Search Results (3,495)

Power battery enterprises are a key link in the new energy vehicle (NEV) industry chain. However, studies analyzing the investment layout of power battery enterprises from a micro perspective are relatively scarce. This study takes Contemporary Amperex Technology Co. Limited (CATL) as a case and employs various spatial analysis methods and an optimal parameter-based geographical detector (OPGD) to analyze the spatiotemporal evolution and driving mechanisms of its investment layout from 2020 to 2024. The results indicate that CATL’s investment center has shifted from Jiangxi to Hubei, and the spatial expansion axis has changed from a northwest–southeast to a southwest–northeast direction. The investment layout has evolved from a “one core with two secondary cores” structure to a “provincial dual core, multi-core outside the province” structure and, ultimately, to a nationwide networked pattern. By 2024, CATL’s investment network covered the southeastern coast, the Yangtze River Delta (YRD), the Pearl River Delta (PRD), central China, and southwestern regions. County-level spatial autocorrelation analysis shows that the investment agglomeration effect has continuously strengthened (with the global Moran’s I increasing from 0.006 to 0.025). High–high agglomeration areas gradually expanded from the southeastern coast to Xiamen and several provinces in central and western China, while high–low agglomeration areas, as early signals of investment diffusion, initially expanded and then contracted. The driving mechanism analysis reveals that fiscal support (q = 0.668), industrial structure upgrading (q = 0.585), tax burden (q = 0.543), and economic development (q = 0.536) are the primary factors driving investment layout, with significant synergistic effects between these factors. The synergy between industrial structure upgrading and clean energy supply stands out as particularly prominent. These findings contribute to optimizing the spatial layout of the NEV industry and promoting regional economic development. Full article

Oral infections caused by antibiotic-resistant bacteria represent an emerging biomedical hazard and growing challenge for modern dentistry. To address this issue, Ag– and Cu–ZnO nanocomposites (NCs) were synthesized using ZnO carrier to combat the oral pathogens Streptococcus mutans and Streptococcus sobrinus. A comprehensive analysis of chemically synthesized metal oxide nanocomposites (MONCs) was performed, combining physicochemical characterization (TEM, XRD, ζ-potential, DLS, pH, and PFO/PSO kinetic models) with biological toxicity assessment (MIC, ATR–FTIR, SEM, and FAMEs) to better understand their antimicrobial mechanisms. The results confirmed that the synthesized nanoproducts fulfill the criteria for nanomaterials (NMs) (particle size < 100 nm). Among them, Ag–ZnO exhibited the highest antibacterial activity against both strains (MIC = 50 mg L⁻¹). Kinetic modeling revealed faster and more efficient Ag ion release from Ag–ZnO NCs compared to Cu from Cu–ZnO NCs. Molecular analyses indicated strong MONC–bacterial interactions at the cell surface, leading to changes in protein secondary structures, alterations in lipid composition, and disruption of Gram-positive bacterial membranes. Additionally, Ag–ZnO inhibited chain and cluster formation in both bacterial species, while Cu–ZnO affected only S. sobrinus. Overall, Ag– and Cu–ZnO NCs show strong potential as antimicrobial agents against oral pathogens. Full article

Siponimod, a selective sphingosine 1-phosphate (S1P) receptor modulator, represents a next-generation therapeutic drug for active secondary progressive multiple sclerosis. This study conducted in-depth forced degradation studies of siponimod in solid state subjected to acidic, alkaline, oxidative, photolytic, and thermal conditions, in compliance with ICH guidelines Q1A (R2) and Q3A (R2). An HPLC method was developed to quantify siponimod and separate its degradation products (DPs). The DPs were characterized using LC-HRMS/MS and LC-MSⁿ techniques. Moreover, the toxicological profiles of siponimod and its DPs were evaluated through the in silico tools ProTox 3.0 and ADMETlab 3.0, with molecular docking and dynamics simulations assessing their binding to the S1P1 receptor. Siponimod was stable to light but degraded under acidic, alkaline, oxidative, and thermal stress, producing five products: DP-1 (acidic), DP-2/3 (oxidative), DP-4 (hydrolytic), and DP-5 (thermal). The toxicity prediction suggested that neither siponimod nor its DPs exhibited carcinogenic or mutagenic potential, and the molecular modeling analysis revealed that DP-2 and DP-3 demonstrated favorable binding affinities, with stable dynamic profiles and thermodynamic properties that closely resembled those of siponimod. As far as we know, this is the first study on the structural elucidation of the DPs of siponimod by LC-HRMS/MS and LC-MSⁿ. Full article

(1) Background: The non-consensual dissemination of intimate images constitutes a severe form of online gender-based violence (OGBV) that inflicts profound harm on victims’ sexual privacy, psychological well-being, and social functioning. Taiwan enacted comprehensive legislative reforms in 2023—commonly referred to as the “Four Acts on Sexual Violence Prevention”—to strengthen criminal responses and expand victim protection mechanisms. However, the extent to which these reforms have translated into effective frontline practice remains insufficiently examined. (2) Methods: This qualitative study employed reflexive thematic analysis to investigate frontline professionals’ experiences with enforcing intimate image offence legislation and delivering victim support services. Semi-structured, in-depth interviews were conducted with 20 practitioners, including social workers, police officers, prosecutors, and lawyers. (3) Results: Three superordinate themes emerged across macro, meso, and micro structural levels. At the macro level, limited public awareness and persistent victim-blaming attitudes undermine prevention, help-seeking, and reporting. At the meso level, legislative fragmentation, challenges in preserving and analysing digital evidence, and inter-agency coordination gaps constrain enforcement capacity. At the micro level, procedural delays, risks of secondary victimization, and perceived inadequacies in compensation and support mechanisms weaken victims’ trust in institutional responses. (4) Conclusions: While Taiwan’s legislative reforms represent a significant institutional advancement, legal reform alone is insufficient to address digital sexual violence effectively. Comprehensive responses require integrated public education initiatives, enhanced inter-agency coordination, strengthened digital investigation capacity, and trauma-informed victim protection practices across all structural levels. In particular, the findings underscore an urgent public health need to establish rapid digital evidence preservation and takedown mechanisms to limit the proliferation of non-consensual sexual images and mitigate the associated mental health harms among victims. Full article

Parental involvement is widely recognized as a key component of effective schooling, particularly in educational environments that emphasize community, developmental continuity, and holistic pedagogy. Alternative education models such as Waldorf schools have expanded internationally, yet empirical evidence on how parents perceive and structure their experiences within these institutions remains limited. This study investigates parental perceptions of Waldorf education in Hungary through a nationwide questionnaire survey of 585 parents whose children attend Waldorf schools. To explore the latent structure of parental evaluations, Exploratory Factor Analysis was conducted, followed by Confirmatory Factor Analysis to test the stability of the resulting model. The analyses identified four coherent dimensions of parental experience: Trust and Pedagogy, Community and Engagement, Perceived Long-Term Educational Prosperity, and Information and Transparency. Additional analyses examined how these dimensions vary according to institutional characteristics, parental participation in school community activities, and intentions regarding long-term enrollment. The results indicate that pedagogical trust constitutes a relatively stable evaluative dimension across institutions, while perceptions related to community engagement, long-term educational prospects, and transparency are more strongly associated with institutional maturity. Parents who intend to remain in Waldorf education until the completion of upper secondary schooling report consistently higher evaluations across all dimensions. By empirically identifying the structure of parental experiences in a European alternative education context, the study contributes to research on parental engagement, school choice, and the institutional cultures of alternative schooling. Full article

The rapid growth of the digital economy has transformed the tourism industry, yet the industrial linkages and environmental impacts of this integration remain underexplored. This study employs an input–output framework to examine the interactions between the digital economy and tourism and their carbon footprint effects in China. Multi-year digital economy–tourism input–output tables for 2017, 2018, 2020, 2022, and 2023 are constructed using sectoral disaggregation and the RAS updating method. Results indicate increasing integration, with tourism more dependent on the digital economy sectors and both industries exerting the strongest influence on the secondary sector. The digital economy shows a gradual shift from hardware manufacturing to information services. Structural decomposition analysis and structural path analysis reveal that technological progress significantly reduces emissions, whereas population growth drives increases. These findings offer empirical evidence for guiding digital–tourism integration and supporting low-carbon strategies in the tourism sector. Full article

Baicalin, a natural plant-derived compound, holds promise in addressing clinical bacterial resistance when combined with antibiotics. This study evaluated the antibacterial activity of the combination of baicalin and cefotaxime and explored its mechanism of action on the cell wall and biofilm of multidrug-resistant Pseudomonas aeruginosa (MRPA). The results showed that the combination of baicalin and cefotaxime exerted a synergistic inhibitory effect on the growth of MRPA, with a fractional inhibitory concentration index (FICI) of 0.28. Mechanistically, compared with cefotaxime alone, the combination of baicalin and cefotaxime enhanced the permeability of the cell membrane and cell wall of MRPA, thereby increasing cell damage. It also exhibited stronger antibiofilm activity by inhibiting numerous virulence factors (pyocyanin, elastase, lectin), reducing cellular metabolic activity, and downregulating the expression of biofilm genes (pslA, pelA, algD) and quorum-sensing genes (lasl, lasR, rhll, rhlR, pqsA, pqsR). The molecular docking results revealed that baicalin could stably bind to wbpE, LasR, and RhlR. Therefore, this interaction may indirectly influence the processes related to antibiotic resistance and biofilm formation in bacterial cells. Metabolomic analysis revealed that the combination of baicalin and cefotaxime upregulated 863 metabolites and downregulated 587 metabolites. These metabolites mainly included amino acids, lipids, nucleotides, carbohydrates, and secondary metabolites. The combination primarily enriched key pathways such as amino acid metabolism, lipid metabolism (sphingolipid metabolism) and secondary metabolite biosynthesis. Through these pathways, it triggers significant metabolic reprogramming, thereby interfering with the supply of cell wall synthesis precursors, membrane structural stability, and the generation of biomembrane matrix. Ultimately, it synergistically enhances the effects of cell wall damage and biomembrane inhibition. In conclusion, this study confirms that the combination of baicalin and cefotaxime exerts significant synergistic antibacterial activity against MRPA. It also reveals the mechanism of action of the combination on the cell wall and biofilm of MRPA at the metabolic level, providing theoretical support for the development of novel strategies to combat MRPA. Full article

Deep shale of the Lower Cambrian Qiongzhusi Formation in the Sichuan Basin represents a critical frontier for shale gas exploration in China. However, systematic understanding of the multi-scale links among lamination type, mechanical anisotropy, and fracture complexity remains limited. Based on lamination characteristics and total organic carbon (TOC) content, core samples were classified into four types. Using a multi-scale approach (uniaxial compression, Brazilian splitting, in situ CT scanning, QEMSCAN, and SEM), this study elucidates how lamination structure controls mechanical anisotropy, failure modes, and fracture mechanisms. The novelties of this work are threefold: (1) quantitatively linking specific lamination types (ORM, OPM, PAFC, PAF) to anisotropic mechanical responses; (2) introducing 3D fractal dimensions to evaluate fracture network complexity; and (3) integrating micro- (SEM) and macro-scale tests to reveal the coupled control of weak planes and brittle minerals on fracture propagation. Results indicate that laminated shales exhibit pronounced mechanical anisotropy. Loading parallel to laminations induces tensile splitting along weak planes, significantly reducing strength. Conversely, perpendicular loading generates complex fracture networks of horizontal secondary fractures along laminae and vertical main fractures through the matrix. Furthermore, 3D fractal dimension analysis quantifies fracture network complexity as follows: organic-poor clay-feldspar laminated shale > organic-poor clay-feldspar-calcareous laminated shale > organic-rich massive shale. Microscopic observations confirm that fracture propagation is jointly governed by weak plane systems and brittle mineral content, which collectively determine macroscopic failure patterns. These findings clarify how lamination type controls the laboratory mechanical response and fracture morphology of deep shale and provide a laboratory-scale framework for comparing lamination-related differences in mechanical anisotropy and fracture complexity in the Qiongzhusi Formation. Full article

Background: Depression is highly prevalent among individuals with chronic pain and strongly impacts pain intensity, psychological functioning, and health-related quality of life. Self-efficacy has emerged as a potentially modifiable resilience factor within this interplay, yet large-scale real-world evidence integrating self-efficacy into multidimensional pain–depression models remains limited. Methods: This cross-sectional registry-based analysis evaluated standardized patient-reported measures from chronic pain patients enrolled in the German Pain e-Registry. All variables were directionally harmonized and transformed into standardized deviation scores (hSDSs) relative to patients without depression. Group-level hSDS profiles for five DASS-21 depression severity strata (none, mild, moderate, severe, extreme) were compared across pain intensity, disability, psychological well-being, affective pain processing, quality of life, neuropathic pain features, and pain-related self-efficacy (PSEQ). Correlations and exploratory principal component analysis (PCA) were used to assess multivariate structure. PCA-informed path models were estimated to evaluate directional relationships between pain, function, depression, and self-efficacy. All directional and mediation models represent exploratory, theory-informed statistical frameworks and do not imply causal or mechanistic relationships. Results: Across all domains, hSDS values increased monotonically with depression severity, while self-efficacy showed the strongest inverse gradient. Exploratory PCA revealed a dominant severity component explaining most variance and a secondary affective–self-efficacy axis, supporting the conceptual separation between functional–physical and psychological–affective symptom clusters. In the bottom-up path model (pain → function → self-efficacy → depression), self-efficacy showed the largest indirect statistical contribution within the proposed path models, and the model explained 55% of depression variance (R² = 0.55). In the top-down model (depression → affective pain → self-efficacy → pain), 45% of pain intensity variance was explained (R² = 0.45), again with self-efficacy as a central mediating construct. Associations remained robust after adjustment for age, sex, and BMI, as well as during sensitivity analyses. Conclusions: This large real-world cohort demonstrates a highly coherent pattern of associations across biopsychosocial domains and highlights pain-related self-efficacy as a central statistical construct linking pain, functional impairment, and depressive symptom burden within the applied exploratory models. The findings suggest that self-efficacy occupies a key position in the interplay between pain and mood, and that pharmacological and non-pharmacological treatments traditionally used in chronic pain management may be associated with changes in this construct. Importantly, all directional and mediation analyses are exploratory and do not imply causal or mechanistic relationships. Therapeutic strategies aimed at enhancing self-efficacy may therefore represent promising targets for future research within multimodal pain management frameworks. Full article

Prenatal whole-genome sequencing (WGS) is a comprehensive genetic test for fetal anomalies, enabling simultaneous detection of aneuploidies, copy number variants (CNVs), single-nucleotide variants (SNVs), small insertions/deletions, structural variants, and regions of absence of heterozygosity. However, its clinical performance, optimal sequencing strategies, and implementation challenges remain incompletely defined. We conducted a narrative review of PubMed-indexed studies (1966–December 2025) evaluating prenatal WGS in fetuses with structural anomalies. Across 29 studies, diagnostic yield ranged from approximately 20% to 40%, influenced by phenotype complexity, sequencing depth, and study design. Low-coverage WGS (≤5×) reliably detected large chromosomal abnormalities with a performance comparable to chromosomal microarray analysis. Moderate-coverage WGS (20–40×) additionally enabled detection of SNVs and structural variants, providing up to 30% incremental diagnostic yield after uninformative standard testing. Turnaround times were typically 14–21 days. Higher sequencing depth increases detection of variants of uncertain significance (0.6% to 35.7%) and secondary/incidental findings (1.6–30.8%). Prenatal WGS offers meaningful diagnostic value but requires careful patient selection, multidisciplinary expertise, and structured pre- and post-test genetic counseling to ensure responsible integration into routine clinical practice, with careful consideration of clinical benefit and economic feasibility. Full article

Histidine triad (HIT) family proteins contain a conserved histidine triad motif and play key roles in fungal metabolism and pathogenicity. This study focused on VD9136, a member of the HIT family in Verticillium dahliae, aiming to elucidate its biological function and mechanism underlying its role in cotton pathogenesis. A systematic investigation of the VD9136 gene in V. dahliae was conducted using bioinformatics analysis, gene knockout, genetic complementation, and pathogenicity assays. The results showed that VD9136 protein consists of 136 amino acids and is a stable, neutral, and weakly hydrophilic protein that lacks transmembrane domains and signal peptides; it is localized to the extracellular space via a non-classical secretion pathway. Its secondary structure is predominantly composed of α-helices and random coils. Phylogenetic analysis revealed that VD9136 is closely related to VliHIT, a homologous protein from V. longisporum, the pathogen responsible for Verticillium wilt in rapeseed. The promoter region of VD9136 contains multiple cis-acting elements, including light-responsive, hormone-responsive, and stress-responsive elements, indicating that its transcription may be regulated by multiple signaling pathways. VD9136 was significantly upregulated during the early stage of cotton infection (6–24 h post-inoculation). Pathogenicity assays demonstrated that V. dahliae knockout mutants lacking VD9136 exhibited a significant reduction in virulence, as evidenced by a lower disease index, decreased fungal biomass within plant tissues, and attenuated vascular browning in cotton plants. The pathogenic phenotype was successfully restored in genetic complementation strains. This study identified VD9136 as a key regulatory factor in the pathogenic process of V. dahliae, and its loss of function reduces the pathogenicity of V. dahliae. The findings provide a theoretical basis for elucidating the pathogenic mechanism of cotton Verticillium wilt and for developing corresponding prevention and control strategies. Full article

Abscisic acid (ABA) regulates diverse aspects of plant growth and secondary metabolism, yet its concentration-dependent effects on rhizomatous spice crops remain poorly understood at the systems level. Here, we investigated the phenotypic, physiological, hormonal, and multi-omics responses of ginger (Zingiber officinale) to foliar-applied ABA across a concentration gradient. Exogenous ABA modulated ginger growth in a distinctly non-linear manner. Low-to-moderate concentrations (5–15 mg/L) significantly enhanced aboveground branching and belowground rhizome yield, whereas high concentration (35 mg/L) inhibited branching while promoting structural carbohydrate accumulation, revealing a concentration-dependent trade-off between growth and secondary wall deposition. Hormone profiling uncovered global reprogramming of the endogenous hormonal network, with optimal ABA (15 mg/L) coordinately elevating growth-promoting hormones and defense-related signals, while high concentrations suppressed multiple hormone pathways and triggered negative feedback inhibition of endogenous ABA biosynthesis. Integrated metabolomic and transcriptomic analyses identified convergent enrichment on phenylpropanoid biosynthesis, gingerol biosynthesis, and plant hormone signal transduction. Co-expression network analysis revealed a highly interconnected module of 583 genes linking hormone signaling to secondary metabolism, with coordinated up-regulation of key enzymes from phenylalanine ammonia-lyase (PAL) to polyketide synthase under 15 mg/L ABA explaining the 64% increase in 6-gingerol content. This study establishes a mechanistic chain from ABA perception to improved ginger yield and quality, mediated by hormonal crosstalk and transcriptional activation of the phenylpropanoid-gingerol network. We propose an “ABA optimization window” of 5–15 mg/L for precision cultivation of high-quality ginger, providing a systems-level framework for understanding hormone-mediated regulation of secondary metabolism in medicinal and spice crops. Full article

At present, the characteristics of key enzyme genes in the upstream pathway for triterpenoid saponin biosynthesis in P. grandiflorum, as well as their expression patterns over the growth duration, have not been systematically analyzed. This study, at the whole-genome level, conducts the first bioinformatics and expression analyses of the SS and SE gene families in P. grandiflorum. Four PgSS and seven PgSE genes were identified and distributed across six chromosomes. Members within the same subfamily exhibited highly conserved sequences and structures, while distinct structural divergence was observed between different subfamilies. Phylogenetic analysis showed that PgSS and PgSE genes were closely related to those of dicotyledons such as Panax ginseng and Polygala tenuifolia, suggesting high evolutionary conservation. Promoter analysis revealed abundant light- and hormone-responsive elements and MYB/MYC binding sites, indicating regulation by multiple signals. Protein secondary structures were dominated by the Alpha helix and were structurally stable. Quantitative real-time polymerase chain reaction (qPCR) demonstrated that expression levels of PgSS and PgSE in one-year-old Platycodonis Radix were significantly higher than in perennial Platycodonis Radix, especially for the PgSE family. This study characterized the basic biological features and growth-stage-dependent expression patterns of the SS and SE gene families in P. grandiflorum. The results identify key candidate genes and molecular targets for regulating triterpenoid saponin biosynthesis, and provide data supporting quality improvement and active metabolite research in this medicinal plant. Full article

Background: Stroke remains a significant health and economic challenge both globally and in the Czech Republic. Although a structured network of specialized stroke centres exists, comparative data on patient outcomes and healthcare costs across hospital types are still lacking in the Czech context. This study analyzed real-world administrative data to assess 90-day mortality and healthcare costs after ischemic stroke, categorized by intervention and provider type. Methods: Claims data from six Czech health insurance companies, covering approximately 44% of the population, were used for the years 2017–2020. Patients aged 18 and older with a primary diagnosis of ischemic stroke (ICD-10 code I63) were included. Interventions were categorized as thrombectomy, thrombolysis, or other treatment, and providers were classified as comprehensive stroke centres (CSCs), primary stroke centres (PSCs), secondary referral hospitals (SRHs), or others. Costs were calculated from the payer perspective using administrative claims data, and standardized 90-day mortality and effective cost per survivor (ECPS) were computed. Funnel plots were used to evaluate provider variability in outcomes and costs. The analysis included 23,568 patients (47% female; mean age 70.6). Results: Thrombectomy was associated with the highest mean costs (€13,385), the highest 90-day mortality (29.3%), and the highest ECPS (€18,880). Patients receiving other treatments had the lowest costs (€2725) and lower mortality (14.4%). CSCs recorded the highest average costs (€5087) and mortality (16.7%), while SRHs had the lowest costs (€2204) and mortality (13.7%). Funnel plots revealed greater variability in costs, mainly driven by primary hospitalization, while mortality rates showed less variation. Conclusions: These findings suggest that while stroke outcomes are relatively consistent across providers, costs differ, possibly reflecting efficiency differences and case-mix severity. The study is limited by the lack of clinical severity data, highlighting the need to link administrative data with clinical registries for more comprehensive future evaluations. Full article

To investigate how natural inulin (FI) influences the quality of heat-induced beef myofibrillar protein (BMP) gels, BMP gel systems were prepared with graded FI concentrations (1%, 2%, 3%, 4%, and 5%). Texture analysis (TA), low-field nuclear magnetic resonance (LF-NMR), rheological measurements, scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FT-IR) were used to systematically characterise changes in gel properties, water migration and distribution, microstructure, and protein secondary structure. The results showed that the improvement in gel quality produced by inulin was concentration-dependent. FI at addition levels of 1–2% promoted the ordered intermolecular cross-linking of beef myofibrillar proteins, thereby facilitating the formation of a homogeneous and compact three-dimensional gel network, as confirmed by SEM and CLSM observations. Notably, 2% FI was identified as the optimal addition level for the BMP gel system. Compared with the control group, this treatment produced the highest relative β-sheet content (82%) among all groups, optimised the internal water distribution of the gel by reducing the proportion of free water, enhanced the water-holding capacity of the gels (p < 0.05), and preserved the elasticity-dominated solid-state characteristics of the BMP gel system (tan δ < 1), indicating that FI improved gel strength without changing its fundamental properties. These findings provide an important theoretical basis and practical technical parameters for the development of functional beef products with both desirable texture and high dietary fibre content. Full article