The microstructural observation,the mass loss test,potentiodynamic polarization measurements and corrosion morphology examinations were conducted to study the influence of microstructural characteristics on corrosion ...The microstructural observation,the mass loss test,potentiodynamic polarization measurements and corrosion morphology examinations were conducted to study the influence of microstructural characteristics on corrosion behavior of Mg–5Sn–3In alloys in Hank’s solution after extrusion.The results show that the corrosion rate of the as-cast alloy is similar to that of as-extruded alloy;however,the local corrosion susceptibility is greatly weakened in the as-extruded alloy,especially in the extrusion direction.The relatively uniform corrosion morphology of the as-extruded alloy is attributed to refined Mg_(2)Sn particles,uniform distribution of Mg_(2)Sn particles and favorable crystal orientation.Meanwhile,the cytotoxicity tests confirm that the Mg–5Sn–3In alloy exhibits cytotoxicity of Grade 0−1 for NIH3T3 cells,suggesting an acceptable cytotoxicity of this alloy in the vitro assay.展开更多
Due to the worldwide epidemic of allergic disease and a cure nowhere in sight,there is a crucial need to explore its pathophysiological mechanisms.As allergic disease has been associated with gut dysbiosis,we searched...Due to the worldwide epidemic of allergic disease and a cure nowhere in sight,there is a crucial need to explore its pathophysiological mechanisms.As allergic disease has been associated with gut dysbiosis,we searched for a possible mechanism from the perspective of the molecular interface between host and microbiota with concurrent metabolomics and microbiome composition analysis.Sprague-Dawley rats were injected with Artemisia pollen extract to stimulate a hyper reaction to pollen.This hyper reaction decreased the circulation of valine,isoleucine,aspartate,glutamate,glutamine,indole-propionate(IPA),and myo-inositol,and reduced short-chain fatty acids(SCFAs)in feces.Several beneficial genera belonging to Ruminococcaceae,Lachnospiraceae,and Clostridiales declined in the model group,whereas Helicobacter and Akkermansia were only expressed in the model group.Furthermore,the expression of intestinal claudin-3 and liver fatty acid binding protein was downregulated in the model group and associated with metabolic changes and bacteria.Our results suggest that alterations in amino acids as well as their derivatives(especially valine,and IPA which is the reductive product of tryptophan),SCFAs,and the gut microbiome(specifically Akkermansia and Helicobacter)may disrupt the intestinal barrier function by inhibiting the expression of claudin proteins and affecting the mucus layer,which further results in hay fever.展开更多
BACKGROUND Chronic hepatitis B virus(HBV)infection is a leading cause of liver morbidity and mortality worldwide.Liver fibrosis resulting from viral infection-associated inflammation and direct liver damage plays an i...BACKGROUND Chronic hepatitis B virus(HBV)infection is a leading cause of liver morbidity and mortality worldwide.Liver fibrosis resulting from viral infection-associated inflammation and direct liver damage plays an important role in disease management and prognostication.The mechanisms underlying the contribution of the liver microenvironment to fibrosis in HBV patients are not fully understood.There is an absence of effective clinical treatments for liver fibrosis progression;thus,establishing a suitable in vitro microenvironment in order to design novel therapeutics and identify molecular biomarkers to stratify patients is urgently required.AIM To examine a subset of pre-selected microenvironment factors of chronic HBV patients that may underlie fibrosis,with a focus on fibroblast activation.METHODS We examined the gene expression of key microenvironment factors in liver samples from patients with more advanced fibrosis compared with those with less severe fibrosis.We also used the human stellate cell line LX-2 in the in vitro study.Using different recombinant cytokines and growth factors or their combination,we studied how these factors interacted with LX-2 cells and pinpointed the crosstalk between the aforementioned factors and screened the most important factors.RESULTS Of the secreted factors examined,transforming growth factor(TGF)-β1,interleukin(IL)-1βand tumor necrosis factor(TNF)-αwere increased in patients with advanced fibrosis.We found that besides TGF-β1,IL-1βcan also induce a profibrotic cascade by stimulating the expression of connective tissue growth factor and platelet-derived growth factor(PDGF)in LX-2 cells.Furthermore,the proinflammatory response can be elicited in LX-2 cells following treatment with IL-1βand TNF-α,suggesting that stellate cells can respond to proinflammatory stimuli.By combining IL-1βand TGF-β1,we observed not only fibroblast activation as shown byαlpha-smooth muscle actin and PDGF induction,but also the inflammatory response as shown by increased expression of IL-1β.CONCLUSION Collectively,our data from HBV patients and in vitro studies demonstrate that the hepatic microenvironment plays an important role in mediating the crosstalk between profibrotic and proinflammatory responses and modulating fibrosis in chronic HBV patients.For the establishment of a suitable in vitro microenvironment for HBV-induced liver fibrosis,not only TGF-β1 but also IL-1βshould be considered as a necessary environmental factor.展开更多
Mesoporous silicas with different morphologies have attracted great interest in the fields of catalysis,separation and so on. In this study, silica hollow tubes with ordered mesopores were synthesized via a novel sol-...Mesoporous silicas with different morphologies have attracted great interest in the fields of catalysis,separation and so on. In this study, silica hollow tubes with ordered mesopores were synthesized via a novel sol-gel method with an ionic liquid 1-decyl-3-methylimidazolium chloride（[Dmim]Cl） and a nonionic surfactant P123（PEO_（20）PPO_（70）PEO_（20）） as the co-template. Comparatively, silica hollow spheres with disordered mesopores were synthesized with only [Dmim]Cl as the template. The template dosage is the key factor in controlling the morphology. The micelles assembly mechanism based on hydrogen bonding interactions is proposed to be responsible for the formation of the final silica morphology and mesostructure.展开更多
Berberine(BBR)is an isoquinoline alkaloid extracted from Coptis chinensis that improves diabetes,hyperlipidemia and inflammation.Due to the low oral bioavailability of BBR,its mechanism of action is closely related to...Berberine(BBR)is an isoquinoline alkaloid extracted from Coptis chinensis that improves diabetes,hyperlipidemia and inflammation.Due to the low oral bioavailability of BBR,its mechanism of action is closely related to the gut microbiota.This study focused on the CYP51 enzyme of intestinal bacteria to elucidate a new mechanism of BBR transformation by demethylation in the gut microbiota through multiple analytical techniques.First,the docking of BBR and CYP51 was performed;then,the pharmacokinetics of BBR was determined in ICR mice in vivo,and the metabolism of BBR in the liver,kidney,gut microbiota and single bacterial strains was examined in vitro.Moreover,16S rRNA analysis of ICR mouse feces indicated the relationship between BBR and the gut microbiota.Finally,recombinant E.coli containing cyp51 gene was constructed and the CYP51 enzyme lysate was induced to express.The metabolic characteristics of BBR were analyzed in the CYP51 enzyme lysate system.The results showed that CYP51 in the gut microbiota could bind stably with BBR,and the addition of voriconazole(a specific inhibitor of CYP51)slowed down the metabolism of BBR,which prevented the production of the demethylated metabolites thalifendine and berberrubine.This study demonstrated that CYP51 promoted the demethylation of BBR and enhanced its intestinal absorption,providing a new method for studying the metabolic transformation mechanism of isoquinoline alkaloids in vivo.展开更多
Magnesium （Mg） has been widely accepted as osteoconductive biomaterial, but osseointegration of Mg device at different implantation sites is still unclear. In the present study, high-purity magnesium （HP Mg） pins ...Magnesium （Mg） has been widely accepted as osteoconductive biomaterial, but osseointegration of Mg device at different implantation sites is still unclear. In the present study, high-purity magnesium （HP Mg） pins were implanted into femoral shaft and condyle of New Zealand rabbits concurrently. 2, 8, 12 and 16 weeks after surgery, rabbit femurs were harvested for micro-computed tomography （micro-CT） scanning and subsequent histological examinations. HP Mg pins were retrieved for scanning electron microscope and energy dispersive spectrum （SEM/EDS） analyses. HP Mg pins at both implantation sites performed stable corrosion with mineral deposition and bone incorporation on surface. However, difference in distribution of contact osteogenesis centers and biological properties of peri-implant bone tissues was detected between femoral shaft and femoral condyle. In femoral condyle, contact osteogenesis centers originated from both periosteum and cancellous bones and the whole HP Mg pin was encapsuled in trabecular bone at 16 weeks. Meanwhile, bone volume to total bone volume （BV/TV） and bone mineral density （BMD） of peri-implant bone tissues were above those of normal bone tissues. In femoral shaft, contact osteogenesis centers were only from periosteum and direct bone contact was confined in cortical bone, while BV/TV and BMD kept lower than normal. Furthermore, new formation of peri-implant bone tissues was more active in femoral condyle than in femoral shaft at 16 weeks. Therefore, although HP Mg performed good biocompatibility and corrosion behavior in vivo, its bioadaption of osseointegration at different implantations sites should be taken into consideration. Bone metaphysic was suitable for Mg devices where peri-implant bone tissues regenerated rapidly and the biological properties were close to normal bone tissues.展开更多
Magnesium(Mg)is a promising biomedical metal because of its biodegradability.The crevice between tissue and Mg implant can not be neglected in some implantation sites due to inducing crevice corrosion of Mg.In this pa...Magnesium(Mg)is a promising biomedical metal because of its biodegradability.The crevice between tissue and Mg implant can not be neglected in some implantation sites due to inducing crevice corrosion of Mg.In this paper,a new single mold was designed to build the in vitro experimental setup and four kinds of solutions,i.e.the deionized water(DW),the 0.9 wt.%sodium chloride solution(NaCl),the phosphate buffer saline(PBS)and the modified simulated body fluid(m-SBF)were used to explore necessary factors of crevice corrosion in Mg.It was observed that crevice corrosion in Mg sheets would occur in NaCl and PBS solution under 0.2,0.5 and 0.8 mm crevice thickness.And it was found that there were two necessary factors,i.e.chloride ion and crevice dimension,in crevice corrosion.For the high-purity Mg cannulated screws,crevice corrosion could occur inside tunnel when immersed in PBS.展开更多
Bone screws encounter complex mechanical environment in fracture fixation of weight-bearing bone.In the present study, high-purity magnesium（HP Mg） screws were applied in fixation of rabbit femoral intracondylar fra...Bone screws encounter complex mechanical environment in fracture fixation of weight-bearing bone.In the present study, high-purity magnesium（HP Mg） screws were applied in fixation of rabbit femoral intracondylar fracture with 3 mm gap. In the control group, HP Mg screws of the same design were implanted at corresponding position of contralateral leg. At 4, 8 and 16 weeks after surgery, retrieved femurs went through micro-computed tomography（micro-CT） scanning and hard tissue processing. Under mechanical stress involved in fracture fixation, bending of screw bolt was observed at the portion exposed to facture gap at 4 weeks. Then local corrosion at the same portion was detected 16 weeks after surgery,which indicated the accumulation effect of mechanical stress on Mg corrosion. HP Mg screws in the fracture group had no significant difference with the control group in screw volume, surface area, surfaceto-volume ratio（S/V）. And peri-implant bone volume/tissues volume（BV/TV） and bone volume density（BMD） in the fracture group was comparable to that in the control group. Furthermore, histological analysis showed new formed bone tissues in fracture gap and fracture healing 16 weeks after surgery. Under mechanical stress, HP Mg screw suffered bolt bending and local corrosion at the portion exposed to fracture gap. But it had no influence on the integral corrosion behaviors, osseointegration of HP Mg screw and the fracture healing. Therefore, HP Mg screws possessed good potential in fracture fixation of weightbearing bones.展开更多
Morinda officinalis oligosaccharides(MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. H...Morinda officinalis oligosaccharides(MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. Here, we show that oral MOO acted on tryptophan → 5-hydroxytryptophan(5-HTP) → serotonin(5-HT) metabolic pathway in the gut microbiota. MOO could increase tryptophan hydroxylase levels in the gut microbiota which accelerated 5-HTP production from tryptophan;meanwhile, MOO inhibited 5-hydroxytryptophan decarboxylase activity, thus reduced 5-HT generation,and accumulated 5-HTP. The raised 5-HTP from the gut microbiota was absorbed to the blood, and then passed across the blood-brain barrier to improve 5-HT levels in the brain. Additionally, pentasaccharide,as one of the main components in MOO, exerted the significant anti-depressant effect through a mechanism identical to that of MOO. This study reveals for the first time that MOO can alleviate depression via increasing 5-HTP in the gut microbiota.展开更多
The progression of hyperuricemia disease is often accompanied by damage to renal function.However,there are few studies on hyperuricemia nephropathy,especially its association with intestinal flora.This study combines...The progression of hyperuricemia disease is often accompanied by damage to renal function.However,there are few studies on hyperuricemia nephropathy,especially its association with intestinal flora.This study combines metabolomics and gut microbiota diversity analysis to explore metabolic changes using a rat model as well as the changes in intestinal flora composition.The results showed that amino acid metabolism was disturbed with serine,glutamate and glutamine being downregulated whilst glycine,hydroxyproline and alanine being upregulated.The combined glycine,serine and glutamate could predict hyperuricemia nephropathy with an area under the curve of 1.00.Imbalanced intestinal flora was also observed.Flavobacterium,Myroides,Corynebacterium,Alcaligenaceae,Oligella and other conditional pathogens increased significantly in the model group,while Blautia and Roseburia,the shortchain fatty acid producing bacteria,declined greatly.At phylum,family and genus levels,disordered nitrogen circulation in gut microbiota was detected.In the model group,the uric acid decomposition pathway was enhanced with reinforced urea liver-intestine circulation.The results implied that the intestinal flora play a vital role in the pathogenesis of hyperuricemia nephropathy.Hence,modulation of gut microbiota or targeting at metabolic enzymes,i.e.,urease,could assist the treatment and prevention of this disease.展开更多
Multicomponent metal sulfides have been recognized as promising anode materials for lithium/sodiumion storage given their enticing theoretical capacities. However, the simplification of synthetic processes and the con...Multicomponent metal sulfides have been recognized as promising anode materials for lithium/sodiumion storage given their enticing theoretical capacities. However, the simplification of synthetic processes and the construction of heterogeneous interfaces of multimetal sulfides remain great challenges. Herein,a hierarchical 1T-MoS2/carbon nanosheet decorated Co1–xS/N-doped carbon(Co1–xS/NC@MoS2/C) hollow nanofiber was designed and constructed via a one-pot hydrothermal method using a cobalt-based coordination polymer nanofiber. This nanofiber can transform in-situ into conductive N-doped carbon hollow fibers embedded with active Co1–xS nanoparticles, enabling the epitaxial growth of MoS2 nanosheets.Consequently, the Co1–xS/NC@MoS2/C composites achieve exceptional lithium/sodium-ion storage performance. Compared to MoS2/C microspheres and Co1–xS/NC hollow nanofibers alone, the Co1–xS/NC@MoS2/C hollow nanofibers deliver higher discharge capacities(1085.9 mAh g^-1 for lithium-ion batteries(LIBs) and 748.5 mAh g^-1 for sodium-ion batteries(SIBs) at 100 mA g^-1), better capacity retention(910 mAh g^-1 for LIBs and 636.5 mAh g^-1 for SIBs after 150 cycles at 100 mA g^-1), and increased cycling stability(407.2 mAh g^-1 after 1000 cycles for SIBs at 1000 m A g^-1). Furthermore, the kinetic analysis shows that the lithium/sodium-ion storage processes of the Co1–xS/NC@MoS2/C electrode are mainly controlled by pseudocapacitance behavior. The excellent electrochemical properties can thus be ascribed to the synergy of the MoS2/C nanosheets with the enlarged interlayer spacing, good conductivity of the carbon layers, and the Co1–xS nanoparticles embedded in the hollow nanofibers with extensive reaction sites.展开更多
基金the National Key Research and Development Program of China(No.2017YFA0403803)the National Natural Science Foundation of China(Nos.52022017,51974058,51525401,51927801,81974325)+1 种基金the Science and Technology Commission of Shanghai Municipality,China(No.18ZR1428700)the Liaoning Revitalization Talents Program,China(No.XLYC1808005).
文摘The microstructural observation,the mass loss test,potentiodynamic polarization measurements and corrosion morphology examinations were conducted to study the influence of microstructural characteristics on corrosion behavior of Mg–5Sn–3In alloys in Hank’s solution after extrusion.The results show that the corrosion rate of the as-cast alloy is similar to that of as-extruded alloy;however,the local corrosion susceptibility is greatly weakened in the as-extruded alloy,especially in the extrusion direction.The relatively uniform corrosion morphology of the as-extruded alloy is attributed to refined Mg_(2)Sn particles,uniform distribution of Mg_(2)Sn particles and favorable crystal orientation.Meanwhile,the cytotoxicity tests confirm that the Mg–5Sn–3In alloy exhibits cytotoxicity of Grade 0−1 for NIH3T3 cells,suggesting an acceptable cytotoxicity of this alloy in the vitro assay.
基金supported by the National Natural Science Foundation of China(81971515 and 81973290)CAMS Innovation Fund for Medical Sciences(2016-I2M-3-011 and 2016-I2M-1-003)+4 种基金the Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study(Z141102004414062)the National Megaproject for Innovative Drugs(2018ZX09711001-002-002)Beijing Natural Sciences Fund Key Projects(7181007)the Fundamental Research Fund for Central Universities of Peking Union Medical College(3332020037)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support(ZYLX201826)。
文摘Due to the worldwide epidemic of allergic disease and a cure nowhere in sight,there is a crucial need to explore its pathophysiological mechanisms.As allergic disease has been associated with gut dysbiosis,we searched for a possible mechanism from the perspective of the molecular interface between host and microbiota with concurrent metabolomics and microbiome composition analysis.Sprague-Dawley rats were injected with Artemisia pollen extract to stimulate a hyper reaction to pollen.This hyper reaction decreased the circulation of valine,isoleucine,aspartate,glutamate,glutamine,indole-propionate(IPA),and myo-inositol,and reduced short-chain fatty acids(SCFAs)in feces.Several beneficial genera belonging to Ruminococcaceae,Lachnospiraceae,and Clostridiales declined in the model group,whereas Helicobacter and Akkermansia were only expressed in the model group.Furthermore,the expression of intestinal claudin-3 and liver fatty acid binding protein was downregulated in the model group and associated with metabolic changes and bacteria.Our results suggest that alterations in amino acids as well as their derivatives(especially valine,and IPA which is the reductive product of tryptophan),SCFAs,and the gut microbiome(specifically Akkermansia and Helicobacter)may disrupt the intestinal barrier function by inhibiting the expression of claudin proteins and affecting the mucus layer,which further results in hay fever.
基金National Natural Science Foundation for the Youth of China,No.81500460,No.81700550.
文摘BACKGROUND Chronic hepatitis B virus(HBV)infection is a leading cause of liver morbidity and mortality worldwide.Liver fibrosis resulting from viral infection-associated inflammation and direct liver damage plays an important role in disease management and prognostication.The mechanisms underlying the contribution of the liver microenvironment to fibrosis in HBV patients are not fully understood.There is an absence of effective clinical treatments for liver fibrosis progression;thus,establishing a suitable in vitro microenvironment in order to design novel therapeutics and identify molecular biomarkers to stratify patients is urgently required.AIM To examine a subset of pre-selected microenvironment factors of chronic HBV patients that may underlie fibrosis,with a focus on fibroblast activation.METHODS We examined the gene expression of key microenvironment factors in liver samples from patients with more advanced fibrosis compared with those with less severe fibrosis.We also used the human stellate cell line LX-2 in the in vitro study.Using different recombinant cytokines and growth factors or their combination,we studied how these factors interacted with LX-2 cells and pinpointed the crosstalk between the aforementioned factors and screened the most important factors.RESULTS Of the secreted factors examined,transforming growth factor(TGF)-β1,interleukin(IL)-1βand tumor necrosis factor(TNF)-αwere increased in patients with advanced fibrosis.We found that besides TGF-β1,IL-1βcan also induce a profibrotic cascade by stimulating the expression of connective tissue growth factor and platelet-derived growth factor(PDGF)in LX-2 cells.Furthermore,the proinflammatory response can be elicited in LX-2 cells following treatment with IL-1βand TNF-α,suggesting that stellate cells can respond to proinflammatory stimuli.By combining IL-1βand TGF-β1,we observed not only fibroblast activation as shown byαlpha-smooth muscle actin and PDGF induction,but also the inflammatory response as shown by increased expression of IL-1β.CONCLUSION Collectively,our data from HBV patients and in vitro studies demonstrate that the hepatic microenvironment plays an important role in mediating the crosstalk between profibrotic and proinflammatory responses and modulating fibrosis in chronic HBV patients.For the establishment of a suitable in vitro microenvironment for HBV-induced liver fibrosis,not only TGF-β1 but also IL-1βshould be considered as a necessary environmental factor.
基金financially supported by the National Natural Science Foundation of China (Nos. 21206118, 21328601)
文摘Mesoporous silicas with different morphologies have attracted great interest in the fields of catalysis,separation and so on. In this study, silica hollow tubes with ordered mesopores were synthesized via a novel sol-gel method with an ionic liquid 1-decyl-3-methylimidazolium chloride（[Dmim]Cl） and a nonionic surfactant P123（PEO_（20）PPO_（70）PEO_（20）） as the co-template. Comparatively, silica hollow spheres with disordered mesopores were synthesized with only [Dmim]Cl as the template. The template dosage is the key factor in controlling the morphology. The micelles assembly mechanism based on hydrogen bonding interactions is proposed to be responsible for the formation of the final silica morphology and mesostructure.
基金The project was supported by CAMS Innovation Fund for Medical Sciences(CIFMS,Grant No.:2016-I2M-3-011,China)the National Natural Science Foundation of China(Grant Nos.:81803613 and 81973290)+2 种基金Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study(Grant No.:Z141102004414062,China)Beijing Natural Sciences Fund Key Projects(Grant No.:7181007)the National Megaproject for Innovative Drugs(Grant No.:2018ZX09711001-002-002).
文摘Berberine(BBR)is an isoquinoline alkaloid extracted from Coptis chinensis that improves diabetes,hyperlipidemia and inflammation.Due to the low oral bioavailability of BBR,its mechanism of action is closely related to the gut microbiota.This study focused on the CYP51 enzyme of intestinal bacteria to elucidate a new mechanism of BBR transformation by demethylation in the gut microbiota through multiple analytical techniques.First,the docking of BBR and CYP51 was performed;then,the pharmacokinetics of BBR was determined in ICR mice in vivo,and the metabolism of BBR in the liver,kidney,gut microbiota and single bacterial strains was examined in vitro.Moreover,16S rRNA analysis of ICR mouse feces indicated the relationship between BBR and the gut microbiota.Finally,recombinant E.coli containing cyp51 gene was constructed and the CYP51 enzyme lysate was induced to express.The metabolic characteristics of BBR were analyzed in the CYP51 enzyme lysate system.The results showed that CYP51 in the gut microbiota could bind stably with BBR,and the addition of voriconazole(a specific inhibitor of CYP51)slowed down the metabolism of BBR,which prevented the production of the demethylated metabolites thalifendine and berberrubine.This study demonstrated that CYP51 promoted the demethylation of BBR and enhanced its intestinal absorption,providing a new method for studying the metabolic transformation mechanism of isoquinoline alkaloids in vivo.
基金supported by the National Natural Science Foundation of China(Nos.51271117 and 81371935)the Biomedical Program of Science and Technology Innovation Project supported by Shanghai(Nos.14441901800 and 14441901802)
文摘Magnesium （Mg） has been widely accepted as osteoconductive biomaterial, but osseointegration of Mg device at different implantation sites is still unclear. In the present study, high-purity magnesium （HP Mg） pins were implanted into femoral shaft and condyle of New Zealand rabbits concurrently. 2, 8, 12 and 16 weeks after surgery, rabbit femurs were harvested for micro-computed tomography （micro-CT） scanning and subsequent histological examinations. HP Mg pins were retrieved for scanning electron microscope and energy dispersive spectrum （SEM/EDS） analyses. HP Mg pins at both implantation sites performed stable corrosion with mineral deposition and bone incorporation on surface. However, difference in distribution of contact osteogenesis centers and biological properties of peri-implant bone tissues was detected between femoral shaft and femoral condyle. In femoral condyle, contact osteogenesis centers originated from both periosteum and cancellous bones and the whole HP Mg pin was encapsuled in trabecular bone at 16 weeks. Meanwhile, bone volume to total bone volume （BV/TV） and bone mineral density （BMD） of peri-implant bone tissues were above those of normal bone tissues. In femoral shaft, contact osteogenesis centers were only from periosteum and direct bone contact was confined in cortical bone, while BV/TV and BMD kept lower than normal. Furthermore, new formation of peri-implant bone tissues was more active in femoral condyle than in femoral shaft at 16 weeks. Therefore, although HP Mg performed good biocompatibility and corrosion behavior in vivo, its bioadaption of osseointegration at different implantations sites should be taken into consideration. Bone metaphysic was suitable for Mg devices where peri-implant bone tissues regenerated rapidly and the biological properties were close to normal bone tissues.
基金financially supported by the Natural Science Foundation of China(No.51571142)the National Key Research and Development Program of China(No.2018YFC1106600)。
文摘Magnesium(Mg)is a promising biomedical metal because of its biodegradability.The crevice between tissue and Mg implant can not be neglected in some implantation sites due to inducing crevice corrosion of Mg.In this paper,a new single mold was designed to build the in vitro experimental setup and four kinds of solutions,i.e.the deionized water(DW),the 0.9 wt.%sodium chloride solution(NaCl),the phosphate buffer saline(PBS)and the modified simulated body fluid(m-SBF)were used to explore necessary factors of crevice corrosion in Mg.It was observed that crevice corrosion in Mg sheets would occur in NaCl and PBS solution under 0.2,0.5 and 0.8 mm crevice thickness.And it was found that there were two necessary factors,i.e.chloride ion and crevice dimension,in crevice corrosion.For the high-purity Mg cannulated screws,crevice corrosion could occur inside tunnel when immersed in PBS.
基金supported by the National Natural Science Foundation of China (Nos. 51271117 and 81371935)the Biomedical Program of Science and Technology Innovation Project supported by Shanghai (Nos. 14441901800 and 14441901802)
文摘Bone screws encounter complex mechanical environment in fracture fixation of weight-bearing bone.In the present study, high-purity magnesium（HP Mg） screws were applied in fixation of rabbit femoral intracondylar fracture with 3 mm gap. In the control group, HP Mg screws of the same design were implanted at corresponding position of contralateral leg. At 4, 8 and 16 weeks after surgery, retrieved femurs went through micro-computed tomography（micro-CT） scanning and hard tissue processing. Under mechanical stress involved in fracture fixation, bending of screw bolt was observed at the portion exposed to facture gap at 4 weeks. Then local corrosion at the same portion was detected 16 weeks after surgery,which indicated the accumulation effect of mechanical stress on Mg corrosion. HP Mg screws in the fracture group had no significant difference with the control group in screw volume, surface area, surfaceto-volume ratio（S/V）. And peri-implant bone volume/tissues volume（BV/TV） and bone volume density（BMD） in the fracture group was comparable to that in the control group. Furthermore, histological analysis showed new formed bone tissues in fracture gap and fracture healing 16 weeks after surgery. Under mechanical stress, HP Mg screw suffered bolt bending and local corrosion at the portion exposed to fracture gap. But it had no influence on the integral corrosion behaviors, osseointegration of HP Mg screw and the fracture healing. Therefore, HP Mg screws possessed good potential in fracture fixation of weightbearing bones.
基金supported by Key Project of Beijing Natural Science Foundation (No.7181007,China)the CAMS Innovation Fund for Medical Sciences (CIFMS+2 种基金Nos.2016-I2M-3-011,20211-I2M-007,2021-I2M-1-027,and 2021-I2M-1-028,China)National Natural Science Foundation of China (Nos.81973290 and 82173888)Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study (Z141102004414062,China)。
文摘Morinda officinalis oligosaccharides(MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. Here, we show that oral MOO acted on tryptophan → 5-hydroxytryptophan(5-HTP) → serotonin(5-HT) metabolic pathway in the gut microbiota. MOO could increase tryptophan hydroxylase levels in the gut microbiota which accelerated 5-HTP production from tryptophan;meanwhile, MOO inhibited 5-hydroxytryptophan decarboxylase activity, thus reduced 5-HT generation,and accumulated 5-HTP. The raised 5-HTP from the gut microbiota was absorbed to the blood, and then passed across the blood-brain barrier to improve 5-HT levels in the brain. Additionally, pentasaccharide,as one of the main components in MOO, exerted the significant anti-depressant effect through a mechanism identical to that of MOO. This study reveals for the first time that MOO can alleviate depression via increasing 5-HTP in the gut microbiota.
基金supported by the National Natural Science Foundation of China(Nos.81573493 and 81973290)CAMS Innovation Fund for Medical Sciences(CIFMS,No.2016-I2M-3-011,China)+2 种基金Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study(Z141102004414062,China)the National Megaproject for Innovative Drugs(Nos.2018ZX09711001-002-002 and2018ZX09302015,China)Beijing Natural Sciences Fund Key Projects(NO.7181007).
文摘The progression of hyperuricemia disease is often accompanied by damage to renal function.However,there are few studies on hyperuricemia nephropathy,especially its association with intestinal flora.This study combines metabolomics and gut microbiota diversity analysis to explore metabolic changes using a rat model as well as the changes in intestinal flora composition.The results showed that amino acid metabolism was disturbed with serine,glutamate and glutamine being downregulated whilst glycine,hydroxyproline and alanine being upregulated.The combined glycine,serine and glutamate could predict hyperuricemia nephropathy with an area under the curve of 1.00.Imbalanced intestinal flora was also observed.Flavobacterium,Myroides,Corynebacterium,Alcaligenaceae,Oligella and other conditional pathogens increased significantly in the model group,while Blautia and Roseburia,the shortchain fatty acid producing bacteria,declined greatly.At phylum,family and genus levels,disordered nitrogen circulation in gut microbiota was detected.In the model group,the uric acid decomposition pathway was enhanced with reinforced urea liver-intestine circulation.The results implied that the intestinal flora play a vital role in the pathogenesis of hyperuricemia nephropathy.Hence,modulation of gut microbiota or targeting at metabolic enzymes,i.e.,urease,could assist the treatment and prevention of this disease.
基金This work was supported by the National Natural Science Foundation of China(51673117,21805193 and 51973118)Postdoctoral Science Foundation of China(2019M650212)+2 种基金Key R&D Program of Guangdong Province(2019B010929002 and 2019B010941001)Science and Technology Innovation Commission of Shenzhen(JCYJ20170817094628397,JCYJ20170818093832350,JCYJ20170818112409808,JCYJ20170818100112531,JCYJ20180507184711069,and JCYJ20180305125319991)The authors also thank the Materials and Devices Testing Center of Tsinghua University Shenzhen Graduate School.
文摘Multicomponent metal sulfides have been recognized as promising anode materials for lithium/sodiumion storage given their enticing theoretical capacities. However, the simplification of synthetic processes and the construction of heterogeneous interfaces of multimetal sulfides remain great challenges. Herein,a hierarchical 1T-MoS2/carbon nanosheet decorated Co1–xS/N-doped carbon(Co1–xS/NC@MoS2/C) hollow nanofiber was designed and constructed via a one-pot hydrothermal method using a cobalt-based coordination polymer nanofiber. This nanofiber can transform in-situ into conductive N-doped carbon hollow fibers embedded with active Co1–xS nanoparticles, enabling the epitaxial growth of MoS2 nanosheets.Consequently, the Co1–xS/NC@MoS2/C composites achieve exceptional lithium/sodium-ion storage performance. Compared to MoS2/C microspheres and Co1–xS/NC hollow nanofibers alone, the Co1–xS/NC@MoS2/C hollow nanofibers deliver higher discharge capacities(1085.9 mAh g^-1 for lithium-ion batteries(LIBs) and 748.5 mAh g^-1 for sodium-ion batteries(SIBs) at 100 mA g^-1), better capacity retention(910 mAh g^-1 for LIBs and 636.5 mAh g^-1 for SIBs after 150 cycles at 100 mA g^-1), and increased cycling stability(407.2 mAh g^-1 after 1000 cycles for SIBs at 1000 m A g^-1). Furthermore, the kinetic analysis shows that the lithium/sodium-ion storage processes of the Co1–xS/NC@MoS2/C electrode are mainly controlled by pseudocapacitance behavior. The excellent electrochemical properties can thus be ascribed to the synergy of the MoS2/C nanosheets with the enlarged interlayer spacing, good conductivity of the carbon layers, and the Co1–xS nanoparticles embedded in the hollow nanofibers with extensive reaction sites.
