Blocking CTLA-4 promotes pressure overload-induced heart failure via activating Th17 cells.

Targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) with specific antibody offers long-term benefits for cancer immunotherapy but can cause severe adverse effects in the heart. This study aimed to investigate the role of anti-CTLA-4 antibody in pressure overload-induced cardiac remodeling and dysfunction. Transverse aortic constriction (TAC) was used to induce cardiac hypertrophy and heart failure in mice. Two weeks after the TAC treatment, mice received anti-CTLA-4 antibody injection twice a week at a dose of 10 mg/kg body weight. The administration of anti-CTLA-4 antibody exacerbated TAC-induced decline in cardiac function, intensifying myocardial hypertrophy and fibrosis. Further investigation revealed that anti-CTLA-4 antibody significantly elevated systemic inflammatory factors levels and facilitated the differentiation of T helper 17 (Th17) cells in the peripheral blood of TAC-treated mice. Importantly, anti-CTLA-4 mediated differentiation of Th17 cells and hypertrophic phenotype in TAC mice were dramatically alleviated by the inhibition of interleukin-17A (IL-17A) by an anti-IL-17A antibody. Furthermore, the C-X-C motif chemokine receptor 4 (CXCR4) antagonist AMD3100, also reversed anti-CTLA-4-mediated cardiotoxicity in TAC mice. Overall, these results suggest that the administration of anti-CTLA-4 antibody exacerbates pressure overload-induced heart failure by activating and promoting the differentiation of Th17 cells. Targeting the CXCR4/Th17/IL-17A axis could be a potential therapeutic strategy for mitigating immune checkpoint inhibitors-induced cardiotoxicity.

Cobalt/Iron Bimetallic Biochar Composites for Lead(II) Adsorption: Mechanism and Remediation Performance.

The performance of nano-zero-valent iron for heavy metal remediation can be enhanced via incorporation into bimetallic carbon composites. However, few economical and green approaches are available for preparing bimetallic composite materials. In this study, novel Co/Fe bimetallic biochar composites (BC@Co/Fe-X, where X = 5 or 10 represents the CoCl2 concentration of 0.05 or 0.1 mol L-1) were prepared for the adsorption of Pb2+. The effect of the concentration of cross-linked metal ions on Pb2+ adsorption was investigated, with the composite prepared using 0.05 mol L-1 Co2+ (BC@Co/Fe-5) exhibiting the highest adsorption performance. Various factors, including the adsorption period, Pb2+ concentration, and pH, affected the adsorption of Pb2+ by BC@Co/Fe-5. Further characterisation of BC@Co/Fe-5 before and after Pb2+ adsorption using methods such as X-ray diffraction and X-ray photoelectron spectroscopy suggested that the Pb2+ adsorption mechanism involved (i) Pb2+ reduction to Pb0 by Co/Fe, (ii) Co/Fe corrosion to generate Fe2+ and fix Pb2+ in the form of PbO, and (iii) Pb2+ adsorption by Co/Fe biochar. Notably, BC@Co/Fe-5 exhibited excellent remediation performance in simulated Pb2+-contaminated water and soil with good recyclability.

Aldosterone-stimulated endothelial epithelial sodium channel (EnNaC) plays a role in cold exposure-induced hypertension in rats.

Background: Previous studies have demonstrated that activated endothelial epithelial sodium channel (EnNaC) impairs vasodilatation, which contributes to salt-sensitive hypertension. Here, we investigate whether mesenteric artery (MA) EnNaC is involved in cold exposure-induced hypertension (CIH) and identify the underlying mechanisms in SD rats. Methods: One group of rats was housed at room temperature and served as control. Three groups of rats were kept in a 4°C cold incubator for 10 h/day; among which two groups were administrated with either benzamil (EnNaC blocker) or eplerenone (mineralocorticoid receptor antagonist, MR). Blood pressure (BP), vasodilatation, and endothelial function were measured with tail-cuff plethysmography, isometric myograph, and Total Nitric Oxide (NO) Assay kit, respectively. A cell-attached patch-clamp technique, in split-open MA, was used to determine the role of EnNaC in CIH rats. Furthermore, the plasma aldosterone levels were detected using an ELISA kit; and Western blot analysis was used to examine the relative expression levels of Sgk1 and Nedd4-2 proteins in the MA of SD rats. Results: We demonstrated that cold exposure increased BP, impaired vasodilatation, and caused endothelial dysfunction in rats. The activity of EnNaC significantly increased, concomitant with an increased level of plasma aldosterone and activation of Sgk1/Nedd4-2 signaling. Importantly, CIH was inhibited by either eplerenone or benzamil. It appeared that cold-induced decrease in NO production and impairment of endothelium-dependent relaxation (EDR) were significantly ameliorated by either eplerenone or benzamil in MA of CIH rats. Moreover, treatment of MAs with aldosterone resulted in an activation of EnNaC, a reduction of NO, and an impairment of EDR, which were significantly inhibited by either eplerenone or GSK650394 (Sgk1 inhibitor) or benzamil. Conclusion: Activation of EnNaC contributes to CIH; we suggest that pharmacological inhibition of the MR/Sgk1/Nedd4-2/EnNaC axis may be a potential therapeutic strategy for CIH.

Pyrene[4,5-d]imidazole-Based Derivatives with Hybridized Local and Charge-Transfer State for Highly Efficient Blue and White Organic Light-Emitting Diodes with Low Efficiency Roll-Off.

A family of pyrene[4,5-d]imidazole derivatives, PyPA, PyPPA, PyPPAC, and PyPAC, with different excited states are successfully developed. Among them, PyPPA and PyPPAC possess hybridized local and charge-transfer (HLCT) state, endowing them with pure blue fluorescence as well as high quantum yields. The nondoped organic light-emitting diode (OLED) based on PyPPA displays Commission Internationale de L'Eclairage coordinates of (0.14, 0.13) and achieves a maximum external quantum efficiency (EQE) of 8.47%, which are among the highest value reported to date for nondoped blue HLCT OLEDs. The nondoped OLED based on PyPPAC exhibits a maximum luminance of 50,046 cd m-2 located in the blue region with CIE coordinates of (0.15, 0.21) and an EQE of 6.74% even when the luminance reached over 10,000 cd m-2. In addition, they both reveal ultimate exciton utilizing efficiencies of nearly 100%. The potential of a blue emitter of PyPPA with an HLCT character for application in white OLED (WOLED) is further tested. The efficient two-color hybrid warm WOLED is successfully achieved, which provides the total EQE, power efficiency, and current efficiency of up to 21.19%, 61.46 lm W-1, and 62.13 cd A-1, respectively. The nondoped blue OLEDs and hybrid WOLEDs present good color stabilities with low efficiency roll-offs. Our results prove that taking advantage of the HLCT state, nondoped blue OLEDs as well as hybrid WOLEDs with high performance could be realized, which have a promising prospect for the displays and lightings in the future.

Complete nucleotide sequence of Klebsiella phage P13 and prediction of an EPS depolymerase gene.

The complete genome of Klebsiella phage P13 was sequenced and analyzed. Bacteriophage P13 has a double-stranded linear DNA with a length of 45,976 bp and a G+C content of 51.7 %, which is slightly lower than that of Klebsiella pneumoniae KCTC 2242. The codon biases of phage P13 are very similar to those of SP6-like phages and K. pneumoniae KCTC 2242. Bioinformatics analysis shows that the phage P13 genome has 282 open reading frames (ORFs) that are greater than 100 bp in length, and 50 of these ORFs were identified as predicted genes with an average length of 833 bp. Among these genes, 41 show homology to known proteins in the GenBank database. The functions of the 24 putative proteins were investigated, and 13 of these were found to be highly conserved. According to the homology analysis of the 50 predicted genes and the whole genome, phage P13 is homologous to SP6-like phages. Furthermore, the morphological characteristics of phage P13 suggest that it belongs to the SP6-like viral genus of the Podoviridae subfamily Autographivirinae. Two hypothetical genes encoding an extracellular polysaccharide depolymerase were predicted using PSI-BLAST. This analysis serves as groundwork for further research and application of the enzyme.