Scientific Reports最新文献

Chalcone synthase (CHS) is the entry-point enzyme of the flavonoid biosynthetic pathway, catalyzing the first committed step toward the production of diverse bioactive metabolites with antioxidant, anti-inflammatory, and anticancer properties. Here, we conducted a comparative in silico characterization of CHS from 13 medicinal plants, with Arabidopsis thaliana included as reference species. Protein sequences retrieved from UniProtKB were aligned using ClustalW, revealing strong conservation of key motifs, particularly the catalytic triad (Cys-His-Asn), GFGPG motif, and catalytic loop. Physicochemical profiling indicated interspecies variability in predicted protein stability, hydrophobicity, and thermostability, reflecting structural adaptation rather than direct functional divergence. AlphaFold-predicted structures consistently adopted the conserved thiolase-like αβαβα-fold characteristic of type III polyketide synthases, while exhibiting species-specific variations in the substrate-binding channel architecture. These variations are interpreted as structural features that may influence substrate accommodation and selectivity. To assess functional relevance, molecular docking with p-coumaroyl-CoA further confirmed stable substrate placement within the conserved catalytic pocket across species. Furthermore, 100-ns molecular dynamics simulations of representative crystal-derived and AlphaFold-predicted CHS-ligand complexes confirmed conformational stability, which was supported by MM-PBSA calculations revealing favorable binding energetics dominated by van der Waals interactions. Collectively, this study integrates sequence, structural, and dynamic analyses to establish a computational framework for comparative CHS characterization in medicinal plants. While the findings are derived exclusively from in silico approaches, they provide structurally grounded hypotheses that may guide future experimental validation, enzyme engineering, and pathway-oriented exploration of flavonoid biosynthesis.

When two types of fillers are incorporated into a polymer matrix, their interaction can be classified as additive, synergistic, or antagonistic. Although synergistic effects are frequently reported in three-phase polymer nanocomposites, their quantification remains inconsistent due to the absence of a unified and physically meaningful methodology. In this work, existing synergy formulations are critically reviewed, and their limitations in capturing nanoscale effects and filler functionality are identified. Modified equations are then developed by incorporating volume-weighted contributions and explicitly accounting for the functional roles of individual fillers. The proposed framework enables quantitative distinction between cooperative, asymmetric and inhibiting interactions in three-phase systems. The applicability of new formulations is demonstrated through comprehensive analysis of reported polymer nanocomposites systems, covering mechanical, thermal, electrical and functional properties. The results show that cases previously classified as antagonistic using classical equations are consistently identified as synergistic using the modified formulations. This work provides a robust quantitative framework for evaluating synergy in polymer nanocomposites and offers a rational basis for the design of multifunctional hybrid filler systems.

Sepsis is frequently complicated by non-thyroidal illness syndrome (NTIS). Although thyroid hormones are essential for cardiovascular and respiratory stability, their supplementation in sepsis remains controversial due to conflicting evidence. This study aimed to evaluate the impact of thyroid hormone supplementation on 28 day mortality, mechanical ventilation, vasopressor use, ICU length of stay, and changes in SOFA scores in patients with sepsis. We analyzed 20,231 septic patients from the Medical Information Mart for Intensive Care Database IV (MIMIC-IV) database, comparing those treated with levothyroxine sodium within seven days to a control group using 1:4 propensity score matching. Early levothyroxine sodium administration was significantly associated with increased 28 day mortality in both the original (HR 2.48, 95% CI 1.96-3.15; P < 0.001) and propensity score matching (PSM) cohorts (HR 2.38, 95% CI 1.75-3.23; P < 0.001). The treatment group required higher cumulative norepinephrine equivalents (P = 0.006) and longer vasoactive support duration. Multistate modeling revealed that the treatment group had fewer days alive without mechanical ventilation (17.8 vs. 21.8 days; P < 0.001) and fewer days discharged alive (11.3 vs. 13.4 days; P = 0.006). In patients with less severe sepsis, levothyroxine sodium administration should be approached with particular caution, as it may be associated with adverse clinical outcomes.

In the research, the method of reducing the levels of all noises caused by uncontrollable interfering factors has been generalized and extended to surface eddy current conductivity meters of the substrate under a layer of non-ferromagnetic metal coating. The method is applied at the probe design stage as a result of Taguchi's optimization search for a combination of ECP parameters that reduces the influence of noise factors. The designs of self-differential UECPs were analyzed. Dynamic measurements of substrate conductivity were considered. Variants of TO structures with non-magnetic and weakly magnetic substrates were investigated, i.e., eddy current conductivity measurements were extended to objects with weakly magnetic substrates. As a result of confirmatory experiments, the effectiveness of the obtained optimal combinations of parameters for both variants of TO structures was proven. The option with rectangular coils was selected as the one with the maximum SNR among the optimized alternative designs of the ECP. The variance analysis established the ranks of the influence of the measuring parameters on the SNR. The statistical significance of the analyzed parameters was determined. The Monte Carlo numerical-experimental method demonstrated the advantages of optimal designs, which are characterized by lower signal variability under the influence of noise factors.

In recent years, research in block cipher cryptanalysis has been significantly influenced by the development of differential meet in the middle techniques. Originally put forward by Boura et al., this approach has proven to be both adaptable and effective for evaluating modern symmetric-key designs. It has since been successfully employed in the analysis of several block ciphers, including multiple variants of SKINNY, CRAFT, and AES. However, identifying such attacks manually-especially on bit-oriented ciphers with large block sizes-can be a complex and error-prone process, which underscores the growing importance of automated solutions in this domain. To address these challenges, we develop an automated framework that systematically searches for and optimizes differential meet in the middle attacks on bit-oriented block ciphers. Our approach is specifically tailored to AndRX-based constructions, enabling the efficient identification of attack configurations that would be difficult to derive manually. Our method relies on a constraint-based formulation that automatically identifies optimal single-key differential characteristics in AndRX ciphers. Building on this, we propose a unified bitwise CP model to automatically construct optimized differential MITM attacks within the same design framework. Furthermore, we incorporate two dedicated optimization strategies-namely, the equivalent subkey technique and the selective key guessing technique-both of which are tailored to the structural properties of AndRX ciphers and significantly enhance key recovery efficiency. Additionally, we apply two additional optimization techniques: the parallel partitioning technique and reducing data with imposed conditions techniques to further enhance the differential MITM attack on AndRX ciphers. We validate the practicality of our approach through an extensive evaluation on the full SIMON and Simeck families, which are well-known instances of AndRX-based block ciphers. Our analysis leads to enhanced attack results compared to previously reported findings. In particular, our findings extend the round coverage beyond that achieved by previously reported classical meet in the middle and Demirci-Selçuk-type attacks for the respective variants of SIMON and Simeck. These findings highlight the strength and flexibility of our automated tool. Notably, our automated framework for constructing differential meet in the middle attacks works at the bit level and is generic in design, allowing it to be applied to a wide range of bit-oriented block ciphers beyond the AndRX family.

Obesity is a growing global health concern that leads to metabolic imbalances and progressive cardiac remodelling. This study investigated whether semaglutide (SMG) can counteract the disruption to the gut-heart-metabolic axis and associated myocardial injury caused by obesity. Twenty-one male Wistar rats were assigned to control, obese (OB), and obese+semaglutide (OB + SMG) groups. The control group was fed a normal diet, while the obese groups were given a cafeteria diet for 16 weeks. In addition, the OB + SMG group received 150 mcg/kg of SMG subcutaneously once a week for the last four weeks. The following were measured alongside HOMA indices: Lipid profile, cardiac enzymes, leptin, insulin, TMAO and LPS levels. Myocardial and intestinal samples were assessed biochemically and histopathological for the levels of MMP-2/MMP-9, TIMP-1, TGF-β, IL-1β, HO-1, occludin, ZO-1 and claudin. Obesity markedly increased body weight, fasting glucose, leptin, insulin resistance, the atherogenic index and cardiac risk, while also increasing LPS, TMAO, TGF-β, IL-1β, MMP-2/MMP-9 activity and decreasing TIMP-1. Semaglutide significantly reversed these abnormalities, improving metabolic indices, restoring the balance between MMPs and TIMPs, and reducing inflammatory mediators. Histological analysis revealed reduced cardiomyocyte degeneration and enhanced intestinal epithelial architecture in the OB + SMG group. Semaglutide notably enhanced the expression of occludin, claudin, and ZO-1, supporting strengthened intestinal barrier integrity, and restored HO-1 expression, indicating improved antioxidant defenses. These findings suggest that semaglutide provides cardioprotection in obesity by restoring gut barrier function, reducing inflammation and normalizing extracellular matrix turnover. By stabilizing the gut-heart-metabolic axis and mitigating structural myocardial injury, semaglutide may interrupt the progression from metabolic dysfunction to cardiomyopathy. This highlights its therapeutic potential in the treatment of obesity-related cardiovascular disease, extending beyond glycemic control.

This study aims to optimize the incremental sheet metal forming (ISMF) process for conical miniature cups by simultaneously improving formability, dimensional accuracy, energy efficiency, and sustainability. An L9 Taguchi experimental design was employed to investigate four key process parameters: feed rate, forming depth, step size, and sheet material. Multiple performance responses, including wall angle, thickness reduction, surface roughness, forming time, springback, and power consumption, were evaluated. Operational Competitiveness Rating Analysis (OCRA) was integrated with the Taguchi approach to rank alternatives and identify the optimal parameter combination. The proposed framework was further validated through confirmation experiments, ANOVA, repeatability and reproducibility tests, sensitivity analysis with multiple MCDA methods, dimensional and surface quality assessment, cross-validation using different geometries, and a simplified use-phase life cycle assessment. The optimized condition (90 mm/min feed rate, 0.10 mm depth, 0.25 mm step size, and copper sheet) reduced forming time by 18.75%, power consumption by 56.25%, and per-part energy use and CO₂ emissions by about 64.5% compared with the non-optimized condition. Surface roughness and springback were also reduced, while dimensional accuracy and repeatability remained within acceptable limits. Cross-validation confirmed good transferability to cylindrical geometries, although moderate deviations were observed for prismatic parts. Overall, the study presents a robust Taguchi-OCRA-based decision framework for sustainable ISMF optimization.