Casing parts are regarded as key components of aero-engines.Most casing parts are attached to convex structures of diferent shapes,whose heights range from hundreds of microns to tens of millimeters.Using profling blo...Casing parts are regarded as key components of aero-engines.Most casing parts are attached to convex structures of diferent shapes,whose heights range from hundreds of microns to tens of millimeters.Using profling blocky electrodes for electrochemical machining(ECM)of casing parts is a commonly adopted method,especially when highly convex structures.However,with an increase in the convex structure height,the fow felds of the machining areas become more complex,and short circuits may occur at any time.In this study,a method to improve the fow feld characteristics within a machining area by adjusting the backwater pressure is proposed and validated through simulation and experiment analyses.The simulation results demonstrated that the back-pressure method can signifcantly improve the uniformity of the fow feld around the convex structure compared with the extraction and open outlet modes.Subsequently,the back-pressure value was optimized at 0.5 MPa according to the simulation results.The experimental results showed that using the optimized back-pressure parameters,the cathode feed-rate increased from 0.6 to 0.7 mm/min,and a 16.1 mm tall convex structure was successfully machined.This indicates that the back-pressure method is suitable and efective for electrochemical machining of highly convex structures with blocky electrodes.In this study,we propose a method to improve the electrochemical machining stability of a convex structure on a casing surface using backwater pressure,which has achieved remarkable results.展开更多
Mesenchymal stem/stromal cells(MSCs)possess robust immunoregulatory functions and are promising therapeutics for inflammatory disorders.This capacity is not innate but is activated or‘licensed’by inflammatory cytoki...Mesenchymal stem/stromal cells(MSCs)possess robust immunoregulatory functions and are promising therapeutics for inflammatory disorders.This capacity is not innate but is activated or‘licensed’by inflammatory cytokines.The licensing mechanism remains unclear.Here,we examined whether inflammatory cytokines metabolically reprogrammed MSCs to confer this immunoregulatory capacity.In response to stimulation by inflammatory cytokines,MSCs exhibited a dramatic increase in the consumption of glucose,which was accompanied by an enhanced use of nicotinamide adenine dinucleotide(NAD^(+))and increased expression of nicotinamide phosphoribosyltransferase(NAMPT),a central enzyme in the salvage pathway for NAD^(+) production.When NAD^(+) synthesis was blocked by inhibiting or depleting NAMPT,the immunosuppressive function of MSCs induced by inflammatory cytokines was greatly attenuated.Consequently,when NAD^(+) metabolism in MSCs was perturbed,their therapeutic benefit was decreased in mice suffering from inflammatory bowel disease and acute liver injury.Further analysis revealed that NAMPT-driven production of NAD^(+) was critical for the inflammatory cytokine-induced increase in glycolysis in MSCs.Furthermore,the increase in glycolysis led to succinate accumulation in the tricarboxylic acid cycle,which led to hypoxia-inducible factor 1α(HIF-1α)stabilization and subsequently increased the transcription of key glycolytic genes,thereby persistently maintaining glycolytic flux.This study demonstrated that unlike its proinflammatory role in immune cells,NAD^(+) metabolism governs the anti-inflammatory function of MSCs during inflammation.展开更多
基金Supported by National Natural Science Foundation of China(Grant No.51775484)China Postdoctoral Science Foundation(Grant No.2020M670791).
文摘Casing parts are regarded as key components of aero-engines.Most casing parts are attached to convex structures of diferent shapes,whose heights range from hundreds of microns to tens of millimeters.Using profling blocky electrodes for electrochemical machining(ECM)of casing parts is a commonly adopted method,especially when highly convex structures.However,with an increase in the convex structure height,the fow felds of the machining areas become more complex,and short circuits may occur at any time.In this study,a method to improve the fow feld characteristics within a machining area by adjusting the backwater pressure is proposed and validated through simulation and experiment analyses.The simulation results demonstrated that the back-pressure method can signifcantly improve the uniformity of the fow feld around the convex structure compared with the extraction and open outlet modes.Subsequently,the back-pressure value was optimized at 0.5 MPa according to the simulation results.The experimental results showed that using the optimized back-pressure parameters,the cathode feed-rate increased from 0.6 to 0.7 mm/min,and a 16.1 mm tall convex structure was successfully machined.This indicates that the back-pressure method is suitable and efective for electrochemical machining of highly convex structures with blocky electrodes.In this study,we propose a method to improve the electrochemical machining stability of a convex structure on a casing surface using backwater pressure,which has achieved remarkable results.
基金supported by grants from the National Key R&D Program of China(2021YFA1100600 and 2022YFA0807300)the National Natural Science Foundation of China(82202032,81930085 and 32150710523)the Jiangsu Province International Joint Laboratory for Regenerative Medicine Fund and the Suzhou Foreign Academician Workstation Fund(SWY202202).
文摘Mesenchymal stem/stromal cells(MSCs)possess robust immunoregulatory functions and are promising therapeutics for inflammatory disorders.This capacity is not innate but is activated or‘licensed’by inflammatory cytokines.The licensing mechanism remains unclear.Here,we examined whether inflammatory cytokines metabolically reprogrammed MSCs to confer this immunoregulatory capacity.In response to stimulation by inflammatory cytokines,MSCs exhibited a dramatic increase in the consumption of glucose,which was accompanied by an enhanced use of nicotinamide adenine dinucleotide(NAD^(+))and increased expression of nicotinamide phosphoribosyltransferase(NAMPT),a central enzyme in the salvage pathway for NAD^(+) production.When NAD^(+) synthesis was blocked by inhibiting or depleting NAMPT,the immunosuppressive function of MSCs induced by inflammatory cytokines was greatly attenuated.Consequently,when NAD^(+) metabolism in MSCs was perturbed,their therapeutic benefit was decreased in mice suffering from inflammatory bowel disease and acute liver injury.Further analysis revealed that NAMPT-driven production of NAD^(+) was critical for the inflammatory cytokine-induced increase in glycolysis in MSCs.Furthermore,the increase in glycolysis led to succinate accumulation in the tricarboxylic acid cycle,which led to hypoxia-inducible factor 1α(HIF-1α)stabilization and subsequently increased the transcription of key glycolytic genes,thereby persistently maintaining glycolytic flux.This study demonstrated that unlike its proinflammatory role in immune cells,NAD^(+) metabolism governs the anti-inflammatory function of MSCs during inflammation.