Dynamic changes and characterization of the protein and carbohydrate fractions of native grass grown in Inner Mongolia during ensiling and the aerobic stage.

OBJECTIVE: To improve the utility of native grass resources as feed in China, we investigated the dynamics of protein and carbohydrate fractions among Inner Mongolian native grasses, during ensiling and the aerobic stage, using the Cornell Net Carbohydrate and Protein System. METHODS: Silages were prepared without or with lactic acid bacteria (LAB) inoculant. We analyzed the protein and carbohydrate fractions and fermentation quality of silages at 0, 5, 15, 20, 30, and 60 d of ensiling, and the stability at 0.5, 2, 5, and 10 d during the aerobic stage. RESULTS: Inner Mongolian native grass contained 10.8% crude protein (CP) and 3.6% water-soluble carbohydrates (WSC) on a dry matter basis. During ensiling, pH and CP and WSC content decreased (p<0.05), whereas lactic acid and ammonia nitrogen (N) content increased (p<0.05). Non-protein N (PA) content increased significantly, whereas rapidly degraded true protein (PB1), intermediately degraded true protein (PB2), total carbohydrate (CHO), sugars (CA), starch (CB1), and degradable cell wall carbohydrate (CB2) content decreased during ensiling (p<0.05). At 30 d of ensiling, control and LAB-treated silages were well preserved and had lower pH (<4.2) and ammonia-N content (<0.4 g/kg of fresh matter [FM]) and higher lactic acid content (>1.0% of FM). During the aerobic stage, CP, extract ether, WSC, lactic acid, acetic acid, PB1, PB2, true protein degraded slowly (PB3), CHO, CA, CB1, and CB2 content decreased significantly in all silages, whereas pH, ammonia-N, PA, and bound true protein (PC) content increased significantly. CONCLUSION: Control and LAB-treated silages produced similar results in terms of fermentation quality, aerobic stability, and protein and carbohydrate fractions. Inner Mongolian native grass produced good silage, nutrients were preserved during ensiling and protein and carbohydrate losses largely occurred during the aerobic stage.

Lenalidomide Enhances CAR-T Cell Activity Against Solid Tumor Cells.

Chimeric antigen receptor (CAR) T-cell immunotherapy still faces many challenges in the treatment of solid tumors, one of which is T-cell dysfunction or exhaustion. Immunomodulator lenalidomide may improve CAR T-cell function. In this study, the effects of lenalidomide on CAR T-cell functions (cytotoxicity, cytokine secretion, and cell proliferation) were investigated. Two different CAR T cells (CD133-specific CAR and HER2-specific CAR) were prepared, and the corresponding target cells including human glioma cell line U251 CD133-OE that overexpress CD133 and human breast cancer cell line MDA-MB-453 were used for functional assay. We found that lenalidomide promoted the killing of U251 CD133-OE by CD133-CAR T cells, the cytokine secretion, and the proliferation of CD133-CAR T cells. Lenalidomide also enhanced the cytotoxicity against MDA-MB-453 and the cytokine secretion of HER2-CAR T cells but did not affect their proliferation significantly. Furthermore, lenalidomide may regulate the function of CAR T cells by inducing the degradation of transcription factors Ikaros and Aiolos.

Galunisertib enhances chimeric antigen receptor-modified T cell function.

Chimeric antigen receptor (CAR) T cell therapy still faces the challenge of immunosuppression when treating solid tumors. TGF-ß is one of the critical factors in the tumor microenvironment to help tumors escape surveillance by the immune system. Here we tried using the combination of a small molecule inhibitor of TGF-ß receptor I, Galunisertib, and CAR T cells to explore whether Galunisertib could enhance CAR T cell function against solid tumor cells. In vitro experiments showed Galunisertib could significantly enhance the specific cytotoxicity of both CD133- and HER2-specific CAR T cells. However, Galunisertib had no direct killing effect on target cells. Galunisertib significantly increased the cytokine secretion of CAR T cells and T cells that do not express CAR (Nontransfected T cells). Galunisertib did not affect the proliferation of T cells, the antigen expression on target cells and CD69 on CAR T cells. We found that TGF-ß was secreted by T cells themselves upon activation, and Galunisertib could reduce TGF-ß signaling in CAR T cells. Our findings can provide the basis for further preclinical and clinical studies of the combination of Galunisertib and CAR T cells in the treatment of solid tumors.

Growth performance, apparent digestibility, and N balance in Mongolian lambs and hoggs fed diets supplemented with a Chinese traditional herbal medicine complex.

We evaluated the effects of dietary supplementation with Chinese traditional herbal medicine (CTHM) on the growth performance, apparent digestibility, and nitrogen balance in Mongolian lambs and hoggs. The CTHM used as a dietary supplement consisted of 30% pine needles, 20% mugwort, 40% garlic, and 10% Astragalus mongholicus on a dry matter (DM) basis. The basal diet was prepared from corn stover, corn grain, wheat bran, rapeseed meal, shell meal, dicalcium phosphate, salt, vitamin premix, and mineral premix. In total, 16 Mongolian lambs (20.75 kg initial body weight [BW]) and 16 hoggs (33.81 kg initial BW) were allocated randomly to one of two treatments, the basal diet without and with CTHM, with the group receiving CTHM fed 98.5% basal diet + 1.5% CTHM complex on a DM basis. Lamb and hogg growth trials showed that CTHM supplementation improved the final live weight, gain, and feed conversion ratio (p < 0.01). A digestibility trial showed that the diet with CTHM improved the digestibility of DM, organic matter (OM), crude protein (CP), and neutral detergent fiber in lambs and hoggs. Finally, CTHM supplementation decreased (p < 0.0001) fecal and urinary nitrogen and increased (p = 0.0004) nitrogen (N) retention. Overall, the addition of CTHM to the diets of lambs and hoggs has beneficial effects on growth.