Search Results (192)

This study systematically investigates the impact of Cu²⁺ doping on the structural, magnetic, and magnetocaloric properties of Cu_xCo_1−xCr₂O₄ nanoparticles synthesized via a solution combustion method. Cu incorporation up to x = 20% induces a progressive structural transformation from a cubic spinel to a trigonal corundum phase, as confirmed by X-ray diffraction and Raman spectroscopy. The doping process also leads to increased particle size, improved crystallinity, and reduced agglomeration. Magnetic measurements reveal a transition from hard to soft ferrimagnetic behavior with increasing Cu content, accompanied by a notable rise in the Curie temperature from 97.7 K (x = 0) to 140.2 K (x = 20%). The magnetocaloric effect (MCE) is significantly enhanced at higher doping levels, with the 20% Cu-doped sample exhibiting a maximum magnetic entropy change (−ΔS_M) of 2.015 J/kg-K and a relative cooling power (RCP) of 58.87 J/kg under a 60 kOe field. Arrott plot analysis confirms that the magnetic phase transitions remain second-order in nature across all compositions. These results demonstrate that Cu doping is an effective strategy for tuning the magnetostructural response of CoCr₂O₄ nanoparticles, making them promising candidates for low-temperature magnetic refrigeration applications. Full article

Background: This study aimed to compare the effects of an eight-week horizontal versus vertical vector resistance training program on swim start performance and lower-limb neuromuscular function in competitive swimmers. Methods: A total of 16 collegiate swimmers (14 males and 2 females; height: 176.3 ± 10 cm; body mass: 68.8 ± 10.3 kg; age: 20.5 ± 2.3 year) were assigned to either a horizontal vector training (HOR) or a vertical vector training (VER) group and completed an eight-week training program. Pre- and post-intervention assessments included flight time, flight distance, underwater speed, 15 m swim speed, 25 m swim speed, and force–time metrics within both concentric and eccentric phases of the countermovement jump and squat jumps. Results: No group or interaction effects were observed. However, time effects were found for flight distance (↑ 4.1–5.5%), flight time (↑ 6.2–12%), 15 m swim speed (↑ 0.3–0.7%), and jump performance. The HOR showed more favorable within-group trends in regards to swim start performance and concentric performance of countermovement and squat jumps. Moderate correlations (r = 0.450–0.476) were found between changes in concentric jump variables and 15 m swim speed. Conclusions: These results suggest that both vertical and horizontal vector resistance training can improve lower-limb neuromuscular performance and swim start performance. Full article

Alginate lyases are critical enzymes in hydrolyzing alginate into alginate oligosaccharides (AOS), which are bioactive compounds known for their antioxidant properties and ability to lower serum glucose and lipid concentrations. However, elucidating catalytic mechanisms and discovering enzymes with enhanced catalytic efficiency remain long-term challenges. Here, we report AlgL2491, a novel bifunctional and cold-adapted alginate lyase from Pseudoalteromonas carrageenovora ASY5, belonging to the polysaccharide lyase family 18. This enzyme uniquely cleaves both polyguluronic (polyG) and polymannuronic (polyM), predominantly releasing disaccharides, trisaccharides, and tetrasaccharides after 12 h of hydrolysis. The enzyme achieves peak catalytic efficiency at 35 °C and pH 7.5, with activity increasing 5.5-fold in 0.5 M of NaCl. Molecular dynamics simulations demonstrate that salt ions enhance structural stability by minimizing conformational fluctuations and strengthening interdomain interactions, providing mechanistic insights into its salt-activated behavior. The alginate oligosaccharides (AOS) exhibit excellent free radical-scavenging activities of 86.79 ± 0.31%, 83.42 ± 0.18%, and 71.28 ± 2.27% toward hydroxyl, ABTS, and DPPH radicals, with IC50 values of 8.8, 6.74, and 9.71 mg/mL, respectively. These findings not only reveal the salt-activation mechanism of AlgL2491 and highlight the potential value of its hydrolysate in antioxidant activity but also provide a sustainable industrial solution in industrial-scale AOS production directly from marine biomass, eliminating the need for energy-intensive desalination of alginate, which may inform future biocatalyst design for marine polysaccharide valorization. Full article

In conventional hydrology, a short-duration design rainstorm is typically used to estimate the design discharge in urban sewer systems. The reason for using a short duration is that engineers believe the time of concentration in urban watersheds is relatively small. The short-duration hyetograph is supposed to generate a flow hydrograph that accurately reflects the rainfall-runoff processes. In this study, we developed a street-sewer runoff model for an urban district of 2470 hectares. Detailed field flooding records were utilized to verify the stormwater model’s capability for inundation simulations. Subsequently, different rainfall series extracted from the recorded rainstorm data were used to investigate the causes of flooding corresponding to different durations of rainstorms. The results indicate that a 90 min main concentrated rainstorm causes small-scale flooding only; however, a 24 h rainfall series results in an extensive range of inundations. We further conducted similar short- and long-duration hyetograph tests in 16 urban drainage partitions (ranging from 2.3 to 193.5 hectares) to confirm the above findings. The results indicate that the maximum discharge in most partitions can only be found when the hyetograph duration exceeds 1080 min, which essentially contradicts previous engineering designs in urban watersheds in Taiwan. Full article

Background/Objective: Avapritinib is an orally bioavailable tyrosine kinase inhibitor and was approved by the FDA in 2020 for gastrointestinal stromal tumor treatments. Although avapritinib is known to be chiral, its stereochemistry was initially established randomly. This study aims to develop a definitive method for determining avapritinib’s absolute configuration and propose a universal methodology for stereochemical characterization of flexible chiral drugs. Methods: The absolute configuration of avapritinib was determined through an integrated approach combining chiral resolution, chiroptical spectroscopy and synthetic validation. Enantiomeric separation was achieved via chiral liquid chromatography, followed by comprehensive chiroptical characterization including electronic circular dichroism (ECD), specific optical rotation and optical rotatory dispersion. Conformational analysis and density functional theory (DFT) calculations correlated experimental spectra with theoretical predictions, facilitating definitive configurational assignment. The stereochemical determination were further verified through ECD derivatization and chemical synthesis. Finally, the enantiomers’ kinase inhibition profiles against c-KIT D816V were quantitatively assessed. Results: Two enantiomers of avapritinib were resolved via chiral HPLC and a Chiralpak IG column. Through combined experimental ECD spectra and time-dependent DFT calculations employing the core extraction method, the levo-isomer was unambiguously determined as S configuration. This stereochemical assignment was confirmed by p-cyanobenzaldehyde derivatization and de novo synthesis. Biological evaluation revealed (S)-(−)-avapritinib exhibited superior c-KIT D816V inhibitory activity compared to its (R)-(+)-counterpart, a finding corroborated by molecular docking studies elucidating their differential target interactions. Conclusions: This study advances avapritinib stereochemical understanding and establishes a definitive protocol for its absolute configuration assignment, serving as a paradigm for flexible chiral drug characterization. Full article

The creation of coatings by the cathodic arc evaporation method has outstanding advantages: these coatings are highly durable and wear-resistant, especially since the method has an intense ionization process and the atoms can penetrate deep into the surface substrates, resulting in excellent adhesion. Furthermore, this approach provides precise control over the chemical composition and thickness of the coating, ensuring consistent quality across the entire surface. However, uneven evaporation and ejection of molten metal droplets from the cathode during cathode arc deposition produce particles and droplets, resulting in an uneven coating surface. This study presents a new design for a magnetically controlled cathode arc source to effectively reduce particles and droplets during the cathodic arc deposition of multi-component alloy targets for nitride-based hard coatings. The study compares the performance of a new source with a conventional magnetic-controlled arc source for depositing TiAlNbSiN and AlCrSiN films. In the conventional source, the magnetic field is generated by a permanent magnet (PM), whereas in the new source, it is generated and controlled using an electromagnet (EM). Both films are produced using multi-component alloy targets (TiAlNbSi and AlCrSi) with identical composition ratios. The plasma characteristics of the two different arc sources are investigated using an optical emission spectrometer (OES), and the surface morphology, structural characteristics, deposition rate, uniformity, and surface roughness (Sa) are examined using scanning electron microscopy (SEM). When the EM was applied to have high plasma density, the hardness of the TiAlNbSiN film deposited with the novel arc source measured 31.2 ± 1.9 GPa, which is higher than that of the PM arc source (28.3 ± 1.4 GPa). In contrast, the AlCrSiN film created using a typical arc source exhibited a hardness of only 25.5 ± 0.6 GPa. This lower hardness may be due to insufficient ion kinetic energy to enhance stress blocking and increase hardness, or the presence of the h-AlN phase in the film, which was not detected by XRD. The electromagnet arc source, with its adequate ion bombardment velocity, facilitated a complementary effect between grain growth and stress blocking, leading to a remarkable hardness of 32.6 ± 0.5 GPa. Full article

Background: The relationship between sarcopenia and the incidence of coronary artery disease (CAD) is not well understood. This study aimed to investigate this relationship and the modifying effect of potential risk factors. Methods: We conducted a prospective study including 439,295 individuals from the UK Biobank. The primary outcome was the incidence of CAD. The main physical capability markers for sarcopenia, grip strength and muscle mass, were investigated as risk factors of interest. Grip strength was measured using a Jamar J00105 (Lafayette, IN, USA) hydraulic hand dynamometer, while muscle mass was estimated through bioelectrical impedance. Cox proportional hazard models were employed to analyze the associations between the exposures and the risk of CAD. Results: A total of 41,564 incident cases of CAD were identified after a median follow-up of 13.15 years (IQR 12.29–13.88 years). Compared with the lowest quintile of grip strength, the adjusted HRs for incidences of CAD from the second to the fifth quintile were 0.81 (95% CI: 0.79–0.83), 0.71 (95% CI: 0.69–0.73), 0.61 (95% CI: 0.60–0.63), and 0.49 (95% CI: 0.48–0.51). The association remained significant in subgroup analysis and interactions were observed between the two exposures and sex, age, smoking status, inflammatory diseases, metabolic syndrome, and genetic predisposition (all p for interactions < 0.05). Conclusions: Physical capability markers of sarcopenia, grip strength and muscle mass, were independently associated with a dose–response decreased risk for CAD incidence, regardless of genetic predisposition and potential modifying risk factors. Full article

Hip fractures significantly affect mortality and quality of life in the elderly population. Although alpha-blockers are commonly prescribed for lower urinary tract symptoms after transurethral resection of the prostate (TURP), their long-term safety regarding fracture risk remains controversial. This study aimed to investigate whether long-term alpha-blocker use after TURP affects the risk of hip fractures requiring surgery in elderly men. This study included 6853 male patients aged ≥50 years who underwent TURP between 2000 and 2018. The alpha-blocker group (n = 1371) included patients who continued alpha-blocker treatment after TURP, while the control group (n = 5482) included those who had discontinued the medication. The primary outcome was hip fracture requiring surgical intervention. During follow-up (3.80 ± 1.64 years), hip fracture occurred in 4.2% of the alpha-blocker group versus 5.6% of controls. After adjusting for baseline characteristics and competing risk analysis, alpha-blocker use was associated with a significantly lower risk of hip fracture (p = 0.005). Subgroup analysis revealed particularly strong protective effects in patients with diabetes. Long-term use of alpha-blockers after TURP was associated with reduced hip fracture risk, particularly in patients with diabetes. These findings suggest the safety of continued alpha-blocker therapy after TURP in these patients. Full article

Tanypodinae, a highly diverse subfamily within Chironomidae (Diptera), has been poorly represented in mitochondrial genome (mitogenome) databases, with only a limited number of complete or partial sequences available. To address this gap, we present the first complete mitogenome sequences of 16 Tanypodinae species and 1 Podonominae species. By integrating these novel data with previously published chironomid mitogenomes, we conducted a comprehensive comparative mitogenomic analysis of 21 Tanypodinae species. Our results reveal that Tanypodinae mitogenomes maintain a conserved structural organization, preserving the ancestral insect gene arrangement. The nucleotide composition exhibits significant bias, with the control region demonstrating the highest A + T content among all genomic regions. Evolutionary analysis indicates that all protein-coding genes (PCGs) are subject to purifying selection, with ATP8 exhibiting the most rapid evolutionary rate. Phylogenetic reconstruction based on PCG amino acid sequences delineates seven well-supported clades within Tanypodinae, corresponding to the tribes Pentaneurini, Natarsiini, Procladiini, Tanypodini, Clinotanypodini, Macropelopiini, and Anatopyniini. These findings significantly advance our understanding of mitogenomic architecture and provide critical insights into the phylogenetic relationships within Tanypodinae. Full article

This study aimed to assess the impact of radish sprouts on the gut microbiota of healthy individuals. Radish sprout additives, subjected to short-term storage and steam treatment, were used to intervene in an in vitro culture of human gut microbiota. The influence of radish sprouts on the gut microbiota was evaluated by monitoring short-chain fatty acid (SCFA) content and proportion in the fermentation broth, and microbial diversity was assessed using 16S rDNA amplicon sequencing. The results indicated that the gut microbiota produced a substantial amount of SCFA within 48 h of fermentation, with a right-skewed distribution across all groups. The addition of both digestates enhanced Firmicutes diversity, while Bacteroidetes and Proteobacteria diversity remained stable between the control and fresh sprout groups. The 30 s steam treatment group showed an increase in Bacteroidetes and a decrease in Proteobacteria diversity. The abundance of Bacilli, Bacillaceae, and Bacillus was significantly higher in both the fresh and steam-treated groups compared to the control. Both fresh and steam-treated radish sprout digestates enriched gut microbiota diversity, with steam treatment showing superior effects. These findings suggest that radish sprout consumption may positively influence gut microbiota, with steam treatment potentially enhancing these benefits. Full article

Ubiquitin-conjugating enzyme E2 T (UBE2T) is a crucial E2 enzyme in the ubiquitin-proteasome system (UPS), playing a significant role in the ubiquitination of proteins and influencing a wide range of cellular processes, including proliferation, differentiation, apoptosis, invasion, and metabolism. Its overexpression has been implicated in various malignancies, such as lung adenocarcinoma, gastric cancer, pancreatic cancer, liver cancer, and ovarian cancer, where it correlates strongly with disease progression. UBE2T facilitates tumorigenesis and malignant behaviors by mediating essential functions such as DNA repair, apoptosis, cell cycle regulation, and the activation of oncogenic signaling pathways. High levels of UBE2T expression are associated with poor survival outcomes, highlighting its potential as a molecular biomarker for cancer prognosis. Increasing evidence suggests that UBE2T acts as an oncogene and could serve as a promising therapeutic target in cancer treatment. This review aims to provide a detailed overview of UBE2T’s structure, functions, and molecular mechanisms involved in cancer progression as well as recent developments in UBE2T-targeted inhibitors. Such insights may pave the way for novel strategies in cancer diagnosis and treatment, enhancing our understanding of UBE2T’s role in cancer biology and supporting the development of innovative therapeutic approaches. Full article

This study focuses on the development of polymer–bioglass composite bone scaffolds for the treatment of bone defects. PCL particles and 45s5 bioglass powder were employed as raw materials to fabricate PCL/45s5 composite wires with mass fractions of 5 wt%, 10 wt%, and 20 wt% via the twin-screw extrusion method. A cylindrical porous model was established using 3D modeling software, and a porous composite scaffold was constructed through the melt deposition manufacturing process. The macroscopical characterization of composite stock and composite powder was analyzed. The melt flow rate, water contact angle, elastic modulus, in vitro degradation rate, and antibacterial property of composite scaffold were measured. The experimental results showed that the incorporation of 45s5 bioglass into PCL material gave the composite better antibacterial properties, effectively reduced the flow rate of the material, increased the hydrophobicity of the material, and improved the rigidity and biocompatibility of the PCL material. This study offers initial insights into the use of synthetic bone tissue engineering scaffolds for clinical bone repair treatments. Full article

Sleep deprivation (SD) disrupts circadian rhythms; however, its effects on SD and the mechanisms involved require further investigation. Previous studies on SD were mainly conducted on rodents, such as mice, with few studies on its effects on the liver of large diurnal animals, such as sheep. In this study, we used a Tibetan sheep model for the first time to investigate the effects of SD on the liver by exposing Tibetan sheep (Ovis aries) to 7 days of SD (6 h/day) and performed transcriptome sequencing analysis on liver samples taken at 4 h intervals over 24 h. The results revealed that SD significantly altered the circadian expression of genes and their expression patterns in the liver of Tibetan sheep. Enrichment analysis of the circadian rhythm-altered genes revealed changes in the pathways related to lipid metabolism in the liver. Further evidence from serum markers and gene expression analyses using qualitative real-time polymerase chain reaction and Oil Red O and apoptosis staining indicated that SD leads to abnormal lipid metabolism in the liver, potentially causing liver damage. Therefore, our results suggest that SD disrupts the circadian rhythms of metabolism-related genes in the Tibetan sheep liver, thereby affecting metabolic homeostasis. Full article

Dicer, a cytoplasmic type III RNase, is essential for the maturation of microRNAs (miRNAs) and is implicated in cancer progression and chemoresistance. Our previous research demonstrated that phosphorylation of Dicer at S1016 alters miRNA maturation and glutamine metabolism, contributing to gemcitabine (GEM) resistance in pancreatic ductal adenocarcinoma (PDAC). In this study, we focused on the role of Dicer phosphorylation at S1728/S1852 in GEM-resistant PDAC cells. Using shRNA to knock down Dicer in GEM-resistant PANC-1 (PANC-1 GR) cells, we examined cell viability through MTT and clonogenic assays. We also expressed phosphomimetic Dicer 2E (S1728E/S1852E) and phosphomutant Dicer 2A (S1728A/S1852A) to evaluate their effects on GEM resistance and metabolism. Our results show that phosphorylation at S1728/S1852 promotes GEM resistance by reprogramming glutamine metabolism. Specifically, phosphomimetic Dicer 2E increased intracellular glutamine, driving pyrimidine synthesis and raising dCTP levels, which compete with gemcitabine’s metabolites. This metabolic shift enhanced drug resistance. In contrast, phosphomutant Dicer 2A reduced GEM resistance. These findings highlight the importance of Dicer phosphorylation in regulating metabolism and drug sensitivity, offering insights into potential therapeutic strategies for overcoming GEM resistance in pancreatic cancer. Full article