Chronic diabetic wounds remain a globally recognized clinical challenge.They occur due to high concentrations of reactive oxygen species and vascular function disorders.A promising strategy for diabetic wound healing ...Chronic diabetic wounds remain a globally recognized clinical challenge.They occur due to high concentrations of reactive oxygen species and vascular function disorders.A promising strategy for diabetic wound healing is the delivery of exosomes,comprising bioactive dressings.Metformin activates the vascular endothelial growth factor pathway,thereby improving angiogenesis in hyperglycemic states.However,multifunctional hydrogels loaded with drugs and bioactive substances synergistically promote wound repair has been rarely reported,and the mechanism of their combinatorial effect of exosome and metformin in wound healing remains unclear.Here,we engineered dual-loaded hydrogels possessing tissue adhesive,antioxidant,self-healing and electrical conductivity properties,wherein 4-armed SH-PEG cross-links with Ag^(+),which minimizes damage to the loaded goods and investigated their mechanism of promotion effect for wound repair.Multiwalled carbon nanotubes exhibiting good conductivity were also incorporated into the hydrogels to generate hydrogen bonds with the thiol group,creating a stable three-dimensional structure for exosome and metformin loading.The diabetic wound model of the present study suggests that the PEG/Ag/CNT-M+E hydrogel promotes wound healing by triggering cell proliferation and angiogenesis and relieving peritraumatic inflammation and vascular injury.The mechanism of the dual-loaded hydrogel involves reducing the level of reactive oxygen species by interfering with mitochondrial fission,thereby protecting F-actin homeostasis and alleviating microvascular dysfunction.Hence,we propose a drug-bioactive substance combination therapy and provide a potential mechanism for developing vascular function-associated strategies for treating chronic diabetic wounds.展开更多
Developing sulfur cathodes with high catalytic activity on accelerating the sluggish redox kinetics of lithium polysulfides(Li PSs) and unveiling their mechanisms are pivotal for advanced lithium–sulfur(Li–S)batteri...Developing sulfur cathodes with high catalytic activity on accelerating the sluggish redox kinetics of lithium polysulfides(Li PSs) and unveiling their mechanisms are pivotal for advanced lithium–sulfur(Li–S)batteries. Herein, MoS2 is verified to reduce the Gibbs free energy for rate-limiting step of sulfur reduction and the dissociation energy of lithium sulfide(Li2 S) for the first time employing theoretical calculations. The Mo S2 nanosheets coated on mesoporous hollow carbon spheres(MHCS) are then reasonably designed as a sulfur host for high-capacity and long-life Li–S battery, in which MHCS can guarantee the high sulfur loading and fast electron/ion transfer. It is revealed that the shuttle effect is efficiently inhibited because of the boosted conversion of Li PSs. As a result, the coin cell based on the MHCS@Mo S2-S cathode exhibits stable cycling performance maintaining 735.7 mAh g^(-1) after 500 cycles at 1.0 C. More importantly, the pouch cell employing the MHCS@Mo S2-S cathodes achieves high specific capacity of1353.2 m Ah g^(-1) and prominent cycle stability that remaining 960.0 m Ah g^(-1) with extraordinary capacity retention of 79.8% at 0.1 C after 170 cycles. Therefore, this work paves a new avenue for developing practical high specific energy and long-life pouch-type Li–S batteries.展开更多
Tumor vaccines trigger tumor-specific immune responses to prevent or treat tumors by activating the hosts’immune systems,and therefore,these vaccines have potential clinical applications.However,the low immunogenicit...Tumor vaccines trigger tumor-specific immune responses to prevent or treat tumors by activating the hosts’immune systems,and therefore,these vaccines have potential clinical applications.However,the low immunogenicity of the tumor antigen itself and the low efficiency of the vaccine delivery system hinder the efficacy of tumor vaccines that cannot produce high-efficiency and long-lasting antitumor immune effects.Here,we constructed a nanovaccine by integrating CD47KO/CRT dual-bioengineered B16F10 cancer cell membranes and the unmethylated cytosine-phosphate-guanine(CpG)adjuvant.Hyperbranched PEI25k was used to load unmethylated cytosine-phosphate-guanine(CpG)through electrostatic adsorption to prepare PEI25k/CpG nanoparticles(PEI25k/CpG-NPs).CD47KO/CRT dual-bioengineered cells were obtained by CRISPR-Cas9 gene editing technology,followed by the cell surface translocation of calreticulin(CRT)to induce immunogenic cell death(ICD)in vitro.Finally,the extracted cell membranes were coextruded with PEI25k/CpG-NPs to construct the CD47KO/CRT dual-bioengineered cancer cell membrane-coated nanoparticles(DBE@CCNPs).DBE@CCNPs could promote endocytosis of antigens and adjuvants in murine bone marrow derived dendritic cells(BMDCs)and induce their maturation and antigen cross-presentation.To avoid immune checkpoint molecule-induced T cell dysfunction,the immune checkpoint inhibitor,the anti-PD-L1 antibody,was introduced to boost tumor immunotherapy through a combination with the DBE@CCNPs nanovaccine.This combination therapy strategy can significantly alleviate tumor growth and may open up a potential strategy for clinical tumor immunotherapy.展开更多
Stem cell research has become a hot topic in biology,as the understanding of stem cell biology can provide new insights for both regenerative medicine and clinical treatment of diseases.Accurately deciphering the fate...Stem cell research has become a hot topic in biology,as the understanding of stem cell biology can provide new insights for both regenerative medicine and clinical treatment of diseases.Accurately deciphering the fate of stem cells is the basis for understanding the mechanism and function of stem cells during tissue repair and regeneration.Cre-loxP-mediated recombination has been widely applied in fate mapping of stem cells for many years.However,nonspecific labeling by conventional cell lineage tracing strategies has led to discrepancies or even controversies in multiple fields.Recently,dual recombinase-mediated lineage tracing strategies have been developed to improve both the resolution and precision of stem cell fate mapping.These new genetic strategies also expand the application of lineage tracing in studying cell origin and fate.Here,we review cell lineage tracing methods,especially dual genetic approaches,and then provide examples to describe how they are used to study stem cell fate plasticity and function in vivo.展开更多
Electrode materials which can reversibly react with anions are of interest for aqueous dual-ion batteries.Herein,we propose a novel anion electrode,Cu3(PO4)2,for constructing an aqueous dual-ion cell.The Cu3(PO4)2 ele...Electrode materials which can reversibly react with anions are of interest for aqueous dual-ion batteries.Herein,we propose a novel anion electrode,Cu3(PO4)2,for constructing an aqueous dual-ion cell.The Cu3(PO4)2 electrode can operate in a quasi-neutral condition and deliver a reversible capacity of 115.6 mAh g^−1 with a well-defined plateau at−0.17 V versus Ag/AgCl.Its reaction mechanism shows that Cu3(PO4)2 decomposes into Cu2O and subsequently is converted into Cu during the initial discharge process.In the following charge process,Cu is oxidized into Cu2O.It suggests Cu3(PO4)2 reacts with OH−ions instead of PO43−ions after the initial discharge process and its potential thereby depends upon the OH−ions concentration in electrolyte.Additionally,an aqueous dual-ion cell is built by using pretreated Cu3(PO4)2 and Na0.44MnO2 as anode and cathode,respectively.During cycling,OH−ions and Na^+ions in electrolyte can be stored and released.Such a cell can provide a discharge capacity of 52.6 mAh g^−1 with plateaus at 0.70 and 0.45 V,exhibiting the potential of application.This work presents an available aqueous dual-ion cell and provides new insights into renewable energy storage and adjustment of the OH−ions concentration in aqueous buffer solution.展开更多
基金supported by National Natural Science Foundation of China Youth Science Fund Project(No.82002039)National Natural Science Foundation of China(81530064)+1 种基金National Natural Science Foundation of China(81772071)National Natural Science Foundation of China(No.82172210).
文摘Chronic diabetic wounds remain a globally recognized clinical challenge.They occur due to high concentrations of reactive oxygen species and vascular function disorders.A promising strategy for diabetic wound healing is the delivery of exosomes,comprising bioactive dressings.Metformin activates the vascular endothelial growth factor pathway,thereby improving angiogenesis in hyperglycemic states.However,multifunctional hydrogels loaded with drugs and bioactive substances synergistically promote wound repair has been rarely reported,and the mechanism of their combinatorial effect of exosome and metformin in wound healing remains unclear.Here,we engineered dual-loaded hydrogels possessing tissue adhesive,antioxidant,self-healing and electrical conductivity properties,wherein 4-armed SH-PEG cross-links with Ag^(+),which minimizes damage to the loaded goods and investigated their mechanism of promotion effect for wound repair.Multiwalled carbon nanotubes exhibiting good conductivity were also incorporated into the hydrogels to generate hydrogen bonds with the thiol group,creating a stable three-dimensional structure for exosome and metformin loading.The diabetic wound model of the present study suggests that the PEG/Ag/CNT-M+E hydrogel promotes wound healing by triggering cell proliferation and angiogenesis and relieving peritraumatic inflammation and vascular injury.The mechanism of the dual-loaded hydrogel involves reducing the level of reactive oxygen species by interfering with mitochondrial fission,thereby protecting F-actin homeostasis and alleviating microvascular dysfunction.Hence,we propose a drug-bioactive substance combination therapy and provide a potential mechanism for developing vascular function-associated strategies for treating chronic diabetic wounds.
基金supported by the funding from the Strategy Priority Research Program of Chinese Academy of Science (Grant No. XDA17020404)DICP&QIBEBT (DICP&QIBEBT UN201702)+8 种基金R&D Projects in Key Areas of Guangdong Province (2019B090908001)Science and Technology Innovation Foundation of Dalian (2018J11CY020)Defense Industrial Technology Development Program (JCKY2018130C107)National Natural Science Foundation of China (Grants 51872283)Liao Ning Revitalization Talents Program (Grant XLYC1807153)Natural Science Foundation of Liaoning Province (Grant 20180510038)DICP (DICP ZZBS201708, DICP ZZBS201802)DNL Cooperation FundCAS (DNL180310, DNL180308, DNL201912, and DNL201915)。
文摘Developing sulfur cathodes with high catalytic activity on accelerating the sluggish redox kinetics of lithium polysulfides(Li PSs) and unveiling their mechanisms are pivotal for advanced lithium–sulfur(Li–S)batteries. Herein, MoS2 is verified to reduce the Gibbs free energy for rate-limiting step of sulfur reduction and the dissociation energy of lithium sulfide(Li2 S) for the first time employing theoretical calculations. The Mo S2 nanosheets coated on mesoporous hollow carbon spheres(MHCS) are then reasonably designed as a sulfur host for high-capacity and long-life Li–S battery, in which MHCS can guarantee the high sulfur loading and fast electron/ion transfer. It is revealed that the shuttle effect is efficiently inhibited because of the boosted conversion of Li PSs. As a result, the coin cell based on the MHCS@Mo S2-S cathode exhibits stable cycling performance maintaining 735.7 mAh g^(-1) after 500 cycles at 1.0 C. More importantly, the pouch cell employing the MHCS@Mo S2-S cathodes achieves high specific capacity of1353.2 m Ah g^(-1) and prominent cycle stability that remaining 960.0 m Ah g^(-1) with extraordinary capacity retention of 79.8% at 0.1 C after 170 cycles. Therefore, this work paves a new avenue for developing practical high specific energy and long-life pouch-type Li–S batteries.
基金The authors are thankful to the National Key R&D Program of China(2021YFB3800900)National Natural Science Foundation of China(51925305,51873208,51973217)+2 种基金Taishan Scholar Foundation of Shandong Province(qnts20161035)Natural Science Foundation of Shandong Province(ZR2019ZD24,ZR2019YQ30)Jilin Province Science and Technology Development Program(20200201075JC,20210509005RQ).
文摘Tumor vaccines trigger tumor-specific immune responses to prevent or treat tumors by activating the hosts’immune systems,and therefore,these vaccines have potential clinical applications.However,the low immunogenicity of the tumor antigen itself and the low efficiency of the vaccine delivery system hinder the efficacy of tumor vaccines that cannot produce high-efficiency and long-lasting antitumor immune effects.Here,we constructed a nanovaccine by integrating CD47KO/CRT dual-bioengineered B16F10 cancer cell membranes and the unmethylated cytosine-phosphate-guanine(CpG)adjuvant.Hyperbranched PEI25k was used to load unmethylated cytosine-phosphate-guanine(CpG)through electrostatic adsorption to prepare PEI25k/CpG nanoparticles(PEI25k/CpG-NPs).CD47KO/CRT dual-bioengineered cells were obtained by CRISPR-Cas9 gene editing technology,followed by the cell surface translocation of calreticulin(CRT)to induce immunogenic cell death(ICD)in vitro.Finally,the extracted cell membranes were coextruded with PEI25k/CpG-NPs to construct the CD47KO/CRT dual-bioengineered cancer cell membrane-coated nanoparticles(DBE@CCNPs).DBE@CCNPs could promote endocytosis of antigens and adjuvants in murine bone marrow derived dendritic cells(BMDCs)and induce their maturation and antigen cross-presentation.To avoid immune checkpoint molecule-induced T cell dysfunction,the immune checkpoint inhibitor,the anti-PD-L1 antibody,was introduced to boost tumor immunotherapy through a combination with the DBE@CCNPs nanovaccine.This combination therapy strategy can significantly alleviate tumor growth and may open up a potential strategy for clinical tumor immunotherapy.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19000000 and XDA16010507)the National Key Research and Development Program of China(2019YFA0110403 and 2019YFA0802000)National Natural Science Foundation of China(31730112,31625019,91849202,and 82008810001)。
文摘Stem cell research has become a hot topic in biology,as the understanding of stem cell biology can provide new insights for both regenerative medicine and clinical treatment of diseases.Accurately deciphering the fate of stem cells is the basis for understanding the mechanism and function of stem cells during tissue repair and regeneration.Cre-loxP-mediated recombination has been widely applied in fate mapping of stem cells for many years.However,nonspecific labeling by conventional cell lineage tracing strategies has led to discrepancies or even controversies in multiple fields.Recently,dual recombinase-mediated lineage tracing strategies have been developed to improve both the resolution and precision of stem cell fate mapping.These new genetic strategies also expand the application of lineage tracing in studying cell origin and fate.Here,we review cell lineage tracing methods,especially dual genetic approaches,and then provide examples to describe how they are used to study stem cell fate plasticity and function in vivo.
基金This work is supported by NSAF joint Fund(U1830106)Ningbo S&I Innovation 2025 Major Special Program(2018B10061)K.C.Wong Magna Fund in Ningbo University.
文摘Electrode materials which can reversibly react with anions are of interest for aqueous dual-ion batteries.Herein,we propose a novel anion electrode,Cu3(PO4)2,for constructing an aqueous dual-ion cell.The Cu3(PO4)2 electrode can operate in a quasi-neutral condition and deliver a reversible capacity of 115.6 mAh g^−1 with a well-defined plateau at−0.17 V versus Ag/AgCl.Its reaction mechanism shows that Cu3(PO4)2 decomposes into Cu2O and subsequently is converted into Cu during the initial discharge process.In the following charge process,Cu is oxidized into Cu2O.It suggests Cu3(PO4)2 reacts with OH−ions instead of PO43−ions after the initial discharge process and its potential thereby depends upon the OH−ions concentration in electrolyte.Additionally,an aqueous dual-ion cell is built by using pretreated Cu3(PO4)2 and Na0.44MnO2 as anode and cathode,respectively.During cycling,OH−ions and Na^+ions in electrolyte can be stored and released.Such a cell can provide a discharge capacity of 52.6 mAh g^−1 with plateaus at 0.70 and 0.45 V,exhibiting the potential of application.This work presents an available aqueous dual-ion cell and provides new insights into renewable energy storage and adjustment of the OH−ions concentration in aqueous buffer solution.
