Search Results (132)

Pantoea piersonii (formerly Kalamiella piersonii) is a recently reclassified environmental Gram-negative bacterium belonging to the family Erwiniaceae. Human infections caused by this organism are extremely rare. Here, we report a rare case of implantable venous access port-associated soft tissue infection caused by P. piersonii in a 49-year-old immunocompromised woman with lung cancer. The pathogen was isolated from purulent discharge obtained from the port site and identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Whole-genome sequencing confirmed species-level identification based on average nucleotide identity (ANI) analysis and phylogenomic reconstruction. The isolate exhibited broad antimicrobial susceptibility to the tested agents. Following complete device removal and empirical antimicrobial therapy, the patient recovered uneventfully. This study reports the first documented case of P. piersonii infection in China and provides a comprehensive clinical and genomic characterization of a newly isolated clinical strain. Full article

Background/Objective: Persistent infection with human papillomavirus type 16 (HPV-16) is the principal cause of cervical high-grade squamous intraepithelial lesions (cHSIL) and cervical cancer, yet the established treatments remain limited to ablative or excisional procedures that carry reproductive risk and do not eliminate the underlying infection. We report the preclinical development of ARV-2001, a messenger RNA (mRNA)–lipid nanoparticle (LNP) immunotherapeutic encoding mutated, non-oncogenic HPV-16 E6 and E7 fused to a SARS-CoV-2 spike S2 subdomain enriched in human CD4 helper epitopes, formulated in a novel cholesterol-derived ionizable lipid (ARV-T1). Methods: Interactions of ARV-2001-expressed antigens with p53 and retinoblastoma (Rb) were evaluated in human cervical carcinoma cell line C33A, in lentiviral constructs in primary human keratinocytes, and in soft-agar colony-formation assays. ARV-2001 was administrated by intramuscular (IM) or intradermal (ID) injection in naive mice or in the TC-1 tumor models. Tumor size and survival were monitored over time and tumor-infiltrated lymphocytes were characterized by flow cytometry. Intracellular cytokine staining and Elispot were used to evaluate immunogenicity. Results: In vitro, the mutated E6/E7–S2 antigen lost the ability to degrade p53, to deregulate the retinoblastoma (Rb) pathway, and to support anchorage-independent growth, suggesting abrogation of oncogenic activity. The S2 domain and imiquimod administration each augmented antitumor activity and intratumoral CD8⁺ T-cell infiltration while reducing myeloid-derived suppressor cells in the syngeneic HPV-16 E6/E7 TC-1 tumor models. In addition, ID administration of ARV-2001 into TC-1 tumor-bearing mice was superior to IM administration in terms of both tumor growth inhibition and survival. ID vaccination with ARV-2001 in mice consistently elicited a more potent E6/E7-specific T-cell response than the same dose given IM. Dose-escalation studies showed a dose-dependent T cell response against E6/E7 in ID-injected mice. Conclusions: This study supports future human evaluation of intradermally administrated ARV-2001 for treatment of HPV-16+ cHSIL in clinical trials. Full article

Apoptosis is traditionally considered a definitive barrier against oncogenesis, as caspase activation typically eliminates damaged and genetically unstable cells. Here, we report that caspase-8, an initiator of extrinsic apoptosis, paradoxically promotes genetic instability and carcinogenesis following exposure to radiation. We observed that a substantial fraction of mammalian cells exposed to ionizing radiation can survive despite caspase-8 activation. This sublethal activation of caspase-8 facilitated persistent DNA damage, which was attenuated by the expression of a dominant-negative caspase-8 (C360A, Casp8DN) or short hairpin RNA (shRNA)-mediated knockdown of caspase-8 in mammalian cells. The facilitative role of caspase-8 in radiation-induced genomic instability was further validated in caspase-8 heterozygous mice. Moreover, inhibition of caspase-8 abolished iron-ion radiation-induced oncogenic transformation in both soft agar and nude mice. Mechanistically, sublethal caspase-8 activation promoted the nuclear translocation of mitochondrial endonuclease G and persistent DNA damage, accompanied by activation of non-canonical nuclear factor κB (NF-κB) signaling. Collectively, our findings demonstrate that caspase-8 can act as a causative driver of radiation-induced malignancy, challenging the dogma of caspases as universal anticancer barriers and providing important insights into the long-term health risks associated with space radiation and radiotherapy. Full article

Background: Ignatzschineria species are rare emerging human pathogens that are typically associated with myiasis. Methods: We report the first case of Ignatzschineria indica bacteraemia in Greece in a male patient presenting with maggot-infested wounds of the thorax, shoulders, and arms. The isolate was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and antimicrobial susceptibility testing was performed according to EUCAST guidance. A review of the published literature on I. indica bacteraemia was also conducted. Results: The patient was diagnosed with bacteraemia caused by a multisusceptible I. indica isolate and was successfully treated with antibiotic therapy, resulting in complete recovery. This represents the first reported case of I. indica infection in Greece. Review of the literature showed that most published I. indica isolates were susceptible to a broad range of antimicrobial agents, and all reported patients survived, although some required limb amputation because of severe underlying soft tissue disease. Conclusions: Ignatzschineria indica infection should be considered in patients with neglected, maggot-infested wounds. Increased awareness of this emerging pathogen, together with the use of modern microbiological identification methods, may improve recognition of these uncommon infections. Socio-economic inequalities and the changing distribution of insect vectors due to climate change may contribute to the occurrence of such infections. Full article

Finite element (FE) modeling is widely used in biomechanical research, enabling computational investigations of anatomical structures. To develop accurate FE models, high-resolution medical imaging such as computed tomography (CT) is essential. However, CT exposes patients to ionizing radiation. Recently, radiation-free three-dimensional zero-echo-time magnetic resonance imaging (3D ZTE MRI) has shown promising results for bone visualization. Therefore, this feasibility study investigated whether 3D ZTE MRI is reliable for creating subject-specific FE models. Human femora from four female subjects were imaged using 3D ZTE MRI. Static FE analyses of the femora were performed in Abaqus/CAE, assuming a biphasic homogenous linear-elastic material. A sensitivity analysis was conducted to evaluate varying bone material properties. After loading with 2000 N, the mean displacement of the femoral head amounted to −1.30 ± 0.26 mm (vertical) and −9.03 ± 2.21 mm (horizontal), while the femoral neck exhibited compressive (inferior: −1366.03 ± 182.70 µm/m) and tensile (superior: 1038.69 ± 135.82 µm/m) strains. Overall, the results demonstrate displacement and strain predictions similar to previous experimental and computational studies based on CT data. Therefore, despite several simplifications, these findings confirm the feasibility of radiation-free 3D ZTE MRI for subject-specific FE modeling, enabling future simultaneous assessment of bone morphology and surrounding soft tissues. Full article

When pregnant patients undergo diagnostic and therapeutic radiological procedures, the unborn child is exposed to an increased risk due to the use of ionizing radiation; therefore, the fetal dose must be estimated and optimized. Tools and methods routinely used for fetal dose estimation lack better personalization of patients. To address this, we developed a software tool for creating phantoms at different pregnancy stages and with varying patient anatomies to further personalize fetal dose estimation using measurements and Monte Carlo simulations. The tool is developed and incorporated into 3DSlicer version 5.6.2 as a plugin. Phantoms are created based on a real patient phantom, Tena, and physiological data for use in radiological protection. Phantoms are developed with only soft, lung, and bone tissue substitutes, represented for the mother and unborn child. This enables the construction of segmented voxel models as well as mesh models (with the ability to export geometries to DICOM format) of the anatomical structures of pregnant women. Additionally, it allows real patient image registration to enable better personalization of the phantom. The tool can help decrease uncertainty in fetal dose estimation, as well as simplify and accelerate the process of fetal dose estimation. It is released publicly to enable further research. Full article

Melanin-like polymers, particularly polydopamine, have gained significant attention as photothermal materials due to their broad light absorption (ultraviolet to near-infrared), high photothermal conversion efficiency, negligible fluorescence, good biocompatibility regarding unmodified melanin-like polymers, and universal adhesion. Upon light irradiation, these bioinspired polymers convert absorbed optical energy into heat through molecular vibration and electron–phonon coupling, making them ideal for diverse photothermal applications. This review comprehensively summarizes recent advances in using melanin-like polymers for photothermal purposes. In biomedical engineering, they serve as efficient agents for photothermal therapy and synergistic antibacterial treatment. In catalysis, their photothermal effect enhances pollutant degradation, hydrogen production, and chemical warfare agent detoxification. For water remediation, melanin-like polymers are fabricated into evaporators, membranes, and aerogels for solar-driven steam generation, desalination, and oil spill cleanup. They also enable sensitive photothermal sensing, near-infrared imaging, and laser desorption ionization mass spectrometry imaging. Furthermore, these materials are incorporated into soft actuators and self-healing elastomers for light-controlled shape memory, programmable folding, and remote manipulation. Finally, we discuss remaining challenges such as long-term stability, biocompatibility, scalability, and color limitations and provide future perspectives for advancing melanin-like photothermal materials toward practical applications. Full article

Emerging organic pollutants (EOPs) in aquatic environments have attracted increasing attention because many occur at trace levels, undergo transformation during environmental transport, and contribute to poorly resolved mixture risks. Traditional targeted analysis is inherently restricted to predefined compounds, whereas high-resolution mass spectrometry (HRMS)-based full-scan workflows provide broader opportunities for discovering known unknowns and previously unrecognized contaminants. This review critically synthesizes an omics-based analytical framework for aquatic environments, covering sample digitalization, instrumental analysis and acquisition modes, chemical fingerprint/non-target screening, suspect screening, effect-directed analysis, and confidence-based structural identification. Particular emphasis is placed on practical decision points and trade-offs, including dissolved versus particulate-associated analytes, LC-HRMS versus GC-HRMS coverage, hard versus soft ionization, DDA- versus DIA-type acquisition, database dependence, and the persistent difficulty of linking analytical features to toxicological relevance. The review also discusses emerging directions involving artificial intelligence, chemometrics, organometallic contaminants, and microplastic-associated chemicals. By clarifying conceptual boundaries and highlighting current limitations, this article aims to support the development of more critical, transparent, and risk-oriented workflows for the discovery and prioritization of emerging pollutants in aquatic environments. Full article

Despite their significance as forensic targets, alkyl nitrites, classified as illegal drugs, have received little attention in forensic analysis due to their high volatility and chemical instability. Here, we present a high-performance analytical approach using a pulsed dc soft plasma ionization-quadrupole mass spectrometry (pulsed dc SPI-MS) system, uniquely designed to operate using ambient air as the discharge gas. In this system, the modulation of the duty ratio functions as a “structural probe” to identify reactive isomers. Unlike conventional dielectric barrier discharge (DBD) sources that typically operate at atmospheric pressure, our SPI system utilizes a controlled pressure regime of several kPa, where the nitrogen in the ambient air effectively functions as a third-body gas to suppress excessive internal energy. The control of the duty ratio in our pulsed dc SPI source allowed for the successful manipulation of ion–molecule reaction pathways for highly reactive analytes. By optimizing several parameters, including duty ratio and discharge pressure, we achieved a unique ionization regime where the molecular-related ion [2 M − 3 H]⁺ was predominantly detected as the base peak with minimal fragmentation. Notably, by reducing the duty ratio from 50% to 5%, both the target ion occupancy and signal intensity were significantly enhanced, achieving a limit of detection (LOD) as low as 0.16 parts per million by volume (ppmv). This sensitivity is several orders of magnitude higher than previously reported thresholds, enabling rapid identification of C4–C6 alkyl nitrite isomers. This method transforms the duty ratio into a powerful diagnostic tool for identifying reactive intermediates, providing a practical and efficient approach for the onsite identification of illegal alkyl nitrites in forensic and security fields. Full article

Background: Although magnetic resonance imaging (MRI) provides excellent soft-tissue contrast for most spinal evaluations, computed tomography (CT) is still always required for preoperative planning to assess osseous anatomy and determine surgical device size, increasing the radiation exposure and workflow complexity. CT-like images enable visualization of precise bone morphology without ionizing radiation. In addition, these images often provide CT myelography-like contrasts, allowing the simultaneous depiction of the spinal canal area (SCA). This study aimed to evaluate whether CT-like images provide measurement accuracy equivalent to conventional CT and MRI for pedicle screw planning and spinal canal area assessment. Methods: We retrospectively analyzed paired lumbar CT and MRI datasets obtained within ≤1 month in 51 patients. Pedicle width and length were measured on CT and CT-like images, whereas SCA was measured on T2 weighed-images and CT-like images. A total of 224 vertebrae were analyzed. Annotated images were independently evaluated by two readers in a randomized order. Inter-modality agreement was assessed using intraclass correlation coefficients (ICCs) and a Bland–Altman analysis. Results: CT-like images demonstrated an excellent agreement with CT for pedicle measurements (ICCs: 0.968–0.985 for width; 0.922–0.966 for length). Mean differences were ≤0.1 mm for pedicle width and approximately 1 mm for pedicle length, which are unlikely to affect screw selection. The agreement with T2WI for SCA was good to excellent (ICCs: 0.766–0.945). Conclusions: CT-like images provide comparable performance for quantitative pedicle assessment and show high agreement for SCA evaluation, supporting comprehensive preoperative assessment with a single MRI examination. Full article

This study elucidates the regulatory mechanisms of methoxy substitution and photoexcitation on the antioxidant properties of pterostilbene (PTE) versus resveratrol (RES), employing a combined approach of multi-reference calculations, density functional theory (DFT), time-dependent DFT (TD-DFT), and molecular docking. Spectral analysis indicates that trans isomers exhibit a significant redshift (~13 nm) and have oscillator strengths more than double those of cis isomers. A pivotal difference in photoisomerization kinetics was identified: methoxy substitution drastically lowers the isomerization barrier for RES, indicating that PTE is more readily photoisomerized. Regarding radical scavenging, thermodynamic data confirm that Hydrogen Atom Transfer (HAT) and Radical Adduct Formation (RAF) are spontaneous pathways; notably, the O1 site of trans-PTE serves as the optimal hydrogen donor. Conceptual DFT (CDFT) analysis reveals that photoexcitation triggers a dramatic electronic reconfiguration, particularly for cis-PTE, whose ionization potential in the S1 state drops sharply to 4.66 eV, accompanied by an increased softness of 0.38 eV⁻¹, rendering it a highly potent electron donor. Furthermore, molecular docking demonstrates that trans-PTE robustly occupies the Keap1 Kelch pocket (binding energy: −7.478 kcal/mol) to inhibit Nrf2 binding via its favorable planar geometry. Full article

Antimicrobial resistance (AMR) remains a serious public health concern, and methicillin-resistant Staphylococcus aureus (MRSA) continues to limit treatment options. This laboratory-based comparative study evaluated antibiotic resistance patterns and nanoparticle (NP) susceptibility among 110 S. aureus isolates recovered from human skin and soft tissue infections (n = 80) and camel milk (n = 30). Proteomic identification utilizing matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) was carried out for all isolates under study. Phenotypic differentiation between MRSA and methicillin-sensitive S. aureus (MSSA) was performed via the cefoxitin disk diffusion method, and antimicrobial susceptibility testing was carried out using the disk diffusion method as stated in international guidelines. Multidrug resistance (MDR) was defined by established criteria. The antibacterial activity of silver nanoparticles (AgNPs) and gold nanoparticles (AuNPs) was detected by broth microdilution to determine minimum inhibitory concentration values (MIC₅₀ and MIC₉₀). The ability to develop reduced susceptibility was evaluated through ten serial sub-inhibitory passages followed by stability testing without using nanoparticles. MRSA prevalence was 52.5% among human isolates and 70% among camel milk isolates. Overall, 56.4% of isolates met MDR criteria, with a significantly higher MDR rate among MRSA compared with MSSA. Both human and camel isolates showed similar resistance patterns. AgNPs exhibited strong antibacterial activity, with MIC₅₀ and MIC₉₀ values of 0.0078 mg/mL and 0.0156 mg/mL, respectively; nevertheless, AuNPs demonstrated higher MIC values. Response to NPs was similar between isolates, independent of methicillin resistance or MDR. Serial sub-inhibitory exposure resulted in increased MIC values in all tested isolates, and stable resistance persisted in 50% of cases. These results indicate ongoing MRSA circulation in human and animal settings and reinforce the need for careful and controlled use of NP-based antimicrobials. Full article

Stimuli-responsive liposomal membranes have attracted growing interest as dynamic soft materials capable of regulating permeability, fusion, and cargo release in response to external or internal triggers. By incorporating functional molecular or nanostructured guests, such as photochromic compounds, plasmonic nanoparticles, or ionizable lipids, bilayers can be endowed with reversible and tunable properties. These modifications often rely on the precise control of lipid packing, phase behaviour, and the formation of transient membrane defects that facilitate molecular transport. This review aims to provide an overview of the molecular design strategies and underlying mechanisms used to engineer such responsive liposomal systems, with particular emphasis on light- and heat-triggered behaviours and on supramolecular approaches that modulate membrane structure and dynamics. Emerging trends, current limitations, and opportunities for future development in functional lipid-based materials and biointerfaces will also be discussed. Full article

We aimed to establish a rapid and precise method for identifying and quantifying multi-species vegetable oil (corn oil, olive oil (OLO), soybean oil, and sunflower oil (SUO)) adulterations in camellia oil (CAO), using soft ionization by chemical reaction in transfer–high-resolution mass spectrometry (SICRIT-HRMS) and machine learning methods. The results showed that SICRIT-HRMS could effectively characterize the volatile profiles of pure and adulterated CAO samples, including binary, ternary, quaternary, and quinary adulteration systems. The low m/z region (especially 100–300) exhibited importance to oil classification in multiple feature-selection methods. For qualitative detection, binary classification models based on convolutional neural networks (CNN), Random Forest (RF), and gradient boosting trees (GBT) algorithms showed high accuracies (98.70–100.00%) for identifying CAO adulteration under no dimensionality reduction (NON), principal component analysis (PCA), and uniform manifold approximation and projection (UMAP) strategies. The RF algorithm exhibited relatively high accuracy (96.25–99.45%) in multiclass classification. Moreover, the five models, including CNN, RF, support vector machines (SVM), logistic regression (LR), and GBT, exhibited different performances in distinguishing pure and adulterated CAO. Among 1093 blind oil samples, under NON, PCA, and UMAP: 10, 5, and 67 samples were misclassified by CNN model; 6, 7, and 41 samples were misclassified by RF model; 8, 9, and 82 samples were misclassified by SVM model; 17, 18, and 78 samples were misclassified by LR model; 7, 9, and 43 samples were misclassified by GBT model. For quantitative prediction, the PCA-CNN model performed optimally in predicting adulteration levels in CAO, especially with respect to OLO and SUO, exhibiting a high coefficient of determination for calibration ($R_C^2$, 0.9664–0.9974) and coefficient of determination for prediction ($R_p^2$, 0.9599–0.9963) values, low root mean square error of calibration (RMSEC, 0.9–5.3%) and root mean square error of prediction (RMSEP, 1.1–5.8%) values, and RPD (5.0–16.3) values greater than 3.0. These results indicate that SICRIT-HRMS combined with machine learning can rapidly and accurately identify and quantify multi-species vegetable oil adulterations in CAO, which provides a reference for developing non-targeted and high-throughput detection methods in edible oil authenticity. Full article

Subsurface deposition determines whether soils, aquifers, or ocean sediment represent a sink or temporary reservoir for microplastics. Deposition is generally studied by applying the Smoluchowski–Levich equation to determine a particle’s sticking efficiency, which relates the number of particles filtered by sediment to the probability of attachment occurring from an interaction between particles and sediment. Sticking efficiency is typically measured using column experiments or estimated from theory using the Interaction Force Boundary Layer (IFBL) model. However, there is generally a large discrepancy (orders of magnitude) between the values predicted from IFBL theory and the experimental column measurements. One way to bridge this gap is to directly measure a microparticle’s interaction forces using Atomic Force Microscopy (AFM). Herein, an AFM method is presented to measure sticking efficiency for a model polystyrene microparticle (2 μm) on a model geomaterial surface (glass or quartz) in environmentally relevant, synthetic freshwaters of varying ionic strength (de-ionized water, soft water, hard water). These data, collected over nanometer length scales, are compared to sticking efficiencies determined through traditional approaches. Force measurement results show that AFM can detect extremely low sticking efficiencies, surpassing the sensitivity of column studies. These data also demonstrate that the 75th to 95th percentile, rather than the mean or median force values, provides a better approximation to values measured in model column experiments or field settings. This variability of the methods provides insight into the fundamental mechanics of microplastic deposition and suggests AFM is isolating the physicochemical interactions, while column experiments also include physical interactions like straining. Advantages of AFM over traditional column/field experiments include high throughput, small volumes, and speed of data collection. For example, at a ramp rate of 1 Hz, 60 sticking efficiency measurements could be made in only a minute. Compared to column or field experiments, the AFM requires much less liquid (μL volume) making it effortless to examine the impact of solution chemistry (temperature, pH, ionic strength, valency of dissolved ions, presence of organics, etc.). Potential limitations of this AFM approach are presented alongside possible solutions (e.g., baseline correction, numerical integration). If these challenges are successfully addressed, then AFM would provide a completely new approach to help elucidate which subsurface minerals represent a sink or temporary storage site for microparticles on their journey from terrestrial to oceanic environments. Full article