Search Results (8,470)

Post-fire assessment of structural steel typically relies on residual mechanical properties, although thermally induced changes in deformation behaviour may emerge before conventional strength parameters are clearly affected. This study examines whether mechanically referenced acoustic emission (AE) descriptors can reveal such changes in S235 steel after exposure to 700, 900, and 1100 °C for 40, 80, and 120 min, followed by air cooling. Thirty specimens were subjected to tensile testing with two-channel AE monitoring. The two channels were recorded independently and were not combined. Channel 2 was used consistently for quantitative comparisons, whereas channel 1 served as a control of signal transmission and sensor coupling. Median cumulative AE counts were evaluated at 75% of the lower yield load, the lower yield point, ultimate tensile strength, and fracture. Thermal exposure altered both the magnitude and distribution of AE activity, with the greatest differences occurring before or near yielding. After exposure to 900 °C for 120 min, the mean lower yield strength decreased by approximately 14%, while pre-yield AE counts increased by approximately 210% relative to the reference condition. Specimens exposed to 1100 °C for 40 min showed similar final AE counts to the reference specimens but markedly different distributions across the loading stages. Stage-resolved AE analysis therefore provides information complementary to residual mechanical properties and final AE counts. Although the proposed pre-yield descriptor is retrospective and cannot be applied directly as a field-diagnostic threshold, it provides a sensitive experimental basis for comparing thermally modified deformation histories and for future development of independently defined AE-based assessment criteria. Full article

Philadelphia chromosome-positive (Ph+) B-cell acute lymphoblastic leukemia (ALL), driven by the BCR-ABL1 fusion, remains highly aggressive, with poor prognosis despite tyrosine kinase inhibitor (TKI) therapy. Aberrant PI3K/Akt/mTOR pathway activation contributes to resistance, warranting identification of predictive kinase biomarkers. To identify and validate critical phospho-kinase markers within the PI3K/Akt/mTOR axis as candidate adaptive signaling nodes and exploratory prognostic markers in Ph+ B-ALL. Network pharmacology using STRING and Cytoscape mapped the protein–protein interactions, identifying high-centrality nodes. Functional enrichment analyses (GO/KEGG) were then performed via ShinyGO. Experimentally, phospho-kinase arrays profiled 39 kinase phosphorylation sites in Ph+ B-ALL cells (SUPB-15) treated with PI3K/Akt/mTOR inhibitors (Rapamycin, GDC-0941, GSK690693, Perifosine). Gene expression was validated by RT-qPCR in 100 Ph+ B-ALL patients and protein validation employed Western blot in 50 patient samples with 15 and five healthy controls, respectively. Network analysis identified CREB1 and GSK3 isoforms as central hub regulators. Phospho-kinase profiling revealed p-CREB (Ser133) phosphorylation upregulation following Perifosine, GDC-0941, and Rapamycin treatment, with no statistically significant change after GSK690693. p-GSK3α/β (Ser21/9) phosphorylation showed a statistically significant increase after Perifosine, with non-significant trends after GDC-0941, and a significant reduction following Rapamycin. Hierarchical clustering then divided proteins into four distinct clusters positioning CREB1 in cluster 3 and GSK3α/β in cluster 2 as candidate adaptive response markers based on their phosphorylation profiles. RT-qPCR demonstrated marked downregulation of GSK3α (approximately 71%), GSK3β (63%), and CREB1 (65%) transcripts in patients versus controls, with even greater suppression seen in cell lines. Conversely, Western blot revealed a significant 2.49 fold elevated p-CREB (Ser133) (β = 1.317, p = 0.000347) and a phospho-GSK3α/β (Ser21/9) level that did not differ significantly between patients and controls (β = 0.467, p = 0.466), revealing mRNA–protein discordance indicative of compensatory post-transcriptional and post-translational regulation. These findings represent treatment-associated and disease-state associations between altered phosphorylation states and the Ph+ B-ALL context; functional validation remains an essential next step. mRNA–protein discordance with transcriptional downregulation (63–71%) contrasting with elevated p-CREB levels (2.49-fold, p = 0.000347) suggests post-translational compensatory mechanisms under therapeutic pressure. CREB1 and GSK3 isoforms emerge as central network nodes that might potentially mediate adaptive resistance, although functional validation is required. It should be noted that the evidence presented is associative rather than causal and a direct link between the observed phosphorylation changes and clinical drug resistance has not been established in this study. Sustained CREB phosphorylation despite PI3K/Akt/mTOR inhibition implicates alternative kinase pathways (MAPK/ERK, CaMK), supporting rational combination therapy strategies. These findings position p-CREB and p-GSK-3α/β as candidate biomarkers, highlighting the value of phospho-proteomics over transcriptomics alone in capturing pathway activation. Multi-omics integration may prove essential for overcoming adaptive resistance in ALL patients. Full article

Voice interfaces to anthropomorphic robotic arms are typically evaluated without a formal safety layer, or with safety as a post hoc filter trusting the transcript, leaving transcript corruption unaddressed. This paper presents the DAS3 Neuro-Voice Controller, a voice-driven pipeline for a musculoskeletal arm model, evaluated here as a kinematic surrogate for upper-limb exoskeleton and prosthetic control, built on three commitments: on-device intent classification via a 44 M-parameter DistilBERT classifier over a bounded nine-command vocabulary; a deterministic three-layer Gatekeeper enforcing semantic validation, kinematic feasibility, and hard safety constraints independent of classifier confidence; and an upstream Phonetic Interceptor sanitising characteristic ASR mutilations of anatomical and safety terms (“four arm” → “forearm”). Trained on a class-balanced corpus of 3591 expressions and evaluated on fourteen non-native English speakers, the classifier reached 99.95% top-1 accuracy across 1847 oracle-resolvable utterances; the Gatekeeper reduced Priority Override Failure to 0.0%, rejected 100% of out-of-domain speech, and held false-rejection at 2.02%. Against a keyword-spotter baseline the pipeline delivered a 17.4-fold improvement in end-to-end success; the acoustic front-end remains the main weakness. Upstream input repair and downstream deterministic gating emerge as first-class components of safety-critical voice interfaces for assistive systems. Full article

Abdominal pain is a common presentation in the emergency department (ED). Ultrasound is the first-line diagnostic imaging modality for right upper quadrant pain. Point-of-care ultrasound (POCUS) is a focused examination that can be performed at the patient’s bedside to evaluate acute and emergent biliary pathology. The advantages of POCUS include avoiding the potential safety risks associated with transporting critically ill patients, no exposure to ionizing radiation, potentially reduced costs, and rapid diagnosis. This narrative review synthesizes key sonographic findings and techniques for emergent and non-emergent biliary diseases that physicians should recognize at first glance. We present significant and interesting images of cholelithiasis, acute cholecystitis, emphysematous gallbladder, choledocholithiasis or sludge, Mirizzi syndrome, post-operative biliary obstruction, gallbladder polyps, biliary neoplasms, and malignant-appearing lesions or masses. Finally, this review integrates POCUS into clinical pathways to guide decisions regarding additional abdominal imaging, such as computed tomography or radiology-performed ultrasound, and surgical consultation. Full article

Several potential applications of rare-earth-free magnets have been identified in emerging technological domains such as renewable energy and e-mobility in smart cities, with emphasis on electric bikes and scooters, as well as in the field of autonomous vehicles. In all these applications, with operability at high temperatures, there is considerable interest in nanocomposite magnetic alloys based on MnAl binary systems. The reason for such interest is represented by the occurrence of the τ-MnAl phase, which is magnetic and structurally compatible with L1₀ tetragonal phases. While the research on MnAl and MnAl-derived magnets has been extensive, alloys with the addition of post-transitional metals with an orthorhombic structure, such as Ga, are less often investigated. The purpose of such additions is to promote and preserve the formation and stability of the τ-MnAl phase, which has promising magnetic properties. The paper illustrates the thermal stability and optimized magnetic properties of τ-MnAl in an alloy based on an off-equiatomic MnAl system with 4 at% Ga addition. A thorough thermal analysis involving a differential scanning calorimetry study is reported, powered by kinetic analysis using two complementary iso-conversional methods: Friedman and Ozawa–Flynn–Wall. Structural characterization is performed using XRD, with the results supported through full-profile MAUD analysis (version 2.99, University of Trento, Italy), revealing that the hexagonal ε phase, predominant in the as-cast sample, transforms massively into the tetragonal τ phase, which becomes predominant upon annealing. Magnetic measurements are employed to fully characterize the alloy’s magnetic properties. It is shown that the phase transformation creates very good conditions for achieving good remanence values of about 210 kA/m and large intrinsic coercivities of about 446 kA/m at ambient temperatures. Full article

Urinary incontinence remains one of the most frequent and distressing complications after radical prostatectomy and can substantially affect quality of life. Physiotherapy, particularly pelvic floor muscle training (PFMT), is widely used as part of conservative postoperative management; however, substantial variation exists in patient populations, surgical and perioperative factors, intervention protocols, timing of initiation, adjunctive modalities, outcome definitions, and follow-up. This narrative review summarizes current evidence on pelvic floor rehabilitation after radical prostatectomy, focusing on prehabilitation, PFMT, biofeedback, electrical stimulation, neuromodulation, and emerging modalities such as transfer energy capacitive and resistive (TECAR) therapy. PFMT is the most widely studied conservative physiotherapy intervention and may accelerate early recovery of continence in some patients, although its effects on longer-term continence rates are less certain. The role of biofeedback and electrical stimulation remains unclear because of heterogeneous protocols and inconsistent outcome reporting. Evidence for neuromodulation is limited and should be interpreted according to the specific intervention and study population. TECAR therapy currently lacks direct clinical evidence supporting its efficacy in post-prostatectomy urinary incontinence. Across the literature, differences in continence definitions, intervention content and dose, baseline symptom severity, surgical techniques, timing of treatment, and follow-up complicate direct comparison and may confound observed improvements because spontaneous recovery is common after surgery. Current evidence supports PFMT as a reasonable core component of conservative management after radical prostatectomy, particularly for accelerating early continence recovery, whereas long-term superiority and the added value of adjunctive modalities remain uncertain. Full article

Seed development in Brassica napus is tightly regulated at many stages. Microproteins (miPs), small regulatory peptides derived from larger ancestral proteins, have emerged as key post-translational modulators in plants; however, their role in seed development remains poorly understood. Here, a genome-wide screen for putative miPs in B. napus was performed, identifying 32 candidates. Among these, MIF1 (BnaC06g35530D), with domain similarity to ZF-HD transcription factors (TFs), showed robust expression dynamics. The integration of RNA-seq profiling, qRT-PCR, co-expression network modeling, and protein–protein interaction revealed a strong regulatory association between MIF1 and its predicted TF partner, i.e., ZHD (BnaC01g16510D), particularly at the zygote and bending cotyledon stages. Promoter analysis identified shared cis-elements among co-expressed genes, while structural modeling supported a stable MIF1–ZHD interaction interface. Evolutionary analysis demonstrated the conservation of zinc finger motifs, syntenic neighborhoods, and purifying selection on MIF1 across Brassicaceae species. Collectively, our findings suggest that MIF1 potentially functions as a conserved post-translational repressor of ZHD during seed development, contributing to fine-tuned transcriptional regulation in polyploid oilseed crops. This study provides a testable hypothesis about the interaction between MIF1 and ZHD and also paves the way for the future functional characterization of miP-TF modules in plant development. Full article

Background/Objectives: Antimicrobial resistance has been recognized as a major global health threat, with multidrug-resistant Acinetobacter baumannii identified as one of the most critical pathogens. To address the limitations of conventional antibiotics, phage therapy has been proposed as a complementary or alternative intervention. In this study, experimental data were integrated into a deterministic differential-equation-based model to capture phage–bacteria–antibiotic–host immune system interactions. Methods: The model extended a previous phage–host immune system synergy framework by incorporating phage–antibiotic synergy and a time-dependent reduction in phage adsorption as a phenomenological representation of population-level reduction in phage susceptibility. This formulation does not explicitly model the molecular mechanisms or evolutionary emergence of resistance. In vitro observations of phage-induced resensitization to ceftazidime informed model parameterization, while remaining parameters were estimated from experimental observations or literature values. Simulations evaluated bacterial dynamics under phage-only, antibiotic-only, and immunity-only conditions, as well as combined therapeutic scenarios. Results: Model predictions indicated the greatest bacterial reduction when phages, antibiotics, and host innate immunity acted together. Phage–antibiotic synergy further enhanced predicted bacterial clearance, particularly for ceftazidime-resistant populations, while a population-level reduction in phage susceptibility was predicted approximately 4 h post-infection, consistent with experimental observations. Combined scenarios involving continuous antibiotic infusion, phage plus host immunity, or low-dose antibiotic regimens predicted accelerated bacterial declines when synergistic interactions were active. Conclusions: This framework integrates experimental observations with mathematical modeling to explore therapeutic interactions and temporal changes in phage susceptibility, while assessing parameter sensitivity and guiding future experimental and preclinical studies. Full article

Outbreaks of the sharp-toothed bark beetle, Ips acuminatus, have become increasingly frequent across Europe, yet little is known about how natural enemy communities vary between bark beetle population phases. This study compared the composition, diversity, emergence patterns, and relationships of natural enemies associated with I. acuminatus in two Scots pine (Pinus sylvestris) forest areas representing endemic and post-outbreak population conditions in Latvia. Bark beetle colonized stem sections were collected and maintained under controlled laboratory conditions to quantify emerging insects. Community composition and diversity were analysed, and linear mixed-effects models were used to evaluate relationships between bark beetle and natural enemy densities. A total of 5468 insects representing 21 taxa emerged, including 12 natural enemy taxa. Natural enemy community composition and Shannon diversity were similar between areas/populations. However, the relationship between densities of I. acuminatus and natural enemies differed significantly between the two areas (p = 0.002), with a substantially stronger positive relationship detected in the one with an endemic population. Under laboratory conditions, parasitoids emerged synchronously with the I. acuminatus, whereas predator emergence peaked later. These findings indicate that compositionally similar natural enemy assemblages can exhibit different density relationships between systems representing contrasting bark beetle population conditions, emphasizing the importance of considering abundance relationships alongside community composition. Full article

Plant molecular farming has emerged as a promising platform to produce recombinant biopharmaceuticals. The expression of foreign proteins changes the host proteome and metabolome, and these changes might have an effect on the accumulation of recombinant proteins. In this study, we investigated how fusion partners and ER-retention strategies influence host responses during transient production of recombinant human interleukin-15 (IL-15) in Nicotiana benthamiana. Four IL-15 constructs carrying either an 8 × His tag or an IgG1 Fc fusion, with or without an N-terminal signal peptide and C-terminal SEKDEL motif (KD), were compared at 4 days post-infiltration. Western blot analysis detected IL-15 only in the Fc-fusion constructs. Plants expressing IL15-Fc accumulated more antioxidant enzymes and phenylpropanoid-derived phenolics. Expression of IL15-Fc with the SP/KD construct showed increased abundance of proteins involved in protein folding and translation, together with reduced representation of secondary metabolic pathways. Overall, the results demonstrate that fusion partner and SP/KD targeting strategy jointly shape the host response to recombinant IL-15 expression and should therefore be evaluated together during construct design for plant molecular farming. Full article

Recurrent pregnancy loss (RPL), a multifactorial condition in reproductive medicine, affects approximately 1–3% of couples. Increasing evidence implicates endometrial dysfunction, immune dysregulation, impaired angiogenesis, and oxidative stress (OS) in its pathophysiology, highlighting the need for biologically targeted therapeutic strategies. In this context, platelet-rich plasma (PRP) has emerged as a regenerative approach with the potential to modulate these underlying mechanisms. This narrative review critically evaluates the biological rationale and current clinical evidence supporting PRP as an adjunctive treatment for RPL while proposing a precision medicine framework for biologically guided patient selection. A comprehensive narrative synthesis of the literature was performed, focusing on studies investigating PRP in RPL and related reproductive conditions, including thin endometrium and recurrent implantation failure (RIF). Mechanistically, PRP promotes angiogenesis through vascular endothelial growth factor (VEGF)-mediated pathways, enhances endometrial regeneration by stimulating stromal and epithelial cell proliferation, and modulates immune responses by promoting regulatory T-cell activity while attenuating pro-inflammatory signaling. In addition, PRP-derived extracellular vesicles (EVs) and microRNAs may contribute to the post-transcriptional and epigenetic regulation of implantation-related genes, including leukemia inhibitory factor (LIF) and HOXA10. Clinical studies in RIF and thin endometrium populations suggest that PRP may improve endometrial thickness, implantation, and clinical pregnancy outcomes; however, these findings constitute indirect evidence for RPL. Direct RPL-specific evidence remains very limited and is insufficient to establish a reduction in miscarriage or an improvement in live birth. These biological features instead provide a rationale for investigating PRP in defined patient subgroups characterized by impaired endometrial receptivity, defective angiogenesis, immune dysregulation, or unexplained RPL with suspected endometrial dysfunction. Accordingly, we propose that future clinical investigation of PRP should move beyond empirical use toward biomarker-informed, precision reproductive medicine strategies. Although PRP represents a biologically plausible and promising adjunctive therapy, robust randomized controlled trials incorporating standardized PRP protocols and biologically stratified patient populations are required before its routine clinical use can be recommended. Full article

Post-burn hypertrophic scar (HTS) formation is influenced by the dynamic balance between keratinocyte proliferation and differentiation, a process critical for maintaining skin homeostasis. Serine/threonine kinase 33 (STK33) has emerged as a potential therapeutic target in oncology. However, its role in HTS formation remains unclear, and its effects on keratinocytes are poorly understood. We isolated human HTS-derived keratinocytes (HTSKs) from post-burn HTS tissues and treated them with ML281, originally developed as an STK33 inhibitor. We examined markers associated with keratinocyte phenotypes and functions, including proliferation (proliferating cell nuclear antigen, c-Myc, keratins 5, 14, 6, 16, and 17), epithelial–mesenchymal transition (EMT; snail1, slug, twist1, e-cadherin, n-cadherin, and vimentin), differentiation (keratins 1 and 10, involucrin, loricrin, Notch1, p21, and p27), and apoptosis (cytochrome c, cleaved caspase3, Bid, Bad, Bax, and Bcl-2). mRNA and protein expression levels were assessed using reverse transcription–quantitative PCR, Western blotting, and immunocytochemistry. In HTSKs, ML281 increased STK33 enzymatic activity and STK33 mRNA and protein expression, rather than inhibiting STK33 activity. ML281 treatment reduced the expression of proliferation-associated markers, promoted an EMT-associated phenotype, modulated the expression of differentiation-associated markers, and induced apoptosis-associated changes. Collectively, these findings suggest that ML281 alters post-burn HTSK phenotypes associated with proliferation, EMT, differentiation, and apoptosis. Full article

In recent years, short plant peptides have emerged as highly promising, innovative bioregulators of crop growth and resilience. Activating systemic defense using synthetic plant peptides represents a potent strategy to improve crop resistance against pathogenic threats. Potato virus Y (PVY) causes devastating economic losses in potato (Solanum tuberosum) crops. In this study, we investigated the protective activity of synthetic analogs of systemin, a classic defense peptide originally discovered within the Solanaceae family. We synthesized the putative potato octadecapeptide systemin (AVHSTPPSKRDPPKMQTD) along with two 17-mer variants, each truncated by a single amino acid residue at either the N- or C-terminus, for foliar application. The defensive efficacy of these peptides was evaluated using inoculation and monitoring viral accumulation under controlled growth chamber conditions. Foliar application of all three synthetic peptides significantly reduced the accumulation of the PVY^O ordinary strain over a one-month post-infection period with comparable efficacy. Furthermore, we demonstrated the antiviral effect of the synthetic octadecapeptide against the exceptionally devastating and widespread recombinant PVY^NTN strain. These findings suggest that synthetic derivatives of potato systemin could serve as potential tools for developing eco-friendly antiviral strategies for sustainable crop protection. Full article

The article begins by examining the “post-1990 consensus,” an international orientation—emerging in the mid-twentieth century and consolidating after 1990—that promoted diversity, equity, inclusion, human rights, multiculturalism, and postmodernism as guiding values of the global order. Education was seen as both the site and the instrument for advancing this vision of a new socio-political world. However, this consensus has been undermined by what the authors term the “denudation of the post-1990 consensus”, an analytical turn that emerged in the early twenty-first century amid intensifying global tensions and the erosion of liberal-democratic ideals. (The term ‘denudation’ is borrowed from the science of geology, where it refers to the stripping away of layers of material, thereby exposing deeper, formerly hidden layers.) The article introduces the construct of the “denudation of the post-1990 consensus” as an analytical turn in interpreting how contemporary political transformations reshape the conditions under which citizenship and education operate. This turn is characterised by various interconnected processes, including democratic regression, deglobalisation, populism, nationalism, rising inequality, and social fragmentation, all of which point to the weakening or the stripping away of the normative foundations of diversity, equity, inclusion, and the liberal-democratic citizenship that lay at the heart of the post-1990 consensus. They have also been weakening or stripping away the foundational values that previously informed global educational reform. However, in its current form, the concept of liberal-democratic citizenship is not suitably equipped to meet the challenges brought about by the turn of events referred to as the “denudation of the post-1990 consensus”. It must, therefore, be reconceptualised as a critical, multilayered, human-rights-based, intercultural, and capability-oriented field of formation. It is contended that, in view of the “denudation” process, a reconceptualised form of citizenship education, capable of addressing fragmented identities, democratic instability, and multilayered forms of belonging, may offer an appropriate educational response to contemporary global turbulence. Full article

Marine-derived Streptomyces are among the most prolific producers of structurally diverse and biologically active natural products. Adaptation to unique marine environments, including deep-sea sediments, hydrothermal vents, mangrove ecosystems, marine invertebrates, and hypersaline habitats, has promoted the evolution of specialized biosynthetic systems capable of generating a broad spectrum of secondary metabolites. These metabolites include polyketides, non-ribosomal peptides (NRPs), ribosomally synthesized and post-translationally modified peptides (RiPPs), terpenoids, alkaloids, and hybrid compounds with significant antibacterial, antifungal, antiviral, antiparasitic, anti-inflammatory, and anticancer activities. Recent advances in genome sequencing, bioinformatics, genome mining, metabolomics, synthetic biology, and artificial intelligence (AI)-assisted discovery have substantially expanded marine natural product research by enabling the identification and prioritization of previously inaccessible biosynthetic gene clusters (BGCs). However, major challenges remain, including silent biosynthetic pathways, low cultivation efficiency, rediscovery of known compounds, metabolite yield instability, dereplication bottlenecks, and limited ecological interpretation. These constraints continue to impede the translation of biosynthetic potential into pharmaceutical applications. This review summarizes current strategies for marine natural product discovery and highlights emerging translational approaches integrating multi-omics technologies, pathway engineering, and AI-guided prioritization. Collectively, these advances provide a roadmap for advancing marine Streptomyces research from descriptive omics-based exploration toward experimentally validated and clinically relevant drug discovery. Full article