Multi-omics analysis reveals substantial linkages between the oral-gut microbiomes and inflamm-aging molecules in elderly pigs.

Introduction: The accelerated aging of the global population has emerged as a critical public health concern, with increasing recognition of the influential role played by the microbiome in shaping host well-being. Nonetheless, there remains a dearth of understanding regarding the functional alterations occurring within the microbiota and their intricate interactions with metabolic pathways across various stages of aging. Methods: This study employed a comprehensive metagenomic analysis encompassing saliva and stool samples obtained from 45 pigs representing three distinct age groups, alongside serum metabolomics and lipidomics profiling. Results: Our findings unveiled discernible modifications in the gut and oral microbiomes, serum metabolome, and lipidome at each age stage. Specifically, we identified 87 microbial species in stool samples and 68 in saliva samples that demonstrated significant age-related changes. Notably, 13 species in stool, including Clostridiales bacterium, Lactobacillus johnsonii, and Oscillibacter spp., exhibited age-dependent alterations, while 15 salivary species, such as Corynebacterium xerosis, Staphylococcus sciuri, and Prevotella intermedia, displayed an increase with senescence, accompanied by a notable enrichment of pathogenic organisms. Concomitant with these gut-oral microbiota changes were functional modifications observed in pathways such as cell growth and death (necroptosis), bacterial infection disease, and aging (longevity regulating pathway) throughout the aging process. Moreover, our metabolomics and lipidomics analyses unveiled the accumulation of inflammatory metabolites or the depletion of beneficial metabolites and lipids as aging progressed. Furthermore, we unraveled a complex interplay linking the oral-gut microbiota with serum metabolites and lipids. Discussion: Collectively, our findings illuminate novel insights into the potential contributions of the oral-gut microbiome and systemic circulating metabolites and lipids to host lifespan and healthy aging.

A Review on Zoonotic Pathogens Associated with Non-Human Primates: Understanding the Potential Threats to Humans.

Non-human primates (NHP) share a close relationship with humans due to a genetic homology of 75-98.5%. NHP and humans have highly similar tissue structures, immunity, physiology, and metabolism and thus often can act as hosts to the same pathogens. Agriculture, meat consumption habits, tourism development, religious beliefs, and biological research have led to more extensive and frequent contact between NHPs and humans. Deadly viruses, such as rabies virus, herpes B virus, Marburg virus, Ebola virus, human immunodeficiency virus, and monkeypox virus can be transferred from NHP to humans. Similarly, herpes simplex virus, influenza virus, and yellow fever virus can be transmitted to NHP from humans. Infectious pathogens, including viruses, bacteria, and parasites, can affect the health of both primates and humans. A vast number of NHP-carrying pathogens exhibit a risk of transmission to humans. Therefore, zoonotic infectious diseases should be evaluated in future research. This article reviews the research evidence, diagnostic methods, prevention, and treatment measures that may be useful in limiting the spread of several common viral pathogens via NHP and providing ideas for preventing zoonotic diseases with epidemic potential.

Matters arising: methodological issues on evaluating agreement between medical students' attitudes towards drugs/alcohol use during pregnancy by Cohen's kappa analysis.

BACKGROUND: The purpose of this article is to discuss the statistical methods for agreement analysis used in Richelle's article (BMC Med Educ 22:335, 2022). The authors investigated the attitudes of final-year medical students regarding substance use during pregnancy and identified the factors that influence these attitudes. METHODS: We found that Cohen's kappa value for measuring the agreement between these medical students' attitudes towards drugs/alcohol use during pregnancy was questionable. In addition, we recommend using weighted kappa instead of Cohen's kappa for agreement analysis at the presence of three categories. RESULTS: The agreement improved from "good" (Cohen's kappa) to "very good" (weighted kappa) for medical students' attitudes towards drugs/alcohol use during pregnancy. CONCLUSION: To conclude, we recognize that this does not significantly alter the conclusions of the Richelle et al. paper, but it is necessary to ensure that the appropriate statistical tools are used.

HYOU1 promotes cell proliferation, migration, and invasion via the PI3K/AKT/FOXO1 feedback loop in bladder cancer.

BACKGROUND: Hypoxia up-regulated 1 (HYOU1) was identified as a proto-oncogene and involved in tumorigenesis and progression in several cancer. Nonetheless, the biological function and mechanism of HYOU1 in bladder cancer (BCa) remian unclear. METHODS: The HYOU1 level in BCa tissues and cells was examined using RT-qPCR and western blot methods. The relationship between HYOU1 expression and clinicopathologic characteristics of BCa was analyzed. The biological role of HYOU1 on BCa cell proliferation, apoptosis, migration and invasion were analyzed via counting kit-8 (CCK-8), flow cytometry, wound healing and Transwell assays, respectively. The association between HYOU1 and the PI3K/AKT/Forkhead box O1 (FOXO1) signalling was assessed via western blot assay, meanwhile the the association of FOXO1 with HYOU1 was also investigated. RESULTS: HYOU1 was up-regulated in BCa tissues and cell lines, and the high level of HYOU1 was associated with bladder cancer histological grade and pathologic stage. Moreover, patients with high expression of HYOU1 showed poor overall survival from Kaplan-Meier Plotter. HYOU1 depletion impeded cell proliferation, migration and invasion, and induced cell apoptosis, while HYOU1 overexpression promoted cell proliferation, migration and invasion. Mechanically, our results showed that HYOU1 knockdown repressed PI3K/AKT/FOXO1 pathway and HYOU1 was negative regulated by FOXO1 in BCa. Significantly, we confirmed that the HYOU1/PI3K-AKT/FOXO1 negative feedback loop was involved in BCa cell proliferation, migration and invasion. CONCLUSION: These findings revealed that HYOU1 acted as a pro-oncogene on BCa progression, and it will be a possible target for BCa treatment.

Chicken intestinal microbiota modulation of resistance to nephropathogenic infectious bronchitis virus infection through IFN-I.

BACKGROUND: Mammalian intestinal microbiomes are necessary for antagonizing systemic viral infections. However, very few studies have identified whether poultry commensal bacteria play a crucial role in protecting against systemic viral infections. Nephropathogenic infectious bronchitis virus (IBV) is a pathogenic coronavirus that causes high morbidity and multiorgan infection tropism in chickens. RESULTS: In this study, we used broad-spectrum oral antibiotics (ABX) to treat specific pathogen free (SPF) chickens to deplete the microbiota before infection with nephropathogenic IBV to analyze the impact of microbiota on IBV infections in vivo. Depletion of the SPF chicken microbiota increases pathogenicity and viral burden following IBV infection. The gnotobiotic chicken infection model further demonstrated that intestinal microbes are resistant to nephropathogenic IBV infection. In addition, ABX-treated chickens showed a severe reduction in macrophage activation, impaired type I IFN production, and IFN-stimulated gene expression in peripheral blood mononuclear cells and the spleen. Lactobacillus isolated from SPF chickens could restore microbiota-depleted chicken macrophage activation and the IFNAR-dependent type I IFN response to limit IBV infection. Furthermore, exopolysaccharide metabolites of Lactobacillus spp. could induce IFN-ß. CONCLUSIONS: This study revealed the resistance mechanism of SPF chicken intestinal microbiota to nephropathogenic IBV infection, providing new ideas for preventing and controlling nephropathogenic IBV. Video abstract.

Clinicopathological Characteristics and Survival Outcomes of Primary Renal Leiomyosarcoma.

Background: Primary renal leiomyosarcoma (LMS) is an exceedingly rare entity with a poor prognosis. We summarized the clinicopathological characteristics, treatment choice, and survival outcomes of LMS from the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Renal LMS and kidney renal clear cell carcinoma (KIRC) data from 1998 to 2016 were collected from the SEER database. The continuous variables were analyzed using t-tests, while the categorical variables were analyzed using Pearson's chi-squared or Fisher's exact tests. Propensity score matching (PSM) was also performed. The cancer-specific survival (CSS) and overall survival (OS) curves were estimated using Kaplan-Meier analyses and compared by log-rank tests. The risk factors for CSS and OS were estimated using univariable and multivariable Cox proportional hazard regression models. Results: A total of 140 patients with renal LMS and 75,401 patients with KIRC were enrolled. These groups differed significantly in sex, race, tumor size, grade, SEER stage, surgery, radiation, and chemotherapy. Renal LMS exhibited poorer CSS and OS compared with KIRC before and after PSM. For renal LMS, the univariate Cox proportional hazard regression model indicated that larger tumor size, higher tumor grade, higher SEER stage, and chemotherapy were risk factors for CSS and OS, while surgery appeared to be a protective factor. However, only tumor grade, SEER stage, and receiving surgery remained independent prognostic factors in the multivariable Cox proportional hazard regression model. In addition, subgroup analyses indicated that surgery remained a protective factor for advanced renal LMS. However, there was no survival benefit for patients receiving chemotherapy. Conclusions: Primary renal LMS is an exceedingly rare entity with distinct clinicopathological features and a poor prognosis. A higher tumor grade and late stage may indicate a poor prognosis. Complete tumor resection remains to be the first treatment choice, while chemotherapy may be a palliative treatment for patients with advanced disease.

Interactions between Autophagy and DNA Viruses.

Autophagy is a catabolic biological process in the body. By targeting exogenous microorganisms and aged intracellular proteins and organelles and sending them to the lysosome for phagocytosis and degradation, autophagy contributes to energy recycling. When cells are stimulated by exogenous pathogenic microorganisms such as viruses, activation or inhibition of autophagy is often triggered. As autophagy has antiviral effects, many viruses may escape and resist the process by encoding viral proteins. At the same time, viruses can also use autophagy to enhance their replication or increase the persistence of latent infections. Here, we give a brief overview of autophagy and DNA viruses and comprehensively review the known interactions between human and animal DNA viruses and autophagy and the role and mechanisms of autophagy in viral DNA replication and DNA virus-induced innate and acquired immunity.

DEV induce autophagy via the endoplasmic reticulum stress related unfolded protein response.

Duck enteritis virus (DEV) can infect ducks, geese, and many other poultry species and leads to acute, septic and highly fatal infectious disease. Autophagy is an evolutionarily ancient pathway that plays an important role in many viral infections. We previously reported that DEV infection induces autophagy for its own benefit, but how this occurs remains unclear. In this study, endoplasmic reticulum (ER) stress was triggered by DEV infection, as demonstrated by the increased expression of the ER stress marker glucose-regulated protein 78 (GRP78) and the dilated morphology of the ER. Pathways associated with the unfolded protein response (UPR), including the PKR-like ER protein kinase (PERK) and inositol-requiring enzyme 1 (IRE1) pathways, but not the activating transcription factor 6 (ATF6) pathway, were activated in DEV-infected duck embryo fibroblast (DEF) cells. In addition, the knockdown of both PERK and IRE1 by small interfering RNAs (siRNAs) reduced the level of LC3-II and viral yields, which suggested that the PERK-eukaryotic initiation factor 2α (eIF2α) and IRE1-x-box protein1 (XBP1) pathways may contribute to DEV-induced autophagy. Collectively, these data offer new insight into the mechanisms of DEV -induced autophagy through activation of the ER stress-related UPR pathway.

Swine Leukocyte Antigen Diversity in Canadian Specific Pathogen-Free Yorkshire and Landrace Pigs.

The highly polymorphic swine major histocompatibility complex (MHC), termed swine leukocyte antigen (SLA), is associated with different levels of immunologic responses to infectious diseases, vaccines, and transplantation. Pig breeds with known SLA haplotypes are important genetic resources for biomedical research. Canadian Yorkshire and Landrace pigs represent the current specific pathogen-free (SPF) breeding stock maintained in the isolation environment at the Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences. In this study, we identified 61 alleles at five polymorphic SLA loci (SLA-1, SLA-2, SLA-3, DRB1, and DQB1) representing 17 class I haplotypes and 11 class II haplotypes using reverse transcription-polymerase chain reaction (RT-PCR) sequence-based typing and PCR-sequence specific primers methods in 367 Canadian SPF Yorkshire and Landrace pigs. The official designation of the alleles has been assigned by the SLA Nomenclature Committee of the International Society for Animal Genetics and released in updated Immuno Polymorphism Database-MHC SLA sequence database [Release 2.0.0.3 (2016-11-03)]. The submissions confirmed some unassigned alleles and standardized nomenclatures of many previously unconfirmed alleles in the GenBank database. Three class I haplotypes, Hp-37.0, 63.0, and 73.0, appeared to be novel and have not previously been reported in other pig populations. One crossover within the class I region and two between class I and class II regions were observed, resulting in three new recombinant haplotypes. The presence of the duplicated SLA-1 locus was confirmed in three class I haplotypes Hp-28.0, Hp-35.0, and Hp-63.0. Furthermore, we also analyzed the functional diversities of 19 identified frequent SLA class I molecules in this study and confirmed the existence of four supertypes using the MHCcluster method. These results will be useful for studying the adaptive immune response and immunological phenotypic differences in pigs, screening potential T-cell epitopes, and further developing the more effective vaccines.

Autophagy activated by duck enteritis virus infection positively affects its replication.

Duck enteritis virus (DEV) is an acute, septic, sexually transmitted disease that occurs in ducks, geese and other poultry. Autophagy is an evolutionarily ancient pathway that is important in many viral infections. Despite extensive study, the interplay between DEV and autophagy of host cells is not clearly understood. In this study, we found that DEV infection triggers autophagy in duck embryo fibroblast (DEF) cells, as demonstrated by the appearance of autophagosome-like double- or single-membrane vesicles in the cytoplasm of host cells and the number of GFP-LC3 dots. In addition, increased conversion of the autophagy marker protein LC3-I and LC3-II and decreased p62/SQSTM1 indicated complete autophagy flux. Heat-inactivated DEV infection did not induce autophagy, suggesting that the trigger of autophagy in DEF cells depended on DEV replication. When autophagy was pharmacologically inhibited by LY294002 or wortmannin, DEV replication decreased. The DEV offspring yield decreased when small interference RNA was used to interfere with autophagy related to the genes Beclin-1 and ATG5. In contrast, after treating DEF cells with rapamycin, an inducer of autophagy, DEV replication increased. These results indicated that DEV infection induced autophagy in DEF cells and autophagy facilitated DEV replication.