The structural integrity of the sperm flagellum is essential for proper sperm function.Flagellar defects can result in male infertility,yet the precise mechanisms underlying this relationship are not fully understood....The structural integrity of the sperm flagellum is essential for proper sperm function.Flagellar defects can result in male infertility,yet the precise mechanisms underlying this relationship are not fully understood.CCDC181,a coiled-coil domain-containing protein,is known to localize on sperm flagella and at the basal regions of motile cilia.Despite this knowledge,the specific functions of CCDC181 in flagellum biogenesis remain unclear.In this study,Ccdc181 knockout mice were generated.The absence of CCDC181 led to defective sperm head shaping and flagellum formation.Furthermore,the Ccdc181 knockout mice exhibited extremely low sperm counts,grossly aberrant sperm morphologies,markedly diminished sperm motility,and typical multiple morphological abnormalities of the flagella(MMAF).Additionally,an interaction between CCDC181 and the MMAF-related protein LRRC46 was identified,with CCDC181 regulating the localization of LRRC46 within sperm flagella.These findings suggest that CCDC181 plays a crucial role in both manchette formation and sperm flagellum biogenesis.展开更多
Poly(St-co-BuA)/silica nanocomposite latexes were synthesized via conventional emulsion polymerization in the presence of 3-(trimethoxysilyl)propyl methacrylate modified colloidal nano-silica. The effects of surfa...Poly(St-co-BuA)/silica nanocomposite latexes were synthesized via conventional emulsion polymerization in the presence of 3-(trimethoxysilyl)propyl methacrylate modified colloidal nano-silica. The effects of surface property, particle size and content of colloidal nano-silica as well as the concentrations of monomer and surfactant on the morphology of nanocomposite latex particles were investigated by transmission electron microscope (TEM) and scanning electron microscope (SEM) in detail. Various interesting morphologies such as grape-like, Chinese gooseberry-like, pomegranate-like and normal core-shell structures were observed. Droplet nucleation mechanism competing with micelle nucleation mechanism was proposed to explain the morphological evolution of the nanocomposite particles.展开更多
Objective:Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impai...Objective:Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for HLD.Methods:Mice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe2+) and trivalent iron (Fe3+) levels, as well as malondialdehyde (MDA), glutathione(GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) stress.Results:Ovarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine,a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron,Fe2+, MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4)expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) pathway.Conclusion:Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress.展开更多
The process of semen collection plays a key role in the quality of semen specimens.However,the association between semen collection time and semen quality is still unclear.In this study,ejaculates by masturbation from...The process of semen collection plays a key role in the quality of semen specimens.However,the association between semen collection time and semen quality is still unclear.In this study,ejaculates by masturbation from 746 subfertile men or healthy men who underwent semen analysis were examined.The median(interquartile range)semen collection time for all participants was 7.0(5.0-11.0)min,and the median time taken for semen collection was lower in healthy men than that in subfertile men(6.0 min vs 7.0 min).An increase in the time required to produce semen samples was associated with poorer semen quality.Among those undergoing assisted reproductive technology(ART),the miscarriage rate was positively correlated with the semen collection time.After adjusting for confounders,the highest quartile(Q4)of collection time was negatively associated with semen volume and sperm concentration.A longer time to produce semen samples(Q3 and Q4)was negatively correlated with progressive and total sperm motility.In addition,there was a significant negative linear association between the semen collection time and the sperm morphology.Higher risks of asthenozoospermia(adjusted odds ratio[OR]=2.06,95%confidence interval[CI]:1.31-3.25,P=0.002)and teratozoospermia(adjusted OR=1.98,95%CI:1.10-3.55,P=0.02)were observed in Q3 than those in Q1.Our results indicate that a higher risk of abnormal semen parameter values was associated with an increase in time for semen collection,which may be related to male fertility through its association with semen quality.展开更多
To the Editor:Hyperuricemia,the second most common metabolic disease after diabetes mellitus in China,is characterized by the elevated serum uric concentration which is due to the overactive uric acid production or un...To the Editor:Hyperuricemia,the second most common metabolic disease after diabetes mellitus in China,is characterized by the elevated serum uric concentration which is due to the overactive uric acid production or underexcretion.[1]Recent study supported the notion that hyperuricemia is implicated in renal tubular injury,subsequent tubulointerstitial fibrosis,and finally gouty nephropathy.[2]However,the lack of a suitable and stable mouse model to study hyperuricemia and gout nephropathy delays and limits the development of mechanism research and new drugs.Further understanding of the pathogenesis of hyperuricemia and gouty nephropathy has been largely hampered by a lack of preclinical animal models that reliably capture the characteristic phenotypes of hyperuricemia and gouty nephropathy.In this study,we aimed to develop a novel mouse model for hyperuricemia and gouty nephropathy.展开更多
Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects.Most cases are due to mutations in genes encoding the components of sperm flagella,which have an ultrastructure similar to that of m...Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects.Most cases are due to mutations in genes encoding the components of sperm flagella,which have an ultrastructure similar to that of motile cilia.Coiled-coil domain containing 103(CCDC103)is an outer dynein arm assembly factor,and pathogenic variants of CCDC103 cause primary ciliary dyskinesia(PCD).However,whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined.Whole-exome sequencing(WES)was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family.A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified(ENST00000035776.2,c.461A>C,p.His154Pro).CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD,though the reproductive phenotype of these PCD individuals is unknown.Transmission electron microscopy(TEM)of affected individuals’spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms,similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation.Thus,our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia.展开更多
Single-handed helical silica nanotubes were prepared according to the literature procedures,using the self-assemblies of a pair of chiral cationic low-molecular-weight gelators as the templates.A chirality indicator,...Single-handed helical silica nanotubes were prepared according to the literature procedures,using the self-assemblies of a pair of chiral cationic low-molecular-weight gelators as the templates.A chirality indicator,4,4'-bis(triethoxysilyl)-1,1'-biphenyl,was developed to determine the chirality of the silica nanotubes.The chirality of the surfaces and the bulky walls of the silica nanotubes were understood from the twist of the biphenylene rings.展开更多
基金supported by the National Natural Science Foundation of China(82071709,81971446,82171599,82374212)Global Select Project(DJK-LX-2022010)of the Institute of Health and Medicine,Hefei Comprehensive National Science CenterJoint Fund for New Medicine of USTC(YD9100002034)。
文摘The structural integrity of the sperm flagellum is essential for proper sperm function.Flagellar defects can result in male infertility,yet the precise mechanisms underlying this relationship are not fully understood.CCDC181,a coiled-coil domain-containing protein,is known to localize on sperm flagella and at the basal regions of motile cilia.Despite this knowledge,the specific functions of CCDC181 in flagellum biogenesis remain unclear.In this study,Ccdc181 knockout mice were generated.The absence of CCDC181 led to defective sperm head shaping and flagellum formation.Furthermore,the Ccdc181 knockout mice exhibited extremely low sperm counts,grossly aberrant sperm morphologies,markedly diminished sperm motility,and typical multiple morphological abnormalities of the flagella(MMAF).Additionally,an interaction between CCDC181 and the MMAF-related protein LRRC46 was identified,with CCDC181 regulating the localization of LRRC46 within sperm flagella.These findings suggest that CCDC181 plays a crucial role in both manchette formation and sperm flagellum biogenesis.
基金This research was financially supported by the Key Project of China Educational Ministry (No. 103064)the Doctoral Foundation of University (No. 20020246031)
文摘Poly(St-co-BuA)/silica nanocomposite latexes were synthesized via conventional emulsion polymerization in the presence of 3-(trimethoxysilyl)propyl methacrylate modified colloidal nano-silica. The effects of surface property, particle size and content of colloidal nano-silica as well as the concentrations of monomer and surfactant on the morphology of nanocomposite latex particles were investigated by transmission electron microscope (TEM) and scanning electron microscope (SEM) in detail. Various interesting morphologies such as grape-like, Chinese gooseberry-like, pomegranate-like and normal core-shell structures were observed. Droplet nucleation mechanism competing with micelle nucleation mechanism was proposed to explain the morphological evolution of the nanocomposite particles.
基金supported by the National Natural Science Foundation of China (No. 82374212, No. 81971446 and No. 81673811)the Clinical Special Translational Project of the Anhui Provincial Science and Technology Department (No. 202204295107020044)the Key Project of the Anhui Provincial Department of Education (No. 2022AH050523)。
文摘Objective:Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for HLD.Methods:Mice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe2+) and trivalent iron (Fe3+) levels, as well as malondialdehyde (MDA), glutathione(GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) stress.Results:Ovarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine,a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron,Fe2+, MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4)expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) pathway.Conclusion:Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress.
基金This study was supported by the National Natural Science Foundation of China(81901543,81971446,81971333 and 82071709)the National Key R&D Program of China(2018YFC1003900)the National Key Research and Development Project(2019YFA0802600).
文摘The process of semen collection plays a key role in the quality of semen specimens.However,the association between semen collection time and semen quality is still unclear.In this study,ejaculates by masturbation from 746 subfertile men or healthy men who underwent semen analysis were examined.The median(interquartile range)semen collection time for all participants was 7.0(5.0-11.0)min,and the median time taken for semen collection was lower in healthy men than that in subfertile men(6.0 min vs 7.0 min).An increase in the time required to produce semen samples was associated with poorer semen quality.Among those undergoing assisted reproductive technology(ART),the miscarriage rate was positively correlated with the semen collection time.After adjusting for confounders,the highest quartile(Q4)of collection time was negatively associated with semen volume and sperm concentration.A longer time to produce semen samples(Q3 and Q4)was negatively correlated with progressive and total sperm motility.In addition,there was a significant negative linear association between the semen collection time and the sperm morphology.Higher risks of asthenozoospermia(adjusted odds ratio[OR]=2.06,95%confidence interval[CI]:1.31-3.25,P=0.002)and teratozoospermia(adjusted OR=1.98,95%CI:1.10-3.55,P=0.02)were observed in Q3 than those in Q1.Our results indicate that a higher risk of abnormal semen parameter values was associated with an increase in time for semen collection,which may be related to male fertility through its association with semen quality.
基金Supported by grants from the Science and Technology Planning Project of Guangdong Province(No.2017A020211007),Chinathe Key Project of Natural Science Foundation of Guangdong Province(No.2016A030311014),China+2 种基金the National Natural Science Foundation of China(No.81870420)Special Project on the Integration of Industry,Education and Research of Guangdong Province(No.2014B090902002)Science and Technological Program for Dongguan’s Social Development(No.2016108101043).
文摘To the Editor:Hyperuricemia,the second most common metabolic disease after diabetes mellitus in China,is characterized by the elevated serum uric concentration which is due to the overactive uric acid production or underexcretion.[1]Recent study supported the notion that hyperuricemia is implicated in renal tubular injury,subsequent tubulointerstitial fibrosis,and finally gouty nephropathy.[2]However,the lack of a suitable and stable mouse model to study hyperuricemia and gout nephropathy delays and limits the development of mechanism research and new drugs.Further understanding of the pathogenesis of hyperuricemia and gouty nephropathy has been largely hampered by a lack of preclinical animal models that reliably capture the characteristic phenotypes of hyperuricemia and gouty nephropathy.In this study,we aimed to develop a novel mouse model for hyperuricemia and gouty nephropathy.
基金supported by the National Natural Science Foundation of China(No.81971446).
文摘Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects.Most cases are due to mutations in genes encoding the components of sperm flagella,which have an ultrastructure similar to that of motile cilia.Coiled-coil domain containing 103(CCDC103)is an outer dynein arm assembly factor,and pathogenic variants of CCDC103 cause primary ciliary dyskinesia(PCD).However,whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined.Whole-exome sequencing(WES)was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family.A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified(ENST00000035776.2,c.461A>C,p.His154Pro).CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD,though the reproductive phenotype of these PCD individuals is unknown.Transmission electron microscopy(TEM)of affected individuals’spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms,similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation.Thus,our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia.
基金supported by the Natural Science Foundation of Jiangsu Province(No.BK2011354)the Priority Academic Program Development of Jiangsu High Education Institutions(PAPD)the National Natural Science Foundation of China(Nos.21071103 and 21074086)
文摘Single-handed helical silica nanotubes were prepared according to the literature procedures,using the self-assemblies of a pair of chiral cationic low-molecular-weight gelators as the templates.A chirality indicator,4,4'-bis(triethoxysilyl)-1,1'-biphenyl,was developed to determine the chirality of the silica nanotubes.The chirality of the surfaces and the bulky walls of the silica nanotubes were understood from the twist of the biphenylene rings.