Search Results (661)

The therapeutic use of non-steroidal anti-inflammatory drugs (NSAIDs) is limited by gastrointestinal and renal adverse effects caused by non-selective COX-1 and COX-2 inhibition. To address this issue, a new series of naproxen–azetidinone hybrids was rationally designed and synthesized to enhance COX-2 selectivity and reduce off-target toxicity. The synthesis involved esterification, hydrazide formation, Schiff base condensation, and intramolecular cyclization with chloroacetyl chloride. Structural characterization was achieved through FT-IR, ¹H NMR, and ¹³C NMR analyses. In silico ADMET profiling confirmed compliance with Lipinski’s rule and predicted favorable gastrointestinal absorption. Molecular docking revealed high COX-2 binding affinities (−11.93 to −9.72 kcal/mol), while MM/GBSA analysis identified compound N4_c (ΔG = −62.27 kcal/mol) as the most stable complex, surpassing meloxicam and naproxen. DFT (B3LYP/6-31G(d,p)) frontier molecular orbital analysis indicated a narrow HOMO–LUMO gap (ΔE = 2.97 eV) for N4_c, suggesting high electronic reactivity and strong enzyme interaction. Molecular dynamics simulations confirmed complex stability. In vivo anti-inflammatory testing using an egg-white-induced rat paw edema model showed that N4_d, N4_e, and N4_f achieved higher inhibition (19.22%, 16.98%, and 16.98%) than naproxen (4.3%). These results highlight 2-azetidinone–naproxen hybrids as promising selective COX-2 inhibitors with enhanced pharmacokinetic and electronic properties. Full article

Low-complexity domains (LCDs) are protein regions characterized by a simple amino acid composition and low sequence complexity, as they are typically composed of repeats or a limited set of a few amino acids. Historically dismissed as “garbage sequences”, these regions are now acknowledged as critical functional elements. This review systematically explores the structural characteristics, biological functions, pathological roles, and research methodologies associated with LCDs. Structurally, LCDs are marked by intrinsic disorder and conformational dynamics, with their amino acid composition (e.g., G/Y-rich, Q-rich, S/R-rich, P-rich) dictating structural tendencies (e.g., β-sheet formation, phase separation ability). Functionally, LCDs mediate protein–protein interactions, drive liquid–liquid phase separation (LLPS) to form biomolecular condensates, and play roles in signal transduction, transcriptional regulation, cytoskeletal organization, and nuclear pore transportation. Pathologically, LCD dysfunction—such as aberrant phase separation or aggregation—is implicated in neurodegenerative diseases (e.g., ALS, AD), cancer (e.g., Ewing sarcoma), and prion diseases. We also summarize the methodological advances in LCD research, including biochemical (CD, NMR), structural (cryo-EM, HDX-MS), cellular (fluorescence microscopy), and computational (MD simulations, AI prediction) approaches. Finally, we highlight current challenges (e.g., structural heterogeneity, causal ambiguity of phase separation) and future directions (e.g., single-molecule techniques, AI-driven LCD design, targeted therapies). This review provides a comprehensive perspective on LCDs, illuminating their pivotal roles in cellular physiology and disease, and offering insights for future research and therapeutic development. Full article

Low-permeability glutenite reservoirs in the Qaidam Basin, NW China, exhibit intricate pore networks and strong heterogeneity that hinder effective hydrocarbon development. Here, we integrate thin-section petrography, scanning electron microscopy (SEM), mercury injection capillary pressure (MICP), and nuclear magnetic resonance (NMR) to characterize pore types and establish quantitative links between fractal dimension and petrophysical properties. The reservoirs are mainly pebbly sandstones and sandy conglomerates with 15–23% quartz, 27–37% feldspar, and 2–20% carbonate/muddy matrix. Helium porosity ranges from 5.12% to 18.11% (mean 9.39%) and air permeability from 60 to 3270 mD (mean 880 mD). Fine pores (1–10 μm) dominate, throats are short and poorly connected, and illite (up to 16.76%) lines pore walls, further reducing permeability. Fractal analysis yields weighted-average dimensions of 2.55, 2.50, and 2.15 for macro-, meso-, and micropores, respectively, giving an overall dimension of 2.52. Higher dimensions correlate negatively with porosity and permeability. Empirical models (quadratic for porosity and exponential for permeability) predict core data within 0.86% and 5.4% error, validated by six blind wells. Reservoirs are classified as Class I (>12%, >1.0 mD), Class II (8–12%, 0.5–1.0 mD), and Class III (<8%, <0.5 mD), providing a robust tool for stimulation design and numerical simulation. Full article

Motivated by the plant’s ethnopharmacological importance and the health conditions of the Sahrawi people, who have been living as refugees for over 50 years, this study comprehensively assessed the nutritional profile, secondary metabolite composition, in vitro bioaccessibility, and toxicological safety of Atriplex halimus L. leaves. The proximate analysis demonstrated richness in dietary fiber (44.41 ± 0.11 g/100 g) and essential macro/microelements, notably iron (142.0 ± 2.41 mg/100 g). The lipid profile features essential polyunsaturated fatty acids, specifically linoleic and α-linolenic acid, accounting for 40.6 ± 7.0% of total fatty acids. The UPLC-HR--MS characterization of two extracts tentatively identified 13 specialized metabolites, including uncommon flavonoids such as highly glycosylated forms of isorhamnetin and syringetin. Caffeic acid 3-sulfate and caffeic acid 4-sulfate were identified by NMR. Although in vitro antioxidant activity (DPPH/FRAP tests) was minimal, the traditional decoction showed high total polyphenol bioaccessibility (71.52 ± 0.46%) during simulated gastrointestinal digestion following the harmonized static protocol. The Ames test (using Salmonella typhimurium TA98 and TA1535) confirmed toxicological safety, as neither extract induced mutagenic or genotoxic effects. In conclusion, the robust nutritional composition, in vitro proven safety, and high polyphenol bioaccessibility suggest A. halimus leaves as a promising, nutrient-rich functional ingredient. Full article

G-quadruplexes (G4s) are four-stranded DNA or RNA structures formed by guanine-rich sequences. They occur in functional regions of the genomic material, including the promoter part of genes, regulatory region, and telomeric threads. G4s play a key role in various biological processes, including transcription, replication, and telomere maintenance. Guanidine-containing derivatives can bind to G-quadruplexes, either by intercalating into the structure or by interacting with the grooves or loops. The binding can stabilize the G-quadruplex, potentially affecting its biological function. In this paper, the ability of guanidinium-containing hordatines to interact with G4 was evaluated. Analogues lacking the guanidinium group or showing the benzofuran system instead of the dihydrobenzofuran core were prepared and tested as well. NMR titration and docking calculations were used to probe the binding of the compounds to G4 of c-MYC oncogene. Spectroscopic analyses were consistent with a significant interaction of benzofurans 3 and 4 at the 5′-end and 3′-end tetrads and with the formation of ligand/G-quadruplex complexes with a 2:1 stoichiometry. The resulting data were supported by docking simulations. Cytotoxic activity was evaluated on a model of U2OS osteosarcoma (ATCC HTB-96) and breast cancer (MDA-MB-231) cell lines, further highlighting the key role of the guanidinium fragment and the benzofuran core in the G-quadruplex stabilization. Full article

Profile control is widely employed to improve oil recovery in fractured-vuggy carbonate reservoirs. However, the limitation of current experimental evaluation methods restricts their practical guidance for field applications. In this study, urea-formaldehyde resin gel (URG) is studied using SEM, rheological analysis, FTIR, and Raman spectroscopy. Typical structural models of fractured-vuggy reservoirs are fabricated by 3D printing technology. The distribution patterns of the URG in different fractured-vuggy models are also investigated by using online NMR analysis and core slice characterization. Results show that URG exhibits a kind of 3D mesh structure with a size of 10 μm after gelation at 140 °C. The storage modulus (G′) and loss modulus (G″) of the URG gel are 387.51 Pa and 131.48 Pa, respectively. Chemical composition analysis reveals that URG is mainly composed of amide groups and sulfonate groups, showing excellent thermal stability and salt tolerance. Furthermore, after injecting URG into three types of typical models, URG displays a longitudinally decreasing distribution pattern from the injection side to the outlet side, accompanied by transverse accumulation phenomenon along the fracture walls in the slab fracture model. In the fractured-vuggy model, the gel shows continuous longitudinal distribution and uniform transverse distribution characteristics. In the beaded-vug train model, the gel’s distribution morphology gradually transforms from a “pipeline-filling” pattern at the injection side to a “conduit-dominant” pattern toward the outlet side, with a stepped distribution in the transverse direction. The breakthrough pressures during subsequent water flooding are as follows: beaded-vug train model (11.6 MPa) > fractured-vuggy model (8.1 MPa) > slab fracture model (5.9 MPa). Field application results show that the water cut is reduced from 85% to 30%, with a total incremental oil production of 2416 tons. This study conducts experimental investigations on the distribution patterns of URG in simulated fractured-vuggy models, thereby establishing a novel technical evaluation method for profile control in actual fractured-vuggy carbonate reservoirs. Full article

Understanding the microscopic occurrence states of shale oil—particularly the distribution between adsorbed and free phases—is essential for optimizing the development of unconventional reservoirs. In this study, we propose an integrated methodology that combines experimental techniques with molecular dynamics simulations to investigate shale oil behavior within kerogen nanopores. Specifically, pyrolysis–gas chromatography–mass spectrometry (PY-GC-MS), solid-state ¹³C nuclear magnetic resonance (¹³C NMR), Fourier transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) were performed to construct a representative kerogen molecular model based on shale samples from the Lianggaoshan Formation in the Sichuan Basin. Grand Canonical Monte Carlo (GCMC) simulations and a theoretical occurrence model were applied to quantify the adsorption characteristics of n-dodecane under varying pore sizes, temperatures, and pressure. The results show that temperature exerts a stronger influence than pore diameter on adsorption capacity, with adsorption decreasing by over 50% at higher temperatures, and pressure has a limited effect on the adsorption amount of dodecane molecules. This study offers a robust workflow for evaluating shale oil occurrence states in complex pore systems and provides guidance for thermal stimulation strategies in tight oil reservoirs. Full article

Elucidating the characteristics of methane adsorption in coal is essential for accurately assessing coalbed methane (CBM) potential. Methane adsorption is primarily governed by the compositional complexity of coal and its pore structure. Molecular simulation enables characterization of coal’s molecular composition at the microscopic level and facilitates the construction of nanoscale pore models. In this study, Nuclear Magnetic Resonance (NMR), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Photoelectron Spectroscopy (XPS) were used to characterize the molecular structure of coal. Pore models of various sizes were constructed in Materials Studio (MS) to simulate methane adsorption under different temperatures and pressures. To further clarify the influence of molecular structure, a reconstructed macromolecular model (RMM) was compared with a graphite model, revealing differences in methane adsorption behavior across varying pore sizes, temperatures, and pressures. The results show that absolute methane adsorption increases with pore size, while excess adsorption behavior is strongly associated with the adsorption layer. In the pore size range of 0.4 nm to 1.2 nm, excess adsorption increases due to spatial confinement, but decreases as pore size exceeds 1.2 nm. Structural differences between the RMM and graphite models also resulted in distinct temperature responses, with the graphite model underestimating methane adsorption capacity, highlighting the importance of realistic macromolecular representations in adsorption studies. Full article

Interpreting multi-component ¹H NMR spectra is difficult due to peak overlap, concentration variability, and low-abundance signals. We cast mixture identification as a single-pass multi-label task. A compact CNN–Transformer (“Hybrid”) model was trained end-to-end on domain-informed and realistically simulated spectra derived from a 13-component flavor library; the model requires no real mixtures for training. On 16 real formulations, the Hybrid attains micro-F1 = 0.990 and exact-match (subset) accuracy = 0.875, outperforming CNN-only and Transformer-only ablations, while remaining efficient (~0.47 M parameters; ~0.68 ms on GPU, V100). The approach supports abstention and shows robustness to simulated outsiders. Although the evaluation set was small, and the macro-ECE (per-class, 15 bins) was inflated by sparse classes (≈0.70), the micro-averaged Brier is low (0.0179), and temperature scaling had negligible effect (T ≈ 1.0), indicating the good overall probability quality. The pipeline is readily extensible to larger libraries and adjacent applications in food authenticity and targeted metabolomics. Classical chemometric baselines trained on simulation failed to transfer to real measurements (subset accuracy 0.00), while the Hybrid model maintained strong performance. Full article

Magnetic nanoparticles (MNPs) perturb magnetic field homogeneity, influencing transverse relaxation and the full width at half maximum (FWHM) of nuclear magnetic resonance (NMR) spectra. In Nuclear Magnetic Resonance (NMR), this appears as decay of the free induction decay (FID) signal, whose relaxation rate determines spectral FWHM. In D₂O containing MNPs, both nanoparticles and solvent molecules undergo Brownian motion and diffusion. Under a vertical main field ($B_0$), MNPs respond to their magnetization behavior, evolving toward a dynamic steady state in which the time-averaged distribution of local field fluctuations remains stable. The resulting spatial magnetic field can thus characterize field homogeneity. Within this framework, Monte Carlo simulations of spatial field distributions approximate the dynamic environment experienced by nuclear spins. NMR experiments confirm that increasing MNP concentration and particle size significantly broadens FWHM, while stronger $B_0$ enhances sensitivity to MNP-induced inhomogeneities. Full article

This study is based on an experiment and a molecular dynamics simulation to investigate the distribution states and property variation laws of crude oil in nanopores, aiming to provide theoretical support for efficient unconventional oil and gas development. Focus is placed on the distribution mechanisms of multicomponent crude oil in oil-wet siltstone (SiO₂) and dolomitic rock (dolomite, CaMg₃(CO₃)₄) nanopores, with comprehensive consideration of key factors including pore size, rock type, and CO₂ flooding on crude oil distribution at 353 K and 40 MPa. It is revealed that aromatic hydrocarbons (toluene) in multicomponent crude oil are preferentially adsorbed on pore walls due to π-π interactions, while n-hexane diffuses toward the pore center driven by hydrophobic effects. Pore size significantly affects the distribution states of crude oil: ordered adsorption structures form for n-hexane in 2 nm pores, whereas distributions become dispersed in 9 nm pores, with adsorption energy changing as pore size increases. Dolomite exhibits a significantly higher adsorption energy than SiO₂ due to surface roughness and calcium–magnesium ion crystal fields. CO₂ weakens the interaction between crude oil and pore walls through competitive adsorption and reduces viscosity via dissolution, promoting crude oil mobility. Nuclear magnetic resonance (NMR) experiments further verified the effect of CO₂ on crude oil stripping in pores. This study not only clarifies the collaborative adsorption mechanisms and displacement regulation laws of multi-component crude oil in nanopores but also provides a solid theoretical basis for CO₂ injection strategies in unconventional reservoir development. Full article

Background/Objective: The rise in bacterial resistance necessitates novel therapeutic strategies beyond conventional antibiotics. Antimicrobial peptides represent promising candidates but face challenges such as instability, enzymatic degradation, and host toxicity. To overcome these limitations, conjugation and structural modifications are being explored. This study focuses on designing peptide-based inhibitors of the quorum-sensing (QS) regulator LasR in Pseudomonas aeruginosa, a key mediator of biofilm formation and antibiotic resistance. Methods: Rationally designed tripeptides and dipeptides conjugated with coumarin-3-carboxylic acid and dihydro-3-amino-2-(3H)-furanone were evaluated using molecular docking. The most promising ligand–protein complexes were further analyzed using molecular dynamics (MD) simulations conducted with the CHARMM-GUI and AMBER tools to assess the stability of the ligand–protein complex systems, and the binding affinities were evaluated using Molecular Mechanics–Poisson Boltzmann Surface Area (MM-PBSA) calculations. Pharmacokinetic and toxicity profiles were predicted using ADMETLab 3.0. Selected compounds were synthesized via solid-phase peptide synthesis, structurally confirmed by ¹H NMR and ESI-MS, and tested for antibacterial and antibiofilm activity against P. aeruginosa ATCC 27853. Results: Computational analyses identified several promising inhibitors with stronger binding affinities than the native autoinducer OdDHL. Coumarin conjugates C004 and C006 showed superior docking scores, while MM-PBSA indicated P004 and C004 had the most favorable binding energies. MD simulations confirmed stable ligand–protein complexes. ADMET predictions highlighted C004 and C006 as having excellent pharmacokinetic properties. Experimental assays showed moderate antibacterial activity (MIC 512–1024 µg/mL) and strong antibiofilm inhibition, particularly for C004 (83% inhibition at ½ MIC). Conclusions: The study demonstrates that peptide–coumarin conjugates, especially C004, are promising tools for disrupting QS and biofilm formation in P. aeruginosa. Further optimization and in vivo validation are needed to advance these compounds toward therapeutic application. Full article

This study introduces an innovative microfluidic-based approach for extracting drugs from oral fluids using self-assembled tripeptide hydrogels as sorbents. Peptide microfiber derived from the heterochiral tripeptide ^DLeu-^LPhe-^LPhe was formed in situ within the 14 mm-long microchannel of a two-inlet microfluidic device. The methodology enables the laminar flow-driven mixing of buffer solutions, inducing hydrogel formation at their interface. The resulting fiber exhibited a well-defined morphology and β-sheet structure, confirmed by Raman spectroscopy and Thioflavin T fluorescence. The peptide fibers co-assembled successfully with 5-fluorouracil (5-FU) and naproxen (39.8 ± 1.4 nmol of 5-FU and 27.4 ± 6.6 nmol of naproxen per 112 nmol of peptide used to prepare the fiber), resulting in a molar ratio drug/peptide ratio of approximately 1:3 and 1:4, respectively, demonstrating versatility in drug entrapment. The use of the gel fiber as a sorbent phase was first assessed in buffer, and subsequently, the optimized method was applied to saliva. Adsorption studies under stopped-flow conditions showed a significant drug adsorption capability from buffered solutions by the pre-formed hydrogel (32.8 ± 0.9% of 5-FU and 36.4 ± 3.3% of naproxen per fiber preformed with 112 nmol of peptide), demonstrating their suitability as sorbent material. The extension of the methodology to simulated saliva samples allowed extraction of 36% of 5-FU by the fiber, as determined by ¹⁹F NMR spectroscopy on microcoils, which enabled us to work with the small volume of fluid extracted from the microfluidic device and provided clean spectra and quantitative results. These findings highlight the potential of this tripeptide hydrogel as a sorbent material for therapeutic drug monitoring and toxicological analysis via a simple, non-invasive and rapid approach for drug detection in oral fluids. Full article

Antibiotic resistance is a major health problem globally, highlighting the need for alternative antimicrobials that may potentially reduce the emergence of resistance compared to conventional antibiotics. Antimicrobial peptides (AMPs) are promising candidates because of their broad-spectrum activity. In this study, we designed three derivatives (i.e., Analog-1, -2, and -3) of the native peptide, Wuchuanin-A1, for improving their antibacterial activity against Staphylococcus aureus and Escherichia coli. The hypothesis is that the antibacterial activity of these peptides can be improved by increasing their amphipathicity (evaluated using hydrophobic moment analysis), α-helical stability, and membrane binding properties. In this case, the residues of native peptide were mutated to form an amphipathic peptide, referred to here as Analog-1. Then, the N- and C-termini of Analog-1 were capped with acetyl and amide groups, respectively, to produce Analog-2. Finally, the Asp and Arg residues in Analog-2 were mutated to Glu and Lys residues, respectively, in Analog-3. Circular dichroism (CD) spectra in trifluoroethanol (TFE) or methanol (MeOH) showed that Analog-3 has the highest α-helical stability, followed by Analog-2 and Analog-1. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations studies indicated that Analog-2 and -3 have a stable continuous α-helical structure. Both Analog-2 and -3 can form dimer or oligomer at higher concentrations. All three analogs can bind to model membranes of Gram-positive and Gram-negative bacteria, with Analog-3 as the best membrane binding affinity through Langmuir monolayer analysis. Both Analog-2 and -3 have better antibacterial activities against S. aureus and E. coli compared to Analog-1 and the native peptide, with minimum inhibitory concentration (MIC) values 3.91 µg/mL against S. aureus and 62.5 µg/mL against E. coli, which are 2–32-fold lower than those of Analog-1. In addition, Analog-2 and -3 have better activity against S. aureus than E. coli bacteria. We proposed that the increase in antibacterial activity of Analog-2 and -3 was due to the α-helical stability, amphipathic structure, and membrane binding properties. Full article

Antimicrobial peptides (AMPs), also referred to as host defense peptides, are promising molecules in the development of the next generation of antibiotics against drug-resistant bacterial pathogens. Thanatin comprises a family of naturally occurring cationic AMPs derived from several species of insects. The first thanatin, 21 residues long, was identified from the spined soldier bug, and more thanatin peptides have been discovered in recent studies. The 16-residue thanatin from Anasa tristis, or Ana-thanatin, represents the shortest sequence in the family. However, the antimicrobial activity and mechanistic process underpinning bacterial cell killing have yet to be reported for Ana-thanatin peptide. In this work, we examined the antibacterial activity, structures, and target interactions of Ana-thanatin. Our results demonstrated that Ana-thanatin exerts potent antibiotic activity against strains of Gram-negative and Gram-positive bacteria. Biophysical studies demonstrated that Ana-thanatin interacts with LPS outer membrane and can permeabilize the OM barrier in the process. Atomic-resolution structures of the peptide in free solution and in complex with lipopolysaccharide (LPS) micelle were solved by NMR, determining canonical β-sheet structures. Notably, in complex with LPS, the β-sheet structure of the peptide was better defined in terms of the packing of amino acid residues. Further, MD simulations demonstrated rapid binding of the Ana-thanatin peptide with the LPS molecules within the lipid bilayers. These studies have revealed structural features which could be responsible for LPS-OM disruption of the Gram-negative bacteria. In addition, NMR heteronuclear single quantum coherence (HSQC) studies have demonstrated that Ana-thanatin can strongly interact with the LPS transport periplasmic protein LptA_m, potentially inhibiting OM biogenesis. Taken together, we surmise that the Ana-thanatin peptide could serve as a template for the further development of novel antibiotics. Full article