Search Results (3,820)

Pathogens causing candidiasis encompass a diverse group of ascomycetous yeasts that have become essential models for studying fungal adaptability, pathogenicity, and host–pathogen interactions. Although many candidiasis-promoting species exist as commensals within host microbiota, several have acquired virulence traits that enable opportunistic infections, positioning them as a leading cause of invasive fungal disease in humans. Deciphering the molecular and genetic determinants that underpin the biology of organisms responsible for candidiasis has long been a central objective in medical and molecular mycology. However, research progress has been constrained by intrinsic biological challenges, including noncanonical codon usage and the absence of a complete sexual cycle in diploid species, which have complicated traditional genetic manipulation. CRISPR-Cas9 genome editing has overcome many of these limitations, providing a precise, efficient, and versatile framework for targeted genomic modification. This system has facilitated functional genomic studies ranging from single-gene deletions to high-throughput mutagenesis, yielding new insights into the mechanisms governing virulence, antifungal resistance, and stress adaptation. Since its initial application in Candida albicans, CRISPR-Cas9 technology has been refined and adapted for other clinically and industrially relevant species, including Nakaseomyces glabratus (formerly referred to as Candida glabrata), Candida parapsilosis, and Candida auris. The present work provides an overview of the evolution of genetic approaches employed in research directed against candidiasis-associated species, with a particular focus on the development and optimization of CRISPR-based systems. It highlights how recent advancements have improved the genetic tractability of these pathogens and outlines emerging opportunities for both fundamental and applied studies in fungal biology. Full article

In this study, two nitrogen-doping strategies for magnesium oxide—an in situ method and a post-synthesis modification—were developed, and their visible-light photocatalytic activity was evaluated using methylene blue (MB) as a model organic pollutant. The materials were characterized using a combination of structural (SEM–EDX), spectroscopic (WAXRD, FTIR, Raman), optical (UV–DRS, PL), and thermal (TGA–MS) analyses. Both nitrogen-doped MgO samples exhibited significantly enhanced MB degradation compared to commercial MgO. Additional photocatalytic tests using phenol, a colorless contaminant, as a probe molecule suggested the occurrence of two distinct degradation pathways: direct photocatalysis for the in situ nitrogen-doped MgO, and a sensitization-mediated degradation process for the post-synthesis nitrogen-doped MgO. Based on the experimental results, a reaction mechanism is proposed. Full article

This study aims to address the issue of asphalt pavement performance deterioration caused by chloride salt erosion. Layered double hydroxides (CLDHs) calcined at different temperatures, including 400 °C, 500 °C, and 600 °C, were used for the modification of asphalt binder. The structural evolution and chloride ion adsorption characteristics of CLDHs were analyzed. The adsorption kinetic behavior of CLDHs for chloride ions was investigated by combining adsorption kinetic experiments and electrochemical titration experiments. Through characterizing the interfacial adhesion performance between CLDH-modified asphalt binder and aggregates, the chemical composition of asphalt–ash binder before and after salt corrosion, and the leaching stability of organic substances in an environment with abundant chloride ions, the influence of CLDHs on the salt corrosion resistance of asphalt–ash binder was quantified. The results indicate that chloride adsorption by CLDHs is predominantly chemisorption-driven. With increasing calcination temperature, the chloride adsorption capacity of CLDHs gradually improved. In chloride-rich environments, CLDHs significantly enhanced the interfacial adhesion between asphalt binder and aggregates, particularly for coarse aggregates with a particle size of 9.5–13.2 mm. Furthermore, CLDHs effectively suppressed the formation of carbonyl and sulfoxide groups during salt corrosion and substantially decreased the leaching of organic components from asphalt binder. In summary, CLDHs can specifically enhance the salt corrosion resistance of asphalt binder, with the 600 °C-CLDHs demonstrating the most significant improvement, followed by the 400 °C-CLDHs, while the 500 °C-CLDHs performed the least effectively. Full article

The pursuit of sustainable ammonia production has accelerated the development of electrocatalytic pathways capable of operating under ambient conditions with renewable electricity. Recent studies have revealed that the efficiency and selectivity of both electrochemical nitrogen reduction reaction (eNRR) and nitrate reduction reaction (eNO₃RR) are not governed solely by catalyst composition, but by the synergistic interplay among electrolyte identity, interfacial solvation structure, and catalyst architecture. Hydrated cations such as Li⁺ profoundly reshape the electric double layer, polarize interfacial water, and lower activation barriers for key proton–electron transfer steps, thereby redefining the electrolyte as an active promoter. Parallel advances in structural engineering, including alloying, heteroatom doping, controlled defect formation, and nanoscale morphological control, have enabled the optimization of intermediate adsorption energies while simultaneously suppressing competing hydrogen evolution. In addition, the emergence of metal–organic-framework (MOF)-derived single-atom catalysts has demonstrated that atomically dispersed transition-metal centers anchored within dynamically adaptable matrices can deliver exceptional Faradaic efficiencies, high turnover rates, and long-term operational durability. These developments highlight a unified strategy in which electrolyte–catalyst coupling, rational structural modification, and atomic-scale design principles converge to enable predictable and high-performance ammonia electrosynthesis. This review integrates mechanistic insights across these domains and outlines future directions for translating molecular-level understanding into scalable technologies for green ammonia production. Full article

A representative cluster-based model of the batch process of ethanol production by Kluyveromyces sp. is proposed. Experimental data from fermentation processes of 17 different strains of K. marxianus are used; each of them potentially exhibits different metabolic and kinetic behavior. Three algorithms for clustering are applied. Two modifications of Principal Component Analysis (PCA)—hierarchical clustering and k-means clustering; and InterCriteria Analysis (ICrA) are used to simplify a large dataset into a smaller set while preserving as much information as possible. The experimental data are organized into two main clusters. As a result, the most representative fermentation processes are identified. For each of the fermentation processes in the clusters, structural and parameter identification are performed. Four different structures describing the specific substrate (glucose) consumption rate are applied. The best structure is used to derive the representative model using the data from the first cluster. Verification of the derived model is performed using experimental data of the second cluster. Model parameter identification is performed by applying an evolutionary optimization algorithm. Full article

Biological membranes are dynamic, information-rich platforms whose structural and functional properties are dictated by lipid composition rather than acting as passive barriers. Recent advances in lipidomics have revealed that variations in lipid headgroups, acyl-chain length and saturation, sn-positional architecture, and oxidative modifications profoundly influence membrane mechanics, lateral organization, and protein–lipid interactions. These features collectively regulate fundamental cellular processes, including signaling, trafficking, curvature generation, and transbilayer asymmetry. In parallel, a wide range of pathological conditions—including cancer, metabolic disorders, neurodegeneration, and inflammatory diseases—are increasingly associated with coordinated lipid remodeling that reshapes membrane material properties and electrostatic landscapes. In this review, we integrate biophysical principles with lipidomics-based evidence to elucidate how lipid chemical diversity translates into membrane-level behavior. We discuss the roles of major membrane lipid classes, the functional consequences of acyl-chain and sn-positional remodeling, and the biological significance of lipid asymmetry and lateral heterogeneity. Particular attention is given to disease-associated lipid reprogramming and extracellular vesicle lipidomes as functional extensions of cellular membranes. Finally, we examine key analytical barriers in modern lipidomics and outline strategies required to connect lipid structural information with biological function. Together, this framework highlights membrane lipid architecture as a central determinant of cellular physiology and a promising axis for mechanistic insight and translational biomarker discovery. Full article

Rosin, a renewable natural resin derived from pine trees, is a promising biomass material for sustainable product development, though its distinct intrinsic odor limits broader use. This study implemented a comprehensive analytical strategy to mitigate the odor by incorporating essential oils (EOs)—eucalyptus (EUC) and peppermint (MINT)—and to conduct a multi-analytical characterization of the modified rosin jewelry. By integrating complementary analytical techniques, including LC-Q/TOF-MS for non-volatile components and GC-Q/TOF-MS for volatile organic compounds (VOCs), we achieved a systematic chemical profiling of the materials. The core composition of rosin, dominated by abietic acid (>48%), remained stable across all samples. The incorporation of EOs significantly altered the VOC profiles: The total VOC signal (summed peak area) in MINT-modified rosin was 2.57-fold that of the EUC-modified sample, with monoterpenoids comprising 87.62% of its VOC signature. Eucalyptol and limonene were tentatively identified as the major components in the EUC sample, whereas menthone, menthol, and limonene predominated in the MINT sample. Multivariate statistical analysis highlighted that variations in specific VOCs—particularly menthone, menthol, eucalyptol, and allo-ocimene—were closely associated with differences in the scent profiles of each modification. This work illustrates how a multi-technique analytical strategy can both guide and assess the functional modification of sustainable biomass materials. The findings offer a practical approach to improving rosin’s functional properties while providing a methodological framework for the integrated characterization of complex biomaterials, supporting the development of eco-friendly products aligned with green chemistry and sustainable design principles. Full article

The exponential growth and complexity of legal agreements pose significant Big Data challenges and strategic risks for modern organizations, often overwhelming traditional, manual contract management workflows. While AI has enhanced legal research, most current applications require extensive domain-specific fine-tuning or substantial annotated data, and Large Language Models (LLMs) remain susceptible to hallucination risk. This paper presents an AI-based Agreement Management System that addresses this methodological gap and scale. The system integrates a Python 3.1.2/MySQL 9.4.0-backed centralized repository for multi-format document ingestion, a role-based Collaboration and Access Control module, and a core AI Functions module. The core contribution lies in the AI module, which leverages zero-shot learning with OpenAI’s GPT-4o and structured prompt chaining to perform advanced contractual analysis without domain-specific fine-tuning. Key functions include automated metadata extraction, executive summarization, red-flag clause detection, and a novel feature for natural-language contract modification. This approach overcomes the cost and complexity of training proprietary models, democratizing legal insight and significantly reducing operational overhead. The system was validated through real-world testing at a leading industry partner, demonstrating its effectiveness as a scalable and secure foundation for managing the high volume of legal data. This work establishes a robust proof-of-concept for future enterprise-grade enhancements, including workflow automation and predictive analytics. Full article

Background/Objectives: While excessive body fat is commonly linked to metabolic disorders (metabolically unhealthy obesity, MUO), a subset of individuals remain metabolic healthy despite obesity (metabolically healthy obesity, MHO). This work aims to determine how these phenotypes influence responses to lifestyle modification (LSM) in older adults. Methods: A 12-month lifestyle modification (LSM) intervention based on the Mediterranean Diet (MedDiet) and regular physical activity (PA) was conducted in 43 older adults (70% women) classified according to World Health Organization (WHO) criteria as MHO (22 subjects) or MUO (21 subjects). Clinical, dietary, and PA parameters were assessed at baseline and follow-up. Peripheral blood mononuclear cells were analyzed for mitochondrial fusion (OPA1, MFN2), mitophagy (PINK1), biogenesis (TFAM), and the respiratory chain (COX IV) using Western blot and RT-qPCR techniques. Results: At baseline, MUO showed significant lower OPA1-L, MFN2, and TFAM along with MFN2 degradation products and PINK1 accumulation. After 12 months of LSM, MUO participants exhibited greater metabolic profile improvements, such as significantly reduced MFN2 degradation products and higher COX IV. Changes in mitochondrial proteins were associated with nutrient intake and PA and clinical parameters with phenotype-specific patterns. In MUO, protein and cholesterol intake improved MFN2 fusion (rho = 0.446, p = 0.043; rho = 0.581, p = 0.006), while carbohydrates were negatively associated with OPA1 in MHO (rho = −0.596, p = 0.025). PA was positively related to fusion proteins in both phenotypes. Clinically, significant improvements in BMI, waist circumference, and HDL were found in MUO but not in MHO. Conclusions: Older adults with obesity show phenotype-specific mitochondrial impairments that shape distinct responses to LSM, highlighting the relevance of tailoring LSM interventions by metabolic phenotype. Full article

The trade-off between the ionic conductivity and the stability of the proton exchange membrane (PEM) is a major concern in the development of PEM water electrolysis (PEMWE). This review focuses on the design and fabrication of homogeneous and composite PEMs for water electrolysis and establishes the structure–performance relationships between the membrane chemical/physical structures and their efficiency metrics—specifically, proton conductivity, hydrogen permeability, and chemical and mechanical stability. A special focus is placed on the fundamental connection between the microstructure and performance of membrane materials. At the molecular level, we systematically illustrate the design principles for main chains, side chains, and sulfonate groups, covering both fluorinated PEMs (encompassing perfluorinated and partially fluorinated membranes) and non-fluorinated PEMs (including aromatic polymers with heteroatom backbones and all-carbon backbones). At the macroscopic level, the review provides an in-depth exploration of two primary modification strategies: creating composites with organic polymers and with inorganic nanofillers. In summary, this review elucidates how these composite approaches leverage material synergies to improve the membrane’s mechanical integrity, proton conduction efficiency, and chemical resistance and offers a theoretical framework for the rational design of next-generation, high-performance PEMs to advance the commercialization of PEMWE technology. Full article

Higher-order chromatin structures (HOCS) are fundamental to genome organization, gene regulation, and cellular homeostasis. This review examines the epigenetic mechanisms shaping HOCS, including DNA methylation, histone modifications, chromatin remodeling, and RNA-based regulatory processes. We also discuss the role of architectural proteins in maintaining chromatin topology while allowing dynamic changes to chromatin structure, thereby influencing gene expression. Growing evidence indicates that disruptions in HOCS contribute to a diverse array of human diseases, including cancer, aging-related disorders, and congenital abnormalities, primarily through aberrant gene regulation. We further discuss the concept of distinct genomic areas, in which specific chromatin regions orchestrate three-dimensional (3D) genome dynamics, positioning them as potential biomarkers and therapeutic targets. By emphasizing chromatin architecture on a global scale rather than at the level of individual genes, this review underscores its emerging relevance to precision medicine. Finally, we synthesize current technical advances, outline future directions for leveraging chromatin topology in disease diagnosis and treatment, and highlight key biological insights to reshape our understanding of genome function. Full article

Nanofertilizers have attracted increasing attention as an approach to improve the low nutrient use efficiency of conventional fertilizers, in which only a limited fraction of applied nitrogen, phosphorus, and potassium is ultimately taken up by crops. Beyond their capacity to minimize nutrient losses, nanofertilizers have attracted increasing attention for their possible role in addressing environmental issues, including soil eutrophication and the contamination of groundwater systems. Owing to their nanoscale characteristics, including large specific surface area and enhanced adsorption capacity, these materials enable more precise nutrient delivery to the rhizosphere and sustained release over extended periods, while also influencing soil–plant–microbe interactions. In this review, nanofertilizers are classified into six major categories—macronutrient-based, micronutrient-based, organic, controlled-release, composite, and nano-enhanced formulations—and representative examples and preparation routes are summarized, including green synthesis approaches and conventional chemical methods. The agronomic mechanisms associated with nanofertilizer application are discussed, with emphasis on enhanced nutrient uptake, modification of soil physicochemical properties, and shifts in microbial community composition. Reported studies indicate that nanofertilizers can increase crop yield across different crop species and formulations, while also contributing to improved nutrient cycling. Despite these advantages, several limitations continue to restrict their broader adoption. These include uncertainties regarding long-term environmental behavior, relatively high production costs compared with conventional fertilizers, and the absence of well-defined regulatory and safety assessment frameworks in many regions. Overall, this review highlights both the opportunities and challenges associated with nanofertilizer application and points to the need for further development of cost-effective formulations and standardized evaluation systems that account for their distinct environmental interactions. Full article

Histone lysine acetylation is a widespread posttranslational modification, essential for vital functions in eukaryotic organisms. Histone lysine acetyltransferases (KATs) employ acetyl-coenzyme A as a universal acetyl donor for acetylation of lysine residues in histone and non-histone proteins. Despite the biomedicinal importance of modulation of the KAT activity, application of the acetyl-coenzyme A cosubstrate structure for the design of potent and selective inhibitors has been underexplored. Here, we developed functionalized coenzyme A analogs as inhibitors against human histone lysine acetyltransferases GCN5, KAT8, and HAT1. In contrast to the unmodified coenzyme A, which was found to be a poor inhibitor of GCN5 and KAT8 (IC₅₀ > 150 μM), we showed that a ketone-substituted coenzyme A was the most potent inhibitor of GCN5 and KAT8 (IC₅₀ = 10.9 μΜ and 13.6 μΜ, respectively). Coenzyme A and an acetamide-substituted coenzyme A efficiently inhibited HAT1 (IC₅₀ = 7.3 μΜ and IC₅₀ = 3.9 μΜ, respectively). Our work demonstrates that human KATs can be efficiently and selectively inhibited by S-functionalized coenzyme A, the results exhibiting significant potential towards development of highly active chemical probes for biomedically important KATs. Full article

In response to the complexity and uncertainty in assessing the safety and economic impacts of the Changed Product Rule (CPR) in civil aviation products’ airworthiness certification, this paper constructs a comprehensive evaluation model based on a cost–benefit analysis framework. In previous research, studies on aircraft modification costs have consistently been conducted from the perspective of design organizations, focusing on modeling and optimizing the one-time engineering costs of the modifications themselves or remaining confined to the level of safety performance without addressing the calculation of economic value. The model proposed in this paper considers the entire aircraft service lifecycle and uniformly quantifies potential impacts into monetary terms for comparison. The model encompasses safety improvements, cost estimation, and discounted cash flow analysis, aiming to provide decision-makers with quantitative tools for determining the applicability of the “impracticality exception” standard. This ensures that modifications to aviation products balance safety with economic viability. Through case studies involving fuel tank access panel design changes and Auxiliary Power Unit (APU) inlet duct fire protection requirements, the effectiveness and practicality of the model are validated, offering an empirical foundation for future policy formulation and industry regulation. Nevertheless, the parameters in the model depend on historical data, and appropriate parameters must be carefully selected. Although the model has taken into account the entire lifecycle of the aircraft, it is still based on static assumptions and fails to consider the impact of the rapid development of the aviation industry over time. Ongoing model refinement, international data collection, and integration of non-economic factors remain key directions for future research. Full article

Background/Objectives: Cisplatin (CDDP) is widely used in the treatment of non-small cell lung cancer (NSCLC); however, its clinical efficacy is limited by severe systemic toxicity. Hyaluronic acid (HA) modification enables the targeting of CD44-overexpressing cancer cells, enhances biocompatibility, provides controlled drug release, and prolongs systemic circulation. This study aimed to develop high-molecular-weight hyaluronic acid-modified, cisplatin-loaded mesoporous silica nanoparticles (HA-MSN-CDDP) to selectively target CD44-overexpressing lung adenocarcinoma cells. Methods: HA-MSN-CDDP nanoparticles were synthesized via the sol–gel method and characterized by FTIR, DLS, SEM, and TEM methods. Antitumor efficacy was evaluated using both in vitro and in vivo xenograft lung cancer models in mice. Results: HA modification enabled controlled and sustained release of cisplatin from the HA-MSN-CDDP drug delivery system. Through HA-mediated receptor-dependent endocytosis, the nanoparticles exhibited enhanced cellular uptake and selective cytotoxicity toward CD44-positive cells. HA-MSN-CDDP significantly reduced the cytotoxic, genotoxic, and oxidative stress effects of free cisplatin on healthy cells while markedly enhancing apoptosis in A549-Luc-C8 cells. The system showed excellent hemocompatibility, supporting its potential for intravenous use. In vivo, HA-MSN-CDDP effectively suppressed tumor growth, mitigated lipid peroxidation, and preserved antioxidant enzyme activities (SOD and CAT) in major organs. Histological analyses confirmed reduced cisplatin-induced nephrotoxicity. Conclusions: HA-MSN-CDDP demonstrates strong potential as a targeted chemotherapeutic platform for NSCLC, combining high antitumor efficacy with reduced systemic toxicity. Full article