The assembly of neurons into complex circuits relies upon appropriate axonal navigation to distant targets.Although considerable progress has been made toward understanding the regulation of the guidance and branching...The assembly of neurons into complex circuits relies upon appropriate axonal navigation to distant targets.Although considerable progress has been made toward understanding the regulation of the guidance and branching of axon extension,the molecular and cellular mechanisms underlying the coordination of the motility of the axon tip,axon growth,and branching remain largely unknown(Sudhof,2017).The Drosophila mushroom body(MB),the major site for associative learning and memory,is a powerful model system to investigate complex axon behaviors.The MB is a bilaterally symmetric central brain structure,mainly composed of Kenyon cells,MB output neurons,and dopaminergic neurons(Li et al.,2020).Among the seven neuronal subtypes of~2000 Kenyon cells,Y,a/β,and a/β'subtypes extend axons in a fascicle and bifurcate to produce two sister branches,one projecting into the dorsal lobe and the other into the medial lobe.展开更多
Current treatment of hyperuricemia relies on xanthine oxidase(XO)inhibitors that block uric acid production.This study investigated two fish maw(FM)types,from miiuy croaker and silver carp,as novel sources of peptides...Current treatment of hyperuricemia relies on xanthine oxidase(XO)inhibitors that block uric acid production.This study investigated two fish maw(FM)types,from miiuy croaker and silver carp,as novel sources of peptides with XO inhibition(XOI)benefit.Alcalase 2L was the most effective protease to hydrolyze the FM.Hydrolysates from freshwater FM exhibited stronger XOI activity than hydrolysates from medicinal FM,with XOI activity of 80.33%±1.64%and 65.94%±0.08%,respectively,and IC_(50)of 9.08±0.24 mg/mL and 11.23±0.31 mg/mL,respectively.In silico screening and molecular docking simulations identified four candidate peptides,EFF and DSLGF from freshwater FM,and EQGF and PSGPQ from medicinal FM,with the highest binding affinity to the XO receptor.The binding primarily consisted of hydrogen bonds,hydrophobic interactions and cation interactions.Phe residues on peptide sequences were key contributors to XO-peptide interactions.This was further validated by DFT quantum calculations.Phenyl rings on F-3(EFF),F-5(DSLGF)and the carbonyl group of E-1(EQGF),and Q-5(PSGPQ)were identified as key reactive sites by DFT calculations.When tested in vitro,the XOI of the four peptides decreased in the order:EFF(47.54%±0.19%)>EQGF(40.13%±0.86%)>DSLGF(34.91%±0.55%)>PSGPQ(34.84%±0.12%).These findings suggest that both low-value silver carp FM and medicinal miiuy croaker FM are potential source of peptides with anti-hyperuricemia functions.Moreover,combining computational tools like molecular docking simulations and DFT could be effective in elucidating peptide-receptor target interactions and structure-activity relationships.展开更多
基金supported by research grants from the National Natural Science Foundation of China(31871461 and 31671510 to H.H.).
文摘The assembly of neurons into complex circuits relies upon appropriate axonal navigation to distant targets.Although considerable progress has been made toward understanding the regulation of the guidance and branching of axon extension,the molecular and cellular mechanisms underlying the coordination of the motility of the axon tip,axon growth,and branching remain largely unknown(Sudhof,2017).The Drosophila mushroom body(MB),the major site for associative learning and memory,is a powerful model system to investigate complex axon behaviors.The MB is a bilaterally symmetric central brain structure,mainly composed of Kenyon cells,MB output neurons,and dopaminergic neurons(Li et al.,2020).Among the seven neuronal subtypes of~2000 Kenyon cells,Y,a/β,and a/β'subtypes extend axons in a fascicle and bifurcate to produce two sister branches,one projecting into the dorsal lobe and the other into the medial lobe.
基金supported by the earmarked fund for CARS(CARS-45).
文摘Current treatment of hyperuricemia relies on xanthine oxidase(XO)inhibitors that block uric acid production.This study investigated two fish maw(FM)types,from miiuy croaker and silver carp,as novel sources of peptides with XO inhibition(XOI)benefit.Alcalase 2L was the most effective protease to hydrolyze the FM.Hydrolysates from freshwater FM exhibited stronger XOI activity than hydrolysates from medicinal FM,with XOI activity of 80.33%±1.64%and 65.94%±0.08%,respectively,and IC_(50)of 9.08±0.24 mg/mL and 11.23±0.31 mg/mL,respectively.In silico screening and molecular docking simulations identified four candidate peptides,EFF and DSLGF from freshwater FM,and EQGF and PSGPQ from medicinal FM,with the highest binding affinity to the XO receptor.The binding primarily consisted of hydrogen bonds,hydrophobic interactions and cation interactions.Phe residues on peptide sequences were key contributors to XO-peptide interactions.This was further validated by DFT quantum calculations.Phenyl rings on F-3(EFF),F-5(DSLGF)and the carbonyl group of E-1(EQGF),and Q-5(PSGPQ)were identified as key reactive sites by DFT calculations.When tested in vitro,the XOI of the four peptides decreased in the order:EFF(47.54%±0.19%)>EQGF(40.13%±0.86%)>DSLGF(34.91%±0.55%)>PSGPQ(34.84%±0.12%).These findings suggest that both low-value silver carp FM and medicinal miiuy croaker FM are potential source of peptides with anti-hyperuricemia functions.Moreover,combining computational tools like molecular docking simulations and DFT could be effective in elucidating peptide-receptor target interactions and structure-activity relationships.
