White spot lesions(WSLs), due to enamel demineralization, occur frequently in orthodontic treatment. We recently developed a novel rechargeable dental composite containing nanoparticles of amorphous calcium phosphate(...White spot lesions(WSLs), due to enamel demineralization, occur frequently in orthodontic treatment. We recently developed a novel rechargeable dental composite containing nanoparticles of amorphous calcium phosphate(NACP) with long-term calcium(Ca) and phosphate(P) ion release and caries-inhibiting capability. The objectives of this study were to develop the first NACPrechargeable orthodontic cement and investigate the effects of recharge duration and frequency on the efficacy of ion re-release.The rechargeable cement consisted of pyromellitic glycerol dimethacrylate(PMGDM) and ethoxylated bisphenol A dimethacrylate(EBPADMA). NACP was mixed into the resin at 40% by mass. Specimens were tested for orthodontic bracket shear bond strength(SBS) to enamel, Ca and P ion initial release, recharge and re-release. The new orthodontic cement exhibited an SBS similar to commercial orthodontic cement without CaP release(P40.1). Specimens after one recharge treatment(e.g., 1 min immersion in recharge solution repeating three times in one day, referred to as "1 min 3 times") exhibited a substantial and continuous re-release of Ca and P ions for 14 days without further recharge. The ion re-release did not decrease with increasing the number of recharge/re-release cycles(P40.1). The ion re-release concentrations at 14 days versus various recharge treatments were as follows: 1 min 3 times43 min 2 times41 min 2 times46 min 1 time43 min 1 time41 min 1 time. In conclusion, although previous studies have shown that NACP nanocomposite remineralized tooth lesions and inhibited caries, the present study developed the first orthodontic cement with Ca and P ion recharge and long-term release capability. This NACP-rechargeable orthodontic cement is a promising therapy to inhibit enamel demineralization and WSLs around orthodontic brackets.展开更多
Objective:To observe the effect of Xuebijing,a complex traditional Chinese preparation,on inflammation and prognosis of patients with pneumonia.Methods:The patients with ventilator-associated pneumonia in the intensiv...Objective:To observe the effect of Xuebijing,a complex traditional Chinese preparation,on inflammation and prognosis of patients with pneumonia.Methods:The patients with ventilator-associated pneumonia in the intensive care unit(ICU)were randomly divided into the control group and the treatment group with 35 cases in each group.Both groups were given routine treatment such as anti-inflammatory drugs,rehydration,expectorant,and nutritional support,while the treatment group was additionally given Xuebijing injection.Serum C-reactive protein(CRP),clinical pulmonary infection score(CPIS),acute physiology,and chronic health scoreⅡ(APACHEⅡ)were recorded before treatment,the 3rd and 7th day after treatment.The duration of antibiotic use,mechanical ventilation,ICU stay,and mortality during 28 days was recorded.Results:There was no significant difference in CRP,CPIS,and APACHEⅡbetween the two groups before treatment(P>0.05).The improvement of CRP,CPIS,and APACHEⅡin the treatment group was better than those in the control group on the 3 and 7 days after treatment,and the differences were statistically significant(P<0.05).The duration of antibiotic use,mechanical ventilation,and ICU stay in the treatment group were less than those in the control group(P<0.05).The 28-day mortality of the treatment group was lower than that of the control group,but the difference was not statistically significant(P>0.05).Conclusions:Xuebijing injection can improve the inflammatory indexes of patients with ventilator-associated pneumonia,and can partly improve the prognosis.展开更多
The regeneration of hierarchical osteochondral units is challenging due to difficulties in inducing spatial,directional and controllable differentiation of mesenchymal stem cells(MSCs)into cartilage and bone compartme...The regeneration of hierarchical osteochondral units is challenging due to difficulties in inducing spatial,directional and controllable differentiation of mesenchymal stem cells(MSCs)into cartilage and bone compartments.Emerging organoid technology offers new opportunities for osteochondral regeneration.In this study,we developed gelatin-based microcryogels customized using hyaluronic acid(HA)and hydroxyapatite(HYP),respectively for inducing cartilage and bone regeneration(denoted as CH-Microcryogels and OS-Microcryogels)through in vivo self-assembly into osteochondral organoids.The customized microcryogels showed good cytocompatibility and induced chondrogenic and osteogenic differentiation of MSCs,while also demonstrating the ability to self-assemble into osteochondral organoids with no delamination in the biphasic cartilage-bone structure.Analysis by mRNA-seq showed that CH-Microcryogels promoted chondrogenic differentiation and inhibited inflammation,while OS-Microcryogels facilitated osteogenic differentiation and suppressed the immune response,by regulating specific signaling pathways.Finally,the in vivo engraftment of pre-differentiated customized microcryogels into canine osteochondral defects resulted in the spontaneous assembly of an osteochondral unit,inducing simultaneous regeneration of both articular cartilage and subchondral bone.In conclusion,this novel approach for generating self-assembling osteochondral organoids utilizing tailor-made microcryogels presents a highly promising avenue for advancing the field of tissue engineering.展开更多
Aedes aegypti(Ae.aegypti)is a major vector of dengue virus(DENV)and Zika virus(ZIKV).Understanding the complex interaction mechanisms between mosquito vectors and arboviruses is essential to interrupt virus trans-miss...Aedes aegypti(Ae.aegypti)is a major vector of dengue virus(DENV)and Zika virus(ZIKV).Understanding the complex interaction mechanisms between mosquito vectors and arboviruses is essential to interrupt virus trans-mission.This study constructed CYP4C21 knockout(KO)Aag2 cells(Ae.aegypti cells)and confirmed that CYP4C21 KO reduced DENV2 and ZIKV copies in Aag2 cells,which suggests that CYP4C21 may play an impor-tant role in mosquito infection with arboviruses.Furthermore,it is the first report of the CYP4 family related to viral infection,which lays the foundation for exploring the role of the CYP4C21 in the interaction of Ae.aegypti and arbovirus and provides novel insights into the function of cytochrome family proteins.展开更多
The construction of a lunar base is considered to be an important step towards deep-space exploration by humanity,and will rely on the utilisation of in situ lunar resources.In this paper,we discuss the current knowle...The construction of a lunar base is considered to be an important step towards deep-space exploration by humanity,and will rely on the utilisation of in situ lunar resources.In this paper,we discuss the current knowledge on the feasibility of converting lunar soil to high-performance fibres that can be used for the construction of a lunar base.This fibre would be combined with further portions of lunar soil to generate fibre-reinforced composites,which is utilized as multi-functional materials for lunar base construction.We discuss and analyse the latest findings regarding the composition of lunar soil simulants and their fibrisation properties,and techniques for fibre spinning and system integration.Finally,we suggest how the achievements made so far could be applied to the construction of a lunar base.展开更多
Mesenchymal stem cells(MSCs)can be effective in alleviating the progression of osteoarthritis(OA).However,low MSC retention and survival at the injection site frequently require high doses of cells and/or repeated inj...Mesenchymal stem cells(MSCs)can be effective in alleviating the progression of osteoarthritis(OA).However,low MSC retention and survival at the injection site frequently require high doses of cells and/or repeated injections,which are not economically viable and create additional risks of complications.In this study,we produced MSC-laden microcarriers in spinner flask culture as cell delivery vehicles.These microcarriers containing a low initial dose of MSCs administered through a single injection in a rat anterior cruciate ligament(ACL)transection model of OA achieved similar reparative effects as repeated high doses of MSCs,as evaluated through imaging and histological analyses.Mechanistic investigations were conducted using a co-culture model involving human primary chondrocytes grown in monolayer,together with MSCs grown either within 3D constructs or as a monolayer.Co-culture supernatants subjected to secretome analysis showed significant decrease of inflammatory factors in the 3D group.RNA-seq of co-cultured MSCs and chondrocytes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis revealed processes relating to early chondrogenesis and increased extracellular matrix interactions in MSCs of the 3D group,as well as phenotypic maintenance in the co-cultured chondrocytes.The cell delivery platform we investigated may be effective in reducing the cell dose and injection frequency required for therapeutic applications.展开更多
Quinolones (QNs) are widely used for their broad antibacterial spectrum and good antibacterial activities,desirable pharmacokinetic characteristics and few cross reactions with other therapeutic agents. However,QNs ha...Quinolones (QNs) are widely used for their broad antibacterial spectrum and good antibacterial activities,desirable pharmacokinetic characteristics and few cross reactions with other therapeutic agents. However,QNs have adverse effects including chondrotoxicity in juvenile animals,so the use of QNs is contraindicated in children and adolescents. In regarding to the chondrotoxicity of QNs,numerous studies have been done. The current hypothesis suggests that QNs compete with the β1 integrin receptors residing on chondrocyte surface for extracellular Mg ions,which leads to alternation in β1 integrin expression,or function and eventually results in chondrocyte death. Stupack et al (2001)demonstrated that caspase-8 could be recruited to unligated integrins in adherent cells and further initiate apoptosis in a death receptor-independent manner. Sheng et al (2008) found that ofloxacin induced rabbit's chondrocyte apoptosis by causing disturbance of β1 integrin functions and subsequently through caspase-8-dependent mitochondrial pathway.Apoptosis could be initiated through the stimulation of death receptors and through an intrinsic pathway from mitochondria. Santangelo and Bertone (2011) and Wu et al (2011) found that TNFα could be expressed in human primary condrocytes inducing by interleukin-1beta (IL-1) or lipopolysaccharide (LPS). However,to date there have not been sufficient results to support that signaling from the death receptors was involved in QNs-induced chondrocyte apoptosis.In addition,dilated cisternae of rough endoplasmic reticulum (ER) have been noticed in QNs-induced arthropathy.ER can participate in the initiation of apoptosis. Varieties of harmful cellular stimuli could lead to ERs (ER stress). Elevated ERs results in cellular apoptosis. But whether ERs mediates apoptosis in QNs-treated chondrocytes is not clear yet.In this study,we chose two QNs agents and chondrocytes were treated with ofloxacin and marbofloxacin at final concentrations of 20 μg / mL,50 μg / mL and 100 μg / mL respectively in vitro for 2 h,8 h and 24 h. Cell survival rate,cell apoptosis rate and death receptor pathway factors TNFα (intracellular tumor necrosis factor-alpha),TNFR1 (TNF receptor-1),TRADD (TNF receptor 1 associated via death domain),FADD (Fas-associated protein with death domain),caspase-8 and ERs mediated apoptosis factors caspase-12,GADD153 (CHOP or DDIT3),GRP78 (Bip),calpain,and anti-apoptosis factors Bcl-2 (B-cell lymphoma 2),NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) gene expression levels were measured by quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) analysis to determine the dose-response relationship. We further silenced the expression of TNFR1 successfully by transferring TNFR1-siRNA to chondrocytes to confirm whether TNFα / TNFR1 signaling pathways are involved ofloxacin and marbofloxacin-induced apoptosis. Furthermore,expression of death receptor pathway representative proteins TNFα / TNFR1 and endocytoplasmic reticulum (ER) pathway representative protein caspase-12 were confirmed using Western Blot.We have found that ofloxacin and marbofloxacin could induce apoptosis of chondrocytes in a time-and dose-dependent fashion within 24 h. mRNA of TNFα,TNFR1,TRADD,FADD and caspase-8 (caspase-8 of ofloxacin treated group were at 24 h) were highly expressed at 8 h,and GADD153,GRP78,calpain and caspase-12 at 8 h or 24 h,and antiapoptosis factors NF-κB and Bcl-2 were also raised after 2 h,all in a dose-dependent fashion. Expression of caspase-8was downregulated after silenced TNFR1. TNFα and TNFR1 proteins were expressed at 8 h and caspase-12 proteins were expressed at 24 h. In addition,ofloxacin showed a higher toxicity.Our results indicate that death receptor pathway TNF / TNFR1 and ERs mediated apoptosis factors are involved in ofloxacin and marbofloxacin-induced apoptosis of in vitro cultured juvenile dog joint chondrocytes within 24 h.展开更多
基金supported by NIH R01 DE17974(Hockin HK Xu)National Science Foundation of China 81200820(to Xian-Ju Xie),81400487(to Lin Wang)+1 种基金Beijing Nova Program xx2014B060(to Xian-Ju Xie)University of Maryland School of Dentistry bridging fund(to Hockin HK Xu)
文摘White spot lesions(WSLs), due to enamel demineralization, occur frequently in orthodontic treatment. We recently developed a novel rechargeable dental composite containing nanoparticles of amorphous calcium phosphate(NACP) with long-term calcium(Ca) and phosphate(P) ion release and caries-inhibiting capability. The objectives of this study were to develop the first NACPrechargeable orthodontic cement and investigate the effects of recharge duration and frequency on the efficacy of ion re-release.The rechargeable cement consisted of pyromellitic glycerol dimethacrylate(PMGDM) and ethoxylated bisphenol A dimethacrylate(EBPADMA). NACP was mixed into the resin at 40% by mass. Specimens were tested for orthodontic bracket shear bond strength(SBS) to enamel, Ca and P ion initial release, recharge and re-release. The new orthodontic cement exhibited an SBS similar to commercial orthodontic cement without CaP release(P40.1). Specimens after one recharge treatment(e.g., 1 min immersion in recharge solution repeating three times in one day, referred to as "1 min 3 times") exhibited a substantial and continuous re-release of Ca and P ions for 14 days without further recharge. The ion re-release did not decrease with increasing the number of recharge/re-release cycles(P40.1). The ion re-release concentrations at 14 days versus various recharge treatments were as follows: 1 min 3 times43 min 2 times41 min 2 times46 min 1 time43 min 1 time41 min 1 time. In conclusion, although previous studies have shown that NACP nanocomposite remineralized tooth lesions and inhibited caries, the present study developed the first orthodontic cement with Ca and P ion recharge and long-term release capability. This NACP-rechargeable orthodontic cement is a promising therapy to inhibit enamel demineralization and WSLs around orthodontic brackets.
基金This work was supported by the Talent Funding Project of Tangshan City in Hebei Province(No.a201902005).
文摘Objective:To observe the effect of Xuebijing,a complex traditional Chinese preparation,on inflammation and prognosis of patients with pneumonia.Methods:The patients with ventilator-associated pneumonia in the intensive care unit(ICU)were randomly divided into the control group and the treatment group with 35 cases in each group.Both groups were given routine treatment such as anti-inflammatory drugs,rehydration,expectorant,and nutritional support,while the treatment group was additionally given Xuebijing injection.Serum C-reactive protein(CRP),clinical pulmonary infection score(CPIS),acute physiology,and chronic health scoreⅡ(APACHEⅡ)were recorded before treatment,the 3rd and 7th day after treatment.The duration of antibiotic use,mechanical ventilation,ICU stay,and mortality during 28 days was recorded.Results:There was no significant difference in CRP,CPIS,and APACHEⅡbetween the two groups before treatment(P>0.05).The improvement of CRP,CPIS,and APACHEⅡin the treatment group was better than those in the control group on the 3 and 7 days after treatment,and the differences were statistically significant(P<0.05).The duration of antibiotic use,mechanical ventilation,and ICU stay in the treatment group were less than those in the control group(P<0.05).The 28-day mortality of the treatment group was lower than that of the control group,but the difference was not statistically significant(P>0.05).Conclusions:Xuebijing injection can improve the inflammatory indexes of patients with ventilator-associated pneumonia,and can partly improve the prognosis.
基金funded by grants from Beijing Natural Science Foundation(7212118,L222087)Natural Science Foundation of China(81973606,82272538).
文摘The regeneration of hierarchical osteochondral units is challenging due to difficulties in inducing spatial,directional and controllable differentiation of mesenchymal stem cells(MSCs)into cartilage and bone compartments.Emerging organoid technology offers new opportunities for osteochondral regeneration.In this study,we developed gelatin-based microcryogels customized using hyaluronic acid(HA)and hydroxyapatite(HYP),respectively for inducing cartilage and bone regeneration(denoted as CH-Microcryogels and OS-Microcryogels)through in vivo self-assembly into osteochondral organoids.The customized microcryogels showed good cytocompatibility and induced chondrogenic and osteogenic differentiation of MSCs,while also demonstrating the ability to self-assemble into osteochondral organoids with no delamination in the biphasic cartilage-bone structure.Analysis by mRNA-seq showed that CH-Microcryogels promoted chondrogenic differentiation and inhibited inflammation,while OS-Microcryogels facilitated osteogenic differentiation and suppressed the immune response,by regulating specific signaling pathways.Finally,the in vivo engraftment of pre-differentiated customized microcryogels into canine osteochondral defects resulted in the spontaneous assembly of an osteochondral unit,inducing simultaneous regeneration of both articular cartilage and subchondral bone.In conclusion,this novel approach for generating self-assembling osteochondral organoids utilizing tailor-made microcryogels presents a highly promising avenue for advancing the field of tissue engineering.
基金supported by the Young Talents Project 2019(2019BJRC05).
文摘Aedes aegypti(Ae.aegypti)is a major vector of dengue virus(DENV)and Zika virus(ZIKV).Understanding the complex interaction mechanisms between mosquito vectors and arboviruses is essential to interrupt virus trans-mission.This study constructed CYP4C21 knockout(KO)Aag2 cells(Ae.aegypti cells)and confirmed that CYP4C21 KO reduced DENV2 and ZIKV copies in Aag2 cells,which suggests that CYP4C21 may play an impor-tant role in mosquito infection with arboviruses.Furthermore,it is the first report of the CYP4 family related to viral infection,which lays the foundation for exploring the role of the CYP4C21 in the interaction of Ae.aegypti and arbovirus and provides novel insights into the function of cytochrome family proteins.
基金This work was supported by the Western Light Program of the Chinese Academy of Sciences(CAS,2019-JCTD-001)the Poverty Alleviation Program of CAS(KFJ-FP-202103)the Shanghai Cooperation Organization Science and Technology Partnership Program and the International Science and Technology Cooperation Program(2021E01007).
文摘The construction of a lunar base is considered to be an important step towards deep-space exploration by humanity,and will rely on the utilisation of in situ lunar resources.In this paper,we discuss the current knowledge on the feasibility of converting lunar soil to high-performance fibres that can be used for the construction of a lunar base.This fibre would be combined with further portions of lunar soil to generate fibre-reinforced composites,which is utilized as multi-functional materials for lunar base construction.We discuss and analyse the latest findings regarding the composition of lunar soil simulants and their fibrisation properties,and techniques for fibre spinning and system integration.Finally,we suggest how the achievements made so far could be applied to the construction of a lunar base.
文摘Mesenchymal stem cells(MSCs)can be effective in alleviating the progression of osteoarthritis(OA).However,low MSC retention and survival at the injection site frequently require high doses of cells and/or repeated injections,which are not economically viable and create additional risks of complications.In this study,we produced MSC-laden microcarriers in spinner flask culture as cell delivery vehicles.These microcarriers containing a low initial dose of MSCs administered through a single injection in a rat anterior cruciate ligament(ACL)transection model of OA achieved similar reparative effects as repeated high doses of MSCs,as evaluated through imaging and histological analyses.Mechanistic investigations were conducted using a co-culture model involving human primary chondrocytes grown in monolayer,together with MSCs grown either within 3D constructs or as a monolayer.Co-culture supernatants subjected to secretome analysis showed significant decrease of inflammatory factors in the 3D group.RNA-seq of co-cultured MSCs and chondrocytes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis revealed processes relating to early chondrogenesis and increased extracellular matrix interactions in MSCs of the 3D group,as well as phenotypic maintenance in the co-cultured chondrocytes.The cell delivery platform we investigated may be effective in reducing the cell dose and injection frequency required for therapeutic applications.
文摘Quinolones (QNs) are widely used for their broad antibacterial spectrum and good antibacterial activities,desirable pharmacokinetic characteristics and few cross reactions with other therapeutic agents. However,QNs have adverse effects including chondrotoxicity in juvenile animals,so the use of QNs is contraindicated in children and adolescents. In regarding to the chondrotoxicity of QNs,numerous studies have been done. The current hypothesis suggests that QNs compete with the β1 integrin receptors residing on chondrocyte surface for extracellular Mg ions,which leads to alternation in β1 integrin expression,or function and eventually results in chondrocyte death. Stupack et al (2001)demonstrated that caspase-8 could be recruited to unligated integrins in adherent cells and further initiate apoptosis in a death receptor-independent manner. Sheng et al (2008) found that ofloxacin induced rabbit's chondrocyte apoptosis by causing disturbance of β1 integrin functions and subsequently through caspase-8-dependent mitochondrial pathway.Apoptosis could be initiated through the stimulation of death receptors and through an intrinsic pathway from mitochondria. Santangelo and Bertone (2011) and Wu et al (2011) found that TNFα could be expressed in human primary condrocytes inducing by interleukin-1beta (IL-1) or lipopolysaccharide (LPS). However,to date there have not been sufficient results to support that signaling from the death receptors was involved in QNs-induced chondrocyte apoptosis.In addition,dilated cisternae of rough endoplasmic reticulum (ER) have been noticed in QNs-induced arthropathy.ER can participate in the initiation of apoptosis. Varieties of harmful cellular stimuli could lead to ERs (ER stress). Elevated ERs results in cellular apoptosis. But whether ERs mediates apoptosis in QNs-treated chondrocytes is not clear yet.In this study,we chose two QNs agents and chondrocytes were treated with ofloxacin and marbofloxacin at final concentrations of 20 μg / mL,50 μg / mL and 100 μg / mL respectively in vitro for 2 h,8 h and 24 h. Cell survival rate,cell apoptosis rate and death receptor pathway factors TNFα (intracellular tumor necrosis factor-alpha),TNFR1 (TNF receptor-1),TRADD (TNF receptor 1 associated via death domain),FADD (Fas-associated protein with death domain),caspase-8 and ERs mediated apoptosis factors caspase-12,GADD153 (CHOP or DDIT3),GRP78 (Bip),calpain,and anti-apoptosis factors Bcl-2 (B-cell lymphoma 2),NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) gene expression levels were measured by quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) analysis to determine the dose-response relationship. We further silenced the expression of TNFR1 successfully by transferring TNFR1-siRNA to chondrocytes to confirm whether TNFα / TNFR1 signaling pathways are involved ofloxacin and marbofloxacin-induced apoptosis. Furthermore,expression of death receptor pathway representative proteins TNFα / TNFR1 and endocytoplasmic reticulum (ER) pathway representative protein caspase-12 were confirmed using Western Blot.We have found that ofloxacin and marbofloxacin could induce apoptosis of chondrocytes in a time-and dose-dependent fashion within 24 h. mRNA of TNFα,TNFR1,TRADD,FADD and caspase-8 (caspase-8 of ofloxacin treated group were at 24 h) were highly expressed at 8 h,and GADD153,GRP78,calpain and caspase-12 at 8 h or 24 h,and antiapoptosis factors NF-κB and Bcl-2 were also raised after 2 h,all in a dose-dependent fashion. Expression of caspase-8was downregulated after silenced TNFR1. TNFα and TNFR1 proteins were expressed at 8 h and caspase-12 proteins were expressed at 24 h. In addition,ofloxacin showed a higher toxicity.Our results indicate that death receptor pathway TNF / TNFR1 and ERs mediated apoptosis factors are involved in ofloxacin and marbofloxacin-induced apoptosis of in vitro cultured juvenile dog joint chondrocytes within 24 h.
