Micro-nanofiber composite biomimetic conduits promote long-gap peripheral nerve regeneration in canine models

Peripheral nerve injuries may result in severe long-gap interruptions that are challenging to repair.Autografting is the gold standard surgical approach for repairing long-gap nerve injuries but can result in prominent donor-site complications.Instead,imitating the native neural microarchitecture using synthetic conduits is expected to offer an alternative strategy for improving nerve regeneration.Here,we designed nerve conduits composed of high-resolution anisotropic microfiber grid-cordes with randomly organized nanofiber sheaths to interrogate the positive effects of these biomimetic structures on peripheral nerve regeneration.Anisotropic microfiber-grids demonstrated the capacity to directionally guide Schwann cells and neurites.Nanofiber sheaths conveyed adequate elasticity and permeability,whilst exhibiting a barrier function against the infiltration of fibroblasts.We then used the composite nerve conduits bridge 30-mm long sciatic nerve defects in canine models.At 12 months post-implant,the morphometric and histological recovery,gait recovery,electrophysiological function,and degree of muscle atrophy were assessed.The newly regenerated nerve tissue that formed within the composite nerve conduits showed restored neurological functions that were superior compared to sheaths-only scaffolds and Neurolac nerve conduit controls.Our findings demonstrate the feasibility of using synthetic biophysical cues to effectively bridge long-gap peripheral nerve injuries and indicates the promising clinical application prospects of biomimetic composite nerve conduits.

Modification of physicochemical properties and degradation of barley flour upon enzymatic extrusion

In order to evaluate the application potential of enzyme-extruded barley flour(EEBF)in the brewing of whole-barley beer,the physicochemical properties,mashing and fermentation effects of EEBF were studied,and conventional extruded barley flour(CEBF)and steam-cooked barley flour(SCBF)were taken as controls.The water solubility index(WSI)of EEBF(46.88%-52.63%)was much higher than that of CEBF(6.70%)and SCBF(4.59%).The results of degree of gelatinization(DG)and enthalpy(ΔH)suggested that EEBF was almost completely gelatinized,and the rapid visco analyzer(RVA)exhibited that the peak viscosity of EEBF was drastically reduced.The weight-average molecular weight of EEBF(<10^(6) g/mol)was significantly lower than that of CEBF and SCBF.Scanning electron microscopy(SEM)showed that the heat-treatments caused starch granules to break and aggregate,and there were many hydrolyzed pores on the surface of EEBF.Both the long-and short-range order of EEBF were destroyed.Although EEBF caused serious filtration blocking,it greatly improved the alcohol content of finished beer(5.41%vol).Overall,the thermal modification of barley flour by enzyme-extrusion meets the needs of fermentation,and could improve the problem of limited leaching of unmalted barley,which was benefit for the production of whole-barley beer.

Effects of extrusion and enzymatic debranching on the structural characteristics and digestibility of corn and potato starches

Amylose content has a profound impact on the contents of slowly digestible starch and resistant starch.Enzymatic debranching is a safe method to increase the amylose content,however,the lower substrate concentration and high viscosity of fully gelatinized starch limit the efficiency and yield of this method.This paper aims to explore the effects of extrusion and enzymatic debranching on increasing the amylose content thereby increasing slowly digestible starch and resistant starch contents.Different starch concentrations (10%,15%,and 20%) of extruded corn starch (ECS) and extruded potato starch (EPS) were used to debranch.Both debranched ECS and debranched EPS showed high amylose content of approximately 90%,indicating that all samples with different starch concentrations achieved high-efficiency enzymatic debranching.The high-performance liquid chromatograph results indicated that the samples were mainly short amylose.The samples exhibit a typical B-type crystalline structure and the relative crystallinity of them exceeds 37%.The short amylose exhibited rapid rearrangement ability,with the gelatinization temperature range of rescanning determined as 80–125℃,this will facilitate the formation of slowly digestible starch and resistant starch.The slowly digestible starch and resistant starch contents of the samples (debranched ECS and debranched EPS) were between 23% and 30% and between 31% and 37%,respectively.These results indicate that the extrusion and enzymatic debranching of a high substrate concentration can efficiently increase the amylose content,thereby significantly reducing the digestibility of starch,and has broad prospects of the actual production of slowly digestible starch and resistant starch.

Discovery of 4-cyclopropyl-3-(2-((1-cyclopropyl-1H-pyrazol-4-yl) amino) quinazolin-6-yl)-N-(3-(trifluoromethyl) phenyl) benzamides as potent discoidin domain receptor inhibitors for the treatment of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis(IPF)is a chronic fatal lung disease with a median survival time of 3–5 years.Inaccurate diagnosis,limited clinical therapy and high mortality together indicate that the development of effective therapeutics for IPF is an urgent need.In recent years,it was reported that DDRs are potential targets in anti-fibrosis treatment.Based on previous work we carried out further structure modifications and led to a more selective inhibitor 47 by averting some fibrosis-unrelated kinases,such as RET,AXL and ALK.Extensive profiling of compound 47 has demonstrated that it has potent DDR1/2 inhibitory activities,low toxicity,good pharmacokinetic properties and reliable in vivo anti-fibrosis efficacy.Therefore,we confirmed that discoidin domain receptors are promising drug targets for IPF,and compound 47 would be a promising candidate for further drug development.