Introduction Severe obesity often present with nonalcoholic fatty liver disease (NAFLD) and obstructive sleep apnea (OSA). Emerging researches suggest OSA plays an important role in NAFLD development and progression while the relationship between OSA and NAFLD is still conflicting . The interaction of OSA and NAFLD should be further evaluated as obesity surges. The purpose of this study was to assess the prevalence of OSA and NAFLD in patients with obesity undergoing bariatric surgery, and evaluate the association between OSA and severity of NAFLD. Methods 141 patients with severe obesity undergoing preoperative polysomnography and intraoperative liver biopsy during bariatric surgery was investigated. Clinical, anthropometric variables, liver enzymes, fasting blood glucose, fasting serum insulin, and homeostasis model assessment (HOMA-IR) were measured. The severity of NAFLD was assessed by degree of steatosis, ballooning, intralobular inflammation and NAFLD activity score (NAS). The diagnosis and severity assessment of OSA was based on an apnea/hypopnea index (AHI). Results OSA was diagnosed in 127 (90.07%), NAFLD in 124 (87.94%), and non-alcoholic steatohepatitis (NASH) in 72 (51.06%) patients. There was a statistically difference in body mass index (BMI), waist circumstance, neck circumstance, high-density lipoprotein-cholesterol (HDL), fasting insulin, and HOMA-IR among the three groups divided by the severity of AHI. In addition, the distribution of hepatic steatosis grades among the three groups was statistically different (P=0.025). AHI was significantly associated with HOMA-IR and hepatic steatosis when assessing the association between OSA parameters and liver histology in NAFLD(P< 0.05). Patients with steatosis of grade 1-3 had significantly elevated aspartate aminotransferase(AST), alanine aminotransferase(ALT), gamma glutamyl transferase (GGT),triglycerides (TG), fasting insulin, fasting glucose, HOMA-IR, and AHI compared with the patients with steatosis of grade 0. In a multivariable logistic analysis, the positive association between AHI and hepatic steatosis attenuated after adjusting for HOMA-IR. Conclusion Prevalence of OSA and NAFLD was high in patients with obesity eligible for bariatric procedures. HOMA-IR, but not AHI, was an independent risk factor for hepatic steatosis in this population.
Wiedemann-Rautenstrauch syndrome (WDRTS) is an extremely rare autosomal recessive neonatal disorder. Currently, over 50 cases with variable phenotypes of WDRTS have been reported. In our cohort of prenatal and postnatal growth retardation, a female proband was found to have general growth retardation, neurocutaneous syndrome, and anemia. Karyotype test and array-CGH detected no obvious chromosomal aberrations. Trio-based whole-exome sequencing (Trio-WES) identified bi-allelic compound mutations in the coding sequence (CDS) of POLR3A gene (c.3342C > T, p.Ser1114 = and c.3718G > A, p.Gly1240Ser). For the mild anemia phenotype, the underlying causal genetic factors could be attributed to the compound heterozygous mutations in FANCA gene (c.2832dup, p.Ala945CysfsTer6 and c.1902 T > G, p.Asp634Glu). Mini-gene reporter assays revealed that the synonymous variant of POLR3A and the missense variant of FANCA could affect pre-mRNA splicing of each gene. For POLR3A, the synonymous mutation (c.3342C > T, p.Ser1114=) generated three types of aberrant isoforms. Therefore, the female patient was finally diagnosed as WDRTS caused by POLR3A. For FANCA, the missense variant (c.1902 T > G, p.Asp634Glu) disrupted the normal splicing between exon 21 and 22, and produced two types of abnormal isoforms, one carrying the 1902G and the other spliced between exon 21 and 23 to exclude exon 22. Network analysis showed that POLR3A and FANCA could be STRINGed, indicating both proteins might collaborate for some unknown functions. Current investigation would broaden the knowledge for clinicians and genetic counselors and remind them to interpret those synonymous or predicted "benign" variants more carefully.
Electroencephalography (EEG) is an indispensable tool in epilepsy, sleep, and behavioral research. In rodents, EEG recordings are typically performed with metal electrodes that traverse the skull into the epidural space. In addition to requiring major surgery, intracranial EEG is difficult to perform for more than a few electrodes, is time-intensive, and confounds experiments studying traumatic brain injury. Here, we describe an open-source cost-effective refinement of this technique for chronic mouse EEG recording. Our alternative two-channel (EEG2) and sixteen-channel high-density EEG (HdEEG) arrays use electrodes made of the novel, flexible 2D nanomaterial titanium carbide (Ti 3 C 2 T x ) MXene. The MXene electrodes are placed on the surface of the intact skull and establish an electrical connection without conductive gel or paste. Fabrication and implantation times of MXene EEG electrodes are significantly shorter than the standard approach, and recorded resting baseline and epileptiform EEG waveforms are similar to those obtained with traditional epidural electrodes. Applying HdEEG to a mild traumatic brain injury (mTBI) model in mice of both sexes revealed that mTBI significantly increased spike–wave discharge (SWD) preictal network connectivity with frequencies of interest in the β-spectral band (12–30 Hz). These findings indicate that the fabrication of MXene electrode arrays is a cost-effective, efficient technology for multichannel EEG recording in mice that obviates the need for skull-penetrating surgery. Moreover, increased preictal β-frequency network connectivity may contribute to the development of early post-mTBI SWDs.
ABSTRACT The red‐eared slider ( Trachemys scripta elegans ) can adapt to brackish water, which can endanger its biodiversity. Spermatogonial stem cells (SSCs) are essential for establishing and maintaining spermatogenesis and are regulated by the gut–brain–gonad axis. However, the effect of salinity on SSCs is unclear. We investigated the influence of salinity stress on the composition of the gut microbiota in T. s. elegans to determine whether it regulates SSC self‐renewal and differentiation via the gut–brain–gonad axis. Three salinity groups (0‰, 5‰, and 10‰) were used in this study, and samples were obtained after 6 months of feeding. The mRNA expression of self‐renewing genes (GFRα‐1, RAS, and ERK) and meiotic initiation genes (RARα, NRG3, and ERBB4) in SSCs decreased with increasing salinity, indicating that salinity affects renewal and differentiation. In addition, harmful bacteria such as Enterococcus and Clostridium were increased in the S10 group, and lower levels of g_norank_f_Eubacteriaceae were negatively associated with γ‐aminobutyric acid (GABA), whereas higher Turicibacter levels were positively associated with GABA levels, resulting in increased GABA content in the S5 group. The results show that salinity affects the secretion of neurotransmitters in the brain and negatively regulates the synthesis of reproductive hormones by changing the composition of intestinal microorganisms and metabolites, which affect SSC function. In conclusion, salinity influences the reproductive ability of T. s. elegans through the gut–brain–gonad axis. This study provides a new perspective for understanding the adaptation of T. s. elegans to brackish water.
Cellular immunotherapy has become a potential therapeutic method for different diseases.Herein, we reported clinical trial results of Cytokine-induced killer (CIK) cells used for patients with hepatitis B, cirrhosis and liver cancers from 2000 to 2015.Results showed CIK cell therapeutic effects were closely positively associated with CIK cell numbers, treated times and HBV genotypes.Different stages of HBV patients treated with > 10 10 CIK cells per time for more than ten times exhibited remarkable decrease of HBV DNA numbers (P < 0.01), ALT and AST gradually recovered to normal scope, cytokine factors such as IFN-g, IL-1b, IL-2, IL-4, IL-6, IL-10, IL-22 and IL-27 exhibited obvious increase, lifespan of patients with cirrhosis and hepatocellular carcinoma were extended, and that all the patients felt better in sleep, diet and pain during the period of CIK therapy.In conclusion, CIK cell therapy is a good alternative therapeutic method and can be effectively used for treatment of different stages of HBV patients.
Freshwater acidification (FA) has become a global environmental problem, posing a potential threat to freshwater ecosystems. The gut microbiota plays a crucial role in the host’s response and adaptation to new environments. In this study, we investigated the changes in microbial communities in Red-eared slider (Trachemys scripta elegans) under acidic conditions to reveal the ecological impacts of acidification on freshwater turtles. The results showed that there were significant differences in β-diversity (p = 0.03), while there were no significant differences in the α-diversity of gut microbiota in T. s. elegans between the different levels of acidification (pH of 5.5, 6.5, 7.5). Both the Gut Microbiome Health Index (GMHI) and the Microbial Dysbiosis Index (MDI) exhibited significant differences when comparing environments with a pH of 5.5 to those with a pH of 6.5 (p < 0.01). A comparative analysis between pH levels of 5.5 and 6.5 also revealed substantial differences (p < 0.01). Likewise, a comparative analysis between pH levels of 6.5 and 7.5 also revealed substantial differences (p < 0.01). At the phylum level, Firmicutes, Fusobacteria, and Bacteroidota formed a major part of the gut microbial community, Fusobacteria showed significant differences in different acidity environments (p = 0.03). At the genus level, Cetobacterium, Turicibacter, unclassified Eubacteriaceae, and Anaerorhabdus_furcosa_group showed significant differences in different acidity environments. The pH reduced interactivity in the gut microbiota of T. s. elegans. In addition, LEfSe analysis and functional prediction revealed that the potentially_pathogenic and stress_tolerant functional characteristics also showed significant differences in different acidity environments. The findings underscore the pivotal role of the gut microbiota in T. s. elegans in response to freshwater acidification and provide a foundation for further exploration into the impacts of acidification on freshwater ecosystems.
Neurogenin3-driven deletion of tuberous sclerosis complex 1 (Tsc1) activated mechanistic target of rapamycin complex 1 (mTORC1) measured by the upregulation of mTOR and S6 phosphorylation in islet cells. Neurogenin3-Tsc1-/- mice demonstrated a significant increase in average islet size and mean area of individual islet cell. Insulin mRNA and plasma insulin levels increased significantly after weaning. Glucagon mRNA and plasma levels increased in neonate followed by modest reduction in adult. Somatostatin mRNA and plasma levels markedly increased. Neurogenin3-Tsc1-/- mice fed standard chow demonstrated a significant improvement in glucose tolerance and no alteration in insulin sensitivity. In Neurogenin3-Tsc1-/- mice fed 45% high-fat diets, both glucose tolerance and insulin sensitivity were significantly impaired. Rapamycin reversed the activation of mTORC1, attenuated β cells hypertrophy and abolished the improvement of glucose tolerance. TSC1-mTORC1 signaling plays an important role in the development of pancreatic endocrine cells and in the regulation of glucose metabolism.
