Search Results (13,737)

This work presents an atomistic investigation of the structural and mechanical properties of Li–Mg alloys with 5, 10, and 20 at.% Mg using Monte Carlo and Molecular Dynamics simulations, elastic constant calculations, and uniaxial tensile tests. Structural equilibration revealed that Mg species promote enhanced relaxation and a tendency to form B2-type ordering. The elastic constants showed that Mg primarily increases the longitudinal stiffness while the shear-related components remained nearly unchanged. Derived mechanical properties confirm this strengthening trend, and comparison with recent experimental data shows good qualitative agreement. Tensile tests showed composition-dependent deformation mechanisms: the 0 and 5 at.% Mg samples underwent complete BCC-to-FCC transformation accompanied by strong stress reduction, the 10 at.% Mg alloy exhibited a similar transition while preserving positive stresses, and the 20 at.% Mg alloy displayed an abrupt shear-band instability that interrupted the transformation. These results provide insights into the role of Mg as an element that enhances the structural stability and mechanical stiffness of Li-Mg alloys, supporting their improved performance as electrode materials. Full article

Background/Objectives: Colistin (polymyxin E) has re-emerged as a last-hope treatment against MDR Gram-negative pathogens due to the development of extensively drug-resistant Gram-negative bacteria. Unfortunately, rapid global resistance towards colistin has emerged, which represents a major public health concern. In this context (CBD), a lipophilic molecule derived from Cannabis sativa, exhibits antimicrobial activity mainly against Gram-positive bacteria but is generally ineffective against Gram-negative species. However, synergistic antibacterial activity between CBD and polymyxin B has been reported. The objective of this work is to analyze the colistin–CBD synergy against clinically relevant Gram-negative isolates displaying diverse mechanisms of colistin resistance and to explore the basis of the possible mechanism of action involved in the first steps of this synergy. Methods: Microbiological assays, minimal inhibitory concentration, cell culture, synergy tests by checker board and time kill, biofilm inhibition evaluation by crystal violet and MTT, SEM (scanning electron microscopy), molecules interaction analysis by nuclear magnetic resonance (NMR). Results: The colistin–CBD combination displayed synergy in colistin resistant Gram-negative bacteria and also disrupted preformed biofilms and killed bacteria within them. Time-kill assays revealed rapid bactericidal activity and SEM showed mild surface alterations on bacterial outer membranes after sublethal colistin monotherapy. Furthermore, a series of sequential treatment assays on colistin-resistant Escherichia coli showed that simultaneous exposure to both compounds was required for activity, as introducing a washing step between treatments abolished the antibacterial effect. In order to obtain deeper insight into this mechanism, NMR analyses were performed, revealing specific molecular interactions between CBD and colistin molecules. Conclusions: These results provide evidence for the first time that both molecules engage through a specific and structurally meaningful interaction and only display synergy when acting together on colistin-resistant bacteria. Full article

Accurate post-mortem diagnosis of sepsis remains a critical challenge in forensic pathology, as conventional morphological findings often lack specificity. Circulating microRNAs (miRNAs) have been proposed as stable molecular biomarkers, yet their diagnostic value in cadaveric samples is still unclear. This exploratory study investigated the expression of three candidate miRNAs (miR-122-5p, miR-125b-5p, and miR-27a-3p) in post-mortem peripheral whole blood to assess their association with sepsis-related death versus non-infective controls. Out of 58 cases, 45 met quality-control criteria (26 sepsis-related deaths and 19 controls). miRNA expression was quantified by qRT-PCR, normalized to miR-320, and analyzed using ΔCt values. Group differences were evaluated using linear regression models with adjustment for age, sex, and post-mortem interval, with Benjamini–Hochberg correction for multiple testing. In adjusted models, miR-125b-5p and miR-27a-3p showed evidence of association with sepsis status, whereas miR-122-5p did not. These results support the feasibility of miRNA quantification in post-mortem samples and motivate validation in larger, independent cohorts and within multimodal post-mortem diagnostic frameworks. Full article

Tuber melanosporum, the black truffle, is a fungus of high economic and ecological value, but its underground detection remains a challenge due to the lack of reliable, non-invasive methods. This study presents the development and proof of concept of a portable optoelectronic nose that integrates nine optical sensors and one electrochemical sensor for the in vitro identification of T. melanosporum. The optical sensors use colorimetric and fluorogenic molecular indicators supported on UVM-7, alumina, and silica. Tests were performed with truffles at different depths and in the presence of soil and compost to evaluate the device’s multi-source response. Partial least squares discriminant analysis (PLS-DA) models showed robust discrimination between soil, compost, and truffles, with an accuracy of 0.91 under most conditions. Detection at 30 cm showed an accuracy of 0.94, confirming the system’s ability to differentiate between sample types. Performance improved in simplified scenarios based on the presence or absence of truffles. Furthermore, the artificial neural network models achieved optimal results in binary classification. Taken together, the results support the system’s potential as an accurate, non-invasive tool with possible application to the agronomic management of truffle orchards. Full article

Determining the drivers of phenotypic evolution and their role on shaping regional phenotypic diversity is a fundamental aspect of mimicry research. Beetles of the genus Ceroglossus are well known for their rampant color diversity, and species have been shown to exhibit convergence in elytral coloration when in sympatry. Despite solid phylogenetic evidence showing that color convergence is not the result of shared ancestry, more direct evidence of the role of selection on color evolution is lacking. In this study, we used two different, but complementary approaches to test whether selection plays a role in color divergence and whether predators are responsible for its maintenance. We first used molecular data to assess gene flow. Subsequently, we used the sequence data to conduct coalescent simulations and generate expectations for color fixation under the hypothesis of genetic drift. Second, we conducted field experiments to test whether predators exhibited different preferences on mimetic versus non-mimetic phenotypes. Results from the coalescent simulations showed that color fixation exhibited strong deviations from the genetic drift expectation, implying that selection must be responsible for color divergence. Field experiments showed that translocated beetles (into areas where they were not mimics) suffered higher rates of attacks than those beetles that mimicked the locally abundant phenotypes. Thus, our study supports the hypothesis of selection as a driving force of color evolution in Ceroglossus beetles and provides the context that explains and supports previous claims of Müllerian mimicry. Full article

Chronic stress disrupts neuroendocrine regulation, neurotransmitter balance, and neuronal redox homeostasis, thereby contributing to the development of anxiety-related neuropathology. Arecoline, the predominant alkaloid of Areca catechu L., displays diverse neuropharmacological properties, yet its role in stress-induced emotional dysfunction has not been fully elucidated. This study examined the anxiolytic-like and neuroprotective effects of arecoline in mice exposed to chronic unpredictable mild stress (CUMS). Arecoline administration markedly improved behavioral outcomes, reflected by increased central exploration in the open-field test, prolonged time in the light compartment, and enhanced open-arm activity in the elevated plus maze. These behavioral benefits were accompanied by normalization of serum corticosterone levels, restoration of hippocampal neurotransmitters, reinforcement of antioxidant enzyme activities, and attenuation of pro-inflammatory cytokines. At the molecular level, arecoline elevated brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), cAMP response element-binding protein (CREB), N-methyl-D-aspartate receptor (NMDAR), and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), indicating enhanced synaptic plasticity, while concurrently diminishing oxidative and inflammatory stress. Collectively, the findings suggest that arecoline exerts multifaceted neuroprotective actions under chronic stress by coordinating neuroendocrine modulation, neurotransmitter homeostasis, antioxidant defenses, and synaptic plasticity. This study provides new mechanistic evidence supporting the potential relevance of arecoline as a functional neuroactive compound for managing stress-induced anxiety disorders. Full article

Microbial toxicity tests in the rhizosphere play an important role in the risk assessment and phytoremediation of chemical compounds in the environment. Tests for the inhibition of nodule number (NN), Rhizobia in the rhizosphere (RhR), Rhizobium in nodules (RhN) and arbuscular mycorrhizal fungi (AMFs) are important to evaluate the toxicity as well as the removal of total petroleum hydrocarbons (TPHs), 15 linear alkanes (LAs), and total linear alkanes (TLAs). The inhibition and removal was evaluated at 60 (vegetative stage, VS) and 154 days (reproductive stage, RS) of the life cycle of Crotalaria incana and Crotalaria pallida in soil with four doses of CRO (3, 15, 30, and 45 g/kg) plus a control (16 treatments). Results indicated that RhN and five structures of the AMFs present an index of toxicity (IT < 1), and the microbiological variable is inhibited by the CRO. RhR exhibits a hormesis index (IT > 1) that is stimulated by the CRO in the VS and RS for C. incana and C. pallida. The highest removal of TPHs (77%) was in the rhizosphere of C. incana in the RS with 45 g/kg of CRO. C. pallida removed the greatest amount of TLA (91%). There was a positive correlation between the RhR and the removal of TPHs, TLA, and LAs (higher molecular weight). It could be argued that symbiotic microorganisms are significant for use in toxicity testing, and the rhizosphere of C. incana and C. pallida can be used for the phytoremediation of HTPs and ALs in loamy-clay soil contaminated with CRO. Full article

Background: Cholera, caused by Vibrio cholerae, remains endemic in many developing countries, including Pakistan. The extensive use of antibiotics has led to the emergence of antimicrobial resistance in V. cholerae, limiting available treatment options. In this study, we performed molecular characterisation of antibiotic-resistant V. cholerae serotype Ogawa isolates from a recent cholera outbreak in Khyber Pakhtunkhwa, Pakistan. Methodology: Suspected cholera stool samples were collected from hospitalised patients at various district hospitals of Khyber Pakhtunkhwa Province (KPK), Pakistan. The samples were transported to the Public Health Reference Microbiology Laboratory at Khyber Medical University, Peshawar. V. cholerae were identified based on colonial morphology, Gram staining, and biochemical tests using EPI 10E. For serotype identification, monovalent antisera were used. Antibiotic susceptibility testing (AST) was performed using CLSI M45 and EUCAST guidelines. DNA was extracted from pure colonies of multidrug-resistant (MDR) V. cholerae and subjected to whole-genome sequencing (WGS) for genomic characterisation using an Illumina MiSeq platform. Results: Of the 350 active diarrheal cases investigated, 70 were confirmed as V. cholerae. The outbreak was initially reported in Dir and was subsequently followed by a high incidence of cholera in the Peshawar district of KPK. All strains belong to the Ogawa serotype, which shows high antibiotic resistance, particularly to ampicillin (n = 62, 88.57%), Sulfamethoxazole/Trimethoprim (n = 60, 85.71%), Erythromycin (n = 59, 84.29%), and Tetracycline (n = 53, 75.71%). The lowest resistance was against Meropenem (n = 1, 1.4%), followed by amikacin (n = 7, 10.0%) and levofloxacin (n = 13, 18.57%). Furthermore, 34 (48.57%) of the isolates were MDR, while 13 (18.57%) were extensively drug-resistant. Six samples were selected for whole-genome sequencing. The selection of six V. cholerae samples for WGS was based on their drug resistance pattern and origin of isolation. At the genomic level, all sequenced V. cholerae strains harboured multiple antimicrobial resistance determinants. Quinolone resistance was associated with mutations and genes in gyrA, gyrB, parC, and parE; resistance to sulfamethoxazole–trimethoprim with folA, folP, and dfr; tetracycline resistance with tetA and tet35; chloramphenicol resistance with catB and S10p; and aminoglycoside resistance with hns, S12p, and gigB. In addition, β-lactam resistance was linked to the presence of efflux and β-lactamase genes, including blaSHV and mox-3. Mutations were identified in gyrA at positions S83I, S177A, and S202A, and in parC at positions S85L and I231V. Collectively, the presence of these resistance determinants likely enables V. cholerae to survive exposure to high concentrations of multiple antibiotics. Conclusions: Our V. cholerae isolates showed close genetic relatedness to previously sequenced strains from Pakistan (2010 and 2022), as well as to recently reported international strains from the USA, Australia, and China. These findings highlight both the long-term persistence of these lineages within Pakistan and their international dissemination, likely facilitated by globalisation. Full article

Background: Durvalumab, a PD-L1 inhibitor used as consolidation therapy after chemoradiation in unresectable stage III non–small cell lung cancer (NSCLC), can induce immune-related adverse events, among which immune-mediated pneumonitis represents one of the most severe. Differentiating checkpoint inhibitor pneumonitis (CIP) from infectious pneumonia is challenging due to overlapping clinical and radiologic findings. Case presentation: We describe a 67-year-old woman with stage III lung adenocarcinoma treated with chemotherapy, radiotherapy, and durvalumab, who presented with progressive dyspnea and extensive bilateral ground-glass opacities on CT imaging. Laboratory tests revealed leukopenia and elevated inflammatory markers. Despite broad-spectrum antibiotic and antiviral therapy, her condition worsened, requiring high-flow nasal cannula oxygen therapy. Multiplex molecular testing on sputum identified human metapneumovirus (HMPV), while blood cultures and urinary antigens for Streptococcus pneumoniae and Legionella pneumophila were negative. A pulmonology consultation raised suspicion for severe durvalumab-induced pneumonitis exacerbated by viral infection. High-dose methylprednisolone (2 mg/kg/day) followed by a four-week taper led to gradual clinical and radiologic resolution. Durvalumab was permanently discontinued. Discussion: To our knowledge, this is the first reported case of HMPV-associated pneumonitis in a patient receiving durvalumab. This case highlights the potential synergistic interplay between viral infection and immune checkpoint blockade, resulting in severe lung injury. Comprehensive microbiologic evaluation, including molecular diagnostics, is essential to guide therapy and distinguish infectious from immune-mediated causes. Conclusions: Early recognition of mixed infectious and immune-mediated pneumonitis, and timely corticosteroid therapy are critical to achieving favorable outcomes and preventing irreversible pulmonary damage. Full article

Osteoporosis is highly prevalent in postmenopausal women, causing chronic pain, fractures, and limited mobility that burden individuals and society. While resistance exercise benefits bone health, its role in osteoporotic bone injury healing and underlying mechanisms remain unclear. This study aimed to explore the effects of 10-week weight-bearing ladder climbing exercise on ovariectomy (OVX)-induced osteoporosis and subsequent bone injury healing, and to investigate whether these effects are associated with the myostatin (MSTN) and Wnt/β-catenin pathways. Fifty-four 12-week-old female SD rats were randomized into Sham, OVX, and OVX + EX groups. Rats in the OVX and OVX + EX groups underwent ovariectomy to induce postmenopausal osteoporosis, and those in the OVX + EX group received 10-week weight-bearing ladder climbing. After the exercise intervention, 6 rats in each group were sacrificed; the remaining rats underwent femoral midshaft drilling to establish bone injury. The improvement in osteoporosis was evaluated via Micro-CT, biomechanical tests, RT-qPCR for mRNA detection, and Western blot for measuring protein levels of MSTN and Wnt/β-catenin pathway-related molecules at post-exercise and 21 days post-injury. Bone healing was reflected by the bone volume fraction at the bone injury site detected via Micro-CT at 10 and 21 days post-injury. This exercise significantly enhanced muscle strength and improved femoral bone mineral density (BMD), trabecular microstructure, and biomechanical properties in OVX rats. Meanwhile, the level of MSTN in the OVX + EX group was decreased, the expression of its downstream signaling pathways was inhibited, and the mRNA and protein expressions of Wnt/β-catenin were upregulated. Moreover, 21 days after exercise intervention, the biomechanical properties and bone microstructure of the OVX + EX group were still significantly superior to those of the OVX group, and the aforementioned molecular regulatory effect remained. In addition, pre-conducted exercise was able to promote increases in bone volume fraction at the bone injury site 10 and 21 days after drilling, which was conducive to bone injury healing. Ten-week weight-bearing ladder climbing ameliorates OVX-induced bone loss and promotes osteoporotic bone repair via regulating the MSTN/ActRIIB/Smad3 and Wnt/β-catenin pathways, providing evidence for exercise as a safe non-pharmacological intervention. Full article

Breast cancer remains the most common malignancy worldwide and the leading cause of cancer-related mortality. Recently, extracellular vesicles (EVs) derived from adipose tissue-derived stem cells (ADSCs) have attracted increasing attention for their potential to modulate inflammatory signaling and influence tumor cell behavior. This in vitro study was designed to investigate the effects of ADSC-EVs on MCF-7 breast cancer cells. EVs were isolated from ADSC culture supernatants and applied to MCF-7 cells at concentrations ranging from 0 to 80% (v/v). Cell viability, migration, and expression of IL-6/STAT3 pathway-related genes were evaluated using MTT, scratch assays, and qRT-PCR. Statistical analysis was performed using one-way ANOVA followed by Tukey’s post hoc test, with significance set at p < 0.05. The results showed that 20% EV treatment markedly inhibited MCF-7 cell activity, significantly reducing viability and almost completely blocking migration, with wound closure rates of 35.4% ± 3.80 at 24 h and 47.6% ± 4.2 at 48 h, compared with 48% ± 4.6 and 67% ± 4.2 in the control group, respectively. Notably, expression levels of IL-6, IL-6RST, and STAT3 were significantly downregulated (fold changes 0.155 ± 0.02 and 0.258 ± 0.012, p < 0.01), accompanied by severe disruption of the microtubule network. Immunofluorescence imaging revealed a disorganized microtubule architecture and irregular filament distribution in EV-treated cells, corresponding with decreased expression of TubA1 and CALR genes. These findings indicate that ADSC-EVs not only suppress IL-6/STAT3 inflammatory signaling but also destabilize the intracellular microtubule system, collectively contributing to the inhibition of MCF-7 breast cancer cell migration and survival. This provides an important molecular basis for developing novel EV-based therapeutic strategies in breast cancer treatment. Full article

Magnetic biochars (MBCs) have been shown to inhibit the horizontal transfer of antibiotic resistance genes (ARGs) in soils, both with and without microplastics (MPs); however, the underlying molecular biological mechanisms remain unclear. This study examined the effects of MBCs and coexisting polybutylene adipate terephthalate microplastics (PBAT MPs) on the physiological characteristics of Serratia marcescens ZY01 (a host strain carrying the tet gene) and further investigated their relationships with the absolute abundance of the tet gene in soil. The results demonstrated that MBCs promoted prodigiosin synthesis in Serratia marcescens ZY01 by mediating the electron transfer process, the effect of which was further enhanced in the presence of PBAT MPs. In treatments without PBAT MPs, MBCs generally suppressed the production of both proteins and polysaccharides in the extracellular polymeric substances. In contrast, in treatments containing PBAT MPs, the protein content gradually decreased with decreasing iron-to-biochar ratios, while the polysaccharide content remained largely unchanged. MBCs also elevated intracellular ROS levels due to the increased oxidative stress, particularly in treatments with PBAT MPs. A positive correlation between intracellular ROS levels and cell membrane permeability indicates that intracellular ROS was the primary driver of the increased cell membrane permeability. The presence of MBCs and PBAT MPs generally provided favorable habitats for Serratia marcescens ZY01, thereby enhancing its cell viability. Mantel test analysis indicated that MBCs influenced Serratia growth in soil by modulating its cell viability. Furthermore, the increased intracellular ROS level was significantly positively correlated with the absolute abundance of the tet gene in soil, implying the horizontal transfer of the tet gene at the intra-genus level. These findings offer helpful insights for developing environmental remediation strategies based on biochar–iron composites. Full article

Background: Mismatch repair (MMR) and microsatellite instability (MSI) testing have become essential biomarkers in the molecular classification of endometrial cancer (EC), guiding adjuvant treatment decisions and eligibility for immune checkpoint inhibition. Although international guidelines recommend universal testing, real-world implementation remains heterogeneous. This study aimed to evaluate trends in MMR and MSI testing and associated molecular diagnostics in Germany between 2018 and 2022. Methods: A retrospective multicenter analysis was conducted across German tertiary care centers. Data from patients with histologically confirmed EC between 2018 and 2022 were extracted from standardized electronic pathology records. Annual testing rates for MSI, MMR, POLE, TP53, and L1CAM were analyzed using descriptive statistics and trend analysis (Chi-square test for trend, p < 0.05). Therapeutic data were collected to assess the use of immune checkpoint inhibitors. Results: There was a significant increase in the annual rates of molecular testing for MSI, POLE, TP53, and L1CAM over the five-year observation period (all p < 0.05). TP53 testing showed the highest increase (13.1% → 78.6%), while MSI testing rose from 82.9% to 97.4%. Both POLE and L1CAM testing were virtually absent in 2018 (0% and 1.6%) but reached 15.7% by 2022. Conclusions: This study demonstrates a rapid and substantial implementation of MMR and MSI testing in German clinical practice, reflecting successful translation of trial results into routine care. However, implementation of testing in guidelines appeared time-shifted. For bridging this gap, annual guideline updates seem to be necessary. Full article

One significant trend in the research of plant treatment methods is that regarding the use of natural-based methods in plant protection. In this study, antimicrobial activity and changes in MdPR10 gene expression were tested for a total of five plant pathogens in a model of apple fruits, where strawberry and ivy EOs were used. The vapor-phase chemical composition of both EOs was profiled using HS-GC-MS. qRT-PCR was applied for a bacterial response analysis, together with disk diffusion assays, and minimum inhibitory concentrations were determined. To elucidate the molecular basis of the antibacterial potential of essential oils (EOs), docking analyses were performed. For Xanthomonas arboricola and Pectobacterium carotovorum, the presence of EOs resulted in the downregulation of MdPR10. Strawberry EO was more effective against weakly virulent strains of bacteria; ivy EO had greater inhibitory effects. HS-GC-MS detected 13 volatiles in strawberry EO—dominated by ethyl butyrate, ethyl 2-methylbutanoate, ethyl hexanoate, and ethyl 3-methylbutanoate—and 16 in ivy EO, characterized by monoterpenes and monoterpenoids with 1,8-cineole as the principal component. P-cymene showed the most potent binding activity against D-alanine–D-alanine ligase. Ivy EO has the potential to be effective as a natural preservative alternative mainly in postharvest technology. Full article

Recent advancements in molecular tools for plant genetic engineering, particularly CRISPR-based technologies, have created new opportunities for targeted genome editing. However, applying these tools remains challenging in crop species such as sunflower (Helianthus annuus) that lack established and effective transformation pipelines, including transient reagent delivery methods for functional screening and validation of genetic engineering tools. To address this gap, three major reagent delivery platforms, namely protoplast transfection, leaf infiltration, and Agrobacterium-mediated tissue co-culture, were systematically adapted and assessed for use in sunflower seedlings. While each method enabled successful reagent delivery, they differed in their levels of scalability and efficiency. With these platforms, delivery by different Agrobacterium strains and the effectiveness of various reporter gene expression cassettes were compared to define the most experimentally suitable components for different applications in sunflowers. Together, these results establish a foundational toolkit for transient functional testing in sunflower and pave the way for more sophisticated genetic engineering approaches in this agriculturally important oilseed, confectionary seed, and horticultural crop. Full article