Summary Aims The purpose of this study was to examine the effectiveness of beinaglutide on body weight, glycated haemoglobin (HbA 1c ), blood pressure and lipid profiles in patients with type 2 diabetes mellitus (T2DM) in a real‐world setting in China. Materials and methods This was a multicentre, observational, retrospective, open‐label study conducted in China. Data were collected from T2DM patients who started treatment with beinaglutide between 2017 and 2018. Results A total of 314 patients were included in the study. After 3 months of treatment with beinaglutide, there were significant reductions in body weight (−10.05 kg [95% confidence interval −9.29 to −10.80]), HbA 1c (−2.87% [−2.62 to −3.11]), 2‐h postprandial plasma glucose (−5.46 mmol L −1 [−4.96 to −5.95]) and fasting plasma glucose (−3.04 mmol L −1 [−2.78 to −3.31]) (all p < 0.0001). In addition, 84.96% and 72.18% of the patients achieved weight loss of ≥5% and ≥10%, respectively. Subgroup analyses showed that weight loss was significantly greater in patients with ≥28 kg m −2 of baseline body mass index and 0.60 mg of beinaglutide doses ( p = 0.007 and p < 0.0001, respectively). HbA 1c reductions were significantly greater in patients with ≥9.0% baseline HbA 1c and in those administered 0.40–0.48 mg of beinaglutide doses (all p < 0.0001). Weight loss at 3 months was positively correlated with baseline BMI and the dose of beinaglutide. Positive determinants for HbA 1c reduction after 3 months were baseline HbA 1c and the dose of beinaglutide. Conclusions These observational results confirmed the benefits of beinaglutide in weight loss and glycaemic control and support the use of beinaglutide as an effective treatment for T2DM.
Fusarium-derived mycotoxin deoxynivalenol (DON) usually induces diarrhea, vomiting and gastrointestinal inflammation. We studied the cytotoxic effect of DON on porcine small intestinal epithelium using the intestinal porcine epithelial cell line IPEC-J2. We screened out differentially expressed genes (DEGs) using RNA-seq and identified 320 upregulated genes and 160 downregulated genes. The enrichment pathways of these DEGs focused on immune-related pathways. DON induced proinflammatory gene expression, including cytokines, chemokines and other inflammation-related genes. DON increased IL1A, IL6 and TNF-α release and DON activated the phosphorylation of extracellular signal-regulated kinase-1 and-2 (ERK1/2), JUN N-terminal kinase (JNK) and p38 MAPK. A p38 inhibitor attenuated DON-induced IL6, TNF-α, CXCL2, CXCL8, IL12A, IL1A, CCL20, CCL4 and IL15 production, while an ERK1/2 inhibitor had only a small inhibitory effect on IL15 and IL6. An inhibitor of p38 MAPK decreased the release of IL1A, IL6 and TNF-α and an inhibitor of ERK1/2 partly attenuated protein levels of IL6. These data demonstrate that DON induces proinflammatory factor production in IPEC-J2 cells by activating p38 and ERK1/2.
The prevalence of antimicrobial resistance in zoonotic Salmonella is a significant ongoing concern over the world. Several reports have investigated the prevalence of Salmonella infections in the farm animals in China; however, there is only limited knowledge about the Salmonella cross-contamination in the slaughterhouses. Moreover, the application of genomic approaches for understanding the cross-contamination in the food-animal slaughterhouses is still in its infancy in China. In the present study, we have isolated 105 Salmonella strains from pig carcasses and environment samples collected from four independent slaughterhouses in Jiangsu, China. All the Salmonella isolates were subjected to whole genome sequencing, bioinformatics analysis for serovar predictions, multi-locus sequence types, antimicrobial resistance genes, and plasmid types by using the in-house Galaxy platform. The antimicrobial resistance of Salmonella isolates was determined using a minimal inhibitory concentration assay with 14 antimicrobials. We found that the predominant serovar and serogroup was S. Derby and O:4(B), with a prevalence of 41.9 and 55%, respectively. All the isolates were multidrug-resistant and the highest resistance was observed against antimicrobials tetracycline (95.4%) and trimethoprim and sulfamethoxazole (90.9%). Additionally, the colistin-resistant determinant mcr-1 gene was detected in five (4.8%) strains. Our study demonstrated the prevalence of antimicrobial resistance in Salmonella strains isolated from pig slaughterhouses in China and suggested that the genomic platform can serve as routine surveillance along with the food-chain investigation.
The Chinese forest musk deer ( Moschus berezovskii ; FMD) is an artiodactyl mammal and is both economically valuable and highly endangered. To investigate the genetic mechanisms of musk secretion and adaptive immunity in FMD, we compared its genome to nine other artiodactyl genomes. Comparative genomics demonstrated that eight positively selected genes (PSGs) in FMD were annotated in three KEGG pathways that were related to metabolic and synthetic activity of musk, similar to previous transcriptome studies. Functional enrichment analysis indicated that many PSGs were involved in the regulation of immune system processes, implying important reorganization of the immune system in FMD. FMD-specific missense mutations were found in two PSGs ( MHC class II antigen DRA and ADA ) that were classified as deleterious by PolyPhen-2, possibly contributing to immune adaptation to infectious diseases. Functional assessment showed that the FMD-specific mutation enhanced the ADA activity, which was likely to strengthen the immune defense against pathogenic invasion. Single nucleotide polymorphism-based inference showed the recent demographic trajectory for FMD. Our data and findings provide valuable genomic resources not only for studying the genetic mechanisms of musk secretion and adaptive immunity, but also for facilitating more effective management of the captive breeding programs for this endangered species.
Raptors are carnivorous birds including accipitrids (Accipitridae, Accipitriformes) and owls (Strigiformes), which are diurnal and nocturnal, respectively. To examine the evolutionary basis of adaptations to different light cycles and hunting behavior between accipitrids and owls, we de novo assembled besra (Accipiter virgatus, Accipitridae, Accipitriformes) and oriental scops owl (Otus sunia, Strigidae, Strigiformes) draft genomes. Comparative genomics demonstrated four PSGs (positively selected genes) (XRCC5, PRIMPOL, MDM2, and SIRT1) related to the response to ultraviolet (UV) radiation in accipitrids, and one PSG (ALCAM) associated with retina development in owls, which was consistent with their respective diurnal/nocturnal predatory lifestyles. We identified five accipitrid-specific and two owl-specific missense mutations and most of which were predicted to affect the protein function by PolyPhen-2. Genome comparison showed the diversification of raptor olfactory receptor repertoires, which may reflect an important role of olfaction in their predatory lifestyle. Comparison of TAS2R gene (i.e. linked to tasting bitterness) number in birds with different dietary lifestyles suggested that dietary toxins were a major selective force shaping the diversity of TAS2R repertoires. Fewer TAS2R genes in raptors reflected their carnivorous diet, since animal tissues are less likely to contain toxins than plant material. Our data and findings provide valuable genomic resources for studying the genetic mechanisms of raptors’ environmental adaptation, particularly olfaction, nocturnality and response to UV radiation.
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