Search Results (6,466)

Background/Objectives: Ginger (Zingiber officinale Roscoe) is a flowering plant widely used as a spice and natural medicine for millennia. Ginger demonstrates multiple protective effects, regulates cholesterol, and may reduce the risk of cancer and colitis. However, little attention has been paid to its potential to cause herb–drug interactions (HDIs). The aim of this study was to investigate the interaction of ginger extract and its major components [⁶]-gingerol and [⁶]-shogaol with clinically relevant uptake and efflux transporters in vitro. Methods: Transporter-overexpressing cell lines of 25 uptake transporters and inside-out membrane vesicles containing 8 efflux transporters were employed to measure potential interactions. Results: Zingiber officinale extract at 150 µg/mL interacted with 17 of 33 transporters examined. These were further investigated for interactions with the purified active components. Seven and 16 transporters interacted with pure [⁶]-gingerol (100 µM) and [⁶]-shogaol (100 µM), respectively. To evaluate the risk of in vivo inhibition, IC₅₀ values were determined for the affected transporters. Based on standard risk assessment calculations, we confirmed previously reported inhibitory effects of ginger components on MDR1 (67.64 µM) and BCRP (9.931 µM), and revealed novel potential interactions with renal OAT3 (0.956 µM) and URAT1 (5.887 µM), hepatic OCT1 (4.287 µM) and BSEP (25.45 µM), and the ubiquitously expressed ENT1 (11.62 µM) ([⁶]-shogaol IC₅₀ values are shown in parentheses). Strong and isoform-selective inhibition of OAT3 by [⁶]-shogaol is particularly intriguing. Additionally, via cell viability experiments on a set of human cervical, breast, and oropharyngeal cancer cell lines, we demonstrated the antiproliferative effect of [⁶]-shogaol in vitro. Conclusions: Prolonged consumption of high-dose ginger supplements may pose a risk of transporter-mediated HDIs when consumed concomitantly with conventional medications. Our study encourages follow-up of the suspected effects in vivo. Full article

The World Health Organization estimates that about 15% of couples in their adult years in industrialized countries experience infertility, which is described as the inability of a sexually active and non-contraceptive couple to achieve spontaneous pregnancy within a year. Environmental pollution is a significant health concern worldwide and one of the possible risk factors leading to male infertility. Cadmium is a common heavy toxin derived from industrial activities, a ubiquitous environmental pollutant, and can cause severe harm to various organs including the testis. Cadmium toxicity can lead to severe impairment of male germ cells in both rodents and humans, which can result in azoospermia. The negative effects of cadmium on the testicles are caused by its induction of oxidative stress, spermatogenic apoptosis, and testicular inflammation or its detriment to androgenic and sperm cell functions, which damages the vascular endothelium and blood–testis barrier. Overall, this review describes the detrimental impact of cadmium on the testicles and its effect on male infertility. Therefore, by considering recent research findings and identifying future research directions, this review underlines the need to develop new treatments for male infertility related to heavy metal exposure. Full article

Background/Objectives: The hepcidin–ferroportin (Fpn1) axis is central to intestinal iron absorption, and dysregulation of this axis underlies all known forms of iron disorders. Hemochromatosis, the most common iron overload disorder in humans, results from systemic iron accumulation due to decades of uncontrolled intestinal absorption. Despite major advances in medicine in recent years, strategies for iron overload management are still lagging as they primarily rely on iron chelation and repeated phlebotomies. Fpn1, the cellular iron exporter, is ubiquitously expressed and plays a critical role in maintaining systemic iron homeostasis. Methods: To investigate the specific contribution of intestinal Fpn1 to systemic iron overload, we employed a CRISPR-based adenoviral hepcidin knockout mediated mouse iron overload model, combined with intestine-specific deletion of Fpn1. Results: An initial time-dependent experiment establishes the efficiency of hepcidin knockout (KO) by as early as 1 week of adenovirus injection. At 2 weeks of injection, a perfect reciprocal relationship between hepcidin gene suppression and liver iron levels (5–7-fold induction from the baseline) was established. Finally, intestine-specific Fpn1 deletion effectively prevented iron accumulation in hepcidin KO mice, as evidenced by nearly 4-fold lower liver iron levels compared to hepcidin KO animals with intact intestinal Fpn1. Conclusions: In summary, our results demonstrate that ablation of intestinal Fpn1 is sufficient to attenuate systemic iron accumulation in this mouse model of hemochromatosis. These findings suggest that selective targeting of intestinal Fpn1 may represent a promising strategy for the management of iron overload. Full article

The family Arenaviridae encompasses zoonotic, rodent-borne pathogens (e.g., Lassa, Machupo, and Junín viruses) that cause severe viral hemorrhagic fevers with high case fatality rates. The current therapeutic landscape is severely limited, underscoring the urgent need for novel antiviral strategies. A promising approach involves combining directly acting antivirals with host-targeted antivirals. A compelling host-targeted antiviral target is the aryl hydrocarbon receptor (AHR). This ubiquitous ligand-activated transcription factor is a recognized pro-viral host factor across multiple viral families. Building on prior work with Junín and Tacaribe viruses, we investigated whether the AHR inhibitor CH223191 could enhance the virus-directed antiviral activity of favipiravir against these viruses. First, we evaluated the toxicity and antiviral potential of CH223191 against a lethal Junín virus infection in male and female hTfR1 mice. After demonstrating substantial protection, we conducted preliminary assays to study the antiviral effects of combining CH223191 and favipiravir on Tacaribe virus (TCRV) infections in the Vero cell culture model. We observed synergistic interaction with all four models (ZIP, Loewe, Bliss, and HSA). We next determined the sub-optimal dose of favipiravir and conducted an antiviral combination study in the male and female AG129 mouse model infected with TCRV. The combination effectively protected mice from a lethal TCRV infection and showed cooperative effects, reducing weight loss and viral loads. Overall, these results show that the AHR is a promising pharmacological target for the development of novel antivirals. Furthermore, we discovered a cooperative interaction between the activities of favipiravir and CH223191. Full article

Metaphor is ubiquitous in daily communication and makes language expression more vivid. Identifying metaphorical words, known as metaphor detection, is crucial for capturing the real meaning of a sentence. As an important step of metaphorical understanding, the correct interpretation of metaphorical words directly affects metaphor detection. This article investigates how to use metaphor interpretation to enhance metaphor detection. Since previous approaches for metaphor interpretation are coarse-grained or constrained by ambiguous meanings of substitute words, we propose a different interpretation mechanism that explains metaphorical words by means of gloss-based interpretations. To comprehensively explore the optimal joint strategy, we go beyond previous work by designing diverse model architectures. We investigate both classification and sequence labeling paradigms, incorporating distinct component designs based on MIP and SPV theories. Furthermore, we integrate Part-of-Speech tags and external knowledge to further refine the feature representation. All methods utilize pre-trained language models to encode text and capture semantic information of the text. Since this mechanism involves both metaphor detection and metaphor interpretation but there is a lack of datasets annotated for both tasks, we have enhanced three datasets with glosses for metaphor detection: one Chinese dataset (PSUCMC) and two English datasets (TroFi and VUA). Experimental results demonstrate that the proposed joint methods are superior to or at least comparable to state-of-the-art methods on the three enhanced datasets. Results confirm that joint learning of metaphor detection and gloss-based interpretation makes metaphor detection more accurate. Full article

Multiphase flow in porous media is ubiquitous in physical processes, yet modeling it consistently remains difficult, and sometimes it can be coupled with solid-phase decomposition and phase change, such as in hydrate dissociation or internal erosion processes. Recent code comparison studies have highlighted this difficulty, revealing clear inconsistencies in numerical results across different research groups for the same benchmark problem. This paper presents a new, reliable benchmark test and a hybrid explicit-implicit finite element method adaptable to various scenarios. In our mathematical framework, the solid decomposition is described by a rate equation for porosity that depends on the fluid pressure, and the phase change is modeled via mass source terms. The hybrid explicit-implicit finite element method features a novel three-stage updating strategy, which incorporates an artificial diffusion term and carefully selects the transport equation for the final saturation update. Validation results demonstrate that our proposed method achieves substantial agreement with those of the fully implicit finite volume method, confirming its reliability. Furthermore, our analysis confirms that the saturation update must use the transport equation of the incompressible fluid phase, and that the artificial diffusion term is critical for capturing physically correct saturation profiles, even when advection is not dominant. Overall, this work provides a consistent and effective tool for simulating complex multiphase flow scenarios and serves as a valuable complement to future benchmark studies. Full article

New-generation communications aim for ubiquitous and pervasive communications with high data rates. Electromagnetic spectrum saturation and increasing data volumes can employ the use of free-space optical communication to ease capacity loads in modern networks. In this writing, we review the impact of the atmospheric channel on the optical signal dynamics for long-range data links between high-speed and maneuverability suborbital platforms in full atmosphere. This work presents the main propagation constraints, such as path loss, turbulence, and aero-optics, which are environment-dependent and geometry-dependent for this worst-case scenario. To carry out our study, we recall experimental results collected in the literature since the early times, showing system constraints and performance limits. This provides a historical timeline perspective. Theoretical models and channel management techniques that appeared through time are briefly summarized, and their impact on link budget and stability on reference link geometries is addressed through analytical simulation. In conclusion, this paper shows that an integrated approach to this kind of link is successful mainly with a convergence of mitigation techniques and tailored engineering, which cannot neglect the knowledge of the operating environment and strongly relies on accurate physics modeling, which remains an area of active open research. Full article

This paper assesses the use of ‘plastic age’ and ‘glass age’ terms, using a bibliometric approach to identify their proponents, purposes, and connections to debates in Anthropocene and heritage studies. This study explores how glass and plastic have been portrayed as age-defining materials and how this concept relates with what is expected to be preserved for future generations. Are these materials so ubiquitous that they become invisible? If visible, are they considered waste or heritage? Both materials appear in the Anthropocene discussion as stratigraphic indicators. The term ‘glass age’ is related with the marketing of glass (not only new glass formulations and new products, but also as an alternative to other more polluting materials), and the term ‘plastic age’ appears to be related to the multitude of plastics in our everyday lives and all the problems associated with their disposal. Although there are few examples of bibliometric research on glass and plastic as heritage, there is currently great investment in the study of glass and plastic from the perspective of conservation viability; this perspective needs to be promoted so that these materials can be included in heritage policies and museum collections as a reflection of today’s society. Full article

Smartphones are ubiquitous and continuously carried high-performance devices equipped with speech recognition capabilities that enable the analysis of surrounding conversations. When leveraged for public purposes, networks of smartphones can function as a large-scale sensing infrastructure capable of detecting and reporting early signs of serious crimes or terrorist activities. This paper proposes the concept of “Smartphone as Societal Safety Guard” as an approach to substantially enhancing public safety through relatively low additional cost and the combination of existing technologies (first pillar). At the same time, this concept entails serious risks of privacy infringement, as exemplified by the potential introduction of always-on eavesdropping through operating system updates. The originality of this study lies in redefining smartphones not merely as personal tools but as public safety infrastructure within democratic societies, and in systematizing the conditions for their social acceptability from the perspective of institutional design. This research presents a reference architecture and a regulatory framework, and organizes six key challenges that must be addressed to reconcile public safety with privacy protection: external attacks, mitigation of privacy information, false positives, expansion of the scope of application, discriminatory use, and misuse by authorized insiders. In particular, misuse by authorized insiders is positioned as the core challenge. As a necessary condition for acceptance in democratic societies (second pillar), this paper proposes a privacy-protective infrastructure centered on the Verifiable Record of AI Output (VRAIO). By combining on-device two-stage urgency classification with the review and recording of AI outputs by independent third-party entities, the proposed framework aims to provide a mechanism that can ensure, as a design requirement, that information unrelated to emergencies is not released outside the device. In summary, this paper presents a design framework for reconciling enhanced public safety with the protection of privacy. Full article

Background: Plasticisers with endocrine-disrupting potential are ubiquitous and associate with obesity and type-2 diabetes (T2D), with higher levels reported in the Middle East. However, no data exist on plasticiser exposure in Bahrain where T2D affects 15% of the national population. Methods: An observational exploratory study in T2D (n = 60) and controls (n = 96), analysed for 24 h urinary plasticiser levels (liquid chromatography tandem mass spectrometry (LC-MS/MS)). Correlation and generalised linear model (GLM) analyses were employed to examine associations. Results: T2D were older (p < 0.001), had higher body mass index (BMI) (p < 0.001), body weight (p < 0.001) and glycosylated haemoglobin A1c (HbA1c) (p < 0.001). Correlation analysis revealed differences in inter-plasticiser, and plasticiser and biomarker relationships, with loss or reversal in T2D compared to controls. Mono-n-butyl phthalate (MnBP) levels were higher in T2D (p = 0.04); however, regression analysis revealed significant association with age. The GLM analyses demonstrated marked differences in the levels of mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), monoethyl phthalate (MEP) and bisphenol S (BPS), with lower levels in T2D versus controls (B = −3.41, p = 0.01; B = −5.28, p < 0.001; B = −8.94, p < 0.001; B = −6.09, p = 0.006, respectively); however, these contrasts appeared to be substantially confounded by BMI and/or age. Positive influence of age and negative influence of BMI when observed across the full dataset were generally reversed in T2D. Levels were complementary to those previously reported for the Middle East. Conclusions: The study indicates the phthalate levels in Bahrain are elevated though complementary to studies of phthalates in the Middle East; within those levels, the study indicates differential exposure–response relationships with plasticisers, influenced by age and BMI, in those with T2D compared to healthy controls. Full article

Gammaretroviruses are ubiquitous pathogens, often associated with the induction of neoplasia, especially leukemia, lymphoma, and sarcoma, and with a propensity to target the germline. The latter trait has left extensive evidence of their infectious competence in vertebrate genomes, the human genome being no exception. Despite the continuing activity of gammaretroviruses in mammals, including Old World monkeys, apes, and gibbons, humans have apparently evaded novel infections by the virus class for the past 30 million years or so. Nevertheless, from the 1970s onward, cell culture studies repeatedly discovered gammaretroviral components and/or virus replication in human samples. The last novel ‘human’ gammaretrovirus, identified in prostate cancer tissue, culminated in the XMRV frenzy of the 2000s. In the end, that discovery was shown to be due to lab contamination with a murine gammaretrovirus. Contamination is also the likely source of the earlier findings. Complementation between genes of partially defective endogenous proviruses could have been another source of the virions observed. However, the capacity of many gammaretroviruses to replicate in human cell lines, as well as the presence of diverse infectious gammaretroviral species in our animal companions, for instance in mice, cats, pigs, monkeys, chickens, and bats, does not make a transmission to humans an improbable scenario. This review will summarize evidence for, or the lack of, gammaretrovirus infections in humans in the past, present, and near future. Aspects linked to the probabilities of novel gammaretrovirus infections in humans, regarding exposure risk in connection to modern lifestyle, geography, diet, and habitat, together with genetic and immune factors, will also be part of the review, as will be the estimated consequences of such novel infections. Full article

Boron-dipyrromethene (BODIPY) dyes belong to a class of organoboron compounds that have become ubiquitous for researchers in areas of fluorescence imaging, photodynamic therapy, and optoelectronics. The intrinsic qualities of BODIPY dyes and their meso-modified structural analogs, Aza-BODIPY dyes, have propelled their recent increase in use in biomedical applications. The two scaffolds have high quantum yields, narrow absorption, and emission bandwidths with large Stokes’ shifts, and high photostability and thermal stability. Because their properties are independent of solvent polarity and dye functionality, they can be tuned to promote novel analytical methods, resulting in the adaptation of the physicochemical and spectral properties of the dyes. In this review of BODIPY and Aza-BODIPY scaffolds, we will summarize their spectral properties, synthetic methods of preparation, and applications reported between 2014 and 2025. This review aims to summarize the advances in chemosensing, especially pH sensor development, and the advances in NIR-II window bioimaging probes. We hope that this succinct overview of Aza-BODIPY scaffolds will highlight their untapped potential, elucidating insights that may catalyze novel ideas in the physical organic realm of BODIPY. Full article

Zinc (Zn), a ubiquitous environmental transition metal primarily existing as Zinc ions (Zn²⁺), plays a critical role in various biological processes. Its extensive application in agriculture, industry, and healthcare has led to significant environmental contamination. However, the mechanistic contribution of Zn²⁺ to bacterial antibiotic resistance and virulence remains insufficiently understood. This review explores the sources, cycling, and environmental accumulation of Zn²⁺ in a One Health context, emphasizing their impact on bacterial antibiotic resistance and virulence. Zn²⁺ promote bacterial antibiotic resistance by regulating efflux pumps, biofilm formation, expression and transfer of antibiotic resistance genes, as well as synergistic effects with other heavy metals and antibiotics. Meanwhile, Zn²⁺ promote bacterial virulence by regulating quorum sensing, secretion and metal homeostasis systems, as well as oxidative stress response and virulence factor expression. Additionally, it highlights the potential of targeting Zn homeostasis as a strategy to combat environmental antibiotic resistance. Collectively, these findings provide key insights into the mechanisms by which Zn²⁺ regulate bacterial antibiotic resistance and pathogenicity, offering valuable guidance for developing strategies to mitigate the global threat of antibiotic resistance. Full article

This study investigates flooding and erosion impacts and human responses in Aoraki Mount Cook and Westland Tai Poutini national parks in Aotearoa New Zealand. These fast-eroding landscapes provide important test cases and insights for considering the public access dimensions of climate change. Our objectives were to explore and characterise the often-overlooked role of public access as a ubiquitous concern for protected areas and other area-based conservation approaches that facilitate connections between people and nature alongside their protective functions. We employed a mixed-methods approach including volunteered geographic information (VGI) from a park user survey (n = 273) and detailed case studies of change on two iconic mountaineering routes based on geospatial analyses of digital elevation models spanning 1986–2022. VGI data identified 36 adversely affected locations while 21% of respondents also identified beneficial aspects of recent landscape changes. Geophysical changes could be perceived differently by different stakeholders, illustrating the potential for competing demands on management responses. Impacts of rainfall-triggered erosion events were explored in case studies of damaged access infrastructure (e.g., roads, tracks, bridges). Adaptive responses resulted from formal or informal (park user-led) actions including re-routing, rebuilding, or abandonment of pre-existing infrastructure. Three widely transferable dimensions of public access management are identified: providing access that supports the core functions of protected areas; evaluating the impacts of both physical changes and human responses to them; and managing tensions between stakeholder preferences. Improved attention to the role of access is essential for effective climate change adaptation in parks and reserves. Full article

Antibiotics have become an integral part of human life and production. The presence of sulfachloropyridazine (SCP), one of the most ubiquitous antibiotics, in water has been a growing concern owing to its long persistence and the difficulty in removing it by conventional water treatment processes. This study introduced ozone (O₃)-activated sodium percarbonate (SPC) as an innovative technique of advanced oxidation processes (AOPs), and the degradation of SCP from water by this method was thoroughly investigated. The impact of a variety of parameters, such as the dosage of SPC, the dosage of O₃, the pH value, and water matrix constituents, on the removal of SCP was evaluated with regard to the pseudo-first-order kinetic model. It was found that the removal effectiveness of SCP improved initially and then decreased with the rising dosage of SPC, with an optimal SPC dose achieved at 20 mg/L. Moreover, •OH, ${\mathrm{O}}_2^{•-}$ and ¹O₂ played important roles during SCP degradation based on radical quenching tests and electron paramagnetic resonance (EPR) tests. The SCP degradation pathways were predicted using density functional theory (DFT), which primarily involves the cleavage of S-C or S-N bonds and Smiles-type rearrangements, accompanied by hydroxylation. Furthermore, the toxicity of degradation intermediates was evaluated by the ECOSAR 1.1 software in terms of acute toxicity and chronic toxicity, and most of them exhibited lower levels of toxicity. The results can expand the research scope of SPC and reveal significant insights for SPC’s application in controlling antibiotic contamination. Full article