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UCA1 copy number gain in serum cfDNA predicts next-generation antiandrogen resistance in metastatic castration-resistant prostate cancer
Abstract Enzalutamide (ENZA) is a second-generation antiandrogen therapy that provides overall survival (OS) benefit for prostate cancer (PC) patients. However, many patients have baseline or develop resistance to ENZA. Currently, no biomarkers are used in clinical decision making to predict the efficacy of ENZA therapy. We aimed to identify cell-free DNA (cfDNA) biomarkers for metastatic castration-resistant prostate cancer (mCRPC) predictive to ENZA response. Comparative whole-exome and transcriptome sequencing was performed on three ENZA-resistant and parental ENZA-sensitive PC cell line pairs. Bioinformatic analysis identified UCA1 , ORM1 , and androgen receptor (AR) as candidate markers for serum cfDNA testing. Digital droplet PCR was used to analyze UCA1 , ORM1 and AR in cfDNA from serum samples of mCRPC patients who underwent ENZA ( n = 20), abiraterone (ABI; n = 20) and 40 docetaxel (DOC; n = 40) treatment. UCA1 copy number gain was significantly associated with reduced OS in ENZA-treated patients ( p = 0.030). AR gain correlated with poorer OS in ABI-treated patients ( p = 0.039), whereas no association was observed in DOC-treated patients. Normal AR and UCA1 levels were associated with significantly better OS in ENZA and ABI-treated patients. These findings suggest that UCA1 gain may predict reduced efficacy of ENZA treatment, while AR gain indicates decreased effectiveness of ABI but not ENZA and DOC therapies. These results may help support therapeutic decisions in the clinical settings.
Role of doping concentration on the RWGS performance of Cu doped CeO2 catalysts
Coronary artery stenosis segmentation using U-Net architecture with customised loss function
Pt nanoparticles immobilized on a cobalt-doped Zif8 manganese tetraphenylporphyrin bentonite chitosan composite as a durable and poison-tolerant catalyst for ethanol electrooxidation
Identification of macrophage-enriched genes in ovarian cancer by single-cell RNA sequencing and establishment of a prognosis model
Hydrophilicity-switchable deep eutectic solvent-based ultrasound-assisted liquid-phase microextraction for the green and efficient spectrofluorimetric determination of verapamil in human plasma
Preclinical evaluation of the newly developed carina platform in robotic-assisted proctectomy with porcine and cadaveric models
Phytochemical profiling and multi-target antibacterial in silico potential of Algerian wild sea buckthorn leaves
Abstract This study investigates the phytochemical profile and mechanistic bioactivity of sea buckthorn ( Hippophae rhamnoides L.) leaves harvested from wild Algerian species. The research integrates quantitative HPLC profiling with in vitro and in silico assays to elucidate the molecular basis of its biological potential, specifically targeting the transpeptidase domain of Penicillin-Binding Protein 3. Two extracts (pure ethanol and 50:50 hydroethanol) were evaluated for their total phenolic, flavonoid, and tannin contents, along with antioxidant and antimicrobial activities. Key bioactive compounds identified through HPLC were subjected to Molecular Docking, Density Functional Theory, and 100 ns Molecular Dynamics (MD) simulations to assess their interactions with Penicillin-Binding Protein 3, as the primary target for molecular dynamics, while FtsZ and DNA Gyrase B were evaluated to assess multi-targeting potential. The hydroethanolic extract exhibited a higher yield (10.9%) compared to the ethanolic extract (3.7%), as well as superior levels of total phenolics (207.07 ± 0.94 mg GAE/g DW), flavonoids (4.19 ± 0.21 mg CE/g DW), and tannins (191.76 ± 1.55 mg CE/g DW). While the ethanolic extract showed higher antioxidant activity (IC 50 of 0.147 mg/mL), the hydroethanolic extract displayed greater antimicrobial activity, particularly against Staphylococcus aureus (14.37 mm inhibition zone). HPLC analysis identified catechin (72.35 µg/g DW) and myricetin (6.34 µg/g DW) as the predominant compounds. In silico analysis revealed that while myricetin exhibited the highest initial binding affinity (− 8.1 kcal/mol) and the highest chemical reactivity, kaempferol demonstrated superior structural stability and compactness during the 100 ns MD simulations. The 7ONN-Kaempferol complex maintained high stability with a low root-mean-square deviation (RMSD, ~ 1.5–2.0 Å) and minimal residue fluctuations (RMSF < 0.8 Å). These findings provide a computational basis for the mechanistic link between specific flavonoid aglycones and the simultaneous disruption of bacterial cell wall synthesis, bacterial division, and DNA replication. This study highlights the potential of sea buckthorn leaves as a sustainable source of natural bioactive compounds with promising therapeutic applications.
Affective reactivity to upward social comparisons rather than social media use predicts increases in early adolescents’ depressive symptoms
Abstract Youths differ substantially in how they emotionally respond to daily experiences. Repeated episodes of heightened negative affect in daily life may accumulate over time and increase vulnerability for developing depressive disorders. This study examined whether individual differences in negative affective reactivity to daily social experiences (i.e., social media use and upward social comparisons) predict changes in depressive symptoms over two weeks. Using a 14-day diary design with 200 early adolescents (103 female; ages 10–14), we assessed daily social media use, daily upward social comparisons, daily negative affect, and depressive symptoms at pre- and posttest. We employed multilevel structural equation modeling, estimating the within-person coupling between daily social media use (Model 1) or upward social comparisons (Model 2) and daily negative affect and tested whether between-person differences in the strength of this coupling predicted average negative affect and depressive symptom change. Findings revealed that a stronger within-person coupling between upward social comparisons and negative affect, but not between social media use and negative affect, was associated with an increase in depressive symptoms via elevated negative affect across the study. These results highlight the importance of capturing dynamic affective responses to daily social comparison processes when assessing psychological risk in early adolescence.
Lateral distribution of electrical defect concentration in SA TG coplanar IGZO TFTs extracted via low frequency noise analysis
Abstract This study presents a methodology for extracting the lateral distribution of electrical defect concentration ( N B ) associated with gate-insulator traps contributing to low-frequency noise (LFN) of self-aligned top-gate (SA TG) coplanar indium–gallium–zinc oxide (IGZO) thin-film transistors (TFTs) using low-frequency noise (LFN) analysis. The proposed approach utilizes modulation of the effective channel length by drain voltage (or source voltage) together with an LFN power spectral density model to obtain the average defect concentration corresponding to different effective channel lengths, from which the lateral defect distribution can be derived. The extracted results reveal that pristine devices exhibit a relatively uniform defect distribution along the channel with slightly higher values near the source and drain regions. After the application of saturation stress, a noticeable increase in the defect concentration is observed near the drain side of the channel, indicating localized degradation of the gate insulator. These findings demonstrate that LFN analysis can be used to experimentally probe the spatial distribution of gate-insulator defects in SA TG coplanar IGZO TFTs, providing a useful diagnostic approach for studying reliability degradation mechanisms in advanced display backplane devices.
Tropical climate modes control strength and distribution of thermal stress mitigation in a coral reef refugia
Abstract Tropical coral reefs are threatened by rising seawater temperatures. However, cold-water intrusions to coral reefs by oceanic processes such as upwelling or internal waves, which propagate along the thermocline, can offer refugia from global warming. How reef temperatures and coral responses vary in such locations remains poorly understood due to limited in-situ observations. We present monthly subsurface temperature and coral response records based on coral skeletal geochemistry from the Andaman Sea, a known thermal refugia. Coral Sr/Ca-temperature indicates subsurface reef cooling varied at interannual to decadal timescales, driven by large-scale wind and thermocline changes, and was most pronounced during the combined positive Indian Ocean Dipole and El Niño event of 1997/98. Coral carbon isotopes indicate relative shifts from autotrophy to heterotrophy during most coral bleaching events observed in the Andaman Sea, except during the 1998 event when we found strong and widespread subsurface reef cooling by thermocline shoaling leading to enhanced influence of internal waves. Our results indicate tropical climate modes such as the Indian Ocean Dipole and the El Niño-Southern Oscillation controlled the strength and spatial distribution of thermal stress mitigation by oceanic processes through time, suggesting some coral reef refugia will be variable under future climate change.