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Recently, reactive cobalt (Co) species, including Co(IV)-oxo and Co(II)-OOSO3- complexes, were proposed to be the primary intermediates formed during the process of activating peroxymonosulfate (PMS) by Co(II), mainly based on the observation that the methyl phenyl sulfoxide (MPSO) probe was transformed to methyl phenyl sulfone (MPSO2) in this process. However, in this work, we rationalized the results of the MPSO probe assay based on the chemistry of aqueous Co(III), an alternative reactive Co species. Moreover, 18O-labeled water experiments and Raman spectroscopy analysis clearly proved the Co(III) formation in the Co(II)/PMS system. In parallel, sulfate radicals (SO4â¢-) and hydroxyl radicals (HOâ¢) were also involved in this system. Further, the relative contribution of Co(III) to the abatement of carbamazepine (CBZ), a representative micropollutant, in the Co(II)/PMS system was significantly increased by increasing the Co(II) dosage but was dramatically decreased by improving the PMS dosage and increasing the pH from 3 to 7. Additionally, the degradation pathway of CBZ by Co(III) and the Co(II)/PMS system was comparatively explored, confirming that Co(III) participated in the hydroxylation, carbonylation, deacetylation, and ring reduction of CBZ by the Co(II)/PMS system. Our work addresses the controversy regarding the reactive Co species involved in the Co(II)/PMS system with evidence of Co(III) as the chief one, which highlights the significance of re-evaluating the relative contribution of Co(III) in relevant environmental decontamination processes.
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BACKGROUND: Breast cancer (BC) remains a prevalent and common form of cancer with high heterogeneity. Making efforts to explore novel molecular biomarkers and serve as potential disease indicators, which is essential to effectively enhance the prognosis and individualized treatment of BC. FBXO proteins act as the core component of E3 ubiquitin ligase, which play essential regulators roles in multiple cellular processes. Recently, research has indicated that FBXOs also play significant roles in cancer development. However, the molecular functions of these family members in BC have not been fully elucidated. METHODS: In this research, we investigated the expression data, survival relevance and mutation situation of 10 FBXO members (FBXO1, 2, 5, 6, 16, 17, 22, 28, 31 and 45) in patients with BC from the Oncomine, GEPIA, HPA, Kaplan-Meier Plotter, UALCAN and cBioPortal databases. The high transcriptional levels of FBXO1 in different subtypes of BC were verified by immunohistochemical staining and the specific mutations of FBXO1 were obtained from COSMIC database. Top 10 genes with the highest correlation to FBXO1 were identified through cBioPortal and COXPRESdb tools. Additionally, functional enrichment analysis, PPI network and survival relevance of FBXO1 and co-expressed genes in BC were obtained from DAVID, STRING, UCSC Xena, GEPIA, bc-GenExMiner and Kaplan-Meier Plotter databases. FBXO1 siRNAs were transfected into MCF-7 and MDA-MB-231 cell lines. Expression of FBXO1 in BC cell lines was detected by western-blot and RT-qPCR. Cell proliferation was detected by using CCK-8 kit and colony formation assay. Cell migration was detected by wound-healing and transwell migration assay. RESULTS: We found that FBXO2, FBXO6, FBXO16 and FBXO17 were potential favorable prognostic factors for BC. FBXO1, FBXO5, FBXO22, FBXO28, FBXO31 and FBXO45 may be the independent poor prognostic factors for BC. All of them were correlated to clinicopathological staging. Moreover, knockdown of FBXO1 in MCF7 and MDA-MB-231 cell lines resulted in decreased cell proliferation and migration in vitro. We identified that FBXO1 was an excellent molecular biomarker and therapeutic target for different molecular typing of BC. CONCLUSION: This study implies that FBXO1, FBXO2, FBXO5, FBXO6, FBXO16, FBXO17, FBXO22, FBXO28, FBXO31 and FBXO45 genes are potential clinical targets and prognostic biomarkers for patients with different molecular typing of BC. In addition, the overexpression of FBXO1 is always found in breast cancer and predicts disadvantageous prognosis, implicating it could as an appealing therapeutic target for breast cancer patients.
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BACKGROUND: Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) is a promising candidate antigen for a blood-stage malaria vaccine. However, antigenic variation and diversity of PfAMA-1 are still major problems to design a universal malaria vaccine based on this antigen, especially against domain I (DI). Detail understanding of the PfAMA-1 gene polymorphism can provide useful information on this potential vaccine component. Here, general characteristics of genetic structure and the effect of natural selection of DIs among Bioko P. falciparum isolates were analysed. METHODS: 214 blood samples were collected from Bioko Island patients with P. falciparum malaria between 2011 and 2017. A fragment spanning DI of PfAMA-1 was amplified by nested polymerase chain reaction and sequenced. Polymorphic characteristics and the effect of natural selection were analysed using MEGA 5.0, DnaSP 6.0 and Popart programs. Genetic diversity in 576 global PfAMA-1 DIs were also analysed. Protein function prediction of new amino acid mutation sites was performed using PolyPhen-2 program. RESULTS: 131 different haplotypes of PfAMA-1 were identified in 214 Bioko Island P. falciparum isolates. Most amino acid changes identified on Bioko Island were found in C1L. 32 amino acid changes identified in PfAMA-1 sequences from Bioko Island were found in predicted RBC-binding sites, B cell epitopes or IUR regions. Overall patterns of amino acid changes of Bioko PfAMA-1 DIs were similar to those in global PfAMA-1 isolates. Differential amino acid substitution frequencies were observed for samples from different geographical regions. Eight new amino acid changes of Bioko island isolates were also identified and their three-dimensional protein structural consequences were predicted. Evidence for natural selection and recombination event were observed in global isolates. CONCLUSIONS: Patterns of nucleotide diversity and amino acid polymorphisms of Bioko Island isolates were similar to those of global PfAMA-1 DIs. Balancing natural selection across DIs might play a major role in generating genetic diversity in global isolates. Most amino acid changes in DIs occurred in predicted B-cell epitopes. Novel sites mapped on a three dimensional structure of PfAMA-1 showed that these regions were located at the corner. These results may provide significant value in the design of a malaria vaccine based on this antigen.
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Antígenos de Protozoos/genética , Variación Genética , Proteínas de la Membrana/genética , Plasmodium falciparum/genética , Proteínas Protozoarias/genética , Selección Genética , Antígenos de Protozoos/metabolismo , Guinea Ecuatorial , Proteínas de la Membrana/metabolismo , Plasmodium falciparum/metabolismo , Proteínas Protozoarias/metabolismoRESUMEN
This study investigated the roles of diverse free available chlorine (FAC) species including HOCl/OCl-, H2OCl+, Cl2O, and Cl2 in the degradation of micropollutants. The degradation of 5 micropollutants was significantly affected by pH, FAC dosage, and chloride (Cl-) concentration. The reaction orders in FAC (n) of 5 micropollutants (acetaminophen, carbamazepine, naproxen, gemfibrozil, and mecoprop) ranged from 1.4 ± 0.2 to 2.1 ± 0.3 at pH 3 - 5, evidencing the importance of Cl2O and Cl2 for micropollutant abatement. A simplified method for the determination of second-order rate constants (k) of specific FAC species with micropollutants was developed. Herein, the k for neutral/dissociated forms of 5 micropollutants with Cl2 and Cl2O were determined in the ranges of 9.3 (± 0.2) × 102 â¼ 2.9 (± 0.2) × 109 M-1 s-1 and 1.8 (± 0.1) × 104 â¼ 3.7 (± 0.6) × 109 M-1 s-1, respectively. They were 4 - 7 orders of magnitude higher than those of HOCl, whereas those of OCl- and H2OCl+ were negligible. By using kinetic modeling, Cl2 was more important under acidic conditions and higher Cl- levels with contributions of 37.9 - 99.2% at pH 5 in pure water. Cl2O played a dominant role in micropollutant degradation in pure water (56.4 - 87.3%) under neutral conditions. Furthermore, both Cl2 and Cl2O played vital roles in the formation of disinfection byproducts (DBPs) during chlorination of carbamazepine and natural organic matter. This study highlights the overlooked roles of Cl2O and Cl2 in micropollutant abatement and DBP formation during chlorination.
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Contaminantes Químicos del Agua , Purificación del Agua , Halogenación , Purificación del Agua/métodos , Concentración de Iones de Hidrógeno , Cinética , Cloro , Desinfección , CarbamazepinaRESUMEN
Background: TCIRG1, also known as V-ATPase-a3, is critical for cellular life activities through its dependent acidification. Prior to the present research, its relationship with prognostic and tumor immunity in clear cell renal cell carcinoma (ccRCC) had not yet been investigated. Methods: We assessed TCIRG1 expression in normal and tumor tissues using data from TCGA, GEO, GTEX, and IHC. We also analyzed the relationship between TCIRG1 and somatic mutations, TMB, DNA methylation, cancer stemness, and immune infiltration. We evaluated the relevance of TCIRG1 to immunotherapy and potential drugs. Finally, we explored the effect of TCIRG1 knockdown on tumor cells. Results: TCIRG1 was overexpressed in tumor tissue and predicted a significantly unfavorable clinical outcome. High TCIRG1 expression may be associated with fewer PBRM1 and more BAP1 mutations and may reduce DNA methylation, thus leading to a poor prognosis. TCIRG1 was strongly associated with CD8+ T-cell, Treg, and CD4+ T-cell infiltration. Moreover, TCIRG1 was positively correlated with TIDE scores and many drug sensitivities. Finally, experiments showed that the knockdown of TCIRG1 inhibited the migration of ccRCC cells. Conclusions: TCIRG1 may have great potential in identifying prognostic and immunomodulatory mechanisms in tumor patients and may provide a new therapeutic strategy for ccRCC.
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The solid solution in the system Zr-Mo-W-O with composition ZrW(1.75)Mo(0.25)O(8) (zirconium tungsten molybdenum octa-oxide) was prepared by solid-state reactions as a polycrystalline material. Its structure has cubic symmetry (space group P2(1)3)â at room temperature. The structure contains a network of corner-sharing ZrO(6) octa-hedra (.3. symmetry) and MO(4) (M = W, Mo) tetra-hedra (.3. symmetry). Along the main threefold axis of the cubic unit cell, the MO(4) tetra-hedra are arranged in pairs forming M(2)O(8) units in which the M1O(4) tetra-hedra have larger distortions in terms of bond distances and angles than the M2O(4) tetra-hedra. These units are disordered over two possible orientations, with the M-O(terminal) vectors pointing to the [111] or [] directions. The reversal of the orientations of the M(2)O(8) units results from the concerted flips of these units. The time-averaged proportions of flipped and unflipped M(2)O(8) units were determined and the fraction of unflipped M(2)O(8) units is about 0.95. The order degree of the M(2)O(8) unit orientation is about 0.9. During the reversal process, the M-atom site has a migration about 0.93â Å, one of the O-atom sites has a 0.25â Å migration distance, whereas two other O-atom sites migrate marginally (≃ 0.08â Å). The results prove the constraint strategy to be a reasonable approach based on the ratcheting mechanism.