Search Results (6,600)

SOX (SRY-related HMG-box) transcription factors are key regulators of embryogenesis and vascular development, with emerging roles in cancer biology. In non-small-cell lung cancer (NSCLC), the contributions of SOX18 and SOX30 remain insufficiently understood, particularly regarding their epigenetic regulation and network interactions with angiogenic and immune-modulatory pathways. We examined 800 NSCLC specimens (400 lung adenocarcinomas, 400 squamous cell carcinomas) using immunohistochemistry, RT-qPCR, Western blotting, and spatial transcriptomics to profile SOX18, SOX30, and related signaling partners (SOX7, SOX17, MEF2C—Myocyte Enhancer Factor 2C, VCAM1—Vascular Cell Adhesion Molecule 1, p-STAT3—Signal Transducer and Activator of Transcription 3). Epigenetic regulation was assessed via droplet digital methylation-specific PCR of promoter CpG islands, while functional validation employed adenoviral delivery of hsa-miR-24-3p in NSCLC cell lines and 3D spheroid cultures. SOX18 protein was markedly overexpressed in both NSCLC subtypes, despite reduced transcript levels and consistent promoter hypermethylation, suggesting post-transcriptional regulation. In contrast, SOX30 expression was uniformly downregulated at both mRNA and protein levels, frequently linked to promoter hypermethylation, especially in squamous carcinoma. Spatial transcriptomics revealed SOX18 enrichment at tumor cores and invasive borders, co-localizing with MEF2C, VCAM1, and p-STAT3 in vascular and stromal niches, while SOX30 expression remained low across all tumor regions. Functional assays demonstrated that hsa-miR-24-3p suppressed SOX18 expression and partially modulated SOX30 and MEF2C, reinforcing a miRNA-driven regulatory axis. In summary, SOX18 and SOX30 play divergent roles in NSCLC progression: SOX18 functions as a pro-oncogenic factor driving angiogenesis and tumor–stroma interactions, while SOX30 acts as an epigenetically silenced tumor suppressor. Regulation of SOX18 by miR-24-3p highlights a potential therapeutic vulnerability. These findings underscore the significance of SOX transcription factors as biomarkers and potential targets for novel treatment strategies in NSCLC. Full article

This study aimed to investigate the chemical composition, antioxidant activity, and in vitro antidiabetic properties of extracts obtained from ripe, unripe, and fermented (unripe) cornelian cherry (Cornus mas L.) fruits. Polyphenols were identified using UPLC-ESI-qTOF-MS/MS and quantified by HPLC-PDA. Antioxidant activity was evaluated using ABTS, DPPH, and FRAP assays, while enzyme inhibitory activity was determined for α-glucosidase and α-amylase. Additionally, the effects of C. mas extracts on insulin sensitivity in adipocytes were investigated. The study’s results showed that each of the extracts tested contained varying proportions of substances with proven health-promoting properties. The extract from ripe fruits was characterized by the highest loganic acid content, whereas the extract from fermented unripe fruits contained a high amount of gallic acid, released through the hydrolysis of tannins during fermentation. The extract from unripe fruits exhibited the highest tannin content and the strongest antioxidant activity. All extracts inhibited α-glucosidase and α-amylase to a similar extent and improved insulin-stimulated glucose uptake in 3T3-L1 adipocytes without affecting INSR or SLC2A4 expression. In conclusion, extracts from unripe and fermented C. mas fruits may represent promising agents for alleviating insulin resistance and preventing type 2 diabetes. Full article

Staphylococcal enterotoxins (SEs), particularly enterotoxin C (SEC), are potent superantigens primarily known for causing food poisoning, but recent studies have highlighted their potential role in immune-mediated intestinal diseases. Despite the widespread use of food preservatives, their influence on SEC production—especially from coagulase-negative staphylococci (CNS)—remains poorly understood. In this study, we evaluated the effects of commonly used preservatives, including sodium chloride, potassium nitrate, and sorbic acid, on the expression and production of SEC₃ and SEC_epi in Staphylococcus aureus and S. epidermidis, respectively. Using ELISA and RT-qPCR, we analyzed toxin levels at both the protein and mRNA levels. Proliferation assays on human PBMCs assessed the mitogenic potential of culture supernatants. While sodium chloride and potassium nitrate did not significantly alter SEC levels or bacterial growth, only sorbic acid at 0.07% consistently inhibited both mRNA expression and protein production of SEC₃ and SEC_epi. Furthermore, supernatants from sorbic acid-treated cultures induced significantly lower PBMC proliferation. These results suggest that even sub-emetic concentrations of enterotoxins may have immunomodulatory effects, and sorbic acid could be a promising agent in mitigating such risks. Full article

This study evaluated hot-water infusion as a practical and sustainable extraction method for functional flower petal teas. Six edible flowers—Tagetes erecta, Lonicera japonica, Celosia argentea var. cristata, Centaurea cyanus, Hibiscus sabdariffa, and Malva sylvestris—were compared under hot-water and 80% ethanol extraction. Hot-water extraction was performed at 100 °C for 15 min. Hot-water extracts showed 1.3–4.0 times higher total phenolic content (TPC) and stronger antioxidant activities (ABTS, DPPH, and FRAP) than 80% ethanol extracts, reflecting efficient extraction of hydrophilic phenolic acids. UPLC-ESI-Q-TOF-MS and GC–MS analyses of hot-water extracts revealed chlorogenic acid, caffeic acid, coumaric acid derivatives, flavonoid glycosides, and aroma volatiles such as hexanal and α-pinene. These findings confirm that simple hot-water infusion effectively recovers both bioactive and aroma-active compounds, supporting its application in developing safe, natural, and functional flower teas. Full article

The construction industry faces urgent challenges in reducing its carbon footprint, particularly in geotechnical engineering where conventional methods often involve high-emission materials. Artificial Ground Freezing (AGF) presents a sustainable, material-saving alternative for stabilizing water-rich strata, but its efficiency relies on accurate characterization of frozen soil behavior under in situ conditions. This study advances the understanding of AGF’s sustainability by investigating the directional shear behavior of pressurized frozen saturated medium sand (Fujian ISO standard sand) at −10 °C using a novel hollow cylinder apparatus. Through systematic testing under varying mean principal stresses (p = 0.5–6 MPa) with fixed intermediate principal stress coefficient (b = 0.5) and principal stress direction (α = 30°), we demonstrate that pressurized freezing creates a fundamentally different soil–ice composite compared to conventional unpressurized freezing. Key findings reveal (1) a linear strength increase described by the failure criterion q_f = 1.17p + 3.77 (R² = 0.98) without pressure melting effects within the tested range; (2) a distinct brittle-to-ductile transition at p ≈ 4 MPa, with associated failure mode changes from localized shear bands to homogeneous plastic flow; (3) a stable peak stress ratio (q/p ≈ 1.8) for p ≥ 4 MPa. These findings enable more reliable and potentially less conservative frozen wall design, directly contributing to reduced energy consumption in AGF operations. The research provides mechanical insights and practical parameters that enhance AGF’s viability as a low-carbon ground stabilization technology, supporting the construction industry’s transition toward sustainable underground development. Full article

Cold-water fish, particularly stenothermal species, are increasingly affected by rising temperatures driven by global warming. To explore the hepatic metabolism mode of Amur grayling under warming, Thymallus grubii was selected as the experimental model. Here, we measured the oxygen consumption rate (MO₂), energy metabolism enzymes, and transcription profiling in Thymallus grubii that was exposed to increased temperatures (9, 12, 15, 18, 21, and 24 °C) with the same flow velocity (34 cm/s). In this study, MO₂ initially increased and then decreased with rising temperature, with peak sensitivity between 12 and 15 °C (Q₁₀ = 5.30). Hemoglobin increased significantly at 12–18 °C but decreased in the 18–24 °C group (p < 0.05). Additionally, hepatic glycogen content (the amount of stored sugar in the liver, which serves as an energy reserve) also first increased and then decreased markedly (p < 0.05). Lactic acid in plasma and muscle contents increased, but creatine phosphate and glucose levels significantly decreased (p < 0.05). The result of transcriptome analysis showed that individuals in the 15 °C group could supply energy through glucose and amino acid metabolism. In contrast, individuals under 21 °C exposure could mainly supply energy through the lipid metabolism pathway. Our study underscores the vulnerability of Amur grayling to environmental temperature and identifies the instantaneous metabolic limit range, providing numerical limits (e.g., maximum river temperature) that managers can use to protect wild populations. Full article

Background: Kawasaki Disease (KD) is an acute vasculitis affecting children under five years of age, with atypical presentations posing diagnostic challenges and a higher risk of coronary complications when untreated. Methods: We report on a 2-year-old girl with persistent fever, limb edema, erythema, and non-purulent conjunctivitis, without cervical lymphadenopathy or the typical rash. Inflammatory markers were assessed, and a cytokine expression profile was obtained using qRT-PCR. Results: Laboratory analysis showed elevated C-reactive protein (11.1 mg/dL), high fibrinogen (468 mg/dL), borderline D-dimer (484 ng/mL), and a normal platelet count. The cytokine profile revealed marked upregulation of IFN-α, IFN-β, IFN-γ, IL-1α, IL-1β, IL-5, IL-8, and IL-12, with downregulation of IL-2 and IL-4, as well as low TNF-α levels. These findings, although not pathognomonic, were consistent with an inflammatory profile compatible with atypical KD, in which a preceding viral infection may have played a role, although causality cannot be established. Conclusions: This case highlights the diagnostic utility of cytokine profiling in suspected atypical KD, particularly when clinical criteria are incomplete. The integration of immunological data may aid in earlier recognition and therapeutic intervention, thereby helping to prevent cardiovascular sequelae. Cytokine analysis may serve as a promising adjunct for atypical KD diagnosis, although confirmation in larger cohorts is needed. Full article

The inverter is the key element that converts the intermittent DC power of the PV array into a quality AC flow to the grid and simultaneously performs functions such as power factor control, reactive services, and grid code compliance. Therefore, the detailed operating profile of the inverter, how the power, dynamics, power quality, and efficiency evolve over time, is critical for both the scientific understanding of the system and the daily operation (O&M). Monitoring only aggregated energy indicators or single KPIs (e.g., PR) is often insufficient: it does not distinguish weather-related variations from technical limitations (clipping, curtailment), does not show dynamic loads (ramp rate), and does not provide confidence in the quality of the injected energy (PF, P–Q behavior). These deficiencies motivate research that simultaneously covers the physical side of the conversion, the operational dynamics, and the climatic reference of the resource. The analysis covers the window of 25 January–15 April 2025 (winter→spring). Due to the pronounced seasonality of the solar resource and temperature regime, all quantitative results and conclusions regarding efficiency, dynamics, clipping, and degradation are valid only for this window; generalizations to other seasons require additional data. In the next stage, we will add ≥12 months of data and perform a comparable seasonal analysis. Full specifications of the measuring equipment (DC/AC current/voltage, clock synchronization, separate high-frequency $PQ$-logger) and quantitative uncertainty estimates, including distribution to key indicators ($\eta$, $PR$, $THD$, $I_{DC}$), are presented. The PVGIS per-kWp climate reference is anchored to the nameplate DC peak and cross-checked against percentile scaling; $a\pm \epsilon$ scale error shifts $PR$ by $\epsilon$ and changes $\Delta E$ proportionally only on hours with $\widehat{P}>P$. The capacity for the climate reference (PVGIS per-kWp) is calibrated to the tabulated DC peak power $C_{cert}$ and is cross-validated using a percentile scale ($Q_{0.99}$). Full article

Background/Objectives: Silodosin (SLD) is a selective α1A-adrenoceptor antagonist used in the treatment of benign prostatic hyperplasia. Bioequivalence failures have been reported for hard capsule formulations, largely due to the effect of disintegrant excipients, making soft capsules a promising alternative dosage form. This study investigated the stability of SLD soft capsules stored in two different packaging materials, PVC/PVDC and AquaBa^®. Methods: Storage temperatures at 25 °C/60%, 30 °C/65% RH, 30 °C/75% RH, and 40 °C/75% RH, and sampling were performed according to the International Council for Harmonisation (ICH) stability conditions. Assays were performed by HPLC and UV, and mass detection. Results: Degradation analysis revealed that temperature played a critical role in SLD degradation and the formation of its primary degradation products, dehydrosilodosin and impurity 1. Conclusions: AquaBa^® demonstrated superior protective properties compared to PVC/PVDC, preserving SLD content above 95% for over 12 months under 25 °C and 30 °C conditions while limiting the formation of degradation products. Nevertheless, impurity 1 exceeded its ICH Q3B (R2) specification limit (0.3%) after six months under all conditions tested, suggesting a critical interaction between SLD and excipients such as Capryol^® 90. Kinetic modeling confirmed first-order degradation kinetics for both dehydrosilodosin and impurity 1, with a faster degradation rate observed in PVC/PVDC blisters. These findings highlight the critical role of packaging in pharmaceutical stability. While AquaBa^® emerges as the preferred option for SLD soft capsules, formulation optimization remains necessary to limit impurity formation, extend shelf life, and ensure regulatory compliance. Full article

Ferroelectricity in hafnium oxide (HfO₂)-based thin films has emerged as a scalable pathway toward CMOS-compatible non-volatile memories and logic devices. This study examines how dopant chemistry and film thickness influence the stabilization of the ferroelectric phase in ALD-grown HfO₂ thin films doped with Zr, Al, and Y. Structural, morphological, and electrical characterizations were carried out using AFM, GIXRD, P–E, in-plane I/W–E, and C–V measurements on films with thicknesses of 7 nm and 100 nm. AFM revealed atomically smooth and dense surfaces (R_q < 0.5 nm), while GIXRD confirmed the stabilization of the orthorhombic Pca2₁ phase in doped 7 nm films and its relaxation toward the monoclinic phase at 100 nm. The 7 nm HfZrO and HfYO films exhibited robust ferroelectric hysteresis with remanent polarization values up to 60 μC·cm⁻², whereas HfAlO showed a narrower but still distinct switching response. In-plane I/W–E characteristics indicated a combination of Poole–Frenkel and injection-limited conduction, consistent with defect-assisted polarization reversal and asymmetric contact barriers. At 100 nm, all films showed reduced polarization and partially dielectric behavior, as corroborated by the C–V data. These results demonstrate that nanoscale confinement, dopant-induced strain, and oxygen vacancy related defect chemistry collectively stabilize the orthorhombic ferroelectric phase, with Zr doping providing the most favorable balance between polarization strength and leakage control. Full article

In 2023, the detection rate of porcine rotavirus (PoRV) surpassed that of porcine epidemic diarrhea virus (PEDV) for the first time, establishing PoRV as the predominant pathogen responsible for viral diarrhea in pigs. To systematically investigate the epidemiology and molecular characteristics of PoRV in Southwest China, a total of 196 diarrheal clinical samples were collected from 29 large-scale pig farms across the region during 2024–2025. RT-qPCR results revealed a high PoRV positivity rate of 57.14% (112/196) with group A porcine rotavirus (PoRVA) being the most prevalent at 46.43%, representing the predominant group. Genotyping and phylogenetic analysis of the VP4 and VP7 genes indicated that the P genotype P[13] was most prevalent (77.78%, 21/27), while the major G genotypes were G4 (39.28%) and G9 (35.71%). The most common G/P combinations were G9P[13] and G4P[13]. Furthermore, a PoRV strain was successfully isolated and identified through whole-genome sequencing, indirect immunofluorescence assay (IFA), and transmission electron microscopy (TEM). The isolate was designated RVA/Pig-wt/SCLS-JW/2024/G1P[7], with a whole-genome constellation of G1-P[7]-I5-R1-C1-M1-A8-N1-T1-E1-H1. The structural proteins VP1-4 and VP6-7, along with nonstructural genes NSP1 and NSP5, shared high sequence identity with porcine strains, whereas the nonstructural genes NSP2–NSP4 clustered more closely with human rotaviruses. These findings indicate a higher prevalence of PoRV in southwestern China compared to other regions; the dominant circulating genotypes have shifted to G9 and G4; the isolated G1P[7] strain is relatively rare in China and might be a genetic recombinant of human and porcine rotaviruses. This study provides valuable data and theoretical support for understanding the current epidemiology of PoRV, and facilitates vaccine development and the formulation of prevention and control strategies. Full article

Spotty liver disease (SLD), primarily caused by Campylobacter hepaticus and (less frequently) by Campylobacter bilis, significantly impacts commercial layer hens by causing liver lesions, reducing egg production, and increasing mortality, meaning it can result in serious economic losses for farmers. This study explored the relationship between infection, liver dysfunction, and reproduction, aiming to identify host genetic markers for tracking SLD progression. Hens were orally inoculated with the C. hepaticus strain NSW44L and monitored over a seven-day period. Pathogen colonisation was quantified using qPCR across the liver, bile, caeca, spleen, and ovarian follicles, while liver lesions were scored and hepatic transcriptomes analysed using RNA-seq. C. hepaticus was detected in the liver, caeca, and spleen from one day post-inoculation (dpi) (1.44–1.68 log₁₀ CFU/mL), appeared in bile by the third dpi (3.64 log₁₀ CFU/mL), and reached the follicles by the fourth dpi (3.25 log₁₀ CFU/mL). The highest bacterial loads were found in bile on days six and seven (up to 7.18 CFU/mL). Liver lesions were first observed on the fourth dpi, reaching their peak at the sixth and seventh dpi. Gene expression analysis in liver tissue revealed a notable downregulation of yolk-precursor and metabolic genes, such as prolactin receptor (PRLR), 7-dehydrocholesterol reductase (DHCR7), and malic enzyme 1 (ME1). In contrast, from days three to seven post-infection, there was significant upregulation of avidin (AVD), a biotin-binding protein, and versican (VCAN), which is linked to tissue remodelling and inflammation. These findings correlate with the disease’s progression from initial liver infection to widespread bacterial presence, suggesting value as host biomarkers for effective SLD monitoring and the development of targeted therapies. Full article

Cinnamon essential oil (CEO), a safe, medicinal, and edible Traditional Chinese Medicine (TCM) component, was investigated for its anti-Candida albicans property and ability to relieve intestinal inflammation. The anti-Candida albicans ability of CEO was evaluated by Minimum Inhibitory Concentration (MIC), 2,3-Bis-(2-Methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT), and Scanning Electron Microscope (SEM) methods. By constructing ulcerative colitis (UC) mice intestinally colonized by C. albicans, the CEO effects on the regulation of flora, the relief of intestinal inflammation, and possible related signal pathway were discussed. The results showed that CEO has a significant effect on inhibiting C. albicans, where the MIC₈₀ value was 265 μg/mL, and the Sessile Minimum Inhibitory Concentration (SMIC)₈₀ value was 530 μg/mL. SEM showed the CEO could inhibit C. albicans mycelium growth and biofilm formation. CEO can regulate the flora disturbance, reduce inflammatory factors level, and play a protective role in intestinal mucosal damage. Network pharmacology predicts CEO may be associated with Janus Kinase-Signal Transducer and Activator of Transcription (JAK-STAT) pathway. It was proved that CEO had an inhibitory effect on the JAK-STAT pathway by qPCR determination. These findings suggest CEO may have therapeutic potential for C. albicans–associated UC. Full article

Background: Frailty is a major barrier to healthy ageing, yet early identification strategies remain limited. The serum creatinine-to-cystatin C ratio (sarcopenia index, SI) has emerged as a cost-effective biomarker of muscle mass and function, while physical activity (PA) is a key protective factor. However, their combined role in predicting frailty is unclear. This study aimed to investigate the independent and joint associations of SI and PA with incident frailty in middle-aged and older adults. Methods: We analyzed 5307 participants aged ≥45 years from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2018). SI was calculated from serum creatinine and cystatin C levels, and PA was assessed using standardized questionnaires. Frailty was defined using a 32-item Frailty Index (FI ≥ 0.25). Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of SI and PA with incident frailty, adjusting for sociodemographic and health-related factors. Effect modification by PA was formally tested. Results: Over the follow-up period, 1483 participants developed frailty (27.9%). Higher SI was inversely associated with frailty in a dose–response manner: compared with the lowest quartile, HRs (95% CIs) were 0.84 (0.73–0.97) for Q2, 0.83 (0.72–0.96) for Q3, and 0.69 (0.59–0.82) for Q4 (p-trend < 0.001). Each 10-unit increase in SI corresponded to a 6% lower frailty risk (HR = 0.94, 95% CI: 0.91–0.97). PA significantly modified this relationship (interaction p < 0.05), with the strongest protective effect of SI observed among individuals with low PA, and attenuation at higher PA levels. Conclusions: SI is independently associated with a lower risk of incident frailty, particularly among less physically active individuals. These findings support the potential use of SI as a feasible biomarker for early frailty risk stratification and highlight the importance of integrating biomarker-based screening with lifestyle interventions to prevent frailty. Full article

As an essential highway safety facility, roadside W-beam guardrails effectively prevent errant vehicles from entering hazardous zones or causing secondary collisions by blocking and redirecting them, thereby reducing accident severity. With the rapid development of the automotive industry, the front bumper height of small passenger cars generally ranges between 405 mm and 485 mm. However, the lower edge height of the current Chinese Class A W-beam guardrail is 444 mm above the ground, which leads to a high risk of “underride” during collisions, resulting in elevated occupant injury risks. To address this issue, this paper proposes an optimized guardrail structure composed of a double W-beam and a C-type beam, aiming to reduce the underride risk for small passenger cars while accommodating multi-vehicle protection needs. In this design, the double W-beam is installed at a height of 560 mm and the C-type beam at 850 mm, connected to circular posts using a regular hexagonal anti-obstruction block. The beam thickness is uniformly 3 mm, while the thickness of other components is 4 mm. To systematically evaluate the impact of material strength on both safety performance and cost, two material configurations are proposed: Scheme 1 uses Q235 carbon steel for all components; Scheme 2 reduces the thickness of the C-type beam to 2.5 mm and employs Q355 high-strength low-alloy steel, with the thickness of the connected anti-obstruction block reduced to 3.5 mm, while the other components retain Q235 steel and unchanged structural dimensions. Using finite element simulation, collisions involving small passenger cars, medium trucks, and buses are simulated, and performance comparisons are conducted based on vehicle trajectory and guardrail deformation. For the small passenger car scenario, risk quantification indicators—Acceleration Severity Index (ASI), Theoretical Head Impact Velocity (THIV), and Post-impact Head Deceleration (PHD)—are introduced to assess occupant injury. The results demonstrate that Scheme 2 not only meets the required protection level but also significantly reduces occupant risk for small passenger cars, lowering the injury rating from Class C to Class B. Moreover, the overall structural mass is reduced by approximately 1407 kg per kilometer, with material costs decreased by about RMB 10,129, demonstrating favorable economic efficiency. The proposed structural optimization not only effectively mitigates small car underride and improves multi-vehicle protection performance but also provides the industry with a novel guardrail geometric design directly applicable to engineering practice. The technical approach of enhancing material strength and reducing component thickness also offers a feasible reference for lightweight design, material savings, and cost optimization of guardrail systems, contributing significantly to improving the safety and sustainability of road transportation infrastructure. Full article