Search Results (558)

The oncogene KRAS drives tumor growth by activating pathways such as MAPK and PI3K-AKT in a constitutive manner. Although direct KRAS inhibitors exist, they are often limited in clinical use due to therapeutic resistance and toxicity. Therefore, alternative combinatorial therapeutic strategies are urgently needed. This study examined the knockout of five KRAS-related proteins—galectin-3 (GAL3), phosphodiesterase delta (PDEδ), nucleophosmin (NPM1), IQ motif-containing GTPase-activating protein 1 (IQGAP1), and SHOC2—using CRISPR-Cas9 in adenocarcinoma cell lines harboring the KRAS(G12V) oncogenic mutation, as well as in the noncancerous HEK-293 cell line. These proteins act as critical modulators that regulate KRAS activity, cellular localization, and that of its downstream signaling components. We analyzed the downstream activation of ERK and AKT kinases and evaluated subsequent cancer cell proliferation. Knockout of GAL3 and PDEδ was highly effective, significantly reducing MAPK and PI3K-AKT pathway activity and substantially impairing cell proliferation. SHOC2 knockout selectively and potently disrupted MAPK activation, while NPM1 knockout resulted in the complex, reciprocal modulation of the two major pathways. Notably, knocking out IQGAP1 enhanced PI3K–AKT and mTORC2–AKT signaling without affecting the MAPK pathway. These distinct modulatory roles highlight the non-redundant functions of the accessory proteins. In conclusion, our findings establish GAL3 and PDEδ, two KRAS-associated proteins, as promising combinatorial drug targets. Targeting these modulators provides an effective alternative strategy to overcome resistance mechanisms and enhance the clinical utility of existing KRAS inhibitors. Full article

Ectomycorrhizal (ECM) symbiosis is a fundamental mutualism crucial for forest eco-system health. Its establishment is governed by sophisticated molecular dialogue preceding physical colonization. This review synthesizes this pre-colonization crosstalk, beginning with reciprocal signal exchange where root exudates trigger fungal growth, and fungal lipochitooligosaccharides activate host symbiotic programming, often via the common symbiosis pathway. Successful colonization requires fungi to navigate plant immunity. They employ effectors, notably mycorrhiza-induced small secreted proteins (MiSSPs), to suppress defenses, e.g., by stabilizing jasmonate signaling repressors or inhibiting apoplastic proteases, establishing a localized “mycorrhiza-induced resistance.” Concurrent structural adaptations, including fungal hydrophobins, expansins, and cell wall-modifying enzymes like chitin deacetylase, facilitate adhesion and apoplastic penetration. While this sequential model integrates immune suppression with structural remodeling, current understanding is predominantly derived from a limited set of model systems. Significant knowledge gaps persist regarding species-specific determinants in non-model fungi and hosts, the influence of environmental variability and microbiome interactions, and methodological challenges in capturing early signaling in situ. This review’s main contributions are: providing a synthesized sequential model of molecular crosstalk; elucidating the dual fungal strategy of simultaneous immune suppression and structural remodeling; and identifying crucial knowledge gaps regarding non-model systems and species-specific determinants, establishing a research roadmap with implications for forest management and ecosystem sustainability. Full article

Fiber laser surface texturing was applied to AA1050 aluminum to improve friction and wear performance of PTFE coatings. A Taguchi L16 design varied texture geometry (square, diamond, hexagon, circle), scanned area ratio (20% to 80%), and laser power (40 to 100 W) prior to primer plus PTFE topcoat deposition (25 to 35 µm). Dry reciprocating sliding against a 6 mm 100Cr6 ball was conducted at 20 N, 1 Hz, and 50 m, and wear track geometry was measured by non-contact profilometry. The non-textured reference exhibited an average COF of 0.143, whereas the lowest mean COF was achieved with diamond 60% and 40 W (0.095) and the highest with hexagon 60% and 100 W (0.156); hexagon 20% and 60 W matched the reference. ANOVA indicated scanned area ratio as the dominant contributor to COF (39.72%), followed by geometry (35.07%) and power (25.21%). Profilometry confirmed reduced coating penetration for optimized textures: the reference wear track was approximately 1240 µm wide and 82 µm deep, compared with 930 µm and 34 µm for square 80% and 40 W, 997 µm and 39 µm for diamond 60% and 40 W, and 965 µm and 36 µm for hexagon 40% and 40 W. Full article

With the rapid advancement of Transformer-based large language models (LLMs), these models have found widespread applications in industrial domains such as code generation and non-functional requirement (NFR) classification in software engineering. However, recent research has primarily focused on optimizing linear matrix operations, while nonlinear operators remain relatively underexplored. This paper proposes hardware-efficient approximation and acceleration methods for the Softmax and RMSNorm operators to reduce resource cost and accelerate Transformer inference while maintaining model accuracy. For the Softmax operator, an additional range reduction based on the SafeSoftmax technique enables the adoption of a bipartite lookup table (LUT) approximation and acceleration. The bit-width configuration is optimized through Pareto frontier analysis to balance precision and hardware cost, and an error compensation mechanism is further applied to preserve numerical accuracy. The division is reformulated as a logarithmic subtraction implemented with a small LOD-driven lookup table, eliminating expensive dividers. For RMSNorm, LOD is further leveraged to decompose the reciprocal square root into mantissa and exponent parts, enabling parallel table lookup and a single multiplication. Based on these optimizations, an FPGA-based pipelined accelerator is implemented, achieving low operator-level latency and power consumption with significantly reduced hardware resource usage while preserving model accuracy. Full article

A stripline-type circulator is essential for the initial low-power characterization of vacuum electron devices such as magnetrons, enabling accurate measurements of startup behavior, oscillation frequency, and mode structure while minimizing reflections and protecting diagnostic equipment. In this study, two broadband S-band stripline circulator prototypes operating in the 2–4 GHz and 3–4 GHz bands were designed, fabricated, and experimentally characterized. A unified design methodology was implemented by using the same ferrite material and coupling angle in both structures, providing procurement simplicity, cost reduction, and technological standardization. This approach also enabled a direct assessment of how bandwidth variations influence circulator behavior. The design goals targeted a transmission efficiency above 90%, isolation exceeding 15 dB, and a voltage standing-wave ratio (VSWR) of 1.2:1. Experimental evaluations, including magnetic field mapping, low-power S-parameter measurements, and high-power tests, confirmed that both prototypes satisfy these specifications, consistently achieving at least 90% transmission across their respective operating bands. Additionally, a comparative analysis between a locally fabricated ferrite and a commercial ferrite sample was conducted, revealing the influence of material properties on transmission stability and high-power behavior. The results demonstrate that broadband stripline circulators employing a common ferrite material can be adapted to different S-band applications, offering a practical, cost-effective, and reliable solution for RF systems. Full article

Background: Children with autism spectrum disorder (ASD) commonly experience persistent difficulties in social communication, emotional regulation, and social engagement. In recent years, artificial intelligence (AI)-based technologies, particularly socially assistive robots and intelligent sensing systems, have been explored as complementary tools to support psychosocial interventions in this population. Objective: This systematic review aimed to critically evaluate recent evidence on the effectiveness of AI-based interventions in improving social, emotional, and cognitive functioning in children with ASD. Methods: A systematic literature search was conducted in PubMed following PRISMA guidelines, targeting English-language studies published between 2020 and 2025. Eligible studies involved children with ASD and implemented AI-driven tools within therapeutic or educational settings. Eight studies met inclusion criteria and were analyzed using the PICO framework. Results: The reviewed interventions included humanoid and non-humanoid robots, gaze-tracking systems, and theory of mind-oriented applications. Across studies, AI-based interventions were associated with improvements in joint attention, social communication and reciprocity, emotion recognition and regulation, theory of mind, and task engagement. Outcomes were assessed using standardized behavioral measures, observational coding, parent or therapist reports, and physiological or sensor-based indices. However, the studies were characterized by small and heterogeneous samples, short intervention durations, and variability in outcome measures. Conclusions: Current evidence suggests that AI-based systems may serve as valuable adjuncts to conventional interventions for children with ASD, particularly for supporting structured social and emotional skill development. Nonetheless, methodological limitations and limited long-term data underscore the need for larger, multi-site trials with standardized protocols to better establish efficacy, generalizability, and ethical integration into clinical practice. Full article

A reflective all-fiber optical current transformer based on a spatial non-reciprocal phase modulation technique is investigated by theoretical analysis and experimental measurement. The modulation unit, composed of a phase delay wave plate (LiNbO₃) and two Faraday rotators, achieves flexible frequency adjustment by converting modulation from the time domain to the spatial domain. Therefore, the avoidance of the impact caused by delay coils is achieved in principle. The absence of intrinsic frequency limitations eliminates the demand for precise timing control in demodulation, thereby simplifying the demodulation circuit and reducing the cost and size of the transformer. In previous studies, redundancies were identified in the optical path coupling devices. The half-wave voltage of the modulator is excessively high, and its size is considerable due to constraints inherent in the manufacturing process. The measurement range is within 1800 A. The scheme simplifies some optical path components. By optimizing the phase delay wave plate, the half-wave voltage of the modulator is significantly reduced by a factor of 150. Experimental results demonstrate that the current transformer exhibits excellent detection consistency within the rated current range of 30–3600 A (1–120%), the response time is within 3 ms, and the measurement error and peak error reach 0.052% and 0.127%. This configuration provides a novel option for the design and practical application of all-fiber optical current transformers. Full article

We present a utilization of the magnon Kerr effect to generate nonreciprocal genuine microwave entanglement in a hybrid system consisting of a yttrium iron garnet (YIG) sphere and three microwave cavities. Based on the quantum Langevin theory and linearization method under the condition of strong magnon driving, the system dynamics and covariance evolution are deduced and then applied to determinate the quantum correlations. It is found that three microwave cavities entangle with each other at the steady state. The basic root is that the Kerr nonlinearity can not only induce the enhanced parametric amplification of magnon but also cause the magnon frequency shift. Naturally, when the direction of the externally applied bias magnetic field is changed, switching of the magnon Kerr coefficient from positive to negative occurs and nonreciprocal tripartite entanglement among three microwave photons can be achieved. This may provide a fundamental resource for practical applications in quantum information processing and quantum networks. Full article

In this paper, we theoretically investigate nonlinearly tunable Fano resonance by employing a light tunneling heterostructure with one-dimensional defective photonic crystals and a lossy metallic film. We find that the phenomenon of Fano resonance can be created by coupling the Fabry–Pérot cavity mode with the topological optical Tamm state. We emphasize that the local field confinement induced by Fano resonance can ensure that the large nonlinear permittivity of metal can be utilized sufficiently. We show that the Fano-type transmission spectrum can be actively modulated by altering the input power intensity of light. We also illustrate that the hysteresis effects and nonreciprocal transmission behaviors can be obtained directly by using the Fano resonant heterostructure, allowing for the realization of high-performance all-optical switches and diodes. Our findings may open up new prospects for the nonlinear topological photonic systems with classical analogue–quantum phenomena. Full article

Accurate determination of the propagation constant ($\gamma$) in uniform microwave lines is critical but challenging due to the requirement for complex calibration and susceptibility to measurement noise. In order to overcome these limitations, a new objective function has been derived for improved propagation constant $\gamma$ measurement of uniform lines with symmetric reflections through calibration-free line–line measurements. Well-known methods in the literature on the determination of propagation constants with reflection asymmetry and non-reciprocal behavior structures are investigated and compared. To this end, mathematical derivations related to theory of microwave networks are validated by measurements in microwave frequency range X-band (8.2–12.4 GHz). Its advantage relies on the fact that it uses a term which is in the product form of determinants of two characteristic terms, whose value is close to unity both in theory and experiments. Eigenfactor (complex exponential) and $\gamma$ measurements of an X-band uniform (empty) waveguide section with symmetric reflections were carried out to validate our proposed formalism. Full article

Background/Objectives: The delayed effects of organophosphate poisoning may manifest years after exposure, often masked by age-related diseases. The aim of this retrospective cohort study was to identify the biochemical “trace” that could remain in patients decades after poisoning. We determined a wide range of biochemical parameters, along with the spectrum of esterified and non-esterified fatty acids (EFAs and NEFAs, respectively), in the blood plasma of a cohort of elderly patients diagnosed with occupational pathology (OP) due to (sub)chronic exposure to organophosphates in the 1980s. Methods: Elderly patients with and without a history of exposure to organophosphates were retrospectively divided into two groups: controls (n = 59, aged 73 ± 4, men 29% and women 71%) and those with OP (n = 84, aged 74 ± 4, men 29% and women 71%). The period of neurological examination and blood sampling for subsequent analysis was from mid-2022 to the end of 2023. Determination of the content of biomarkers of metabolic syndrome, NEFAs, and EFAs in blood plasma was performed by HPLC-MS/MS and GC-MS. Results: The medical histories of the examined elderly individuals with OP and the aged control group included common age-related diseases. However, patients with OP more often had hepatitis, gastrointestinal diseases, polyneuropathy, and an increased BMI. Analysis of metabolic biomarkers revealed, in the OP group, a decrease in the concentrations of 3-hydroxybutyrate (p < 0.05), 2-hydroxybutyrate (p < 0.0001), and acetyl-L-carnitine (p < 0.001) and the activity of butyrylcholinesterase (BChE) (p < 0.05), but an increase in the esterase activity of albumin (p < 0.05). Correlation analysis revealed significant relationships between albumin esterase activity and arachidonic acid concentrations in the OP group (0.64, p < 0.0001). A study of a wide range of fatty acids in patients with OP revealed reciprocal relationships between EFAs and NEFAs. A statistically significant decrease in concentration was shown for esters of margaric, stearic, eicosadienoic, eicosatrienoic, arachidonic, eicosapentaenoic, and docosahexaenoic fatty acids. A statistically significant increase in concentration was shown for non-esterified heptadecenoic, eicosapentaenoic, eicosatrienoic, docosahexaenoic, γ-linolenic, myristic, eicosenoic, arachidonic, eicosadienoic, oleic, linoleic, palmitic, linoelaidic, stearic, palmitoleic, pentadecanoic, and margaric acids. Decreases in the ratios of omega-3 to other unsaturated fatty acids were observed only for the esterified forms. Conclusions: The data obtained allow us to consider an increased level of NEFAs as one of the main cytotoxic factors for the vascular endothelium. Modification of albumin properties and decreased bioavailability of docosahexaenoic acid could be molecular links that cause specific manifestations of organophosphate-induced pathology at late stages after exposure. Full article

A constantly increasing incidence of chronic diseases is a challenge for healthcare worldwide, being directly associated with physical inactivity, which is considered an important cause of most chronic diseases. In contrast, physical exercise has been proven as a powerful instrument of healthcare to protect individuals against health-to-disease transition and against disease progression. Nonetheless, a number of studies warn against inappropriate high-intensity and/or unaccustomed exercise that exceeds an individual’s physical capacity. Indeed, extensive cardiac activity during prolonged exercise leads to significantly increased cardiac dimensions, triggering cardiac complications that may result in arrhythmogenic sudden cardiac death. The remarkable plasticity of mitochondria allows these organelles to sense and adapt to a variety of stressors and respond to stimuli by molecular signalling, regulating bioenergetics and cellular homeostasis, decisive for repair processes, proliferation, apoptosis, and tissue regeneration to combat degeneration, with whole body outcomes. Mitochondria act as biosensors in the human body; they are reactive to stimuli and protective against health-to-disease transition. To perform this life-important function throughout life, mitochondria need supportive measures, including physical activity, considered an essential pillar of mitochondrial medicine. This article highlights reciprocity between the quality of mitochondrial health and homeostasis on one hand and physical fitness and exercise intervention on the other hand. The proposed novelty relates to the monitoring of mitochondrial homeostasis, which is strongly recommended for creating individualised training programmes, and monitoring exercise efficacy during and after the programme is completed. To this end, a patient-friendly non-invasive approach is already established, utilising tear fluid multi-omics, mitochondria as the vital biosensors, and AI-based multi-professional data interpretation. Full article

Prostate cancer (PCa) exhibits a unique propensity to metastasize to bone, where it predominantly generates osteoblastic lesions. The formation of these lesions is a complex and dynamic process driven by reciprocal interactions between tumor cells and the bone microenvironment. Emerging evidence indicates that extracellular vesicles (EVs) play pivotal roles in the establishment of metastatic colonies and disease progression, as well as in local tumor–bone interactions. Through their diverse cargos, including proteins, lipids, and non-coding RNAs, EVs mediate bidirectional communication that regulates osteoclastogenesis, osteoblast activation, and osteocyte function, ultimately reshaping the bone niche to favor tumor growth. Importantly, EVs exhibit dual and context-dependent functions, acting either as promoters or suppressors of malignancy depending on the cellular source and microenvironmental context. These insights highlight EVs not only as mechanistic drivers of PCa bone metastases but also as promising therapeutic targets. Approaches aimed at modulating EV biogenesis, eliminating deleterious EVs, or harnessing EVs as drug delivery vehicles hold significant potential for advancing treatment strategies against PCa bone metastases. Full article

Background/Objectives. Self-harm is a heterogeneous behaviour with a lifetime prevalence of around 20% in young people aged 16–25 years old. Recent neurocognitive evidence suggests that, for some individuals, self-harm is associated with motivational processes similar to addiction, including maladaptive mental imagery, reward anticipation, and goal pursuit. However, our knowledge of young people’s subjective experiences of rewards and goals in relation to self-harm behaviour remains limited. Our study aimed to investigate how young people who self-harm experience enjoying and wanting rewards and pursuing goals in daily life and whether this experience changes during periods of self-harm. We also explored their use of mental imagery as a key cognitive process to support motivation. Methods. We conducted two parallel focus groups online (total of N = 12) with young people (mean age = 12.2, SD = 3; nine women, two men, and one non-binary) with a past-year history of self-harm behaviour. Qualitative data was analysed using inductive thematic analysis. Two young people with lived experience of self-harm informed the topic guide and data interpretation. Examples of questions were “Do you think your experiences of enjoying and/or looking forward to pleasant things are related in any way to self-harm, or not?” and “Do you visualise things you enjoy or may look forward to? If you do, how is that experience?”. Results. There were six themes: rewards need deserving, high self-standards, keeping control, trapped into long-term goals, unhelpful mental imagery, and self-harm alters the experience and anticipation of rewards and goal attainment. Most young people reported enjoying conditional rewards and working towards long-term goals that tend to be unattainable and beyond their control. Imagining these goals was experienced as unhelpful by most. For all young people, periods of self-harm thwarted enjoyment and goal achievement, shifted the preference to short-term immediate gratification, including from self-harm behaviour, and devalued long-term goals. However, our data cannot determine if these experiences are specific to young people who self-harm. Conclusions. Our findings indicate that the reciprocal relationship between motivational processes and self-harm behaviour in young people warrants further investigation. Helping individuals develop more adaptive rewards and goals, including appreciation of short-term goals and use of motivational mental imagery, could represent valued support for young people with self-harm. Full article

Background: Numerical cognition and motor performance rely on overlapping brain systems, yet the extent of their reciprocal interaction remains unclear. This systematic review explores how number processing influences motor execution and how motor activity shapes numerical cognition, emphasizing the neural mechanisms underlying these associations. Methods: A comprehensive search of Scopus, PubMed, MEDLINE, SPORTDiscus, PsycINFO, and SpringerLink, as well as journal citations and conference proceedings (up to August 2025), identified experimental studies examining the interplay between numerical cognition and motor performance in healthy adults. Both randomized and non-randomized designs were included. Two reviewers independently screened, extracted data, and assessed study quality following PRISMA and Cochrane Risk of Bias guidelines. Results: Twelve studies met the inclusion criteria. Most showed that numerical stimuli facilitated motor responses, with congruent number–movement pairings yielding faster reactions and more efficient kinematics. Mental calculation often enhanced motor output (e.g., force, jump height), though interferences emerged under high cognitive load. Conversely, motor actions consistently biased numerical judgments, aligning with spatial–numerical associations. Conclusions: Evidence suggests a predominant pattern of facilitation, likely reflecting shared networks between cognitive and motor resources. These findings advance theoretical understanding and highlight promising translational applications in education, sport, and neurorehabilitation. Full article