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The reduction of extracellular matrix production and the promotion of endochondral osteogenesis by Chsy1 knockdown could be rescued by BMP signaling inhibitor LDN193189. Furthermore, the abnormally enhanced BMP signaling and the high expression of OA biomarker Mmp3 in primary cells of OA rats could be rescued by either LDN193189 or Chsy1 overexpression. These results implicate a role for Chsy1 in regulating extracellular matrix production and endochondral osteogenesis through BMP signaling; and a lack of Chsy1 could aggravate the cartilage damage of osteoarthritis.Zinc finger CCHC-type containing protein 3 (ZCCHC3) acts as an antiviral factor that interacts with RIG-I and cGAS to modulate innate signaling against viral infections. Here, we investigated the role of porcine ZCCHC3 during pseudorabies virus (PRV) proliferation. We found that porcine ZCCHC3 plays an inhibitory role in the proliferation of PRV by regulating cellular innate immune responses. Further, overexpression of ZCCHC3 inhibited gB protein levels and viral titers, whereas knockdown of ZCCHC3 promoted viral growth. ZCCHC3 overexpression increased IFN-β expression to upregulate downstream gene expression, thus leading to the suppression of viral replication. However, PRV infection reduced the endogenous expression of ZCCHC3 in permissive cells. Importantly, PRV-encoded UL13 and UL24 proteins were identified to inhibit the expression of ZCCHC3, thus antagonizing its antiviral effect. Collectively, our data underscore the important role of ZCCHC3 against PRV infection and promote understandings of viral proteins in PRV pathogenesis.

Obesity is a chronic complex disease with great prevalence for children all over the world. Characterized for low-grade inflammation associated with several comorbidities such as resistance and type 2 diabetes mellitus (T2DM).

To investigate whether genetic variants in IL10, IL1RL1, IL1B, IRF4, TNF, IL6, and IL33 genes are associated with being overweight in children.

We performed the genotyping of 1004 children using Illumina 2.5 Human Omni bead chip, and association analysis on the genetic variants and the overweight through logistic regression adjusted for sex, age and components principal.

Of the seven genes analyzed, 16 SNVs significantly associated. Eleven variants in IL1RL1, two in IL1B and one in IRF4 genes increased overweight risk and two SNVs in IL1RL1 were associated with protection against overweight. The rs2287047-A was negatively associated (OR 0.66, CI95% 0.19-0.45) and had a reduced IL1RL1 expression in whole blood (p 0.033) in silico eQTL. The rs12203592-T, in IRF4, was positively associated with being overweight, and led to an increased gene expression in whole blood (p<0.001) and adipose tissue (p<0.001).

These results suggest that genetic variants in inflammatory genes may play an important role in the development of overweight in children.

These results suggest that genetic variants in inflammatory genes may play an important role in the development of overweight in children.Sheath Blight (SB) disease in rice is caused by the infection from the fungal pathogen Rhizoctonia solani (R. solani). SB is one of the most severe rice diseases that can cause up to 50% yield losses in rice. Naturally occurring rice varieties resistant to SB have not been reported yet. We have performed a Time-Series RNA-Seq analysis on a widely cultivated rice variety BPT-5204 for identifying transcriptome level response signatures during R. solani infection at 1st, 2nd and 5th day post infection (dpi). In total, 428, 3225 and 1225 genes were differentially expressed in the treated rice plants on 1, 2 and 5 dpi, respectively. GO and KEGG enrichment analysis identified significant processes and pathways differentially altered in the rice plants during the fungal infection. Machine learning and network based integrative approach was used to construct rice Transcriptional Regulatory Networks (TRNs) for the three time points. TRN analysis identified SUB1B, MYB30 and CCA1 as important regulatory hub transcription factors in rice during R. solani infection. Jasmonic acid, salicylic acid, ethylene biogenesis and signaling were induced on infection. SAR was up regulated, while photosynthesis and carbon fixation processes were significantly down regulated. Involvement of MAPK, CYPs, peroxidase, PAL, chitinase genes were also observed in response to the fungal infection. The integrative analysis identified seven putative SB resistance genes differentially regulated in rice during R. solani infection.Acrylamide is a potent neurotoxin produced during industrial production or food processing at high temperatures, and its effect on glycolytic processes may be critical in triggering neurotoxicity. Our work investigated the neurotoxic effects of acrylamide based on glycolysis using immortalized mouse microglia cell line BV2. The results showed that 1.5 mM acrylamide significantly inhibited the expression and activity of triphosphate isomerase and 3-phosphoglyceraldehyde dehydrogenase. Moreover, acrylamide limited the expression of pyruvate kinase and the decrease of pyruvate and lactate content of glycolysis products. In addition, acrylamide could increase intracellular methylglyoxal content and further affect its detoxification system. Not only that, subsequent cellular responses resulting from methylglyoxal accumulation, such as oxidative stress, activation of ERK, upregulation of NF-κB inflammatory signaling pathway, and elevated pro-inflammatory factor TNF-α, were found in the acrylamide-treated cell model. Therefore, we suggest that acrylamide's perturbation of the glycolytic process leads to methylglyoxal accumulation, which may be responsible for its key to neurotoxicity.Nonalcoholic fatty liver disease (NAFLD) is a complex pathogenesis of liver disease combined with liver inflammation and gut microbiota dysbiosis. Tectorigenin (Tg) is derived from many plants with excellent anti-inflammation activity. However, the beneficial effect of Tg on NAFLD associated with gut microbiota remained unclear. This study aimed to investigate the underlying beneficial effect of Tg on NAFLD in high-fat diet (HFD)-fed mice. Results showed that Tg alleviated lipid profiles and liver steatosis, and reduced serum lipopolysaccharide (LPS) and total bile acid (TBA) levels. RHPS 4 mw Besides, RT-qPCR and Western blot suggested that Tg alleviated hepatic lipid accumulation through inhibiting the lipogenesis and promoting the lipolysis, prevented gut-derived LPS-induced liver inflammatory via restoring intestinal barrier and restraining pro-inflammatory cytokines release, meanwhile, promoted the BA circulation via activating BA receptor and promoting BA synthesis. Moreover, Tg reverted the HFD-induced gut microbial dysbiosis by promoting the growth of beneficial Akkermansia, and inhibiting the proportions of harmful microbes, including Blautia, Lachnoclostridium, Lachnospiraceae_UCG-006, Roseburia, Romboutsia and Faecalibaculum, which were highly correlated with NAFLD-related parameters in serum and liver. Thus, Tg could attenuate NAFLD through mediating the liver-gut axis, and it could be used as a dietary supplement for NAFLD treatment via its anti-inflammatory and prebiotic effects.

Roux-en Y gastric bypass surgery (GB) and sleeve gastrectomy (SG) alter prandial glucose metabolism, producing lower nadir glucose values and predisposing susceptible individuals to prandial hypoglycemia. The glycemic phenotype of GB or SG is associated with prandial hyperinsulinemia and hyperglucagonemia along with an increased influx of ingested glucose. Following insulin-induced hypoglycemia, glucagon is the most important stimulus for hepatic glucose production (HGP). It is unclear whether prandial hyperglucagonemia after GB or SG changes HGP under hyperinsulinemic hypoglycemia conditions. This study examined the hypothesis that prandial glucose production is reduced after GB and SG during hypoglycemia.

Glucose kinetics and islet-cell and gut hormone secretion during hyperinsulinemic (120mU.m

.min

) hypoglycemic clamp (~3.2mM) were measured before and after mixed meal ingestion in 9 non-diabetic subjects with GB, 7 with SG, and 5 matched non-operated controls (CN).

Systemic appearance of ingested lycemia in this population.Human infertilities are disorders that afflict many people all over the world. Both male and female reproductive systems must work together in a precise and coordinated manner and infertility has a wide range of problems for this system. Recent advances in nanomedicine immensely helped design the diagnostic and therapeutic approaches to alleviate human infertility in both sexes. Nanoscience has recently been used by researchers to increase the detection limit of infertility-related biomarkers via fabricating sensitive nanobiosensors for detecting follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-müllerian hormone (AMH), pregnancy-associated plasma protein-A (PAPP-A), progesterone, and testosterone. At the same time, a variety of nanostructures, including magnetic nanoparticles (i.e., zinc nanoparticles, cerium nanoparticles, gold nanoparticles, silver nanoparticles), nano-vitamins, extracellular vesicles, and spermbots, have shown promising outcomes in the treatment of human infertilities. Despite recent advancements, some nanostructures might have toxic effects on cells, especially germ cells, and must be optimized with the right ingredients, such as antioxidants, nutrients, and vitamins, to obtain the right strategy to treat and detect human infertilities. This review presents recent developments in nanotechnology regarding impairments still faced by human infertility. New perspectives for further use of nanotechnology in reproductive medicine studies are also discussed. In conclusion, nanotechnology, as a tool for reproductive medicine, has been considered to help overcome current impairments.Engineered heart muscle (EHM) can be implanted epicardially to remuscularize the failing heart. In case of a severely scarred ventricle, excision of scar followed by transmural heart wall replacement may be a more desirable application. Accordingly, we tested the hypothesis that allograft (rat) and xenograft (human) EHM can also be administered as transmural heart wall replacement in a heterotopic, volume-loaded heart transplantation model. We first established a novel rat model model to test surgical transmural left heart wall repair. Subsequently and in continuation of our previous allograft studies, we tested outcome after implantation of contractile engineered heart muscle (EHM) and non-contractile engineered connective tissue (ECT) as well as engineered mesenchymal tissue (EMT) allografts as transmural heart wall replacement. Finally, proof-of-concept for the application of human EHM was obtained in an athymic nude rat model. Only in case of EHM implantation, remuscularization of the surgically created transmural defect was observed with palpable graft vascularization. Taken together, feasibility of transmural heart repair using bioengineered myocardial grafts could be demonstrated in a novel rat model of heterotopic heart transplantation.Good mothering has profound impact on both the mother's and the young's well-being. Consequently, experiencing inadequate maternal care - or even neglect - in the first stages of life is a major risk factor for the development of psychiatric disorders, and even for poor parenting towards the future offspring. Thus, understanding the neurobiological basis of maternal neglect becomes crucial. Along with other neurotransmitters and neuropeptides, oxytocin (OXT) has long been known as one of the main modulators of maternal behavior. In rodents, disruptions of central OXT transmission have been associated with poor maternal responses, like impaired onset of nursing behaviors, and reduced care and defense of the pups. Importantly, such behavioral and molecular deficits can be transmitted through generations, creating a vicious circle of low-quality maternal behavior. Similarly, evidence from human studies shows that OXT signaling is defective in conditions of inadequate mothering and child neglect. On those premises, this review aims at providing a comprehensive overview of animal and human studies linking perturbed OXT transmission to poor maternal behavior.

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