This study aimed to evaluate the effects of Saccharomyces cerevisiae, and their combination on rumen fermentation and growth performance of heat-stressed goats. Twelve heat-stressed goats (20.21 ± 2.30 kg) were divided equally into four groups: control group (CG, fed the basal diet, Saccharomyces cerevisiae supplemented group (SC, 0.60% Saccharomyces cerevisiae added to the basal diet), Clostridium butyricum supplemented group (CB, 0.05% Clostridium butyricum added to the basal diet), and their combination supplemented group (COM 0.60% Saccharomyces cerevisiae and 0.05% Clostridium butyricum added to the basal diet) and were assigned to a 4 × 3 incomplete Latin square design. The rumen fluid and feces were collected for fermentation parameters and feed digestibility analysis, and animal growth performance was also assessed during all the experiment periods. The results showed that rumen pH, rumen cellulolytic enzymes (avicelase, CMCaes, cellobiase, and xylanase) activities, and the concentrations of rumen total volatile fatty acid (TVFA), acetic acid, and propionic acid were significantly increased with Saccharomyces cerevisiae, Clostridium butyricum, and their combination supplementation (p < 0.05). Besides, the dry matter intake (DMI), average daily gain (ADG), and the digestibility of dry matter (DM), neutral detergent fiber (NDF), and acidic detergent fiber (ADF) were significantly increased (p < 0.05) with supplemented these probiotics. However, the ammonia nitrogen (NH3-N) concentration only significantly increased in CB and A/P ratio (acetic acid to propionic acid ratio) only significantly increased in SC and CB. These results indicated that the supplementation with these probiotics could ameliorate rumen fermentation and growth performance of heat-stressed goats.

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This study was performed to explore the predominant responses of rumen microbiota with thymol supplementation as well as effective dose of thymol on rumen fermentation. Thymol at different concentrations, i.e., 0, 100 mg/L, 200 mg/L, and 400 mg/L (four groups × five replications) was applied for 24 h of fermentation in a rumen fluid incubation system. Illumina MiSeq sequencing was applied to investigate the ruminal microbes in addition to the examination of rumen fermentation. Thymol doses reached 200 mg/L and significantly decreased (p < 0.05) total gas production (TGP) and methane production; the production of total volatile fatty acids (VFA), propionate, and ammonia nitrogen, and the digestibility of dry matter and organic matter were apparently decreased (p < 0.05) when the thymol dose reached 400 mg/L. A thymol dose of 200 mg/L significantly affected (p < 0.05) the relative abundance of 14 genera of bacteria, three species of archaea, and two genera of protozoa. Network analysis showed that bacteria, archaea, and protozoa significantly correlated with methane production and VFA production. This study indicates an optimal dose of thymol at 200 mg/L to facilitate rumen fermentation, the critical roles of bacteria in rumen fermentation, and their interactions with the archaea and protozoa.

Although combination chemoimmunotherapy shows promising clinical results for cancer treatment, this approach is largely restricted by variable objective response rate and severe systemic adverse effects of immunotherapeutic antibody and chemotherapeutic drugs. Therefore, an in situ-formed therapeutic silk-chitosan composite scaffold is fabricated in this study to allow local release of the chemotherapeutic drug doxorubicin (DOX) and JQ1 (small molecular inhibitor used for the extraterminal protein BRD4 and bromodomain) with control release kinetics. DOX-JQ1@Gel contains a pH-degradable group that releases therapeutics in a weak acidic tumor microenvironment. The released DOX could directly kill tumor cells or lead to immunogenic cell death, thereby triggering the response of antitumor immunity. Meanwhile, chemotherapy-triggered antigen release and JQ1-mediated PD-L1 checkpoint blockade cumulatively contribute to trigger the response of antitumor immunity. Finally, the DOX-JQ1@Gel is locally injected to evaluate its synergistic cancer therapeutic effect, which is expected to improve objective response rate of immunotherapy and minimize systemic side effects. Graphical Abstract