Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of cela...Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of celastrol in breast cancer.Method:A quantitative chemical biology approach was used to investigate the protein targets and molecular mechanisms of celastrol in breast cancer cells.Results:Low-concentration celastrol exerted an anti-tumor effect by directly binding to hydroxysteroid dehydrogenase-like 2(HSDL2)and inhibiting its expression.Moreover,the expression of the pro-apoptotic protein,Bcl-2-associated X(BaX),increased,the level of the anti-apoptotic protein,B-cell lymphoma-2(Bcl-2),decreased,and the rate of apoptosis increased.After the transfection of cells with si-HSDL2,the apoptosis rate was similar to that observed after the administration of celastrol.However,apoptosis was reversed by the overexpression of HSDL2.Furthermore,our mass spectrometry(MS)data indicated a relationship between HSDL2 and the mitogen-activated protein kinase(MAPK)signaling pathway.We also found that the expression of HSDL2 was directly related to the degree of extracellular signal-regulated kinase(ERK)phosphorylation.Conclusion:Celastrol may promote apoptosis by suppressing the HSDL2/MAPK/ERK signaling pathway.展开更多
A novel multivariate similarity clustering analysis (MSCA) approach was used to estimate a biogeographical division scheme for the global terrestrial fauna and was compared against other widely used clustering algorit...A novel multivariate similarity clustering analysis (MSCA) approach was used to estimate a biogeographical division scheme for the global terrestrial fauna and was compared against other widely used clustering algorithms. The faunal dataset included almost all terrestrial and freshwater fauna, a total of 4631 families, 141,814 genera, and 1,334,834 species. Our findings demonstrated that suitable results were only obtained with the MSCA method, which was associated with distinct hierarchies, reasonable structuring, and furthermore, conformed to biogeographical criteria. A total of seven kingdoms and 20 sub-kingdoms were identified. We discovered that the clustering results for the higher and lower animals did not differ significantly, leading us to consider that the analysis result is convincing as the first zoogeographical division scheme for global all terrestrial animals.展开更多
Choroidal neovascularization(CNV) is a leading cause of visual loss in age-related macular degeneration(AMD). However, the molecular mechanism for CNV progression is still unclear. This study aimed to identify CNV-rel...Choroidal neovascularization(CNV) is a leading cause of visual loss in age-related macular degeneration(AMD). However, the molecular mechanism for CNV progression is still unclear. This study aimed to identify CNV-related circular RNAs(circRNAs), a novel class of non-coding RNAs with diverse functions. A total of 117 circRNAs were differentially expressed in the murine CNV model by microarrays. Gene ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis were performed to identify the functions of selected circRNAs. The host genes of these circRNAs were predicted to be targeted to neurogenesis(ontology: biological process), proteinaceous extracellular matrix(ECM)(ontology: cellular component), and binding(ontology: molecular function). Differentially expressed circRNAs-mediated regulatory networks were enriched in ECM receptor interaction. Most of the dysregulated circRNAs could potentially bind to five different mi RNAs by Target Scan and mi Randa. Specifically, circ_15752 was identified in this circRNAs pool which may facilitate vascular endothelial cell proliferation, migration, and tube formation, suggesting a critical role in endothelial angiogenesis. Our work suggests that dysregulated circRNAs may be involved in CNV pathogenesis and serve as potential biomarkers for CNV.展开更多
Waterlogging is frequently stressed rapeseed growth. Under this stress, plant is in state of hypoxia which limits aerobic respiration and energy metabolism. Promoting root growth is an adaptive strategy of terrestria...Waterlogging is frequently stressed rapeseed growth. Under this stress, plant is in state of hypoxia which limits aerobic respiration and energy metabolism. Promoting root growth is an adaptive strategy of terrestrial plants in response to waterlogging stress. Auxin plays important roles in root growth. However, the effects of auxin on rapeseed root growth under waterlogging stress remain largely unknown. In this study, we investigated endoge-nous IAA levels and root growth of rapeseed under hypoxia stress （H）, hypoxia treatment with IAA（HI）f PCIB （an auxin action inhibitor, HP） or TIBA（an auxin polar-transport inhibi-tor, HT） through hydroponic experiment. Pot experiment was further employed to evaluate effects of exogenous IAA on growth of rapeseed under waterlogging stress by foliar spray-ing. Results from hydroponic showed that compared with control （CK）, hypoxia significantly decreased rapeseed growth after 48 hours treatment, while HI dramatically alleviated the depression. In contrast, HP and HT aggravated growth depression by hypoxia stress, as indicated by obvious decrease in root and shoot dry weight. Under hypoxia stress, alter-ation in root growth, especially for lateral roots with a diameter 〈1.5 mm was positively related with IAA levels in roots. Pot experiment further proved those findings. These results suggested that endogenous IAA might be involved in root growth of rapeseed response to waterlogging stress. Furthermore, foliar spraying with moderate IAA increased rapeseed growth underwaterlogging stress through promoting endogenous lAA-caused root growth. This work provided an available method to improve rapeseed tolerance to waterlogging in soil.展开更多
The outstanding advantages of lightweight and flexibility enable flexible perovskite solar cells(PSCs)to have great application potential in mobile energy devices.Due to the low cost,low-temperature processibility,and...The outstanding advantages of lightweight and flexibility enable flexible perovskite solar cells(PSCs)to have great application potential in mobile energy devices.Due to the low cost,low-temperature processibility,and high electron mobility,SnO_(2) nanocrystals have been widely employed as the electron transport layer in flexible PSCs.To prepare high-quality SnO_(2) layers,a monodispersed nanocrystal solution is normally used.However,the SnO_(2) nanocrystals can easily aggregate,especially after long periods of storage.Herein,we develop a green and cost-effective strategy for the synthesis of high-quality SnO_(2) nanocrystals at low temperatures by introducing small molecules of glycerol,obtaining a stable and well-dispersed SnO_(2)-nanocrystal isopropanol dispersion successfully.Due to the enhanced dispersity and super wettability of this alcohol-based SnO_(2)-nanocrystal solution,large-area smooth and dense SnO_(2) films are easily deposited on the plastic conductive substrate.Furthermore,this contributes to effective charge transfer and suppressed non-radiative recombination at the interface between the SnO_(2) and perovskite layers.As a result,a greatly enhanced power conversion efficiency(PCE)of 21.8%from 19.2%is achieved for small-area flexible PSCs.A large-area 5 cm×5 cm flexible perovskite solar mini-module with a champion PCE of 16.5%and good stability is also demonstrated via this glycerol-modified SnO_(2)-nanocrystal isopropanol dispersion approach.展开更多
Erratum to Nano Research,2024,17(4):2704-2711 https://doi.org/10.1007/s12274-023-6115-y(1)In the article,the table of contents(TOC)image was unfortunately mispresented.
3-Hydroxybutyrate(3HB)is a small ketone body molecule produced endogenously by the body in the liver.Previous studies have shown that 3HB can reduce blood glucose level in type 2 diabetic(T2D)patients.However,there is...3-Hydroxybutyrate(3HB)is a small ketone body molecule produced endogenously by the body in the liver.Previous studies have shown that 3HB can reduce blood glucose level in type 2 diabetic(T2D)patients.However,there is no systematic study and clear mechanism to evaluate and explain the hypoglycemic effect of 3HB.Here we demonstrate that 3HB reduces fasting blood glucose level,improves glucose tolerance,and ameliorates insulin resistance in type 2 diabetic mice through hydroxycarboxylic acid receptor 2(HCAR2).Mechanistically,3HB increases intracellular calcium ion(Ca^(2+))levels by activating HCAR2,thereby stimulating adenylate cyclase(AC)to increase cyclic adenosine monophosphate(cAMP)concentration,and then activating protein kinase A(PKA).Activated PKA inhibits Raf1 proto-oncogene serine/threonine-protein kinase(Raf1)activity,resulting in a decrease in extracellular signal-regulated kinases 1/2(ERK1/2)activity and ultimately inhibiting peroxisome proliferator-activated receptorγ(PPARγ)Ser273 phosphorylation in adipocytes.Inhibition of PPARγSer273 phosphorylation by 3HB altered the expression of PPARγregulated genes and reduced insulin resistance.Collectively,3HB ameliorates insulin resistance in type 2 diabetic mice through a pathway of HCAR2/Ca^(2+)/cAMP/PKA/Raf1/ERK1/2/PPARγ.展开更多
In ophthalmology,the quality of fundus images is critical for accurate diagnosis,both in clinical practice and in artificial intelligence(AI)-assisted diagnostics.Despite the broad view provided by ultrawide-field(UWF...In ophthalmology,the quality of fundus images is critical for accurate diagnosis,both in clinical practice and in artificial intelligence(AI)-assisted diagnostics.Despite the broad view provided by ultrawide-field(UWF)imaging,pseudocolor images may conceal critical lesions necessary for precise diagnosis.To address this,we introduce UWF-Net,a sophisticated image enhancement algorithm that takes disease characteristics into consideration.Using the Fudan University ultra-wide-field image(FDUWI)dataset,which includes 11294 Optos pseudocolor and 2415 Zeiss true-color UWF images,each of which is rigorously annotated,UWF-Net combines global style modeling with feature-level lesion enhancement.Pathological consistency loss is also applied to maintain fundus feature integrity,significantly improving image quality.Quantitative and qualitative evaluations demonstrated that UWF-Net outperforms existing methods such as contrast limited adaptive histogram equalization(CLAHE)and structure and illumination constrained generative adversarial network(StillGAN),delivering superior retinal image quality,higher quality scores,and preserved feature details after enhancement.In disease classification tasks,images enhanced by UWF-Net showed notable improvements when processed with existing classification systems over those enhanced by StillGAN,demonstrating a 4.62%increase in sensitivity(SEN)and a 3.97%increase in accuracy(ACC).In a multicenter clinical setting,UWF-Net-enhanced images were preferred by ophthalmologic technicians and doctors,and yielded a significant reduction in diagnostic time((13.17±8.40)s for UWF-Net enhanced images vs(19.54±12.40)s for original images)and an increase in diagnostic accuracy(87.71%for UWF-Net enhanced images vs 80.40%for original images).Our research verifies that UWF-Net markedly improves the quality of UWF imaging,facilitating better clinical outcomes and more reliable AI-assisted disease classification.The clinical integration of UWF-Net holds great promise for enhancing diagnostic processes and patient care in ophthalmology.展开更多
A new method,multivariate similarity clustering analysis(MSCA)method,was established for biogeographical distribution analyzing.General similarity formula(GSF),the core of MSCA method,can be used to calculate the simi...A new method,multivariate similarity clustering analysis(MSCA)method,was established for biogeographical distribution analyzing.General similarity formula(GSF),the core of MSCA method,can be used to calculate the similarity coefficients between 2 and among any≥3 geographical units.Taking the global insects as example,we introduced the steps to use of GSF and consequent clustering processes of this method in details.Firstly,geographical distributions of certain taxa(e.g.Insecta)were categorized into basic geographical units(BGUs);Secondly,similarity coefficients between 2 and among n BGUs were calculated using GSF.Thirdly,hierarchical clustering was conducted according to values of similarity coefficients(from high to low);then a clustering diagram was generated.Finally,a framework of biogeographical division map was established for the target taxa(e.g.Insecta).We concluded that the MSCA method was efficiently applied in analyzing the biogeographical distribution of given biological taxa;the geographical regions regarding global insects were categorized into 7 Realms with 20 sub-Realms based on the results of MSCA method.展开更多
Retinal pigment epithelial(RPE) is primarily impaired in age-related macular degeneration(AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization(CNV). mTOR has been proposed as ...Retinal pigment epithelial(RPE) is primarily impaired in age-related macular degeneration(AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization(CNV). mTOR has been proposed as a promising therapeutic target, while the usage of its specific inhibitor,rapamycin, was greatly limited. To mediate the mTOR pathway in the retina by a noninvasive approach, we developed novel biomimetic nanocomplexes where rapamycin-loaded nanoparticles were coated with cell membrane derived from macrophages(termed as MRaNPs). Taking advantage of the macrophage-inherited property, intravenous injection of MRaNPs exhibited significantly enhanced accumulation in the CNV lesions, thereby increasing the local concentration of rapamycin. Consequently, MRaNPs effectively downregulated the mTOR pathway and attenuate angiogenesis in the eye. Particularly, MRaNPs also efficiently activated autophagy in the RPE, which was acknowledged to rescue RPE in response to deleterious stimuli. Overall, we design and prepare macrophage-disguised rapamycin nanocarriers and demonstrate the therapeutic advantages of employing biomimetic cell membrane materials for treatment of AMD.展开更多
基金the National Key Research and Development Program of China(2020YFA0908000,2022YFC2303600)the National Natural Science Foundation of China(81903866,82274182)and the Central Public Welfare Research Institutes(ZZ13-YQ-105,ZZ15-YQ-065,ZZ14-YQ-058).
文摘Objective:Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb,Tripterygium wilfordii.This study aims to provide a scientific basis for the rational development and use of celastrol in breast cancer.Method:A quantitative chemical biology approach was used to investigate the protein targets and molecular mechanisms of celastrol in breast cancer cells.Results:Low-concentration celastrol exerted an anti-tumor effect by directly binding to hydroxysteroid dehydrogenase-like 2(HSDL2)and inhibiting its expression.Moreover,the expression of the pro-apoptotic protein,Bcl-2-associated X(BaX),increased,the level of the anti-apoptotic protein,B-cell lymphoma-2(Bcl-2),decreased,and the rate of apoptosis increased.After the transfection of cells with si-HSDL2,the apoptosis rate was similar to that observed after the administration of celastrol.However,apoptosis was reversed by the overexpression of HSDL2.Furthermore,our mass spectrometry(MS)data indicated a relationship between HSDL2 and the mitogen-activated protein kinase(MAPK)signaling pathway.We also found that the expression of HSDL2 was directly related to the degree of extracellular signal-regulated kinase(ERK)phosphorylation.Conclusion:Celastrol may promote apoptosis by suppressing the HSDL2/MAPK/ERK signaling pathway.
文摘A novel multivariate similarity clustering analysis (MSCA) approach was used to estimate a biogeographical division scheme for the global terrestrial fauna and was compared against other widely used clustering algorithms. The faunal dataset included almost all terrestrial and freshwater fauna, a total of 4631 families, 141,814 genera, and 1,334,834 species. Our findings demonstrated that suitable results were only obtained with the MSCA method, which was associated with distinct hierarchies, reasonable structuring, and furthermore, conformed to biogeographical criteria. A total of seven kingdoms and 20 sub-kingdoms were identified. We discovered that the clustering results for the higher and lower animals did not differ significantly, leading us to consider that the analysis result is convincing as the first zoogeographical division scheme for global all terrestrial animals.
基金supported by the National Natural Science Foundation of China(No.81525006,81670864,and 81730025 to C.Z.)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(No.2018PT32019 to C.Z.)。
文摘Choroidal neovascularization(CNV) is a leading cause of visual loss in age-related macular degeneration(AMD). However, the molecular mechanism for CNV progression is still unclear. This study aimed to identify CNV-related circular RNAs(circRNAs), a novel class of non-coding RNAs with diverse functions. A total of 117 circRNAs were differentially expressed in the murine CNV model by microarrays. Gene ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis were performed to identify the functions of selected circRNAs. The host genes of these circRNAs were predicted to be targeted to neurogenesis(ontology: biological process), proteinaceous extracellular matrix(ECM)(ontology: cellular component), and binding(ontology: molecular function). Differentially expressed circRNAs-mediated regulatory networks were enriched in ECM receptor interaction. Most of the dysregulated circRNAs could potentially bind to five different mi RNAs by Target Scan and mi Randa. Specifically, circ_15752 was identified in this circRNAs pool which may facilitate vascular endothelial cell proliferation, migration, and tube formation, suggesting a critical role in endothelial angiogenesis. Our work suggests that dysregulated circRNAs may be involved in CNV pathogenesis and serve as potential biomarkers for CNV.
文摘Waterlogging is frequently stressed rapeseed growth. Under this stress, plant is in state of hypoxia which limits aerobic respiration and energy metabolism. Promoting root growth is an adaptive strategy of terrestrial plants in response to waterlogging stress. Auxin plays important roles in root growth. However, the effects of auxin on rapeseed root growth under waterlogging stress remain largely unknown. In this study, we investigated endoge-nous IAA levels and root growth of rapeseed under hypoxia stress （H）, hypoxia treatment with IAA（HI）f PCIB （an auxin action inhibitor, HP） or TIBA（an auxin polar-transport inhibi-tor, HT） through hydroponic experiment. Pot experiment was further employed to evaluate effects of exogenous IAA on growth of rapeseed under waterlogging stress by foliar spray-ing. Results from hydroponic showed that compared with control （CK）, hypoxia significantly decreased rapeseed growth after 48 hours treatment, while HI dramatically alleviated the depression. In contrast, HP and HT aggravated growth depression by hypoxia stress, as indicated by obvious decrease in root and shoot dry weight. Under hypoxia stress, alter-ation in root growth, especially for lateral roots with a diameter 〈1.5 mm was positively related with IAA levels in roots. Pot experiment further proved those findings. These results suggested that endogenous IAA might be involved in root growth of rapeseed response to waterlogging stress. Furthermore, foliar spraying with moderate IAA increased rapeseed growth underwaterlogging stress through promoting endogenous lAA-caused root growth. This work provided an available method to improve rapeseed tolerance to waterlogging in soil.
基金supported by the National Key Research and Development Plan(No.2019YFE0107200)the National Natural Science Foundation of China(Nos.22279099,52202292,and 52172230)+3 种基金Guangdong Basic and Applied Basic Research Fund(No.2021B1515120003)the NSF of Hubei Province(No.2021CFB051)the Fundamental Research Funds for the Central Universities(No.WUT:2023IVA074)the National Research Foundation of Korea(NRF)(No.2019K1A3A1A61091345).
文摘The outstanding advantages of lightweight and flexibility enable flexible perovskite solar cells(PSCs)to have great application potential in mobile energy devices.Due to the low cost,low-temperature processibility,and high electron mobility,SnO_(2) nanocrystals have been widely employed as the electron transport layer in flexible PSCs.To prepare high-quality SnO_(2) layers,a monodispersed nanocrystal solution is normally used.However,the SnO_(2) nanocrystals can easily aggregate,especially after long periods of storage.Herein,we develop a green and cost-effective strategy for the synthesis of high-quality SnO_(2) nanocrystals at low temperatures by introducing small molecules of glycerol,obtaining a stable and well-dispersed SnO_(2)-nanocrystal isopropanol dispersion successfully.Due to the enhanced dispersity and super wettability of this alcohol-based SnO_(2)-nanocrystal solution,large-area smooth and dense SnO_(2) films are easily deposited on the plastic conductive substrate.Furthermore,this contributes to effective charge transfer and suppressed non-radiative recombination at the interface between the SnO_(2) and perovskite layers.As a result,a greatly enhanced power conversion efficiency(PCE)of 21.8%from 19.2%is achieved for small-area flexible PSCs.A large-area 5 cm×5 cm flexible perovskite solar mini-module with a champion PCE of 16.5%and good stability is also demonstrated via this glycerol-modified SnO_(2)-nanocrystal isopropanol dispersion approach.
文摘Erratum to Nano Research,2024,17(4):2704-2711 https://doi.org/10.1007/s12274-023-6115-y(1)In the article,the table of contents(TOC)image was unfortunately mispresented.
基金supported by the National Natural Science Foundation of China(Grant No.31870859)and Tsinghua Chunfeng Foundation.
文摘3-Hydroxybutyrate(3HB)is a small ketone body molecule produced endogenously by the body in the liver.Previous studies have shown that 3HB can reduce blood glucose level in type 2 diabetic(T2D)patients.However,there is no systematic study and clear mechanism to evaluate and explain the hypoglycemic effect of 3HB.Here we demonstrate that 3HB reduces fasting blood glucose level,improves glucose tolerance,and ameliorates insulin resistance in type 2 diabetic mice through hydroxycarboxylic acid receptor 2(HCAR2).Mechanistically,3HB increases intracellular calcium ion(Ca^(2+))levels by activating HCAR2,thereby stimulating adenylate cyclase(AC)to increase cyclic adenosine monophosphate(cAMP)concentration,and then activating protein kinase A(PKA).Activated PKA inhibits Raf1 proto-oncogene serine/threonine-protein kinase(Raf1)activity,resulting in a decrease in extracellular signal-regulated kinases 1/2(ERK1/2)activity and ultimately inhibiting peroxisome proliferator-activated receptorγ(PPARγ)Ser273 phosphorylation in adipocytes.Inhibition of PPARγSer273 phosphorylation by 3HB altered the expression of PPARγregulated genes and reduced insulin resistance.Collectively,3HB ameliorates insulin resistance in type 2 diabetic mice through a pathway of HCAR2/Ca^(2+)/cAMP/PKA/Raf1/ERK1/2/PPARγ.
基金supported by the National Natural Science Foundation of China(82020108006 and 81730025 to Chen Zhao,U2001209 to Bo Yan)the Excellent Academic Leaders of Shanghai(18XD1401000 to Chen Zhao)the Natural Science Foundation of Shanghai,China(21ZR1406600 to Weimin Tan).
文摘In ophthalmology,the quality of fundus images is critical for accurate diagnosis,both in clinical practice and in artificial intelligence(AI)-assisted diagnostics.Despite the broad view provided by ultrawide-field(UWF)imaging,pseudocolor images may conceal critical lesions necessary for precise diagnosis.To address this,we introduce UWF-Net,a sophisticated image enhancement algorithm that takes disease characteristics into consideration.Using the Fudan University ultra-wide-field image(FDUWI)dataset,which includes 11294 Optos pseudocolor and 2415 Zeiss true-color UWF images,each of which is rigorously annotated,UWF-Net combines global style modeling with feature-level lesion enhancement.Pathological consistency loss is also applied to maintain fundus feature integrity,significantly improving image quality.Quantitative and qualitative evaluations demonstrated that UWF-Net outperforms existing methods such as contrast limited adaptive histogram equalization(CLAHE)and structure and illumination constrained generative adversarial network(StillGAN),delivering superior retinal image quality,higher quality scores,and preserved feature details after enhancement.In disease classification tasks,images enhanced by UWF-Net showed notable improvements when processed with existing classification systems over those enhanced by StillGAN,demonstrating a 4.62%increase in sensitivity(SEN)and a 3.97%increase in accuracy(ACC).In a multicenter clinical setting,UWF-Net-enhanced images were preferred by ophthalmologic technicians and doctors,and yielded a significant reduction in diagnostic time((13.17±8.40)s for UWF-Net enhanced images vs(19.54±12.40)s for original images)and an increase in diagnostic accuracy(87.71%for UWF-Net enhanced images vs 80.40%for original images).Our research verifies that UWF-Net markedly improves the quality of UWF imaging,facilitating better clinical outcomes and more reliable AI-assisted disease classification.The clinical integration of UWF-Net holds great promise for enhancing diagnostic processes and patient care in ophthalmology.
基金This study was financially supported by the Zhengzhou Science and Technology Leading Talent Project(131PLJRC654)。
文摘A new method,multivariate similarity clustering analysis(MSCA)method,was established for biogeographical distribution analyzing.General similarity formula(GSF),the core of MSCA method,can be used to calculate the similarity coefficients between 2 and among any≥3 geographical units.Taking the global insects as example,we introduced the steps to use of GSF and consequent clustering processes of this method in details.Firstly,geographical distributions of certain taxa(e.g.Insecta)were categorized into basic geographical units(BGUs);Secondly,similarity coefficients between 2 and among n BGUs were calculated using GSF.Thirdly,hierarchical clustering was conducted according to values of similarity coefficients(from high to low);then a clustering diagram was generated.Finally,a framework of biogeographical division map was established for the target taxa(e.g.Insecta).We concluded that the MSCA method was efficiently applied in analyzing the biogeographical distribution of given biological taxa;the geographical regions regarding global insects were categorized into 7 Realms with 20 sub-Realms based on the results of MSCA method.
基金supported by the grants from National Natural Science Foundation of China (Grant No.81525006)Program of Shanghai Academic Research Leader (Grant No.18XD1401000,China)Shanghai Outstanding Academic Leaders (Grant No.2017BR013,China)。
文摘Retinal pigment epithelial(RPE) is primarily impaired in age-related macular degeneration(AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization(CNV). mTOR has been proposed as a promising therapeutic target, while the usage of its specific inhibitor,rapamycin, was greatly limited. To mediate the mTOR pathway in the retina by a noninvasive approach, we developed novel biomimetic nanocomplexes where rapamycin-loaded nanoparticles were coated with cell membrane derived from macrophages(termed as MRaNPs). Taking advantage of the macrophage-inherited property, intravenous injection of MRaNPs exhibited significantly enhanced accumulation in the CNV lesions, thereby increasing the local concentration of rapamycin. Consequently, MRaNPs effectively downregulated the mTOR pathway and attenuate angiogenesis in the eye. Particularly, MRaNPs also efficiently activated autophagy in the RPE, which was acknowledged to rescue RPE in response to deleterious stimuli. Overall, we design and prepare macrophage-disguised rapamycin nanocarriers and demonstrate the therapeutic advantages of employing biomimetic cell membrane materials for treatment of AMD.
