Single-Cell RNA Sequencing of hESC-Derived 3D Retinal Organoids Reveals Novel Genes Regulating RPC Commitment in Early Human Retinogenesis.

The development of the mammalian retina is a complicated process involving the generation of distinct types of neurons from retinal progenitor cells (RPCs) in a spatiotemporal-specific manner. The progression of RPCs during retinogenesis includes RPC proliferation, cell-fate commitment, and specific neuronal differentiation. In this study, by performing single-cell RNA sequencing of cells isolated from human embryonic stem cell (hESC)-derived 3D retinal organoids, we successfully deconstructed the temporal progression of RPCs during early human retinogenesis. We identified two distinctive subtypes of RPCs with unique molecular profiles, namely multipotent RPCs and neurogenic RPCs. We found that genes related to the Notch and Wnt signaling pathways, as well as chromatin remodeling, were dynamically regulated during RPC commitment. Interestingly, our analysis identified that CCND1, a G1-phase cell-cycle regulator, was coexpressed with ASCL1 in a cell-cycle-independent manner. Temporally controlled overexpression of CCND1 in retinal organoids demonstrated a role for CCND1 in promoting early retinal neurogenesis. Together, our results revealed critical pathways and novel genes in early retinogenesis of humans

A Higher Correlation of HCV Core Antigen with CD4+ T Cell Counts Compared with HCV RNA in HCV/HIV-1 Coinfected Patients

Development of HCV infection is typically followed by chronic hepatitis C (CHC) in most patients, while spontaneous HCV viral clearance (SVC) occurs in only a minority of subjects. Compared with the widespread application of HCV RNA testing by quantitative RT-PCR technique, HCV core antigen detection may be an alternative indicator in the diagnosis of hepatitis C virus infections and in monitoring the status of infectious individuals. However, the correlation and differences between these two indicators in HCV infection need more investigation, especially in patients coinfected by HIV-1. In this study, a total of 354 anti-HCV and/or anti-HIV serum positive residents from a village of central China were enrolled. Besides HCV-related hepatopathic variables including clinical status, ALT, AST, anti-HCV Abs, as well as the altered CD4+/CD8+ T cell counts, HCV core antigen and HCV viral load were also measured. The concentration of serum HCV core antigen was highly correlated with level of HCV RNA in CHC patients with or without HIV-1 coinfection. Of note, HCV core antigen concentration was negatively correlated with CD4+ T cell count, while no correlation was found between HCV RNA level and CD4+ T cell count. Our findings suggested that quantitative detection of plasma HCV core antigen may be an alternative indicator of HCV RNA qPCR assay when evaluating the association between HCV replication and host immune status in HCV/HIV-1 coinfected patients

Changes in the expression of the Toll-like receptor system in the aging rat kidneys.

BACKGROUND: The mechanisms of kidney aging are not yet clear. Studies have shown that immunological inflammation is related to kidney aging. Toll-like receptors (TLRs) are one of the receptor types of the body's innate immune system. The function of the TLR system and the mechanisms by which it functions in renal aging remain unclear. In the present study, we, for the first time, systematically investigated the role of the TLR system and the inflammation responses activated by TLRs during kidney aging. METHODS: We used western blot and immunohistochemistry to systematically analyze the changes in the expression and activation of the endogenous TLR ligands HSP70 and HMGB1, the TLRs (TLR1-TLR11), their downstream signaling pathway molecules MyD88 and Phospho-IRF-3, and the NF-κB signaling pathway molecules Phospho-IKKβ, Phospho-IκBα (NF-κB inhibition factor α), NF-κBp65, and Phospho-NF-κBp65 (activated NF-κB p65) in the kidneys of 3 months old (youth group), 12 months old (middle age group), and 24 months old (elderly group) rats. We used RT-qPCR to detect the mRNA expression changes of the proinflammatory cytokines CCL3, CCL4, CCL5, CD80, TNF-α, and IL-12b in the rat renal tissues of the various age groups. RESULTS: We found that during kidney aging, the HSP70 and HMGB1 expression levels were significantly increased, and the expression levels of TLR1, 2, 3, 4, 5, and 11 and their downstream signaling pathway molecules MyD88 and Phospho-IRF-3 were markedly elevated. Further studies have shown that in the aging kidneys, the expression levels of the NF-κB signaling pathway molecules Phospho-IKKβ, Phospho-IκBα, NF-κBp65, and Phospho-NF-κBp65 were obviously increased, and those of the proinflammatory cytokines CCL3, CCL4, CCL5, CD80, TNF-α, and IL-12b were significantly upregulated. CONCLUSIONS: These results showed that the TLR system might play an important role during the kidney aging process maybe by activating the NF-κB signaling pathway and promoting the high expression of inflammation factors

Increased functional dynamics in civil aviation pilots: Evidence from a neuroimaging study.

Civil aviation is a distinctive career. Pilots need to monitor the entire system in real time. However, the psychophysiological mechanism of flying is largely unknown. The human brain is a large-scale interconnected organization, and many stable intrinsic large-scale brain networks have been identified. Among them are three core neurocognitive networks: default mode network (DMN), central executive network (CEN), and salience network (SN). These three networks play a critical role in human cognition. This study aims to examine the dynamic properties of the three large-scale brain networks in civil aviation pilots. We collected resting-state functional magnetic resonance imaging data from pilots. Independent component analysis, which is a data-driven approach, was combined with sliding window dynamic functional connectivity analysis to detect the dynamic properties of large-scale brain networks. Our results revealed that pilots exhibit an increased interaction of the CEN with the DMN and the SN along with a decreased interaction within the CEN. In addition, the temporal properties of functional dynamics (number of transitions) increased in pilots compared to healthy controls. In general, pilots exhibited increased between-network functional connectivity, decreased within-network functional connectivity, and a higher number of transitions. These findings suggest that pilots might have better functional dynamics and cognitive flexibility

Single-Cell RNA Sequencing of hESC-Derived 3D Retinal Organoids Reveals Novel Genes Regulating RPC Commitment in Early Human Retinogenesis.

The development of the mammalian retina is a complicated process involving the generation of distinct types of neurons from retinal progenitor cells (RPCs) in a spatiotemporal-specific manner. The progression of RPCs during retinogenesis includes RPC proliferation, cell-fate commitment, and specific neuronal differentiation. In this study, by performing single-cell RNA sequencing of cells isolated from human embryonic stem cell (hESC)-derived 3D retinal organoids, we successfully deconstructed the temporal progression of RPCs during early human retinogenesis. We identified two distinctive subtypes of RPCs with unique molecular profiles, namely multipotent RPCs and neurogenic RPCs. We found that genes related to the Notch and Wnt signaling pathways, as well as chromatin remodeling, were dynamically regulated during RPC commitment. Interestingly, our analysis identified that CCND1, a G1-phase cell-cycle regulator, was coexpressed with ASCL1 in a cell-cycle-independent manner. Temporally controlled overexpression of CCND1 in retinal organoids demonstrated a role for CCND1 in promoting early retinal neurogenesis. Together, our results revealed critical pathways and novel genes in early retinogenesis of humans

RT-qPCR primer sequences and the lengths of the products.

<p>F, forward; R, reverse; IL-6: interleukin-6; CCL3: chemokine ligand 3; CCL4: chemokine ligand 4; CCL5: chemokine ligand 5; ICAM-1: intercellular adhesion molecule-1; TNF-α: tumor necrosis factor-α; IL-12b: interleukin-12b; GAPDH: glyceraldehyde-3-phosphate dehydrogenase (internal reference).</p

Expression of NF-κB signaling pathway molecules in rat kidney tissues in different age groups.

<p>(<b>A</b>) Western blot detection of the expression of NF-κB signaling pathway proteins in various rat groups. (<b>B</b>) Quantitative analysis of gray scale. Compared with the 3-month-old group, * indicates P<0.05; compared with the 12-month-old group, # indicates P<0.05.</p

Protective effect of glucagon-like peptide-1 agents on reperfusion injury for acute myocardial infarction: a meta-analysis of randomized controlled trials

<p><b>Background:</b> The cardioprotective properties of glucagon-like peptide-1 (GLP-1) receptor agonists in acute myocardial infarction (AMI) patients against reperfusion injury remain unclear. We performed a meta-analysis to assess their role in the acute phase of AMI.</p> <p><b>Methods and results:</b> Randomized controlled trials (RCTs) comparing GLP-1 agents with placebo in AMI patients undergoing percutaneous coronary intervention were identified by searching PubMed, Embase and Cochrane libraries. Six RCTs with 800 patients were included in the meta-analysis. Compared with placebo, GLP-1 agents improved left ventricular ejection fraction (LVEF) by 2.46 [95% confidence interval (CI): 0.23–4.70%] and reduced the infarct size in grams as well as in percentage of the area at risk [weighted mean difference (WMD) − 5.29, 95% CI: −10.39 to −0.19; WMD −0.08, 95% CI: −0.12 to −0.04, respectively]. The incidence of cardiovascular events appeared to be lower with GLP-1 therapy, but the statistical significance was not reached [relative risk (RR): 0.78; 95% CI: 0.58–1.06]. In terms of safety evaluation, GLP-1 treatment increased the risk of gastrointestinal adverse events (RR: 5.50, 95% CI: 2.85–10.60).</p> <p><b>Conclusions:</b> Our analysis shows that in patients with AMI undergoing PCI, GLP-1 treatment is associated with improved LVEF and reduced infarct size.</p

Immunohistochemical analysis of TLR2 expression level in rat renal tissues in different age groups.

<p>Immunohistochemical analysis of TLR2 expression level in rat renal tissues in different age groups.</p