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Considering these good performances, this work may prove new ideas for the generation of complex optical field and find wide applications in polarization imaging.In higher plants, chloroplast ATP synthase has a unique redox switch on its γ subunit that modulates enzyme activity to limit ATP hydrolysis at night. To understand the molecular details of the redox modulation, we used single-particle cryo-EM to determine the structures of spinach chloroplast ATP synthase in both reduced and oxidized states. The disulfide linkage of the oxidized γ subunit introduces a torsional constraint to stabilize the two β hairpin structures. Once reduced, free cysteines alleviate this constraint, resulting in a concerted motion of the enzyme complex and a smooth transition between rotary states to facilitate the ATP synthesis. We added an uncompetitive inhibitor, tentoxin, in the reduced sample to limit the flexibility of the enzyme and obtained high-resolution details. Our cryo-EM structures provide mechanistic insight into the redox modulation of the energy regulation activity of chloroplast ATP synthase.The antidiabetic drug canagliflozin is reported to possess several cardioprotective effects. However, no studies have investigated protective effects of canagliflozin in isoprenaline (ISO)-induced cardiac oxidative damage-a model mimicking sympathetic nervous system (SNS) overstimulation-evoked cardiac injuries in humans. Therefore, we investigated protective effects of canagliflozin in ISO-induced cardiac oxidative stress, and their underlying molecular mechanisms in Long-Evans rat heart and in HL-1 cardiomyocyte cell line. Peficitinib mouse Our data showed that ISO administration inflicts pro-oxidative changes in heart by stimulating production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). In contrast, canagliflozin treatment in ISO rats not only preserves endogenous antioxidants but also reduces cardiac oxidative stress markers, fibrosis and apoptosis. Our Western blotting and messenger RNA expression data demonstrated that canagliflozin augments antioxidant and anti-inflammatory signaling involving AMP-activated protein kinase (AMPK), Akt, endothelial nitric oxide synthase (eNOS), nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). In addition, canagliflozin treatment attenuates pro-oxidative, pro-inflammatory and pro-apoptotic signaling mediated by inducible nitric oxide synthase (iNOS), transforming growth factor beta (TGF-β), NADPH oxidase isoform 4 (Nox4), caspase-3 and Bax. Consistently, canagliflozin treatment improves heart function marker in ISO-treated rats. In summary, we demonstrated that canagliflozin produces cardioprotective actions by promoting multiple antioxidant and anti-inflammatory signaling.Although approved programmed cell death protein (PD)-1 inhibitors show durable responses, clinical benefits to these agents are only seen in one-third of patients in most cancer types. Therefore, strategies for improving the response to PD-1 inhibitor for treating various cancers including non-small cell lung cancer (NSCLC) are urgently needed. Compared with genome and transcriptome, tumor DNA methylome in anti-PD-1 response was relatively unexplored. We compared the pre-treatment methylation status of cis-regulatory elements between responders and non-responders to treatment with nivolumab or pembrolizumab using the Infinium Methylation EPIC Array, which can profile ~850,000 CpG sites, including ~350,000 CpG sites located in enhancer regions. Then, we analyzed differentially methylated regions overlapping promoters (pDMRs) or enhancers (eDMRs) between responders and non-responders to PD-1 inhibitors. We identified 1007 pDMRs and 607 eDMRs associated with the anti-PD-1 response. We also identified 1109 and 1173 target genes putatively regulated by these pDMRs and eDMRs, respectively. We found that eDMRs contribute to the epigenetic regulation of the anti-PD-1 response more than pDMRs. Hypomethylated pDMRs of Cytohesin 1 Interacting Protein (CYTIP) and TNF superfamily member 8 (TNFSF8) were more predictive than programmed cell death protein ligand 1 (PD-L1) expression for anti-PD-1 response and progression-free survival (PFS) and overall survival (OS) in a validation cohort, suggesting their potential as predictive biomarkers for anti-PD-1 immunotherapy. The catalog of promoters and enhancers differentially methylated between responders and non-responders to PD-1 inhibitors presented herein will guide the development of biomarkers and therapeutic strategies for improving anti-PD-1 immunotherapy in NSCLC.We study the change in magnetisation with paramagnetic Al addition in the CoFeNi0.5Cr0.5-Alx (x 0, 0.5, 1, and 1.5) complex concentrated alloy. The compositions were developed utilising the Mulliken electronegativity and d-electron/atom ratio. Spherical FeCr rich nanoprecipitates are observed for X 1.0 and 1.5 in an AlCoNi-rich matrix. A ~ 5 × increase in magnetisation (from 22 to 96 Am2/kg) coincides with this nanoprecipitate formation-the main magnetic contribution is determined to be from FeCr nanoprecipitates. The magnetisation increase is strange as paramagnetic Al addition dilutes the ferromagnetic Fe/Co/Ni additions. In this paper we discuss the magnetic and structural characterisation of the CoFeNi0.5Cr0.5-Alx composition and attempt to relate it to the interfacial energy.Vascular endothelial growth factor A (VEGF-A) and its binding to VEGFRs is an important angiogenesis regulator, especially the earliest-known isoform, VEGF-A165a. Yet several additional splice variants play prominent roles in regulating angiogenesis in health and in vascular disease, including VEGF-A121 and an anti-angiogenic variant, VEGF-A165b. Few studies have attempted to distinguish these forms from their angiogenic counterparts, experimentally. Previous studies of VEGF-AVEGFR binding have measured binding kinetics for VEGFA165 and VEGF-A121, but binding kinetics of the other two pro- and all anti-angiogenic splice variants are not known. We measured the binding kinetics for VEGF-A165, -A165b, and -A121 with VEGFR1 and VEGF-R2 using surface plasmon resonance. We validated our methods by reproducing the known affinities between VEGF-A165aVEGFR1 and VEGF-A165aVEGFR2, 1.0 pM and 10 pM respectively, and validated the known affinity VEGF-A121VEGFR2 as KD = 0.66 nM. We found that VEGF-A121 also binds VEGFR1 with an affinity KD = 3.