Search Results (6,265)

Azomethine ylides (AMYs) have a nitrogen–carbon double bond and an electron lone pair on the nitrogen atom. They are essential 1,3-dipoles for [3+2] cycloadditions in the synthesis of pyrrolidine-containing heterocycles. Significant progress in 1,3-diplolar cycloadditions has been made in the construction of novel heterocyclic scaffolds, with efforts to broaden substrate scope, enhance stereoselectivity, and integrate green chemistry principles. This article summarizes double cycloadditions of AMYs derived from amino esters and amino acids for the synthesis of novel polyheterocycles. The design of double cycloadditions through the pot, atom, and step economic (PASE) method to increase the reaction efficiency is discussed. The examples presented in this paper may be applied to the synthesis of biologically active molecules. Full article

Background/Objective: Proteotoxic stress induced by inhibitors of the ubiquitin–proteasome system has been successful in multiple myeloma but not in solid cancers such as prostate cancer. Our objective is to find a combination with proteasome inhibitors that increases apoptotic cell death in all types of prostate cancer without harming non-cancer cells. Methods: The effectiveness of rencofilstat, a pan-cyclophilin inhibitor, combined with the ixazomib proteasome inhibitor, was investigated in multiple prostate cancer and non-cancer cells. Inducible knockdown of stress response XBP1s and cyclophilins A/B and inducible expression of XBP1s and cyclophilin B were developed in prostate cancer to determine functional roles. Results: Rencofilstat + ixazomib increased apoptotic cell death in prostate cancer but not in non-cancer cells. We investigated the effects on XBP1s and PERK, important unfolded protein response factors required for cells to survive proteotoxic stress. The results revealed that XBP1s had a pro-survival role early, but maintenance at later times of rencofilstat + ixazomib treatment resulted in cell death. In addition, decreased PERK and phospho-eIF2α likely maintained protein synthesis to further enhance proteotoxic stress. In contrast, rencofilstat + ixazomib did not alter XBP1s or PERK in non-cancer cells. Additional genetic experiments showed that the RCF targets cyclophilins A, B, and D had protective effects. Rencofilstat increased extracellular secretion of cyclophilin B, but rencofilstat + ixazomib reduced glycosylation and, likely, the biological function of CD147 (CypB receptor) and decreased downstream ERK signaling. Conclusions: Rencofilstat + ixazomib may be a new strategy for increasing proteotoxic stress and apoptotic cell death in advanced prostate cancer cells with less toxic side effects. Full article

This review provides a comprehensive overview of the therapeutic potential of omaveloxone (OMA) for the treatment of Friedreich’s ataxia (FA), along with an analysis of the historical development and current status of the synthetic strategies for OMA production. OMA activates the nuclear factor-2-(erythroid-2)-related (Nrf2) pathway in vitro and in vivo, in both animal models and humans. The Nrf2 pathway plays a crucial role in the cellular response to oxidative stress. Furthermore, OMA has been shown to mitigate mitochondrial dysfunction, restore redox homeostasis and downregulate nuclear factor-κB (NF-κB), a key mediator of inflammatory responses. Through these mechanisms, OMA contributes to tissue protection and inflammation reduction in patients with FA. The review also highlights future perspective, focusing on the challenges associated with OMA reprofiling through innovative drug delivery approaches and its potential repurposing for diseases beyond FA. Full article

This research prepared and characterised novel mixed coordination complexes derived from escitalopram with eugenol and curcumin to form (L₁) and (L₂), respectively. The complexes were prepared via Williamson ether synthesis and analysed by FTIR, UV–Vis, ¹H-NMR spectroscopy, elemental analysis, molar conductivity, and magnetic susceptibility. The results confirmed their octahedral geometries. Magnetic investigation reported high-spin configurations for Mn(II), Co(II), and Ni(II) complexes, whereas Cu(II) exhibited a distorted octahedral arrangement with characteristic d–d transitions. In addition, the calculation of Density functional theory (DFT) provided more insight into the detailed structural and electronic properties of the new ligand and its complexes. Antimicrobial compounds were evaluated against Escherichia coli, Staphylococcus aureus, and Candida albicans through the agar well diffusion method. The reported results revealed that Cobalt complexes showed antimicrobial activity followed by Copper (Cu), Nickel (Ni) and Manganese(Mn) complexes, respectively, due to an increase in Co-lipophilicity, which leads to improved diffusion through microbial cell membranes. The research findings confirmed that escitalopram-based mixed ligands coordinate with transition metals and could have significant biological applications. Full article

Fish species’ biological vocalizations serve as essential acoustic signatures for passive acoustic monitoring (PAM) and ecological assessments. However, limited availability of high-quality acoustic recordings, particularly for region-specific species like the brown croaker (Miichthys miiuy), hampers data-driven bioacoustic methodology development. In this study, we present a framework for reconstructing brown croaker vocalizations by integrating fk14 wavelet synthesis, PSO-based parameter optimization (with an objective combining correlation and normalized MSE), and deep learning-based validation. Sensitivity analysis using a normalized Bartlett processor identified delay and scale (length) as the most critical parameters, defining valid ranges that maintained waveform similarity above 98%. The reconstructed signals matched measured calls in both time and frequency domains, replicating single-pulse morphology, inter-pulse interval (IPI) distributions, and energy spectral density. Validation with a ResNet-18-based Siamese network produced near-unity cosine similarity (~0.9996) between measured and reconstructed signals. Statistical analyses (95% confidence intervals; residual errors) confirmed faithful preservation of SPL values and minor, biologically plausible IPI variations. Under noisy conditions, similarity decreased as SNR dropped, indicating that environmental noise affects reconstruction fidelity. These results demonstrate that the proposed framework can reliably generate acoustically realistic and morphologically consistent fish vocalizations, even under data-limited scenarios. The methodology holds promise for dataset augmentation, PAM applications, and species-specific call simulation. Future work will extend this framework by using reconstructed signals to train generative models (e.g., GANs, WaveNet), enabling scalable synthesis and supporting real-time adaptive modeling in field monitoring. Full article

The escalating global crisis of antimicrobial resistance demands innovative therapeutic strategies that transcend conventional approaches. This comprehensive review examines the groundbreaking synergistic integration of silver nanoparticles (AgNPs) with silk proteins (fibroin and sericin from Bombyx mori) to create advanced nanocomposite materials for biomedical applications. While extensive literature exists for AgNPs and silk proteins individually, a limited number of studies have explored their synergistic combination. This review consolidates this fragmented knowledge to establish the foundational framework for an emerging field. The unique properties of silk proteins as natural reducing, stabilizing, and capping agents enable environmentally friendly AgNPs synthesis while creating intelligent therapeutic platforms with emergent properties. These hybrid materials demonstrate superior performance in terms of antimicrobial efficacy, biocompatibility, and accelerated wound healing compared to the individual components. The nanocomposites exhibit broad-spectrum activity against multidrug-resistant pathogens while maintaining exceptional biocompatibility and promoting tissue regeneration. This integration represents a promising evolution toward biomimetic therapeutic platforms that work in harmony with biological systems, offering sustainable solutions to contemporary healthcare challenges. Full article

This review synthesizes the current knowledge of the various natural and human-caused processes that influence the evolution of sandy beaches and explores ways to improve predictions. Short-term storm-driven dynamics have been extensively studied, but long-term changes remain poorly understood due to a limited grasp of non-wave drivers, outdated topo-bathymetric (land–sea continuum digital elevation model) data, and an absence of systematic uncertainty assessments. In this study, we classify and analyze the various drivers of beach change, including meteorological, oceanographic, geological, biological, and human influences, and we highlight their interactions across spatial and temporal scales. We place special emphasis on the role of remote sensing, detailing the capacities and limitations of optical, radar, lidar, unmanned aerial vehicle (UAV), video systems and satellite Earth observation for monitoring shoreline change, nearshore bathymetry (or seafloor), sediment dynamics, and ecosystem drivers. A case study from the Langue de Barbarie in Senegal, West Africa, illustrates the integration of in situ measurements, satellite observations, and modeling to identify local forcing factors. Based on this synthesis, we propose a structured framework for quantifying uncertainty that encompasses data, parameter, structural, and scenario uncertainties. We also outline ways to dynamically update nearshore bathymetry to improve predictive ability. Finally, we identify key challenges and opportunities for future coastal forecasting and emphasize the need for multi-sensor integration, hybrid modeling approaches, and holistic classifications that move beyond wave-only paradigms. Full article

Galls of the Cynipidae, such as the Knopper gall, are abnormal plant outgrowths induced by insect activity. These structures not only protect the developing larvae but also alter the biochemical properties of host plant tissues. In this study, we report the green synthesis of silver nanoparticles (AgNPs) using ethanolic extracts of Quercus robur Knopper galls. AgNPs were synthesized via reduction of AgNO₃ and characterized using ATR-FTIR analysis, UV-Vis spectrophotometry, powder X-ray diffraction (PXRD), and transmission electron microscopy (TEM). The UV-Vis analysis showed a strong surface plasmon resonance (SPR) peak at 418 nm. A face-centered cubic (fcc) crystalline structure with an average crystallite size of about 12 nm was verified by PXRD patterns. TEM imaging revealed well-dispersed spherical nanoparticles, consistent with the size obtained via PXRD. ATR-FTIR analysis indicated the involvement of polyphenolic and protein-related functional groups in reduction and stabilization. The synthesized AgNPs exhibited strong growth inhibition capacity against B. subtilis and S. aureus, and moderate capacity against E. coli and P. aeruginosa. These findings highlight the potential of Knopper gall extract as a sustainable source for the eco-friendly synthesis of biologically active nanoparticles. Full article

The convergence of nanotechnology with nuclear medicine has led to the development of theranostic nanoplatforms that combine targeted imaging and therapy within a single system. This review provides a critical and updated synthesis of the current state of nanoplatform-based theranostics, with a particular focus on their application in oncology. We explore multifunctional nanocarriers that integrate diagnostic radionuclides for SPECT/PET imaging with therapeutic radioisotopes (α-, β-, or Auger emitters), chemotherapeutics, and biological targeting ligands. We highlight advances in nanomaterial engineering—such as hybrid architectures, surface functionalization, and stimuli-responsive designs—that improve tumor targeting, biodistribution, and therapeutic outcomes. Emphasis is placed on translational challenges including pharmacokinetics, toxicity, regulatory pathways, and GMP-compliant manufacturing. The article closes with a forward-looking perspective on how theranostic nanoplatforms could reshape the future of personalized oncology through precision-targeted diagnostics and radiotherapy. Full article

Coumarin derivatives, whether natural or synthetic, have attracted considerable interest from medicinal chemists due to their versatile biological properties. Their appealing pharmacological activities—such as anticancer, anti-inflammatory, neuroprotective, anticoagulant, and antioxidant effects—combined with the ease of their synthesis and the ability to introduce chemical modifications at multiple positions have made them a widely explored class of compounds. In the scientific literature, there are many examples. On the other hand, dithiocarbamates, originally employed as pesticides and fungicides in agriculture, have recently emerged as potential therapeutic agents for the treatment of serious diseases such as cancer and microbial infections. Moreover, dithiocarbamates bearing diverse organic functionalities have demonstrated significant antifungal properties against resistant phytopathogenic fungi, presenting a promising approach to combat the growing global issue of fungal resistance. Dithiocarbamates linked to coumarin derivatives have been shown to exhibit cytotoxic activity against various human cancer cell lines, including MGC-803 (gastric), MCF-7 (breast), PC-3 (prostate), EC-109 (esophageal), H460 (non-small cell lung), HCCLM-7 (hepatocellular carcinoma), HeLa (cervical carcinoma), MDA-MB-435S (mammary adenocarcinoma), SW480 (colon carcinoma), and Hep-2 (laryngeal carcinoma). Numerous studies have revealed that the inclusion of a dithiocarbamate moiety can provide central nervous system (CNS) activity, particularly through inhibitory potency and selectivity toward acetylcholinesterase (AChE) and monoamine oxidases (MAO-A and MAO-B). Recently, it has been reported that coumarin–dithiocarbamate derivatives exhibit α-glucosidase inhibitory effects and also possess promising antimicrobial activity. This study presents an overview of recent progress in the chemistry of coumarin–dithiocarbamate derivatives, with a focus on their biological activity. Previous review papers focused on coumarin derivatives as multitarget compounds for neurodegenerative diseases and described various types of compounds, with dithiocarbamate derivatives representing only a small part of them. Our work deals exclusively with coumarin dithiocarbamates and their biological activity. Full article

The development of cost-effective and highly sensitive hydrogen peroxide (H₂O₂) biosensors with robust stability is critical due to the pivotal role of H₂O₂ in biological processes and its broad utility across various applications. In this work, porous ceria hollow microspheres (CeO₂-phm) were synthesized using a solvothermal synthesis method and employed in the construction of an electrochemical biosensor for H₂O₂ detection. The resulting CeO₂-phm featured a uniform pore size centered at 3.4 nm and a high specific surface area of 168.6 m²/g. These structural attributes contribute to an increased number of active catalytic sites and promote efficient electrolyte penetration and charge transport, thereby enhancing its electrochemical sensing performance. When integrated into screen-printed carbon electrodes (CeO₂-phm/cMWCNTs/SPCE), the CeO₂-phm/cMWCNTs/SPCE-based biosensor exhibited a wide linear detection range from 0.5 to 450 μM, a low detection limit of 0.017 μM, and a high sensitivity of 2070.9 and 2161.6 μA·mM⁻¹·cm⁻²—surpassing the performance of many previously reported H₂O₂ sensors. In addition, the CeO₂-phm/cMWCNTs/SPCE-based biosensor possesses excellent anti-interference performance, repeatability, reproducibility, and stability. Its effectiveness was further validated through successful application in real sample analysis. Hence, CeO₂-phm with solvothermal synthesis has great potential applications as a sensing material for the quantitative determination of H₂O₂. Full article

This umbrella review provides a comprehensive synthesis of the available evidence on the relationship between digital device use and adolescent sleep. It summarizes results from systematic reviews and meta-analyses, presenting the magnitude and direction of observed associations. A total of seven systematic reviews, including five qualitative reviews and two meta-analyses, were included, comprising 127 primary studies with a combined sample of 867,003 participants. The findings suggest a negative impact of digital device use on various sleep parameters, including sleep duration, bedtime procrastination, and sleep quality. Devices such as smartphones and computers were found to have a greater adverse effect, while television use showed a weaker association. The most significant disruptions were observed in relation to social media and internet use, with problematic usage leading to delayed bedtimes, shorter sleep duration, and increased sleep onset latency. The review also highlights the role of timing and duration of device use, with late-night use particularly contributing to sleep disturbances. Biological, psychological, and social mechanisms are proposed as potential pathways underlying these effects. Despite moderate evidence supporting the negative impact of digital media on sleep, there is considerable heterogeneity across studies, and many relied on self-reported data, which may limit the generalizability of the findings. Future research should aim to standardize exposure and outcome measures, incorporate objective data collection methods, and explore causal relationships through longitudinal studies. This umbrella review underscores the importance of developing targeted public health strategies, parental guidance, and clinical awareness to mitigate the potential adverse effects of digital device use on adolescent sleep and mental health. Full article

Cytisine, a naturally occurring alkaloid and partial agonist of nicotinic acetylcholine receptors (nAChRs), has long been used as a smoking cessation aid and serves as the pharmacophore for varenicline. Recent research has expanded its therapeutic scope to neurodegenerative and neurological disorders, motivating the development of new cytisine derivatives. Among these, N-propargylcytisine combines the biological activity of the parent compound with the synthetic versatility of the terminal alkyne group. Herein, we report the synthesis and characterization of N-propargylcytisine, and its symmetrical dimer linked through 1,3-diyne moiety obtained via a copper-mediated Glaser–Hay oxidative coupling. The products were analyzed by NMR, FT-IR, and mass spectrometry, confirming the introduction of the propargyl moiety and the formation of the diyne bridge. Solvatochromic study of both compounds were performed using UV-VIS absorption spectroscopy in solvents of varying polarity, including protic solvents capable of hydrogen bonding. The 1,3-diyne motif, commonly found in bioactive natural products, endows the resulting dimer with potential for further derivatization and biological evaluation. This study demonstrates the utility of the Glaser–Hay reaction in the functionalization of alkaloid scaffolds and highlights the prospects of N-propargylcytisine derivatives in drug discovery targeting the central nervous system. Full article

Curcumin (CUR) is the primary metabolite isolated from the Curcuma longa L. rhizome. Most synthetic and biological studies have focused mainly on the curcumin molecule due to its essential biological activity as an antioxidant, anti-cancer, and anti-Alzheimer’s disease agent. However, the natural extract of turmeric also contains two essential curcuminoids (demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC)), which altogether comprise the so-called C-3 complex. They are present in commercial compositions for treating biliary or digestive ailments. The vegetal rhizome’s extraction typically leads to a mixture of the three main curcuminoids, CUR, DMC, and BDMC, in variable proportions, and each of these metabolites has reported specific synthetic routes. Herein, we have performed the synthesis and isolation of the three major curcuminoids using the method called scrambling of aldehydes followed by aldol di-condensation reactions. A density functional theory (DFT) approach supported the experimental results by inspecting the predicted energies for the aldol condensation. Thus, the di-condensation reaction is substantially favoured (ΔG° = −2685.9 kJ/mol) over the mono-condensation reaction (ΔG° = −1393.753 kJ/mol). Our approach allows us to mimic closely the proportions of these curcuminoids found in extracts from natural sources that follow the order CUR > DMC > BDMC, respectively. The proportion of aldehydes can be modified in the scrambling reaction with an adequate mixture of aldehydes to render the order DMC > CUR > BDMC. This is an advantageous way to increase the amount of the unsymmetric DMC metabolite. Full article

This study aims to elucidate the molecular mechanisms underlying cyanogenic glycoside accumulation in flax. As an important oil and fiber crop, the nutritional value of flax is compromised by the toxicity of cyanogenic glycoside. To clarify the key genetic regulators and temporal patterns of cyanogenic glycoside biosynthesis, transcriptomic sequencing was performed on seeds from high- and low-cyanogenic glycoside flax varieties (‘MONTANA16’ and ‘Xilibai’) at three developmental stages: bud stage, full flowering stage, and capsule-setting stage. A total of 127.25 Gb of high-quality data was obtained, with an alignment rate exceeding 87.80%. We identified 31,623 differentially expressed genes (DEGs), which exhibited distinct variety- and stage-specific expression patterns. Principal component analysis (PCA) and hierarchical clustering demonstrated strong reproducibility among biological replicates and revealed the seed pod formation stage as the period with the most significant varietal differences, suggesting it may represent a critical regulatory window for cyanogenic glycoside synthesis. GO and KEGG enrichment analyses indicated that DEGs were primarily involved in metabolic processes (including secondary metabolism and carbohydrate metabolism), oxidoreductase activity, and transmembrane transport functions. Of these, the cytochrome P450 pathway was most significantly enriched at the full bloom stage (H2 vs. L2). A total of 15 LuCYP450 and 13 LuUGT85 family genes were identified, and their expression patterns were closely associated with cyanogenic glycoside accumulation: In high-cyanogenic varieties, LuCYP450-8 was continuously upregulated, and LuUGT85-12 was significantly activated during later stages. Conversely, in low-cyanogenic varieties, high expression of LuCYP450-2/14 may inhibit synthesis. These findings systematically reveal the genetic basis and temporal dynamics of cyanogenic glycoside biosynthesis in flax and highlight the seed pod formation stage as a decisive regulatory window for cyanogenic glycoside synthesis. This study provides new insights into the coordinated regulation of cyanogenic pathways and establishes a molecular foundation for breeding flax varieties with low CNG content without compromising agronomic traits. Full article