Bimetallic clusterzymes-loaded dendritic mesoporous silica particle regulate arthritis microenvironment via ROS scavenging and YAP1 stabilization

Clusterzymes are synthetic enzymes exhibiting substantial catalytic activity and selectivity,which are uniquely driven by single-atom constructs.A dramatic increase in antioxidant capacity,158 times more than natural trolox,is noted when single-atom copper is incorporated into gold-based clusterzymes to form Au_(24)Cu_(1).Considering the inflammatory and mildly acidic microenvironment characteristic of osteoarthritis(OA),pH-dependent dendritic mesoporous silica nanoparticles(DMSNs)coupled with PEG have been employed as a delivery system for the spatial-temporal release of clusterzymes within active articular regions,thereby enhancing the duration of effectiveness.Nonetheless,achieving high therapeutic efficacy remains a significant challenge.Herein,we describe the construction of a Clusterzymes-DMSNs-PEG complex(CDP)which remarkably diminishes reactive oxygen species(ROS)and stabilizes the chondroprotective protein YAP by inhibiting the Hippo pathway.In the rabbit ACLT(anterior cruciate ligament transection)model,the CDP complex demonstrated inhibition of matrix metalloproteinase activity,preservation of type Ⅱ collagen and aggregation protein secretion,thus prolonging the clusterzymes’protective influence on joint cartilage structure.Our research underscores the efficacy of the CDP complex in ROS-scavenging,enabled by the release of clusterzymes in response to an inflammatory and slightly acidic environment,leading to the obstruction of the Hippo pathway and downstream NF-κB signaling pathway.This study illuminates the design,composition,and use of DMSNs and clusterzymes in biomedicine,thus charting a promising course for the development of novel therapeutic strategies in alleviating OA.

Injectable self-healing hydrogel with siRNA delivery property for sustained STING silencing and enhanced therapy of intervertebral disc degeneration

Inflammatory responses of nucleus pulposus(NP)can induce imbalanced anabolism and catabolism of extracellular matrix,and the cytosolic dsDNA accumulation and STING-NF-κB pathway activation found in NP inflammation are considered as fairly important cause of intervertebral disc(IVD)degeneration.Herein,we constructed a siSTING delivery hydrogel of aldehyde hyaluronic acid(HA-CHO)and poly(amidoamine)PAMAM/siRNA complex to intervene the abnormal STING signal for IVD degeneration treatment,where the formation of dynamic Schiff base bonds in the system(siSTING@HPgel)was able to overcome the shortcomings such as low cellular uptake,short half-life,and rapid degradation of siRNA-based strategy.PAMAM not only formed complexes with siRNA to promote siRNA transfection,but also served as dynamic crosslinker to construct hydrogel,and the injectable and self-healing hydrogel efficiently and steadily silenced STING expression in NP cells.Finally,the siSTING@HPgel significantly eased IVD inflammation and slowed IVD degeneration by prolonging STING knockdown in puncture-induced IVD degeneration rat model,revealing that STING pathway was a therapeutic target for IVD degeneration and such novel hydrogel had great potential for being applied to many other diseases for gene delivery.

Effects of phytonutrients on growth performance, antioxidative status,and energy utilization of broilers fed low energy diets

Two experiments were conducted to investigate the effects of phytonutrients(PN)on growth performance.antioxidant status,intestinal morphology,and nutrient utilization of birds fed low energy diets.In Exp.1.a total of 1.440 one-day-old Ross 308 male broiler chickens were randomly divided into 3 treatment groups,with 16 replicates per treatment(48 pens;30 birds per pen).Birds in treatment 1 were fed diets with normal energy content(NE).Birds in treatment 2 were fed NE diet but with 60 kcal removed(LE).Birds in treatment 3 were assigned to LE diet supplemented with PN(LE + PN).Results indicated that LE diet increased feed conversion ratio(FCR)compared with NE from d 1 to 38.while LE + PN diet prevented this response(P= 0.02).At d 26.birds in the LE + PN group had the highest ileal and jejunal villus height to crypt depth(VH:CD)ratio.At d 39.PN supplementation improved ileal and jejunal VH:CD ratio,compared with LE group.Moreover,birds fed PN diets received a better economic profit,In Exp.2,360 one-day-old Ross 308 male broiler chickens were used in a metabolism study.The treatments used in Exp.2 were the same as those in Exp.1,with 4 replicates(pens)and 30 birds in each replicate.Dietary apparent metabolism energy(AME),energy and protein digestibility were determined between 21 and 28 d of age.Results showed that chickens fed LE + PN diet tended to have greater AME(P= 0.02)and nictrogen-corrected apparent metabolism energy(AMEn)(P= 0.03)than birds fed LE diets.It was concluded that LE+ PN showed a potential advantage to improve feed conversion and gut health of broilers,as well as economic profits.

Hierarchical porous hollow graphitized carbon@MoS_(2)with wideband EM dissipation capability

Core-shell materials are promising broadband electromagnetic(EM)absorption materials since the highly component manipulation performance,interfacial effect etc.Herein,a well-defined core-shell shaped structure constructed by 2-dimensional Mo S_(2)nanosheets-coated porous hollow carbon has been successfully designed with controlled pore-sizes of the core,adjustable shell content,and structure.By effectively optimizing the parameters for these factors,the as-prepared hierarchical porous hollow C@Mo S_(2)sample enables an ultra-width EM absorption ability(covering 11.4-18.0 GHz)at a thickness of only 2.0 mm.The detailed contributions of each component and structure on the excellent EM absorption capability have been investigated.These encouraging results indicate that the development of core-shell composites with multiple controllable physical factors is of great significance for the future ultra-wideband electromagnetic absorbers.