Complete skeletal muscle repair and regeneration due to severe large injury or disease is still a challenge.Biochemical cues are critical to control myoblast cell function and can be utilized to develop smart biomater...Complete skeletal muscle repair and regeneration due to severe large injury or disease is still a challenge.Biochemical cues are critical to control myoblast cell function and can be utilized to develop smart biomaterials for skeletal muscle engineering.Citric acid-based biodegradable polymers have received much attention on tissue engineering,however,their regulation on myoblast cell differentiation and mechanism was few investigated.Here,we find that citrate-based polycitrate-polyethylene glycol-polyethylenimine(POCG-PEI600)nanoclusters can significantly enhance the in vitro myoblast proliferation by probably reinforcing the mitochondrial number,promote the myotube formation and full-thickness skeletal muscle regeneration in vivo by activating the myogenic biomarker genes expression of Myod and Mhc.POCG-PEI600 nanoclusters could also promote the phosphorylation of p38 in MAP kinases(MAPK)signaling pathway,which led to the promotion of the myoblast differentiation.The in vivo skeletal muscle loss rat model also confirmed that POCG-PEI600 nanoclusters could significantly improve the angiogenesis,myofibers formation and complete skeletal muscle regeneration.POCG-PEI600 nanocluster could be also biodegraded into small molecules and eliminated in vivo,suggesting their high biocompatibility and biosafety.This study could provide a bioactive biomaterial-based strategy to repair and regenerate skeletal muscle tissue.展开更多
The authors regret that the fluorescent image for FPC-7day in Figure 5A was reproduced incorrectly,although which did not affect the conclusion of this work.
It is highly desirable,while still challenging,to obtain noble metal nanocrystals with custom capping ligands,because their colloidal synthesis relies on specific capping ligands for the shape control while convention...It is highly desirable,while still challenging,to obtain noble metal nanocrystals with custom capping ligands,because their colloidal synthesis relies on specific capping ligands for the shape control while conventional ligand exchange processes suffer from“the strong replaces the weak”limitation,which greatly hinders their applications.Herein,we report a general and effective ligand exchange approach that can replace the native capping ligands of noble metal nanocrystals with virtually any type of ligands,producing flexibly tailored surface properties.The key is to use diethylamine with conveniently switchable binding affinity to the metal surface as an intermediate ligand.As a strong ligand,it in its original form can effectively remove the native ligands;while protonated,it loses its binding affinity and facilitates the adsorption of new ligands,especially weak ones,onto the metal surface.By this means,the irreversible order in the conventional ligand exchange processes could be overcome.The efficacy of the strategy is demonstrated by mutual exchange of the capping ligands among cetyltrimethylammonium,citrate,polyvinylpyrrolidone,and oleylamine.This novel strategy significantly expands our ability to manipulate the surface property of noble metal nanocrystals and extends their applicability to a wide range of fields,particularly biomedical applications.展开更多
The completed skeletal muscle regeneration resulted from severe injury and muscle-related disease is still a challenge.Here,we developed an injectable muscle-adhesive antioxidant conductive bioactive photothermo-respo...The completed skeletal muscle regeneration resulted from severe injury and muscle-related disease is still a challenge.Here,we developed an injectable muscle-adhesive antioxidant conductive bioactive photothermo-responsive nanomatrix for regulating the myogenic differentiation and promoting the skeletal muscle regeneration in vivo.The multifunctional nanomatrix was composed of polypyrrole@polydopamine(PPy@PDA,342±5.6 nm)nanoparticles-crosslinked Pluronic F-127(F127)-polycitrate matrix(FPCP).The FPCP nanomatrix demonstrated inherent multifunctional properties including excellent photothermo-responsive and shear-thinning behavior,muscle-adhesive feature,injectable ability,electronic conductivity(0.48±0.03 S/m)and antioxidant activity and photothermal function.The FPCP nanomatrix displayed better photothermal performance with near-infrared irradiation,which could provide the photo-controlled release of protein(91%±2.6%of BSA was released after irradiated 3 times).Additionally,FPCP nanomatrix could significantly enhance the cell proliferation and myogenic differentiation of mouse myoblast cells(C2C12)by promoting the expressions of myogenic genes(MyoD and MyoG)and myosin heavy chain(MHC)protein with negligible cytotoxicity.Based on the multifunctional properties,FPCP nanomatrix efficiently promoted the full-thickness skeletal muscle repair and regeneration in vivo,through stimulating the angiogenesis and myotube formation.This study firstly indicated the vital role of multifunctional PPy@PDA nanoparticles in regulating myogenic differentiation and skeletal muscle regeneration.This work also suggests that rational design of bioactive matrix with multifunctional feature would greatly enhance the development of regenerative medicine.展开更多
Background:Previous research demonstrated that a homozygous mutation of g.136372044G>A(S12N)in caspase recruitment domain family member 9(CARD9)is critical for producing Aspergillus fumigatus-induced(Af-induced)T h...Background:Previous research demonstrated that a homozygous mutation of g.136372044G>A(S12N)in caspase recruitment domain family member 9(CARD9)is critical for producing Aspergillus fumigatus-induced(Af-induced)T helper 2(T_(H)2)-mediated responses in allergic bronchopulmonary aspergillosis(ABPA).However,it remains unclear whether the CARD9^(S12N)mutation,especially the heterozygous occurrence,predisposes the host to ABPA.Methods:A total of 61 ABPA patients and 264 controls(including 156 healthy controls and 108 asthma patients)were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA.A series of in vivo and in vitro experiments,such as quantitative real-time polymerase chain reaction,flow cytometry,and RNA isolation and quantification,were used to illuminate the involved mechanism of the disease.Results:The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients,regardless of Aspergillus sensitivity.Relative to healthy controls without relevant allergies,the mutation of p.S12N was associated with a significant risk of ABPA(OR:2.69 and 4.17 for GA and AA genotypes,P=0.003 and 0.029,respectively).Compared with patients with asthma,ABPA patients had a significantly higher heterozygous mutation(GA genotype),indicating that p.S12N might be a significant ABPA-susceptibility locus(aspergillus sensitized asthma:OR:3.02,P=0.009;aspergillus unsensitized asthma:OR:2.94,P=0.005).The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9^(S12N),which contributes to its functional alterations to facilitate Af-induced T_(H)2-mediated ABPA development.In terms of mechanism,Card9 wild-type(Card9^(WT))expression levels decreased significantly due to Af-induced decay of its messenger RNA compared to the heterozygous Card9 S12N.In addition,ABPA patients with heterozygous CARD9^(S12N)had increased Af-induced interleukin-5 production.Conclusion:Our study provides the genetic evidence showing that the heterozygous mutation of CARD9^(S12N),followed by allele expression imbalance of CARD9^(S12N),facilitates the development of ABPA.展开更多
Dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome 1 (DAX1) deficiency is a rare disorder presents X-Linked adrenal hypoplasia congenital,impaired sexual development and inf...Dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome 1 (DAX1) deficiency is a rare disorder presents X-Linked adrenal hypoplasia congenital,impaired sexual development and infertility.Mutational gene of DAX1 was identified as NROB1 [1] which expresses in adrenal gland and hypothalamic-pituitary-gonad axis,restrains progenitor stem cells from differentiating into steroidogenic cells prematurely.Therefore,DAX1 deficiency usually manifests primary adrenal insufficiency and hypogonadotropic hypogonadism.However,we observed a patient whose testosterone elevated in early infancy.展开更多
Hybrids composed of biocompatible polymers reinforced with inorganic nanomaterials are useful for many biomedical applications including implantation and tissue regeneration and engineering.In this work,we report a ne...Hybrids composed of biocompatible polymers reinforced with inorganic nanomaterials are useful for many biomedical applications including implantation and tissue regeneration and engineering.In this work,we report a new type of hybrid prepared by doping ultrathin nanowires of lanthanide hydroxycarbonates into classical biocompatible poly(citrates-siloxane).The doping of the inorganic nanowires imparts the hybrids with excellent miscibility with the polymeric matrix,producing hybrids with high elasticity and high tensile strength.The hybrids containing Eu(III)and Gd(III)display their respective luminescence and magnetic properties and thus,offer opportunities to monitor the fate of such hybrids when used in vivo.Insignificant degradation and excellent biocompatibility of these hybrids have also been demonstrated.Together,these favorable traits portend useful applications of the newly developed hybrid elastomers.展开更多
基金supported by National Natural Science Foundation of China(Grant No.51872224)Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research,College of Stomatology,Xi’an Jiaotong University(Grant No.2018LHMKFKT004)+1 种基金Special Guidance Funds for the Construction of World-class Universities(disciplines)and Characteristic Development in Central Universities(grant No.PY3A078)the Fundamental Research Funds for the Central Universities(grant No.xzy022019050)。
文摘Complete skeletal muscle repair and regeneration due to severe large injury or disease is still a challenge.Biochemical cues are critical to control myoblast cell function and can be utilized to develop smart biomaterials for skeletal muscle engineering.Citric acid-based biodegradable polymers have received much attention on tissue engineering,however,their regulation on myoblast cell differentiation and mechanism was few investigated.Here,we find that citrate-based polycitrate-polyethylene glycol-polyethylenimine(POCG-PEI600)nanoclusters can significantly enhance the in vitro myoblast proliferation by probably reinforcing the mitochondrial number,promote the myotube formation and full-thickness skeletal muscle regeneration in vivo by activating the myogenic biomarker genes expression of Myod and Mhc.POCG-PEI600 nanoclusters could also promote the phosphorylation of p38 in MAP kinases(MAPK)signaling pathway,which led to the promotion of the myoblast differentiation.The in vivo skeletal muscle loss rat model also confirmed that POCG-PEI600 nanoclusters could significantly improve the angiogenesis,myofibers formation and complete skeletal muscle regeneration.POCG-PEI600 nanocluster could be also biodegraded into small molecules and eliminated in vivo,suggesting their high biocompatibility and biosafety.This study could provide a bioactive biomaterial-based strategy to repair and regenerate skeletal muscle tissue.
文摘The authors regret that the fluorescent image for FPC-7day in Figure 5A was reproduced incorrectly,although which did not affect the conclusion of this work.
基金C.G.acknowledges the support from the National Natural Science Foundation of China(21671156)the Fundamental Research Funds for the Central Universities+3 种基金the World-Class Universities(Disciplines)and the Characteristic Development Guidance Funds for the Central Universities,and the Tang Scholar Program from Cyrus Tang FoundationT.C.acknowledges the support from the Collaborative Innovation Center of Suzhou Nano Science and Technology,the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)the 111 ProjectY.Y.acknowledges the support from the U.S.National Science Foundation(CHE-1308587).
文摘It is highly desirable,while still challenging,to obtain noble metal nanocrystals with custom capping ligands,because their colloidal synthesis relies on specific capping ligands for the shape control while conventional ligand exchange processes suffer from“the strong replaces the weak”limitation,which greatly hinders their applications.Herein,we report a general and effective ligand exchange approach that can replace the native capping ligands of noble metal nanocrystals with virtually any type of ligands,producing flexibly tailored surface properties.The key is to use diethylamine with conveniently switchable binding affinity to the metal surface as an intermediate ligand.As a strong ligand,it in its original form can effectively remove the native ligands;while protonated,it loses its binding affinity and facilitates the adsorption of new ligands,especially weak ones,onto the metal surface.By this means,the irreversible order in the conventional ligand exchange processes could be overcome.The efficacy of the strategy is demonstrated by mutual exchange of the capping ligands among cetyltrimethylammonium,citrate,polyvinylpyrrolidone,and oleylamine.This novel strategy significantly expands our ability to manipulate the surface property of noble metal nanocrystals and extends their applicability to a wide range of fields,particularly biomedical applications.
基金This work was supported by National Natural Science Foundation of China(Grant No.51872224,51802227)Special Support Program for High Level Talents of Shaanxi Province(Grant No.7122200063)+4 种基金Special Guidance Funds for the Construction of World-class Universities(disciplines)Characteristic Development in Central Universities(grant No.PY3A078)China Postdoctoral Science Foundation(Grant No.2019M653754)Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research,College of Stomatology,Xi’an Jiaotong University(Grant No.2018LHM-KFKT004)Wenzhou Science and Technology Bureau Project(Grant No.ZY2019003,Y20190123,Y2020236).
文摘The completed skeletal muscle regeneration resulted from severe injury and muscle-related disease is still a challenge.Here,we developed an injectable muscle-adhesive antioxidant conductive bioactive photothermo-responsive nanomatrix for regulating the myogenic differentiation and promoting the skeletal muscle regeneration in vivo.The multifunctional nanomatrix was composed of polypyrrole@polydopamine(PPy@PDA,342±5.6 nm)nanoparticles-crosslinked Pluronic F-127(F127)-polycitrate matrix(FPCP).The FPCP nanomatrix demonstrated inherent multifunctional properties including excellent photothermo-responsive and shear-thinning behavior,muscle-adhesive feature,injectable ability,electronic conductivity(0.48±0.03 S/m)and antioxidant activity and photothermal function.The FPCP nanomatrix displayed better photothermal performance with near-infrared irradiation,which could provide the photo-controlled release of protein(91%±2.6%of BSA was released after irradiated 3 times).Additionally,FPCP nanomatrix could significantly enhance the cell proliferation and myogenic differentiation of mouse myoblast cells(C2C12)by promoting the expressions of myogenic genes(MyoD and MyoG)and myosin heavy chain(MHC)protein with negligible cytotoxicity.Based on the multifunctional properties,FPCP nanomatrix efficiently promoted the full-thickness skeletal muscle repair and regeneration in vivo,through stimulating the angiogenesis and myotube formation.This study firstly indicated the vital role of multifunctional PPy@PDA nanoparticles in regulating myogenic differentiation and skeletal muscle regeneration.This work also suggests that rational design of bioactive matrix with multifunctional feature would greatly enhance the development of regenerative medicine.
基金supported by grants from the National Natural Science Foundation of China(Nos.81925001,81970036,and 31970889)the Innovation Program of Shanghai Municipal Education Commission(Nos.202101070007-E00097 and 201901070007E00022)+2 种基金the Program of Shanghai Municipal Science and Technology Commission(No.21DZ2201800)the Shanghai Municipal Health Commission(Nos.201740019 and ZY2018-2020 FWTX3022)Innovative Research Ream of High-Level Local Universities in Shanghai.
文摘Background:Previous research demonstrated that a homozygous mutation of g.136372044G>A(S12N)in caspase recruitment domain family member 9(CARD9)is critical for producing Aspergillus fumigatus-induced(Af-induced)T helper 2(T_(H)2)-mediated responses in allergic bronchopulmonary aspergillosis(ABPA).However,it remains unclear whether the CARD9^(S12N)mutation,especially the heterozygous occurrence,predisposes the host to ABPA.Methods:A total of 61 ABPA patients and 264 controls(including 156 healthy controls and 108 asthma patients)were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA.A series of in vivo and in vitro experiments,such as quantitative real-time polymerase chain reaction,flow cytometry,and RNA isolation and quantification,were used to illuminate the involved mechanism of the disease.Results:The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients,regardless of Aspergillus sensitivity.Relative to healthy controls without relevant allergies,the mutation of p.S12N was associated with a significant risk of ABPA(OR:2.69 and 4.17 for GA and AA genotypes,P=0.003 and 0.029,respectively).Compared with patients with asthma,ABPA patients had a significantly higher heterozygous mutation(GA genotype),indicating that p.S12N might be a significant ABPA-susceptibility locus(aspergillus sensitized asthma:OR:3.02,P=0.009;aspergillus unsensitized asthma:OR:2.94,P=0.005).The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9^(S12N),which contributes to its functional alterations to facilitate Af-induced T_(H)2-mediated ABPA development.In terms of mechanism,Card9 wild-type(Card9^(WT))expression levels decreased significantly due to Af-induced decay of its messenger RNA compared to the heterozygous Card9 S12N.In addition,ABPA patients with heterozygous CARD9^(S12N)had increased Af-induced interleukin-5 production.Conclusion:Our study provides the genetic evidence showing that the heterozygous mutation of CARD9^(S12N),followed by allele expression imbalance of CARD9^(S12N),facilitates the development of ABPA.
文摘Dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome 1 (DAX1) deficiency is a rare disorder presents X-Linked adrenal hypoplasia congenital,impaired sexual development and infertility.Mutational gene of DAX1 was identified as NROB1 [1] which expresses in adrenal gland and hypothalamic-pituitary-gonad axis,restrains progenitor stem cells from differentiating into steroidogenic cells prematurely.Therefore,DAX1 deficiency usually manifests primary adrenal insufficiency and hypogonadotropic hypogonadism.However,we observed a patient whose testosterone elevated in early infancy.
基金supported by the National Natural Science Foundation of China(grant nos.21971117,21522106,and 51872224)China Postdoctoral Science Foundation(grant no.2018M642133)+4 种基金the National Key R&D Program of China(grant no.2017YFA0208000)the Fundamental Research Funds for the Central Universities,Nankai University(grant nos.63201071 and ZB19500202)State Key Laboratory of Rare Earth Resource Utilization(grant no.RERU2019001)the 111 Project(grant no.B18030)from ChinaBeijing-Tianjin-Hebei Collaborative Innovation Project(grant no.63201058).
文摘Hybrids composed of biocompatible polymers reinforced with inorganic nanomaterials are useful for many biomedical applications including implantation and tissue regeneration and engineering.In this work,we report a new type of hybrid prepared by doping ultrathin nanowires of lanthanide hydroxycarbonates into classical biocompatible poly(citrates-siloxane).The doping of the inorganic nanowires imparts the hybrids with excellent miscibility with the polymeric matrix,producing hybrids with high elasticity and high tensile strength.The hybrids containing Eu(III)and Gd(III)display their respective luminescence and magnetic properties and thus,offer opportunities to monitor the fate of such hybrids when used in vivo.Insignificant degradation and excellent biocompatibility of these hybrids have also been demonstrated.Together,these favorable traits portend useful applications of the newly developed hybrid elastomers.