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Rationale & Objective: In the general population, neighborhood socioeconomic status (SES) has been found to be associated with cardiovascular risk, but this relationship has not been well studied among patients with chronic kidney disease (CKD). This study seeked to evaluate the association between neighborhood SES and cardiovascular outcomes in a CKD cohort. Study Design: Multicenter prospective cohort. Setting & Participants: In total, 3,197 participants in the Chronic Renal Insufficiency Cohort Study without cardiovascular disease at baseline. Exposure: Neighborhood SES quartiles using a validated neighborhood-level SES summary measure for 6 census-derived variables. Outcome: Incident heart failure, myocardial infarction, and all-cause death. Analytical Approach: Cox proportional hazards. Results: During median follow-up of 8.8 years, there were 465 incident heart failure events, 297 myocardial infarctions, and 891 deaths. In a fully adjusted model, among individuals with estimated glomerular filtration rate ≥45 mL/min/1.73 m2, lowest neighborhood SES quartile was associated with higher risk of heart failure (HR, 1.96 [95% CI, 1.04-3.67]) compared with the highest quartile. This association was not significant among those with estimated glomerular filtration rate

TaAs single crystals were grown by a standard chemical vapor transport method. The single-crystallinity and homogeneous distribution of elements were confirmed by transmission electron microscope and x-ray diffraction observations. Positron annihilation measurements revealed that the atomic vacancy concentration was kept below 10 − 5 at. %. However, inductively coupled plasma analysis showed an As-deficient (7–9 at. %) off-stoichiometry. First-principles calculations implied that the off-stoichiometry could be compensated for with excess Ta antisite defects, thereby inducing metallic states. Nevertheless, excellent semimetallic transport properties of a well-suppressed carrier density (≲ 10 18 cm − 3 ), ultrahigh carrier mobility (≳ 10 6 cm 2 /V/s), and large transverse magnetoresistance (> --> 200 000 % at 9 T) with the quantum oscillation were obtained at 1.7 K. This indicated the robustness of semimetallic transport properties against the off-stoichiometric disorder and the quenching of metallic conduction associated with excess Ta atoms. The negative longitudinal magnetoresistance, which is considered evidence of a Weyl semimetal (chiral anomaly), was not observed. These data were discussed with theoretical calculations. [ABSTRACT FROM AUTHOR]

More patients are discharged directly to home (DDH) after intensive care admission. This single-centre study compared admission characteristics, length of stay and discharge outcomes of DDH patients after mechanical ventilation, compared to patients discharged to wards (DW). Of 161 eligible patients, 32.9% were DDH and 68.1% were DW. DDH patients were significantly younger with lower APACHE II scores. They were ventilated for a shorter length of time, and overall length of stay was 7 days shorter. Physical function scores (CPAx) were significantly higher in DDH. There were no differences in re-admission or 90-day mortality. In certain patients, discharge direct to home may be a safe option., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Intensive Care Society 2024.)

Evaporable indano[60]fullerene ketone (FIDO) was converted to indano[60]fullerene thioketone (FIDS) in high yield by using Lawesson's reagent. Three compounds with different substituents in para position were successfully converted to the corresponding thioketones, showing that the reaction tolerates compounds with electron-donating and electron-withdrawing substituents. Computational studies with density functional theory revealed the unique vibrations of the thioketone group in FIDS. The molecular structure of FIDS was confirmed by single-crystal X-ray analysis. Bulk heterojunction organic solar cells using three evaporable fullerene derivatives (FIDO, FIDS, C 60 ) as electron-acceptors were compared, and the open-circuit voltage with FIDS was 0.16 V higher than that with C 60 ., (Copyright © 2024, Zhai et al.)

A chelating fabric was prepared by graft polymerization of glycidyl methacrylate (GMA) onto a nonwoven fabric, followed by attachment reaction of N-methyl-D-glucamine (NMDG) using an organic solvent-free process. The graft polymerization was performed by immersing the gamma-ray pre-irradiated fabric into the GMA emulsion, while the attachment reaction was carried out by immersing the grafted fabric in the NMDG aqueous solution. The chelating capacity of the chelating fabric prepared by reaction in the NMDG aqueous solution without any additives reached 1.74 mmol/g, which further increased to above 2.0 mmol/g when surfactant and acid catalyst were added in the solution. The boron chelation of the chelating fabric was evaluated in a batch mode. Fourier transform infrared spectrophotometer (FTIR) was used to characterize the fabrics. The chelating fabric can quickly chelate boron from water to form a boron ester, and a high boron chelating ability close to 18.3 mg/g was achieved in the concentrated boron solution. The chelated boron can be eluted completely by HCl solution. The regeneration and stability of the chelating fabric were tested by 10 cycles of the chelation-elution operations. Considering the organic solvent-free preparation process and the high boron chelating performance, the chelating fabric is promising for the boron removal from water.

Gonorrhea is a common, sexually transmitted disease caused by Neisseria gonorrhoeae Multidrug-resistant N. gonorrhoeae is an urgent threat, and the development of a new antimicrobial agent that functions via a new mechanism is strongly desired. We evaluated the in vitro and in vivo activities of a DNA gyrase/topoisomerase IV inhibitor, TP0480066, which is a novel 8-(methylamino)-2-oxo-1,2-dihydroquinoline derivative. The MICs of TP0480066 were substantially lower than those of other currently or previously used antimicrobials against gonococcal strains demonstrating resistance to fluoroquinolones, macrolides, β-lactams, and aminoglycosides (MICs, ≤0.0005 μg/ml). Additionally, no cross-resistance was observed between TP0480066 and ciprofloxacin. The frequencies of spontaneous resistance to TP0480066 for N. gonorrhoeae ATCC 49226 were below the detection limit (<2.4 × 10 -10 ) at concentrations equivalent to 32× MIC. TP0480066 also showed potent in vitro bactericidal activity and in vivo efficacy in a mouse model of N. gonorrhoeae infection. These data suggest that TP0480066 is a candidate antimicrobial agent for gonococcal infections., (Copyright © 2021 American Society for Microbiology.)

The global increase in multidrug-resistant pathogens has caused severe problems in the treatment of infections. To overcome these difficulties, the advent of a new chemical class of antibacterial drug is eagerly desired. We aimed at creating novel antibacterial agents against bacterial type II topoisomerases, which are well-validated targets. TP0480066 (compound 32) has been identified by using structure-based optimization originated from lead compound 1, which was obtained as a result of our previous lead identification studies. The MIC 90 values of TP0480066 against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and genotype penicillin-resistant Streptococcus pneumoniae (gPRSP) were 0.25, 0.015, and 0.06 μg/mL, respectively. Hence, TP0480066 can be regarded as a promising antibacterial drug candidate of this chemical class., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A nonwoven fabric adsorbent loaded with 2-ethylhexyl hydrogen-2-ethylhexylphosphonate (EHEP) was developed for the separation and recovery of dysprosium (Dy) and neodymium (Nd) from an aqueous solution. The adsorbent was prepared by the radiation-induced graft polymerization of a methacrylate monomer with a long alkyl chain onto a nonwoven fabric and the subsequent loading of EHEP by hydrophobic interaction and chain entanglement between the alkyl chains. The adsorbent was evaluated by batch and column tests with a Dy (III) and Nd (III) aqueous solution. In the batch tests, the adsorbent showed high Dy (III) adsorptivity close to 25.0 mg/g but low Nd (III) adsorptivity below 1.0 mg/g, indicating that the adsorbent had high selective adsorption. In particular, the octadecyl methacrylate (OMA)-adsorbent showed adsorption stability in repeated tests. In the column tests, the OMA-adsorbent was also stable and showed high Dy (III) adsorptivity and high selectivity in repeated adsorption-elution circle tests. This result suggested that the OMA-adsorbent may be a promising adsorbent for the separation and recovery of Dy (III) and Nd (III) ions.

DNA gyrase and topoisomerase IV are well-validated pharmacological targets, and quinolone antibacterial drugs are marketed as their representative inhibitors. However, in recent years, resistance to these existing drugs has become a problem, and new chemical classes of antibiotics that can combat resistant strains of bacteria are strongly needed. In this study, we applied our hit-to-lead (H2L) chemistry for the identification of a new chemical class of GyrB/ParE inhibitors by efficient use of thermodynamic parameters. Investigation of the core fragments obtained by fragmentation of high-throughput screening hit compounds and subsequent expansion of the hit fragment was performed using isothermal titration calorimetry (ITC). The 8-(methylamino)-2-oxo-1,2-dihydroquinoline derivative 13e showed potent activity against Escherichia coli DNA gyrase with an IC 50 value of 0.0017 μM. In this study, we demonstrated the use of ITC for primary fragment screening, followed by structural optimization to obtain lead compounds, which advanced into further optimization for creating novel antibacterial agents., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

The design and synthesis of a novel class of low-absorbable SGLT1 inhibitors are described. To achieve low absorption in the new series, we performed an optimization study based on a strategy to increase TPSA. Fortunately, the optimization of an aglycon moiety and a side chain of the distal aglycon moiety led to the identification of compound 30b as a potent and low-absorbable SGLT1 inhibitor. Compound 30b showed a desirable PK profile in Sprague-Dawley (SD) rats and a favorable glucose-lowering effect in diabetic rats., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The artificial photosynthesis technology known as the Honda-Fujishima effect, which produces oxygen and hydrogen or organic energy from sunlight, water, and carbon dioxide, is an effective energy and environmental technology. The key component for the higher efficiency of this reaction system is the anode electrode, generally composed of a photocatalyst formed on a glass substrate from electrically conductive fluorine-doped tin oxide (FTO). To obtain a highly efficient electrode, a dense film composed of a nanoparticulate visible light responsive photocatalyst that usually has a complicated multi-element composition needs to be deposited and adhered onto the FTO. In this study, we discovered a method for controlling the electronic structure of a film by controlling the aerosol-type nanoparticle deposition (NPD) condition and thereby forming films of materials with a band gap smaller than that of the prepared raw material powder, and we succeeded in extracting a higher current from the anode electrode. As a result, we confirmed that a current approximately 100 times larger than those produced by conventional processes could be obtained using the same material. This effect can be expected not only from the materials discussed (GaN-ZnO) in this paper but also from any photocatalyst, particularly materials of solid solution compositions.

7-Methoxy-6-[4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-5-yl]-1,3-benzothiazole 11 (TASP0382088) was synthesized and evaluated as transforming growth factor-β (TGF-β) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitor. Compound 11, a potent and selective ALK5 inhibitor, exhibited good enzyme inhibitory activity (IC50=4.8 nM) as well as inhibitory activity against TGF-β-induced Smad2/3 phosphorylation at a cellular level (IC50=17 nM). The introduction of a methoxy group to the benzothiazole ring in 1 and the break up of the planarity between the imidazole ring and the thiazole ring improved the solubility in the lotion base of 11. Furthermore, the topical application of 3% 11 lotion significantly inhibited Smad2 phosphorylation in mouse skin at 8 h after application (71% inhibition, compared with vehicle-treated animals).

A series of 5-(1,3-benzothiazol-6-yl)-4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazole derivatives was synthesized as transforming growth factor-β (TGF-β) type I receptor (also known as activin-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and for their TGF-β-induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. As a representative compound, 16i was a potent and selective ALK5 inhibitor, exhibiting a good enzyme inhibitory activity (IC(50) = 5.5 nM) as well as inhibitory activity against TGF-β-induced Smad2/3 phosphorylation at a cellular level (IC(50) = 36 nM). Furthermore, the topical application of 3% 16i lotion significantly inhibited Smad2 phosphorylation in Mouse skin (90% inhibition compared with vehicle-treated animals)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

A novel series of 4-thiazolylimidazoles was synthesized as transforming growth factor-β (TGF-β) type I receptor (also known as activin receptor-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and their TGF-β-induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. N-{[5-(1,3-benzothiazol-6-yl)-4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazol-2-yl]methyl}butanamide 20, a potent and selective ALK5 inhibitor, exhibited good enzyme inhibitory activity (IC(50)=8.2nM) as well as inhibitory activity against TGF-β-induced Smad2/3 phosphorylation at a cellular level (IC(50)=32nM)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We have identified a novel series of ring-fused pyrazole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC(50)s <1nM) as well as excellent cellular activity against mixed lymphocyte reaction (MLR) (IC(50)s <1nM)., (Copyright 2009 Elsevier Ltd. All rights reserved.)

We have described the synthesis, enzyme inhibitory activity, structure-activity relationships, and proposed binding mode of a novel series of pyrrole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC(50)s <10nM) for Lck kinase inhibition., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Improvement of the physical properties of pyrazole derivative 1, which we reported previously as a potent and selective 20-HETE synthase inhibitor (IC(50) 5.7 nM), is described. Introduction of a sufficient substituted-amino group on the side chain enhanced the water-solubility of 1 (0.014 mg/mL at pH 6.8). Among the products, 2-piperazinoethoxy derivatives 3e and 6b showed solubility suitable for injection and potent inhibitory activity toward 20-HETE synthase (IC(50) 21.2 and 14.0 nM, respectively).

In a previous paper, we reported that an imidazole derivative 1 exhibited a potent inhibitory activity of 20-HETE synthase (1; IC(50) value of 5.7 nM), but this compound also exhibited little selectivity for cytochrome P450s (CYPs). We examined some derivatives of imidazole 1 which had an amino group on the side chain, and found that a dimethylaminohexyloxy derivative (3g; IC(50) value of 8.8 nM) showed potent and selective inhibitory activity.