Improved GSO Optimized ESN Soft-Sensor Model of Flotation Process Based on Multisource Heterogeneous Information Fusion

For predicting the key technology indicators (concentrate grade and tailings recovery rate) of flotation process, an echo state network (ESN) based fusion soft-sensor model optimized by the improved glowworm swarm optimization (GSO) algorithm is proposed. Firstly, the color feature (saturation and brightness) and texture features (angular second moment, sum entropy, inertia moment, etc.) based on grey-level co-occurrence matrix (GLCM) are adopted to describe the visual characteristics of the flotation froth image. Then the kernel principal component analysis (KPCA) method is used to reduce the dimensionality of the high-dimensional input vector composed by the flotation froth image characteristics and process datum and extracts the nonlinear principal components in order to reduce the ESN dimension and network complex. The ESN soft-sensor model of flotation process is optimized by the GSO algorithm with congestion factor. Simulation results show that the model has better generalization and prediction accuracy to meet the online soft-sensor requirements of the real-time control in the flotation process

Structures of heat shock factor trimers bound to DNA

Summary: Heat shock factor 1 (HSF1) and 2 (HSF2) play distinct but overlapping regulatory roles in maintaining cellular proteostasis or mediating cell differentiation and development. Upon activation, both HSFs trimerize and bind to heat shock elements (HSEs) present in the promoter region of target genes. Despite structural insights gained from recent studies, structures reflecting the physiological architecture of this transcriptional machinery remains to be determined. Here, we present co-crystal structures of human HSF1 and HSF2 trimers bound to DNA, which reveal a triangular arrangement of the three DNA-binding domains (DBDs) with protein-protein interactions largely mediated by the wing domain. Two structural properties, different flexibility of the wing domain and local DNA conformational changes induced by HSF binding, seem likely to contribute to the subtle differential specificity between HSF1 and HSF2. Besides, two more structures showing DBDs bound to “two-site” head-to-head HSEs were determined as additions to the published tail-to-tail dimer-binding structures

ALKBH5 inhibitors as a potential treatment strategy in heart failure—inferences from gene expression profiling

Heart Failure (HF) is a complex clinical syndrome in which the heart is unable to provide enough blood flow to meet metabolic needs and lacks efficient venous return. HF is a major risk factor for morbidity and mortality with cardiovascular diseases globally. Despite enormous research, the molecular markers relevant to disease prognosis and management remain not well understood. Here, we analyzed the whole transcriptomes of 18 failing hearts and 15 non-failing hearts (predominantly of Caucasian origin), by applying the standard in silico tools. The analyses revealed novel gene-markers including ALKBH5 of mRNA demethylation and KMT2E of histone modification processes, significantly over-expressed in the HF compared with the non-failing hearts (FDR < 0.05). To validate the over-expression of ALKBH5, we determined the global m6A level in hypoxic H9c2 cells using a dot blot assay. The global m6A level was found markedly lower in the hypoxic H9c2 cells than in the control cells. Additionally, the expression of ALKBH5 in the H9c2 cells was quantified by the qPCR and found to be 1.18 times higher at 12 h (p < 0.05), and 1.67 times higher at 24 h of hypoxia (p < 0.01) compared with the control cells, indicating a likely role of ALKBH5 in the failing cardiac cells. Furthermore, we identified several compounds through the virtual screening of 11,272 drug-like molecules of the ZINC15 database to inhibit the ALKBH5 in a molecular docking process. Collectively, the study revealed novel markers potentially involved in the pathophysiology of HF and suggested plausible therapeutic molecules for the management of the disease

Ticagrelor reduces doxorubicin-induced pyroptosis of rat cardiomyocytes by targeting GSK-3β/caspase-1

Doxorubicin (Dox) is a widely used clinical drug whose cardiotoxicity cannot be ignored. Pyroptosis (inflammatory cell death) has gradually gained attention in the context of Dox-induced cardiotoxicity. In addition to the inhibition of platelet activation by ticagrelor, little is known about its other pharmacological effects. Glycogen synthase kinase 3β (GSK-3β) has been shown to contribute to the pathological process of pyroptosis, but whether it is related to the potential role of ticagrelor is unclear. In this study, we investigated the effects of ticagrelor on Dox-induced pyroptosis in cardiomyocytes. Rats were treated with ticagrelor (7.5 mg/kg, i.g.) 1 h before intravenous injection of Dox (2.5 mg/kg), once every 3 days, six times in total. Hearts were collected for histochemical analysis and western blot detection 8 weeks after the last administration. Ticagrelor was shown to significantly improve cardiac function by inhibiting GSK-3β/caspase-1/GSDMD activation. In vitro experiments were conducted using rat cardiac myocytes (RCMs) and rat embryonic cardiac-derived H9c2 cells. Pretreatment with ticagrelor (10 μm) significantly inhibited Dox (1 μm)-induced hypertrophy and reversed the upregulation of GSDMD-NT expression. We showed that ticagrelor suppressed the activation of Akt caused by Dox in the heart tissue as well as in RCMs/H9c2 cells caused by Dox. When GSK-3β expression was absent in H9c2 cells, the inhibitory effect of ticagrelor on Dox-induced caspase-1/GSDMD activation was weakened. These data showed that ticagrelor reduced Dox-induced pyroptosis in rat cardiomyocytes by targeting GSK-3β/caspase-1

Matrix Effects on the Microcystin-LR Fluorescent Immunoassay Based on Optical Biosensor

Matrix effects on the microcystin-LR fluorescent immunoassay based on the evanescent wave all-fiber immunosensor (EWAI) and their elimination methods were studied. The results indicated that PBS and humic acid did not affect the monitoring of samples under the investigated conditions. When the pH was less than 6 or higher than 8, the fluorescence signals detected by immunosensor systems were obviously reduced with the decrease or increase of pH. When the pH ranged from 6 to 8, IC50 and the linear working range of MC-LR calculated from the detection curves were 1.01∼1.04 μg/L and 0.12∼10.5 μg/L, respectively, which was favourable for an MC-LR immunoassay. Low concentrations of Cu2+ rarely affected the detection performance of MC-LR. When the concentration of CuSO4 was higher than 5 mg/L, the fluorescence signal detected by EWAI clearly decreased, and when the concentration of CuSO4 was 10 mg/L, the fluorescence signal detected was reduced by 70%. The influence of Cu2+ on the immunoassay could effectively be compromised when chelating reagent EDTA was added to the pre-reaction mixture

A Chinese patent medicine’s long-term efficacy on non-dialysis patients with CKD stages 3–5: a retrospective cohort study

BackgroundChinese patent medicine is commonly used in China as an important treatment mechanism to thwart the progression of chronic kidney disease (CKD) stages 3–5, among which Niaoduqing granules are a representative Chinese patent medicine; however, its long-term efficacy on CKD prognosis remains unclear.MethodsPatients were grouped according to Niaoduqing granule prescription duration (non-Niaoduqing granule (non-NDQ) group vs Niaoduqing granule (NDQ) group). Serum creatinine (SCr) variation was compared using a generalized linear mixed model (GLMM). Multivariate Cox regression models were constructed, adjusting for confounding factors, to explore the risk of composite outcomes (receiving renal replacement therapy (RRT) or having an estimated glomerular filtration rate (eGFR)<5 mL/min/1.73 m2, ≥50% decline in the eGFR from the baseline, and doubling of SCr) in individuals consuming Niaoduqing granules.ResultsA total of 1,271 patients were included, with a median follow-up duration of 29.71 (12.10, 56.07) months. The mean SCr Z-scores for the non-NDQ group and NDQ group were −0.175 and 0.153, respectively, at baseline (p = 0.015). The coefficients of the NDQ group from visit 1 to visit 5 were −0.207 (95% CI: −0.346, −0.068, p = 0.004), −0.214 (95% CI: 0.389, −0.039, p = 0.017), −0.324 (95% CI: 0.538, −0.109, p = 0.003), −0.502 (95% CI: 0.761, −0.243, p = 0.000), and −0.252 (95% CI: 0.569, 0.065, p = 0.119), respectively. The survival probability was significantly higher in the NDQ group (p = 0.0039). Taking Niaoduqing granules was a significant protective factor for thwarting disease progression (model 1: HR 0.654 (95% CI 0.489–0.875, p = 0.004); model 2: HR 0.646 (95% CI 0.476, 0.877, p = 0.005); and model 3: HR 0.602 (95% CI 0.442, 0.820, p = 0.001)).ConclusionThe long-term use of Niaoduqing granules improved SCr variation and lowered the risk of CKD progression by 39.8%

Functional brain activity in patients with amnestic mild cognitive impairment: an rs-fMRI study

BackgroundAmnestic mild cognitive impairment (aMCI) is an early stage of Alzheimer’s disease (AD). Regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) are employed to explore spontaneous brain function in patients with aMCI. This study applied ALFF and ReHo indicators to analyze the neural mechanism of aMCI by resting-state functional magnetic resonance imaging (rs-fMRI).MethodsTwenty-six patients with aMCI were included and assigned to the aMCI group. The other 26 healthy subjects were included as a healthy control (HC) group. Rs-fMRI was performed for all participants in both groups. Between-group comparisons of demographic data and neuropsychological scores were analyzed using SPSS 25.0. Functional imaging data were analyzed using DPARSF and SPM12 software based on MATLAB 2017a. Gender, age, and years of education were used as covariates to obtain ALFF and ReHo indices.ResultsCompared with HC group, ALFF decreased in the left fusiform gyrus, left superior temporal gyrus, and increased in the left cerebellum 8, left inferior temporal gyrus, left superior frontal gyrus (BA11), and right inferior temporal gyrus (BA20) in the aMCI group (p < 0.05, FWE correction). In addition, ReHo decreased in the right middle temporal gyrus and right anterior cuneiform lobe, while it increased in the left middle temporal gyrus, left inferior temporal gyrus, cerebellar vermis, right parahippocampal gyrus, left caudate nucleus, right thalamus, and left superior frontal gyrus (BA6) (p < 0.05, FWE correction). In the aMCI group, the ALFF of the left superior frontal gyrus was negatively correlated with Montreal Cognitive Assessment (MoCA) score (r = −0.437, p = 0.026), and the ALFF of the left superior temporal gyrus was positively correlated with the MoCA score (r = 0.550, p = 0.004). The ReHo of the right hippocampus was negatively correlated with the Mini-Mental State Examination (MMSE) score (r = −0.434, p = 0.027), and the ReHo of the right middle temporal gyrus was positively correlated with MMSE score (r = 0.392, p = 0.048).ConclusionFunctional changes in multiple brain regions rather than in a single brain region have been observed in patients with aMCI. The abnormal activity of multiple specific brain regions may be a manifestation of impaired central function in patients with aMCI