Search Results (1,993)

Background: Uveal melanoma (UM) represents the most prevalent primary intraocular malignancy in adults, yet patients harboring GNAQ/GNA11 mutations face particularly poor prognoses with median survival of merely 6–12 months following metastasis. Multi-targeted combination therapy offers a promising strategy to circumvent drug resistance. The present study investigated the synergistic anti-tumor efficacy and mechanistic basis of Isoliquiritigenin (ISL), Quercetin (Que) and Methylnissolin (Meth), three bioactive constituents from Astragalus membranaceus (Huangqi, a widely used traditional Chinese medicinal herb) against UM. Methods: Molecular docking and 100 ns molecular dynamics simulations assessed binding stability between the compounds and their respective targets (Gαq, MEK and YAP). Synergistic interactions were quantified using the Zero Interaction Potency (ZIP) model, a reference synergy model that compares observed combination effects to predicted non-interaction baselines across full dose–response matrices, based on CCK-8 assays. Cell cycle distribution, apoptosis and mitochondrial membrane potential were analyzed by flow cytometry. Western blotting detected target proteins and apoptotic markers. A male BALB/c nude mouse xenograft model validated therapeutic efficacy and systemic safety. Results: Molecular docking revealed binding energies <−7.0 kcal·mol⁻¹ for all three drug–target pairs, with molecular dynamics trajectories confirming stable complex conformations (RMSD < 3 Å). In vitro, the ISL-Que-Meth (IQM) combination exhibited strong synergism (ZIP scores > 10), significantly increasing apoptotic rates, collapsing mitochondrial membrane potential and upregulating cleaved-caspase 9 expression compared with monotherapy, and a modest G2/M phase accumulation was also observed, although the magnitude was limited relative to apoptotic induction. In vivo, the triple combination achieved approximately 50% reduction in tumor growth compared with the control group, with effects comparable to or exceeding those of the clinical reference agent Trametinib, and reduced Ki67 proliferation indices while elevating cleaved-caspase 9 levels, without eliciting hepatorenal toxicity. While these data demonstrate therapeutic efficacy, they do not establish in vivo synergy, as single-agent and dual-combination arms were not included in the xenograft design. Conclusions: These findings demonstrate that IQM synergistically suppresses UM growth in association with coordinated modulation of Gαq/MEK/YAP axis components and caspase 9-dependent apoptosis via the intrinsic mitochondrial pathway, providing preclinical evidence for natural product-based multi-targeted therapy against UM. Full article

The formation mechanisms of Urban Vitality have been constrained by the limitations of traditional linear driving hypotheses, and the fragmented analysis of subjective and objective factors. Integrating the explainable machine learning model XGBoost-SHAP with multi-source geospatial data, this study constructs a systematic analysis framework at the community scale, comprising 275 community units across five administrative districts in Changsha. It constructs a systematic analysis framework that unifies objective environmental conditions and subjective perceptions—a deliberate departure from the fragmented approaches dominant in previous vitality research. Through this objective-subjective integrated lens, it explores the spatial patterns, non-linear driving mechanisms, and variable interaction effects of Urban Vitality. The XGBoost model achieves a cross-validated R² of 0.794 and an RMSE of 0.031, ensuring interpretative reliability for exploring non-linear mechanisms. The results indicate that Urban Vitality exhibits a spatial pattern characterized by “high-value aggregation in the core, gradient decay in the periphery, and local fragmentation,” with a significant siphon effect observed in the core area. Partial Dependence Plot (PDP) analysis reveals that the impacts of variables on vitality can be categorized into four patterns: continuous upward, threshold leap, inverted U-shaped, and weak or sample-concentrated. Univariate dependence plots further delineates fine-grained threshold effects, including “threshold triggering, nterval suitability, high-value suppression, and co-occurrence signals.” Furthermore, bivariate interactions reveal four synergistic mechanisms: Building Density must match road network support; Functional Aggregation should synergize with locational value; transportation nodes must integrate with activity-support capacity; and Street View quality and human demand mutually regulate each other. The conclusion asserts that urban stock renewal must transcend the mindset of single-factor maximization and shift towards a precision governance approach of “threshold activation, synergistic matching, and zoning intervention,” thereby providing a quantitative decision-making basis for human-oriented, fine-grained urban regulation. Full article

The transport sector contributes significantly to greenhouse gases and airborne pollutants. This study focuses on the co-benefits related to decreases in air pollutants and CO₂ emissions under various mitigation scenarios. The associated mitigations in PM_2.5 concentrations are predicted by establishing a random forest (RF) model and the health benefits are evaluated with the global exposure mortality model (GEMM). Environmental tax values and carbon trading prices are integrated alongside traditional elasticity coefficients and coordinate-based approaches to transform reductions into economic advantages. The results indicate that in the most favorable scenario (ELC), CO₂ emissions are expected to peak in 2032 with a reduction of 51.71%; this is supported by the marginal CO₂ emission curve, which intersects the zero axis around that same year, while the air pollution equivalents (APeq) are projected to decline by 25.65% in 2050. The efficiency of synergistic reductions between air pollutants and CO₂ ranks as SO₂ > NO_X > CO > HC > PM_2.5 > PM₁₀, and the elasticity coefficients for all pollutants are gradually aligning toward 1, suggesting that stricter mitigation efforts will enhance co-benefits. Furthermore, the economic benefits attributable to CO₂ reduction are anticipated to be 10.81 billion CNY by 2050, and 17,297 premature deaths associated with PM_2.5 exposure could be prevented. The findings in this study could provide essential insights for the co-management of CO₂ and air pollutants from road mobile sources. Full article

Magnetic Flux Leakage (MFL) sensors are pivotal for the non-destructive inspection of oil and gas pipelines. However, the accuracy of defect quantification is severely compromised by pervasive noise in field-acquired MFL sensor signals, leading to substantial measurement uncertainty. To address this, we introduce a novel hybrid denoising framework that synergizes Improved Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (ICEEMDAN) and Wavelet Packet Decomposition (WPD). The key innovation is the employment of the Rime Optimization Algorithm (RIME) to automatically fine-tune the critical parameters of ICEEMDAN—the signal-to-noise ratio (SNR) and the number of noise additions—thereby customizing the decomposition for superior sensor signal enhancement. This optimization effectively suppresses mode aliasing and yields intrinsic mode functions that faithfully represent underlying defect features. The framework’s efficacy is rigorously validated through mathematical modeling, COMSOL Multiphysics 6.3-based finite element simulation, and real-field MFL sensor data. Results demonstrate remarkable improvements in sensor signal quality: a 53.69% increase in the SNR and reductions of 61.03% in MAE and 62.05% in RMSE over conventional methods. Crucially, the method achieved a Feature Preservation Rate (FPR) of 97.18% on simulated defects, underscoring its exceptional capability to retain critical metrological features for defect sizing. This work provides a robust signal-processing framework that significantly advances the measurement fidelity of MFL sensors, enabling more reliable pipeline integrity assessment. Full article

Coronary heart disease (CHD) is a global cardiovascular disease with high morbidity and mortality, and its complex pathological mechanism poses great challenges to clinical prevention and treatment. Paeoniflorin (PA), a monoterpene glycoside active ingredient from Ranunculaceae plants, has shown potential in cardiovascular protection, but its specific anti-CHD molecular targets and systematic regulatory networks remain unclear. In this study, a mouse model of CHD was established, and a multi-omics strategy combining label-free quantitative proteomics and metabolomics was adopted to explore the mechanism of PA in treating CHD. The results showed that PA significantly improved cardiac function, alleviated myocardial pathological injury and fibrosis, and regulated lipid metabolism in CHD model mice, with the high-dose group showing the optimal effect. Proteomic analysis identified 51 key differentially expressed proteins (DEPs) reversed by PA, which were mainly enriched in complement and coagulation cascades, and neutrophil extracellular trap formation pathways, with the C3-Cfd-C3aR signaling axis as the core hub. Further verification confirmed that PA could downregulate the expression of C3, Cfd, C3aR, and their downstream molecule BTK, thereby inhibiting myocardial inflammatory response and cardiomyocyte apoptosis. In addition, PA downregulated the expression of platelet activation markers ITGA2B/ITGB3. Metabolomic analysis revealed that PA reversed 57 abnormal metabolites in CHD mice, which were enriched in GABAergic synapse, retrograde endocannabinoid signaling and other pathways. Molecular docking confirmed that PA could stably bind to C3, Cfd, C3aR, BTK, and ITGA2B/ITGB3 with strong binding activity. In conclusion, PA exerts anti-CHD effects through a multi-target and multi-pathway synergism, mainly by targeting the C3-Cfd-C3aR axis to inhibit inflammation, apoptosis and platelet activation, and regulating metabolic disorders. This study provides experimental evidence and theoretical support for the clinical application of PA as a multi-target therapeutic drug for CHD. Full article

To address the pervasive engineering challenges of rigid interference and subpar machining efficiency encountered during the complex freeform surface polishing of P20 mold steel, this study proposes and fabricates a structurally designed, five-petal composite compliant polishing tool via fused granulation fabrication (FGF). The tool structurally integrates a passive thermoplastic polyurethane (TPU) compliant buffer layer with an active PA66/diamond micro-cutting functional layer, achieving monolithic precision assembly through dual-temperature-zone 3D printing. Tensile mechanical characterization (n = 6) reveals that the composite interface attains an average ultimate tensile strength (UTS) of 59.39 ± 15.41 MPa (with a peak of 78.90 MPa) and an average elongation at break of 27.42 ± 7.41%, demonstrating exceptional structural robustness and fracture toughness under heavy-load abrasive machining conditions. During adaptive polishing validations on complex convex topographies and deep concave mold cavities, the compliant tool effectively compensated for normal vector spatial errors intrinsic to three-axis CNC machining via passive geometric adaptation. Topographical evaluations suggest a ductile-regime, differential asperity planarization material removal paradigm, which is attributed to the macroscopic 3D elastic deformation of the tool synergized with the proposed compliance of the polymer matrix. Following high-intensity sequential polishing regimens, the original macroscopic milling striations were substantially reduced. Quantitative profilometric analysis reveals that the average surface roughness of the convex profiles decreased from an initial 13.33 µm to 7.42 µm, while that of the restrictive deep concave features was reduced from 10.84 µm to 4.11 µm. Ultimately, this technological framework circumvents the traditional reliance on capital-intensive, six-degree-of-freedom robotic platforms, providing a scalable automated polishing protocol compatible with standard CNC systems for the cost-effective surface planarization of precision molds. Full article

The contamination of microplastics (MPs) and heavy metals (HMs) in water has caused widespread concern, while their effects on submerged macrophytes have rarely been reported. Experiments were carried out to investigate the toxic effects of polyamide microplastics (PAMPs; 0.1%, 0.3%, and 1.0% w/w) and cadmium (Cd; 0.3 and 1.0 mg/L), alone or in combination, on the submerged macrophyte Vallisneria natans (V. natans). The results showed that PAMPs significantly reduced Cd accumulation in leaves (decrease of 2.38%~26.12%) but elevated Cd accumulation in roots. Both Cd exposure and high PAMP exposure alone inhibited plant growth. The combined stress showed concentration-dependent effects: the low Cd concentration (0.3 mg/L) and PAMPs synergistically exacerbated toxicity (synergism, MDR > 1.3), as PAMPs disrupted the sediment structure and enhanced the bioavailability of Cd, whereas when V. natans was co-exposed to the high Cd concentration (1.0 mg/L) and PAMPs, the PAMPs blunted the toxicity of Cd by efficiently adsorbing it (antagonism, MDR < 0.7). Both individual and combined exposures decreased chlorophyll a and chlorophyll b synthesis and increased superoxide dismutase (SOD) and peroxidase (POD) activities as well as malondialdehyde (MDA) content in plant tissues. However, exposure to low and medium concentrations of MPs (0.1% and 0.3% w/w) alone had positive effects on plant growth and photosynthesis systems, while combined exposures exacerbated the damaging effects of PAMPs on the antioxidant defense system in V. natans. These results allow for a better understanding of the synergistic effect of co-contamination of microplastics and heavy metals in freshwater ecosystems, and highlight the necessity of ecological risk assessment during phytoremediation using submerged macrophytes. Full article

Background: CDK4/6 inhibitors induce G1/S cell-cycle arrest in bladder cancer; however, adaptive resistance limits their therapeutic efficacy. The role of the m⁶A reader IGF2BP3 in regulating sensitivity to CDK4/6 inhibition remains largely unknown. Methods: Transcriptomic profiling was performed in palbociclib-treated bladder cancer cell lines (T24, RT112, and UMUC-3) to identify m⁶A regulators associated with drug response. The expression and clinical significance of IGF2BP3 were evaluated using The Cancer Genome Atlas (TCGA) data and an independent clinical cohort. Gain- and loss-of-function assays were conducted to investigate the effects of IGF2BP3 on cell proliferation and cell-cycle progression. Mechanistic studies, including RNA-binding, mRNA stability, ubiquitination, and in vivo tumorigenesis assays, were performed to elucidate the underlying regulatory network. Results: IGF2BP3 was identified as the only m⁶A regulator differentially expressed following palbociclib treatment. IGF2BP3 expression was significantly elevated in bladder cancer tissues compared with normal tissues and was associated with poor prognosis and Ki67 positivity. Functionally, IGF2BP3 overexpression (OE) promoted G1/S transition, increased MYC and downstream cell-cycle regulators, and partially rescued palbociclib-induced cell-cycle arrest, whereas IGF2BP3 knockdown (KD) suppressed cell proliferation in an MYC-dependent manner. Mechanistically, IGF2BP3 bound to MYC mRNA in an m⁶A-dependent manner and enhanced its stability. Furthermore, MKRN2 was identified as an E3 ubiquitin ligase that directly interacted with IGF2BP3, promoted its ubiquitination, and facilitated its proteasomal degradation. In vivo, MKRN2 co-overexpression attenuated IGF2BP3-driven tumor growth and synergized with palbociclib to maximally suppress tumor volume, reduce MYC and Ki67 expression, and induce apoptosis. Conclusions: These findings establish the MKRN2–IGF2BP3–MYC axis as a critical regulator of CDK4/6 inhibitor sensitivity in bladder cancer. Targeting IGF2BP3 or enhancing MKRN2 activity may represent a promising strategy to overcome adaptive resistance and improve the therapeutic efficacy of CDK4/6 inhibitors. Full article

Within the domain of Earth observation, tracking terrestrial transitions via high-resolution optical data plays a fundamental role. Nevertheless, current methods face critical challenges, including the difficulty in collaborative modeling of local details and global features and the singularity of bi-temporal difference representation, along with insufficient cross-scale feature communication, thereby constraining both the precision and resilience of models when applied to complicated environments. To solve these problems, we propose LADENet (Locally Adaptive Mamba and Multi-scale Feature Enhancement Network), an innovative framework that synergizes CNN, Transformer, and Mamba paradigms. By leveraging customized local contextual refinement alongside sophisticated hierarchical fusion, this integration delivers highly precise and resilient detection performance. LADENet adopts a weight-sharing multi-level Transformer encoder combined with a sequence reduction mechanism to generate multi-scale global features, achieving precise alignment of bi-temporal features and global context modeling while reducing computational complexity. To realize accurate localization and local enhancement of changed regions, we design a dual spatiotemporal adaptive local feature marking module based on State-Space Scanning (SSS). This module screens high-saliency changed regions through an adaptive scanning strategy, realizes pixel-aligned spatiotemporal feature fusion via cross-temporal state-space scanning, and introduces a sliding window boundary calibration mechanism to alleviate boundary information loss caused by window segmentation. To strengthen the feature representation of changed regions, a dual-branch difference enhancement module is constructed, which collaboratively captures global change trends and fine-grained local features through an attention-enhanced difference branch and a multi-scale convolution concatenation branch, effectively suppressing background interference. To address the semantic gap between cross-scale features, a global cross-scale spatial feature fusion decoder is proposed, which balances local detail preservation and global context perception through the synergy of spatial attention and two-dimensional selective scanning, completing refined multi-scale feature fusion and spatial resolution recovery. To rigorously validate the proposed LADENet, comprehensive experiments were conducted across four widely adopted bi-temporal benchmarks: LEVIR-CD, WHU-CD, CLCD-CD, and GVLM-CD. The presented architecture establishes substantial superiority over existing cutting-edge methodologies across primary evaluation criteria. Specifically, it yields an F1-measure of 91.06% alongside an IoU of 85.28% in the LEVIR-CD tests, while registering 90.51% (F1) and 82.45% (IoU) for WHU-CD. Similarly, robust outcomes are delivered on CLCD-CD (82.15% F1, 72.83% IoU) as well as GVLM-CD (89.12% F1, 77.78% IoU). These results demonstrate that LADENet possesses excellent detection accuracy, boundary delineation capability and generalization performance in diverse and intricate bi-temporal observation environments. Full article

The rise in antimicrobial resistance and the resilience of microbial biofilms demand innovative strategies that combine, for instance, membrane-active agents with marketed drugs. Arginine-based surfactants are promising alternatives to conventional quaternary ammonium compounds, but comparative data on their antimicrobial, antibiofilm and modulatory activities remain limited. Five arginine-derived surfactants, the single-chain Nα-lauroyl-L-arginine methyl ester (LAM) and ethyl ester (LAE), together with their double-chain homologues LANHC₃, LANHC₅ and LANHC₈ were evaluated against Gram-positive and Gram-negative bacteria and four Candida spp. Minimum inhibitory (MIC) and lethal (MLC) concentrations were determined by broth microdilution method. Antibiofilm activity was assessed through minimum biofilm inhibitory (MBIC) and eradication (MBEC) concentrations. Checkerboard assays were used to evaluate the synergism between the surfactants and conventional therapeutic antibacterial and antifungal agents. LANHC₃ and LANHC₈ exhibited uniform antibacterial MICs of 19.53 µg/mL, while LAM and LANHC₅ showed MICs of 19.53 µg/mL for most strains, with Enterococcus faecalis requiring 39.06 µg/mL. LANHC₃ was the most potent surfactant over Candida spp. With MICs of 9.76 µg/mL for all species, and similarly to LAM, both were fungicidal at 39.06 µg/mL. LAM and LANHC₃ also showed the lowest MBIC and MBEC values, inhibiting the Candida biofilm formation at 39.06 µg/mL and eradicating mature biofilms at 78.12 µg/mL, while the other surfactants required higher concentrations to disrupt the microbial biofilms. Synergic or additive interactions were found between the surfactants and selected β-lactam and macrolide antibiotics, as well as azole antifungals, with no antagonism observed. LAM and particularly LANHC₃ combined broad-spectrum antimicrobial activity, relevant antibiofilm effects and the ability to potentiate the activity of conventional agents, supporting their choice as alternative or complementary antimicrobial adjuvants over resistant microorganisms and their biofilms. Full article

The Tarim Basin, as the core strategic replacement area for oil and gas resources in western China, holds immense deep oil and gas development potential. However, this region features extensive deserts, fragile saline–alkali ecosystems, and extreme geological conditions—160°C high temperatures, high-salt/high-alkali formation fluids, and well-developed microfractures—that impose stringent dual requirements on drilling fluids for both engineering performance and environmental compatibility. Traditional drilling fluids suffer severe performance deterioration under high-temperature/high-salt coupling, and their poorly biodegradable, toxic additives exacerbate ecological pollution upon disposal, failing to meet green development demands. To address these issues, this study prepared four eco-friendly, temperature- and salt-resistant drilling fluid additives via chemical modification of natural degradable materials, and constructed a 160°C-resistant eco-friendly water-based drilling fluid system using orthogonal experiments. Furthermore, an innovative “waste-to-resource” strategy was proposed to repurpose spent drilling fluid for saline–alkali land restoration, investigating its improvement effects and environmental safety. The results show that the system withstands 160 °C and 15% NaCl, with excellent engineering performance (HTHP filtration loss ≤ 9.0 mL at 160 °C, friction coefficient ≤ 0.18) and compliance with national environmental standards (EC₅₀ = 36,000 mg/L, BOD₅/COD = 6.8%). Applied at an optimal 10–15% dosage, the spent fluid significantly improves saline–alkali soil properties, promotes Haloxylon ammodendron growth, and achieves >90% pollutant degradation within 3 months without secondary pollution. This integrated technology synergizes drilling engineering and ecological protection, providing technical support for green oil and gas development and saline–alkali land restoration in the Tarim Basin. Full article

Tetracyclines (TCs) are antibiotics widely used in human and veterinary medicine as well as in agricultural practices. They may be retained in soil or drift into freshwater, thereby exerting effects on non-target organisms and deteriorating ecological quality. In this study, tetracycline (T), oxytetracycline (OT), chlortetracycline (CT), and their binary and ternary mixtures were evaluated using a battery of bioassays including terrestrial plants, aquatic crustaceans, a ciliate protist and a bacterial species. Results showed a concentration-dependent effect for parameter immobilization in Daphnia magna and Artemia salina, seed germination in the terrestrial plants, and bioluminescence inhibition and growth inhibition in Aliivibrio fischeri and Tetrahymena thermophila, respectively. For A. fischeri, statistically significant interactions were observed between dose and exposure time. A. salina demonstrated greater sensitivity than D. magna in all cases. Both A. salina and A. fischeri showed increased toxicity to OT and the ternary mixture. Dicots presented greater sensitivity than the monocot species in all cases. In the combined exposures, there was a deviation from the concentration addition (CA) model, with possible synergism for CT + T and the ternary mixture for A. fischeri. The concurrent environmental exposure of non-target organisms to TCs should be investigated further. Full article

Sugarcane polyphenols (SP) are investigated for their antidepressant potential using a CUMS-induced mouse model and a corticosterone-induced neuronal injury cell model. Results demonstrate that SP alleviates depressive-like behaviors, inhibits hippocampal neuronal apoptosis, and reduces neuroinflammation. Mechanistically, SP activates the MAPK/ERK pathway, which in turn suppresses NLRP3 inflammasome-mediated pyroptosis; this effect is attenuated by the MAPK/ERK inhibitor PD98059. Furthermore, SP synergizes with the caspase-1 inhibitor VX-765 to inhibit pyroptosis. Full article

Spinel NiCo₂O₄ has emerged as a promising microwave absorption material due to its unique crystal structure and abundant defect sites. Nevertheless, its low intrinsic electrical conductivity leads to insufficient conductive loss and unsatisfactory high-frequency impedance matching, severely limiting the simultaneous realization of strong electromagnetic attenuation and broad absorption bandwidth. Fe³⁺ doping is an effective modification strategy for NiCo₂O₄ by virtue of its matched ionic radius and dual modulation capability for dielectric and magnetic properties. Herein, pristine and Fe-doped NiCo₂O₄ absorbers with different doping contents (4%, 6%, 8%) were fabricated via a hydrothermal–calcination route, and the correlation between Fe doping concentration, microstructure, electronic structure, electromagnetic properties, and microwave absorption performance was systematically investigated. Benefiting from moderate 6% Fe doping, the optimized F6 sample exhibits a refined porous nano-agglomerate structure, which provides abundant heterogeneous interfaces and pore channels for electromagnetic wave scattering and attenuation. The introduced oxygen vacancies and balanced Ni²⁺/Ni³⁺, Co²⁺/Co³⁺, and Fe²⁺/Fe³⁺ mixed-valence states effectively strengthen interfacial and dipole polarization, while the optimized electrical conductivity and magnetic properties synergistically boost conductive and magnetic losses. Owing to the dual-loss synergism and superior impedance matching (58% proportion of Δ < 0.4), the F6 sample achieves an excellent minimum reflection loss of −62.7 dB at 2.2 mm and a wide effective absorption bandwidth of 4.6 GHz. This work clarifies the intrinsic structure–performance mechanism of Fe-doped NiCo₂O₄, providing a reliable and feasible strategy for the design and preparation of high-performance spinel-type microwave-absorbing materials. Full article

Glioblastoma remains the most aggressive primary brain malignancy, with poor survival despite maximal safe resection, radiotherapy, and temozolomide-based chemotherapy. A major obstacle to effective treatment is the spatially heterogeneous blood–brain barrier/blood–tumor barrier, which restricts drug penetration into infiltrative tumor regions and limits uniform intratumoral exposure. Albumin-based delivery is attractive in glioblastoma because it addresses several formulation-level barriers at once: poor aqueous solubility of hydrophobic payloads, short systemic exposure, and the need for a biocompatible carrier that can interact with albumin-handling pathways such as gp60/albondin, SPARC, FcRn, and caveolin-associated transport. This review examines albumin-based strategies explored for glioblastoma, with an emphasis on albumin-bound paclitaxel nanoparticles, engineered albumin nanoparticles, dual-payload systems, albumin-binding photosensitizers, macrophage-assisted delivery, and albumin-bound pathway-directed agents. Preclinical evidence suggests that these platforms can improve brain-tumor drug exposure, support rational combinations, and synergize with BBB/BTB-opening technologies. Early clinical studies combining low-intensity pulsed ultrasound with microbubbles and albumin-bound paclitaxel provide human proof of concept for regional pharmacokinetic enhancement in recurrent glioblastoma, although survival benefit remains unproven. The available evidence supports albumin-based delivery as a rational formulation strategy. Its clinical value in GBM will depend on three testable requirements: spatial pharmacokinetic confirmation, biomarker-guided patient selection, and reproducible BBB/BTB modulation. Full article