Autophagy plays an important role in cellular responses to pathogens. However, the impact of the autophagy machinery on classical swine fever virus (CSFV) infection is not yet confirmed. In this study, we showed that CSFV infection significantly increases the number of autophagy-like vesicles in the cytoplasm of host cells at the ultrastructural level. We also found the formation of 2 ubiquitin-like conjugation systems upon virus infection, including LC3-I/LC3-II conversion and ATG12–ATG5 conjugation, which are considered important indicators of autophagy. Meanwhile, high expression of ATG5 and BECN1 was detected in CSFV-infected cells; conversely, degradation of SQSTM1 was observed by immunoblotting, suggesting that CSFV infection triggered a complete autophagic response, most likely by the NS5A protein. Furthermore, by confocal immunofluorescence analysis, we discovered that both envelope protein E2 and nonstructural protein NS5A colocalized with LC3 and CD63 during CSFV infection. Examination by immunoelectron microscopy further confirmed the colocalization of both E2 and NS5A proteins with autophagosome-like vesicles, indicating that CSFV utilizes the membranes of these vesicles for replication. Finally, we demonstrated that alteration of cellular autophagy by autophagy regulators and shRNAs affects progeny virus production. Collectively, these findings provide strong evidence that CSFV infection needs an autophagy pathway to enhance viral replication and maturity in host cells.

Type 2 diabetes mellitus (T2DM) is closely correlated with chronic low-grade inflammation and gut dysbiosis.

As a component of the innate immune cell population, γδ T cells are involved in tumor immunosurveillance and host defense against viral invasion. In this study, we demonstrated a novel function of human γδ T cells as regulatory cells by detecting their suppressive effect on the proliferation of autologous naive CD4+ T cells. These regulatory γδ T cells (γδ Tregs) could be generated in vitro by stimulating with anti-TCRγδ in the presence of TGF-β and IL-2. Similar to CD4+Foxp3+ Tregs, γδ Tregs also expressed Foxp3. Additionally, they primarily belonged to the Vδ1 subset with a CD27+CD25high phenotype. Furthermore, these γδ Tregs showed an immunoregulatory activity mainly through cell-to-cell contact. Importantly, this γδ regulatory population decreased in the peripheral blood of systemic lupus erythematosus patients, suggesting a potential mechanism in understanding the pathogenesis of systemic lupus erythematosus.

Esophageal cancer (EC) is the seventh most common cancer worldwide with over 570,000 new cases annually. In China, the incidence of EC is particularly high where approximately 90% of cases are defined as esophageal squamous cell carcinoma (ESCC). Although various risk factors have been identified, the knowledge of genetic drivers for ESCC is still limited due to high mutational loading of the cancer and lack of appropriate EC models, resulting in inadequate treatment choices for EC patients. Currently, surgery, chemotherapy, radiation, and limited targeted therapy options can only bring dismal survival advantages; thus, the prognosis for ESCC is very poor. However, cancer immunotherapy has unleashed a new era of cancer treatment with extraordinary therapeutic benefits for cancer patients, including EC patients. This review discusses the latest understanding of the risk factors and clinical rational for EC treatment and provides accumulated information, which describes the ongoing development of immunotherapy for EC with a specific emphasis on ESCC, the most prevalent EC subtype in the Chinese population.

Background: Type 2 diabetes mellitus (T2DM) is closely associated with hyperglycemia, abnormal lipid profiles, chronic low-grade inflammation and gut dysbiosis. Dietary intervention plays a crucial role in the control of diabetes. Flaxseed oil (FO), a plant-derived omega-3 (ω-3) polyunsaturated fatty acids (PUFAs), is rich in α-linolenic acid (ALA) which has been proved to benefit for chronic metabolic disease. However, the exact effects of dietary FO on T2DM remains largely unclear.Methods: In the present study, SD rats were randomly allocated into four groups: pair-fed (PF) with corn oil (CO) group (PF/CO); DM with CO group (DM/CO); PF with FO group (PF/FO); DM with FO group (DM/FO). A diabetic rat model was generated by a single intraperitoneal injection of streptozotocin-nicotinamide (STZ-NA). After 5 weeks of intervention, rats were euthanized and associated indications were investigated.Results: Dietary FO significantly reduced fasting blood glucose (FBG), glycated hemoglobin (GHb), blood lipid, plasma lipopolysaccharide (LPS), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-6, IL-17A and malondialdehyde (MDA), compared to control group, respectively. Moreover, body mass (BM) and superoxide dismutase (SOD) in DM/FO group were dramatically increased respectively, compared with those in DM/CO group. But insulin (INS) and homeostasis model assessment of insulin resistance (HOMA-IR) remained no significant difference between DM/CO group and DM/FO group. Sequencing analysis of gut microbiota showed a reduction in the relative abundance of Firmicutes and Blautia, as well as a reduction in the ratio of Bacteroidetes-Firmicutes in DM/FO group compared to DM/CO group. An elevation in the relative abundance of Bacteroidetes and Alistipes were detected in DM/FO group. Acetic acid, propionic acid and butyric acid belonging to short chain fatty acids (SCFAs) as gut microbiota metabolites, were dramatically increased after FO intervention. Correlation analysis revealed that the relative abundance of Firmicutes and Blautia were positively correlated with IL-1β, TNF-α, IL-6, IL-17A or LPS, respectively. Additionally, Bacteroidetes and Alistipes were negatively correlated with LPS.Conclusions: Taken together, dietary FO ameliorated T2DM via suppressing inflammation and modulating gut microbiota, which may potentially contribute to dietary control of diabetes.

Programmed cell death protein 1 (PD-1) and its ligand PD-L1 have attracted wide attention from researchers in the field of immunotherapy. PD-1/PD-L1 have been shown to exist in many types of cells in addition to T lymphocytes, and studies have accordingly extended from their suppressive effect on T cell activation and function to examining their role in other cells. In this review, we summarize recent research on PD-1/PD-L1 in macrophages, with the aim of furthering our understanding of PD-1/PD-L1 and their detailed roles in macrophages. This information may provide additional insights for researchers, enrich the basic theory of anti-PD-1/PD-L1 immunotherapy, and thus ultimately benefit more patients.

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