Search Results (1,161)

Background/Objectives: Ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA) are critical therapeutic options for multidrug-resistant Gram-negative infections; however, their comparative pharmacodynamics against carbapenem-resistant Pseudomonas aeruginosa (CRPA) remain incompletely defined. This study aimed to compare the bactericidal activity of C/T and CZA administered by intermittent infusion (II) or continuous infusion (CI) using a hollow fiber infection model (HFIM) against a clinical isolate of CRPA. Methods: Clinically relevant concentration–time profiles for C/T and CZA based on prescribing information were simulated in the HFIM. The standard P. aeruginosa strain ATCC 27853 and a GES-producing clinical CRPA isolate were utilized. The primary endpoint was bactericidal activity (≥3 log₁₀ CFU/mL reduction from baseline), while secondary endpoints included regrowth prevention and resistance development based on population analysis profiles (PAPs). Results: Against the standard strain, both agents achieved rapid killing without regrowth. However, for the GES-producing clinical isolate, C/T failed to achieve bactericidal activity. In contrast, CZA demonstrated sustained bacterial killing activity with the most pronounced early-phase bactericidal activity with CI of CZA (−4.25 log₁₀ CFU/mL at 24 h). The bactericidal activity was persistent over 7 days without bacterial regrowth after treatment discontinuation. Conversely, bacterial regrowth occurred with II of CZA after drug withdrawal. PAPs showed the lack of resistance development against CZA, whereas resistance to C/T developed within 48 h after initiating therapy. Conclusions: In this HFIM study, CI of CZA demonstrated the most sustained suppression of bacterial growth and prevented resistance emergence against the tested clinical isolate of CRPA producing GES β-lactamases. Future clinical studies are warranted to assess the effectiveness of the CI regimen. Full article

The security of biometric data is a critical challenge in modern information security due to their uniqueness and non-revocability. Compromise of biometric characteristics leads to irreversible consequences; therefore, storing or transmitting them in plaintext is unacceptable. This paper addresses the confidentiality and integrity of fingerprint data using cryptographic protection methods. Considering the specific nature of biometrics, fingerprint features are used only to generate a cryptographic secret rather than being stored directly. To protect the derived secret, a modified threshold secret-sharing scheme based on non-positional polynomial notation and the Chinese Remainder Theorem is proposed. The method generates a cryptographic secret from fingerprint minutiae described by spatial coordinates and ridge orientation. Concatenating minutiae coordinates and converting them into binary form produces a unique value deterministically linked to a specific user. Compared to the classical Shamir scheme, the modified scheme reduces the computational complexity of secret reconstruction from O($n {log}^{2}n$) to O(k log k), decreases data storage requirements by 30–40% through compact polynomial remainders, and increases successful secret reconstruction by 12–15% in the presence of noise in biometric samples. The results show that the proposed algorithm can be effectively applied in biometric authentication systems to protect personal data in distributed environments. Security analysis confirms resistance to major attack classes and demonstrates practical applicability in real-world systems. Full article

The sustainability of higher education systems increasingly depends on the integrity, transparency, and long-term verifiability of academic credentials. Widespread diploma fraud, unauthorized modification of academic records, and fragmented verification mechanisms undermine institutional trust, graduate mobility, and public confidence in educational outcomes. These challenges directly affect the social and governance dimensions of sustainable development, particularly in the context of universities’ digital transformation. This study proposes a blockchain-based approach to support the sustainable governance of academic documents by strengthening transparency, accountability, and auditability. The proposed system employs cryptographic hash anchoring and smart contract–based enforcement to verify academic credentials such as diplomas, transcripts, and certificates. Document contents are processed and stored off-chain, while cryptographic representations and essential metadata are immutably recorded on an EVM-compatible blockchain, ensuring data privacy and resistance to tampering. Any modification to a document results in a mismatch between the original and recomputed hashes, making fraudulent alterations immediately detectable. A web-based application and a role-restricted smart contract were implemented to support document issuance, verification, and immutable audit logging. System evaluation based on blockchain transaction evidence confirms reliable document registration, deterministic verification outcomes, and verifiable linkage between institutional actions and on-chain records. The results indicate that blockchain-based document verification can contribute to the reduction in corruption risks and improve transparency, strengthening institutional trust and supporting sustainable digital governance in higher education systems. Full article

Over the past decade, antibacterial materials have become a promising strategy to address both antibiotic-resistant and biomaterial-associated infections in clinical settings. Despite substantial progress, a gap remains between promising antibacterial performance in vitro and limited therapeutic outcomes in vivo. Herein, we present a mechanistic framework for understanding formulation-dependent antibacterial performance across five representative formulation architectures: nanoparticle-based systems, nanofibrous scaffolds, hydrogel matrices, surface coatings, and vesicular or microencapsulated carriers. We impart how structural organization and delivery dynamics regulate antibacterial mechanisms such as contact-mediated killing, controlled therapeutic release, and reactive oxygen species (ROS) generation and discuss their context-dependent suitability for diverse infection scenarios; these include acute wound infections, biofilm-associated implant infections, and chronic infected wounds. Particular emphasis is placed on factors contributing to the frequent failure of high in vitro log reduction efficacy translating into clinical success, including protein corona formation, biological barrier penetration, and dynamic host–pathogen interactions. Finally, we propose a comparative formulation-selection framework based on infection type, tissue environment, and therapeutic objectives to guide the rational design of next-generation antibacterial materials. This perspective bridges the gap between material innovation and clinical translation by highlighting formulation architecture as a central determinant of antibacterial performance in biomedical applications. Full article

Mountainous areas are prone to extreme climatic conditions, and the lack of modern infrastructure makes it difficult to achieve sustainable construction. To overcome the challenges of thermal comfort, robustness, and post-occupancy performance in hazard zones like the Neelum Valley in Pakistan, this research proposes a Digital–Vernacular Integration Model (DVIM), which integrates traditional architectural expertise with modern digital technology. The research design was based on mixed-methods research with the integration of qualitative information obtained through interviews and household surveys (n = 120), and quantitative measures of indoor thermal environments and hazards-based spatial analysis. Vernacular buildings made of wood, stone, and mud were digitally reconstructed using geometric modeling with SketchUp and Autodesk Revit with building information (BIM)-based modeling for assigning materials’ properties. Simulations were carried out using DesignBuilder software with EnergyPlus engines for assessing thermal environment, snow resistance, and seismic resistance to local hazards. The incorporation of the double-layered wall resulted in the improvement of heat retention by 12 to 15%. Moreover, the optimized roof and walls of the hybrid model resulted in the reduction of the sensible heating demand by 42% when compared to the conventional log houses and nearly 80% when compared to the conventional concrete block houses of the modern era. The proposed hybrid model resulted in R-values ranging from 33 to 40 m²·K/W, which are significantly higher when compared to the R-values for conventional timber walls (R = 15 m²·K/W) and concrete block walls (R = 1.0 to 1.3 m²·K/W). These results show the effectiveness of the digitally optimized hybrid model in improving the thermal performance in severe climatic conditions. The results clearly show that the integration of traditional architecture with digital simulation can ensure that modern comfort and safety standards are met without affecting the cultural identity of the region. The proposed framework will be implemented in pilot projects to ensure that the hybrid architectural models are incorporated into regional building regulations. Full article

Klebsiella pneumoniae poses a severe global health threat due to its extensive antibiotic resistance. However, to date, no vaccine against this pathogen has been approved for clinical use worldwide. Although self-assembling nanocarriers present distinct advantages for vaccine design, their ability to effectively load polysaccharide antigens and further elicit mucosal immunity remains unclear. Here, we developed a modular, self-assembling nanovaccine (CNP-OPS_KpO1) against K. pneumoniae by loading of K. pneumoniae O1 polysaccharide antigen onto a cholera toxin B subunit (CTB)-based nanoparticle (CNP). After determining the safety of the vaccine via intranasal immunization, we further evaluated its immune efficacy. CNP-OPS_KpO1 elicited stronger systemic IgG and mucosal sIgA responses than non-nanoparticulate controls. In a non-lethal pulmonary infection model, CNP-OPS_KpO1 vaccination reduced lung bacterial burden by over 5 logs compared to controls, achieving near-complete bacterial clearance. Histopathological analysis further confirmed minimal lung damage in vaccinated animals. In addition, in a lethal pulmonary challenge model, it conferred 90% survival, whereas all mice in the antigen-alone control group died within 4 days. Our work not only provides a safe, effective, and adjuvant-free candidate vaccine against K. pneumoniae but also advances a versatile platform for developing broad-spectrum mucosal vaccines against other pathogens. Full article

Niobium is a strategic critical mineral that supports emerging energy and high-end manufacturing. The geophysical parameters of carbonatite-alkaline rock-type niobium deposits constitute essential baseline data for regional geophysical exploration and prospecting target delineation. To clarify the geophysical response characteristics and exploration the significance of the Dagele niobium deposit in the Eastern Kunlun Region (western China). This study focuses on drill hole ZK3202. Samples from ore bodies, mineralized zones, and wall rocks of different lithologies were continuously measured. Combined with 1001.8 m of full-hole core digital logging data, statistical methods, including box plots, histograms, multi-parameter cross-plots, and correlation coefficient analysis, were applied to quantitatively investigate the physical property responses of lithologies such as calcite-biotite rock (ore body), calcite-bearing pyroxenite (mineralized zone) and amphibolite in the vertical profile. Lithological identification thresholds were established to divide the drill-hole into lithological and mineralized ore layers. The results show that the ore-bearing lithofacies exhibit a distinctive geophysical signature characterized by high density, strong magnetism, medium-low resistivity, high polarizability, and slightly elevated natural radioactivity, which clearly distinguishes them from surrounding from wall rocks. Based on five key parameters—density, magnetic susceptibility, resistivity, polarizability, and natural gamma—a lithological identification model for amphibolite and mineralized altered rock assemblages was established. This study also summarizes the multi-parameter coupling mechanism of ore-bearing lithofacies, which can effectively delineate favorable niobium-bearing horizons. This work fills a gap in the geophysical property characterization of carbonatite-alkaline complex-type niobium deposits in the Eastern Kunlun region and provides data support and regional reference for integrated gravity-magnetic-electrical-radioactive geophysical exploration, prospecting target delineation, and the exploration of similar niobium deposits in western China. Full article

Background: Cancer patients are highly susceptible to microbial infections due to immune suppression, necessitating therapeutic strategies that integrate anticancer efficacy with effective antimicrobial intervention. Chalcone-derived nitrogen-fused heterocycles represent a promising platform for developing multi-target agents with relevance to antimicrobial drug delivery, particularly for localized infections. Methods: A series of chalcone-based pyrazoline-thiadiazole nitrogen-fused azole hybrids was synthesized via thiosemicarbohydrazide-functionalized intermediates and fully characterized. Antiproliferative activity was evaluated against MCF-7, HepG-2, HeLa, and HCT-116 cell lines, alongside selectivity toward WI-38 normal fibroblasts. Antibacterial, antibiofilm, and in vivo efficacy were assessed against methicillin-resistant Staphylococcus aureus (MRSA USA300) and Acinetobacter baumannii AB5057. Mechanistic investigations included cell-cycle analysis, apoptosis assays, ERK2, RIPK3, p53, BAX/Bcl-2 quantification, DNA gyrase inhibition, molecular docking, molecular dynamics simulations, and density functional theory calculations. Results: Compound 13 exhibited potent cytotoxicity, particularly against MCF-7 (IC₅₀ = 3.87 ± 0.2 µM), outperforming doxorubicin (IC₅₀ = 4.17 ± 0.2 µM), with high selectivity indices (SI = 10.7 for MCF-7). Mechanistically, compound 13 induced G₂/M arrest (40.16% vs. 14.15% control), increased apoptosis to 32.89%, up-regulated ERK2 (3.17-fold), RIPK3 (11.97-fold), and p53 (3.54-fold), and markedly increased the BAX/Bcl-2 ratio (~42-fold). Compounds 7 and 13 displayed bactericidal activity against MRSA and A. baumannii (MIC/MBC = 10 mg/mL), potent antibiofilm effects, and significant in vivo efficacy in an MRSA skin infection model. Compound 13 reduced bacterial load by ~5 log units, outperforming vancomycin. DNA gyrase inhibition (IC₅₀ = 17.10 ± 0.17 µM) and computational studies supported target engagement. Conclusions: Pyrazoline-thiadiazole-based nitrogen-fused azole hybrids, particularly compound 13, demonstrated quantifiable anticancer and antimicrobial efficacy with strong in vivo validation, supporting their potential as multi-target candidates relevant to antimicrobial drug delivery in infection-prone cancer patients. Full article

Diabetic wounds infected with multidrug-resistant bacteria represent a major clinical challenge due to delayed healing and limited therapeutic options. In this study, we evaluated the therapeutic efficacy and biosafety of a biopolymeric skin patch loaded with the predatory bacterium Bdellovibrio bacteriovorus HD100 in a murine model of diabetic wounds infected with Pseudomonas aeruginosa. In vitro assays demonstrated that B. bacteriovorus HD100 reduced P. aeruginosa populations by approximately 3 log units within 48 h. In vivo, diabetic mice treated with the B. bacteriovorus-loaded patch achieved complete wound closure within $12\pm 1$ days, compared with $16\pm 1$ days in mice treated with conventional antibiotic therapy (piperacillin/tazobactam, 16 mg/kg; single dose). Non-diabetic mice treated with biopolymeric patches, with or without the predatory bacterium, exhibited complete wound closure within 9–10 days. Molecular analysis by PCR revealed no detectable dissemination of B. bacteriovorus DNA to internal organs (liver, spleen, kidney, or brain), indicating the systemic biosafety of topical application. Overall, these results demonstrate that B. bacteriovorus-based skin patches significantly accelerate wound closure in infected diabetic wounds and represent a promising localized biological alternative to conventional antibiotic therapy. Full article

Fully maintenance-free smart collars for range cattle, sheep and deer must survive years of uncontrolled grazing under highly variable shade and motion conditions. This paper presents an ultra-low-power buck converter governed by a fast integral terminal sliding mode controller (FITSMC) with a fixed-time observer. A new reaching law retains the initial sliding manifold and a negative-power term maintains the constant switching gain to preserve robustness near the surface while attenuating chattering without widening the bandwidth. The fixed-time observer estimates the irradiance and load changes and provides a feed-forward correction, tightening the output regulation regardless of initial conditions. Load step tests with moderate resistance swings showed the proposed method recovers noticeably faster and exhibits slightly lower overshoot than a recent method based on a two-phase power reaching law, while visible inductor current spikes are also suppressed. Simulations under daily grazing profiles confirmed tight output regulation adequate for microwatt data logging and periodic long-range (LoRa) bursts. The sleep mode quiescent current remained in the 9 microamps range, eliminating the need for manual recharge across multi-season field deployments. By integrating robust power electronics with collar-grade solar harvesting, the circuit offers a truly maintenance-free energy path for untethered livestock wearables and supports sustainable precision agriculture. Full article

Objectives: Multidrug-resistant (MDR) Pseudomonas aeruginosa represents a major clinical challenge, driven in part by resistance–nodulation–division (RND) efflux pumps that reduce intracellular antibiotic concentrations and limit the efficacy of many antibacterial agents, including fluoroquinolones. The aim of this study was to identify and characterize TXA11114 as a small-molecule efflux pump inhibitor (EPI) capable of restoring the activity of the fluoroquinolone levofloxacin against MDR P. aeruginosa. Methods: The antibacterial activity of the TXA11114–levofloxacin combination was evaluated using minimum inhibitory concentration (MIC) assays against panels of clinical isolates. Mechanistic studies included levofloxacin accumulation assays, ethidium bromide accumulation assays, outer-membrane permeability measurements, and whole-genome sequencing of mutants with altered potentiation phenotypes. In vivo efficacy was evaluated in murine thigh and lung infection models, while preliminary safety and drug-like properties were assessed using cytotoxicity assays and in vitro ADME profiling. Results: The TXA11114–levofloxacin combination produced > 1 log₁₀ CFU reductions in bacterial burden in murine thigh and lung infection models, exceeding the activity of levofloxacin monotherapy. TXA11114 markedly potentiated levofloxacin activity, producing substantial reductions in levofloxacin MIC values across multiple MDR clinical isolates, and also enhanced the activity of several additional efflux pump substrates, including β-lactams, tetracyclines, chloramphenicol, and trimethoprim–sulfamethoxazole. Mechanistic experiments demonstrated increased intracellular accumulation of efflux substrates without evidence of nonspecific membrane disruption, and mutations in ompH were associated with altered potentiation phenotypes. Conclusions: The TXA11114–levofloxacin combination produced significantly greater bacterial reductions than levofloxacin monotherapy in murine infection models. Levofloxacin was selected because fluoroquinolone resistance in P. aeruginosa is frequently driven by efflux-mediated mechanisms. While this study focused on levofloxacin potentiation, future work will evaluate additional efflux pump substrates and further define the molecular target of TXA11114. Full article

The polished stone value (PSV) is a key parameter for assessing the resistance of aggregates to polishing in the laboratory. It is included in technical specifications and serves as both a regulatory and contractual criterion for selecting aggregates for wearing courses. Its determination requires non-negligible amounts of material, long testing durations, and skilled operators. This study aims to develop a predictive modeling approach to estimate the polished stone value (PSV) from the mineralogical and chemical composition of aggregates. A curated database was compiled from the peer-reviewed literature, and compositional data were transformed using Isometric Log-Ratio (ILR) to generate physically interpretable balances and avoid constant-sum artifacts. Machine learning algorithms, including Gradient Boosting, CatBoost, and Multivariate Adaptive Regression Splines (MARS), were trained and evaluated using repeated 10 × 2 K-Fold cross-validation with preprocessing embedded within the loop. CatBoost achieved the highest accuracy, with 90.4% of predictions within ±20% of the measured PSV. Model interpretability using permutation feature importance and SHAP analysis identified meaningful drivers, highlighting the roles of CO₂/SO₃ versus the major-oxide framework, and silica-rich oxides versus CaO/MgO, consistent with petrographic expectations. The proposed workflow provides a practical and interpretable approach for predicting PSV from compositional data. It offers a time- and resource-efficient alternative to conventional laboratory tests, while also providing insight into the material factors that control aggregate polishing resistance. Limitations related to dataset size and inter-source variability are discussed. Full article

Background: Enterococcus faecalis is a major cause of complicated urinary tract infections (UTIs), characterized by intrinsic resistance and pronounced biofilm formation. Nitroxoline (NTX), a metal-chelating uroantiseptic, accumulates in urine and exhibits antibiofilm activity. Hydroquinone (HQ), the active urinary metabolite of arbutin-containing herbal preparations, is also excreted into urine and may contribute to antimicrobial activity in situ. This study investigated the antimicrobial and antibiofilm effects of NTX and HQ, individually and in combination, against uropathogenic E. faecalis isolates. Methods: Minimum inhibitory (MIC), bactericidal (MBC), and anti-adhesion (MAC) concentrations were determined using broth microdilution. Interaction was assessed by the checkerboard method and expressed as the fractional inhibitory concentration index (FICI). Biofilm inhibition was quantified by colony-forming unit (CFU) enumeration following exposure to subinhibitory concentrations. Ultrastructural alterations of E. faecalis following exposure to NTX and HQ were examined by transmission electron microscopy (TEM). Results: NTX demonstrated MIC values ranging from 0.002–0.016 mg/mL (MIC50/MIC90: 0.004/0.008 mg/mL), while HQ exhibited MIC values of 0.78–1.56 mg/mL (MIC50/MIC90: 0.78/1.56 mg/mL). Synergistic interactions (FICI ≤ 0.5) were observed in selected isolates, with up to eightfold and sixteenfold reductions in NTX and HQ concentrations, respectively. Additive effects predominated in the remaining isolates without antagonism. The combination achieved 3–5 log₁₀ reductions in adherent bacterial counts compared to untreated controls and up to 4 log₁₀ reductions compared to single-agent exposure. In several strains, complete inhibition of adhesion was observed. TEM analysis revealed marked envelope disruption, cytoplasmic condensation, and structural collapse following combined treatment. Conclusions: Given that both NTX and HQ are active within the urinary environment, their combination may represent a pharmacologically relevant strategy targeting both bacterial growth and early biofilm establishment in enterococcal UTIs. These findings support further in vivo and pharmacokinetic investigations to evaluate the clinical applicability of this combination. Full article

Candidozyma auris (formerly Candida auris) is frequently multidrug-resistant, resulting in limited treatment options and high mortality. Comparable mortality between C. auris candidemia and non-C. auris candidemia in recent studies requires confirmation in the Middle East after adjustment for confounders. This study aimed to compare mortality rates between patients with candidemia by C. auris and non-C. auris Candida species. We retrospectively analyzed 94 cases with candidemia between January 2019 and October 2025, including C. auris candidemia (n = 30) and non-C. auris candidemia (n = 64). Inverse probability weighting was used to balance baseline confounders between groups. The primary analysis used a weighted Cox proportional hazards model. Patients in the C. auris group had more comorbidities, greater healthcare exposure, and longer hospital stays. Crude 30-day all-cause cumulative mortality was comparable between the C. auris and non-C. auris groups (log-rank test, p = 0.8). The 30-day mortality of C. auris candidemia was similar to that of non-C. auris candidemia (adjusted HR 0.40; 95% CI 0.16–1.04; p = 0.060). Large multicenter studies involving diverse populations across different regions are warranted to validate these findings. Full article

The commercialization of V-based catalysts for the selective catalytic reduction of NOx by NH₃ (NH₃-SCR) is hindered by their narrow operating temperature window, insufficient low-temperature (LT) activity, and severe SO₂-to-SO₃ oxidation. To bridge this gap, we herein introduced Nb and hexagonal BN into a VW/TiO₂ system to simultaneously enhance its LT SCR activity, suppress undesired side reactions, and improve durability. Nb incorporation promoted V⁵⁺/V⁴⁺ redox cycling and enhanced lattice oxygen mobility, thus reducing the apparent activation energy and suppressing SO₂ oxidation at elevated temperatures. However, excessive Nb loading induced NH₃ oxidation and N₂O formation. This drawback was mitigated by introducing BN as a dispersion promoter, which helped secure high catalytic performance at a reduced Nb content. The VWNb/Ti-BN catalyst achieved superior NOx conversion and N₂ selectivity over a wide temperature range and benefited from notably suppressed NH₃ oxidation and SO₂-to-SO₃ oxidation. Kinetic analysis revealed that Nb primarily lowered the reaction energy barrier via redox property enhancement, whereas BN accelerated surface reaction turnover by stabilizing and dispersing active acidic sites, markedly increasing the turnover frequency without reducing the activation energy. In situ spectroscopic analysis confirmed the accelerated consumption of adsorbed NH₃ species and enhanced formation of reactive NOx intermediates, indicating SCR pathway enhancement. After aging in the presence of SO₂ and H₂O, the best-performing honeycomb-type monolithic catalyst retained and NOx conversion of >80%, demonstrating excellent long-term durability under practical conditions. A composition-aware machine learning model based on log-ratio-transformed variables quantitatively identified the synergistic balance among V, Nb, W, BN, and TiO₂ as the dominant factor governing LT SCR performance. Thus, this work provides valuable mechanistic insights and a strategy for designing wide-temperature-window SCR catalysts with improved activity, selectivity, and resistance to sulfur poisoning. Full article