Search Results (10,284)

The intrinsic weakness of the budding yeast Saccharomyces cerevisiae in xylose utilization limits its application in biological manufacturing using lignocellulosic biomass. Although the natural yeast strain S. cerevisiae YB-2625 exhibits superior innate xylose-fermenting capability, the underlying mechanisms remain largely unexplored. Here, we employed comparative multi-omics to systematically dissect the molecular basis of its high stress tolerance and superior xylose consumption. Comparative genomics revealed 73,842 single nucleotide polymorphisms (SNPs) and 5191 small insertions/deletions (InDels) in YB-2625 relative to S288C, with significant enrichment in genes associated with chromatin remodeling, transcriptional regulation, and stress signaling. Integration of genomic and transcriptomic data identified candidate variants in key regulators. Functional validation further demonstrated that Tra1, a component of the SAGA, SLIK, and NuA4 histone acetyltransferase complexes, acts as a global regulator with growth-coupled effects on stress tolerance and xylose metabolism. Deletion of TRA1 significantly reduced the final biomass in xylose medium. Moreover, deletion of RTT109 specifically impaired growth on xylose without affecting any of the tested stress tolerance phenotypes. We further examined global chromatin accessibility changes upon deletion of the histone acetyltransferase gene NGG1, a manipulation previously shown to substantially enhance xylose utilization in the engineered YB-2625 background. ATAC-seq analysis revealed that loss of Ngg1 alters chromatin accessibility at loci governing carbohydrate metabolism and stress responses, thereby establishing a direct link between epigenetic remodeling and the superior phenotype of YB-2625. Our findings provide a basis for deciphering the regulatory circuitry governing xylose utilization in recombinant yeast and for the rational engineering of robust strains for lignocellulosic bioconversion. Full article

Anthropogenic pollution of aquatic ecosystems presents a significant global challenge, underscoring the urgent need for resilient, biologically mediated remediation strategies. In this context, microalgae have emerged as a compelling solution, owing to their inherent adaptability to diverse environments and their capacity for efficient contaminant mitigation through bioremediation. These organisms possess the potential to sequester and remove a broad spectrum of pollutants from wastewater streams, including excess nutrients, organic substrates, heavy metals, and various emerging contaminants. Specifically, their metabolic versatility allows these microorganisms to tolerate and degrade complex substances such as recalcitrant micropollutants and hydrocarbons even under fluctuating environmental conditions. This review evaluates extremophilic microalgae as specialized biological agents capable of functioning under harsh anthropogenic stressors that may constrain the performance of microalgal strains commonly investigated for wastewater treatment. Their distinctive stress tolerance may provide advantages for treating wastewater characterized by extreme physicochemical conditions. By examining the unique metabolic pathways of these extremophiles, this analysis addresses critical gaps in the current bioremediation literature regarding the practical scalability and economic viability of integrating such specialized biomass into large-scale treatment infrastructure. Full article

The functional expression of plant growth-promoting (PGP) traits in soil actinobacteria is conditioned by abiotic factors, yet the combined effects of pH and temperature on their metabolic profiles and the stability of these profiles after encapsulated formulation and post-processing stress remain insufficiently characterized. This study aimed to evaluate the physiological plasticity of native actinobacteria and the expression of plant growth-promoting (PGP) traits under different pH and temperature conditions, as well as their stability after encapsulation, dehydration, and exposure to UV irradiation. Strains isolated from a semi-arid agricultural soil were analyzed to determine their ability to produce indole-3-acetic acid (IAA), siderophores, and phosphatases, as well as their ability to fix nitrogen, degrade cellulose, and tolerate salt stress. Temperature and pH significantly affected all evaluated PGP traits (p < 0.001), and their expression was not directly associated with biomass production. Two strains, S1 and S4, exhibited the highest overall PGP indices. Strain S1 maximized IAA and siderophore production under neutral conditions (pH 7.0, 30 °C), whereas strain S4 maintained more stable phosphatase activity across the tested pH and temperature ranges. Cell viability remained above 85% after encapsulation and dehydration. Dehydration enhanced IAA and siderophore production in strain S1, while strain S4 exhibited transient metabolic activation under UV irradiation in non-dehydrated capsules. The encapsulation matrix preserved cell viability more effectively than it preserved the complete PGP functional profile, indicating that viability alone is an insufficient criterion for evaluating the technological success of alginate-based bioinoculant formulations. These findings highlight the importance of integrating environmental preconditioning and functional stability assessments into the development of robust microbial bioinoculants adapted to agricultural systems subjected to fluctuating environmental conditions. Full article

Background: Streptococcus suis serotype 2 is a major zoonotic pathogen responsible for severe systemic infections in pigs and humans, including septicemia, meningitis, and high mortality outcomes. Cefquinome, a fourth-generation β-lactam antibiotic widely used in veterinary medicine, is commonly applied for the treatment of S. suis infections. However, optimized dosing strategies remain insufficiently defined, particularly under conditions of varying bacterial burden, inoculum size, and reduced susceptibility or resistance phenotypes. These factors may significantly alter pharmacodynamic responses and compromise the predictive value of conventional MIC-based approaches. Objectives: This study aimed to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of cefquinome against S. suis serotype 2 using an integrated ex vivo serum time-kill experiments and semi-mechanistic PK/PD modeling. A secondary objective was to evaluate optimized dosing regimens across different inoculum levels and susceptibility phenotypes, including a cefquinome-resistant mutant. Methods: Cefquinome pharmacokinetics following intramuscular administration at 2 and 4 mg/kg in piglets were described using a two-compartment model. Dose proportionality, exposure linearity, and clearance parameters were assessed. Ex vivo serum time-kill experiments were conducted using a parental strain and a cefquinome-resistant mutant (M1) under normal-inoculum (NI), high-inoculum (HI), and mutant/resistant (MS) conditions. A semi-mechanistic PK/PD model incorporating logistic bacterial growth, sigmoidal Emax killing, nutrient limitation, and a time-delay function was developed to describe dynamic bacterial responses. Model parameters (k₀, k_max, EC₅₀) were estimated using nonlinear least-squares regression (Scientist v2.0), and simulations were performed by integrating time-varying PK input functions. Results: Cefquinome demonstrated linear pharmacokinetics with dose-proportional increases in Cmax and AUC between 2 and 4 mg/kg, with comparable clearance across doses. Ex vivo studies revealed time-dependent antibacterial activity with a pronounced inoculum effect. Higher bacterial burdens significantly reduced bactericidal efficiency and promoted regrowth during declining drug exposure. No tested concentrations achieved ≥3-log₁₀ killing in HI or MS conditions, whereas the NI group achieved a maximal reduction of 3.5-log₁₀ CFU/mL. MIC values in serum and medium were consistent (0.03, 0.06, and 0.24 µg/mL for NI, HI, and MS, respectively), indicating minimal protein binding influence. The semi-mechanistic model accurately described observed bacterial dynamics (R² > 0.99; MSC > 1.5), capturing delayed drug effects, inoculum-dependent growth suppression, and regrowth phenomena. Growth rates were reduced under serum conditions, reflecting nutrient limitation. Importantly, inoculum size exerted a stronger impact on pharmacodynamic outcomes than resistance phenotype, as reflected by reductions in kmax and increases in EC₅₀ under HI conditions. Although %T>MIC exceeded conventional β-lactam targets (>40%) in most regimens, MIC-based indices poorly correlated with observed dynamic killing responses. Conclusions: Cefquinome exhibited time-dependent antibacterial activity against S. suis serotype 2, strongly modulated by inoculum size and reduced susceptibility. The developed semi-mechanistic PK/PD model provided robust prediction of bacterial time-kill behavior and outperformed MIC-based metrics in guiding dose optimization. Simulation results support 2 mg/kg every 24 h for normal infections and 2 mg/kg every 12 h for high-inoculum or less susceptible infections, emphasizing the value of model-informed dosing strategies for optimizing β-lactam therapy. Full article

The discrepancy between in situ microbial abundance and actual metabolic performance represents a critical challenge for interpreting microbial function from meta-omic data. Here, we integrated metagenomic and metatranscriptomic sequencing to investigate this decoupling between microbial abundance and cultivation-based physiological potential in Shanxi aged vinegar (SAV) solid-state fermentation. Lactobacillus acetotolerans dominated the community at both the genomic (40.89%) and transcriptomic (55.36%) levels, whereas Pediococcus acidilactici accounted for only 0.11%—a canonical rare-biosphere member. Source tracking via Sankey analysis showed that genes involved in acetate production were primarily attributed to Acetobacter pasteurianus, whereas genes involved in lactate production were predominantly associated with Lactobacillus spp. However, L. acetotolerans exhibited limited acid tolerance and lactic acid production, whereas the low-abundance P. acidilactici AAF1-5 displayed robust stress tolerance and superior lactic acid production under fermentation-relevant conditions—a striking contrast between microbial abundance and physiological performance. Metabolic interaction network analysis predicted that P. acidilactici may be co-inhibited by L. acetotolerans (I_xy = −2.737, resource competition) and A. pasteurianus (I_xy = −1.887, acid stress). To test whether ecological constraints, rather than intrinsic metabolic capacity, underlie this low abundance, we heterologously expressed the heat shock co-chaperone gene grpE from A. pasteurianus in P. acidilactici AAF1-5 as an experimental tool. The recombinant strain P. acidilactici-grpE exhibited significantly enhanced viability under acetic acid stress and, in simulated SAV fermentation, lactic acid content increased by 23.63% compared with the wild-type control. These results demonstrate that meta-omic abundance does not necessarily predict physiological performance and that low abundance may reflect ecological constraints rather than intrinsic functional deficiency. Our study provides an ecological framework for linking microbial abundance with physiological function beyond sequence-based abundance inference in complex fermentation microbiomes. Full article

The application of two-dimensional molybdenum disulfide (MoS₂) in asphalt binder modification is limited by its inherent chemical inertness and severe agglomeration. In this study, four surface-functionalization strategies, including (3-aminopropyl)triethoxysilane (APTES) silanization, polydopamine (PDA) coating, tannic acid (TA)–APTES co-deposition, and PDA–APTES hybrid modification, were used to improve the dispersion and compatibility of MoS₂ nanosheets in styrene–butadiene–styrene (SBS)-modified asphalt binders. Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD) results indicated that surface functionalization introduced organic functional groups, reduced nanosheet restacking, and preserved the intrinsic 2H-MoS₂ crystal structure. Binder-level rheological tests and thermogravimetry–differential scanning calorimetry (TG–DSC) analysis showed that surface-functionalized MoS₂ improved the high-temperature deformation resistance, creep recovery, fatigue resistance, low-temperature relaxation capacity, and thermal stability of SBS-modified asphalt. Among the investigated binders, PDA–APTES-functionalized MoS₂/SBS-modified asphalt exhibited the most balanced performance. At 3.2 kPa, its recovery rate reached 79.5%, while its non-recoverable creep compliance decreased to 0.105 kPa⁻¹. Its fatigue life at 15% strain increased by 76.8% compared with SBS-modified asphalt, and its creep stiffness at −24 °C decreased to 222 MPa. Mechanistic interpretation suggests that the PDA–APTES hybrid layer may act as an organic–inorganic interfacial transition region, improving MoS₂ dispersion and compatibility with the SBS–asphalt phase and facilitating more effective integration of the nanosheets into the composite structure. These results indicate that PDA–APTES-functionalized MoS₂ nanosheets are promising interfacial modifiers for improving the rheological and thermal performance of SBS-modified asphalt binders. Full article

Endophytes are diverse microorganisms inhabiting plant tissues that can promote plant growth, enhance stress tolerance, or suppress pathogens. However, the ecological roles of endophytes after host senescence and death remain poorly understood. This review examines how a subset of endophytes helps maintain ecosystem function in living plants, senescent tissues, litter, and associated microbial environments. Mechanisms of endophyte-mediated plant protection in living plants include pathogen inhibition, host regulation, nutrient acquisition, and abiotic stress tolerance. We also investigate post-senescence persistence and potential roles in litter decomposition and nutrient cycling via microbial and functional legacies, priority effects, extracellular enzyme activities, and community reassembly. Vertical transmission and horizontal dispersal can move microorganisms among stages, whereas host filtering acts after arrival to determine which microorganisms establish within host tissues. However, a full same-strain life-history loop has not been established. We propose an open, non-linear ecological continuum for selected endophytes that connects endophytic colonisation, saprotrophic persistence, and potential new-host establishment. In the future, longitudinal, strain-resolved, multi-omics, and synthetic-community studies will be conducted to verify the cross-stage connections and offer a microbial framework for plant protection, litter management, and ecological restoration. Full article

Agricultural intensification has weakened natural pest regulation by reducing habitat resources for natural enemies and limiting plant-mediated resistance. Here, we conducted field experiments during 2024–2025 to evaluate the combined effects of Cnidium monnieri field-margin planting and maize seeds coated with the endophytic fungal strains YC (Beauveria bassiana) and PL (Purpureocillium lilacinum) on predator conservation, pest suppression, and biological control in maize agroecosystems. Compared with natural grass margins, C. monnieri significantly increased predator abundance, species richness, and Shannon diversity, particularly of ladybirds, minute pirate bugs, and spiders (p < 0.05). Gut-content analysis detected C. monnieri DNA in ladybirds collected 10–40 m from field margins, confirming predator resource use and spillover into maize fields. Importantly, endophytic fungus-coated seeds did not reduce predator abundance or diversity. Moreover, combining C. monnieri with endophytic fungi enhanced pest suppression and achieved control efficacy comparable to imidacloprid (p > 0.05). These findings demonstrate that integrating functional plants with endophytic fungi simultaneously strengthens top-down biological control and endophyte-associated bottom-up pest suppression, providing an effective and environmentally sustainable strategy for pest management in maize. Full article

Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy caused by extracellular deposition of misfolded proteins, most commonly immunoglobulin light chains (AL) or transthyretin (ATTR). Once considered a rare disease, CA is increasingly recognised due to improved diagnostic strategies and the availability of disease-modifying therapies. Early diagnosis is crucial, as treatment efficacy and clinical outcomes are strongly influenced by the stage of cardiac involvement. Multimodality cardiac imaging plays a central role in the diagnostic pathway, risk stratification, and evaluation of therapeutic response in CA. Echocardiography represents the first-line imaging modality and is essential for raising clinical suspicion through the identification of characteristic structural and functional abnormalities, including ventricular wall thickening, diastolic dysfunction, and distinctive strain patterns. Bone scintigraphy has revolutionised the non-invasive diagnosis of ATTR-CA, allowing accurate identification of transthyretin-related disease in the absence of monoclonal gammopathy, which needs to be excluded via serum and urinary immunofixation. Cardiovascular magnetic resonance provides advanced tissue characterisation through late gadolinium enhancement and quantitative mapping techniques, enabling detection of early myocardial involvement and robust prognostic stratification. Emerging imaging modalities, including dual-energy (spectral) computed tomography and positron emission tomography tracers, show promise in myocardial amyloid quantification and subtype differentiation, although their role is still evolving. Integration of imaging findings with clinical and laboratory parameters allows comprehensive disease assessment, facilitating early diagnosis, guiding therapeutic decisions, and improving risk stratification. This review summarises the current role of multimodality imaging in CA, highlighting its contribution from early detection to prognostic evaluation and monitoring of treatment efficacy, with particular emphasis on the emerging role of quantitative imaging in monitoring treatment response. Full article

Future foods are driving an urgent need for sustainable and functional protein resources, and synthetic biology is emerging as a powerful platform to produce such proteins efficiently. Here, we designed a yeast protein (YP)–sanxan composite hydrogel obtained. The introduction of YP significantly improved thermal stability (by 5–15 °C) and ensured polymer compatibility. Rheological analysis indicated a frequency-dependent weak gel (tan δ = 0.1–0.3), making it suitable for safe swallowing. The material exhibited Type III nonlinear viscoelastic behavior, characterized by inter-cycle strain softening and a weak overshoot in G″, with Lissajous curves revealing a strain-induced transition from solid-like to fluid-like behavior. Crucially, YP-reinforced gels (5–20%) exhibited higher elastic moduli, indicating that the incorporation of YP strengthened the gel network and increased its structural rigidity, as further confirmed by Strain Sweep. With its tunable rheology and superior thermal stability, this hydrogel holds great potential for functional foods, 3D food printing, delivery systems, and biomedical scaffolds. Full article

4′-Hydroxymethoxychalcones represent structurally diverse chalcone derivatives that are attractive substrates for microbial functionalization; however, the impact of methoxy substitution position on their cascade biotransformation by fungi remains poorly understood. In this study, three regioisomeric 4′-hydroxymethoxychalcones, featuring ortho-, meta-, or para-methoxy groups on ring B, were transformed using eight entomopathogenic fungal strains belonging to the genera Beauveria, Isaria, and Metarhizium. Metabolic profiles were monitored over a 10-day period using ultra-high-performance liquid chromatography coupled with diode-array detection (UHPLC-DAD), and the structures of the major products were elucidated primarily by one- and two-dimensional nuclear magnetic resonance (NMR) spectroscopy and further supported by high-resolution electrospray ionization quadrupole time-of-flight mass spectrometry (HR-ESI-QTOF-MS). The investigated microorganisms catalyzed multistep transformations encompassing the reduction of the α,β-unsaturated carbonyl system, methylglucosylation, O-demethylation, and the formation of secondary polar metabolites. Although ene-reduction constituted the predominant initial reaction for all substrates, the relative distribution of subsequent metabolites varied depending on both the fungal strain and, to a lesser extent, the position of the methoxy group. The ortho-methoxy derivative exhibited the highest propensity for O-demethylation; the meta-substituted substrate generated the most heterogeneous secondary metabolite profiles, whereas the para-methoxy analogue showed the most consistent accumulation of methylglucosylated dihydrochalcones. These findings indicate that methoxy substitution position does not alter the common core biotransformation pathway, but can modulate the relative efficiency of individual steps and the extent of secondary metabolism. Full article

Coffee fermentation is a critical yet under-optimized stage of the coffee value chain, with significant implications for beverage quality, process consistency, and smallholder livelihoods. Pichia species, together with several non-Saccharomyces yeasts historically associated with the genus, are frequently detected in natural and semi-dry coffee fermentation; however, their functional roles remain insufficiently characterized, constraining evidence-based starter-culture design. Direct coffee evidence implicates P. kudriavzevii, P. kluyveri, and Meyerozyma guilliermondii (formerly Pichia guilliermondii) in substrate transformation, fermentation dynamics, and sensory quality development. However, these findings are derived exclusively from studies conducted on single farms during single harvest seasons, without independent validation across multiple farms, harvest seasons, origins, or production environments, limiting their broader applicability. In contrast, ecologically prevalent species, including P. fermentans, Wickerhamomyces anomalus (formerly Pichia anomala), and Debaryomyces hansenii (formerly Pichia hansenii), remain largely unexplored in the context of coffee fermentation. To contextualize the current knowledge and identify promising avenues for future research, this review synthesizes evidence from cocoa, Baijiu, bakery, vinegar, dairy, and other solid-state fermentation systems. Across these diverse matrices, Pichia and related non-Saccharomyces yeasts frequently exert a disproportionate influence on flavor development, microbial succession, and process stability relative to their population abundance. The reported mechanisms include ester and higher-alcohol production, modulation of bacterial community dynamics, extracellular enzymatic activity, and bioprotective effects. Notably, functional impact often occurs without numerical dominance; ester production can increase alongside declining ethanol yield, and ecological persistence may increase despite declining absolute abundance, implicating community-level interactions in addition to direct metabolic activity. However, both the mechanisms and the magnitudes of these effects vary across fermentation systems, underscoring that functions demonstrated in one matrix cannot be assumed to translate directly to coffee without experimental validation. Future progress will require strain-level characterization, mechanistic studies, deliberate multi-species consortium design, process optimization, and field-scale validation in diverse coffee-producing environments. Such efforts will provide a scientific foundation for evidence-based starter-culture development capable of improving coffee quality, consistency, and producer value. Full article

(1) Background: methicillin‑resistant Staphylococcus aureus (MRSA) is a zoonotic pathogen, and its hemolysins serve as key virulence factors. Functional membrane microdomains (FMMs) are protein-enriching platforms and regulate diverse physiological functions by recruiting and assembling various proteins. However, whether and how FMMs regulate the hemolytic ability of MRSA remains unclear. This study aimed to investigate FMM-mediated regulation of MRSA hemolysins and the underlying mechanisms. (2) Methods: Homologous recombination was employed to generate FMM-disrupted (N315ΔfloA) and complemented (N315ΔfloA::floA) strains from the MRSA N315 wild-type strain (N315 WT). The three strains were compared with respect to hemolytic activity, transcript levels of key virulence and regulatory genes, and in vivo virulence. (3) Results: Disruption of FMMs significantly enhanced hemolytic activity compared with N315 WT and complemented strains. Meanwhile, FMM disruption repressed the two-component system genes (vraS and vraR), while activating the agr operon (agrB, agrD, agrC and agrA) and its effector molecule RNAIII, leading to upregulation of hemolysin genes (hla, hlb, hld). In vivo, N315ΔfloA infection markedly increased mortality in G. mellonella larvae and BALB/c mice, with significantly elevated pro-inflammatory factors (TNF-α, IL-6, and IL-1β) in mouse plasma. All these phenotypes were effectively reversed in N315ΔfloA::floA. (4) Conclusions: Disruption of FMMs potentiates both hemolytic activity and overall virulence in MRSA, with the potential underlying mechanism involving the VraS/R-Agr regulatory axis that drives transcriptional upregulation of hemolysin-encoding genes. Full article

Sugarcane (Saccharum spp.) is a globally vital high-biomass sugar crop with a massive demand for potassium (K). Low-K⁺ stress severely restricts its yield and stress resistance. Plasma membrane intrinsic proteins (PIPs) play pivotal roles in transmembrane water transport and ion homeostasis; however, their evolutionary characteristics and molecular mechanisms underlying nutritional stress responses in the complex polyploid sugarcane remain poorly understood. In this study, genome-wide identification in the sugarcane cultivar XTT22 yielded 149 PIP gene family members (comprising 54 PIP1s and 95 PIP2s). Phylogenetic and chromosomal localization analyses demonstrated that the sugarcane PIP family underwent drastic paralogous expansion during evolution, with tandem duplication acting as the core driving force for the dramatic expansion of the PIP2 subfamily. Spatiotemporal expression profiling unveiled significant modular functional division among PIP genes, identifying a core co-expression group driving rapid early seedling elongation and a PIP2-specific expression cluster dedicated to the physiological homeostasis of mature stems. Notably, the core member ScPIP2-70 exhibited significant early-induced responses at both transcriptional and protein levels in roots under low-K⁺ stress. Functional complementation assays in the K⁺-uptake deficient yeast strain R5421 further confirmed that the heterologous expression of ScPIP2-70 effectively rescued the growth defects of yeast under low-K⁺ conditions, demonstrating its potential transmembrane K⁺ transport activity. This study not only comprehensively elucidates the evolutionary dynamics and spatiotemporal expression profiles of the sugarcane PIP gene family but also uncovers the novel pleiotropic function of ScPIP2-70 in mediating low-K⁺ stress tolerance, providing critical theoretical support and candidate gene resources for breeding “potassium-efficient” sugarcane cultivars via modern biotechnology. Full article

Titanium alloys are widely used for implants, yet corrosion, bacterial colonization and incomplete osseointegration remain important causes of interfacial failure. This review critically analyzes major biomedical functional coating fabrication techniques employed to enhance the surface properties of titanium alloys, including micro-arc oxidation, anodic oxidation, magnetron sputtering, electrochemical deposition, electrophoretic deposition, plasma spraying, physical vapor deposition, plasma immersion ion implantation, laser surface treatment, and hybrid (composite) approaches. For each method, key operational principles, structural and functional characteristics, performance advantages and limitations, and representative application domains are critically analyzed. Across these routes, biological performance depends on coating continuity, pore or nanotube geometry, interfacial bonding, phase composition and ion release. Calcium- and phosphorus-rich oxides and hydroxyapatite deposits generally promote cell adhesion, proliferation, alkaline phosphatase activity, mineralization and osteogenic differentiation. Dense oxide, nitride, tantalum and carbon-based films strengthen corrosion barriers, whereas Mn, Zn, Cu and Ag containing surfaces can inhibit bacterial adhesion and biofilm formation. Excessive ion release, however, may compromise cytocompatibility. Reported outcomes also vary with test medium, exposure time, bacterial strain and cell model. Standardized quantitative endpoints and longer-term corrosion, biofilm and osseointegration studies are required to guide clinically reliable multifunctional coatings. Full article