Search Results (108)

Background/Objectives: To evaluate the intraday and interday reliability of seated horizontal upper body (UB) isometric push and pull tests performed with the VALD DynaMo Max dynamometer. Methods: Fifty-two recreationally active individuals (41 men, 11 women; 25.0 ± 6.1 years) completed two sessions 48 h apart, each comprising three maximal-effort push and pull trials at 90° elbow flexion using a custom-built rig with the attached dynamometer. Peak force (PF), peak rate of force development (RFD), impulse, and time-to-PF were extracted from 1200 Hz force–time data. Reliability was assessed using the intraclass correlation coefficient (ICC), coefficient of variation (CV%), standard error of measure (SEM) and minimal detectable change (MDC). Results: PF demonstrated excellent reliability (ICC = 0.97–0.99) with low absolute error (CV < 6%; MDC = 128–149 N). Impulse showed good-to-excellent reliability (ICC = 0.90–0.94; CV < 10%; MDC ≈ 755–790 N·s), whereas RFD displayed good reliability but greater variability (ICC = 0.80–0.81; CV < 20%; MDC = 2574–2925 N·s⁻¹). Time-to-PF was the least reliable (ICC = 0.68–0.71; CV > 24%; MDC = 1.5–1.7 s). Conclusions: Horizontal isometric push and pull tests using the VALD DynaMo Max dynamometer provide reliable measures of PF and impulse for athlete profiling and tracking substantial longitudinal changes. Peak RFD may be cautiously used for broad cross-sectional comparisons, although its higher variability limits precision in distinguishing smaller inter-individual differences and appears less sensitive to within-individual changes. Time-to-PF demonstrated insufficient reliability for practical application. Full article

This study examines the impact of an unintended fire at the Drava International plastic processing facility near Osijek, Croatia, on soil quality and the potential human health risks associated with agricultural soils within a 10 and 20 km radius. Surface soil samples (0–5 cm) were collected from ten locations within 10 km three days after the incident, and eight composite samples were taken from sites 10–20 km away 17 days’ post-event. Additionally, 18 control samples previously collected for soil fertility or quality monitoring were included for comparative analysis. In total, 36 agricultural soil samples were analyzed for pH, organic matter, total phosphorus, potassium, calcium, magnesium, and trace elements (Cr, Co, Ni, Cu, Zn, As, Pb). Eighteen post-fire samples were also analyzed for polycyclic aromatic hydrocarbons (PAHs), dioxins, and perfluoroalkyl substances (PFAS). Ecological risk was assessed using the pollution load index (PLI) and enrichment factor (EF), while human health risk was evaluated through the estimation of incremental lifetime cancer risk (ILCR) and individual carcinogenic risks (CRi) for As, Cr, Ni, and Pb. Results showed that concentrations of dioxins (TEQ LB and UB), dioxin-like PCBs, and non-dioxin-like PCBs in samples within 10 km were either below detection limits or present in trace amounts (4.0 × 10⁻⁶ mg/kg). PFAS compounds were not detected (<0.0005 mg/kg). The total concentration of non-dioxin-like PCBs ranged from 0.0023 to 0.0047 mg/kg, well below the maximum permissible levels. Post-fire contamination profiles revealed consistently higher PAH concentrations in the 0–10 km zone (mean 0.100 mg/kg) compared to the 10–20 km zone (mean 0.062 mg/kg). Twenty PLI values exceeded the threshold of 1 (range: 1.00–1.26), indicating moderate pollution, while the remaining values (PLI 0.82–0.99) suggested no pollution. EF values indicated minimal to moderate enrichment (EF < 2), supporting the conclusion that metal presence was predominantly geological with limited anthropogenic influence. All ILCR values for adults and children remained below the acceptable threshold of 1 × 10⁻⁴, indicating low carcinogenic risk under both pre- and post-fire conditions. CRi values followed a consistent decreasing trend across exposure pathways: ingestion > dermal absorption > inhalation. Full article

The L-band radiative transfer-forward modeling plays a crucial role in data assimilation for meteorological forecasting. By utilizing information from the underlying surface (typically land surface parameters and variables), such as soil moisture, soil temperature, snow cover, freeze–thaw status, and vegetation, the corresponding brightness temperatures can be simulated through the physical processes described by radiative transfer models. Data assimilation becomes meaningful when the errors introduced by the simulated brightness temperatures are smaller than the simulation accuracy of the land surface variables. However, radiative transfer models at the L-band cannot accurately simulate TB operationally. In this study, four machine learning methods, including random forest (RF), long short-term memory (LSTM), support vector machine (SVM), and deep neural networks (DNN), are employed to reconstruct the forward relationship from land surface parameters to brightness temperatures, serving as an alternative to traditional radiative transfer models. The performance of these methods is evaluated using ground-truthed soil moisture data, soil texture static data, and leaf area index (LAI). The results indicate that DNN and RF exhibit superior performance, with DNN achieving the lowest average unbiased root mean square error (ubRMSE) of 6.238 K for vertical polarization brightness temperature (TBv) and 9.033 K for horizontal polarization brightness temperature (TBh). Regarding correlation coefficients between the retrieved brightness temperatures and satellite measurements, RF leads for H-polarized TB with a value of 0.943, while both RF and SVM perform well for V-polarized TB with values of 0.930 and 0.932, respectively. In conclusion, our study shows that DNN is the optimal method for retrieving brightness temperatures, outperforming other machine learning approaches regarding error metrics and correlation with satellite measurements. These findings highlight the potential of DNN in improving data assimilation processes in meteorological forecasting. Full article

The histone H2A variant H2AZ plays pivotal roles in shaping chromatin architecture and regulating gene expression. We recently identified H2AZ.2 in histone H2A lysine 119 ubiquitination (H2AK119ub)-enriched nucleosomes, but it is not known whether its highly related isoform H2AZ.1 also regulates this modification. In this study, we employed isoform-specific epitope-tagged knock-in mouse embryonic stem cell (ESC) lines to dissect the roles of each isoform in Polycomb Repressive Complex 1 (PRC1)-mediated H2AK119ub. Our results show that H2AZ.1 and H2AZ.2 share highly overlapping genomic binding profiles, both co-localizing extensively with H2AK119ub-enriched loci. The knockdown of either isoform led to reduced H2AK119ub levels; however, the two isoforms appear to function through distinct mechanisms. H2AZ.1 facilitates the recruitment of Ring1B, the catalytic subunit of PRC1, thereby promoting the deposition of H2AK119ub. In contrast, H2AZ.2 does not significantly affect Ring1B recruitment but instead functions as a structural component that stabilizes H2AK119ub-modified nucleosomes. In vitro ubiquitination assays indicate that H2AZ.1-containing nucleosomes serve as more efficient substrates for PRC1-mediated ubiquitination compared to those containing H2AZ.2. Thus, these findings define the distinct mechanisms of the two H2AZ variants in regulated PRC1-mediated H2AK119 ubiquitination and highlight a functional division of labor in epigenetic regulation. Full article

Immunotherapy has emerged as a key modality in cancer treatment, yet its effectiveness varies significantly among patients, often due to the metabolic stress imposed by the tumor microenvironment. Hypoxia, a major factor in the tumor microenvironment, results from the high metabolic rate of tumor cells and inadequate vascularization, impairing immune cells’ function and potentially influencing gene expression profiles. Despite the widespread use of quantitative real-time PCR in immunological studies, to the best of our knowledge, data on reference gene stability in human peripheral blood mononuclear cells under hypoxic conditions is limited. In our study, we assessed the expression stability of commonly used reference genes (S18, HPRT, IPO8, RPL13A, SDHA, PPIA, and UBE2D2) in both non-stimulated and CD3/CD28-activated peripheral blood mononuclear cells cultured under normoxic, hypoxic (1% O₂), and chemically induced hypoxic conditions for 24 h. Analysis using four different algorithms—delta Ct, geNorm, NormFinder, and BestKeeper—identified RPL13A, S18, and SDHA as the most suitable reference genes for human peripheral blood mononuclear cells under hypoxic conditions. In contrast, IPO8 and PPIA were found to be the least suitable housekeeping genes. The study provides essential insights into the stability of reference genes in peripheral blood mononuclear cells under hypoxic conditions, a critical but understudied aspect of immunological research. Given the significant impact of hypoxia on T cell metabolism and function in the tumor microenvironment, selecting reliable reference genes is crucial for accurate gene expression analysis. Our findings will be valuable for future studies investigating hypoxia-driven metabolic reprogramming in immune cells, ultimately contributing to a better understanding of T cell responses in cancer immunotherapy. Full article

We investigated the configurational conditions influencing primary and secondary school teachers’ behavioral intentions (BIs) and usage behavior (UB) in adopting digital learning tools by using fuzzy set qualitative comparative analysis (fsQCA) and Tobit analysis. Based on the extended unified theory of acceptance and use of technology (UTAUT2) and by integrating TPK, configurations that drive or hinder teachers’ use of digital tools were identified. The results revealed that BI formation is driven by the core combination of facilitating conditions (FC) and hedonic motivation (HM); the synergy of FC, HM, and TPK; and the interplay of TPK and HM. UB was significantly promoted by the combinations of H with BI and TPK with BI. Conversely, the low levels of H and BI, or H and TPK lowered the levels of UB. By integrating fsQCA and Tobit analysis, the complex and asymmetric effects in digital tool adoption were understood, and recommendations were proposed to develop differentiated support strategies based on these configurational findings. Full article

Background: Unresolved inflammation is a major predictor of heart failure following myocardial infarction. Exogenous ubiquitin (eUB) is shown to decrease inflammatory response and confer cardioprotection in mice 3 days post-ischemia/reperfusion (I/R) injury. Here, we hypothesized that eUB differentially modulates the phenotype and function of M1 and M2 macrophages. Methods and Results: Peritoneal macrophages, pretreated with UB for 30 min, were exposed to IFN-γ (M1 polarization) or IL-4 (M2 polarization) for 72 h. Cytokine/chemokine levels were measured in conditioned media, while cells were used for functional and biochemical assays. eUB reduced TNF-α secretion in M1, and TNF-α and IL-10 secretion in M2 macrophages. eUB induced cytoskeletal reorganization and reduced surface area in M1 macrophages. eUB enhanced M1 migration; however, it decreased M2 macrophage migration and efferocytosis. It decreased STAT1 and FAK phosphorylation in M1, while increasing STAT6 and FAK phosphorylation in M2 macrophages. Total protein ubiquitination remained unchanged. In non-activated macrophages, eUB altered morphology, suppressed IL-1β, IL-2, and IL-5 secretion, and enhanced efferocytosis. Conclusion: eUB modulates macrophage polarization, reduces pro-inflammatory cytokine secretion, and alters functional parameters and intracellular signaling. These effects may contribute to the cardioprotective potential of eUB 3 days post-I/R injury. Full article

Extracellular vesicles (EVs) play pivotal roles in tumor progression and metastasis by mediating intercellular communication within the tumor microenvironment. In this study, we identified two novel EX cargo proteins—UBE2NL and HIST2H3PS2—derived from highly aggressive epithelial ovarian cancer (EOC) cells and mesenchymal-type ovarian stromal progenitor cells (MSC-OCSPCs) but absent in less aggressive SKOV3 cells. Quantitative proteomic profiling via LC-MS/MS and TCGA-integrated analysis revealed that high expression of these genes correlated with advanced tumor stages and poor overall survival in EOC, and high HIST2H3PS2 expression predicted poor survival in endometrial cancer (EC). Functionally, UBE2NL and HIST2H3PS2 overexpression promoted EOC cell invasiveness, which was further enhanced by EX-mediated autocrine and paracrine effects. In contrast, the knockdown of UBE2NL reduced cell invasiveness and prolonged mouse survival in vivo. Moreover, HIST2H3PS2-enriched EXs significantly increased peritoneal dissemination and ascites in murine models. These findings suggest that EX-packaged UBE2NL and HIST2H3PS2 drive tumor aggressiveness and metastasis in gynecologic cancers, highlighting their potential as prognostic biomarkers and therapeutic targets. Full article

Cyclacenes with the general formula C_4nH_2n are cyclic analogs of acenes. Acenes are well-known for their high reactivity, which increases with the number of fused benzene rings. The cyclic strain, absence of a Clar sextet, and diradical or polyradical nature are expected to render cyclacenes highly reactive under ambient conditions. Their primary decomposition pathway is anticipated to involve dimerization or polymerization. We explore the reaction pathway of the [_π4_s + _π4_s] dimerization of [n]-cyclacenes for 6 ≤ n ≤ 20 by density functional theory (DFT) using spin-unrestricted and thermally-assisted-occupation (TAO) formalisms. Computational analysis predicts a stepwise reaction mechanism that starts with the formation of a van der Waals complex and proceeds through a transition state to an intermediate with a single new C–C bond and two unsaturated valences. A subsequent second transition state results in the formation of the dimerization product. However, for smaller cyclacenes (n < 10), neither the van der Waals complex nor the first transition state is involved, and the intermediate is formed without a barrier. The largest [20]-cyclacene investigated exhibits the highest barriers for these processes. However, with a barrier as low as 3.9 kcal/mol at the UB3LYP-D3(BJ)/6-31G(d) level of theory, dimerization is anticipated to occur very rapidly. Full article

Podocyte injury is a hallmark of both focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD), ultimately reflected in foot process effacement and proteinuria. Triggers and pathogenic pathways leading to podocyte cytoskeleton rearrangements are, however, incompletely explained. Here, we aimed to contribute to the understanding of these pathways using tissue bottom-up proteomic profiling of laser-capture microdissected glomeruli from MCD and FSGS. Forty-six differentially expressed proteins were identified between the two groups (p < 0.05, |FC| ≥ 1.2). Pathway analysis showed that 16 out of 46 proteins were associated with the immune system, with E2 ubiquitin-conjugating enzyme (UBE2K) and complement factor H-related protein-1 (CFHR1) yielding the highest fold change in FSGS compared to MCD. The two target proteins were further validated through immunohistochemistry, confirming the podocyte localization of UBE2K and endothelial staining of CFHR. Additionally, several other differentially expressed proteins were linked to the cytoskeleton structure and its regulation. Our results point to the possibility that complement dysregulation may be the source of cytoskeleton rearrangement in FSGS. Full article

South America (SA) features diverse land cover types and varied climate conditions, both of which significantly influence the variability of soil moisture (SMO). Obtaining ground-truth measurements for SMO is often costly and labor-intensive, and the limited number of ground SMO stations in SA further complicates the evaluation of satellite-derived SMO products. In this work, we proposed an approach that integrates some statistical methods to assess the reliability of Soil Moisture Active Passive (SMAP), the H113 dataset from the Advanced Scatterometer (ASCAT), and Soil Moisture and Ocean Salinity (SMOS) satellite-derived SMO products in SA from 14 May 2015 to 31 December 2016. The integrated methods are error metrics (correlation (R), bias, and ubiased root mean square error (ubRMSE)), Triple Collocation Method (TCM), and Hovmöller diagrams. ERA5 and GLDAS-Noah SM products were used as references for validation. The quality of SMO products was assessed by considering environmental variables, including land cover, vegetation density, and precipitation, within the different climate zones of SA. The results presented that SMAP overall outperforms SMOS and ASCAT, with the highest average correlation (0.55 with GLDAS and 0.61 with ERA5), slight average bias (−0.058 with GLDAS and −0.014 with ERA5), and lowest average ubRMSE (0.045 with GLDAS and 0.041 with ERA5). In arid, semi-arid, and moderate vegetation regions, the SMAP satellite outperforms SMOS and ASCAT, achieving better statistics values with GLDAS and ERA5 datasets, and achieving low error variance and high S/N in the TCM analysis. While the ASCAT H113 product showed good performance, which makes it a good alternative to SMAP, it still has limitations in more dense vegetation regions. SMOS showed the lowest performance across SA, especially in the Amazon basin. The Amazon basin emerges as a critical region where all SMO products displayed a significant SMO variability; however, SMAP showed slightly better results than ASCAT and SMOS. In the absence of ground truths, the proposed approach provides a better evaluation of satellite SMO products. Meanwhile, it provides new spatiotemporal statistical insights into satellite SMO retrieval performance evaluation within diverse climate zones of SA. This research provides valuable guidance for improving SMO monitoring and agricultural management in tropical and semi-arid ecosystems. Full article

Histone modifications serve as molecular switches controlling critical cellular processes. The ubiquitination of histone H2A at lysines 13 and 15 (H2AK13/15ub) is a crucial epigenetic modification that coordinates DNA repair and genome stability during the DNA damage response (DDR). This epigenetic mark is dynamically regulated by three functional protein groups: “writer” enzymes (e.g., E3 ubiquitin ligase RNF168 that catalyzes H2AK13/15ub formation), “reader” proteins (including 53BP1 and BRCA1-BARD1 that recognize the mark to guide DNA repair), and “eraser” deubiquitinases (such as USP3 and USP16 that remove the modification). Dysregulation of the precisely coordinated network of H2AK13/15ub is strongly associated with various diseases, including RIDDLE syndrome, neurodegenerative disorders, immune deficiencies, and breast cancer. This review systematically analyzes the dynamic regulation of H2AK13/15ub in DDR and explores its therapeutic potential for disease intervention. Full article

Background/Objectives: The compound (±)-UB006 ((4SR,5SR)-4-(hydroxymethyl)-3-methylene-5-octyldihydrofuran-2(3H)-one) is a promising anti-cancer molecule. The enantiomer (–)-UB006 displays a potent cytotoxic effect in several tumor cell lines, particularly the ovarian cancer OVCAR-3 cell line, with a 40-fold increase in potency compared with the fatty acid synthase (FAS) inhibitor C75. Furthermore, in vivo, (–)-UB006 reduced the tumor burden in neuroblastoma xenografts. This effect was attributed to FAS inhibition and upregulation of apoptotic markers. However, CoA adducts of UB006 presented low solubility. Methods: We synthesized several (±)-UB006 derivatives by elongating the carbon chain of the primary alcohol and/or by adding hydroxyl groups with the aim of finding more potent and soluble anti-cancer compounds. Results: Our results showed a decrease in cytotoxicity when the carbon chain was elongated by more than two carbons. However, ethyl or propyl polyhydroxylated four-branched compounds showed an increased or maintained potency and solubility. The most promising compound was (±)-UB035 (IC50: 2.1 ± 0.2 µM), with a 2.5-fold increase in cytotoxicity in the OVCAR-3 cell line and a >4-fold increase in solubility (>2 mM) compared with (±)-UB006. Full article

DNA damage repair (DDR) plays a key role in maintaining genomic stability and developing inflammatory bowel disease (IBD). However, no report about the causal association between DDR and IBD exists. Whether DDR-related genes are the precise causal association to IBD in etiology remains unclear. Herein, we employed a multi-omics summary data-based Mendelian randomization (SMR) approach to ascertain the potential causal effects of DDR-related genes in IBD. Methods: Summary statistics from expression quantitative trait loci (eQTL), DNA methylation QTL (mQTL), and protein QTL (pQTL) on European descent were included. The GWAS summarized data for IBD and its two subtypes, Crohn’s disease (CD) and ulcerative colitis (UC), were acquired from the FinnGen study. We elected from genetic variants located within or near 2000 DDR-related genes in cis, which are closely associated with DDR-related gene changes. Variants were selected as instrumental variables (IVs) and assessed for causality with IBD and its subtypes using both SMR and two-sample MR (TSMR) approaches. Colocalization analysis was employed to evaluate whether a single genetic variant simultaneously influences two traits, thereby validating the pleiotropy hypothesis. Results: We identified seven DDR-related genes (Arid5b, Cox5a, Erbb2, Ube2l3, Gpx1, H2bcl2, and Mapk3), 33 DNA methylation genes, and two DDR-related proteins (CD274 and FCGR2A) which were all causally associated with IBD and its subtypes. Beyond causality, we integrated the multi-omics data between mQTL-eQTL and conducted druggability values. We found that DNA methylation of Erbb2 and Gpx1 significantly impacted their gene expression levels offering insights into the potential regulatory mechanisms of risk variants on IBD. Meanwhile, CD247 and FCGR2A could serve as targets for potential pharmacological interventions in IBD. Conclusions: Our study demonstrates the causal role of DDR in IBD based on the data-driven MR. Moreover, we found potential regulatory mechanisms of risk variants on IBD and potential pharmacological targets. Full article

To reduce the risk of syncope, trained breath-hold divers (BHDs) use a specialized breathing technique after surfacing called “hook breathing” (HB). It consists of a full inspiration followed by a Valsalva-like maneuver and with subsequent exhalation performed against resistance to generate continuous positive airway pressure during exhalation. This study analyzed the influence of HB on oxygen saturation recovery after a −40 m depth apnea dive in trained BHDs. Thirteen BHDs performed two dives to −40 m at different days, one followed by HB after a dive and the other using usual breathing (UB). To detect signs of lung edema, ultrasound B-line measurements were conducted before, 10 min after the dive, and within 1 h after the dive. To detect oxygen saturation recovery, pulse oximetry was recorded before and immediately after surfacing. Both groups exhibited significant increases in SpO₂ over time (UB: F (2.25, 24.7) = 22.1, p < 0.001, ηg2 = 0.612; HB: F (2.11, 23.2) = 29.0, p < 0.001, ηg2 = 0.688). Significant differences in SpO₂ were observed between the HB and UB groups at 30–45 s post-apnea, with higher SpO₂ values in the HB group; between 1.64 and 5.08% of SpO₂ in favor of the HB intervention. Four participants showed ultrasound B-lines within ten minutes post-dive. After a 40 m apnea dive, the results revealed significant SpO₂ recovery from 30 s to 45 s, with the HB recovering more rapidly. No differences were found at earlier (10–25 s) or later time points (50–60 s). Full article