Search Results (116)

Ice nucleation temperatures and associated ice growth rates are critical parameters in defining the initial ice morphology template, which governs dry layer resistance during sublimation and therefore impacts primary drying kinetics and overall process time. In this study, we developed a through-vial impedance spectroscopy (TVIS) method to determine both ice nucleation temperature and average ice growth rate, from which future estimation of average ice crystal size may be possible. Whereas previous TVIS applications were limited to solutions containing simple, uncharged solutes such as sugars, our adapted approach enables the analysis of conductive solutions (5% sucrose with 0%, 0.26%, and 0.55% NaCl), covering osmolarities below and above isotonicity. We established that the real part capacitance at low and high frequencies—either side of the dielectric relaxation of ice—provides the following: (i) a temperature-sensitive parameter for detecting the onset of ice formation, and (ii) a temperature-insensitive parameter for determining the end of the ice growth phase (unaffected by temperature changes in the frozen solution). This expanded capability demonstrates the potential of TVIS as a process analytical technology (PAT) for non-invasive, in situ monitoring of freezing dynamics in pharmaceutical freeze-drying. Full article

The pyrrolo[2,3-d]pyrimidine (7-deazapurine) scaffold is a unique heterocyclic system included in the composition of most nucleotides. In this study, series of the pyrrolo[2,3-d]pyrimidine-imines and 3-halo-substituted pyrrolo[2,3-d]pyrimidines were designed and prepared in high yields. Condensed pyrimidines are obtained via carbonyl-amine condensation and carbon-halogen bond formation. Pyrrolo[2,3-d]pyrimidine-imines containing a bromine substituent at position C-4 of the phenyl ring and azepine side-ring exhibited superior antitumor activity on the colon cancer HT-29 cell line; IC₅₀ values were 4.55 and 4.01 µM, respectively. These results revealed an interesting pattern, where condensed pyrimidinones containing an azepine ring demonstrated selective antitumor activity on the colon cancer cell line HT-29. In addition, the molecular docking results suggest that compound 8g provided a thorough understanding of its interactions with the DDR2 active site. This could pave the way for further development and optimization of DDR-targeting drugs, contributing to advancements in cancer therapeutics. This lead compound may serve as design templates for further studies. Full article

Metal sulfides are promising anode candidates for sodium–ion batteries (SIBs) due to their high theoretical capacities. However, their practical application is limited by significant volume extension and sluggish Na⁺ diffusion during cycling, which lead to rapid capacity degradation and poor long-term stability. In this work, we report the rational design of a hollow triple-shelled high-entropy sulfide (NaFeZnCoNiMn)₉S₈, synthesized through sequential templating method under hydrothermal conditions. Transmission electron microscopy confirms its well-defined three-shelled architecture. The inter-shell voids effectively buffer Na⁺ insertion/desertion-induced volume extension, while the tailored high-entropy matrix enhances electronic conductivity and accelerates Na⁺ transport. This synergistic design yields outstanding performance, including a high initial Coulombic efficiency (ICE) of 94.1% at 0.1 A g⁻¹, low charge-transfer resistance (0.32~2.54 Ω), fast Na⁺ diffusion efficiency (10^−8.5–10^−10.5 cm² s⁻¹), and reversible capacity of 582.6 mAh g⁻¹ after 1600 cycles at 1 A g⁻¹ with 91.2% capacity retention. These results demonstrate the potential of high-entropy, multi-shelled architectures as a robust platform for next-generation durable SIB anodes. Full article

Extensive use of classical antibiotics has led to the growing emergence of many resistant strains of pathogenic bacteria. To combat this challenge, researchers have turned to the antimicrobial peptides (AMPs). Aurein 1.2 (GLFDIIKKIAESF-NH2) was demonstrated to have broad spectrum bi-functionality against bacterial and cancer cells. The Solid Phase Peptide Synthesis (Fmoc-strategy) was used for the synthesis of new analogs of aurein 1.2. The purity of all compounds was monitored by HPLC, and their structures were proven using mass spectrometry. Cytotoxicity and antiproliferative effects were studied using 3T3 NRU and MTT tests, respectively. The antibacterial activity was estimated against Gram-positive and Gram-negative bacteria using broth microdilution method in concentrations from 0 to 320 µg/mL to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). The antiproliferative activity test shows that the peptide analog EH [Orn]⁸ has the highest activity (IC₅₀ = 44 ± 38 μM) for the three cell lines studied (MCF-12F, MCF-7, and MDA-MB-231). The same compound exhibited good antimicrobial activity. The obtained results reveal that replacement of Lys with non-proteinogenic amino acids can increase both the potency and activity spectra of natural template peptides, making them suitable candidates for new drug development. Full article

This paper addresses the challenge of misalignment in cantilever-based mechanical interlocking structures used for the heterogeneous integration of integrated circuits (ICs). As IC applications expand into flexible and multi-functional platforms, precise alignment becomes critical to maintaining optimal mechanical and electrical performance. We investigate the effects of X and Y misalignment on snap-through forces in cantilever arrays, focusing on their impact on mechanical integrity. The experimental results demonstrate that for X-axis misalignments below 15%, the increase in the required snap-through force is less than 5%. In contrast, Y-axis misalignment shows an even more negligible impact, with less than a 5% reduction in force for up to 20% misalignment. Additionally, through polynomial fits of the model across a range of cantilever angles, this study provides a design template for future exploration of cantilever interactions using nonlinear mechanics while minimizing computational load. These findings offer valuable insights for optimizing misalignment tolerance and improving the design of interlocking structures for IC integration, contributing to the development of robust systems for next-generation IC devices. Full article

Background/Objectives: Gundelia tournefortii (Kenger) is a traditional medicinal plant and exhibits potential anticancer properties. This study investigates the cytotoxic and apoptotic effects of its water extract on human lung carcinoma A549 cells. Methods: A lung cancer cell line was treated with Gundelia tournefortii extract. The metabolic content of the extract that plays key roles in anticancer was detected by high-performance liquid chromatography. Anticancer properties were further detected by a flow cytometer apoptosis assay, and signaling pathways were determined by a PCR array through hub gene expression alteration. Gene enrichment analysis and network pharmacology correlated metabolites and pathways that were involved in anticancer effects. Results: The metabolite content of G. tournefortii was analyzed, and gallic acid, clorogenic acid, hydroxybenzoic acid, caffeic acid, epicatechin, p-coumaric acid, salicylic acid, apigenin 7 glucoside, and cinnamic acid were detected as key compounds. Lung cancer cell line A549 was treated with the extract at increasing concentrations for 24, 48, and 72 h, and its effects on cell viability were determined by MTT analysis. A statistically significant difference was observed for IC₅₀ concentrations depending on incubation times. It was also observed that the G. tournefortii water extract significantly increased apoptosis in A549 cells in comparison with the control group. G. tournefortii extract’s effect on lung cancer cell line was measured using the signal pathway PCR array gene set. Gene enrichment analysis of the array expression data confirmed activation of apoptosis-related pathways, particularly the upregulation of BAX and downregulation of HSP90. Conclusions: These findings suggest that G. tournefortii metabolites provide promising selective anticancer drug candidates and potential drug templates to prevent side effects and resistance of current clinical drug treatments. Full article

Fifteen compounds (1–15) constructed on a hybrid structure combining a β-phenyl-α,β-unsaturated carbonyl template and a 2-aminothiazol-4(5H)-one scaffold were designed and synthesized as potential novel anti-tyrosinase substances. Two compounds (10 and 15) showed more potent inhibition against mushroom tyrosinase than kojic acid, and the inhibitory activity of 10 (IC₅₀ value: 1.60 μM) was 11 times stronger than that of kojic acid. Lineweaver–Burk plots indicated that these two compounds were competitive inhibitors that bound to the mushroom tyrosinase active site, which was supported by in silico experiments. Compound 10 was an anti-tyrosinase and anti-melanogenic substance in B16F10 cells and was more potent than kojic acid, without cytotoxicity. Compound 15 exhibited the most potent effect on zebrafish larval depigmentation and showed a depigmentation effect comparable to kojic acid, even at a concentration 200 times lower. Compounds 8 and 10 exhibited strong antioxidant capacities, scavenging 2,2-diphenyl-1-picrylhydrazyl, (2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid)⁺ radicals, and reactive oxygen species. Hybrid compounds 10 and 15 are potential therapeutic agents for skin hyperpigmentation disorders. Full article

Coagulation factor XIa is a new serine-protease family drug target for next-generation anticoagulants. With the snake venom Kunitz-type peptide BF9 as the scaffold, we obtained a highly active XIa inhibitor BF9-N17K in our previous work, but it also inhibited the hemostatic target plasmin. Here, in order to enhance the selectivity of BF9-N17K toward XIa, four mutants, BF9-N17K-L19A, BF9-N17K-L19S, BF9-N17K-L19D, and BF9-N17K-L19K, were further designed using the P2′ amino acid classification scanning strategy. The anticoagulation assay showed that the four P2′ single-point mutants still had apparent inhibitory anticoagulation activity that selectively inhibited the human intrinsic coagulation pathway and had no influence on the extrinsic coagulation pathway or common coagulation pathway, which indicated that the single-point mutants had minimal effects on the anticoagulation activity of BF9-N17K. Interestingly, the enzyme inhibitor assay experiments showed that the XIa and plasmin inhibitory activities were significantly changed by the P2′ amino acid replacements. The XIa inhibitory activity of BF9-N17K-L19D was apparently enhanced, with an IC₅₀ of 19.28 ± 2.53 nM, and its plasmin inhibitory was significantly weakened, with an IC₅₀ of 459.33 ± 337.40 nM. BF9-N17K-L19K was the opposite to BF9-N17K-L19D, which had enhanced plasmin inhibitory activity and reduced XIa inhibitory activity. For BF9-N17K-L19A and BF9-N17K-L19S, no apparent changes were found in the serine protease inhibitory activity, and they had similar XIa and plasmin inhibitory activities to the template peptide BF9-N17K. These results suggested that the characteristics of the charge of the P2′ site might be associated with the drug selectivity between the anticoagulant target XIa and hemostatic target plasmin. In addition, according to the molecular diversity and sequence conservation, a common motif GR/PCR/KA/SXIP-XYGGC is proposed in the XIa-inhibitory Kunitz-type peptides, which might provide a new clue for further peptide engineering. In conclusion, through P2′ amino acid classification scanning with the snake venom Kunitz-type peptide scaffold, a new potent and selective XIa inhibitor, BF9-N17K-L19D, was discovered, which provides a new XIa-targeting lead drug template for the treatment of thrombotic-related diseases. Full article

This study presents a comprehensive workflow for developing and deploying Multi-Layer Perceptron (MLP)-based soft sensors on embedded FPGAs, addressing diverse deployment objectives. The proposed workflow extends our prior research by introducing greater model adaptability. It supports various configurations—spanning layer counts, neuron counts, and quantization bitwidths—to accommodate the constraints and capabilities of different FPGA platforms. The workflow incorporates a custom-developed, open-source toolchain ElasticAI.Creator that facilitates quantization-aware training, integer-only inference, automated accelerator generation using VHDL templates, and synthesis alongside performance estimation. A case study on fluid flow estimation was conducted on two FPGA platforms: the AMD Spartan-7 XC7S15 and the Lattice iCE40UP5K. For precision-focused and latency-sensitive deployments, a six-layer, 60-neuron MLP accelerator quantized to 8 bits on the XC7S15 achieved an MSE of 56.56, an MAPE of 1.61%, and an inference latency of 23.87 $\mu$s. Moreover, for low-power and energy-constrained deployments, a five-layer, 30-neuron MLP accelerator quantized to 8 bits on the iCE40UP5K achieved an inference latency of 83.37 $\mu$s, a power consumption of 2.06 mW, and an energy consumption of just 0.172 $\mu$J per inference. These results confirm the workflow’s ability to identify optimal FPGA accelerators tailored to specific deployment requirements, achieving a balanced trade-off between precision, inference latency, and energy efficiency. Full article

Multi-target-directed ligands (MTDLs) represent a promising frontier in tackling the complexity of multifactorial pathologies like Alzheimer’s disease (AD). The synergistic inhibition of MAO-B, MAO-A, and AChE is believed to enhance treatment efficacy. A novel coumarin-based molecule substituted with O-phenylpiperazine via three- and four-carbon linkers at the 5- and 7-positions, has been identified as an effective MTDL against AD. Employing a medicinal chemistry approach, combined with molecular docking, molecular dynamic simulation, and ΔG_bind estimation, two series of derivatives emerged as potent MTDLs: 8-acetyl-7-hydroxy-4-methylcoumarin (IC₅₀: 1.52–4.95 μM for hAChE, 6.97–7.65 μM for hMAO-A) and 4,7-dimethyl-5-hydroxycoumarin (IC₅₀: 1.88–4.76 μM for hMAO-B). They displayed binding free energy (ΔG_bind) of −76.32 kcal/mol (11) and −70.12 kcal/mol (12) against AChE and −66.27 kcal/mol (11) and −62.89 kcal/mol (12) against MAO-A. It is noteworthy that compounds 11 and 12 demonstrated efficient binding to both AChE and MAO-A, while compounds 3 and 10 significantly reduced MAO-B and AChE aggregation in vitro. These findings provide structural templates for the development of dual MAO and AChE inhibitors for the treatment of neurodegenerative diseases. Full article

Porous hydrogels have brought more advantages than conventional hydrogels when used as chromatographic materials, controlled release vehicles for drugs and proteins, matrices for immobilization or separation of molecules and cells, or as scaffolds in tissue engineering. Polysaccharide-based porous hydrogels, in particular, can address challenges related to bioavailability, solubility, stability, and targeted delivery of natural antioxidant compounds. Their porous structure enables the facile encapsulation and controlled release of these compounds, enhancing their therapeutic effectiveness. In this context, in the present study, the cryogelation technique has been adopted to prepare novel dextran (Dx)-based porous hydrogels embedding polyphenol-rich natural extract from Picea abies spruce bark (SBE). The entrapment of the SBE within the Dx network was proved by FTIR, SEM, and energy-dispersive X-ray spectroscopy (EDX). SEM analysis showed that entrapment of SBE resulted in denser cryogels with smaller and more uniform pores. Swelling kinetics confirmed that higher concentrations of Dx, EGDGE, and SBE reduced water uptake. The release studies demonstrated the effective stabilization of SBE in the Dx-based cryogels, with minimal release irrespective of the approach selected for SBE incorporation, i.e., during synthesis (~3–4%) or post-synthesis (~15–16%). In addition, the encapsulation of SBE within the Dx network endowed the hydrogels with remarkable antioxidant and antimicrobial properties. These porous biomaterials could have broad applications in areas such as biomedical engineering, food preservation, and environmental protection, where stability, efficacy, and safety are paramount. Full article

In this paper, a new method involving a wear-resistant and reusable template is proposed for the preparation of high-mechanical-strength superhydrophobic polymer film based on wire electrical discharge machining (WEDM). A solid−liquid-contact-angle simulation model was established to obtain surface-texture types and sizes that may achieve superhydrophobicity. The experimental results from template preparation show that there is good agreement between the simulation and experimental results for the contact angle. The maximum contact angle on the template can reach 155.3° given the appropriate triangular surface texture and WEDM rough machining. Besides, the prepared superhydrophobic template exhibits good wear resistance and reusability. PDMS superhydrophobic polymer films were prepared by the template method, and their properties were tested. The experimental results from the preparation of superhydrophobic polymer films show that the maximum contact angle of the polymer films can be up to 154.8° and that these films have good self-cleaning and anti-icing properties, wear resistance, bending resistance, and ductility. Full article

Cellulose nanofibers (NF) were extracted from kapok fibers using TEMPO oxidation, followed by a combination of mechanical grinding and ultrasonic processing. The TEMPO-mediated oxidation significantly impacted the mechanical disintegration behavior of the kapok fibers, resulting in a high NF yield of 98%. This strategy not only improved the fibrillation efficiency but also reduced overall energy consumption during NF preparation. An ultralight and highly porous NF-based aerogel was successfully prepared using a simple ice-templating technique. It had a low density in the range of 3.5–11.2 mg cm⁻³, high compressional strength (160 kPa), and excellent thermal insulation performance (0.024 W m⁻¹ K⁻¹). After silane modification, the aerogel displayed an ultralow density of 7.9 mg cm⁻³, good hydrophobicity with a water contact angle of 128°, and excellent mechanical compressibility with a high recovery of 92% at 50% strain. Benefiting from the silene support structure, it showed a high oil absorptive capacity (up to 71.4 g/g for vacuum pump oil) and a remarkable oil recovery efficiency of 93% after being reused for 10 cycles. These results demonstrate that our strategy endows nanocellulose-based aerogels with rapid shape recovery and high liquid absorption capabilities. Full article

In this study, the antifungal activity of cumin seed oil (CSO) was tested on Fusarium graminearum. (i) Minimum inhibitory concentrations (MICs) and related concentrations (IC₇₅, IC₅₀, and IC₂₅) were detected; (ii) toxicity was evaluated by a water-soluble tetrazolium salt-1 (WST-1) assay; (iii) genomic/epigenomic alterations were evaluated by the coupled restriction enzyme digestion-random amplification (CRED-RA) method; (iv) oxidative stress was investigated by CAT expression, catalase activity, and DCF-DA staining; (v) deoxynivalenol biosynthesis was evaluated by tri6 expression; (vi) and potential effects of CSO on wheat were tested by a water loss rate (WLR) assay. MIC, IC₇₅, IC₅₀ and IC₂₅ values were detected at 0.5, 0.375, 0.25, and 0.125 mg mL⁻¹. In WST-1 assays, significant decreases (p < 0.001) were detected. Genomic template stability (GTS) related to methylation differences ranged from 94.60% to 96.30%. Percentage polymorphism for HapII/MspI values were as 9.1%/15.8%. CAT (oxidative stress-related catalase) and tri6 (zinc finger motif transcription factor) gene expressions were recorded between 5.29 ± 0.74 and 0.46 ± 0.10 (p < 0.05). Increased catalase activity was detected (p < 0.05) by spectrophotometric assays. DCF-DA-stained (oxidative stressed) cells were increased in response to increased concentrations, and there were no significant changes in WLR values. It was concluded that CSO showed strong antifungal activity on F. graminearum via different physiological levels. Full article

In order to improve the preparation efficiency, quality stability, and large-area preparation of superhydrophobic thin films, a roll-to-roll continuous micro–nano imprinting method for the efficient preparation of superhydrophobic polymer films is proposed. A wear-resistant mold roller with hierarchical microstructure is prepared by wire electrical discharge machining (WEDM). The rheological filling model is constructed for revealing the forming mechanism of superhydrophobic polymer films during continuous micro/nano imprinting. The effects of imprinting temperature, rolling speed and the surface texture size of the template on the surface texture formation rate of polymer films are analyzed. The experimental results show that, compared with other process methods, the template processed by WEDM shows excellent wear resistance. Moreover, the optimal micro/nano imprinting parameters are the mold temperature of 190 °C (corresponding film temperature of 85 ± 5 °C), rolling speed of 3 rpm and roller gap of 0.1 mm. The maximum contact angle of the polymer film is 154°. In addition, the superhydrophobic polymer thin film has been proven to have good self-cleaning and anti-icing performance. Full article