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Abstract Sphingosine 1-phosphate receptor 1 (S1PR1), a G protein-coupled receptor, is required for lymphocyte trafficking, and is a promising therapeutic target in inflammatory diseases. Here, we synthesize a competitive S1PR1 antagonist, KSI-6666, that effectively suppresses pathogenic inflammation. Metadynamics simulations suggest that the interaction of KSI-6666 with a methionine residue Met124 in the ligand-binding pocket of S1PR1 may inhibit the dissociation of KSI-6666 from S1PR1. Consistently, in vitro functional and mutational analyses reveal that KSI-6666 causes pseudoirreversible inhibition of S1PR1, dependent on the Met124 of the protein and substituents on the distal benzene ring of KSI-6666. Moreover, in vivo study suggests that this pseudoirreversible inhibition is responsible for the persistent activity of KSI-6666.

The thymus has the ability to regenerate from acute injury caused by radiation, infection, and stressors. In addition to thymocytes, thymic epithelial cells in the medulla (mTECs), which are crucial for T cell self-tolerance by ectopically expressing and presenting thousands of tissue-specific antigens (TSAs), are damaged by these insults and recover thereafter. However, given recent discoveries on the high heterogeneity of mTECs, it remains to be determined whether the frequency and properties of mTEC subsets are restored during thymic recovery from radiation damage. Here we demonstrate that acute total body irradiation with a sublethal dose induces aftereffects on heterogeneity and gene expression of mTECs. Single-cell RNA-sequencing (scRNA-seq) analysis showed that irradiation reduces the frequency of mTECs expressing AIRE, which is a critical regulator of TSA expression, 15 days after irradiation. In contrast, transit-amplifying mTECs (TA-mTECs), which are progenitors of AIRE-expressing mTECs, and Ccl21a-expressing mTECs, were less affected. Interestingly, a detailed analysis of scRNA-seq data suggested that the proportion of a unique mTEC cluster expressing Ccl25 and a high level of TSAs was severely decreased by irradiation. In sum, we propose that the effects of acute irradiation disrupt the heterogeneity and properties of mTECs over an extended period, which potentially leads to an impairment of thymic T cell selection.

An oxygen pump sensor was constructed using yttria-stabilized zirconia, which is an oxide ion conductor, and oxygen was discharged from steam to generate hydrogen. The oxygen pump sensor consisted of a pump that discharges oxygen and a sensor that controls the oxygen partial pressure by having electrodes in two places. Oxygen was discharged by applying a current to the pump by controlling the potential of the sensor. Hydrogen was then generated from water vapor. Furthermore, an oxygen pump sensor was installed in the second stage, oxygen was supplied by the pump, and the amount of generated hydrogen was measured in situ. This measurement showed that the oxygen partial pressure of the atmosphere decreased as hydrogen was generated. Specifically, the partial pressure of the water vapor generated more hydrogen at 30.8 vol.% than at 12.2 vol.%. Moreover, the amounts of oxygen discharged and hydrogen generated inversely correlated with the potential.

Ni coatings with high catalytic efficiency were synthesised in this work, obtained by increasing the active surface and modifying Pd as a noble metal. Porous Ni foam electrodes were obtained by electrodeposition of Al on a nickel substrate. Deposition of Al was carried out with potential −1.9 V for a time of 60 min in NaCl–KCl-3.5 mol%AlF3 molten salt mixture at 900 °C, which is connected with the formation of the Al-Ni phase in the solid state. Dissolution of Al and Al-Ni phases was performed by application of the potential −0.5 V, which provided the porous layer formation. The obtained porous material was compared to flat Ni plates in terms of electrocatalytic properties for ethanol oxidation in alkaline solutions. Cyclic voltammetry measurements in the non-Faradaic region revealed the improvement in morphology development for Ni foams, with an active surface area 5.5-times more developed than flat Ni electrodes. The catalytic activity was improved by the galvanic displacement process of Pd(II) ions from dilute chloride solutions (1 mM) at different times. In cyclic voltammetry scans, the highest catalytic activity was registered for porous Ni/Pd decorated at 60 min, where the maximum oxidation peak for 1 M ethanol achieved +393 mA cm−2 compared to the porous unmodified Ni electrode at +152 mA cm−2 and flat Ni at +55 mA cm−2. Chronoamperometric measurements in ethanol oxidation showed that porous electrodes were characterised by higher catalytic activity than flat electrodes. In addition, applying a thin layer of precious metal on the surface of nickel increased the recorded anode current density associated with the electrochemical oxidation process. The highest activity was recorded for porous coatings after modification in a solution containing palladium ions, obtaining a current density value of about 55 mA cm−2, and for a flat unmodified electrode, only 5 mA cm−2 after 1800 s.

Crimean-Congo Hemorrhagic Fever virus (CCHFV) is a tick-borne pathogen that causes severe acute fever disease in humans and requires a biosafety level 4 laboratory for handling. Hazara virus (HAZV), belonging to the same virus genus as CCHFV, does not exhibit pathogenesis in humans. To investigate host RNA-binding proteins (RBPs) that regulate CCHFV replication, we generated a series of mutant RAW264.7 cells by CRISPR/Cas9 system and these cells were infected with HAZV. The viral titers in the supernatant of these cells was investigated, and HuR (ELAVL1) was identified. HuR KO RAW264.7 cells reduced HAZV replication. HuR is an RBP that enhances mRNA stability by binding to adenyl-uridine (AU)-rich regions in their 3' non-coding region (NCR). HuR regulates innate immune response by binding to host mRNAs of signaling molecules. The expression of cytokine genes such as Ifnb, Il6, and Tnf was reduced in HuR KO cells after HAZV infection. Although HuR supports the innate immune response during HAZV infection, we found that innate immune activation by HAZV infection did not affect its replication. We then investigated whether HuR regulates HAZV genome RNA stability. HAZV RNA genome was precipitated with an anti-HuR antibody, and HAZV genome RNA stability was lowered in HuR KO cells. We found that HuR associated with HAZV RNA and stabilized it to enhance HAZV replication. Furthermore, HuR-deficiency reduced CCHFV minigenome replication. CCHFV is a negative-strand RNA virus and positive-strand RNA is produced during replication. HuR was associated with positive-strand RNA rather than negative-strand RNA, and AU-rich region in 3'-NCR of S segment was responsible for immunoprecipitation with anti-HuR antibody and minigenome replication. Additionally, HuR inhibitor treatment reduced CCHFV minigenome replication. Our results indicate that HuR aids replication of the CCHFV minigenome by associating with the AU-rich region in the 3'-NCR., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ikegawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this work, biopolymer chitosan and natural clay were used to obtain composite materials. The overall aim of this study was to improve the properties (porosity, thermal stability and density) of pure chitosan beads by the addition of clay and to obtain a chitosan-based composite material for the adsorption of heavy metals from an aqueous solution, using Mongolian resources, and to study the adsorption mechanism. The natural clay was pre-treated with acid and heat to remove the impurities. The chitosan and pre-treated clay were mixed in different ratios (8:1, 8:2 and 8:3) for chemical processing to obtain a composite bead for the adsorption of chromium ions. The adsorption of Cr(III) and Cr(VI) was studied as a function of the solution pH, time, temperature, initial concentration of the chromium solution and mass of the composite bead. It was found that the composite bead obtained from the mixture of chitosan and treated clay with a mass ratio of 8:1 and 8:2 had the highest adsorption capacity (23.5 and 17.31 mg·g -1 ) for Cr(III) and Cr(VI), respectively, in the optimum conditions. The properties of the composite materials, prepared by mixing chitosan and clay with a ratio of 8:1 and 8:2, were investigated using XRD, SEM-EDS, BET and TG analysis. The adsorption mechanism was discussed based on the XPS analysis results. It was confirmed that the chromium ions were adsorbed in their original form, such as Cr(III) and Cr(VI), without undergoing oxidation or reduction reactions. Furthermore, Cr(III) and Cr(VI) were associated with the hydroxyl and amino groups of the composite beads during adsorption. The kinetic, thermodynamic and isothermal analysis of the adsorption process revealed that the interaction between the chitosan/clay composite bead and Cr(III) and Cr(VI) ions can be considered as a second-order endothermic reaction, as such the adsorption can be assessed using the Langmuir isotherm model. It was concluded that the composite bead could be used as an adsorbent for the removal of chromium ions.

In this study, we applied the concept of the "contribution factor of the first kind (CFFK)" to the original electron-transfer (ET) rate theory proposed by Marcus. Mathematical derivations provided simple and convenient formulas for estimating the relative contributions of ten physical and chemical parameters involved in the Marcus ET rate formula: (1) the maximum strength of the electronic coupling energy between two molecules, (2) the exponential decay rate of the electronic coupling energy versus the distance between both molecules, (3) the distance between both molecules, (4) the equilibrium distance between both molecules, (5) the Gibbs free energy, (6) reorganization free energy in the prefactor of the Marcus ET rate equation, (7) reorganization free energy in the denominator of the exponential term, (8) reorganization free energy in the argument of the exponential term, (9) Boltzmann constant times absolute temperature in the prefactor of the rate equation, and (10) Boltzmann constant times absolute temperature in the denominator of the exponential term. We applied our theories to (i) ET reactions at bacterial photosynthesis reaction centers, PSI and PSII, and soluble ferredoxins (Fd); (ii) intraprotein ET reactions for designed azurin mutants; and (iii) ET reactions in flavodoxin (Fld). The formulas and calculations suggest that the theory behind the CFFK is useful for quantitatively identifying major and minor physical and chemical factors and corresponding trade-offs, all of which affect the magnitude of the Marcus ET rate.

This is the first detailed characterization of the microbiota and chemistry of different arid habitats from the State of Qatar. Analysis of bacterial 16S rRNA gene sequences showed that in aggregate, the dominant microbial phyla were Actinobacteria (32.3%), Proteobacteria (24.8%), Firmicutes (20.7%), Bacteroidetes (6.3%), and Chloroflexi (3.6%), though individual soils varied widely in the relative abundances of these and other phyla. Alpha diversity measured using feature richness (operational taxonomic units [OTUs]), Shannon's entropy, and Faith's phylogenetic diversity (PD) varied significantly between habitats ( P  = 0.016, P  = 0.016, and P  = 0.015, respectively). Sand, clay, and silt were significantly correlated with microbial diversity. Highly significant negative correlations were also seen at the class level between both classes Actinobacteria and Thermoleophilia (phylum Actinobacteria ) and total sodium ( R = -0.82 and P  = 0.001 and R = -0.86, P  = 0.000, respectively) and slowly available sodium ( R = -0.81 and P  = 0.001 and R = -0.8 and P  = 0.002, respectively). Additionally, class Actinobacteria also showed significant negative correlation with sodium/calcium ratio ( R = -0.81 and P  = 0.001). More work is needed to understand if there is a causal relationship between these soil chemical parameters and the relative abundances of these bacteria. IMPORTANCE Soil microbes perform a multitude of essential biological functions, including organic matter decomposition, nutrient cycling, and soil structure preservation. Qatar is one of the most hostile and fragile arid environments on earth and is expected to face a disproportionate impact of climate change in the coming years. Thus, it is critical to establish a baseline understanding of microbial community composition and to assess how soil edaphic factors correlate with microbial community composition in this region. Although some previous studies have quantified culturable microbes in specific Qatari habitats, this approach has serious limitations, as in environmental samples, approximately only 0.5% of cells are culturable. Hence, this method vastly underestimates natural diversity within these habitats. Our study is the first to systematically characterize the chemistry and total microbiota associated with different habitats present in the State of Qatar.

Amine catalysts have emerged as an invaluable tool in organic synthesis. Iminium, enamine, and enamine radical cation species are representative activation modes of amine catalysis. However, the development of new amine catalysis activation modes that enable novel synthetic strategies remains highly desirable. Herein, we report streptocyanine as a new amine catalysis activation mode, which enables the skeletal editing of pyridine rings to benzene rings. N -Arylation of pyridines bearing an alkenyl substituent at the 3-position generates the corresponding N -arylpyridiniums. The resulting pyridinum reacts with a catalytic amount of piperidine to afford a streptocyanine intermediate. Catalytically generated streptocyanine forms a benzene ring via a ring-closing reaction, thereby releasing the amine catalyst. Consequently, the alkene moiety in the starting pyridines is incorporated into the benzene ring of the products. Pyridiniums bearing various alkene moieties were efficiently converted to formyl-substituted benzene derivatives. Mechanistic studies support the postulation that the present catalytic process was intermediated by streptocyanine. In this reaction system, streptocyanine could be regarded as a new activation mode of amine catalysis., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

In this work, low-cost ceramic membranes (CMs) were prepared from ultrafine starting powders such as kaolin, clay, and starch by a dry compaction method. The ceramic membranes were sintered at different temperatures and times and were characterized by XRD, XRF, TG-DTA, SEM-EDS, N 2 -BET, water absorption, compressive strength, and pure water flux. The optimal membrane, sintered at 1000 °C for 3 h, possessed water absorption of 27.27%, a compressive strength of 31.05 MPa, and pure water flux of 20.74 L/h m 2 . Furthermore, chitosan crosslinked with glutaraldehyde was coated on the surface of the ceramic membrane by the dip coating method, and the pore size of the chitosan-coated ceramic membrane (CCCM) was 16.24 nm. Eventually, the separation performance of this membrane was assessed for the removal of chromium(VI) from aqueous solution. The ultrafine filtration of Cr(VI) was studied in the pH range of 2-7. The maximum removal of Cr(VI) was observed to be 71.25% with a pH of 3. The prepared CCCM showed good membrane properties such as mechanical stability and ultrafine structure, which have important applications for the treatment of wastewater including such heavy metals.

Competing Interests: None declared.

Pattern recognition receptors (PRRs) play critical roles in recognizing pathogen-derived nucleic acids and inducing innate immune responses, such as inflammation and type I interferon production. PRRs that recognize nucleic acids include members of endosomal Toll-like receptors, cytosolic retinoic acid inducible gene I-like receptors, cyclic GMP-AMP synthase, absent in melanoma 2-like receptors, and nucleotide binding oligomerization domain-like receptors. Aberrant recognition of self-derived nucleic acids by these PRRs or unexpected activation of downstream signaling pathways results in the constitutive production of type I interferons and inflammatory cytokines, which lead to the development of autoimmune or autoinflammatory diseases. In this review, we focus on the nucleic acid-sensing machinery and its pathophysiological roles in various inflammatory diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kano, Ong, Ori and Kawai.)

Herein, we report the transition-metal-free O-arylation of alcohols and phenols with S -arylphenothiaziniums, which can be easily synthesized from boronic acids. Aryl substituents derived from arylboronic acids were selectively introduced into the hydroxy groups in alcohols and phenols, and a variety of aryl ethers were synthesized. This selectivity is supported by theoretical calculations.

In this study, a method of removing an anionic surfactant sodium dodecyl sulfate (SDS) from an aqueous solution by cellulose modified with quaternary ammonium cation was discussed. Cellulose, as the adsorbent, was obtained from medical cotton balls, and the quaternary ammonium cation (synthesized from dodecyl dimethyl tertiary amine and epichlorohydrin) was grafted onto the sixth hydroxyl group of D-glucose in the cellulose by the Williamson reaction under alkaline conditions. The modified cellulose was characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS); and the zeta potential of the material was also measured after confirmation of the synthesis of quaternary ammonium salts by nuclear magnetic resonance (NMR). From these analyses, a peak of the quaternary ammonium group was observed at 1637 cm -1 ; and it was found that the surface of the material exhibited a positive charge in pH 2-7. The optimal conditions for SDS adsorption by modified cellulose were pH of 7, contact time of 3 h, and temperature of 60 °C in this study. Typical adsorption isotherms (Langmuir and Freundlich) were determined for the adsorption process, and the maximal adsorption capacity was estimated as 32.5 mg g -1 . The results of adsorption kinetics were more consistent with the pseudo-second-order equation, indicating that the adsorption process was mainly controlled by chemical adsorption. Furthermore, thermodynamic analysis indicated that the adsorption process of SDS on the modified cellulose was endothermic and spontaneous and that an increasing temperature was conducive to adsorption.

The innate immune system is an immediate defense against infectious pathogens by the production of inflammatory cytokines and other mediators. Deficiencies of epigenetic regulatory enzymes, such as Tet1 and Dnmt1 , cause dysregulation of cytokine expression. However, it is unclear if DNA methylation at a single CpG dinucleotide in a specific gene locus can regulate gene expression. In this study, we demonstrated that CpG+286 and CpG+348 in exon 2 of the Il6 gene are similar in various primary mouse cells. In lipopolysaccharide-stimulated condition, hypomethylated CpG+286 promoted Il6 expression whereas deletion of CpG+348 led to a reduction in Il6 expression associated with enhanced CTCF binding to the Il6 locus. Moreover, hypomethylation at CpG+286 in alveolar macrophages from aged mice led to higher Il6 expression in response to LPS compared with young mice. Thus, DNA methylation at specific CpG dinucleotides plays an important regulatory role in Il6 expression., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Author(s).)

A 40-year-old man presented at our hospital with anaemia that had been undiagnosed for 2 years. Blood tests, endoscopy, and contrast-enhanced computed tomography were performed, but a definitive diagnosis could not be made. A subsequent bone marrow biopsy revealed basophilic stippling in transformed red blood cells, which led to a differential diagnosis of lead poisoning. Additional tests revealed elevated levels of lead in the blood. Basophilic stippling is generally found on a peripheral blood smear in lead poisoning patients; however, in this case, basophilic stippling was found only on the bone marrow smear and not in the blood smear. Even if basophilic stippling is not found in the peripheral blood, lead poisoning cannot be excluded.

Background: This study aimed to clarify P-wave duration (PWD) ability before pacemaker implantation to predict worsening atrial fibrillation (AF) burden after the procedure., Methods: We retrospectively investigated 75 patients who underwent permanent pacemaker implantation due to sick sinus syndrome (SSS) at Komaki City Hospital between January 2006 and May 2019. Worsening AF burden was defined as an increase in the number of AF episodes, each lasting ≥5.5 hours a day., Results: In the study population, 17 patients (23%) had worsening AF burden during the follow-up period. These patients had significantly longer PWD in lead Ⅱ (117.9 ± 19.9 ms vs 101.3 ± 20.0 ms, P  = .002) than the patients without worsening AF burden. The best discriminative cutoff value for PWD in lead Ⅱ was 108 ms (sensitivity, 77%; specificity, 67%). In multivariate analysis, PWD in lead II ≥108 ms (hazard ratio, 5.395; 95% confidence interval, 1.352-21.523; P  = .017) was an independent predictor of worsening AF burden. Patients with PWD in lead II <108 ms showed a significantly higher event-free rate against worsening AF burden than those with PWD in lead II ≥108 ms (81% vs 9%, P  = .005)., Conclusions: Prolonged PWD before pacemaker implantation was the most important independent predictor of worsening AF burden after the procedure. In patients with SSS, prolonged PWD can be a useful marker for predicting worsening of AF burden after pacemaker implantation., Competing Interests: Authors declare no conflict of interests for this article., (© 2021 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of Japanese Heart Rhythm Society.)

Chitosan (CS) modified with ethylenediamine tetraacetic acid (EDTA) was further modified with the zeolite imidazole framework (ZIF-8) by in situ growth method and was employed as adsorbent for the removal of rare-earth elements (REEs). The material (EDTA-CS@ZIF-8) and ZIF-8 and CS were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM), and nitrogen adsorption/desorption experiments (N 2 - Brunauer-Emmet-Teller (BET)). The effects of adsorbent dosage, temperature, the pH of the aqueous solution, contact time on the adsorption of REEs (La(III), Eu(III), and Yb(III)) by EDTA-CS@ZIF-8 were studied. Typical adsorption isotherms (Langmuir, Freundlich, and Dubinin-Radushkevich (D-R)) were determined for the adsorption process, and the maximal adsorption capacity was estimated as 256.4 mg g -1 for La(III), 270.3 mg g -1 for Eu(III), and 294.1 mg g -1 for Yb(III). The adsorption kinetics results were consistent with the pseudo-second-order equation, indicating that the adsorption process was mainly chemical adsorption. The influence of competing ions on REE adsorption was also investigated. After multiple cycles of adsorption/desorption behavior, EDTA-CS@ZIF-8 still maintained high adsorption capacity for REEs. As a result, EDTA-CS@ZIF-8 possessed good adsorption properties such as stability and reusability, which have potential application in wastewater treatment.

Objectives: Information on the relationship between myocardial damage assessed by myocardial scintigraphy and prognosis in patients with Anderson-Fabry disease (AFD) is lacking. We therefore aimed to investigate the prognostic impacts of myocardial thallium-201 ( 201 Tl) and iodine-123 beta-methyl 15-para-iodophenyl 3(R, S)-methylpentadecanoic acid ( 123 I-BMIPP) dual scintigraphy in patients with AFD., Methods: Eighteen consecutive patients with AFD underwent resting myocardial 201 Tl/ 123 I-BMIPP dual scintigraphy. Total defect scores (TDS) on both images were calculated visually according to the 17-segment model using a 5-point scoring system. The mismatch score (MS) was calculated as 'TDS on 123 I-BMIPP-TDS on 201 Tl'., Results: Six major adverse cardiac events (MACEs) were recorded during a mean follow-up of 6.7 ± 4.2 years (three heart failure requiring hospitalization and three cardiac deaths). Left ventricular mass index, left atrial diameter, brain natriuretic peptide, TDS on 123 I-BMIPP, and MS were all significantly greater in patients with MACEs compared with those without. Kaplan-Meier analysis indicated that high TDS on 123 I-BMIPP and high MS were associated with poor event-free survival., Conclusion: TDS on 123 I-BMIPP was a better prognostic determinant in patients with AFD than TDS on 201 Tl. Myocardial 201 Tl/ 123 I-BMIPP dual scintigraphy may thus be a useful noninvasive modality for evaluating prognosis in patients with AFD.

The Kaifukuki-Rehabilitation Ward (KRW) is a type of inpatient rehabilitation facility in Japan. In the KRW of our institute, mortality and frequency of emergency referrals in 2013 were rather high, 2.6% and 4.3%, respectively. We aimed to investigate the usefulness of an original gatekeeping system to reduce mortality and morbidity from cardiac complications, and to improve the quality of medical care in the KRW. A total of 370 consecutive patients admitted to the KRW of Kobayashi Memorial Hospital between 1 May 2015 and 31 March 2016 were enrolled in this prospective observational study. All patients underwent a screening evaluation in which we defined patients as being screen positive (SC-positive) if they had at least one of 20 diagnostic ECG codes and/or BNP level over 140 pg/dL at admission. A cardiologist provided weekly interventions to those among SC-positive patients who needed cardiac disease treatment during hospitalization. In all, 129 patients were classified as SC-positive (mean age 80 years, 124 [32%] male), and weekly intervention was needed in 28 patients, including start of cardiac medication in 17 cases. Mortality and frequency of emergency transfer due to cardiac disease during hospital stay were 0.3% and 0.3%, respectively. Our gatekeeping system involving a screening evaluation at admission and weekly intervention in selected patients by a cardiologist may be useful in reducing mortality and rate of transfer due to cardiac disease and may improve quality of medical care in KRWs., Competing Interests: All authors have nothing to disclose.

An experiment on the adsorption of uranium (VI) by chitosan was conducted to investigate the efficiency of chitosan as an adsorbent for U(VI). The adsorption potential of U(VI) by chitosan was investigated with ICP-MS by varying the experimental conditions such as the pH in order to obtain the optimum conditions. Adsorption dependence on the pH was confirmed, and the highest uptake of U(VI) was observed at pH 5. In addition, to scrutinize the experimental results, quantum chemistry calculations were performed. The results, taking into account the experimental conditions, show that the adsorption efficiency increases as the total charge of the adsorbent and adsorbate species decreases if both of them are positively charged. It was also found that a slight change in the adsorption geometric configuration controls the adsorption efficiency.

Left ventricular hypertrophy (LVH) and proteinuria are known as independent predictors of cardiovascular death in hypertension. However, LVH and its association with proteinuria have not been investigated in adult hypertensive patients in Afghanistan. The objective of this research was to determine the prevalence of LVH and the correlation between LVH and proteinuria among the Afghan adult hypertensive population visiting an outpatient clinic in Afghanistan. We retrospectively evaluated 789 hypertensive patients (mean age is 56 years and 46% were men) who visited the clinic between December 2014 and August 2016. Patient characteristics and laboratory and clinical findings were recorded. The rate of LVH among hypertensive patients was 54.4%. Patients with proteinuria had a significantly higher LVH percentage compared to those without proteinuria (73.2% versus 55.8%; P <0.001). There was a significant correlation between LVH and proteinuria among hypertensive patients (r=0.182, P <0.001). Based on a multivariate regression analysis, age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02-1.05), proteinuria (OR, 1.69; 95% CI, 1.19-2.41), and female sex (OR, 0.09; 95% CI, 0.06-0.13) were significant factors. In conclusion, the prevalence of LVH was more than 50% in the Afghan adult hypertensive population. This study indicates that there is a significant relationship between LVH detected by ECG and the presence of proteinuria among such subjects.

The purpose was to clarify the effects of Helicobacter pylori ( H. pylori ) eradication on the changes in serum lipid levels by comparing subjects with and without continuous H. pylori infection. The study subjects were 774 individuals (males 536, females 238, mean age 52.6 years) who visited between April 2013 and March 2016 for annual medical checkups. Serum total cholesterol, high-density lipoprotein cholesterol (HDLC), low-density lipoprotein cholesterol (LDLC), and triglyceride levels, and LDLC/HDLC ratio were compared between the subjects with and without H. pylori infection, as well as those with H. pylori eradication subjects. The HDLC level in the H. pylori -positive group was significantly lower as compared to the H. pylori -negative group. The serum level of HDLC in subjects with successful eradication of H. pylori tended to be higher, while the serum levels of total cholesterol, LDLC, and triglycerides tended to be lower in comparison to subjects with continuous H. pylori infection. In addition, the LDLC/HDLC ratio in the H. pylori -positive group was significantly higher than that in the H. pylori -negative group, and successful H. pylori eradication tended to reduce that ratio. In conclusion, successful eradication of H. pylori may have favorable effects on lipid metabolism., Competing Interests: No potential conflicts of interest were disclosed.

Background: Myocardial fibrosis is associated with poor prognosis in nonischemic dilated cardiomyopathy (NIDCM) patients. The Selvester QRS score on 12-lead electrocardiogram is associated with both the amount of myocardial scar and poor prognosis in myocardial infarction patients. However, its use in NIDCM patients is limited. We investigated the prognostic value of the QRS score and its association with collagen volume fraction (CVF) in NIDCM patients., Methods: We enrolled 91 consecutive NIDCM patients (66 men, 53±13 years) without permanent pacemakers or cardiac resynchronization therapy devices. The Selvester QRS score was calculated by two expert cardiologists at NIDCM diagnosis. All patients were followed up over 4.5±3.2 years. Cardiac events were defined as a composite of cardiac death, hospitalization for worsening heart failure, and lethal arrhythmia. We also evaluated CVF using endomyocardial biopsy samples., Results: At baseline, the left ventricular ejection fraction was 32±9%, plasma brain natriuretic peptide level was 80 [43-237] pg/mL, and mean Selvester QRS score was 4.1 points. Twenty cardiac events were observed (cardiac death, n=1; hospitalization for worsening heart failure, n=16; lethal arrhythmia, n=3). Cox proportional hazard regression analysis revealed that the Selvester QRS score was an independent determinant of cardiac events (hazard ratio, 1.32; 95% confidence interval, 1.05-1.67; p=0.02). The best cut-off value was determined as 3 points, with 85% sensitivity and 47% specificity (area under the curve, 0.688, p=0.011). In Kaplan-Meier survival analysis, the QRS score ≥3 group had more cardiac events than the QRS score <3 group (log-rank, p=0.007). Further, there was a significant positive correlation of Selvester QRS score with CVF (r=0.46, p<0.001)., Conclusions: The Selvester QRS score can predict future cardiac events in NIDCM, reflecting myocardial fibrosis assessed by CVF., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

The COS-7 (CV-1 in Origin with SV40 genes) cells are known as non-steroidogenic cells because they are derived from kidney cells and the kidney is defined as a non-steroidogenic organ. Therefore, COS-7 cells are used for transfection experiments to analyze the actions of functional molecules including steroids. However, a preliminary study suggested that COS-7 cells metabolize [ 3 H]testosterone to [ 3 H]androstenedione. These results suggest that COS-7 cells are able to metabolize steroids. Therefore, the present study investigated the expression of steroidogenic enzymes and the metabolism of steroids in COS-7 cells. RT-PCR analyses demonstrated the expressions of several kinds of steroidogenic enzymes, such as cytochrome P450 side-chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase/Δ 5 -Δ 4 isomerase, cytochrome P450 7α-hydroxylase, cytochrome P450 17α-hydroxylase/17,20-lyase, 17β-hydroxysteroid dehydrogenase, 5α-reductase, cytochrome P450 21-hydroxylase, cytochrome P450 11β-hydroxylase, and cytochrome P450 aromatase in COS-7 cells. In addition, steroidogenic enzymes 3β-HSD, P4507α, 5α-reductase, P450c17, P450c21, P450c11β, and 17β-HSD actively metabolized various steroids in cultured COS-7 cells. Finally, we demonstrated that 17β-HSD activity toward androstenedione formation was greater than other steroidogenic enzyme activities. Our results provide new evidence that COS-7 cells express a series of steroidogenic enzyme mRNAs and actively metabolize a variety of steroids.

In this work, chitosan bead materials were modified by cross-linking with epichlorohydrin (EP) and glutaraldehyde (GA) for the removal of heavy metals in wastewater. Using these cross-linked chitosan materials, the dependence of adsorption of chromate anions on pH was investigated experimentally and theoretically. The experimental results show that the adsorption process of the chromate (Cr) ions greatly depends on the pH of the solution, with the chitosan modified by cross-linking being an efficient adsorbent for chromate. On the other hand, quantum chemistry calculations were conducted to find out the factor determining the pH dependence of the adsorption efficiency of chromate ions on the dimer chitosan molecule, and show results similar to those found in the experiment. Both the experimental and numerical results show that the total charge numbers of the adsorbent and the adsorbate species and their relative molecular geometries are crucial in determining the adsorption efficiency., Competing Interests: The authors declare no conflict of interest.

Aim: Fast-progressing vascular calcification (VC) is accompanied by renal atrophy and functional deterioration along with atherosclerosis in patients with chronic kidney disease (CKD). However, the relationship between VC progression and renal functional and/or morphological changes remains unclear., Methods: We included 70 asymptomatic patients with CKD without hemodialysis in our study. To identify temporal variations, the coronary artery calcification score (CACS), abdominal aortic calcification index (ACI), and renal parenchymal volume index (RPVI) were determined via spiral computed tomography scans taken during the study. We investigated significant factors related to annualized variations of CACS (ΔCACS/y) and ACI (ΔACI/y)., Results: During the follow-up period (4.6 years), median values of CACS [in Agatston units (AU)] and ACI increased from 40.2 to 113.3 AU (p=0.053) and from 13.2 to 21.7% (p=0.036), respectively. Multivariate analysis revealed that CACS at baseline (p＜0.001) and diabetes mellitus (DM) status (p=0.037) for ΔCACS/y and ACI at baseline (p=0.017) and hypertension (HT) status (p= 0.046) for ΔACI/y were significant independent predictors. Furthermore, annualized RPVI variation was significantly related to both ΔCACS/y and ΔACI/y (R=-0.565, p＜0.001, and R=-0.289, p=0.015, respectively). On the other hand, independent contributions of the estimated glomerular filtration rate (eGFR) and annualized eGFR variation to VC progression were not confirmed., Conclusion: The degree of VC at baseline, DM, HT, and changes in renal volume, but not eGFR, had a strong impact on VC progression in patients with CKD.

Background: Catecholamine sensitivity estimated using a dobutamine stress test (DST) is recognized as a measure of the beta-adrenergic myocardial contractile reserve, which is involved with left ventricular reverse remodeling (LV-RR). We investigated whether the prognostic ability of the DST for LV-RR could predict cardiac events., Methods: There was a total of 192 enrolled patients with dilated cardiomyopathy (DCM). DCM was defined as a LV ejection fraction (LV-EF) ≤45% and LV end-diastolic dimension (LVDd) ≥55mm. One hundred patients were subjected to micromanometer-based measurement of the maximal first derivative of LV pressure (LVdP/dt max ), an index of LV contractility, at baseline and following the infusion of dobutamine (10μg/kg/min) via a pigtail catheter. Percentage changes in LVdP/dt max from the baseline to peak values under dobutamine stress (ΔLVdP/dt max ) were also calculated. After excluding 17 patients who received cardiac resynchronization therapy within 3 months of undergoing DST (n=15) and who did not receive follow-up echocardiography (n=2), 83 patients were enrolled (52.5±12.3 years)., Results: During the follow-up period (4.7±2.6 years), LV-RR was recognized in 49 of 83 patients (59.0%). A multivariate logistic regression analysis revealed that ΔLVdP/dt max (hazard ratio: 1.024, p=0.007) and the symptom duration (hazard ratio: 0.977, p=0.003) were independent predictors of LV-RR. A receiver operating characteristic curve analysis revealed a ΔLVdP/dt max cut-off value of 75.1% for LV-RR and a significantly lower cardiac event rate in the ΔLVdP/dt max ≥75.1% group (p=0.045)., Conclusions: ΔLVdP/dt max estimated using DST was a useful predictor of LV-RR and cardiac events in patients with DCM., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)