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The potential of fungal probiotics as ruminant feed additives has not been extensively studied. This study aimed to evaluate the effect of A. oryzae and T. longibrachiatum supplementation on Angus cattle during the early stages of fattening. In this study, 80 Angus cattle aged approximately 9~10 months (40 males and 40 females), with an average initial body weight (BW) of 276.46 ± 27.92 kg, were randomly assigned to four groups. Each group included 4 replicates (2 replicates of males and 2 replicates of females). Each replicate contained 5 male or 5 female Angus cattle. Cattle in the control group received a total mixed ration (TMR) without additives, while those in test groups 1, 2, and 3 received a TMR supplemented with complex probiotics (CPs) at 1.0, 2.0, and 3.0 g·kg−1 of feed dry matter (DM), respectively. The adaptation and experimental periods were 7 and 60 days, respectively. Compared with those in the control group, the apparent digestibility of ether extract, calcium, and acid detergent fiber (ADF) was higher in test group 3. Test group 2 exhibited increased apparent digestibility of hemicellulose. Meanwhile, test group 3 exhibited increased levels of acetate, propionate, butyrate, and total volatile fatty acids and decreased pH. CPs increased the abundance of the SR1 phylum, Solibacillus, Lysinibacillus, and Planococcaceae_Bacillus and decreased the proportions of Lactococcus, Ruminococcus, and Ophryoscolex. Solibacillus was associated with the apparent digestibility of CP, Ca, and ADF. Planococcaceae_Bacillus was associated with increased apparent digestibility of CP, ADF, and hemicellulose. This suggests that CPs improve crude protein and cellulose digestion by increasing the proportions of Solibacillus and Planococcaceae_Bacillus. Therefore, the optimal CP dietary supplementation dose for Angus cattle was 3 g·kg−1 of DM.

This study aimed to evaluate the effects of modified corn straw dietary fiber (MCDF) on growth performance, nutrient metabolism, serum biochemistry, antioxidant capacity, intestinal morphology and hepatic lipid deposition in broilers. A total of 200 one-day-old Arbor Acres broilers were randomly allotted to four groups: the control group was fed basal diet, while three treatment groups supplemented with MCDF at 0.5%, 1%, and 1.5% of the basal diet, respectively. The results revealed that MCDF reduced ADG (p = 0.008) and increased feed/gain (p = 0.028) in the early stage, with no significant effects on ADG and feed/gain in the later or overall rearing periods (p > 0.05). In the early stage, 1% and 1.5% MCDF reduced ether extract metabolizability (p = 0.001), and 0.5–1.5% MCDF reduced phosphorus metabolizability (p < 0.001). Compared to the control group, 0.5–1.5% MCDF had no significant effects on nutrient metabolism in later stage and slaughter performance, but it reduced the 24 h pH of breast muscle and serum levels of LDL-C, HDL-C, TG, TC, and GLU (p < 0.05). The 1% MCDF decreased L* at 15 min and 24 h of leg muscle (p < 0.05). The 0.5% and 1% MCDF increased serum T-AOC levels and 1% MCDF increased CAT (p < 0.05), whereas 1.5% MCDF decreased SOD (p < 0.05). MCDF increased the villus height-to-crypt depth ratio by reducing crypt depth (p < 0.05) and improved the histomorphology of hepatocytes, accompanied by a reduction in the number of lipid droplets in the liver. Therefore, 0.5–1.5% MCDF can be recommended in broiler diets in the later stage, as it had no negative effects on growth performance, nutrient metabolism, and effectively reduced blood lipids and glucose levels, enhanced antioxidant capacity, and ameliorated hepatic vacuolar degeneration and lipid deposition.

Complex interactions in soil carbon and nitrogen (C-N) synchronisation in tropical perennial orchards are highly responsive to fertiliser chemistry. However, the intensity and stage-specific dynamics of these interactions are not well quantified. Six nitrogen regimes, namely, urea (URT), ammonium (AMT), nitrate (NT), slow-release fertiliser (SRT), bio-organic fertiliser (BFT), and an unfertilised control, were assessed at the vegetative, flowering, fruit-set, and maturity stages of durian cultivated on highly weathered tropical soils. A two-way ANOVA indicated high to very high treatment × phenology interactions for almost all soil properties (p < 0.001), indicating that nutrient responses were highly stage-dependent. The highest soil organic carbon (SOC) and cation exchange capacity (CEC) values were consistently obtained with the BFT, which was often associated with significant differences compared with synthetic treatments. In contrast, the SRT showed the most consistent nutrient release behaviour, especially in flowering. On the other hand, soil pH did not differ significantly among the treatments during the vegetative and maturity stages. A significant decrease in pH was observed for the URT and NT treatments during the flowering stage, indicating temporary acidification at this stage and steep increases in nitrate nitrogen (NO3—N), indicating strong nitrification and attenuated carbon (C) stabilisation. Leaf nutrient responses were increased in phosphorus (P), potassium (K), calcium (Ca), and magnesium (Mg) by 23% in response to the SRT and BFT. The NT and URT tended to enhance leaf nitrogen (N) primarily, and PCA (59–69% variance explained) clearly displayed clustering of the fertiliser effects, with the maximum difference at flowering, the peak period of nutrient demand in the crop. In general, fertiliser chemistry and phenophase jointly controlled the C-N partitioning, soil chemical paths, and nutrient yield correlations. The BFT and SRT showed the greatest significant gains in soil fertility and nutrient retention, making them the best high-performance alternatives in sustainable durian production in tropical systems.

It has been demonstrated that Chikusetsusaponin IVa (CsIVa) possesses abundant biological activities. Herein, using LPS to establish acute inflammation model of mouse liver and cell line inflammation model, we investigated whether miR-155/GSK-3β regulated NF-κB signaling pathway, and CsIVa exerted anti-inflammatory effects by regulating miR-155/GSK-3β signaling pathway. Our results showed that LPS induced high expression of miR-155 and miR-155 promoted macrophage activation through GSK-3β. In addition, CsIVa inhibited inflammatory responses in LPS-induced mouse liver and RAW264.7 cells. Furthermore, we demonstrated that CsIVa improved the inflammatory response in LPS-induced RAW264.7 cells by inhibiting miR-155, increasing GSK-3β expression, and inhibiting NF-κB signaling pathway. In conclusion, our study reveals that CsIVa suppresses LPS-triggered immune response by miR-155/GSK-3β-NF-κB signaling pathway.

Icariin (ICA) is the main active ingredient of Epimedium brevicornu Maxim (Berberidaceae), which is used in the immune, reproductive, neuroendocrine systems, and anti-aging. To evaluate the effect of ICA on natural aging rat. 16-month-old Sprague-Dawley (SD) rats were randomly divided into aging, low and high-dose ICA groups (n = 8); 6-month-old rats were taken as the adult control (n = 8). Rats were fed regular feed (aging and adult control) or feed containing ICA (ICA 2 and 6 mg/kg group) for 4 months. HE and Nissl staining were used to assess pathological changes. Western blot was used to test the expression of autophagy (LC3B, p62, Atg5, Beclin1) and p-AMPK, p-mTOR and p-ULK1 (ser 757). Immunofluorescence was used to detect the co-localization of LC3 and neurons. ICA improved neuronal degeneration associated with aging and increased the staining of Nissl bodies. Western blot showed that ICA up-regulated autophagy-related proteins LC3B (595%), Beclin1 (73.5%), p-AMPK (464%) protein (p < 0.05 vs. 20 M) in the cortex and hippocampus of aging rats, down-regulated the expression of p62 (56.9%), p-mTOR (53%) and p-ULK1 (ser 757) (65.4%) protein (p < 0.05 vs. 20 M). Immunofluorescence showed that the fluorescence intensity of LC3 decreased in the aging rat brain, but increased and mainly co-localized with neurons after ICA intervention. Further research needs to verify the expression changes of AMPK/mTOR/ULK1 and the improvement effect of ICA in elderly. These results will further accelerate the applications of ICA and the treatment for senescence.

Purpose: Ultrasound nanobubbles (NBs) can kill tumor cells, mediated by their effects of cavitation and acoustic perforation through ultrasound, while as novel drug carriers, biomaterial-modified NBs release drugs at a target region. In this work, the ultrasound NBs bridged by biotin-streptavidin were prepared simultaneously to be loaded with both programmed death ligand 1 monoclonal antibody (PD-L1 mAb) and doxorubicin (DOX), which are immune checkpoint inhibitors (ICIs) and chemotherapeutic agents, to synergize immunotherapy and chemotherapy combined with sonodynamic therapy (SDT). Methods: The PD-L1 mAb/DOX NBs, using bridging affinity biotin (BRAB) technology as a bridge, were prepared by thinfilm hydration and mechanical oscillation for the targeted delivery of biotinylated PD-L1 mAb and DOX. Characterization and pharmacokinetic studies of PD-L1 mAb/DOX NBs were performed in vitro and in vivo. The antitumor effect of ultrasound-mediated PD-L1 mAb/DOX-NBs was studied in the subcutaneously transplanted tumor of the H22 hepatoma model, and the mechanism of synergistic tumor repression was investigated. Results: The data of in vitro targeting experiments, contrast-enhanced ultrasound imaging (CEUS), in vivo imaging of the small animals imaging system (IVIS), and frozen sections showed that PD-L1 mAb/DOX-NBs have well-targeted aggregation in the tumor. By observing tumor inhibition rate, tissue cell apoptosis, and apoptosis-related gene and protein expression, the PD-L1 mAb/DOXNBs group showed the best immunotherapy effects, and its tumor volume and mass inhibition rates were about 69.64% and 75.97%, respectively (P < 0.01). Therefore, blocking the PD-1/PD-L1 pathway could improve immune cells' tumor-killing ability. Antitumor immune cytokines were further enhanced when combined with DOX-induced tumor cell apoptosis and immunogenic cell death (ICD). Conclusion: In summary, ultrasound-mediated PD-L1 mAb/DOX-NBs showed significant synergistic antitumor effects, providing a potential combined immunotherapy strategy for HCC. Keywords: ultrasound targeted nanobubble destruction, tumor immune therapy, immune checkpoint inhibitors, immunogenic cell death, drug delivery

To solve the problem of multimissile coordinated interception of maneuvering targets, an adaptive super‐twisting cooperative guidance law (ASTCGL) was proposed. First, a super‐twisting control algorithm and algebraic graph theory were combined to design a robust cooperative guidance law. Secondly, the RBF neural network is used to estimate the maneuvering ability of the target, and the buffeting control system is designed to adjust the gain function on line. Finally, the stability of the whole guidance and control system is proved based on Lyapunov′s direct method, and the numerical simulation of four missiles′ cooperative intercepting maneuvering targets is carried out. The simulation results show the effectiveness and superiority of the proposed cooperative guidance law.

Immune checkpoint inhibitors (ICIs) and sonodynamic therapy (SDT) are types of immunotherapy. In order to combine soluble programmed cell death protein 1 (sPD-1)-mediated immune checkpoint therapy and chlorin e6 (Ce6)-assisted SDT, nanobubbles (NBs) were generated to simultaneously load sPD-1 and Ce6. The sPD-1/Ce6-NBs, which were prepared by thin-film hydration and mechanical oscillation, had a stable physical condition, and delivered sPD-1 and Ce6 in a targeted manner. NBs could strengthen tumor suppression by increasing tumor-targeting accumulation of Ce6 and sPD-1, and by inducing ultrasound-targeted NB destruction. A mouse H22 cell hepatoma xenograft model was used to evaluate the synergetic immunotherapeutic effect and mechanism of sPD-1/Ce6-NBs. By observing the tumor inhibition rate, tissue and cell apoptosis, apoptosis-related genes and protein expression, the best immunotherapeutic effect was exhibited by the sPD-1/Ce6-NBs group. The immunotherapeutic mechanism initially demonstrated that when tumor cells were transfected by sPD-1 delivered by NBs, which downregulated the expression of programmed death-ligand 1 (PD-L1) in tumor cells, and blocked the PD-1/PD-L1 signaling pathway, which improved T-cell-mediated tumor inhibition. Furthermore, ICIs combined with SDT induced immunogenic cell death by translocating calreticulin to the cell surface and then synergistically enhancing antitumor immune responses. In conclusion, sPD-1/Ce6-NBs were successfully designed. Ultrasound-mediated sPD-1/Ce6-NBs are potentially effective delivery systems for combination immunotherapy of hepatocellular carcinoma.

Liver diseases, particularly chronic conditions leading to cirrhosis and hepatocellular carcinoma, represent a major global health burden with high mortality rates, necessitating innovative diagnostic and therapeutic approaches. Ultrasound-targeted microbubble destruction (UTMD) technology has emerged as a promising theranostic platform, combining enhanced contrast imaging with targeted drug/gene delivery capabilities. When activated by ultrasound, these microbubbles exhibit unique biophysical behaviors that significantly improve drug penetration, tissue perfusion, and site-specific delivery. This review comprehensively examines recent advancements in UTMD-based strategies for liver disease management, including microbubble design and imaging-targeted functionalization, and mechanisms of ultrasound-enhanced drug delivery, especially emerging theranostic applications. We further discuss the underlying biophysical principles governing microbubble-ultrasound interactions and their translational potential, providing insights for developing next-generation precision medicine approaches for hepatic disorders.

In order to alleviate the toxic effects of aflatoxins B1 (AFB1) on inflammatory responses in the intestine, liver, and kidney of broilers, the aflatoxin B1-degrading enzyme, montmorillonite, and compound probiotics were selected and combined to make a triple-action compound mycotoxin detoxifier (CMD). The feeding experiment was divided into two stages. In the early feeding stage (1–21 day), a total of 200 one-day-old Ross broilers were randomly divided into four groups; in the later feeding stage (22–42 day), 160 broilers aged at 22 days were assigned to four groups: Group A: basal diet (4.31 μg/kg AFB1); Group B: basal diet with 40 μg/kg AFB1; Group C: Group A plus 1.5 g/kg CMD; Group D: Group B plus 1.5 g/kg CMD. After the feeding experiment, the intestine, liver, and kidney tissues of the broilers were selected to investigate the molecular mechanism for CMD to alleviate the tissue damages. Analyses of mRNA abundances and western blotting (WB) of inflammatory factors, as well as immunohistochemical (IHC) staining of intestine, liver, and kidney tissues showed that AFB1 aggravated the inflammatory responses through NF-κB and TN-α signaling pathways via TLR pattern receptors, while the addition of CMD significantly inhibited the inflammatory responses. Phylogenetic investigation showed that AFB1 significantly increased interleukin-1 receptor-associated kinase (IRAK-1) and mitogen-activated protein kinase (MAPK) activities (p < 0.05), which were restored to normal levels by CMD addition, indicating that CMD could alleviate cell inflammatory damages induced by AFB1.