Search Results (22,557)

Background: Fibrotic remodelling of the lamina cribrosa (LC) is a defining pathological feature of glaucomatous optic neuropathy and contributes to progressive optic nerve head deformation and axonal vulnerability. LC cells from glaucomatous donors exhibit a myofibroblast-like phenotype characterised by excessive extracellular matrix (ECM) production, a process associated with chronic cellular stress. cAMP responsive element-binding protein 3-like 1 (CREB3L1) is an endoplasmic reticulum–resident transcription factor implicated in stress-responsive regulation of collagen synthesis and matrix homeostasis. The role of CREB3L1 in glaucomatous LC cells, however, remains poorly defined. Methods: Primary human LC cells derived from donors with confirmed glaucoma (GLC; n = 3) and age-matched non-glaucomatous controls (NLC; n = 3) were examined. CREB3L1 expression was assessed at the mRNA and protein levels using quantitative RT-PCR and Western immunoblotting. The functional effects of CREB3L1 suppression were evaluated using siRNA-mediated knockdown in GLC cells, followed by analysis of ECM gene transcription (α-smooth muscle actin, collagen type I alpha 1, fibronectin) and cellular metabolic activity using an MTS assay. Results: CREB3L1 mRNA and protein expression were significantly elevated in GLC cells compared with NLC cells. siRNA-mediated knockdown of CREB3L1 effectively reduced its expression in GLC cells and was associated with significant suppression of profibrotic ECM gene transcription. In addition, CREB3L1 knockdown resulted in a marked reduction in cellular metabolic activity in glaucomatous LC cells. Conclusions: These findings identify CREB3L1 as a regulator of ECM-associated gene expression and cellular behaviour in glaucomatous lamina cribrosa cells. While preliminary, the data suggest that CREB3L1 may contribute to pathological fibrotic remodelling at the optic nerve head. Further mechanistic and in vivo studies will be required to determine whether modulation of CREB3L1-mediated pathways represents a viable therapeutic strategy in glaucoma. Full article

Solid polymer electrolytes (SPEs) hold great potential in high-safety energy storage but face two key bottlenecks: low room-temperature ionic conductivity and insufficient mechanical strength. This study proposes a synergistic optimization strategy of “long-carbon-chain regulation of polymer microstructure combined with porous polyimide (PI) support”. A linear random copolyester, poly(1,3-propylene-co-1,4-butylene succinate-co-sebacate) (PBPSS), was synthesized via melt polycondensation using 1,3-propanediol, 1,4-butanediol, succinic acid, and sebacic acid as monomers. Subsequently, the PBPSS-75 composite electrolyte was prepared with this copolyester as the matrix and porous PI as support. Results show that long-carbon-chain sebacic acid effectively regulates polymer segment flexibility and free volume, synergistically enhancing ionic conductivity and interfacial mechanical stability with lithium metal. Experimental data indicate that PBPSS-75 composite electrolyte exhibits an ionic conductivity of up to 4.25 × 10⁻⁵ S cm⁻¹ (30 °C), a lithium-ion transference number of 0.81, and an electrochemical stability window of 4.48 V (vs. Li/Li⁺). In LiFePO₄//Li batteries, it maintains nearly 100% capacity retention after 300 cycles at 0.5 C, and achieves stable cycling for over 800 h in lithium symmetric cells. This study confirms that the combined strategy effectively addresses the conductivity-mechanical property trade-off of SPEs, providing theoretical guidance and technical reference for high-performance solid-state battery material design. Full article

Cuticular proteins (CPs)—key components of the insect exoskeleton—not only regulate development but also serve as structural barriers that enhance resistance against environmental stressors. This study identified CP gene families in Apis mellifera and analyzed their expression patterns during the worker capped brood development stages from mature larva to pre-eclosion. Using a comprehensive genome-wide bioinformatic approach, we identified 85 CP genes in A. mellifera which comprise six families: CPR (n = 43), CPAPs (n = 27), CPF (n = 2), Tweedle (n = 2), CPLCP (n = 8) and Apidermin (n = 3). Analysis of CP gene evolutionary relationship revealed that each CP family forms a distinct, relatively independent clade. Domain and motif analyses confirmed that all CPR members harbor a conserved Chitin_Bind_4 domain, consistent with CPR family structures in other taxa. Additionally, CPAP members possess one or three Chitin-binding Peritrophin-A domain (CBM_14), CPF members possess a conserved Pupal cuticle protein C1 domain (Cuticle_3), and Tweedle members contain a conserved domain of unknown function (DUF243). In addition, the analysis found no conserved domain within the CPLCP and Apidermin families. RNA-seq data revealed dynamic expression patterns of AmCPs during pupal development, with each gene family displaying a relatively characteristic temporal profile. Quantitative PCR validation of eight highly expressed CPR genes at 9 days post-capping confirmed the RNA-seq results. This work provides a comprehensive bioinformatic characterization and transcriptional analysis of CP genes in A. mellifera, offering a foundation for future functional studies on cuticle formation and identifying candidate genes potentially involved in cuticle development in honeybees. This work relies on transcriptomic data and in silico analyses. All proposed biological roles are hypothetical and require experimental validation. Full article

Indonesia’s financial system is bank-centric, with banks managing approximately 78% of the nation’s financial assets; therefore, the effectiveness of monetary policy transmission depends on banks’ responsiveness to the central bank’s interest rate policy (the BI Rate). However, a policy-relevant anomaly persists: deposit rate pricing is more strongly anchored to the Deposit Insurance benchmark (IDIC Rate) than to the BI Rate. This study argues that this research is significant because it identifies a “Dual Benchmark System” that traditional single-anchor models fail to address, representing a critical friction in emerging market transmission. This study examines this dual-benchmark paradigm and the associated asymmetric risks using a panel VAR with a Generalized Impulse Response Function (GIRF) on quarterly data for 63 commercial banks from 2010 to 2024. The results indicate that IDIC Rate shocks have a larger and more persistent effect on deposit rates than BI Rate shocks, generating asymmetric transmission risks. This dominance creates a structural “price ceiling” that keeps funding costs high, ultimately raising lending rates for borrowers and distorting deposit growth rates. Furthermore, this analysis reveals that external policy signals are far more influential than internal financial performance. This suggests that under the Basel III framework and prevailing financial regulations, banks prioritize liquidity compliance and safety net protection over internal operational efficiency. Macroeconomic shocks remain weaker than policy shocks and dissipate more quickly. This finding reveals a potential systemic coordination risk, implying an urgent need for tighter policy coordination between the Central Bank and the IDIC to reduce structural frictions, maintain transmission effectiveness, and protect long-term financial stability. Full article

This qualitative study examined how a 21-day integrated program fosters interoceptive awareness and mind–body integration among urban adults in mainland China (n = 11). The intervention combined daily nasal breathing regulation, spontaneous mandala making, and descriptive journaling, complemented by weekly group sharing. Using a cultural–psychological lens, we investigated how an inward–turning tradition in Chinese culture shapes embodied experience and meaning–making. Applying Interpretative Phenomenological Analysis to diaries, drawings, and focus-group data, we identified three interrelated processes: (1) the refinement of bodily attention; (2) a shift from deliberate control to natural immersion; and (3) the symbolization of feeling through artistic expression and social resonance. Findings indicate that systematic engagement in the “breath–mandala” intervention heightened sensitivity to chest-centered embodied sensations and promoted the integration of bodily experience into personal narratives; a non-goal-directed, relaxed practice style facilitated the transition from control to absorption, activating self-regulatory mechanisms; and non-evaluative awareness deepened flow while supporting cognitive reorganization and reflective capacity. The study delineates a core pathway by which breath-triggered interoceptive work operates within mind–body interventions, offering a theoretical basis and practical direction for tailored regulation programs across diverse populations. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a globally prevalent condition with a complex pathogenesis. While both m6A RNA methylation regulators and gut microbiota have been independently implicated in MASLD, their potential causal interplay remains unexplored. This study aimed to investigate the causal relationships among m6A regulatory genes, gut microbiota, and MASLD, and to assess the mediating role of gut microbiota. Methods: We performed a two-sample Mendelian randomization (MR) analysis using publicly available genome-wide association study (GWAS) data. Genetic instruments for m6A regulators were derived from blood expression quantitative trait loci (eQTL) data. Gut microbiota and MASLD data were obtained from large-scale metagenomic and disease GWAS, respectively. The inverse-variance weighted method was the primary analysis, supplemented by sensitivity and mediation analyses to evaluate potential mediating pathways. Results: Genetically predicted levels of four m6A regulators showed significant causal associations with MASLD risk: ALKBH3 increased risk (OR = 1.17), whereas ALKBH5 (OR = 0.89), CBLL1 (OR = 0.76), and RBM15B (OR = 0.83) were protective. Nineteen gut microbial taxa were causally linked to MASLD. Among these, seven taxa were influenced by the four identified m6A genes. Although no mediation effects reached strict statistical significance, the pathway from ALKBH5 to MASLD via Parabacteroides abundance showed a suggestive indirect effect accounting for 21.9% of the total effect (p = 0.068). Given the limited statistical power of mediation analyses in MR settings, this observation should be interpreted with caution and requires validation in larger, well-powered studies. Conclusions: This MR study provides genetic evidence supporting causal roles of specific m6A regulators in MASLD and suggests that gut microbiota may partially mediate these relationships. The findings highlight a potential “m6A–gut microbiota–liver” axis in MASLD pathogenesis. Full article

Background/Objectives: Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and remains associated with poor prognosis despite multimodal therapy. Metabolic reprogramming, particularly increased dependence on glutamine, supports GBM bioenergetic, biosynthetic, and redox demands. This study aimed to systematically identify glutamine-associated metabolic regulators with prognostic relevance and biological plausibility in GBM. Methods: Transcriptomic data from TCGA and GTEx were analyzed using GEPIA2, with survival validation performed using the CGGA. Functional pathway enrichment, protein expression assessment, protein–protein interaction network analysis, tumor microenvironment evaluation, epigenetic profiling, and single-cell RNA sequencing validation were integrated to contextualize candidate genes. Pharmacogenomic correlation analysis and structure-based molecular docking were applied as supportive validation layers. Results: Ceruloplasmin (CP), Solute Carrier Family 25 Member 13 (SLC25A13), and Solute Carrier Family 38 Member 2 (SLC38A2) were selectively dysregulated and associated with poor clinical outcomes in GBM. CP was linked to redox regulation and stress-adaptive survival programs, SLC25A13 to mitochondrial metabolite exchange and glutamine-coupled nucleotide biosynthesis, and SLC38A2 to glutamine uptake, nutrient sensing, and mTORC1-MYC-associated growth signaling. Conclusions: CP, SLC25A13, and SLC38A2 emerge as clinically relevant glutamine-associated metabolic regulators in GBM, linking redox regulation, mitochondrial metabolite exchange, and glutamine-driven growth signaling. These findings highlight transport- and exchange-centered metabolic nodes as potential biomarkers and candidates for future metabolic targeting in GBM. Full article

Economic goals and non-economic goals often conflict in practice. Taking China as an example, this paper examines the impact of Administrative Approval Center (AAC) establishment on urban green innovation. A multi-period difference-in-difference (DID) method is applied to city-level panel data (2000–2022) in China to estimate the effect of AAC establishment on urban green innovation. The research results indicate that the establishment of AAC reduces urban green innovation due to the increased fiscal burden on local governments. This negative impact is particularly evident in the eastern and central regions, cities with stronger environmental regulations, or low-administrative-level cities. The conclusions of this paper have reference significance for other developing countries. To achieve sustainable development, central governments should enhance fiscal support and safeguards, local governments should implement differentiated environmental regulations, and digital technologies should be leveraged to reduce physical infrastructure costs and alleviate fiscal pressures. Full article

Rapeseed (Brassica napus L.) faces escalating threats from abiotic and biotic stresses, notably blackleg caused by Leptosphaeria maculans. Due to limited chemical control efficacy and stringent GMO regulations, marker-assisted selection (MAS) leveraging natural genetic variation has become an indispensable strategy for crop improvement. This study identified novel molecular markers for blackleg resistance by integrating genome-wide association study (GWAS) results with high-throughput genotyping by Diversity Arrays Technology sequencing. Phenotypic screening across the population demonstrated a wide spectrum of disease severity (scores 0–6), confirming the segregation of key resistance genes. The DArTseq platform identified nearly 104,000 markers, comprising 61% SilicoDArTs and 39% SNPs. Among the 33 most significant markers associated with resistance (p < 0.01), 76% were SilicoDArTs. Transcriptomic data further validated these findings, revealing 13 marker-linked genes expressed during infection, seven of which exhibited significant differential expression. Comprehensive functional annotation of Arabidopsis thaliana orthologs associated these genes with diverse cellular and plant-wide processes, particularly during stress responses. Collectively, these findings emphasize the complex polygenic nature of blackleg resistance and provide robust genomic tools for the accelerated breeding of resilient B. napus cultivars. Full article

Compliance checks are a critical aspect of any agricultural production and supply chain. These comprise a chain of activities and responsibilities shared by producers and regulators. Currently, the responsibility for collecting and processing data primarily lies with the regulators. Regulators are the primary users of regulatory technologies, while producers, such as farmers, have limited capabilities. This has been due to a lack of reliable hardware and software technology that can be deployed at the producer’s sites. However, recent advancements in Artificial Intelligence (AI), the Industrial Internet of Things (IIoT), and cloud computing have significantly increased reliability and reduced deployment costs. This paper reviews the regulatory landscape of agriculture, regulatory technologies, IIoT, and their feasibility for producers, using a new Technology Readiness Framework for Compliance, specifically designed for Regulatory Technologies (RegTech) and regulation compliance. It classifies technologies into three categories: Early Stage, Emerging, and Established. It concludes that most essential agricultural issues already have mature technological solutions within the scope of IIoT that producers can use directly without supervision, while still maintaining the integrity and validity of the data. The paper discusses and measures the maturity of IIoT and other electronic and digital technologies for integration into RegTech. This categorization offers a new perspective on technology readiness and lays the foundation for future RegTech platform design, e.g., by decentralizing and empowering producers with reliable technologies. Full article

To address the unobservability of distribution networks caused by insufficient coverage of measurement terminals as well as communication failures and missing data, and to cope with operating-state fluctuations induced by distributed generation integration and external environmental disturbances, this paper proposes an integrated state-estimation and voltage-regulation strategy that combines distribution-network-partitioning-based optimal PMU placement with pseudo-measurement construction using power transfer distribution factors (PTDFs). First, nodal reactive-power sensitivity information is derived from the power-flow Jacobian matrix, and an improved modularity function is employed to obtain the optimal partitioning of the distribution network, based on which PMUs are deployed at partition boundary buses. Second, PTDF-based power pseudo-measurements are constructed for unobservable buses and incorporated into the measurement model via a measurement transformation; a weighted least-squares method is then adopted to achieve system-wide state estimation. Finally, the estimated voltage states are fed into flexible voltage-regulation devices to enable fast and continuous voltage adjustment across buses. Case studies on the IEEE 33-bus system demonstrate that the proposed method effectively improves voltage quality. Full article

Bone tissue is among the most commonly transplanted tissues worldwide. The treatment of critical-sized bone defects remains a significant challenge, as there is currently no universally accepted experimental model or therapeutic standard. Recent advances in fundamental cell biology are driving a paradigm shift in approaches to bone regeneration, highlighting the transformative potential of biofabrication technologies that integrate tissue engineering with personalized regenerative strategies. Three-dimensional (3D) bioprinting technology enables precise control over the architecture and spatial distribution of cellular and biologically active components, facilitating the creation of complex, personalized bone constructs. Central to this process are bioinks and biomaterials that mimic the extracellular matrix (ECM) and provide an optimal microenvironment for cellular function. Despite the substantial body of accumulated data, a comprehensive theoretical framework for functional bone biofabrication has not yet been fully established, emphasizing both the challenges and the innovative potential of the field. This integrative review synthesizes current knowledge on bone biology—from embryogenesis and cell–matrix interactions to molecular and neural regulation—and links it to the opportunities offered by biofabrication. Particular attention is given to bioinks as mediators between cell biology and engineering sciences, as well as to strategies for creating biomimetic ECM, optimizing scaffold design, and guiding future research toward clinically translatable bone regeneration. Full article

Background: Post-traumatic stress disorder (PTSD) affects millions globally, with 40–50% of patients not responding adequately to first-line treatments. Prism neurofeedback, an FDA-cleared electroencephalography (EEG)-based system targeting amygdala-derived biomarkers, has demonstrated efficacy in randomized controlled trials (RCTs) and multicenter studies. Real-world implementation data from community clinical practice remain limited. Objective: To evaluate clinical outcomes and patient-developed self-regulation strategies of Prism neurofeedback in patients with PTSD in community clinical practice. Methods: Retrospective case series of 28 consecutive patients with PTSD treated with Prism neurofeedback in a community psychiatry practice. The primary outcome was change in PTSD Checklist for DSM-5 (PCL-5) from baseline to end of treatment. Results: Twenty-one of 28 patients (75.0%) completed treatment. Mean PCL-5 reduction was 37.0 ± 18.2 points (Cohen’s d = 2.03). Response rates were 100% for any improvement and 90.5% for clinically significant improvement (≥10-point reduction). Five patients (23.8%) achieved excellent response with ≥50-point reduction. Limited follow-up data (1–3 months post-treatment) were available for three patients; two of three (67%) exceeded their end-of-treatment gains. Four patients receiving booster sessions showed continued improvement. Limitations: The uncontrolled, retrospective design precludes causal attribution of improvements to the intervention versus placebo effects or regression to the mean. The 25% early discontinuation rate may introduce attrition bias. Durability data are available for only three patients. Conclusions: This case series provides real-world evidence supporting the feasibility and potential clinical utility of Prism neurofeedback in community practice, with outcomes comparable to controlled studies and preliminary evidence of durable treatment effects. These findings complement existing RCT evidence by demonstrating successful implementation outside research settings. Full article

This study conducts a bibliometric and content analysis of ‘artificial intelligence-enabled auditing’ over three decades. The use of artificial intelligence (AI) tools in auditing has evolved and is now an imperative practice in the auditing space. Using bibliometric methods via Bibliometrix R-package (Biblioshiny) and VOSviewer, this research mainly examines the scholarly discussion on AI-enabled auditing, using the Scopus database. The main themes identified are: Theme 1: AI in auditing: readiness, representation, and implementation; Theme 2: data-driven audit ecosystems and digital technologies; and Theme 3: audit quality, professional skepticism, and ethical governance. On the descriptive end, publication trends, prominent authors, articles, and sources are identified. The findings highlight a significant increase in AI-enabled auditing studies since 2018, coinciding with growing global awareness on the importance of AI across all spheres of business. The outcome of this research contributes to a wide array of stakeholders, including businesses, audit firms, shareholders, and policymakers; it should give insights to business organizations on the capabilities of AI-assisted auditing, while policymakers should have access to verifiable, auditable and regulatory-compliant systems for the implementation of their regulations. Investors may further enhance their knowledge in terms of how AI-assisted auditing increases the quality of their investment decisions and, at the same time, the risks involved. Finally, auditing firms should further invest in improving the application of technology in the auditing environment and ensure quality, evidence-based audit outcomes, and reporting. Full article

Long-term oncological outcomes are significantly influenced by dietary patterns and nutritional status. Emerging evidence suggests that specific nutrients and dietary behaviors modulate the biological pathways involved in cancer initiation, progression, and therapeutic response. Understanding these nutritional mechanisms is essential for optimizing cancer prevention strategies, improving treatment efficacy, and enhancing long-term prognosis. Dieting is a modifiable factor influencing cancer prevention, progression, and survivorship. This review is a molecular, clinical, and epidemiological data amalgamation that aims to figure out the first of the three aspects, i.e., how dietary patterns and nutrients affect carcinogenesis, therapeutic tolerance, and long-term outcomes in long-term oncology. The current review moves from diet-dependent core cancer mechanisms that lead cancer pathways through metabolic reprogramming, inflammation, oxidative stress regulation, and epigenetic alterations. Protective dietary patterns, e.g., plant-based, Mediterranean-style, fiber-rich, and omega-3-fed diets, typically provide lower oxidative and inflammatory loads while also facilitating immune surveillance and metabolic stability. Therapy-personalized nutrition that is high in energy–protein and functional foods is instrumental to treatment tolerance, reduction in complication incidence, and cachexia relief. The newest research highlights the significant influence of epigenetic remodeling and the gut–brain–immune axis as the main processes that connect nutrition to tumor behavior and psychosocial outcomes. Translation into clinical practice changes is still dependent on thoughtfully designed trials, the existence of standard guidelines, and the provision of equal access to digital nutrition tools, despite this advancement. Diet is positioned as a low-toxicity co-therapeutic strategy that supports prevention, treatment efficacy, and long-term survivorship. Full article