Di Wu

Abstract The effective treatment of advanced cervical cancer remains challenging. Herein, single‐nucleus RNA sequencing (snRNA‐seq) and SpaTial enhanced resolution omics‐sequencing (Stereo‐seq) are used to investigate the immunological microenvironment of cervical squamous cell carcinoma (CSCC). The expression levels of most immune suppressive genes in the tumor and inflammation areas of CSCC are not significantly higher than those in the non‐cancer samples, except for LGALS9 and IDO1 . Stronger signals of CD56 + NK cells and immature dendritic cells are found in the hypermetabolic tumor areas, whereas more eosinophils, immature B cells, and Treg cells are found in the hypometabolic tumor areas. Moreover, a cluster of pro‐tumorigenic cancer‐associated myofibroblasts (myCAFs) are identified. The myCAFs may support the growth and metastasis of tumors by inhibiting lymphocyte infiltration and remodeling of the tumor extracellular matrix. Furthermore, these myCAFs are associated with poorer survival probability in patients with CSCC, predict resistance to immunotherapy, and might be present in a small fraction (< 30%) of patients with advanced cancer. Immunohistochemistry and multiplex immunofluorescence staining are conducted to validate the spatial distribution and potential function of myCAFs. Collectively, these findings enhance the understanding of the immunological microenvironment of CSCC and shed light on the treatment of advanced CSCC.

The aim of this study was to investigate the effects of the combination of probiotics replacing antibiotics on growth performance, serum biochemical parameters, intestinal morphology, and expression of tight junction proteins in intestinal mucosa of broilers. A total of 168 Arbor Acres broilers (45.04 ± 0.92 g) were randomly divided into three treatments, with seven replicates per treatment, and eight broilers per replicate. The experiment included phases 1 (d 0 to 21) and 2 (d 21 to 42). The dietary treatments contained a corn soybean meal-based diet (control group; CON); an antibiotic group (basal diet + 75 mg/kg chlortetracycline; CTC), and a probiotics group (basal diet + probiotics (500 mg/kg in phase 1 and 300 mg/kg in phase 2; Bacillus subtilis 5 × 109 CFU/g, Bacillus licheniformis 2.5 × 1010 CFU/g and Saccharomyces cerevisiae 1 × 109 CFU/g; PB). The results showed broilers fed PB had improved (p < 0.05) feed conversion ratio (FCR) in phase 1 and increased (p < 0.05) average daily gain (ADG) in phase 2, as well as improved (p < 0.05) ADG and FCR overall (d 0 to 42). The apparent total tract digestibility (ATTD) of dry matter, organic matter, gross energy, and crude protein was increased (p < 0.05) in broilers fed PB, while the ATTD of dry matter and organic matter was enhanced in broilers fed CTC compared with CON. Broilers fed PB showed increased (p < 0.05) serum total antioxidant capacity concentrations and tended to have higher (p = 0.06) level of serum immunoglobulin M in phase 1 compared with CON. These broilers also had increased (p < 0.05) level of serum immunoglobulin A in phase 2 in comparison with CON and CTC. Moreover, broilers fed CTC and PB showed increased (p = 0.05) villus height to crypt depth ratio in duodenum, as well as higher (p < 0.05) mRNA expression of zonula occludens-1 in jejunum compared with CON. In conclusion, dietary supplementation with PB as chlortetracycline substitute could improve the growth performance, nutrient digestibility, serum antioxidant capacity, jejunal mucosal barrier function, and intestinal morphology of broilers.

High-fat diet is regarded as crucial inducers of oxidative stress, inflammation, and metabolic imbalance. In order to investigate the ameliorative potential of resveratrol against the progression of liver injury towards steatohepatitis, common carp ( Cyprinus carpio ) were distributed into six experimental groups and were fed with a normal-fat diet, a high-fat diet, and supplemented with resveratrol (0.8, 1.6, 2.4, and 3.2 g/kg diet) for 8 weeks. The high-fat diet decreased the antioxidant capacities, as well as causing the inflammatory response and lipid deposition of common carp. Resveratrol induced a marked elevation in the final body weight, weight gain rate, condition factor and significant decrease in the feed conversion ratio. Moreover, dietary resveratrol showed a significant decrease in the alanine aminotransferase, aspartate aminotransferase, triglyceride and low-density lipoprotein levels, which was accompanied by an increase in high-density lipoprotein concentration in serum. A significant elevation in total superoxide dismutase, catalase, glutathione peroxidase and a decreased malondialdehyde content were observed, along with a substantial elevation in antioxidant activities were found. Additionally, fish fed with resveratrol had an up-regulation of hepatic catalase, copper, zinc superoxide dismutase, glutathione peroxidase 1a, and glutathione peroxidase 1b gene expression via Nrf2 signaling pathway. Expectedly, our results also demonstrated that resveratrol regulates hepatic lipid metabolism in fish by inhibiting the expression of hepatic lipogenesis genes (acetyl-CoA carboxylase 1, fatty acid synthase, and sterol regulatory element binding protein 1), fatty acid uptake-related genes of lipoprotein lipase, and β-oxidation-related genes via PPAR-γ signaling pathway. Furthermore, dietary resveratrol reduced inflammation, as evident by down-regulating the interleukin-1β, interleukin-6, interleukin-8, and tumor necrosis factor-α expression levels and upregulating the interleukin-10 and transforming growth factor-β2 expression levels via NF-κB signaling pathway. As a whole, our results demonstrated that resveratrol defensed the impacts against high-fat diet on the serum biochemical, hepatic antioxidants, inflammation, and lipid metabolism.

Plant extracts have been proved as natural antioxidants resources as well as alternative feed additives in livestock and poultry species. Chestnut wood extract (CWE) as a source of hydrolysable tannic acid was used to evaluate the growth performance, nutrient retention, meat quality, antioxidant status, and immune function of broilers. A total of 168, day-old Arbor Acre male broilers (weight 46.59 ± 0.44 g) were randomly divided to 3 treatments, 7 replicate pens per treatment, 8 broilers per pen. The treatments contain a control diet, CON (corn-soybean meal basal diet); an antibiotic diet, CTC (basal diet + 75 mg/kg chlortetracycline); and chestnut wood extract diet, CWE (basal diet + 1,000 mg/kg chestnut tannins). At the finisher phase, final body weight was higher (P < 0.05) in CWE supplemented diet than in CON. Average daily body weight gain was higher (P < 0.05) and feed gain ratio was lower (P < 0.05) in broilers fed CWE than in those fed CON at the finisher phase. Crude protein digestibility was higher (P < 0.05) in broilers offered CWE than that in broilers fed CON and CTC diets. Breast muscle pH value at 24 h (pH24 h) was higher (P < 0.05) in broilers fed CWE than that in those fed CON and CTC diets. The bursa weight was higher (P < 0.05) in broilers offered CWE than that in those fed CON and CTC. Total antioxidant capacity (T-AOC), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) values were higher (P < 0.05) in both breast muscle and thigh muscle of broilers offered CWE supplemented diet than those in broilers fed CON and CTC diets. Similarly, broilers offered with CWE diets showed higher (P < 0.05) T-AOC, GSH-PX, and SOD value in serum than those fed CON and CTC diets. Serum concentration of IgG was higher (P < 0.05) in broilers offered with CWE diets than that in those fed CON and CTC diets. Total cholesterol, low-density lipoprotein cholesterol, and urea-N concentration were lower (P < 0.05) in broilers offered CWE diet than those in broilers fed CON and CTC diets. It was recommended to supply CWE at the 1,000 mg/kg level for improving antioxidant status, cholesterol metabolism, and growth performance without affecting normal meat quality in broilers.