Quercetin’s multifaceted effects on testicular function and fertility: a comprehensive review of the underlying molecular mechanisms

Beyond direct impact: Exploring inward FDI’s multifaceted effects on new venture creation

TGF-β-mediated suppression of NK cell function and targeting strategies in tumor immunotherapy.

A novel peptide explicitly induces prostate cancer cell death by destabilizing AR and inhibiting AR-mediated transcription.

A multifunctional hydrogel promotes diabetic wound healing by remodeling iron balance and energy metabolism.

Synergistic multifaceted effects of tea saponin concentration on the foaming properties of wheat aqueous phase protein: A next-generation approach to food foam production

Aims and Objectives/Purpose/Research Questions: This study examines the narrative production of English-Mandarin bilingual and monolingual Mandarin-speaking school-aged children (aged 9), focusing on the invariance of narrative abilities across languages and the influence of language proficiency. Design/Methodology/Approach: A mixed-methods approach was used, including parent-completed questionnaires on children’s background and language abilities, as well as narrative data collection from 20 English-Mandarin bilingual children in both languages, and 20 monolingual Mandarin-speaking children. Data and Analysis: Narratives were analysed both quantitatively and descriptively. Comparisons were made between the Mandarin narratives of the monolingual and bilingual groups, and the English and Mandarin narratives among the bilingual group. The bilinguals were further divided in two groups based on balanced versus unbalanced language proficiency, and differences in narrative production were explored to examine the effect of language proficiency. Findings/Conclusions: The English narratives of the bilingual children contained substantially more macrostructural components and provided more behavioural descriptions than their Mandarin narratives. However, the bilinguals produced similar macrostructural complexity across their two languages. The difference in total macrostructural components production may be attributed to the imbalance in language proficiency in the bilinguals’ two languages, though macrostructural complexity is less sensitive to this proficiency disparity. Moreover, compared to their monolingual peers, the bilinguals’ Mandarin narratives included less concrete beginnings yet considerably more internal states, especially the emotions of the story characters. Originality: This study contributes original insights into the debate on bilingual narrative development by examining the multifaceted effects of language proficiency across two languages and comparing bilingual and monolingual narrative production in Mandarin. Significance/Implications: These findings emphasise the differential impact of language proficiency on various aspects of narrative development and the importance of considering both linguistic and cultural factors when assessing bilingual narrative competence, offering implications for educational practices and future research in bilingualism and language development.

The increasing antimicrobial resistance of T. pyogenes, one of the principal pathogens associated with endometritis, presents a formidable challenge in veterinary medicine. Astragaloside IV (AS-IV) is a triterpene saponin compound isolated from the traditional Chinese medicine Astragalus membranaceus. While recognized as the primary bioactive constituent of Astragalus membranaceus with diverse pharmacological properties, its potential to counteract T. pyogenes-induced endometritis has yet to be elucidated. In the current study, T. pyogenes infection models were successfully established in both mouse uteri and cultured goat endometrial epithelial cells (gEECs). Integrating histopathology, molecular biology and transcriptomic technology, this study characterized the multifaceted biological effects of AS-IV. Transcriptomic analysis indicates that the regulatory effects of AS-IV on T. pyogenes-induced infection are primarily associated with the enrichment of signaling pathways related to inflammation, apoptosis, and oxidative stress. Subsequent validation demonstrated that AS-IV treatment effectively alleviated T. pyogenes-induced endometrial damage by suppressing inflammation, apoptosis, and oxidative stress. These effects were mediated through Nrf2 and its downstream target HO-1, a mechanism further confirmed by the loss of protection upon Nrf2 inhibition. In summary, AS-IV protects the endometrium against T. pyogenes-induced inflammatory and oxidative damage by activating the Nrf2/HO-1 signaling pathway.

Sulforaphane (SFN), an aliphatic isothiocyanate derived from cruciferous vegetables such as broccoli, has emerged as a chemopreventive dietary agent. SFN exerts multifaceted anticancer effects through the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathways, inhibition of histone deacetylases (HDACs) and hypoxia-inducible factor-1α (HIF-1α), and regulation of apoptosis and autophagy. Epidemiological studies have consistently associated cruciferous vegetable intake with reduced cancer risk, while mechanistic research has elucidated the capacity of SFN to modulate redox balance, detoxification pathways, and epigenetic processes. Recent clinical trials have further demonstrated its potential to reduce carcinogenic biomarker levels and support metabolic detoxification. This review integrates evidence from epidemiological observations, molecular mechanisms, and clinical studies to provide a comprehensive understanding of the role of SFN in cancer prevention and therapy. Finally, translational challenges, including limited bioavailability, dose optimization, and standardization of broccoli-derived preparations, are discussed as critical factors for successfully translating SFN therapies from bench to bedside.

This study examines the multifaceted effects of Artificial Intelligence (AI) on human beings physically, mentally, and environmentally while emphasizing the need for sustainable and ethical integration. Drawing on interdisciplinary research, the paper explores AI’s dual role as both an enabler of efficiency and a driver of risk. It highlights how AI technologies influence occupational health, psychological well-being, and environmental sustainability. Guided by Socio-Technical Systems Theory, Technological Determinism, and Sustainability Transition Theory, the study synthesizes evidence from academic and industry sources to assess AI’s consequences and opportunities. Findings suggest that AI’s benefits are substantial but require governance frameworks that align innovation with human welfare and environmental responsibility. The paper concludes with recommendations for policies, regulations, and collaborative initiatives that promote sustainable AI deployment.

THGP [3-(trihydroxygermyl) propanoic acid], an organogermanium compound, has been confirmed to exert multifaceted effects in mammalian and eukaryotic cells. Focusing on the characteristic trihydroxyl germanium moiety of THGP, we aimed to discover its novel pharmacological abilities and effects against multidrug-resistant Acinetobacter baumannii, a prokaryote with critical implications on global public health. In all assays, spectrometric determinations (OD) were conducted using a 96-well microtiter plate: OD489 for β-lactamase activity, OD600 for bacterial mass, OD570 for biofilm mass, OD340 for alcohol dehydrogenase (ADH) activity, and OD460 for dehydrogenases-NAD(P)-NAD(P)H system activity. THGP was observed to exhibit β-lactamase activity inhibition ability, which actually presents synergistic effects with cephem antibiotics against A. baumannii. We also revealed ADH activity inhibition ability, which contributes to the anti-proliferative effect of THGP, a weak organic acid, against A. baumannii. However, low permeability of THGP through the bacterial cell because of its high hydrophilicity seemed to attenuate this intracellular effect. Furthermore, THGP was postulated to possess preventive effects on biofilm formation at sub-MIC (below the minimum inhibitory concentration) via an unknown mechanism. To our knowledge, this study is the first to report the antimicrobial effects of an organogermanium compound and demonstrates the inhibition abilities of THGP against two ubiquitous enzymes in pathogenic bacteria. However, the findings of this study are insufficient for clinical applications. Further studies are warranted to promote the development of clinically useful organogermanium compounds. Nevertheless, our findings provide important baseline information for future exploratory studies.

Reduced levels of circulating gonadal hormones in post-menopausal women can negatively affect various physiological functions, including brain and gut deficits. There is an urgent need to find novel strategies to mitigate estrogen-gut-microbiome-brain axis (EGMBA) dysfunction. This study aimed to investigate the effect of fructooligosaccharide (FOS), a non-digestible prebiotic fiber, on estrogen deficiency-induced alterations in the EGMBA using an ovariectomized (OVX) rat model. Adult female SD rats were bilaterally OVX to induce estrogen deficiency and associated EGMBA dysfunction. Rats were administered FOS (50 mg kg-1 p.o.-1) for 28 consecutive days. To assess EGMBA dysfunction, after 28 days, we performed behavioral tests, biochemical estimations (oxidative stress), molecular estimations (inflammatory markers via ELISA), gene expression analysis (HPA axis, monoamine neurotransmission, apoptosis, gut microbiota alterations, & gut barrier integrity via RT-PCR/qPCR), and histopathological analysis. Administration of FOS significantly improved behavioral outcomes (reducing anxiety and depression, and improving memory). FOS also attenuates oxidative stress and inflammatory markers. FOS regulates apoptosis (upregulation of BCL-2 and downregulation of Bax), HPA axis functioning (corticosterone, GR, MR, & CRH), and monoamine neurotransmission (MAO-A & COMT) in the hippocampus of OVX rats. FOS also promoted healthy cell growth and prevented apoptosis. Additionally, FOS restored gut microbial eubiosis, improved mucus secretion (MUC-2), preserved tight junction protein expression (Lipocalin-2, Claudin, & TLR-4), and maintained the colon microstructure. FOS exerts multifaceted protective effects on the EGMBA by modulating gut and brain functions. These findings support its potential as a non-hormonal therapeutic approach for managing postmenopausal complications.

Autophagy is one of the best-characterized "pro-survival" pathways, which, paradoxically, in its extreme activation, can lead to cell death. Under conditions of moderate physiological disturbances, autophagy plays a crucial role in maintaining homeostasis within the human organism. Currently, in the context of treating cancer, researchers are exploring novel methods to modulate autophagic processes. Nanomedicine, which leverages nanoparticles (NPs) for targeted therapies, has become a prominent focus in numerous scientific studies. It has been observed that NPs can be employed to either stimulate or inhibit autophagic processes. Due to their diverse physicochemical properties, nanomaterials can influence cellular compartments directly involved in autophagy. This review examines the multifaceted effects of nanoparticle exposure on autophagy, with a focus on mechanisms that deviate from the classical autophagic flux. By dissecting the molecular crosstalk between nanomaterials and autophagy-related signaling networks, we aim to elucidate how NPs reshape cellular behavior and contribute to therapeutic outcomes in malignancy. Particular attention has been directed toward significant challenges in determining whether autophagy activation exerts protective or deleterious effects on cancer cells. A comprehensive understanding of the effects of nanotechnology-driven autophagy on biological systems could yield groundbreaking discoveries for advanced strategies in combating cancer and other proliferative diseases.

Deoxynivalenol (DON), a prevalent mycotoxin in grains and feed, poses a serious threat to animal health by inducing intestinal dysfunction. While some probiotics are known to mitigate DON toxicity, the multifaceted protective effects of Lactobacillus rhamnosus MY-1-a strain with high DON-degradation capacity and a proven safety profile-require comprehensive evaluation. This study aimed to systematically assess the ability of MY-1 to alleviate DON-induced oxidative stress, inflammation, and gut microbiota dysbiosis, and to elucidate its underlying mechanisms. Investigations were conducted in vitro using IPEC-J2 cells and in vivo using a BALB/c mouse model. We examined the effects of MY-1 on cell viability, ultrastructure, oxidative stress markers (MDA, T-AOC), inflammatory cytokines (TNF-α, IL-1α, IL-4), apoptosis-related genes (BAX, Caspase-3, BCL-2), and tight junction protein (ZO-1, Occludin, Claudin-1) expression. Gut microbiota composition was analyzed via alpha (Chao1, Simpson, Shannon) and beta diversity indices. The MY-1 supernatant restored IPEC-J2 cell viability and ameliorated DON-induced ultrastructural damage. MY-1 alleviated oxidative stress by reducing MDA and enhancing T-AOC, while inhibiting pro-inflammatory cytokines (TNF-α, IL-1α) and promoting the anti-inflammatory cytokine IL-4. In mice, MY-1 mitigated DON-induced growth inhibition and intestinal pathological damage, restored tight junction protein expression, and regulated apoptosis-related genes. Gut microbiota analysis showed that MY-1 reversed DON-induced dysbiosis, restoring alpha diversity and beta diversity structure, and modulated the abundances of dominant genera such as Bacteroides and Dubosiella. This study demonstrates that Lactobacillus rhamnosus MY-1 exerts comprehensive protective effects against DON-induced intestinal toxicity through integrated mechanisms, including direct detoxification, antioxidant and anti-inflammatory activities, and microbiota modulation. These findings underscore the value of MY-1 as a well-characterized probiotic candidate for mitigating mycotoxin effects in animal production.

Myocardial infarction (MI) is a severe cardiovascular disorder characterized by an irreversible myocardial necrosis caused by acute ischemia. The typical manifestations of MI include persistent substernal chest pain, dyspnea, nausea, vomiting, and diaphoresis. Astragaloside IV (AS-IV), a major bioactive component of Astragalus membranaceus, has been extensively investigated over the past decade. Evidence indicates that AS-IV exerts multifaceted protective effects against MI by modulating various key signaling pathways involved in anti-inflammatory, anti-oxidative stress, and antifibrotic activities, the inhibition of cardiomyocyte apoptosis, and the maintenance of mitochondrial homeostasis. These pathways include TLR4/NF-[Formula: see text]B, PI3K/AKT, TGF-[Formula: see text]/Smad2, ROS/caspase-1/GSDMD, Wnt/[Formula: see text]-catenin, AMPK/ACSS2/PPAR[Formula: see text], Sirt3/Drp1, and PINK1/Parkin. Although mechanistic studies have substantially advanced, the clinical application of AS-IV in MI remains in the exploratory stage. Further well-designed clinical trials are necessary in order to validate the therapeutic efficacy and safety of AS-IV, thereby facilitating its translation from experimental research to clinical practice, and offering new insights and potential strategies for MI management.

Lung cancer is one of the most prevalent types of cancer. Although current treatments such as immunotherapy, targeted therapy, and chemotherapy provide clinical benefits, they are often associated with serious side effects, including drug resistance. Myricetin has demonstrated promising anticancer properties; however, its underlying biological mechanisms and gene interaction networks related to patient survival remain insufficiently explored. This study employs a network pharmacology approach to investigate the interaction network between myricetin and lung cancer–related targets, followed by molecular docking for validation. The analysis revealed 101 nodes and 207 edges within the protein-protein interaction (PPI) network. Centrality analysis identified six key target proteins, and subsequent KEGG pathway enrichment narrowed these to five key proteins, HSP90AA1, CYP19A1, MAPK14, SRC, and AKR1C3, which are involved in seven critical pathways associated with lung cancer progression. Molecular docking demonstrated that myricetin exhibits stronger binding affinities compared to Gefitinib across all targets, with the most favorable binding energy observed with AKR1C3 (-10.6 kcal/mol) and Gefitinib to AKR1C3 (-9.3 kcal/mol). These findings suggest that myricetin exerts multifaceted anticancer effects by modulating key biological processes, including cell proliferation, angiogenesis, inflammation, oxidative stress, and hormonal signaling. Thus, myricetin has the potential to be developed as a therapeutic agent for lung cancer. Therefore, further in vitro analyses are required to evaluate myricetin's anticancer activity in lung cancer cells, along with gene expression studies and safety assessments in normal cells.

Background: Digital media addiction—including problematic use of social media, smartphones, and internet platforms—is a growing mental health concern among adolescents and young adults. This systematic review synthesizes recent evidence (Jan 2020 to Feb 2025) on the impacts of digital media addiction on mental health and academic performance. Methods: A systematic search was conducted across 7 academic databases, including Web of Science, ScienceDirect, Scopus, PubMed, Google Scholar, Magiran, and IranDoc. Studies involving individuals aged 12–25 and addressing mental health (e.g., anxiety, depression, stress) or academic performance were included. Screening and selection followed PRISMA guidelines, and methodological quality was assessed using the CASP checklist. Results: Findings were narratively synthesized and categorized into mental health and academic performance outcomes. Among 17 included studies, 12 (70.6%) reported a significant link between digital media addiction and anxiety/depression, while 8 (47%) found negative academic outcomes such as procrastination or low GPA. Social media addiction was associated with increased symptoms of anxiety and depression. Smartphone overuse was frequently linked to sleep disturbances, emotional dysregulation, and reduced academic performance. Adolescents with poor self-regulation and females were found to be especially vulnerable. Overall, different forms of digital media addiction contribute to psychological distress and hinder academic success. Conclusion: This review confirms the adverse effects of digital media addiction on youth mental health and academic performance. Unlike prior reviews that examined these outcomes separately, our study provides an integrated perspective by analyzing both domains simultaneously in the post-pandemic era. These findings highlight the need for targeted interventions that improve emotional regulation, reduce screen time, and enhance academic engagement, offering novel insights to inform policymakers, educators, and mental health professionals in developing prevention and support programs.

Abstract Background : Urbanization is a dynamic process with multifaceted effects on agriculture. While facilitating land use changes, it is also influencing market access, technical efficiency of farming, land prices, and regulatory frameworks. This study aims to understand the effects of urbanization on the resilience of the farming systems in the peri-urban areas of Hyderabad, India. Methods : The resilience of the farming systems is characterized by the three capacities of resilience i.e. robustness, adaptability, and transformability. Indicators were identified for the attributes that contribute to the capacities of resilience. For primary data collection, six focus group discussions were conducted followed by a household survey of 400 farm households in the blocks around Hyderabad. We use factor analysis to combine these indicators of resilience capacities into indexes. Results : Our findings suggest that urbanization has a mixed impact on the resilience of the farming systems. The farming system Diversified Cropping with Dairy is more robust while the farming system Diversified Cropping without Livestock is more adaptable and transformable as compared to the other farming systems in the study area. Conclusion : The indirect effects of urbanization, i.e., market effect and the technical efficiency effect contribute positively to the adaptability and transformability of the farming systems by facilitating market access, demand for high-value crops, access to infrastructure, and agricultural services. It directly affects the robustness of the farming systems negatively by constraining access to natural resources i.e. land and water.

Non-small cell lung cancer (NSCLC) with spinal metastasis represents a clinical challenge due to its aggressive nature, limited treatment options, and profound impact on patient quality of life. Here, we report the development of an innovative upconversion mesoporous silica nanoparticle (UCMS) platform co-loaded with celecoxib and rose bengal (UCMS@CXB/RB), engineered to synergistically combine photodynamic therapy (PDT) and cyclooxygenase-2 (COX-2) inhibition. Upon near-infrared (NIR) irradiation, UCMS@CXB/RB generated abundant reactive oxygen species, triggered immunogenic cell death, and significantly suppressed prostaglandin E2 signaling, leading to reduced angiogenesis and improved antitumor immunity. In vitro and in vivo studies confirmed that this nanoplatform effectively remodeled the tumor microenvironment, inhibited tumor growth, and alleviated cancer-induced spinal dysfunction. Single-cell multi-omics analysis further revealed dynamic crosstalk among immune cells, tumor cells, and endothelial populations, providing mechanistic insights into the multifaceted therapeutic effects of UCMS@CXB/RB. Our results underscore the clinical potential of integrating PDT with targeted COX-2 blockade to address the complex pathophysiology of NSCLC spinal metastasis. This study presents a promising minimally invasive therapeutic strategy with strong translational relevance for managing metastatic NSCLC and improving patient outcomes.

This paper the effects of a technology-driven increase in crop and livestock productivity on key agricultural, land-use, and environmental indicators in Greece, using the FABLE (Food, Agriculture, Biodiversity, Land Use, and Energy) Calculator. Through empirical evidence and sophisticated modelling techniques, we analyze the intricate interplay between agricultural productivity and environmental sustainability. Our scenario-based projections show that higher agricultural productivity substantially reduces greenhouse gas emissions, primarily through lower livestock emissions, diminished pressure on pastureland, and increased emission withdrawals from land-use changes. Enhancing productivity in the livestock and crop sector reduces GHG emissions from agriculture by 29% until 2030 and 62% until 2050, compared to a business-as-usual scenario. The result is amplified when we embed the productivity surge in a holistic transformational strategy following Greece’s national commitment including a shift to healthy dietary consumption. Moreover, costs decline markedly, by almost 50% in the long run, driven mainly by the reduction in pesticide use. In addition to its empirical findings, this paper delineates policy recommendations to support cutting-edge technologies within the Greek agricultural sector, focusing on horizontal and vertical measures. We highlight key precision agriculture technologies that align with current trends in Greece, particularly in the areas of drone applications, advanced sensors, and variable rate technology, alongside innovations in precision livestock management. Overall, our findings demonstrate that boosting agricultural productivity can generate a double dividend—lower emissions and enhanced competitiveness—particularly when supported by holistic policy measures.