Search Results (7,965)

This study investigates the subsurface rooting of the Merija anticline in the Missour Basin, Morocco, with a focus on copper mineralization exploration. A sequential geophysical workflow was implemented, combining gravity surveys, electrical resistivity (ER), and induced polarization (IP) methods. The gravity data, acquired along spaced profiles extending from outcropping areas to Quaternary-covered zones, clearly delineated the structural continuity of the anticline beneath the cover. The application of trend filtering in covered areas allowed the removal of regional effects, successfully isolating residual anomalies associated with the buried continuation of the anticline. Interpolated Bouguer anomaly maps highlighted a major regional fault, interpreted as controlling the deep rooting of the anticline. A resistivity profile was then deployed perpendicular to this fault, providing detailed imaging of the anticline’s geometry and lithological contrasts. Complementary IP profiles conducted near the mine site targeted the detection of chargeability anomalies associated with copper mineralization dominated by malachite, confirming the electrical signature of copper mineralization, particularly within the sandstone and conglomerate formations of the Lower Cretaceous. To validate the geophysical interpretations, a drilling campaign was conducted, which confirmed the presence of the identified lithological units and the anticline rooting, as revealed by geophysical data. This approach provides a robust framework for copper exploration in the Merija area and can be adapted to similar geological contexts elsewhere. Full article

Tumor heterogeneity encompasses genetic, epigenetic, and phenotypic diversity, impacting treatment response and resistance. Spatial heterogeneity occurs both inter- and intra-lesionally, while temporal heterogeneity results from clonal evolution. High-throughput technologies like next-generation sequencing (NGS) enhance tumor characterization, but conventional biopsies still do not adequately capture genetic heterogeneity. Liquid biopsy (LBx), analyzing circulating tumor DNA (ctDNA), provides a minimally invasive alternative, offering real-time tumor evolution insights and identifying resistance mutations overlooked by tissue biopsies. This study evaluates the capability of LBx to capture tumor heterogeneity by comparing genetic profiles from multiple metastatic lesions and LBx samples. Eight patients from the Augsburger Longitudinal Plasma Study with various types of cancer provided 56 postmortem tissue samples, which were compared against pre-mortem LBx-derived circulating-free DNA sequenced by NGS. Tissue analyses revealed significant mutational diversity (4–12 mutations per patient, VAFs: 1.5–71.4%), with distinct intra- and inter-lesional heterogeneity. LBx identified 51 variants (4–17 per patient, VAFs: 0.2–31.1%), which overlapped with mutations from the tissue samples by 33–92%. Notably, 22 tissue variants were absent in LBx, whereas 18 LBx-exclusive variants were detected (VAFs: 0.2–2.8%). LBx effectively captures tumor heterogeneity, but should be used in conjunction with tissue biopsies for comprehensive genetic profiling. Full article

Despite significant advances in prostate cancer treatment over the past two decades, metastatic castration-resistant prostate cancer (mCRPC) remains incurable. We present the case of a patient with aggressive prostate cancer diagnosed 20 years ago, underscoring the value of longitudinal genomic profiling and advanced imaging to guide clinical decisions. After multiple treatment failures, genomic analyses of tissue and liquid biopsies revealed dynamic changes in tumor biology and the emergence of resistance mechanisms, particularly AR amplification, identified with a liquid biopsy test and validated by [¹⁸F]-FDHT PET scan. This finding guided treatment with bipolar androgen therapy (BAT), which achieved a dramatic clinical response, reduced AR expression, improved symptoms, and restored sensitivity to enzalutamide. This case exemplifies the utility of serial liquid biopsies in uncovering mechanisms of tumor evolution and resistance, and the crucial role of cutting-edge diagnostics in personalized cancer treatment. Full article

Background: Vascular dysfunction is increasingly recognized as a shared contributor to both cognitive impairment and late-life depression (LLD). However, the combined diagnostic value of cerebral hemodynamics, neuroimaging markers, and neuropsychological outcomes remains underexplored. This study aimed to investigate the associations be-tween transcranial Doppler (TCD) ultrasound parameters, cognitive performance, and depressive symptoms in older adults with mild cognitive impairment (MCI) and LLD. Importantly, we evaluated the integrative value of TCD-derived indices alongside MRI-confirmed white matter lesions (WMLs) and standardized neurocognitive and affective assessments. Methods: In this cross-sectional study, 96 older adults were enrolled including 78 cognitively unimpaired individuals and 18 with MCI. All participants underwent structured clinical, neuropsychological, and imaging evaluations including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Geriatric Depression Scale (GDS-15), MRI-based Fazekas scoring of WMLs, and TCD ultrasonography of the middle cerebral artery. Hemodynamic variables included mean blood flow velocity (MBFV), end-diastolic velocity (EDV), pulsatility index (PI), and resistive index (RI). Logistic regression and receiver operating characteristic (ROC) analyses were used to identify independent predictors of MCI. Results: Participants with MCI showed significantly lower MBFV and EDV, and higher PI and RI (p < 0.05 for all) compared with cognitively unimpaired participants. In multivariate analysis, lower MBFV (OR = 0.64, p = 0.02) and EDV (OR = 0.70, p = 0.03), and higher PI (OR = 3.2, p < 0.01) and RI (OR = 1.9, p < 0.01) remained independently associated with MCI. ROC analysis revealed excellent discriminative performance for RI (AUC = 0.919) and MBFV (AUC = 0.879). Furthermore, PI correlated positively with depressive symptom severity, while RI was inversely related to the GDS-15 scores. Conclusions: Our findings underscore the diagnostic utility of TCD-derived hemodynamic parameters—particularly RI and MBFV—in identifying early vascular contributions to cognitive and affective dysfunction in older adults. The integration of TCD with MRI-confirmed WML assessment and standardized cognitive/mood measures represents a novel and clinically practical multi-modal approach for neurovascular profiling in aging populations. Full article

Blood flow restriction training (BFRT) offers notable advantages, including simplicity and time efficiency. However, no meta-analysis has yet comprehensively evaluated its effects on glucose and lipid metabolism in overweight or obese adults. This meta-analysis examines the potential efficacy of BFRT in improving glycemic and lipid control in overweight/obese adults. The literature was searched in six databases, with the search period up to 31 March 2025. A total of eight randomized controlled trials involving 267 participants were identified. Data were analyzed using Stata 18.0 and RevMan 5.4 with random effects models. Outcomes included fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and lipid profiles, and risk of bias and publication bias (Egger’s test) were assessed. BFRT significantly reduced FBG (Hedges’ g = −1.13, 95% CI: −1.65 to −0.62, p < 0.01; I² = 66.34%) and HOMA-IR (Hedges’ g = −0.98, 95% CI: −1.35 to −0.61, p < 0.01; I² = 17.33%) compared with the controls. However, no significant changes were observed in lipid profiles. Our analysis demonstrates that BFRT exhibits the favorable effect of improving glucose metabolism in overweight/obese adults; however, current evidence does not support significant advantages of BFRT for lipid metabolism improvement. Full article

Background/Objectives: The rapid emergence of multidrug-resistant bacterial infections demands innovative non-antibiotic therapeutic strategies. Dual-modal photoresponse therapy integrating photodynamic (PDT) and photothermal (PTT) effects offers a promising rapid antibacterial approach, yet designing single-material systems with synergistic enhancement remains challenging. This study aims to develop uniform Cu-based metal–organic framework micrometer cubes (Cu-BN) for efficient PDT/PTT synergy. Methods: Cu-BN cubes were synthesized via a one-step hydrothermal method using Cu(NO₃)₂ and 2-amino-p-benzoic acid. The material’s dual-mode responsiveness to visible light (420 nm) and near-infrared light (808 nm) was characterized through UV–Vis spectroscopy, photothermal profiling, and reactive oxygen species (ROS) generation assays. Antibacterial efficacy against multidrug-resistant Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was quantified via colony counting under dual-light irradiation. Results: Under synergistic 420 + 808 nm irradiation for 15 min, Cu-BN (200 μg/mL) achieved rapid eradication of multidrug-resistant E. coli (99.94%) and S. aureus (99.83%). The material reached 58.6 °C under dual-light exposure, significantly exceeding single-light performance. Photodynamic analysis confirmed a 78.7% singlet oxygen (¹O₂) conversion rate. This enhancement stems from PTT-induced membrane permeabilization accelerating ROS diffusion, while PDT-generated ROS sensitized bacteria to thermal damage. Conclusions: This integrated design enables spatiotemporal PDT/PTT synergy within a single Cu-BN system, establishing a new paradigm for rapid-acting, broad-spectrum non-antibiotic antimicrobials. The work provides critical insights for developing light-responsive biomaterials against drug-resistant infections. Full article

Aim: Antibiotic de-escalation (ADE) is essential, but appears to be underperformed although being possible, which we refer to as a ‘missed opportunity’. We aimed to analyze the ADE missed opportunities in Gram-negative bloodstream infections (BSIs) in a setting with a high antimicrobial resistance profile. Methods: A retrospective, two-centered cohort study was performed from 1 January 2018 to 30 June 2019, including adults with mono- or polymicrobial Gram-negative BSIs. All ADE episodes and 30-day mortality were noted. Results/Discussion: Out of 273 BSIs (43 ADE vs. 230 no-ADE episodes), 101 were considered a ‘missed’ opportunity of ADE (36.9%, 101/273). In multivariate analysis, ADE opportunities were missed 4.4 times more (OR = 4.4; 95% CI 1.24–15.9) in the presence of hematological malignancy and 6.2 times more (OR = 6.2; 95% CI 1.76–22.2) in ESBL. Contrary to this, ADE opportunities were missed 0.24 times less (OR = 0.24; 95% CI 0.09–0.61) among patients with E. coli BSIs, and 0.17 less (OR = 0.17; 95% CI 0.05–0.67) if ertapenem was used as an empirical agent. The ADE missed opportunity group had a higher mortality rate, which is statistically significant in univariate analysis, but not in multivariate analysis. Conclusion: The presence of ESBL and hematological malignancy were the significant barriers to appropriate ADE practice in our study. A good stewardship program must address physician hesitation in ADE practice. Full article

The secondary metabolites of the fungus Penicillium thymicola, fumiquinazolines F and G, have antibacterial and antifungal characteristics; however, their potential anti-tumor action against human cancer cells remains unknown. The goal of our study was to determine the biological efficacy of fumiquinazolines F and G on breast and prostate cancer cells. Cancer cell proliferation and migration were monitored in real time using xCELLigence technology and flow cytometry. Alterations in mRNA and protein expression were assessed by RT-qPCR, ELISA, and Western blotting. Our data indicate that fumiquinazolines F and G are more effective in inhibiting breast cancer cell proliferation than prostate cancer cells. Fumiquinazoline F is active against both hormone-dependent epithelial MCF-7 (IC₅₀ 48 μM) and hormone-resistant triple-negative mesenchymal MDA-MB-231 breast cancer cells (IC₅₀ 54.1 μM). The metabolite has low cytotoxicity but slows cell cycle progression. In fumiquinazoline F-treated MDA-MB-231 cells, the levels of proteins implicated in epithelial–mesenchymal transition (EMT) (such as E-cadherin, vimentin, and CD44) fluctuate, resulting in a decrease in cell migratory rate and adhesion to a hyaluronic acid-coated substrate. Thus, fumiquinazolines F and G exhibit anticancer activity by inhibiting EMT, cell proliferation, and migration, hence reverting malignant cells to a less pathogenic phenotype. The compound’s multi-target anticancer profile underscores its potential for further exploration of novel EMT-regulating pathways. Full article

One hundred presumptive Pseudomonas isolates, recovered from 15 sites impacted by anthropogenic activity in the Foggia district (Italy), were screened for key adaptive and functional traits important for environmental applications. The isolates were phenotypically characterized for their ability to grow under combined pH (5.0–8.0) and temperature (15–37 °C) conditions, to produce proteolytic enzymes, pigments, and exopolysaccharides, and to tolerate SDS. Moreover, the resistance to six environmentally relevant heavy metals (Cd, Co, Cu, Ni, Zn, As) was qualitatively assessed. The results highlighted wide inter-strain variability, with distinct clusters of isolates showing unique combinations of stress tolerance, enzymatic potential, and resistance profile. PERMANOVA analysis revealed significant effects of both the isolation site and the metal type, as well as their interaction, on the observed resistance patterns. A subset of isolates showed co-tolerance to elevated temperatures and heavy metals. These findings offer an initial yet insightful overview of the adaptive diversity of soil-derived Pseudomonas, laying the groundwork for the rational selection of strains for bioaugmentation in contaminated soils. Full article

Antimicrobial resistance (AMR) is a growing global health threat, with wild birds increasingly recognized as potential reservoirs of resistant pathogens and as sentinels of environmental AMR. This study investigated the occurrence and AMR profiles of Gram-negative bacteria isolated from wild birds that died at the Wildlife Rescue Center in Vanzago, Lombardy, in 2024. Cloacal swabs were collected from 112 birds representing various ecological categories. A total of 157 Gram-negative bacteria were isolated and identified, including clinically relevant genera and species, such as Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Salmonella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii. Antimicrobial susceptibility testing revealed resistance to first-line and critically important antimicrobials, including those exclusively authorized for human use. Notably, a phenotype compatible with Extended-Spectrum Beta-Lactamase (ESBL) production was detected in four out of ten (40%) K. pneumoniae isolates. In addition, 20 out of the 157 (12.7%) isolated bacteria phenotypically exhibited a resistance profile indicative of AmpC beta-lactamase (AmpC) production, including Enterobacter spp. and P. aeruginosa. Resistance patterns were particularly interesting in birds with carnivorous, scavenging, or migratory-associated behaviors. These findings highlight the role of wild birds in the ecology and dissemination of antimicrobial-resistant bacteria (ARB) and highlight the need for wildlife-based AMR monitoring programs as part of a One Health approach. Full article

Background/Objectives: This study examines how seasonality, pollution, and sample type (water and sediment) influence the presence and distribution of antibiotic resistance genes (ARGs), with a focus on antibiotic resistance genes (ARGs) located on plasmids (the complete set of plasmid-derived sequences, including ARGs) in a tropical urban river. Methods: Samples were collected from three sites along a pollution gradient in the Virilla River, Costa Rica, during three seasonal campaigns (wet 2021, dry 2022, and wet 2022). ARGs in water and sediment were quantified by qPCR, and metagenomic sequencing was applied to analyze chromosomal and plasmid-associated resistance profiles in sediments. Tobit and linear regression models, along with multivariate ordination, were used to assess spatial and seasonal trends. Results: During the wet season of 2021, the abundance of antibiotic resistance genes (ARGs) such as sul-1, intI-1, and tetA in water samples decreased significantly, likely due to dilution, while intI-1 and tetQ increased in sediments, suggesting particle-bound accumulation. In the wet season 2022, intI-1 remained low in water, qnrS increased, and sediments showed significant increases in tetQ, tetA, and qnrS, along with decreases in sul-1 and sul-2. Metagenomic analysis revealed spatial differences in plasmid-associated ARGs, with the highest abundance at the most polluted site (Site 3). Bacterial taxa also showed spatial differences, with greater plasmidome diversity and a higher representation of potential pathogens in the most contaminated site. Conclusions: Seasonality and pollution gradients jointly shape ARG dynamics in this tropical river. Plasmid-mediated resistance responds rapidly to environmental change and is enriched at polluted sites, while sediments serve as long-term reservoirs. These findings support the use of plasmid-based monitoring for antimicrobial resistance surveillance in aquatic systems. Full article

As a typical porous medium, unsaturated loess demonstrates critical hydro-mechanical coupling properties that fundamentally influence geohazard mitigation, groundwater resource evaluation, and foundation stability in geotechnical engineering. This investigation develops a novel theoretical framework to overcome the limitations of existing models in converting electrical resistivity tomography (ERT) profiles into water content distributions for unsaturated loess through quantitative inversion modeling. Systematic laboratory investigations on remolded loess specimens with controlled density and water content conditions revealed distinct resistivity–water interaction mechanisms. A characteristic two-stage decay pattern was identified: resistivity exhibited an exponential decrease from 420 Ω·m (water saturation (S_w = 10%)) to 90 Ω·m (S_w = 40%), followed by asymptotic stabilization at S_w ≥ 40%. The derived quantitative correlation provides a robust mathematical basis for water content profile inversion. Field validation through integrated ERT and borehole data demonstrated exceptional predictive accuracy in shallow strata (<20 m depth), achieving mean absolute errors of <5%. However, inversion reliability decreased with depth (>20 m), primarily attributed to density-dependent charge transport mechanisms. This underscores the necessity of incorporating coupled thermo-hydro-mechanical processes for deep-layer characterization. This study provides a robust framework for engineering applications of ERT in loess terrains, offering significant advancements in geotechnical monitoring and geohazard prevention. Full article

Background: The COVID-19 pandemic has profoundly altered the clinical and microbiological landscape of respiratory tract infections (RTIs), potentially reshaping pathogen distribution and antimicrobial resistance (AMR) profiles across care settings. Objectives: The objective of this study was to assess temporal trends in respiratory bacterial pathogens, antimicrobial resistance, and polymicrobial infections across three pandemic phases—pre-COVID (2018–2019), COVID (2020–2022), and post-COVID (2022–2024)—in hospitalized and ambulatory patients. Methods: We retrospectively analyzed 1827 respiratory bacterial isolates (hospitalized patients, n = 1032; ambulatory patients, n = 795) collected at a tertiary care center in Northern Italy. Data were stratified by care setting, anatomical site, and pandemic phase. Species identification and susceptibility testing followed EUCAST guidelines. Statistical analysis included chi-square and Fisher’s exact tests. Results: In hospitalized patients, a significant increase in Pseudomonas aeruginosa (from 45.5% pre-COVID to 58.6% post-COVID, p < 0.0001) and Acinetobacter baumannii (from 1.2% to 11.1% during COVID, p < 0.0001) was observed, with 100% extensively drug-resistant (XDR) rates for A. baumannii during the pandemic. Conversely, Staphylococcus aureus significantly declined from 23.6% pre-COVID to 13.7% post-COVID (p = 0.0012). In ambulatory patients, polymicrobial infections peaked at 41.2% during COVID, frequently involving co-isolation of Candida spp. Notably, resistance to benzylpenicillin in Streptococcus pneumoniae reached 80% (4/5 isolates) in hospitalized patients during COVID, and carbapenem-resistant P. aeruginosa (CRPA) significantly increased post-pandemic in ambulatory patients (0% pre-COVID vs. 23.5% post-COVID, p = 0.0014). Conclusions: The pandemic markedly shifted respiratory pathogen dynamics and resistance profiles, with distinct trends observed in hospital and community settings. Persistent resistance phenotypes and frequent polymicrobial infections, particularly involving Candida spp. in outpatients, underscore the need for targeted surveillance and antimicrobial stewardship strategies. Full article

The kallikrein–kinin system and its B1 and B2 receptors are key regulators in metabolic disorders such as obesity, diabetes, and insulin resistance. Obesity, a chronic and multifactorial condition often associated with comorbidities like type 2 diabetes and dyslipidemia, remains poorly understood at the metabolic level. The kinin B2 receptor (B2R) is involved in blood pressure regulation and glucose metabolism, promoting glucose uptake in skeletal muscle via bradykinin. Studies in B2R-KO mice demonstrate that the absence of this receptor predisposes animals to glucose intolerance under a high-fat diet and impairs adaptive thermogenesis, indicating a protective role for B2R in metabolic homeostasis and insulin sensitivity. In contrast, the kinin B1 receptor (B1R) is inducible under pathological conditions and is activated by kinin metabolites. Mouse models lacking B1R exhibit improved metabolic profiles, including protection against high-fat diet-induced obesity and insulin resistance, enhanced energy expenditure, and increased leptin sensitivity. B1R inactivation in adipocytes enhances insulin responsiveness and glucose tolerance, supporting its role in the development of insulin resistance. Moreover, B1R deficiency improves energy metabolism and thermogenic responses to adrenergic and cold stimuli, promoting the activation of brown adipose tissue and the browning of white adipose tissue. Collectively, these findings suggest that B1R and B2R represent promising therapeutic targets for the treatment of metabolic disorders. Full article

Early blight, caused by the pathogen Alternaria solani, is a major fungal disease impacting potato production globally, with reported yield losses of up to 40% in susceptible varieties. As one of the most common diseases affecting potatoes, its incidence has been steadily increasing year after year. This study aimed to elucidate the molecular mechanisms underlying resistance to early blight by comparing gene expression profiles in resistant (B1) and susceptible (D30) potato seedlings. Transcriptome sequencing was conducted at three time points post-infection (3, 7, and 10 dpi) to identify differentially expressed genes (DEGs). Weighted Gene Co-expression Network Analysis (WGCNA) and pathway enrichment analyses were performed to explore resistance-associated pathways and hub genes. Over 11,537 DEGs were identified, with the highest number observed at 10 dpi. Genes such as LOC102603761 and LOC102573998 were significantly differentially expressed across multiple comparisons. In the resistant B1 variety, upregulated genes were enriched in plant–pathogen interaction, MAPK signaling, hormonal signaling, and secondary metabolite biosynthesis pathways, particularly flavonoid biosynthesis, which likely contributes to biochemical defense against A. solani. WGCNA identified 24 distinct modules, with hub transcription factors (e.g., WRKY33, MYB, and NAC) as key regulators of resistance. These findings highlight critical molecular pathways and candidate genes involved in early blight resistance, providing a foundation for further functional studies and breeding strategies to enhance potato resilience. Full article