Search Results (641)

Background/Objectives: Momordica charantia L. (Cucurbitaceae) (MC), commonly known as bitter melon, is a prominent therapeutic and edible species deeply rooted in traditional medicine for the management of diverse metabolic and infectious pathologies. Increasing evidence suggests that MC is a significant source of antiviral compounds that could act against many different types of viruses in humans. This narrative review summarizes the current knowledge regarding the antiviral properties of MC, with a focus on molecular mechanisms and therapeutic perspectives. Methods: A comprehensive literature search was conducted across the PubMed, Scopus and Web of Science databases, using the keywords “Momordica charantia”, “bitter melon”, “antiviral” and “MAP30”. Original in vitro, in vivo, in silico and mechanistic studies were included. Results: MC harbors diverse antiviral molecules acting through conserved and virus-specific mechanisms. Ribosome-inactivating proteins (RIPs) purified from MC display potent antiviral activity by catalyzing the depurination of viral RNA and DNA, inactivating host ribosomes and blocking protein synthesis. RIPs, especially MAP30, are among the most potent natural antiviral proteins described to date. Cucurbitane-type triterpenoids and other phytochemicals from MC also show antiviral activity. Conclusions: MC emerges as a promising candidate for the prevention/treatment of viral diseases through nutraceutical, topical and pharmaceutical applications. MC extracts could represent a resource to support the immune system and provide broad-spectrum benefits against viral infections or a tool for local treatments. Moreover, MC is a valuable source of various bioactive compounds that, after thorough pharmacological characterization, could be further developed into specific antiviral agents. Full article

Tail docking, serving as an important management intervention in animal husbandry, plays a significant role in regulating tail fat deposition and improving production performance and health status in fat-tailed sheep. This study systematically revealed the reprogramming effects of tail docking on the epigenetic landscape and transcriptome of fat-tailed sheep by integrating whole-genome bisulfite sequencing (WGBS) and RNA m6A methylated immunoprecipitation sequencing (MeRIP-seq). At the DNA level, the tail-docked group exhibited a pronounced trend of hypomethylation across multiple functional genomic regions, including promoters, exons, and introns. Differentially methylated regions (DMRs) were significantly enriched in pathways related to tissue development and stress response, such as the Hippo signaling pathway and adherens junctions. Pyrosequencing validation of the promoter region of the key gene DGAT1 further confirmed the reliability of the WGBS data. At the RNA level, RNA m6A modifications showed an overall up-regulated pattern: the tail-docked group displayed higher numbers of m6A peaks, greater total peak length, and increased genomic coverage compared to the control group, along with better overall prediction of modification sites. Genes associated with differential m6A peaks were closely related to processes such as stem cell pluripotency and cytoskeleton regulation. qPCR validation of several methylation-related enzyme genes (e.g., METTL3, FTO, YTHDF1) yielded results consistent with the sequencing trends. Through integrated analysis of DNA methylation and RNA methylation, we identified 143 genes with concurrent changes in methylation and mRNA expression, among which 41 genes were regulated by both DNA and RNA methylation. These genes were primarily enriched in the adherens junction pathway. Notably, two core genes CITED4 and ZNF644 showed significant changes across all three levels: DNA methylation, RNA methylation, and mRNA expression. This study systematically elucidates the epigenetic mechanism by which tail docking stress induces coordinated DNA hypo-methylation and RNA m6A hyper-methylation to regulate transcriptomic reprogramming in response to environmental intervention. The findings provide novel insights into the molecular basis of trait formation in livestock. Full article

The Damietta–Port Said coast, Nile Delta, has experienced extreme morphological change over the past four decades due to sediment reduction due to Aswan High Dam and continued anthropogenic pressures. Using multi-temporal Landsat (1985–2025) and high-resolution RapidEye and PlanetScope imagery with 50 m-spaced transects, the study documents major shoreline shifts: the Damietta sand spit retreated by >1 km at its proximal apex while its distal tip advanced by ≈3.1 km southeastward under persistent longshore drift. Sectoral analyses reveal typical structure-induced patterns of updrift accretion (+180 to +210 m) and downdrift erosion (−50 to −330 m). To improve predictive capability beyond linear DSAS extrapolation, Nonlinear Autoregressive Exogenous (NARX) and Bidirectional Long Short-Term Memory (BiLSTM) neural networks were applied to forecast the 2050 shoreline. BiLSTM demonstrated superior stability, capturing nonlinear sediment transport patterns where NARX produced unstable over-predictions. Furthermore, coupled wave–flow modeling validates a sustainable management strategy employing successive short groins (45–50 m length, 150 m spacing). Simulations indicate that this configuration reduces longshore current velocities by 40–60% and suppresses rip-current eddies, offering a sediment-compatible alternative to conventional breakwaters and seawalls. This integrated remote sensing, hydrodynamic, and AI-based framework provides a robust scientific basis for adaptive, sediment-compatible shoreline management, supporting the long-term resilience of one of Egypt’s most vulnerable deltaic coasts under accelerating climatic and anthropogenic pressures. Full article

A principled, model-agnostic framework for structural feature extraction in time series is presented, grounded in topological data analysis (TDA). The motivation stems from two gaps identified in the literature: First, compact and interpretable representations that summarise the global geometric organisation of trajectories across scales remain scarce. Second, a unified, task-agnostic protocol for evaluating structure preservation against established non-topological families is still missing. To address these gaps, time-delay embeddings are employed to reconstruct phase space, sliding windows are used to generate local point clouds, and Vietoris–Rips persistent homology (up to dimension two) is computed. The resulting persistence diagrams are summarised with three transparent descriptors—persistence entropy, maximum persistence amplitude, and feature counts—and concatenated across delays and window sizes to yield a multiscale representation designed to complement temporal and spectral features while remaining computationally tractable. A unified experimental design is specified in which heterogeneous, regularly sampled financial series are preprocessed on native calendars and contrasted with competitive baselines spanning lagged, calendar-driven, difference/change, STL-based, delay-embedding PCA, price-based statistical, signature (FRUITS), and network-derived (NetF) features. Structure preservation is assessed through complementary criteria that probe spectral similarity, variance-scaled reconstruction fidelity, and the conservation of distributional shape (location, scale, asymmetry, tails). The study is positioned as an evaluation of representations, rather than a forecasting benchmark, emphasising interpretability, comparability, and methodological transparency while outlining avenues for adaptive hyperparameter selection and alternative filtrations. Full article

RNA dysregulation mediated by aberrant RNA-binding proteins (RBPs) is closely associated with tumorigenesis. However, the tumorigenic mechanisms of each RBP remained unclear. In this study, we demonstrate that downregulation of Splicing factor 3A1 (SF3A1) markedly suppressed the proliferation of colorectal cancer (CRC) cells, with minimal cytotoxicity observed in non-cancerous epithelial cells. The tumor-promoting function of SF3A1 was further validated in an HCT116 xenograft mouse model. Multiple apoptosis assays—including TdT-mediated dUTP nick end labeling (TUNEL) staining, poly-ADP-ribose polymerase (PARP) immunoblotting, and caspase-3/7 activity measurements—showed that SF3A1 inhibited apoptotic signaling in CRC cells. Transcriptome analysis, combined with RNA-immunoprecipitation (RIP), identified Syntaxin 12 (STX12) as a downstream effector of SF3A1. Knockdown of STX12 induced apoptosis in CRC cells but had no effect on the viability of non-cancerous HCEC-1CT epithelial cells. Furthermore, STX12 mRNA levels were significantly reduced following SF3A1 knockdown, indicating that SF3A1-mediated stabilization of STX12 contributes to apoptosis resistance in CRC cells. Collectively, our findings establish that SF3A1 promotes CRC progression by stabilizing STX12 mRNA and selectively inhibiting apoptosis in malignant cells, thereby identifying the SF3A1–STX12 regulatory axis as a novel and selective therapeutic target for CRC. Full article

Detecting rip currents from satellite imagery offers valuable information for the characterization and assessment of this coastal hazard. While recent advances in deep learning have enabled automatic detection from close-view beach images, the broader geospatial context available in far-view satellite imagery has not yet been fully exploited. The main challenge lies in identifying rips as small objects within large and visually complex scenes that include both beach and non-beach areas. To address this, we proposed a detection pipeline which partitions high-resolution satellite images into small regions on which rip currents are detected using a deep learning object detection model that merges the results. The merged results are processed by applying a deep learning classification model to filter out non-beach scenes, followed by applying the detection model on augmented images to remove spurious detection. The proposed pipeline achieved an overall accuracy of 98.4%, a recall of 0.890, a precision of 0.633, and an F2 score of 0.823 on the testing dataset, demonstrating its effectiveness in locating rip currents within complex coastal scenes and its potential applicability to other regions. In addition, a new rip image dataset containing far-view satellite imagery was constructed. With the new dataset, we demonstrated a potential application of the proposed method in characterizing rip occurrences and found that rip currents tended to occur at open beaches under moderate-energy, onshore-directed waves conditions. Overall, the proposed pipeline, unlike existing near-real-time rip current monitoring systems, provides a high-accuracy offline analysis tool for rip current assessment using satellite imagery. Along with the new dataset introduced in this work, it can represent a valuable step towards expanding available resources for improving automated detection methods and rip current research. Full article

Bacterial and viral diseases significantly reduce soybean (Glycine max) yield and quality. RNA modifications, particularly N⁶-methyladenosine (m⁶A), are increasingly recognized as having a regulatory role in plant–pathogen interactions, but the m⁶A methylome of soybean during viral and bacterial infection has not yet been characterized. Here, we performed transcriptome sequencing and MeRIP-seq (methylated RNA immunoprecipitation followed by high-throughput sequencing) of soybean leaves infected with Soybean mosaic virus (SMV) and/or Pseudomonas syringae pv. glycinea (Psg). In general, m⁶A peaks were highly enriched near stop codons and in 3′-UTR regions of soybean transcripts, and m⁶A methylation was negatively correlated with transcript abundance. Multiple genes showed differential methylation between infected and control plants: 1122 in Psg-infected plants, 539 in SMV-infected plants, and 2269 in co-infected plants; 195 (Psg), 84 (SMV), and 354 (Psg + SMV) of these transcripts were both differentially methylated and differentially expressed. Interestingly, viral infection was predominantly associated with hypermethylation and downregulation, whereas bacterial infection was predominantly associated with hypomethylation and upregulation. GO and KEGG enrichment analysis revealed shared processes likely affected by changes in m⁶A methylation during bacterial and viral infection, including ATP-dependent RNA helicase activity, RNA binding, and endonuclease activity, as well as specific processes affected by only one pathogen. Our findings shed light on the role of m⁶A modifications during pathogen infection and highlight potential targets for epigenetic editing to increase the broad-spectrum disease resistance of soybean. Full article

Necroptosis is an antiviral form of programmed cell death modulated by proteins that interact via RIP Homotypic Interaction Motifs (RHIMs). The result of the signaling pathways depends on which RHIM-containing proteins are involved: although both host and viral proteins contain RHIMs, virally encoded RHIM proteins, such as murine cytomegalovirus (MCMV)-encoded viral inhibitor of RIP activation (vIRA) serve to prevent cell death. Although every RHIM contains the same core four-amino-acid pattern, there are variations in individual sequences that we hypothesized would determine the differential outcomes in necroptotic signaling. As such, we replaced the RHIM in vIRA with the RHIMs from other proteins involved in the signaling cascade (RIPK1, RIPK3, ZBP1, ICP6) to assess the effect on necroptosis during MCMV infection. Although these RHIM-swap vIRA constructs remained able to bind to RIPK3, in the context of MCMV infection, they lost the ability to prevent necroptosis. These results are consistent with other studies that demonstrate that RHIM-containing proteins form amyloid fibrils unique to the proteins interfacing. Our results provide biological context for the growing model that the outcome of RHIM-based signaling is influenced by the specific amyloid fibril structures that are driven by the unique amino-acid sequences of each RHIM present. Full article

This work investigates the relationship between the parastrophes of some notion of inverses in quasigroups. Our findings reveal that, of the 5 parastrophes of LIP quasigroup, (23) parastrophe is a LIP quasigroup, (12) and (132) parastrophes are RIP quasigroups, while (13) and (132) parastrophes are an anti-commutative quasigroup. Similarly, the (12) and (132) parastrophes of a RIP quasigroup are LIP quasigroups; the (13) parastrophe of a RIP quasigroup is a RIP quasigroup, while the (23) and (123) parastrophes are anti-commutative quasigroups. As for the CIP quasigroup, only the (12) parastrophe is a CIP quasigroup; other parastrophes are symmetric quasigroups of order two. Finally, the (12) parastrophe of the WIP quasigroup is an IP quasigroup, the (13), (23), and (132) parastrophes of the WIP quasigroup are CIP quasigroups, while the (123) parastrophe of the WIP quasigroup is a WIP quasigroup. Full article

Background/Objectives: Necroptosis is a critical process in the pathogenesis of myocardial ischemia–reperfusion injury (MIRI). Tilianin (Til), a natural flavonoid glycoside derived from Dracocephalum moldavica L., exhibits significant therapeutic potential in cardiovascular diseases. However, its efficacy and mechanisms in mitigating necroptosis-induced MIRI remain incompletely understood. This study aimed to elucidate the molecular mechanisms by which Til regulates cardiomyocyte necroptosis to alleviate MIRI. Methods: A rat model of MIRI was established by ligating the left anterior descending coronary artery. Necroptosis in H9c2 cardiomyocytes was induced by oxygen–glucose deprivation/reoxygenation (H/R) combined with Z-VAD-FMK. Myocardial infarct size was assessed using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Histopathological injury in cardiac tissue was examined by hematoxylin–eosin (HE) staining. Fluorescent probes were used to detect reactive oxygen species (ROS) and mitochondria. The molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) method was used to predict the binding energy between Til and RIP3. Furthermore, RIP3 overexpression and knockdown, along with inhibition of the downstream protein CaMKII, were used to further investigate the mechanism. Results: Til treatment significantly reduced MIRI in rats, decreased myocardial infarct size, histopathological injury, and regulated myocardial enzyme levels. Til pretreatment effectively inhibited necroptosis in H9c2 cells induced by H/R and Z-VAD-FMK, as evidenced by reduced necroptosis rates, decreased inflammatory cytokine release, improved mitochondrial function, and suppressed phosphorylation of the necroptosis marker MLKL. Molecular docking and dynamics simulation demonstrated stable binding of Til to RIP3, which was verified through Western blot. The protective effects of Til on necroptosis were reversed by RIP3 overexpression. Furthermore, the CaMKII inhibitor KN93 abolished Til’s effect on mitochondria. Conclusions: Til alleviates MIRI by targeting RIP3 to inhibit the necroptosis pathway and mPTP opening. These findings provide a new therapeutic strategy for MIRI and necroptosis-related diseases. Full article

Bone remodeling is maintained through the coordinated actions of osteoblasts, osteoclasts, and osteocytes, among which osteocytes serve as major regulators of osteoclast-mediated bone resorption through the receptor activator of the nuclear factor-κB ligand (RANKL)–osteoprotegerin (OPG) signaling axis. While molecular signals regulating osteocytic RANKL-OPG expression are fairly understood, how post-transcriptional mechanisms impact osteocyte function remains poorly defined. HuR (human antigen R) encoded by Elavl1 (embryonic lethal abnormal vision-like 1), a ubiquitously expressed RNA-binding protein, is known for stabilizing AU-rich element-containing transcripts involved in inflammatory and stress responses; however, its role in osteocyte-derived bone resorption is unknown. In this study, we examined the effect of HuR loss on osteocyte–osteoclastogenesis. Short hairpin RNA (shRNA)-mediated HuR knockdown in MLO-Y4 osteocyte-like cells resulted in a significant increase in OPG mRNA and its protein expression, whereas RANKL levels remained unchanged, leading to a significantly reduced RANKL/OPG ratio. Both co-culture and conditioned-medium assays demonstrated that HuR-deficient osteocytes produced a markedly diminished osteoclastogenic environment. Actinomycin D chase experiments showed no alteration in OPG mRNA decay kinetics, and RNA immunoprecipitation (RIP)-PCR failed to detect HuR–OPG interactions, indicating that HuR regulates OPG expression through indirect mechanisms rather than mRNA binding. These findings identify HuR as an indirect regulator of osteocyte-derived OPG expression that impacts osteoclast differentiation and reveal a previously unrecognized mechanism by which HuR contributes to bone remodeling. Full article

Chemorepulsion mechanisms for eukaryotic cells are poorly understood. We performed proteomics and phosphoproteomics to elucidate how Dictyostelium discoideum responds to its two endogenous chemorepellent signals, the protein AprA and inorganic polyphosphate (polyP). AprA and polyP affected levels of more than 200 proteins, with an overlap of both upregulating 25 proteins and downregulating two proteins. Two proteins were upregulated by AprA but downregulated by polyP, while two others showed the opposite trend. Surprisingly, many of the AprA- and polyP-regulated proteins are associated with RNA metabolism and ribosomes. AprA increased phosphorylation of 15 proteins and decreased phosphorylation of 36 proteins. PolyP increased phosphorylation of 12 proteins and decreased phosphorylation of 12 proteins. As expected, the two chemorepellents affected phosphorylation of signal transduction/ motility proteins, but unexpectedly affected phosphorylation of RNA-associated proteins. Both AprA and polyP decreased phosphorylation of five proteins including the Ras-interacting protein RipA and guanine nucleotide exchange factors (GEFs) such as the RacGEF GxcT. Mutants lacking RipA or GxcT were unresponsive to both AprA and polyP chemorepulsion. Together, this work supports the idea that rather than activating the same chemorepulsion mechanism, AprA and polyP activate only partially overlapping chemorepulsion mechanisms, and identifies two new components that are used by both chemorepellents. Full article

Transmissible gastroenteritis virus (TGEV) represents a critical intestinal pathogen responsible for acute enteritis in pigs, posing significant challenges to global swine production biosecurity. N⁶-methyladenosine (m⁶A), the most abundant epitranscriptomic mark in eukaryotic messenger RNA, has emerged as a regulatory factor in host–virus interactions. Despite its recognized importance, the functional significance of m⁶A modifications during TGEV infection of porcine jejunal epithelial (IPEC-J2) cells remains unexplored. Here, we established a TGEV-infected IPEC-J2 cell model and we employed methylated RNA immunoprecipitation sequencing (MeRIP-seq) to comprehensively profile the m⁶A epitranscriptomic landscape and identify N⁶-methyladenosine-bearing transcripts in IPEC-J2 cells following TGEV challenge. A total of 14,813 m⁶A peaks were identified in the IPEC-J2, distributed in 7728 genes, mainly enriched in the CDS and 3′-UTRs. After TGEV infection, we identified 832 m⁶A peaks and 1660 genes with significant changes. Integrative analysis revealed a direct positive relationship between N⁶-methyladenosine modification abundance and transcript expression levels. Through integrated examination of MeRIP-Seq and RNA-Seq datasets, we identified 105 transcripts bearing m⁶A modifications, which were mainly enriched in the mTOR signaling pathway. Protein–protein interaction (PPI) network and RT-qPCR analysis demonstrated that SOS2 probably acts an important moderator in TGEV infection. This work contributes to understanding the m⁶A modification landscape in the TGEV-swine model and suggests SOS2 as potential target for future antiviral strategies. Full article

Epstein–Barr virus (EBV) infection is closely associated with gastric cancer, yet its role in m6A-dependent gene regulation remains poorly understood. In this study, we investigated how EBV infection alters the m6A methylation pattern in gastric cancer cells and examined its impact on TSC22D1 mRNA stability through interaction with the m6A reader protein YTHDF1. m6A RNA immunoprecipitation sequencing (MeRIP-seq) revealed a significant reduction in m6A methylation of TSC22D1 in EBV-infected gastric cancer cells (AGS-EBV) compared with EBV-negative cells (AGS). Moreover, YTHDF1 knockdown increased both the stability and expression of TSC22D1. These findings demonstrate that YTHDF1 binds to TSC22D1 mRNA and promotes its m6A-dependent degradation. Collectively, our results suggest that EBV infection modulates m6A modification to regulate gene stability and identify the YTHDF1–TSC22D1 axis as a potential therapeutic target in EBV-associated gastric cancer. Full article

Background: Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in China, often diagnosed at advanced stages. The 5-methylcytosine (m5C) RNA modification plays a crucial role in tumorigenesis, influencing cell proliferation, differentiation, metabolism, invasion, metastasis, and immune evasion. NSUN2, a key m5C methyltransferase, has been implicated in various cancers, but its role in NPC remains unclear. Methods: NSUN2 expression in NPC tissues was explored by bioinformatics analysis, qPCR, Western blot, and immunohistochemistry. Functional roles of NSUN2 in proliferation, apoptosis, migration, and invasion were evaluated in NPC cell lines using CCK-8, colony formation, flow cytometry, wound-healing and transwell assays. The mechanism by which NSUN2 regulates TP53 was investigated by m5C-RIP, RNA stability assays, dual-luciferase reporter assay and rescue experiments. The NSUN2/TP53 axis was further validated in vivo through xenograft mouse models. Results: NSUN2 is significantly overexpressed in NPC tissues, and its high expression correlates with poor prognosis. Functional assays reveal that NSUN2 promotes NPC cell proliferation, migration, and invasion and inhibits apoptosis. Mechanistically, NSUN2 negatively regulates TP53 expression by increasing m5C modification at the CDS 1228 site, thereby decreasing TP53 mRNA stability and expression. Knockdown of TP53 counteracts the inhibitory effects of NSUN2 knockdown on proliferation, migration, and invasion in NPC cells. Additionally, in vivo experiments revealed that NSUN2 knockdown suppresses tumor growth in xenograft models, while TP53 knockdown reverses the growth-inhibitory effect of NSUN2 knockdown on xenograft tumors. Conclusions: Our findings indicate that NSUN2 partially negatively regulates TP53 mRNA stability, promoting malignant progression and acting as an oncogene in NPC by downregulating TP53 through m5C modification. Thus, targeting the NSUN2/TP53 axis could be a potential therapeutic strategy for NPC. Full article