Table_1_Seasonal variation in the detection rate and all-cause in-hospital mortality of AKI in China: A nationwide cohort study.pdf

BackgroundAcute kidney injury (AKI) is a severe clinical syndrome that places a massive burden on medical systems worldwide, yet the seasonality of AKI remains unexplored in China. The aim of this study was to describe the seasonal variation in the detection rate and all-cause in-hospital mortality of AKI in China based on a nationwide cohort study.MethodsThis was a retrospective cohort recruiting a national sample of 7,291 adult patients treated in hospitals in 22 provinces of mainland China during January or July 2013. AKI was defined according to the 2012 Kidney Disease Improving Global Outcomes AKI creatinine criteria or expanded criteria of increase or decrease in serum creatinine level of 50% during the hospital stay. The seasonal group was determined according to the corresponding admission date for each patient. The detection rate of AKI refers to the ratio of identified AKI cases to the total number of adult admissions from the same regional or seasonal group.ResultsBoth the detection rate (2.31 vs. 2.08%, p = 0.001) and in-hospital mortality rate (13.3 vs. 10.7%, p = 0.001) of AKI were higher in winter than in summer. The patients with AKI detected in winter had higher proportions of prehistory diseases, cardiac or vascular kidney injury factors, and severe comorbidities than those in summer (all p ConclusionThe detection rate and all-cause in-hospital mortality of AKI showed a winter predominance in patients with AKI in China. Winter appeared to be an independent risk factor for all-cause in-hospital mortality in patients with AKI. Environmental factors, including lower ambient temperature, higher relative humidity level, and living in temperate continental climatic regions, were each independently associated with increased risks of in-hospital mortality in patients with AKI.</p

Identifying Catalytically Active Mononuclear Peroxoniobate Anion of Ionic Liquids in the Epoxidation of Olefins

The organic carboxylic acid coordinated monomeric peroxoniobate-based ionic liquids (ILs) [TBA]­[NbO­(OH)₂(R)] (TBA = tetrabutylammonium; R = lactic acid (LA), glycolic acid (GLY), malic acid (MA)) were prepared and fully characterized by elemental analysis, NMR, IR, Raman, TGA, ⁹³Nb NMR, and HRMS. These IL catalysts exhibited not only high catalytic activity for the epoxidation of olefins under very mild reaction conditions, as the turnover frequency of [TBA]­[NbO­(OH)₂(LA)] reached up to 110 h^–1, but also satisfactory recyclability in the epoxidation by using only 1 equiv of hydrogen peroxide as an oxidant. Meanwhile, this work revealed that the ILs underwent structural transformation from [NbO­(OH)₂(R)]⁻ to [Nb­(O–O)₂(R)]⁻ (R = LA, GLY, MA) in the presence of H₂O₂ by a subsequent activity evaluation, characterization, and first-principles calculations. Moreover, the organic carboxylic acid coordinated monomeric peroxoniobate-based ILs were investigated using density functional theory (DFT) calculations, which identified that [Nb­(O–O)₂LA]⁻ was more advantageous than [Nb­(O–O)₂(OOH)₂]⁻ for the epoxidation of olefins. Due to the coordination between the α-hydroxy acids and the monomeric peroxoniobate anions, the functionalized ILs can efficiently catalyze the epoxidation of a wide range of olefins and allylic alcohols under very mild conditions. Additionally, the effect of solvents on the reaction is illustrated. It was found that methanol can lower the epoxidation barriers by forming a hydrogen bond with a peroxo ligand attached to the niobium center

Table_1_Functional Variant rs3135500 in NOD2 Increases the Risk of Multiple System Atrophy in a Chinese Population.DOCX

<p>Background: Given the overlap of clinical manifestations and pathological characteristics between Parkinson's disease (PD) and multiple system atrophy (MSA), we investigated the associations between five functional polymorphisms of nucleotide-binding oligomerization domain protein 2 (NOD2) which were associated with PD, and MSA in a Chinese population.</p><p>Methods: A cohort of 431 MSA patients and 441 unrelated healthy controls (HCs) were included in the study. Five polymorphisms in NOD2, including P268S, R702W, G908R, 1007fs, and rs3135500, were genotyped. The mRNA expression of NOD2 in peripheral mononuclear cells (PBMCs) in 32 MSA patients were analyzed using RT-PCR, and the concentration of NOD2 and α-synuclein from plasma of 57 MSA patients were also measured by ELISA analysis.</p><p>Results: No heterozygous or homozygous for R702W, G908R, and 1007fs were found in all the subjects. For rs3135500, differences in genotype distributions, dominant and additive genetic models, were found between MSA and HCs, and between MSA Parkinsonism (MSA-P) patients and HCs. Interestingly, patients carrying the “A” allele of rs3135500 had higher mRNA NOD2 level from PBMCs and NOD2 protein from plasma than patients without this allele (p = 0.028 and p = 0.036, respectively). In addition, we also found the concentration of NOD2 in plasma was positively correlated with the levels of NOD2 mRNA in PBMC and α-synuclein in plasma (R = 0.761 and 0.832, respectively).</p><p>Conclusion: Our findings suggest that the rs3135500 variant in the NOD2 gene might increase the risk for MSA and might provide new evidence that inflammation mediated by NOD2 involved in the pathogenesis of MSA. Further association studies involving a larger number of participants, as well as functional studies, are needed to confirm our current findings.</p

Table_2_Functional Variant rs3135500 in NOD2 Increases the Risk of Multiple System Atrophy in a Chinese Population.DOCX

<p>Background: Given the overlap of clinical manifestations and pathological characteristics between Parkinson's disease (PD) and multiple system atrophy (MSA), we investigated the associations between five functional polymorphisms of nucleotide-binding oligomerization domain protein 2 (NOD2) which were associated with PD, and MSA in a Chinese population.</p><p>Methods: A cohort of 431 MSA patients and 441 unrelated healthy controls (HCs) were included in the study. Five polymorphisms in NOD2, including P268S, R702W, G908R, 1007fs, and rs3135500, were genotyped. The mRNA expression of NOD2 in peripheral mononuclear cells (PBMCs) in 32 MSA patients were analyzed using RT-PCR, and the concentration of NOD2 and α-synuclein from plasma of 57 MSA patients were also measured by ELISA analysis.</p><p>Results: No heterozygous or homozygous for R702W, G908R, and 1007fs were found in all the subjects. For rs3135500, differences in genotype distributions, dominant and additive genetic models, were found between MSA and HCs, and between MSA Parkinsonism (MSA-P) patients and HCs. Interestingly, patients carrying the “A” allele of rs3135500 had higher mRNA NOD2 level from PBMCs and NOD2 protein from plasma than patients without this allele (p = 0.028 and p = 0.036, respectively). In addition, we also found the concentration of NOD2 in plasma was positively correlated with the levels of NOD2 mRNA in PBMC and α-synuclein in plasma (R = 0.761 and 0.832, respectively).</p><p>Conclusion: Our findings suggest that the rs3135500 variant in the NOD2 gene might increase the risk for MSA and might provide new evidence that inflammation mediated by NOD2 involved in the pathogenesis of MSA. Further association studies involving a larger number of participants, as well as functional studies, are needed to confirm our current findings.</p

Structural Optimization and Pharmacological Evaluation of Inhibitors Targeting Dual-Specificity Tyrosine Phosphorylation-Regulated Kinases (DYRK) and CDC-like kinases (CLK) in Glioblastoma

The DYRK family contains kinases that are up-regulated in malignancy and control several cancer hallmarks. To assess the anticancer potential of inhibitors targeting DYRK kinases, we developed a series of novel DYRK inhibitors based on the 7-azaindole scaffold. All compounds were tested for their ability to inhibit DYRK1A, DYRK1B, DYRK2, and the structurally related CLK1. The library was screened for anticancer efficacy in established and stem cell-like glioblastoma cell lines. The most potent inhibitors (IC₅₀ ≤ 50 nM) significantly decreased viability, clonogenic survival, migration, and invasion of glioblastoma cells. Target engagement was confirmed with genetic knockdown and the cellular thermal shift assay. We demonstrate that DYRK1A’s thermal stability in cells is increased upon compound treatment, confirming binding in cells. In summary, we present synthesis, structure–activity relationship, and efficacy in glioblastoma-relevant models for a library of novel 7-azaindoles