Abstract: Streptococcus pneumoniae (pneumococcus) is a significant human pathogen responsible for a range of diseases from mild infections to invasive pneumococcal disease, particularly affecting children, the elderly, and immunocompromised individuals. Despite pneumococcal conjugate vaccines reducing the incidence of pneumococcal diseases, challenges persist due to serotype diversity, vaccine coverage gaps, and antibiotic resistance. The LytA autolysin, an N-acetylmuramoyl-L-alanine amidase, is a key enzyme in pneumococcal biology, regulating autolysis and contributing to virulence by facilitating bacterial clearance, inflammation, and biofilm dynamics. LytA also plays an important role in pneumococcal immune evasion by modulating complement activation. Its activity is influenced by environmental factors, genetic regulation, and spatial control and is linked to competence for genetic transformation. Beyond its biological role, LytA is a potential therapeutic target, with studies exploring its application in bacteriolytic treatments, vaccine development, and synergistic antibiotic strategies. Various compounds, including synthetic peptides, plant extracts, and small molecules, have been investigated for their ability to induce LytA-mediated bacterial lysis. Future research aims to develop novel anti-pneumococcal strategies leveraging LytA’s properties, while also addressing limitations in vaccine efficacy and emerging antibiotic resistance. Human challenge models and animal studies continue to refine our understanding of pneumococcal pathogenesis and treatment.

Abstract: Background/Objectives: This study piloted a 24-week bodybuilding program, combining resistance training (RT) with a dietary bulk and cut protocol, in middle-aged adult males. Methods: Eleven untrained males (34 ± 3.5 years) were introduced to a 24-week intervention combining RT with a dietary protocol consisting of 12-week cycles of caloric bulking (0-12 weeks) and cutting (12-24 weeks). Of the 11 participants, 7 males with obesity (BMI=35.04.6 kg/m2, body fat=365 %) completed the program, yielding a 64% retention rate. The compliance to training was at 96.7% and adherence to dietary cycles over 93%. To assess preliminary efficacy of the intervention, venous blood samples, and measurements of body composition (BodPod), muscle strength, and VO2max (cycle ergometer) were collected at baseline (week 0) and following the bulking (week 12) and cutting (week 24) cycles. Circulating lipids (triglycerides, total, low-density and high-density cholesterol), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured in serum. Results: The training led to significant increases in muscle strength, especially in the deadlift (+46%, p<0.001) and the squat (+65%, p<0.001). Improvements in body composition were characterized by an increase in fat-free mass, and a decrease in body fat percentage over the 24-week intervention (+3% and -6%, respectively, p<0.05). Lipids, CRP, IL-6, and IL-10 did not change significantly, but there was a notable reduction in TNF-α (time effect p=0.05, pη2=0.39), with 15% lower concentrations at week 24 compared to baseline, indicating reduced inflammation. Conclusions: Overall, the pilot intervention was feasible and led to improvements in body composition and lower resting TNF-α concentrations in a group of adult males with overweight and obesity.

Abstract: The pharmaceutical supply chain faces increasing complexities due to stringent regulatory requirements, rapid technological advancements, and the need for enhanced collaboration among stakeholders. This paper explores the advancement of Product Lifecycle Management (PLM) within this critical sector, highlighting its role in optimizing processes from drug development through to market delivery. We analyze the integration of PLM systems with emerging technologies such as artificial intelligence, blockchain, and IoT, which facilitate real-time data sharing and decision-making. By employing case studies and industry insights, we illustrate how effective PLM strategies can lead to improved compliance, reduced time-to-market, and enhanced product quality. This research underscores the necessity for pharmaceutical companies to adopt robust PLM frameworks to navigate the evolving landscape and meet the demands of patients and healthcare providers effectively. Implementing these frameworks not only streamlines operations but also fosters innovation, enabling companies to respond swiftly to market changes and emerging health challenges. This adaptability is crucial in a sector where regulatory requirements and consumer expectations are constantly shifting, making it essential for companies to stay ahead of the curve. By leveraging advanced technologies such as artificial intelligence and data analytics, organizations can further optimize their PLM processes, ensuring they remain agile and competitive in a fast-paced environment.

Abstract: Climate change is no longer a looming possibility—it is an active force reshaping agriculturewith alarming urgency. The crucial to world diets, vegetable crops such tomatoes, peppers, andleafy greens provide crucial vitamins A and C; nevertheless, they are also more susceptible.Rising temperatures lower yields: irregular rainfall disturbs growth cycles; and new pestpressures take advantage of these vulnerabilities, therefore endangering food security for billionsof people. Though fundamental to the history of agriculture, traditional breeding techniques need10 to 15 years to create a new variety-a timeframe made extinct by the fast speed ofenvironmental change. Using state-of-the-art technology to hasten the creation of robustvegetable crops, the Quantum-AI Genomic Frontier Platform presents a transforming answer. Itforecasts plant stress responses with an 83% accuracy rate (Pearson correlation coefficient of0.83) and increases stress tolerance by 12–15% by integrating quantum-inspired computing,sophisticated artificial intelligence (AI), and thorough multi-omics datasets. While a virtualreality (VR) interface promotes worldwide cooperation, real-time IoT sensor data guaranteesmodels mirror field reality. This open-source platform, which is described here, not only showsits field trial results and architecture but also establishes itself as pillar for precision farming. Itprovides a scalable, team able structure to protect food systems against a warming planet.

Abstract: Background/Objectives: Handgrip strength (HGS) has been used as an important health indicator due to its ability to predict morbidity and mortality risks in various populations. The aim was to investigate the relationship between HGS and health parameters among public sector workers. Methods: A cross-sectional study was carried out, including the participation of 129 workers. The body composition, presence of chronic non-communicable diseases (CNCDs), physical activity level, and physical capacity (flexibility, HGS, and lower limb endurance) of the workers were evaluated. Results: The results showed that most of the employees, regardless of sex, work in the administrative sector, are aged 40 years or older, have chronic non-communicable diseases (CNCDs), and are physically inactive. The majority of women have a body mass index (BMI) within the normal range and are more flexible. On the other hand, men demonstrated greater lower limb endurance. Low HGS was associated with a higher BMI, the presence of a CNCD, and lower limb endurance. A negative correlation was observed between HGS and age, BMI, and body fat. Conversely, a positive correlation was found between HGS and muscle mass as well as with lower limb muscle endurance. Conclusions: It can be concluded that individuals with low HGS are more likely to have a high BMI, develop a CNCD, and present lower muscular endurance. Additionally, HGS was found to be reduced in older individuals and/or those with higher levels of body fat, and to be higher in those with normal physical capacity and body composition.

Abstract: Next-generation sequencing (NGS) has been well applied to assess genetic abnormalities in various biological samples to investigate disease mechanisms. With the advent of high-throughput and automatic testing platforms, NGS can identify radiation-sensitive and dose-responsive biomarkers, contributing to triage patients and determining risk groups for treatment in a nuclear emergency. While bulk NGS provides a snapshot of the average gene expression or genomic changes within a group of cells after the radiation, it does not give information on individual cells within the population. On the other hand, single-cell sequencing involves isolating individual cells and sequencing the genetic material from each cell separately. This approach allows for the identification of gene expression and genomic changes in individual cells, providing a high-resolution view of cellular diversity and heterogeneity within a sample. Single-cell sequencing is particularly useful to identify cell-specific features of dose-response and organ-response genes. Although single-cell RNA sequencing (scRNA-seq) technology is still in its infancy in radiation research, it has great potential for identifying biomarkers associated with radiation exposure and for personalized post-radiation medical care. The aim of this review is to focus on current dosimetry methods, recently identified radiation-induced biomarkers, as well as the application of NGS techniques in facing a nuclear accident, specifically the single-cell sequencing technology.

Abstract:

This study explores the neuropharmacological potential of various molecular and amino acid components derived from Syzygium aromaticum (clove), an aromatic spice with a long history of culinary and medicinal use. Key bioactive compounds such as eugenol, α-humulene, β-caryophyllene, gallic acid, quercetin, and luteolin demonstrate antioxidant, anti-inflammatory, and neuroprotective properties by scavenging free radicals, modulating calcium channels, and reducing neuroinflammation and oxidative stress. Moreover, gallic acid and asiatic acid exhibit protective effects, including apoptosis inhibition, while other useful properties of clove phytocompounds include NF-κB pathway inhibition, membrane stabilization, and suppression of pro-inflammatory pathways, further contributing to neuroprotection and cognitive enhancement. Amino acid analysis revealed essential and non-essential amino acids such as aspartic acid, serine, glutamic acid, glycine, histidine, and arginine in various clove parts (buds, fruits, branches, and leaves). These amino acids play crucial roles in neurotransmitter synthesis, immune modulation, antioxidant defense, and metabolic regulation. Collectively, these bioactive molecules and amino acids contribute to clove’s antioxidant, anti-inflammatory, neurotrophic, and neurotransmitter-modulating effects, highlighting its potential as a preventive and therapeutic candidate for neurodegenerative disorders. While preliminary preclinical studies support these neuroprotective properties, further research, including clinical trials, is needed to validate the efficacy and safety of clove-based interventions in neuroprotection.

Abstract:

Forests can simultaneously provide a variety of ecosystem functions and services (ecosystem multifunctionality, EMF). Different stand types, influenced by biotic and abiotic factors, play a key role in determining EMF. To clarify the impact of stand type, as well as biotic and abiotic factors, on EMF, this study quantified EMF across three stand types: Betula platyphylla pure forest (BP), B. platyphylla-Larix principis-rupprechtii mixed forest (BL), and L. principis-rupprechtii pure forest (LP). The multiple-threshold approach was employed to quantify EMF, while structural equation modeling was used to analyze the primary factors influencing EMF. The results indicated that: (1) BL had higher stand productivity than both BP and LP; (2) BL exhibited significantly higher functional diversity and soil fertility maintenance compared to LP, with no significant difference between BP and BL; (3) BP demonstrated a significantly stronger nutrient cycling function than LP, with no significant difference between LP and BL; (4) the ranking of EMF at all threshold levels was BL>BP>LP; (5) soil was an effective driver of EMF across all threshold levels; and (6) both the niche complementarity effect and the mass ratio effect jointly drove EMF at the low threshold (<50%), with the influence of both effects diminishing as the threshold increased. This study enhances understanding of the key drivers of EMF in forest ecosystems and provides valuable insights for informing multifunctional forest management practices.

Abstract:

Avian infectious bronchitis virus (IBV) is a globally prevalent, highly contagious avian pathogen that imposes substantial disease burden and economic losses on the poultry industry. Due to the challenges associated with vaccine immunization, there is an urgent need to develop novel anti-IBV therapeutic strategies. In this study, a synthesized novel compound N-phenethylphenazine-1-carboxamide (SQXA-12) was investigated for its significant inhibitory effects on IBV replication. SQXA-12 exhibited low cytotoxicity and high antiviral efficacy, with a CC₅₀ value of 122.98 μM and an EC₅₀ value of 12.25 μM. Sensitivity tests against VSV, HCoV-OC43, PEDV, NDV, PRRSV, and AIV-H9N2 revealed that SQXA-12 possesses potential broad-spectrum antiviral activity against both positive- and negative-sense RNA viruses. These findings highlight the promising therapeutic potential of SQXA-12 for IBV infection.

Abstract: Insects demonstrate remarkable adaptability to extremely cold environments, a critical survival trait contributing to their evolutionary success and ecological distribution. This manuscript explores the mechanisms of insect cold hardiness, focusing on cryoprotectants—biochemical substances that mitigate damage caused by freezing temperatures. Important cryoprotectants, such as glycerol, trehalose, and amino acids, are discussed in detail, highlighting their mechanisms of action, which include colligative and non-colligative effects, membrane stabilization, ice nucleation inhibition, and osmotic regulation. Case studies of species-specific adaptations illustrate the diversity of strategies that insects employ, ranging from the accumulation of a single cryoprotectant to complex combinations that enhance resilience. The manuscript also addresses the relationship between cryoprotectants and other adaptations, such as antifreeze proteins and ice-nucleating proteins, emphasizing the integrated nature of insect survival strategies. By linking these findings to broader ecological and agricultural contexts, the manuscript underscores the importance of understanding insect cold hardiness in the face of climate change. Trehalose and glycerol are the predominant cryoprotectants. Among insect orders, Coleoptera exhibits the highest diversity of both cryoprotectants and species, reflecting their broad range of ecological strategies. Lepidoptera demonstrates notable diversity in cryoprotectants, which align with their adaptations for overwintering at different life stages, including larvae and pupae. Future research directions are proposed to uncover regulatory pathways, explore lesser-known cryoprotectants, and apply these insights to manage insect populations in dynamic environments. This review provides a comprehensive framework for understanding insect cold hardiness's biochemical, physiological, and ecological dimensions, with implications for both fundamental biology and applied sciences.

Abstract: In an effort to enhance wheat's resilience against rust diseases, our research explores the genetic underpinnings of resistance in a diverse collection of winter bread wheat accessions. Leaf rust (Puccinia triticina), yellow rust (Puccinia striiformis f. sp. tritici), and stem rust (Puccinia graminis f. sp. tritici) are significant threats to global wheat production. By leveraging host genetic resistance, we can improve disease management strategies. Our study evaluated 55 wheat accessions, including germplasm from Kazakhstan, from Uzbekistan, from Russia, from Kyrgyzstan, France, and CIMMYT under field conditions in southern Kazakhstan from 2022 to 2024. The results showed a robust resistance profile: 49.1% of accessions exhibited high to moderate resistance to leaf rust, 12.7% to yellow rust, and 30.9% to stem rust. Notably, ten accessions demonstrated resistance to multiple rust species, while seven showed resistance to two rusts. Twenty accessions were selected for further seedling resistance and molecular analysis. Three accessions proved resistant to six isolates of P. triticina, two to four isolates of P. striiformis, and four to five isolates of P. graminis. Although no genotypes were found to be universally resistant to all rust species at the seedling stage, two accessions — Bezostaya 100 (Russia) and KIZ 90 (Kazakhstan) — displayed consistent resistance to leaf and stem rust in both seedling and field evaluations. Molecular analysis revealed the presence of key resistance genes, including Lr1, Lr3, Lr26, Lr34, Yr9, Yr18, Sr31, Sr57, and the 1AL.1RS translocation. This work provides valuable insights into the genetic landscape of wheat rust resistance and contributes to the development of new wheat cultivars that can withstand these diseases, enhancing global food security.

Abstract: The impact of heat stress on intestinal bacterial antimicrobial resistance (AMR) and its mechanisms is not fully understood. In this study, SPF mouse model were used and divided into a control group (25°C) and a heat stress group (42°C for 1 hour, twice daily for 55 days). Intestinal tissues of mice were analyzed for intestinal function and bacterial resistance. RT-qPCR and histopathology showed intestinal damage and significant upregulation of stress, integrity, and inflammation-related genes, indicating the damage of intestinal function due to the heat stress and the successful establishment of the mouse heat stress model. Antibiotic susceptibility testing revealed increased resistance to erythromycin, chloramphenicol, and tetracycline among Enterococcus strains. Clonal analysis showed that resistant strains were clonally unrelated. Sequencing identified a novel ermB-carrying integrative and conjugative element (ICEFZMF) among 4 erythromycin-resistant strains, capable of transferring resistance within and between species. The rectum harbored a higher proportion of erythromycin-resistant Enterococcus strains, with higher minimum inhibitory concentrations (MICs) after 25 days of heat stress. Colonization assays confirmed that heat stress led to the accumulation of erythromycin-resistant Enterococcus in the rectum, suggesting the colonization preference of erythromycin-resistant Enterococci in the rectal environment after heat stress. Metagenomic sequencing revealed significant changes in microbial composition, favoring anaerobic metabolism. This study suggests that chronic heat stress can promote the emergence of antibiotic-resistant strains through ICE transfer, providing insight for environmental safety.

Abstract: Ensuring a fair income for farmers, as one of the key objectives of the Common Agricultural Policy (CAP), focuses on economic dimension of sustainable agricultural development. Achieving the economic viability of farms is often prioritized in developing countries, as the economic dimension is crucial for the farm survival in the long term. This paper aims to assess the economic viability of farms and to examine the impact of various factors on their viability. The study focuses on family farms that were part of Serbian Farm Accountancy Data Network (FADN) sample over a seven-year period from 2015 to 2021. Farm economic viability is evaluated using the opportunity cost approach. The results have shown that the highest proportion of economically viable farms was found in field crop farming. Conversely, grazing livestock farms were the least economically viable due to extensive farming methods they usually employ. Among the determinants of farm viability, the most important one was the asset turnover ratio, which positively affected the economic viability of all types of farming. The obtained results may help farm managers identify the primary obstacles to achieving optimal performance in the long run. Moreover, agricultural policymakers could improve existing measures and introduce new ones to strengthen the overall economic viability of farms.

Abstract:

Colocasia esculenta, also known as Chinese taro or taro, is a crop of great importance for the Colombian Pacific region. However, it is threatened by corm rot, which affects the food security of Afro-descendant and indigenous communities in the area. This study aimed to identify some of the phytopathogenic agents responsible for this disease and explore their control using an aqueous extract of Dysphania ambrosioides (paico). Through morphological analyses and ITS gene sequencing, two fungi responsible for the rot were identified: Fusarium solani and Mycoleptodiscus suttonii, and their roles as causal agents of the rot were confirmed in greenhouse experiments. Paico proved effective in controlling the growth of these fungi, with concentrations of 12.5% and 17.5% for M. suttonii, and 17.5% for F. solani. These findings highlight the importance of organic control to ensure food security and sustainable production in vulnerable areas of Colombia, emphasizing the relevance of this study for local communities.

Abstract: To develop a strategy for sustainable bioremediation of heavy metal-contaminated environments it is needed to understand the mechanisms of remediation using microorganisms. A huge bioremediation potential is possessed by fungi. Fusarium culmorum with their wide range of plant hosts can be the basis for creating sustainable phytoremediation technologies and for creating sustainable agriculture methods. Exopolymers (EPS) produced by F. culmorum can be an excellent metal sorbents and basic factors in the biosorption mechanism. The sorption capacities of Zn, Pb, and Cd by the EPS of a pathogenic DEMFc37 strain and two non-pathogenic strains (PGPF-DEMFc2 and DRMO-DEMFc5) were compared, as well as the effects of these metals on EPS synthesis by the three strains was determined. EPS samples were chemically characterized in regards to sugars, protein and phenolic compounds contents and used to study of metal binding. The concentration of metals bound/adsorbed to EPS was determined by Atomic Absorption Spectroscopy. The EPS of all the strains bound more than 80% of Zn as well as 64-84% of Cd and 74-79% of Pb, respectively. Thus, it has been clearly shown, that the use of F. culmorum EPS can be the basis for creating sustainable bioremediation, including phytoremediation.

Abstract: The growing field of nutraceuticals and food technology is significantly advancing due to the integration of novel bioactive compounds such as marine saponins. These so-called thalassochemicals exhibit a broad spectrum of pharmacological activities, including antitumor, hypolipidemic, antioxidant, and antimicrobial effects, distinguishing them from their terrestrial counterparts due to unique molecular features like sulfated sugar residues. Their amphiphilic nature influences their biological interactions, making them promising candidates for nutraceutical development. This review comprehensively explores marine saponins' structural, biochemical, and physicochemical properties and their potential applications in functional foods and therapeutic formulations. It discusses the challenges associated with their extraction, stability, and bioavailability and emphasizes innovative solutions such as supercritical fluid extraction, encapsulation techniques, and nanotechnology-based delivery systems. These advancements bridge the gap between pharmacology and food science, enhancing the efficacy and controlled release by using marine saponins. Furthermore, we examine their bioactivity at the molecular level, focusing on interactions with cellular receptors and key signaling pathways involved in inflammation, immune modulation, and metabolic regulation. While computational studies, including molecular dynamics and docking, have begun to elucidate structure-activity relationships (SARs), applying machine learning in predicting bioactivity remains an underexplored yet promising approach. Incorporating quantitative structure-activity relationship (QSAR) models may provide a predictive framework for assessing marine saponins' functional properties, facilitating identifying new therapeutic applications. Finally, we discuss the regulatory landscape and consumer perspectives influencing the commercialization of marine saponins in functional foods and nutraceuticals, highlighting sustainability considerations in sourcing and production. This review outlines a roadmap for leveraging marine saponins as key components of next-generation health-promoting products by integrating recent advancements in food technology, computational modeling, and bioinformatics.

Abstract:

Bird cherry-oat aphid (Rhopalosiphum padi L.; Hemiptera: Aphididae) and English grain aphid (Sitobion avenae Fabricius; Hemiptera: Aphididae) are important vectors of barley yellow dwarf virus (BYDV) in cereal crops traditionally managed using synthetic chemical insecticides. Exploiting the genetic diversity within different wheat varieties offers an alternative to current controls for managing both aphid pests and virus transmission. Confining individual aphids onto specific plant parts using a clip cages is often used to screen for resistance traits in host plants. However, clip cages can damage plants and influence aphid performance. In this study, the performance of bird cherry-oat aphid and English grain aphid was recorded when aphids were ‘confined’ or left ‘free’ on different wheat varieties. Aphid performance was found to be affected by both confinement method and cereal variety, highlighting the complexity of these interactions. Performance of English grain aphid was increased when ‘confined’ while performance of bird cherry-oat aphid was increased when left ‘free’. These differences reflect species-specific differences to feeding sites and responses to microclimate. Differences in aphid performance were also recorded in response to cereal variety, with the lowest performance recorded on the BYDV resistant variety Wolverine. While none of the varieties tested were ‘truly’ resistant, useful traits for aphid management may already be present in commercial wheat varieties.

Abstract: Parkinson’s disease (PD) is the second most prevalent neurodegenerative disorder, yet effective agents for its prevention and therapy remain highly limited. Epicoccin A, a significant secondary metabolite from Exserohilum sp., demonstrates various biological activities, however, its neuroprotective effects have not been elucidated. Here, we investigated the therapeutic potential of epicoccin A for PD by evaluating its impact on neural phenotype, reactive oxygen species (ROS) generation, and locomotor activity in PD-like zebrafish. Transcriptomic analysis and molecular docking were conducted, with key gene expressions further verified using real-time qPCR. As a result, epicoccin A notably mitigated dopaminergic neuron loss, neural vasculature deficiency, nervous system injury, ROS accumulation, locomotor impairments, and abnormal expressions of hallmark genes associated with PD and oxidative stress. Underlying mechanism investigation indicated epicoccin A may alleviate PD-like symptoms by activating PINK1/Parkin-dependent mitophagy, as evidenced by the reversal of aberrant gene expressions related to PINK1/Parkin pathway and its upstream mTOR/FoxO pathway following epicoccin A co-treatments. This finding was further confirmed by the robust interactions between epicoccin A and these mitophagy regulators. Our results suggest that epicoccin A relieves PD symptoms by activating PINK1/Parkin-dependent mitophagy and inhibiting excessive oxidative stress, highlighting its potential as a therapeutic approach for PD.

Abstract:

HIV-1 integrase (IN), an essential viral protein that catalyzes integration, also influences non-integration functions such as particle production and morphogenesis. The mechanism by which non-integration functions is mediated is not completely understood. Several factors influence this non-integration function including ability of IN to bind to viral RNA. INI1/SMARCB1 is an integrase binding host factor that influences HIV-1 replication at multiple stages, including particle production and particle morphogenesis. IN mutants defective for binding to INI1 are also defective for particle morphogenesis, similar to RNA-binding-defective IN mutants. Studies have indicated that the highly conserved Repeat (Rpt)1, the IN-binding domain of INI1, structurally mimics TAR RNA and that the Rpt1 and TAR RNA compete for binding to IN. Based on the RNA mimicry, we propose that INI1 may function as a “place-holder” for viral RNA to facilitate proper ribonucleoprotein complex formation required during the assembly and particle morphogenesis of the HIV-1 virus. These studies suggest that drugs that target IN/INI1 interaction may lead to dual inhibition of both IN/INI1 and IN/RNA interactions to curb HIV-1 replication.

Abstract: The ubiquitin-proteasome system (UPS) is a critical cellular mechanism involved in protein turnover, influencing processes such as cell cycle regulation, gene expression, and stress responses. Dysregulation of the UPS contributes to the pathogenesis of chronic diseases, including neurodegeneration, cardiovascular disorders, and cancer. This review explores the potential of circulating phenolic metabolites — bioactive metabolites derived from dietary (poly)phenols — as modulators of UPS activity. Using comprehensive analysis, we summarize evidence linking phenolic metabolites, such as valerolactones, benzoic acids, urolithins, and hydroxycinnamic acids, to proteasome modulation through mechanisms like autophagy activation, inflammatory mediator reduction, and oxidative stress prevention. Despite the growing interest, significant gaps remain, including limited data on physiological concentrations, metabolite availability, and exposure conditions in cellular and in vivo models. Advancing the understanding of phenolic metabolites in UPS regulation could unlock new therapeutic strategies for managing chronic diseases, highlighting the need for further research integrating clinical and mechanistic insights.