BACKGROUND Keratosis pilaris is a hereditary abnormal keratosis of the hair follicle orifice.Gray-brown keratotic plugs in the pores and dark red keratotic papules at the openings of hair follicles can be seen,which c...BACKGROUND Keratosis pilaris is a hereditary abnormal keratosis of the hair follicle orifice.Gray-brown keratotic plugs in the pores and dark red keratotic papules at the openings of hair follicles can be seen,which contain coiled hair and are often accompanied by perifollicular erythema and pigmentation.Glycolic acid can correct the abnormalities of hair follicular duct keratosis and eliminate excessive accumulation of keratinocytes.It also promotes skin metabolism and accelerates the melanin metabolism.The therapeutic effect is related to the glycolic acid concentration.AIM To evaluate the efficacy and safety of a high concentration of glycolic acid in the treatment of keratosis pilaris,and to observe the outcomes at 5-year of follow-up.METHODS Twenty-five participants were recruited and areas with typical keratosis pilaris were selected as testing sites.High concentrations of glycolic acid(50%or 70%)were applied to a circular area(d=8 cm,S=50 cm2)and repeated four times,on days 0,20,40 and 60.Before each treatment and 20 d after the last treatment,on days 0,20,40,60,and 80 and at a 5-year follow-up,The number of follicular keratotic papules were counted and the extent of perifollicular erythema and pigmentation was determined.At the same time,the participants provided subjective evaluations of treatment efficacy and safety.RESULTS Treatment effectiveness was indicated by the percentage of keratotic papules in the test site,on days 20,40,60 and 80,which were 8%,12%,36%,and 60%,respectively.Compared with day 0,each difference was significant(P<0.05).Compared with day 0,differences in melanin content(M)in the skin and skin lightness(L)on days 40,60 and 80,the were statistically significant(P<0.05);skin hemoglobin content(E)on days 60 and 80 was statistically different as compared with before treatment(P<0.05).There were no significant differences in the number of keratotic papules,M,L,and E in 9 participants at the 5-year follow-up compared with before treatment(P>0.05%).CONCLUSION A high concentration of glycolic acid significantly improved skin roughness as well as follicular hyperpigmentation of patients with keratosis pilaris.The treatment was relatively safe,but there was no significant difference at the 5-year follow-up compared to before treatment.展开更多
An understanding of the origin of elastic strain is extremely important for both crystalline materials and amorphous materials. Owing to the lack of a long range order in their structure, it is arduous to dynamically ...An understanding of the origin of elastic strain is extremely important for both crystalline materials and amorphous materials. Owing to the lack of a long range order in their structure, it is arduous to dynamically study the elastic mechanism of amorphous materials experimentally at atomic scale compared with their crystalline counterparts. Here, the elastic deformation mechanism of amorphous silica nanowires(NWs) has been studied for the first time via in situ elastic tensile tests in a transmission electron microscope. Radial distribution functions(RDFs) calculated from the corresponding selected area electron diffraction patterns(SAEDPs) at different strains were used to reconstruct a structural model based on the reverse Monte-Carlo(RMC) method. The result interestingly indicates that the elastic strain of silica glass NWs can be mainly attributed to the elastic elongation of the bond length accompanied by a change in the bond angle distribution. This work is useful for understanding the high strength of amorphous materials.展开更多
Autism spectrum disorder(ASD) is defined by impairments of social interaction and the presence of obsessive behaviors. The ''twin'' nonapeptides oxytocin(OXT) and arginine-vasopressin(AVP) are known to play ...Autism spectrum disorder(ASD) is defined by impairments of social interaction and the presence of obsessive behaviors. The ''twin'' nonapeptides oxytocin(OXT) and arginine-vasopressin(AVP) are known to play regulatory roles in social behaviors. However, the plasma levels and behavioral relevance of OXT and AVP in children with ASD have seldom been investigated. It is also unknown whether their mothers have abnormal plasma peptide levels. Here, using well-established methods of neuropeptide measurement and a relatively large sample size, we determined the plasma levels of the two neuropeptides in 85 normal children, 84 children with ASD, and 31 mothers from each group of children.As expected, children with ASD had lower plasma OXT levels than gender-matched controls(P = 0.028). No such difference was found for plasma AVP concentrations. Correlation analysis showed that ASD children with higher plasma OXT concentrations tended to have less impairment of verbal communication(Rho =-0.22,P = 0.076), while those with higher plasma AVP levels tended to have lower levels of repetitive use of objects(Rho =-0.231, P = 0.079). Unlike the findings in children, maternal plasma OXT levels showed no group difference. However, plasma AVP levels in the mothers of ASD children tended to be lower than in the mothers of normal children(P = 0.072). In conclusion, our results suggest that the OXT system is dysregulated in children with ASD, and that OXT and AVP levels in plasma seem to be associated with specific autistic symptoms. The plasma levels of OXT or AVP in mothers and their ASD children did not seem to change in the same direction.展开更多
Beyond glycemic control, applications of glucagon-like peptide-1 receptor (GLP-1r) agonists (GLP-1 RAs) inhibit inflammationand plaque development in murine atherosclerotic models. However, whether they modulate hemat...Beyond glycemic control, applications of glucagon-like peptide-1 receptor (GLP-1r) agonists (GLP-1 RAs) inhibit inflammationand plaque development in murine atherosclerotic models. However, whether they modulate hematopoietic stem/progenitor cells(HSPCs)to prohibit skewed myelopoiesis in hypercholesteremia remains unknown. In this study, GLP-1r expression in fluorescenceactivated cell sorting (FACS)-sorted wild-type HSPCs was determined by capillary western blotting. Bone marrow cells (BMCs)of wild-type or GLP-1r−/− mice were transplanted into lethally irradiated low-density lipoprotein receptor deficient (LDLr−/−)recipients followed by high-fat diet (HFD) for chimerism analysis by FACS. In parallel, LDLr−/− mice were placed on HFD for 6weeks and then treated with saline or Exendin-4 (Ex-4) for another 6 weeks. HSPC frequency and cell cycle were analyzed byFACS, and intracellular metabolite levels were assessed by targeted metabolomics. The results demonstrated that HSPCs expressedGLP-1r and transplantation of GLP-1r−/− BMCs resulted in skewed myelopoiesis in hypercholesterolemic LDLr−/− recipients.In vitro, Ex-4 treatment of FACS-purified HSPCs suppressed cell expansion and granulocyte production induced by LDL. In vivo, Ex-4treatment inhibited plaque progression, suppressed HSPC proliferation, and modified glycolytic and lipid metabolism in HSPCs ofhypercholesteremic LDLr−/− mice. In conclusion, Ex-4 could directly inhibit HSPC proliferation induced by hypercholesteremia.展开更多
Genotyping of structural variations considering copy number variations(CNVs)is an infancy and challenging problem.CNVs,a prevalent form of critical genetic variations that cause abnormal copy numbers of large genomic ...Genotyping of structural variations considering copy number variations(CNVs)is an infancy and challenging problem.CNVs,a prevalent form of critical genetic variations that cause abnormal copy numbers of large genomic regions in cells,often affect transcription and contribute to a variety of diseases.The characteristics of CNVs often lead to the ambiguity and confusion of existing genotyping features and algorithms,which may cause heterozygous variations to be erroneously genotyped as homozygous variations and seriously affect the accuracy of downstream analysis.As the allelic copy number increases,the error rate of genotyping increases sharply.Some instances with different copy numbers play an auxiliary role in the genotyping classification problem,but some will seriously interfere with the accuracy of the model.Motivated by these,we propose a transfer learning-based method to genotype structural variations accurately considering CNVs.The method first divides the instances with different allelic copy numbers and trains the basic machine learning framework with different genotype datasets.It maximizes the weights of the instances that contribute to classification and minimizes the weights of the instances that hinder correct genotyping.By adjusting the weights of the instances with different allelic copy numbers,the contribution of all the instances to genotyping can be maximized,and the genotyping errors of heterozygote variations caused by CNVs can be minimized.We applied the proposed method to both the simulated and real datasets,and compared it to some popular algorithms including GATK,Facets and Gindel.The experimental results demonstrate that the proposed method outperforms the others in terms of accuracy,stability and efficiency.The source codes have been uploaded at github/TrinaZ/CNVtransfer for academic use only.展开更多
文摘BACKGROUND Keratosis pilaris is a hereditary abnormal keratosis of the hair follicle orifice.Gray-brown keratotic plugs in the pores and dark red keratotic papules at the openings of hair follicles can be seen,which contain coiled hair and are often accompanied by perifollicular erythema and pigmentation.Glycolic acid can correct the abnormalities of hair follicular duct keratosis and eliminate excessive accumulation of keratinocytes.It also promotes skin metabolism and accelerates the melanin metabolism.The therapeutic effect is related to the glycolic acid concentration.AIM To evaluate the efficacy and safety of a high concentration of glycolic acid in the treatment of keratosis pilaris,and to observe the outcomes at 5-year of follow-up.METHODS Twenty-five participants were recruited and areas with typical keratosis pilaris were selected as testing sites.High concentrations of glycolic acid(50%or 70%)were applied to a circular area(d=8 cm,S=50 cm2)and repeated four times,on days 0,20,40 and 60.Before each treatment and 20 d after the last treatment,on days 0,20,40,60,and 80 and at a 5-year follow-up,The number of follicular keratotic papules were counted and the extent of perifollicular erythema and pigmentation was determined.At the same time,the participants provided subjective evaluations of treatment efficacy and safety.RESULTS Treatment effectiveness was indicated by the percentage of keratotic papules in the test site,on days 20,40,60 and 80,which were 8%,12%,36%,and 60%,respectively.Compared with day 0,each difference was significant(P<0.05).Compared with day 0,differences in melanin content(M)in the skin and skin lightness(L)on days 40,60 and 80,the were statistically significant(P<0.05);skin hemoglobin content(E)on days 60 and 80 was statistically different as compared with before treatment(P<0.05).There were no significant differences in the number of keratotic papules,M,L,and E in 9 participants at the 5-year follow-up compared with before treatment(P>0.05%).CONCLUSION A high concentration of glycolic acid significantly improved skin roughness as well as follicular hyperpigmentation of patients with keratosis pilaris.The treatment was relatively safe,but there was no significant difference at the 5-year follow-up compared to before treatment.
基金supported by the National Natural Science Foundation of China (51301011 and 11374029)Research Fund for the Doctoral Program of Higher Education of China (20131102120053)+5 种基金Fundamental Research Funds for the Central Universities (YWF-14-HHXY-013)Foundation for the Author of National Excellent Doctoral Dissertation of China (201214)Beijing Nova Program (Z121103002512017)Key Project of National Natural Science Foundation of China (11234011)Henry Fok of the Ministry of Education Fund (141008)Beijing City Board of Education Project (KM201310005009)
文摘An understanding of the origin of elastic strain is extremely important for both crystalline materials and amorphous materials. Owing to the lack of a long range order in their structure, it is arduous to dynamically study the elastic mechanism of amorphous materials experimentally at atomic scale compared with their crystalline counterparts. Here, the elastic deformation mechanism of amorphous silica nanowires(NWs) has been studied for the first time via in situ elastic tensile tests in a transmission electron microscope. Radial distribution functions(RDFs) calculated from the corresponding selected area electron diffraction patterns(SAEDPs) at different strains were used to reconstruct a structural model based on the reverse Monte-Carlo(RMC) method. The result interestingly indicates that the elastic strain of silica glass NWs can be mainly attributed to the elastic elongation of the bond length accompanied by a change in the bond angle distribution. This work is useful for understanding the high strength of amorphous materials.
基金supported by grants from the Research Special Fund for Public Welfare Industry of Health of China (201302002-11)the National Natural Science Foundation of China (81271507)
文摘Autism spectrum disorder(ASD) is defined by impairments of social interaction and the presence of obsessive behaviors. The ''twin'' nonapeptides oxytocin(OXT) and arginine-vasopressin(AVP) are known to play regulatory roles in social behaviors. However, the plasma levels and behavioral relevance of OXT and AVP in children with ASD have seldom been investigated. It is also unknown whether their mothers have abnormal plasma peptide levels. Here, using well-established methods of neuropeptide measurement and a relatively large sample size, we determined the plasma levels of the two neuropeptides in 85 normal children, 84 children with ASD, and 31 mothers from each group of children.As expected, children with ASD had lower plasma OXT levels than gender-matched controls(P = 0.028). No such difference was found for plasma AVP concentrations. Correlation analysis showed that ASD children with higher plasma OXT concentrations tended to have less impairment of verbal communication(Rho =-0.22,P = 0.076), while those with higher plasma AVP levels tended to have lower levels of repetitive use of objects(Rho =-0.231, P = 0.079). Unlike the findings in children, maternal plasma OXT levels showed no group difference. However, plasma AVP levels in the mothers of ASD children tended to be lower than in the mothers of normal children(P = 0.072). In conclusion, our results suggest that the OXT system is dysregulated in children with ASD, and that OXT and AVP levels in plasma seem to be associated with specific autistic symptoms. The plasma levels of OXT or AVP in mothers and their ASD children did not seem to change in the same direction.
基金supported by grants from the National Natural Science Foundation of China(81670765 and 82070841)to Y.F.
文摘Beyond glycemic control, applications of glucagon-like peptide-1 receptor (GLP-1r) agonists (GLP-1 RAs) inhibit inflammationand plaque development in murine atherosclerotic models. However, whether they modulate hematopoietic stem/progenitor cells(HSPCs)to prohibit skewed myelopoiesis in hypercholesteremia remains unknown. In this study, GLP-1r expression in fluorescenceactivated cell sorting (FACS)-sorted wild-type HSPCs was determined by capillary western blotting. Bone marrow cells (BMCs)of wild-type or GLP-1r−/− mice were transplanted into lethally irradiated low-density lipoprotein receptor deficient (LDLr−/−)recipients followed by high-fat diet (HFD) for chimerism analysis by FACS. In parallel, LDLr−/− mice were placed on HFD for 6weeks and then treated with saline or Exendin-4 (Ex-4) for another 6 weeks. HSPC frequency and cell cycle were analyzed byFACS, and intracellular metabolite levels were assessed by targeted metabolomics. The results demonstrated that HSPCs expressedGLP-1r and transplantation of GLP-1r−/− BMCs resulted in skewed myelopoiesis in hypercholesterolemic LDLr−/− recipients.In vitro, Ex-4 treatment of FACS-purified HSPCs suppressed cell expansion and granulocyte production induced by LDL. In vivo, Ex-4treatment inhibited plaque progression, suppressed HSPC proliferation, and modified glycolytic and lipid metabolism in HSPCs ofhypercholesteremic LDLr−/− mice. In conclusion, Ex-4 could directly inhibit HSPC proliferation induced by hypercholesteremia.
基金supported by the National Natural Science Foundation of China (Grant No.31701150)the Fundamental Research Funds for the Central Universities (CXTD2017003).
文摘Genotyping of structural variations considering copy number variations(CNVs)is an infancy and challenging problem.CNVs,a prevalent form of critical genetic variations that cause abnormal copy numbers of large genomic regions in cells,often affect transcription and contribute to a variety of diseases.The characteristics of CNVs often lead to the ambiguity and confusion of existing genotyping features and algorithms,which may cause heterozygous variations to be erroneously genotyped as homozygous variations and seriously affect the accuracy of downstream analysis.As the allelic copy number increases,the error rate of genotyping increases sharply.Some instances with different copy numbers play an auxiliary role in the genotyping classification problem,but some will seriously interfere with the accuracy of the model.Motivated by these,we propose a transfer learning-based method to genotype structural variations accurately considering CNVs.The method first divides the instances with different allelic copy numbers and trains the basic machine learning framework with different genotype datasets.It maximizes the weights of the instances that contribute to classification and minimizes the weights of the instances that hinder correct genotyping.By adjusting the weights of the instances with different allelic copy numbers,the contribution of all the instances to genotyping can be maximized,and the genotyping errors of heterozygote variations caused by CNVs can be minimized.We applied the proposed method to both the simulated and real datasets,and compared it to some popular algorithms including GATK,Facets and Gindel.The experimental results demonstrate that the proposed method outperforms the others in terms of accuracy,stability and efficiency.The source codes have been uploaded at github/TrinaZ/CNVtransfer for academic use only.