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t BM apelin levels increase with long- and short-term overnutrition, possibly via maternal hyperinsulinemia and transcriptional upregulation of MG apelin expression in myoepithelial cells. Apelin regulates many physiological processes, including energy metabolism, digestive function, and development. Further studies are needed to unravel the consequences of such changes in offspring development.Synucleinopathies are age-related neurological disorders characterized by the progressive deposition of α-synuclein (α-syn) aggregates and include Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Although cell-to-cell α-syn transmission is thought to play a key role in the spread of α-syn pathology, the detailed mechanism is still unknown. Neuroinflammation is another key pathological feature of synucleinopathies. Previous studies have identified several immune receptors that mediate neuroinflammation in synucleinopathies, such as Toll-like receptor 2 (TLR2). However, the species of α-syn aggregates varies from study to study, and how different α-syn aggregate species interact with innate immune receptors has yet to be addressed. Therefore, we investigated whether innate immune receptors can facilitate the uptake of different species of α-syn aggregates. Here, we examined whether stimulation of TLRs could modulate the cellular uptake and degradation of α-syn fibrils despite a lack of direct interaction. We observed that stimulation of TLR2 in vitro accelerated α-syn fibril uptake in neurons and glia while delaying the degradation of α-syn in neurons and astrocytes. Internalized α-syn was rapidly degraded in microglia regardless of whether TLR2 was stimulated. However, cellular α-syn uptake and degradation kinetics were not altered by TLR4 stimulation. In addition, upregulation of TLR2 expression in a synucleinopathy mouse model increased the density of Lewy-body-like inclusions and induced morphological changes in microglia. Together, these results suggest that cell type-specific modulation of TLR2 may be a multifaceted and promising therapeutic strategy for synucleinopathies; inhibition of neuronal and astroglial TLR2 decreases pathogenic α-syn transmission, but activation of microglial TLR2 enhances microglial extracellular α-syn clearance.Membrane proteins are key in a large number of physiological and pathological processes. Their study often involves a prior detergent solubilization step, which strips away the membrane and can jeopardize membrane protein integrity. A recent alternative to detergents encompasses maleic acid based copolymers (xMAs), which disrupt the lipid bilayer and form lipid protein nanodiscs (xMALPs) soluble in aqueous buffer. Although xMALPs are often referred to as native nanodiscs, little is known about the resemblance of their lipid and protein content to the native bilayer. Here we have analyzed prokaryotic and eukaryotic xMALPs using lipidomics and in-gel analysis. Our results show that the xMALPs content varies with the chemical properties of the used xMA.The present study reports the upcycling process of waste plastics into value-added product graphene nanosheets (GNs) and their subsequent applications in dye sensitized solar cells (DSSCs) and supercapacitors. Bentonite nanoclay has been used as an agent for the degradation of waste plastics with two step pyrolysis processes at 450 °C and 945 °C in an inert atmosphere of N2 gas to obtain GNs. The GNs with few layers were confirmed by the RAMAN spectroscopy, XRD and HRTEM analyses. Further, FT-IR and EDX analyses also performed for the identification and quantitative analysis of functional groups in GNs. The GNs thus synthesized from plastic waste have been used for the fabrication of DSSCs and supercapacitors. The DSSC fabrication with GNs as part of photo-anode with polymeric electrolyte showed a high fill factor of 86.4% and high Voc of 0.77 V, which were also supported by the computational findings. On the other hand, the utilization of GNs as an active layer material of supercapacitor electrodes offered a high specific capacitance of 398 F/g with a scan rate of 0.005 V/s. The supercapacitor also exhibited significant energy density (Ed) and power density (Pd) of 38 Wh/kg and 1009.74 W/kg, respectively. Thus, the process illustrated the utility of waste plastics upcycling for conservation of EEE i.e., ecology, economy and energy for better tomorrow.The mucosa microenvironment is critical for intestinal stem cell self-renewal and reconstruction of the epithelial barrier in inflammatory bowel disease (IBD), where the mechanisms underlying cross-talk between intestinal crypts and the microenvironment remain unclear. Here, we firstly identified miR-494-3p as an important protector in colitis. miR-494-3p levels were decreased and negatively correlated with the severity in human IBD samples, as well as in colitis mice. In colitis crypts, a notable cytokine-cytokine receptor, miR-494-3p-targeted EDA2R and the ligand EDA-A2, suppressed colonic stemness and epithelial repair by inhibiting β-catenin/c-Myc. In differentiated IECs, miR-494-3p inhibits macrophage recruitment, M1 activation and EDA-A2 secretion by targeting IKKβ/NF-κB in colitis. A miR-494-3p agomir system notably ameliorated the severity of colonic colitis in vivo. Collectively, our findings uncover a miR-494-3p-mediated cross-talk mechanism by which macrophage-induced intestinal stem cell impairment aggravates intestinal inflammation.

Clinimetric cross-sectional cohort study in adults with paraplegic spinal cord injury (SCI) and neuropathic pain (NP).

To assess the reliability of standardized quantitative pain drawings in patients with NP following SCI.

Hospital-based research facility at the Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland.

Twenty individuals with chronic thoracic spinal cord injury and neuropathic pain were recruited from a national and local SCI registry. A thorough clinical examination and pain assessments were performed. Pain drawings were acquired at subsequent timepoints, 13 days (IQR 7.8-14.8) apart, in order to assess test-retest reliability.

The average extent [%] and intensity [NRS 0-10] of spontaneous NP were 11.3% (IQR 4.9-35.8) and 5 (IQR 3-7), respectively. Pain extent showed excellent inter-session reliability (intraclass correlation coefficient 0.96). Sensory loss quantified by light touch and pinprick sensation was associated with larger pain extent (r

 = -0.47, p = 0.04; r

 = -0.64, p < 0.01).

Assessing pain extent using quantitative pain drawings is readily feasible and reliable in human SCI. Relating information of sensory deficits to the presence of pain may provide distinct insights into the interaction of sensory deafferentation and the development of neuropathic pain after SCI.

Assessing pain extent using quantitative pain drawings is readily feasible and reliable in human SCI. Relating information of sensory deficits to the presence of pain may provide distinct insights into the interaction of sensory deafferentation and the development of neuropathic pain after SCI.Some plant trans-1,4-prenyltransferases (TPTs) produce ultrahigh molecular weight trans-1,4-polyisoprene (TPI) with a molecular weight of over 1.0 million. Although plant-derived TPI has been utilized in various industries, its biosynthesis and physiological function(s) are unclear. Here, we identified three novel Eucommia ulmoides TPT isoforms-EuTPT1, 3, and 5, which synthesized TPI in vitro without other components. Crystal structure analysis of EuTPT3 revealed a dimeric architecture with a central hydrophobic tunnel. Mutation of Cys94 and Ala95 on the central hydrophobic tunnel no longer synthesizd TPI, indicating that Cys94 and Ala95 were essential for forming the dimeric architecture of ultralong-chain TPTs and TPI biosynthesis. A spatiotemporal analysis of the physiological function of TPI in E. ulmoides suggested that it is involved in seed development and maturation. Thus, our analysis provides functional and mechanistic insights into TPI biosynthesis and uncovers biological roles of TPI in plants.RNA-based therapies have great potential to treat many undruggable human diseases. However, their efficacy, in particular for mRNA, remains hampered by poor cellular delivery and limited endosomal escape. Development and optimisation of delivery vectors, such as lipid nanoparticles (LNPs), are impeded by limited screening methods to probe the intracellular processing of LNPs in sufficient detail. We have developed a high-throughput imaging-based endosomal escape assay utilising a Galectin-9 reporter and fluorescently labelled mRNA to probe correlations between nanoparticle-mediated uptake, endosomal escape frequency, and mRNA translation. Furthermore, this assay has been integrated within a screening platform for optimisation of lipid nanoparticle formulations. RO4929097 inhibitor We show that Galectin-9 recruitment is a robust, quantitative reporter of endosomal escape events induced by different mRNA delivery nanoparticles and small molecules. We identify nanoparticles with superior escape properties and demonstrate cell line variances in endosomal escape response, highlighting the need for fine-tuning of delivery formulations for specific applications.Whether the first trimester maternal mean arterial pressure (MAP), placental growth factor (PlGF), and pregnancy-associated plasma protein A (PAPP-A) can predict hypertensive disorders of pregnancy (HDP) is unclear. We conducted a retrospective case-control study with the total population of 539 gravidas, of these 447 had normal pregnancy, 27 had gestational hypertension (GH), 36 had preeclampsia (PE), and 29 had preeclampsia with severe features (SPE). Prediction for HDP was determined by the area under curve (AUC). Compared to the healthy group, the multiple of the median (MoM) for MAP was increased in the study groups, while PlGF and PAPP-A were decreased. When the cutoff values for MAP, PlGF, and PAPP-A were 1.069, 0.769, and 0.673 MoM, respectively, the sensitivities for predicting HDP were 0.517, 0.446, and 0.500 and the specificities were 0.744, 0.826, and 0.769, respectively. To predict GH, the highest AUC was 0.755 (95% CI 0.655-0.856, p  less then  0.001) based on MAP, PlGF, and PAPP-A. The combined PlGF and PAPP-A had the highest AUC (0.683 [95% CI 0.584-0.782, p  less then  0.001] and 0.755 [95% CI 0.682-0.829, p  less then  0.001]) for prediction of PE and SPE. We found that MAP, serum levels of PlGF, and PAPP-A in the first trimester pregnancy are markers that predict HDP in the third trimester. The combination of markers is far superior to single markers alone. To improve the diagnostic value, specific cutoff values should be applied to GH, PE, SPE in each condition.

The objective of this study was to assess the structural-functional relationship in choroideremia (CHM) patients using optical coherence tomography (OCT) and autofluorescence (AF) images.

In this study, 53 eyes of 28 CHM patients were included. Demographic, ocular and clinical fundus features were recorded. Fundus AF and OCT images were analysed. Patients were classified into two groups based on AF features group 1, CHM patients where the foveal island was present and group 2, CHM patients where the foveal island was absent. Inner and outer retinal layer thicknesses, retinal pigment epithelium (RPE) and subfoveal choroidal thickness (SFCT) were measured and correlated with visual acuity (VA).

There were 26 eyes in group 1 and 27 eyes in group 2. Mean age in groups 1 and 2 were 51.7 ± 13.4 and 63.6 ± 11.6 years, respectively. Age (p = 0.001) and VA (p < 0.001) between the two groups were significantly different. The retinal and SFCT showed significant differences that were analysed for each eye between the two groups.