Recombinant porcine interferon delta 8 inhibits swine acute diarrhoea syndrome coronavirus infection in vitro and in vivo.

Swine acute diarrhoea syndrome coronavirus (SADS-CoV), which originates from zoonotic transmission of bat coronaviruses in the HKU2 lineage, causes severe illness in pigs and carries a high risk of spreading to humans. At present, there are no licenced therapeutics for the treatment of SADS-CoV. In this study, we examined the effectiveness of recombinant porcine interferon delta 8 (IFN-δ8) against SADS-CoV both in vitro and in vivo. In vitro experiments showed that IFN-δ8 inhibited SADS-CoV proliferation in a concentration-dependent manner, with complete inhibition occurring at a concentration of 5 µg/mL. In vivo experiments demonstrated that two 50 µg/kg doses of IFN-δ8 injected intraperitoneally protected piglets against lethal challenge, blocked viral shedding, attenuated intestinal damage, and decreased the viral load in the jejunum and ileum. Further findings suggested that IFN-δ8 inhibited SADS-CoV infection by increasing the expression of IFN-stimulated genes. These results indicate that IFN-δ8 shows promise as a biological macromolecule drug against SADS-CoV infection.

Adverse Weather Target Detection Algorithm Based on Adaptive Color Levels and Improved YOLOv5.

With the continuous development of artificial intelligence and computer vision technology, autonomous vehicles have developed rapidly. Although self-driving vehicles have achieved good results in normal environments, driving in adverse weather can still pose a challenge to driving safety. To improve the detection ability of self-driving vehicles in harsh environments, we first construct a new color levels offset compensation model to perform adaptive color levels correction on images, which can effectively improve the clarity of targets in adverse weather and facilitate the detection and recognition of targets. Then, we compare several common one-stage target detection algorithms and improve on the best-performing YOLOv5 algorithm. We optimize the parameters of the Backbone of the YOLOv5 algorithm by increasing the number of model parameters and incorporating the Transformer and CBAM into the YOLOv5 algorithm. At the same time, we use the loss function of EIOU to replace the loss function of the original CIOU. Finally, through the ablation experiment comparison, the improved algorithm improves the detection rate of the targets, with the mAP reaching 94.7% and the FPS being 199.86.

Re-emergence of severe acute diarrhea syndrome coronavirus (SADS-CoV) in Henan, central China, 2023.

Severe acute diarrhea syndrome coronavirus (SADS-CoV) was first detected in Guangdong province of China in 2017. And yet from May 2021 to Jun 2023, there were no SADS-CoV outbreaks. In this study, we reported the recent outbreak of SADS-CoV in China on Jun 2023. Phylogenetic analysis showed the novel strain was derived from the ongoing transmission and evolution of SADS-CoV in China, rather than a separate cross-species transmission from bats. Also, the novel strain was found to participate in a recombant event as a minor parent and a missing base in the genome was discovered indicating an novel evolutionary pathway. Through virulence assays in piglets, we further determined that novel strain (SADS-CoV/HNNY/2023) was a highly virulent SADS-CoV strain with typical clinical symptoms: acute diarrhea, vomiting, rapid weight loss. Therefore, the re-emergence of SADS-CoV strains should be brought to people's attention.

Recombinant porcine interferon δ8 inhibited porcine deltacoronavirus infection in vitro and in vivo.

Porcine deltacoronavirus (PDCoV) poses a significant threat to both the pig industry and public safety, and has recently been identified in humans. Currently, there are no commercially available vaccines or antiviral treatments for PDCoV. In this study, recombinant porcine interferon δ8 (rINF-δ8) expressed by the HEK 293F expression system was used to evaluated its antiviral activity against PDCoV both in vitro and in vivo. Results demonstrated that rIFN-δ8 displayed non-toxic to ST cells and primary PAMs, and effectively inhibited PDCoV replication in a dose-dependent manner in vitro, with complete suppression of virus replication at a concentration of 2 µg/ml. Treatment of piglets with two doses of 25 µg/kg of rIFN-δ8 reduced clinical symptoms, decreased virus shedding, alleviated intestinal damage, and lowered the viral load in the jejunum and ileum. Furthermore, the levels of interferon-stimulated genes (ISGs) such as Viper, Mx1, ISG15, IFIT1, OSA, and IFITM1 were significantly increased both in vitro and in vivo, with elevated ISG levels sustained for at least 3 days in vivo. These findings suggest that rIFN-δ8 has the potential to serve as an effective antiviral agent for preventing PDCoV in pigs in the future.

Curcumin supplementation alleviates hepatic fat content associated with modulation of gut microbiota-dependent bile acid metabolism in patients with nonalcoholic simple fatty liver disease: a randomized controlled trial.

BACKGROUND: Our previous studies showed that curcumin prevented hepatic steatosis in animal models. OBJECTIVES: This study aimed to assess the effects of curcumin on hepatic fat content, body composition, and gut microbiota-dependent bile acid (BA) metabolism in patients with nonalcoholic simple fatty liver (NASFL). METHODS: In a 24-wk double-blind randomized trial, 80 patients with NASFL received 500 mg/d curcumin or placebo. Hepatic fat content was measured using FibroTouch-based controlled attenuation parameters (CAPs). Microbial composition and BA metabolites were analyzed using 16S rRNA sequencing and metabolomics. RESULTS: Curcumin consumption significantly reduced CAP value compared with placebo (-17.5 dB/m; 95% confidence interval [CI]: -27.1, -7.8 dB/m; P < 0.001). This corresponded to reduction in weight (-2.6 kg; 95% CI: -4.4, -0.8 kg; P < 0.001) and BMI (-1.0 kg/m2; 95% CI: -2.0, -0.1 kg/m2; P = 0.032) compared with placebo group. Additionally, free fatty acid (-0.12 mmol/L; 95% CI: -0.20, -0.04 mmol/L; P = 0.004), triglycerides (-0.29 mmol/L; 95% CI: -0.41, -0.14 mmol/L; P < 0.001), fasting blood glucose (-0.06 mmol/L; 95% CI: -0.12, -0.01 mmol/L; P = 0.038), hemoglobin A1c (-0.06%; 95% CI: -0.33, -0.01%; P = 0.019), and insulin (-4.94 µU/L; 95% CI: -9.73, -0.15 µU/L; P = 0.043) showed significant reductions in the curcumin group compared with placebo group. Gut microbiota analysis indicated that curcumin significantly decreased Firmicutes to Bacteroidetes ratio and significantly increased Bacteroides abundance. Serum levels of deoxycholic acid, the most potent activator of Takeda G protein-coupled receptor 5 (TGR5), were significantly elevated after curcumin intervention (37.5 ng/mL; 95% CI: 6.7, 68.4 ng/mL; P = 0.018). Curcumin treatment also increased TGR5 expression in peripheral blood mononuclear cells and serum glucagon-like peptide-1 levels (0.73 ng/mL; 95% CI: 0.16, 1.30 ng/mL; P = 0.012). CONCLUSIONS: Improvements in gut microbiota-dependent BA metabolism and TGR5 activation after 24-wk curcumin intervention were associated with a reduction in hepatic fat content in patients with NASFL, providing evidence that curcumin is a potential nutritional therapy for NASFL. The trial was registered at www.chictr.org.cn as ChiCTR2200058052.

Capsule neural tensor networks with multi-aspect information for Few-shot Knowledge Graph Completion.

Few-shot Knowledge Graph Completion (FKGC) has recently attracted significant research interest due to its ability to expand few-shot relation coverage in Knowledge Graphs. Prevailing FKGC approaches focus on exploiting the one-hop neighbor information of entities to enhance few-shot relation embedding. However, these methods select one-hop neighbors randomly and neglect the rich multi-aspect information of entities. Although some methods have attempted to leverage Long Short-Term Memory (LSTM) to learn few-shot relation embedding, they are sensitive to the input order. To address these limitations, we propose the Capsule Neural Tensor Networks with Multi-Aspect Information approach (short for InforMix-FKGC). InforMix-FKGC employs a one-hop neighbor selection strategy based on how valuable they are and encodes multi-aspect information of entities, including one-hop neighbors, attributes and literal description. Then, a capsule network is responsible for integrating the support set and deriving few-shot relation embedding. Moreover, a neural tensor network is used to match the query set with the support set. In this way, InforMix-FKGC can learn few-shot relation embedding more precisely so as to enhance the accuracy of FKGC. Extensive experiments on the NELL-One and Wiki-One datasets demonstrate that InforMix-FKGC significantly outperforms ten state-of-the-art methods in terms of Mean Reciprocal Rank and Hits@K.

Bisphenol A induced hepatic steatosis by disturbing bile acid metabolism and FXR/TGR5 signaling pathways via remodeling the gut microbiota in CD-1 mice.

Dysregulation of gut microbiota-mediated bile acid (BA) metabolism plays an important role in the pathogenesis of hepatic steatosis and nonalcoholic fatty liver disease (NAFLD). Our previous studies found that bisphenol A (BPA) exposure induced hepatic steatosis and gut microbiota dysbiosis. However, whether the gut microbiota-dependent BA metabolism alterations were involved in BPA-induced hepatic steatosis remains unclear. Therefore, we explored the gut microbiota-related metabolic mechanisms of hepatic steatosis induced by BPA. Male CD-1 mice were exposed to low-dose BPA (50 µg/kg/day) for 6 months. Fecal microbiota transplantation (FMT) and broad-spectrum antibiotic cocktail (ABX) treatment were further adopted to test the role of gut microbiota in the adverse effects of BPA. We found that BPA induced hepatic steatosis in mice. Additionally, 16S rRNA gene sequencing showed that BPA reduced the relative abundance of Bacteroides, Parabacteroides and Akkermansia, which are associated with BA metabolism. Metabolomic analyses demonstrated that BPA significantly altered the ratio of conjugated to unconjugated BAs and increased the total level of taurine-α/ß-muricholic acid while decreasing the level of chenodeoxycholic acid, thus inhibiting the activation of special receptors, including farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), in the ileum and liver. The inhibition of FXR reduced short heterodimer partner and subsequently induced cholesterol 7α-hydroxylase and sterol regulatory element-binding protein-1c expression, which is related to hepatic BA synthesis and lipogenesis, eventually leading to liver cholestasis and steatosis. Furthermore, we found that mice that received FMT from BPA-exposed mice developed hepatic steatosis, and the influences of BPA on hepatic steatosis and FXR/TGR5 signaling pathways could be eliminated by ABX treatment, confirming the role of gut microbiota in BPA effects. Collectively, our study illustrates that suppressed microbiota-BA-FXR/TGR signaling pathways may be a potential mechanism for hepatic steatosis induced by BPA, providing a new target for the prevention of BPA-induced NAFLD.

VEGF-conjugated alginate hydrogel prompt angiogenesis and improve pancreatic islet engraftment and function in type 1 diabetes.

Type 1 diabetes was a life-long disease that affected numerous people around the world. Insulin therapy has its limitations that may involve hyperglycemia and heavy burden of patient by repeated dose. Islet transplantation emerged as a promising approach to reach periodical reverse of diabetes, however, transplanted islets suffer from foreign body reaction and lack of nutrition and oxygen supply, especially in the blood-vessel-shortage subcutaneous site which was preferred by patient and surgeon. In this study, we designed and synthesized a vascular endothelial growth factor (VEGF) conjugated alginate material to encapsulate the transplanted islets via 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) reaction, and successful conjugation was confirmed by Nuclear Magnetic Resonance H1 spectrum. The best VEGF concentration (100ng/ml) was determined by the combined studies of the mechanical property and endothelial cell growth assay. In vivo study, conjugated VEGF on alginate exhibited sustained promoting angiogenesis property after subcutaneous transplantation by histology study and islets encapsulated in this material achieved long term therapeutic effect (up to 50days) in the diabetic mice model. In conclusion, this study establishes a simple biomaterial strategy for islet transplantation to enhance islet survival and function, which could be a feasible therapeutic alternative for type 1 diabetes.