Background:We aimed to reveal the mechanism of functional constipation in the treatment of Atractylodes macrocephala Koidz.(AMK)and Paeonia lactiflora Pall.(PLP).Methods:The main active ingredients of AMK and PLP were...Background:We aimed to reveal the mechanism of functional constipation in the treatment of Atractylodes macrocephala Koidz.(AMK)and Paeonia lactiflora Pall.(PLP).Methods:The main active ingredients of AMK and PLP were screened by the Traditional Chinese Medicine Systems Pharmacology(TCMSP)platform.A database of functional constipation targets was established by GeneCard and OMIM.An“ingredient-target”network map was constructed with Cytoscape software(version 3.7.1),and molecular docking analysis was performed on the components and genes with the highest scores.The rats in the normal group were given saline,and those in the other groups were given 10 mg/kg diphenoxylate once a day for 14 days.The serum and intestinal tissue levels of adenosine monophosphate(cAMP),protein kinase A(PKA),and adenylyl cyclase(AC)of the rats and aquaporin(AQP)1,AQP3,and AQP8 were measured.Results:AMK and PLP had a significant role in the regulation of targets in the treatment of functional constipation.After treatment with AMK,PLP,or mosapride,the serum and intestinal tissue levels of AC,cAMP,and PKA were significantly downregulated.Groups receiving AMK and PLP or mosapride exhibited a reduction in the level of AQP1,AQP3,and AQP8 to varying degrees.Conclusion:Molecular docking analysis revealed that AMK and PLP had a significant role in the regulation of targets in the treatment of functional constipation.Studies have confirmed that AMK and PLP can also affect AC,cAMP,and PKA.AC,cAMP,and PKA in model rats were significantly downregulated.AQP expression is closely related to AC,cAMP,and PKA.AMK and PLP can reduce the expression of AQP1,AQP3,and AQP9 in the colon of constipated rats.展开更多
A new pyridoxal-5-phosphate (PLP) derivative FHMDP was developed for the transamination of different pep- tides with three most hindered amino acid residues (Leu, Ile, Val) as their N-terminus. Compared to the pre...A new pyridoxal-5-phosphate (PLP) derivative FHMDP was developed for the transamination of different pep- tides with three most hindered amino acid residues (Leu, Ile, Val) as their N-terminus. Compared to the previously reported reactions of PLP derivatives, the N-terminus transamination could be accomplished efficiently with the new compound.展开更多
Vanishing white matter disease (VWMD, MIM #603896), also known as childhood ataxia with central nervous system (CNS) hypomyelination (CACH), is an inherited autosomal-recessive leukodystrophy (van der Knaap et ...Vanishing white matter disease (VWMD, MIM #603896), also known as childhood ataxia with central nervous system (CNS) hypomyelination (CACH), is an inherited autosomal-recessive leukodystrophy (van der Knaap et al., 2006). The neurological signs of VWMD, such as cerebellar ataxia and spasticity, usually begin in late infancy or early childhood. VWMD is chronic and progressive, with additional episodes of rapid deterioration after febrile infection or minor head trauma. Most patients die within a few years of disease onset. VWMD patients display cystic cavitations of the white matter in the CNS. In contrast, the CNS gray matter and the other organs are generally spared. The grossly affected white matter shows profound myelin loss.展开更多
This letter proposes a new burst assembly technique for supporting QoS in optical burst switching (OBS) networks. It consists of the adaptive-threshold burst assembly mechanism and QoS-based random offset-time scheme....This letter proposes a new burst assembly technique for supporting QoS in optical burst switching (OBS) networks. It consists of the adaptive-threshold burst assembly mechanism and QoS-based random offset-time scheme. The assembly mechanism, which is fit well to multi-class burst assembly, not only matches with IP QoS mechanism based on packet classification, and also utilizes fairly and efficiently assembly capacity. Based on token-bucket model and burst segment selective discard (BSSD), the offset-time scheme can smooth the traffic to support OBS QoS. The simulation results show that the technique can improve the performance in terms of packet loss probability (PLP).展开更多
基金supported by the Project of Zhejiang Natural Science Foundation(LY19H280004)the Exploration Project of Zhejiang Natural Science Foundation(LQ21H270002)。
文摘Background:We aimed to reveal the mechanism of functional constipation in the treatment of Atractylodes macrocephala Koidz.(AMK)and Paeonia lactiflora Pall.(PLP).Methods:The main active ingredients of AMK and PLP were screened by the Traditional Chinese Medicine Systems Pharmacology(TCMSP)platform.A database of functional constipation targets was established by GeneCard and OMIM.An“ingredient-target”network map was constructed with Cytoscape software(version 3.7.1),and molecular docking analysis was performed on the components and genes with the highest scores.The rats in the normal group were given saline,and those in the other groups were given 10 mg/kg diphenoxylate once a day for 14 days.The serum and intestinal tissue levels of adenosine monophosphate(cAMP),protein kinase A(PKA),and adenylyl cyclase(AC)of the rats and aquaporin(AQP)1,AQP3,and AQP8 were measured.Results:AMK and PLP had a significant role in the regulation of targets in the treatment of functional constipation.After treatment with AMK,PLP,or mosapride,the serum and intestinal tissue levels of AC,cAMP,and PKA were significantly downregulated.Groups receiving AMK and PLP or mosapride exhibited a reduction in the level of AQP1,AQP3,and AQP8 to varying degrees.Conclusion:Molecular docking analysis revealed that AMK and PLP had a significant role in the regulation of targets in the treatment of functional constipation.Studies have confirmed that AMK and PLP can also affect AC,cAMP,and PKA.AC,cAMP,and PKA in model rats were significantly downregulated.AQP expression is closely related to AC,cAMP,and PKA.AMK and PLP can reduce the expression of AQP1,AQP3,and AQP9 in the colon of constipated rats.
基金Project supported by the National Natural Science Foundation of China (Nos. 20932006 and 21002056).
文摘A new pyridoxal-5-phosphate (PLP) derivative FHMDP was developed for the transamination of different pep- tides with three most hindered amino acid residues (Leu, Ile, Val) as their N-terminus. Compared to the previously reported reactions of PLP derivatives, the N-terminus transamination could be accomplished efficiently with the new compound.
基金supported by grants from the National Multiple Sclerosis Society (RG4813-A-2 and RG 5239A-3)
文摘Vanishing white matter disease (VWMD, MIM #603896), also known as childhood ataxia with central nervous system (CNS) hypomyelination (CACH), is an inherited autosomal-recessive leukodystrophy (van der Knaap et al., 2006). The neurological signs of VWMD, such as cerebellar ataxia and spasticity, usually begin in late infancy or early childhood. VWMD is chronic and progressive, with additional episodes of rapid deterioration after febrile infection or minor head trauma. Most patients die within a few years of disease onset. VWMD patients display cystic cavitations of the white matter in the CNS. In contrast, the CNS gray matter and the other organs are generally spared. The grossly affected white matter shows profound myelin loss.
基金This work was supported by National Hi-Tech Research and Development Program of China (863 Program) under contract No. 2002AA122021.
文摘This letter proposes a new burst assembly technique for supporting QoS in optical burst switching (OBS) networks. It consists of the adaptive-threshold burst assembly mechanism and QoS-based random offset-time scheme. The assembly mechanism, which is fit well to multi-class burst assembly, not only matches with IP QoS mechanism based on packet classification, and also utilizes fairly and efficiently assembly capacity. Based on token-bucket model and burst segment selective discard (BSSD), the offset-time scheme can smooth the traffic to support OBS QoS. The simulation results show that the technique can improve the performance in terms of packet loss probability (PLP).