Search Results (159,702)

Pharmacological cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have reshaped the treatment landscape of HR-positive, HER2-negative (HR+/HER2−) breast cancer and are increasingly being explored across diverse malignancies. By preventing retinoblastoma (RB) phosphorylation and enforcing G1-S cell cycle arrest, these agents achieve durable tumour control with a more favourable toxicity profile than conventional chemotherapy. Beyond their canonical cytostatic effects, prolonged CDK4/6 inhibitor treatments induce cellular senescence, a stable, proliferative arrest accompanied by profound transcriptional, epigenetic, and secretory changes. This review summarises current knowledge on CDK4/6 inhibitor-induced senescence in both cancer and normal cells as a central biological mechanism that links tumour suppression and microenvironmental remodelling. Importantly, this process is highly context-dependent, differing between tumour and non-malignant cells, with a distinct senescence-associated secretory phenotype (SASP) that shapes immune responses and tissue homeostasis. We also discuss how CDK4/6 inhibitor-induced senescence influences the tumour microenvironment by modulating immune surveillance, stromal interactions, and cancer cell plasticity. Finally, we examine emerging resistance mechanisms and rational combination strategies for CDK4/6 inhibitors, including targeting compensatory signalling pathways, immune checkpoint blockades, and senescence-directed sequential therapies. Collectively, CDK4/6 inhibitor-induced senescence represents both a challenge and a therapeutic opportunity, underscoring the need to integrate cell cycle control with the modulation of cellular states. Full article

With the expansion of the digital economy, platform-based content creation has become a common route through which young people participate in flexible employment. However, the occupational identity of young we-media bloggers remains unstable because platform work combines low entry barriers, ambiguous labour relations, algorithmic governance and uncertain income. This qualitative study examines factors shaping occupational identity among young we-media bloggers in Hangzhou and Shaoxing, China. Data were collected through participatory observation and semi-structured interviews with 20 bloggers active on Xiaohongshu, TikTok and Bilibili. Fifteen interviews were used for open, axial and selective coding, and five additional interviews were used to assess theoretical saturation. The analysis identifies five key factors: perceived occupational competence, occupational development expectations, perceived occupational meaning, external environmental conditions and platform mechanisms. These factors operate through the interaction of internal cognition and external conditions: competence, future expectations and meaning provide internal support for occupational identity, whereas family attitudes, social evaluation, industry conditions, platform feedback and monetisation opportunities shape its stability. The findings suggest that young bloggers’ occupational identity is not a fixed status but a negotiated process formed through content production, platform feedback and social recognition. Full article

Studies addressing seasonal changes in diet quality and hormones are important for understanding the interactions between ecology and physiology. We collected fecal samples from free-ranging adult female pronghorn (Antilocapra americana) to examine the relationships between indicators of nutrition and glucocorticoid activity. This occurred during three population-level, life-history-correlated sampling periods across five subpopulations. We evaluated nutrition via fecal nitrogen, fecal 2,6-diaminopimelic acid (DAPA), and assessed glucocorticoid activity using fecal glucocorticoid metabolites (FGM). We found positive relationships between fecal nitrogen and DAPA, whereas DAPA and fecal nitrogen with FGM varied in influence and strength, depending upon life history stage. Generally, correlations between DAPA and FGM were strongest during late gestation sampling, whereas correlations between those two measures and fecal nitrogen lacked consistency across life history stages and years. We found that maternal nutrition and stress were associated with notable changes in the relative intake of dietary protein from plant functional groups across sampling periods. Pronghorn appeared to shift between diets high in nitrogen or digestible energy content, depending upon life history stage and associated metabolic demands. We feel these results will assist wildlife managers in further understanding relationships between physiological parameters and how pronghorn meet the metabolic requirements of life history stages. Full article

Alterations in microbiota, transcript and metabolites are critical to intestinal homeostasis and host health. This study used a combination of 16s rRNA, transcriptome sequencing and liquid chromatography–mass spectrometry to investigate intestinal microbiota, genes and metabolic profiles in the ileum of Hu sheep fed broccoli extract. Here, we randomly allocated 14 Hu sheep to two diets: a basal diet without any supplementation (NC) and a basal diet supplemented with 200 mg/kg broccoli tail (BT). After 60 days of treatment, blood and jejunal samples were collected for serum biochemical indicators and multi-omics analysis. In this study, the extract of broccoli tails had a significant effect on the serum biochemical indicators, including white blood cells, red blood cells, mean corpuscular volume, mean corpuscular hemoglobin concentration, mean platelet volume, triglycerides and total protein in Hu sheep (p < 0.05). Transcriptomic analysis showed that the 672 differentially expressed genes between the NC and BT groups were primarily enriched in linoleic acid metabolism, steroid hormone biosynthesis, and cholesterol metabolism. Metabolomics analysis using Kyoto Encyclopedia of Genes and Genomes enrichment showed that the 41 differentially abundant metabolites were mainly enriched in bile secretion, vitamin B6 metabolism, and the mTOR signaling pathway. 16S rRNA sequencing results indicated that the extract of broccoli tails increased the relative abundance of Peptostreptococcaceae and decreased the relative abundance of Lachnospiraceae, Lachnospirales, and Bacteroidaceae. Integrated transcriptome, metabolome, and microbiome analysis showed that the gut microbiota and host transcriptomic changes may participate in systemic metabolic regulation by modulating amino acid metabolism, lipid signal transduction, nucleotide metabolism, and vitamin B6-related metabolic pathways. These findings demonstrate that the extract of broccoli tails modulates intestinal gene expression, systemic metabolism, and gut microbial ecology in Hu sheep, providing new insights into the utilization of agricultural byproducts as a functional feed supplement for ruminants. Full article

Background: H₂ gas inhalation has been proposed as a selective modulator of reactive oxygen species (ROS), potentially mitigating treatment-related oxidative damage. This study investigated the effects of adjunctive H₂ gas inhalation on serum metabolomic profiles and clinical toxicities in patients with LAHNC undergoing CCRT. Methods: Twenty patients were prospectively randomized to receive either standard CCRT alone (Group A) or CCRT combined with adjunctive H₂ gas inhalation (Group B). Serum samples collected before and after treatment were analyzed using untargeted ultra-high-performance liquid chromatography coupled with ion mobility quadrupole time-of-flight high-resolution mass spectrometry (UHPLC-IM-QTOF-HRMS)-based metabolomics. Results: One patient in Group B discontinued participation, leaving 19 patients for the final analysis. Patients receiving adjunctive H₂ gas inhalation tended to exhibit numerically lower frequencies of moderate treatment-related toxicities, fewer chemotherapy delays, and a shorter overall treatment duration than those receiving CCRT alone. Metabolomic profiling in the CCRT-alone group revealed exploratory alterations in metabolites associated with arginine metabolism, glutathione metabolism, and purine metabolism following treatment. Ornithine, uric acid, and tetrahydrodeoxycorticosterone were among the candidate discriminative metabolites with exploratory discriminatory performance after CCRT. In contrast, patients receiving adjunctive H₂ gas inhalation showed a more limited pattern of pathway mapping, with exploratory evidence from an illustrative single-hit pathway assignment suggesting possible involvement of purine metabolism. Altered uric acid levels together with changes in several lipid-related metabolites may collectively reflect metabolic responses associated with treatment-related oxidative stress during CCRT. Consistent with these findings, direct between-group comparison of within-subject changes (Δ = post − pre) indicated a numerically smaller reduction in serum uric acid levels in the adjunctive H₂ gas inhalation group; however, this difference did not reach statistical significance. Conclusions: Adjunctive H₂ gas inhalation during CCRT may be associated with reduced moderate treatment-related toxicities and exploratory changes in systemic metabolic profiles in patients with LAHNC. However, the study was not designed to evaluate oncological outcomes, and the metabolomic findings, particularly the pathway-level interpretations, should be considered exploratory because several pathway assignments were based on only one or a few mapped metabolites, together with the limited sample size, patient heterogeneity, and lack of independent external validation. Further validation in larger, independent cohorts using comprehensive between-group metabolomic analyses is warranted. Full article

Despite decades of research, there is still a lack of calibrated data on acoustic leak signatures typical of common types of water supply pipes. This study addresses this gap by providing leak signatures recorded with calibrated, high-sensitivity accelerometers in a controlled laboratory environment. The study also investigates how different leak configurations at nominal static pressures of 2.8–4.2 bars influence the power spectrum of the pipe-wall acceleration. The results show a great variability, i.e., 5 orders of magnitude, in the power spectrum. The amplitude and shape of this spectrum depend on whether the leak is through a valve-controlled nozzle, hole directly drilled in the pipe wall, or a longitudinal or traverse slit. The coherence in the leak signals as a function of the distance between the accelerometers is determined and used to estimate the leak signal attenuation. Crucially, the results reveal that longitudinal slits, which represent the most common failure mode in plastic pipes, produce the weakest acoustic signals, making them difficult to detect and locate using standard acoustic equipment. It is expected that the calibrated data collected from this study will support high-fidelity computer simulations and development of better signal processing algorithms to predict and to detect hidden leaks in water distribution networks in the presence of background noise and high acoustic attenuation. The recorded data are made available to a wider community through a dedicated data depository. Full article

Obesity is a critical public health issue in the United States, which disproportionately affects Latinx youth compared to youth in other racial/ethnic groups. While research suggests fathers can influence their children’s dietary intake and physical activity behaviors, few studies have included fathers in pediatric obesity studies and examined what mechanisms shape youth health outcomes. A greater understanding about fathers’ role modeling and expectations for their youth can provide critical evidence in addressing Latinx youth health outcomes. This research examined the extent to which fathers’ role modeling, expectations, family congruence, and warmth relate to youth energy balance-related behaviors. This study used cross-sectional data collected at baseline before Latinx fathers and children entered an obesity prevention program (n = 193). Latent moderation structural analyses tested the theorized pathways based on Palkovitz’s conceptual framework of father involvement, including youth age and sex as covariates. Fathers’ physical activity role modeling significantly predicted youth moderate-to-vigorous physical activity, p = 0.002. Fathers’ warmth significantly moderated vegetable role modeling, $\mathsf{\beta }$ = 0.263, p = 0.019. By testing Palkovitz’s conceptual framework of father involvement, this study increases the understanding about the theorized pathways between fathers’ role modeling/expectations and youth health outcomes. Full article

This study investigates how sustainable leadership enhances green performance in the tourism and hospitality sector, specifically among managers and supervisors working in five-star hotels and travel agencies, by examining the mediating roles of green innovation and green self-efficacy through the lenses of the Resource-Based View (RBV) and Dynamic Capabilities Theory (DCT). A quantitative research approach was adopted, utilizing survey data collected from 788 managers and supervisors employed in Egyptian five-star hotels and travel agencies operating within a highly competitive tourism destination context. The findings indicate that sustainable leadership has a significant positive effect on green performance and positively influences both green innovation and green self-efficacy. Moreover, green innovation and green self-efficacy significantly contribute to green performance and partially mediate the relationship between sustainable leadership and environmental outcomes. This study contributes to the literature on sustainability, tourism, and organizational behavior by providing an integrated framework that links sustainable leadership with organizational innovation capabilities and employees’ environmental competencies. In addition, the findings extend the explanatory power of RBV and DCT in explaining how sustainable leadership practices translate into enhanced environmental performance in tourism and hospitality organizations. From a practical perspective, the study highlights the importance of adopting leadership practices that foster green innovation, strengthen employees’ environmental confidence, and promote proactive environmental behavior within organizations. Full article

Honey is a high-value food product that is vulnerable to adulteration with exogenous sugars, posing challenges for food authenticity and consumer protection. This study applied Stable Isotope Ratio Analysis (SIRA) to assess the authenticity of honey collected from three major honey-producing regions of Ghana (Volta, Bono and Bono East). A total of 28 honey samples were analysed by elemental analysis–isotope ratio mass spectrometry (EA-IRMS) to obtain carbon (δ¹³C), nitrogen (δ¹⁵N) and sulphur (δ³⁴S) isotope composition. Honey authenticity was evaluated according to AOAC Official Method 998.12 by comparing δ¹³C values of bulk honey and the corresponding protein fraction. The δ¹⁵N and δ³⁴S values in honey protein were used to investigate environmental and regional variability. Samples without detectable C4 adulteration exhibited δ¹³C_protein values consistent with C3 floral sources, whereas several samples showed Δδ¹³C values more negative than −1.0‰, indicating the presence of C4-derived sugars above the AOAC adulteration threshold. Calculated C4 sugar contents ranged from 8 to 12% in moderately adulterated samples to as high as 78–79% in severely adulterated samples, confirming substantial dilution with C4 sugars. Nitrogen and sulphur isotope ratios provide additional information on environmental and regional variability among the sampled regions. Principal Component Analysis revealed that the first two principal components (PC1 and PC2) accounted for 83.8% of the total variance 83.8% of the total variance and showed separation between samples with detectable C4 adulteration and those without, while highlighting regional isotopic differences. These results demonstrate that stable isotope analysis is an effective tool for detecting C4 sugar adulteration in honey and that the combined use of carbon, nitrogen and sulphur isotopes can provide additional information on environmental and regional variability. These findings provide preliminary isotopic data on honey collected from three major honey-producing regions of Ghana and support the application of the stable isotope approach for honey authenticity assessment and quality control. Full article

Background: It is observed that there are a limited number of scientific studies investigating the effect of cocaine use disorder on microRNA (miRNA) levels in human peripheral blood. This study aimed to identify candidate miRNAs that may play a role in the regulation of cocaine addiction by detecting changes in the expression of some miRNAs (miR-9-5p, miR-26b-5p, miR-132-3p, and miR-134-5p) in the peripheral whole blood of cocaine addicts. Methods: Peripheral blood samples were collected from 12 Turkish male individuals with cocaine abuse, 11 Turkish male individuals undergoing treatment for cocaine abuse, and 16 healthy Turkish male individuals without any substance abuse. The change in the expression of microRNAs was determined by quantitative real-time polymerase chain reaction (RT-qPCR). In statistical analyses, ΔCt values were analyzed for the expression of miRNAs. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic adequacy of peripheral blood miRNAs. Results: miR-132-3p and miR-134-5p were downregulated in the addict group compared to the control group (p < 0.05). The areas under the curves (AUCs) of the ROC curve of miR-132-3p and miR-134-5p were significant at 0.778 and 0.744, respectively. Conclusions: This study suggests that miR-132-3p and miR-134-5p may have function as therapeutic markers in the treatment of cocaine use disorder. Full article

High-altitude ecosystems are characterized by extreme environmental conditions that strongly influence microbial community structure and function. However, whether soil and water microbiomes exhibit similar ecological responses to environmental variation in alpine meadow ecosystems on the Qinghai–Tibetan Plateau remains poorly understood. Here, we combined 16S rRNA gene amplicon sequencing and metagenomic sequencing to compare soil and water microbiomes across two regions (LZ and NQ) with distinct physicochemical profiles. Environmental heterogeneity was more pronounced in water habitats, where all measured parameters (pH, total nitrogen, total organic carbon, and chemical oxygen demand) varied significantly between sites (p < 0.001). Correspondingly, water microbiomes exhibited greater regional differentiation than soil microbiomes, evidenced by stronger beta-diversity separation (PERMANOVA, R² = 0.667 vs. 0.376) and a lower proportion of shared ASVs (65.3% vs. 97.2%). Ecological assembly analysis revealed a sharp contrast: water communities were primarily governed by deterministic processes (accounting for >80% of assembly, with heterogeneous selection as the dominant driver), whereas soil microbiomes were dominated by stochastic processes (>50%). Furthermore, water microbiomes underwent more intense network restructuring, with interaction complexity increasing significantly from 70 nodes and 268 edges in the LZ region to 130 nodes and 577 edges in the NQ region, whereas soil networks remained relatively stable (146 nodes/368 edges to 128 nodes/391 edges). Functional profiling further indicated broader regional redistribution in water compared to the relatively conserved functional framework of soil communities. Resistome analysis identified distinct ARG structures between habitats while revealing 25 overlapping categories, suggesting potential ecological connectivity. Collectively, our findings demonstrate that water microbiomes are more sensitive to regional environmental variation than soil microbiomes, with aquatic communities responding through deterministic restructuring and heightened interaction complexity. These results provide quantitative evidence that high-altitude soil and water microbiomes adopt distinct ecological strategies, offering new insights into the mechanisms governing microbial adaptation and antibiotic resistance distribution. Full article

Wildfires in California increasingly threaten communities and ecosystems. However, comprehensive estimation of fire dynamics and fuel structure remains limited. Recent advances in Uncrewed Aerial Vehicle (UAV) technology and high-spatial-resolution mapping have provided increasingly important tools for estimating wildfire fuel-height loss across fuel types. This study used a one-year Uncrewed Aerial Vehicle (UAV) time series to quantify fuel-height loss and vegetation regrowth associated with a prescribed upslope canyon fire near Salinas, California, USA. Multispectral, infrared, and visible UAV imagery collected before, during, and after burning was used to generate orthomosaic, digital surface models (DSMs), fuel-type classifications, and surface-volume estimates. To enable reliable pre- and post-fire comparison, ground control points and tie points were used to train linear regression calibrations that corrected angular discrepancies and elevation offsets among time-series DSMs. Calibrated DSMs were then integrated with ecological field measurements to map fuel-height consumption and post-fire recovery at the individual-plant scale. UAV-derived fuel-height change was associated with in situ twig-diameter measurements, which provide field-based indicators of fire effects in chaparral vegetation, while the maximum recorded temperature explained only a small proportion of variation in fuel-height loss. This workflow can support integrated fire ecology and remote-sensing studies by providing repeatable measurements of post-fire changes in vegetation structure. Full article

Monitoring the condition of grasslands is essential given their vital role in food security, carbon sequestration and other ecosystem services. Harvested aboveground biomass (HAB) and aboveground net primary production (ANPP) are among the most important grassland state indicators. However, spatially explicit production estimates are largely lacking, and grassland area estimations also remain uncertain. This study addresses these gaps for drought-prone Central European grasslands over 2017–2024. We synthesized grassland extent data, collected extensive field measurements on biomass (BM), and used remote sensing-based biophysical proxies to build an ensemble of six linear models for spatial extrapolation at 10 m resolution. Bayesian framework was used for the linear model fitting that also considers uncertainty of the observations. The ensemble mean ANPP was 310.7 ± 19 gBM m⁻², with modest interannual variability. Upscaled country-wide mean ANPP was 34.3 ± 13.3 Mt year⁻¹. The results indicate that, within the frame of the present study, the remote sensing-based linear model selection has a larger influence on the country totals than the grassland area database selection. The results highlight that both grassland area uncertainty and model construction are major sources of uncertainty in biomass estimation that have to be addressed in future studies. Full article

Background: Cervical dumbbell-shaped neurogenic tumors occurring at two noncontiguous levels are rare, and postoperative cerebrospinal fluid (CSF) collection causing cord compression is an uncommon but serious complication after intradural tumor resection. Case Presentation: A 30-year-old man presented with a 3-month history of progressive gait disturbance. Neurological examination revealed grade 3 paraparesis with upper motor neuron signs. Magnetic resonance imaging (MRI) demonstrated two discrete dumbbell-shaped neurogenic tumors located at the C1-2 and C7-T1 levels. The lesions were simultaneously resected. Complete removal of the C1-2 tumor required total sacrifice of the left C2 nerve root, while the C7-T1 lesion was excised through a T-shaped dural incision. The dura was closed primarily with watertight sutures reinforced with dural sealant, and no CSF leakage was observed during intraoperative Valsalva testing. Two months postoperatively, the patient developed worsening upper back and trapezial pain with severe scapular swelling. MRI revealed a large CSF collection extending from C6 to T5, causing moderate cord compression. Urgent revision surgery was performed. Controlled drainage was attempted to prevent intracranial hypotension, but significant CSF egress occurred. The dural defect was repaired using an autologous muscle plug reinforced with fibrin glue. The patient recovered uneventfully after revision surgery and was discharged without recurrence or complications. Conclusions: This case highlights that delayed, extensive postoperative CSF collection can occur despite apparently watertight primary closure and negative intraoperative Valsalva testing. Clinical vigilance for this complication is essential when patients present with new axial pain or localized swelling following cervical intradural surgery, even in the absence of classic low-pressure headaches. Full article