Search Results (285)

In this article, we investigate the influence of viscosity on the evolution of the cosmos within the framework of the newly proposed $f(Q,L_m)$ gravity. We have considered a linear functional form $f(Q,L_m)=\alpha Q+\beta L_m$ with a bulk viscous coefficient $\zeta ={\zeta }_0+{\zeta }_{1}H$ for our analysis and obtained exact solutions to the field equations associated with a flat FLRW metric. In addition, we utilized Cosmic Chronometers (CC), CC + BAO, CC + BAO + GRB, and GRB data samples to determine the constrained values of independent parameters in the derived exact solution. The likelihood function and the Markov Chain Monte Carlo (MCMC) sampling technique are combined to yield the posterior probability using Bayesian statistical methods. Furthermore, by comparing our results with the standard cosmological model, we found that our considered model supports the acceleration of the universe in late time. Full article

In this paper, we calibrate the luminosity relation of gamma−ray bursts (GRBs) by employing artificial neural networks (ANNs) to analyze the Pantheon+ sample of type Ia supernovae (SNe Ia) in a manner independent of cosmological assumptions. The A219 GRB dataset is used to calibrate the Amati relation ($E_{\mathrm{p}}$-$E_{\mathrm{iso}}$) at low redshift with the ANN framework, facilitating the construction of the Hubble diagram at higher redshifts. Cosmological models are constrained with GRBs at high redshift and the latest observational Hubble data (OHD) via the Markov chain Monte Carlo numerical approach. For the Chevallier−Polarski−Linder (CPL) model within a flat universe, we obtain ${\Omega }_{\mathrm{m}}={0.321}_{-0.069}^{+0.078}$, $h={0.654}_{-0.071}^{+0.053}$, $w_0={-1.02}_{-0.50}^{+0.67}$, and $w_a={-0.98}_{-0.58}^{+0.58}$ at the 1 −$\sigma$ confidence level, which indicates a preference for dark energy with potential redshift evolution ($w_a\ne 0$). These findings using ANNs align closely with those derived from GRBs calibrated using Gaussian processes (GPs). Full article

Background: Current cosmological fits typically assume a direct relation between cosmic time (t) and the scale factor ($a\left(t\right)$), yet this ansatz remains largely untested across diverse observations. Objectives: We (i) test whether a single power-law scaling ($a\left(t\right)\propto t^{\alpha }$) can reproduce late- and early-time cosmological data and (ii) explore whether a dynamically evolving ($\alpha \left(t\right)$), modeled as a scalar–tensor field, naturally induces directional asymmetry in cosmic evolution. Methods: We fit a constant-$\alpha$ model to four independent datasets: 1701 Pantheon+SH0ES supernovae, 162 gamma-ray bursts, 32 cosmic chronometers, and the Planck 2018 TT spectrum (2507 points). The CMB angular spectrum is mapped onto a logarithmic distance-like scale ($\mu ={log}_{10}{D}_{\ell }$), allowing for unified likelihood analysis. Each dataset yields slightly different preferred values for $H_0$ and $\alpha$; therefore, we also perform a global combined fit. For scalar–tensor dynamics, we integrate $\alpha \left(t\right)$ under three potentials—quadratic, cosine, and parity breaking (${\alpha }^{3}sin\alpha$)—and quantify directionality via forward/backward evolution and Lyapunov exponents. Results: (1) The constant-$\alpha$ model achieves good fits across all datasets. In combined analysis, it yields $H_0\simeq 70\mathrm{km}{\mathrm{s}}^{-1}{\mathrm{Mpc}}^{-1}$ and $\alpha \simeq 1.06$, outperforming $\Lambda$CDM globally ($\Delta \mathrm{AIC}\simeq 401254$), though $\Lambda$CDM remains favored for some low-redshift chronometer data. High-redshift GRB and CMB data drive the improved fit. Numerical likelihood evaluations are approximately three times faster than for $\Lambda$CDM. (2) Dynamical $\alpha \left(t\right)$ models exhibit time-directional behavior: under asymmetric potentials, forward evolution displays finite Lyapunov exponents (${\lambda }_L\sim {10}^{-3}$), while backward trajectories remain confined (${\lambda }_L<0$), realizing classical arrow-of-time emergence without entropy or quantum input. Limitations: This study addresses only homogeneous background evolution; perturbations and physical derivations of potentials remain open questions. Conclusions: The time-scaling approach offers a computationally efficient control scenario in cosmological model testing. Scalar–tensor extensions naturally introduce classical time asymmetry that is numerically accessible and observationally testable within current datasets. Code and full data are available. Full article

High-altitude pulmonary edema (HAPE) is a severe condition associated with high-altitude environments, and its molecular mechanism has not been fully elucidated. This study systematically analyzed the DNA methylation status of HAPE patients and healthy controls using reduced-representation bisulfite sequencing (RRBS) and 850K DNA methylation chips, identifying key differentially methylated regions (DMRs). Targeted bisulfite sequencing (TBS) revealed significant abnormalities in DMRs of five genes, azurocidin 1 (AZU1), growth factor receptor bound protein 7 (GRB7), mannose receptor C-type 2 (MRC2), RUNX family transcription factor 3 (RUNX3), and septin 9 (SEPT9). The abnormal expression of AZU1 was validated using peripheral blood leukocytes from HAPE patients and normal controls, as well as rat lung tissue, indicating its potential importance in the pathogenesis of HAPE. To further validate the function of AZU1, we conducted experimental studies using a hypobaric hypoxia injury model in Human Umbilical Vein Endothelial Cells (HUVEC). The results showed that AZU1 was significantly upregulated under hypobaric hypoxia. Knocking down AZU1 mitigates the reduction in HUVEC proliferation, angiogenesis, and oxidative stress damage induced by acute hypobaric hypoxia. AZU1 induces cellular oxidative stress via the p38/mitogen-activated protein kinase (p38/MAPK) signaling pathway. This study is the first to elucidate the mechanism of AZU1 in HAPE via the p38/MAPK pathway, offering novel insights into the molecular pathology of HAPE and laying a foundation for future diagnostic and therapeutic strategies. Full article

GIGYF2 (Grb10-interacting GYF protein 2) functions as a versatile adaptor protein that regulates gene expression at various levels. At the transcriptional level, GIGYF2 facilitates VCP/p97-mediated extraction of ubiquitylated Rpb1 from stalled RNA polymerase II complexes during DNA damage response. In mRNA surveillance, GIGYF2 participates in ribosome collision-induced quality control, nonsense-mediated decay, no-go decay, and non-stop decay pathways. Furthermore, GIGYF2 interacts with key factors including 4EHP, TTP, CCR4-NOT, DDX6, ZNF598, and TNRC6A to mediate translational repression and mRNA degradation. Additionally, dysregulation of GIGYF2 has been implicated in various pathological conditions, including metabolic diseases, vascular aging, viral infections, and neurodegenerative disorders. This review summarizes the structural and functional characteristics of GIGYF2, highlighting its importance in transcriptional regulation, mRNA surveillance, translational inhibition, and mRNA degradation, while also elucidating its potential as a therapeutic target for disease treatment. Full article

Objectives: This study aims to investigate the impact of Gossypol on human cervical cancer cells and elucidate its mechanism of action to establish a foundation for further clinical investigations. Methods: Cell proliferation, migration, and invasion were evaluated through CCK−8, wound healing, and Transwell assays. Fe₃O₄-BP-Gossypol (Fe₃O₄@Gossypol) conjugates were synthesized by linking Fe₃O₄ with Gossypol using benzophenone crosslinking. Successful conjugation was confirmed through scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and ultraviolet–visible spectrophotometry (UV-Vis). Subsequent to co-incubation with HeLa cell lysates, Fe₃O₄@Gossypol complexes facilitated the magnetic enrichment and purification of target proteins, which were identified using high-resolution mass spectrometry (HR-MS). The identified targets underwent KEGG pathway and GO analyses, followed by molecular docking with Gossypol. HeLa cells were exposed to Gossypol at concentrations of 7.48, 14.96, and 29.92 μmol·L⁻¹ for 48 h, and protein expression levels were quantified via Western blotting. Results: Gossypol notably suppressed cervical cancer cell proliferation, migration, and invasion. The integration of target fishing, network pharmacology, and molecular docking highlighted PIK3R2, MAPK1, and GRB2 as potential therapeutic targets. Western blot analysis revealed a dose-dependent reduction in PIK3R2, GRB2, and MAPK1 expression in Gossypol-treated groups compared to controls (p < 0.05). Conclusions: Gossypol may exhibit anti-cervical cancer effects by modulating the PI3K/AKT signaling pathway. Full article

Background: The Quantitative Analysis of Multi-components by Single-marker (QAMS) method has been developed as an alternative to the External Standards Method (ESM) for the quality control of medicinal herbs. Objectives: In this study, QAMS was developed to determine saponins in the raw materials of Panax vietnamensis using HPLC-PDA/ELSD. Methods: The method was developed and validated. The relative conversion factors F_x were calculated based on the linear regression for HPLC-PDA and the logarithm equation for HPLC-ELSD. The Standard Method Difference (SMD) was determined to indicate the difference in the results of QAMS and EMS. Results: Relative conversion factors (F_x) were determined for each detector to quantify five saponins (ginsenoside Rb₁, Rd, Rg₁, majnoside R2, and vina-ginsenoside R2) in VG root. The F_x values were calculated based on the ratio of the slopes of the regression equations of a single standard and an external standard. For HPLC-PDA, G-Rb1 was used as a single standard with the F_x values of 1.00 (G-Rb₁), 1.08 (G-Rd), 1.32 (G-Rg₁), and 0.04 (M-R2). For HPLC-ELSD, G-Rb₁ was used for determining the content of G-Rg₁ and G-Rb₁ with the F_x values of 1.00 (G-Rb₁) and 0.95 (G-Rg₁), while M-R2 was used for quantitating M-R2 and V-R2 with F_x of 1.00 (M-R2) and 1.05 (V-R2). An SMD value less than 5.00% confirms the close alignment of the QAMS method with ESM. Conclusions: The QAMS method proved to be a feasible and promising method for the quality control of P. vietnamensis. Full article

De novo metastatic breast cancer (dnMBC) accounts for 3–10% of newly diagnosed cases, with 20–40% presenting as a bone-only metastatic disease, which can achieve survival outcomes exceeding 10 years with multimodal therapy. However, the role of multimodal therapy remains controversial in the guidelines. Objective: This study aims to identify dnBOMBC subgroups to develop a pragmatic staging system for guiding locoregional therapy decisions. Materials and Methods: Data from the MF07-01 phase III randomized trial (2021, median follow-up time (mFT): 40 months (range 1–131)) and the BOMET prospective multi-institutional registry trial (2021, mFT: 34 months (range 25–45)) were combined for analysis, including only patients who presented with bone-only metastases. Exclusion criteria were patients under 18 and those with a history of prior cancer or cancer metastases. Patients with missing data and positive surgical margins were excluded. Out of 770 patients, 589 were included. Survival analyses were first conducted according to molecular subgroups, after which patients were further stratified by hormone receptor status, human epidermal human epidermal growth factor receptor 2 (HER2) status, tumor grade, and clinical T (cT) stage. Group A (GrA) included hormone receptor (HR)-positive, low- or intermediate-grade tumors at any cT; HR-positive, high-grade tumors with cT0–3; or any HER2-positive tumors. Group B (GrB) included HR-positive, high-grade tumors with cT4 disease or any triple-negative (TN) tumors. Results: The hazard of death (HoD) was 43% lower in GrA than in GrB. Median OS was 65 months (39–104) for GrA patients and 44 months (28–72) for GrB patients (HR 0.57, 95% CI 0.41–0.78, p = 0.0003). Primary tumor surgery (PTS) significantly improved OS in GrA patients, regardless of the number of metastases (solitary: HR, 0.375, 95% CI 0.259–0.543, p < 0.001; multiple: HR 0.435, 95% CI 0.334–0.615, p < 0.001). Conversely, GrB patients did not experience a significant benefit from PTS. Conclusions: This study demonstrates that GrA patients have better OS than GrB patients, and PTS reduces the HoD in GrA patients compared to systemic therapy alone. These findings support using a modified staging system in dnBOBMC to identify patients who may benefit from multimodal therapy including PTS. Full article

We reanalyze the spectral lag data for 56 Gamma-Ray Bursts (GRBs) in the cosmological rest frame to search for Lorentz Invariance Violation (LIV) using frequentist inference. For this purpose, we use the technique of profile likelihood to deal with the nuisance parameters, corresponding to a constant time lag in the GRB rest frame and an unknown intrinsic scatter, while the parameter of interest is the energy scale for LIV ($E_{QG}$). With this method, we do not obtain a global minimum for ${\chi }^2$ as a function of $E_{QG}$ up to the Planck scale. Thus, we can obtain one-sided lower limits on $E_{QG}$ in a seamless manner. Therefore, the 95% c.l. lower limits which we thus obtain on $E_{QG}$ are then given by $E_{QG}\ge 2.07\times {10}^{14}$ GeV and $E_{QG}\ge 3.71\times {10}^5$ GeV, for linear and quadratic LIV, respectively. Full article

Background: Caffeine has become the psychostimulant with the highest use worldwide by different segments of the population. This is mainly due to the wide variety of benefits it offers in different contexts of use. It is available in various forms, with caffeine chewing gum recently generating great interest due to its characteristics and absorption time. Methods: A placebo-controlled study was conducted in which 20 healthy university students were exposed to three different conditions (single dose, partial dose, and placebo). The intervention consisted of a dual task in which heart rate, perceived exertion, and reaction time were monitored using the Stroop test and choice reaction time test while participants performed two blocks of cycloergometer exercise. Results: A t-test comparison between blocks showed differences in the Stroop test under all conditions, with the single dose having the best performance (Gr.A p < 0.001; Gr.B p < 0.029; Gr.C p < 0.009). The single dose group also showed favorable results for the HR/RPE ratio (p < 0.044) and an increase in the rate of perceived exertion (p < 0.006). No changes in reaction time were observed under any condition of the choice reaction time test. Conclusions: These results suggest that caffeine supplementation has positive effects on variables related to psychophysiological performance during a dual task. A single dose showed the best results in this study; however, longer intervention designs could be considered in the future to see the effect of partial doses of caffeine over time. Full article

We present early follow-up observations of Einstein Probe (EP) X-ray transients, following its first year of operation. EP is a dedicated wide-field X-ray observatory that is transforming our understanding of the dynamic X-ray universe. During its first year, EP successfully detected a diverse range of high-energy transients—including gamma-ray bursts (GRBs), tidal disruption events (TDEs), and fast X-ray transients (FXTs), besides many stellar flares, disseminating 128 alerts in the aggregate. Ground-based optical follow-up observations, particularly those performed by our BOOTES telescope network, have played a crucial role in multi-wavelength campaigns carried out so far. Out of the 128 events, the BOOTES Network has been able to follow up 58 events, detecting 6 optical counterparts at early times. These complementary optical measurements have enabled rapid identification of counterparts, precise redshift determinations (such as EP250215a at $z=4.61$), and detailed characterization of the transient phenomena. The synergy between EP’s cutting-edge X-ray monitoring and the essential optical follow-up provided by facilities, such as the above-mentioned BOOTES Global Network or other Spanish ground-based facilities we have access to, underscores the importance and necessity of coordinated observations in the era of time-domain and multi-messenger astrophysics. Full article

Observations of several gamma-ray bursts (GRBs) that are temporally and spatially compatible with energetic supernovae (hypernovae) have established their common origin. In one case (GRB 111209A/SN 2011kl), the associated supernova was classified as superluminous (SN 2011kl). The exceptional duration of the observed gamma-ray prompt emission of GRB 111209A (about 7 h) is widely considered key to unlocking the physics behind the still mysterious origin of superluminous supernovae (SLSNe). We review the main observational and theoretical findings that may link some ultra-long GRBs to SLSNe. Specifically, we examine notable events and the role of progenitors and host galaxies in shaping these phenomena and focus on the proposed models. While a magnetar central engine is a plausible mechanism for both luminous and long-duration GRBs, a conclusive answer remains elusive, as alternative explanations are still viable. Further observational and theoretical work is required to clarify progenitor pathways and explosion mechanisms, potentially extending the classical GRB-SN connection to rare superluminous hypernovae. Full article

Linker for activation of T cells (LAT) is an essential adaptor protein in early T cell receptor (TCR) signaling that propagates multiple signaling pathways. However, how LAT spatial organization facilitates signal initiation and propagation after TCR triggering is not clear. To differentiate de novo assembly in the plasma membrane from pre-existing LAT vesicles and clusters, we developed imaging protocols and analyses to capture the organization and dynamics of single LAT molecules immediately after TCR engagement. We could observe individual LAT molecules in the plasma membrane that assembled into immobile signaling entities requiring LAT phosphorylation. This step-wise assembly process was temporally highly coordinated via the zeta-chain-associated protein kinase 70 (Zap70)-LAT-growth factor receptor-bound protein 2 (Grb2) pathway. While multiple spatial organization co-existed even within the plasma membrane, our data suggest that de novo plasma membrane assemblies facilitated signal propagation. Full article

The development and selection of ovarian follicles are essential for continuous egg production in chickens. Non-coding RNAs, particularly circular RNAs (circRNAs), play a critical regulatory role in follicle selection, a process heavily involving granulosa cells (GCs). In this study, we analyzed circRNA expression profiles in small yellow follicles (SYFs) and large yellow follicles (LYFs) of Taihang chickens using RNA sequencing. We identified 14,586 circRNAs, with 57 showing differential expression (DE-circRNAs) between SYFs and LYFs. Functional enrichment analysis revealed that these DE-circRNAs are involved in key biological processes, including signal transduction, cell membrane formation, and nuclear enzymatic regulation. We focused on circGRB14, a circRNA derived from the growth factor receptor-bound protein 14 (GRB14) gene, as a potential regulator of follicle selection. Using qPCR, CCK-8 proliferation assays, and Annexin V/PI apoptosis analysis, we demonstrated that circGRB14 inhibits GC proliferation and promotes apoptosis. In contrast, miR-12264-3p and miR-6660-3p, validated as direct targets of circGRB14 via Dual-Luciferase Reporter assays, exhibited opposing effects by promoting GC proliferation and inhibiting apoptosis. These findings highlight the circGRB14-miR-12264-3p/miR-6660-3p axis as a key regulatory mechanism in GC dynamics during follicle selection. This study provides novel insights into the functional interplay between circRNAs and miRNAs in avian follicle development, offering potential targets for improving egg production in poultry. Full article

Gamma-Ray Bursts(GRBs) are the most violent and energetic astrophysical phenomena, which I dare call “the Energy Monsters of the Universe”. Indeed, they show an enormous emitted isotropic energy ranging from ∼3 × ${10}^{46}$ erg (GRB 170817A) to ∼${10}^{55}$ erg (GRB 221009A) and a duration ranging from ≈milliseconds to ∼${10}^4$ s. In this review—which I agreed to write as a scientist not directly involved in the field of GRBs—I will present the history of GRBs from the time of their discovery by chance until the new era whose beginning was marked by the detection of gravitational waves coming from the merger of two neutron stars. I will discuss the experimental results and their physical interpretation, which is still a source of heated debate within the scientific community. Due to the reasonable length of this review and especially given my limited knowledge, I do not claim to have exhausted the complicated topic of GRBs, but to have contributed in making this subject easy to read for non-experts, providing a critical contribution that is hopefully useful to the whole community. Full article