Search Results (76,252)

Background: Long noncoding RNAs (lncRNAs) have emerged as critical regulators of hepatic metabolism and disease progression. The hepatocyte nuclear factor 1 alpha antisense 1 (HNF1A-AS1) lncRNA modulates liver-specific transcription factors; however, its physiological role in diet-dependent lipid homeostasis remains poorly defined. Methods: In this study, we investigated the mouse ortholog, Hnf1a opposite strand 1 (Hnf1aos1), using AAV-mediated knockdown in C57BL/6J mice fed either a chow diet (10% kcal from fat) or a high-fat diet (HFD; 60% kcal from fat) for 12 weeks. Metabolic phenotyping included hepatic lipid quantification, histological analysis, serum biochemistry, and quantitative gene expression profiling. Results: Loss of Hnf1aos1 produced distinct, diet-dependent alterations in hepatic lipid handling. Under chow conditions, knockdown mice exhibited selective hepatic cholesterol accumulation (6.10 ± 2.9 mg/g tissue vs. 3.51 ± 1.1 mg/g in controls), accompanied by dysregulation of cholesterol clearance pathways. In contrast, under HFD conditions, knockdown precipitated severe macrovesicular degeneration, with hepatic triglyceride levels approximately doubled relative to HFD-fed controls (51.72 ± 19.8 mg/g vs. 26.34 ± 11.9 mg/g) and a numerically elevated triglyceride-to-cholesterol ratio (TG:TC ≈ 6.1:1; p = 0.0621, trend). Chow/Kd mice gained significantly less weight than chow-fed controls, whereas HFD/Kd mice exhibited weight gain comparable to HFD controls despite severe hepatic steatosis. This paradoxical phenotype suggests impaired metabolic feedback at the post-transcriptional level, in which compensatory upregulation of Hnf1a mRNA is insufficient to suppress lipid-associated genes such as Cd36, despite profound lipid overload; however, HNF1A protein levels were not directly measured in this study. Conclusion: Collectively, these findings identify Hnf1aos1 as a regulator of hepatic lipid homeostasis whose loss produces a phenotype consistent with inappropriate lipid accumulation during nutrient excess, without defining the underlying molecular mechanism. Our results support a role for Hnf1aos1 in shaping hepatic metabolic plasticity and provide insight into lncRNA-associated MASLD phenotypes. Full article

High-quality, large-weight alloy wires (>200 kg per coil) for aerospace fasteners require intermediate annealing prior to final cold drawing, as well as subsequent solution and aging heat treatments, which are critical processes during their manufacturing. However, the evolution of microstructure and mechanical properties during these procedures has not been systematically investigated. In this study, different cooling methods after intermediate annealing were comparatively investigated to clarify their influence on the microstructure evolution, precipitation behavior, and mechanical properties of Al–Zn–Mg–Cu alloy wires. The results revealed that the cold heading performance of alloy wires is determined by the strength–ductility balance, crystallographic texture, and precipitation behavior. Furnace cooling promoted η′ phase coarsening, resulting in lower strength and higher ductility, which enhanced deformation homogeneity and cold heading formability. The near-zero Δr reduced strain localization and cracking susceptibility, whereas higher Δr in water- and air-cooling samples increased anisotropy and cracking tendency. After heat treatment, strength differences became negligible, whereas elongation remained texture dependent, with the weaker texture in the furnace-cooling sample yielding superior ductility. Full article

Background: Wugeng San (WGS) is a traditional Tibetan medicinal preparation that has long been used to treat inflammatory and arthritic conditions. However, its contemporary pharmacological validation and the mechanisms underlying its action in rheumatoid arthritis (RA) have not been fully investigated. Objective: For the first time, this study aimed to systematically investigate the therapeutic effects of WGS on RA, identify its potential targets, and elucidate its action mechanisms. Methods: This study, as the first comprehensive investigation of WGS in RA, employed integrated multiple approaches including chemical component identification via UPLC-Q-TOF/MS, network pharmacology, bioinformatics, machine learning, and in vivo efficacy assessment and mechanism verification in a collagen-induced arthritis (CIA) rat model, a widely accepted experimental model that mimics the key pathological features of RA. Results: The results demonstrated that WGS reduced the severity of arthritis in a dose-dependent manner, as evidenced by decreased paw swelling, normalized body weight, and restored levels of pro- and anti-inflammatory cytokines. The high dose of WGS (252 mg/kg) showed an effect comparable to that of methotrexate (0.2 mg/kg). Histological analysis revealed that WGS reduced synovial hyperplasia, cartilage erosion and bone destruction, decreased osteoclast numbers, and promoted osteoblast activity. Eighty-four compounds were identified using UPLC-Q-TOF/MS. Network pharmacology and machine learning analyses indicated SYK as a key target enriched in the NF-κB signaling and osteoclast differentiation pathways. Experimental validation confirmed that WGS suppressed the phosphorylation of SYK and NF-κB pathway components (p65, IκBα, and IKKα/β), decreased MMP1/MMP3 levels, and modulated the Bax/Bcl-2 ratio to promote apoptosis. Conclusions: In conclusion, WGS exhibits strong anti-arthritic effects through “multi-component, multi-target, and multi-pathway” mechanisms, likely attributable to the inhibition of the SYK/NF-κB signaling axis, suppression of matrix degradation, and regulation of cellular apoptosis. This research offers a pharmacological basis for repurposing WGS as a promising natural candidate for RA therapy. Full article

Agricultural byproducts cellulose-rich (~40%) sugarcane bagasse (SCB) and rice husk (RH) wastes may be used as fiber sources in biomaterials manufacturing. The hybrid biomass fibers are two kinds of fibers that should generate a biocomposite according to the functions and physical, chemical, and mechanical properties of materials. The biocomposite was synthesized using the solvothermal method. The FeCl₃.6H₂O was dissolved in C₂H₃NaO₂ and C₆H₆O₂ and later heated at 60 °C. The SCB and RH fiber (1:1) are added with HDMA into the mixture, then placed in a Teflon stainless steel autoclave at 200 °C for 6 h. The biocomposite was employed as a green adsorbent to treat wastewater through simultaneous adsorption. The biocomposite had 2.637 mmol g⁻¹ of amine groups, which makes smaller magnetic particles and a high surface area of up to 79%. The pseudo-second-order kinetic model followed the Cu(II) and Pb(II) ions adsorption for 4 h (240 min), and the maximum adsorption capacities were 35.042 mg g⁻¹ and 67.127 mg g⁻¹, respectively, at the pH of 5. The biocomposite not only got rid of metal ions, but it also worked well to get rid of dye, total suspended solids (TSSs), and chemical oxygen demand (COD) as pollutants in wastewater. The biocomposite still worked well after being used four times. Full article

Background/Objectives: A sub-anesthetic dose of ketamine has shown promise in reducing craving, withdrawal symptoms, and use of drugs such as alcohol, cocaine, and opioids among individuals with substance use disorders. Ketamine’s therapeutic potential for tobacco use is unknown. Here, we investigated a single sub-anesthetic dose among adults with tobacco use disorder who were not interested in changing their smoking behavior. Methods: Utilizing a randomized, within-subject crossover, double-blinded, counter-balanced, midazolam-controlled design, participants (n = 18) received a 0.71 mg/kg infusion of ketamine and a 0.025 mg/kg infusion of midazolam (i.e., active placebo) at least two weeks apart. Participants were asked to abstain from smoking after the infusions until the post-infusion sessions, 1 day following infusion, where participants completed measures of smoking behavior, craving, and withdrawal symptoms. Participants continued to record their smoking behavior over the 7 days following infusion. Participants also completed a semi-structured qualitative interview regarding their experiences. Results: Compared to midazolam, ketamine infusion led to a non-significant reduction (p = 0.10, ƞ_p² = 0.153) in the number of cigarettes smoked during the requested abstinence period. Following this period, there were no significant differences in ad lib smoking. Ketamine showed no effect on craving or withdrawal symptoms. Participants reported more intense psychological experiences following ketamine infusion (p < 0.001, ƞ_p² = 0.830) and about half reported it felt easier to abstain from smoking after the ketamine infusion. Conclusions: While well tolerated, these findings suggest ketamine has little to no direct effect on quantitative measures of cigarette smoking, craving, or withdrawal. However, the qualitative measures suggest ketamine improves mood and reduces craving in some individuals for several days. Future studies should investigate whether ketamine can indirectly support smoking cessation among individuals with comorbid psychiatric indications for ketamine treatment. Full article

Desert steppe is a typical ecosystem in arid and semi-arid regions and an important component of the global carbon cycle. Under the background of global climate change, the increasing frequency of extreme precipitation events and changes in precipitation patterns can significantly affect water- and heat-sensitive desert steppe ecosystems, thereby regulating soil CO₂ flux; however, the underlying mechanisms remain unclear. To investigate the effects of precipitation changes on soil CO₂ flux and their roles in carbon cycling and ecological sustainability, this study was conducted in a desert steppe. Seven precipitation treatments were established, including a control (CK) and ±15%, ±30%, and ±45% precipitation gradients. Based on the static chamber-gas chromatography method, combined with principal component analysis (PCA), correlation analysis, random forest modeling, and stepwise regression, the main influencing factors and their diurnal variation patterns of soil CO₂ flux were analyzed over 24 h periods from June to August. The results show that CO₂ flux ranged from −68.33 to 77.59 mg·m⁻²·h⁻¹. During the study period, CO₂ flux exhibited a diurnal pattern characterized by daytime emissions and weak nighttime emissions or uptake, along with clear seasonal variation. The ±30% precipitation treatment showed the largest fluctuation in CO₂ flux. Soil hydrothermal factors were identified as the key drivers of CO₂ flux. With changes in precipitation intensity, the combined effects of multiple factors increased ecosystem complexity, and the controlling factors showed clear seasonal differences. The results from different analytical methods were generally consistent, providing a reference for predicting CO₂ flux, developing carbon sink strategies, and supporting sustainable ecological management in desert steppe regions. Full article

Although adding phosphorus (P) and zinc (Zn) fertilizers to rhizobial inoculation improves nutrient accumulation in chickpeas, it is unclear which is most effective. This study evaluated whether inoculating chickpeas grown in silty-loam or silty-clay-loam soil with liquid- or peat-based rhizobial inoculants, in addition to P and/or Zn fertilizer, alters shoot nutrient concentration. The following genotypes were used: ICCV3110, ICCV8101, ICCV97024 and ICCV92944. The following levels of fertilizer were used: no addition of fertilizer, 10 kg/ha Zn, 40 kg/ha P, and Zn plus P. The following combinations of fertilizer and rhizobial inoculation were used: Zn plus P (peat-based inoculant), denoted as Zn + P + R_P, and Zn plus P (liquid-based inoculant), denoted as Zn + P + R_L. Our results showed that ICCV97024 exhibited increased shoot P, Ca, Mg, Fe and Zn concentrations when grown in silty-loam soil and increased shoot Ca, Zn, Mn and B concentrations when grown in silty-clay-loam soil. Adding P, or P plus Zn, increased shoot P, while adding Zn, or Zn plus P + R_L, enhanced shoot P, Fe and B. Adding Zn increased shoot Zn, K and Ca, and adding Zn plus P + RP increased shoot Ca. Overall, chickpeas grown in silty-loam soil accumulated the most nutrients. Adding P, P plus Zn and Zn + P + R_L improved shoot P, while adding Zn and Zn + P + R_P enhanced shoot Zn and Ca, respectively. Full article

To address the emerging multidrug-resistance crisis caused by Klebsiella pneumoniae, we expressed the endolysin Lys59 derived from phage VB_KpP_HS106 and performed a comprehensive analysis of its antibacterial activity and structural features. Molecular modeling revealed that Lys59 carries a highly positively charged N-terminus and an amphipathic helix at the C-terminus. In vitro antibacterial assays showed that Lys59 exhibited significant bactericidal activity against K. pneumoniae with an approximately 4 log reduction at 50 µg/mL in 2 h. Meanwhile, Lys59 exhibited potent, broad-spectrum activity against both Gram-negative and Gram-positive bacteria. Stability analysis indicated that Lys59 retained high activity over a pH range of 3–9 and a temperature range of 4–55 °C. Notably, the antibacterial activity of Lys59 was found to be regulated by metal ions. Molecular docking indicated that K⁺ can enhance binding stability by interacting with ASN35 and VAL57. In contrast, Mg²⁺ and Ca²⁺ suppressed catalytic function by binding to the essential GLU17 residue. Furthermore, treatment with 200 µg/mL of Lys59 resulted in a 44.6% reduction in K. pneumoniae biofilm biomass. Overall, this study identified a phage-derived endolysin with broad-spectrum antimicrobial activity and demonstrated its potential as an antibacterial agent against multidrug-resistant K. pneumoniae. Full article

A detailed analysis of the effects of magnesium on the microstructure of hypereutectic Al–20Si alloys is provided in this study. Experimental results show that the addition of Mg significantly refines the primary silicon phase relative to the unmodified Al–20Si alloy, transforming its morphology from a complex form to a singular plate-like structure. Notably, for the first time, equiaxed aluminum grains appear in the aluminum matrix under conventional solidification conditions. The generation of these grains is closely related to the quenching effect caused by rapid cooling during metal mold casting, which promotes the generation of equiaxed aluminum grains within tightly constrained temporal and spatial parameters. The Al–Si eutectic structure exhibits a regular lamellar morphology, with an average eutectic silicon spacing of 930.97 nm. The phase analysis shows that the alloy mainly consists of Al, Si, and Mg₂Si phases after the addition of Mg. With the increase in Mg concentration, the diffraction peaks for Al(200) and Si(220) first shift to lower angles and then move to higher angles, along with significant peak broadening. Ambient temperature mechanical testing indicates that tensile strength first increases with increasing Mg concentration, then declines, with the highest tensile strength of 235.1 MPa at 3 wt.% Mg in the Al–20Si alloy. The fracture mechanism of the testing specimens changes from cleavage fracture to ductile fracture. Microhardness testing indicates a continuous increase in the hardness of the aluminum matrix with rising Mg concentration; the hardness of primary silicon declines first and then increases, whereas the hardness of the eutectic structure exhibits a first increase followed by a decline. Full article

Groundwater contamination by dissolved metals and metalloids in the Chiang Mai Basin is an important drinking-water concern, yet the coupled depth patterns, hydrogeochemical controls, composite contamination status, and screening-level health implications have not previously been assessed in an integrated basin-scale framework. This study evaluated 120 groundwater samples from alluvial wells classified by depth as shallow (≤30 m, n = 40), intermediate (31–60 m, n = 35), and deep (>60 m, n = 45). Samples were analyzed for nine dissolved metals and metalloids (Fe, Mn, As, Cd, Pb, Cr, Zn, Hg, and Se) together with pH, Eh, and total dissolved solids (TDS). The highest exceedance frequencies were observed for Fe (72.5% of samples, >0.3 mg/L acceptability threshold), Mn (65.0%, >0.08 mg/L), and As (45.8%, >10 μg/L). Fe and Mn increased significantly with depth, whereas As was enriched in deep wells but showed no statistically significant depth dependence. Pearson correlation and principal component analysis consistently identified a dominant redox-associated component in which Fe, Mn, and As covaried negatively with Eh, supporting redox-sensitive co-enrichment in deeper groundwater. Contamination factors calculated relative to selected global groundwater background values were >6 for all seven evaluated metals (Fe, Mn, As, Cd, Pb, Cr, and Zn), and the overall pollution load index (PLI) was 9.11, with the highest depth-specific PLI in deep wells (10.42). These indices are interpreted here as background-relative screening tools rather than stand-alone regulatory measures. A screening-level ingestion risk assessment identified arsenic as the dominant toxicological driver, with hazard quotients (HQ) of 1.97 for adults and 4.60 for children, and an estimated lifetime cancer risk (LCR) of 8.87 × 10^–4. The results support targeted monitoring of deeper wells, routine screening for As and Mn, and treatment strategies that can address the co-occurring Fe–Mn–As assemblage in alluvial groundwater. Full article

The Yangtze River, the largest river system in Asia, continues to receive substantial nitrogen loads despite the implementation of management measures. Within this vast and complex system, the spatial patterns and drivers of key nitrogen transformation processes, such as nitrification and denitrification, remain poorly constrained. In particular, systematic isotopic evidence from studies spanning the entire upstream–midstream–downstream continuum remains scarce. This study integrates multiple isotopes (δ¹⁵N-NO₃⁻, δ¹⁸O-NO₃⁻, δ¹⁵N-NH₄⁺) with hydrochemical techniques to elucidate the dominant controls on nitrogen transport and transformation and their spatial heterogeneity across the Yangtze River Basin. Results indicate that dissolved inorganic nitrogen (DIN) is the dominant form of nitrogen pollution in the basin. NO₃⁻ concentrations exhibited significant spatial variability, following the pattern downstream (2.86 mg/L) > upstream (1.83 mg/L) > midstream (1.75 mg/L). Isotopic signatures revealed that nitrification is the dominant process controlling the formation and transformation of NO₃⁻ throughout the basin. Most δ¹⁸O-NO₃⁻ values (−5.20‰ to +12.78‰) fell within or close to the theoretical range for nitrification, and a strong positive correlation was observed between δ¹⁵N-NO₃⁻ and δ¹⁵N-NH₄⁺ (R² = 0.72, p < 0.01), collectively confirming that the conversion of NH₄⁺ to NO₃⁻ is the primary pathway. Conversely, denitrification was significantly suppressed under the prevailing high dissolved oxygen conditions (mean 9.78 ± 2.46 mg/L), as further evidenced by the lack of a significant correlation between δ¹⁵N-NO₃⁻ and ln(NO₃⁻). Furthermore, preferential assimilation of NH₄⁺ by phytoplankton reduced the efficiency of nitrate removal via biological assimilation and influenced isotopic composition. These findings provide a scientific basis for identifying priority nitrogen sources and optimizing targeted nitrogen management strategies in the Yangtze River Basin. Full article

Black rice is rich in anthocyanins with potential antioxidant benefits, but their specific role in storage stability remains unclear due to confounding genetic backgrounds in previous studies. In this study, we used CRISPR/Cas9-mediated gene editing to generate OsKala4 knockout lines in the black rice cultivar Heizhen (HZ), creating an isogenic system to test whether endogenous anthocyanins contribute to storage-related quality stability. Knockout lines showed blocked anthocyanin biosynthesis (0.5–0.6 vs. 155.6 mg/100 g, p < 0.001) and altered grain composition. Under accelerated aging (45 °C, 90% RH, 2 weeks), HZ maintained higher antioxidant capacity (p < 0.05) and exhibited less pronounced starch aging than the representative knockout line KO2. Apparent amylose content increased less in HZ than in KO2 (16.7% vs. 28.1%, p < 0.05). HZ also showed smaller changes in pasting, thermal, and structural properties. XRD and FTIR analyses further suggested better maintenance of starch crystallinity and molecular order in HZ under accelerated aging conditions. These results suggest that endogenous anthocyanins were associated with storage-related quality stability in black rice. However, direct mechanistic evidence and validation under natural storage conditions are still needed. Full article

A heteroatom-rich pyridine-based adsorbent (Pyridine PC) was synthesized through a multicomponent strategy and structurally confirmed by ¹H/¹³C NMR spectroscopy and mass spectrometry. To further enhance adsorption activity and surface reactivity, waste-derived CuO nanoparticles were immobilized onto the porous heterocyclic framework, generating a sustainable CuO@Pyridine PC hybrid nanocomposite. Batch adsorption experiments demonstrate highly efficient removal of malachite green (MG) dye and Cd(II) ions from aqueous solutions. Kinetic analysis reveals that adsorption follows the pseudo-second-order model, while equilibrium data are best described by the Freundlich isotherm, indicating adsorption on heterogeneous surfaces. Thermodynamic parameters confirm that the adsorption processes are spontaneous and exothermic. Surface and structural characterization using SEM/EDX, elemental mapping analysis and FT-IR before and after adsorption verifies strong pollutant binding and highlights the role of nitrogen- and oxygen-containing functional groups as dominant interaction sites. BET measurements show that CuO incorporation increases surface area and pore volume, while zeta potential analysis indicates excellent colloidal stability of the composite in aqueous media. Consequently, the CuO-modified sorbent exhibits enhanced adsorption capacities, increasing from 169.8 to 176.13 mg g⁻¹ for MG and from 276.5 to 368 mg g⁻¹ for Cd(II). The adsorbent demonstrated effective pollutant removal from real wastewater. The adsorption mechanism involves synergistic interactions between functional groups in the Pyridine PC matrix and CuO nanoparticles, providing enhanced active binding sites. Full article

Background: Acquired resistance to the third-generation EGFR tyrosine kinase inhibitor osimertinib, often mediated by EGFR triple mutations, poses a major clinical challenge in non-small cell lung cancer (NSCLC) treatment. Among these, some rare mutations, such as L858R/T790M/L792H and L858R/T790M/G796R, create steric hindrance that directly interferes with osimertinib binding, yet effective targeted therapeutic strategies for these specific mutations remain lacking. Cudratricusxanthone A (CTXA), a natural xanthone derivative isolated from Cudrania tricuspidata Bur., has demonstrated various pharmacological activities, but its effects against EGFR triple-mutant NSCLC have not been systematically investigated. Methods: Stable Ba/F3 and NIH/3T3 cell lines expressing EGFR L858R/T790M/L792H or L858R/T790M/G796R triple mutations were generated via electroporation. The antiproliferative effects of CTXA were evaluated by MTT/MTS assays, colony formation, and wound healing assays. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Protein expression of EGFR signaling pathway components (p-EGFR, p-ERK, p-AKT, p-STAT3) and cell cycle regulators (Cyclin D1, CDK4) were examined by Western blotting. Molecular docking and 200 ns molecular dynamics simulations were performed to investigate the stability and binding modes of CTXA to the mutant EGFR kinase domains. Results: The successfully established triple-mutant cell lines exhibited high EGFR expression, IL-3-independent growth, and significant resistance to osimertinib. CTXA inhibited the proliferation of all triple-mutant cell lines in a time- and concentration-dependent manner, with 48 h IC₅₀ values ranging from 0.362 to 2.488 μM. Mechanistically, CTXA suppressed EGFR autophosphorylation and downregulated downstream p-ERK, p-AKT, and p-STAT3. CTXA induced G1 phase cell cycle arrest by downregulating Cyclin D1 and CDK4, significantly promoted apoptosis, and inhibited cell migration. Molecular docking revealed that while osimertinib binding was blocked by steric hindrance from His-792 or Arg-796, CTXA adapted to the mutated ATP-binding pockets through multiple hydrogen bonds and extensive hydrophobic interactions. Molecular dynamics simulations confirmed the stable binding of CTXA to both mutant EGFR proteins over the 200 ns simulations. Conclusions: This study demonstrates for the first time that the natural compound CTXA possesses antitumor efficacy against EGFR L858R/T790M/L792H and L858R/T790M/G796R mutants by regulating EGFR-ERK/AKT/STAT3 signaling. Our findings position CTXA as a promising lead compound for tackling this challenging form of acquired resistance and highlight the value of natural products in multi-target antitumor drug discovery. Full article

Yellow and pink calcite samples from the Huanggangliang and Xilingol mining areas in Inner Mongolia were investigated to elucidate the relationships among chemical composition, unit-cell parameters, coloration, and luminescence. Electron probe micro-analysis, laser ablation inductively coupled plasma mass spectrometry, X-ray diffraction, infrared spectroscopy, Raman spectroscopy, UV-Vis absorption spectroscopy, and photoluminescence measurements show that samples of yellow and pink calcite differ significantly in impurity incorporation and optical behavior. Yellow calcite is relatively enriched in Mg and rare earth elements, especially Y and Ce, whereas pink calcite contains markedly higher Mn and Fe contents. The pink calcite has smaller lattice parameters and unit-cell volume, consistent with greater substitution of Ca²⁺ by smaller-radius cations. Spectra reveal that the pink coloration is mainly related to Mn-associated absorption bands at 402 and 527 nm, whereas the yellow color is attributed to weak impurity- and defect-related absorption. Under ultraviolet excitation, yellow calcite exhibits a broad blue–white emission centered at ~470 nm, whereas pink calcite shows an intense orange–red emission near 625 nm characteristic of Mn²⁺. Variable-temperature photoluminescence further demonstrates that the pink calcite has higher thermal stability, with a thermal-quenching activation energy of 0.218 eV, compared with 0.074 eV for the yellow calcite. These results demonstrate that trace element incorporation plays a key role in regulating the coloration and luminescence of calcite and provide useful insight into the optical behavior of carbonate minerals. Full article