The dorsal lingual epithelium,which is composed of taste buds and keratinocytes differentiated from K14^(+)basal cells,discriminates taste compounds and maintains the epithelial barrier.N6-methyladenosine(m^(6)A)is th...The dorsal lingual epithelium,which is composed of taste buds and keratinocytes differentiated from K14^(+)basal cells,discriminates taste compounds and maintains the epithelial barrier.N6-methyladenosine(m^(6)A)is the most abundant mRNA modification in eukaryotic cells.How METTL3-mediated m^(6)A modification regulates K14^(+)basal cell fate during dorsal lingual epithelium formation and regeneration remains unclear.Here we show knockout of Mettl3 in K14^(+)cells reduced the taste buds and enhanced keratinocytes.Deletion of Mettl3 led to increased basal cell proliferation and decreased cell division in taste buds.Conditional Mettl3 knock-in mice showed little impact on taste buds or keratinization,but displayed increased proliferation of cells around taste buds in a protective manner during post-irradiation recovery.Mechanically,we revealed that the most frequent m^(6)A modifications were enriched in Hippo and Wnt signaling,and specific peaks were observed near the stop codons of Lats1 and FZD7.Our study elucidates that METTL3 is essential for taste bud formation and could promote the quantity recovery of taste bud after radiation.展开更多
In order to investigate the reaction mechanism of intramolecular C-H insertion by Rh(II)-mediated carbenoids with trans-(2-phenylcyclopropyl) carbinal radical as the mechanistic probe, diazo compounds 2-(2-phenylcyclo...In order to investigate the reaction mechanism of intramolecular C-H insertion by Rh(II)-mediated carbenoids with trans-(2-phenylcyclopropyl) carbinal radical as the mechanistic probe, diazo compounds 2-(2-phenylcyclopropyl)ethyl diazoacetoacetate 8a and methyl 2-diazo-3oxo-6-(2-phenylcyclopropyl) hexanoate 8b have been synthesized. Preliminary investigation of the intramolecular C-H insertion with Rh2(OAc)4 as catalyst supports a concerted insertion process.展开更多
NLRP3 inflammasome-mediated cell pyroptosis aggravates the development of cerebral ischemia/reperfusion(I/R)injury,and the aim of this study is to investigate the potential utilization of the Chinese medicine,Puerarin...NLRP3 inflammasome-mediated cell pyroptosis aggravates the development of cerebral ischemia/reperfusion(I/R)injury,and the aim of this study is to investigate the potential utilization of the Chinese medicine,Puerarin,in treating this disease.Through conducting in vitro and in vivo experiments,the present study illustrated that Puerarin regulated LncRNA double homeobox A pseudogene 8(DUXAP8)/miR-223-3p axis to inactivate NLRP3-mediated pyroptotic cell death,resulting in the attenuation of I/R injury.Specifically,the cerebral I/R injury in rat models and hypoxia/reoxygenation(H/R)in primary hippocampus neuron(PHN)cells were inducted,which were subsequently exposed to Puerarin treatment.As expected,we validated that Puerarin suppressed cell pyroptosis and rescued cell viability in I/R rat hippocampus tissues and H/R PHN cells.Next,through bioinformatics analysis,we noticed that miR-223-3p targeted both LncRNA DUXAP8 and NLRP3 mRNA,and both LncRNA DUXAP8 ablation and miR-223-3p overexpression inactivate NLRP3-mediated cell pyroptosis to rescue cell viability in H/R PHN cells.Interestingly,we evidenced that Puerarin restrained LncRNA DUXAP8 expressions,but upregulated miR-223-3p in I/R rat tissues and H/R PHN cells,and the protective effects of Puerarin on H/R PHN cells were abrogated by overexpressing LncRNA DUXAP8 and silencing miR-223-3p.Collectively,we concluded that Puerarin regulated LncRNA DUXAP8/miR-223-3p/NLRP3 signaling cascade to attenuate I/R injury.展开更多
基金supported by the National Natural Science Foundation of China(81970913 and 82125006)。
文摘The dorsal lingual epithelium,which is composed of taste buds and keratinocytes differentiated from K14^(+)basal cells,discriminates taste compounds and maintains the epithelial barrier.N6-methyladenosine(m^(6)A)is the most abundant mRNA modification in eukaryotic cells.How METTL3-mediated m^(6)A modification regulates K14^(+)basal cell fate during dorsal lingual epithelium formation and regeneration remains unclear.Here we show knockout of Mettl3 in K14^(+)cells reduced the taste buds and enhanced keratinocytes.Deletion of Mettl3 led to increased basal cell proliferation and decreased cell division in taste buds.Conditional Mettl3 knock-in mice showed little impact on taste buds or keratinization,but displayed increased proliferation of cells around taste buds in a protective manner during post-irradiation recovery.Mechanically,we revealed that the most frequent m^(6)A modifications were enriched in Hippo and Wnt signaling,and specific peaks were observed near the stop codons of Lats1 and FZD7.Our study elucidates that METTL3 is essential for taste bud formation and could promote the quantity recovery of taste bud after radiation.
文摘In order to investigate the reaction mechanism of intramolecular C-H insertion by Rh(II)-mediated carbenoids with trans-(2-phenylcyclopropyl) carbinal radical as the mechanistic probe, diazo compounds 2-(2-phenylcyclopropyl)ethyl diazoacetoacetate 8a and methyl 2-diazo-3oxo-6-(2-phenylcyclopropyl) hexanoate 8b have been synthesized. Preliminary investigation of the intramolecular C-H insertion with Rh2(OAc)4 as catalyst supports a concerted insertion process.
基金supported by the Project of Scientific Research Fund of Traditional Chinese Medicine of Zhejiang Province(No.2020ZB230).
文摘NLRP3 inflammasome-mediated cell pyroptosis aggravates the development of cerebral ischemia/reperfusion(I/R)injury,and the aim of this study is to investigate the potential utilization of the Chinese medicine,Puerarin,in treating this disease.Through conducting in vitro and in vivo experiments,the present study illustrated that Puerarin regulated LncRNA double homeobox A pseudogene 8(DUXAP8)/miR-223-3p axis to inactivate NLRP3-mediated pyroptotic cell death,resulting in the attenuation of I/R injury.Specifically,the cerebral I/R injury in rat models and hypoxia/reoxygenation(H/R)in primary hippocampus neuron(PHN)cells were inducted,which were subsequently exposed to Puerarin treatment.As expected,we validated that Puerarin suppressed cell pyroptosis and rescued cell viability in I/R rat hippocampus tissues and H/R PHN cells.Next,through bioinformatics analysis,we noticed that miR-223-3p targeted both LncRNA DUXAP8 and NLRP3 mRNA,and both LncRNA DUXAP8 ablation and miR-223-3p overexpression inactivate NLRP3-mediated cell pyroptosis to rescue cell viability in H/R PHN cells.Interestingly,we evidenced that Puerarin restrained LncRNA DUXAP8 expressions,but upregulated miR-223-3p in I/R rat tissues and H/R PHN cells,and the protective effects of Puerarin on H/R PHN cells were abrogated by overexpressing LncRNA DUXAP8 and silencing miR-223-3p.Collectively,we concluded that Puerarin regulated LncRNA DUXAP8/miR-223-3p/NLRP3 signaling cascade to attenuate I/R injury.
