Search Results (305)

Type 2 diabetes mellitus (T2DM) demands safer and more effective therapies to control postprandial hyperglycemia. Here, we report the synthesis and in vitro evaluation of ten salicylic acid-derived Schiff base derivatives (4a–4j) as α-glucosidase inhibitors. Compounds 4e, 4g, 4i, and 4j exhibited potent enzyme inhibition, with IC₅₀ values ranging from 14.86 to 18.05 µM—substantially better than acarbose (IC₅₀ = 45.78 µM). Molecular docking and 500 ns molecular dynamics simulations revealed stable enzyme–ligand complexes driven by π–π stacking, halogen bonding, and hydrophobic interactions. Density Functional Theory (DFT) calculations and molecular electrostatic potential (MEP) maps highlighted key electronic factors, while ADMET analysis confirmed favorable drug-like properties and reduced nephrotoxicity. Structure–activity relationship (SAR) analysis emphasized the importance of halogenation and aromaticity in enhancing bioactivity. Full article

Background: Intraoperative neurophysiological monitoring (IONM) is increasingly used during spinal surgery to reduce the risk of neurological complications. This systematic review evaluates both the clinical outcomes and cost-effectiveness of IONM in contemporary spinal surgery. Methods: A comprehensive literature search was conducted to identify studies evaluating IONM in spinal surgery. Twenty-three studies were included: twenty-one reporting clinical outcomes and two focusing on economic analysis. Data on neurological deficits, monitoring accuracy, and cost-effectiveness were extracted and analyzed. Results: Analysis of the included studies showed that IONM reduced the risk of neurological deficits across various types of spinal surgery. The diagnostic accuracy varied by modality, with MEP showing the highest sensitivity (90.2%) and SSEP demonstrating high specificity (97.1%). The greatest benefit was observed in deformity surgery and spinal tumors. D-wave monitoring showed efficacy for intramedullary tumors. Economic analysis demonstrated that IONM is cost-effective when the neurological complication rate exceeds 0.3%, with potential savings of over USD 23,000 per case. Conclusions: IONM significantly improves neurological outcomes in spinal surgery and is cost-effective in most clinical scenarios, particularly in high-risk procedures. Multimodal monitoring approaches provide the most comprehensive neurological assessment. These findings support the routine use of IONM in contemporary spinal surgery, especially for complex cases. Full article

This study focuses on exploring potential inhibitors of the Marburg virus interferon inhibitory domain protein (MARV-VP35), which is responsible for immune evasion and immunosuppression during viral manifestation. A combination of in silico techniques was applied, including structure-based pharmacophore virtual screening, molecular docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis, molecular dynamics (MD), and molecular stability assessment of the identified hits. The docking scores of the 14 selected ligands ranged between −6.88 kcal/mol and −5.28 kcal/mol, the latter being comparable to the control ligand. ADMET and drug likeness evaluation identified Mol_01 and Mol_09 as the most promising candidates, both demonstrating good predicted antiviral activity against viral targets. Density functional theory (DFT) calculations, along with relevant quantum chemical descriptors, correlated well with the docking score hierarchy, and molecular electrostatic potential (MEP) mapping confirmed favorable electronic distributions supporting the docking orientation. Molecular dynamics simulations further validated complex stability, with consistent root mean square deviation (RMSD), root mean square fluctuation (RMSF), and secondary structure element (SSE) profiles. These findings support Mol_01 and Mol_09 as viable candidates for experimental validation. Full article

We report on the synthesis and characterization of a novel fluorenyl-methoxycarbonyl (Fmoc)-containing thioxo-triazole-bearing dipeptide 5, evaluated for potential therapeutic applications. The compound was tested for its antioxidant and antimicrobial properties, demonstrating significant effects in scavenging reactive oxygen species (ROS) and inhibiting microbial growth, particularly when combined with plant extracts from an endemic Peonia species from the Caucasus. Circular dichroism (CD) binding studies with bovine serum albumin (BSA) and calf thymus DNA revealed important interactions, suggesting the dipeptide’s potential in biomedically relevant conditions that involve DNA modulation. Molecular docking and CD spectra deconvolution provided additional insights into the binding mechanisms and structural characteristics of the formed complexes with the biomolecular targets. The Fmoc group enhances the dipeptide’s lipophilicity, which may facilitate its interaction with cellular membranes, supporting efficient drug delivery. A computational evaluation at the ωB97XD/aug-cc-pVDZ level of theory was carried out, confirming the experimental results and revealing a powerful potential of the peptide as an antioxidant, through FMOs, MEP analysis, and antioxidant mechanism assessments. Together, these findings suggest that this dipeptide could be valuable as an antimicrobial and antioxidant agent, with potential applications in pathologies involving oxidative stress, DNA modulation, and microbial infections. Full article

Background: Local recurrence for high-risk extremities/trunk soft tissue sarcoma (STS) after treatment can range from 15 to 30%. The modified Eilber protocol (MEP) using low-dose intravenous chemotherapy with a reduced dosage of radiation in the preoperative setting has demonstrated excellent local control and reduced wound complications in these patients. The aim of the current study was to assess long-term local control and overall survival in patients with STS treated with the MEP versus standard preoperative or postoperative radiotherapy. Methods: Patients diagnosed with STS from 2004 to 2016 were identified using the Alberta Cancer Registry. Patients with STS treated with the MEP, preoperative or postoperative radiotherapy, were included. Patient and tumor characteristics, treatments and outcomes were abstracted from the registry and primary chart review. Characteristics were compared using one-way ANOVA for continuous variable and chi-square test and Fisher test for the categorical outcomes. Local recurrence-free survival and overall survival were analyzed using Kaplan–Meier Analysis with Log-rank test. Results: A total of 242 patients with STS were included, among which 100 (41.3%) received the MEP prior to surgery, 91 (37.6%) had preoperative radiation, and 51 (21.1%) had postoperative radiation. After a median follow up of 4.9 years, there were no significant differences in local recurrence or local recurrence-free survival between patients treated with the MEP vs. preoperative or postoperative radiotherapy (10 vs. 6.6% and 7.8%, respectively, p-value NS). There were also no significant differences between groups for recurrence-free survival and overall survival. Conclusions: This study demonstrates that the use of the MEP has non-inferior oncologic outcomes compared to standard preoperative or postoperative radiation in a population-based analysis despite reducing the overall dosage of radiation administered. The modified Eilber preoperative chemoradiation protocol may be considered as an additional option for patients with STS. Full article

Concrete plays a pivotal role in modern methods of construction due to its enhanced strength, durability, and adaptability to advanced building technologies. Compressive strength (CS) and workability (flow) are two important performance measures of concrete, and this paper investigates how two evolutionary machine learning methods, gene expression programming (GEP) and multi-expression programming (MEP), might be used for this purpose. An experimental dataset with ten crucial input parameters was employed to develop and assess the models. While the GEP model demonstrated strong predictive capability (R² = 0.910 for CS and 0.882 for flow), the MEP model exhibited superior precision, attaining R² values of 0.951 for CS and 0.923 for flow. Model evaluation through statistical indices and correlation metrics further supported the robustness of the MEP approach. To enhance interpretability and material design insight, Shapley additive explanation (SHAP) analysis was conducted, identifying water-to-binder ratio and slag content as critical predictors for CS, and water and slag as dominant factors for flow. These results underscore the potential of MEP as a reliable decision-support tool in the sustainable design and optimization of concrete for advanced construction applications. Full article

This study presents an integrated experimental and theoretical investigation of two pharmacologically significant neolignans—magnolol and honokiol—with the aim of characterizing their structural and spectroscopic properties in detail. Experimental Fourier-transform infrared (FT-IR), ultraviolet–visible (UV-Vis), and nuclear magnetic resonance (¹H NMR) spectra were recorded and analyzed. To support and interpret these findings, a series of density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations were conducted using several hybrid and long-range corrected functionals (B3LYP, CAM-B3LYP, M06X, PW6B95D3, and ωB97XD). Implicit solvation effects were modeled using the CPCM approach across a variety of solvents. The theoretical spectra were systematically compared to experimental data to determine the most reliable computational approaches. Additionally, natural bond orbital (NBO) analysis, molecular electrostatic potential (MEP) mapping, and frontier molecular orbital (FMO) visualization were performed to explore electronic properties and reactivity descriptors. The results provide valuable insight into the structure–spectrum relationships of magnolol and honokiol and establish a computational benchmark for further studies on neolignan analogues. Full article

Introduction: Intradural extramedullary and intramedullary spinal tumors are rare, complex to treat, and require advanced surgical techniques. Ultrasonic aspirators, commonly used for tumor removal, can cause sensory and motor deficits, including loss of motor evoked potentials (MEPs). This study aims to evaluate the safety and efficacy of ultrasonic aspirators in intramedullary tumor surgery using a swine model, comparing different systems and techniques. Methods: Ten pigs underwent D1-D3 laminectomy and myelotomy, with adipose tissue simulating a tumor. The ultrasonic aspirators were tested under varying conditions (fragmentation power, suction, application time, and vibration mode). The primary endpoint is to evaluate the impact of the chosen variables on motor function damage. The secondary endpoints are histological evaluation of the type of damage caused by ultrasound aspirators and the effect of steroid drugs on MEPs’ impairment recovery. Results: Ultrasound aspirators can cause a significant MEP signal reduction when used in continuous mode, with fragmentation power >30 for more than 2 min (p < 0.001). Suction does not affect MEPs. When used in alternating/pulsatile mode, fragmentation power and application time do not affect MEPs. The two-way ANOVA analysis on the interaction between fragmentation power and application time in continuous mode did not demonstrate a significant interaction (p = 0.155). Time alone does not affect motor damage (p = 0.873). Betamethasone can restore MEPs’ signal after damage if administered immediately. Conclusions: Using ultrasonic aspirators in an animal model of intramedullary tumor surgery is safe. The main factor that resulted in the responsibility of motor function impairment is the fragmentation power. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant clinical challenge due to its resistance to multiple antibiotics. The urgent need for new therapeutic approaches has led to the exploration of natural compounds as potential treatments, particularly those targeting the key bacterial proteins involved in antibiotic resistance. This study focused on the multidrug ABC transporter and MecA proteins, which play crucial roles in MRSA′s pathogenicity and resistance mechanisms. Using computational techniques and molecular docking methods, we assessed the interactions of 80 natural compounds with S. aureus multidrug ABC transporter SAV1866 (SAV1866) and MecA proteins. Our analysis revealed 14 compounds with robust binding to SAV1866 and one compound with a strong affinity for MecA. Notably, these compounds showed weaker affinities for the MgrA, MepR, and arlR proteins, suggesting specificity in their interactions. Among the 15 promising compounds identified, 1′,2-Binaphthalen-4-one-2′,3-dimethyl-1,8′-epoxy-1,4′,5,5′,8,8′-hexahydroxy-8-O-β-glucopyranosyl-5′-O-β-xylopyranosyl(1→6)-β-glucopyranoside; Cis-3,4-dihydrohamacanthin b; and Mamegakinone exhibited the highest binding affinities to S. aureus SAV1866. These compounds represent diverse chemical classes, including alkaloids, indole derivatives, naphthalenes, and naphthoquinones, offering a range of structural scaffolds for further drug development. Our findings provide valuable insights into potential new antibacterial agents targeting S. aureus SAV1866 and MecA proteins. These results lay the groundwork for future in vitro and in vivo studies to validate these compounds′ efficacy for combating MRSA infections, potentially leading to the development of novel therapeutic strategies against antibiotic-resistant bacteria. Full article

Evoked potentials (EPs), including somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs), are used to assess neural conduction in spinal cord injury (SCI) and multiple sclerosis (MS), conditions marked by demyelination, inflammation, and axonal damage. Machine learning (ML), using data-driven algorithms, enhances EPs’ prognostic utility, but evidence synthesis is limited. This meta-analysis evaluated the predictive performance of EP-based ML models for SCI recovery (ASIA scale) and MS progression (EDSS) using a random-effects model. Five studies (n = 583) were included, extracting accuracy and area under the curve (AUC). Pooled results showed high predictive accuracy of 77.7% (95% CI, 75.1–80.3%; I² = 57%) and AUC 0.82 (95% CI, 0.79–0.85; I² = 55%). Stratified analyses by disease type (SCI vs. MS) or injury severity were not feasible due to the limited number of studies (n = 5). Sensitivity analysis excluding a rat model (N = 551) showed stable results (accuracy 76.9%; AUC 0.81). SSEP latency and MEP time series were key predictors, with amplitude critical in SCI and multimodal approaches enhancing performance. Moderate heterogeneity (I² = 55–57%) and limited studies constrain generalizability. This meta-analysis highlights EPs’ prognostic potential in ML-driven precision neurology, advocating for further human studies to validate multimodal approaches. Full article

This study investigates the main insects and endophytic fungi that promote the formation of agarwood in Aquilaria sinensis (Lour.) Spreng. and elucidates the effects and mechanisms of different ‘insect + fungus’ combinations on agarwood formation. The results showed that 16 strains of endophytic fungi were isolated from A. sinensis. Fusarium solani, Penicillium chrysogenum, Fusarium equiseti, and Phaeoacremonium alvesii were identified as dominant fungi promoting agarwood formation, while Nadezhdiella cantori was recognized as the dominant insect facilitating this process. The optimal ‘insect + fungus’ combination was Nadezhdiella cantori + Fusarium equiseti. The average agarotetrol contents were 0.046% and 0.054% in February and June, respectively, which were significantly higher than those in cold drilling, fungal-only, and insect-only treatments. RNA sequencing revealed 23,801 differentially expressed unigenes in cjYB1Z4 (optimal combination) versus control BMZ. Upregulated unigenes were enriched in isoflavone biosynthesis, flavonoid biosynthesis, and sesquiterpenoid and triterpene biosynthesis. Fifty sesquiterpene-related differential unigenes encoded seven key enzymes in the MVA pathway, seven key enzymes in the MEP pathway, and seven terpene synthases. Co-expression network analysis indicated that transcription factors (e.g., WRKY33, ABF, WRKY2) potentially regulate agarwood sesquiterpene formation. This work elucidates preliminary effects and molecular mechanisms of insect- and fungi-induced agarwood formation in A. sinensis, advancing agarwood induction technology. Full article

With the growing concern for environmental issues, progress has been made recently in the promotion of new technologies in the field of renewable energies. This article studies a new wave energy converter that uses the heel generated by the mechanical energy of the waves to transform it into electrical energy by means of a mobile mass, coupled to an electrical generator, which moves from port to starboard and vice versa. The advantage of this converter is that it is capable of incorporating the energy conversion unit inside the converter, as well as allowing the placement of a set of several devices within the same collector, and of modifying the roll period to adapt it to the wave conditions of the installation area. To do this, on one side, two models of wave energy converters were compared by varying the beam to check whether it is better to have a smaller or larger beam by carrying out roll decay tests and simulations for different waves. Moreover, the maximum power available in the moving mass of the power take-off was calculated theoretically for two situations of different transverse metacentric height to check which is more efficient, reaching 2 MW for some waves. Full article

Background: Aquaculture faces significant challenges due to bacterial infections, particularly Piscirickettsia salmonis, leading to extensive antibiotic use and raising concerns about antimicrobial resistance. In this context, bacteriophages and bacterial defense systems play a critical role in the evolutionary dynamics of P. salmonis. Objective. This study aimed to investigate the genomic landscape of prophage regions and antiphage defense systems in Piscirickettsia salmonis to better understand their co-evolutionary dynamics and explore their potential role in alternative disease control strategies for aquaculture. Methods: We analyzed 79 genomes of Piscirickettsia salmonis using bioinformatic tools to identify and characterize prophage regions and antiphage defense systems. Results: At the chromosomal level, 70% of the strains contained prophage regions, with a total of 92 identified regions, most of which were classified as intact. At the plasmid level, 75% of plasmids carried prophage regions, with a total of 426 identified regions, predominantly associated with Escherichia phage RCS47, Burkholderia phage Bcep176, and Enterobacteria phage mEp235. Prophage regions were enriched in transposases, head proteins, tail proteins, and phage-like proteins. The analysis of antiphage defense systems revealed that P. salmonis predominantly harbors dGTPase, AbidD, and SoFIC at the chromosomal level, whereas MazEF was the most frequent system in plasmids. A strong positive correlation was found between the number of prophage regions and defense systems in chromosomes (ρ = 0.72, p = 6.3 × 10⁻¹⁴), while a weaker correlation was observed in plasmids. These findings highlight the complex interplay between P. salmonis and its bacteriophages, with implications for disease control in aquaculture. Conclusions: Overall, these insights into the prophage and defense system dynamics provide potential avenues for developing alternative strategies to combat P. salmonis infections and reduce reliance on antibiotics in aquaculture systems. Full article

The characteristic minty-like aroma of ‘Rucheng Baimaocha’ black tea (RCBT) enhances the tea’s unique flavor profile, driving high demand among consumers. The dynamic changes in key aroma compounds in minty-like RCBT were elucidated by sensory evaluation and gas chromatography olfactometry quadrupole time of flight mass spectrometry (GC × GC-O-Q-TOF-MS). The results indicated that during processing, the aroma of RCBT transitions from a fresh to floral, sweet, and minty-like aroma. Among the 189 identified volatile compounds, alcohols constitute the predominant category (over 50%), with 71 compounds identified as key differential compounds across all stages. Aroma analysis revealed that 28 compounds with odor activity values (OAV) > 1 were the primary contributors during RCBT processing. Notably, minty-like odorants in RCBT were primarily derived from the metabolic pathways of the methylerythritol phosphate (MEP) and mevalonic acid (MVA), lipid oxidation, and phenylalanine. These findings offer theoretical insights for improving unique black tea quality and optimizing processing techniques. Full article

Peptoids are peptidomimetics in which the side chain is attached to the nitrogen of the amide group rather than the α-carbon. This alteration in the backbone structure is highly valued because it endows beneficial properties, including enhanced resistance to proteolysis, greater immunogenicity, improved biostability, and superior bioavailability. In this current study, we focused on the Ugi-4CR-based one-pot synthesis of peptoids using 1,4-dithiane-2,5-diol as the carbonyl component together with amine, carboxylic acid, and isocyanides. Four new peptoids—5a, 5b, 5c, and 5d—were designed and efficiently prepared in good chemical yields and were subjected to DFT investigations for their electronic behavior. These compounds have free OH, SH, and terminal triple bonds for further chemistry. In a computational analysis, the spectral data of compounds 5a–5d were juxtaposed with calculated spectral values derived from the B3LYP/6-311G(d,p) level. The electronic excitation and orbital contributions of 5a–5d were predicted using TD-DFT calculations. A natural bond order (NBO) analysis was utilized to investigate the electronic transition of newly synthesized peptoids, focusing on their charge distribution patterns. Furthermore, MEP and NPA analyses were conducted to predict charge distribution in these compounds. The reactivity and stability of the targeted peptoids were evaluated by global reactivity descriptors, which were determined with frontier molecular orbital analysis. The DFT results revealed that compound 5c displayed marginally higher reactivity compared to 5a, 5b, and 5d, possibly due to its extended conjugation. Full article