Objective Ulcerative colitis is a prevalent immunoinflammatory disease.Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis.The actin cytoskeleton contributes to...Objective Ulcerative colitis is a prevalent immunoinflammatory disease.Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis.The actin cytoskeleton contributes to regulating the proliferation,differentiation,and migration of Th17 and Treg cells.Wdr63,a gene containing the WD repeat domain,participates in the structure and functional modulation of actin cytoskeleton.Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition.This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis.Methods We constructed Wdr63-/-mice,induced colitis in mice using dextran sulfate sodium salt,collected colon tissue for histopathological staining,collected mesenteric lymph nodes for flow cytometry analysis,and collected healthy mouse feces for microbial diversity detection.Results Compared with wild-type colitis mice,Wdr63-/-colitis mice had a more pronounced shortening of colonic tissue,higher scores on disease activity index and histological damage index,Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes,a lower level of anti-inflammatory cytokine IL-10,and a higher level of pro-inflammatory cytokine IL-17A.In addition,WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis.It maintains the balance of Bacteroidota and Firmicutes,promoting the formation of beneficial intestinal bacteria linked to immune inflammation.Conclusion Wdr63 deletion aggravates ulcerative colitis in mice,WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.展开更多
Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A;p. Ala632Thr) in a 7-year-old boy exhibi...Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A;p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca2+ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^(−/−) OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^(−/−) OPCs in vitro and myelination in Tmem63a^(−/−) mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca^(2+) influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.展开更多
We present new data on the^(63)Cu(γ,n)cross-section studied using a quasi-monochromatic and energy-tunableγbeam produced at the Shanghai Laser Electron Gamma Source to resolve the long-standing discrepancy between e...We present new data on the^(63)Cu(γ,n)cross-section studied using a quasi-monochromatic and energy-tunableγbeam produced at the Shanghai Laser Electron Gamma Source to resolve the long-standing discrepancy between existing measurements and evaluations of this cross-section.Using an unfolding iteration method,^(63)Cu(γ,n)data were obtained with an uncertainty of less than 4%,and the inconsistencies between the available experimental data were discussed.Theγ-ray strength function of^(63)Cu(γ,n)was successfully extracted as an experimental constraint.We further calculated the cross-section of the radiative neutron capture reaction^(62)Cu(n,γ)using the TALYS code.Our calculation method enables the extraction of(n,γ)cross-sections for unstable nuclides.展开更多
文摘Objective Ulcerative colitis is a prevalent immunoinflammatory disease.Th17/Treg cell imbalance and gut microbiota dysregulation are key factors in ulcerative colitis pathogenesis.The actin cytoskeleton contributes to regulating the proliferation,differentiation,and migration of Th17 and Treg cells.Wdr63,a gene containing the WD repeat domain,participates in the structure and functional modulation of actin cytoskeleton.Recent research indicates that WDR63 may serve as a regulator of cell migration and metastasis via actin polymerization inhibition.This article aims to explore the effect of Wdr63 deletion on Th17/Treg cells and ulcerative colitis.Methods We constructed Wdr63-/-mice,induced colitis in mice using dextran sulfate sodium salt,collected colon tissue for histopathological staining,collected mesenteric lymph nodes for flow cytometry analysis,and collected healthy mouse feces for microbial diversity detection.Results Compared with wild-type colitis mice,Wdr63-/-colitis mice had a more pronounced shortening of colonic tissue,higher scores on disease activity index and histological damage index,Treg cells decreased and Th17 cells increased in colonic tissue and mesenteric lymph nodes,a lower level of anti-inflammatory cytokine IL-10,and a higher level of pro-inflammatory cytokine IL-17A.In addition,WDR63 has shown positive effects on maintaining intestinal microbiota homeostasis.It maintains the balance of Bacteroidota and Firmicutes,promoting the formation of beneficial intestinal bacteria linked to immune inflammation.Conclusion Wdr63 deletion aggravates ulcerative colitis in mice,WDR63 inhibits colonic inflammation likely by regulating Th17/Treg balance and maintains intestinal microbiota homeostasis.
基金supported by grants from the National Key R&D Program of China(2019YFA0801603)the Guangdong High Level Innovation Research Institute(2021B0909050004)+2 种基金the National Natural Science Foundation of China(32330044,32170951,82201615,and 82101393)the Natural Science Foundation of Jiangsu Province(BK20201255 and BK20210008)the Fundamental Research Funds for the Central Universities(021414380533).
文摘Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A;p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca2+ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^(−/−) OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^(−/−) OPCs in vitro and myelination in Tmem63a^(−/−) mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca^(2+) influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
基金supported by the National Key Research and Development Program(Nos.2023YFA1606901 and 2022YFA1602400)National Natural Science Foundation of China(Nos.U2230133,12275338,and 12388102)Open Fund of the CIAE Key Laboratory of Nuclear Data(No.JCKY2022201C152).
文摘We present new data on the^(63)Cu(γ,n)cross-section studied using a quasi-monochromatic and energy-tunableγbeam produced at the Shanghai Laser Electron Gamma Source to resolve the long-standing discrepancy between existing measurements and evaluations of this cross-section.Using an unfolding iteration method,^(63)Cu(γ,n)data were obtained with an uncertainty of less than 4%,and the inconsistencies between the available experimental data were discussed.Theγ-ray strength function of^(63)Cu(γ,n)was successfully extracted as an experimental constraint.We further calculated the cross-section of the radiative neutron capture reaction^(62)Cu(n,γ)using the TALYS code.Our calculation method enables the extraction of(n,γ)cross-sections for unstable nuclides.
