Search Results (290)

Background/Objectives: Prenatal exposure to famine can lead to lasting health effects through changes in DNA methylation. This study aims to evaluate the impact of prenatal exposure to the Chinses Great Famine (1959–1961) on human epigenome and the subsequent influence on blood lipids. Methods: We conducted an epigenome-wide association study (EWAS) of peripheral blood-based DNA methylation and prenatal exposure to the Chinese Great Famine as well as blood lipids among eight participants exposed to famine and eight sex-matched participants (born ≤ 3 years after the famine). Genome-wide DNA methylation sites were profiled using the Illumina EPIC BeadChip, which covers 850K methylation positions. Results: After EWAS analyses, seven probes in genes C8orf31, ELAVL1, U6, GBA2, SHOX2, SLC1A4, and NPHP4 reached p < 1 × 10⁻⁵. Of these, famine exposure was associated with decreased methylation levels of a GBA2 exonic probe cg08258661 (p = 4.9 × 10⁻⁶). After false discovery rate (FDR) correction, pathway enrichment analyses for genes harboring nominally significant (p < 0.05) probes identified 44 significant pathways (q < 0.05), and 5 pathways were related to lipid metabolism. After FDR correction in each pathway, probes cg02622866 (5’UTR of ATF2, p = 1.09 × 10⁻³), cg07316730 (body of GRB2, p = 1.32 × 10⁻³), and cg01105385 (body of PIK3R1, p = 1.94 × 10⁻³) in the PI2K-Akt signaling pathway were associated with blood LDL-C (q ≤ 0.04); probes cg09180702 (3’UTR of PIGQ, p = 9.21 × 10⁻⁵, and q = 0.04) and cg01421548 (body of HS3ST4, p = 5.23 × 10⁻⁵, and q = 0.01) in the metabolism pathway were associated with blood LDL-C and HDL-C, respectively; In addition, probe cg08460387 (5’UTR of MAN1C1, p = 1.09 × 10⁻⁴, and q = 0.02) in the vesicle-mediated transport pathway was associated with log-transformed blood triglycerides. Conclusions: Through an epigenetic study of the Chinese Great Famine, we identified six novel genes involved in lipid metabolism. Full article

The first detection of gravitational waves from the binary black merger GW150914 started the era of gravitational astronomy. The observation of the binary neutron star merger GW170817 and of its associated electromagnetic counterpart GRB 170817A started multi-messenger gravitational astronomy. This short review discusses the discovery of GW170817 and the follow-up of the electromagnetic counterpart, together with the broad range of results in astrophysics and fundamental physics, including the Gamma-Ray Burst field. The GW170817/GRB 170817A observation showed that binary neutron star mergers can explain at least a fraction of short Gamma-Ray Bursts. The optical and infrared evolution of the associated AT 2017gfo transient showed that binary neutron star mergers are sites of r-process nucleo-synthesis. The combination of gravitational and electromagnetic observations has been used to estimate the Hubble parameter, the speed of gravitational waves, and the equation of state of nuclear matter. The increasing sensitivity of interferometric detectors and the forthcoming operation of third generation detectors will lead to an improved statistics of binary neutron star mergers. Full article

We present optical photometry for the afterglow of GRB 201015A, which can be classified as a medium-luminosity gamma-ray burst ($L_{\gamma ,\mathrm{iso}}\approx 2.55\times {10}^{49}\mathrm{erg}{\mathrm{s}}^{-1}$ ) and the associated underlying supernova SN 201015A. A millisecond magnetar engine has been widely suggested to exist in gamma-ray burst (GRB) phenomena. In this paper, we study the effects of the magnetar engine on GRB 201015A/SN 201015A by light curve analysis. We use a smooth broken power-law plus magnetar spin-down model to fit the X-ray and optical light curves of GRB 201015A/SN 201015A. The best-fitting results reveal that the magnetar initial spin period and surface magnetic field at the pole are constrained to be $P_0=16.{80}_{-0.47}^{+0.24}\mathrm{ms}$ and $B_{\mathrm{p}}=0.{80}_{-0.32}^{+0.34}\times {10}^{15}\mathrm{G}$, respectively, and the SN ejected a total mass of $M_{\mathrm{ej}}=2.{55}_{-0.37}^{+1.12}{M}_{\odot }$ and an ejecta velocity of $v_{\mathrm{ej}}$ = ${\mathrm{30,000}}_{-2500}^{+4800}\mathrm{km}{\mathrm{s}}^{-1}$, inferring a kinetic energy of $E_{\mathrm{SN},\mathrm{K}}\approx 1.37\times {10}^{52}\mathrm{erg}$. From our analysis, we find that the central engine of GRB 201015A/SN 201015A may well be a magnetar, and the emission from a magnetar central engine can be solely responsible for powering SN 201015A. Full article

The detection of gamma-ray burst GRB 221009A has attracted significant attention due to its record brightness and first-ever detection of multi-TeV $\mathit{\gamma }$-rays from a GRB. Located at redshift $z=0.151$, this event is relatively nearby by GRB standards yet remains cosmologically distant, making the survival of multi-TeV photons surprising. The Large High Altitude Air Shower Observatory detected photons with energies up to ∼13 TeV during the early afterglow phase, challenging standard EBL models. We investigate whether several theoretical frameworks can explain this anomalous emission: reduced EBL opacity due to cosmic voids along the line of sight, novel emission mechanisms within the GRB environment, secondary $\mathit{\gamma }$-ray production through cosmic-ray cascades, and new physics scenarios involving Lorentz invariance violation or axion-like particles. Our analysis reveals areas of consensus regarding the exceptional nature of this event, while highlighting ongoing theoretical tensions about the dominant physical processes. We discuss the limitations of current models and identify specific observational signatures that future multi-wavelength and multi-messenger observations could provide to discriminate between competing explanations. The continued study of similar events with next-generation facilities will be crucial for resolving these theoretical challenges and advancing our understanding of extreme particle acceleration processes in astrophysical environments. Full article

This study aims to develop a gelatin methacryloyl (GelMA)-based ginsenoside Rb3 (G-Rb3) drug delivery system and investigate its application in the treatment of periodontitis and the underlying mechanisms. Periodontal ligament stem cells (PDLSCs) were obtained and identified. The appropriate concentration ranges of G-Rb3 and lipopolysaccharide (LPS) were investigated by the CCK-8 experiments. Quantitative RT-PCR, ELISA, and Western blot were performed to assess the effects of GelMA@G-Rb3 on LPS-treated PDLSCs. The possible mechanisms were determined through network pharmacology analysis and Western blot. The therapeutic effects of GelMA@G-Rb3 in rat periodontitis animal models were systematically evaluated using Micro-CT, H&E staining, Masson staining, and immunofluorescence staining. PDLSCs were successfully isolated and characterized. The in vitro results indicated that GelMA@G-Rb3 significantly alleviated LPS-induced inflammation in PDLSCs by inhibiting the p38/ERK signaling pathway and activating the PI3K/AKT signaling pathway. In vivo experiments confirmed that GelMA@G-Rb3 significantly reduced alveolar bone resorption, and promoted periodontal tissue regeneration, while simultaneously demonstrating significant regulatory effects on the MAPK signaling pathway. This study demonstrated the efficacy of the GelMA@G-Rb3 system in modulating the inflammatory responses of periodontitis and improving the periodontal tissue regeneration, which establish a solid foundation and proposed innovative therapeutic approaches for the treatment of periodontitis. Full article

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