Search Results (5,576)

Neuroblastoma is a highly aggressive pediatric malignancy originating from neural crest progenitor cells, predominantly in the adrenal medulla. Amplification of the MYCN oncogene occurs in 20–30% of all neuroblastoma cases and approximately 50% of high-risk tumors, strongly correlating with poor prognosis, relapse, and multidrug resistance. MYCN-driven oncogenesis promotes tumor progression by suppressing apoptotic signaling and enhancing survival pathways, including autophagy—a key mechanism underlying resistance to chemotherapy and immunotherapy. This review examines current therapeutic strategies and resistance mechanisms in MYCN-amplified neuroblastoma, while introducing emerging approaches utilizing exosomes as precision drug delivery systems. Exosomes, nanoscale extracellular vesicles secreted by the tumor cells, exhibit natural tropism and can be engineered to selectively target neuroblastoma-specific biomarkers such as glypican-2 (GPC2), which is highly expressed in MYCN-amplified tumors. Leveraging this property, neuroblastoma-derived exosomes can be purified, modified, and loaded with small interfering RNA (siRNA) to silence MYCN expression, combined with chloroquine—an FDA-approved autophagy inhibitor—to simultaneously inhibit autophagy and induce apoptotic signaling. This dual-targeted approach aims to overcome drug resistance, reduce off-target toxicity, and enhance therapeutic efficacy through exosome-mediated specificity. Furthermore, gut dysbiosis has emerged as a critical factor influencing tumor progression and diminishing treatment efficacy in MYCN-amplified neuroblastoma. We propose integrating microbiota-derived exosomes engineered to deliver anti-inflammatory microRNAs (miRNAs) to the gut mucosa, restoring eubiosis and potentiating systemic anti-tumor responses. Collectively, exosome-based strategies represent a paradigm shift in formulating combination therapies, offering a multifaceted approach to target MYCN amplification, inhibit autophagy, induce apoptosis, and modulate the tumor-microbiome axis. These innovations hold significant promise for improving clinical outcomes in high-risk MYCN-amplified neuroblastoma patients. Full article

Type 2 diabetes mellitus (T2DM) is characterized not only by chronic hyperglycemia but also by profound adipose tissue dysfunction, including impaired lipid handling, low-grade inflammation, mitochondrial dysfunction, and extracellular matrix (ECM) remodeling. These adipose tissue alterations play a central role in the development of systemic insulin resistance, ectopic lipid accumulation, and cardiometabolic complications. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), particularly semaglutide, have emerged as highly effective therapies for T2DM and obesity. While their glucose-lowering and appetite-suppressive effects are well established, accumulating evidence indicates that semaglutide exerts pleiotropic metabolic actions that extend beyond glycemic control, with adipose tissue representing a key target organ. This review synthesizes current preclinical and clinical evidence on the molecular and cellular mechanisms through which semaglutide modulates adipose tissue biology in T2DM. We discuss depot-specific effects on visceral and subcutaneous adipose tissue, regulation of adipocyte lipid metabolism and lipolysis, enhancement of mitochondrial biogenesis and oxidative capacity, induction of beige adipocyte programming, modulation of adipokine and cytokine secretion, immunometabolic remodeling, and attenuation of adipose tissue fibrosis and ECM stiffness. Collectively, available data indicate that semaglutide promotes a functional shift in adipose tissue from a pro-inflammatory, lipid-storing phenotype toward a more oxidative, insulin-sensitive, and metabolically flexible state. These adipose-centered adaptations likely contribute to improvements in systemic insulin sensitivity, reduction in ectopic fat deposition, and attenuation of cardiometabolic risk observed in patients with T2DM. Despite compelling mechanistic insights, much of the current evidence derives from animal models or in vitro systems. Human adipose tissue-focused studies integrating molecular profiling, advanced imaging, and longitudinal clinical data are therefore needed to fully elucidate the extra-glycemic actions of semaglutide and to translate these findings into adipose-targeted therapeutic strategies. Full article

Although probiotics are widely used in the food industry due to their health-promoting effects, their application is often limited by low stability and poor viability under processing, storage, and gastrointestinal conditions. Encapsulation has emerged as a promising strategy to address these issues, offering enhanced protection and controlled release of probiotic strains. This review summarizes recent advances in encapsulation techniques relevant to food applications, including spray drying, freeze drying, coacervation, and liposome formation, as well as novel approaches such as multilayer nanocoatings and dual-core systems. The use of natural biopolymers such as alginate, chitosan, and pectin, along with food-grade synthetic materials, has greatly improved the stability of probiotics in complex food matrices. Furthermore, emerging technologies such as cell-mediated coatings offer improved resistance to gastric acid and oxygen, enhancing probiotic survival through the gastrointestinal tract. These advances contribute to the development of functional foods with better health benefits. However, challenges remain regarding scalability, strain-specific encapsulation efficiency, and regulatory approval. Future research should focus on optimizing food-grade materials, exploring synergistic effects with bioactive compounds, and ensuring consistent performance across food systems. Full article

Under the pressing imperative of achieving “dual carbon” goals and advancing urban low-carbon transitions, understanding how neighborhood spatial environments influence carbon emissions has become a critical challenge for enabling refined governance and precise planning in urban carbon reduction. Taking the central urban area of Xining as a case study, this research establishes a high-precision estimation framework by integrating Semantic Segmentation of Street View Images and Point of Interest data. This study employs a Geographically Weighted XGBoost model to capture the spatial non-stationarity of emission drivers, achieving a median R² of 0.819. The results indicate the following: (1) Socioeconomic functional attributes, specifically POI Density and POI Mixture, exert a more dominant influence on carbon emissions than purely visual features. (2) Lane Marking General shows a strong positive correlation by reflecting traffic pressure, Sidewalks exhibit a clear negative correlation by promoting active travel, and Building features display a distinct asymmetric impact, where the driving effect of high density is notably less pronounced than the negative association observed in low-density areas. (3) The development of low-carbon neighborhoods should prioritize optimizing functional mixing and enhancing pedestrian systems to construct resilient and low-carbon urban spaces. This study reveals the non-linear relationship between street visual features and neighborhood carbon emissions, providing an empirical basis and strategic references for neighborhood planning and design oriented toward low-carbon goals, with valuable guidance for practices in urban planning, design, and management. Full article

The mechanisms underlying wound healing mediated by cannabinoid receptor 1 (CB1)—known for its neuromodulatory functions—remain incompletely understood. Therefore, we investigated the impact of activating CB1 using specific agonists, both in vitro and in vivo, with a focus on wound healing. In the in vitro study, fibroblasts were isolated and cultured from the dermis of human skin and treated with a CB1 agonist, 2-arachidonyl glyceryl ether (2-AGE). In the in vivo study, a mouse acute wound model was created using a skin biopsy punch and treated with the CB1 agonist arachidonoyl 2′-chloroethylamide (ACEA). The in vitro study revealed that 2-AGE increased cell proliferation and differentiation, upregulated the expression of alpha-smooth muscle actin (α-SMA), N-cadherin, and vimentin, and enhanced cell migration as well as the synthesis of type I and III collagen and fibronectin in normal human dermal fibroblasts. The CB1 antagonist AM251 abolished 2-AGE-induced expression of α-SMA, type I collagen, and fibronectin. In vivo, ACEA treatment accelerated wound closure, increased expression of α-SMA, type I collagen, and fibronectin, and ultimately increased epidermal and dermal thickness. Overall, these findings suggest that the activation of CB1 promotes wound healing and provides evidence for the therapeutic potential of CB1 agonists in wound treatment. Full article

Tomato spotted wilt virus (TSWV) is one of the most important plants segmented negative-strand RNA viruses (NSVs). Plants employ the ubiquitin–proteasome system (UPS) and autophagy pathways to degrade viral effector proteins, forming a key antiviral defense layer. SnRK1 functions as a central energy sensor and plays pivotal roles in plant growth and development, as well as immune defense. However, whether SnRK1 modulates the infection of plant segmented NSVs and the underlying regulatory mechanisms remains elusive. In this study, we found that nonstructural protein NSs, a viral suppressor of RNA silencing (VSR) encoded by TSWV, specifically interacts with the catalytic α subunit of host SnRK1 (SnRK1α). NbSnRK1α promotes the degradation of NSs via the 26S proteasome pathway, independently of autophagy. Transient silencing of NbSnRK1α led to increased accumulation of the NSs protein. Furthermore, we found that NbSnRK1α significantly impairs the VSR activity of NSs by promoting its degradation, thereby restoring the host’s RNAi-mediated antiviral defense. Subsequent viral infection assays confirmed that NbSnRK1α inhibits TSWV replication, whereas silencing NbSnRK1α enhances the susceptibility of Nicotiana. benthamiana to TSWV infection and facilitates systemic viral spread and disease symptom development. Our study uncovers a new antiviral defense case by which NbSnRK1α enhances host antiviral immunity through targeting a segmented negative-strand RNA viral effector for 26S proteasomal degradation, broadening the understanding of the NbSnRK1’s role in broad-spectrum antiviral defense. Full article

This paper constructs a two-way fixed effects model using data from 4623 Chinese A-share listed enterprises from 2011 to 2022, confirming that firm digital transformation can enhance access to sustainable trade credit. Specifically, for every 1% increase in the standard deviation of digital transformation, the trade credit obtained by enterprises increases by 2.14% in relation to their average value. We employed instrumental variable (IV) and propensity score matching (PSM) methods, utilizing the Broadband China pilot policy as a quasi-natural experiment to conduct a multi-period propensity score matching-difference in differences (PSM-DID) analysis to address potential issues of reverse causality and sample selection bias. Mechanism analysis indicates that the diversification of supplier structures, R&D innovation, and market share facilitated by digitalization are three main channels. This effect is particularly significant in state-owned enterprises, mature enterprises, and those with higher social trust. Finally, the study also found that the spillover effects of digital transformation encourage client enterprises to allocate credit resources to downstream firms, thereby promoting the sustainable development of supply chain finance. Furthermore, the digital transformation primarily alleviates short-term credit challenges for enterprises and reduces their reliance on bank credit. Full article

Aging is accompanied by progressive gastrointestinal structural and functional decline, increased intestinal permeability, dysbiosis, and impaired mucosal immunity, collectively elevating susceptibility to infections, chronic inflammation, and multimorbidity. These age-related changes are further exacerbated by polypharmacy, metabolic disorders, and lifestyle factors, positioning the gastrointestinal tract as a central driver of systemic physiological decline. Gut-centered interventions have emerged as critical strategies to mitigate these vulnerabilities and support healthy aging. Dietary modulation, prebiotic and probiotic supplementation, and microbiota-targeted approaches have demonstrated efficacy in improving gut microbial diversity, enhancing short-chain fatty acid production, restoring epithelial integrity, and modulating immune signaling in older adults. Beyond nutritional strategies, non-nutritional interventions such as molecular hydrogen and medical ozone offer complementary mechanisms by selectively neutralizing reactive oxygen species, reducing pro-inflammatory signaling, modulating gut microbiota, and promoting mucosal repair. Hydrogen-based therapies, administered via hydrogen-rich water or inhalation, confer antioxidant, anti-inflammatory, and cytoprotective effects, while ozone therapy exhibits broad-spectrum antimicrobial activity, enhances tissue oxygenation, and stimulates epithelial and vascular repair. Economic considerations further differentiate these modalities, with hydrogenated water positioned as a premium wellness product and ozonated water representing a cost-effective, scalable option for geriatric gastrointestinal care. Although preclinical and early clinical studies are promising, evidence in older adults remains limited, emphasizing the need for well-designed, age-specific trials to establish safety, dosing, and efficacy. Integrating dietary, microbiota-targeted, and emerging non-nutritional gut-centered interventions offers a multimodal framework to preserve gut integrity, immune competence, and functional health, potentially mitigating age-related decline and supporting overall health span in older populations. Full article

Background: Tendinopathy remains a prevalent musculoskeletal disorder with limited disease-modifying pharmacotherapy. This study aimed to identify a reparative agent from the traditional medicinal herb Eucommiae Cortex and elucidate its mechanism of action. Methods: A bioactive fraction was first identified through a bioactivity-guided strategy using tenocyte cytoprotection and migration assays, then characterized by UHPLC-HRMS/MS. Its major constituent, aucubin (AU), which mirrors the fraction’s key pharmacological activities, was evaluated both in vitro and in vivo. In H₂O₂-injured tenocytes, AU’s effects on viability, apoptosis, oxidative stress (ROS, MDA, SOD) and inflammation (IL-1β, TNF-α) were assessed, with specific focus on estrogen receptor (ER) pathway involvement using pharmacological tools (17β-estradiol and (R, R)-THC). In a collagenase-induced Achilles tendinopathy model using male SD rats, AU’s therapeutic efficacy was evaluated via multimodal assessment: ultrasonography, histopathology (H&E, Masson’s trichrome, Sirius red), TEM, immunohistochemistry, and biochemical analysis of tissue markers. Results: AU effectively attenuated H₂O₂-induced tenocyte injury by enhancing viability, reducing apoptosis, and mitigating oxidative/inflammatory stress. These effects were mimicked by 17β-estradiol and reversed by the selective ERβ antagonist (R, R)-THC, indicating ERβ dependence. In vivo, AU treatment promoted structural and functional recovery, improved collagen maturity (increased Col I/Col III ratio and fibril diameter), suppressed matrix degradation (MMP-3, MMP-13) and apoptosis, and reduced oxidative stress and inflammation in tendon tissue. Conclusions: This study identifies aucubin as a novel phytoestrogenic compound from Eucommiae Cortex that promotes tendon repair through an ERβ-mediated mechanism. These findings position ERβ activation as a promising therapeutic strategy for tendinopathy and highlight AU as a promising lead compound for further development. Full article

Digital Light Processing (DLP), which operates through a layer-by-layer deposition, has proven to be a promising technique for obtaining complex and customized architectures. However, there are still numerous unresolved challenges in ceramics additive manufacturing, among which is delamination due to suboptimal adhesion between the layers, which threatens the structural integrity and properties of samples. According to recent findings, excess surface hydroxyl groups were identified as being responsible for this defect; a suitable calcination pre-treatment of the ceramic powder could be effective in significantly mitigating delamination flaws in mullite DLP printed bodies. Therefore, in addition to optimizing the printable slurry formulation and printing parameters (mainly in terms of curing energy and layer resolution), this work aimed at investigating the influence of the calcination of a commercial mullite powder (added with magnesium nitrate hexahydrate, as a precursor of the sintering aid MgO) as a simple and effective treatment to additively shape ceramic bodies with limited flaws and enhanced density. The surface characteristics evolution of the mullite powder was investigated, specifically comparing samples after magnesium nitrate hexahydrate addition and ball-milling in water (labeled as BM), and after an additional calcination (BMC). In particular, the effect of the superficial -OH groups detected by FTIR analysis in the BM powder, but not in the BMC sample, was studied and correlated to the properties of the respective ceramic slurry in terms of rheological behavior and curing depth. The hydrophilicity of BM powders, due to superficial hydroxyls groups, affects ceramic powder dispersion and wettability by the resin, causing a weak interface. At the same time, it promotes photopolymerization of the light-sensitive resin, thus inducing the as-printed matrix embrittlement. Anyhow, its photopolymerization degree, equal to 67% and 55% for BM and BMC, respectively, was enough to guarantee the printability of both slurries. However, the use of BMC significantly reduced flaw occurrence in the as-printed bodies and the final density of the samples sintered at 1450 °C (without an isothermal step) was increased (approx. 60% and 50% of the theoretical value for BMC and BM, respectively). Thus, the target porosity of the ceramic bodies was guaranteed, and their structural integrity achieved without any increase in sintering temperature but with a simple powder treatment. Full article

Tax incentives play a crucial role in enhancing firm dynamism and aiding a nation in becoming a significant trade power. Drawing on data from the Annual Survey of Industrial Firms Database and the Chinese Customs Database for the period 2010 to 2013, this study employs a difference-in-differences approach to assess the impact of China’s transition from a business tax to a value-added tax (RBTVAT) on the export diversification of manufacturing firms. The findings indicate that the tax reform significantly decreases the number of export categories, increases export value, and elevates the export unit price for manufacturing firms. Specifically, by promoting specialized production and encouraging the manufacture of products with higher export tax rebate rates, the reforms have led firms to narrow their range of export categories. This effect is particularly pronounced among firms experiencing higher financing constraints, lower profitability, weaker innovation capabilities, and larger size. Furthermore, a consistent negative impact is observed for both state-owned and non-state-owned enterprises. These results provide novel insights and empirical evidence for understanding the relationship between tax reform and export diversification. Full article

Speed breeding represents a pivotal technology for enhancing crop breeding efficiency. This study systematically examined the regulation of LED light environments, planting density, and gibberellic acid (GA₃) on rice growth cycle progression in plant factories, establishing an integrated speed breeding protocol. The experimental design comprised three components: (1) coupling seedling age (9–25 days, variety-dependent) with LED environments and planting densities (25–100 plants/tray); (2) combining light intensity gradients (450 and 900 μmol·m⁻²·s⁻¹) with photoperiod control; (3) applying GA₃ gradients (0–120 ppm) to enhance immature seed germination. Results indicated that high planting densities (>50 plants/tray) prolonged the growth cycle and decreased yield, whereas 25 plants/tray optimally balanced growth cycle shortening and yield maximization. Under short-day induction, Nipponbare (Nip) and Wufeng B (WFB) reached heading at 39 and 58 days after sowing (DAS), respectively. Stage-specific light responses were observed: 450 μmol·m⁻²·s⁻¹ during the basic vegetative phase (BVP) promoted morphological development, whereas 900 μmol·m⁻²·s⁻¹ during the photoperiod-sensitive phase (PSP) accelerated tillering and panicle differentiation. GA₃ treatment (60 ppm) enhanced the germination rate of immature seeds by 31%. The optimized lightregimes comprised natural light + 900 μmol·m⁻²·s⁻¹ (NL–900) and 450 μmol·m⁻²·s⁻¹ + 900 μmol·m⁻²·s⁻¹ (450–900), combined with density control (25 plants/tray) and GA₃-mediated immature seed utilization, shortened the generation time to 54 days and 70 days for Nip and WFB, respectively. This integrated protocol establishes an efficient strategy for rice speed breeding in plant factories. Full article

Background/Objectives: The arrangement and positioning of genes on chromosomes are non-random in plant genomes. Adjacent gene pairs often exhibit similar co-expression patterns and regulatory mechanisms. However, the genomic and epigenetic features influencing such co-expression, particularly in perennial crops like tea (Camellia sinensis), remain largely uncharacterized. Methods: Firstly, we identified 771 specific neighboring gene pairs (SNGs) in C. sinensis (YK10) and investigated the contributions of intergenic distance and gene length to SNGs’ co-expression. Secondly, we integrated multi-omics data including transcriptome, ATAC-seq, Hi-C and histone modification data to explore the factors influencing their co-expression. Thirdly, we employed logistic regression models to individually assess the contributions of nine factors—ATAC-seq, H3K27ac, Hi-C, GO, distance, length, promoter, enhancer, and expression level—to the co-expression of SNGs. Finally, by integrating co-expression networks with metabolic profiles, several transcription factors potentially involved in the regulation of catechin metabolic pathways were identified. Results: Intergenic distance was significantly negatively correlated with co-expression strength, while gene length showed a positive correlation. Furthermore, these two features exerted synergistic effects with threshold characteristics and functional significance. SNGs marked by either ATAC-seq or H3K27ac peaks displayed significantly higher expression levels, suggesting that epigenetic regulation promotes co-expression. In addition, correlation analysis revealed that the expression of certain SNGs was closely associated with catechin accumulation, particularly epicatechin gallate (EGC) and epigallocatechin gallate (EGCG), highlighting their potential role in modulating tissue-specific catechin levels. Conclusions: Collectively, this study reveals a multilayered regulatory framework governing SNG co-expression and provides theoretical insights and candidate regulators for understanding metabolic regulation in tea plants. Full article

Orthodontic tooth movement (OTM), a complex biological process driven by orchestrated bone remodeling, involves osteoclastic bone resorption and osteoblastic bone formation in response to mechanical force. Traditionally, OTM-related cell death has been discussed in terms of apoptosis and necrosis. However, recent advances in cell death research have revealed various forms of regulated cell death (RCD) beyond these conventional categories. This review summarizes the current understanding of the diverse RCD pathways and their roles in various cell populations during OTM. It delineates the involvement of distinct RCD mechanisms, including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis. On the compression side, these RCD pathways in periodontal ligament (PDL) cells, cementoblasts, cementocytes, and bone-related cells actively drive inflammatory responses, promote bone resorption, and contribute to root resorption. Conversely, on the tension side, specific RCD pathways, notably autophagy in the PDL and osteocytes, play crucial roles in promoting osteogenesis and tissue repair. Collectively, cell death is not merely a passive elimination of cells but actively functions as a critical switch for alveolar bone remodeling during OTM. Understanding these multifaceted RCD mechanisms provides novel insights into the biological regulation of tooth movement and identifies potential therapeutic targets for enhancing tooth movement efficiency and mitigating adverse effects. Full article

The strategic balance between strength and electrical conductivity in Al-Mg-Si alloys is a critical challenge that must be overcome to enable their widespread adoption as viable alternatives to copper conductors in power transmission systems. To address this, the present study comprehensively investigates model alloys with Mg/Si ratios ranging from 1.0 to 2.0. A multi-faceted experimental approach was employed, combining tailored thermo-mechanical treatments (solution treatment, cold drawing, and isothermal annealing) with comprehensive microstructural characterization techniques, including electron backscatter diffraction (EBSD) and scanning electron microscopy (SEM). The results elucidate a fundamental competitive mechanism governing property optimization: excess Mg atoms concurrently contribute to solid-solution strengthening via the formation of Cottrell atmospheres around dislocations, while simultaneously enhancing electron scattering, which is detrimental to conductivity. A critical synergy was identified at the Mg/Si ratio of 1.75, which promotes the dense precipitation of fine β″ phase while facilitating extensive recovery of high dislocation density. Furthermore, EBSD analysis confirmed the development of a microstructure comprising 74.1% high-angle grain boundaries alongside a low dislocation density (KAM ≤ 2°). This specific microstructural configuration effectively minimizes electron scattering while providing moderate grain boundary strengthening, thereby synergistically achieving an optimal balance between strength and electrical conductivity. Consequently, this work elucidates the key quantitative relationships and competitive mechanisms among composition (Mg/Si ratio), processing parameters, microstructure evolution, and final properties within the studied Al-xMg-0.5Si alloy system. These findings establish a clear design guideline and provide a fundamental understanding for developing high-performance aluminum-based conductor alloys with tailored Mg/Si ratios. Full article