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Photoreceptor cell death, primarily through apoptosis, related to retinal disorders like retinitis pigmentosa (RP), would result in vision loss. The pathological processes and crucial mutant conditions preceding photoreceptor cell demise are not well understood. This study aims to conduct an in-depth examination of early-stage changes in the widely utilized Pde6brd1/rd1 (rd1) mouse model, which has Pde6b gene mutations representing autosomal recessive RP disorder. We investigated the morphology and ultrastructure of retinal cells, including second-order neurons, during the initial phase of disease progression. Our findings revealed that mitochondrial alterations in rod photoreceptors were present as a predeath mutant state as early as postnatal day 3 (P3). The bipolar and horizontal cells from the rd1 mouse retina exhibited significant morphological changes in response to loss of photoreceptor cells, indicating that second-order neurons rely on these cells for their structures. Subsequent oral administration of idebenone, a mitochondria-protective agent, enhanced retinal function and promoted both photoreceptor cell survival and inner retinal second-order synaptogenesis in rd1 mice at P14. Our findings offer a mechanistic framework, suggesting that mitochondrial damage acts as an early driver for photoreceptor cell death in retinal degeneration. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a chronic inflammatory disease that affects arteries and is the main cause of cardiovascular disease. Atherosclerotic plaque formation is usually asymptomatic and does not manifest until the occurrence of clinical events. Therefore, early diagnosis and treatment of atherosclerotic plaques is particularly important. Here, a series of NIR‐II fluorescent dyes (RBT‐NH) are developed for three photoresponsive NO prodrugs (RBT‐NO), which can be controllably triggered by 808 nm laser to release NO and turn on the NIR‐II emission in the clinical medicine "therapeutic window". Notably, RBT3‐NO is selected for its exhibited high NO releasing efficiency and superior fluorescence signal enhancement. Subsequently, a platelet‐mimicking nano‐prodrug system (RBT3‐NO‐PEG@PM) is constructed by DSPE‐mPEG5k and platelet membrane (PM) for effectively targeted diagnosis and therapy of atherosclerosis in mice. The results indicate that this platelet‐mimicking NO nano‐prodrug system can reduce the accumulation of lipids at the sites of atherosclerotic plaques, improve the inflammatory response at the lesion sites, and promote endothelial cell migration, thereby slowing the progression of plaques. [ABSTRACT FROM AUTHOR]

Phenology is an important agronomic trait for common wheat, which has a great impact to explore its genetic mechanism and effect for wheat breeding and application. In this study, 240 recombinant inbred lines (RILs) derived from Yangmai 158 and Hiller were used to identify the phenology traits in 2-4 environments. A total of 52 QTL were detected on chromosomes 2A, 2D, 3D, 4B, 4D, 5A, 5B, 5D, 6A, 6B, 7A, 7B, and 7D by using the constructed high-density genetic map. QJS/BS/HS/FS/MS.nau-5D.2, QJS/BS/HS/FS/MS.nau-2D.1, and QJS/BS/HS/FS/MS.nau-7B.1 were detected for several years, which explained 4.56%-46.86%, 1.32%-33.40%, and 2.37%-13.27% of phenotypic variation, respectively. QBS/HS.nau-2A.3, QHS/FS.nau-5B.2, QFS.nau-2A.5, QBS.nau-6A.2, QJS.nau-4D.2, QJS.nau-6A.3, QBS.nau-2A.2, QBS/HS.nau-6A.1, QFS.nau-7A.2, QMS.nau-3D, QMS.nau-4D.1, and QMS.nau-6B.1 were new QTL. Pyramiding of multiple phenology loci with large effects or repeated is an effective approach to shorten the growth period in different degrees, which could be used to cultivate early-maturing and high-yield wheat varieties. [ABSTRACT FROM AUTHOR]

Excessive daytime sleepiness (EDS) is associated with quality of life and all-cause mortality in the end-stage renal disease population. This study aims to identify biomarkers and reveal the underlying mechanisms of EDS in peritoneal dialysis (PD) patients. A total of 48 nondiabetic continuous ambulatory peritoneal dialysis patients were assigned to the EDS group and the non-EDS group according to the Epworth Sleepiness Scale (ESS). Ultra-high-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) was used to identify the differential metabolites. Twenty-seven (male/female, 15/12; age, 60.1 ± 16.2 years) PD patients with ESS ≥ 10 were assigned to the EDS group, while twenty-one (male/female, 13/8; age, 57.9 ± 10.1 years) PD patients with ESS < 10 were defined as the non-EDS group. With UHPLC-Q-TOF/MS, 39 metabolites with significant differences between the two groups were found, 9 of which had good correlations with disease severity and were further classified into amino acid, lipid and organic acid metabolism. A total of 103 overlapping target proteins of the differential metabolites and EDS were found. Then, the EDS–metabolite–target network and the protein–protein interaction network were constructed. The metabolomics approach integrated with network pharmacology provides new insights into the early diagnosis and mechanisms of EDS in PD patients. [ABSTRACT FROM AUTHOR]