AIM:To investigate changes in macular vessels and thickness in myopic eyes after intraocular collamer lens(ICL)implantation using quantitative optical coherence tomography angiography(OCTA).METHODS:This retrospective ...AIM:To investigate changes in macular vessels and thickness in myopic eyes after intraocular collamer lens(ICL)implantation using quantitative optical coherence tomography angiography(OCTA).METHODS:This retrospective included 73 myopic eyes of 73 patients(average age,27.53±6.16 y)who underwent ICL implantation(28 eyes were Toric ICL).Axial length(AL),uncorrected visual acuity(UCVA),refractive dioptre(RD),intraocular pressure(IOP)and OCTA were measured and compared with before and 1 wk,1,and 3 mo after surgery.OCTA was used to image vessel density(VD)and skeleton density(SD)in both the superficial(SCP)and deep capillary plexus(DCP).Central retinal thickness(CRT)and ganglion cellinner plexiform layer thickness(GCT)were also measured.Changes between pre-and postoperative measurements were analysed by repeated measures analysis of variance.RESULTS:Compared with preoperative data,postoperative data on UCVA revealed significant improvements in all patients(P<0.05).However,there was no significant difference in IOP.After the operation,CRT and GCT exhibited significant changes(P<0.05).Among these measures,CRT was significantly higher at one and three months postoperative(all P<0.01).GCT was significantly higher at 1 wk,1,and 3 mo postoperative(all P<0.01).Changes in VD and SD were nonsignificant in both the SCP and DCP.There was no difference in postoperative changes between the ICL and Toric ICL groups.CONCLUSION:ICL and Toric ICL implantation both have good efficacy and safety for myopic eyes,but macular area changes that occur after surgery need attention.展开更多
Severe endometrium damage causes pathological conditions such as thin endometrium and intrauterine adhesion,resulting in uterine factor infertility.Mesenchymal stem cell(MSC)therapy is a promising strategy in endometr...Severe endometrium damage causes pathological conditions such as thin endometrium and intrauterine adhesion,resulting in uterine factor infertility.Mesenchymal stem cell(MSC)therapy is a promising strategy in endometrial repair;yet,exogenous MSCs still raise concerns for safety and ethical issues.Human adipose-derived mesenchymal stem cells(ADMSCs)residing in adipose tissue have high translational potentials due to their autologous origin.To harness the high translation potentials of ADMSC in clinical endometrium regeneration,here we constructed an ADMSCs composited porous scaffold(CS/ADMSC)and evaluated its effectiveness on endometrial regeneration in a rat endometrium-injury model.We found that CS/ADMSC intrauterine implantation(i)promoted endometrial thickness and gland number,(ii)enhanced tissue angiogenesis,(iii)reduced fibrosis and(iv)restored fertility.We ascertained the pro-proliferation,pro-angiogenesis,immunomodulating and anti-fibrotic effects of CS/ADMSC in vitro and revealed that the CS/ADMSC influenced extracellular matrix composition and organization by a transcriptomic analysis.Our results demonstrated the effectiveness of CS/ADMSC for endometrial regeneration and provided solid proof for our future clinical study.展开更多
Stem cell-based and stem cell-derived exosome-based therapies have shown promising potential for endometrial regeneration and the clinical treatment of intrauterine adhesions(IUAs).Evidence shows that apoptosis occurs...Stem cell-based and stem cell-derived exosome-based therapies have shown promising potential for endometrial regeneration and the clinical treatment of intrauterine adhesions(IUAs).Evidence shows that apoptosis occurs in a majority of grafted stem cells,and apoptotic bodies(ABs)play a critical role in compensatory tissue regeneration.However,the therapeutic potential of AB-based therapy and its mechanism have not been explored in detail.Here,a cell-free therapeutic strategy was developed by incorporating mesenchymal stem cell-derived ABs into a hyaluronic acid(HA)hydrogel to achieve endometrial regeneration and fertility restoration.Specifically,we found that the ABs could induce macrophage immunomodulation,cell proliferation,and angiogenesis in vitro.The HA hydrogel promoted the retention of ABs and facilitated their continuous release.In a murine model of acute endometrial damage and a rat model of IUAs,in situ injection of the AB-laden HA hydrogel could efficiently reduce fibrosis and promote endometrial regeneration,resulting in the fertility restoration.Consequently,ABs show good potential as therapeutic vesicles,and the AB-laden HA hydrogel appears to be a clinically feasible and cell-free alternative for endometrial regeneration and IUA treatment.展开更多
Diabetic chronic wound,characterized by prolonged inflammation and impaired angiogenesis,has become one of the most serious challenges in clinic and pose a significant healthcare burden worldwide.Although a great vari...Diabetic chronic wound,characterized by prolonged inflammation and impaired angiogenesis,has become one of the most serious challenges in clinic and pose a significant healthcare burden worldwide.Although a great variety of wound dressings have been developed,few of encouraged achievements were obtained so far.In this study,the gene-activated strategy was applied to enhance sustained expression of vascular endothelial growth factor(VEGF)and achieve better healing outcomes by regulating inflammation and promoting angiogenesis.The gene-activated bilayer dermal equivalents(Ga-BDEs),which has good biocompatibility,were fabricated by loading the nano-sized complexes of Lipofectamine 2000/plasmid DNA-encoding VEGF into a collagen-chitosan scaffold/silicone membrane bilayer dermal equivalent.The DNA complexes were released in a sustained manner and showed the effective transfection capacities to up-regulate the expression of VEGF in vitro.To overcome cutaneous contraction of rodents and mimic the wound healing mechanisms of the human,a reformative rat model of full-thickness diabetic chronic wound was adopted.Under the treatment of Ga-BDEs,speeding wound healing was observed,which is accompanied by the accelerated infiltration and phenotype shift of macrophages and enhanced angiogenesis in early and late healing phases,respectively.These proved that Ga-BDEs possess the functions of immunomodulation and pro-angiogenesis simultaneously.Subsequently,the better regeneration outcomes,including deposition of oriented collagen and fast reepithelialization,were achieved.All these results indicated that,being different from traditional pro-angiogenic concept,the up-regulated expression of VEGF by Ga-BDEs in a sustained manner shows versatile potentials for promoting the healing of diabetic chronic wounds.展开更多
Predicting the thermal sensations of building occupants is challenging,but useful for indoor environment conditioning.In this study,a data-driven thermal sensation prediction model was developed using three quality-co...Predicting the thermal sensations of building occupants is challenging,but useful for indoor environment conditioning.In this study,a data-driven thermal sensation prediction model was developed using three quality-controlled thermal comfort databases.Different machine-learning algorithms were compared in terms of prediction accuracy and rationality.The model was further improved by adding categorical inputs,and building submodels and general models for different contexts.A comprehensive data-driven thermal sensation prediction model was established.The results indicate that the multilayer perceptron(MLP)algorithm achieves higher prediction accuracy and more rational results than the other four algorithms in this specific case.Labeling AC and NV scenarios,climate zones,and cooling and heating seasons can improve model performance.Establishing submodels for specific scenarios can result in better thermal sensation vote(TSV)predictions than using general models with or without labels.With 11 submodels corresponding to 11 scenarios,and three general models without labels,the final TSV prediction model achieved higher prediction accuracy,with 64.7%–90.7%fewer prediction errors(reducing SSE by 3.2–4.9)than the predicted mean vote(PMV).Possible applications of the new model are discussed.The findings of this study can help in development of simple,accurate,and rational thermal sensation prediction tools.展开更多
Due to the critical roles of macrophage in immune response and tissue repair,harnessing macrophage phenotypes dynamically to match the tissue healing process on demand attracted many attentions.Although there have dev...Due to the critical roles of macrophage in immune response and tissue repair,harnessing macrophage phenotypes dynamically to match the tissue healing process on demand attracted many attentions.Although there have developed many advanced platforms with dynamic features for cell manipulation,few studies have designed a dynamic chemical pattern to sequentially polarize macrophage phenotypes and meet the immune requirements at various tissue repair stages.Here,we propose a novel strategy for spatiotemporal manipulation of macrophage phenotypes by a UV-induced dynamic Arg-Gly-Asp(RGD)pattern.By employing a photo-patterning technique and the specific interaction between cyclodextrin(CD)and azobenzene-RGD(Azo-RGD),we prepared a polyethylene glycol-dithiol/polyethylene glycol-norbornene(PEG-SH/PEG-Nor)hydrogel with dynamic RGD-patterned surface.After irradiation with 365-nm UV light,the homogeneous RGD surface was transformed to the RGD-patterned surface which induced morphological transformation of macrophages from round to elongated and subsequent phenotypic transition from pro-inflammation to anti-inflammation.The mechanism of phenotypic polarization induced by RGD pattern was proved to be related to Rho-associated protein kinase 2(ROCK2).Sequential modulation of macrophage phenotypes by the dynamic RGD-patterned surface provides a remote and non-invasive strategy to manipulate immune reactions and achieve optimized healing outcomes.展开更多
Genome editing through adeno-associated viral(AAV) vectors is a promising gene therapy strategy for various diseases,especially genetic disorders. However, homologous recombination(HR) efficiency is extremely low in a...Genome editing through adeno-associated viral(AAV) vectors is a promising gene therapy strategy for various diseases,especially genetic disorders. However, homologous recombination(HR) efficiency is extremely low in adult animal models. We assumed that increasing AAV transduction efficiency could increase genome editing activity, especially HR efficiency, for in vivo gene therapy. Firstly, a mouse phenylketonuria(PKU) model carrying a pathogenic R408W mutation in phenylalanine hydroxylase(Pah) was generated. Through co-delivery of the general AAV receptor(AAVR), we found that AAVR could dramatically increase AAV transduction efficiency in vitro and in vivo. Furthermore, co-delivery of SaCas9/sgRNA/donor templates with AAVR via AAV8 vectors increased indel rate over 2-fold and HR rate over 15-fold for the correction of the single mutation in Pah;mice. Moreover, AAVR co-injection successfully increased the site-specific insertion rate of a 1.4 kb Pah cDNA by 11-fold, bringing the HR rate up to 7.3% without detectable global off-target effects. Insertion of Pah cDNA significantly decreased the Phe level and ameliorated PKU symptoms. This study demonstrates a novel strategy to dramatically increase AAV transduction which substantially enhanced in vivo genome editing efficiency in adult animal models, showing clinical potential for both conventional and genome editing-based gene therapy.展开更多
Hyaluronic acid(HA)-based hydrogels have applied widely for biomedical applications due to its biocompatibility and biodegradability.However,the use of initiators or crosslinkers during the hydrogel formation may caus...Hyaluronic acid(HA)-based hydrogels have applied widely for biomedical applications due to its biocompatibility and biodegradability.However,the use of initiators or crosslinkers during the hydrogel formation may cause cytotoxicity and thereby impair the biocompatibility.Inspired by the crosslinking mechanism of fibrin gel,a novel HA-based hydrogel was developed via the in situ supramolecular assembly based on knob-hole interactions between fibrinogen and knob-grafted HA(knob-g-HA)in this study.The knob-grafted HA was synthesized by coupling knob peptides(GPRPAAC,a mimic peptide of fibrin knob A)to HA via Michael addition.Then the translucent fibrinogen/knob-g-HA hydrogels were prepared by simply mixing the solutions of knob-g-HA and fibrinogen at the knob/hole ratio of 1.2.The rheological behaviors of the fibrinogen/knob-g-HA hydrogels with the fibrinogen concentrations of 50,100 and 200 mg/mL were evaluated,and it was found that the dynamic storage moduli(G0)were higher than the loss moduli(G00)over the whole frequency range for all the groups.The SEM results showed that fibrinogen/knob-g-HA hydrogels presented the heterogeneous mesh-like structures which were different from the honeycomb-like structures of fibrinogen/MA-HA hydrogels.Correspondingly,a higher swelling ratio was obtained in the groups of fibrinogen/knob-g-HA hydrogel.Finally,the cytocompatibility of fibrinogen/knob-g-HA hydrogels was proved by live/dead stainings and MTT assays in the 293T cells encapsulation test.All these results highlight the biological potential of the fibrinogen/knob-g-HA hydrogels for 3D cellular engineering.展开更多
An acidic solution based method towards flexible lithium ion battery(LIB)cathodes is developed in this work with perylene diimide(PDI)as the electroactive component and carbon cloth(CC)as the current collector.In this...An acidic solution based method towards flexible lithium ion battery(LIB)cathodes is developed in this work with perylene diimide(PDI)as the electroactive component and carbon cloth(CC)as the current collector.In this approach,PDI is firstly dispersed in concentrated sulfuric acid(H2S04)and then deposited on CC substrate after the dilution of H2S04,which provides an organic solvent-free strategy to construct integrated LIB cathodes.The acdic solution based fabrication process also allows the facile adjusting of loading amounts of PDI in the cathodes,which can effectively influence the battery performances of the PDI/CC cathodes.As the result,the acidic solution processed PDI/CC cathode can deliver a high specific capacity of-36 mAh·g^-1 at the current density of 50 mA·g^-1 in both half cell with lithium foil as anode and full cell with pre-lithiated CC as anode.In both types of the batteries,the PDI/CC cathodes show good cycling stabilities by retaining^84%of the initial capacities after 300 charge-discharge cycles at 500 mA·g^-1.Additionally,the excellent mechanical stability of the PDI/CC cathode enables the LIBs in pouch cell to maintain the electrochemical performances under various bending states,demonstrating their potentials for flexible LIBs.展开更多
Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces,the global regulation based on epigenetic modification is not well explored.N4-methylcytosine(m4C),an abundant...Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces,the global regulation based on epigenetic modification is not well explored.N4-methylcytosine(m4C),an abundant epigenetic marker in Actinomycetes’genome,but its regulatory mechanism remains unclear.In this study,we identify a m4C methyltransferase(SroLm3)in Streptomyces roseosporus L30 and multi-omics studies were performed and revealed SroLm3 as a global regulator of secondary metabolism.Notably,three BGCs inΔsroLm3 strain exhibited decreased expression compared to wild type.In-frame deletion of sroLm3 in S.roseosporus L30 further revealed its role in enhancing daptomycin production.In summary,we characterized a m4C methyltransferase,revealed the function of m4C in secondary metabolism regulation and biosynthesis of red pigment,and mapped a series of novel regulators for daptomycin biosynthesis dominated by m4C methylation.Our research further indicated that m4C DNA methylation may contribute to a metabolic switch from primary to secondary metabolism in Actinomyces.展开更多
文摘AIM:To investigate changes in macular vessels and thickness in myopic eyes after intraocular collamer lens(ICL)implantation using quantitative optical coherence tomography angiography(OCTA).METHODS:This retrospective included 73 myopic eyes of 73 patients(average age,27.53±6.16 y)who underwent ICL implantation(28 eyes were Toric ICL).Axial length(AL),uncorrected visual acuity(UCVA),refractive dioptre(RD),intraocular pressure(IOP)and OCTA were measured and compared with before and 1 wk,1,and 3 mo after surgery.OCTA was used to image vessel density(VD)and skeleton density(SD)in both the superficial(SCP)and deep capillary plexus(DCP).Central retinal thickness(CRT)and ganglion cellinner plexiform layer thickness(GCT)were also measured.Changes between pre-and postoperative measurements were analysed by repeated measures analysis of variance.RESULTS:Compared with preoperative data,postoperative data on UCVA revealed significant improvements in all patients(P<0.05).However,there was no significant difference in IOP.After the operation,CRT and GCT exhibited significant changes(P<0.05).Among these measures,CRT was significantly higher at one and three months postoperative(all P<0.01).GCT was significantly higher at 1 wk,1,and 3 mo postoperative(all P<0.01).Changes in VD and SD were nonsignificant in both the SCP and DCP.There was no difference in postoperative changes between the ICL and Toric ICL groups.CONCLUSION:ICL and Toric ICL implantation both have good efficacy and safety for myopic eyes,but macular area changes that occur after surgery need attention.
基金supported by the National Natural Science Foundation of China(82061160494)the Department of Science and Technology of Zhejiang Province(2023c03033)and the National Health Commission of China(WKJ-ZJ-2301).
文摘Severe endometrium damage causes pathological conditions such as thin endometrium and intrauterine adhesion,resulting in uterine factor infertility.Mesenchymal stem cell(MSC)therapy is a promising strategy in endometrial repair;yet,exogenous MSCs still raise concerns for safety and ethical issues.Human adipose-derived mesenchymal stem cells(ADMSCs)residing in adipose tissue have high translational potentials due to their autologous origin.To harness the high translation potentials of ADMSC in clinical endometrium regeneration,here we constructed an ADMSCs composited porous scaffold(CS/ADMSC)and evaluated its effectiveness on endometrial regeneration in a rat endometrium-injury model.We found that CS/ADMSC intrauterine implantation(i)promoted endometrial thickness and gland number,(ii)enhanced tissue angiogenesis,(iii)reduced fibrosis and(iv)restored fertility.We ascertained the pro-proliferation,pro-angiogenesis,immunomodulating and anti-fibrotic effects of CS/ADMSC in vitro and revealed that the CS/ADMSC influenced extracellular matrix composition and organization by a transcriptomic analysis.Our results demonstrated the effectiveness of CS/ADMSC for endometrial regeneration and provided solid proof for our future clinical study.
基金the funding support by the National Key Research Program of China(2018YFC1004800)the International(Regional)Cooperation and Exchange Program of China(82061160494)+1 种基金the National Natural Science Foundation of China(51873184)the Fundamental Research Funds for the Central Universities(2021FZZX005-16).
文摘Stem cell-based and stem cell-derived exosome-based therapies have shown promising potential for endometrial regeneration and the clinical treatment of intrauterine adhesions(IUAs).Evidence shows that apoptosis occurs in a majority of grafted stem cells,and apoptotic bodies(ABs)play a critical role in compensatory tissue regeneration.However,the therapeutic potential of AB-based therapy and its mechanism have not been explored in detail.Here,a cell-free therapeutic strategy was developed by incorporating mesenchymal stem cell-derived ABs into a hyaluronic acid(HA)hydrogel to achieve endometrial regeneration and fertility restoration.Specifically,we found that the ABs could induce macrophage immunomodulation,cell proliferation,and angiogenesis in vitro.The HA hydrogel promoted the retention of ABs and facilitated their continuous release.In a murine model of acute endometrial damage and a rat model of IUAs,in situ injection of the AB-laden HA hydrogel could efficiently reduce fibrosis and promote endometrial regeneration,resulting in the fertility restoration.Consequently,ABs show good potential as therapeutic vesicles,and the AB-laden HA hydrogel appears to be a clinically feasible and cell-free alternative for endometrial regeneration and IUA treatment.
基金financially supported by the National Natural Science Foundation of China(51873184,81671918)National Key R&D Program of China(2016YFC1101000).
文摘Diabetic chronic wound,characterized by prolonged inflammation and impaired angiogenesis,has become one of the most serious challenges in clinic and pose a significant healthcare burden worldwide.Although a great variety of wound dressings have been developed,few of encouraged achievements were obtained so far.In this study,the gene-activated strategy was applied to enhance sustained expression of vascular endothelial growth factor(VEGF)and achieve better healing outcomes by regulating inflammation and promoting angiogenesis.The gene-activated bilayer dermal equivalents(Ga-BDEs),which has good biocompatibility,were fabricated by loading the nano-sized complexes of Lipofectamine 2000/plasmid DNA-encoding VEGF into a collagen-chitosan scaffold/silicone membrane bilayer dermal equivalent.The DNA complexes were released in a sustained manner and showed the effective transfection capacities to up-regulate the expression of VEGF in vitro.To overcome cutaneous contraction of rodents and mimic the wound healing mechanisms of the human,a reformative rat model of full-thickness diabetic chronic wound was adopted.Under the treatment of Ga-BDEs,speeding wound healing was observed,which is accompanied by the accelerated infiltration and phenotype shift of macrophages and enhanced angiogenesis in early and late healing phases,respectively.These proved that Ga-BDEs possess the functions of immunomodulation and pro-angiogenesis simultaneously.Subsequently,the better regeneration outcomes,including deposition of oriented collagen and fast reepithelialization,were achieved.All these results indicated that,being different from traditional pro-angiogenic concept,the up-regulated expression of VEGF by Ga-BDEs in a sustained manner shows versatile potentials for promoting the healing of diabetic chronic wounds.
基金This study was supported by the National Natural Science Foundation of China(No.52178087)the China National Key R&D Program during the 13th Five-year Plan Period(No.2018YFC0704500)the Fundamental Research Funds for the Central Universities(No.22120210537).The authors would like to thank Guangdong Midea Air-Conditioning Equipment Co.,Ltd.for their support.
文摘Predicting the thermal sensations of building occupants is challenging,but useful for indoor environment conditioning.In this study,a data-driven thermal sensation prediction model was developed using three quality-controlled thermal comfort databases.Different machine-learning algorithms were compared in terms of prediction accuracy and rationality.The model was further improved by adding categorical inputs,and building submodels and general models for different contexts.A comprehensive data-driven thermal sensation prediction model was established.The results indicate that the multilayer perceptron(MLP)algorithm achieves higher prediction accuracy and more rational results than the other four algorithms in this specific case.Labeling AC and NV scenarios,climate zones,and cooling and heating seasons can improve model performance.Establishing submodels for specific scenarios can result in better thermal sensation vote(TSV)predictions than using general models with or without labels.With 11 submodels corresponding to 11 scenarios,and three general models without labels,the final TSV prediction model achieved higher prediction accuracy,with 64.7%–90.7%fewer prediction errors(reducing SSE by 3.2–4.9)than the predicted mean vote(PMV).Possible applications of the new model are discussed.The findings of this study can help in development of simple,accurate,and rational thermal sensation prediction tools.
基金the National Natural Science Foundation of China(51873184)National Key R&D Program of China(2017YFA01049000 and 2018YFC1004800).
文摘Due to the critical roles of macrophage in immune response and tissue repair,harnessing macrophage phenotypes dynamically to match the tissue healing process on demand attracted many attentions.Although there have developed many advanced platforms with dynamic features for cell manipulation,few studies have designed a dynamic chemical pattern to sequentially polarize macrophage phenotypes and meet the immune requirements at various tissue repair stages.Here,we propose a novel strategy for spatiotemporal manipulation of macrophage phenotypes by a UV-induced dynamic Arg-Gly-Asp(RGD)pattern.By employing a photo-patterning technique and the specific interaction between cyclodextrin(CD)and azobenzene-RGD(Azo-RGD),we prepared a polyethylene glycol-dithiol/polyethylene glycol-norbornene(PEG-SH/PEG-Nor)hydrogel with dynamic RGD-patterned surface.After irradiation with 365-nm UV light,the homogeneous RGD surface was transformed to the RGD-patterned surface which induced morphological transformation of macrophages from round to elongated and subsequent phenotypic transition from pro-inflammation to anti-inflammation.The mechanism of phenotypic polarization induced by RGD pattern was proved to be related to Rho-associated protein kinase 2(ROCK2).Sequential modulation of macrophage phenotypes by the dynamic RGD-patterned surface provides a remote and non-invasive strategy to manipulate immune reactions and achieve optimized healing outcomes.
基金partially supported by grants from the National Key R&D Program of China (2019YFA0110802)the National Natural Science Foundation of China (81670470 and 81873685)+2 种基金grants from the Shanghai Municipal Commission for Science and Technology (18411953500 and 20140900201)a grant from the Innovation Program of Shanghai Municipal Education Commission (2019-01-07-00-05-E00054)the Fundamental Research Funds for the Central Universities
文摘Genome editing through adeno-associated viral(AAV) vectors is a promising gene therapy strategy for various diseases,especially genetic disorders. However, homologous recombination(HR) efficiency is extremely low in adult animal models. We assumed that increasing AAV transduction efficiency could increase genome editing activity, especially HR efficiency, for in vivo gene therapy. Firstly, a mouse phenylketonuria(PKU) model carrying a pathogenic R408W mutation in phenylalanine hydroxylase(Pah) was generated. Through co-delivery of the general AAV receptor(AAVR), we found that AAVR could dramatically increase AAV transduction efficiency in vitro and in vivo. Furthermore, co-delivery of SaCas9/sgRNA/donor templates with AAVR via AAV8 vectors increased indel rate over 2-fold and HR rate over 15-fold for the correction of the single mutation in Pah;mice. Moreover, AAVR co-injection successfully increased the site-specific insertion rate of a 1.4 kb Pah cDNA by 11-fold, bringing the HR rate up to 7.3% without detectable global off-target effects. Insertion of Pah cDNA significantly decreased the Phe level and ameliorated PKU symptoms. This study demonstrates a novel strategy to dramatically increase AAV transduction which substantially enhanced in vivo genome editing efficiency in adult animal models, showing clinical potential for both conventional and genome editing-based gene therapy.
基金The authors acknowledge the financial support by the National Natural Science Foundation of China(51673167 and 21434006)the National Key Research Programof China(2017YFA0104901)the Fundamental Research Funds for the Central Universities(2017XZZX008-05).
文摘Hyaluronic acid(HA)-based hydrogels have applied widely for biomedical applications due to its biocompatibility and biodegradability.However,the use of initiators or crosslinkers during the hydrogel formation may cause cytotoxicity and thereby impair the biocompatibility.Inspired by the crosslinking mechanism of fibrin gel,a novel HA-based hydrogel was developed via the in situ supramolecular assembly based on knob-hole interactions between fibrinogen and knob-grafted HA(knob-g-HA)in this study.The knob-grafted HA was synthesized by coupling knob peptides(GPRPAAC,a mimic peptide of fibrin knob A)to HA via Michael addition.Then the translucent fibrinogen/knob-g-HA hydrogels were prepared by simply mixing the solutions of knob-g-HA and fibrinogen at the knob/hole ratio of 1.2.The rheological behaviors of the fibrinogen/knob-g-HA hydrogels with the fibrinogen concentrations of 50,100 and 200 mg/mL were evaluated,and it was found that the dynamic storage moduli(G0)were higher than the loss moduli(G00)over the whole frequency range for all the groups.The SEM results showed that fibrinogen/knob-g-HA hydrogels presented the heterogeneous mesh-like structures which were different from the honeycomb-like structures of fibrinogen/MA-HA hydrogels.Correspondingly,a higher swelling ratio was obtained in the groups of fibrinogen/knob-g-HA hydrogel.Finally,the cytocompatibility of fibrinogen/knob-g-HA hydrogels was proved by live/dead stainings and MTT assays in the 293T cells encapsulation test.All these results highlight the biological potential of the fibrinogen/knob-g-HA hydrogels for 3D cellular engineering.
基金supported by the National Natural Science Foundation of China(Nos.61575121,51772189,21772120,21774072,and 21720102002).
文摘An acidic solution based method towards flexible lithium ion battery(LIB)cathodes is developed in this work with perylene diimide(PDI)as the electroactive component and carbon cloth(CC)as the current collector.In this approach,PDI is firstly dispersed in concentrated sulfuric acid(H2S04)and then deposited on CC substrate after the dilution of H2S04,which provides an organic solvent-free strategy to construct integrated LIB cathodes.The acdic solution based fabrication process also allows the facile adjusting of loading amounts of PDI in the cathodes,which can effectively influence the battery performances of the PDI/CC cathodes.As the result,the acidic solution processed PDI/CC cathode can deliver a high specific capacity of-36 mAh·g^-1 at the current density of 50 mA·g^-1 in both half cell with lithium foil as anode and full cell with pre-lithiated CC as anode.In both types of the batteries,the PDI/CC cathodes show good cycling stabilities by retaining^84%of the initial capacities after 300 charge-discharge cycles at 500 mA·g^-1.Additionally,the excellent mechanical stability of the PDI/CC cathode enables the LIBs in pouch cell to maintain the electrochemical performances under various bending states,demonstrating their potentials for flexible LIBs.
基金This work was supported by National Natural Science Foundation of China(grant number 31730002,2170057)the National Key R&D Program of China(grant number 2019YFA09005400)。
文摘Despite numerous studies on transcriptional level regulation by single genes in drug producing Actinomyces,the global regulation based on epigenetic modification is not well explored.N4-methylcytosine(m4C),an abundant epigenetic marker in Actinomycetes’genome,but its regulatory mechanism remains unclear.In this study,we identify a m4C methyltransferase(SroLm3)in Streptomyces roseosporus L30 and multi-omics studies were performed and revealed SroLm3 as a global regulator of secondary metabolism.Notably,three BGCs inΔsroLm3 strain exhibited decreased expression compared to wild type.In-frame deletion of sroLm3 in S.roseosporus L30 further revealed its role in enhancing daptomycin production.In summary,we characterized a m4C methyltransferase,revealed the function of m4C in secondary metabolism regulation and biosynthesis of red pigment,and mapped a series of novel regulators for daptomycin biosynthesis dominated by m4C methylation.Our research further indicated that m4C DNA methylation may contribute to a metabolic switch from primary to secondary metabolism in Actinomyces.
