Thyroid-associated ophthalmopathy (TAO) is an autoimmune disease that involves the remodeling of orbit and periorbital tissues. Thyroid-stimulating hormone receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R) may stimulate the activation of autoimmunity in TAO, but the exact mechanism is unclear. We investigated whether IGF-1R/TSHR modulation in TAO may involve microRNA regulation.We conducted microarray analysis using RNA from the orbital connective tissue samples of 3 healthy and 3 patients with TAO. The involvement of differentially regulated microRNA in IGF-1R/TSHR modulation in TAO was evaluated in orbital fibroblasts (OFs) and female BALB/c mice.Using hierarchical cluster analysis, we identified that miR-143 was downregulated in TAO. The expression levels of miR-143 in OFs were significantly reduced under IL-1B stimulation. However, OF proliferation and inflammatory responses decreased when miR-143 is overexpressed. In contrast, the suppression of miR-143 increased levels of inflammatory markers (IL-6, IL-8, MCP1) and hyaluronan accumulation. Moreover, overexpression of miR-143 significantly lowers levels of IGF-1R and TSHR. A luciferase assay indicated that miR-143 targets the 3'-UTR of IGF-1R. Increases in the expression of IGF-1R increased the expression of the inflammasome marker NLRP3 and apoptotic marker cleaved caspase-1; however, miR-143 overexpression decreased levels of IGF-1R, TSHR, NLRP3, cleaved caspase 1, IL-1B, and IL-18. In a mouse model of TAO, overexpression of miR-143 significantly reduced levels of IGF-1R and attenuated the adipogenesis associated with TAO.We found that miR-143 directly targets IGF-1R to alleviate the inflammatory response in TAO by indirectly decreasing levels of TSHR and inactivating NLRP3.
We demonstrate dramatic parametric amplifier conversion efficiency enhancement simply by arranging for simultaneously phase-matched idler second-harmonic generation, with 44% pump-to-signal energy conversion (68% pump depletion) in a 48-dB-gain bulk-crystal mid-IR amplifier stage with Gaussian beams.
Background Previous studies investigating the association between X-ray repair cross-complementing group 1 (XRCC1) polymorphisms and thyroid cancer risk have yielded inconsistent results. This meta-analysis was performed to derive a more precise estimation of the relationship between three XRCC1 polymorphisms and thyroid cancer risk. Methods/Principal Findings PubMed and EMBASE database were systematically searched to identify relevant studies. 10 publications were selected for this meta-analysis, including 11 studies for Arg399Gln polymorphism (1726 cases and 3774 controls), 7 studies for Arg194Trp polymorphism (1037 cases and 2487 controls) and 8 studies for Arg280His polymorphism (1432 cases and 3356 controls). The results in total population did not show any significant association between these three polymorphisms and the risk of DTC for all genetic models. However, when stratified by ethnicity, the results showed that Arg280His polymorphism was associated with an increased risk of DTC among Caucasians (Arg/His vs. Arg/Arg: OR = 1.45, 95% CI = 1.09–1.93; dominant model: OR = 1.43, 95% CI = 1.08–1.89; additive model: OR = 1.38, 95% CI = 1.05–1.80), whereas individuals carrying Arg/His genotype have a significantly reduced risk of DTC among Asians (Arg/His vs. Arg/Arg: OR = 0.71, 95% CI = 0.51–0.98). We also detected that 399Gln variant allele carriers might presented an overall decreased risk of DTC in mixed population. Furthermore, subgroup analyses by histological subtype revealed that Arg194Trp polymorphism was significantly associated with reduced risk for papillary thyroid carcinoma (PTC) (dominant model: OR = 0.71, 95% CI = 0.50–0.99). Conclusions This meta-analysis suggests that Arg280His polymorphism might contribute to the susceptibility of DTC among Caucasians, whereas it might provide protective effects in Asians against the risk of DTC. Additionally, our results support the protective role of Arg194Trp polymorphism in developing PTC, and show evidence of an association between Arg399Gln polymorphism and decreased risk of DTC in mixed population.
Parametric amplifiers have allowed breakthroughs in ultrafast, strong-field, and high-energy density laser science and are an essential tool for extending the frequency range of powerful emerging diode-pumped solid-state laser technology. However, their impact is limited by inherently low quantum efficiency due to nonuniform light extraction. Here we demonstrate a new type of parametric amplifier based on hybridized nonlinear optics. Hybridization of parametric amplification with idler second harmonic generation induces unusual evolution dynamics for a fully parametric amplifier - with saturating rather than cyclic gain - observed here for the first time. This allows highly uniform light extraction enabling unprecedented efficiency for a lossless amplifier with Gaussian-like intensity profiles - a 48-dB single-stage gain with 68% quantum efficiency and 44% pump-to-signal energy conversion - a several-fold improvement over the standard. Possessing both laser-like high quantum efficiency and the advantages of thermal-loading free parametric systems, this simple approach can be implemented widely and have significant impact by increasing several-fold the power available for science and industry.
When driven at infrared resonances, crystals possess giant Raman scattering susceptibilities due to nonlinear lattice coupling in the polarizability. A first-principles study of SrTiO3 reveals Stokes and anti-Stokes peaks in the cubic susceptibility with values >10^(-15) m^2/V^2, and large values of chi^(3) representing cross-phase and cross-amplitude modulation that persist from THz to visible frequencies. This implies a new route for achieving strong nonlinear frequency conversion in the infrared over short length scales, and a route for strong light-driven control of material optical properties on ultrafast timescales covering a hyperspectral range. We additionally discuss implications for non-centrosymmetric materials such as LiNbO3.
This study aimed to evaluate the effectiveness of the structured dietary intervention in reducing the risk of developing type 2 diabetes mellitus and improving associated metabolic health indicators. We included 530 participants randomly assigned to an intervention group with a Mediterranean-style diet and a control group with generic dietary guidelines. The incidence of type 2 diabetes mellitus was the primary outcome, whereas changes in fasting plasma glucose, lipid profiles, and body composition were the secondary outcomes. After 24 months, the incidence of type 2 diabetes mellitus was significantly lower among participants in the intervention group than those in the control group (P < 0.05). Fasting glucose, hemoglobin A1c, total cholesterol, and low-density lipoprotein levels were decreased (P < 0.05), and high-density lipoprotein levels were increased among participants in the intervention group than in those in the control group (P < 0.05). Also, body weight, blood pressure, and body mass index, major negative predictors of fasting glucose levels, were significantly decreased in participants in the intervention group than in those in the control group (P < 0.05), irrespective of other covariates. Dietary intervention substantially reduced the risk of developing type 2 diabetes mellitus and improved glycemic control, lipid profiles, and overall metabolic health.
We experimentally demonstrate in diamond that third-harmonic generation can be enhanced by orders of magnitude with polarization dependence through assistance from a Raman resonance, in a process analogous to coherent anti-Stokes Raman scattering.
Study Design. An in vitro biological study. Objective. The aim of this study was to explore the role of bone morphogenetic protein-2 (BMP-2) in the regulation of osteoclast-mediated osteolysis, and the possible mechanism involving BMP-2 and nuclear factor-kappa B (NF-κB) signaling pathways. Summary of Background Data. Recombinant human BMP-2 (rhBMP-2) has been approved as a therapeutic agent in spinal fusion and bone defect repair. However, its efficacy and clinical application are limited by associated complications including osteoclast-mediated bone resorption. The mechanism of BMP-2-induced osteolysis remains unknown. Methods. Bone marrow-derived macrophages (BMMs) were isolated from C57BL/6J mice and cultured with macrophage colony-stimulating factor (M-CSF) and receptor activator for nuclear factor-κB Ligand (RANKL) to induce osteoclast differentiation. An in vitro bone resorption assay was performed by co-culturing BMMs and bone slides. The expression of BMP canonical and NF-κB signaling factors and their interaction during signal transduction were quantitated by reverse transcription polymerase chain reaction, Western blot analysis, confocal microscopy, and co-immunoprecipitation. Results. BMP-2 enhanced osteoclast-mediated bone resorption via inducing osteoclast differentiation in a concentration-dependent manner. In addition, a high concentration of BMP-2 significant upregulated phosphorylation of BMP signaling factors p-Smad1/5/8 and NF-κB downstream factor p65, and promoted the degeneration of IκBα. In addition, BMP-2 induced osteoclast differentiation through coupling between BMP receptor II and RANK. Conclusion. High concentrations of BMP-2 enhanced osteoclast-mediated bone resorption by promoting RANKL-induced pre-osteoclast differentiation, probably by mediating the cross-talk between BMP canonical and NF-κB signaling pathways. Level of Evidence: N/A
During the co-evolution with animals, plants evolved different defense strategies to resist predators and ensure their own survival and reproduction. We investigated the forging preference of nutcrackers (Nucifraga caryocatactes) for seeds in different parts of bending Pinus armandii cones in Southeast Tibet. We measured the morphological characteristics (length, width, thickness, and seed hull thickness) and the physical and chemical properties of concave and convex seeds of P. armandii (crude water, dry-matter at 70 ℃, crude fat, ash, protein and crude fiber). The results showed that there were significant differences in seed shell thickness, kernel percentage and empty shell percentage between the concave and convex seeds. The seed shell thickness of convex seeds (1.11±0.12 mm) was thicker than that of concave seeds (1.07±0.15 mm). The kernel weight percentage of convex seeds (24.0%) was smaller than that of concave seeds (25.4%). The empty shell percentage (11.2%), crude fat content (47.0%) of convex seeds were significantly lower than that of concave seeds (15.8% and 50.5%). The curving cones of P. armandii cause false hints to seed eaters, and protect high-quality seeds from being eaten as much as possible. Therefore, the curving cone is a defensive characteristics of P. armandii against seed predators.动植物协同演化过程中,植物为抵御捕食者的侵害,保证自身的生存和繁衍,会演化出不同方式的防御机制。本研究调查了星鸦对藏东南地区华山松弯曲球果上不同部位种子取食的差异性,并检测了华山松球果凹凸面种子的形态特征(长度、宽度、厚度、种壳厚度)和成分(粗水分、70 ℃干物质、粗脂肪、灰分、蛋白质、粗纤维)含量。结果表明: 华山松球果凹凸两面种子的部分形态特征和种子成分具有显著差异,其中,凸面种子种壳厚度(1.11±0.12 mm)比凹面种子(1.07±0.15 mm)厚,但种仁重占比凸面(24.0%)比凹面(25.4%)小。而凸面种子空壳率(11.2%)和种子成分中粗脂肪含量(47.0%)显著低于凹面种子(分别是15.8%和50.5%)。华山松弯曲球果对食种子动物取食造成错误性暗示,尽可能保护优质种子不被取食,因此球果弯曲是华山松对食种子动物的防御特征。.
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