Background Baicalin and probiotic cocktails are promising feed additives with broad application prospects.While probiotic cocktails are known to enhance intestinal health,the potential synergistic impact of combining ...Background Baicalin and probiotic cocktails are promising feed additives with broad application prospects.While probiotic cocktails are known to enhance intestinal health,the potential synergistic impact of combining baicalin with probiotic cocktails on the gut health of broiler chickens remains largely unexplored.Therefore,this study aims to investigate the influence of the combined administration of baicalin and probiotic cocktails on the composition of ileal and cecal microbiota in broiler chickens to elucidate the underlying mechanisms responsible for the healthpromoting effects.Results A total of 3201-day-old male Arbor Acres broilers were divided into 4 groups,each with 8 replicates of 10 chicks per replicate.Over a period of 42 d,the birds were fed a basal diet or the same diet supplemented with 37.5 g/t baicalin(BC),1,000 g/t probiotic cocktails(PC),or a combination of both BC(37.5 g/t)and PC(1,000 g/t).The results demonstrated that BC+PC exhibited positive synergistic effects,enhancing intestinal morphology,immune function,and barrier function.This was evidenced by increased VH/CD ratio,sIgA levels,and upregulated expression of occludin and claudin-1(P<0.05).16S rRNA analysis indicated that PC potentiated the effects of BC,particularly in the ileum,where BC+PC significantly increased theα-diversity of the ileal microbiota,altered itsβ-diversity,and increased the relative abundance of Flavonifractor(P<0.05),a flavonoid-metabolizing bacterium.Furthermore,Flavonifractor positively correlated with chicken ileum crypt depth(P<0.05).While BC+PC had a limited effect on cecal microbiota structure,the PC group had a very similar microbial composition to BC+PC,suggesting that the effect of PC at the distal end of the gut overshadowed those of BC.Conclusions We demonstrated the synergistic enhancement of gut health regulation in broiler chickens by combining baicalin and probiotic cocktails.Probiotic cocktails enhanced the effects of baicalin and accelerated its metabolism in the ileum,thereby influencing the ileal microbiota structure.This study elucidates the interaction mechanism between probiotic cocktails and plant extract additives within the host microbiota.These findings provide compelling evidence for the future development of feed additive combinations.展开更多
Lung cancer is one of the most common malignant tumors with the fastest increase in the incidence rate and mortality.Even after maximum tumor resection assistance with a radiotherapy and chemotherapy combination,the r...Lung cancer is one of the most common malignant tumors with the fastest increase in the incidence rate and mortality.Even after maximum tumor resection assistance with a radiotherapy and chemotherapy combination,the recurrence of non-small cell lung cancer is still inevitable.In addition,low targeting efficiency and poor permeability of drug delivery systems strongly affect the therapeutic efficiency of anti-cancer drugs on non-small cell lung cancer.Here we designed a gemcitabine(GEM)loaded arginineglycine-aspartic acid-cysteine(RGDc)-modified gold mineralization“hybrid nanozyme bomb”(RGTG)to overcome those obstacles.RGDc modification improved the active targeting of liposomes to the tumor tissues with the second near-infrared(NIR-Ⅱ)-triggered gold-shell disruption and GEM release.The collapsed gold-shell particles with a smaller size could penetrate the tumor solid barrier and act as photothermal therapy(PTT)agents to improve PTT therapy and starvation therapy via generating gluconic acid and reactive oxygen species(ROS).Moreover,the resting reversal effect of gold particles on tumor fibroblasts can achieve accelerating tumor penetration of gold particles and GEM.Compared to monotherapy,RGTG showed significant improvement in tumor inhibition,with a tumor volume reduction of 83%compared to the control group,which provides a promising tumor treatment platform for non-small cell lung cancer(NSCLC).展开更多
Second near-infrared(NIR-Ⅱ)light triggered in-situ tumor vaccination(ISTV)represents one of the most promising strategies in boosting the whole-body antitumor immunity.While most of previously developed nano-adjuvant...Second near-infrared(NIR-Ⅱ)light triggered in-situ tumor vaccination(ISTV)represents one of the most promising strategies in boosting the whole-body antitumor immunity.While most of previously developed nano-adjuvants for NIR-Ⅱ-triggered ISTV are“all-in-one”formulations,which may indiscriminately damage both the tumor cells and the immune cells,limiting the overall effect of immune response.To overcome this obstacle,we designed a“cocktail”nano-adjuvant by physically mixing hyaluronidases(HAase)-decorated gold nanostars(HA)for NIR-Ⅱlight triggered in situ production of tumor-associated antigens and CpG functionalized gold nanospheres(CA)for immune cells activation.Compared to“all-in-one”formulation,the“cocktail”nano-adjuvants displayed a significantly stronger immune response on NIR-Ⅱlight induced dendritic cells(DCs)mutation and T cells differentiation,greater effect on tumor-growth inhibition,and higher efficacy in inhibition of pulmonary metastases.What is more,increasing the molar ratio of HA to CA led to an enhanced anticancer immune responses.This study highlight the nano-adjuvant formulation effects on the treatment of tumors with multiple targets.展开更多
There is increasing evidence shows that either electrical stimulation(ES)or metal ion is an effective way to accelerate ulcerative wound healing.However,less attention is paid to investigating the synergistic effect b...There is increasing evidence shows that either electrical stimulation(ES)or metal ion is an effective way to accelerate ulcerative wound healing.However,less attention is paid to investigating the synergistic effect between them.Herein,we explore the combined effects of ES and multiple metal ions on dia-betic wound healing assisted by a triboelectric nanogenerator(TENG).Firstly,the novel Eggshell@CuFe_(2)O_(4)nanocomposites(NCs)are prepared,which show unique structure and intrinsic antimicrobial properties.Subsequently,the as-prepared nanocomposites are embedded in oxidized starch hydrogel to form a mul-tifunctional composite gel,which is further assembled into a wearable ionic triboelectric nanogenerator(iTENG)patch with polydimethylsiloxane(PDMS).It can convert the mechanical energy produced by a human body motion to electric energy and mediate the sequential release of metal ions(Fe^(2+)/Ca^(2+)/Cu^(2+)),thereby resulting in the“cocktail effect”on impaired tissue.Under their effects,a satisfying healing re-sult in diabetic mouse is identified,which can effectively accelerate wound healing process by relieving inflammation,promoting angiogenesis and collagen deposition.The work puts forward the cocktail effect of electric simulation coupled with the multiple metal ions,and opens up a new perspective in designing iTENG patch towards repair of hard-to-heal wounds.展开更多
基金funded by National Key R&D Program of China(2022YFD1300403,2021YFD1300404)China Agriculture Research System program(CARS-40,CARS-41-G11)Beijing Natural Science Foundation(6222036).
文摘Background Baicalin and probiotic cocktails are promising feed additives with broad application prospects.While probiotic cocktails are known to enhance intestinal health,the potential synergistic impact of combining baicalin with probiotic cocktails on the gut health of broiler chickens remains largely unexplored.Therefore,this study aims to investigate the influence of the combined administration of baicalin and probiotic cocktails on the composition of ileal and cecal microbiota in broiler chickens to elucidate the underlying mechanisms responsible for the healthpromoting effects.Results A total of 3201-day-old male Arbor Acres broilers were divided into 4 groups,each with 8 replicates of 10 chicks per replicate.Over a period of 42 d,the birds were fed a basal diet or the same diet supplemented with 37.5 g/t baicalin(BC),1,000 g/t probiotic cocktails(PC),or a combination of both BC(37.5 g/t)and PC(1,000 g/t).The results demonstrated that BC+PC exhibited positive synergistic effects,enhancing intestinal morphology,immune function,and barrier function.This was evidenced by increased VH/CD ratio,sIgA levels,and upregulated expression of occludin and claudin-1(P<0.05).16S rRNA analysis indicated that PC potentiated the effects of BC,particularly in the ileum,where BC+PC significantly increased theα-diversity of the ileal microbiota,altered itsβ-diversity,and increased the relative abundance of Flavonifractor(P<0.05),a flavonoid-metabolizing bacterium.Furthermore,Flavonifractor positively correlated with chicken ileum crypt depth(P<0.05).While BC+PC had a limited effect on cecal microbiota structure,the PC group had a very similar microbial composition to BC+PC,suggesting that the effect of PC at the distal end of the gut overshadowed those of BC.Conclusions We demonstrated the synergistic enhancement of gut health regulation in broiler chickens by combining baicalin and probiotic cocktails.Probiotic cocktails enhanced the effects of baicalin and accelerated its metabolism in the ileum,thereby influencing the ileal microbiota structure.This study elucidates the interaction mechanism between probiotic cocktails and plant extract additives within the host microbiota.These findings provide compelling evidence for the future development of feed additive combinations.
基金supported by the National Natural Science Foundation of China(No.81972892)。
文摘Lung cancer is one of the most common malignant tumors with the fastest increase in the incidence rate and mortality.Even after maximum tumor resection assistance with a radiotherapy and chemotherapy combination,the recurrence of non-small cell lung cancer is still inevitable.In addition,low targeting efficiency and poor permeability of drug delivery systems strongly affect the therapeutic efficiency of anti-cancer drugs on non-small cell lung cancer.Here we designed a gemcitabine(GEM)loaded arginineglycine-aspartic acid-cysteine(RGDc)-modified gold mineralization“hybrid nanozyme bomb”(RGTG)to overcome those obstacles.RGDc modification improved the active targeting of liposomes to the tumor tissues with the second near-infrared(NIR-Ⅱ)-triggered gold-shell disruption and GEM release.The collapsed gold-shell particles with a smaller size could penetrate the tumor solid barrier and act as photothermal therapy(PTT)agents to improve PTT therapy and starvation therapy via generating gluconic acid and reactive oxygen species(ROS).Moreover,the resting reversal effect of gold particles on tumor fibroblasts can achieve accelerating tumor penetration of gold particles and GEM.Compared to monotherapy,RGTG showed significant improvement in tumor inhibition,with a tumor volume reduction of 83%compared to the control group,which provides a promising tumor treatment platform for non-small cell lung cancer(NSCLC).
基金financially supported by the National Natural Science Foundation of China(No.52273163)the Science Technology and Innovation Commission of Shenzhen Municipality(No.JCYJ20190807163003704)Open Research Fund of Jiangsu Key Laboratory of Environmentally Friendly Polymeric Materials(No.PML2201)。
文摘Second near-infrared(NIR-Ⅱ)light triggered in-situ tumor vaccination(ISTV)represents one of the most promising strategies in boosting the whole-body antitumor immunity.While most of previously developed nano-adjuvants for NIR-Ⅱ-triggered ISTV are“all-in-one”formulations,which may indiscriminately damage both the tumor cells and the immune cells,limiting the overall effect of immune response.To overcome this obstacle,we designed a“cocktail”nano-adjuvant by physically mixing hyaluronidases(HAase)-decorated gold nanostars(HA)for NIR-Ⅱlight triggered in situ production of tumor-associated antigens and CpG functionalized gold nanospheres(CA)for immune cells activation.Compared to“all-in-one”formulation,the“cocktail”nano-adjuvants displayed a significantly stronger immune response on NIR-Ⅱlight induced dendritic cells(DCs)mutation and T cells differentiation,greater effect on tumor-growth inhibition,and higher efficacy in inhibition of pulmonary metastases.What is more,increasing the molar ratio of HA to CA led to an enhanced anticancer immune responses.This study highlight the nano-adjuvant formulation effects on the treatment of tumors with multiple targets.
基金supported financially by the Natural Science Foundation of Shanxi Province Grants(No.202203021211157)Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering(No.2023SX-FR006)The Science and Technology Major Special Plan Project“Reveal the Tile”of Quanzhou Province(No.2022NZ1).
文摘There is increasing evidence shows that either electrical stimulation(ES)or metal ion is an effective way to accelerate ulcerative wound healing.However,less attention is paid to investigating the synergistic effect between them.Herein,we explore the combined effects of ES and multiple metal ions on dia-betic wound healing assisted by a triboelectric nanogenerator(TENG).Firstly,the novel Eggshell@CuFe_(2)O_(4)nanocomposites(NCs)are prepared,which show unique structure and intrinsic antimicrobial properties.Subsequently,the as-prepared nanocomposites are embedded in oxidized starch hydrogel to form a mul-tifunctional composite gel,which is further assembled into a wearable ionic triboelectric nanogenerator(iTENG)patch with polydimethylsiloxane(PDMS).It can convert the mechanical energy produced by a human body motion to electric energy and mediate the sequential release of metal ions(Fe^(2+)/Ca^(2+)/Cu^(2+)),thereby resulting in the“cocktail effect”on impaired tissue.Under their effects,a satisfying healing re-sult in diabetic mouse is identified,which can effectively accelerate wound healing process by relieving inflammation,promoting angiogenesis and collagen deposition.The work puts forward the cocktail effect of electric simulation coupled with the multiple metal ions,and opens up a new perspective in designing iTENG patch towards repair of hard-to-heal wounds.
