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We found that protection of inner retinal neurons in glaucomatous eyes by pharmacological blockade of gap junctions or genetic ablation of connexin 36 largely prevented outer retinal damage.<br />Together, our results indicate that outer retinal impairments in glaucoma are a secondary sequalae of primary damage in the inner retina. The finding that neuroprotection of the inner retina can also prevent outer retinal damage has important implications with regard to the targets for effective neuroprotective therapy.<br />Together, our results indicate that outer retinal impairments in glaucoma are a secondary sequalae of primary damage in the inner retina. The finding that neuroprotection of the inner retina can also prevent outer retinal damage has important implications with regard to the targets for effective neuroprotective therapy.<br />Differentiated from adult stem cells (ASCs), transit-amplifying cells (TACs) play an important role in tissue homeostasis, development, and regeneration. This study aimed to characterize the gene expression profile of a candidate TAC population in limbal basal epithelial cells using single-cell RNA sequencing (scRNA-seq).<br />Single cells isolated from the basal corneal limbus were subjected to scRNA-seq using the 10x Genomics platform. Cell types were clustered by graph-based visualization methods and unbiased computational analysis. BrdU proliferation assays, immunofluorescent staining, and real-time reverse transcription quantitative polymerase chain reaction were performed using multiple culture models of primary human limbal epithelial cells to characterize the TAC pool.<br />Single-cell transcriptomics of 16,360 limbal basal cells revealed 12 cell clusters. A unique cluster (3.21% of total cells) was identified as a TAC entity, based on its less differentiated progenitor status and enriched exclusive proli corneal homeostasis and diseases.<br />Many patients undergo percutaneous coronary intervention (PCI) multiple times before being referred for coronary artery bypass grafting (CABG), in which bypass grafts are often anastomosed to small distal targets with higher risk of graft failure. We aimed to assess whether multiple PCIs adversely affect the long-term outcomes of patients who undergo CABG subsequently.<br />A cohort of 368 patients with no history of PCI underwent initial isolated CABG between 2003 and 2013 (no PCI group). Ninety-seven patients who had undergone PCI 2 or more times preoperatively during the same period constituted the multiple PCI group. After propensity score matching, the group outcomes were compared.<br />There were no significant differences in the 10-year all-cause mortality and major adverse cardiac and cerebrovascular event rates in both groups. Although the left ventricular end-diastolic dimension in the multiple PCI group did not change markedly (from 48.0 ± 6.0 to 47.2 ± 7.9 mm; P = 0.25), it decreased significantly in the no PCI group (from 48.3 ± 6.1 to 44.9 ± 9.1 mm; P &lt; 0.001). The left ventricular end-systolic dimension in the no PCI group decreased significantly (from 34.1 ± 8.7 to 31.4 ± 8.6 mm; P = 0.024), while it in the multiple PCI group did not (from 33.6 ± 8.3 to 32.7 ± 8.6 mm; P = 0.21).<br />For complex coronary artery disease, early surgical intervention could be considered with respect to postoperative left ventricular remodelling during the long-term follow-up.<br />For complex coronary artery disease, early surgical intervention could be considered with respect to postoperative left ventricular remodelling during the long-term follow-up.Drug abuse is a dramatic challenge for the whole society because of high relapse rate. Environmental cues are crucial for the preference memory of drug abuse. Extinction therapy has been developed to inhibit the motivational effect of drug cues to prevent the reinstatement of morphine abuse. However, extinction therapy alone only forms a new kind of unstable inhibitory memory. We found that morphine conditioned place preference (CPP) extinction training increased the association of nitric oxide synthase (nNOS) with its carboxy-terminal PDZ ligand (CAPON) in the dorsal hippocampus (dHPC) significantly and blocking the morphine-induced nNOS-CAPON association using Tat-CAPON-12C during and after extinction training reversed morphine-induced hippocampal neuroplasticity defect and prevented the reinstatement and spontaneous recovery of morphine CPP. Moreover, in the hippocampal selective ERK2 knock-out or nNOS knockout mice, the effect of Tat-CAPON-12C on the reinstatement of morphine CPP and hippocampal neuroplasticity disappeared, suggesting ERK2 is necessary for the effects of Tat-CAPON-12C. Together, our findings suggest that nNOS-CAPON interaction in the dHPC may affect the consolidation of morphine CPP extinction and dissociating nNOS-CAPON prevents the reinstatement and spontaneous recovery of morphine CPP, possibly through ERK2-mediated neuroplasticity and extinction memory consolidation, offering a new target to prevent the reinstatement of drug abuse.Loss of B lymphocyte regeneration in the bone marrow (BM) is an immunological hallmark of advanced age, which impairs the replenishment of peripheral B-cell subsets and results in impaired humoral responses, thereby contributing to immune system dysfunction associated with aging. A better understanding of the mechanism behind this loss may suggest ways to restore immune competence and promote healthy aging. In the present work, we uncover an immune-endocrine regulatory circuit that mediates cross-talk between peripheral B-cells and progenitors in the BM, to balance B-lymphopoiesis in both human and mouse aging. [https://www.selleckchem.com/products/crt0066101-dihydrochloride.html CRT0066101] We found that tumor necrosis factor alpha (TNFα), which is highly produced by peripheral B-cells in aging, stimulates the production of insulin-like growth factor-binding protein 1 (IGFBP-1), which binds and sequesters insulin-like growth factor 1 (IGF1) in the circulation, thereby restraining its activity in promoting B-lymphopoiesis in the BM. Upon B-cell depletion in aged humans and mice, circulatory TNFα decreases, resulting in increased IGF1 and reactivation of B-lymphopoiesis. Perturbation of this circuit by administration of IGF1 to old mice or anti-TNFa antibodies to human patients restored B-lymphopoiesis in the BM. Hence, we suggest that in both human and mouse aging, peripheral B-cells utilize the TNFα/IGFBP-1/IGF1 axis to repress B-lymphopoiesis.