This review critically synthesizes current knowledge on foodborne microplastics (MPs) to establish a scientific foundation for risk assessment and control. Despite their widespread presence in food systems, research is hindered by a lack of standardized detection methods and unresolved uncertainties regarding their health implications. Our synthesis shows that the toxicity of MPs arises from a combination of physical abrasion, chemical leaching, and a “Trojan horse” mechanism that carries co-pollutants, collectively triggering oxidative stress and inflammation. A primary challenge remains the absence of harmonized analytical protocols, especially for nanoplastics. Key conclusions emphasize the need for a multi-tiered control strategy, spanning from source reduction to the development of safer alternatives. While vigilance is warranted, the likely existence of a dose-response relationship argues against undue alarm. Future work should focus on standardizing methods and using human-relevant models to inform evidence-based food safety policies.

Pancreatic adenocarcinoma (PAAD) has a poor prognosis. Its microenvironment is closely associated with tumor progression and immune evasion. This study combines single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to reveal the critical role of tumor-associated macrophages (TAMs) in PAAD. Ras association domain family member 1 C (RASSF1C) is significantly upregulated under hypoxia, enhancing glycolysis by promoting the Warburg effect. This generates lactate and contributes to acidification of the tumor microenvironment (TME). Lactate activates TAMs and reprograms their lipid metabolism, promoting PAAD migration and invasion. Further investigation demonstrated that lactate suppressed ubiquitin-fold modifier 1 ligating enzyme 1 (UFL1) protein levels in macrophages, thereby weakening the protective effect of UFL1-mediated interferon regulatory factor 7 (IRF7) UFMylation. This suppression led to enhanced K48-linked ubiquitination of IRF7 and accelerated proteasomal degradation, ultimately reducing IRF7 stability and impairing lipid metabolic functions in macrophages. Additional mechanistic evidence showed that UFL1-UFMylation axis maintains IRF7 homeostasis by counteracting K48-linked ubiquitin-mediated degradation. Moreover, immunohistochemical (IHC) validation using tissue microarrays from 20 human pancreatic ductal adenocarcinoma (PDAC) specimens revealed that the overall expression of RASSF1C and hypoxia-inducible factor-1 alpha (HIF-1α) was higher than that of UFL1 and IRF7. RASSF1C expression was significantly positively correlated with HIF-1α and negatively correlated with UFL1 and IRF7. Clinicopathological correlation analysis further showed that high RASSF1C expression was associated with poor differentiation and advanced TNM stage, whereas low UFL1 and IRF7 expression was associated with lymph node metastasis. Collectively, this study demonstrated that the hypoxia-RASSF1C-HIF-1α axis reshaped TAM function through lactate-mediated immunometabolic regulation and promoted PAAD progression by inhibiting UFL1-mediated IRF7 UFMylation, thereby reducing IRF7 stability. These findings identify potential therapeutic targets for combined metabolic and immune interventions in PAAD. Graphic abstract. Schematic illustration of the molecular mechanism by which the RASSF1C-HIF-1α axis induces glycolytic reprogramming, drives lactate accumulation in the acidic TME, and promotes lactate flux into macrophages, thereby facilitating UFL1-IRF7 interaction and ultimately accelerating PAAD progression.

Chemoresistance greatly impairs the effectiveness of chemotherapy in gastric cancer (GC) patients. According to our prior results, Cadherin-17 (CDH17) contributes to chemoresistance in GC through activating the Wnt/β-catenin pathway; however, its specific molecular mechanisms require further elucidation. We compared the Wnt/β-catenin pathway activation levels between cisplatin (DDP)-resistant GC cell lines and their parental cell lines. Subsequently, we carried out loss-of-function and gain-of-function tests to investigate CDH17 for its effect on regulating β-catenin expression, nuclear transport, as well as transcriptional activity within DDP-resistant GC cells. Additionally, CDH17 was examined for its role in the expression of four ABC transporters using molecular assays. Finally, rescue experiments were carried out using the Wnt signaling pathway agonist CP21R7 and inhibitor IWR-1 to elucidate the specific mechanism of CDH17 in promoting chemotherapy resistance of GC cells. The results showed that the activation level of the Wnt/β-catenin signaling pathway was significantly elevated in DDP-resistant GC cell lines compared to their parental cell lines. Silencing CDH17 resulted in reduced expression, impaired nuclear translocation, and decreased transcriptional activity of β-catenin, whereas overexpression of CDH17 had the opposite effects. Notably, CDH17 was shown to specifically regulate the expression of ABCB1 (protein name: P-glycoprotein, P-gp) in resistant cells, with no observable impact on the other three ABC transporters (ABCC1, ABCG2, and ABCC2) examined. Importantly, treatment with IWR-1 effectively reversed the enhancing effect of CDH17 overexpression on P-gp protein expression, as well as its suppressive effects on DDP accumulation and chemosensitivity. Conversely, administration of CP21R7 attenuated the inhibitory consequences of CDH17 silencing on P-gp expression, DDP efflux, and drug resistance. In conclusion, CDH17 promotes the expression and nuclear translocation of β-catenin in GC cells, leading to activation of the Wnt/β-catenin signaling pathway, which subsequently upregulates ABCB1/P-gp expression and enhances cellular capacity for DDP efflux. These findings imply that targeting CDH17 could be a potential strategy for overcoming chemotherapy resistance in GC.

p-Hydroxy-p-methylbutyrate (HMB) is a metabolite of the essential amino acid leucine, which can be produced naturally in mammals and is also found in trace amounts in citrus fruits and fish. Studies have shown that HMB plays an important role in maintaining human health by improving muscle health and inhibiting muscle catabolism. This review summarises the synthesis and metabolism of HMB and discusses its potential use as a nutrient, highlighting and analysing the importance of HMB supplementation for athletes' physical recovery and the treatment of muscular dystrophy-related diseases between 2019 and 2025. This study will help us to deepen our understanding of the application of HMB as a dietary supplement for the treatment of different diseases, providing the latest insights into its sustainability.

Hyperuricemia (HUA) is a primary trigger for gout and poses a serious threat to human health. Metabolites from Monascus purpureus exhibit lipid-lowering and nephroprotective effects, while Sanghuangporus extracts have been proven to effectively reduce uric acid (UA) levels. However, the effects and underlying mechanisms of their co-culture (CMS) fermentation products remain unclear. This study examined the therapeutic effects and mechanisms of action of fermented products from Monascus purpureus M1 (MPF), Sanghuangporus vaninii (SVF), and their CMS in alleviating HUA. In vitro assays revealed MPF, SVF, and CMS substantially suppressed XOD activity. In vivo, they reduced UA levels in PO/HX-induced HUA mice, mitigated renal injury, and alleviated renal inflammation and oxidative stress. Mechanistically, these effects were associated with renal reabsorption transporters GLUT9/URAT1, upregulated secretory transporters OAT1/ABCG2, and increased intestinal UA transporters ABCG2 and GLUT9. Gut microbiota analysis revealed enrichment of Lactobacillus in the CMS group. Notably, CMS exhibited a more pronounced tendency toward efficacy compared with the individual fermentation products. Collectively, CMS fermentation of MPF and SVF shows potential as a natural strategy for the management of HUA through coordinated regulation of UA metabolism and gut microbiota. Practical Application: This study developed a novel fermentation strategy using the CMS of MPF and SVF. The metabolites derived from CMS demonstrated potential hypouricemic activity via multifaceted mechanisms-including modulation of xanthine oxidase (XOD) activity, regulation of urate transporters in the kidneys and intestines, and alteration of to the gut microbiota. This work not only provides a proof-of-concept for utilizing microbial CMS technology to develop novel functional foods but also opens a new avenue for converting edible and medicinal fungal resources into high-value health products.

Density dependence is a key characteristic of quorum sensing (QS) in fungi; however, no relevant reports have been found in Monascus. Therefore, this study aimed to investigate the effects of initial spore density on the morphological development and polyketide secondary metabolism of Monascus purpureus to elucidate the regulatory role of QS. At the high initial spore density, more active conidial development and secondary metabolism were observed in the early fermentation stage, accompanied by rougher hyphal surfaces, increased secretion and larger vacuoles. Gene set enrichment analysis (GSEA) based on transcriptomic data revealed that high initial spore density activated ribosome biosynthesis to support rapid cell growth and secondary metabolism, whereas low initial spore density upregulated genes associated with peroxisome biosynthesis, the enzymatic antioxidant system, fatty acid degradation, fatty acid biosynthesis, and asexual sporulation. Furthermore, the reduction in linoleic acid content at high initial spore density suggested that linoleic acid and its derivatives may function as putative quorum sensing molecules (QSMs). Finally, a potential regulatory network integrating initial spore density with secondary metabolism and development was proposed. These findings enhance the understanding of the QS network in Monascus and offer a theoretical basis for the optimization of fermentation processes.

Indigo, a historically significant blue dye widely used in textiles such as denim, was originally derived from plants. However, traditional extraction faced issues like low yield and high land use, while later chemical synthesis relied on toxic compounds, creating environmental and health concerns. Recently, microbial synthesis has emerged as a sustainable alternative, requiring only 10% of the time of plant-based methods and 80% less water than chemical production. Besides textiles, indigo is also applied in medicine, food, cosmetics, and semiconductors. This review covers the history, biosynthesis, detection, and diverse applications of indigo, addressing current challenges and highlighting its potential for eco-friendly dye manufacturing.

This study reports the complete genome sequence of Saccharothrix sp. NBAS 001, a strain isolated from soil near the shore of Nanhu Lake in Wuhan, Hubei Province, China. The genome comprises a single circular chromosome of 10,561,717 bp and encodes 9,388 CDS.

Inflammatory bowel disease (IBD) is a chronic disease influenced by a complex interplay of factors, including genetics, environmental, and gut microbiota. This study aimed to explore the therapeutic potential of the natural polyphenolic compound hydroxytyrosol (HT) in modulating dextran sodium sulfate (DSS)-induced colitis in mice. The findings demonstrate that oral administration of HT significantly alleviated colitis symptoms, as evidenced by a reduction in the disease activity index and improvements in colonic pathology. HT was found to inhibit the release of pro-inflammatory cytokines, enhance antioxidant status, and mitigate oxidative stress. Furthermore, HT contributed to the restoration of the gut barrier by reinstating tight junction proteins, reducing the inflammatory marker lipopolysaccharide (LPS), and suppressing inflammation-related genes. This compound also modulated the NLRP3-Cas-1-GSDMD-IL-1β inflammatory pathway and inhibited the NF-κB (nuclear factor kappa B) pathway, thereby alleviating colitis. Gut microbial analysis revealed that HT enriched the abundance of Bacteroidota and altered the balance between Bacteroidota and Firmicutes in mice. Correlation analysis between bacterial microbiota and inflammatory factors suggested that HT may alleviate colitis by modulating the relative abundance of Alistipes, Bacteroides, and unclassified_f__Muribaculaceae. These findings underscore the potential of HT as a therapeutic agent in the treatment of colitis.

Ergothioneine (EGT) is a naturally occurring thiol-containing amino acid derivative synthesized by certain fungi and bacteria, with humans acquiring it exclusively through dietary intake. It has gained increasing attention due to its exceptional antioxidant, cytoprotective, and metal-chelating properties. EGT shows high stability under physiological conditions and can accumulate in specific tissues via the highly selective transporter OCTN1. Emerging evidence reveals its antioxidant activities-mitigating oxidative stress, lipid peroxidation, mitochondrial dysfunction, and inflammation-supporting therapeutic applications in neurodegenerative, cardiovascular, metabolic, and age-related diseases. In the food industry, EGT offers promise as a natural preservative to enhance shelf-life and nutritional value, while in cosmetics, it functions as an anti-aging and anti-photoaging agent. Recent advances in fermentation, metabolic engineering, and chemical synthesis have significantly improved EGT production, supporting its transition from a niche compound to an industrially relevant bioactive ingredient. However, clinical trials and regulatory assessments remain limited, and further research is needed to explore its bioavailability, and synergistic effects with other functional compounds. This review provides a comprehensive summary of EGT's biological functions, application potential, and current production strategies, offering insights into its future development as a high-value nutraceutical and pharmaceutical ingredient.

β-Hydroxy-β-methylbutyrate (HMB), a metabolite of the essential amino acid leucine, is acknowledged for its powerful role in facilitating muscle protein synthesis, reducing muscle catabolism, and promoting fat-free mass accumulation. With well-documented anticatabolic, anabolic, and lipolytic effects, HMB has been extensively studied in clinical settings and has exhibited potential in mitigating muscle loss induced by aging, cancer cachexia, and sarcopenia. Moreover, HMB finds applications in specialized medical nutrition, sports nutrition, and animal husbandry, with recent research illustrating its benefits in enhancing animal growth and immunity. This review highlights the current understanding of HMB’s physiological mechanisms, its diverse applications, and recent advancements in detection methods such as High-Performance Liquid Chromatography (HPLC), Gas Chromatography (GC), and Liquid Chromatography–Mass Spectrometry (LC–MS). Additionally, it discusses the future prospects of HMB bio-manufacturing. The establishment of standardized guidelines for its safe use and testing is crucial for its broader adoption in the food industry. Future research should focus on further elucidating HMB’s muscle growth mechanisms and broadening its applications across the food, health, and agricultural sectors. In sum, future studies should prioritize mechanistic exploration, safety and synergy, along with standardization to fully harness HMB’s potential.

Fungal hyphae self-assemble a variety of cellular macrostates, ranging from suspended mycelium to dense pellets, all inextricably linked to their productivity. In this study, using CRISPR/Cas technology, we constructed a ctnA knockout strain (Delta ctnA) and an overexpression strain (A2) so as to investigate the effects of interfering with citrinin biosynthesis on the growth, morphology and pigmentation of M.purpureus. Results indicated that deletion of ctnA in M. purpureus RP2 led to increased mycelium length, delayed conidium formation, and a citrinin content of 22% of the wild-type strain. Conversely, ctnA overexpression in strain A2 resulted in delayed mycelial growth, normal conidium formation, and a citrinin content of 120% compared to the wild-type strain, with minimal effects on pigments content. Notably, the Delta ctnA strain formed small, tightly structured pellets (mean diameter 1.2 +/- 0.06 mm) and exhibited low citrinin content, promoting pigments production. Our findings suggest a complex interplay between citrinin biosynthesis and morphological development, providing insights for optimizing metabolite production in industrial applications.

Citrinin is a common mycotoxin found in food and poses risks to both human and animal health. While extensive research has been conducted on the nephrotoxicity of citrinin itself, the nephrotoxicity of its metabolites remains unclear. Therefore, this study investigated the nephrotoxic mechanism of citrinin and its metabolites (CIMs) using density functional theory, network toxicology, and computer simulations. Our findings revealed that CIMs also have potential toxicity, such as nephrotoxicity. Density functional theory explained the structural basis of the toxicity of CIMs. A total of 255 targets related to nephrotoxicity induced by CIMs were predicted by network toxicology. Notably, the enrichment results indicated the importance of multiple forms of programmed cell death in CIMs-induced nephrotoxicity. In addition, four key targets (TP53, MAPK1, MAPK3, and HSP90AA1) were identified, with molecular dynamics simulations validating stable binding between the four targets and CIMs. Van der Waals forces were the main driving force for stabilizing complexes formed between CIMs and the four targets through the binding free energy and independent gradient model analysis. Our research provides the theoretical basis and new insights for an in-depth study of the nephrotoxicity mechanism of CIMs and offers a new paradigm/approach for investigating the toxicity mechanism of other mycotoxins in the future.

This study explores the grafting of syringic acid onto fucoidan and assesses the resultant graft's (FS) enhanced functional properties and therapeutic potential in a histamine-induced liver injury model. Utilizing a redox system of ascorbic acid and hydrogen peroxide, the grafting process achieved a grafting rate of 290.45 mg CAE/g, confirmed through UV-Vis spectroscopy, FT-IR spectroscopy, scanning electron microscopy, and thermogravimetric analysis. In vivo investigations using histamine-sensitive mice demonstrated that FS significantly mitigated histamine-induced damage, evidenced by improvements in body weight, organ index, and colon length. FS exhibited superior efficacy in restoring liver function indices (ALT, AST, ALP, GGT), enhancing antioxidant defenses (GSH, SOD), and reducing oxidative stress markers (MDA). Anti-inflammatory effects included reduced levels of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) and modulation of apoptosis-related proteins (BCl2, BAX). Additionally, FS upregulated key antioxidant genes in the Nrf2/KEAP1 pathway and downregulated inflammatory genes in the NF-κB pathway. Restoration of colonic tight junction proteins (ZO-1, Occludin, Claudin-1) and normalization of gut microbiota composition further underscored the therapeutic potential of FS. The study highlights the significant enhancement in functional properties of fucoidan through SA grafting, presenting FS as a promising candidate for developing functional foods and nutraceuticals aimed at preventing and mitigating liver damage and related disorders.

Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide. The present study aimed to investigate the functional role and related mechanism of long non-coding RNA neuropeptide S receptor 1-antisense RNA 1 (NPSR1-AS1) in CRC pathogenesis. Cell viability and proliferative capacity were evaluated using MTT and colony formation assays. The localization of NPSR1-AS1 in cytoplasm and nucleus was confirmed by subcellular fractionation assays. Flow cytometry was employed to assess cell cycle distribution and apoptosis rates. The interactions between microRNA (miR)-365b-3p and its upstream factor NPSR1-AS1 or downstream target YRDC were validated through luciferase reporter assays, RNA pull-down assays and RNA immunoprecipitation assays.The results demonstrated that NPSR1-AS1 was significantly upregulated in CRC cell lines (4-5 folds) and primarily localized in the cytoplasm of HT29 cells (77 ± 7.55%) and SW620 cells (82 ± 8.03%). Sh-NPSR1-AS1#1 markedly reduced optical density by nearly 50% at 72 h. NPSR1-AS1 knockdown strongly reduced HT29 cell colonies to 36 ± 3.29 and 39 ± 3.57 compared to sh-NC group (145 ± 13.67). It also increased G1-phase cell proportion (57.33 ± 5.24% and 56.47 ± 5.28% vs. 48.23 ± 4.26%) and decreased S-phase cells (28.62 ± 2.51% and 29.5 ± 2.63% vs. 38.31 ± 3.52%). Apoptosis rates rose significantly upon NPSR1-AS1 silencing (26.59 ± 1.24% and 26.28 ± 1.09% vs. 6.91 ± 0.64%). Similar effects were observed in another cell line SW620. NPSR1-AS1 functioned as a competing endogenous RNA (ceRNA) by binding to miR-365b-3p, thereby upregulating YRDC expression. Additionally, the suppressive effects of NPSR1-AS1 knockdown on cell malignancy could be partially reversed by overexpression of YRDC (p < 0.05). Overall, NPSR1-AS1 contributes to CRC cell growth by elevating YRDC expression via sequestration of miR-365b-3p.

Hydroxytyrosol (HT), a potent phenolic compound derived from olives, has attracted significant attention due to its exceptional antioxidant, anti-inflammatory, and antimicrobial properties. This review comprehensively examines recent advances in the synthesis, biological functions, safety profiles, and legal regulations of HT. We discuss both natural and biotechnological synthesis routes, including enzyme-mediated, non-transgenic, and transgenic biosynthetic methods, highlighting recent innovations that have improved yield and purity. The review further explores the multifaceted biological activities of HT, ranging from its role in cardiovascular protection and neuroprotection to its anticancer and metabolic regulatory effects. Safety assessments from animal and human studies are analyzed, demonstrating low toxicity and favorable metabolic profiles at physiologically relevant doses. Additionally, we compare international regulatory frameworks from the United States, China, and the European Union, which underscore the compound’s safe use in food, pharmaceuticals, and cosmetics. Finally, the review outlines future research directions aimed at optimizing production methods, enhancing bioavailability, and addressing long-term toxicological outcomes, thereby reinforcing HT’s potential as a high-value functional ingredient in various industries.

The increasing global prevalence of hyperuricemia (HUA), particularly among younger populations, underscores the urgent need for safe and effective dietary interventions. Monascus fungi, long utilized in East Asian food culture, ferment rice to produce red yeast rice (RYR), a functional food rich in monacolin K and Monascus pigments. Among these, Monascus yellow pigments (MYPs)—natural azaphilone compounds used as food additives and colorants—have shown antioxidant, anti-inflammatory, and metabolic regulatory activities. However, their potential to alleviate hyperuricemia remains unexplored. This study investigates the urate-lowering and organ-protective effects of MYPs through a combination of in vitro, in vivo, and gut microbiota analyses. MYPs exhibited significant xanthine oxidase (XOD) inhibitory activity, and molecular docking confirmed that monascin (MS) and ankaflavin (AK) competitively bind to the XOD active site. In a murine HUA model, MYPs significantly reduced serum uric acid (SUA) levels without causing hepatic or renal toxicity. Mechanistically, MYPs downregulated renal UA reabsorption transporters (URAT1, GLUT9) and upregulated the excretory transporter ABCG2, enhancing uric acid (UA) excretion. These findings highlight MYPs as promising food-derived bioactives with dual XOD inhibition and uricosuric effects, offering a novel nutraceutical strategy for hyperuricemia prevention and management.

Ergothioneine (EGT), a natural thiol compound with potent antioxidant properties, exhibits diverse biological functions, including anti-inflammatory, neuroprotective, and cardioprotective effects. Despite its promising health and food applications, current production methods, such as mushroom-based liquid fermentation, are hindered by low yields and complex processes. Advances in biosynthetic fermentation, including heterologous expression of key pathway genes and optimization of cultivation conditions, offer promising solutions to these challenges. Recent discoveries, such as the catalytic efficiency of mononuclear non-heme iron enzymes like Egt1 and EgtB, have streamlined EGT biosynthetic pathways, reducing steps and increasing yield. The compound’s active transport via the OCTN1 protein facilitates its distribution across tissues, enhancing its therapeutic efficacy and potential in functional foods. Currently employed as an antioxidant and antimelanogenic agent in aquatic products, EGT holds vast potential for broader applications in food systems. This review explores the advancements in EGT production and biosynthesis while emphasizing its prospects as a safe, versatile, and effective natural ingredient for health and industrial applications.

Chili sauce, a traditional fermented food, relies on high salt content for flavor and preservation, yet excessive sodium poses health risks. This study aimed to develop low-salt fermented chili sauce with improved flavor and quality by preparing three groups with reduced salt concentrations (8 %, 10 %, and 12 %) and introducing L. acidophilus and K. bulderi to enhance fermentation. Analyses of physicochemical properties, biogenic amines, volatile compounds, and microbial communities demonstrated that reduced salt significantly increased amino acid nitrogen levels and elevated key aroma volatiles, enhancing flavor complexity. However, lower salt concentrations correlated with higher biogenic amine production, primarily linked to fungal activity, with Kazachstania species identified as critical contributors to flavor enhancement. These findings advance strategies for producing healthier low-salt fermented chili sauces without compromising sensory quality, offering theoretical insights into microbial roles in flavor development and biogenic amine regulation during reduced-salt fermentation.

Hyperuricemia (HUA), marked by elevated serum uric acid (SUA) levels, is a prevalent metabolic disorder associated with gout and chronic conditions such as cardiovascular diseases and malignancies. Synthetic drugs, including xanthine oxidase inhibitors and uricosuric agents, effectively lower SUA but often lead to side effects such as gastrointestinal distress, allergic reactions, and renal toxicity. In contrast, natural substances like flavonoids and polyphenols have demonstrated the ability to reduce UA levels and alleviate inflammation with fewer adverse effects, driving interest in their therapeutic potential. This review comprehensively explores HUA treatment strategies, examining the mechanisms, efficacy, and safety of synthetic drugs and natural substances. Recent advancements in pharmacological therapies, including novel drug delivery systems, are highlighted alongside bioactive compounds from plants, fungi, and marine organisms. In addition, this review innovatively summarizes recent studies on the synergistic effects between traditional drugs and natural substances within novel therapeutic frameworks, confirming that such synergism can reduce drug toxicity while maintaining targeted blood uric acid control. This discovery has opened new avenues for optimizing existing treatment protocols, providing fresh directions for enhancing therapeutic efficacy and minimizing adverse effects. It particularly highlights how pharmaceutical technologies such as metal complexation can address the low bioavailability issues of natural products. This integrative perspective underscores the importance of combining modern pharmacological advancements with natural substances, paving the way for the development of safer and more effective treatments for HUA.