The effects of photochemical aging and interactions with secondary organic aerosols on cellular toxicity of combustion particles.

Fine particulate matter (PM2.5) is associated with numerous adverse health effects, including pulmonary and cardiovascular diseases and premature death. Significant contributors to ambient PM2.5 include combustion particles and secondary organic aerosols (SOA). Combustion particles enter the atmosphere and undergo an aging process that changes their shape and composition, but there is limited study on the health effects of combustion particle aging and interactions with SOA. This study aimed to understand how biological responses to combustion particles would be affected by atmospheric aging and interaction with anthropogenic SOA. Fresh combustion particles underwent photochemical aging in a potential aerosol mass (PAM) oxidation flow reactor and interacted with SOA produced by the oxidation of toluene vapor in the PAM reactor. Photochemical aging and SOA interactions lead to significant changes in the PAH content and oxidative potential of the particle. Photochemical aging and SOA interactions also affected the biological responses, such as the inflammatory response and CYP1A1 induction of the particles in monoculture and coculture cells. These findings highlight the significance of photochemical aging and SOA interactions on the composition and cellular responses of combustion particles.

Upconversion nanoparticles-CuMnO2 nanoassemblies for NIR-excited imaging of reactive oxygen species in vivo.

Here, we designed a ratiometric luminescent nanoprobe based on lanthanide-doped upconversion nanoparticles-CuMnO2 nanoassemblies for rapid and sensitive detection of reactive oxygen species (ROS) levels in living cells and mouse. CuMnO2 nanosheets exhibit a wide absorption range of 300-700 nm, overlapping with the visible-light emission of upconversion nanoparticles (UCNPs), resulting in a significant upconversion luminescence quenching. In an acidic environment, H2O2 can promote the redox reaction of CuMnO2, leading to its dissociation from the surface of UCNPs and the restoration of upconversion luminescence. The variation in luminescence intensity ratio (UCL475/UCL450) were monitored to detect ROS levels. The H2O2 nanoprobe exhibited a linear response in the range of 0.314-10 µM with a detection limit of 11.3 nM. The biological tests proved the excellent biocompatibility and low toxicity of obtained UCNPs-CuMnO2 nanoassemblies. This ratiometric luminescent nanoprobe was successfully applied for the detection of exogenous and endogenous ROS in live cells as well as in vivo ROS quantitation. The dual transition metal ions endow this probe efficient catalytic decomposition capabilities, and this sensing strategy broadens the application of UCNPs-based nanomaterials in the field of biological analysis and diagnosis.

Mn/S diatomic sites in C3N4 to enhance O2 activation for photocatalytic elimination of emerging pollutants.

Oxygen activation leading to the generation of reactive oxygen species (ROS) is essential for photocatalytic environmental remediation. The limited efficiency of O2 adsorption and reductive activation significantly limits the production of ROS when employing C3N4 for the degradation of emerging pollutants. Doping with metal single atoms may lead to unsatisfactory efficiency, due to the recombination of photogenerated electron-hole pairs. Here, Mn and S single atoms were introduced into C3N4, resulting in the excellent photocatalytic performances. Mn/S-C3N4 achieved 100% removal of bisphenol A, with a rate constant 11 times that of pristine C3N4. According to the experimental results and theoretical simulations, S-atoms restrict holes, facilitating the photo-generated carriers' separation. Single-atom Mn acts as the O2 adsorption site, enhancing the adsorption and activation of O2, resulting the generation of ROS. This study presents a novel approach for developing highly effective photocatalysts that follows a new mechanism to eliminate organic pollutants from water.

Conversion of albumin into a BODIPY-like photosensitizer by a flick reaction, tumor accumulation and photodynamic therapy.

The accumulation of photosensitizers (PSs) in lesion sites but not in other organs is an important challenge for efficient image guiding in photodynamic therapy. Cancer cells are known to express a significant number of albumin-binding proteins that take up albumin as a nutrient source. Here, we converted albumin to a novel BODIPY-like PS by generating a tetrahedral boron environment via a flick reaction. The formed albumin PS has almost the same 3-dimensional structural feature as free albumin because binding occurs at Sudlow Site 1, which is located in the interior space of albumin. An i.v. injection experiment in tumor-bearing mice demonstrated that the human serum albumin PS effectively accumulated in cancer tissue and, more surprisingly, albumin PS accumulated much more in the cancer tissue than in the liver and kidneys. The albumin PS was effective at killing tumor cells through the generation of reactive oxygen species under light irradiation. The crystal structure of the albumin PS was fully elucidated by X-ray crystallography; thus, further tuning of the structure will lead to novel physicochemical properties of the albumin PS, suggesting its potential in biological and clinical applications.

Fluorescence and photoacoustic (FL/PA) dual-modal probe: Responsive to reactive oxygen species (ROS) for atherosclerotic plaque imaging.

Accurate and early detection of atherosclerosis (AS) is imperative for their effective treatment. However, fluorescence probes for efficient diagnosis of AS often encounter insufficient deep tissue penetration, which hinders the reliable assessment of plaque vulnerability. In this work, a reactive oxygen species (ROS) activated near-infrared (NIR) fluorescence and photoacoustic (FL/PA) dual model probe TPA-QO-B is developed by conjugating two chromophores (TPA-QI and O-OH) and ROS-specific group phenylboronic acid ester. The incorporation of ROS-specific group not only induces blue shift in absorbance, but also inhibits the ICT process of TPA-QO-OH, resulting an ignorable initial FL/PA signal. ROS triggers the convertion of TPA-QO-B to TPA-QO-OH, resulting in the concurrent amplification of FL/PA signal. The exceptional selectivity of TPA-QO-B towards ROS makes it effectively distinguish AS mice from the healthy. The NIR emission can achieve a tissue penetration imaging depth of 0.3 cm. Moreover, its PA775 signal possesses the capability to penetrate tissues up to a thickness of 0.8 cm, ensuring deep in vivo imaging of AS model mice in early stage. The ROS-triggered FL/PA dual signal amplification strategy improves the accuracy and addresses the deep tissue penetration problem simultaneously, providing a promising tool for in vivo tracking biomarkers in life science and preclinical applications.

pH-responsive and nanoenzyme-loaded artificial nanocells relieved osteomyelitis efficiently by synergistic chemodynamic and cuproptosis therapy.

Osteomyelitis is an osseous infectious disease that primarily affects children and the elderly with high morbidity and recurrence. The conventional treatments of osteomyelitis contain long-term and high-dose systemic antibiotics with debridements, which are not effective and lead to antibiotic resistance with serious side/adverse effects in many cases. Hence, developing novel antibiotic-free interventions against osteomyelitis (especially antibiotic-resistant bacterial infection) is urgent and anticipated. Here, a bone mesenchymal stem cell membrane-constructed nanocell (CFE@CM) was fabricated against osteomyelitis with the characteristics of acid-responsiveness, hydrogen peroxide self-supplying, enhanced chemodynamic therapeutic efficacy, bone marrow targeting and cuproptosis induction. Notably, mRNA sequencing was applied to unveil the underlying biological mechanisms and found that the biological processes related to copper ion binding, oxidative phosphorylation, peptide biosynthesis and metabolism, etc., were disturbed by CFE@CM in bacteria. This work provided an innovative antibiotic-free strategy against osteomyelitis through copper-enhanced Fenton reaction and distinct cuproptosis, promising to complement the current insufficient therapeutic regimen in clinic.

The Synergy between Antibiotics and the Nanoparticle-Based Photodynamic Effect.

Antimicrobial resistance (AMR) is a growing global health concern, necessitating innovative strategies beyond the development of new antibiotics. Here, we employed NdYVO4:Eu3+ nanoparticles, which can persistently produce reactive oxygen species (ROS) after stopping the light, as a model of photodynamic nanoparticles and demonstrated that the photodynamic effect can serve as an adjuvant with antibiotics to effectively reduce their minimum inhibitory concentration. These preirradiated nanoparticles could penetrate the bacterial cell membrane, significantly enhancing the potency of antibiotics. We showed that the synergy effect could be attributed to disrupting crucial cellular processes by ROS, including damaging cell membrane proteins, interfering with energy supply, and inhibiting antibiotic metabolism. Our findings suggested that complementing the photodynamic effect might be a robust strategy to enhance antibiotic potency, providing an alternative antibacterial treatment paradigm.

TLR2 reprograms glucose metabolism in CD4+ T cells of rheumatoid arthritis patients to mediate cell hyperactivation and TNF-α secretion.

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which activated CD4+ T cells participate in the disease process by inducing inflammation. We aimed to investigate the role of Toll-like receptor 2 (TLR2) on CD4+ T cells in RA patients, and to elucidate the underlying mechanisms by which TLR2 contributes to the pathogenesis of RA. METHODS: Serum samples were collected from RA patients and healthy controls. Soluble TLR2 levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Flow cytometry was employed to assess the TLR2 expression level, activation status, cytokine production, reactive oxygen species (ROS) levels, and glucose uptake capacity of CD4+ T cells. Quantitative polymerase chain reaction (qPCR) was used to measure the expression of enzymes associated with glucose and lipid metabolism. The concentration of lactic acid in the culture supernatant was determined using a dedicated detection kit. RESULTS: RA patients had higher levels of TLR2 in their serum, which positively correlated with C-reactive protein and rheumatoid factor. The expression level of TLR2 in CD4+ T cells of RA patients was increased, and TLR2+ cells showed higher activation levels than TLR2- cells. Activation of TLR2 in CD4+ T cells of RA patients promoted their activation, TNF-α secretion, and increased production of ROS. Furthermore, TLR2 activation led to changes in enzymes related to glucose metabolism, causing a shift in glucose metabolism towards the pentose phosphate pathway. Blocking oxidative phosphorylation and the pentose phosphate pathway had varying effects on CD4+ T cell function. CONCLUSION: TLR2 reprograms the glucose metabolism of CD4+ T cells in RA patients, contributing to the development of RA through ROS-mediated cell hyperactivation and TNF-α secretion. Key Points • TLR2 is upregulated in CD4+ T cells of RA patients and correlates with disease severity markers such as CRP and RF. • Activation of TLR2 in CD4+ T cells promotes cell activation, TNF-α secretion, and increased ROS production, contributing to the pathogenesis of RA. • TLR2 activates glucose metabolism in CD4+ T cells, shifting towards the pentose phosphate pathway, which may be a novel therapeutic target for RA treatment. • Blocking glucose metabolism and ROS production can reduce CD4 + T cell hyperactivation and TNF-α secretion, indicating potential therapeutic strategies for RA management.

A Robust ROS Generation and Ferroptotic Lipid Modulation Nanosystem for Mutual Reinforcement of Ferroptosis and Cancer Immunotherapy.

Ferroptosis initiation is often utilized for synergistic immunotherapy. While, current immunotherapy is limited by an immunosuppressive tumor microenvironment (TME), and ferroptosis is limited by insufficient reactive oxygen species (ROS) and ferroptotic lipids in tumor cells. Here, an arachidonic acid (AA) loaded nanosystem (CTFAP) is developed to mutually reinforce ferroptosis and cancer immunotherapy by augmenting ROS generation and modulating ferroptotic lipids. CTFAP is composed of acid-responsive core calcium peroxide (CaO2) nanoparticles, ferroptotic lipids sponsor AA, tetracarboxylic porphyrin (TCPP) and Fe3+ based metal-organic framework structure, and biocompatible mPEG-DSPE for improved stability. Once endocytosed by tumor cells, CTFAP can release oxygen (O2) and hydrogen peroxide (H2O2) in the acidic TME, facilitating TCPP-based sonodynamic therapy and Fe3+-mediated Fenton-like reactions to generate substantial ROS for cell ferroptosis initiation. The immunogenic cell death (ICD) after ferroptosis promotes interferon γ (IFN-γ) secretion to up-regulate the expression of long-chain family member 4 (ACSL4), cooperating with the released AA from CTFAP to accelerate the accumulation of lipid peroxidation (LPO) and thereby promoting ferroptosis in cancer cells.CTFAP with ultrasound treatment efficiently suppresses tumor growth, has great potential to challenges in cancer immunotherapy.

A novel C-4-modified isotetrone acts as a potent bio-enhancer to augment the activities of anti-tuberculosis drugs against Mycobacterium tuberculosis.

Mycobacterium tuberculosis is a deadly pathogen that claims millions of lives every year. Current research focuses on finding new anti-tuberculosis drugs that are safe and effective, with lesser side effects and toxicity. One important approach is to identify bio-enhancers that can improve the effectiveness of anti-tuberculosis drugs, resulting in reduced doses and shortened treatment times. The present study investigates the use of C-4 modified isotetrones as bio-enhancers. A series of studies suggest an isotetrone, labeled as C11, inhibits growth, improves MIC, MBC and enhances the killing of M. tuberculosis H37Rv strain when used in combination with the first line and injectable anti-TB drugs in a dose-dependent manner. The combination of C11 and rifampicin also reduces the generation of spontaneous mutants against rifampicin and reaches a mutation prevention concentration (MPC) with moderate rifampicin concentrations. The identified compounds are effective against the MDR strain of M. tuberculosis and non-cytotoxic in HepG2 cells. We find that C11 induces the generation of reactive oxygen species (ROS) inside macrophages and within bacteria, resulting in better efficacy.

Chlorella-enriched hydrogels protect against myocardial damage and reactive oxygen species production in anin vitroischemia/reperfusion model using cardiac spheroids.

Microalgae have emerged as promising photosynthetic microorganisms for biofabricating advanced tissue constructs, with improved oxygenation and reduced reactive oxygen species production. However, their use in the engineering of human tissues has been limited due to their intrinsic growth requirements, which are not compatible with human cells. In this study, we first formulated alginate-gelatin (AlgGel) hydrogels with increasing densities ofChlorella vulgaris. Then, we characterised their mechanical properties and pore size. Finally, we evaluated their effects on cardiac spheroid (CS) pathophysiological response under control and ischemia/reperfusion (I/R) conditions. Our results showed that the addition ofChlorelladid not affect AlgGel mechanical properties, while the mean pore size significantly decreased by 35% in the presence of the 107cells mL-1microalgae density. Under normoxic conditions, the addition of 107Chlorellacells mL-1significantly reduced CS viability starting from 14 days in. No changes in pore size nor CS viability were measured for hydrogels containing 105and 106Chlorellacells mL-1. In our I/R model, allChlorella-enriched hydrogels reduced cardiac cell sensitivity to hypoxic conditions with a corresponding reduction in reactive oxygen species (ROS) production, as well as protected against I/R-induced reduction in cell viability. Altogether, our results support a promising use ofChlorella-enriched Alg-Gel hydrogels for cardiovascular tissue engineering. .

Singlet oxygen-mediated photochemical cross-linking of an engineered fluorescent flavoprotein iLOV.

Genetically-encoded photoactive proteins are integral tools in modern biochemical and molecular biological research. Within this tool box, truncated variants of the phototropin 2 light-oxygen-voltage (LOV) flavoprotein have been developed to photochemically generate singlet oxygen (1O2) in vitro and in vivo, yet the effect of 1O2 on these genetically encoded photosensitizers remains underexplored. In this study, we demonstrate that the "improved" LOV (iLOV) flavoprotein is capable of photochemical 1O2 generation. Once generated, 1O2 induces protein oligomerization via covalent cross-linking. The molecular targets of protein oligomerization by cross-linking are not endogenous tryptophans or tyrosines, but rather primarily histidines. Substitution of surface-exposed histidines for serine or glycine residues effectively eliminates protein cross-linking. When used in biochemical applications, such protein-protein cross-links may interfere with native biological responses to 1O2, which can be ameliorated by substitution of the surface exposed histidines of iLOV or other 1O2-generating flavoproteins.

Famotidine increases cellular phospho-tyrosine levels.

While vaccines were being developed, the SARS-CoV-2 pandemic triggered a race to find known drugs that could be quickly repurposed to treat patients. One such candidate was famotidine, which retrospective cohort studies had shown increased survival in hospitalized patients. Computational studies had suggested that famotidine may target early viral proteases; however, ultimately, famotidine was shown not to function as a viral inhibitor. In contrast, we have observed a change in the cellular levels of phospho-tyrosine in A549 lung epithelial cells following treatment with famotidine. This quick change in phosphorylation was due mainly to a dose-dependent increase in cellular production of H2O2. Notably, these changes in phospho-tyrosine levels were able to affect cell signaling; we detected an increased short- and long-term response to IFNα stimulation. Our results suggest that famotidine can increase the anti-viral state of non-infected cells thereby potentially increasing viral resistance.

Assessment of the effect of ascorbic acid, sodium isoascorbate and calcium ascorbate treatments on the browning and wound healing process of fresh-cut potatoes.

Browning significantly affects consumer perception, while texture hardening due to wound healing further reduces the commercial value of fresh-cut potatoes. This study evaluated the effects of 5 g L-1 ascorbic acid (AA), sodium isoascorbate (SI), and calcium ascorbate (CA) on browning and wound healing during ambient storage. The results indicated that AA and SI were more effective than CA and the control in delaying browning and wound healing. By day 3, browning levels in the AA and SI groups were reduced to 65 % and 62 % of the control, respectively, while lignin content decreased by 35 % and 40 %. Additionally, AA and SI treatments reduced reactive oxygen species (ROS) and improved antioxidant capacity, preserving appearance and texture. This study provides insights into the mechanisms of browning and wound healing, suggesting potential strategies for extending the shelf life and improving the quality of fresh-cut potatoes.

When Metal Complexes Evolve, and a Minor Species Is the Most Active: the Case of Bis(Phenanthroline)Copper in the Catalysis of Glutathione Oxidation and Hydroxyl Radical Generation.

Several copper-ligands, including 1,10-phenanthroline (Phen), have been investigated for anticancer purposes based on their capacity to bind excess copper (Cu) in cancer tissues and form redox active complexes able to catalyse the formation of reactive oxygen species (ROS), ultimately leading to oxidative stress and cell death. Glutathione (GSH) is a critical compound as it is highly concentrated intracellularly and can reduce and dissociate copper(II) from the ligand forming poorly redox-active copper(I)-thiolate clusters. Here we report that Cu-Phen2  speciation evolves in physiologically relevant GSH concentrations. Experimental and computational experiments suggest that at pH 7.4 mostly copper(I)-GSH clusters are formed, but a minor species of copper(I) bound to one Phen and forming ternary complexes with GSH (GS-Cu-Phen) is the redox active species, oxidizing quite efficiently GSH to GSSG and forming HO• radicals. This minor active species becomes more populated at lower pH, such as typical lysosomal pH 5, resulting in faster GSH oxidation and HO• production. Consistently, cell culture studies showed lower toxicity of Cu-Phen2 upon inhibition of lysosomal acidification. Overall, this study underscores that sub-cellular localisation can considerably influence the speciation of Cu-based drugs and that minor species can be the most redox- and biologically- active.

Single-Atom Catalysts with Isolated Cu1-N4 Sites for Atopic Dermatitis Cascade Catalytic Therapy via Activating PPAR Signaling.

Atopic dermatitis (AD) is one of the most common allergic skin disorders affecting over 230 million people worldwide, while safe and efficient therapeutic options for AD are currently rarely available. Reactive oxygen species (ROS) accumulation plays a key role in AD's disease progression. Therefore, a novel single-atom catalyst is designed with isolated Cu1-N4 sites anchored on carbon support (Cu1-N4 ISAC), featuring triple antioxidant enzyme-mimicking activities, for efficient AD cascade catalytic therapy (CCT). The excellent superoxide dismutase (SOD)-, glutathione peroxidase (GPx)-, and ascorbate peroxidase (APx)-like activities of Cu1-N4 ISACs enable the sequential conversion of O2•- to H2O2 and then to harmless H2O, thereby protecting keratinocytes from oxidative stress damage. Notably, two novel experimental methods are developed to directly prove the SOD-GPx and SOD-APx cascade catalytic activities for the first time. In vivo experiments show that Cu1-N4 ISACs are more potent than a recommended typical medicine (halcinonide solution). Additionally, RNA sequencing and bioinformatic analysis reveal that Cu1-N4 ISACs reduce inflammation and inhibit ROS production by activating PPAR signaling, which is aberrantly reduced in AD. Therefore, the synthesized catalytic medicine offers an alternative to alleviate AD and has the potential to serve as PPAR agonists for treating similar diseases.

Oral colon-targeted pH-responsive polymeric nanoparticles loading naringin for enhanced ulcerative colitis therapy.

An oral colon-targeted drug delivery system holds great potential in preventing systemic toxicity and preserving the therapeutic benefits of ulcerative colitis (UC) treatment. In this study, we developed a negatively charged PLGA-PEG nanoparticle system for encapsulating naringin (Nar). Additionally, chitosan and mannose were coated on the surface of these nanoparticles to enhance their mucosal adsorption and macrophage targeting abilities. The resulting nanoparticles, termed MC@Nar-NPs, exhibited excellent resistance against decomposition in the strong acidic gastrointestinal environment and specifically accumulated at inflammatory sites. Upon payload release, MC@Nar-NPs demonstrated remarkable efficacy in alleviating colon inflammation as evidenced by reduced levels of pro-inflammatory cytokines in both blood and colon tissues, as well as the scavenging of reactive oxygen species (ROS) in the colon. This oral nanoparticle delivery system represents a novel approach to treating UC by utilizing Chinese herbal ingredient-based oral delivery and provides a theoretical foundation for local and precise intervention in specific UC treatment.

Protective effect of long-chain polyunsaturated fatty acids on hepatorenal syndrome in rats.

BACKGROUND: Hepatorenal syndrome (HRS) is the most prevalent form of acute kidney injury in cirrhotic patients. It is characterized by reduced renal blood flow and represents the most severe complication in cirrhotic patients with advanced disease. Previous research has indicated that antioxidants can delay the onset of a hyperdynamic circulatory state in cirrhosis and improve renal function in HRS patients. Regular omega-3 supplementation has significantly reduced the risk of liver disease. This supplementation could represent an additional therapy for individuals with HRS. AIM: To evaluated the antioxidant effect of omega-3 polyunsaturated fatty acid supplementation on the kidneys of cirrhotic rats. METHODS: Secondary biliary cirrhosis was induced in rats by biliary duct ligation (BDL) for 28 d. We used 24 male Wistar rats divided into the following groups: I (control); II (treated with omega-3, 1 g/kg of body weight); III (BDL treated with omega-3, 1 g/kg of body weight); and IV (BDL without treatment). The animals were killed by overdose of anesthetic; the kidneys were dissected, removed, frozen in liquid nitrogen, and stored in a freezer at -80℃ for later analysis. We evaluated oxidative stress, nitric oxide (NO) metabolites, DNA damage by the comet assay, cell viability test, and apoptosis in the kidneys. Data were analyzed by one-way analysis of variance, and means were compared using the Tukey test, with P ≤ 0.05. RESULTS: Omega-3 significantly decreased the production of reactive oxygen species (P < 0.001) and lipoperoxidation in the kidneys of cirrhotic rats treated with omega-3 (P < 0.001). The activity of the antioxidant enzymes superoxide dismutase and catalase increased in the BDL+omega-3 group compared to the BDL group (P < 0.01). NO production, DNA damage, and caspase-9 cleavage decreased significantly in the omega-3-treated BDL group. There was an increase in mitochondrial electrochemical potential (P < 0.001) in BDL treated with omega-3 compared to BDL. No changes in the cell survival index in HRS with omega-3 compared to the control group (P > 0.05) were observed. CONCLUSION: The study demonstrates that omega-3 can protect cellular integrity and function by increasing antioxidant enzymes, inhibiting the formation of free radicals, and reducing apoptosis.

Unveiling superior phenol detoxification and degradation ability in Candida tropicalis SHC-03: a comparative study with Saccharomyces cerevisiae BY4742.

This study examined the phenol degradation capabilities and oxidative stress responses of Candida tropicalis SHC-03, demonstrating its metabolic superiority and resilience compared to Saccharomyces cerevisiae BY4742 in a culture medium with phenol as the sole carbon source. Through comparative growth, transcriptomic, and metabolomic analyses under different phenol concentrations, this study revealed C. tropicalis SHC-03's specialized adaptations for thriving in phenol as the sole carbon source environments. These include a strategic shift from carbohydrate metabolism to enhanced phenol degradation pathways, highlighted by the significant upregulation of genes for Phenol 2-monoxygenase and Catechol 1,2-dioxygenase. Despite phenol levels reaching 1.8 g/L, C. tropicalis exhibits a robust oxidative stress response, efficiently managing ROS through antioxidative pathways and the upregulation of genes for peroxisomal proteins like PEX2, PEX13, and PMP34. Concurrently, there was significant upregulation of genes associated with membrane components and transmembrane transporters, enhancing the cell's capacity for substance exchange and signal transduction. Especially, when the phenol concentration was 1.6 g/L and 1.8 g/L, the degradation rates of C. tropicalis towards it were 99.47 and 95.91%, respectively. Conversely, S. cerevisiae BY4742 shows limited metabolic response, with pronounced growth inhibition and lack of phenol degradation. Therefore, our study not only sheds light on the molecular mechanisms underpinning phenol tolerance and degradation in C. tropicalis but also positions this yeast as a promising candidate for environmental and industrial processes aimed at mitigating phenol pollution.