Search Results (334)

Local adaptation allows animal populations to persist in diverse and changing environments, yet its genomic underpinnings remain poorly characterized in livestock. Chinese indigenous pigs, renowned for their rich phenotypic and ecological diversity, offer a powerful model for investigating environmental adaptation. Here, we integrated whole-genome resequencing data, environmental variables, genotype–environment association (GEA) analyses, and functional annotation to explore the adaptive genomic landscape of 46 native pig breeds across China. Based on 578 individuals and 17.7 million SNPs, we performed genome-wide GEA using latent factor mixed models (LFMMs), identifying 8644 SNPs significantly associated with environmental factors, including 310 linked to precipitation in the wettest quarter (BIO16). Redundancy analysis (RDA) and gradient forest modeling identified BIO16 as a major environmental driver of genomic variation. Functional annotation of BIO16-associated SNPs revealed significant enrichment in regulatory elements and genes highly expressed in the lung, spleen, hypothalamus, and intestine, implicating immune and metabolic pathways in local adaptation. Among the candidate loci, MS4A7 exhibited strong association signals, population differentiation, and tissue-specific regulation, suggesting a role in precipitation-mediated adaptation. This work enhances our understanding of livestock adaptation and informs climate-resilient conservation and breeding strategies. Full article

This paper presents a novel EEG-based learning system designed to enhance the efficiency and effectiveness of studying by dynamically adjusting the difficulty level of learning materials based on real-time attention levels. In the training phase, EEG signals corresponding to high and low concentration levels are recorded while participants engage in quizzes to learn and memorize Chinese characters. The attention levels are determined based on performance metrics derived from the quiz results. Following extensive preprocessing, the EEG data undergoes several feature extraction steps: removal of artifacts due to eye blinks and facial movements, segregation of waves based on their frequencies, similarity indexing with respect to delay, binary thresholding, and (PCA). These extracted features are then fed into a k-NN classifier, which accurately distinguishes between high and low attention brain wave patterns, with the labels derived from the quiz performance indicating high or low attention. During the implementation phase, the system continuously monitors the user’s EEG signals while studying. When low attention levels are detected, the system increases the repetition frequency and reduces the difficulty of the flashcards to refocus the user’s attention. Conversely, when high concentration levels are identified, the system escalates the difficulty level of the flashcards to maximize the learning challenge. This adaptive approach ensures a more effective learning experience by maintaining optimal cognitive engagement, resulting in improved learning rates, reduced stress, and increased overall learning efficiency. Our results indicate that this EEG-based adaptive learning system holds significant potential for personalized education, fostering better retention and understanding of Chinese characters. Full article

Since the initial use of biological ion channels to detect single-stranded genomic base pair differences, label-free and highly sensitive resistive pulse sensing (RPS) with nanopores has made remarkable progress in single-molecule analysis. By monitoring transient ionic current disruptions caused by molecules translocating through a nanopore, this technology offers detailed insights into the structure, charge, and dynamics of the analytes. In this work, the RPS platforms based on biological, solid-state, and other sensing pores, detailing their latest research progress and applications, are reviewed. Their core capability is the high-precision characterization of tiny particles, ions, and nucleotides, which are widely used in biomedicine, clinical diagnosis, and environmental monitoring. However, current RPS methods involve bottlenecks, including limited sensitivity (weak signals from sub-nanometer targets with low SNR), complex sample interference (high false positives from ionic strength, etc.), and field consistency (solid-state channel drift, short-lived bio-pores failing POCT needs). To overcome this, bio-solid-state fusion channels, in-well reactors, deep learning models, and transfer learning provide various options. Evolving into an intelligent sensing ecosystem, RPS is expected to become a universal platform linking basic research, precision medicine, and on-site rapid detection. Full article

Background/Objectives: The RTK-RAS signaling cascade is a central axis in colorectal cancer (CRC) pathogenesis, governing cellular proliferation, survival, and therapeutic resistance. Somatic alterations in key pathway genes—including KRAS, NRAS, BRAF, and EGFR—are pivotal to clinical decision-making in precision oncology. However, the integration of these genomic events with clinical and demographic data remains hindered by fragmented resources and a lack of accessible analytical frameworks. To address this challenge, we developed AI-HOPE-RTK-RAS, a domain-specialized conversational artificial intelligence (AI) system designed to enable natural language-based, integrative analysis of RTK-RAS pathway alterations in CRC. Methods: AI-HOPE-RTK-RAS employs a modular architecture combining large language models (LLMs), a natural language-to-code translation engine, and a backend analytics pipeline operating on harmonized multi-dimensional datasets from cBioPortal. Unlike general-purpose AI platforms, this system is purpose-built for real-time exploration of RTK-RAS biology within CRC cohorts. The platform supports mutation frequency profiling, odds ratio testing, survival modeling, and stratified analyses across clinical, genomic, and demographic parameters. Validation included reproduction of known mutation trends and exploratory evaluation of co-alterations, therapy response, and ancestry-specific mutation patterns. Results: AI-HOPE-RTK-RAS enabled rapid, dialogue-driven interrogation of CRC datasets, confirming established patterns and revealing novel associations with translational relevance. Among early-onset CRC (EOCRC) patients, the prevalence of RTK-RAS alterations was significantly lower compared to late-onset disease (67.97% vs. 79.9%; OR = 0.534, p = 0.014), suggesting the involvement of alternative oncogenic drivers. In KRAS-mutant patients receiving Bevacizumab, early-stage disease (Stages I–III) was associated with superior overall survival relative to Stage IV (p = 0.0004). In contrast, BRAF-mutant tumors with microsatellite-stable (MSS) status displayed poorer prognosis despite higher chemotherapy exposure (OR = 7.226, p < 0.001; p = 0.0000). Among EOCRC patients treated with FOLFOX, RTK-RAS alterations were linked to worse outcomes (p = 0.0262). The system also identified ancestry-enriched noncanonical mutations—including CBL, MAPK3, and NF1—with NF1 mutations significantly associated with improved prognosis (p = 1 × 10⁻⁵). Conclusions: AI-HOPE-RTK-RAS exemplifies a new class of conversational AI platforms tailored to precision oncology, enabling integrative, real-time analysis of clinically and biologically complex questions. Its ability to uncover both canonical and ancestry-specific patterns in RTK-RAS dysregulation—especially in EOCRC and populations with disproportionate health burdens—underscores its utility in advancing equitable, personalized cancer care. This work demonstrates the translational potential of domain-optimized AI tools to accelerate biomarker discovery, support therapeutic stratification, and democratize access to multi-omic analysis. Full article

Ergonomic risk classification during manual lifting tasks is crucial for the prevention of workplace injuries. This study addresses the challenge of classifying lifting task risk levels (low, medium, and high risk, labeled as 0, 1, and 2) using multi-modal time-series data comprising raw facial landmarks and bio-signals (electrocardiography [ECG] and electrodermal activity [EDA]). Classifying such data presents inherent challenges due to multi-source information, temporal dynamics, and class imbalance. To overcome these challenges, this paper proposes a Multi-Adaptive Functional Neural Network (Multi-AdaFNN), a novel method that integrates functional data analysis with deep learning techniques. The proposed model introduces a novel adaptive basis layer composed of micro-networks tailored to each individual time-series feature, enabling end-to-end learning of discriminative temporal patterns directly from raw data. The Multi-AdaFNN approach was evaluated across five distinct dataset configurations: (1) facial landmarks only, (2) bio-signals only, (3) full fusion of all available features, (4) a reduced-dimensionality set of 12 selected facial landmark trajectories, and (5) the same reduced set combined with bio-signals. Performance was rigorously assessed using 100 independent stratified splits (70% training and 30% testing) and optimized via a weighted cross-entropy loss function to manage class imbalance effectively. The results demonstrated that the integrated approach, fusing facial landmarks and bio-signals, achieved the highest classification accuracy and robustness. Furthermore, the adaptive basis functions revealed specific phases within lifting tasks critical for risk prediction. These findings underscore the efficacy and transparency of the Multi-AdaFNN framework for multi-modal ergonomic risk assessment, highlighting its potential for real-time monitoring and proactive injury prevention in industrial environments. Full article

The analysis of anomalous diffusion characteristics within single-particle tracking data is a key problem in several applied-science domains, including biosignal processing, bioinformatics, and biotechnology. This task becomes particularly challenging in the presence of short trajectories, localization errors, and non-ergodicity, features that are common in real experimental data. To address these limitations, this work proposes an approach that improves the robustness and accuracy of estimating the anomalous diffusion exponent α, even for very short trajectories of up to 10 points. The approach includes an ensemble-based variance estimation of the exponent α, along with a bias correction based on time–ensemble averaged mean squared displacement, which reduces the systematic bias. These components integrate well into neural network architectures and are suitable for analyzing experimental trajectories in biotechnology and bioprocess engineering applications. Full article

Background/Objectives: The Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway is a critical mediator of immune regulation, inflammation, and cancer progression. Although implicated in colorectal cancer (CRC) pathogenesis, its molecular heterogeneity and clinical significance remain insufficiently characterized—particularly within early-onset CRC (EOCRC) and across diverse treatment and demographic contexts. We present AI-HOPE-JAK-STAT, a novel conversational artificial intelligence platform built to enable the real-time, natural language-driven exploration of JAK/STAT pathway alterations in CRC. The platform integrates clinical, genomic, and treatment data to support dynamic, hypothesis-generating analyses for precision oncology. Methods: AI-HOPE-JAK-STAT combines large language models (LLMs), a natural language-to-code engine, and harmonized public CRC datasets from cBioPortal. Users define analytical queries in plain English, which are translated into executable code for cohort selection, survival analysis, odds ratio testing, and mutation profiling. To validate the platform, we replicated known associations involving JAK1, JAK3, and STAT3 mutations. Additional exploratory analyses examined age, treatment exposure, tumor stage, and anatomical site. Results: The platform recapitulated established trends, including improved survival among EOCRC patients with JAK/STAT pathway alterations. In FOLFOX-treated CRC cohorts, JAK/STAT-altered tumors were associated with significantly enhanced overall survival (p < 0.0001). Stratification by age revealed survival advantages in younger (age < 50) patients with JAK/STAT mutations (p = 0.0379). STAT5B mutations were enriched in colon adenocarcinoma and correlated with significantly more favorable trends (p = 0.0000). Conversely, JAK1 mutations in microsatellite-stable tumors did not affect survival, emphasizing the value of molecular context. Finally, JAK3-mutated tumors diagnosed at Stage I–III showed superior survival compared to Stage IV cases (p = 0.00001), reinforcing stage as a dominant clinical determinant. Conclusions: AI-HOPE-JAK-STAT establishes a new standard for pathway-level interrogation in CRC by empowering users to generate and test clinically meaningful hypotheses without coding expertise. This system enhances access to precision oncology analyses and supports the scalable, real-time discovery of survival trends, mutational associations, and treatment-response patterns across stratified patient cohorts. Full article

Decomposing Electrodermal Activity (EDA) into phasic (short-term, stimulus-linked responses) and tonic (longer-term baseline) components is essential for extracting meaningful emotional and physiological biomarkers. This study presents a comparative analysis of knowledge-driven, statistical, and deep learning-based methods for EDA signal decomposition, with a focus on in-the-wild data collected from wearable devices. In particular, the authors introduce the Feel Transformer, a novel Transformer-based model adapted from the Autoformer architecture, designed to separate phasic and tonic components without explicit supervision. The model leverages pooling and trend-removal mechanisms to enforce physiologically meaningful decompositions. Comparative experiments against methods such as Ledalab, cvxEDA, and conventional detrending show that the Feel Transformer achieves a balance between feature fidelity (SCR frequency, amplitude, and tonic slope) and robustness to noisy, real-world data. The model demonstrates potential for real-time biosignal analysis and future applications in stress prediction, digital mental health interventions, and physiological forecasting. Full article

This paper presents a methodology for extracting and simulating arterial pulse waveform signals from Fabry–Perot interferometric measurements, emphasizing a practical approach for noninvasive cardiovascular assessment. A key novelty of this work is the presentation of a complete Python-based processing pipeline, which is made publicly available as open-source code on GitHub (git version 2.39.5). To the authors’ knowledge, no such repository for demodulating these specific interferometric signals to obtain a raw arterial pulse waveform previously existed. The proposed system utilizes accessible Python-based preprocessing steps, including outlier removal, Butterworth high-pass filtering, and min–max normalization, designed for robust signal quality even in settings with common physiological artifacts. Key features such as the rate of change, the Hilbert transform of the rate of change (envelope), and detected extrema guide the signal reconstruction, offering a computationally efficient pathway to reveal its periodic and phase-dependent dynamics. Visual analyses highlight amplitude variations and residual noise sources, primarily attributed to sensor bandwidth limitations and interpolation methods, considerations critical for real-world deployment. Despite these practical challenges, the reconstructed arterial pulse waveform signals provide valuable insights into arterial motion, with the methodology’s performance validated on measurements from three subjects against synchronized ECG recordings. This demonstrates the viability of Fabry–Perot sensors as a potentially cost-effective and readily implementable tool for noninvasive cardiovascular diagnostics. The results underscore the importance of precise yet practical signal processing techniques and pave the way for further improvements in interferometric sensing, bio-signal analysis, and their translation into clinical practice. Full article

This review provides a comprehensive analysis of recent advancements in lower limb exoskeleton systems, focusing on applications, control strategies, hardware architecture, sensing modalities, human-robot interaction, evaluation methods, and technical innovations. The study spans systems developed for gait rehabilitation, mobility assistance, terrain adaptation, pediatric use, and industrial support. Applications range from sit-to-stand transitions and post-stroke therapy to balance support and real-world navigation. Control approaches vary from traditional impedance and fuzzy logic models to advanced data-driven frameworks, including reinforcement learning, recurrent neural networks, and digital twin-based optimization. These controllers support personalized and adaptive interaction, enabling real-time intent recognition, torque modulation, and gait phase synchronization across different users and tasks. Hardware platforms include powered multi-degree-of-freedom exoskeletons, passive assistive devices, compliant joint systems, and pediatric-specific configurations. Innovations in actuator design, modular architecture, and lightweight materials support increased usability and energy efficiency. Sensor systems integrate EMG, EEG, IMU, vision, and force feedback, supporting multimodal perception for motion prediction, terrain classification, and user monitoring. Human–robot interaction strategies emphasize safe, intuitive, and cooperative engagement. Controllers are increasingly user-specific, leveraging biosignals and gait metrics to tailor assistance. Evaluation methodologies include simulation, phantom testing, and human–subject trials across clinical and real-world environments, with performance measured through joint tracking accuracy, stability indices, and functional mobility scores. Overall, the review highlights the field’s evolution toward intelligent, adaptable, and user-centered systems, offering promising solutions for rehabilitation, mobility enhancement, and assistive autonomy in diverse populations. Following a detailed review of current developments, strategic recommendations are made to enhance and evolve existing exoskeleton technologies. Full article

Introduction: Early-onset colorectal cancer (EOCRC) is rising rapidly, particularly among the Hispanic/Latino (H/L) populations, who face disproportionately poor outcomes. The transforming growth factor-beta (TGF-β) signaling pathway plays a critical role in colorectal cancer (CRC) progression by mediating epithelial-to-mesenchymal transition (EMT), immune evasion, and metastasis. However, integrative analyses linking TGF-β alterations to clinical features remain limited—particularly for diverse populations—hindering translational research and the development of precision therapies. To address this gap, we developed AI-HOPE-TGFbeta (Artificial Intelligence agent for High-Optimization and Precision Medicine focused on TGF-β), the first conversational artificial intelligence (AI) agent designed to explore TGF-β dysregulation in CRC by integrating harmonized clinical and genomic data via natural language queries. Methods: AI-HOPE-TGFbeta utilizes a large language model (LLM), Large Language Model Meta AI 3 (LLaMA 3), a natural language-to-code interpreter, and a bioinformatics backend to automate statistical workflows. Tailored for TGF-β pathway analysis, the platform enables real-time cohort stratification and hypothesis testing using harmonized datasets from the cBio Cancer Genomics Portal (cBioPortal). It supports mutation frequency comparisons, odds ratio testing, Kaplan–Meier survival analysis, and subgroup evaluations across race/ethnicity, microsatellite instability (MSI) status, tumor stage, treatment exposure, and age. The platform was validated by replicating findings on the SMAD4, TGFBR2, and BMPR1A mutations in EOCRC. Exploratory queries were conducted to examine novel associations with clinical outcomes in H/L populations. Results: AI-HOPE-TGFbeta successfully recapitulated established associations, including worse survival in SMAD4-mutant EOCRC patients treated with FOLFOX (fluorouracil, leucovorin and oxaliplatin) (p = 0.0001) and better outcomes in early-stage TGFBR2-mutated CRC patients (p = 0.00001). It revealed potential population-specific enrichment of BMPR1A mutations in H/L patients (OR = 2.63; p = 0.052) and uncovered MSI-specific survival benefits among SMAD4-mutated patients (p = 0.00001). Exploratory analysis showed better outcomes in SMAD2-mutant primary tumors vs. metastatic cases (p = 0.0010) and confirmed the feasibility of disaggregated ethnicity-based queries for TGFBR1 mutations, despite small sample sizes. These findings underscore the platform’s capacity to detect both known and emerging clinical–genomic patterns in CRC. Conclusions: AI-HOPE-TGFbeta introduces a new paradigm in cancer bioinformatics by enabling natural language-driven, real-time integration of genomic and clinical data specific to TGF-β pathway alterations in CRC. The platform democratizes complex analyses, supports disparity-focused investigation, and reveals clinically actionable insights in underserved populations, such as H/L EOCRC patients. As a first-of-its-kind system studying TGF-β, AI-HOPE-TGFbeta holds strong promise for advancing equitable precision oncology and accelerating translational discovery in the CRC TGF-β pathway. Full article

Flight behavior in pigeons is governed by intricate neural mechanisms that regulate movement patterns and flight dynamics. Among various kinematic parameters, flight acceleration provides critical information for the brain to modulate movement intensity, speed, and direction. However, the neural representation mechanisms underlying flight acceleration remain insufficiently understood. To address this, we conducted outdoor free-flight experiments in homing pigeons, during which GPS data, flight posture, and eight-channel local field potentials (LFPs) were synchronously recorded. Our analysis revealed that gamma-band activity in the dorsal intermediate arcopallium (AId) region was more prominent during behaviorally demanding phases of flight. In parallel, local functional network analysis showed that the clustering coefficient of gamma-band activity in the AId followed a nonlinear, U-shaped relationship with flight acceleration—exhibiting the strongest and most widespread connectivity during deceleration, moderate connectivity during acceleration, and the weakest network coupling during steady flight. This pattern likely reflects the increased neural demands associated with flight phase transitions, where greater cognitive and sensorimotor integration is required. Furthermore, using LFP signals from five distinct frequency bands as input, machine learning models were developed to decode flight acceleration, further confirming the role of gamma-band dynamics in motor regulation during natural flight. This study provides the first evidence that gamma-band activity in the avian AId region encodes flight acceleration, offering new insights into the neural representation of motor states in natural flight and implications for bio-inspired flight control systems. Full article

Prostate cancer (PCa) is the second most common cancer and the second leading cause of cancer-related mortality among men. Gene expression analysis has been crucial in understanding tumor biology and providing disease progression markers. Cell surface glycoproteins and those in the extracellular matrix play significant roles in the PCa microenvironment by promoting migration, invasion, and metastasis. The molecular and histopathological heterogeneity of prostate tumors necessitates a new marker discovery to better stratify patients at risk for poor prognosis. In this study, our objectives were to investigate and characterize the localization and expression of SLIT/ROBO in PCa samples from transgenic mice and human tumor samples, aiming to identify novel prognostic markers and potential therapeutic targets. We conducted histopathological, immunohistochemical, and bioinformatics analyses on prostate tumors from two knockout mice models (Pb-Cre4/Pten^f/f and Pb-Cre4/Trp53^f/f;Rb1^f/f) and human prostate tumors. Transcriptomic analyses revealed special changes in the expression of genes related to the SLIT/ROBO neural signaling pathway. We further characterized the gene and protein expression of the SLIT/ROBO pathway in knockout animal samples, and protein expression in the PCa samples of patients with different Gleason scores. Public datasets with clinical data from patients (The Human Protein Atlas, cBioPortal, SurvExpress and CamcAPP) were used to validate the gene and protein expression of SLIT1, SLIT2, ROBO1, and ROBO4, correlating these alterations with the prognosis of subgroups of patients. Our findings highlight potential biomarkers of the SLIT/ROBO pathway with prognostic and predictive value, as well as promising therapeutic targets for PCa. Full article

Background: Yiqi Zengmian (YQZM) functions as an immunopotentiator by enhancing both cellular and humoral immunity. However, its pharmacodynamic active constituents, particularly those absorbed into the bloodstream, and mechanism of action remain unclear. This study aimed to investigate the immunopotentiating effects and mechanisms of YQZM in mice immunized with the BBIBP-CorV (Beijing Bio-Institute of Biological Products Coronavirus Vaccine). Methods: Serum pharmacochemistry and ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) were employed to identify bioavailable components of YQZM. The mice received the BBIBP-CorV twice on days 1 and 14, while YQZM was orally administered for 28 days. Neutralization assays and ELISA quantified antigen-specific antibodies (abs), flow cytometry (FC) and intracellular cytokine staining (ICS) were used to assess immune cell populations and their cytokines, and an enzyme-linked immunospot assay (ELISpot) quantified memory T and B cells (MBs and MTs). To identify underlying mechanisms, network pharmacology, RNA sequencing (RNA-Seq), molecular docking, Western blotting (WB), and quantitative reverse transcription PCR (RT-qPCR) were performed. Results: YQZM significantly enhanced antigen-specific antibody titers, immune cell proportions, cytokine levels, and memory lymphocyte functions. UPLC-MS/MS analysis identified 31 bioactive compounds in YQZM. KEGG enrichment analysis based on RNA-Seq and network pharmacology implicated the TLR-JAK-STAT signaling pathway in YQZM’s immune-enhancing effects. WB and RT-PCR validated that YQZM upregulated the expression of critical nodes in the TLR-JAK-STAT signaling pathway. Furthermore, molecular docking indicated that YQZM’s primary active components exhibited strong binding affinity for critical proteins. Conclusions: YQZM effectively enhances vaccine-induced innate and adaptive immunity via a multi-component, multi-target mechanism, among which the TLR-JAK-STAT signaling pathway is a validated molecular target. Full article

Zizania latifolia (Jiaobai) is an economically important aquatic crop characterized by unique gall formation through interaction with the smut fungus Ustilago esculenta. Understanding factors influencing this interaction is crucial for cultivation. This study investigates the non-target effects of the fungicide Fenaminosulf (FM) on Z. latifolia’s growth, physiology, and underlying molecular pathways. We demonstrate that FM exerts striking concentration-dependent effects, revealing its potential as a modulator of plant development and symbiosis. Physiological measurements showed that a moderate FM concentration (1.25 g/L) promoted key vegetative growth parameters, including plant height and leaf length, while maintaining chlorophyll content, suggesting a potential bio-stimulant effect. In contrast, higher FM concentrations (2.5 g/L and 5 g/L) inhibited vegetative growth but significantly enhanced gall formation, particularly at 2.5 g/L, indicating that FM can redirect plant resources or alter susceptibility to favor the fungal interaction under specific conditions. Transcriptomic analysis provided mechanistic insights, revealing extensive gene expression reprogramming, especially under high FM treatment (5 g/L). Key pathways related to plant-pathogen interaction, phenylpropanoid biosynthesis, and hormone signal transduction were significantly modulated. Notably, FM treatment suppressed key immune-related genes, including Xa21 and PBL19, potentially reducing plant resistance and facilitating gall formation. Hormone signaling analysis revealed inhibition of auxin, cytokinin, brassinosteroid, and jasmonic acid metabolism, indicating a comprehensive molecular recalibration of plant developmental processes. The study provides novel insights into the molecular mechanisms by which FM influences Z. latifolia growth and gall formation. The concentration-dependent effects of FM suggest its potential as a strategic tool for agricultural management, offering a nuanced approach to crop development. These findings contribute to understanding plant-chemical interactions and provide valuable directions for optimizing Z. latifolia cultivation strategies. Full article