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T cell engagers (TCEs) are a class of T cell–redirecting therapeutics that enhance antitumor immunity by bringing T cells into close proximity with malignant cells. Following their success in hematologic malignancies, TCEs are now being increasingly investigated for the treatment of solid tumors. The recent approval of tarlatamab for small cell lung cancer (SCLC) offers renewed hope in this setting. Nevertheless, clinical efficacy in solid tumors remains limited by immunosuppressive tumor microenvironments (TME), on-target/off-tumor toxicity, and intrinsic or acquired resistance to TCEs. This review summarizes recent advances in TCE development for solid tumors, including refinements in molecular design, biomarker-guided patient selection, and rational combination strategies aimed at overcoming resistance and improving therapeutic outcomes. We also discuss emerging next-generation approaches, such as engager platforms that redirect other immune effector cells. Collectively, these innovations underscore the potential of more precise and effective engager-based therapies for solid tumors.

Heat stress is a major abiotic stress that limits growth performance, health, and physiological responses of sheep. Although Hu sheep possess innate mechanisms for managing heat stress, prolonged exposure impairs their performance and health. Rumen microbiota served as key players in responding to environmental fluctuations and mediating major regulatory functions. This study was conducted to explore the effects of different proportions of concentrate replaced with fermented mulberry leaves (FML) on rumen fermentation and bacterial and fungal community structures in rumen fluid in Hu sheep. A total of 45 Hu sheep with similar body weight (26.42 ± 3.57 kg) were randomly divided into three groups: the control group (CONT) was fed a basal diet, and the treatment groups (FML Treatment) FT1 and FT2 were fed experimental diets in which 10% and 20% concentrate, respectively, were replaced by FML. The pretest lasted for 7 days, and the formal period lasted for 90 days. The average daily gain in the FT1 group increased at the first month of the formal period compared to the CONT group ( P  < 0.05). Lower feed conversion ratio, feed weight gain cost ( P  < 0.05), and higher apparent digestibility of acid detergent fiber and crude protein ( P  < 0.05) were observed in the FT1 group. Moreover, the concentrations of acetate, propionate, valerate, and ammonia nitrogen in the FT1 group were significantly higher than those in the CONT group ( P  < 0.05). Further analysis of the rumen microbiota indicated that the relative abundance of Succiniaclassicum and Eubacterium_ventriosum_group decreased, whereas that of Prevotellaceae_UCG_003 and unclassified_Selenomonadaceae increased in the FT1 group. Internal transcribed spacer sequencing indicated that FML significantly increased the relative abundance of beneficial fungi in the rumen of heat-stressed Hu sheep, including Aspergillus_alabamensis , Aspergillus_versicolor , Aspergillus_flavus , and Candida in the FT1 group. Correlation analysis suggested that the apparent digestibility of nutrients in fattening Hu sheep under heat stress was highly correlated with bacteria. Our findings indicate that the replacement of concentrate with FML can improve production performance, increase the apparent digestibility of nutrients, and enhance the rumen fermentation efficiency of fattening Hu sheep under heat stress. These changes are highly correlated with the changes in the composition and structure of bacteria and fungi in the rumen fluid. Key points 10% FML Treatment enhanced feed conversion ratio and nutrient digestibility. 10% FML Treatment enhanced the rumen fermentation efficiency. 10% FML Treatment altered bacterial and fungal structures in rumen fluid.

We present a precise measurement of the asymptotic normalization coefficient (ANC) for the 16O ground state (GS) through the 12C(11B, 7Li)16O transfer reaction using the Quadrupole‐3‐Dipole (Q3D) magnetic spectrograph. The present work sheds light on the existing discrepancy of more than 2 orders of magnitude between the previously reported GS ANC values. This ANC is believed to have a strong effect on the 12C(α, γ)16O reaction rate by constraining the external capture to the 16O ground state, which can interfere with the high-energy tail of the 2+ subthreshold state. Based on the new ANC, we determine the astrophysical S-factor and the stellar rate of the 12C(α, γ)16O reaction. An increase of up to 21% in the total reaction rate is found within the temperature range of astrophysical relevance compared with the previous recommendation of a recent review. Finally, we evaluate the impact of our new rate on the pair-instability mass gap for black holes (BH) by evolving massive helium core stars using the MESA stellar evolution code. The updated 12C(α, γ)16O reaction rate decreases the lower and upper edges of the BH gap about 12% and 5%, respectively.

This study evaluated the protective effects of magnolol, rutin, and gallic acid in broilers fed oxidized soybean oil. Four hundred seven-day-old male Arbor Acre broilers were randomly assigned to five treatments with eight replicates each: CON (4% fresh oil), OOC (4% oxidized oil), and OOC supplemented with 200 mg/kg of magnolol (MAG), rutin (RUT), or gallic acid (GAA). OOC significantly reduced 42-day body weight (BW), average daily gain (ADG), and average daily feed intake (ADFI), reduced serum antioxidant enzyme activities (T-SOD, GSH-Px) and elevated malondialdehyde and triglyceride levels. It also upregulated hepatic lipogenic (FASN, ACACA, SREBP-1) and inflammation (NF-κB1/2) genes, damaged intestinal morphology, reduced cecal Erysipelatoclostridium and Shuttleworthia abundances, and elevated oxidized lipids (9,10-DiHOME and prostaglandin G2) in breast muscle. All three polyphenols increased ADFI (22–42 d), ileal villus height and ZO-1 expression, while reducing serum triglycerides, ileal MDA, and hepatic NF-κB2 expression. Both magnolol and rutin further enhanced BW (42 d) and ADG (7–42 d), decreased ACACA expression, and elevated cecal Lachnoclostridium abundance. Additionally, magnolol significantly decreased the contents of 9,10-DiHOME and malondialdehyde, while rutin reduced prostaglandin G2 levels in the breast muscle. In conclusion, polyphenol supplementation alleviated oxidized oil-induced adverse effects, with magnolol and rutin being more effective.

Background Salmonella pullorum is one of the most harmful pathogens to avian species. Magnolol and honokiol, natural compounds extracted from Magnolia officinalis , exerts anti-inflammatory, anti-oxidant and antibacterial activities. This study was conducted to evaluate the effects of dietary supplemental magnolol and honokiol in broilers infected with S. pullorum . A total of 360 one-day-old broilers were selected and randomly divided into four groups with six replicates: the negative control group (CTL), S. pullorum -infected group (SP), and the S. pullorum -infected group supplemented with 300 mg/kg honokiol (SPH) or magnolol (SPM). Results The results showed that challenging with S. pullorum impaired growth performance in broilers, as indicated by the observed decreases in body weight ( P  < 0.05) and average daily gains ( P  < 0.05), along with increased spleen ( P  < 0.01) and bursa of Fabricus weights ( P  < 0.05), serum globulin contents, and the decreased intestine villus height and villus/crypt ratios ( P  < 0.05). Notably, supplemental magnolol and honokiol attenuated these adverse changes, and the effects of magnolol were better than those of honokiol. Therefore, we performed RNA-Seq in ileum tissues and 16S rRNA gene sequencing of ileum bacteria. Our analysis revealed that magnolol increased the α-diversity (observed species, Chao1, ACE, and PD whole tree) and β-diversity of the ileum bacteria ( P  < 0.05). In addition, magnolol supplementation increased the abundance of Lactobacillus ( P  < 0.01) and decreased unidentified Cyanobacteria ( P  < 0.05) both at d 14 and d 21. Further study confirmed that differentially expressed genes induced by magnolol and honokiol supplementation enriched in cytokine-cytokine receptor interactions, in the intestinal immune network for IgA production, and in the cell adhesion molecule pathways. Conclusions Supplemental magnolol and honokiol alleviated S. pullorum- induced impairments in growth performance, and the effect of magnolol was better than that of honokiol, which could be partially due to magnolol’s ability to improve the intestinal microbial and mucosal barrier.

Present and future rare isotope accelerator facilities provide new opportunities to explore the structure of unstable nuclei. We report the measurements of the elastic scattering angular distributions of 21Na and 22Na on the doubly magic 40Ca above the Coulomb barrier energies, using high-purity post-accelerated ISOL beams from Beijing Radioactive Ion Beam Facility (BRIF). Angular distributions were measured with a silicon detector telescope array, and relative cross sections were determined with a CaF2 target on Au backing. The data were well reproduced by optical model calculations with Woods–Saxon and USNP potentials, the latter giving better agreement. These results confirm the stable operation and performance of the BRIF ISOL production and post-acceleration system, demonstrate its capability to provide radioactive beams of useful intensity and purity for future investigations of reaction dynamics and astrophysically relevant processes involving proton-rich nuclei, and simultaneously extend proton-rich elastic scattering studies to heavier systems.

This study aimed to investigate the role of chitosan oligosaccharide (COS) as an additive in the feed of laying hens with fatty liver syndrome (FLS). Effects on production performance, egg quality as well as ovarian function were determined. A total of 360 Lohmann Pink-shell laying hens (28 weeks old) were randomly assigned to 5 groups (6 replicates × 12 birds). Hens were fed with a basal diet and a high-energy low-protein (HELP) diet supplemented with 0, 200, 400 and 800 mg/kg COS. COS reversed the lowered laying rates, increased feed-to-egg ratios and decreased albumen heights and Haugh units induced by the HELP diet. Additionally, COS improved the ovarian morphologies damaged by the HELP diet. Furthermore, COS enhanced antioxidant enzyme activities, reduced malonaldehyde levels and downregulated the mRNA expressions of nuclear factor kappa B, pro-inflammation cytokine genes and pro-apoptosis-related genes, while it upregulated the mRNA expression of anti-apoptosis-related genes in the ovaries of HELP-diet-fed hens. These findings suggested that dietary COS supplementation could improve production performance and egg quality in laying hens with FLS, and these beneficial effects were linked to improved ovarian morphology, which was attributed to decreased oxidative stress, inflammation and apoptosis in the ovaries.

Leucine (Leu) is a multifunctional essential amino acid that plays crucial role in various cellular processes. However, the integral effect of Leu on the hepatic proteome remains largely unknown. Here, we for the first time applied an isobaric tags for relative and absolute quantification (iTRAQ)-based comparative proteomics strategy to investigate the proteome alteration induced by Leu deprivation in human hepatocellular carcinoma (HepG2) cells. A total of 4,111 proteins were quantified; 43 proteins were further identified as differentially expressed proteins between the normal and Leu deprivation groups. Bioinformatics analysis showed that the differentially expressed proteins were involved in various metabolic processes, including amino acid and lipid metabolism, as well as degradation of ethanol. Interestingly, several proteins involved in the fatty acid β-oxidation pathway, including ACSL1, ACADS, and ACOX1, were up-regulated by Leu deprivation. In addition, Leu deprivation led to the reduction of cellular triglycerides in HepG2 cells. These results reveal that the fatty acid β-oxidation pathway is activated by Leu deprivation in HepG2 cells, and provide new insights into the regulatory function of Leu in multiple cellular processes, especially fatty acid metabolism.

Maternal nutrition exerts a profound effect on the postnatal performance of offspring, especially during the weaning period. The multifunctional bioactive component magnolol (MAG) has shown promise as a dietary supplement. This study aimed to explore the effects of maternal MAG supplementation on the antioxidant capacity, gut health, gut microbiome, and metabolome composition of weanling piglets. Fifty pregnant sows were randomly divided into two equally sized groups, the control group and the group supplemented with 100 g/t MAG during the gestation and lactation periods, and 7 days postweaning, the pups were euthanized. The microbiome and metabolome features of weanling piglet colons were compared. Our results revealed that maternal MAG supplementation modified the serum redox status of weanling piglets by decreasing malondialdehyde concentration and increasing superoxide dismutase activity and total antioxidant capacity. Moreover, the decreased indicators of diarrhea were accompanied by improved gut barrier function, in which serum diamine oxidase concentration was decreased, and expressions of zona occludens-1, claudin-1, and intestinal alkaline phosphatase were increased in the colon of weanling piglets from sows supplemented with MAG. Further analysis of the gut microbiota indicated that maternal MAG supplementation significantly increased the relative abundance of beneficial bacteria in the colon of weanling piglets, including Faecalibacterium prausnitzii and Oscillospira. Metabolome analysis identified 540 differential metabolites in the colon of piglets from MAG-fed dams, of which glycerophospholipid classes were highly correlated with progeny gut health and key beneficial bacteria. Our findings indicated that maternal MAG supplementation can improve the oxidative status and gut health of weanling piglets, possibly due to alterations in the gut microbiota and metabolites.

To obtain high-quality silage and better understand the mechanism underlying silage fermentation, a study was conducted to investigate the effects of konjac flour (KF), Lactiplantibacillus plantarum (LP) and their combination on fermentation quality, aerobic stability, and microbial community of high-moisture forage rape after 60 days of ensiling. Results showed that the KF and LP treatments increased the lactic acid content, decreased the pH value, and inhibited the production of butyric acid in ensiled forage rape (p < 0.05). The additives also altered the bacterial community of forage rape silages, showing reduced Shannon and Simpson indexes (p < 0.05), while the abundance of desirable Lactobacillus was increased, and the abundance of undesirable bacteria, such as enterobacteria and clostridia, was decreased (p < 0.05). In addition, their combination significantly improved the aerobic stability (96 h vs. 28 h, p < 0.05) and exhibited notable influence on the bacterial community, with the highest abundance of Lactobacillus. These results indicated that KF and LP improved the silage quality of high-moisture forage rape, and their combination displayed a beneficial synergistic effect.