Search Results (242)

Triboelectric nanogenerators (TENGs) provide a powerful route for translating mechanical interactions into electrical signals, offering unique opportunities for self-powered sensing and human-machine interfaces (HMIs). Yet a persistent gap remains between high-performance laboratory demonstrations and reliable, scalable systems for real-world use. This gap arises not only from triboelectric materials or device configurations, but also from the electrode, which has long been viewed as a passive charge collector. In practical TENG systems, electrodes must simultaneously enable efficient charge extraction, stable electromechanical contact, mechanical compliance, environmental robustness and manufacturable integration. These requirements are strongly coupled and often conflicting, making electrode design a central bottleneck in the development of application-ready TENGs. In this Review, we position electrode engineering as an integrated strategy that connects material design, structural configuration and fabrication methodology. We discuss how these dimensions jointly define device output, durability, scalability and application boundaries, with particular emphasis on self-powered HMIs. By reframing electrodes as active functional interfaces, this Review provides design principles for next-generation triboelectric devices and intelligent self-powered systems. Full article

High-precision long-baseline coordinate transfer is essential for maintaining spatial reference frames, and the modernized multi-frequency signals of BDS-3 provide new opportunities for this task. However, existing long-baseline network solutions still rely mainly on legacy frequency combinations, and quantitative evidence for pure new-frequency BDS-3 combinations in large-scale coordinate transfer remains limited. This study evaluates the applicability of BDS-3 high- and low-frequency signal combinations for long-baseline position datum transfer and investigates frequency-combination selection. Seven continuous stations were used to form 21 long baselines. Five dual-frequency schemes were tested, including four BDS-3 combinations, namely B1I/B3I, B1I/B2a, B1C/B2a, and B1C/B3I, and one GPS reference combination, L1/L5. Double-differenced ionosphere-free baseline processing and three-dimensional constrained network adjustment were applied. Performance was assessed using carrier-phase precision, normalized root mean square (NRMS), baseline vector quality, and point-transfer differences. The results show that the BDS-3 B1C/B2a new-frequency combination achieved the best overall consistency among the BDS-3 schemes, with an average high-frequency carrier-phase precision of 6.3 mm, a mean NRMS of 0.23, millimeter-level baseline vector formal-error RMS, and a 19.7 mm point difference at the unknown station DCMS. Given that the evaluation is based on seven consecutive days of observations, the long-term applicability of the proposed strategy requires further validation. Full article

Squamous cell carcinoma of the anal canal (SCAC) is a rare malignancy whose incidence has been steadily increasing worldwide. Persistent infection with high-risk human papillomavirus (HPV), particularly HPV16 and HPV18 genotypes, is the main etiological factor and plays a central role in tumor development. While combined chemoradiotherapy remains the standard treatment for localized disease and achieves high rates of tumor control, a considerable proportion of patients experience recurrence or present with advanced disease. For the latter, therapeutic options remain limited. Over the last decade, advances in genomic profiling have significantly expanded our understanding of SCAC biology. Recurrent alterations affecting the PI3K/AKT/mTOR pathway, especially PIK3CA mutations, have emerged as the most common molecular events, particularly in HPV-positive tumors. Additional alterations involve receptor tyrosine kinase signaling, chromatin remodeling genes, DNA damage response pathways, and components of the MAPK cascade. Moreover, HPV-positive and HPV-negative tumors display distinct molecular features with important prognostic implications. Immunotherapy has recently become an important component of treatment for advanced SCAC, although reliable predictive biomarkers are still lacking. This review summarizes the current evidence on the molecular landscape of SCAC, discusses emerging prognostic and predictive biomarkers, and highlights potential opportunities for the development of more personalized therapeutic strategies. Full article

Future low Earth orbit (LEO) communication constellations are evolving into integrated multi-mission infrastructure. Their signals of opportunity (SoP) are therefore becoming attractive for Doppler positioning. However, the conventional coverage- or rate-optimized configurations may not provide favorable Doppler geometry under realistic link-quality constraints. This paper considers this emerging requirement at the constellation-configuration design level and proposes a multi-layer Walker optimization framework for integrated communication and SoP Doppler positioning. A system-level positioning metric is developed to move beyond visibility and dilution-of-precision indicators. A link-quality-constrained multi-epoch Fisher information matrix (FIM) incorporates $C/N_0$-based link measurability and a general carrier-to-noise-density-dependent Doppler-noise formulation. In the reported simulations, $C/N_0$ controls observation admission, while all admitted Doppler observations use a fixed noise standard deviation of 0.5 m/s. An effective position-error bound is then obtained by marginalizing clock-drift and frequency-bias nuisance states. Based on a unified satellite–ground geometry, weighted service coverage, weighted best-link achievable rate, and the proposed positioning metric are jointly optimized using a constrained mixed-integer multi-objective artificial hummingbird algorithm (CMI-MOAHA). The FIM-based metric is consistent with the positioning root mean square error (RMSE) from a separately implemented nonlinear Doppler solver under matched observation and noise assumptions. With the total number of satellites fixed at 2000, the Pareto archive reveals clear trade-offs among coverage, best-link achievable rate, and positioning. When the positioning objective is included, the best obtained positioning metric decreases across all tested constellation sizes, with a maximum reduction of 77.1%. These results show that constellation-level joint optimization is warranted when LEO communication satellites also serve as SoP for Doppler positioning. Full article

Background: Teachers routinely encounter children whose behaviour reflects emotional distress and dysregulation, yet they have limited opportunities to practise the relational skills required to respond effectively. These challenges are particularly pronounced in Alternative Provision (AP), which serves children who frequently present with histories of trauma, neurodevelopmental differences, and complex emotional and behavioural needs. Mentalization, the capacity to understand behaviour in terms of underlying mental states, is central to effective relational practice in such contexts. Conversational Artificial Intelligence (AI) may offer a scalable means of supporting this form of skills development, but its feasibility as a teacher-training modality remains largely unexplored. Methods: This mixed-methods proof-of-concept feasibility study evaluated MentaClassAI, a novel AI-based training tool in which educators engaged in simulated voice conversations with AI child characters portraying classroom dysregulation and subsequently received individualised, mentalization-informed feedback. Eleven staff members from a single AP school (four teachers and seven teaching assistants) completed a single training session and were allocated to either a psychoeducation video condition (n = 6) or a no-video condition (n = 5). The video condition received a brief introduction to mentalization and epistemic trust prior to engaging with the simulation. Pre- and post-engagement measures included the Reflective Functioning Questionnaire (RFQ-8) and a Teacher Self-Efficacy Scale. Post-engagement measures included an 18-item acceptability questionnaire, a Technology Acceptance Model scale, and open-ended questions analysed using thematic analysis. Results: Acceptability was high, with 84.8% of questionnaire responses falling within the positive range (overall M = 5.60/7). Feedback accuracy (M = 6.55) and clarity (M = 6.36) received the highest ratings. Participants reported higher teacher self-efficacy after the session than before (d = 1.20, p = 0.003), with 10 of 11 participants demonstrating improvement. Self-reported hypomentalizing was lower after the session (d = −0.86, p = 0.017). Between-condition differences (video versus no-video) were not statistically significant. The video condition scored numerically higher on the directional indicators. Qualitative analysis identified five themes: the value of consequence-free rehearsal; the specificity and usefulness of feedback; appreciation of the focus on the child’s emotional experience; limitations in the ecological diversity of AI child characters; and a desire for more naturalistic interaction. Conclusions: These findings provide preliminary support for the feasibility and acceptability of AI-based mentalization practice for AP staff. The principal value of the tool appears to lie not only in the simulation itself but in the quality of the reflective feedback generated. Although based on a small sample, the observed pre–post changes provide an encouraging signal that may justify a controlled trial. The contribution of pre-session psychoeducation to training outcomes remains an important question for future research. Full article

Background/Objectives: Microsatellite-stable colorectal cancer (MSS CRC) accounts for the vast majority of CRC cases and remains largely resistant to immune checkpoint inhibitors. Emerging evidence suggests that the gut microbiome is an important regulator of antitumor immunity and may contribute to immunotherapy resistance through multiple mechanisms involving the tumor microenvironment. This review aims to summarize current knowledge of the microbiome–immunity–therapy axis in MSS CRC and to explore microbiome-based strategies to enhance immunotherapy responsiveness. Methods: A narrative review of the recent literature was conducted, focusing on studies published within the last five years that investigated gut microbiota composition, microbial metabolites, tumor immune regulation, immunotherapy response, and microbiome-targeted therapeutic interventions in CRC. Evidence from mechanistic studies, translational research, clinical investigations, and multi-omics analyses was integrated. Results: Current evidence indicates that gut dysbiosis contributes to immune resistance in MSS CRC through immune exclusion, myeloid-driven immunosuppression, T-cell dysfunction, chronic inflammation, and altered microbial metabolite signaling. Specific microorganisms, including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, pks-positive Escherichia coli, and other CRC-associated pathobionts, have been implicated in tumor progression and modulation of antitumor immunity. Microbial metabolites such as short-chain fatty acids, tryptophan-derived compounds, bile acids, succinate, and inosine represent key functional mediators linking microbial communities to host immune responses. Emerging microbiome-targeted interventions, including fecal microbiota transplantation, next-generation probiotics, postbiotics, selective microbial depletion, and engineered bacterial therapeutics, have shown promising results in preclinical models and early translational or clinical studies, although robust clinical evidence remains limited. In parallel, advances in metagenomics, metabolomics, spatial transcriptomics, and artificial intelligence are facilitating the development of precision immuno-microbiome oncology approaches. Conclusions: The gut microbiome functions as a critical regulator of immune resistance in MSS CRC through coordinated effects on microbial composition, metabolite production, and tumor immune remodeling. Microbiome-targeted interventions, combined with multi-omics-based patient stratification, may provide new opportunities to overcome immunotherapy resistance and expand the clinical benefits of immune checkpoint blockade in this traditionally refractory disease. Full article

We examine whether board activity (B_ACTIV), board size (B_SIZE), board independence (BIND), and board tenure (BOARD_TEN) are associated with the performance of South African real estate investment trusts (REITs) over the period 2013 to 2025. The REIT framework provides a rigorous setting to evaluate corporate governance theory, as statutory distribution mandates constrain payout discretion and contracted-income business models limit managerial opportunism, suggesting that governance effects concentrate within specific performance channels. We estimate dynamic panel models using a two-step system GMM framework with collapsed instruments, year fixed effects, Windmeijer-corrected standard errors, and firm-level controls for firm size (SIZE), leverage (LEV), and asset growth (GROWTH) to address endogeneity, unobserved heterogeneity, and performance persistence. We evaluate robustness through an endogenous-regressor specification, a bootstrap bias-corrected LSDVC estimator, and outlier-adjusted estimations. The sample comprises 30 JSE-listed REITs. We evaluate performance across funds from operations per share (FFO_PS), dividend yield (DIV_YIELD), return on assets (ROA), return on equity (ROE), return on invested capital (ROIC), and earnings per share (EPS). Our findings reveal that B_SIZE exhibits a statistically significant negative association with accounting profitability, where each additional director corresponds to a 1.0 percentage point reduction in ROE and a 0.32 percentage point reduction in ROA. The ROE effect remains robust across every identification strategy, including specifications treating board composition as endogenous and estimations winsorizing the dependent variables. Because firm SIZE remains statistically insignificant while LEV and GROWTH display their expected theoretical signs, the B_SIZE effect is isolated from firm scale. BIND demonstrates a directionally positive but specification-sensitive association with returns and payouts, whereas BOARD_TEN shows no robust association with any performance metric, and B_ACTIV effects attenuate once endogeneity is addressed. Overall, governance effects concentrate in operating efficiency and payout measures while remaining absent from per-share metrics, reflecting the precise channels through which boards exercise authority. Our findings caution against board expansion in this sector, highlight board scale as a transparent governance screen for investors, and demonstrate that meeting frequency and tenure benchmarks offer no reliable performance signal. Full article

The nucleolus has emerged as a dynamic and multifunctional subnuclear organelle that integrates ribosome biogenesis with cellular growth and stress signalling. Dysregulation of nucleolar function is increasingly recognised as a central driver of human disease, linking altered ribosome production and nucleolar surveillance pathways to cancer, ribosomopathies, premature ageing syndromes, neurodegeneration, and immune disorders. In this review, we integrate structural, molecular, and disease-level perspectives on nucleolar biology to define how ribosome biogenesis and nucleolar surveillance regulate cellular state across physiological and pathological contexts, positioning the nucleolus as an active regulator of cell function. We outline areas of convergence, identify key unresolved questions, and highlight therapeutic vulnerabilities that arise, including opportunities for small-molecule inhibitors and gene-based approaches. Full article

Cancer is responsible for systemic burdens, most notably cachexia and immunosuppression, that extend far beyond local tumor growth and collectively dictate poor outcomes. While often studied separately, these debilitating syndromes are deeply interconnected. On the basis of emerging evidence of growth differentiation factor 15 (GDF15)’s dual actions in immunity and metabolism, we propose that the stress-responsive hormone GDF15 is hijacked by tumors and repurposed as a central metaboceptive hub that integrates diverse oncogenic stress signals to launch a coordinated, dual pathological cascade. Systemically, it disrupts brain–body communication via glial cell line-derived neurotrophic factor family receptor alpha-like (GFRAL) activation in the brainstem, driving anorexia, metabolic rewiring, and progressive wasting of skeletal muscle and adipose tissue that define cachexia. GDF15 acts as a potent immunosuppressor within the local tumor microenvironment, impairing T cell cytotoxicity and increasing the abundance of regulatory T cells. Crucially, these effects are not parallel but interlinked, forming a self-reinforcing detrimental cycle that accelerates host deterioration and therapeutic failure. This positions the GDF15-GFRAL axis as a unique dual-benefit therapeutic target with the potential to simultaneously ameliorate cachexia, improve patient function and quality of life, and revitalize anti-tumor immunity. Reframing cancer through the lens of a hijacked metabolic sensing system provides an integrated perspective that transforms this formidable challenge of concurrent host wasting and immune evasion into a druggable opportunity, charting a course for novel host-directed therapies that restore systemic homeostasis. Full article

Pharmacological cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have reshaped the treatment landscape of HR-positive, HER2-negative (HR+/HER2−) breast cancer and are increasingly being explored across diverse malignancies. By preventing retinoblastoma (RB) phosphorylation and enforcing G1-S cell cycle arrest, these agents achieve durable tumour control with a more favourable toxicity profile than conventional chemotherapy. Beyond their canonical cytostatic effects, prolonged CDK4/6 inhibitor treatments induce cellular senescence, a stable, proliferative arrest accompanied by profound transcriptional, epigenetic, and secretory changes. This review summarises current knowledge on CDK4/6 inhibitor-induced senescence in both cancer and normal cells as a central biological mechanism that links tumour suppression and microenvironmental remodelling. Importantly, this process is highly context-dependent, differing between tumour and non-malignant cells, with a distinct senescence-associated secretory phenotype (SASP) that shapes immune responses and tissue homeostasis. We also discuss how CDK4/6 inhibitor-induced senescence influences the tumour microenvironment by modulating immune surveillance, stromal interactions, and cancer cell plasticity. Finally, we examine emerging resistance mechanisms and rational combination strategies for CDK4/6 inhibitors, including targeting compensatory signalling pathways, immune checkpoint blockades, and senescence-directed sequential therapies. Collectively, CDK4/6 inhibitor-induced senescence represents both a challenge and a therapeutic opportunity, underscoring the need to integrate cell cycle control with the modulation of cellular states. Full article

Bone metastasis develops within a specialized marrow ecosystem where hematopoiesis, immune regulation, vascular trafficking, and skeletal remodeling intersect. Neutrophil-lineage cells occupy a unique position in this setting because they are generated, retained, mobilized, aged, and reprogrammed within the same bone marrow niches that disseminated tumor cells exploit for homing and survival. This review examines how neutrophils, tumor-associated neutrophils, immature neutrophils, low-density neutrophils, and PMN-MDSCs shape skeletal colonization. We discuss tumor-to-marrow signaling, CXCR2-dependent recruitment, CXCR4/CXCL12-mediated marrow retention, neutrophil–circulating tumor cell interactions, vascular arrest, dormancy escape, NET-mediated matrix remodeling, immune suppression, and effects on osteoclast–osteoblast coupling. Evidence is strongest in breast and prostate cancer models, where pathways such as CXCL5/CXCR2, CTNND1–CXCR4/CXCL12, PR3–RAGE, and DKK1–CKAP4–STAT6–CHI3L3 link neutrophil-lineage cells to skeletal progression and immunotherapy resistance. However, several mechanisms, including CTC–neutrophil clustering and NET-driven dormancy awakening, remain partly extrapolated from non-skeletal models. We therefore emphasize evidence hierarchy, methodological limitations, and therapeutic opportunities, arguing that selective reprogramming or functional inhibition of pro-metastatic neutrophil states may be more promising than indiscriminate neutrophil depletion in metastatic bone disease. A clearer understanding of these context-dependent neutrophil programs may help refine biomarker development and guide combination therapies for patients with skeletal metastases. Full article

Marine pollution monitoring increasingly relies on Biological Early Warning Systems (BEWSs), which use living organisms as continuous, integrative sentinels of water quality. The moon jellyfish Aurelia aurita is a sensitive but under-exploited candidate for this role. We present a computer-vision BEWS pipeline that is unsupervised at inference time and operates without labelled pollution-response data, converting side-view aquarium video of single A. aurita medusae into a binary pollution alarm. Per-frame YOLO bounding-box detections are reduced to a continuous bell-area signal and a centroid trajectory, from which eleven pulsation, kinematic, and detection-quality features are extracted on 60 s sliding windows. A per-animal baseline is fitted on a clean-water baseline (recommended ≥15 min), and a two-layer detector—fast outlier detection on the mean absolute z-score with a k-of-N rule, plus one-sided CUSUM (cumulative sum) accumulation—flags any sustained deviation. Validation on six adult medusae exposed to diesel-WAF detected all six animals (95% CI 54–100%) and produced no false alarms in 203 clean-window opportunities (exact 95% upper bound 1.8%; rule-of-three estimate ≈1.5%). First-alarm latencies ranged from 1.0 to 23.7 min, and the observed responses were described as three descriptive patterns in this pilot dataset: sharp step-change, slow drift, and mixed. The deployed anomaly scoring step contains no neural-network weights, runs in under 300 lines of Python, and is designed for field-portable use in settings where a stationary side-view camera can be positioned alongside an aquarium, although field validation remains required. Per-animal anomaly detection accommodates the strong inter-individual variability of the diesel-WAF response that limits supervised clean-versus-polluted classification at this sample size. Full article

Fatty acid-binding protein 7 (FABP7) is a multifunctional lipid chaperone that is enriched in radial glia and astrocytes within the central nervous system (CNS) and is frequently upregulated in glioma. Beyond its established roles in glial development, lipid homeostasis, and circadian regulation, growing evidence positions FABP7 at the intersection of tumor metabolism, neuronal activity, and immune modulation in the brain. In this review, we integrate the physiological functions of FABP7 in glial cells with its tumor-intrinsic and microenvironmental roles in glioma. We summarize how gliomas co-opt FABP7-dependent metabolic, transcriptional, and post-transcriptional programs to promote stemness, lipid remodeling (e.g., altered fatty acid composition, lipid droplet formation, and lipid peroxidation resistance), inflammatory signaling, and invasive growth, including nuclear FABP7-mediated transcriptional activation linked to oncogene status. Furthermore, we discuss the role of FABP7 in shaping the tumor–neuro–immune interface, including regulating immunosuppressive gene networks, pro-tumoral macrophage polarization, resistance to T-cell-induced ferroptosis and immunotherapy, and tumor microtube-mediated integration into neuronal circuits to support glioma progression. Finally, we highlight therapeutic opportunities and challenges, including small-molecule FABP7 inhibitors, brain-directed delivery strategies, chronotherapeutic considerations, and combination approaches with immunotherapy. Collectively, this work positions FABP7-centered metabolic, circadian, and neuro-immune networks as potential vulnerabilities in glioma, linking fundamental glial biology to glioma therapeutics. Full article

Triple-positive breast cancer (TPBC) is characterized by the overexpression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), making its management a therapeutic challenge. Despite the availability of targeted therapies, patients with TPBC often experience recurrence and poor clinical outcomes due to intrinsic and acquired resistance mechanisms. This review summarizes current therapeutic approaches and their limitations, highlights the molecular mechanisms underlying treatment resistance and recurrence, and explores opportunities for drug repurposing, particularly involving multi-target inhibitors. Special emphasis is placed on the interaction between hormone receptor and growth factor receptor pathways, compensatory signaling mechanisms, and predictive biomarkers of recurrence. Furthermore, emerging strategies for drug repurposing using clinically available drugs are analyzed, including in silico, in vitro, and clinical trial evidence, along with their translational implications. Finally, we conclude that drug repurposing and multi-target approaches offer a compelling rationale for the development of novel therapeutic strategies in triple-positive breast cancer. However, their clinical utility remains to be validated through appropriately designed experimental and clinical studies before their impact on recurrence outcomes can be established. Full article

Janus kinase 2 (JAK2) occupies a central position in cytokine signaling and plays essential roles in hematopoiesis, immune regulation, and cancer. Although recent advances in structural biology, cryo-EM, receptor modeling, and biophysical analysis have substantially expanded current views of JAK2 function, key mechanistic questions remain regarding how receptor geometry, JH2-mediated autoinhibition, and disease-associated mutations are structurally integrated. In this review, we discuss the multidomain organization of JAK2 and examine how the FERM–SH2 module, the pseudokinase domain (JH2), and the catalytic kinase domain (JH1) cooperate to govern receptor specificity, allosteric control, and cytokine-induced activation. We further analyze how pathogenic mutations rewire this regulatory system by weakening autoinhibitory contacts, altering linker-mediated communication, or stabilizing active dimeric conformations. Finally, we assess current and emerging therapeutic strategies, from ATP-competitive inhibitors to macrocyclic and JH2-selective allosteric modulators, with emphasis on how structural insight can guide next-generation drug design. These advances support a more integrated view of JAK2 regulation and define new opportunities for selective therapeutic intervention. Full article