Badanie wstępne ekspresji i wartości klinicznej oznaczenia czynnika wzrostu pochodzenia płytkowego BB, czynnika indukowanego hipoksją-1α i receptora chemokiny C-C typu 2 we krwi obwodowej w patogenezie choroby Gravesa-Basedowa

Introduction: Platelet-derived growth factor BB (PDGF-BB) plays an important role in the development of GD (Graves’ disease). However, it is still unknown whether PDGF-BB is expressed in peripheral blood and whether the expression of PDGF-BB contributes to GD. We aim to study the expression of PDGF-BB, hypoxia inducible factor (HIF)-1α and C-C motif chemokine receptor (CCR)-2 in peripheral blood of patients with GD and explore its effect and potential mechanism in pathogenesis. Material and methods: 41 patients with GD (GD group) and forty-five healthy people (control group) were chosen. The concentration of PDGF-BB and HIF-1α in peripheral blood specimens were detected and compared between the two groups. The expression of CCR2 in macrophages in the peripheral blood specimens were examined using FCM (Flow Cytometry). Results: Both PDGF-BB and HIF-1α were expressed in human peripheral blood from the two groups. Compared with specimens from healthy people, there were statistically increased concentrations of PDGF-BB and HIF-1α in the GD group (P < 0.05). The proportion of CCR2-positive macrophages in peripheral blood in the GD group was significantly higher than that in the control group (P < 0.05). Conclusions: CCR2-positive macrophages may induce the expression of PDGF-BB through HIF-1α signal, and the high expression of PDGF-BB may be involved in the pathogenesis of GD.Wprowadzenie: Czynnik wzrostu pochodzenia płytkowego BB (platelet-derived growth factor BB, PDGF-BB) odgrywa ważną rolę w roz­woju choroby Gravesa-Basedowa (Graves’ disease, GD). Jednak wciąż nie wiadomo, czy PDGF-BB ulega ekspresji we krwi obwodowej i czy ekspresja PDGF-BB przyczynia się do GD. Badanie przeprowadzono w celu zbadania ekspresji PDGF-BB, czynnika indukowanego hipoksją-1α (hypoxia inducible factor-1α, HIF-1α) i receptora chemokiny C-C typu 2 (C-C motif chemokine receptor-2, CCR-2) we krwi obwo­dowej pacjentów z GD i zbadania wpływu tych cząsteczek i potencjalnego mechanizmu ich działania w patogenezie choroby. Materiał i metody: Do badania włączono 41 pacjentów z GD (grupa GD) i 45 osób zdrowych (grupa kontrolna). Stężenie PDGF-BB i HIF-1α w próbkach krwi obwodowej oznaczono i porównano między grupami. Do pomiaru ekspresji CCR2 w makrofagach krwi obwodowej zastosowano metodę cytometrii przepływowej (flow cytometry, FCM). Wyniki: W obu grupach badanych stwierdzono ekspresję PDGF-BB i HIF-1α we krwi obwodowej. W grupie GD odnotowano istotne statystycznie wyższe stężenia PDGF-BB i HIF-1α niż u osób zdrowych (p &lt; 0,05). Odsetek makrofagów CCR2-dodatnich we krwi obwo­dowej w grupie GD był istotnie wyższy niż w grupie kontrolnej (p &lt; 0,05). Wnioski: Makrofagi CCR2-dodatnie mogą indukować ekspresję PDGF-BB za pośrednictwem sygnału HIF-1α, a wysoka ekspresja PDGF­BB może odgrywać rolę w patogenezie GD

Distinct intraseasonal oscillation modes over the tropical Indo-Pacific oceans

Funding: This work was supported by the National Key Program for Developing Basic Science (Grants 2022YFF0801702 and 2022YFE0106600), the National Natural Science Foundation of China (Grants 42175060 and 42175021), the Jiangsu Province Science Foundation (Grant BK20250200302). The authors are thankful for the support of the Jiangsu Provincial Innovation Center for Climate Change.In boreal winter, the Madden-Julian Oscillation (MJO) is the dominant mode of tropical intraseasonal oscillation (ISO), which bridges weather and climate. In addition to the dominant eastward propagating MJO mode, this study identifies the existence of the westward propagating and stationary oscillating ISO modes according to the spatio-temporal evolution of large-scale precipitation. At the pentad timescale, each ISO mode tends to suppress the occurrence of the other two. The diagnostic of column-integrated moist static energy (MSE) tendency anomalies reveals the dominant contribution from horizontal MSE advection to each ISO mode. Synthesis results indicate that vertical zonal wind shear anomalies exhibit opposite distributions between the propagating and stationary oscillating ISO events over the tropical Indo-Pacific Oceans. Subsequent simulations prove that the easterly (westerly) wind shear anomalies could suppress the eastward (westward) propagating convection of the ISO, thus favoring a stationary oscillating ISO.Peer reviewe

Molecular mechanisms of exercise intervention in alleviating the symptoms of autism spectrum disorder: Targeting the structural alterations of synapse

Autism spectrum disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder characterized by stereotyped behaviors, specific interests, and impaired social and communication skills. Synapses are fundamental structures for transmitting information between neurons. It has been reported that synaptic deficits, such as the increased or decreased density of synapses, may contribute to the onset of ASD, which affects the synaptic function and neuronal circuits. Therefore, targeting the recovery of the synaptic normal structure and function may be a promising therapeutic strategy to alleviate ASD symptoms. Exercise intervention has been shown to regulate the structural plasticity of synapses and improve ASD symptoms, but the underlying molecular mechanisms require further exploration. In this review, we highlight the characteristics of synaptic structural alterations in the context of ASD and the beneficial effects of an exercise intervention on improving ASD symptoms. Finally, we explore the possible molecular mechanisms of improving ASD symptoms through exercise intervention from the perspective of regulating synaptic structural plasticity, which contributes to further optimizing the related strategies of exercise intervention promoting ASD rehabilitation in future

Development and verification of a combined immune- and cancer-associated fibroblast related prognostic signature for colon adenocarcinoma

IntroductionTo better understand the role of immune escape and cancer-associated fibroblasts (CAFs) in colon adenocarcinoma (COAD), an integrative analysis of the tumor microenvironment was performed using a set of 12 immune- and CAF-related genes (ICRGs).MethodsUnivariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses were used to establish a prognostic signature based on the expression of these 12 genes (S1PR5, AEN, IL20RB, FGF9, OSBPL1A, HSF4, PCAT6, FABP4, KIF15, ZNF792, CD1B and GLP2R). This signature was validated in both internal and external cohorts and was found to have a higher C-index than previous COAD signatures, confirming its robustness and reliability. To make use of this signature in clinical settings, a nomogram incorporating ICRG signatures and key clinical parameters, such as age and T stage, was developed. Finally, the role of S1PR5 in the immune response of COAD was validated through in vitro cytotoxicity experiments.ResultsThe developed nomogram exhibited slightly improved predictive accuracy compared to the ICRG signature alone, as indicated by the areas under the receiver operating characteristic curves (AUC, nomogram:0.838; ICRGs:0.807). The study also evaluated the relationships between risk scores (RS) based on the expression of the ICRGs and other key immunotherapy variables, including immune checkpoint expression, immunophenoscore (IPS), and microsatellite instability (MSI). Integration of these variables led to more precise prediction of treatment efficacy, enabling personalized immunotherapy for COAD patients. Knocking down S1PR5 can enhance the efficacy of PD-1 monoclonal antibody, promoting the cytotoxicity of T cells against HCT116 cells ((p&lt;0.05).DiscussionThese findings indicate that the ICRG signature may be a valuable tool for predicting prognostic risk, evaluating the efficacy of immunotherapy, and tailoring personalized treatment options for patients with COAD

Does Economic Policy Uncertainty Affect CO2 Emissions? Empirical Evidence from the United States

This paper aims to examine the effects of economic policy uncertainty (measured by the World Uncertainty Index&mdash;WUI) on the level of CO2 emissions in the United States for the period from 1960 to 2016. For this purpose, we consider the unit root test with structural breaks and the autoregressive-distributed lag (ARDL) model. We find that the per capita income promotes CO2 emissions in the long run. Similarly, the WUI measures are positively associated with CO2 emissions in the long run. Energy prices negatively affect CO2 emissions both in the short run and the long run. Possible implications of climate change are also discussed

Autophagic Clearance of PolyQ Proteins Mediated by Ubiquitin-Atg8 Adaptors of the Conserved CUET Protein Family

SummarySelective ubiquitin-dependent autophagy plays a pivotal role in the elimination of protein aggregates, assemblies, or organelles and counteracts the cytotoxicity of proteins linked to neurodegenerative diseases. Following substrate ubiquitylation, the cargo is delivered to autophagosomes involving adaptors like human p62 that bind ubiquitin and the autophagosomal ubiquitin-like protein Atg8/LC3; however, whether similar pathways exist in lower eukaryotes remained unclear. Here, we identify by a screen in yeast a new class of ubiquitin-Atg8 adaptors termed CUET proteins, comprising the ubiquitin-binding CUE-domain protein Cue5 from yeast and its human homolog Tollip. Cue5 collaborates with Rsp5 ubiquitin ligase, and the corresponding yeast mutants accumulate aggregation-prone proteins and are vulnerable to polyQ protein expression. Similarly, Tollip depletion causes cytotoxicity toward polyQ proteins, whereas Tollip overexpression clears human cells from Huntington’s disease-linked polyQ proteins by autophagy. We thus propose that CUET proteins play a critical and ancient role in autophagic clearance of cytotoxic protein aggregates