Selective Properties Research Articles

Molecular Diversity of Photosensitive Protein Opsins and Their High Potential for Optogenetic Applications.

Because G protein coupled receptors (GPCRs) represent the largest family of drug targets in clinical trials, GPCR signaling cascades are closely related to various physiological phenomena, attracting significant attention in pharmaceutical science. Opsins (also known as animal rhodopsins) are photoreceptive proteins containing retinal as a chromophore, which function as GPCRs and underlie the molecular basis of photoreception in animals. Recently, opsins have been progressively applied in an innovative technology called optogenetics to regulate biological activities using light. A wide variety of opsins have been identified in metazoans and characterized at the molecular and physiological levels, providing a foundation for their optogenetic applications. In this review, I briefly introduce the diversity of opsins in terms of their molecular functions, including G protein selectivity and photoreaction properties. This diversity provides a significant advantage for optically manipulating a wide variety of GPCR signaling cascades with high temporal resolution. Additionally, I discuss the rich array of opsin-based optogenetic tools used to control various physiological processes and their potential as therapeutic tools for vision restoration. Based on the introduction, I expect that the optogenetic approach will offer powerful tools to provide valuable insights into the molecular mechanisms of various physiological phenomena and next-generation treatment options for diseases beyond the capacity of traditional drugs.

On traditional Menger and Rothberger variations

We present a comprehensive report on the relationships between variations of the Menger and Rothberger selection properties with respect to w-covers and k-covers in the most general topological setting and address the finite productivity of some of these properties. We collect various examples that separate certain properties and we carefully identify which separation axioms simplify aspects of these properties. We finish with a consolidated list of open questions focused on topological examples.

The challenge of harvesting common sole (Solea solea) in highly selective trawl fisheries

Common sole (Solea solea) is an economically important species in several European trawl fisheries, yet little is known about the size selective properties of codends used in bottom trawl fisheries targeting sole. This study presents results from a sea trial conducted in the inner Danish waters where common sole is fished in a seasonal trawl fishery using a 90 mm diamond mesh codend with a mandatory large mesh escape panel. To improve understanding of the selectivity in this gear, we in addition tested a plain 90 mm diamond mesh codend without an escape panel. This combination of codend mesh size and large mesh escape panel is part of an ambitious management plan aimed at eliminating bycatch of cod (Gadus morhua) in trawl fisheries in the inner Danish waters. In the fishery for common sole, we found a severe mismatch between gear regulations and minimum conservation reference size of the target species. The outcome is a highly inefficient fishery in which only 22 % (CI: 18–27 %) by weight of the marketable sole is retained in the 90 mm diamond mesh codend. Further, we estimated that 25 % (CI: 16–35 %) of the sole entering the codend would contact the mandatory escape panel and escape, resulting in a total loss of 83 % (CI: 79–87 %) of marketable sole through the mandatory gear. The inefficiency in this fishery demonstrates the need for other means than gear specifications to regulate this type of fishery.

Network Intrusion Detection Based on Convolutional Recurrent Neural Network, Random Forest, and Federated Learning

This paper presents a novel network intrusion detection framework that combines convolutional recurrent neural networks (CRNN) and random forest (RF) models within a federated learning setting. The proposed approach aims to address the challenges of data privacy, computational efficiency, and model generalization in traditional network intrusion detection methods. By leveraging the spatial feature extraction capabilities of CRNN and the feature selection and noise reduction properties of RF, the framework enhances the accuracy and robustness of attack detection. The integration of federated learning enables collaborative model training without compromising data privacy. Extensive experiments on benchmark datasets demonstrate the superiority of the proposed method compared to state-of-the-art techniques, achieving high performance metrics such as accuracy, precision, recall, F1 score, and AUC. The proposed framework offers a promising solution for secure and efficient network intrusion detection in real-world scenarios, contributing to the advancement of cybersecurity practices.

Enhanced Hydrophobicity and Oleophilicity of Modified Activated Carbons Derived from Agro-Wastes Biomass for the Removal of Crude Oil from Aqueous Medium

Crude oil spillage has tremendous environmental impacts and poses severe pollution problems worldwide due to the continuous activities and operations in the oil and gas sector. This has resulted in the urgent need for clean-up techniques such as the use of natural adsorbents which is considered a relatively low-cost, readily-available, efficient, eco-friendly, and easy-to-deploy mode of addressing oil spillage due to its high oil sorption capacity/efficiency, high oil selectivity, oleophilic, enduring, reusability and biodegradable properties. Empty palm fruit bunch and coconut coir were used as precursors to produce activated carbons for oil spill remediation. The influence of varying parameters was investigated using a batch experimental procedure resulting in the crude oil adsorption capacity increasing with a corresponding increase in contact time, initial oil concentration, temperature, agitation speed, and particle size but decreasing in adsorbent dosage. The combination of surface morphological modification and hydrophobicity enhancement resulted in significantly improved adsorption capacity for crude oil removal (2710.0 mg/g and 4859.5 mg/g for EPFBAC<SUB>LA</SUB> and CCAC<SUB>L.A</SUB> respectively), as evidenced by both FTIR and SEM analyses. The experimental isotherm data were analysed using various isotherm models and the best-fitted isotherm model was the Freundlich model with a correlation coefficient (R<sup>2 </sup>= 0.991 and R<sup>2 </sup>= 0.999) for EPFB<SUB>L.A</SUB> and CCAC<SUB>L.A</SUB> respectively. The kinetic behaviour of the adsorption process was best described by pseudo-second order with R<sup>2</sup> values of 0.970 and 0.999 for EPFBAC<SUB>LA</SUB> and CCAC<SUB>L.A</SUB> respectively while Boyd model revealed that the adsorption was controlled by an internal transport mechanism and film diffusion was the rate-limiting step. The crude oil adsorption was chemisorption and endothermic owing to the positive enthalpy values (ΔH<sup>o</sup> = 183.890 KJ/mol for EPFBAC<SUB>L.A </SUB>and ΔH<sup>o</sup> = 69.656 KJ/mol for CCAC<SUB>L.A</SUB>), the positive value of entropy suggested that the adsorption process was accompanied by an increase in the degree of randomness or disorder at the interface between the adsorbent and the adsorbate. A temperature rise led to a decline in Gibbs energy (ΔG<sup>o</sup>), suggesting that adsorption became more feasible and spontaneous at higher temperatures and the significant activation energies indicated the existence of a substantial energy barrier that must be overcome to initiate the reaction. The results showed the significant capability of the prepared adsorbents to be used as a low-cost, re-generable and eco-friendly adsorbent in oil spill clean-up and is recommended to exploit its usage on a large scale.

Dibenzodioxin-Based Polymers of Intrinsic Microporosity with Enhanced Transport Properties for Lithium Ions in Aqueous Media.

Boosting the transport and selectivity properties of membranes based on polymers of intrinsic microporosity (PIMs) toward one specific working analyte of interest is challenging. In this work, a novel family of PIM membranes, prepared by casting and exhibiting optima mechanical properties and high thermal stability, was synthesized from 4,4'-(2,2,2-trifluoro-1-phenylethane-1,1-diyl) bis(benzene-1,2-diol) and two tetrafluoro-nitrile derivatives. Gas permeability measurements evidenced a CO2/CH4 selectivity up to 170% relative to the reference polymer, PIM-1, in agreement with their calculated fractional free volume and the analysis of the textural properties by N2 and CO2 gas adsorption. Besides, the chemical modification by acid hydrolysis of the PIM membranes favored the permeability for lithium ions (LiCl 2M, 6 × 10-9 cm2·s-1) compared to other alkali metal analogs such as sodium (NaCl 2M, 7.38 × 10-10 cm2·s-1) and potassium (KCl 2M, 1.05 × 10-9 cm2·s-1). Moreover, the complete mitigation of the crossover of redox species with higher molecular sizes than the ions from alkali metal salts was confirmed by using in-line benchtop NMR methods. Additionally, the modified PIM membranes were measured in a symmetric electrochemical flow cell using an aqueous electrolyte by combining lithium ferro/ferricyanide redox compounds and lithium chloride. The electrochemical tests showed low polarization, high-rate capability, and capacity retention values of 99% when cycled at 10 mA·cm-2 for over 50 cycles. Based on these results, these polymers could be used as highly selective and conducting membranes in electrodialysis for lithium separation and lithium-based redox flow batteries and as a protective layer in high-energy density lithium metal batteries.

Metal-free carbon-dots nanozyme with oxidase-like activity as photocatalysts for highly efficient detection/reduction of Cr(VI) and antibacterial application

Wastewater containing Cr(VI) and bacteria indicated significant challenges and threats to public health and ecological environments. Hence, it is necessary to construct novel method for detecting and treatment such wastewater. Non-metal-doped carbon dots nanozyme (TA-CDs) were effectively synthesized by one-pot hydrothermal method utilizing tartaric acid (TA) and L-tryptophan (L-trp) as ingredients. TA-CDs revealed excellent water solubility, optical stability, and biocompatibility. Particularly noteworthy, TA-CDs (150 μg/mL) exhibited outstanding light-responsive oxidase-like activity, efficiently generating e-, O2∙- and CO2∙-. Furthermore, TA-CDs illustrated an exceptional linear relationship with Cr(VI) in an extensive detection range and low detection limits (0.51 μM), as well as high selectivity and anti-interference properties. Simultaneously, TA-CDs also demonstrated significant photocatalytic activity, achieving approximately 70.26 % reduction in 40 mg/L Cr(VI) and realized excellent antimicrobial performance (inhibition rates of 97.18 % and 82.67 % against E. coli and S. aureus, respectively). In short, this research not only provided a multifunctional carbon-dots nanoenzyme for recognition, photoreduction of Cr(VI), and photodynamic antibacterial application, but also offered novel strategy and methodology for detection and treatment of water containing heavy metals and microorganisms.

Preparation of CeO2QDs-g-C3N4/C composites and electrochemical determination of aflatoxin B1

The presence of Aflatoxin B1 (AFB1) in food represents a significant threat to human health, leading to the development of cancer. The key factor for effective trace detection technology lies in the utilization of sensor materials that exhibit excellent selectivity and high sensitivity properties. In this study, a successfully synthesis of g-C3N4/C with a high specific surface area uses melamine and houttuynia cordata stem as starting materials. A CeO2QDs-g-C3N4/C composite was prepared by hydrothermally anchoring cerium oxide quantum dots (CeO2QDs) onto the surface of g-C3N4/C, the high redox efficiency of CeO2QDs and the small size limitation effect significantly improve the sensing performance. The composite was characterized by XRD, XPS, SEM, TEM, and N2 adsorption-desorption. The results revealed that, the CeO2QDs-g-C3N4/C composite sensor material exhibited significant advantages with a large specific surface area, a well-defined micropore structure, and abundant reactive sites. In addition, electrochemical activity tests are conducted using EIS, CV, and DPV for the purpose of electrochemical investigations. The CeO2QDs-g-C3N4/C/GCE exhibits exceptional electrocatalytic activity against AFB1, with a wide linear response range of 100–1300 pg ml-1, an impressively low detection limit (LOD) of 6.61 fg ml-1 (S/N = 3), and a sensitivity of 0.985 pg μM ml-1μA-1. Furthermore, the stability, repeatability, and interference experimental response errors all remain below 5 %. It is also noteworthy that, the sensor material demonstrates excellent practicality in AFB1 assays conducted on real samples, which serves to illustrate its immense potential for applications in food safety evaluation.

Strongly ROS-Correlated, Time-Dependent, and Selective Antiproliferative Effects of Synthesized Nano Vesicles on BRAF Mutant Melanoma Cells and Their Hyaluronic Acid-Based Hydrogel Formulation.

Cutaneous metastatic melanoma (CMM) is the most aggressive form of skin cancer with a poor prognosis. Drug-induced secondary tumorigenesis and the emergency of drug resistance worsen an already worrying scenario, thus rendering urgent the development of new treatments not dealing with mutable cellular processes. Triphenyl phosphonium salts (TPPSs), in addiction to acting as cytoplasmic membrane disruptors, are reported to be mitochondria-targeting compounds, exerting anticancer effects mainly by damaging their membranes and causing depolarization, impairing mitochondria functions and their DNA, triggering oxidative stress (OS), and priming primarily apoptotic cell death. TPP-based bola amphiphiles are capable of self-forming nanoparticles (NPs) with enhanced biological properties, as commonly observed for nanomaterials. Already employed in several other biomedical applications, the per se selective potent antibacterial effects of a TPP bola amphiphile have only recently been demonstrated on 50 multidrug resistant (MDR) clinical superbugs, as well as its exceptional and selective anticancer properties on sensitive and MDR neuroblastoma cells. Here, aiming at finding new molecules possibly developable as new treatments for counteracting CMM, the effects of this TPP-based bola amphiphile (BPPB) have been investigated against two BRAF mutants CMM cell lines (MeOV and MeTRAV) with excellent results (even IC50 = 49 nM on MeOV after 72 h treatment). With these findings and considering the low cytotoxicity of BPPB against different mammalian non-tumoral cell lines and red blood cells (RBCs, selectivity indexes up to 299 on MeOV after 72 h treatment), the possible future development of BPPB as topical treatment for CMM lesions was presumed. With this aim, a biodegradable hyaluronic acid (HA)-based hydrogel formulation (HA-BPPB-HG) was prepared without using any potentially toxic crosslinking agents simply by dispersing suitable amounts of the two ingredients in water and sonicating under gentle heating. HA-BPPB-HA was completely characterized, with promising outcomes such as high swelling capability, high porosity, and viscous elastic rheological behavior.

Data-driven bio-mimetic composite design: Direct prediction of stress–strain curves from structures using cGANs

Designing high-performance composites requires integrating tasks, including material selection, structural arrangement, and mechanical property characterization. Accurate prediction of composite mechanical properties requires a comprehensive understanding of their mechanical response, particularly the failure mechanisms under high deformations. As traditional computational methods struggle to exhaustively explore every composite configuration in the vast design space for optimal design search, machine learning offers rapid identification of optimal composite designs. This study presents a cGAN-based deep learning model for predicting stress–strain curves directly from composite structures using an image-to-vector approach. The model incorporates fully connected layers within a U-Net generator for stress–strain curve generation and utilizes a PatchGAN discriminator for realism assessment. This end-to-end mapping from structures to mechanical response effectively eliminates the need for extensive simulations and labor-intensive post-analyses. Phase-field simulations were conducted to model the material failure process, generating stress–strain curves for various composite structures used as ground truth data to train and test the surrogate model. This study incorporates various composite structures in the dataset, including random (RS), layered (LS), chessboard-like (CS), soft-scaffold (SS), and hard-scaffold (HS), enhancing the representation of design diversity. Despite being trained on a limited dataset (approximately 1.5% for each bio-mimetic structure and 10−72% for RS composites), the model achieves highly accurate predictions in stress–strain curves, with MAE loss converging to 0.01 for training and 0.05 for testing after 2 million iterations. High evaluation scores on training data (R2>0.997, MAPE <1.08%) and testing data (R2>0.946, MAPE <5.53%) demonstrate the model’s accuracy in predicting mechanical properties such as Young’s modulus, strength, and toughness across all composite structures. Overall, the study provides a proof of concept for using machine learning to simplify the design process, demonstrating its potential for solving inverse composite design problems.

Biosensor Based on ZIF-67-HRP and MWCNTs Nanocomposite Modified Glass Carbon Electrode for the Detection of Luteolin in Vegetables.

Luteolin has various pharmacological properties, including anti-inflammatory, antioxidant, and antitumor characteristics. Due to its potential value in drugs and functional foods, it is important to develop an efficient method for detecting luteolin. In this work, the poor selectivity of existing luteolin nonenzymatic sensors was solved by translating the enzyme-catalyzed reaction from bulk solution to the surface of a horseradish peroxidase (HRP) modified electrode through an electrocatalytic oxidation process. Here, we modified the surface of a glassy carbon electrode (GCE) with metal-organic frameworks (MOFs; ZIF-67 here, abbreviated as ZIF), functional nanomaterials, and HRP and finally covered it with Nafion (NF). In this case, luteolin acts as a hydrogen donor, and the electrode acts as a hydrogen acceptor; the oxidation reaction occurs on the electrode surface. The use of ZIF-67 ensured the conformational stability of HRP to ensure the selectivity and anti-interference property, and SDS-dispersed multiwalled carbon nanotubes (MWCNTs) enhanced the electrode conductivity. The use of NF avoids shedding of the electrode material during the testing process. A UV-vis spectrophotometer was used to study the selectivity of luteolin by HRP and the compatibility between HRP and ZIF. The materials were characterized and analyzed by scanning electron microscopy and transmission electron microscopy. Due to the synergistic effect of these nanomaterials, the linear range of NF/ZIF-HRP/MWCNTs-SDS/GCE was 1.0 × 10-2 to 6.0 μM, with detection limits of 25.3 nM (S/N = 3). The biosensor showed long-term stability and reproducibility, with a relative standard deviation of 4.2% for the peak current (n = 5). Finally, the biosensor was successfully used to detect luteolin in carrots, celery, and cauliflower.

Functionalized expanded graphite foam supported by PVDF skeleton for cationic dyes selectively separating and purifying

In order to fully utilize the advantages of expandable graphite (large specific surface area and porous structure), a solvent-free method was used to provide a supporting skeleton for expandable graphite through melting, bonding and solidification of polyvinylidene fluoride (PVDF). Based on its porous structure and enhanced mechanical stability, the formed PVDF/expandable graphite composite foam, amounts of functional groups were introduced throughout the foam (outside on the surface and inner side in the expandable graphite) by deposition of tannic acid (TA) and dopamine (DA), endowing it selective adsorption characteristics. The functioned foam exhibited excellent dynamic dye adsorption capacity by capturing dye molecules firmly through π-π interaction, hydrogen bonding, and charge attraction between the functional groups and dyes. Furthermore, with low zeta potential (-24.9 mV), the functional groups showed selective adsorption properties resulting in rapid separation of cationic dyes and anionic dyes. The functionalized PVDF/expandable graphite composite foam contact these two materials together in order to complement each other's advantages, showing a new research orientation for the treatment of different types of dyestuff wastewater.

In vitro assessment of skin permeation properties of enzymatically derived oil-based fatty acid esters of vitamin C.

Current topical formulations containing vitamin C face limitations in therapeutic effectiveness due to the skin's selective properties that impede drug deposition. Consequently, the widespread use of toxic and irritating chemical permeation enhancers is common. Hereby, we investigated enzymatically derived fatty acid ascorbyl esters (FAAEs) obtained using natural oils for their skin permeation properties using the Strat-M® skin model in a Franz cell diffusion study. By evaluating various cosmetic formulations without added enhancers, we found that emulgel is most suitable for enhancing the cutaneous and transdermal delivery of FAAEs. Furthermore, medium-chain coconut oil-derived FAAEs exhibited faster diffusion rates compared to sunflower oil-based FAAEs with long-side acyl residues, including the commonly applied ascorbyl palmitate. Experimental data were successfully fitted using the Peppas and Sahlin model, which accounted for a lag phase and the combined effect of Fickian diffusion and polymer relaxation. In the case of long-chain esters, the lag phase was prolonged, and the calculated effective diffusion coefficients (Deff) were lower compared to medium-chain FAAEs. Accordingly, the highest Deff value was observed for ascorbyl caprylate, being even 60 times higher than for ascorbyl palmitate. These results suggest the emerging potential of emulgel with incorporated coconut oil-derived FAAEs for efficiently delivering vitamin C into the skin.

PVA-based formulations as a design-technology platform for orally disintegrating film matrices

In the majority of pharmaceutical applications, polymers are employed extensively in a diverse range of pharmaceutical products, serving as indispensable components of contemporary solid oral dosage forms. A comprehensive understanding of the properties of polymers and selection the appropriate methods of characterization is essential for the design and development of novel drug delivery systems and manufacturing processes. Orally disintegrating film (ODF) formulations are considered to be a potential substitute to traditional oral dosage forms and an alternative method of drug administration for children and uncooperative adult patients, including those with swallowing difficulties. A multitude of pharmaceutical formulations with varying mechanical and biopharmaceutical properties have emerged from the modification of the original polymeric bulk. Here we propose different formulation approaches, i.e. solvent casting (SC), 3D printing (3DP), electrospinning (ES), and lyophilization (LP) that enabled us to adjust the disintegration time and the release profile of poorly water soluble haloperidol (HAL, BCS class II) from PVA (polyvinyl alcohol) based polymer films while maintaining similar hydrogel composition. In this study, the solubility of haloperidol in aqueous solution was improved by the addition of lactic acid. The prepared films were evaluated for their morphology (SEM, micro-CT), physicochemical and biopharmaceutical properties. TMDSC, TGA and PXRD were employed for extensive thermal and structural analysis of fabricated materials and their stability. These results allowed us to establish correlations between preparation technology, structural characteristics and properties of PVA films and to adapt the suitable manufacturing technique of the ODFs to achieve appropriate HAL dissolution behaviour.

Discovery of 6,7-Dihydropyrazolo[1,5-a]pyrazin-4(5H)-one Derivatives as mGluR2 Negative Allosteric Modulators with In Vivo Activity in a Rodent's Model of Cognition.

Allosteric modulators of the metabotropic group II receptors, mGluR2 and mGluR3, have been widely explored due to their ability to modulate cognitive and neurological functions in mood disorders, although none have been approved yet. In our search for new and selective mGluR2 negative allosteric modulators (NAMs), series of 6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives were identified from our published series of 1,3,5-trisubstituted pyrazoles. SAR evolution of the initial hit resulted in 100-fold improvement in the mGluR2 NAM potency and subsequent selection of compound 11 based on its overall profile, including selectivity and ADMET properties. Further pharmacokinetic-pharmacodynamic (PK-PD) relationship built showed that compound 11 occupied the mGluR2 receptor in a dose-dependent manner. Additionally, the compound revealed in vivo activity in V-maze as a model of cognition from a dose of 0.32 mg/kg. Compound 11 was selected to be evaluated further.

Hydrogen-releasing magnesium hydrogel mitigates post laminectomy epidural fibrosis through inhibition of neutrophil extracellular traps

Epidural fibrosis is a primary contributor to the failure of laminectomy surgeries, leading to the development of failed back surgery syndrome (FBSS). Post-laminectomy, neutrophils infiltrate the surgical site, generating neutrophil extracellular traps (NETs) that contribute to epidural fibrosis. Reactive oxygen species (ROS) play a pivotal role in mediating NETs formation. Molecular hydrogen, recognized for its selective antioxidant properties and biosafety, emerges as a potential therapeutic gas in suppressing epidural fibrosis. In this study, we developed an in-situ hydrogen release hydrogel that inhibits the formation of NETs and mitigates epidural scarring. Biodegradable magnesium (Mg) microspheres served as a hydrogen source, coated with PLGA to regulate hydrogen release. These microspheres (Mg@PLGA) were then incorporated into a PLGA-PEG-PLGA thermosensitive hydrogel (Mg@PLGA@Gel), providing a surgical implant for sustained, long-term hydrogen release. In vitro experiments confirmed the biocompatibility of the system, demonstrating that hydrogen produced by Mg@PLGA effectively neutralizes neutrophil intracellular ROS and inhibits NETs formation. Histological analyses, including H&E staining, MRI, Masson staining, and immunohistochemistry, collectively indicate that Mg@PLGA@Gel is biocompatible and effectively inhibits epidural fibrosis post-laminectomy. Furthermore, Mg@PLGA@Gel inhibits ROS accumulation and NETs formation at the surgical site. These findings suggest that Mg@PLGA@Gel ensures continuous, therapeutic hydrogen concentration, providing relief from epidural fibrosis in a laminectomy mouse model. Statement of significance•The hydrogen-releasing hydrogel combines the therapeutic effects of a physical barrier with immunomodulation.•In situ-generated molecular hydrogen scavenges ROS caused by surgical stress and suppresses NETs formation.•The hydrogen-releasing hydrogel is demonstrated to exhibit high biocompatibility and inhibit epidural scar formation in vivo.

Performance regulation of the TFC NF membrane via the introduction of oleic acid into different organic solvents

AbstractBACKGROUNDTailored design of high‐performance nanofiltration membranes is desirable. The physicochemical properties of the organic phaseare essential for the preparation of nanofiltration membranes. Therefore, byfine‐tuning the organic phase, it is possible to achieve nanofiltrationmembranes with enhanced performance.RESULTSIn this work, oleic acid, a naturally extracted fatty acid, wasintroduced into three different organic solvents (n‐heptane, n‐octane andisopar G) to construct special oil phases for interfacial polymerization. Testingresults showed that proper dosage of oleic acid addition can effectivelydecrease the nanofiltration membrane pore size and enhance the salt rejectionregardless of the solvent type. Taking n‐octane as example, 5% oleic acidaddition in it can decrease the mean pore size from 0.500 nm to 0.341 nm and improve the MgSO4 rejection from 52.4% to 95.5%. Further characterizationindicated that the introduction of oleic acid into organic solvent cansignificantly reduce the interfacial tension and promote the diffusion of piperazinefrom aqueous phase to the oil phase. In addition, oleic acid could react with piperazineand produce some white particles that could be embed into the polyamide layer, thus altering the surface morphology.CONCLUSIONIn this work, a novel modified thin film composite nanofiltration membrane was prepared by a simple and controllable oleic acid assisted interfacial polymerization strategy, which exhibits good water permeability, solute selectivity and antifouling property. Without changing the existing process, our strategy opens up a simple, environmentally friendly and operable route for the synthesis of thin film composite nanofiltration membranes. © 2024 Society of Chemical Industry (SCI).

Design, preparation and biological evaluation of new Rociletinib-inspired analogs as irreversible EGFR inhibitors to treat non-small-cell-lung cancer

Epidermal growth factor receptor (EGFR) kinase has been implicated in the uncontrolled cell growth associated with non-small cell lung cancer (NSCLC). This has prompted the development of 3 generations of EGFR inhibitors over the last 2 decades due to the rapid development of drug resistance issues caused by clinical mutations, including T790M, L858R and the double mutant T790M & L858R. In this work we report the design, preparation and biological assessment of new irreversible 2,4-diaminopyrimidine-based inhibitors of EGFR kinase. Twenty new compounds have been prepared and evaluated which incorporate a range of electrophilic moieties. These include acrylamide, 2-chloroacetamide and (2E)-3-phenylprop-2-enamide, to allow reaction with residue Cys797. In addition, more polar groups have been incorporated to provide a better balance of physical properties than clinical candidate Rociletinib. Inhibitory activities against EGFR wildtype (WT) and EGFR T790M & L858R have been evaluated along with cytotoxicity against EGFR-overexpressing (A549, A431) and normal cell lines (HepG2). Selectivity against JAK3 kinase as well as physicochemical properties determination (logD7.4 and phosphate buffer solubility) have been used to profile the compounds. We have identified 20, 21 and 23 as potent mutant EGFR inhibitors (≤20 nM), with comparable or better selectivity over WT EGFR, and lower activity at JAK3, than Osimertinib or Rociletinib. Compounds 21 displayed the best combination of EGFR mutant activity, JAK3 selectivity, cellular activity and physicochemical properties. Finally, kinetic studies on 21 were performed, confirming a covalent mechanism of action at EGFR.

Ultra-Photostable Bacterial-Seeking Near-Infrared CPDs for Simultaneous NIR-II Bioimaging and Antibacterial Therapy.

Bacterial infections can pose significant health risks as they have the potential to cause a range of illnesses. These infections can spread rapidly and lead to complications if not promptly diagnosed and treated. Therefore, it is of great significance to develop a probe to selectively target and image pathogenic bacteria while simultaneously killing them, as there are currently no effective clinical solutions available. This study presents a novel approach using near-infrared carbonized polymer dots (NIR-CPDs) for simultaneous in vivo imaging and treatment of bacterial infections. The core-shell structure of the NIR-CPDs facilitates their incorporation into bacterial cell membranes, leading to an increase in fluorescence brightness and photostability. Significantly, the NIR-CPDs exhibit selective bacterial-targeting properties, specifically identifying Staphylococcus aureus (S.aureus)while sparing Escherichia coli (E. coli). Moreover, under 808nm laser irradiation, the NIR-CPDs exhibit potent photodynamic effects by generating reactive oxygen species that target and damage bacterial membranes. In vivo experiments on infected mouse models demonstrate not only precise imaging capabilities but also significant therapeutic efficacy, with marked improvements in wound healing. The study provides the dual-functional potential of NIR-CPDs as a highly effective tool for the advancement of medical diagnostics and therapeutics in the fight against bacterial infections.

An Efficient and Cost-effective Modified Carbon Paste Electrodes for Diltiazem Hydrochloride Determination in Tablets

Background and Objective: This study presented new sensitive and selective modified carbon paste (MCPE) potentiometric sensors modified with different ion pairs for the determination of the antihypertensive drug diltiazem hydrochloride (DTM-HCl) in biological fluids, pharmaceutical preparations, and in its pure form. Methods: Plasticizers, ion pair type, ion pair content, response time, temperature, and pH were just a few of the experimental factors evaluated that were found to affect electrode efficiency. The two electrodes that show the best sensitivity were prepared by mixing diltiazem-tetraphenyl borate (DTM-TPB) ion pair, graphite, and TCP or o-NPOE as a plasticizer. Result: Over the concentration ranges of 1.0x10-5–1.0x10-2, the produced electrodes I and II demonstrated monovalent Nernstian responses of 55.7±0.902 and 57.6±0.451 mV decade-1. The selectivity property of the suggested electrodes was used to study the interference ions. The concentration of DTM-HCl in pharmaceutical formulations and biological fluids was measured using these modified electrodes. During the validation procedure, metrics like linearity, accuracy, precision, limit of detection, limit of quantification, and specificity were used. Conclusion: The obtained results showed good agreement with the HPLC technique as indicated by the F and t-test values and can conclude the possibility of using this potentiometric method in the routine analysis of DTM-HCl.