Serine protease 50(PRSS50/TSP50)is highly expressed in spermatocytes.Our study investigated its role in testicular development and spermatogenesis.Initially,PRSS50 knockdown was observed to impair DNA synthesis in spe...Serine protease 50(PRSS50/TSP50)is highly expressed in spermatocytes.Our study investigated its role in testicular development and spermatogenesis.Initially,PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes.To further explore this,we generated PRSS50 knockout(Prss50^(−/−))mice(Mus musculus),which exhibited abnormal spermatid nuclear compression and reduced male fertility.Furthermore,dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50^(−/−)mice,accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells.Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2(ERK1/2)and elevated levels of MAP kinase phosphatase 3(MKP3),a specific ERK antagonist,potentially accounting for testicular dysplasia in adolescent Prss50−/−mice.Taken together,these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis,with the MKP3/ERK signaling pathway playing a significant role in this process.展开更多
During the analysis of benziamidazole-class irreversible proton pump inhibitors,an unusual mass spectral response with the mass-to-charge ratio at[Mt10]t intrigued us,as it couldn't be assigned to any literature k...During the analysis of benziamidazole-class irreversible proton pump inhibitors,an unusual mass spectral response with the mass-to-charge ratio at[Mt10]t intrigued us,as it couldn't be assigned to any literature known relevant structure,intermediate or adduct ion.Moreover,this mysterious mass pattern of[Mt10]t has been gradually observed by series of marketed proton pump inhibitors,viz.omeprazole,pantoprazole,lansoprazole and rabeprazole.All the previous attempts to isolate the corresponding component were unsuccessful.The investigation of present work addresses this kind of signal to a pyridinium thiocyanate mass spectral intermediate(10),which is the common fragment ion of series of labile aggregates.The origin of such aggregates can be traced to the reactive intermediates formed by acid-promoted degradation.These reactive intermediates tend to react with each other and give raise series of complicated aggregates systematically in a water/acetonitrile solution by electrospray ionization.The structure of the corresponding pyridinium thiocyanate species of omeprazole(10a)has been eventually characterized with the help of synthetic specimen(10a′).Our structural proposal as well as its origin was supported by in situ nuclear magnetic resonance,chemical derivatization and colorimetric experiments.展开更多
To screen and characterize the analgesic components from Marasmius androsaceus, the water-soluble extracts from the mycelium of M. androsaceus were isolated by ethanol precipitation followed by macroporous resin chrom...To screen and characterize the analgesic components from Marasmius androsaceus, the water-soluble extracts from the mycelium of M. androsaceus were isolated by ethanol precipitation followed by macroporous resin chromatography and activity-based fractionation. Analgesic activities were found to be associated with glycopeptides. The glycopeptide fractions were further purified by gel-permeation chromatography and two purified glycopeptides, D2H, D2L, were obtained. Next, the physicochemical properties and characteristics of these purified glycopeptides were studied. They were composed of glucose and mannose and 10 different amino acids and with molecular weights of 18,000 and 8000 Da, respectively. The glycosidic linkages in the purified glycopeptides were analysed via methylation analysis. The sugar portion of the glycopeptides was composed of 1 - 4 linked Glc as the main chain with side chains composed primarily of Man linked to the 6 position of the main chain;the non-reducing terminal was composed of Glc. The glycosidic band in the main chain was identified as being in the β-configuration by the IR absorbance at 891 cm-1.展开更多
基金supported by the Research Foundation of Jilin Provincial Science&Technology Development(20210204164YY,YDZJ202201ZYTS524,20230204067YY,20230204069YY)Jilin Province Development and Reform Commission(2022C044-3)Fundamental Research Funds for the Central Universities(135131002)。
文摘Serine protease 50(PRSS50/TSP50)is highly expressed in spermatocytes.Our study investigated its role in testicular development and spermatogenesis.Initially,PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes.To further explore this,we generated PRSS50 knockout(Prss50^(−/−))mice(Mus musculus),which exhibited abnormal spermatid nuclear compression and reduced male fertility.Furthermore,dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50^(−/−)mice,accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells.Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2(ERK1/2)and elevated levels of MAP kinase phosphatase 3(MKP3),a specific ERK antagonist,potentially accounting for testicular dysplasia in adolescent Prss50−/−mice.Taken together,these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis,with the MKP3/ERK signaling pathway playing a significant role in this process.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82030107 and 81872831)the National Science and Technology Major Projects for significant new drugs creation of the 13th five-year plan(Grant Nos.:2017ZX09101001 and 2018ZX09721002007).
文摘During the analysis of benziamidazole-class irreversible proton pump inhibitors,an unusual mass spectral response with the mass-to-charge ratio at[Mt10]t intrigued us,as it couldn't be assigned to any literature known relevant structure,intermediate or adduct ion.Moreover,this mysterious mass pattern of[Mt10]t has been gradually observed by series of marketed proton pump inhibitors,viz.omeprazole,pantoprazole,lansoprazole and rabeprazole.All the previous attempts to isolate the corresponding component were unsuccessful.The investigation of present work addresses this kind of signal to a pyridinium thiocyanate mass spectral intermediate(10),which is the common fragment ion of series of labile aggregates.The origin of such aggregates can be traced to the reactive intermediates formed by acid-promoted degradation.These reactive intermediates tend to react with each other and give raise series of complicated aggregates systematically in a water/acetonitrile solution by electrospray ionization.The structure of the corresponding pyridinium thiocyanate species of omeprazole(10a)has been eventually characterized with the help of synthetic specimen(10a′).Our structural proposal as well as its origin was supported by in situ nuclear magnetic resonance,chemical derivatization and colorimetric experiments.
文摘To screen and characterize the analgesic components from Marasmius androsaceus, the water-soluble extracts from the mycelium of M. androsaceus were isolated by ethanol precipitation followed by macroporous resin chromatography and activity-based fractionation. Analgesic activities were found to be associated with glycopeptides. The glycopeptide fractions were further purified by gel-permeation chromatography and two purified glycopeptides, D2H, D2L, were obtained. Next, the physicochemical properties and characteristics of these purified glycopeptides were studied. They were composed of glucose and mannose and 10 different amino acids and with molecular weights of 18,000 and 8000 Da, respectively. The glycosidic linkages in the purified glycopeptides were analysed via methylation analysis. The sugar portion of the glycopeptides was composed of 1 - 4 linked Glc as the main chain with side chains composed primarily of Man linked to the 6 position of the main chain;the non-reducing terminal was composed of Glc. The glycosidic band in the main chain was identified as being in the β-configuration by the IR absorbance at 891 cm-1.