Coupled fibromodulin and SOX2 signaling as a critical regulator of metastatic outgrowth in melanoma.

We aimed to study mechanisms controlling metastatic outgrowth of melanoma into clinically relevant lesions, a critical process responsible for the majority of melanoma deaths. To this end, we developed novel in vivo models and identified molecular events that can be ascribed to their distinct phenotypes, indolent or highly metastatic. Induction of a proliferative state at distant sites was associated with high levels of the stem-like/progenitor marker, SOX2, and required the upregulation of FMOD, an extracellular matrix component, which modulates tumor-stroma interactions. Functional studies revealed a possible link between FMOD and SOX2; dual FMOD and SOX2 silencing nearly abolished brain metastasis and had a similar effect on distant metastasis to other sites. Our in vitro data suggests that FMOD and SOX2 cooperation plays an important role in tumor vasculogenic mimicry. Furthermore, we found that FMOD and SOX2 functional roles might converge at the activation of transcriptional co-factors YAP and TAZ, possibly via crosstalk with the tumor suppressor Hippo pathway. Finally, high expression of both genes in patient specimens predicted early development of brain metastasis. Thus, our study identifies FMOD and SOX2 cooperation as a novel regulatory mechanism that might be linked functionally to melanoma metastatic competence.

Magnolol Supplementation Alters Serum Parameters, Immune Homeostasis, Amino Acid Profiles, and Gene Expression of Amino Acid Transporters in Growing Pigs.

This study investigated whether dietary supplementation with magnolol affects growth performance, anti-inflammatory abilities, serum and muscle amino acid profiles, and metabolisms in growing pigs. A total of 42 seventy-days-old growing barrows (Duroc × Landrace × Yorkshire) were randomly allocated into two dietary groups: Con, control group (basal diet); and Mag, magnolol group (basal diet supplemented with 400 mg/kg of magnolol). The results revealed that dietary supplementation with magnolol had no effect (p > 0.05) on growth performance. However, magnolol supplementation remarkably increased (p < 0.05) the serum content of albumin, total protein, immunoglobulin G, immunoglobulin M, and interleukin-22. In addition, dietary magnolol supplementation altered the amino acid (AA) profiles in serum and dorsal muscle and particularly increased (p < 0.05) the serum content of arginine and muscle glutamate. Simultaneously, the mRNA expression of genes associated with AA transport in jejunum (SLC38A2, SLC1A5, and SLC7A1) and ileum (SLC1A5 and SLC7A1) was higher (p < 0.05) in the Mag group than in the Con group. Additionally, the serum metabolomics analysis showed that the addition of magnolol significantly enhanced (p < 0.05) arginine biosynthesis, as well as D-glutamine and D-glutamate metabolism. Overall, these results suggested that dietary supplementation with magnolol has the potential to improve the accumulation of AAs, protein synthesis, immunity, and body health in growing pigs by increasing intestinal absorption and the transport of AAs.

Solid-state fermentation improves the quality of chrysanthemum waste as an alternative feed ingredient.

Chrysanthemum waste (CW) is an agricultural and industrial by-product produced during chrysanthemum harvesting, drying, preservation, and deep processing. Although it is nutritious, most CW is discarded, wasting resources and contributing to serious environmental problems. This work explored a solid-state fermentation (SSF) strategy to improve CW quality for use as an alternative feed ingredient. Orthogonal experiment showed that the optimal conditions for fermented chrysanthemum waste (FCW) were: CW to cornmeal mass ratio of 9:1, Pediococcus cellaris + Candida tropicalis + Bacillus amyloliquefaciens proportions of 2:2:1, inoculation amount of 6%, and fermentation time of 10 d. Compared with the control group, FCW significantly increased the contents of crude protein, ether extract, crude fiber, acid detergent fiber, neutral detergent fiber, ash, calcium, phosphorus, and total flavonoids (p < 0.01), and significantly decreased pH and saponin content (p < 0.01). SSF improved the free and hydrolyzed amino acid profiles of FCW, increased the content of flavor amino acids, and improved the amino acid composition of FCW protein. Overall, SSF improved CW nutritional quality. FCW shows potential use as a feed ingredient, and SSF helps reduce the waste of chrysanthemum processing.

Mulberry leaf extract improves intestinal barrier function and displays beneficial effects on colonic microbiota and microbial metabolism in weaned piglets.

BACKGROUND: Mulberry leaf extract (MLE) extracted from mulberry leaves is rich in a variety of bioactive ingredients and can be used as feed additives of weaned piglets. The present study was conducted to evaluate the effects of dietary MLE supplementation on intestinal barrier function, colon microbial numbers and microbial metabolites of weaned piglets. RESULTS: MLE supplementation increased the villus height and the villus height/crypt depth ratio in jejunum and ileum (P < 0.05), increased the mRNA expression of ZO-1, Claudin-1 and MUC-2 in the ileal mucosa (P < 0.05), and decreased the serum level of lipopolysaccharide (P < 0.01). Meanwhile, MLE reduced the mRNA expression of tumor necrosis factor-α and interleukin-1ß (P < 0.05) and increased secretory immunoglobulin A level in the ileal mucosa (P < 0.05). In addition, MLE increased the numbers of beneficial bacteria Bifidobacterium and Lactobacillus (P < 0.05) and decreased the number of potential pathogenic bacteria Escherichia coli (P < 0.05) in the colon. Correspondingly, MLE supplementation reduced the pH value of colonic digesta (P < 0.05) and altered the microbial fermentation pattern of the colon by increasing the concentrations of microbial metabolites derived from carbohydrates fermentation such as lactate, acetate, butyrate and total short-chain fatty acids (P < 0.05), and decreasing the concentrations of microbial metabolites derived from amino acid fermentation such as p-cresol, skatole, spermine, histamine and tryptamine (P < 0.05). CONCLUSION: MLE supplementation improved intestinal barrier function and displayed beneficial effects on colon microbes and microbial metabolism in weaned piglets. © 2022 Society of Chemical Industry.

Exogenous Glutathione Protects IPEC-J2 Cells against Oxidative Stress through a Mitochondrial Mechanism.

The accumulation of reactive oxygen species (ROS) triggers oxidative stress in cells by oxidizing and modifying various cellular components, preventing them from performing their inherent functions, ultimately leading to apoptosis and autophagy. Glutathione (GSH) is a ubiquitous intracellular peptide with multiple functions. In this study, a hydrogen peroxide (H2O2)-induced oxidative damage model in IPEC-J2 cells was used to investigate the cellular protection mechanism of exogenous GSH against oxidative stress. The results showed that GSH supplement improved the cell viability reduced by H2O2-induced oxidative damage model in IPEC-J2 cells in a dose-dependent manner. Moreover, supplement with GSH also attenuated the H2O2-induced MMP loss, and effectively decreased the H2O2-induced mitochondrial dysfunction by increasing the content of mtDNA and upregulating the expression TFAM. Exogenous GSH treatment significantly decreased the ROS and MDA levels, improved SOD activity in H2O2-treated cells and reduced H2O2-induced early apoptosis in IPEC-J2 cells. This study showed that exogenous GSH can protect IPEC-J2 cells against apoptosis induced by oxidative stress through mitochondrial mechanisms.

Effects of dietary citrus extract on growth performance, carcass characteristics and meat quality of pigs.

This study investigated the effects of citrus extract on growth, carcass and meat quality of Duroc × Landrace × Large White pigs. One hundred and eight pigs (54 barrows, 54 females) were assigned to one of three dietary treatments for 138 days. The dietary treatments were (1) basic diet; (2) basic diet supplemented with 75 mg/kg chlortetracycline; and (3) basic diet supplemented with citrus extract (0.25 ml/kg during 56-112 days of age and 0.20 ml/kg during 113-194 days of age). No significant differences among treatments were found for growth performance, carcass characteristics, meat quality and free amino acids (p > 0.05). Feeding citrus extract tended to increase intramuscular fat (p = 0.052). Citrus extract and chlortetracycline increased C15:0 concentration (p = 0.016) and superoxide dismutase activity (p = 0.004). The pigs that received chlortetracycline exhibited the lowest (p = 0.033) muscle malondialdehyde concentration. Overall, citrus extract ameliorated some meat quality indicators without adverse effects on pig growth or carcass performance.

Dietary supplementation with citrus extract alters the plasma parameters, circulating amino acid profiles and gene expression of small intestinal nutrient transporters in Chinese yellow-feathered broilers.

BACKGROUND: This study evaluated the effects of citrus extract (CE) on growth performance, plasma amino acid (AA) profiles, intestinal development and small intestine AA and peptide transporter expression levels in broilers. A total of 540 one-day-old yellow-feathered broilers were fed a basal diet without any antibiotic (control group), or a basal diet containing 10 mg kg-1 zinc bacitracin (antibiotic group), or a basal diet supplemented with 10 mg kg-1 CE (CE group). After 63 days of feeding, two broilers per pen were slaughtered to collect tissues for further analysis. RESULTS: Results showed that CE increased (P < 0.05) the final body weight and average daily gain from day 1 to 63, and decreased (P < 0.05) the feed/gain ratio from day 1 to 63. Dietary CE supplementation increased (P < 0.05) plasma total protein, albumin and glucose concentration, and decreased (P < 0.05) urea concentration. CE supplementation increased (P < 0.05) the villus height in the ileum and the villus height/crypt depth in the jejunum and ileum, but decreased (P < 0.05) the crypt depth in the jejunum and ileum. CE supplementation increased (P < 0.05) most plasma essential AA concentrations. Additionally, CE supplementation upregulated (P < 0.05) ASCT1, b0,+ AT, B0 AT1, EAAT3, rBAT, y+ LAT2 and PepT1 expression in the jejunum, and b0,+ AT, EAAT3, rBAT, y+ LAT2, CAT1 and PepT1 in the ileum. CONCLUSIONS: Collectively, our results indicated that CE supplementation promotes intestinal physiological absorption of AAs by upregulating gene expression of small intestinal key AA and peptide transporters, thereby enhancing the growth performance of broilers. © 2020 Society of Chemical Industry.

Chlorogenic acid: A comprehensive review of the dietary sources, processing effects, bioavailability, beneficial properties, mechanisms of action, and future directions.

Chlorogenic acids (CGAs), a group of hydroxycinnamates, are generally abundant in everyday foods and beverages, most prominently in certain coffee drinks. Among them, the chlorogenic acid (CGA), also termed as 5-O-caffeoylquinic acid (5-CQA), is one of the most abundant, highly functional polyphenolic compounds in the human diet. The evidence of its health benefits obtained from clinical studies, as well as basic research, indicates an inverse correlation between 5-CQA consumption and a lower risk of metabolic syndromes and chronic diseases. This review focuses on the beneficial properties for health and mechanisms of action of 5-CQA, starting with its history, isomers, dietary sources, processing effects, preparation methods, pharmacological safety evaluation, and bioavailability. It also provides the possible molecular mechanistic bases to explain the health beneficial effects of 5-CQA including neuroprotective, cardiovascular protective, gastrointestinal protective, renoprotective, hepatoprotective, glucose and lipid metabolism regulatory, and anticarcinogenic effects. The information summarized here could aid in the basic and clinical research on 5-CQA as a natural dietary additive, potential drug candidate, as well as a natural health promoter.

Effect of amino acids and their derivatives on meat quality of finishing pigs.

Amino acids provide key nutritional value, and significantly contribute to taste and flavor of meat. Here, we review the role of free amino acids in the muscle fibers in meat quality and sensory signals. We furthermore discuss how dietary supplementation of free amino acids and their derivatives (e.g. tryptophan, threonine, arginine, lysine, leucine, glutamate, threonine, sarcosine, betaines, and cysteamine) can influence these attributes. The available data shows that the quality of the meat is subject to the amino acids that are provided in the animal feed.

Lactobacillus reuteri LR1 Improved Expression of Genes of Tight Junction Proteins via the MLCK Pathway in IPEC-1 Cells during Infection with Enterotoxigenic Escherichia coli K88.

Intestinal epithelial barrier damage disrupts immune homeostasis and leads to many intestinal disorders. Lactobacillus reuteri strains have probiotic functions in their modulation of the microbiota and immune system in intestines. In this study, the effects of L. reuteri LR1, a new strain isolated from the feces of weaning piglets, on intestinal epithelial barrier damage in IPEC-1 cells caused by challenge with enterotoxigenic Escherichia coli (ETEC) K88 were examined. It was found that L. reuteri LR1, in large part, offset the ETEC K88-induced increase in permeability of IPEC-1 cell monolayers and decreased the adhesion and invasion of the coliform in IPEC-1 cells. In addition, L. reuteri LR1 increased transcript abundance and protein contents of tight junction (TJ) proteins zonula occluden-1 (ZO-1) and occludin in ETEC K88-infected IPEC-1 cells, whereas it had no effects on claudin-1 and F-actin expression. Using colloidal gold immunoelectron microscopy, these effects of L. reuteri LR1 on ZO-1 and occludin content in IPEC-1 cells were confirmed. By using ML-7, a selective inhibitor of myosin light-chain kinase (MLCK), the beneficial effect of L. reuteri LR1 on contents of ZO-1 and occludin was shown to be dependent on the MLCK pathway. In conclusion, L. reuteri LR1 had beneficial effects on epithelial barrier function consistent with increasing ZO-1 and occludin expression via a MLCK-dependent manner in IPEC-1 cells during challenge with ETEC K88.

Bayesian population pharmacokinetic modeling of florfenicol in pigs after intravenous and intramuscular administration.

Bayesian population pharmacokinetic models of florfenicol in healthy pigs were developed based on retrospective data in pigs either via intravenous (i.v.) or intramuscular (i.m.) administration. Following i.v. administration, the disposition of florfenicol was best described by a two-compartment open model with the typical values of half-life at α phase (t1/2α ), half-life at ß phase (t1/2ß ), total body clearance (Cl), and volume of distribution (Vd ) were 0.132 ± 0.0289, 2.78 ± 0.166 hr, 0.215 ± 0.0102, and 0.841 ± 0.0289 L kg-1 , respectively. The disposition of florfenicol after i.m. administration was best described by a one-compartment open model. The typical values of maximum concentration of drug in serum (Cmax ), elimination half-life (t1/2Kel ), Cl, and Volume (V) were 5.52 ± 0.605 µg/ml, 9.96 ± 1.12 hr, 0.228 ± 0.0154 L hr-1  kg-1 , and 3.28 ± 0.402 L/kg, respectively. The between-subject variabilities of all the parameters after i.m. administration were between 25.1%-92.1%. Florfenicol was well absorbed (94.1%) after i.m. administration. According to Monte Carlo simulation, 8.5 and 6 mg/kg were adequate to exert 90% bactericidal effect against Actinobacillus pleuropneumoniae after i.v. and i.m. administration.

Lactobacillus plantarum Enhanced IL-22 Production in Natural Killer (NK) Cells That Protect the Integrity of Intestinal Epithelial Cell Barrier Damaged by Enterotoxigenic Escherichia coli.

Interleukin (IL)-22-producing Natural Killer (NK) cells protect the gut epithelial cell barrier from pathogens. A strain of probiotics, Lactobacillus plantarum (L. plantarum, LP), was previously found by our laboratory to significantly improve the mucosal barrier integrity and function of the small intestine in pigs. However, it was unclear whether LP benefited the intestinal mucosal barrier via interactions with the intestinal NK cells. The present study, therefore, was focused on the therapeutic effect of NK cells that were stimulated by LP on attenuating enterotoxigenic Escherichia coli (ETEC)-induced the damage to the integrity of the epithelial cell barrier. The results showed that LP can efficiently increase protein levels of the natural cytotoxicity receptor (NCR) family, and the expression levels of IL-22 mRNA and protein in NK cells. Transfer of NK cells stimulated by LP conferred protection against ETEC K88-induced intestinal epithelial barrier damage in NCM460 cells. We found that NK cells stimulated by LP could partially offset the reduction in NCM460 cell monolayers transepithelial electrical resistance (TEER) caused by ETEC K88, and increase ZO-1 and occludin mRNA and protein expressions by ETEC K88-infected NCM460 cells. Furthermore, adding NK cells that were stimulated by LP to ETEC K88-infected NCM460cells, IL-22R1, p-Stat3, and p-Tyk2 expression by NCM460 cells was increased. Mechanistic experiment showed that NK cells stimulated by LP lost the function of maintaining TEER of NCM460 cells challenged with ETEC K88, when polyclonal anti-IL-22 antibody was used to block IL-22 production. Collectively, our results suggested that LP stimulation of NK could enhance IL-22 production, which might be able to provide defense against ETEC-induced damage to the integrity of intestinal epithelial barrier.

Significance of Increasing n-3 PUFA Content in Pork on Human Health.

Evidence for the health-promoting effects of food rich in n-3 polyunsaturated fatty acids (n-3 PUFA) is reviewed. Pork is an important meat source for humans. According to a report by the US Department of Agriculture ( http://www.ers.usda.gov/topics ), the pork consumption worldwide in 2011 was about 79.3 million tons, much higher than that of beef (48.2 million tons). Pork also contains high levels of unsaturated fatty acids relative to ruminant meats (Enser, M., Hallett, K., Hewett, B., Fursey, G. A. J. and Wood, J. D. (1996) . Fatty acid content and composition of English beef, lamb, and pork at retail. Meat Sci. 44:443-458). The available literature indicates that the levels of eicosatetraenoic and docosahexaenoic in pork may be increased by fish-derived or linseed products, the extent of which being dependent on the nature of the supplementation. Transgenic pigs and plants show promise with high content of n-3 PUFA and low ratio of n-6/n-3 fatty acids in their tissues. The approaches mentioned for decreasing n-6/n-3 ratios have both advantages and disadvantages. Selected articles are critically reviewed and summarized.

Malat1 as an evolutionarily conserved lncRNA, plays a positive role in regulating proliferation and maintaining undifferentiated status of early-stage hematopoietic cells.

BACKGROUND: The metastasis-associated lung adenocarcinoma transcription 1 (Malat1) is a highly conserved long non-coding RNA (lncRNA) gene. Previous studies showed that Malat1 is abundantly expressed in many tissues and involves in promoting tumor growth and metastasis by modulating gene expression and target protein activities. However, little is known about the biological function and regulation mechanism of Malat1 in normal cell proliferation. RESULTS: In this study we conformed that Malat1 is highly conserved across vast evolutionary distances amongst 20 species of mammals in terms of sequence, and found that mouse Malat1 expresses in tissues of liver, kidney, lung, heart, testis, spleen and brain, but not in skeletal muscle. After treating erythroid myeloid lymphoid (EML) cells with All-trans Retinoic Acid (ATRA), we investigated the expression and regulation of Malat1 during hematopoietic differentiation, the results showed that ATRA significantly down regulates Malat1 expression during the differentiation of EML cells. Mouse LRH (Lin-Rhodamine(low) Hoechst(low)) cells that represent the early-stage progenitor cells show a high level of Malat1 expression, while LRB (Lin - Hoechst(Low) Rhodamine(Bright)) cells that represent the late-stage progenitor cells had no detectable expression of Malat1. Knockdown experiment showed that depletion of Malat1 inhibits the EML cell proliferation. Along with the down regulation of Malat1, the tumor suppressor gene p53 was up regulated during the differentiation. Interestingly, we found two p53 binding motifs with help of bioinformatic tools, and the following chromatin immunoprecipitation (ChIP) test conformed that p53 acts as a transcription repressor that binds to Malat1's promoter. Furthermore, we testified that p53 over expression in EML cells causes down regulation of Malat1. CONCLUSIONS: In summary, this study indicates Malat1 plays a critical role in maintaining the proliferation potential of early-stage hematopoietic cells. In addition to its biological function, the study also uncovers the regulation pattern of Malat1 expression mediated by p53 in hematopoietic differentiation. Our research shed a light on exploring the Malat1 biological role including therapeutic significance to inhibit the proliferation potential of malignant cells.

Brevibacillus laterosporus: A Probiotic with Important Applications in Crop and Animal Production.

Brevibacillus laterosporus (B. laterosporus) is widely distributed in nature and demonstrates significant potential for applications in biological control, environmental protection, agricultural production, and clinical medicine. This review provides a comprehensive overview of the applications of B. laterosporus in crop cultivation and animal feeding, as well as an examination of the antimicrobial peptides produced by B. laterosporus and their antibacterial mechanisms. B. laterosporus enhances crop cultivation by secreting hydrolases to improve nutrient absorption capabilities, synthesizing hormones to promote crop growth, and producing proteins to inhibit the reproduction of harmful organisms. B. laterosporus has been used to improve animal production by regulating the structure of the intestinal microbiota and inhibiting the growth of pathogenic bacteria through the secretion of various antimicrobial peptides. The bactericidal activity of Brevilaterins secreted by B. laterosporus is attributed to their ability to bind to lipopolysaccharide/lipid II molecules on the cell membrane, thereby altering permeability. Brevilaterins also inhibit bacterial reproduction by affecting relevant gene pathways in the cell membranes of pathogenic bacteria. These pathways include ATP synthesis, peptidoglycan biosynthesis, membrane transport, and cellular metabolism. In conclusion, B. laterosporus exhibits substantial potential as a probiotic activity in crop and animal production. However, applications of B. laterosporus in animal production could be improved, necessitating further research to elucidate the underlying probiotic mechanisms.

Magnolol-driven microbiota modulation elicits changes in tryptophan metabolism resulting in reduced skatole formation in pigs.

Skatole of gut origin has garnered significant attention as a malodorous pollutant due to its escalating emissions, recalcitrance to biodegradation and harm to animal and human health. Magnolol is a health-promoting polyphenol with potential to considerably mitigate the skatole production in the intestines. To investigate the impact of magnolol and its underlying mechanism on the skatole formation, in vivo and in vitro experiments were conducted in pigs. Our results revealed that skatole concentrations in the cecum, colon, and faeces decreased by 58.24% (P = 0.088), 44.98% (P < 0.05) and 43.52% (P < 0.05), respectively, following magnolol supplementation. Magnolol supplementation significantly decreased the abundance of Lachnospira, Faecalibacterium, Paramuribaculum, Faecalimonas, Desulfovibrio, Bariatricus, and Mogibacterium within the colon (P < 0.05). Moreover, a strong positive correlation (P < 0.05) between skatole concentration and Desulfovibrio abundance was observed. Subsequent in silico studies showed that magnolol could dock well with indolepyruvate decarboxylase (IPDC) within Desulfovibrio. Further in vitro investigation unveiled that magnolol addition led to less indole-3-pyruvate diverted towards the oxidative skatole pathway by the potential docking of magnolol towards IPDC, thereby diminishing the conversion of substrate into skatole. Our findings offer novel targets and strategies for mitigating skatole emission from the source.

Integrated Metabolomics and Metagenomics Unveiled Biomarkers of Antioxidant Potential in Fermented Brewer's Grains.

About one-third of the global food supply is wasted. Brewers' spent grain (BSG), being produced in enormous amounts by the brewery industry, possesses an eminence nutritional profile, yet its recycling is often neglected for multiple reasons. We employed integrated metagenomics and metabolomics techniques to assess the effects of enzyme treatments and Lactobacillus fermentation on the antioxidant capacity of BSG. The biotreated BSG revealed improved antioxidant capability, as evidenced by significantly increased (p < 0.05) radical scavenging activity and flavonoid and polyphenol content. Untargeted metabolomics revealed that Lactobacillus fermentation led to the prominent synthesis (p < 0.05) of 15 novel antioxidant peptides, as well as significantly higher (p < 0.05) enrichment of isoflavonoid and phenylpropanoid biosynthesis pathways. The correlation analysis demonstrated that Lactiplantibacillus plantarum exhibited strong correlation (p < 0.05) with aucubin and carbohydrate-active enzymes, namely, glycoside hydrolases 25, glycosyl transferases 5, and carbohydrate esterases 9. The fermented BSG has potential applications in the food industry as a culture medium, a functional food component for human consumption, and a bioactive feed ingredient for animals.

Cancer immunotherapy with enveloped self-amplifying mRNA CARG-2020 that modulates IL-12, IL-17 and PD-L1 pathways to prevent tumor recurrence.

Targeting multiple immune mechanisms may overcome therapy resistance and further improve cancer immunotherapy for humans. Here, we describe the application of virus-like vesicles (VLV) for delivery of three immunomodulators alone and in combination, as a promising approach for cancer immunotherapy. VLV vectors were designed to deliver single chain interleukin (IL)-12, short-hairpin RNA (shRNA) targeting programmed death ligand 1 (PD-L1), and a dominant-negative form of IL-17 receptor A (dn-IL17RA) as a single payload or as a combination payload. Intralesional delivery of the VLV vector expressing IL-12 alone, as well as the trivalent vector (designated CARG-2020) eradicated large established tumors. However, only CARG-2020 prevented tumor recurrence and provided long-term survival benefit to the tumor-bearing mice, indicating a benefit of the combined immunomodulation. The abscopal effects of CARG-2020 on the non-injected contralateral tumors, as well as protection from the tumor cell re-challenge, suggest immune-mediated mechanism of protection and establishment of immunological memory. Mechanistically, CARG-2020 potently activates Th1 immune mechanisms and inhibits expression of genes related to T cell exhaustion and cancer-promoting inflammation. The ability of CARG-2020 to prevent tumor recurrence and to provide survival benefit makes it a promising candidate for its development for human cancer immunotherapy.

Carbon Footprint of the Pork Product Chain and Recent Advancements in Mitigation Strategies.

The carbon footprint of pork production is a pressing concern due to the industry's significant greenhouse gas emissions. It is crucial to achieve low-carbon development and carbon neutrality in pork production. Thus, this paper reviewed the recent studies about various sources of carbon emissions throughout the current pork production chain; feed production, processing, and manure management are the major sources of carbon emissions. The carbon footprint of the pork production chain varies from 0.6 to 6.75 kg CO2e·kg-1 pig live weight, and the carbon footprint of 1 kg of pork cuts is equivalent to 2.25 to 4.52 kg CO2e. A large reduction in carbon emissions could be achieved simultaneously if combining strategies of reducing transportation distances, optimizing farmland management, minimizing chemical fertilizer usage, promoting organic farming, increasing renewable energy adoption, and improving production efficiency. In summary, these mitigation strategies could effectively decrease carbon emissions by 6.5% to 50% in each sector. Therefore, a proper combination of mitigation strategies is essential to alleviate greenhouse gas emissions without sacrificing pork supply.

Dietary Supplementation with Rutin Alters Meat Quality, Fatty Acid Profile, Antioxidant Capacity, and Expression Levels of Genes Associated with Lipid Metabolism in Breast Muscle of Qingyuan Partridge Chickens.

Consumer demand for tasty and quality meat has been quickly increasing. This study investigated how dietary supplemented rutin affects meat quality, muscle fatty acid profile, and antioxidant capacity in the Chinese indigenous Qingyuan partridge chicken. A cohort of 180 healthy 119-day-old chickens was subjected to a randomized assignment into three groups, identified as the control, R200, and R400 groups, with respective supplementation of 0, 200, and 400 mg/kg of rutin. The results revealed insignificance in growth performance, namely, average daily gain, average daily feed intake, and feed-to-gain ratio, across the various treatment groups (p > 0.05). Nevertheless, dietary rutin supplementation increased (p < 0.05) breast muscle yield and intramuscular fat content in breast muscle and decreased (p < 0.05) drip loss in breast muscle. Rutin supplementation increased (p < 0.05) the content of high-density lipoprotein but decreased (p < 0.05) the contents of glucose, triglyceride, and total cholesterol in serum. Rutin supplementation increased (p < 0.05) the levels of DHA (C22:6n-3), total polyunsaturated fatty acids (PUFAs), n-3 PUFAs, decanoic acid (C10:0), the activity of Δ5 + Δ6 (22:6 (n - 3)/18:3 (n - 3)), and the ratio of PUFA/SFA in breast muscle but decreased (p < 0.05) the level of palmitoleic acid (C16:1n-7), the ratio of n-6/n-3 PUFAs, and the activity of Δ9 (16:1 (n - 7)/16:0). Rutin treatment also reduced (p < 0.05) the contents of malondialdehyde in serum and breast muscle, and increased (p < 0.05) the catalase activity and total antioxidant capacity in serum and breast muscle and the activity of total superoxide dismutase in serum. Additionally, rutin supplementation downregulated the expression of AMPKα and upregulated the expression of PPARG, FADS1, FAS, ELOVL7, NRF2, and CAT in breast muscle (p < 0.05). Convincingly, the results revealed that rutin supplementation improved meat quality, fatty acid profiles, especially n-3 PUFAs, and the antioxidant capacity of Qingyuan partridge chickens.