Search Results (22,326)

Achieving dynamic stability in bipedal locomotion against sustained external disturbances remains a significant challenge in humanoid robotics. Traditional methods, such as zero moment point (ZMP) preview control, often lack the reactive compliance and predictive planning necessary for robust performance on uneven terrain or under continuous force. This paper proposes a novel control framework that synergistically integrates a resistance torso compliance controller with a nonlinear model predictive control (NMPC)-based walking pattern generator. The compliance controller actively modulates the torso’s dynamics via impedance control, creating a virtual mass–spring–damper system that absorbs impacts and generates counterforces to resist sustained pushes. Concurrently, the NMPC module reformulates gait generation as a real-time optimization problem, simultaneously determining optimal footstep positions and orientations while respecting nonlinear constraints derived from centroidal momentum dynamics. Simulation results demonstrate that this integrated approach reduces the maximum ZMP error by 34.1% and the RMS ZMP error by 37.3% compared to traditional ZMP preview control, with a 38.9% improvement in settling time after a disturbance. This work establishes that the tight coupling of reactive impedance control and predictive optimization provides a foundational framework for enhancing the robustness and adaptability of bipedal locomotion. 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

Background/Objectives: Glioblastoma (GBM) remains the most aggressive primary brain tumor in adults, with limited therapeutic options and poor prognosis despite maximal surgery, radiotherapy, and chemotherapy. The complex and immunosuppressive tumor microenvironment, pronounced intratumoral heterogeneity, and the presence of the blood–brain barrier (BBB) severely restrict the efficacy of conventional and emerging therapies. In this context, cell-based strategies leveraging macrophages, mesenchymal stromal cells (MSCs), and their derivatives have gained attention as “cellular allies” capable of modulating the GBM microenvironment and acting as targeted delivery platforms. Methods: This review systematically analyzes preclinical and early clinical literature on macrophage- and MSC-based therapeutic strategies in GBM, including engineered cells, extracellular vesicles (EVs), membrane-coated nanoparticles, and hybrid biomimetic systems. Studies were selected based on relevance to GBM biology, delivery across or bypass of the BBB, microenvironmental modulation, and translational potential. Evidence from in vitro models, orthotopic and syngeneic in vivo models, and available clinical trials was critically evaluated, with emphasis on efficacy endpoints, biodistribution, safety, and manufacturing considerations. Results: The reviewed evidence demonstrates that macrophages and MSCs can function as active therapeutic agents or delivery vehicles, enabling localized oncolysis, immune reprogramming, stromal and vascular remodeling, and enhanced delivery of viral, genetic, and nanotherapeutic payloads. EVs and membrane-based biomimetic platforms further extend these capabilities while reducing cellular risks. However, therapeutic efficacy is highly context-dependent, influenced by tumor heterogeneity, BBB integrity, delivery route, and microenvironmental dynamics. Clinical translation remains limited, with most approaches at preclinical or early-phase clinical stages. Conclusions: Cell-based and cell-derived platforms represent a promising but still evolving therapeutic paradigm for GBM. Their successful translation will require rigorous biomarker-driven patient selection, improved models that capture invasive GBM biology, scalable GMP-compliant manufacturing, and rational combination strategies to overcome adaptive resistance mechanisms. Full article

Cancer stem cells (CSCs) represent a small but highly resilient tumor subpopulation responsible for sustained growth, metastasis, therapeutic resistance, and recurrence. Their survival is supported by aberrant activation of developmental and inflammatory pathways, including Wnt/β-catenin, Notch, Hedgehog, PI3K/Akt/mTOR, STAT3, and NF-κB, as well as epithelial–mesenchymal transition (EMT) programs and niche-driven cues. Increasing evidence shows that phytochemicals, naturally occurring bioactive compounds from medicinal plants, can disrupt these networks through multi-targeted mechanisms. This review synthesizes current findings on prominent phytochemicals such as curcumin, sulforaphane, resveratrol, EGCG, genistein, quercetin, parthenolide, berberine, and withaferin A. Collectively, these compounds suppress CSC self-renewal, reduce sphere-forming capacity, diminish ALDH⁺ and CD44⁺/CD24⁻ fractions, reverse EMT features, and interfere with key transcriptional regulators that maintain stemness. Many phytochemicals also sensitize CSCs to chemotherapeutic agents by downregulating drug-efflux transporters (e.g., ABCB1, ABCG2) and lowering survival thresholds, resulting in enhanced apoptosis and reduced tumor-initiating potential. This review further highlights the translational challenges associated with poor solubility, rapid metabolism, and limited bioavailability of free phytochemicals. Emerging nanotechnology-based delivery systems, including polymeric nanoparticles, lipid carriers, hybrid nanocapsules, and ligand-targeted formulations, show promise in improving stability, tumor accumulation, and CSC-specific targeting. These nanoformulations consistently enhance intracellular uptake and amplify anti-CSC effects in preclinical models. Overall, the consolidated evidence supports phytochemicals as potent modulators of CSC biology and underscores the need for optimized delivery strategies and evidence-based combination regimens to achieve meaningful clinical benefit. Full article

The clinical durability of SARS-CoV-2 main protease (M^pro) inhibitors depends on their resilience to emerging resistance mutations. Recent genomic surveillance and functional reports have highlighted substitutions at positions 49, 165, and 301, raising questions about the robustness of the noncovalent inhibitor WU-04 in variant backgrounds. Here, we combined μs-scale, triplicate molecular dynamics simulations with end-state binding free energy estimates and a network-rewiring inference (NRI) framework that maps long-range dynamical communication across the full protease dimer. We evaluated wild type (WT), single mutants M49K, M165V, S301P, and selected double mutants (M49K & M165V, M49K & S301P). Relative to WT, single substitutions produced reductions in computed binding affinity of up to ~12kcal/mol, accompanied by loss or reshaping of the S2 subsite and altered ligand burial. Notably, the M49K/S301P double mutant partially restored WU-04 engagement, narrowing the ΔΔG_restore gap to within ΔΔG_restore of WT and re-establishing key hydrophobic and hydrogen-bond contacts. NRI analysis revealed that distal residue 301 participates in a communication corridor linking the C-terminal helical domain to the active-site cleft; its substitution rewires inter-domain coupling that can compensate for local disruptions at residue 49. Together, these results identify structural hotspots and network pathways that may inform the design of next-generation M^pro inhibitors with improved mutation tolerance—specifically by strengthening interactions that do not rely solely on the mutable S2 pocket and by engaging conserved backbone features near the 165–166 region. Full article

Background/Objectives: Cardiovascular (CV) and cerebrovascular diseases, primarily attributed to atherosclerosis, stand as leading global causes of morbidity and mortality. This study aims to evaluate the impact of preclinical atherosclerosis parameters, including intima-media thickness (IMT) and arterial stiffness, in a seven-year follow-up of 100 patients with CV risk factors but no known history of CV or cerebrovascular diseases. Methods: Between April 2014 and December 2015, 100 patients presenting with suspected ischemic heart disease were enrolled. The study integrates the color Doppler examination of the supra-aortic trunks with the evaluation of preclinical parameters of atherosclerosis, such as intima-media thickness (IMT), βeta index, and pulse wave velocity (PWV), as well as echocardiographic evaluations, including global longitudinal strain (GLS). CV risk factors, metabolic syndrome, and insulin resistance were assessed and measured for each patient using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Two- and seven-year follow-ups assessed various CV events. Results: The study population comprised 67% males and 33% females. Metabolic syndrome, impaired fasting glycemia and hypertension were prevalent. The mean value of IMT was 1.21 ± 0.26 mm, and PWV was 8.47 ± 2.14 m/s. The 7-year follow-up identified IMT, PWV, and HOMA-IR as strong positive predictors of cardiovascular events, with PWV emerging as a particularly sensitive indicator of early events. Conclusions: Insulin resistance and cardiovascular risk factors may contribute to early alterations in myocardial and vascular function, even in the absence of overt disease. PWV, as a recognized surrogate marker of arterial stiffness, may serve as a sensitive tool for the early prediction of cardiovascular events. A comprehensive screening, including the assessment of markers indicating subclinical vascular alterations, along with the implementation of preventive interventions, is crucial for populations at risk. Full article

Melanoma is an aggressive skin cancer that continues to present major therapeutic difficulties. Although targeted drugs and immune checkpoint inhibitors have improved outcomes, resistance and treatment-related toxicity limit long-term benefit. In recent years, nanotechnology has been explored as a way to improve how drugs are delivered and to achieve greater tumor selectivity. Among available nanocarriers, liposomes have attracted particular interest. Built from lipid bilayers, they can carry both hydrophilic and hydrophobic molecules, and they are generally well tolerated. Importantly, their surface can be modified with polymers or targeting ligands to direct the carrier more selectively to melanoma cells. Experimental models show that liposomal drug formulations can increase concentrations in tumor tissue while limiting distribution to healthy organs. They have also been used successfully to combine different types of agents, chemotherapies, immunomodulators, and nucleic acids, within a single delivery system. These findings suggest genuine potential to address several of the shortcomings of conventional treatments. Although translation to the clinic is slowed by challenges such as formulation stability and large-scale production, liposomes represent an important step toward safer and more effective melanoma therapy within the broader field of oncologic nanotechnology. Full article

In both Alzheimer’s disease (AD) patients and animal models, senile plaques are generally observed in the cerebral cortex rather than the cerebellum. The mechanisms underlying the regional resistance of the cerebellum to amyloid plaque deposition remain poorly understood. We investigated this cerebellar resistance using 5xFAD mice, an amyloidosis model with high expression of mutant human APP and PSEN1 in the cortex and cerebellum. In aged 5xFAD mice, the cerebellum had minimal amyloid-β (Aβ) deposition despite robust transgene expression, correlating with lower expression levels of IBA1, CD68, TREM2, and CD36 (although elevated expression of CD45 and MHC I) compared to the cortex. Consistent with the absence of plaques, cerebellar tissue lacked the dystrophic VGLUT1-positive synaptic accumulations prominent in the cortex. Cerebellar microglia maintained a distinct, less inflammatory phenotype yet displayed efficient clearance activity. Notably, ASC inflammasome specks—capable of seeding Aβ aggregation—were paradoxically more abundant in the cerebellum, implying that rapid Aβ clearance prevents these seeds from driving plaque formation. Furthermore, key extracellular matrix (ECM) proteoglycans brevican and aggrecan were elevated in the 5xFAD cerebellum. Cerebellar microglia showed enhanced internalization of brevican alongside small Aβ aggregates, exceeding that in cortical microglia. These findings indicate that region-specific microglial and ECM interactions—particularly efficient uptake and degradation of ECM–Aβ co-aggregates—may underlie the cerebellum’s resilience to amyloid plaque pathology. Full article

Urban underpasses are critical flood-prone hotspots during extreme rainfall, posing significant threats to urban resilience and infrastructure safety. However, a scale gap persists between catchment-scale hydrological models, which often oversimplify local geometry, and high-fidelity hydrodynamic models, which typically lack realistic boundary conditions. To bridge this gap, this study develops a multi-scale framework that integrates the Storm Water Management Model (SWMM) with 3D Computational Fluid Dynamics (CFD). The framework employs a unidirectional integration (one-way forcing), utilizing SWMM-simulated runoff hydrographs as dynamic inlet boundaries for a detailed CFD model of a 2.8 km underpass in Shanghai. Simulations across six design rainfall events (2- to 50-year return periods) revealed two distinct flooding mechanisms: a systemic response at the hydraulic low point, governed by cumulative inflow; and a localized response at entrance concavities, where water depth is rapidly capped by micro-topography. Informed by these mechanisms, an intensity-graded drainage strategy was developed. Simulation results show significant differences between different drainage strategies. Through this framework and optimized drainage system design, significant water accumulation within the underpass can be prevented, enhancing its flood resistance and reducing the severity of disasters. This integrated framework provides a robust tool for enhancing the flood resilience of urban underpasses and offers a basis for the design of proactive disaster mitigation systems. Full article

Resistance to imatinib remains a therapeutic challenge, largely driven by point mutations within the kinase domain of the BCR-ABL, among which the T315I substitution constitutes the most clinically significant barrier. Ponatinib effectively inhibits this mutant form but is limited by dose-dependent cardiovascular toxicity, prompting efforts to develop safer and more selective agents. Recent advances highlight aminopyrimidine-derived scaffolds and their evolution into thienopyrimidines, oxadiazoles, and pyrazines with improved activity against BCR-ABL^T315I. Further progress has been achieved with benzothiazole–picolinamide hybrids incorporating a urea-based pharmacophore, which benefit from strategic hinge-region substitutions and phenyl linkers that enhance potency. Parallel research into dual-mechanism inhibitors, including Aurora and p38 kinase modulators, demonstrates additional opportunities for overcoming resistance. Combination strategies, such as vorinostat with ponatinib, provide complementary therapeutic avenues. Natural-product-inspired approaches utilizing fungal metabolites provided structurally diverse scaffolds that could engage sterically constrained mutant kinases. Hybrid molecules derived from approved TKIs, including GNF-7, olverembatinib, and HG-7-85-01, exemplify rational design trends that balance efficacy with improved safety. Molecular modeling continues to deepen understanding of ligand engagement within the T315I-mutated active site, supporting the development of next-generation inhibitors. In this review, we summarized recent progress in the design, optimization, and biological evaluation of small molecules targeting the BCR-ABL^T315I mutation. Full article

Existing high-voltage alternating current (AC) transmission line fault ranging methods have several drawbacks, including weak transition resistance, a complicated feature extraction process, and difficult calibration of the travelling wave head. To address these issues, a single-end fault ranging method for high-voltage AC transmission lines based on Attention-GRU and modulus amplitude ratio is proposed. Firstly, based on the travelling wave dispersion characteristics, an approximate formula is derived between the fault distance of the high-voltage AC transmission line and the amplitude ratio of the sum of the initial transient voltage travelling wave modes 1 and 2 and the mode 0 components at the ranging location. This shows that a definite nonlinear mapping relationship exists between the two. Secondly, the Attention-GRU is constructed using the multiscale wavelet modal maxima ratio between the sum of the initial transient voltage travelling wave mode 1 and 2 components and the mode 0 component as the input eigenquantities and the fault distance as the output quantity. The fault distance is then calculated using the Attention-GRU and the modal amplitude ratio. The Attention-GRU neural network fault ranging model is then constructed using the distance as the output quantity. After training is completed, the fault feature quantities obtained from the measurement points are inputted into the Attention-GRU model to achieve the purpose of fault ranging. The ranging ability of this model is then compared with that of other neural network models. A large number of simulations verify that the proposed method has high ranging accuracy and that the ranging capability is not affected by the fault type, transition resistance or the initial phase angle of the fault. Full article

An algorithm has been implemented and it is provided in this article as an executable program to extract the five solar cell parameters within the one-diode solar cell model. Boole’s integration rule has been put into practice to integrate the current minus the short-circuit current, yielding a more accurate Co-Content function. Afterwards, the Co-Content function is fitted to a second-degree polynomial in two variables, namely, the voltage and the current minus the short-circuit current, providing six fitting constants. The five solar cells are deduced from these six fitting constants. This algorithm has been implemented in an automatic program that performs the calculations. The program also obtains the standard deviations of the fitting errors, which are used to obtain the standard deviations of the five solar cell parameters. The program reports to the user the results in three text files, from which the user can easily copy-paste the results into softwares like Origin, Word, or Excel. A program to smooth the current voltage curves is also provided. Two videos are also available, one explaining how to profit from this executable program, and the other one how to use the smoothing program. Full article

Top-and-seat angle connections (TSACs) exhibit inherently asymmetric and nonlinear moment–rotation behavior, which can significantly influence the global response of steel frames subjected to combined gravity and lateral loading. In this study, a three-dimensional finite element model of an unstiffened TSAC is developed and validated against experimental moment–rotation data from the literature under monotonic loading conditions. The validated model is then used to investigate the influence of key geometric parameters, including top angle thickness, bolt diameter, and beam depth, on the connection’s moment–rotation response in both positive and negative bending directions. Subsequently, the monotonic connection behavior is incorporated into nonlinear static analyses of steel portal frames to examine the effects of asymmetric connection response and moment reversal on frame-level stiffness degradation and capacity. A practical SAP2000 modeling workflow is proposed in which the finite element-derived monotonic moment–rotation curves are implemented using zero-length rotational link elements, allowing combined consideration of material, geometric, and connection nonlinearities at the structural level. The comparisons between Abaqus and SAP2000 results demonstrate consistent frame-level responses when identical monotonic connection characteristics are employed, highlighting the ability of the proposed workflow to reproduce detailed finite element predictions at the structural analysis level. The results indicate that increasing top angle thickness, bolt diameter, and beam depth enhances the lateral stiffness and base shear resistance of steel frames. Positive and negative bending directions are defined consistently with the applied gravity-plus-lateral loading sequence. Full article

Whole-genome duplication, or tetraploidization, occurs in cells, tissues, or entire organisms. In human cancers, tetraploidization promotes aneuploidy and genomic instability, accelerating tumor progression, metastasis, and drug resistance. These adaptations demand metabolic rewiring, including mitochondrial plasticity. Here, we investigate the relationship between mitochondrial quantity/activity, including the mitochondrial transmembrane potential, the intracellular calcium, and the oxidative stress in diploid versus tetraploid cancer cells (colon, sarcoma, liver) and fungal and yeast models (C. albicans diploid/tetraploid strains; S. cerevisiae haploid/diploid/tetraploid strains). We demonstrate that tetraploid cells, whether from human carcinomas or yeast, exhibit consistently enlarged cell size, elevated mitochondrial content, and heightened metabolic activity compared to diploids. Our findings underscore mitochondrial adaptation as a hallmark of tetraploidization, offering novel therapeutic targets for chromosomally unstable tumors. Full article

The demand for efficient dehumidification in evaporators has become one of the key technical challenges restricting the high-quality development of the refrigerated air dryer industry. To investigate the effects of fin structure on the air-side heat transfer and dehumidification performance of finned-tube evaporators applied in refrigerated air dryers under the operating conditions of 50 °C, RH = 85%, numerical heat and mass transfer models for the air side of evaporators with plain fins and wavy fins were established based on the Ansys Fluent software 2022R1. The study found that wavy fins possess superior heat transfer and moisture removal capabilities. Key performance indicators, including the air-side heat transfer rate (Q), moisture removal amount (Δm), friction factor (f), and the nusselt number (Nu), were all higher for wavy fins compared to plain fins. Building upon this, three types of vortex generators (VGs) were introduced to further optimize the performance of the wavy fins, aiming to balance heat transfer enhancement and flow resistance control. At an attack angle of 30°, the comprehensive performance factor (JF) showed the highest improvement, reaching 43% with the Delta Winglet vortex generators. The 15° configuration also showed improvement, while 45° led to the worst performance due to increased flow resistance. The results indicate that for typical high-temperature and high-humidity environments, the wavy fin is recommended as the preferred choice due to its superior overall performance and simple structure. For applications requiring higher dehumidification capacity, wavy fins equipped with vortex generators can be selected to achieve the most efficient dehumidification. This study provides valuable insights for the design and application of finned-tube evaporators in dehumidification systems under high-temperature, high-humidity conditions for refrigerated air dryers. Full article