The advancement of tissue clearing technology has significantly propelled neuroscience research.Nevertheless,the fluorescent proteins used in traditional transgenic mouse strains were not specifically optimized for ti...The advancement of tissue clearing technology has significantly propelled neuroscience research.Nevertheless,the fluorescent proteins used in traditional transgenic mouse strains were not specifically optimized for tissue clearing procedures,resulting in a substantial decrease in fluorescent intensity after clearing.In this study,we developed the Ci1 reporter mouse strain(where Ci stands for the Chinese Institute for Brain Research,CIBR)based on the bright red fluorescent protein mScarlet.The Ci1 reporter exhibits no fluorescence leakage in various organs or tissue types and can be readily crossed with multiple tissue-specific Cre lines.Compared to the Ai14 mouse strain,the Ci1 reporter strain demonstrates lower non-specific leakage,stronger fluorescence intensity in different tissues,and better preservation of fluorescence following tissue clearing treatment.The creation of the Ci1 reporter provides a more effective tool for both neuroscience and other biomedical research applications.展开更多
Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis(OA),but directly modulating mitochondria in vivo remains a significant challenge.This study is the first to verify a correlation b...Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis(OA),but directly modulating mitochondria in vivo remains a significant challenge.This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients,highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA.Consequently,we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool(FoxO3)and integrated it within a nanoengineered‘truck’(NETT,FoxO3--NETT).This was further encapsulated in injectable hydrogel microspheres(FoxO3-NETT@SMs)to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes.Collectively,these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway.As a result,FoxO3-NETT@SMs stimulate chondrocytes proliferation,migration,and ECM production in vitro,and effectively alleviate OA progression in vivo,demonstrating significant potential for clinical applications.展开更多
The interior environment of articular cartilage in osteoarthritis(OA)presents substantial hurdles,leading to the malfunctionof chondrocytes and the breakdown of collagen II-enriched hyaline cartilage matrix.Despite th...The interior environment of articular cartilage in osteoarthritis(OA)presents substantial hurdles,leading to the malfunctionof chondrocytes and the breakdown of collagen II-enriched hyaline cartilage matrix.Despite this,mostclinical treatments primarily provide temporary relief from OA discomfort without arresting OA progression.This studyaimed to alleviate OA by developing intra-articular injectable dECM-enhanced hyaluronic(HE)microgels.The HEhydrogel was engineered and shaped into uniformly sized microgels using microfluidics and photopolymerizationtechniques.These microgels provided a spatiotemporal cascade effect,facilitating the rapid release of growth factorsand a slower release of ECM macromolecules and proteins.This process assisted in the recovery of OA chondrocytes’function,promoting cell proliferation,matrix synthesis,and cartilage-specific gene expression in vitro.It also effectivelyaided repair of the collagen II-enriched hyaline cartilage and significantly reduced the severity of OA,as demonstratedby radiological observation,gross appearance,histological/immunohistochemical staining,and analysisin an OA rat model in vivo.Collectively,the HE injectable microgels with spatiotemporal release of cartilage-specificmolecules have shown promise as a potential candidate for a cell-free OA therapy approach.展开更多
Although platelet-rich plasma(PRP)plays a significant role in the orthopedic clinical application,it still faces two major problems,namely,uncontrollable factors release,frequent preparation and extraction processes a...Although platelet-rich plasma(PRP)plays a significant role in the orthopedic clinical application,it still faces two major problems,namely,uncontrollable factors release,frequent preparation and extraction processes as well as the inconvenient form of usage.To overcome these shortcomings,freeze-dried PRP(LyPRP)was encapsulated into bioactive Col I hydrogel to induce osteogenic dif-ferentiation of rabbit bone marrow mesenchymal stem cells(rBMSCs).And PRP/Col I composite hydrogel was prepared as a control.Compared with Col I hydrogel,the introduction of platelets significantly improved the mechanical properties of hydrogels.Meanwhile,platelets were evenly distributed in the composite hydrogels network.The sustainable release of related factors in the composite hydrogels could last for more than 14days to maintain its long-term biological activity.Further cell experiments confirmed that PRP and LyPRP could effectively alleviate the contraction of collagen hydrogel in vitro,and promote the adhesion,proliferation and osteogenesis differentia-tion of rBMSCs.The results of osteogenic gene expression indicated that the 10%LyPRP/Col I composite hydrogel could facilitate the early expression of BMP-2 and late osteogenic associated protein formation with higher expression of alkaline phosphatase and Osteocalcin(OCN).These results might provide new insights for the clinical application of 10%LyPRP/Col I composite hydro-gel as practical bone repair injection.展开更多
The shortage of resources and the destruction of the environment have caused serious resource and environmental problems shared by all countries around the world. As a ubiquitous renewable resource, biomass has great ...The shortage of resources and the destruction of the environment have caused serious resource and environmental problems shared by all countries around the world. As a ubiquitous renewable resource, biomass has great prospects for replacing fossil energy and attracted attention from the society. The use of catalytic approach to transform biomass into high-value chemicals is an effective way to use biomass efficiently. In this work, Nisupported catalysts has been developed for the selective cleavage of C–O bonds in lignin model compounds with 2-propanol as the hydrogen source solvent. Among these catalysts, it was indicated that zirconium phosphate(Zr P)-supported Ni catalysts were highly efficient and recyclable for alkyl-aryl ether(α-O-4 and β-O-4) cleavage in lignin model compounds. The further investigation demonstrated that the transfer hydrogenolysis of the C–O bond is highly selective, which afforded phenols and aromatics as dominant products without the products arising from hydrogenation of aromatic rings. Through a series of characterization of the catalyst, it was demonstrated that the medium strong acid sites of the Zr P support promoted the cleavage of alkyl-aryl ethers(α-O-4 and β-O-4),and Br?nsted acid sites favored for achieving high selectivity toward C–O bond cleavage. Additionally, Ni(0) sites on the Zr P catalysts were responsible for the catalytic transfer hydrogenolysis.展开更多
基金supported by the startup funding from the Chinese Institute for Brain Research to Hu Zhao.
文摘The advancement of tissue clearing technology has significantly propelled neuroscience research.Nevertheless,the fluorescent proteins used in traditional transgenic mouse strains were not specifically optimized for tissue clearing procedures,resulting in a substantial decrease in fluorescent intensity after clearing.In this study,we developed the Ci1 reporter mouse strain(where Ci stands for the Chinese Institute for Brain Research,CIBR)based on the bright red fluorescent protein mScarlet.The Ci1 reporter exhibits no fluorescence leakage in various organs or tissue types and can be readily crossed with multiple tissue-specific Cre lines.Compared to the Ai14 mouse strain,the Ci1 reporter strain demonstrates lower non-specific leakage,stronger fluorescence intensity in different tissues,and better preservation of fluorescence following tissue clearing treatment.The creation of the Ci1 reporter provides a more effective tool for both neuroscience and other biomedical research applications.
基金supported by the National Key Research and Development Project of China(2023YFB4605800)the Natural Science Foundation of China(32071353 and 82272561)+1 种基金the Natural Science Foundation of Sichuan Province(2024NSFSC0671,China)the 111 Project of China(B16033).
文摘Mitochondrial dysfunction in chondrocytes is a key pathogenic factor in osteoarthritis(OA),but directly modulating mitochondria in vivo remains a significant challenge.This study is the first to verify a correlation between mitochondrial dysfunction and the downregulation of the FOXO3 gene in the cartilage of OA patients,highlighting the potential for regulating mitophagy via FOXO3 gene modulation to alleviate OA.Consequently,we developed a chondrocyte-targeting CRISPR/Cas9-based FOXO3 gene-editing tool(FoxO3)and integrated it within a nanoengineered‘truck’(NETT,FoxO3--NETT).This was further encapsulated in injectable hydrogel microspheres(FoxO3-NETT@SMs)to harness the antioxidant properties of sodium alginate and the enhanced lubrication of hybrid exosomes.Collectively,these FoxO3-NETT@SMs successfully activate mitophagy and rebalance mitochondrial function in OA chondrocytes through the Foxo3 gene-modulated PINK1/Parkin pathway.As a result,FoxO3-NETT@SMs stimulate chondrocytes proliferation,migration,and ECM production in vitro,and effectively alleviate OA progression in vivo,demonstrating significant potential for clinical applications.
基金supported by the National Key Research Program of China(2023YFB4605800)the Natural Science Foundation of China(32071353)the 111 Project(B16033).
文摘The interior environment of articular cartilage in osteoarthritis(OA)presents substantial hurdles,leading to the malfunctionof chondrocytes and the breakdown of collagen II-enriched hyaline cartilage matrix.Despite this,mostclinical treatments primarily provide temporary relief from OA discomfort without arresting OA progression.This studyaimed to alleviate OA by developing intra-articular injectable dECM-enhanced hyaluronic(HE)microgels.The HEhydrogel was engineered and shaped into uniformly sized microgels using microfluidics and photopolymerizationtechniques.These microgels provided a spatiotemporal cascade effect,facilitating the rapid release of growth factorsand a slower release of ECM macromolecules and proteins.This process assisted in the recovery of OA chondrocytes’function,promoting cell proliferation,matrix synthesis,and cartilage-specific gene expression in vitro.It also effectivelyaided repair of the collagen II-enriched hyaline cartilage and significantly reduced the severity of OA,as demonstratedby radiological observation,gross appearance,histological/immunohistochemical staining,and analysisin an OA rat model in vivo.Collectively,the HE injectable microgels with spatiotemporal release of cartilage-specificmolecules have shown promise as a potential candidate for a cell-free OA therapy approach.
基金This work was sponsored by National Key Research and Development Project of China(Grant No.2018YFC1106800)National Nature Science Foundation of China(Grant Nos 32071352 and 81860392)+2 种基金Sichuan Province Scientific and Technological Achievements Transformation and Guidance Project(Grant No.2016CZYD0004)Sichuan Province Key R&D Program(Grant No.2019YFS0007)Sichuan University Innovation Spark Project(Grant No.2018SCUH0089).
文摘Although platelet-rich plasma(PRP)plays a significant role in the orthopedic clinical application,it still faces two major problems,namely,uncontrollable factors release,frequent preparation and extraction processes as well as the inconvenient form of usage.To overcome these shortcomings,freeze-dried PRP(LyPRP)was encapsulated into bioactive Col I hydrogel to induce osteogenic dif-ferentiation of rabbit bone marrow mesenchymal stem cells(rBMSCs).And PRP/Col I composite hydrogel was prepared as a control.Compared with Col I hydrogel,the introduction of platelets significantly improved the mechanical properties of hydrogels.Meanwhile,platelets were evenly distributed in the composite hydrogels network.The sustainable release of related factors in the composite hydrogels could last for more than 14days to maintain its long-term biological activity.Further cell experiments confirmed that PRP and LyPRP could effectively alleviate the contraction of collagen hydrogel in vitro,and promote the adhesion,proliferation and osteogenesis differentia-tion of rBMSCs.The results of osteogenic gene expression indicated that the 10%LyPRP/Col I composite hydrogel could facilitate the early expression of BMP-2 and late osteogenic associated protein formation with higher expression of alkaline phosphatase and Osteocalcin(OCN).These results might provide new insights for the clinical application of 10%LyPRP/Col I composite hydro-gel as practical bone repair injection.
基金support from the National Natural Science Foundation of China(21773061,21978095)the Open Research Fund of Shanghai Key Laboratory of Green Chemistry and Chemical Processes。
文摘The shortage of resources and the destruction of the environment have caused serious resource and environmental problems shared by all countries around the world. As a ubiquitous renewable resource, biomass has great prospects for replacing fossil energy and attracted attention from the society. The use of catalytic approach to transform biomass into high-value chemicals is an effective way to use biomass efficiently. In this work, Nisupported catalysts has been developed for the selective cleavage of C–O bonds in lignin model compounds with 2-propanol as the hydrogen source solvent. Among these catalysts, it was indicated that zirconium phosphate(Zr P)-supported Ni catalysts were highly efficient and recyclable for alkyl-aryl ether(α-O-4 and β-O-4) cleavage in lignin model compounds. The further investigation demonstrated that the transfer hydrogenolysis of the C–O bond is highly selective, which afforded phenols and aromatics as dominant products without the products arising from hydrogenation of aromatic rings. Through a series of characterization of the catalyst, it was demonstrated that the medium strong acid sites of the Zr P support promoted the cleavage of alkyl-aryl ethers(α-O-4 and β-O-4),and Br?nsted acid sites favored for achieving high selectivity toward C–O bond cleavage. Additionally, Ni(0) sites on the Zr P catalysts were responsible for the catalytic transfer hydrogenolysis.
