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Over recent decades, fine-scale land use and land cover classification in open-pit mine areas (LCCMA) has become very important for understanding the influence of mining activities on the regional geo-environment, and for environmental impact assessment procedure. This research reviews advances in fine-scale LCCMA from the following aspects. Firstly, it analyzes and proposes classification thematic resolution for LCCMA. Secondly, remote sensing data sources, features, feature selection methods, and classification algorithms for LCCMA are summarized. Thirdly, three major factors that affect LCCMA are discussed: significant three-dimensional terrain features, strong LCCMA feature variability, and homogeneity of spectral-spatial features. Correspondingly, three key scientific issues that limit the accuracy of LCCMA are presented. Finally, several future research directions are discussed: (1) unitization of new sensors, particularly those with stereo survey ability; (2) procurement of sensitive features by new sensors and combinations of sensitive features using novel feature selection methods; (3) development of robust and self-adjusted classification algorithms, such as ensemble learning and deep learning for LCCMA; and (4) application of fine-scale mining information for regularity and management of mines.

Osmotic stress and chloride regulate the autophosphorylation and activity of the WNK1 and WNK3 kinase domains. The kinase domain of unphosphorylated WNK1 (uWNK1) is an asymmetric dimer possessing water molecules conserved in multiple uWNK1 crystal structures. Conserved waters are present in two networks, referred to here as conserved water networks 1 and 2 (CWN1 and CWN2). Here, we show that PEG400 applied to crystals of dimeric uWNK1 induces de-dimerization. Both the WNK1 the water networks and the chloride-binding site are disrupted by PEG400. CWN1 is surrounded by a cluster of pan-WNK-conserved charged residues. Here, we mutagenized these charges in WNK3, a highly active WNK isoform kinase domain, and WNK1, the isoform best studied crystallographically. Mutation of E314 in the Activation Loop of WNK3 (WNK3/E314Q and WNK3/E314A, and the homologous WNK1/E388A) enhanced the rate of autophosphorylation, and reduced chloride sensitivity. Other WNK3 mutants reduced the rate of autophosphorylation activity coupled with greater chloride sensitivity than wild-type. The water and chloride regulation thus appear linked. The lower activity of some mutants may reflect effects on catalysis. Crystallography showed that activating mutants introduced conformational changes in similar parts of the structure to those induced by PEG400. WNK activating mutations and crystallography support a role for CWN1 in WNK inhibition consistent with water functioning as an allosteric ligand.

Land cover classification (LCC) in complex surface-mined landscapes has become very important for understanding the influence of mining activities on the regional geo-environment. There are three characteristics of complex surface-mined areas limiting LCC: significant three-dimensional terrain, strong temporal-spatial variability of surface cover, and spectral-spatial homogeneity. Thus, determining effective feature sets are very important as input dataset to improve detailed extent of classification schemes and classification accuracy. In this study, data such as various feature sets derived from ZiYuan-3 stereo satellite imagery, a feature subset resulting from a feature selection (FS) procedure, training data polygons, and test sample sets were firstly obtained; then, feature sets’ effects on classification accuracy was assessed based on different feature set combination schemes, a FS procedure, and random forest algorithm. The following conclusions were drawn. (1) The importance of feature set could be divided into three grades: the vegetation index (VI), principal component bands (PCs), mean filters (Mean), standard deviation filters (StDev), texture measures (Textures), and topographic variables (TVs) were important; the Gaussian low-pass filters (GLP) was just positive; and none were useless. The descending order of their importance was TVs, StDev, Textures, Mean, PCs, VI, and GLP. (2) TVs and StDev both significantly outperformed VI, PCs, GLP, and Mean; Mean outperformed GLP; all other pairs of feature sets had no difference. In general, the study assessed different feature sets’ effects on LCC in complex surface-mined landscapes.

Oxidative stress and cytotoxic damage induced by amyloid beta (Aβ) have been considered pivotal in the pathogenesis of Alzheimer’s disease (AD) and may represent a target for treatment. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway elicits a survival signal to protect against multiple injuries, and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), a downstream target of the PI3K/Akt pathway, can bind to HO-1. Resveratrol, a natural polyphenol derived from grapes, has been widely reported to have diverse antioxidative effects against AD, but the mechanisms have not been fully elucidated. The present study aims to investigate the effects of resveratrol on Aβ1–42-induced cytotoxicity in PC12 cells and to explore the potential mechanisms of these effects. PC12 cells were cultured and treated with Aβ1–42. Oxidative stress was assessed by measuring malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) levels. After treating with resveratrol at different concentrations (0, 10, 20, 40 μM) and for different durations (24, 48, 72 h), the generation of MDA, GSH, and SOD were detected; cell viability was assessed by MTT assay. The production of reactive oxygen species (ROS) was determined using an ROS Assay Kit. Western blotting was used to detect the protein expression. Our studies showed that pretreatment with resveratrol could reduce Aβ1–42-induced oxidative stress in PC12 cells by inhibiting the generation of MDA and ROS and increasing the production of SOD and GSH. Resveratrol markedly attenuated the Aβ1–42-induced loss in cell viability in PC12 cells in both a dose- and time-dependent manner. More importantly, resveratrol stimulated the activation of HO-1, Nrf2, PI3K, and phosphorylated Akt. Notably, the neuroprotective effects of resveratrol were eliminated by the HO-1 inhibitor zinc protoporphyrin IX (ZnPP), Nrf2 small interfering RNA (siRNA), and the PI3K/Akt inhibitor LY294002. Taken together, the findings suggest that the cytoprotection of resveratrol against the cytotoxicity induced by Aβ1–42 in PC12 cells is through the upregulation of HO-1 expression via the activation of the PI3K/AKT/Nrf2 intracellular signaling pathway, which might provide novel insights for understanding the mechanism of the neuroprotective effect of resveratrol as an anti-AD drug.

Background Bone metastasis is a principal cause of mortality in patients with prostate cancer (PCa). Increasing evidence indicates that high expression of stromal interaction molecule 1 (STIM1)-mediated store-operated calcium entry (SOCE) significantly activates the calcium (Ca 2+ ) signaling pathway and is involved in multiple steps of bone metastasis in PCa. However, the regulatory mechanism and target therapy of STIM1 is poorly defined. Methods Liquid chromatography-mass spectrometry analysis was performed to identify tetraspanin 18 (TSPAN18) as a binding protein of STIM1. Co-IP assay was carried out to explore the mechanism by which TSPAN18 inhibits STIM1 degradation. The biological function of TSPAN18 in bone metastasis of PCa was further investigated in vitro and in vivo models. Result We identified that STIM1 directly interacted with TSPAN18, and TSPAN18 competitively inhibited E3 ligase tripartite motif containing 32 (TRIM32)-mediated STIM1 ubiquitination and degradation, leading to increasing STIM1 protein stability. Furthermore, TSPAN18 significantly stimulated Ca 2+ influx in an STIM1-dependent manner, and then markedly accelerated PCa cells migration and invasion in vitro and bone metastasis in vivo. Clinically, overexpression of TSPAN18 was positively associated with STIM1 protein expression, bone metastasis and poor prognosis in PCa. Conclusion Taken together, this work discovers a novel STIM1 regulative mechanism that TSPAN18 protects STIM1 from TRIM32-mediated ubiquitination, and enhances bone metastasis of PCa by activating the STIM1-Ca 2+ signaling axis, suggesting that TSPAN18 may be an attractive therapeutic target for blocking bone metastasis in PCa.

Advanced prostate cancer (PCa) has limited treatment regimens and shows low response to chemotherapy and immunotherapy, leading to poor prognosis. Histone modification is a vital mechanism of gene expression and a promising therapy target. In this study, we characterized WD repeat domain 5 (WDR5), a regulator of histone modification, and explored its potential therapeutic value in PCa. We characterized specific regulators of histone modification, based on TCGA data. The expression and clinical features of WDR5 were analyzed in two dependent cohorts. The functional role of WDR5 was further investigated with siRNA and OICR-9429, a small molecular antagonist of WDR5, and . The mechanism of WDR5 was explored by RNA-sequencing and chromatin immunoprecipitation (ChIP). WDR5 was overexpressed in PCa and associated with advanced clinicopathological features, and predicted poor prognosis. Both inhibition of WDR5 by siRNA and OICR-9429 could reduce proliferation, and increase apoptosis and chemosensitivity to cisplatin and . Interestingly, targeting WDR5 by siRNA and OICR-9429 could block IFN-γ-induced PD-L1 expression in PCa cells. Mechanistically, we clarified that some cell cycle, anti-apoptosis, DNA repair and immune related genes, including AURKA, CCNB1, E2F1, PLK1, BIRC5, XRCC2 and PD-L1, were directly regulated by WDR5 and OICR-9429 in H3K4me3 and c-Myc dependent manner. These data revealed that targeting WDR5 suppressed proliferation, enhanced apoptosis, chemosensitivity to cisplatin and immunotherapy in PCa. Therefore, our findings provide insight into OICR-9429 is a multi-potency and promising therapy drug, which improves the antitumor effect of cisplatin or immunotherapy in PCa.

Background Gitelman syndrome (GS) is an inherited renal tubular disorder characterized by hypokalemic alkalosis and hypomagnesemia, due to biallelic pathogenic variants in the solute carrier family 12 member 3 ( SLC12A3 ) gene encoding a sodium-chloride (Na-Cl) cotransporter (NCC). This work aimed at identifying SLC12A3 variants in the GS pedigree and reveal the effect of the mutations on protein structure and function. Methods Whole-exome sequencing (WES) and Sanger sequencing were performed in the pedigree. Configuration prediction of two mutant NCC proteins were achieved using SWISS-MODEL. The SLC12A3 missense mutants were generated by site-specific mutagenesis, and the protein expression, location and Na + uptake activity were assessed by using the HEK293T cell line. Results Genetic analysis identified novel compound heterozygous SLC12A3 variants (c.718G > A/p.E240K and c.2675T > C/p.L892P) in the patient with typical GS phenotype. Both of her parents, elder brother and her son carried the heterozygous p.L892P variant, but only the elder brother exhibited mild hypokalemia. Bioinformatics tools predicted that both mutations were highly species conserved and pathogenic. The prediction of mutant protein indicated that p.E240K and p.L892P altered protein’s secondary and three-dimensional (3D) structure and stability. Functional experiments revealed decreased protein expression and Na + uptake activity caused by these two variants, especially the p.L892P variant. Conclusion Our study presents the genetic and functional evidence for the novel compound heterozygous loss-of-function variants in SLC12A3 that may synergistically cuase GS, and expands the mutation spectrum of SLC12A3 variants in patients with GS.

To realize simultaneous adsorption of heavy metal and antibiotic pollutants by a BC-based recyclable material, Fe3O4 magnetic biochar (MBC) was prepared by co-precipitation method. Then different ratios of dodecyl dimethyl betaine (BS-12)-modified bentonite (BS-B) were loaded on the surfaces of biochar (BC) and MBC to prepare BS-B-loaded BC and MBC composites, called BS-B/BC and BS-B/MBC, respectively. The physicochemical and structural properties of the composites were characterized by scanning electron microscopy, Fourier transform infrared spectrometry, thermogravimetric analysis, specific surface area (SBET) analysis, and vibrating sample magnetometry, and the adsorption efficiencies of BS-B/BC and BS-B/MBC to Cu2+ and tetracycline (TC) were studied. The following results were obtained. (1) Compared with BS-B/BC, BS-B/MBC had decreased pH and cation exchange capacity (CEC) and increased SBET. The pH, CEC, and SBET of BS-B/BC and BS-B/MBC decreased with the increase in the BS-12 proportion of BS-B. The surface of BS-B/MBC became rough after Fe3O4 loading. (2) The residual rate of BS-B/MBC was higher than that of BS-B/BC after high-temperature combustion, and the residual rate decreased with the increase in the BS-12 proportion of BS-B. The 2D infrared spectra showed that Fe3O4 and BS-12 were modified on the surface of BS-B/MBC. MBC and BS-B/MBC had splendid magnetism and could be separated by external magnetic field. (3) Compared with unmagnetized ones, the adsorption effects of Cu2+ and TC on different BS-B/MBCs improved, and the average adsorption rate reached the largest value of 91.92% and 97.76%, respectively. Cu2+ and TC adsorptions were spontaneous, endothermic, and entropy-increasing processes. The pH and SBET of the material had a great influence on Cu2+ and TC adsorptions, respectively, than CEC.

Background Mild to moderate depression (MMD), as an early stage of depression, has a high incidence and may progress to severe depression, even leading to suicide. The lack of effective screening and treatment is due to the unknown metabolic changes and processes in patients with MMD. Here, we performed metabolite profiling to investigate the key metabolites associated with MMD in plasma. Methods A high-throughput metabolomics method using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to determine the metabolic profiles of patients with MMD. Metabolic network analysis and machine learning models were used to screen and assess potential biomarkers of MMD. Results Forty altered metabolites were identified between patients with MMD and healthy controls, which were mainly involved in seven metabolic pathways associated with amino acid and lipid metabolism. A metabolite-target-disease network was constructed to screen six metabolites as potential key metabolites most relevant to the onset of depression. Furthermore, 12 of the 40 metabolites were found to have a strong linear correlation with scores on the Hamilton depression scale. By combining network analysis with linear correlation, we identified lysophosphatidylethanolamine (Lyso-PE) 22:6 and Lyso-PE 20:4 as being associated with the development of depression. These two metabolites showed potential in distinguishing patients with MMD from healthy controls and exhibited different correlations with other key metabolites. Conclusion Our findings suggest that Lyso-PE 22:6 and Lyso-PE 20:4 are associated with the development of depression, indicating their potential use in future screening applications to prevent the progression of depression. Graphical abstract

Background: Over the past 5 years, many studies have reported the prognostic value of hypoxia-inducible factor-1 alpha (HIF-1α) in nasopharyngeal carcinoma. However, the results have not reached a consensus until now. Therefore, we performed this meta-analysis to investigate the influence of HIF-1α expression on the prognosis and clinical characteristics in nasopharyngeal carcinoma. Methods: We searched PubMed, the Cochrane Library, Embase (via Ovid interface), Web of Science, and China National Knowledge Infrastructure electronic databases from their establishment to 6 December 2017. We calculated the hazard ratio (HR) and the odds ratio (OR) to assess the prognostic and clinicopathological values of HIF-1α, respectively. Q test and I2 statistic were applied to evaluate heterogeneity. We also conducted publication bias and sensitivity analyses. Results: A total of 18 studies with 1476 patients were included in our meta-analysis. We found HIF-1α expression was associated with poor overall survival (HR=1.77; 95% confidence interval (CI) 1.35, 2.32; P<0.001), poor progression-free survival (HR=1.72; 95% CI 1.22, 2.44; P=0.002), a higher rate of lymph node metastasis (OR=3.81; 95% CI 2.60, 5.58, P<0.001), and more advanced tumor stage (OR=2.98; 95% CI 1.79, 4.97; P<0.001). Conclusions: Our study demonstrated that HIF-1α could be an appropriate prognostic biomarker for nasopharyngeal carcinoma patients.