Search Results (64,123)

A new series of isoxazole-fused thiazole–oxazole derivatives (11a–n) was rationally designed and synthesised with the aim of developing potent carbonic anhydrase (CA) I and II inhibitors. The synthesis was achieved in five steps starting from 4-bromoacetophenone, involving key intermediates such as hydroxylamine hydrochloride, hydrazine hydrate, thioisocyanate, and various phenacyl bromide derivatives, using ethanol, triethylamine, tetrahydrofuran (THF), and dimethylformamide (DMF) as solvents. The synthetic route included the formation of a β-ketoester, isoxazole ester, hydrazine adduct, thiourea derivative, and, ultimately, a thiazole ring. The structures of the final compounds were confirmed by ¹H-NMR, ¹³C-NMR, IR spectroscopy, and elemental analysis. All compounds were examined as inhibitors of human carbonic anhydrase (hCA) I and II, and all of them inhibited hCA I and hCA II. Kinetic investigation results revealed that these compounds inhibited hCA I and hCA II in a non-competitive manner. To further explore the molecular basis of their inhibitory activity, in silico studies, including molecular docking and 300 ns molecular dynamics (MD) simulations, were carried out against both CA I and CA II isoforms. These simulations provided detailed insights into the dynamic behaviour, stability, and key binding interactions of the compounds within the enzyme active sites, supporting their potential as promising carbonic anhydrase inhibitors. Full article

Neuroscience is a rapidly advancing field; however, a comprehensive understanding of brain function at the molecular, cellular, and systems levels remains incomplete. Neurological and psychiatric disorders represent a major global health burden, highlighting the need for improved diagnostic and therapeutic strategies. Cerebrospinal fluid (CSF) is one of the most informative biofluids for investigating central nervous system (CNS) pathology due to its close biochemical relationship with brain tissue. Recent advances in neurometabolomics, defined as the comprehensive analysis of small-molecule metabolites in CSF, have been driven by the development of highly sensitive and informative mass spectrometry-based techniques. These approaches enable the identification of disease-associated metabolic signatures. This review summarizes current chromatography–mass spectrometry-based methods used in both untargeted and targeted CSF metabolomics, with particular emphasis on their analytical performance, reproducibility, and limitations. Special attention is given to method standardization and validation, as well as to the identification of reliable metabolic biomarkers for the diagnosis and monitoring of neurological disorders, including neurodegenerative, psychiatric, oncological, and neuroinflammatory diseases. Full article

Background: T-cell acute lymphoblastic leukemia (T-ALL) remains a challenging malignancy with limited targeted therapies. Natural phenanthrene derivatives represent a promising source of antileukemic agents. Objective: We screened a library of natural phenanthrene-type compounds to identify cytotoxic leads in Jurkat T-ALL cells and investigated the mechanisms underlying their activity, including potential synergy with the proteasome inhibitor bortezomib (BTZ). Methods: Jurkat cells were treated with thirteen natural compounds at 10 and 20 µM for 48 h; cell viability was assessed by WST-1 cell viability assay. Dose–response curves were generated to calculate IC₅₀ values. Apoptosis was evaluated by Hoechst 33342/PI staining and Annexin V/PI flow cytometry. Synergy with BTZ was analyzed using a fixed-ratio combination index (CI) approach and IC₅₀ shift analysis. ER stress signaling was characterized by Western blotting, quantitative RT-PCR of UPR genes (GRP78, ATF6), and immunoprecipitation of GRP78 followed by ubiquitin immunoblotting. Results: Among the compounds screened, Cypripedin showed the most potent cytotoxicity with an IC₅₀ of 6.52 µM. It induced a dose-dependent increase in apoptosis. Combination with BTZ yielded a CI < 0.5 and reduced BTZ IC₅₀ from 3.43 to 1.88 ng/mL. Cypripedin activated the unfolded protein response (UPR), modulated key ER stress markers including GRP78, p-PERK, p-eIF2α, p-JNK, and ATF6, downregulated UPR gene transcripts, and promoted GRP78 ubiquitination. Molecular docking predicted strong binding of Cypripedin to the GRP78 ATPase domain (Vina score −7.630 kcal/mol), supporting its mechanism of action. Conclusion: Cypripedin induces apoptosis in Jurkat T-ALL cells, synergizes with BTZ, and modulates ER stress through GRP78 ubiquitination. These findings support its further development as a potential T-ALL therapeutic. Full article

The rising incidence of viral infections demands the creation of innovative, biocompatible antiviral drugs with broad-spectrum effectiveness. This study combines the green synthesis, optimization, and characterization of silver nanoparticles (AgNPs) utilizing Dacryodes edulis (D. edulis) extract, assessing their antiviral, and antimicrobial characteristics. AgNPs were synthesized through the bio-reduction of silver nitrate with D. edulis water extract as a reducing, capping and stabilizing agent. The synthesis was refined through a Design of Experiments methodology. The characterization techniques, UV-Vis, Fourier-transform infrared, transmission electron microscopy, and dynamic light scattering, validated the successful synthesis of AgNPs with an average size of 101.56 ± 28.22 nm (TEM) and 156 ± 0.81 nm (DLS), a polydispersity index of 0.34, and a zeta potential of −22 mV. High-resolution liquid chromatography–tandem mass spectrometry analysis identified some bioactive compounds which enhance the antimicrobial and antiviral properties of the samples. Enzyme kinetics experiments revealed substantial inhibitory efficacy against the SARS-CoV-2 papain-like protease (PL-pro), with AgNPs exhibiting a lower IC₅₀ (0.271 ± 0.051 mg/mL) than the D. edulis extract (0.337 ± 0.043 mg/mL). The AgNPs exhibited MIC of 0.063 mg/mL for E. coli, 0.125 mg/mL for S. aureus and 0.08 mg/mL for S. pyrogens. The corresponding MBC values were 0.125 mg/mL, 0.25 mg/mL and 0.31 mg/mL, respectively. The fungal strains C. glabrata and C. albicans displayed MIC of 0.63 mg/mL and 0.31 mg/mL, respectively, and MBC values of 0.63 mg/mL and 0.31 mg/mL, respectively. This study underscores the potential of D. edulis-derived AgNPs as a cost-efficient, environmentally sustainable, and highly bioactive antibacterial and antiviral nanomaterial, facilitating the advancement of nanotechnology-based therapies for viral infections. Full article

Lilium lancifolium Thunb. is an important economic crop widely cultivated and traded across Asia and has significant pharmacological activity. Despite decades of research on their chemical composition, the spatial distribution patterns of characteristic secondary metabolites within the bulbs remain poorly understood. In this study, we used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) technology to characterize and spatially visualize multiple metabolites within the bulb for the first time. Additionally, ultra-high-performance liquid chromatography-Orbitrap Exploris mass spectrometry (UHPLC-OE-MS) was used to obtain comprehensive metabolite information from the bulbs. Using spatial metabolomics, we successfully identified nine steroidal saponins, three phenolic acid glycerides, and six other metabolites. Subsequently, we analyzed the spatial distribution of steroidal saponins and phenolic acid glycerides, which are key bioactive components. The analysis revealed that most of the steroidal saponins and phenolic acid glycerides, such as deacylbrownioside and regaloside A, exhibited a similar distribution pattern, mainly being enriched in the outer regions (A2, B2) and basal regions (B1, B2) on an individual scale. Further metabolomic and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that 11 substances detected in the bulbs, including diosgenin, phenylalanine, and acetyl-CoA, were jointly associated with 39 metabolic pathways, including “phenylpropanoid biosynthesis” and “terpenoid backbone biosynthesis”. Based on the above findings, we propose biosynthetic pathways and accumulation patterns of steroidal saponins and phenolic acid glycerides in bulbs. This study provides a basis for precise resource utilization of L. lancifolium bulbs and a methodology to elucidate the biosynthesis of plant metabolites. Full article

This study evaluates the influence of harvesting methods and seasonal variability on the physicochemical and antioxidant properties of Tetragonisca fiebrigi honey produced in the tropical dry forest of Bolivia. Despite the growing interest in stingless bee honey, studies addressing the combined effects of seasonality and collection practices in this region remain scarce. Honey samples were collected during winter and spring using three approaches: conventional, optimized (based on good manufacturing practices), and direct racking from natural nests. Physicochemical parameters (pH 4.60–6.15; moisture 28-34%; water activity 0.69–0.75) and sugar composition (glucose 10.60–29.03 g/100 g; fructose 9.01–21.97 g/100 g; sucrose 0.70–3.23 g/100 g) showed variability primarily associated with season rather than harvesting method. Bioactive compounds exhibited a marked seasonal effect, with higher total phenolic content (up to 11.03 mg GAE/100 g), flavonoids (up to 23.08 mg QE/100 g), and antioxidant capacity (DPPH up to 1.33 mol TE/100 g; ORAC up to 25.93 mol TE/100 g) in spring samples. Multivariate analysis (PCA) revealed that honey variability is structured along bioactive and physicochemical axes, with samples obtained using the optimized method showing reduced dispersion and greater compositional consistency. These results indicate that while seasonality governs the compositional and functional properties of T. fiebrigi honey, improved harvesting practices contribute to reducing variability and enhancing product standardization. This study provides one of the first comprehensive datasets on Bolivian stingless bee honey and highlights its potential as a functional food, supporting the development of species-specific quality criteria and sustainable meliponiculture in tropical dry forest ecosystems. Full article

Lost circulation in oil-based drilling fluids (OBDFs) under high-temperature conditions remains a significant challenge in deep and ultra-deep drilling. In this study, a high-temperature-resistant composite lost circulation material (LCM) was developed based on a synergistic strategy combining rigid bridging–consolidation and flexible embedding–filling. Rigid self-consolidating particles were prepared by coating skeleton materials with modified thermosetting resin, while flexible oil-absorbing resin was synthesized via suspension polymerization. The materials exhibited excellent lipophilicity, thermal stability, and structural integrity at 150 °C, with oil absorption capacity up to 3.43 g/g. The optimized composite LCM showed superior plugging performance, achieving compressive strengths above 11 MPa in white oil and 5 MPa in base mud at 150 °C. Effective sealing of 1–3 mm pore structures was obtained with leakage volumes below 10 mL, and fractured formations could be successfully consolidated. Mechanistically, rigid particles provide structural bridging, flexible resin enables pore filling via swelling, and modified resin(thermosetting resin chemically modified to achieve self-consolidation) enhances consolidation and micro-pore sealing, resulting in a dense and high-strength plugging layer. This work provides a promising approach for designing high-performance LCMs for OBDFs in high-temperature drilling environments. Full article

Targeted drug delivery remains difficult because multiple biological barriers interfere with the stable transport of therapeutics to the site of action. Polymeric nanocarriers have gained broad attention as delivery platforms since their composition and surface properties can be adjusted to improve circulation behavior and cellular delivery. This review discusses the major biological barriers involved in targeted drug delivery and describes how polymeric nanocarriers are engineered to overcome them. Major carrier types, including polymeric nanoparticles and micelles, are considered with emphasis on their physicochemical and interfacial features. Particular attention is given to surface engineering and stimuli-responsive design as key strategies for barrier transport and controlled cargo release. The review also highlights representative applications in anticancer, gene, protein, and vaccine delivery, together with translational issues such as biocompatibility, stability, reproducibility, scale-up, and regulatory acceptance. Full article

ASP flooding wastewater contains crude oil, suspended solids, anionic polymers and surfactants, with high viscosity, high zeta potential, difficult demulsification, flocculation and slow separation and sedimentation. In order to solve the problem of wastewater treatment of ASP flooding in oil fields, a magnetic branched core was prepared from ethyl silicate (TEOS), nano Fe₃O₄ and aminopropyl triethoxysilane (APTES), and then reacted with polyamine and methyl acrylate to synthesize the magnetic hyperbranched molecule FSNMN with demulsification ability. Using acrylamide (AM), acryloxyethyl trimethylammonium chloride (DAC) and maleic anhydride (MA) as raw materials, cationic polymer long chain (CAMHA) with flocculating properties was synthesized and grafted with hyperbranched molecules. The demulsification flocculation ability of the product regarding ASP flooding wastewater was evaluated, and the demulsification flocculation mechanism was summarized. The results showed that the average molecular weight of 3-FSNMN₄-C was 4.7 million, the cationic degree was 20.5%, and the saturation magnetization was 20 EMU/g. The removal rate of oil and suspended solids was 93.82% and 91.95% respectively when the simulated sewage was treated by magnetic field for 30 min. Magnetic hyperbranched star chain polymer provides a solution to the serious ecological environment problems caused by ASP flooding. Full article

In this study, bis-1,10-phenanthroline (Biphen) was synthesized via a hydrogen transfer-mediated coupling reaction in a single step. The resulting compound was demonstrated, for the first time, to function as a selective fluorescent probe for Ni²⁺ ions. The presence of Ni²⁺ at a 2:1 molar ratio of Biphen to Ni²⁺ results in complete fluorescence quenching, with a detection limit of 4.34 × 10⁻⁹ M in aqueous medium. Fluorescence is restored upon the introduction of a suitable chelating agent, producing an “on-off-on” fluorescence switching response. Furthermore, fluorescence co-localization studies demonstrate that Biphen functions as a mitochondria-targeted fluorescent probe with excellent cell membrane permeability, enabling rapid, reversible imaging and ultratrace detection of Ni²⁺ in mitochondria of live cells. Overall, this work demonstrates highly selective ultratrace detection of Ni²⁺ in both aqueous and biological environments, providing a promising platform for mitochondrial imaging and potential diagnostic applications. Full article

Cannabis sativa L. is a medicinal plant cultivated globally due to its remarkable historical and scientific relevance. Through the consumption of its flowers, also referred to as inflorescences, which contain a high content of cannabinoids, terpenes and polyphenols, the therapeutic properties of C. sativa can be harnessed. This study therefore aimed to determine the chemical profile, antioxidant and anti-inflammatory activities of the essential oils (EOs) obtained from the fresh and dried flowers of two C. sativa cultivars, Lifter and Cherrywine, grown in Komga, South Africa, to assess which cultivar has greater biological potential. The chemical profiles of the hydro-distilled EOs were analyzed by gas chromatography–mass spectrometry (GC-MS), while the in vitro antioxidant and anti-inflammatory activity of the EOs was analyzed using the DPPH and EAD methods, respectively. The identified constituents from the EOs were molecularly docked against NOX2 and NIK (NF-κB-inducing kinase) protein, which are implicated in oxidative stress. The afforded EOs were yellow (pale and bright yellow) in color with a sweet to mildly sweet aroma description. A total of 51 constituents were identified in both fresh and dry oils from the Lifter cultivar, while the Cherrywine cultivar contained a total of 44 constituents. Eighteen compounds, were found to be the main chemical constituents consistent in the flower EOs of both cultivars, notably, caryophyllene (10.71–19.96%), levo-β-pinene (1.37–13.21%), humulene (5.88–9.77%), caryophyllene oxide (4.32–7.49%), D-limonene (1.40–5.48%), α-pinene (2.22–5.22%), nerolidol (0.63–4.97%), cis-β-ocimene (0.22–4.37%), linalool (1.12–4.28%), selina-3,7(11)-diene (0.15–4.23%), humulene-1,2-epoxide (1.23–3.32%), guaiol (0.17–2.60%), (+)-β-selinene (1.20–2.51%), trans-α-bergamotene (0.68–2.37%), β-ocimene (0.90–2.27%), fenchol exo- (0.15–1.27), terpineol (0.14–1.38%) and α-terpineol (0.19–0.75%). The fresh Lifter flower oil (LFO) showed 50% inhibition at 100 μg/mL, with an IC₅₀ of 69.50 ± 4.05 µg/mL against DPPH, suggesting moderate to low radical scavenging activity. The maximum percentage inhibition response of DLFO, CFO and DCFO remained below 50% at all concentrations. The antioxidant activity of fresh LFO may be attributed to its overall chemical composition. The flower oils showed in vitro inhibition of protein denaturation; however, the high standard deviation relative to the mean IC₅₀ values limited the ability to rank the samples’ potencies. Further in silico studies on the putative constituents in the Lifter and Cherrywine cultivars revealed β-bisabolene and α-curcumene as potential molecular targets, with binding energy scores of −7.7 and −7.9 kcal/mol, respectively. Thus, the study findings highlight the promising biological importance of C. sativa inflorescences in the management of oxidative stress-related conditions. Further studies may investigate the influence of environmental growing conditions on their chemical composition, total ROS analysis, pharmacokinetic properties, and in vivo efficacy against oxidative damage to DNA, proteins and lipids. Evaluating the toxicity of the flower EOs is also recommended. Full article

The fallen Camellia vietnamensis fruits caused by typhoons are usually collected by the farmers to be processed into oil in order to decrease the loss of the disaster. Then, this report investigates the difference in the yield, quality, and antioxidant activity of the seed oil between the fallen fruits caused by the typhoons and the normally harvested fruits. The yield of seed oil from fallen fruits caused by typhoons (HCA) was significantly lower than that of normally harvested fruits (HCB). The physicochemical properties of HCA showed signs of quality deterioration. HCA seemed to optimize the fatty acid composition. HCA exhibited stronger DPPH^· radical scavenging, ABTS^·+ inhibitory, and ferric ion-reducing activities. Thirty-four volatile compounds were identified in both samples. HCA showed higher levels of antioxidant-rich volatiles. Overall, this investigation demonstrates that the fallen fruits caused by typhoons lead to significant seed oil yield losses and measurable quality deterioration, thereby offering clear, evidence-based insights to support more effective typhoon disaster mitigation strategies. Full article

Inspired by natural porphyrin-containing enzymatic active sites, metalloporphyrins have become important platforms for oxygen reduction reaction (ORR) catalysis because of their well-defined structures and tunable coordination environments. Recently, breaking the N₄-coordination environment of cobalt porphyrins by inverting one pyrrolic unit to generate N₃C₁-site, i.e., N-confused porphyrin, has emerged as an effective strategy to promote their electro-catalyzing ORR capability. Herein, we reviewed recent progress in N-confused cobalt porphyrin in catalyzing ORR, with special emphasis on the influence of the catalyst’s architecture. We first summarized the general ORR mechanism on metalloporphyrins and the computational methods commonly used for mechanistic studies. Then, for comparison, the more common modification strategies like meso- and β-position substitution, axial coordination, and dinuclear design were reviewed for cobalt porphyrin-based catalysts. The main part reviewed the N-confused cobalt porphyrins with three different architectures, i.e., molecular, framework, and supported heterogeneous molecular form, highlighting their synthesis, characterization, electrocatalytic ORR behavior, and mechanistic interpretation from both experimental and theoretical perspectives. It summarizes the current understanding of why CoN₃C₁ systems outperform the original CoN₄ porphyrin systems. The architecture of catalysts was found to affect the selectivity and mechanisms of ORR, along with the discussion of pH. The effects of N-confused strategy were compared to other modification strategies. Finally, we proposed possible directions for integrated catalyst design and mechanism studies. Full article

Thyroid cancer (TC) is an endocrine malignant tumor with the fastest-growing incidence worldwide. It has complex pathological types and significant heterogeneity, with great differences in clinical prognosis among different subtypes. Among them, aggressive subtypes, such as radioiodine-refractory (RAI-R) TC and anaplastic thyroid cancer (ATC), have become a major challenge in current clinical diagnosis and treatment, due to limited treatment options and high risks of recurrence and metastasis. Tumor metabolic reprogramming is one of the characteristics of cancer, among which the Warburg effect plays a driving role. As a rate-limiting enzyme in the glycolytic pathway, pyruvate kinase M2 (PKM2), with its unique functional plasticity, has become a linchpin of glycolytic metabolism and malignant phenotypes of tumor cells. This article will systematically review the functional regulatory mechanisms of PKM2, its specific role in TC, and explore the targeted therapeutic strategies and research prospects of TC with PKM2, providing a new theoretical basis and potential plans for the clinical diagnosis and treatment. Full article