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Widespread application of synthetic pesticides and loss of plant diversity are regarded as significant drivers of current global change. The effects of such phenomena on insect performance have been extensively studied separately, yet the interactions of these two drivers have been poorly explored. Here, we subjected the polyphagous grasshopper Pseudochorthippus parallelus (Zetterstedt, 1821) to a full-lifecycle field experiment with 50 cages containing experimental plant communities differing in grass species richness (2 vs. 8 grass species), half of them treated with a phenoxy herbicide commonly employed to control broadleaf plants in grasslands. We measured plant elemental content as a proxy for plant physiology, and a wide range of insect traits in both female and male grasshoppers. In females, grass diversity increased herbivory, insect nitrogen content and egg load, while herbicide reduced herbivory but increased the number of offspring, likely mediated by altered plant community composition. In males, grass diversity also increased herbivory, had positive effects on fat body, muscle volume and lifespan, and negative effects on body mass. Herbicide negatively affected herbivory in both females and males. Overall, plant diversity and herbicides may shift resource allocation in generalist terrestrial insect herbivores, indicating complex and unexpected effects of human-induced environmental change.Lipedema is a chronic, progressive disease of adipose tissue with lack of consistent diagnostic criteria. The aim of this study was a thorough comparative characterization of extracellular microRNAs (miRNAs) from the stromal vascular fraction (SVF) of healthy and lipedema adipose tissue. For this, we analyzed 187 extracellular miRNAs in concentrated conditioned medium (cCM) and specifically in small extracellular vesicles (sEVs) enriched thereof by size exclusion chromatography. C16 price No significant difference in median particle size and concentration was observed between sEV fractions in healthy and lipedema. We found the majority of miRNAs located predominantly in cCM compared to sEV enriched fraction. Surprisingly, hierarchical clustering of the most variant miRNAs showed that only sEVmiRNA profiles - but not cCMmiRNAs - were impacted by lipedema. Seven sEVmiRNAs (miR-16-5p, miR-29a-3p, miR-24-3p, miR-454-p, miR-144-5p, miR-130a-3p, let-7c-5p) were differently regulated in lipedema and healthy individuals, whereas only one cCMmiRNA (miR-188-5p) was significantly downregulated in lipedema. Comparing SVF from healthy and lipedema patients, we identified sEVs as the lipedema relevant miRNA fraction. This study contributes to identify the potential role of SVF secreted miRNAs in lipedema.Insulin analogue X10 has a higher mitogenic potency than native human insulin in vitro and supra-pharmacological doses of insulin X10 increased the incidence of mammary tumours in rats. Compared to native human insulin, insulin X10 has increased binding affinity to the insulin receptor and the IGF-1 receptor, but it is not known whether either or both characteristics are important for stimulation of cell proliferation in vivo. The aim of this study was to explore how increased binding affinity to the insulin receptor or the IGF-1 receptor contributes to stimulation of cell proliferation in vivo. A mouse xenograft model was established with rat L6 myoblast cells transfected with the human insulin receptor (L6hIR cells) and effects of supra-pharmacological doses of native human insulin, insulin X10 or novel insulin analogues with increased binding affinity to either the insulin receptor or the IGF-1 receptor were examined. Treatment with insulin X10 and insulin analogues with increased binding affinity to either the insulin receptor or the IGF-1 receptor increased growth of L6hIR cell xenografts significantly compared to native human insulin. Thus, increased binding affinity to the insulin receptor and the IGF-1 receptor are each independently linked to increased growth of L6hIR cell xenografts in vivo.Diabetic macular edema (DME) refractory to anti-VEGF drugs is a socioeconomic burden. In this retrospective study, we investigated the relationship between DME remission and hyperreflective walls in foveal cystoid spaces, a novel finding on spectral domain optical coherence tomography (SD-OCT) images in DME. In a cross-sectional study, we assessed the relationship between hyperreflective walls in foveal cystoid spaces and other OCT findings in 110 eyes of 110 DME patients. Hyperreflective walls were delineated in 27 of 171 foveal cystoid spaces. Eyes with hyperreflective walls in foveal cystoid spaces had poorer visual acuity and more severe photoreceptor disruption than did those without such findings (P = 0.008 and P  less then  0.001, respectively). In the other longitudinal study, we evaluated the relationship between this finding and the remission in 54 eyes of 51 DME patients treated with as-needed ranibizumab injections for 24 months. Foveal cystoid spaces with hyperreflective walls were often persistent, and the cumulative rates of DME remission among eyes with and without the hyperreflective walls were 7.7% (1 eye) and 48.8% (20 eyes) at 18 months (hazard ratio, 0.092; P = 0.025). We characterized hyperreflective walls in foveal cystoid spaces and designated them as a predictor of no DME remission under ranibizumab injections.The albumin-bilirubin (ALBI) grade has been validated as a significant predictor for hepatocellular carcinoma (HCC). However, there is little information about the impact of postoperative ALBI grade in patients with HCC who are undergoing liver resection. We enrolled 525 HCC patients who received primary resection from April 2001 to March 2017. The impact of the pre- and post-operative ALBI grades on overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis. During the follow-up period (mean, 65 months), 253 (48.1%) patients experienced recurrence, and 85 (16.2%) patients died. Multivariate analysis revealed that diabetes mellitus (DM) (p = 0.011), alpha-fetoprotein levels (AFP) (p  less then  0.001), low platelet count (p = 0.008), liver cirrhosis (p  less then  0.001), and the first year of ALBI grade after resection (p  less then  0.001) were independent predictors for RFS. Additionally, old age (p = 0.006), DM (p = 0.002), AFP (p = 0.027), and ALBI grade at the first year after resection (p  less then  0.

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