Background Adequate level of carbohydrates in aquafeeds help to conserve protein and reduce cost. However, studies have indicated that high-carbohydrate(HC) diet disrupt the homeostasis of the gut–liver axis in large...Background Adequate level of carbohydrates in aquafeeds help to conserve protein and reduce cost. However, studies have indicated that high-carbohydrate(HC) diet disrupt the homeostasis of the gut–liver axis in largemouth bass, resulting in decreased intestinal acetate and butyrate level.Method Herein, we had concepted a set of feeding experiment to assess the effects of dietary sodium acetate(SA) and sodium butyrate(SB) on liver health and the intestinal microbiota in largemouth bass fed an HC diet. The experimental design comprised 5 isonitrogenous and isolipidic diets, including LC(9% starch), HC(18% starch), HCSA(18% starch;2 g/kg SA), HCSB(18% starch;2 g/kg SB), and HCSASB(18% starch;1 g/kg SA + 1 g/kg SB). Juvenile largemouth bass with an initial body weight of 7.00 ± 0.20 g were fed on these diets for 56 d.Results We found that dietary SA and SB reduced hepatic triglyceride accumulation by activating autophagy(ATG101, LC3B and TFEB), promoting lipolysis(CPT1α, HSL and AMPKα), and inhibiting adipogenesis(FAS, ACCA, SCD1 and PPARγ). In addition, SA and SB decreased oxidative stress in the liver(CAT, GPX1α and SOD1) by activating the Keap1-Nrf2 pathway. Meanwhile, SA and SB alleviated HC-induced inflammation by downregulating the expression of pro-inflammatory factors(IL-1β, COX2 and Hepcidin1) through the NF-κB pathway. Importantly, SA and SB increased the abundance of bacteria that produced acetic acid and butyrate(Clostridium_sensu_stricto_1). Combined with the KEGG analysis, the results showed that SA and SB enriched carbohydrate metabolism and amino acid metabolism pathways, thereby improving the utilization of carbohydrates. Pearson correlation analysis indicated that growth performance was closely related to hepatic lipid deposition, autophagy, antioxidant capacity, inflammation, and intestinal microbial composition.Conclusions In conclusion, dietary SA and SB can reduce hepatic lipid deposition;and alleviate oxidative stress and inflammation in largemouth bass fed on HC diet. These beneficial effects may be due to the altered composition of the gut microbiota caused by SA and SB. The improvement effects of SB were stronger than those associated with SA.展开更多
Background:The interaction between nutrition and immunity plays a vital role in nutrient digestion,absorption,and metabolism during poultry production.Recent studies showed that the gut microbiota contributes to the d...Background:The interaction between nutrition and immunity plays a vital role in nutrient digestion,absorption,and metabolism during poultry production.Recent studies showed that the gut microbiota contributes to the development of intestinal mucosal immunity.However,the mechanisms by which gut microbes regulate this process remain unclear.Methods:We compared the intestinal mucosal immunity and gut microbiota of Arbor Acre broilers AA(lower mucosal immunity)and Chinese native Wuliang Mountain Black-bone chickens(WLMB)(higher mucosal immunity)using 16S rDNA sequencing,transcriptomic analysis,and immunoglobulin A(IgA)antibody repertoire sequencing.We then combined 16S rDNA sequencing with transcriptomics to identify the key microbes and found that they were positively correlated with IgA production.Next,we transplanted candidate microbes into 1-day-old broiler to explore their role in intestinal mucosal immunity.Finally,we verified the function of candidate microbial metabolites in regulating the immune function of macrophages and the intestinal-epithelial cells(IECs)using in vitro experiments.Results:WLMB performs stronger mucosal immunity than AA,including higher IgA levels,more diverse IgA antibody repertoire,and higher bacterial affinity.Bacteroides was identified as the key microbes related to the intestinal IgA response.Bacteroides transplantation could increase IgA concentration in the duodenal contents by enhancing the expression of IgA,polymeric immunoglobin receptor(PIgR),B cell-activating factor of the TNF family(BAFF),and activation-induced cytidine deaminase(AID)in the duodenum.Additionally,Bacteroides-derived isovaleric acid promoted M2 macrophage polarization of macrophage via mTOR/PPAR-γ/STAT3 signaling pathways and regulated the immunologic function of IECs to produce cytokines,including interleukin(IL)-10,IL-4,BAFF,and transforming growth factor-beta(TGF-β),thus promoting IgA production in B cells by facilitating AID expression.Conclusion:Our study revealed that Bacteroides modulate the intestinal IgA response and maintain gut health in broilers.Bacteroides may be a promising alternative as an immunomodulatory microbial agent for developing nextgeneration probiotics for broiler production.展开更多
The digitization,informatization,and intelligentization of physical systems require strong support from big data analysis.However,due to restrictions on data security and privacy and concerns about the cost of big dat...The digitization,informatization,and intelligentization of physical systems require strong support from big data analysis.However,due to restrictions on data security and privacy and concerns about the cost of big data collection,transmission,and storage,it is difficult to do data aggregation in real-world power systems,which directly retards the effective implementation of smart grid analytics.Federated learning,an advanced distributed learning method proposed by Google,seems a promising solution to the above issues.Nevertheless,it relies on a server node to complete model aggregation and the framework is limited to scenarios where data are independent and identically distributed.Thus,we here propose a serverless distributed learning platform based on blockchain to solve the above two issues.In the proposed platform,the task of machine learning is performed according to smart contracts,and encrypted models are aggregated via a mechanism of knowledge distillation.Through this proposed method,a server node is no longer required and the learning ability is no longer limited to independent and identically distributed scenarios.Experiments on a public electrical grid dataset will verify the effectiveness of the proposed approach.展开更多
To construct pulsed high magnet, with rapid adjustments to large changes in the field strength, it is a mandatory acces-sory to development a special NMR probes to provide a precise real-time map of the magnetic field...To construct pulsed high magnet, with rapid adjustments to large changes in the field strength, it is a mandatory acces-sory to development a special NMR probes to provide a precise real-time map of the magnetic field. In order to do so, it is necessary to understand the variations of the spin transition and susceptibility of NMR samples in a time dependent longitudinal field. This work analyzes the effect on the spin transition by a time dependent longitudinal field. For a 1/2 spin system, we have derived a simple formula for the prediction of the probabilities of occupation of the 1/2 and ?1/2 states in a non-static field. We also calculate the magnetic susceptibility of the water and give an analysis of the effect on the magnetic susceptibility in a time dependent longitudinal field and RF frequency.展开更多
Rapid capacity decay and inferior kinetics are the vital issues of anodes in the conversion reaction for lithium-ion batteries.Vacancy engineering can efficiently modulate the intrinsic properties of transition-metal ...Rapid capacity decay and inferior kinetics are the vital issues of anodes in the conversion reaction for lithium-ion batteries.Vacancy engineering can efficiently modulate the intrinsic properties of transition-metal oxide(TMO)-based electrode materials,but the effect of oxygen vacancies on electrode performance remains unclear.Herein,abundant oxygen vacancies are in situ introduced into the lattice of different TMOs(e.g.,Co_(3)O_(4),Fe_(2)O_(3),and NiO)via a facile hydrothermal treatment combined with calcination.Taking Co_(3)O_(4)as a typical example,results prove that the oxygen vacancies in Co_(3)O_(4−x)effectively accelerate charge transfer at the interface and significantly increase electrical conductivity and pseudocapacitance contribution.The Li-ion diffusion coefficient of Co_(3)O_(4−x) is remarkably improved by two orders of magnitude compared with that of Co_(3)O_(4).Theoretical calculations reveal that Co_(3)O_(4−x)has a lower Li-insertion energy barrier and more density of states around the Fermi level than Co_(3)O_(4),which is favorable for ion and electron transport.Therefore,TMOs with rich vacancies exhibit superior cycling performance and enhanced rate capability over their counterparts.This strategy regulating the reaction kinetics would provide inspiration for designing other TMObased electrodes for energy applications.展开更多
Subretinal fibrosis is a major cause of the poor visual prognosis for patients with neovascular age-related macular degeneration(nAMD).Myofibroblasts originated from retinal pigment epithelial(RPE)cells through epithe...Subretinal fibrosis is a major cause of the poor visual prognosis for patients with neovascular age-related macular degeneration(nAMD).Myofibroblasts originated from retinal pigment epithelial(RPE)cells through epithelial-mesenchymal transition(EMT)contribute to the fibrosis formation.N^(6)-Methyladenosine(m^(6)A)modification has been implicated in the EMT process and multiple fibrotic diseases.The role of m^(6)A modification in EMT-related subretinal fibrosis has not yet been elucidated.In this study,we found that during subretinal fibrosis in the mouse model of laser-induced choroidal neovascularization,METTL3 was upregulated in RPE cells.Through m^(6)A epitranscriptomic microarray and further verification,high-mobility group AT-hook 2(HMGA2)was identified as thekey downstream target of METTL3,subsequently activating potent EMT-inducing transcription factor SNAIL.Finally,by subretinal injections of adeno-associated virus vectors,we confirmed that METTL3 deficiency in RPE cells could efficiently attenuate subretinal fibrosis in vivo.In conclusion,our present research identified an epigenetic mechanism of METTL3-m^(6)A-HMGA2 in subretinal fibrosis and EMT of RPE cells,providing a novel therapeutic target for subretinal fibrosis secondary to nAMD.展开更多
Although the development of covID-19 vaccines has been a remarkable success,the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict.In this study,blood samples were...Although the development of covID-19 vaccines has been a remarkable success,the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict.In this study,blood samples were collected from 163 participants who next received two doses of an inactivated COvVID-19 vaccine(CoronaVac)at a 28-day interval.Using TMT-based proteomics,we identified 1,715 serum and 7,342 peripheral blood mononuclear cells(PBMCs)proteins.We proposed two sets of potential biomarkers(seven from serum,five from PBMCs)at baseline using machine learning,and predicted the individual seropositivity 57 days after vaccination(AUC=0.87).Based on the four PBMC's potential biomarkers,we predicted the antibody persistence until 180 days after vaccination(AUC=0.79).Our data highlighted characteristic hematological host responses,including altered lymphocyte migration regulation,neutrophil degranulation,and humoral immune response.This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after coVID-19 vaccination,shedding light on immunization mechanisms and individual booster shot planning.展开更多
Hierarchical abstraction is a scalable strategy to deal with large networks.Existing visualization methods have allowed to aggregate the network nodes into hierarchies based on the node attributes or network topology,...Hierarchical abstraction is a scalable strategy to deal with large networks.Existing visualization methods have allowed to aggregate the network nodes into hierarchies based on the node attributes or network topology,each of which has its own advantage.Very few previous system has the capability to enjoy the best of both worlds.This paper presents OnionGraph,an integrated framework for the exploratory visual analysis of heterogeneous multivariate networks.OnionGraph allows nodes to be aggregated based on either node attributes,topology,or a hierarchical combination of both.These aggregations can be split,merged and filtered under the focus+context interaction model,or automatically traversed by the information-theoretic navigation method.Node aggregations that contain subsets of nodes are displayed by the onion metaphor,indicating the level and details of the abstraction.We have evaluated the OnionGraph tool in three real-world cases.Performance experiments demonstrate that on a commodity desktop,our method can scale to million-node networks while preserving the interactivity for analysis.展开更多
基金supported by the Double Support Project (035–2221993229)。
文摘Background Adequate level of carbohydrates in aquafeeds help to conserve protein and reduce cost. However, studies have indicated that high-carbohydrate(HC) diet disrupt the homeostasis of the gut–liver axis in largemouth bass, resulting in decreased intestinal acetate and butyrate level.Method Herein, we had concepted a set of feeding experiment to assess the effects of dietary sodium acetate(SA) and sodium butyrate(SB) on liver health and the intestinal microbiota in largemouth bass fed an HC diet. The experimental design comprised 5 isonitrogenous and isolipidic diets, including LC(9% starch), HC(18% starch), HCSA(18% starch;2 g/kg SA), HCSB(18% starch;2 g/kg SB), and HCSASB(18% starch;1 g/kg SA + 1 g/kg SB). Juvenile largemouth bass with an initial body weight of 7.00 ± 0.20 g were fed on these diets for 56 d.Results We found that dietary SA and SB reduced hepatic triglyceride accumulation by activating autophagy(ATG101, LC3B and TFEB), promoting lipolysis(CPT1α, HSL and AMPKα), and inhibiting adipogenesis(FAS, ACCA, SCD1 and PPARγ). In addition, SA and SB decreased oxidative stress in the liver(CAT, GPX1α and SOD1) by activating the Keap1-Nrf2 pathway. Meanwhile, SA and SB alleviated HC-induced inflammation by downregulating the expression of pro-inflammatory factors(IL-1β, COX2 and Hepcidin1) through the NF-κB pathway. Importantly, SA and SB increased the abundance of bacteria that produced acetic acid and butyrate(Clostridium_sensu_stricto_1). Combined with the KEGG analysis, the results showed that SA and SB enriched carbohydrate metabolism and amino acid metabolism pathways, thereby improving the utilization of carbohydrates. Pearson correlation analysis indicated that growth performance was closely related to hepatic lipid deposition, autophagy, antioxidant capacity, inflammation, and intestinal microbial composition.Conclusions In conclusion, dietary SA and SB can reduce hepatic lipid deposition;and alleviate oxidative stress and inflammation in largemouth bass fed on HC diet. These beneficial effects may be due to the altered composition of the gut microbiota caused by SA and SB. The improvement effects of SB were stronger than those associated with SA.
基金supported by the National Natural Science Foundation of China (31925037)to XHY。
文摘Background:The interaction between nutrition and immunity plays a vital role in nutrient digestion,absorption,and metabolism during poultry production.Recent studies showed that the gut microbiota contributes to the development of intestinal mucosal immunity.However,the mechanisms by which gut microbes regulate this process remain unclear.Methods:We compared the intestinal mucosal immunity and gut microbiota of Arbor Acre broilers AA(lower mucosal immunity)and Chinese native Wuliang Mountain Black-bone chickens(WLMB)(higher mucosal immunity)using 16S rDNA sequencing,transcriptomic analysis,and immunoglobulin A(IgA)antibody repertoire sequencing.We then combined 16S rDNA sequencing with transcriptomics to identify the key microbes and found that they were positively correlated with IgA production.Next,we transplanted candidate microbes into 1-day-old broiler to explore their role in intestinal mucosal immunity.Finally,we verified the function of candidate microbial metabolites in regulating the immune function of macrophages and the intestinal-epithelial cells(IECs)using in vitro experiments.Results:WLMB performs stronger mucosal immunity than AA,including higher IgA levels,more diverse IgA antibody repertoire,and higher bacterial affinity.Bacteroides was identified as the key microbes related to the intestinal IgA response.Bacteroides transplantation could increase IgA concentration in the duodenal contents by enhancing the expression of IgA,polymeric immunoglobin receptor(PIgR),B cell-activating factor of the TNF family(BAFF),and activation-induced cytidine deaminase(AID)in the duodenum.Additionally,Bacteroides-derived isovaleric acid promoted M2 macrophage polarization of macrophage via mTOR/PPAR-γ/STAT3 signaling pathways and regulated the immunologic function of IECs to produce cytokines,including interleukin(IL)-10,IL-4,BAFF,and transforming growth factor-beta(TGF-β),thus promoting IgA production in B cells by facilitating AID expression.Conclusion:Our study revealed that Bacteroides modulate the intestinal IgA response and maintain gut health in broilers.Bacteroides may be a promising alternative as an immunomodulatory microbial agent for developing nextgeneration probiotics for broiler production.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.52007173 and U19B2042)Zhejiang Provincial Natural Science Foundation of China(Grant No.LQ20E070002)Zhejiang Lab’s Talent Fund for Young Professionals(Grant No.2020KB0AA01).
文摘The digitization,informatization,and intelligentization of physical systems require strong support from big data analysis.However,due to restrictions on data security and privacy and concerns about the cost of big data collection,transmission,and storage,it is difficult to do data aggregation in real-world power systems,which directly retards the effective implementation of smart grid analytics.Federated learning,an advanced distributed learning method proposed by Google,seems a promising solution to the above issues.Nevertheless,it relies on a server node to complete model aggregation and the framework is limited to scenarios where data are independent and identically distributed.Thus,we here propose a serverless distributed learning platform based on blockchain to solve the above two issues.In the proposed platform,the task of machine learning is performed according to smart contracts,and encrypted models are aggregated via a mechanism of knowledge distillation.Through this proposed method,a server node is no longer required and the learning ability is no longer limited to independent and identically distributed scenarios.Experiments on a public electrical grid dataset will verify the effectiveness of the proposed approach.
文摘To construct pulsed high magnet, with rapid adjustments to large changes in the field strength, it is a mandatory acces-sory to development a special NMR probes to provide a precise real-time map of the magnetic field. In order to do so, it is necessary to understand the variations of the spin transition and susceptibility of NMR samples in a time dependent longitudinal field. This work analyzes the effect on the spin transition by a time dependent longitudinal field. For a 1/2 spin system, we have derived a simple formula for the prediction of the probabilities of occupation of the 1/2 and ?1/2 states in a non-static field. We also calculate the magnetic susceptibility of the water and give an analysis of the effect on the magnetic susceptibility in a time dependent longitudinal field and RF frequency.
基金supported by the National Natural Science Foundation of China(92163117 and 52072389)the Program of Shanghai Academic Research Leader(20XD1424300)。
文摘Rapid capacity decay and inferior kinetics are the vital issues of anodes in the conversion reaction for lithium-ion batteries.Vacancy engineering can efficiently modulate the intrinsic properties of transition-metal oxide(TMO)-based electrode materials,but the effect of oxygen vacancies on electrode performance remains unclear.Herein,abundant oxygen vacancies are in situ introduced into the lattice of different TMOs(e.g.,Co_(3)O_(4),Fe_(2)O_(3),and NiO)via a facile hydrothermal treatment combined with calcination.Taking Co_(3)O_(4)as a typical example,results prove that the oxygen vacancies in Co_(3)O_(4−x)effectively accelerate charge transfer at the interface and significantly increase electrical conductivity and pseudocapacitance contribution.The Li-ion diffusion coefficient of Co_(3)O_(4−x) is remarkably improved by two orders of magnitude compared with that of Co_(3)O_(4).Theoretical calculations reveal that Co_(3)O_(4−x)has a lower Li-insertion energy barrier and more density of states around the Fermi level than Co_(3)O_(4),which is favorable for ion and electron transport.Therefore,TMOs with rich vacancies exhibit superior cycling performance and enhanced rate capability over their counterparts.This strategy regulating the reaction kinetics would provide inspiration for designing other TMObased electrodes for energy applications.
基金supported by grants from the National Natural Science Foundation of China(81730026)National Key Technologies R&D Program(2017YFA0105301)Shanghai Hospital Development Center(SHDC2020CR2040B and SHDC2020CR5014).
文摘Subretinal fibrosis is a major cause of the poor visual prognosis for patients with neovascular age-related macular degeneration(nAMD).Myofibroblasts originated from retinal pigment epithelial(RPE)cells through epithelial-mesenchymal transition(EMT)contribute to the fibrosis formation.N^(6)-Methyladenosine(m^(6)A)modification has been implicated in the EMT process and multiple fibrotic diseases.The role of m^(6)A modification in EMT-related subretinal fibrosis has not yet been elucidated.In this study,we found that during subretinal fibrosis in the mouse model of laser-induced choroidal neovascularization,METTL3 was upregulated in RPE cells.Through m^(6)A epitranscriptomic microarray and further verification,high-mobility group AT-hook 2(HMGA2)was identified as thekey downstream target of METTL3,subsequently activating potent EMT-inducing transcription factor SNAIL.Finally,by subretinal injections of adeno-associated virus vectors,we confirmed that METTL3 deficiency in RPE cells could efficiently attenuate subretinal fibrosis in vivo.In conclusion,our present research identified an epigenetic mechanism of METTL3-m^(6)A-HMGA2 in subretinal fibrosis and EMT of RPE cells,providing a novel therapeutic target for subretinal fibrosis secondary to nAMD.
基金supported by the National Natural Science Foundation of China(32200763)Key medical disciplines of Hangzhou,the Medical Health Science and Technology Project of Hangzhou municipal Health Commission(A20210205)+1 种基金the National Key R&D Program of China(2020YFE0202200)Funding for Clinical Trials from the Affiliated Drum Tower Hospital,Medical School of Nanjing University(2022-LCYJ-MS-08).
文摘Although the development of covID-19 vaccines has been a remarkable success,the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict.In this study,blood samples were collected from 163 participants who next received two doses of an inactivated COvVID-19 vaccine(CoronaVac)at a 28-day interval.Using TMT-based proteomics,we identified 1,715 serum and 7,342 peripheral blood mononuclear cells(PBMCs)proteins.We proposed two sets of potential biomarkers(seven from serum,five from PBMCs)at baseline using machine learning,and predicted the individual seropositivity 57 days after vaccination(AUC=0.87).Based on the four PBMC's potential biomarkers,we predicted the antibody persistence until 180 days after vaccination(AUC=0.79).Our data highlighted characteristic hematological host responses,including altered lymphocyte migration regulation,neutrophil degranulation,and humoral immune response.This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after coVID-19 vaccination,shedding light on immunization mechanisms and individual booster shot planning.
文摘Hierarchical abstraction is a scalable strategy to deal with large networks.Existing visualization methods have allowed to aggregate the network nodes into hierarchies based on the node attributes or network topology,each of which has its own advantage.Very few previous system has the capability to enjoy the best of both worlds.This paper presents OnionGraph,an integrated framework for the exploratory visual analysis of heterogeneous multivariate networks.OnionGraph allows nodes to be aggregated based on either node attributes,topology,or a hierarchical combination of both.These aggregations can be split,merged and filtered under the focus+context interaction model,or automatically traversed by the information-theoretic navigation method.Node aggregations that contain subsets of nodes are displayed by the onion metaphor,indicating the level and details of the abstraction.We have evaluated the OnionGraph tool in three real-world cases.Performance experiments demonstrate that on a commodity desktop,our method can scale to million-node networks while preserving the interactivity for analysis.