Cigarette smoke and biological age induce degenerative heterogeneity in retinal pigment epithelium.

Environmental exposure such as cigarette smoke induces epigenetic changes that can induce degenerative heterogeneity and accelerate aging. In early age-related macular degeneration (AMD), the leading worldwide cause of blindness among the elderly, retinal pigment epithelial (RPE) cell heterogeneity is a key change. Since smoking is the strongest environmental risk factor for AMD, we hypothesized that cigarette smoke induces degenerative RPE heterogeneity through epigenetic changes that are distinct from aging, and that with aging, the RPE becomes vulnerable to cigarette smoke insult.

Multimodal Phenomap of Stargardt Disease Integrating Structural, Psychophysical, and Electrophysiologic Measures of Retinal Degeneration.

Objective: To cluster the diverse phenotypic features of Stargardt disease (STGD) using unsupervised clustering of multimodal retinal structure and function data.

Design: Retrospective cross-sectional study.

Subjects: Eyes of subjects with STGD and fundus autofluorescence (FAF), OCT, electroretinography (ERG), and microperimetry (MP) data available within 1 year of the baseline evaluation.

Inhibition of calcium imbalance protects hepatocytes from vanadium exposure-induced inflammation by mediating mitochondrial-associated endoplasmic reticulum membranes in ducks.

Vanadium (V) is an essential mineral element in animals, but excessive V can lead to many diseases, affecting the health of humans and animals. However, the molecular crosstalk between mitochondria-associated endoplasmic reticulum membranes (MAMs) and inflammation under V exposure is still at the exploratory stage. This study was conducted to determine the molecular crosstalk between MAMs and inflammation under V exposure in ducks.

Targeting hypoxia-inducible factors with 32-134D safely and effectively treats diabetic eye disease in mice.

Many patients with diabetic eye disease respond inadequately to anti-VEGF therapies, implicating additional vasoactive mediators in its pathogenesis. We demonstrate that levels of angiogenic proteins regulated by HIF-1 and -2 remain elevated in the eyes of people with diabetes despite treatment with anti-VEGF therapy. Conversely, by inhibiting HIFs, we normalized the expression of multiple vasoactive mediators in mouse models of diabetic eye disease.

IKKβ Inhibition Attenuates Epithelial Mesenchymal Transition of Human Stem Cell-Derived Retinal Pigment Epithelium.

Epithelial-mesenchymal transition (EMT), which is well known for its role in embryonic development, malignant transformation, and tumor progression, has also been implicated in a variety of retinal diseases, including proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD), and diabetic retinopathy. EMT of the retinal pigment epithelium (RPE), although important in the pathogenesis of these retinal conditions, is not well understood at the molecular level. We and others have shown that a variety of molecules, including the co-treatment of human stem cell-derived RPE monolayer cultures with transforming growth factor beta (TGF-β) and the inflammatory cytokine tumor necrosis factor alpha (TNF-α), can induce RPE-EMT; however, small molecule inhibitors of RPE-EMT have been less well studied.

GPX4 utilization by selenium is required to alleviate cadmium-induced ferroptosis and pyroptosis in sheep kidney.

Cadmium (Cd), a persistent and harmful heavy metal in the environment, can accumulate in the kidneys and cause nephrotoxicity. Selenium (Se) is a beneficial natural element that alleviates the toxicity of Cd. To ascertain the relationship between the protective mechanism of Se against Cd nephrotoxicity and ferroptosis and pyroptosis, we randomly divided 48 sheep into four groups and treated them with Cd chloride and/or sodium selenite for 50 days.

Selenium alleviates cadmium-induced mitophagy through FUNDC1-mediated mitochondrial quality control pathway in the lungs of sheep.

Cadmium (Cd) is a poisonous metal element that causes mitochondrial dysfunction. Selenium (Se) can reduce the damage of Cd to various organs of animals, but the protective mechanism of Se in Cd-induced lung injury has not been fully elucidated. For purpose of further illustrating the specific mechanism of Se alleviated Cd-triggered pulmonary toxicity, 48 sheep were divided into 4 groups, of which the sheep in the treatment group were taken 1 mg/kg body weight (BW) of Cd, 0.

Inhibition of the BNIP3/NIX-dependent mitophagy aggravates copper-induced mitochondrial dysfunction in duck renal tubular epithelial cells.

The accumulation of copper (Cu) in the organisms could lead to kidney damage by causing mitochondrial dysfunction. Given that mitochondria are one of the targets of Cu poisoning, this study aimed to investigate the role of mitophagy in Cu-induced mitochondrial dysfunction in renal tubular epithelial cells to understand the mechanism of Cu nephrotoxicity. Hence, the cells were treated with different concentrations of Cu sulfate (CuSO ) (0, 100, and 200 μM), and mitophagy inhibitor (Cyclosporine A, 0.

scRNA-sequencing reveals subtype-specific transcriptomic perturbations in DRG neurons of mice in neuropathic pain condition.

Functionally distinct subtypes/clusters of dorsal root ganglion (DRG) neurons may play different roles in nerve regeneration and pain. However, details about their transcriptomic changes under neuropathic pain conditions remain unclear. Chronic constriction injury (CCI) of the sciatic nerve represents a well-established model of neuropathic pain, and we conducted single-cell RNA-sequencing (scRNA-seq) to characterize subtype-specific perturbations of transcriptomes in lumbar DRG neurons on day 7 post-CCI.

Traditional Chinese medicine prescriptions (XJZ, JSS) ameliorate spleen inflammatory response and antioxidant capacity by synergistically regulating NF-κB and Nrf2 signaling pathways in piglets.

Weaning transition generally impairs the immune system, inducing immune disturbance, which may be associated with post-weaning diarrhea and high mortality in piglets. The spleen is a pivotal lymphatic organ that plays a key role in the establishment of the immune system. Traditional Chinese medicine (TCM) prescriptions, XiaoJianZhong (XJZ) and Jiansananli-sepsis (JSS), are widely used prescriptions for treating spleen damage and diarrhea.

Rheological Properties and Early-Age Microstructure of Cement Pastes with Limestone Powder, Redispersible Polymer Powder and Cellulose Ether.

In order to study the synergistic effects of organic and inorganic thickening agents on the rheological properties of cement paste, the rheological parameters, thixotropy cement-paste containing limestone powder (LP), re-dispersible polymer powder (RPP), and hydroxypropyl methylcellulose ether (HPMC) were investigated using the Anton Paar MCR 102 rheometer at different resting times. The early-age hydration process, hydration products, and microstructure were also analyzed with scanning electron microscopy (SEM) and thermogravimetry analyses (TGA). The results showed that the addition of LP, RPP, and HPMC affected the rheological properties of cement paste, but the thickening mechanism between organic and inorganic thickening agents was different.

Aqueous proteins help predict the response of patients with neovascular age-related macular degeneration to anti-VEGF therapy.

BackgroundTo reduce the treatment burden for patients with neovascular age-related macular degeneration (nvAMD), emerging therapies targeting vascular endothelial growth factor (VEGF) are being designed to extend the interval between treatments, thereby minimizing the number of intraocular injections. However, which patients will benefit from longer-acting agents is not clear.MethodsEyes with nvAMD (n = 122) underwent 3 consecutive monthly injections with currently available anti-VEGF therapies, followed by a treat-and-extend protocol.

Effects of Social Capital and Leisure Participation on Self-Rated Health of Urban Residents in Southwest China.

Leisure provides opportunities for urban and rural residents to relax, recover their vitality, and improve their personal growth, development, and well-being. However, the impact of the leisure participation process, types, obstacles, participation motivation, and satisfaction on health is not very clear, especially the impact of leisure behavior on health, and is worthy of in-depth discussion. The objective of this study was to explore the impact of social capital and leisure participation on the self-rated health of urban residents in China so as to provide an important reference for national health promotion activities.

Proteome Landscape of Epithelial-to-Mesenchymal Transition (EMT) of Retinal Pigment Epithelium Shares Commonalities With Malignancy-Associated EMT.

Stress and injury to the retinal pigment epithelium (RPE) often lead to dedifferentiation and epithelial-to-mesenchymal transition (EMT). These processes have been implicated in several retinal diseases, including proliferative vitreoretinopathy, diabetic retinopathy, and age-related macular degeneration. Despite the importance of RPE-EMT and the large body of data characterizing malignancy-related EMT, comprehensive proteomic studies to define the protein changes and pathways underlying RPE-EMT have not been reported.

Transcriptome Landscape of Epithelial to Mesenchymal Transition of Human Stem Cell-Derived RPE.

Purpose: RPE injury often induces epithelial to mesenchymal transition (EMT). Although RPE-EMT has been implicated in a variety of retinal diseases, including proliferative vitroretinopathy, neovascular and atrophic AMD, and diabetic retinopathy, it is not well-understood at the molecular level. To contribute to our understanding of EMT in human RPE, we performed a time-course transcriptomic analysis of human stem cell-derived RPE (hRPE) monolayers induced to undergo EMT using 2 independent, yet complementary, model systems.

βA1-crystallin regulates glucose metabolism and mitochondrial function in mouse retinal astrocytes by modulating PTP1B activity.

βA3/A1-crystallin, a lens protein that is also expressed in astrocytes, is produced as βA3 and βA1-crystallin isoforms by leaky ribosomal scanning. In a previous human proteome high-throughput array, we found that βA3/A1-crystallin interacts with protein tyrosine phosphatase 1B (PTP1B), a key regulator of glucose metabolism. This prompted us to explore possible roles of βA3/A1-crystallin in metabolism of retinal astrocytes.

Knocking Out Non-muscle Myosin II in Retinal Ganglion Cells Promotes Long-Distance Optic Nerve Regeneration.

In addition to altered gene expression, pathological cytoskeletal dynamics in the axon are another key intrinsic barrier for axon regeneration in the central nervous system (CNS). Here, we show that knocking out myosin IIA and IIB (myosin IIA/B) in retinal ganglion cells alone, either before or after optic nerve crush, induces significant optic nerve regeneration. Combined Lin28a overexpression and myosin IIA/B knockout lead to an additive promoting effect and long-distance axon regeneration.

PanoView: An iterative clustering method for single-cell RNA sequencing data.

Single-cell RNA-sequencing (scRNA-seq) provides new opportunities to gain a mechanistic understanding of many biological processes. Current approaches for single cell clustering are often sensitive to the input parameters and have difficulty dealing with cell types with different densities. Here, we present Panoramic View (PanoView), an iterative method integrated with a novel density-based clustering, Ordering Local Maximum by Convex hull (OLMC), that uses a heuristic approach to estimate the required parameters based on the input data structures.

Ovotransferrin ameliorates the dysbiosis of immunomodulatory function and intestinal microbiota induced by cyclophosphamide.

In this study, the regulative effects of ovotransferrin (OVT) on immunomodulatory function and intestinal microbial dysbiosis in a mouse model injected with cyclophosphamide (CP) were investigated. The immunomodulatory effect of OVT was determined by enzyme-linked immune sorbent assay (ELISA). Gut microbial composition was determined by high-throughput sequencing of the V3-V4 region of the 16S rDNA gene.

[Effect of health education on prevention from schistosome infection in engineering construction workers in Poyang Lake area].

Objective: To evaluate the effect of health education on prevention from schistosome infection in engineering construction workers in Poyang Lake area.

Methods: The workers for constructing "De Chang" highway in Poyang Lake area were divided randomly into an experiment group and a control group, "health education + protective skill training" was carried out in the experiment group, whereas, no intervention was implemented in the control group.

Results: In the experiment group, the awareness rates of schistosomiasis control knowledge were 7.

The intrinsic dynamics of Cse1p and Xpot elucidated by coarse-grained models.

Cse1p and Xpot are two karyopherin proteins that transport the corresponding cargos during the nucleocytoplasmic transport. We utilized Elastic Network Model (ENM) and Finite Element Analysis (FEA) to study their conformational dynamics. These dynamics were interpreted by their intrinsic modes that played key roles in the flexibility of karyopherins, which further affected the binding affinities.