Nuclear Magnetic Resonance Research Articles

Recent advances in solid‐state nuclear magnetic resonance studies on membrane fusion proteins

Membrane fusion is an essential biological process that merges two separate lipid bilayers into a whole one. Membrane fusion proteins facilitate this process by bringing lipid bilayers in close proximity to reduce the repulsive energy between membranes. Along with their interactions with membranes, the structures and dynamics of membrane fusion proteins are key to elucidating the mechanisms of membrane fusion. Solid‐state NMR (SSNMR) spectroscopy has unique advantages in determining the structures and dynamics of membrane fusion proteins in their membrane‐bound states. It has been extensively applied to reveal conformational changes in intermediate states of viral membrane fusion proteins and to characterize the critical lipid–membrane interactions that drive the fusion process. In this review, we summarize recent advancements in SSNMR techniques for studying membrane fusion proteins and their applications in elucidating the mechanisms of membrane fusion.

New eco-friendly succinimide linseed oil resin: synthesis, characterization, DFT and docking studies for surface coating

Purpose The purpose of this study is to develop a new protective coating formulation for industrial use, using new eco-friendly succinimide linseed oil resin. Design/methodology/approach Epoxidized linseed oil and N-(4-hydroxy phenyl) succinimide are reacted to create succinimide-modified epoxy (SIE) compounds. The synthesized compound was confirmed by different analyses, gas chromatography, Fourier transform infrared, proton nuclear magnetic resonance and scanning electron microscopy. The prepared compound has been blended with a primer paint formulation, then their physical and mechanical properties have been studied. Density function theory is used to calculate Frontier molecular orbital including highest occupied molecular orbital and least unoccupied molecular orbital to indicate the charge transfer from molecule to biological media and molecular electrostatic potential map was used to indicate the chemically reactive zone suitable for drug action. Findings The results of the paint formulation confirmed their best performance and provided good mechanical properties and high chemical and corrosion resistance. Research limitations/implications Resin compounds are the most used antimicrobial additives. Other functionalities of these compounds, such as corrosion inhibitors, might be studied to see if they are suited for these applications. Practical implications Because of the efficiency of the SIE when incorporated with primer, paint against microbial has also been examined in silico using the docking study which contributed to the analysis of their protein binding. This type of epoxy compound is environmentally friendly and can be used as a biocide with different paint formulations. As a result, paint compositions including this compound as additives can be used as dual-purpose paint and for a variety of industrial applications. Originality/value This research demonstrates how a low-cost paint composition based on synthesized SIE compounds may be used as a dual-function paint for industrial use.

Enhanced Stability and Brightness through Co-Substitution: Promoting Plant Growth with Green-Excited Deep Red Phosphor Ca1-zSrzLi1-xMg2xAl3-xN4:yEu2.

The research utilized a strategy of chemical unit co-substitution, successfully developing a novel blue-green to green excited, deep red-emitting phosphor, Ca1-zSrzLi1-xMg2xAl3-xN4:yEu2+ (CLA-2xM-zS:yEu, 0≤x≤0.8, 0.003≤y≤0.01, 0≤z≤1), through the replacement of [Li-Al]4+ by [Mg-Mg]4+. This phosphor uniquely converts unusable green light to growth-enhancing deep red, optimizing it for outdoor agriculture. Doping with Sr creates traps, causing a redshift in emission peaks, as confirmed by 7Li nuclear magnetic resonance (NMR) spectra, indicating Li presence and lattice changes. Ca0.2Sr0.8Li0.5MgAl2.5N4:0.005Eu2+ (CLAM-0.8S) phosphor maintained high luminescence intensity under extreme conditions of 85°C/85% RH, demonstrating excellent photoluminescence performance and chemical stability, compared with conventional SrLi0.5MgAl2.5N4:0.005Eu2+ (SLMA) and SrLiAl3N4:0.005Eu2+(SLA). Experimental results surprised that the unique Ca0.2Sr0.8Li0.8Mg0.4Al2.8N4:0.005Eu2+ (CLA-0.4M-0.8S) prepared light-converting film, which is mainly excited by green light, demonstrated a 20% increase in optical density of Chlorella compared to the PP film and a remarkable 97.5% increase compared to the control group without any film. These findings suggest that this film has significant potential for applications in outdoor agriculture and other fields.

The potent PHL4 transcription factor effector domain contains significant disorder.

The phosphate-starvation response transcription-factor protein family is essential to plant response to low-levels of phosphate. Proteins in this transcription factor (TF) family act by altering various gene expression levels, such as increasing levels of the acid phosphatase proteins which catalyze the conversion of inorganic phosphates to bio-available compounds. There are few structural characterizations of proteins in this TF family, none of which address the potent TF activation domains. The phosphate-starvation response-like protein-4 (PHL4) protein from this family has garnered interest due to the unusually high TF activation activity of the N-terminal domain. Here, we demonstrate using solution nuclear magnetic resonance (NMR) measurements that the PHL4 N-terminal activating TF effector domain is mainly an intrinsically disordered domain of over 200 residues, and that the C-terminal region of PHL4 is also disordered. Additionally, we present evidence from size-exclusion chromatography, diffusion NMR measurements, and a cross-linking assay suggesting full-length PHL4 forms a trimeric or tetrameric assembly. Together, the data indicate the N- and C-terminal disordered domains in PHL4 flank a central folded region that likely forms the ordered oligomer of PHL4. This work provides a foundation for future studies detailing how the conformations and molecular motions of PHL4 change as it acts as a potent activator of gene expression in phosphate metabolism. Such a detailed mechanistic understanding of TF function will benefit genetic engineering efforts that take advantage of this activity to boost transcriptional activation of genes across different organisms.

Comparative Analysis of Tetravalent Actinide Schiff Base Complexes: Influence of Donor and Ligand Backbone on Molecular Geometry and Metal Binding.

A series of isostructural early actinide AnIV complexes was synthesized in order to investigate the influence of a conjugated framework in the ligand backbone on An bonding. Therefore, the AnIV complexes [An(pyrophen)2] (An = Th, U, Np, and Pu) with the pure N-donor ligand bis(2-pyrrolecarbonylaldehyde)-o-phenylenediamine referred to as pyrophen, were synthesized and characterized. Solid state analysis via single-crystal X-ray diffraction (SC-XRD) reveals two sets of ligands binding in an almost orthogonal arrangement to the actinide center. For the larger actinides Th and U, the coordination sphere allows for additional coordination by a solvent molecule. Nuclear magnetic resonance spectroscopy (NMR) studies show the presence of highly symmetrical complexes in solution in good agreement with the solvent-free solid structures. While SC-XRD suggests mainly ionic binding, an analysis of paramagnetic NMR contributions and quantum chemical bond analysis hint towards significant covalency in the U, Np, and Pu compounds. This series of An complexes allowed for a thorough structural and theoretical comparison of a conjugated system to a closely related N-donor ligand (pyren)[1] as well as to the mixed N,O Schiff base ligands salophen (conjugated) and salen (non-conjugated).

NMR Phase Error Correction with New Modelling Approaches

Nuclear Magnetic Resonance (NMR) spectroscopy is a highly sensitive analytical technique essential for precise molecular identification and quantification. However, accurate results depend on effective pre-processing to correct for various types of errors. Phase error correction, in particular, is crucial for ensuring the reliability of NMR data. Current methods often rely on a single linear model, which may not adequately address all types of phase errors. As a result, this limitation frequently requires manual intervention, making the process both time-consuming and prone to errors. To address these limitations, we propose three modelling approaches for NMR phase error correction: nonlinear shrinkage, multiple models, and a new optimization function called delta absolute net minimization (DANM). Our comparison of seven methods revealed that nonlinear shrinkage outperformed others in both simulated spectra and a diabetes study, followed by multiple models with DANM. Additionally, our spike-in experiments demonstrated that DANM performed quite well in both single and multiple models. Our nonlinear shrinkage approach is a simple yet effective solution. We provide an open-source R package, NMRphasing, available on CRAN (https://cran.r-project.org/web/packages/NMRphasing/) and on GitHub (https://github.com/ajiangsfu/NMRphasing).

Exploring peptide dendrimers for intestinal lymphatic targeting: formulation and evaluation of peptide dendrimer conjugated liposomes for enhancing the oral bioavailability of Asenapine maleate.

Asenapine maleate (ASPM) is a second-generation atypical antipsychotic that is approved for treating acute schizophrenia and bipolar disorder in adults by the US FDA. The major downside of ASPM therapy is rapid, extensive first-pass hepatic metabolism following its oral administration with a very low oral bioavailability of < 2%. In this work, we developed ASPM nanoformulations conjugated with ligands such as arginine-glycine-aspartic acid (RGD) and peptide dendrimers (PDs) with the intention of improving the oral bioavailability of the drug by targeting it to the intestinal lymphatic system (ILS). Peptide dendrimers (PDs), both lipidated and nonlipidated, were synthesized by Fmoc solid phase peptide synthesis (SPPS). Reverse phase high performance chromatography (RP-HPLC) was used to purify the synthesized PDs, and the PDs were characterized by differential scanning calorimetry (DSC) electrospray ionization mass spectroscopy (ESI+-MS), Nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopy. The thin film hydration method was used to prepare liposomes, and the process variables affecting the liposome parameters were optimized using the Box‒Behnken design (BBD).Liposomes were PEGylated using DSPE-PEG-COOH2000 and further conjugated with ligands (RGD, PD-1 and PD-2) using EDC-NHS chemistry. The formulation was characterized using different spectroscopic techniques. In vitro, cell line studies, such as cytotoxicity, cell uptake, uptake mechanism, and receptor saturation studies, were performed on both Caco2 and Raji-B cells. The pharmacokinetic parameters of the developed liposomal formulation were evaluated using pharmacokinetic studies on Sprague- Dawley (SD) rats. The psychostimulant-induced hyperactivity model was used to evaluate the pharmacodynamic performance of the developed formulations by measuring the reversal of hyperlocomotor activity induced by levodopa-carbidopa.

Metabolic Activation and Cytotoxicity of Donepezil Induced by CYP3A4.

Donepezil (DNP) is a selective cholinesterase inhibitor widely used for the therapy of Alzheimer's disease. Instances of liver injury correlated with DNP treatment have been reported, yet the underlying hepatotoxic mechanism remains to be elucidated. This study aimed to explore the contribution of metabolic activation to the hepatotoxicity of DNP. The structure of 6-O-desmethyl DNP (M1), the oxidative metabolite of DNP, was characterized by chemical synthesis, LC-MS/MS, and nuclear magnetic resonance. A reactive quinone methide resulting from the metabolism of DNP was captured by glutathione (GSH) fortified in liver microsomal incubations after exposure to DNP, and the resulting GSH conjugate (M2) was detected in the bile of rats receiving DNP. Recombinant human P450 enzyme incubation studies demonstrated that CYP3A4 was the principal enzyme responsible for the production of M1 and M2. The generation of M2 declined in rat primary hepatocytes pretreated with ketoconazole, an inhibitor of CYP3A4, which also decreased the vulnerability of rat primary hepatocytes to DNP-caused cytotoxicity. These findings suggest that the quinone methide metabolite may contribute to the cytotoxicity and hepatotoxicity caused by the DNP.

Analysis of metabolites associated with ADIPOQ genotypes in individuals with type 2 diabetes mellitus.

Diabetes mellitus (DM) is a significant public health problem and it is known that the identification of molecular markers involved in glycemic control can impact disease control. Although the rs266729 polymorphism located in the promoter of the adiponectin gene (ADP) has been shown to be a candidate for involvement in glycemic control, the genotypic groups have never been characterized in terms of metabolomic aspects. Objective: Analyze the metabolites present in the rs266729 genotype groups. 127 diabetic individuals were compared according to the rs266729 genotype groups CC and GC + GG (RFLP-PCR). Blood plasma metabolites were classified by nuclear magnetic resonance (NMR), and the metabolic pathways of each group using the MetaboAnalyst tool. Insulin therapy (p = 0.049) was more frequent in the GC + GG rs266729 group. Lactate, alanine, glutamine, aspartate, lipid, lysine, isoleucine, citrulline, cholesterol, and fucose impacted the CC group and aspartate, beta-glucose, glutamate, pyruvate, proline, and 2-oxoglutarate impacted the CG + GG group. The glucose-alanine pathway, malate-aspartate transport, and urea cycle impacted the CC group (D-glucose, glutamic acid, L-alanine, oxoglutaric acid, and pyruvic acid). The glutamine/glutamate ratio is likely to be related to the causes of rs266729 influencing the risk of diabetes.

Microstructural Evolution and Damage Mechanism of Water-Immersed Coal Based on Physicochemical Effects of Inorganic Minerals

Coal seam water injection technology enables seam permeability enhancement and facilitates outburst risk reduction. This study investigated the microscale effects of water infiltration on coal and the evolution mechanisms of its mechanical properties. To this end, we systematically analyzed dynamic changes (such as mineral composition, pore structure, and mechanical performance) in coal soaked for various durations using X-ray diffraction, low-field nuclear magnetic resonance (NMR), and uniaxial compression testing. The results indicate: (1) the coal NMR T2 spectrum displays three characteristic peaks, corresponding to rapid water absorption, uniform transition, and stabilization stages of soaking traditionally divided according to peak area variation trends. (2) The coal strength decreases with progressive soaking, influenced by water content, pore volume, mineral composition, etc. Its compressive strength and elastic modulus drop by 22.4% and 19.5%, respectively, compared to the initial values. (3) The expansion of clay minerals during immersion reduces average pore size. In contrast, quartz particle displacement, pore water movement, and soluble mineral dissolution increase pore volume, reducing the overall structure strength. (4) The dominant factors driving the degradation of mechanical properties vary across immersion stages, including water content and specific mineral concentration. This work offers new insights into how hydraulic technology alters coal seams, providing theoretical support for optimizing water injection strategies in the seam.

Phytochemicals from Passiflora coriacea Juss. Have Anti-Inflammatory and Neuroprotective Effects in Mouse Models

Background: Neuroinflammatory diseases trigger an inflammatory response and a state of oxidative stress. Passiflora coriacea Juss. has been used to treat conditions related to inflammatory processes in the central nervous system; however, to date, there has been no study on the anti-inflammatory and neuroprotective effects of this species. Methods: The anti-inflammatory effect of P. coriacea was evaluated in a TPA-induced auricular edema model, and the percentage of edema inhibition (Ei) was recorded. The Morris water maze was used to assess the neuroprotective effect, measuring the latency time (LT), and lipopolysaccharide was administered to induce neuroinflammation. The concentrations of cytokines (IL-6, IL-10, and TNF-α) and activities of antioxidant system components (CAT, SOD, GR, NO, and MDA) were measured in the mouse brains. The chemical composition was determined using chromatographic and nuclear magnetic resonance techniques. Results: T1.1, T2.1, and T3.1 showed anti-inflammatory (Ei = 92.5, 88.3, and 64.8%, respectively) and neuroprotective (LT = 27.2, 22.9, and 27.7 s, respectively) effects. T1.1 was identified as scopolin with immunomodulatory (IL-6 = 3307 pg/g) and antioxidant (CAT = 1198 mmol, SOD = 23%, GR = 5.34 units/mL, NO = 11.5 µM, MDA = 1526 nmol/mL) effects; T2.1 was a mixture of terpenes (fitone, 7-dehydrodiosgenin, tremulone) with immunomodulatory (TNF-α = 857 pg/g) and antioxidant (CAT = 1245 mmol, NO = 8.75 µM) effects; and T3.1 was a mixture of isoquercetin and astragalin with immunomodulatory (IL-6 = 3135 pg/g, IL-10 = 1300 pg/g, TNF-α = 751 pg/g) and antioxidant (SOD = 1204 nmol/mL, CAT = 1131 nmol/mL, NO = 6.37 µM, MDA = 1204 nmol/mL) effects. Conclusions: The administration of P. coriacea treatments generated anti-inflammatory, neuroprotective, immunomodulatory, and antioxidant effects. These effects are attributable to its chemical composition, comprising scopolin, terpenes, and a mixture of isoquercetin and astragalin, which have not previously been described in this species.

Temperature-Sensitive Magnetic Resonance Probes: Leveraging Hyperpolarized Pyridine-2-Carbaldehyde and SABRE for Real-Time Temperature Sensing.

In this study, we developed a novel approach for real-time, temperature-sensitive nuclear magnetic resonance (NMR) measurements using signal amplification by reversible exchange (SABRE). We discovered that pyridine-2-carbaldehyde (A) exhibits different behavior depending on temperature, showing high hyperpolarization efficiency. In contrast, its reversible reaction product, the hemiacetal form (A'), is not affected by temperature. Exploiting this difference, we achieved a reliable polarization enhancement ratio without internal standard materials, even at low concentrations. Our method overcomes challenges associated with SABRE for 2-functionalized pyridines, enabling direct temperature monitoring in real-time NMR studies. We successfully applied it to monitor temperatures in solutions containing SABRE-inactive compounds like caffeine. Furthermore, we demonstrated its efficacy using a 60 MHz benchtop NMR spectrometer, validating its potential in challenging environments where conventional techniques may be limited. This technique shows promise for influencing the magnetic resonance field, potentially facilitating more accurate real-time analyses of molecular reactions and structures. Future research will focus on adapting this method for biological settings, aiming to stimulate advancements in NMR and magnetic resonance imaging (MRI) applications.

Freeze-Thaw Cycle Events Enable the Deep Disintegration of Biochar: Release of Dissolved Black Carbon and Its Structural-Dependent Carbon Sequestration Capacity.

Biochar is widely regarded as a recalcitrant carbon pool. However, the impact of freeze-thaw cycle events on its storage capacity, particularly on the release of dissolved black carbon (DBC), has remained poorly investigated. This study investigated the release behavior of DBC from biochar pyrolyzed at 300-700 °C during freeze-thaw cycles and their retention capacity in soil. Freeze-thaw cycles dramatically promoted DBC release (33.08-230.74 mg C L-1), exhibiting an order of magnitude higher than those without freeze-thaw process. The release kinetics of freeze-thaw-induced DBC varied depending on the pyrolysis temperature of biochar due to the different disintegration mechanisms. Interestingly, the retention capacity of freeze-thaw-induced DBC in soil showed a reduction ranging from 7.7 to 29.5% compared to DBC without the freeze-thaw process. This reduction can be attributed to numerous hydrophilic low-molecular-weight compounds (16.97-75.31%) in freeze-thaw-induced DBC, as evidenced by the results of size exclusion chromatography, fluorescence excitation/emission matrix, Fourier transform infrared spectroscopy, and nuclear magnetic resonance. These compounds tend to concentrate in the aqueous phase rather than being retained in the soil, potentially exacerbating the outflow of dissolved organic carbon. These findings clarify the release behavior of DBC during freeze-thaw cycles and reveal their contribution to the attenuation of carbon pools in cold regions.

Assessment the bioactivity of zinc oxid eugenol sealer after the addition of different concentrations of nano hydroxyapatite-tyrosine amino acid

Aim: Zinc oxide eugenol sealer has been used till now in endodontic obturation. However, despite many improvements in its formula, it still does not have, the essential root canal sealer’s properties which is the apatite forming ability. The aim of the present study is to assess the effect of the incorporation of nano Hydroxyapatite- tyrosine amino acid at different concentrations in the zinc oxide eugenol sealer formula in terms of bioactivity analysis. Methods: The nano hydroxy apatite-tyrosine amino acid was incorporated into the original zinc oxide eugenol (endosell) at different concentrations starting from (10 – 20)%. The chemical changes in zinc oxide eugenol before and after addition were characterized using FTIR and XRD. The setting time test was done according to ADA specification no. 57. The bioactivity analysis for the zinc oxide eugenol before and after the addition was evaluated according to ISO/FDIS 23317:2007(E) by using 28 days of storage in phosphate buffer saline, and then the hydroxyapatite precipitation and Ca/P ratio was evaluated using FESEM/EDX. Results: The FTIR and XRD confirmed the setting reaction occurrence among the (original ZOE, nHAP, and Tyr). The XRD and FESEM/EDX analyses confirmed the HAP precipitation on the ZOE sample surfaces after the addition of (nHAP-Tyr a.a) and this precipitation was increased with increased concentrations of additions. Conclusion: Incorporated (20) % of equal amounts of “nHA-Tyr a.a” can convert the ZOE to bioactive sealer as confirmed by XRD and FESEM/EDX. However, other characteristic analyses like Nuclear magnetic resonance, atomic force microscopy, and in vivo animal study were needed to further confirm the results.

Two‐Phase Extraction, Structural Characterization of the Polysaccharide from Raspberry Pomace and Its Protection Effects against Erythrocyte Hemolysis

AbstractIn present study, a new polysaccharide (RPP) from raspberry pomace is prepared through ultrasound‐assisted aqueous two‐phase extraction (UAATPE) and purification using two‐step column chromatography, the extraction conditions are optimized by response surface method (RSM). Under the optimal parameters: liquid to material ratio of 80 mL g−1, ultrasonic power of 340 W, and ultrasonic time of 39 min, the yield of the polysaccharides is 11.72 ± 0.05%. RPP with average molecular weight (Mw) of 59 300 Da is composed of six monosaccharides. Nuclear magnetic resonance (NMR) analyses confirmed that RPP contains six main glycosidic linkages including α‐l‐Araf‐(1→, →2)‐α‐l‐Rhap‐(1→, →4)‐β‐d‐Manp‐(1→, →4)‐α‐d‐GalAp‐(1→, →3)‐β‐d‐Galp‐(1→, →4)‐β‐d‐Glcp‐(1→. RPP exhibits remarkable protective effects against H2O2‐induced erythrocyte hemolysis, the generations of reactive oxygen species, and malondialdehyde are inhibited, and the activities of glutathione peroxidase and catalase are effectively enhanced. The current findings proved that UAATPE is an effective method to extract the polysaccharide from raspberry pomace and provides a new idea for the utilization of nutrient‐rich raspberry fruit residue.

Metal- and Photocatalyst-Free Sulfonylcyanation of [1.1.1]Propellane with Sulfonyl Cyanide

Background: Bicyclo[1.1.1]pentanes (BCPs), recognized as bioisosteres for para-disubstituted benzene rings, have gained prominence as valuable bioactive scaffolds in drug research. Methods: This study describes a radical-coupling method for the synthesis of sulfonyl-, cy-ano-substituted BCPs from sulfonyl cyanide and [1.1.1]propellane. In this study, the synthet-ic schemes were designed to show the chemical reactions. Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS) were used to identify and characterize the final com-pounds. Results: This method does not require photocatalysts, metals, or light, generating BCP ni-triles as a useful building block. The synthetic potential of this mild protocol was showcased by the diverse transformations. Conclusion: This versatile method significantly expands the range of BCP-type bioisosteres that can be generated.

Decoding Acute Myeloid Leukemia: A Clinician’s Guide to Functional Profiling

Acute myeloid leukemia (AML) is a complex clonal disorder characterized by clinical, genetic, metabolomic, and epigenetic heterogeneity resulting in the uncontrolled proliferation of aberrant blood-forming precursor cells. Despite advancements in the understanding of the genetic, metabolic, and epigenetic landscape of AML, it remains a significant therapeutic challenge. Functional profiling techniques, such as BH3 profiling (BP), gene expression profiling (GEP), proteomics, metabolomics, drug sensitivity/resistance testing (DSRT), CRISPR/Cas9, and RNAi screens offer valuable insights into the functional behavior of leukemia cells. BP evaluates the mitochondrial response to pro-apoptotic BH3 peptides, determining a cell’s apoptotic threshold and its reliance on specific anti-apoptotic proteins. This knowledge can pinpoint vulnerabilities in the mitochondria-mediated apoptotic pathway in leukemia cells, potentially informing treatment strategies and predicting therapeutic responses. GEP, particularly RNA sequencing, evaluates the transcriptomic landscape and identifies gene expression alterations specific to AML subtypes. Proteomics and metabolomics, utilizing mass spectrometry and nuclear magnetic resonance (NMR), provide a detailed view of the active proteins and metabolic pathways in leukemia cells. DSRT involves exposing leukemia cells to a panel of chemotherapeutic and targeted agents to assess their sensitivity or resistance profiles and potentially guide personalized treatment strategies. CRISPR/Cas9 and RNAi screens enable systematic disruption of genes to ascertain their roles in leukemia cell survival and proliferation. These techniques facilitate precise disease subtyping, uncover novel biomarkers and therapeutic targets, and provide a deeper understanding of drug-resistance mechanisms. Recent studies utilizing functional profiling have identified specific mutations and gene signatures associated with aggressive AML subtypes, aberrant signaling pathways, and potential opportunities for drug repurposing. The integration of multi-omics approaches, advances in single-cell sequencing, and artificial intelligence is expected to refine the precision of functional profiling and ultimately improve patient outcomes in AML. This review highlights the diverse landscape of functional profiling methods and emphasizes their respective advantages and limitations. It highlights select successes in how these methods have further advanced our understanding of AML biology, identifies druggable targets that have improved outcomes, delineates challenges associated with these techniques, and provides a prospective view of the future where these techniques are likely to be increasingly incorporated into the routine care of patients with AML.

Reusable nontoxic pyrimidine‐based oleogelators: Phase selectivity and nanostructured structuring

AbstractOver the last few decades, scientists have been working hard to produce edible structural agents those can be used in food, cosmetics, agriculture, pharmaceuticals, and biotechnology. The supramolecular assembly of simple amphiphiles in presence of edible oil is the most ideal system for this purpose because the system has no harmful health consequences. We have attempted to address the aforementioned implications in this article by synthesizing a novel class of structuring agents 2‐alkyl amino pyrimidine‐4‐carboxylic acid amphiphiles named 2‐decylamino‐pyrimidine‐4‐carboxylic acid (DPCA), 2‐dodecylamino‐ pyrimidine‐4‐carboxylic acid (DDPCA) and 2‐tetradecylamino‐pyrimidine‐4‐carboxylic acid (TDPCA), using simple procedure. To our delight, the prepared amphiphiles self‐assemble to a gel matrix in various vegetable oils and mineral oils. Microscopic analyses were used to investigate the nanostructured morphology of molecular gels. Rheological studies revealed that oleogels are mechanically processable and viscoelastic. Temperature dependent and concentration dependent proton nuclear magnetic resonance (1H‐NMR) studies were performed to analyze the hydrogen bonding and π–π interactions. The study discovered that gelators act as reusable phase selective gelators (PSG) of oil in water–oil mixture. The (3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide) (MTT) assay has proven that the synthetic oleogelators are nontoxic.

Preparation and characterization of poly(ethylene glycol)-b-poly(tert-butyl methacrylate) micelles as potential nanocarriers for donepezil

Polymeric micelles were prepared for the delivery of donepezil, a leading Alzheimer’s disease drug, to enhance its transport across the blood–brain barrier (BBB). Poly(ethylene glycol)-b-poly(tert-butyl methacrylate) amphiphilic block copolymers were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymers were characterized by gel permeation chromatography and nuclear magnetic resonance spectroscopy. Empty and donepezil loaded polymer micelles were formed using the dialysis method and characterized by dynamic light scattering and transmission electron microscopy. Drug loading efficiency and release behavior were monitored using UV/Vis spectroscopy, and cytotoxicity was evaluated via colorimetric tests and impedance measurements. Additionally, the permeability of the nanocarriers across an in vitro BBB culture model was assessed. Drug-loaded micelles demonstrated similar permeability to free donepezil but offered sustained release and improved stability. This micellar delivery system holds significant potential for improving therapeutic outcomes in Alzheimer’s treatment by enhancing donepezil’s delivery across the BBB. Improved BBB permeability and sustained drug release could lead to more effective concentration of the drug in the brain, potentially reducing peripheral cholinergic side effects, such as nausea and vomiting, often observed with traditional donepezil administration. This could result in better patient compliance and improved cognitive outcomes, making this nanocarrier system a promising alternative for Alzheimer’s therapy.

Synthesis and evaluation of vanillin Schiff bases as potential antimicrobial agents against ESBL-producing bacteria: towards novel interventions in antimicrobial stewardship.

The escalating challenge of antimicrobial resistance necessitates the development of novel antibacterial agents. In this study, a series of five vanillin Schiff bases (SB-1 to SB-5) were synthesized from vanillin and various aromatic amines. The chemical structures of these compounds were characterized using Thin Layer Chromatography (TLC), Fourier Transform Infrared Spectroscopy (FT-IR), proton nuclear magnetic resonance ( -NMR), carbon-13 NMR ( -NMR), and mass spectrometry techniques. Antibacterial efficacy was evaluated against strains of bacteria producing extended-spectrum beta-lactamases (ESBL), including Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae using the disc diffusion method. Cytotoxic effects were assessed through haemocompatibility and brine shrimp lethality assays. The Schiff bases demonstrated notable antibacterial activities, with SB-1, SB-2, SB-4, and SB-5 exhibiting zones of inhibition up to 16.0, 16.5, 16.6, and 15.5 mm against ESBL E. coli, respectively. SB-3 showed a maximum inhibition zone of 15.0 mm against ESBL K. pneumoniae. In cytotoxicity assays, the compounds exhibited IC values against red blood cells (RBCs) greater than 200 μg/mL and ranging from 45.7 to 50.5 μg/mL for the brine shrimp assay. While demonstrating potent antibacterial properties, the toxicity towards human RBCs suggests that further toxicity evaluations and structural modifications are essential for developing safer therapeutic agents based on vanillin Schiff bases.