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The brain neuromechanism in maintenance hemodialysis patients (MHD) with cognitive impairment (CI) remains unclear. The study aimed to probe the relationship between spontaneous brain activity and CI by using resting-state functional magnetic resonance imaging (rs-fMRI) data. Here, 55 MHD patients with CI and 28 healthy controls were recruited. For baseline data, qualitative data were compared between groups using the χ2 test; quantitative data were compared between groups using the independent samples t-test, ANOVA test, Mann–Whitney U-test, or Kruskal–Wallis test. Comparisons of ALFF/fALFF/ReHo values among the three groups were calculated by using the DPABI toolbox, and then analyzing the correlation with clinical variables. p <.05 was considered a statistically significant difference. Furthermore, back propagation neural network (BPNN) was utilized to predict cognitive function. Compared with the MHD-NCI group, the patients with MHD-CI had more severe anemia and higher urea nitrogen levels, lower mALFF values in the left postcentral gyrus, lower mfALFF values in the left inferior temporal gyrus, and greater mALFF values in the right caudate nucleus (p <.05). The above-altered indicators were correlated with MOCA scores. BPNN prediction models indicated that the diagnostic efficacy of the model which inputs were hemoglobin, urea nitrogen, and mALFF value in the left central posterior gyrus was optimal (R2 = 0.8054), validation cohort (R2 = 0.7328). The rs-fMRI can reveal the neurophysiological mechanism of cognitive impairment in MHD patients. In addition, it can serve as a neuroimaging marker for diagnosing and evaluating cognitive impairment in MHD patients. [ABSTRACT FROM AUTHOR]

Objectives: Hereditary spherocytosis (HS) represents a group of congenital diseases characterized by sphere-shaped erythrocytes on peripheral blood smears. The typical clinical manifestations of HS include haemolysis, jaundice, splenomegaly, and gallstones. Ankyrin1, encoded by the ANK1 gene, is the predominant protein in red blood cells. Defects in ankyrin1 lead to a decrease in erythrocyte surface area, a spherical shape of erythrocytes and, in particular, loss of membrane elasticity and mechanical stability. The purpose of this study was to investigate a Chinese family with HS to determine the causative gene mutation and explore the genotype–phenotype correlation. Methods: A 4-year-old boy was diagnosed with HS based on typical clinical features. In addition, his father had a high possibility of HS. Targeted next-generation sequencing (NGS) followed by Sanger sequencing was performed in the proband and his parents. Results: One mutation in the ANK1 gene was recognized. c1801-1G > C in exon 17, which leads to splicing defects, was detected. To confirm the c1801-1G > C variant, samples from the proband and his parents were analysed by Sanger sequencing, and Sanger verification showed that this mutation was inherited from the father. Conclusion: The present study confirmed that a novel mutation in ANK1 may be causative of HS, which plays an important role in expanding the mutational spectrum of ANK1 mutations. This may contribute to accurate genetic counselling. And it is helpful for understanding the correlation of the genotype and phenotype. [ABSTRACT FROM AUTHOR]

Renal dysfunction and disruption of renal endothelial glycocalyx are two important events during septic acute kidney injury (AKI). Here, the role and mechanism of hyaluronidase 1 (HYAL1) in regulating renal injury and renal endothelial glycocalyx breakdown in septic AKI were explored for the first time. BALB/c mice were injected with lipopolysaccharide (LPS, 10 mg/kg) to induce AKI. HYAL1 was blocked in vivo using lentivirus-mediated short hairpin RNA targeting HYAL1 (LV-sh-HYAL1). Biochemical assays were performed to measure the levels and concentrations of biochemical parameters associated with AKI as well as levels of inflammatory cytokines. Renal pathological lesions were determined by hematoxylin-eosin (HE) staining. Cell apoptosis in the kidney was detected using terminal-deoxynucleoitidyl transferase-mediated nick end labeling (TUNEL) assay. Immunofluorescence and immunohistochemical (IHC) staining assays were used to examine the levels of hyaluronic acid in the kidney. The protein levels of adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling, endothelial glycocalyx, and autophagy-associated indicators were assessed by western blotting. The knockdown of HYAL1 in LPS-subjected mice by LV-sh-HYAL1 significantly reduced renal inflammation, oxidative stress, apoptosis and kidney dysfunction in AKI, as well as alleviated renal endothelial glycocalyx disruption by preventing the release of hyaluronic acid to the bloodstream. Additionally, autophagy-related protein analysis indicated that knockdown of HYAL1 significantly enhanced autophagy in LPS mice. Furthermore, the beneficial actions of HYAL1 blockade were closely associated with the AMPK/mTOR signaling. HYAL1 deficiency attenuates LPS-triggered renal injury and endothelial glycocalyx breakdown in septic AKI in mice. [ABSTRACT FROM AUTHOR]

The evolution of starch synthase (SS) has been extensively analysed in the model plant rice, but there have been few detailed studies directed towards exploring the intron splicing variant effect on the divergence of theSSgene. We report here an example that the alternative splicing of a GC-AG intron induced a new splicing isoform ofSSII-1expressed inOryza sativa japonicacultivar Zhonghua-15. In addition, a GT-AG intron flanking the alternative splicing GC-AG intron was simultaneously spliced at an incorrect position, inducing another intron fragment gained in matureSSII-1RNA. Moreover, when a GT-AG intron fromSSII-3was artificially mutated into the GC-AG intron, a 28 bp fragment from the intron added to the mature RNA could be observed in transgenic rice. In this study, the alternative intron splicing of the GC-AG intron might offer more variants for genetic divergence of the starch synthase gene family in rice. [ABSTRACT FROM PUBLISHER]