Search Results (564)

Background: The profound heterogeneity of glioblastoma and the often-limited efficacy of conventional treatments, including arsenic trioxide (ATO), underscore the urgent and critical demand for innovative combination strategies specifically designed to overcome treatment resistance. Methods: We evaluated the therapeutic effects of ATO as a single agent and in combination with the MNK1 inhibitor AUM001 across patient-derived xenograft (PDX) models and investigated molecular determinants of sensitivity and synergy. Our results demonstrated that GBM models resistant to ATO, particularly those of the mesenchymal subtype, are more likely to show synergistic cytotoxicity when AUM001 is added. The combination significantly reduces the frequency of glioblastoma stem cells (GSCs) compared to either drug alone, especially in ATO-resistant models. Results: These observations suggest that targeting the MNK1 pathway in conjunction with ATO is a promising strategy to specifically eradicate GSCs, which are major drivers of GBM recurrence and therapeutic failure. Transcriptomic analyses revealed that ATO sensitivity correlated with activated translation-related pathways and cell cycle processes, while synergistic responses to the combination were driven by distinct molecular signatures in different GBM subtypes. Overall, synergistic response to the combination therapy is more associated with cellular organization, amino acid transmembrane transporter activity, ion channels, extracellular matrix organization and collagen formation. Conclusions: Our findings highlight that specific molecular pathways and their activities, including those involving translation, cell cycle and ion transport, appear to modulate the synergistic efficacy of the ATO and AUM001 combination, thereby offering potential biomarkers for improved patient stratification in future GBM clinical trials of such ATO-based treatments. Full article

The optimal branch bending angle for Pyrus sinkiangensis Yü (Korla fragrant pear) remains undefined. In this study, the optimal angle was determined by integrating the phenological, nutritional, hormonal, and fruit-quality responses across a 15-day bloom window. Four branch angles (40°, 60°, 80°, and 100°) were applied to 8-year-old trees in spring 2022, and flowering dynamics, bud carbon/nitrogen status, leaf morphology/mineral content, fruiting-shoot architecture, endogenous hormones, and fruit quality were comprehensively evaluated. The 80° angle maximized the fruit set (11.77%) and bud soluble sugar content (8.84 mg/g DW), significantly outperforming the other angles (p < 0.05). The flowering rate peaked at 100° (7.89%) but was statistically comparable to that at 60° and 80° (p > 0.05); calyx removal was greatest at 60° (73.33%), with no significant difference from that at 80° (71%, p > 0.05). These reproductive benefits aligned with enhanced leaf source capacity—80° pulling resulted in the greatest leaf area (59.51 cm²), the greatest amount of chlorophyll (3.11 mg/g DW), and elevated N/Mg/Cu concentrations. Branch architecture was optimized at 80°, with the percentage of medium fruiting spurs reaching 41.1% and the xylem:phloem dry-weight ratio peaking at 1.78, indicating the development of efficient assimilate transport pathways. Hormonally, 80° triggered a distinct cascade: a transient GA₄/GA₇ surge (50.6 and 1.34 ng/g DW) on 28 April, followed by sustained IAA elevation (2.05 ng/g DW) and zeatin stabilization (0.27–0.29 ng/g DW) during ovary development. Consequently, the fruit quality was comprehensively improved at 80°—the single-fruit weight (110.7 g), soluble sugar content (10.08 mg/g DW), and sugar/acid ratio (17.08) were greatest, whereas the stone-cell content was lowest (0.49 mg/g DW). Principal component analysis of 57 traits confirmed 80° as the system-wide optimum (D = 0.718). These results demonstrate that an 80° bending angle synchronizes carbohydrate supply, hormone signaling, and fruit quality in Korla fragrant pear, providing a low-cost, nonchemical benchmark for precision canopy management in high-density orchards. An 80° branch-bending angle optimizes carbon-hormone synergy via a transient GA₄/GA₇ surge and sustained IAA-zeatin signaling, maximizing fruit set and quality in high-density Korla fragrant pear orchards. Full article

Chitosan hydrogels are effective wound dressings that promote healing through the synergy of chitosan’s inherent biological properties and the moist environment they maintain. We previously developed hydrogel microparticles using a highly biocompatible chitosan derivative with superior therapeutic effects. This study aimed to enhance their clinical translation for Endoscopic Sinus Surgery (ESS) by optimizing preparation conditions to achieve an extrusion force of <20 N, facilitating ergonomic, single-handed administration by surgeons. While reducing the particle size alone was insufficient to lower the extrusion force significantly, the introduction of a mechanical “kneading” process to de-agglomerate microparticle aggregates resulted in a substantial reduction in the required force from 213 ± 80 N to approximately 47 N. By further optimizing the polymer concentration to 5.0% (w/v), we successfully reduced the maximum extrusion force to below 20 N (17 ± 1 N). These results demonstrate that the optimized injectable chitosan gel microparticles achieve the practical usability required for precise surgical maneuvers during ESS. Full article

The entire system collapses due to the issues of inadequate centralized storage capacity, poor scalability, low storage efficiency, and susceptibility to single point of failure brought on by huge power consumption data in the smart grid; thus, an alliance chain-driven multi-cloud storage and verifiable deletion method for smart grid data is proposed. By leveraging the synergy between alliance blockchain and multi-cloud architecture, the encrypted power data originating from edge nodes is dispersed across a decentralized multi-cloud infrastructure, which effectively mitigates the danger of data loss resulting from single-point failures or malicious intrusions. The removal of expired and user-defined data is guaranteed through a transaction deletion algorithm integrated into the indexed storage deletion chain and strengthens the flexibility and security of the storage architecture. Based on the Practical Byzantine Fault-Tolerant Consensus Protocol with Ultra-Low Storage Overhead (ULS-PBFT), by the hierarchical grouping of nodes, the system communication overhead and storage overhead are reduced. Security analysis proves that the scheme can resist tampering attacks, impersonation attacks, collusion attacks, double spend attacks, and replay attacks. Performance evaluation shows that the scheme improves compared to similar methods. Full article

Background: Neuromuscular electrical stimulation (NMES) is an effective exogenous neuromuscular activation method widely used in sports training and rehabilitation. However, existing research primarily focuses on land-based sports or single-joint movements, with limited in-depth exploration of its intervention effects and underlying neuromuscular control mechanisms for complex, multi-joint coordinated aquatic activities like breaststroke swimming. This study aimed to investigate the effects of NMES combined with traditional resistance training on neuromuscular function during sport-specific technical movements in breaststroke athletes. Methods: A randomized controlled trial was conducted with 30 national-level or above breaststroke athletes assigned to either an experimental group (NMES combined with traditional squat resistance training) or a control group (traditional squat resistance training only) for an 8-week intervention. A specialized fully waterproof wireless electromyography (EMG) sensor system (Mini Wave Infinity Waterproof) was used to synchronously collect surface EMG signals from 10 lower limb and trunk muscles during actual swimming, combined with high-speed video for movement phase segmentation. Changes in lower limb explosive power were assessed using a force plate. Non-negative matrix factorization (NMF) muscle synergy analysis was employed to compare changes in muscle activation levels (iEMG, RMS) and synergy patterns (spatial structure, temporal activation coefficients) across different phases of the breaststroke kick before and after the intervention. Results: Compared to the control group, the experimental group demonstrated significantly greater improvements in single-leg jump height (Δ = 0.06 m vs. 0.03 m) and double-leg jump height (Δ = 0.07 m vs. 0.03 m). Time-domain EMG analysis revealed that the experimental group showed more significant increases in iEMG values for the adductor longus, adductor magnus, and gastrocnemius lateralis during the leg-retraction and leg-flipping phases (p < 0.05). During the pedal-clamp phase, the experimental group exhibited significantly reduced activation of the tibialis anterior alongside enhanced activation of the gastrocnemius. Muscle synergy analysis indicated that post-intervention, the experimental group showed a significant increase in the weighting of the vastus medialis and biceps femoris within synergy module 4 (SYN4, related to propulsion and posture) (p < 0.05), a significant increase in rectus abdominis weighting within synergy module 3 (SYN3, p = 0.033), and a significant shortening of the activation duration of synergy module 2 (SYN2, p = 0.007). Conclusions: NMES combined with traditional resistance training significantly enhances land-based explosive power in breaststroke athletes and specifically optimizes neuromuscular control strategies during the underwater breaststroke kick. This optimization is characterized by improved activation efficiency of key muscle groups, more economical coordination of antagonist muscles, and adaptive remodeling of inter-muscle synergy patterns in specific movement phases. This study provides novel evidence supporting the application of NMES in swimming-specific strength training, spanning from macroscopic performance to microscopic neural control. Full article

A multifunctional diagnosis and treatment carrier, ZIF-8@CDs, based on carbon quantum dots (CDs) and the zeolitic imidazolate framework-8 (ZIF-8) metal–organic framework which serves as a core structure for constructing the responsive delivery platform, is developed in this paper. The anticancer drug doxorubicin (DOX) and Survivin oligo (siRNA) are loaded to form a ZIF-8@CDs/DOX@siRNA dual loading platform. CDs of 5–10 nm are synthesized by the solvent method and combined with ZIF-8. Electron microscopy shows that the composites are nearly spherical particles of approximately 200 nm, and the surface potential decreases from +36 mV before loading CDs to +25.7 mV after loading. The composite system shows unique advantages: (1) It has Fenton-like catalytic activity, catalyzes H₂O₂ to generate hydroxyl radicals, and consumes glutathione in the tumor microenvironment. The level of reactive oxygen species (ROS) in the ZIF-8@CDs group is significantly higher than that in the control group. (2) To achieve visual diagnosis and treatment, its fluorescence intensity is superior to that of the traditional Fluorescein isothiocyanate (FITC)-labeled vector; (3) It has a high loading capacity, with the loading amount of small nucleic acids reaching 36.25 μg/mg, and the uptake rate of siRNA by liver cancer cells is relatively ideal. The ZIF-8@CDs/DOX@siRNA dual-loading system is further constructed. Flow cytometry shows that the apoptosis rate of HepG2 cells induced by the ZIF-8@CDs/DOX@siRNA dual-loading system is 49%, which is significantly higher than that of the single-loading system (ZIF-8@CDs/DOX: 34.3%, ZIF-8@CDs@siRNA: 24.2%) and the blank vector (ZIF-8@CDs: 12.6%). The platform provides a new strategy for the integration of tumor diagnosis and treatment through the multi-mechanism synergy of chemical kinetic therapy, gene silencing and chemotherapy. Full article

Quinoa (Chenopodium quinoa Willd.) is a strategic crop for climate-smart agriculture in the Andes, yet yield gains are constrained by soil degradation and low-input systems. We tested whether synergistic bioinoculation with a plant growth-promoting rhizobacterium (Azospirillum brasilense) and an arbuscular mycorrhizal fungus (Glomus iranicum var. tenuihypharum) enhances root function and grain productivity under field conditions. A split-plot RCBD was conducted in Ayacucho, Peru (2735 m a.s.l.) using four cultivars, Blanca de Junín (BJ), INIA 441 Señor del Huerto (SH), INIA 415 Pasankalla (RP) and INIA 420 Negra Collana (NC) and four treatments: uninoculated control, Azospirillum, Glomus and co-inoculation. Vegetative, root and yield traits were quantified; ANOVA, Tukey/Dunnett contrasts, correlations and PCA were applied. Co-inoculation consistently outperformed single inoculants, increasing root diameter, length, branching, dry weight and volume dry weight, while also enlarging panicle dimensions and raising grain weight per panicle and thousand-seed weight. Grain yield reached 4.94 ± 0.59 t ha⁻¹ under co-inoculation, almost triple that of the control (1.71 ± 0.28 t ha⁻¹) and about 1.5 times higher than single inoculations. Genotypic effects were pronounced; BJ and SH combined superior root biomass with higher yield, RP maximized grain size and hectoliter weight, whereas NC responded weakly. Significant genotype × treatment interactions indicated cultivar-dependent microbiome benefits. Correlation and PCA linked root biomass and stem/panicle architecture to yield formation, positioning co-inoculation along trait vectors associated with belowground vigor and productivity. These results demonstrate a robust microbial synergy that translates root gains into yield, supporting co-inoculation as a scalable, low-input strategy for sustainable intensification of quinoa in highland agroecosystems. Full article

To identify the emission reduction potential and policy synergies of Tokyo’s road passenger and urban road freight transport under the “carbon neutrality target,” this paper constructs an assessment framework for megacities. First, based on macroeconomic socioeconomic variables (population, GDP, road length, and employment), regression equations are used to predict traffic turnover for different modes of transport from 2021 to 2050. Then, the prediction results are imported into the LEAP (Long-range Energy Alternatives Planning) model. By adjusting three policy levers—vehicle technology substitution (ZEV: EV/FCEV), energy intensity improvement, and upstream electricity and hydrogen supply decarbonization—a “single-factor vs. multi-factor (policy synergy)” scenario matrix is designed for comparison. The results show that the emission reduction potential of a single measure is limited; upstream decarbonization yields the greatest independent emission reduction effect, while the emission reduction effect of deploying zero-emission vehicles and improving energy efficiency alone is small. In the most ambitious composite scenario, emissions will decrease by approximately 83% by 2050 compared to the baseline scenario, with cumulative emissions decreasing by over 35%. Emissions from rail and taxis will approach zero, while buses and freight will remain the primary residual sources. This indicates that achieving net zero emissions in the transportation sector requires not only accelerated ZEV penetration but also the simultaneous decarbonization of electricity and hydrogen, as well as policy timing design oriented towards fleet replacement cycles. The integrated modeling and scenario analysis presented in this paper provide quantifiable evidence for the formulation of a medium- to long-term emissions reduction roadmap and the optimization of policy mix in Tokyo’s transportation sector. Full article

As a core sector of the Belt and Road Initiative (BRI) and dual-circulation pattern, Xinjiang’s cultural tourism industry—its ninth-largest industrial cluster—plays a key role in enhancing industrial competitiveness and regional coordinated development. To fill the research gap of insufficient analysis on China’s western frontier regions in existing tourism cluster studies, this research focuses on 14 prefecture-level cities in Xinjiang (2009–2023) and innovatively adopts a spatiotemporal synergy and dual-dimensional correlation framework, addressing the limitations of previous single-dimensional research. Tourism Location Quotient (TLQ) quantified specialized agglomeration, Local Moran’s I identified spatial correlation patterns, gravity models analyzed horizontal inter-cluster interactions, and Gray Relational Model (GRM) measured vertical driving relationships between cluster development and related dimensions. This approach facilitates an in-depth analysis of the spatiotemporal evolution trajectory of Xinjiang’s tourism clusters and their horizontal-vertical linkage mechanisms. Findings show: (1) Xinjiang’s tourism clusters present a spatial pattern of “Northern Xinjiang as the core, Eastern Xinjiang with differentiated development, and Southern Xinjiang as lagging.” With narrowing regional gaps, their evolution transitions from a “fixed gradient” to “co-evolution.” (2) Agglomeration effects are significant: Urumqi propels Northern Xinjiang to form a “high-high agglomeration zone,” while Southern Xinjiang remains a “low-low agglomeration zone” led by Kashgar. (3) Horizontal linkages evolve from a Urumqi-centered single-core structure to a multi-axis cluster network, and vertical linkages are mainly driven by destination attractiveness and economic support capacity. This study clarifies the spatiotemporal evolution logic and associated driving mechanisms of tourism clusters in arid, multi-ethnic frontier regions, providing a scientific basis for optimizing regional tourism layouts and promoting high-quality development. Full article

Leg dominance has been linked to an increased risk of lower-limb injuries in sports. This study examined bilateral asymmetry in muscle synergy patterns during one-leg stance on stable and multiaxial unstable surfaces. Twenty-five active young adults (25.6 ± 3.9 years) performed unipedal stance tasks on their dominant and non-dominant legs while surface electromyography (EMG) was recorded from seven lower-limb muscles per leg. Muscle synergies were extracted using non-negative matrix factorization (NMF), and structural similarity was assessed via cosine similarity with the Hungarian matching algorithm. Four consistent synergies were identified under both surface conditions, accounting for 88% of the total variance. On the stable surface, significant asymmetry in muscle weightings was observed in the rectus femoris (p = 0.030) for Synergy 1 and in the rectus femoris (p = 0.042), tibialis anterior (p = 0.024), peroneus longus (p = 0.023), and soleus (p = 0.006) for Synergy 2. On the unstable surface, asymmetry was evident in the biceps femoris (p = 0.048) for Synergy 2 and the rectus femoris (p = 0.045) for Synergy 3. Overall, dominance-related asymmetry was more pronounced under stable conditions and became more subtle as postural demand increased, revealing bilateral asymmetry in neuromuscular coordination during unipedal stance. Full article

In recent years, with the growing intensity of extreme weather events, imbalances in energy supply and demand, and frequent regional conflicts, the stability of our energy systems faces increasing challenges. Against this backdrop, the green innovation ecosystem can optimize the energy system’s structure and operational efficiency by promoting multi-actor interaction and multi-element synergy, thereby enhancing its resilience. Accordingly, this study aims to reveal how the green innovation ecosystem drives improvements in energy resilience (ER) through factor configurations and to identify the pathways leading to high-ER outcomes. To address this, this study constructs a research framework of the “core layer–environmental layer–supporting layer” for the green innovation ecosystem, and selects seven conditional variables, namely dual green innovation, multidimensional environmental regulation, green finance, and digital infrastructure. Based on official Chinese statistics, panel data from 30 provinces were compiled, and the dynamic qualitative comparative analysis (QCA) method was used to analyze how multiple factors interacted from 2016 to 2022 to achieve high ER from a spatiotemporal perspective. The results show that: (1) There is no single necessary condition for achieving high ER. (2) Dual green innovation and public participation in environmental regulation play a universal role in achieving high ER. They are combined with green finance, market-based environmental regulation, and digital infrastructure, forming three configuration pathways for achieving high ER. (3) No significant time effect is observed. (4) Pronounced spatial heterogeneity exists. The eastern region focuses on the green finance-enabled pathway, the central region has a high coverage of all three pathways, and the western region has relatively weak overall adaptability. Based on these findings, this study argues that enhancing ER depends on the coordinated allocation of multiple factors, and there is no single optimal pathway. Policymakers should adopt a configurational mindset and select appropriate combinations of elements in light of regional development conditions to enhance ER. Full article

Smart cities and innovative cities are important strategies for enhancing city resilience. By using panel data from 285 Chinese cities from 2009 to 2022 and examining “dual pilot” cities via the concurrent implementation of smart and innovative cities as a quasi-natural experiment, this study employs the difference-in-differences model to examine the impact of the “dual pilot” initiative. Furthermore, quantitative assessments are conducted from multiple perspectives through heterogeneity analysis, mechanism analysis, and spatial spillover effect analysis. The findings are as follows: “Dual pilot” cities have the ability to enhance city resilience and have a synergistic effect. The effect on city resilience is significantly greater than that of the “single pilot” design, but policy synergy effects are sensitive to the policy’s implementation sequence. A mechanism test reveals that innovation and development levels and industrial structure upgrading are important paths for “dual pilot” cities to boost city resilience. The heterogeneity study demonstrates that the positive impact of “dual pilot” cities on city resilience is statistically significant only in ordinary cities; non-resource-dependent cities; and cities across eastern, central, and western regions. A spatial spillover analysis demonstrates that “dual pilot” cities exert positive spillover effects on both the implementing cities and their neighboring areas. The above conclusions can serve as a source of reference and inspiration for building “resilient cities”. Full article

Background: Functional constipation (FC) represents a highly prevalent gastrointestinal disorder, affecting approximately 8.5% of the population in China. It is frequently associated with anxiety and depression, significantly impairing patients’ quality of life. Conventional microecological therapeutic approaches predominantly rely on empirical probiotic–prebiotic combinations. However, these pairings are seldom selected based on strain-specific metabolic characteristics, ultimately leading to suboptimal therapeutic synergy. Methods: The generation time (GT) of four constipation-relief strains was measured across eight oligosaccharides to identify optimal substrates for synbiotic formulation. The GT-optimized synbiotic was verified in a loperamide-induced mouse model vs. single probiotics/prebiotics. The related mechanisms of were assessed through 16S rDNA sequencing, targeted metabolomics, and qPCR. Results: The GT-optimized synbiotic significantly outperformed all single components. Specifically, the synbiotic significantly decreased the time to first black stool and increased fecal water content. Mechanistically, it restored colonic neurotransmitter balance, suppressed aquaporin expression, enriched butyrate-producing bacteria, and repaired barrier integrity. Overall, these effects work together, increasing the moisture content of the feces and accelerating intestinal peristalsis, ultimately alleviating constipation. Conclusions: We propose a GT-guided precision-pairing strategy that identifies optimal prebiotics based on strain-specific generation times, demonstrating synergistic enhancement of short-chain fatty acid (SCFA) production, enteric neurotransmitter signaling, and aquaporin-mediated water transport. This GT guided synbiotic approach shows promise in preclinical models and warrants validation in human trials. Full article

Setting is a fundamental movement in volleyball. While there are several optimal interpreters of the role in professional play, there is a surprising lack of advanced measurement techniques for the evaluation of the movement from a biomechanical perspective. We proposed a comprehensive motion analysis protocol based on kinematics and motor coordination assessment (muscle synergies) for an in-depth analysis of the setting gesture. We also quantified the test–retest performance and discussed in detail the potential of the method. A single experienced player (age 27) tested and retested the protocol. The protocol was quite rapid to perform (about 30 min, including placement of kinematic and electromyography sensors on the patient’s body); we found high test and re-test consistency in different sessions within this participant (ICC > 0.90). These preliminary results suggest that the protocol could support the use of the state-of-the-art methods for motion analysis and biomechanics in volleyball and sports in general. Full article

Soil salinization, characterized by complex ionic compositions, threatens global wheat production. Current research often focuses on single salts, leaving a gap in systematic comparisons of specific salt effects. This study comprehensively evaluated six prevalent salts (NaCl, Na₂SO₄, KCl, NaHCO₃, MgSO₄, and MgCl₂) across concentrations (10–200 mmol/L) during wheat (Triticum aestivum L.) germination. By integrating ten physiological indicators with principal component analysis (PCA), membership function evaluation, and median lethal concentration (LC₅₀) calculation, we identified distinct salt-specific toxicities. Results established a clear toxicity hierarchy: MgCl₂ was consistently most toxic (LC₅₀ = 32.92 mmol/L), indicating Mg²⁺/Cl⁻ synergy, while KCl was least inhibitory (LC₅₀ = 159.66 mmol/L). PCA simplified the 10-trait dataset, extracting 1 principal component (PC, 89.29–92.35% contribution) for most salts (fresh weight as key loading, reflecting growth) and 2 PCs (95.65% cumulative contribution) for MgSO₄ (separating root-growth and germination-vigor responses), thus identifying salt-specific key evaluation traits. Building on this PCA-derived trait screening, this analysis further revealed fresh weight (FW), germination rate (GR), shoot length (SL), and simple vigor index (SVI) as core evaluation indicators, and identified distinct mechanistic pathways: while most salts caused a generalized growth inhibition reflected in biomass reduction, MgCl₂ exerted a more specific and severe inhibitory effect on shoot elongation. MgSO₄ uniquely employed dual pathways, separately affecting root and germination traits. An innovative aspect of this work is the synergistic application of three synergistic evaluation methodologies with multi-physiological parameters, which allows for the rigorous quantitative characterization of distinct salt-specific effects on both early germination and seedling growth in wheat. This laboratory-based study provides a theoretical framework and practical indicators for salt damage risk assessment and preliminary screening of salt-tolerant wheat germplasm and lays a foundation for field validation and targeted management strategies for specific saline–alkali soils. Full article