Search Results (6,643)

Background: Combating antimicrobial resistance and developing dressings that match all aspects of wound healing will always be challenging. Methods: In this study, hydrogel membranes composed of sodium alginate (SA), polyvinyl alcohol (PVA), and Pluronic-f-127 (F-127) loaded with colistin (C) were formulated. The formulations were divided into two groups: group 1 (SA-PVA-C) and group 2 (SA-PVA-F127-C). Results: The membranes were characterized using multiple techniques, which confirmed component compatibility, physical cross-linking, an amorphous structure, and suitable surface morphology with acceptable porosity. Mechanical testing showed that both groups were suitable for wound-dressing applications. Differences in drug release across media (water, normal saline, and phosphate) were non-significant (p value > 0.05). Drug-loaded membranes (n = 3) from both groups showed antibacterial activity against multidrug-resistant Gram-negative Pseudomonas aeruginosa (ZOI = 20.33 ± 2.51 mm, 21.66 ± 2.08 mm). Conclusions: Overall, the developed hydrogel membranes (both group 1 and group 2) demonstrated promising in vitro potential as colistin delivery systems for wound infection management. Full article

4-hydroxy-TEMPO is a water-soluble nitroxide radical with potent antioxidant and redox-modulating properties. Its small molecular weight and membrane permeability enable it to act as a superoxide dismutase mimetic, efficiently scavenging reactive oxygen species and mitigating oxidative damage. In this study, we investigated the physiological and transcriptomic effects of 4-hydroxy-TEMPO in Saccharomyces cerevisiae, using wild-type and mutant strains deficient in key redox and DNA repair pathways (sod1Δ, sod2Δ, yap1Δ, rad52Δ). RNA-Seq analysis revealed widespread transcriptional reprogramming. Treatment with 4-hydroxy-TEMPO impaired cell growth, induced accumulation of cells with 1C (G1 phase) DNA content, and modulated chronological aging in a strain-dependent manner. Notably, low concentrations delayed aging in wild-type, yap1Δ, and rad52Δ strains, while accelerating it in sod1Δ mutants, consistent with a hormetic response. Unlike TEMPO, 4-hydroxy-TEMPO exhibited markedly reduced translational toxicity, preserved polysome structure at high doses, and triggered a non-canonical, redox-dependent transcriptional program characterized by induction of stress-response genes together with unexpected up-regulation of multiple ribosomal protein genes. This was accompanied by a biphasic, genotype-specific hormetic response and a measurable genoprotective effect. RT-qPCR confirmed key transcriptional changes, linking transcriptome remodeling to functional outcomes. Full article

Pulsed electric fields (PEFs) are widely recognized as a non-thermal, selective physical therapy with wide clinical application in tumor ablation. The pulse width determines how electrical energy is distributed across plasma membrane to intracellular organelles. However, under an engineering-defined equal-dose condition (N·E²·tp), which serves as a practical control parameter rather than a measure of true cellular energy absorption, systematic and comparable experimental characterization of cellular and subcellular responses across pulse widths from the microsecond to nanosecond range remains limited. In this study, PEFs with pulse widths ranging from 100 μs to 50 ns were applied under equal-dose constraints, and cellular responses were evaluated using transmission electron microscopy (TEM), multi-organelle fluorescence imaging, and flow cytometry. The results indicate that pulse-width-dependent effects were observed under a fixed pulse-number, dose-equalized framework in which electric field strength varied across conditions. Structural and functional changes were observed in multiple organelles, including the nucleus, mitochondria, endoplasmic reticulum, and Golgi apparatus. Notably, nanosecond pulses were more effective in inducing mitochondrial membrane potential loss and increasing the proportion of apoptotic or non-viable cells. These findings demonstrate that, under equal-dose conditions, pulse width is a key temporal parameter governing PEF-induced biological effects, indicating that identical dose constraints do not necessarily result in equivalent biological responses. This work provides experimental foundation for parameter selection and optimization in PEF-based biomedical applications. Full article

Understanding how plants respond to water limitation is increasingly important under accelerating climate change. Lycoris aurea, a widely distributed ornamental and medicinal bulbous plant, frequently inhabits environments with fluctuating soil moisture, yet its molecular drought-response mechanisms remain largely unexplored. In this study, we investigated L. aurea growing under field-based, in situ soil moisture regimes, comparing low (~20% soil water content) and high (~40% soil water content) conditions. We combined soil property assessments with high-resolution transcriptomic and untargeted metabolomic profiling to characterize the adaptive responses of bulb tissues under contrasting soil water conditions. Although total nitrogen, phosphorus, and potassium levels were comparable across treatments, soil moisture, representing the primary contrasting field condition, and soil pH, a correlated environmental factor, were significantly associated with variation in gene expression and metabolite accumulation (p < 0.05, n = 3). Transcriptome analyses identified a total of 1034 differentially expressed genes enriched in pathways related to amino acid metabolism, cuticle formation, cell wall modification, and osmotic adjustment. Metabolomic analysis identified a total of 1867 differentially expressed metabolites belonging to carboxylic acids and prenol lipids, showing alterations involved in amino acids, lipids, phenolic acids, and alkaloids associated with osmoprotection, membrane stabilization, and structural reinforcement under low soil moisture. Pathway-based integration analysis highlighted four core pathways, including “alanine, aspartate and glutamate metabolism” (p = 0.00371) and “cutin, suberine and wax biosynthesis” (p = 0.00873), as central hubs linking transcriptional regulation with metabolic reconfiguration. Gene-metabolite-soil correlation networks further demonstrated that drought adaptation arises from tightly coordinated biochemical and structural adjustments rather than shifts in nutrient acquisition. Together, this species-specific study provides a comprehensive multi-omics framework for understanding drought tolerance in L. aurea, reveals key molecular targets associated with plant resilience, and offers potential targets and insights for the conservation of drought-resilient Lycoris cultivars. Full article

Candidozyma auris (formerly Candida auris) is an emerging multidrug-resistant fungal pathogen with confirmed cases in over 30 countries. Although whole-genome sequencing (WGS) analysis defined distinct clades during characterization of underlying genetic mechanism behind multidrug resistance, Clade II remains under-evaluated. In this study, a three-level comparative genomic strategy (Global, Clade, Phenotype) was employed by integration of unbiased genome-wide comparative SNP screening (GATK v4.1.9.0), targeted BLAST profiling (BLAST+ v2.17.0), and in silico protein analysis (ColabFold v1.5.5; DynaMut2 v2.0) for systematic evaluation of mechanisms of antifungal resistance in thirty-nine Clade II C. auris clinical isolates and fourteen reference strains. Global and clade-level analyses confirmed that all the clinical isolates belong to Clade II, according to phylogenetic clustering and mating type locus (MTL) conservation. At the phenotype level, a distinct subclade of fluconazole-resistant mutants was identified to have a heterogenous network of mutations in seven key enzymes associated with cell membrane dynamics and the metabolic stress response. Among these, four core mutations (TAC1B, CAN2, NIC96, PMA1) were confirmed as functional drivers based on strict criteria during multitier in silico protein analysis: cross-species conservation, surface exposure, active site proximity, thermodynamic stability, and protein interface interaction. On the other hand, three high-level fluconazole-resistant clinical isolates (≥128 μg/mL) that lacked these functional drivers were subjected to comprehensive subtractive genomic profiling analysis. The absence of coding mutations in validated resistance drivers, yeast orthologs, and convergent variants suggests that there is an alternative novel non-coding or regulatory mechanism behind fluconazole resistance. These findings highlight Clade II’s evolutionary divergence into two distinct trajectories towards the development of a high level of fluconazole resistance: canonical protein alteration versus regulatory modulation. Full article

A group of experts of different specialties involved in the care of prostate cancer (PCa) patients participated in the ENFOCA2 project, promoted by the Spanish Oncology Genitourinary Group (SOGUG), with the aim to review, discuss, and summarize current relevant aspects related to screening, diagnosis, imaging, risk-based approach, and molecular characterization of PCa. A multidisciplinary team (MDT) approach is essential to ensure that patients receive evidence-based care, promoting shared decision-making, and tailoring treatment to the patient’s unique values and preferences. Population-based screening based on risk-stratified algorithms is needed to overcome the limitations of opportunistic screening for detecting clinically significant PCa. Next-generation imaging (NGI) methods, such as prostate-specific membrane antigen (PSMA) PET/CT alone or combined with multiparametric MRI (mpMRI), have a promising role in different scenarios of the diagnostic process due to their high sensitivity. The diagnostic yield of mpMRI should be improved, especially for assessing extraprostatic extension. The use of specific molecular probes as imaging markers for MRI could improve the staging of metastatic disease. Protocols for germline testing developed by international societies, such as the European Association of Urology (EAU) and the National Comprehensive Cancer Network (NCCN), should be adapted at local levels, with BRCA1/2, ATM, PALB2, CHEK2, MLH1, MSH2, MSH6, PMS2, EPCAM, and HOXB13 as the genes to be investigated. Genomic classifier tools help identifying aggressiveness of cancers and aid in personalized treatment decision-making. Joint efforts of multidisciplinary physicians are crucial to improve health outcomes for patients with PCa across the spectrum of this disease. Full article

An organophilic composite membrane, ZIF-67@PDMS, was fabricated to enhance the isolation of natural aromatic compounds. The as-prepared composite membrane was characterized using SEM, EDS, FTIR, XRD, and contact angle measurement. In comparison to pure PDMS, ZIF-67@PDMS, featuring a loading capacity of 2.5 wt% of PDMS and a membrane thickness of 15 μm, demonstrated markedly improved separation performance for the characteristic aroma compounds of strawberries, namely linalool, benzaldehyde, and ethyl acetate. Under optimal conditions, the permeation fluxes of the three compounds were 628.02 mg∙m⁻²∙h⁻¹, 294.82 mg∙m⁻²∙h⁻¹, and 254.14 mg∙m⁻²∙h⁻¹, along with separation factors of 26.48, 7.94, and 6.32, respectively. ZIF-67@PDMS was then employed to isolate aromatic compounds from freshly squeezed strawberry juice. By backfilling the permeate, both the variety and the content of aromatic compounds in strawberry concentrate were notably restored, and its aroma profile also closely resembled that of fresh strawberry juice. Full article

Fabricating polyimide (PI) membranes with outstanding anti-plasticization ability and gas separation performance remains a challenge. In this study, two novel diamine monomers, DAMBO (methyl 3,5-diamino-4-methylbenzoate) and DAPGBO (3-hydroxypropyl 3,5-diamino-4-methylbenzoate), were synthesized through esterification reactions. Then, we copolymerized each of these two new monomers with 4,4′-diaminodiphenylmethane (DAM) and 4,4′-(Hexafluoroisopropylidene) diphthalic anhydride (6FDA) separately to yield two monoesterified PIs. Following this, we further prepared the ester-crosslinked PIs by inducing a transesterification crosslinking reaction within the PI-PGBO membrane via thermal treatment. As expected, we found that the formation of cross-linked structures can effectively regulate the microporous structure, enhance its sieving performance, and thus improve the membrane’s gas selectivity. Furthermore, the resulting network structure endowed the thermally treated PI membrane with excellent anti-plasticization ability. Physical characterization results show that after heat treatment, both the d-spacing and BET surface area of the PI membrane decreased, but the solvent resistance of the thermally treated PIs was significantly improved. Gas separation experiments revealed that the representative membrane (PI-PGBO-300) exhibited the optimal CO₂/CH₄ separation performance, with a CO₂ permeability of 371.05 Barrer, a CO₂/CH₄ selectivity of 28.11, and a CO₂ plasticization pressure exceeding 30 bar. This study provides valuable insights into the design of cross-linked polyimides (PIs) via transesterification reactions, which are capable of enhancing the performance of membrane-based gas separation processes. Full article

The rise of multidrug-resistant tuberculosis (TB) necessitates alternative therapeutic sources. This study investigated the polyphenolic content and the antioxidant, antimycobacterial, and anti-virulence activities of selected medicinal plants traditionally used to treat TB and related symptoms. Total phenolics, tannins, and flavonoids were quantified using colorimetric assays. Antioxidant capacity was assessed via DPPH and ferric-reducing power assays. Antimycobacterial activity against Mycobacterium smegmatis was evaluated using broth microdilution, growth kinetics, cell constituent leakage, and respiratory chain dehydrogenase inhibition assays. Anti-virulence effects were examined using crystal violet biofilm and swarming motility assays. Tarchonanthus camphoratus showed the highest polyphenolic levels and, together with Combretum hereroense, strong antioxidant activity. Extracts of Senecio macroglossus, Nerium oleander, and Tetradenia riparia displayed potent antimycobacterial activity (MIC = 0.16 mg/mL), characterized by delayed exponential growth, membrane damage, and metabolic inhibition. Tabernaemontana elegans exhibited the weakest activity (MIC > 2.5 mg/mL). Most extracts also significantly impaired motility (12–100%) and early-stage biofilm formation. Polyphenolic-rich plant extracts demonstrated promising antimycobacterial and anti-virulence properties against M. smegmatis, highlighting their potential as leads for developing novel anti-TB agents. Full article

Cardiogenic pulmonary edema (CPE) is a life-threatening manifestation of acute heart failure characterized by rapid accumulation of fluid in the interstitial and alveolar spaces, leading to severe dyspnea, hypoxemia, and respiratory failure. The condition arises from elevated left-sided filling pressures that increase pulmonary capillary hydrostatic pressure, disrupt alveolo-capillary barrier integrity, and impair gas exchange. Neurohormonal activation further perpetuates congestion and increases myocardial workload, creating a vicious cycle of hemodynamic overload and respiratory compromise. Respiratory support is a cornerstone of management in CPE, aimed at stabilizing oxygenation, reducing the work of breathing, and facilitating ventricular unloading while definitive therapies, such as diuretics, vasodilators, inotropes, or mechanical circulatory support (MCS), address the underlying cause. Among available modalities, non-invasive ventilation (NIV) with continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) has the strongest evidence base in moderate-to-severe CPE, consistently reducing the need for intubation and providing rapid relief of dyspnea. High-flow nasal cannula (HFNC) represents an emerging alternative in patients with moderate hypoxemia or intolerance to mask ventilation, and should be considered an adjunctive option in selected patients with less severe disease or NIV intolerance, although its efficacy in severe presentations remains uncertain. Invasive mechanical ventilation is reserved for refractory cases, while extracorporeal membrane oxygenation (ECMO) and other advanced circulatory support modalities may be necessary in cardiogenic shock. Integration of respiratory strategies with hemodynamic optimization is essential, as positive pressure ventilation favorably modulates preload and afterload, synergizing with pharmacological unloading. Future directions include personalization of ventilatory strategies using advanced monitoring, novel interfaces to improve tolerability, and earlier integration of MCS. In summary, respiratory support in CPE is both a bridge and a decisive therapeutic intervention, interrupting the cycle of hypoxemia and hemodynamic deterioration. A multidisciplinary, individualized approach remains central to improving outcomes in this high-risk population. Full article

Accurately characterizing the structural state of membrane reflector antennas (MRA) remains challenging due to the difficulty in determining stress distribution through geometric measurement alone. Although photogrammetry provides high-precision geometric data, it falls short of capturing mechanical pre-tension and is notably influenced by gravity, which limits its utility in guiding surface accuracy adjustments. This paper proposed an integrated approach combining photogrammetry with a nonlinear finite element method (NFEM) to achieve high-fidelity imaging and effective shape adjustment of electrostatically formed MRA, explicitly accounting for gravity effects during ground-based measurement and shape control. The proposed method establishes a mechanical model that incorporates real-world geometric data under gravity and performs force–shape matching to reconcile discrepancies between physical and simulation models. Experimental validation demonstrates that the gravity-corrected NFEM model closely aligns with the physical antenna, with a deviation in surface accuracy within 9.9%. Using this refined model, we successfully optimized electrode voltages and cable tensions, improving the surface accuracy of the physical model from an initial 0.7033 mm to 0.5723 mm. This work provides a reliable and efficient strategy for the shape control and adjustment of membrane space structures under gravity, with potential applications in large deployable antennas, solar sails, and other tension-controlled flexible systems. Full article

Microglia-derived small extracellular vesicles (MGEVs) are key mediators of neuroimmune communication, yet their cross-species comparability and translational relevance remain poorly defined. Here, we establish a harmonized framework to compare the molecular and biochemical signatures of sEVs derived from immortalized mouse (BV2) and human (HMC3) microglial cells as well as assess their bioactivity on a human Schwann cell (HuSC) line. MGEVs were isolated via MISEV-aligned size-exclusion chromatography (SEC) and characterized by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and immunoblotting for canonical EV markers CD9, CD63, CD81, TSG101. Human and mouse MGEVs exhibited similar morphology but displayed distinct membrane tetraspanin protein enrichment patterns. Functionally, mouse and human MGEVs attenuated HuSC migration while enhancing HuSC proliferation and their resistance to H₂O₂-induced oxidative stress, with human MGEVs providing stronger protective effects, suggesting they retain similar core functional properties. Short, non-coding-miRNA sequencing analysis identified 196 shared miRNAs (Spearman ρ = 0.72) with species-specific enrichment: human MGEVs-derived miRNAs favored regenerative and metabolic pathways, whereas mouse MGEVs-derived miRNAs aligned more so with inflammatory signaling. This study delivers the first integrated cross-species blueprint of MGEVs, revealing conserved neuroprotective actions alongside species-biased miRNA cargo that define translational boundaries and highlight human-relevant MGEV signatures for therapeutic innovation, therefore contributing to the importance of considering these differences in translational research. Full article

Background and Objectives: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease characterized by alveolar-capillary membrane remodeling and impaired gas diffusion. The diffusing capacity of the lung for nitric oxide (DLNO) has been proposed as a physiological parameter reflecting membrane diffusing capacity and pulmonary vascular involvement, potentially providing complementary information to diffusing capacity of the lung for carbon monoxide (DLCO). This study aimed to evaluate the role of DLNO in the functional assessment of patients with IPF and its correlation with clinical and echocardiographic outcomes. Materials and Methods: This observational, retrospective study included 35 consecutive IPF patients receiving antifibrotic therapy between February and December 2023. All participants underwent plethysmography, combined single-breath DLNO and DLCO testing, six-minute walk test (6MWT), mMRC dyspnea scale assessment, and echocardiography for the estimation of a higher probability of pulmonary hypertension (PH). Results: DLNO was significantly lower in males compared to females (49.3 ± 16.7% vs. 74.6 ± 16.1%, p < 0.001), with a reduced DLNO/DLCO ratio in men. DLNO correlated with oxygen therapy requirement (p = 0.010) and lower oxygen saturation during the 6MWT (p = 0.021). Patients with higher echocardiographic probability of PH showed markedly reduced DLNO values (17.6 ± 7.6%, p = 0.016) and higher FVC/DLNO ratios (2.31 ± 0.85 vs. 1.65 ± 0.64, p = 0.023), together with lower DLCO levels (p = 0.037). Conclusions: DLNO may complement DLCO in the evaluation of gas exchange and alveolar-capillary dysfunction in IPF. Although preliminary, these findings support the potential clinical utility of DLNO as an adjunct parameter in the functional characterization of IPF. Further multicenter studies are warranted to confirm these results. Full article

Plant organic cation transporters (OCTs) are involved in a variety of beneficial biological processes, such as cadaverine transfer in plants and soil, and play an active role in the formation of plant stress resistance. In this study, 52 OCT family genes were identified in tomato, and comprehensive bioinformatics analyses of these numbers, such as promoter cis-acting elements, gene mapping and collinearity, protein characterization and phylogenetic analysis. By analyzing the expression of tomato OCT family genes under cold and salt stresses using transcriptome data and qRT-PCR experiments, a key gene regulating cold stress tolerance, SlOCT20, was identified. Subcellular localization experiments indicated that SlOCT20 was mainly localized in the cell membrane. When the SlOCT20 gene was silenced in tomato, the tolerance to cold stress was significantly reduced and oxidative stress was aggravated, indicating that this gene positively regulates the tolerance to cold stress in tomato. Full article

This study evaluates the chemical profile and antifungal efficacy of essential oils from Piper glabratum, Piper friedrichsthalii, and Piper cumanense against the cocoa pathogens Moniliophthora roreri and Phytophthora palmivora. Microwave-assisted hydrodistillation followed by GC-MS analysis identified 80 constituents, predominantly monoterpenes and sesquiterpenes, which exhibited significant mycelial inhibition comparable to commercial fungicides. Beyond basic characterization, a comprehensive chemoinformatic analysis was conducted to elucidate the molecular mechanisms driving this bioactivity. The computed physicochemical landscape reveals a dominant lipophilic profile (average LogP 3.4) and low polarity (TPSA 11.5 Ų), characteristics essential for effective fungal membrane penetration. Structural mining identified conserved benzene and cyclohexene scaffolds alongside specific 1,3-benzodioxole moieties, while Maximum Common Substructure (MCS) analysis uncovered high similarity clusters among phenylpropanoids and sesquiterpenes. These findings suggest a synergistic mode of action where conserved structural backbones and interchangeable diastereomers facilitate membrane destabilization and ion leakage. Consequently, the integrative chemoinformatic profiling elucidates the molecular basis of this efficacy, positioning these Piper essential oils not merely as empirical alternatives, but as sources of rationally defined synergistic scaffolds for next-generation sustainable fungicides. Full article