Search Results (1,053)

Accurately and promptly acquiring the load history characteristics of impact events on composite aircraft structures is crucial for identifying impact-induced damage and developing high-fidelity digital twin models. To address this need, we propose a method for reconstructing the impact load history on composite structures, leveraging Generalized Cross-Validation (GCV) and a Fiber Bragg Grating (FBG) pattern. An equivalent expansion technique based on discretized time-domain sparse strain sampling is developed to mitigate the local distortion of impact response signals, a common issue arising from the low sampling rates of quasi-distributed FBG. By incorporating Tikhonov regularization, the ill-posed nature of the impact frequency response matrix is effectively managed. Furthermore, an adaptive optimization method based on the GCV criterion is introduced to overcome the limitations of manually selecting regularization parameters and the associated constraints on noise suppression. The results show that the proposed GCV-based reconstruction method achieves an average peak relative error of 11.4% and an average root mean square error of 0.36 N for the reconstructed impact load, demonstrating that the proposed method synergistically enhances both the reconstruction of the overall impact load waveform profile and the precise characterization of transient details, even with low-rate sampling. This provides robust technical support for health monitoring and condition-based maintenance of composite structures. Full article

Fungal pathogens pose a major threat to global agriculture and human health, necessitating alternative antifungal strategies with high efficacy and low resistance potential. Antifungal proteins (AFPs) from filamentous fungi are promising candidates due to their stability, selectivity, and diverse mechanisms of action. Here, we characterize Beauveria brongniartii antifungal protein (BbroAFP), a novel cysteine-rich protein from the entomopathogenic fungus B. brongniartii, and investigate its antifungal activity against Botrytis cinerea. Recombinant BbroAFP was expressed in Pichia pastoris, purified, and verified by liquid chromatography–tandem mass spectroscopy (LC–MS/MS) and in silico modeling. BbroAFP showed potent antifungal activity with minimum inhibitory concentrations (MICs) as low as 1 µM against several phytopathogenic fungi, while exhibiting no significant antibacterial activity. Activity was maintained across a wide range of pH and temperature conditions. Confocal microscopy revealed rapid surface binding followed by cytosolic internalization without major cell wall disruption. BbroAFP induced a rapid, transient burst of reactive oxygen species (ROS), accompanied by nuclear DNA fragmentation. Gene expression analysis revealed a transient increase in aif1, whereas mca1 expression decreased at later time points and mca2 remained largely unchanged, suggesting a metacaspase-independent response. Detached tomato leaf assays showed effective protection against B. cinerea without detectable phytotoxicity. Cytotoxicity assays confirmed a favorable safety profile, supporting further evaluation of BbroAFP for plant protection. Full article

Pediatric episodic vestibular syndrome (pEVS) is a frequent source of diagnostic uncertainty because recurrent vertigo, dizziness, and unsteadiness in children may arise from disorders with markedly different mechanisms, prognostic implications, and management pathways. Symptom descriptions are often imprecise, interictal examination may be normal, and similar recurrent attack patterns may reflect spontaneous, triggered, neurologic, autonomic, audiovestibular, or extravestibular conditions. This Perspective proposes a clinician-oriented, phenotype-first framework for the practical evaluation of pEVS, grounded in the International Classification of Vestibular Disorders and Bárány Society consensus criteria where available. The proposed approach begins with structured history taking and focused bedside examination, emphasizing the core symptom category, attack duration, trigger profile, and associated migraine, auditory, autonomic, and neurologic features. Recurrent attacks are then organized into clinically recognizable phenotypes, including spontaneous non-migraine and migraine-related presentations, auditory phenotypes, ultrabrief stereotyped attacks, trigger-related attacks, orthostatic/autonomic phenotypes, motion- or visually-triggered dizziness, episodic vertigo with transient neurologic signs, and anxiety-related presentations. Rather than providing an exhaustive etiologic review, this framework is intended to support bedside classification, guide selective ancillary testing, and facilitate longitudinal reassessment, as diagnostic reclassification may occur over time. A phenotype-driven approach may improve diagnostic reasoning, support more rational use of ancillary testing, and facilitate earlier recognition of both common and less frequent but clinically important disorders. Full article

Walnut is an important nut with a rich nutritional profile and associated health benefits for the human body. B-box (BBX) proteins containing one or two BBX motifs play pivotal roles in plant growth and developmental processes; nevertheless, the functions of JrBBXs in walnut anthocyanin biosynthesis remain inadequately understood. In this study, 39 JrBBXs in red walnut ‘RW-1’ were identified, with phylogenetic analysis suggesting that they were divided into six classes based on the distribution of conserved domains and unevenly distributed on 14 chromosomes. Promoter analysis demonstrated that JrBBX promoters possessed an abundance of light responsiveness elements, ABA responsiveness elements, MYB binding sites and MYC binding sites. The transcriptome analysis results demonstrated that eight JrBBXs were differently expressed in normal green walnut ‘Zhonglin 1’ and red walnut ‘RW-1’ seed coats. Furthermore, qRT-PCR (quantitative real-time polymerase chain reaction) analysis showed that JrBBX3 exhibited lower expression during seed coat development in ‘RW-1’. Y1H (Yeast One-Hybrid) and LUC (dual-luciferase reporter) assays revealed that JrBBX3 directly inhibited the expression of JrUFGT5, considered a key anthocyanin biosynthesis structural gene in research. Subcellular localization analysis indicated both cytoplasmic and nuclear localization of JrBBX3. Transient overexpression of JrBBX3 in walnut leaves resulted in reduced JrUFGT5 expression and anthocyanin accumulation. Collectively, these findings revealed the negative regulation of JrBBX3 in red walnut anthocyanin biosynthesis, and provided a basis to further study the anthocyanin biosynthesis mechanism of red walnut. Full article

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are consistently associated with alterations in gut microbial communities, although the extent and characteristics of these alterations vary across studies, supporting a potential role of the microbiota in disease pathogenesis and therapeutic modulation. We conducted a systematic review to synthesize current evidence on microbiota alterations in IBD and the clinical application of fecal microbiota transplantation (FMT). A total of 118 studies were included (76 focused on microbiota profiling and 42 evaluated FMT as therapy). Across heterogeneous study designs and microbial characterization methods, reduced microbial diversity was the most consistently reported alteration, generally more pronounced in CD than in UC. Depletion of Faecalibacterium prausnitzii—a key butyrate producer with anti-inflammatory properties—was commonly reported, often accompanied by functional impairment in short-chain fatty acid production. Microbial patterns were frequently associated with mucosal inflammation and varied across disease phenotypes; these patterns have been increasingly explored as predictors of treatment response and relapse, although mechanistic interpretation remains limited and causal relationships are difficult to establish. Evidence from randomized controlled trials suggests potential efficacy of FMT in UC, particularly with intensive or repeated protocols, whereas data in CD remain limited and heterogeneous, with signals of benefit often appearing transient. FMT was generally well tolerated, but long-term safety data remain scarce. Emerging multi-omic approaches are reshaping the field by integrating taxonomic and functional insights, with potential implications for risk stratification, diagnosis, prognosis, and therapeutic optimization. Further standardized, longitudinal, and mechanistically oriented studies are required to translate microbiome research into clinically actionable strategies in IBD. Full article

Colorectal cancer (CRC), characterized by epidermal growth factor receptor (EGFR) overexpression, is often associated with poor prognosis and limited therapeutic response to conventional chemotherapy. In this study, we developed EGFR-targeted extracellular vesicles (EGFR-tEVs) by transiently engineering donor cells to display the GE11 peptide, aiming to enhance the precision of doxorubicin (Dox) delivery. The physicochemical properties of EGFR-tEVs were characterized using TEM, NTA, and Western blot. In vitro, EGFR-tEV-Dox exhibited increased cellular uptake in EGFR-overexpressing HCT-116 cells, leading to the activation of the p53-Bax-cleaved PARP1 apoptotic pathway. Notably, while Dox treatment induced p53 in normal colon fibroblasts (CCD18-Co), it did not trigger significant Bax activation or PARP1 cleavage, suggesting a preference for survival-related signaling in non-malignant cells. In a xenograft mouse model, EGFR-tEVs + Dox administration resulted in a 33.1% reduction in tumor volume and an 82.8% decrease in Ki-67 expression compared to the control group. These results indicate that transient receptor-mediated targeting enhances functional drug delivery to malignant tissues while minimizing pro-apoptotic induction in normal cells. Our findings suggest that EGFR-tEVs + Dox represents a balanced therapeutic strategy that improves antitumor efficacy with a favorable safety profile for EGFR-positive colorectal cancer. Full article

The purpose of this project was to define gene expression changes associated with the acquisition and loss of resilience to diabetic retinopathy (RDR) in individual retinal cell types. A non-immune form of type 1 diabetes mellitus (DM) was induced by injecting male C57Bl6J mice with streptozotocin. Single-cell RNA sequencing was performed on retinas from mice that experienced DM for 5 or 15 days, along with retinas from age-matched, non-DM mice. The resulting data sets were analyzed to identify DM-associated differentially expressed genes and pathway enrichments after each duration of DM. We observed that acquisition of RDR, previously shown to arise after 5 days of DM was linked to altered expression of genes in a subset of retinal cells, mainly Müller cells. Pathway analysis indicated enhancement of numerous modes of protection, including reinforced neurovascular and structural homeostasis through phagocytosis, integrin signaling, and interferon-mediated defense. After 15 days of DM, when we previously showed that RDR is waning this pro-protection surge in gene expression subsided. We conclude that a duration of DM that is too short to cause diabetic retinopathy (DR) nonetheless evoked a profound change in the gene expression profile within a subset of retinal cell types. The nature and timing of this molecular shift indicated that it was not the preamble to DM-related damage that eventually develops. Rather, DM engaged numerous defense programs within Müller cells. The temporal alignment between RDR and activation of Müller cell-based defense provides a molecular foundation for the retina’s transient ability to remain healthy in the face of DM. Full article

Background/Objectives: Influenza remains a primary cause of severe illness and death in adults over 60. In this group, immunosenescence and existing health conditions make infections more dangerous and traditional vaccines less effective. The MF59-adjuvanted vaccine was specifically designed to overcome these limitations by enhancing the body’s immune activation and antigen presentation. While the vaccine shows clear benefits, some recent concerns regarding vaccine safety have been raised without supporting scientific evidence. Therefore, this systematic review focuses on providing a comprehensive evaluation of its safety outcomes compared to standard vaccines. Methods: Following the PRISMA guidelines, a systematic review and meta-analysis were conducted; two researchers independently assessed the eligibility of the studies, and the risk of bias was assessed using RoB2 and ROBINS tools for randomized clinical trials and observational studies, respectively. Pooled risk estimates were calculated using a random-effects model. Results: Ten RCTs and three non-RCTs meeting the inclusion criteria were included. No significant differences were found for severe systemic outcomes: Guillain–Barré syndrome (RR 1.01, 95% CI 0.64–1.80) and encephalitis (RR 1.23, 95% CI 0.85–1.78). For other systemic adverse effects, there were no significant differences between adjuvanted and non-adjuvanted vaccines; only myalgia showed a small but significant increase with adjuvanted vaccines (RR 1.35, 95% CI 1.02–1.78) compared with non-adjuvanted vaccines. Conclusions: MF59-adjuvanted influenza vaccines have a favorable and well-characterized safety profile in adults aged 60 years and older. Adverse events are predominantly mild and transient, with no evidence of increased risk of serious or immune-mediated outcomes compared with non-adjuvanted vaccines. Full article

This paper presents a comprehensive experimental assessment of electromagnetic field (EMF) exposure dynamics during the transition from IEEE 802.11ax (Wi-Fi 6) to IEEE 802.11be (Wi-Fi 7). Using a human-centric experimental setup, we evaluate the impact of Wi-Fi 7’s core innovations—4096-QAM modulation, 320 MHz bandwidth, and Multi-Link Operation—under iPerf3-controlled high-traffic conditions. A key contribution of this study is the analysis of multi-client influence, comparing EMF emission profiles when one versus two devices are active. Our results reveal a significant paradigm shift: while Wi-Fi 7 generates higher near-field peaks (up to 955.92 mV/m in MLO mode at 20 cm) to sustain high-order modulation, it exhibits an aggressive spatial decay, with E-field intensity collapsing by up to 76.6% at one meter. We demonstrate that the transition from a single-client to a dual-client configuration significantly alters the stochastic nature of the field, increasing the probability of transient high-power events, as characterized by our Complementary Cumulative Distribution Function (CCDF) framework. The findings confirm that Wi-Fi 7’s performance gains are decoupled from long-range exposure; the high-intensity field remains strictly localized, providing a natural safety buffer. This study provides new experimental vista into how next-generation WLAN systems trade near-field strength for far-field safety, maintaining compliance with international limits while supporting multi-device gigabit connectivity. Full article

Background: The study aims to analyze the safety and efficacy of Mepolizumab and Dupilumab in the treatment of patients affected by severe chronic rhinosinusitis not controlled with nasal polyposis (CRSwNP) from a tertiary care regional referral center, with the aim of improving the concept of personalized medicine. Methods: A retrospective study was conducted on 72 adult patients selected for biologic therapy according to EPOS/EUFOREA criteria. The patients received either Mepolizumab or Dupilumab. Primary endpoints were reduction in nasal polyp size, improvement in disease-specific quality of life (sinonasal outcome test-22, visual analog scale), olfactory recovery, and asthma control. Secondary outcomes were the assessment of adverse events. Results: Both monoclonal antibodies significantly improved nasal polyps score (NPS), sinonasal outcome test-22 (SNOT-22), and asthma control test (ACT) over time, with no statistically significant differences between Mepolizumab and Dupilumab. In contrast, blood eosinophil counts showed significant differences: Dupilumab was associated with a transient increase in eosinophil levels (absolute Δ = 660.08% Δ = 9%; p < 0.001), while Mepolizumab produced a marked reduction (absolute Δ = 192.52% Δ = 2%; p < 0.001). Both treatments were well tolerated, with only mild adverse events reported. Conclusions: Mepolizumab and Dupilumab are both effective and safe in improving sinonasal symptoms and quality of life in severe uncontrolled CRSwNP. While improvements in NPS, SNOT-22, and ACT scores were comparable, Mepolizumab achieved a significant reduction in eosinophil counts, whereas Dupilumab was associated with faster clinical improvement but a transient eosinophilia. These findings suggest that biologic choice may be guided by individual patient profiles and inflammatory patterns. Full article

Rapid and accurate calculation of lightning-induced electric fields in complex terrain is essential for lightning protection and electromagnetic compatibility analysis. Although conventional full-wave numerical methods such as the finite element method can achieve high-fidelity results, they are computationally expensive and inefficient for large-scale or repetitive engineering analysis. To enable efficient and reliable computation of lightning-induced electrostatic fields over complex terrain, this paper proposes a fast computational framework that integrates multi-level conformal mapping with a multi-objective optimization strategy based on the Non-Dominated Sorting Genetic Algorithm II (NSGA-II). In the proposed method, irregular terrain boundaries are transformed into analytically tractable domains using multi-level conformal mapping, while the critical mapping parameter is reformulated as a dual-objective optimization problem that simultaneously minimizes the maximum local error and the mean global error. Unlike traditional approaches that rely on empirical tuning or exhaustive traversal of mapping parameters, the proposed framework establishes a closed-loop adaptive optimization process that generates a Pareto-optimal solution set, enabling flexible trade-off selection according to practical accuracy requirements. The method is validated against high-fidelity finite element simulations for representative terrain profiles. The results demonstrate that the proposed approach achieves comparable maximum-error performance while reducing mean error and significantly improving parameter-optimization efficiency relative to exhaustive search methods. The proposed framework provides an adaptive and efficient computational solution for preliminary assessment of lightning-induced electric fields in complex terrain environments, and lays a foundation for future extensions toward more realistic multi-dimensional and transient analyses. The improvements in computational accuracy and efficiency offer significant practical value for rapid lightning protection assessment in large-scale complex terrain engineering, enabling parametric analysis and scheme comparison during the preliminary engineering design stage with sufficient reliability. Full article

Background: Radiotherapy is essential for skull base tumor management but carries the risk of radiation-induced brain injury (RIBI). This spectrum ranges from transient radiation-induced contrast enhancement (RICE) to irreversible necrosis. Distinguishing these entities from tumor progression is critical, particularly with the increasing adoption of proton therapy. Methods: A comprehensive narrative review of the peer-reviewed literature was conducted up to October 1, 2025. The search strategy focused on adult patients treated for skull base malignancies, synthesizing data on dose–volume metrics, incidence rates, and modality-specific toxicity profiles. Results: RIBI represents a pathophysiological continuum. (a) Descriptive imaging patterns: In prospective proton therapy series, focal RICE occured in 15% of patients, typically at a median of 12 months, and often resolved spontaneously. (b) Modality comparison: Although proton therapy reduces integral brain dose versus photon therapy, elevated linear energy transfer (LET) at the distal Bragg peak may contribute to focal radiation-associated image changes (RAIC), particularly in the temporal lobes. (c) Risk stratification and diagnosis: Risk increased when >1% of the healthy brain received >57.6 Gy (Relative Biological Energy (RBE)) or when V67Gy exceeded 0.17 cc. Advanced MRI and amino acid positron emission tomography (PET) improved differentiation between radiation effects and tumor recurrence. Conclusions: Post-radiation imaging changes are common and often benign. Distinguishing RICE from progression requires multimodal imaging and adherence to specific dose constraints. Management should prioritize surveillance for asymptomatic lesions. Full article

Accurate prediction of transient melt pool thermal fields in Laser Powder Bed Fusion (LPBF) is essential for understanding melt pool geometry and defect formation mechanisms, yet conventional finite element methods (FEM) impose prohibitive computational costs for parametric process exploration. A variational physics-informed neural network (VPINN) framework is presented for 3D transient thermal modeling of a GH3536 single-track LPBF scan. The framework incorporates a continuously differentiable Goldak double-ellipsoid moving heat source, temperature-dependent thermophysical property surrogates, and an effective heat-capacity treatment of latent heat associated with solid–liquid phase change and vaporization. These components are embedded in a weak-form residual-minimization scheme with octree-adaptive domain decomposition, hierarchical Legendre test functions, and sequential sliding-window time marching. Effective absorptivity is inferred jointly with the network parameters, using sparse experimental melt pool profiles as supervision. Within a parametric study covering laser powers from 100 to 140 W and scan speeds from 1000 to 1500 mm/s, the predicted melt pool width, depth, and aspect ratio agree closely with FEM benchmarks and cross-sectional optical micrograph measurements across both supervised and held-out interpolation conditions, with total relative L₂ nodal temperature errors ranging from 3.23% to 6.75%. Following a one-time offline training investment of 15,323 s that simultaneously resolves the full parametric space, surrogate inference reduces per-condition query time from 3000–4000 s (FEM) to merely 4–5 s, delivering a speedup of two to three orders of magnitude and making the framework increasingly cost-effective for high-throughput parametric studies and digital-twin integration as the number of queried conditions grows. Full article

Background/Objectives: Variants of MYPN, encoding a sarcomeric protein myopalladin, are associated with different types of cardiomyopathies and myopathies. However, the molecular mechanisms of MYPN-associated pathologies are still poorly understood. Methods: In this study, we generated induced pluripotent stem cells (iPSCs) from a hypertrophic cardiomyopathy patient carrying a novel p.N989I (c.2966A>T) variant of MYPN and used iPSC-derived cardiomyocytes to examine the impact of the variant on biophysical characteristics and transcriptomic profile. Results: No significant changes in parameters of calcium transients, sodium current and action potential were found in iPSC-derived cardiomyocytes with the p.N989I (c.2966A>T) variant of MYPN compared to non-isogenic cells from an unrelated healthy donor. At the transcriptomic level, MYPN-N989I cardiomyocytes demonstrated an upregulation of genes linked to cell cycle, mitotic spindle, microtubule cytoskeleton organization, and myogenic program genes. Downregulation of sarcomeric, Z-disc- and cell junction-associated genes, as well as genes involved in ATP synthesis, oxidative phosphorylation, and the SRF-signaling pathway, was also revealed. Conclusions: Our data suggest that the p.N989I (c.2966A>T) variant of MYPN plays a dual role in hypertrophic cardiomyopathy pathogenesis, disrupting not only sarcomeric and cytoskeletal organization but also the regulation of the muscle gene program. Full article

Alternaria brown spot, caused by the tangerine pathotype of Alternaria alternata, is a destructive fungal disease affecting citrus production worldwide. Nucleotide-binding site-leucine-rich repeat (NBS-LRR) genes constitute a major class of plant immune receptors; however, their genome-wide characteristics and potential association with Alternaria brown spot resistance loci in citrus remain poorly understood. In this study, we performed a comprehensive genome-wide identification and comparative analysis of NBS-LRR genes across representative citrus species. A total of 417 and 326 NBS-LRR genes were identified in Citrus reticulata and Citrus clementina, respectively, and were classified into NL, CNL, TNL, and RNL subfamilies based on domain architecture. Phylogenetic reconstruction, gene structure analysis, conserved motif composition, chromosomal distribution, synteny relationships, and promoter cis-element profiling collectively revealed considerable structural variation and lineage-specific expansion of the NBS-LRR gene family in citrus genomes. By integrating previously reported quantitative trait locus (QTL) data for Alternaria brown spot, we identified several NBS-LRR genes located within a resistance-associated genomic interval on chromosome 3. Among these, a candidate gene, designated LRR2, exhibited differential transcriptional responses upon pathogen inoculation and displayed distinct sequence variations between citrus genotypes. Structural modeling and molecular docking analyses suggested potential binding interfaces between LRR2 and multiple host-selective toxins, although the biological relevance of these interactions requires further experimental validation. Subcellular localization assays in Nicotiana benthamiana showed that LRR2 is distributed in both the nucleus and cytoplasm. Notably, transient overexpression of LRR2 triggered hypersensitive response-like cell death and H₂O₂ accumulation. Collectively, this study provides a comprehensive overview of the citrus NBS-LRR gene family and presents a multifaceted characterization of a QTL-anchored candidate gene. These findings establish a genomic and molecular framework for further functional investigations of citrus–Alternaria interactions. Full article