Search Results (15,351)

Background: Medicinal plants continue to offer a promising source of novel bioactive compounds for cancer therapy due to their affordability, biocompatibility, and low toxicity. Rhus punjabensis Stewart, an ethnomedicinal species from the family Anacardiaceae, has long been used in the traditional medicine of northern Pakistan to treat inflammatory, hepatic, and infectious diseases. However, its phytochemical composition and anticancer potential remain largely unexplored. Methods: This study employed a bioactivity-guided isolation strategy to identify and characterize anticancer constituents from R. punjabensis leaves. The plant material was sequentially fractionated using solvents of increasing polarity, followed by purification via column chromatography. Each fraction and purified compound was evaluated using antioxidant (DPPH, total antioxidant capacity, and total reducing power) and cytotoxic assays, including brine shrimp lethality, Sulfo-rhodamine B (SRB) against five human cancer cell lines, protein kinase inhibition, and NF-κB chemo-preventive assays. Results: Comparative analysis of spectral data (UV, 1D/2D NMR, and ESI-MS) led to the identification of three triterpenoid compounds—Lupeol, Cycloartenol, and β-sitosterol—reported for the first time from R. punjabensis. Among them, Lupeol displayed the most potent cytotoxicity against DU-145 prostate (IC₅₀ = 11.2 ± 1.2 μg/mL) and HL-60 leukemia (IC₅₀ = 15.2 ± 1.1 μg/mL) cell lines and showed significant NF-κB inhibitory activity (IC₅₀ = 19.4 ± 1.1 μg/mL), indicating its chemo-preventive potential. Cycloartenoland β-sitosterol exhibited moderate antioxidant and antimicrobial activities. Conclusion: The findings validate the ethnopharmacological use of R. punjabensis and confirm it as a new source of triterpenoids with notable anticancer activity. This study provides the first comprehensive account of its bioactive metabolites, reinforcing the significance of bioactivity-directed isolation as a powerful approach for discovering natural anticancer agents. Further in vivo and mechanistic evaluations are warranted to establish their therapeutic efficacy and safety profiles. Full article

Aiming at the problems of complex image background and numerous interference factors faced by visual navigation systems in orchard environments, this paper proposes an orchard navigation line recognition method based on U-Net. Firstly, the drivable areas in the collected images are labeled using Labelme (a graphical tool for image annotation) to create an orchard dataset. Then, the Spatial Attention (SA) mechanism is inserted into the downsampling stage of the traditional U-Net semantic segmentation method, and the Coordinate Attention (CA) mechanism is added to the skip connection stage to obtain complete context information and optimize the feature restoration process of the drivable area in the field, thereby improving the overall segmentation accuracy of the model. Subsequently, the improved U-Net network is trained using the enhanced dataset to obtain the drivable area segmentation model. Based on the detected drivable area segmentation mask, the navigation line information is extracted, and the geometric center points are calculated row by row. After performing sliding window processing and bidirectional interpolation filling on the center points, the navigation line is generated through spline interpolation. Finally, the proposed method is compared and verified with U-Net, SegViT, SE-Net, and DeepLabv3+ networks. The results show that the improved drivable area segmentation model has a Recall of 90.23%, a Precision of 91.71%, a mean pixel accuracy (mPA) of 87.75%, and a mean intersection over union (mIoU) of 84.84%. Moreover, when comparing the recognized navigation line with the actual center line, the average distance error of the extracted navigation line is 56 mm, which can provide an effective reference for visual autonomous navigation in orchard environments. Full article

Background/Objectives: Hip osteoarthritis (HOA) is a progressive joint disease characterized by cartilage loss, subchondral bone changes, and synovial inflammation. While tumor necrosis factor receptor 1 (TNFR1), interleukin-6 (IL-6), and transforming growth factor-beta 1 (TGF-β1) are recognized as key mediators of joint pathology, their compartment-specific expression in the human hip synovium remains insufficiently characterized. Therefore, we aimed to investigate their localization and expression in the intimal and subintimal compartments of synovial tissue in patients with HOA compared to controls (CTRL). Methods: Synovial membrane samples were obtained from 19 patients with primary HOA undergoing total hip arthroplasty and 10 CTRL subjects undergoing arthroplasty for acute femoral neck fracture without HOA. Specimens were processed for hematoxylin and eosin (H&E) and immunofluorescence staining. Expression of TNFR1, IL-6, and TGF-β1 was quantified in the intima and subintima using ImageJ analysis. Group differences were assessed using two-way Analysis of variance (ANOVA) with Tukey’s test when assumptions were met; for heteroscedastic outcomes we applied Brown–Forsythe ANOVA with Dunnett’s T3 multiple comparisons. Results: Histological analysis confirmed synovitis in HOA samples, with intimal hyperplasia and mononuclear infiltration. IL-6 was significantly upregulated in the intima of HOA synovium compared with CTRLs, while subintimal expression remained unchanged. In contrast, TGF-β1 expression was reduced in the HOA intima, eliminating the normal intima–subintima gradient. For TNFR1, the within-HOA contrast (int > sub) was significant, whereas the intimal HOA vs. CTRL comparison showed a non-significant trend. Transcriptomic analysis supported IL-6 upregulation, while TNFR1 and TGF-β1 did not reach statistical significance at the mRNA level in an orthogonal, non-hip (knee-predominant) dataset. Conclusions: These findings demonstrate compartment-specific cytokine dysregulation in HOA, with increased intimal TNFR1 and IL-6 alongside reduced intimal TGF-β1. The synovial lining emerges as a dominant site of inflammatory signaling, underscoring its importance in disease progression. Full article

Radiation-induced lung inflammation (RILI) is a major complication of thoracic radiotherapy, characterized by excessive inflammation and subsequent fibrosis that compromise pulmonary function and treatment outcomes. This study explores the pharmacological properties of a newly synthesized Lipoxin A4 analogue (CYNC-2) to mitigate RILI by modulating the AMP-activated protein kinase (AMPK)/NOD-like receptor family pyrin domain containing 3(NLRP3) inflammasome pathway. A murine RILI model was established in mice by delivering a single high-dose (ablative) X-ray irradiation to the left lung. Mice in the treatment group received CYNC-2 via tail-vein injection three times per week for 2 weeks. The effects of CYNC-2 on RILI were evaluated histological, immunohistochemical analysis of lung tissues, cytokine profiling, lung function testing using a FlexiVent system, and micro-computed tomography (micro-CT) imaging of lung damage. In parallel, two human lung cell lines—L132 (normal bronchial epithelial cells) and A549 (lung carcinoma cells)—were irradiated with 6 Gy X-rays and treated with CYNC-2 to assess cell viability and changes in AMPK/NLRP3 pathway markers via qPCR and immunofluorescence. Lung tissue sample from patients who underwent thoracic radiotherapy were also examined to validate key findings. CYNC-2 activated AMPK and inhibited mTOR signaling, which suppressed NLRP3 inflammasome activation and led to reduced secretion of pro-inflammatory cytokines (IL-1β, IL-6, and TGF-β1). In vitro, CYNC-2 mitigated radiation-induced inflammatory responses and preserved cellular viability. Overall, CYNC-2 effectively dampened acute pulmonary in the RILI model. These findings suggest that targeting the AMPK/NLRP3 inflammasome pathway via a stable LXA4 analogue such as CYNC-2 is a promising therapeutic strategy to improve clinical outcomes for patients receiving thoracic radiation therapy. Full article

This paper focuses on a deep foundation pit project of a metro shaft constructed by the cover-and-excavation reverse method in a section of Guangzhou Metro Line 13. This study integrates field monitoring data, three-dimensional finite element simulations, and parametric analyses to propose a systematic optimization design framework, providing a more comprehensive and reliable quantitative basis for the design of support structures for deep metro foundation pits constructed using the cut-and-cover top-down method. The study examines the effects of pile diameter, pile spacing, embedment depth, and types of retaining structures on pit deformation. The results indicate that increasing the pile diameter from 800 mm to 1000 mm reduces the maximum lateral displacement of the retaining structure by 30.7%, while decreasing the pile spacing from 2000 mm to 1600 mm results in a 17.5% reduction in deformation. However, beyond these thresholds, the marginal improvement becomes less significant. An embedment depth of 4 m for shallow sections and 2.5 m for deep sections is recommended to balance deformation control and construction economy. Diaphragm walls outperform bored piles and secant piles in deformation control. The optimized design achieves an estimated cost reduction of approximately 15% while maintaining safety requirements. The optimized parameters and comparative conclusions derived from this study can be directly applied to the design of deep foundation pits for metro stations under similar geological conditions. These findings provide crucial data support and theoretical reference for formulating more economical and safer design codes and standards. Full article

Background: Accumulating evidence suggests that cannabidiol (CBD) exerts variable effects on cancer cells that influence cellular activity, including growth. While anecdotal evidence abounds, mechanistic studies have lagged. Methods: Malme-3M cells derived from melanoma and less-aggressive BJ fibroblast cells were incubated with CBD. CE-MS mass spectroscopy was used to measure metabolite changes resulting from CBD treatment. Results: Data indicate a differential response between malignant Malme-3M cells and BJ fibroblasts with respect to metabolites critical for primary metabolic function. A significant reduction in TCA metabolites is seen with a corresponding increase in glycolytic output in the Malme-3M cell line. A similar reduction in TCA activity in BJ fibroblasts appears to differentially activate fatty acid oxidation. ATP is significantly reduced in the Malme-3M cells with a corresponding decrease in metabolites associated with redox maintenance. Conclusions: This is the first metabolomics analyses of malignant Malme-3M cells and less-aggressive BJ fibroblasts after pre-treatment with CBD. The data suggest that the CBD-induced metabolic perturbation could reprogram cellular metabolism and affect ATP production and redox maintenance of the more-aggressive Malme-3M cells. Full article

Improper use of drugs in both animal and human therapy, such as doxycycline (DOX), lead to the accumulation of residues in edible animal tissues as well as in the environment. Plant-derived compounds reduce the adverse effects of drugs. This study aimed to evaluate the effect of cannabidiol (CBD) in two concentrations: lower (1.56 µg/mL) (DOX + C1) and higher (3.125 µg/mL) (DOX + C2) on the cytotoxicity of doxycycline in human cells. The toxicity of DOX and its CBD-containing mixtures was assessed after 72 h of exposure in three human cell lines: neural (SH-SY5Y), hepatic (HepG2), and kidney (HEK-293). The exposure to DOX resulted in inhibition of mitochondrial activity (SH-SY5Y) and inhibition of DNA synthesis (HepG2 and HEK-293). IC₅₀ values for DOX ranged from 9.8 to >200 µg/mL in SH-SY5Y cells, 13.4 to 200 µg/mL in HepG2 cells, and 8.9 to 30.4 µg/mL in HEK-293 cells. The nature of the interaction depended on both the cell lines and the concentration of CBD in the mixture. Both CBD mixtures demonstrated a synergistic interaction in neuronal cells. In HepG2 cells, both mixtures showed additive and antagonistic interactions. In HEK-293 cells, the DOX + C1 mixture exhibited an antagonistic (protective) effect, while the DOX + C2 mixture showed an additive effect. There were no changes in oxidative stress levels; however, alterations in apoptosis levels and cell morphology were observed following exposure to the mixtures. The presence of doxycycline in the diet and the environment poses a health risk to consumers. The increasing consumption of CBD-containing products may reduce the risk associated with the presence of this drug in food. It is worth emphasizing the need for research aimed at minimizing the adverse effects of pharmaceuticals on the health of humans and animals. Full article

Background/Objective: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) lacking targeted therapies and characterized by high tumor heterogeneity. In this study, we evaluated the anticancer activity and mechanistic profile of Simalikalactone D (SKD), a quassinoid compound derived from the endemic Puerto Rican tree Simarouba tulae, in three TNBC cell lines, MDA-MB-468, MDA-MB-231, and SUM-149. Methods: MDA-MB-468, MDA-MB-231 and SUM-149 TNBC cells were evaluated for cell viability, proliferation and migration following SKD treatment. Phospho-antibody array, proteomics, and Western blot analyses were used to explore the SKD mechanism of action in MDA-MB-468 and MDA-MB-231 cell lines. Molecular docking was performed to assess SKD’s interaction with potential intracellular targets. Results: SKD exerted a concentration-dependent effect on the three cell lines. However, MDA-MB-468 cells exhibited an IC₅₀ of 67 nM, while the IC₅₀ values for MDA-MB-231 and SUM-149 were 422 nM and 598 nM, respectively. In MDA-MB-468 cells, 100 nM of SKD induced apoptosis, evidenced by the activated caspase-3 activity, PARP-1 cleavage and decrease in Bcl-2 and survivin protein levels. Sublethal SKD (25 nM) impaired migration in MDA-MB-231 cells and reduced proliferation and motility in SUM149 cells. A 6 h SKD treatment markedly reduced phosphorylation of apoptosis-related proteins (p53, BAD, DAXX, AKT1, JUN) and Jak/STAT pathway components, indicating early disruption of intracellular signaling prior to phenotypic changes. Proteomic profiling showed distinct pathway alterations in both MDA-MB-468 and MDA-MB-231 cells, with reduced Integrin β1 (ITGB1) levels emerging as a shared effector. This suggests that SKD broadly disrupts cell adhesion and migration independently of apoptosis-driven cell death. Western blot validation confirmed reduced ITGB1 protein levels across all three TNBC cell lines examined. In silico docking confirmed favorable binding affinities of SKD to both EGFR (ΔG = −6.718 kcal/mol) and STAT4 (ΔG = −8.481 kcal/mol). Conclusions: Overall, our findings suggest that SKD is a potent anticancer agent in a subgroup of TNBC cells. Full article

This paper presents a low-power CMOS voltage reference with low supply sensitivity, designed and verified in a 180 nm standard CMOS technology. A DIBL-based line-sensitivity (LS) compensation path is incorporated into the conventional PTAT generation circuit to simultaneously provide a reference voltage and a bias current with improved LS. The proposed circuit achieves LS values of 0.01%/V for the voltage reference and 0.07%/V for the bias current reference over a supply voltage range of 1.4 V to 2 V. It generates a reference voltage of 538 mV and a PTAT current of 38 nA, consuming 68 nW. The simulated temperature coefficient is 58 ppm/$℃$ from −40 °C to 130 °C, and the power supply rejection ratio is −59 dB at 100 Hz. Full article

Sodium butyrate has been documented to support gut function and help control pathogens in the gastrointestinal tract. However, the precise mechanisms of dietary sodium butyrate’s control over enteric pathogens in chickens remain unclear. Our study demonstrated that priming chicken bone marrow-derived macrophages (BMDMs) or the HD11 cell line with 1 mM sodium butyrate significantly enhanced their antimicrobial capacity against key bacterial pathogens (Escherichia coli, Salmonella Typhimurium, Pseudomonas aeruginosa, and Staphylococcus aureus) in gentamicin protection assays (p < 0.05; ≥1 log reduction in CFU/mL). This in vitro enhancement was associated with increased production of reactive oxygen species (ROS), as detected by DCFH-DA assays, showing approximately a 30% increase in HD11 cells and a 12% increase in BMDMs. Butyrate priming was observed to result in autophagy activation, potentially through mTOR pathway inhibition, evidenced by changes in related gene expression using RT-qPCR assay and a 2.5-fold increase in GFP-LC3B accumulation. Supporting this, pharmacological inhibition of ROS using the ROS scavenger N-acetyl-L-cystine (NAC) or autophagy with chloroquine reduced the butyrate-enhanced bacterial clearance. Furthermore, the mTOR inhibitor rapamycin synergized with butyrate priming, whereas the mTOR activator L-leucine counteracted enhanced antimicrobial activity. These findings offer crucial insights for improving host defence against bacterial infections and developing novel therapeutic strategies in chickens. Full article

Background: The Wnt/β-catenin signaling pathway plays a pivotal role in embryonic development, maintenance of the central nervous system, and the formation of neuronal circuits. Disruption of this pathway is closely associated with oncogenesis and neurodegenerative diseases, notably Alzheimer’s disease. Flavonoids such as quercetin derivatives have emerged as promising neuroprotective agents. This study investigates the impact of 3-O-methylquercetin (3OMQ), a methylated quercetin metabolite, on Wnt/β-catenin signaling and its potential relevance in neurodegenerative disease models. Methods: The ability of 3OMQ to modulate Wnt/β-catenin activity was analyzed using a luciferase-based reporter assay in both neural and non-neural cell lines. Cell viability assays evaluated cytotoxicity at various concentrations. We mapped 3OMQ activity within the pathway using targeted cell signaling experiments. Docking and molecular dynamics simulations suggested glycogen synthase kinase 3β (GSK3β) as a putative target of 3OMQ. Finally, we employed a mouse model of acute amyloid-β oligomer (AβO) toxicity to assess the in vivo effects of 3OMQ on spatial memory and Wnt-related gene expression. Results: We compared the flavonoids quercitrin, quercetin, and 3-O-methylquercitrin (3OMQ) with pharmacologically active compounds in a gene reporter assay (TOPFLASH) using Wnt-sensitive RKO cells treated with Wnt3a-conditioned medium. XAV-939 and PNU-74654 showed inhibitory activity, while BIO, CHIR99021, quercitrin, and 3OMQ enhanced the Wnt/β-catenin pathway. Notably, 3OMQ potentiated this pathway at concentrations 5–10 times lower than quercitrin and outperformed 1 μM BIO at 10 μM without cytotoxicity, highlighting its remarkable potency. Mechanistically, 3OMQ acts downstream of initial membrane activation and upstream of the β-catenin destruction complex. Consistently, molecular docking indicates a strong interaction with GSK3, a central regulator of the pathway. In adult mice, 3OMQ administration prevented AβO-induced recognition memory deficits and favored normalization of Wnt-related gene expression. Conclusions: These findings identify 3OMQ as a potent positive modulator of the Wnt/β-catenin pathway, with both in vitro and in vivo neuroprotective effects. Targeting Wnt signaling with compounds such as 3OMQ holds promise for maintaining neuronal health and developing therapeutic strategies for neurodegenerative conditions. Full article

The PER2 gene is a crucial component responsible for the proper functioning of the mammalian core circadian clock. The circadian nature of the murine Per2 (mPer2) promoter’s activity has been thoroughly investigated to identify important elements responsible for its oscillatory behavior; however, its human counterpart has not. While there are similarities between murine and human core clocks, there are differences and unconserved elements between their promoter sequences that may influence the nature of rhythms. Further, most studies to date have used murine-based sequences in human cell lines. To fully understand the role(s) of and factors involved in the human PER2 (hPER2) gene, human-derived sequences should be used. To this end, we developed two lentiviral luciferase reporters in well-established, circadian model U2OS cells using different hPER2 promoter regions. Their rhythmic nature was compared to that of the standard mPer2 promoter reporter. We found that hPER2 reporters exhibited stronger oscillations than the mPer2 reporter, and that the frame of the hPER2 promoter affected the period and phase. This work introduces a human sequence-based PER2 promoter in U2OS cells, which should be used for further in vitro tracking of hPER2 activity and to understand PER2 gene dynamics, in lieu of the murine iteration. Full article

Transmission lines often traverse mountainous regions prone to frequent geological hazards, making it of great practical significance to analyze the spatial distribution patterns of landslide traces along the transmission line corridors. This study focuses on the Hubei section of the ±800 kV ultra-high-voltage (UHV) transmission line from the upper reaches of the Jinsha River to Hubei. Based on high-resolution remote sensing imagery provided by Google Earth, a landslide traces inventory was constructed through visual interpretation. In addition, 13 factors, such as elevation, slope, aspect, relief, soil type and land cover, were selected to analyze the spatial distribution of landslides. The results indicate the following: (1) There are at least 18,598 landslides in the study area, with a total area of approximately 2671.82 km². The spatial distribution is uneven, exhibiting a general pattern of “dense in the west, sparse in the east”. The maximum landslide number density (LND) reaches 4.16 km⁻², and the maximum landslide area percentage (LAP) is 0.83%. (2) Landslides are predominantly distributed in areas with elevations of 278–1059 m, slope gradients of 20–30°, northwest and southeast aspects, surface roughness values of 400–600, Triassic and Jurassic strata, evergreen coniferous forest and sparse forest, as well as lixisols and ferrallitic soil. This study established a landslide traces database for the region, preliminarily revealing the distribution characteristics of landslides and their dominant controlling factors. It provides a scientific basis for geological hazard risk assessment and prevention for UHV transmission lines. Full article

In the semi-desert aeolian sand areas of Northern China, surface deformation monitoring with SAR is challenged by loss of coherence due to mobile dunes, seasonal vegetation changes, and large-gradient, nonlinear subsidence from underground mining. This study utilizes PALSAR-2 (L-band, 3 m resolution) and Sentinel-1 (C-band, 30 m resolution) data, applying InSAR and Offset tracking methods combined with differential, Stacking, and SBAS techniques to analyze deformation monitoring effectiveness and propose an efficient dynamic monitoring strategy for the Shendong Coalfield. The main conclusions can be summarized as follows: (1) PALSAR-2 data, which has advantages in wavelength and resolution (L-band, multi-look spatial resolution of 3 m), exhibits better interference effects and deformation details compared to Sentinel-1 data (C-band, multi-look spatial resolution of 30 m). The highly sensitive differential-InSAR (D-InSAR) can promptly detect new deformations, while Stacking-InSAR can accurately delineate the range of rock strata movement. SBAS-InSAR can reflect the dynamic growth process of the deformation range as a whole, and SBAS-Offset is suitable for observing the absolute values and morphology of the surface moving basin. The combined application of Stacking-InSAR and Stacking-Offset methods can accurately acquire the three-dimensional deformation field of mining-induced strata movement. (2) The spatiotemporal process of surface deformation caused by coal mining-induced strata movement revealed by InSAR exhibits good correspondence with both the underground mining progress and the development of ground fissures identified in UAV images. (3) The maximum displacement along the line of sight (LOS) measured in the mining area is approximately 2 to 3 m, which is close to the 2.14 m observed on site and aligns with previous studies. The calculated advance influence angle of the No. 22308 working face in the study area is about 38.3°. The influence angle on the solid coal side is 49°, while that on the goaf side approaches 90°. These findings further deepen the understanding of rock movement and surface displacement parameters in this region. The dynamic monitoring strategy proposed in this study is cost-effective and operational, enhancing the observational effectiveness of InSAR technology for surface deformation due to coal mining in this area, and it enriches the understanding of surface strata movement patterns and parameters in this region. Full article

Studies in cervical and prostate cancer cells have reported that frequent consumption of foods rich in glycine betaine (GB) and choline have beneficial effects against some types of cancer. However, the role of GB against the human colorectal adenocarcinoma cell line HT-29 has not yet been elucidated. Therefore, this study aimed to evaluate the effect of GB on p53 and caspase-3 expression, which regulate cellular processes such as cell proliferation and apoptosis, respectively, on HT-29 cells. HT-29 cells were treated with GB at 5 mg/mL, 15.6 mg/mL, 31.2 mg/mL, and 62.5 mg/mL, after which RNA purification and cDNA synthesis were performed, followed by qPCR to detect the relative expression of p53 and caspase-3, using GAPDH as a reference gene, and protein levels were determined by ELISA. Results indicated that in HT-29 cells treated with GB at 62.5 mg/mL, the protein levels of p53 significantly (p < 0.05) increased to 45 U/mL, as compared with cells without GB (21 U/mL), whereas caspase-3 increased to 30 ng/mL, as compared with control cells (20.13 ng/mL). Therefore, we conclude that GB at high concentrations decreases cell proliferation and induces apoptosis in HT-29 cells. Full article