond appropriately to quinidine without increasing incidence of arrhythmic events.展开更多
Objective Mutations in polymerase gamma gene(POLG)are believed to be an important cause of early and juvenile onset of non-syndromic intractable epilepsy.The aim of this study is to investigate the incidence/prevalenc...Objective Mutations in polymerase gamma gene(POLG)are believed to be an important cause of early and juvenile onset of non-syndromic intractable epilepsy.The aim of this study is to investigate the incidence/prevalence of POLG pathogenic variants in epilespy patients of Han population through sequencing it.Methods Han Chinese patients with seizures prior valproic acid(VPA)exposure at Shanghai Children\Hospital were collected from 2015 to 2019.The clinical diagnosis was based on the 2014 Consensus Statement of Epilepsy by the International League against Epilepsy(ILAE).Blood sampling were performed before VPA treatment.The POLG gene DNA was sequenced by either the first or the next generation sequencing(NGS).The POLG variant burden was illustrated.Liver functions were tested to describe whether they experienced VPA toxicity.Results Ibtally 216 Han Chinese patients were included,aged from 1 month to IS years old,102 were male and 114 were female.The onset age was 1 month old to 13 years old,and the epilepsy course ranged from 2 weeks to about 3 years.VPA treatment was delivered for the generalized or intractable partial seizures at standard dosage.No patient experienced hepatic toxicity following VPA exposure.DNA sequencing data showed no patient had either a homozygous mutation or compound heterozygous mutation of POLG.Single heterozygous mutations of c.1150G>T and p.D384Y were found in 2 patients,and single heterozygous mutation of c.l56_158dupGCA was found in 1 patient.None of these variants showed clinical significance.Conclusions Functional modifying POLG homozygous mutations and compound heterozygous mutations were not detected and VPA toxicity was not seen in the current study.POLG mutation frequency might be rare in Han Chinese,and standard VPA.therapeutic dosage might be safe for Han Chinese patients.展开更多
The repose angle is one of the most significant macroscopic parameters in describing the behavior of granular materials. Under a static condition, the repose angle is the steepest angle at which sediment particles can...The repose angle is one of the most significant macroscopic parameters in describing the behavior of granular materials. Under a static condition, the repose angle is the steepest angle at which sediment particles can rest without motion. In this paper, we use existing data and aeolian physics to analyze the main factors that influence the repose angle of sand dunes, and we investigate different repose angles involving various states and types of materials. We have determined that different factors have differential influence on the magnitude of the repose angle. Our results show that for powdery (〈400-μm diameter) desert sands, the main influential factor on the magnitude of repose angle is the molecular force among particles. Particle size does not influence the repose angle of desert sands directly, but has an indirect impact by affecting the grit sphericity and surface roughness, of which the grit sphericity acts as a major factor. Even at the same average particle size, the repose angle differs with different grain compositions. Furthermore, with increasing unevenness in grain composition, the repose angle increases correspondingly. Sand texture also has a direct influence on the repose angle of desert sands. In two sand samples having the same grain composition but different textures, the repose angles may be different. Water content has a stronger influence on the repose angle than any other factor. However, the relationship between the repose angle and water content is not a simple direct proportion. In fact, with increasing water content, the repose angle first increases and then decreases. These research results will be useful for understanding the mechanisms of dune transport, variations of dune morphology, and the stability and fluidity of dune sands.展开更多
基金supported by National Natural Science Foundation of China (41101187)the Specialized Research Fund for the Doctoral Program of Higher Education (20100211120006)+2 种基金the Ministry of Education, Humanities and Social Science Projects (10YJCZH053)the Fundamental Research Funds for the Central Universities (LZUJBKY-2012-136)the National Science Foundation for Post-Doctoral Scientists of China (2012M512051)
文摘Historical desertification of the Mu Us Sandy Land is linked to both environmental changes and anthropogenic activities. This paper reports on an analysis of grain size parameters as indicative of such changes in the southwestern area of the Mu Us Sandy Land. Combined with analysis of chronologies and historical records, our results indicate that Beidachi Lake and a nearby season- al river have retreated continuously in history and that sand dunes appeared at approximately the end of the Ming dynasty. This study sheds new light on the understanding of spatial-temporal changes of the interior Mu Us Sandy Land in history and has great significance in revealing environmental changes of the interior region of the Mu Us Sandy Land.
基金supported by the Natural Science Foundation of Jiangsu Province of China(Grant No.BK20160134 to LW and BK20191071 to CC)National Natural and Science Foundation of China(Grant No.81900295 to CC)Special Foundation for Clinical Science and Technology of Jiangsu Province(Grant No.BE2017754 to HWC).
文摘Brugada syndrome(BrS)is a complex genetic cardiac ion channel disease that causes a high predisposition to sudden cardiac death.Considering that its heterogeneity in clinical manifestations may result from genetic background,the application of patient-specific induced pluripotent stem cell-derived cardiomyocytes(iPSC-CMs)may help to reveal cell phenotype characteristics underlying different genetic variations.Here,to verify and compare the pathogenicity of mutations(SCN5A c.4213G>A and SCN1B c.590C>T)identified from two BrS patients,we generated two novel BrS iPS cell lines that carried missense mutations in SCN5A or SCN1B,compared their structures and electrophysiology,and evaluated the safety of quinidine in patient-specific iPSC-derived CMs.Compared to the control group,BrS-CMs showed a significant reduction in sodium current,prolonged action potential duration,and varying degrees of decreased Vmax,but no structural difference.After applying different concentrations of quinidine,drug-induced cardiotoxicity was not observed within 3-fold unbound effective therapeutic plasma concentration(ETPC).The data presented proved that iPSC-CMs with variants in SCN5A c.4213G>A or SCN1B c.590C>T are able to recapitulate single-cell phenotype features of BrS and respond appropriately to quinidine without increasing incidence of arrhythmic events.
文摘Objective Mutations in polymerase gamma gene(POLG)are believed to be an important cause of early and juvenile onset of non-syndromic intractable epilepsy.The aim of this study is to investigate the incidence/prevalence of POLG pathogenic variants in epilespy patients of Han population through sequencing it.Methods Han Chinese patients with seizures prior valproic acid(VPA)exposure at Shanghai Children\Hospital were collected from 2015 to 2019.The clinical diagnosis was based on the 2014 Consensus Statement of Epilepsy by the International League against Epilepsy(ILAE).Blood sampling were performed before VPA treatment.The POLG gene DNA was sequenced by either the first or the next generation sequencing(NGS).The POLG variant burden was illustrated.Liver functions were tested to describe whether they experienced VPA toxicity.Results Ibtally 216 Han Chinese patients were included,aged from 1 month to IS years old,102 were male and 114 were female.The onset age was 1 month old to 13 years old,and the epilepsy course ranged from 2 weeks to about 3 years.VPA treatment was delivered for the generalized or intractable partial seizures at standard dosage.No patient experienced hepatic toxicity following VPA exposure.DNA sequencing data showed no patient had either a homozygous mutation or compound heterozygous mutation of POLG.Single heterozygous mutations of c.1150G>T and p.D384Y were found in 2 patients,and single heterozygous mutation of c.l56_158dupGCA was found in 1 patient.None of these variants showed clinical significance.Conclusions Functional modifying POLG homozygous mutations and compound heterozygous mutations were not detected and VPA toxicity was not seen in the current study.POLG mutation frequency might be rare in Han Chinese,and standard VPA.therapeutic dosage might be safe for Han Chinese patients.
基金supported by the National Natural Science Foundation of China (Grant No. 50879033)the National Science Fund for Fostering Talents in Basic Research of the National Natural Science Foundation of China (Grant No.J0730536)
文摘The repose angle is one of the most significant macroscopic parameters in describing the behavior of granular materials. Under a static condition, the repose angle is the steepest angle at which sediment particles can rest without motion. In this paper, we use existing data and aeolian physics to analyze the main factors that influence the repose angle of sand dunes, and we investigate different repose angles involving various states and types of materials. We have determined that different factors have differential influence on the magnitude of the repose angle. Our results show that for powdery (〈400-μm diameter) desert sands, the main influential factor on the magnitude of repose angle is the molecular force among particles. Particle size does not influence the repose angle of desert sands directly, but has an indirect impact by affecting the grit sphericity and surface roughness, of which the grit sphericity acts as a major factor. Even at the same average particle size, the repose angle differs with different grain compositions. Furthermore, with increasing unevenness in grain composition, the repose angle increases correspondingly. Sand texture also has a direct influence on the repose angle of desert sands. In two sand samples having the same grain composition but different textures, the repose angles may be different. Water content has a stronger influence on the repose angle than any other factor. However, the relationship between the repose angle and water content is not a simple direct proportion. In fact, with increasing water content, the repose angle first increases and then decreases. These research results will be useful for understanding the mechanisms of dune transport, variations of dune morphology, and the stability and fluidity of dune sands.