Metabolic control of chromatin and gene expression is emerging as a key mechanism influencing critical neuronal functions. Here, we found that the intermediary metabolite acetate enhanced long-term memory in female mice, which was associated with epigenetic and transcriptional remodeling in the dorsal hippocampus. Acetate-enhanced memory was driven by increased acetylation of the histone variant H2A.Z and increased expression of genes implicated in learning in the female dorsal hippocampus. The effect of acetate on dorsal hippocampal histone modifications and gene expression differed markedly between the sexes during critical windows of memory consolidation and recall, and home cage exposure to acetate without the learning and recall tasks did not recapitulate these effects. These findings elucidate the ways in which acetate exposure enhances memory.

In the present study, we found that OsHIPP53 can directly bind Cd ions and possesses the capability to modulate Cd tolerance and accumulation in rice. Cadmium (Cd) pollution represents a widespread environmental issue in agricultural regions in China, adversely affecting crop productivity and threatening food safety. Heavy metal-associated isoprenylated plant proteins (HIPPs), a major class of metallochaperone proteins, are essential for plant adaptation to diverse biotic and abiotic stress conditions. This study characterizes a previously uninvestigated HIPP gene, OsHIPP53, demonstrating its involvement in modulating Cd accumulation and tolerance in rice. Subcellular localization analysis revealed that OsHIPP53 is primarily localized at the plasma membrane and Cd exposure significantly induced its transcriptional level in root tissues. Heterologous expression of OsHIPP53 in Δycf1 yeast mutants conferred improved Cd resistance and reduced cellular Cd levels relative to yeast cells carrying the empty vector. The results of the in vitro metal-binding assays indicate that OsHIPP53 can directly bind Cd ions. Consistent with yeast findings, in rice, oshipp53 mutant lines (oshipp53-1 and oshipp53-2) exhibited heightened Cd sensitivity, elevated root Cd concentrations, and restricted Cd translocation to the shoots. Conversely, overexpression lines (OsHIPP53-OX-1 and OsHIPP53-OX-2) displayed greater Cd tolerance and Cd accumulation in the shoots. Taken together, these results suggested that OsHIPP53 functions in regulating Cd tolerance and accumulation in rice.

Metastatic melanoma, marked by its poor prognosis and frequent recurrence, is a particularly aggressive skin cancer. Jaceidin, a compound derived from flavonoids abundant in common fruits and vegetables, has attracted interest for its potential anti-cancer properties. Nevertheless, the specific effects of jaceidin on melanoma cells remained unclear before this study. Here, we examined the impact of jaceidin on two metastatic melanoma cell lines, HMY-1 and A2058. Our results demonstrate that jaceidin exerts a significant anti-metastatic effect against both cell lines. This inhibitory action involved modulating the phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase, as well as suppressing proteins associated with epithelial-mesenchymal transition. Furthermore, jaceidin reduced the expression of extracellular matrix degradation proteins MMP-2 and cathepsins A. These compelling findings suggest that jaceidin warrants further investigation as a potential therapeutic agent for melanoma.

Insect wing development involves tissue patterning, cell fate transitions, and hormone signaling, yet its spatiotemporal logic remains unclear. The silkworm, with large wing discs and defined stages, provides an ideal model for high resolution analysis. Here, we construct a spatiotemporal single-cell atlas of the silkworm wing disc across 10 timepoints, identifying 12 major cell types and their developmental transitions. Wing morphogenesis (Wm) cells act as central progenitors, differentiating into epithelial and cuticle lineages under lineage-specific transcription factors. Time‑resolved snRNA‑seq reveals hierarchical transcriptional reprogramming, with Wm cells functioning as early signaling hubs. Functional modules and signaling pathways were activated in spatiotemporal controlled manner. 20‑hydroxyecdysone treatment rapidly accelerates fate transitions and gene expression, recapitulating natural development within hours. Integration of morphology, hormone levels, and gene expression supports a five-stage Gene Transition Model describing progressive fate resolution. This work reveals wing development in silkworm and provides insights into hormone-driven organogenesis and potential manipulation of insect development in agriculture.

The present study aimed to reveal the effects of Astragalus membranaceus polysaccharide (APS) on antioxidant capacity, immune-related gene expression, and inhibition of grass carp reovirus (GCRV) proliferation in grass carp (Ctenopharyngodon idella). Grass carps were fed experimental diets containing either 0.0% or 0.2% APS for 40 days. The results showed that APS supplementation significantly enhanced antioxidant capacity, as evidenced by increased activities of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX). Moreover, APS upregulated immune-related parameters, including immunoglobulin M (IgM), complement 3 (C3), complement factor B (Bf), mannose-binding lectin (MBL), lysozyme (LSZ), and C-X-C motif chemokine 13 (CXCL13), and modulated the expression of inflammatory cytokines such as interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), transforming growth factor β1 (TGF-β1), and interleukin 10 (IL-10). Furthermore, APS feeding markedly induced the expression of antiviral genes, including interferons (IFNs), interferon regulate factors (IRFs), and interferon stimulate genes, (ISGs)in the spleen, kidney, liver, and head kidney. Following intraperitoneal challenge with GCRV, the survival rate of the APS-treated group (76.67%) was significantly higher than that of the control group (43.33%). In addition, APS supplementation substantially reduced the relative protein levels of virus protein 5 (VP5)and virus protein 7 (VP7)during GCRV infection. These findings suggest that dietary APS enhances resistance to GCRV in grass carp by promoting immune fuction and antiviral responses. Collectively, our results demonstrate that APS effectively boosts immune activity and improves capacity of grass carp to combat GCRV infection. This study provides a theoretical basis and practical reference for the application of APS in the prevention and control of fish diseases.

Cyclic GMP-AMP synthase (cGAS) catalyzes the production of cGAMP, which activates the STING-IRF3 signaling pathway. Previous investigations indicated a role for STING-IRF3 in early alcohol-associated liver disease (ALD). In this study, we examined the role of cGAS in liver damage and inflammation in early ALD.

Glyphosate is the most widely used herbicide globally, especially due to the extensive cultivation of genetically modified glyphosate-resistant crops. However, its intensive application has raised public concerns about the risks to food safety and human health. Identifying enzymes capable of metabolizing glyphosate in plants represents an ideal strategy for addressing this issue, but few are known. Here, we identified the rice variety Kitaake with natural tolerance to glyphosate and demonstrated that this tolerance is driven by glyphosate glycosylation metabolism. Seven up-regulated UDP-dependent glycosyltransferase (UGT) genes associated with glyphosate tolerance were identified in Kitaake. Molecular-docking analysis indicated that these UGT proteins have moderate binding affinity for glyphosate. Among these, a deletion of an adenine at position -803 in the promoter region of GLYPHOSATE RESPONSIVE GLYCOSYLTRANSFERASE 1 (GRGT1) enhances its expression in Kitaake. GRGT1 localizes to the endoplasmic reticulum and catalyzes glyphosate glycosylation both in vivo and in vitro. Rice lines complemented with GRGT1-GFP rescue the inability of grgt1 knockout mutants to produce glycosylated glyphosate derivatives. Overexpression of GRGT1 in the susceptible Nipponbare cultivar confers glyphosate tolerance by up-regulating glyphosate metabolism to produce glycosylated glyphosate derivatives M329, M331, and M345. This provides a strategy for developing herbicide-tolerant crops, but also offers a potential approach to consequently reduce glyphosate residues in crops.

CRISPR interference (CRISPRi) screens have emerged as powerful tools for dissecting gene function, yet their application to genes with multiple promoters, which comprise over 60% of human genes, remains poorly understood. Here, we demonstrate that CRISPR-dCas9-based screens exhibit widespread promoter specificity, with untargeted promoters often showing compensatory upregulation to maintain gene expression. Leveraging this selective targeting of individual promoters within the same gene, we developed Isoform-Specific single-cell Perturb-Seq to systematically analyse alternative promoter function. Our analysis revealed that alternative promoters in 51.6% of targeted genes drive distinct transcriptional programs. This suggests that promoter selection represents a fundamental mechanism for generating cellular diversity rather than mere transcriptional redundancy. In breast cancer models, this promoter-specific targeting revealed differential effects on drug sensitivity, where distinct estrogen receptor (ESR1) promoters showed opposing influences on tamoxifen response and patient survival. These findings demonstrate the necessity of promoter-level analysis in functional genomics and suggest new strategies for therapeutic intervention through promoter-specific targeting.

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen for which new antimicrobial strategies are urgently needed. To facilitate the establishment of the infection, P. aeruginosa produces a remarkable assortment of both cell-associated and extracellular virulence factors. The expression of numerous virulence traits is regulated by the pqs quorum sensing (QS) system, which relies on multiple enzymes for the biosynthesis of 2-alkyl-4-quinolone (AQ) signal molecules and on the transcriptional regulator PqsR, whose activity is triggered by AQ binding. Herein, we report on the design and synthesis of novel quinazolinone-based PqsR modulators, which led to the identification of two novel compounds endowed with anti-PqsR activity in the submicromolar range. Additionally, these derivatives inhibited the production of PqsR-controlled virulence factors in laboratory strains and clinical isolates of P. aeruginosa.

Non-small cell lung cancer (NSCLC) treatment faces significant challenges due to drug resistance and toxicity. Emerging evidence suggests that ferroptosis, an iron-dependent form of regulated cell death, is a promising therapeutic strategy. We identify Pinostilbene, a natural stilbenoid, as a potent and novel STING agonist. Our findings reveal that Pinostilbene effectively activates the STING/TBK1/IRF3 pathway, leading to the transcriptional upregulation of downstream cytokines. Importantly, we demonstrate that Pinostilbene significantly enhances the sensitivity of lung cancer cells to RSL3-induced ferroptosis. Mechanistically, Pinostilbene promotes the degradation of the iron-storage protein Ferritin Heavy Chain 1 (FTH1), a key negative regulator of ferroptosis. We uncover a novel mechanism in which Pinostilbene induces FTH1 degradation through the ubiquitin-proteasome system via K48-linked polyubiquitination, a process independent of NCOA4-mediated ferritinophagy. This FTH1 degradation increases the labile iron pool, a critical prerequisite for ferroptosis. In vivo, Pinostilbene exhibits robust antitumor efficacy alone and achieves synergistic tumor growth inhibition when combined with RSL3 in a NSCLC mouse model without systemic toxicity. Its therapeutic effect is linked to STING activation and FTH1 downregulation, which coincides with an increase in the ferroptosis biomarker 4-HNE. Furthermore, Pinostilbene enhances antitumor immunity by upregulating inflammatory cytokines and promoting the infiltration and activation of tumor-killing CD8+ T cells, alongside drving anti-tumor M1 polarization of macrophages. Our study highlights the potential of Pinostilbene as a promising therapeutic agent for NSCLC, offering a multifaceted mechanism of action through ferroptosis sensitization and immunostimulation.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, primarily due to its highly fibrotic and immunosuppressive tumor microenvironment (TME), which limits both drug delivery and immune cell infiltration. Epigenetic dysregulation plays a pivotal role in shaping these barriers by controlling transcriptional programs that govern tumor-immune interactions, stromal remodeling, and immune evasion.This review synthesizes current insights into the contribution of aberrant epigenetic mechanisms to PDAC progression and immune resistance. We outline how epigenetic alterations suppress antigen presentation, sustain immunosuppressive cell populations, such as regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages, and upregulate immune checkpoint molecules across cancer and stromal compartments. Emerging evidence shows that epigenetic therapies targeting DNA methyltransferases, histone deacetylases, histone methyltransferases, or bromodomain proteins can restore tumor immunogenicity, reprogram cancer-associated fibroblasts, and promote cytotoxic T cell infiltration. Furthermore, combining epigenetic modulators with immune checkpoint blockade or targeted therapies has demonstrated the capacity to remodel the PDAC TME and convert immunologically 'cold' tumors into more responsive ones. Therefore, we also summarize key completed and ongoing clinical trials in PDAC and solid tumors, emphasizing outcomes and biomarker discoveries that support the translation of epigenetic-immunotherapy combinations into clinical practice. Finally, we discuss persistent challenges that impede progress, including poor drug penetration through the desmoplastic stroma, off-target effects and toxicity of epigenetic agents, tumor hypoxia, adaptive resistance, and the scarcity of physiologically relevant immuno-oncology models.Findings from preclinical and early clinical studies indicate that epigenetic reprogramming represents a promising avenue to overcome PDAC immunoresistance by reactivating antigen presentation, disrupting immunosuppressive cellular networks, and enhancing antitumor immunity. However, realizing this potential will require rationally designed combination regimens, predictive biomarkers for patient stratification, and a deeper understanding of cell type-specific and context-dependent epigenetic regulation. Only through these advances can the integration of epigenetic modulation with immunotherapy and stroma-targeting approaches ultimately redefine therapeutic strategies for patients with PDAC.

Osimertinib resistance remains a major challenge in the treatment of non-small cell lung cancer (NSCLC). Cancer-associated fibroblasts (CAFs) are the most abundant stromal cells in tumor microenvironment (TME), however, its role in osimertinib resistance in NSCLC is not fully understood. In this study, it was found that CAFs promoted osimertinib resistance in NSCLC cells via elevating RNA m7G modification. Methyltransferase 1 (METTL1) in NSCLC cells mediated CAFs' effect on m7G modification, and METTL1 was associated with NSCLC progression and poor prognosis. Further study demonstrates that CAFs upregulated METTL1 in NSCLC cells by secreting HMGB1. By applying MeRIP-seq and RNA-seq, neuroepithelial cell transforming gene 1 (NET1) was identified as a target of METTL1, and enhanced m7G modification of NET1 increased NET1 expression and activated downstream AKT/NF-κB pathway. Importantly, reducing m7G modification by METTL1 knockdown significantly attenuated CAFs' stimulatory effect on osimertinib resistance both in vitro and in vivo. Our study revealed a novel mechanism that CAFs conferred osimertinib resistance in NSCLC cells through modulating m7G modification. These findings underscore the importance of m7G modification in the communication between cancer cells and the TME, and pave the way for finding novel therapeutic strategies to overcome drug resistance by targeting m7G modification.

Despite the transformative impact of osimertinib as a cornerstone targeted therapy for advanced EGFR-mutant non-small cell lung cancer, the emergence of acquired resistance ultimately limits its long-term efficacy. While genetic alterations, tumor microenvironment dynamics, and cancer stem cells contribute to resistance, they inadequately explain its rapid adaptive evolution. This critical knowledge gap points to an underexplored dimension of resistance: the dynamic reprogramming of the epigenetic landscape. This review establishes dynamic histone plasticity--driven by imbalances in key epigenetic modifications such as acetylation and methylation, along with newly recognized marks including lactylation--as a pivotal epigenetic driver of resistance. Evidence demonstrates that these modifications remodel chromatin architecture, reprogram transcriptional networks, compromise DNA damage repair, and stabilize a drug-tolerant persister state, collectively accelerating tumor adaptation during therapeutic pressure. Beyond mechanism, distinct histone-modification signatures are emerging as promising predictive biomarkers for resistance, simultaneously revealing novel, pharmacologically targetable epigenetic vulnerabilities. Leveraging next-generation technologies, we propose an integrated strategy: multimodal epigenetic therapies combined with real-time liquid biopsy profiling to shift from reactive management toward predictive prevention of resistance. By bridging deep epigenomic mechanistic understanding with innovative diagnostic and therapeutic tools, this roadmap provides a proactive, adaptive framework designed to circumvent tumor evolutionary pathways, overcome therapeutic resistance, and prolong patient survival.

Nanoplastics are emerging environmental pollutants ubiquitously found in natural ecosystems. Although studies have shown that nanoplastics can accumulate in the testes of mice and affect spermatogenic cells, the specific toxicological mechanisms remain unclear. To investigate the specific mechanism by which polystyrene nanoplastics induce ferroptosis in mouse spermatocyte-derived GC-2spd(ts) cells and subsequently lead to male reproductive toxicity, this study exposed mouse germ cell lines (GC-1 spg and GC-2spd(ts)) to PS-NPs of two sizes (50 nm and 90 nm). Cell viability assays indicated that GC-2spd(ts) cells were more sensitive to PS-NPs exposure. Transcriptomic and proteomic analyses revealed that PS-NPs exposure induced intracellular reactive oxygen species (ROS) accumulation and significant alterations in related pathways, specifically activating the ferroptosis signaling pathway. Further mechanistic studies demonstrated that PS-NPs disrupted intracellular iron homeostasis, leading to the accumulation of labile Fe2+ , enhanced lipid peroxidation, depletion of the antioxidant glutathione, and mitochondrial dysfunction. At the molecular level, PS-NPs upregulated the expression of iron uptake-related proteins and significantly downregulated the iron exporter protein ferroportin1 (FPN1). In-depth investigation revealed that PS-NPs did not affect the transcriptional level of FPN1 but promoted FPN1 protein degradation by enhancing its ubiquitination modification, subsequently via the proteasome-dependent pathway. This process resulted in blocked cellular iron efflux, iron ion accumulation, and ultimately triggered ferroptosis. This study elucidates the molecular mechanism by which PS-NPs regulate FPN1 degradation through the ubiquitin-proteasome pathway, disrupt iron metabolic homeostasis, and thereby induce ferroptosis in germ cells, providing novel experimental evidence for assessing the male reproductive toxicity of nanoplastics.

The hypothalamic-pituitary-interrenal (HPI) axis mediates stress responses in fish. Previous work showed that dietary supplementation with B vitamins attenuated cortisol response to acute stress, whereas dietary genistein produced high basal levels of cortisol and altered stress responsiveness. In the present study, we investigated the expression of key genes of the HPI axis and selected hepatic targets to better characterize these responses. Cortisol was correlated with nr3c1 expression in the pituitary of control fish. Conversely, B vitamins supplementation was associated with changes in the relationship between plasma cortisol levels and nr3c1 expression across tissues, including higher basal higher basal expression expression in the head kidney. In parallel, lower hepatic oxidative stress following acute stress in this fish was associated with differences in cortisol levels and liver metabolic responses. Dietary genistein was associated with altered pituitary regulation of pomc paralogs, characterized by reduced pomcb and elevated pomca expression after stress. These expression patterns persisted 4.5 months after dietary exposure, with pomca becoming the only gene showing a positive association with plasma cortisol levels. In addition, genistein supplementation was associated with higher basal expression of the ACTH receptor (mc2r) in the head kidney. Stress challenges performed up to one year after the nutritional intervention revealed convergence of cortisol responses among dietary groups. Overall, these results indicate that dietary components can produce short-term changes in the regulation of the HPI axis. Further studies are required to clarify the mechanisms underlying the dietary effects observed in this study.

Nanoencapsulation, especially in the form of PEGylated niosomes, is considered a novel strategy in drug delivery that improves the solubility and bioavailability of compounds. Silibinin, as a flavonoid, has low bioavailability despite its antioxidant, anti-inflammatory, and neuroprotective properties. Therefore, the present study was designed to investigate the effect of PEGylated niosomal nanoparticles containing Silibinin (Sili-PEG-Nios-NPs) on memory and learning, inflammatory pathways, and morphological changes in the hippocampus in an animal model of Alzheimer's disease. In this study, Sili-PEG-Nios-NPs were synthesized and characterized, followed by Alzheimer's induction in rats via intraventricular Aβ1-42 injection. Rats were divided into five groups (n = 8): a healthy control group, an Alzheimer's model group, a sham group (Alzheimer's model + PBS), an Alzheimer's model group + free Silibinin, and an Alzheimer's model group + Sili-PEG-Nios-NPs. Treatments were administered orally (100 mg/kg for 15 days). Cognitive function was assessed using the Morris water maze and shuttle box tests. Tissue analysis included Real-time PCR for inflammasome genes, Congo red staining for amyloid plaques, and cresyl violet staining for hippocampal pyramidal cells. The results demonstrated that both Silibinin formulations (free and nano-encapsulated) significantly improved spatial memory and learning compared to the disease model group. However, Sili-PEG-Nios-NPs were significantly more effective than free Silibinin and also significantly reduced the expression of inflammasome genes, Aβ plaque formation, and hippocampal neuronal cell destruction. These findings suggest that PEGylated Silibinin-loaded niosomal nanoparticles are an effective option for improving Alzheimer's disease complications by modulating the inflammasome pathway and amyloid plaque aggregation.

Radiation-induced lung injury (RILI) is one of the most prevalent complications of thoracic radiotherapy (RT). Lupenone (LUP) is a bioactive compound isolated from Acacia catechul.f. Willci. and is believed to be capable of treating respiratory and lung diseases.

Ligusticum sinense cv. Chuanxiong (Chuanxiong) is threatened by excessive cadmium (Cd), affecting its safety and quality. This study aimed to characterize Cd distribution in Chuanxiong roots (subcellular level) and clarify its key response mechanisms to Cd stress, using ICP-MS, SEM-EDS, and transcriptome analysis. The results showed that Cd was mainly enriched in root cell walls; Cd stress significantly upregulated the activities of polyphenol oxidase (PPO, +11.50 %), cinnamyl alcohol dehydrogenase (CAD, +31.05 %), catechol O-methyltransferase (COMT, +28.28 %), and isocitrate lyase (ICL, +121.93 %) compared with the control; Cd-related genes (NRAMP5, CAX3, YSL7, etc.) and key transcription factors (BHLH162, ERF109, etc.) were markedly upregulated. Furthermore, Chuanxiong roots achieved growth-stress resistance balance (exhibiting hormesis) via the carbon metabolism pathway (the material and energy basis), the sulfur metabolism (the core detoxification pathway), and the phenylpropanoid biosynthesis (structural and chemical defense). This study provides a theoretical basis for developing precise regulatory techniques to reduce heavy metals (HMs) accumulation in medicinal plants, and thus safeguard their quality and safety.

Microplastics, as a novel environmental pollutant, are now widely distributed in agricultural soils globally and pose a threat to plant growth and development. Within apple orchards, the ageing and degradation of agricultural plastic films leads to soil microplastic contamination, inhibiting the growth of apple trees. This study employed apple rootstocks 'M9' and 'B9' alongside the apple cultivar 'Gala3', treating them with polystyrene nanoplastics (PS-NPs) at varying concentrations (0, 5, 10, 20, 40, 80 mg/L). Results indicate that low PS-NP concentrations promote apple seedling growth, whereas high concentrations inhibit root development and growth while reducing antioxidant capacity. Sensitivity to PS-NPs varies among genotypes, with 'M9' exhibiting the lowest sensitivity and 'Gala3' the highest. Based on these phenotypic differences, transcriptomic and metabolomic sequencing was performed on these two cultivars. Integrated transcriptomic-metabolomic analysis revealed that PS-NPs disrupted zeatin metabolic homeostasis by upregulating CKX gene and downregulating UGT73C gene. This accelerated the metabolism of active zeatin (e.g., trans-zeatin) and leading to dihydrozeatin (DHZ) accumulation, thereby impairing the activation capacity of the antioxidant defence system and ultimately exacerbating oxidative damage. These findings establish a foundation for systematic investigation into the molecular mechanisms underlying apple responses to nanoplastics, offering novel perspectives for future crop production and environmental safety.

Mushrooms have been found to be one of the main sources of nutrients to man, but their nutraceutical approach to life science is still being studied. The proposed concept that mushrooms serve both as food and medicine has placed mushrooms as nutraceuticals. Mushrooms have been discovered to be a good source of a variety of nutritional bioactive compounds with numerous health benefits as well as medicinal properties. The aim of this research was to evaluate the modulatory effect of Pleurotus ostreatus extract on Staphylococcus aureus uspA+ gene expression and antibiotic susceptibility. In this study, indigenous P. ostreatus mushroom extract used was screened for its bioactive phytochemical contents. The effect of P. ostreatus extract on uspA+ S. aureus gene expression and antibiotic susceptibility was conducted using reverse transcriptase polymerase chain reaction (RT-PCR) technique and the Kirby-Bauer test method, respectively. Results obtained showed that uspA genes were domicile in S. aureus and were expressed when exposed to sublethal antibiotic concentrations, whereas the presence of P. ostreatus extract inhibit uspA+ S. aureus gene expression. The susceptibility results showed that inhibition zone diameters (IZDs) were found to be in the ranges between 0- and 8-mm diameter for unexposed S. aureus uspA+ genes to mushroom extract, whereas the IZDs increased to about 15 to 20 mm diameter when exposed to mushroom extract. The mushroom bioactive compounds quantitative analysis showed high flavonoid (63.4 ± 3.6 mg/dL), tannins (29.27 ± 1.0 mg/dL) and phenols (22.0 ± 2.7 mg/dL). Based on these research findings, it shows that P. ostreatus extract can serve as a modulating agent that can be used to regulate the expression of uspA+ gene in S. aureus and can optimize the susceptibility enhancement in antibiotic-mediated S. aureus.