Search Results (16,777)

Arsenic exposure increases lung cancer risk, yet its molecular mechanisms remain unclear but are linked to peroxisome proliferator-activated receptor gamma (PPARγ). We investigated PPARγ-related molecules affected by sodium arsenite (NaAR) in non-small cell lung cancer (NSCLC) cells using immunochemical, gene knockdown, and immunoprecipitation approaches. PPARγ was critical for NSCLC growth, as high PPARγ-expressing A549 cells proliferated more than low-expressing H1299 cells after NaAR treatment. In A549 cells, NaAR upregulated polyubiquitinated PPARγ, activating cell cycle arrest and DNA damage response pathways. Rather than inducing significant caspase-dependent apoptosis, NaAR activated nuclear factor-kappa B and downregulated mixed lineage kinase domain-like (MLKL) via K63-linked polyubiquitinated receptor-interacting protein kinase 1, thereby inhibiting apoptosis and necroptosis. PPARγ knockdown or NAD⁺ supplementation induced PARP-1 hyperactivation and MLKL upregulation, leading to DNA damage and necroptosis. PARP-1 inhibition by 3-aminobenzamide induced apoptosis, indicating that PPARγ regulates apoptosis and necroptosis through PARP-1 activation. Proteasome inhibition increased polyubiquitinated PPARγ but not p53. Leptomycin B induced PPARγ degradation and p53 accumulation, promoting necroptosis and apoptosis, suggesting cytoplasmic p53 contributes to cell death. p62 interacted with PPARγ and p53, and its knockdown suppressed their NaAR-induced upregulation. In conclusion, NaAR-induced PPARγ promotes A549 cell survival by enhancing DNA repair and inhibiting apoptosis and necroptosis via cooperation with p53 and p62, highlighting PPARγ as a potential therapeutic target. Full article

Background/Objectives: Metabolic diseases are increasingly associated with diets low in bioactive compounds. Native maize varieties possess functional potential; however, they remain underutilized. Moringa oleifera leaf flour (MF), rich in protein and polyphenols, represents a promising functional ingredient. This study evaluated the incorporation of MF into red native corn tortillas and its effects on nutritional composition and antioxidant capacity, as well as assessed its hypoglycemic and hypolipidemic effects in Wistar rats. Methods: Tortillas were formulated with 5% MF. Nutritional composition was determined using standard AOAC methods, while bioactive compounds (total phenolics and flavonoids) and antioxidant activity were evaluated using Folin–Ciocalteu, aluminum chloride (AlCl₃) colorimetric, DPPH^•, and ABTS^•+ assays, respectively. Male Wistar rats (12 weeks old, with an approximate weight ofs 360 g; n = 5/group) were fed the experimental diets for 21 days with either a standard diet, a high-fat diet, or high-fat diets supplemented with MF or MF-enriched tortillas. Serum glucose, triglycerides, total cholesterol, and HDL were measured using enzymatic colorimetric methods. Data were analyzed by ANOVA followed by Tukey’s test (p < 0.05). Results: MF incorporation increased protein (+19.85%), dietary fiber (+18.51%), and mineral content (+41.03%) compared to control tortillas. Total phenolics and flavonoids increased by 114.0% and 184.7%, respectively. Antioxidant activity improved significantly, as evidenced by reductions in IC₅₀ values of 41.1% (DPPH^•) and 43.1% (ABTS^•). In vivo, MF-enriched tortillas reduced triglycerides by 68.4%, total cholesterol by 16.2%, and hepatic lipid accumulation by 31.8% compared to the high-fat diet group. Glucose levels showed a reduction of 8.5%, although not statistically significant (p > 0.05). Conclusions: The incorporation of MF into red corn tortillas significantly enhances their nutritional and functional properties. In vivo results also showed improvements in lipid profile and a non-significant reduction in glucose levels. These findings support the development of functional foods based on traditional staples with potential health benefits. Full article

The deep integration of the Internet of Things (IoT) and blockchain technology enables emerging applications in multi-party collaboration and trusted data sharing. However, the scalability constraints of blockchain networks remain a major bottleneck when handling high-frequency interactions in IoT–blockchain systems. Sharding addresses this challenge by partitioning the blockchain network into parallel sub-networks. Nevertheless, it introduces significant coordination overhead for cross-shard transactions. Among mitigation strategies, Broker-based mechanisms (e.g., BrokerChain) have attracted increasing attention for their efficiency in handling cross-shard communication by reducing verification overhead and communication latency. Despite these advantages, existing research typically treats the Broker group as a fixed configuration, neglecting the impact of Broker selection on system performance. To bridge this gap, this paper proposes the Accumulative Activity–Temporal Liveness Broker Selection Strategy (AT-BSS) to optimize cross-shard transaction processing in sharded IoT–blockchains. Specifically, we formally characterize the Accumulative Activity and Temporal Liveness of accounts in the account–transaction network and use these two metrics to identify accounts that maximize transaction-aggregation efficiency. We implement AT-BSS on the BlockEmulator platform and evaluate it against two baselines, namely, ABChain and BrokerChain. Under different settings of the number of Brokers (BrokerNum), number of shards (ShardNum), transaction arrival rate (InjectSpeed), and maximum block size (MaxBlockSize), AT-BSS consistently outperforms both baselines in terms of Transactions Per Second (TPS), Transaction Confirmation Latency (TCL), and Cross-shard Transaction Ratio (CTX). Compared with ABChain, AT-BSS achieves up to 15.5% higher TPS and reduces TCL and CTX by up to 80.2% and 28.7%, respectively. AT-BSS yields more pronounced results over BrokerChain, with TPS improvements of up to 229% and reductions of up to 97.7% in TCL and 80.5% in CTX. Full article

Olive mill wastewater (OMWW) is a highly polluting agro-industrial effluent characterized by elevated organic load, low pH, and high concentrations of phenolic compounds responsible for its phytotoxicity and dark coloration. In this study, 41 non-conventional yeast strains belonging to the University of Basilicata Yeast Collection (UBYC), were tested for both the oleaginous potential traits and OMWW detoxification capacity in comparison to two commercial oleaginous controls, Yarrowia lipolytica ATCC 46483 and Lipomyces tetrasporus Li-0407. Primary screening in synthetic medium under nitrogen-limited conditions revealed widespread intracellular lipid accumulation. Quantitative analysis showed lipid contents above 20% (w/w) in some strains, with Candida tropicalis AII122 (33.3%) and Pichia manshurica ML-3 (29.4%) exhibiting the highest values in synthetic medium. The cultivation of eight selected strains in synthetic medium supplemented with 15% (v/v) of OMWW reduced intracellular lipid accumulation, with the highest value of 6.48% for the 2R1 strain. Levels of phenol reduction and color removal were highly different among all the analyzed strains, and C. tropicalis AII122 achieved the highest phenolic reduction and decolorization ability. These findings demonstrate that indigenous non-conventional yeasts represent a source of natural biodiversity, supporting sustainable waste valorization strategies based on the use of selected microorganisms within a circular bioeconomy framework. Full article

Roselle beverage residue (RBR), a by-product of Hibiscus sabdariffa L. processing, retains bioactive compounds, including soluble and insoluble dietary fiber and polyphenols. Its antihyperglycemic effect in type 2 diabetes mellitus (T2DM) has been previously demonstrated; however, its role in lipid metabolism remains unknown. This study assessed the preventive and therapeutic potential of RBR on dyslipidemia and hepatic steatosis in a rodent model of late-stage T2DM characterized by hyperglycemia and hypoinsulinemia. Male Wistar rats with T2DM induced by a high-fat and high-fructose diet combined with streptozotocin received 6% RBR supplementation as either a preventive intervention (starting at week 1 in healthy rats or week 9 in insulin-resistant rats) or a therapeutic intervention (starting at week 14 in diabetic rats). After 17 weeks, RBR supplementation significantly reduced serum triglycerides and total cholesterol, attenuating hepatic lipid accumulation regardless of the timing of intervention. Hepatic Acadm expression, involved in fatty acid β-oxidation, was significantly upregulated in rats treated with RBR from week 1 and 9, whereas no significant modulation was observed for genes related to fatty acid synthesis or uptake. These findings suggest that RBR supplementation may contribute to improving lipid metabolism and hepatic steatosis in a rat model of late-stage T2DM. Full article

Background and Objectives: Systemic mastocytosis (SM) is a clonal mast cell disorder characterized by abnormal mast cell accumulation and activation in multiple organs, leading to mediator-related symptoms, including anaphylaxis. Drug hypersensitivity reactions (DHRs) are a major clinical challenge in SM, but their frequency and characteristics remain undefined. This study aimed to evaluate the frequency of drug allergy, identify high-risk drug groups, investigate reaction characteristics, and examine the relationship between drug reactions, baseline serum tryptase levels, and SM subtypes in patients with SM. Materials and Methods: We retrospectively analyzed 34 patients diagnosed with SM between 2009 and 2024 at Ege University Faculty of Medicine. Clinical features, SM subtypes, baseline serum tryptase levels, and DHR characteristics were recorded. Reactions to antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, anesthetics, radiocontrast media (RCM), and COVID-19 vaccines were graded using the Ring and Messmer anaphylaxis classification. Results: Among 34 patients, the mean age was 48.6 ± 13.3 years, 53% were male, and 10 (29.4%) had DHRs. The most common culprit drugs were NSAIDs (17.6%) and β-lactam antibiotics (14.7%). Anaphylaxis was the predominant reaction, frequently associated with hypotension. In 5 patients (14.7%), drug-induced anaphylaxis was the initial and only manifestation of SM. No hypersensitivity reactions occurred to quinolones, general anesthetics, or COVID-19 vaccines. Median baseline tryptase was 50.25 µg/L (min–max: 8.59–200.00) overall, and 41.85 µg/L (min–max: 19.00–200.00) among those with DHRs. Conclusions: Patients with SM are at increased risk of severe DHRs, particularly to NSAIDs and beta-lactam antibiotics. In some patients, drug allergy may be the first and only manifestation of SM. Measurement of baseline serum tryptase is essential in patients with drug-induced anaphylaxis. A comprehensive allergy assessment, including tolerance testing and individualized counseling, is crucial to ensure safe pharmacological management. Full article

Excessive acidity restricts the utilization of citrus pulp, a major by-product of the dried tangerine peel industry. To overcome this bottleneck, a functional microbial consortium (BsHpMrF) comprising Bacillus subtilis L4, Hanseniaspora pseudoguilliermondii B4, and Monascus ruber CGMCC 10910 was constructed for efficient biological deacidification. The consortium exhibited a synergistic effect, achieving an 88.23% reduction in total acidity and converting the acidic pulp into a neutral, bio-stabilized substrate. Untargeted metabolomics analysis revealed that this efficiency was driven by the concurrent activation of the TCA cycle and glyoxylate shunt for organic acid mineralization, coupled with membrane lipid remodeling (increased unsaturation) to enhance acid tolerance. Notably, the fermentation process functioned as a “metabolic factory”, significantly enriching the matrix with bioactive lipids (e.g., 10-HDA, nervonic acid) and indole-3-acetic acid (IAA, 414.28 mg/L). Application assays demonstrated that the fermentation products acted as a potent biostimulant for soybean sprouts, significantly promoting lateral roots and eliciting the accumulation of antioxidant phenolics and flavonoids. This study provides a sustainable “waste-to-treasure” strategy, valorizing acidic citrus pulp into a functional biostimulant for high-quality edible sprout production, thereby achieving a sustainable “waste-to-food” circular loop. Full article

Fruit volatile organic compounds (VOCs) are key determinants of plum flavor quality, and esters contribute strongly to the fruity aroma of ripe fruit. However, the molecular basis of cultivar differences in ester formation during ripening has not been systematically clarified. Here, we characterized pulp VOC profiles across ripening in three Chinese plum (Prunus salicina) cultivars (‘WeiWang’ (WW), ‘WeiDi’ (WD), and ‘KongLongDan’ (KLD)) and integrated transcriptome analysis with weighted gene co-expression network analysis (WGCNA) to identify genes associated with ester accumulation. HS-SPME-GC-MS identified 38 VOCs, mainly esters, aldehydes, and alcohols, with ‘WW’ showing the highest total VOC abundance. During ripening, esters became the predominant volatile class in ‘WW’ and ‘WD’, in agreement with their fruity sensory characteristics, whereas ‘KLD’ maintained a more balanced composition of fruity and green-related volatiles. Transcriptomic analyses highlighted Prunus salicina alcohol acyltransferase 3 (PsAAT3) as the most abundant AAT transcript in pulp and strongly induced in ‘WW’. Transient overexpression of PsAAT3 in the low-ester background increased butyl acetate and hexyl acetate by 4.8- and 2.2-fold, respectively. WGCNA further identified ester-associated modules and candidate transcription factors co-expressed with PsAAT3 (JA2L, HY5, NAC073, and PHL13). As a result, this study identifies PsAAT3 as a key determinant of high-ester aroma in Chinese plum and provide candidate targets for aroma improvement and flavor-oriented breeding. Full article

The platformization of urban space is opening new frontiers of capital accumulation, particularly through short-term rentals. Airbnb plays a central role in this process by commodifying housing in tourist destinations. Despite its rapid growth, research on Airbnb in Latin America—especially in small tourist cities—remains limited and largely focused on metropolitan contexts. This article addresses this gap with the objective of analyzing how platform-mediated short-term rentals reorient housing markets beyond traditional urban cores. It is hypothesized that Airbnb expands housing commodification by extending tourism-oriented uses into new residential areas and by redistributing returns unevenly across actors. Using a quantitative and geospatial approach, the results reveal a strong presence of Airbnb in rural and natural areas, from which the highest returns are extracted, as well as a high concentration of accommodation supply among professional hosts. These dynamics reconfigure housing use toward asset-based logics, posing challenges for housing security and social and territorial sustainability in small tourist cities. Full article

Stevia is a natural source of high-intensity sweeteners, collectively known as steviol glycosides (SG), which are approximately 300 times sweeter than sucrose and widely used as sugar substitutes. This study examines the impact of five different red-to-blue (R:B) light ratios on SG content and yield in hydroponic Stevia across four growth stages. Results indicate that the highest and lowest leaf dry weights were recorded in the R1B0 (R:B = 1:0) and R0B1 (R:B = 0:1) groups, at 2.88 and 1.98 g/plant, respectively, reflecting a 45.45% difference. The total SG content in dried leaves was highest in R0B1 (196.32 mg/g) and lowest in R1B0 (115.16 mg/g), with a 70.48% variation. The highest and lowest total SG yields (YSG) per square meter were observed in R0B1 (46.56 g/m²) and R50B37 (35.70 g/m²), differing by 30.42%. Stage-specific optimal YSG values were identified, with designated growth stages P1 (early vegetative growth phase), P2 (early leaf development phase), and P3 (late leaf development phase) favoring R4B1 and P4 (leaf senescence phase) favoring R0B1. These findings suggest an optimized lighting strategy for the four growth stages of hydroponic Stevia, sequentially applying R4B1, R4B1, R4B1 and R0B1 to enhance biomass accumulation and SG production at different developmental stages. Full article

Bovine mastitis is a multifactorial inflammatory disease primarily characterized by inflammatory cell infiltration and the destruction of mammary alveoli. It is a major cause of reduced milk yield and quality. The imbalance between antioxidant defenses and the generation of reactive oxygen species (ROS), which occurs due to the high metabolic activity of the mammary gland during the periparturient period, increases the incidence of mastitis. During early lactation, especially in high-yielding dairy cows, the massive synthesis and secretion of milk increase the energy demand of mammary tissue, leading to excessive ROS accumulation. This results in cell membrane disruption and, ultimately, antioxidant dysfunction in the mammary tissue. This study established an in vitro oxidative stress model by treating bovine mammary epithelial cells (BMECs) with 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH). The optimal concentration of 1000 μmol/L AAPH was determined using the CCK-8 assay. Model validation showed that, compared to the control group, ROS levels were significantly elevated (p < 0.001) and mitochondrial membrane potential was significantly decreased (p < 0.001) in the AAPH-treated group. Transmission electron microscopy (TEM) analysis revealed that AAPH treatment caused ultrastructural damage, including reduced microvilli, mitochondrial swelling, disappearance of cristae, and vacuolization. Mechanistic studies demonstrated that AAPH treatment significantly upregulated the mRNA and protein expression of AMPK, HMOX-1, mTOR, NOS, and SOD (p < 0.001), while significantly downregulating CYP1A1 expression (p < 0.001). Pretreatment with N-acetylcysteine (NAC) effectively alleviated the oxidative stress damage caused by AAPH. This study successfully established an in vitro AAPH-induced oxidative stress model in BMECs and revealed its molecular mechanism of cellular damage. The damage occurs through modulation of the AMPK/mTOR signaling pathway and the regulation of antioxidant-related gene expression. Full article

Permanent magnet synchronous motor (PMSM)-based servo actuators are fundamental to high-performance electromechanical systems. However, in energy-sensitive aerospace applications, the impact of tracking error on system-level efficiency remains insufficiently quantified. This paper establishes an energy-oriented analytical framework linking PMSM tracking accuracy to vehicle-level energy consumption and flight range. By employing a specific mechanical energy formulation, we demonstrate that tracking deviations modify aerodynamic drag and introduce additional dissipative work. Specifically, the accumulated dissipation is shown to admit a lower bound proportional to the integral of the squared tracking error, from which a range degradation bound is derived. These results reveal that “tracking-error energy” imposes a fundamental limit on achievable flight distance. A Lyapunov-based analysis further proves that minimizing this error energy reduces total aerodynamic dissipation without requiring modifications to propulsion scheduling or guidance laws. Numerical simulations comparing a conventional sliding mode controller with an advanced fuzzy-adaptive nonsingular terminal sliding mode controller confirm that enhanced servo precision directly improves velocity retention and range performance. This framework offers practical insights for designing energy-aware PMSM control strategies in energy-constrained aerospace platforms. Full article

This study integrates physical similarity experiments with numerical simulations to examine how overburden lithology influences roof caving behavior and stress field evolution at a longwall mining face. The results demonstrate that overburden strength significantly governs the timing, extent, and periodicity of roof caving, while also strongly affecting the evolution of mining-induced stress. As lithological strength increases, both damage and displacement within the overburden strata decrease. High-strength roofs exhibit larger caving step distances and longer stress accumulation periods. In contrast, low-strength roofs enter the plastic deformation stage earlier, leading to shorter caving step distances, more frequent caving events, and a wider caving range. During coal seam extraction, roof deformation is accompanied by stress concentration and release, which are processes that are closely associated with dynamic disasters. Due to their higher elastic modulus and compressive strength, high-strength rock strata can accumulate greater elastic strain energy prior to failure. Once instability occurs, the rapid release of stored energy leads to intense stress redistribution and dynamic loading. As lithological strength increases, the stress concentration shell evolves from an arch-shaped structure to a flatter configuration. This transition results in higher internal stress levels and stronger stress concentration, thereby increasing the risk of dynamic disasters such as impact instability. Therefore, maintaining the stability of the stress concentration shell and preventing its migration into deeper strata are essential for ensuring surrounding rock stability and safe mining operations. Full article

Achieving high-level self-reliance in science and technology requires a science and technology finance ecosystem that is aligned with the needs of technological innovation. To overcome bottlenecks in core technologies, firms must accelerate R&D, strengthen their core competitiveness, and pursue innovation-led, quality-oriented development. Using provincial-level data for 2013–2023, this paper constructs an index system for China’s science and technology finance ecosystem from four dimensions: science and technology financial services, science and technology capital markets, science and technology financial organizations, and government guidance for science and technology. We then measure the development level of this ecosystem and employ a panel data model to examine its impact on innovation in Specialized and Sophisticated SMEs. The results show that a more developed science and technology finance ecosystem significantly promotes innovation in these firms, with a stronger effect on substantive innovation than on strategic innovation. These findings remain robust across a series of robustness checks. Further analysis reveals significant heterogeneity across regions and levels of government intervention: the positive effect is stronger in eastern China and in regions with weaker government intervention. Mechanism tests indicate that the science and technology finance ecosystem promotes innovation by facilitating the accumulation of R&D capital and the agglomeration of scientific and technological talent. This study enriches the literature on science and technology finance ecosystems and SME innovation, and provides policy-relevant evidence for ecosystem development and the cultivation of Specialized and Sophisticated SMEs. Full article

Human serum albumin (HSA) is the most abundant protein in plasma, and the redox state of circulating HSA has been used as a biomarker of systemic oxidative stress (OS) for decades. While informative, many traditional biomarkers of OS measure short-lived or downstream products of oxidative damage that offer limited perspectives on the dynamic and integrated processes that govern systemic redox biology within human populations. By moving beyond single-analyte damage markers and towards coordinated patterns of protein modifications, HSA-Cys³⁴ adductomics offers a systems-level approach that simultaneously captures change in multiple layers of OS. Because of its high abundance in plasma and HSA’s unique and highly reactive single free thiol (Cys³⁴), HSA-Cys³⁴ serves as an ideal sentinel target for monitoring reactions with reactive oxygen species (ROS), reactive nitrogen species (RNS), and electrophilic species produced by endogenous metabolism and responses to exogenous chemical exposures. The reaction of HSA with ROS, RNS, and reactive electrophiles yields a diverse array of protein modifications, including direct oxidation products (sulfenic, sulfinic, and sulfonic acid), low molecular weight thiol-disulfide exchange, and lipid peroxidation (LPO)-derived reactive aldehydes. With a mean residence time of about a month, these accumulated adducts serve as an integrated picture of oxidative and electrophilic stress that together function as a molecular record of systemic redox physiology. Previous studies using high-resolution mass spectrometry-based adductomics have enabled global untargeted analysis of HSA-Cys³⁴ modifications, yielding an expansive inventory of novel redox signatures of environmental stressors and disease states. In this paper we review the chemistry and biology underlying OS-related modifications of HSA-Cys³⁴ and highlight the important role of HSA-Cys³⁴ adducts as integrative biomarkers of OS at the interface of molecular biology, exposure assessment, and public health research. Full article