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Engineered bacterial therapy suppresses Enterohemorrhagic Escherichia coli through metabolic competition and virulence silencing

Chronic and acute modulator treatment restore wild-type-like activity and stability to the primary cystic fibrosis–causing <i>CFTR</i> variant

Elexacaftor-tezacaftor-ivacaftor has transformed the treatment of people with cystic fibrosis (CF) and the predominant cystic fibrosis transmembrane conductance regulator ( CFTR ) variant F508del by delivering the faulty channel to the plasma membrane and potentiating its activity. However, the action of elexacaftor-tezacaftor-ivacaftor on the molecular behavior of F508del-CFTR is unknown. Here, we investigated the impact of elexacaftor-tezacaftor-ivacaftor on individual human F508del-CFTR Cl − channels using the patch-clamp technique and cells heterologously expressing F508del-CFTR. Chronic treatment of F508del-CFTR-expressing cells with elexacaftor-tezacaftor-ivacaftor, but not pairs of CFTR modulators, stabilized F508del-CFTR, preventing channel deactivation in cell-free membrane patches and conferring upon it the current amplitude of wild-type CFTR with channel activity sustained at a level one-third that of wild-type CFTR. By incubating cells with different drug concentrations, we demonstrated that elexacaftor stabilizes the open-channel conformation of elexacaftor-tezacaftor-ivacaftor-rescued F508del-CFTR, while acute treatment of wild-type CFTR with elexacaftor increased current flow through the channel and potentiated channel gating. Of note, acute treatment of elexacaftor-tezacaftor-ivacaftor-rescued F508del-CFTR Cl − channels with elexacaftor and ivacaftor restored wild-type levels of channel activity to the CFTR variant, albeit its gating pattern was distinct from that of wild-type CFTR and characterized by infrequent prolonged bursts of channel openings. In conclusion, chronic treatment with elexacaftor-tezacaftor-ivacaftor plus acute treatment with elexacaftor and ivacaftor robustly corrects the processing, stability, and gating defects of F508del-CFTR. Our results reveal that elexacaftor is a triple-acting CFTR modulator with corrector, potentiator, and conduction activities, making it a valuable therapeutic to rescue CFTR variants with distinct molecular mechanisms of CFTR dysfunction.

AI based sagittal spinal posture assessment for adolescent screening in low resource school settings

Short-term storage conditions do not affect canine fecal cortisol and secretory immunoglobulin A concentrations

High fat diet remodels the gene regulatory networks in the preoptic area

HPLC–DAD analysis of functional dietary supplements followed by liquid–liquid microextraction-assisted FTIR identification of IR-active ingredients

Longitudinal MR angiographic evaluation of circle of Willis morphologic remodeling and induced aneurysms in Hashimoto rat cerebral aneurysm model

Abstract We aimed to longitudinally characterize morphological remodeling of the Circle of Willis (COW) and aneurysm development in the Hashimoto rat cerebral aneurysm model using serial high-resolution 7T MR imaging. Aneurysm induction was achieved through unilateral carotid and renal artery ligation combined with salt and β-aminopropionitrile loading to induce hemodynamic stress and vascular fragility. TOF-MRA, T2-weighted, and black-blood MR sequences were acquired at four time points over 12 weeks. Morphological changes were quantified by measuring arterial diameters and tortuosity indices. Postmortem scanning electron microscopy (SEM) following vascular corrosion casting was used as the diagnostic reference. Significant asymmetric vascular remodeling was observed predominantly in the posterior circulation, with fusiform aneurysms confirmed by SEM in the left PCA P1 segment in two cases, both associated with subarachnoid hemorrhage. Microaneurysms below MR detection threshold were found at ACA–OA and ICA–MCA bifurcations. The sensitivity and specificity of MR-based aneurysm detection were 40% and 60%, respectively. While spatial resolution limited visualization of smaller lesions, longitudinal MR imaging allowed dynamic tracking of vascular changes and provided insight into early aneurysmogenesis. This platform enables in vivo evaluation of aneurysm initiation, growth, and rupture risk, supporting its potential utility for preclinical assessment of therapeutic strategies.

Sprayable gelatin microparticles prevent delayed gastric bleeding in an anticoagulated swine model

Abstract Delayed bleeding following endoscopic mucosal resection or endoscopic submucosal dissection is a serious concern in patients receiving anticoagulant therapy. We previously established an experimental animal model of delayed gastric bleeding following endoscopic resection under controlled anticoagulation. In this study, we aimed to evaluate the potential preventive effect of hydrophobized microparticles (hMPs), a novel sprayable wound-covering material derived from Alaska pollock gelatin, in preventing delayed bleeding. Twelve gastric mucosal defects were created by endoscopic mucosal resection with ligation in three CLAWN miniature swine. To induce delayed bleeding, systemic heparin was administered after confirming an activated clotting time greater than 220 s. hMPs were endoscopically sprayed into each ulcer base (200 mg/ulcer). Endoscopic examination was performed 24 h later. The primary endpoint was the presence or absence of delayed bleeding. Secondary endpoints included hMP retention, ulcer coverage rate, presence of exposed vessels, and vascular coverage by hMPs. During the 24-hour observation period, no delayed bleeding was observed in any of the three CLAWN miniature swine treated with hMPs. Hemoglobin levels on Day 1 remained stable in all swine. hMPs were present in 100% of the ulcers. Complete ulcer base coverage (100%) was achieved in 55.6% (20/36) of the sections, with ≥ 50% coverage observed in all sections. Exposed vessels were identified in 36.1% (13/36) of ulcers, and all were covered with hMPs. Endoscopic spray application of hMPs demonstrated strong adhesion to gastric ulcers and was associated with the absence of delayed bleeding in this short-term experimental model. These findings suggest that hMPs may represent a promising strategy for reducing the risk of delayed bleeding after gastrointestinal endoscopic surgery.

Sustainable valorization of copper mine waste into construction materials by alkali activation

Synergistic activity of sunlight protectants on some biocontrol agents as a new approach to control the cotton leaf worm, Spodoptera littoralis (Boisduval)

Abstract Bioinsecticides have gained attention as a sustainable and eco-friendly alternative to traditional chemical insecticides. They are target-specific, biodegradable, and reduce the development of insect resistance. However, their use is often limited by environmental instability, particularly under sunlight and UV radiation, which rapidly degrade active ingredients and reduce efficacy. Protective formulation, such as addition of UV-screening agents are needed to improve their durability and efficacy. This study investigates the efficiency of three UV protectants, Octylpalmitate, Tinuvin P, and UV- P in enhancing the persistence of some biocontrol agents, Dipel DF, Tracer, and Diacox under field conditions for 15 days to control the 4th instar larvae of Spodoptera littoralis . After 12 days, the residual effect of the all insecticides had markedly decreased, with Tracer showing the lowest persistence with zero mortality, and Diacox + UV protectant the highest. By 15 days, the sustained efficacy was absent, except for Diacox mixed with Octyl palmitate, Tinuvin P, and UV-P, which still caused 27, 32 and 12% mortality; respectively. The SDS-PAGE of S. littoralis larvae following 15 days of treatments revealed differences in the numbers of protein fragments between treated and control. New protein bands formed in the treated samples, while several normal bands disappeared.

Correction: Insect vectors have personality: first evidence with the tiger mosquito Aedes albopictus

Phytochemical composition and antimicrobial activity of Matricaria chamomilla ethanolic extracts against clinical bacterial isolates in Ibb City, Yemen

Abstract This study aimed to analyze the phytochemical constituents and evaluate the antimicrobial effects of ethanolic extracts from Matricaria chamomilla (chamomile) leaves and flowers against clinical bacterial isolates collected from Ibb City, Yemen. Phytochemical screening revealed presence of alkaloids, tannins, sterols, and terpenoids in both leaves and flowers, while flavonoids, glycosides, saponins, and amino acids were absent. Antibacterial activity was assessed using inhibition zone diameters against pathogens including Staphylococcus aureus , Escherichia coli , Salmonella spp., and Pseudomonas aeruginosa . The extracts showed significant antimicrobial activity, especially against S. aureus , with leaf extract showing a 24 mm inhibition zone and flower extract 15 mm. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests confirmed the potent bactericidal effects at low extract concentrations (100 mg/mL). These findings underscore the therapeutic potential of M. chamomilla as a natural antimicrobial agent relevant to combating bacterial infections, especially in the local Yemeni context. Further studies are recommended to isolate active compounds and evaluate mechanisms of action.

Audience segmentation and messaging approach to gain public support and involvement in coastal social-ecological system management

Abstract Gaining public support and involvement is essential for implementing effective social-ecological system (SES) management. Earlier studies focused on an aggregate level, i.e., measured by average; however, we aimed to address public heterogeneity, determine their support for policy, and identify their involvement in SES management. Accordingly, we applied audience segmentation and a messaging approach in coastal SES management to address oligotrophication in part of the Seto Inland Sea (SIS), Japan. In our experimental study, audience segmentation was applied based on a single-item self-categorization measure regarding public opinion about coastal SES issues and management, and the impact of two messaging conditions on the segments was assessed. Respondents living in coastal SES areas were recruited (N = 1800) and randomly divided into three groups: a control group without messaging and two groups with either “Negative consequences of oligotrophication” or “Collective public involvement” messaging. Four primary segments were identified: alarmed, concerned, cautious, and disengaged-dismissive. The groups exhibited distinctive personal characteristics and decreasing levels of policy support and involvement. For example, those in segment “Disengaged- Dismissive” were generally younger and physically and psychologically distant from the sea, showed less recognition of the problems, and exhibited infrequent related behaviors (e.g., consuming local seafood), with lower values of the sea. Such knowledge informs policymakers in targeting decisions. The two messaging conditions comprised varied impacts on different segments, suggesting that policymakers should select messaging conditions based on the target segment. Our study highlighted the importance of audience segmentation and targeted messaging in enabling policymakers to effectively reach the public sector.

Symptom clusters and symptom network analysis of patients after anterior cervical spine surgery: a cross-sectional study

Quantification and characterization of manufactured nanomaterials shed from face masks

Abstract Face masks are an important public health measure whose use became wide-spread during the pandemic. Manufactured nanomaterials (MNMs) have been incorporated into face masks to enhance their anti-microbial and self-cleaning properties. However, the potential toxicity of certain MNMs raises concerns regarding their use in facemasks. Limited research has addressed the airborne shedding potential of MNMs as it relates to inhalation uptake. This work aimed to address this gap by investigating the potential airborne release of TiO 2 from the outer surface of three general purpose face masks, under two sets of conditions: physically stable and physically agitated. The surface of the face masks was analyzed to determine the mass fraction of TiO 2 and the composition of the particles detected. Particle shedding was quantified via particle counters, particle sizers, electron microscopy, and inductively-coupled-plasma mass spectrometry (ICP-MS). Compositional analysis showed that all tested masks contained different levels of Ti ranging from 80 to 4870 µg/g of mask, with TiO 2 particles detected on the surface of the fibers. Particle shedding was observed only for two of the masks under agitation with low average concentrations of 130 and 520 #/cm 3 . Further analysis of the shed particles did not indicate the presence of TiO 2 nanoparticles. Overall, these findings suggest that while TiO 2 was present in the face masks, its airborne release under typical conditions may be unlikely. Although additional efforts are needed to characterize a wider range of facemasks and expand on these data, this study contributes to the understanding of inhalation uptake from MNMs shedding to inform future risk assessments.

Efficacy and mechanism of supervised adapted physical activity on quality of life for patients with fibromyalgia: single-center, prospective, randomised clinical and neuroimaging study

Quantum optimized hierarchical chunk encoding with robust embedding for perceptual integrity and compression tolerant visual data protection

Quantitative risk assessment for the compound drought-wildfire disaster

Multi-objective optimization of ice-based thermal storage for enhanced combined cycle power plant performance under hot climate conditions

Gut microbiota and resistome profiles of Swiss expatriates in Africa revealed by Nanopore metagenomics

Abstract The gut microbiota and resistome may change upon exposure to environments with high prevalence of multidrug-resistant pathogens, potentially impacting health and contributing to the spread of antimicrobial resistance genes (ARGs). In this context, expatriates may acquire endemic microbial communities and ARGs while living abroad. In this work, we investigated the microbiota and resistome of Swiss expatriates living in African countries using Nanopore shotgun metagenomics (SMS). Stool samples from expatriates residing in African and European countries ( n  = 33 and n  = 39, respectively) were sequenced using Nanopore V14 chemistry. Taxonomic and resistome profiling was performed with Kraken2 and ResFinder, respectively. Diversity metrics (e.g., Shannon, Simpson) assessed microbial composition. ARG and bacteria associations were determined using GTDB-Tk on metagenome-assembled genomes (MAGs). Plasmid-borne ARGs were characterized with PlasmidFinder. Our results indicated that microbiota composition did not differ between expatriates in African and European countries. However, resistome analysis revealed a higher prevalence of tetracycline ( tet ) and folate pathway antagonist ( dfr , sul ) ARGs in those residing in Africa, suggesting adaptation to the local microbial environment or antibiotic policy. Unique plasmid families were also identified in Gram-negative (IncF) and -positive (repUS43) bacteria across African and European cohorts, indicating the potential for ARG dissemination via mobile genetic elements. Overall, Nanopore-based SMS may provide an alternative approach to monitor microbiota and resistome dynamics, and thus assisting early epidemiological surveys.