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Herbal medicine, particularly in developing regions, remains highly popular due to its cost-effectiveness, accessibility, and minimal risk of adverse effects. Curcuma longa L., commonly known as turmeric, exemplifies such herbal remedies with its extensive history of culinary and medicinal applications across Asia for thousands of years. Traditionally utilized as a dye, flavoring, and in cultural rituals, turmeric has also been employed to treat a spectrum of medical conditions, including inflammatory, bacterial, and fungal infections, jaundice, tumors, and ulcers. Building on this longstanding use, contemporary biochemical and clinical research has identified curcumin-the primary active compound in turmeric-as possessing significant therapeutic potential. This review hypothesizes that curcumin's antioxidant properties are pivotal in preventing and treating chronic inflammatory diseases, which are often precursors to more severe conditions, such as cancer, and neurological disorders, like Parkinson's and Alzheimer's disease. Additionally, while curcumin demonstrates a favorable safety profile, its anticoagulant effects warrant cautious application. This article synthesizes recent studies to elucidate the molecular mechanisms underlying curcumin's actions and evaluates its therapeutic efficacy in various human illnesses, including cancer, inflammatory bowel disease, osteoarthritis, atherosclerosis, peptic ulcers, COVID-19, psoriasis, vitiligo, and depression. By integrating diverse research findings, this review aims to provide a comprehensive perspective on curcumin's role in modern medicine and its potential as a multifaceted therapeutic agent.

Gallium-doped zinc oxide (GZO) has demonstrated significant potential in gas-sensing applications due to its enhanced electrical and chemical properties. This study focuses on the synthesis, characterization, and gas-sensing performance of GZO nanoparticles (NPs), specifically targeting CO₂ detection, which is crucial for environmental monitoring and industrial safety. The GZO samples were synthesized using a sol-gel method, and their crystal structure was determined through X-ray diffraction (XRD), confirming the successful incorporation of gallium into the ZnO lattice. X-ray photoelectron spectroscopy (XPS) was employed to analyze the samples' elemental composition and chemical state, revealing the presence of Ga in the ZnO matrix and providing insights into the doping effects. Transmission electron microscopy (TEM) combined with energy-dispersive X-ray spectroscopy (EDS) was used to confirm the purity and elemental distribution of the synthesized samples, ensuring the homogeneity of the Ga doping. In-situ TEM measurements were also conducted on one of the three samples, with the smallest size. The experiment involved exposing the sample to argon (Ar) as a reference gas and carbon dioxide (CO₂) as the target gas to evaluate the sensor's response under real-time conditions. The in-situ TEM provided nanoscale observation of changes in the crystal structure parameters, particularly the d-spacing, which exhibited significant alterations exceeding 3.2% when exposed to CO₂ and Ar gases. Furthermore, electron paramagnetic resonance (EPR) and optical joint density of states (OJDS) analyses were performed to examine the presence of paramagnetic defects and to comprehensively understand the electronic structure within the GZO sample, respectively., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

A well-defined α,ω-dialdehyde polyisoprene-b-polystyrene block copolymer, synthesized using anionic polymerization high-vacuum techniques, is employed to prepare vitrimers with tris(2-aminoethyl)amine as the cross-linking agent. The vitrimer network, featuring dynamic imine cross-links, results in robust, flexible, and solvent-resistant films, which are applicable in thin film composite membranes. These vitrimer membranes, with molecular weight cut-offs in the nanofiltration range, are successfully used for organic solvent separation and evaluated for gas separation. The cross-linking density, controlled by the cross-linker, affects the material's gas permeability and affinity for CO₂. The dynamic nature of the imine cross-links enables the vitrimer's self-healing ability, activated by heat treatment at temperatures as low as 50 °C. Additionally, the vitrimer membranes can be reprocessed through solvent dissolution in the presence of the excess cross-linking agent., (© 2024 Wiley‐VCH GmbH.)

This study aimed to optimize mesalamine (MES)-nanoparticles (NPs) using Box Behnken Design and investigate its in vivo antioxidant potential in colon drug targeting. The formulation was prepared using oil/water (O/W) emulsion solvent evaporation technique for time dependent colonic delivery. The optimal formulation with the following parameters composition was selected: polymer concentration (% w/w) (A) = 0.63, surfactant concentration (% w/w) (B) = 0.71, sonication duration (min) (C) = 6. The outcomes showed that ethyl cellulose (EC) NP containing MES has particles size of 142 ± 2.8 nm, zeta potential (ZP) of -24.8 ± 2.3 mV, % EE of 87.9 ± 1.6%, and PDI of 0.226 ± 0.15. Scanning electron microscopy revealed NPs has a uniform and spherical shape. The in-vitro release data disclosed that the EC NPs containing MES showed bursts release of 52% ± 1.6% in simulated stomach media within 2 h, followed by a steady release of 93% ± 2.9% in simulated intestinal fluid that lasted for 48 h. The MES release from NP best match with the Korsmeyer-Peppas model ( R 2 = 0.962) and it followed Fickian diffusion case I release mechanism. The formulation stability over six-months at 25 °C ± 2 °C with 65% ± 5% relative humidity, and 40 °C ± 2 °C with 75% ± 5% relative humidity showed no significant changes in colour, EE, particle sizes and ZP. As per in vivo results, MES-NP effectively increased glutathione, SOD level and reduces the LPO level as compared to other treatment groups. The findings hold promise that the developed formulation can suitably give in ulcerative colitis., (Creative Commons Attribution license.)

This paper presents a comprehensive comparative analysis of biomarkers for head and neck cancer (HNC), a prevalent but molecularly diverse malignancy. We detail the roles of key proteins and genes in tumourigenesis and progression, emphasizing their diagnostic, prognostic, and therapeutic relevance. Our bioinformatic validation reveals crucial genes such as AURKA, HMGA2, MMP1, PLAU, and SERPINE1, along with microRNAs (miRNA), linked to HNC progression. OncomiRs, including hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-196a-5p, and hsa-miR-200c-3p, drive tumourigenesis, while tumour-suppressive miRNAs like hsa-miR-375 and hsa-miR-145-5p inhibit it. Notably, hsa-miR-155-3p correlates with survival outcomes in addition to the genes RAI14, S1PR5, OSBPL10, and METTL6, highlighting its prognostic potential. Future directions should focus on leveraging precision medicine, novel therapeutics, and AI integration to advance personalized treatment strategies to optimize patient outcomes in HNC care.

Aqueous ammonium ion batteries have garnered significant research interest due to their safety and sustainability advantages. However, the development of reliable ammonium-based full batteries with consistent electrochemical performance, particularly in terms of cycling stability, remains challenging. A primary issue stems from the lack of suitable anode materials, as the relatively large NH 4 + ions can cause structural damage and material dissolution during battery operation. To address this challenge, an Aza-based covalent organic framework (COF) material is introduced as an anode for aqueous ammonium ion batteries. This material exhibits superior ammonium storage capabilities compared to existing anode materials. It operates effectively within a negative potential range of 0.3 to‒1.0 V versus SCE, achieves high capacity even at elevated current densities (≈74 mAh g -1 at 10 A g -1 ), and demonstrates exceptional stability, retaining a capacity over 20 000 cycles at 1.0 A g -1 . Furthermore, by pairing this COF anode with a Prussian blue cathode, an ammonium rocking-chair full battery is developedd that maintains 89% capacity over 20 000 cycles at 1.0 A g -1 , surpassing all previously reported ammonium ion full batteries. This study offers insights for the design of future anodes for ammonium ion batteries and holds promise for high-energy storage solutions., (© 2024 Wiley‐VCH GmbH.)

Bacterial resistance to antibiotics and the number of patients infected by multi-drug-resistant bacteria have increased significantly over the past decade. This study follows a computational approach to identify potential antibacterial compounds from wild mushrooms. Twenty-six known compounds produced by wild mushrooms were docked to assess their affinity with drug targets of antibiotics such as penicillin-binding protein-1a (PBP1a), DNA gyrase, and isoleucyl-tRNA synthetase (ILERS). Docking scores were further validated by multiple receptor conformer (MRC)-based docking studies. Based on the MRC-based docking results, eight molecules were shortlisted for ADMET analysis. Molecular dynamics (MD) simulations were further performed to evaluate the conformational stability of the ligand-protein complexes. Binding energies were computed by the gmx_MMPBSA method. The data were obtained in terms of root-mean square deviation, and root-mean square fluctuation justified the stability of Austrocortilutein A, Austrocortirubin, and Confluentin in complex with several proteins under physiological conditions. Among these, Austrocortilutein A displayed better binding affinity with PBP1a and ILERS when compared with their respective reference ligands. This study is preliminary and aims to help drive the search for compounds that have the capacity to overcome the anti-microbial resistance of prevalent bacteria, using natural compounds produced by wild mushrooms. Further experimental validation is required to justify the clinical use of the studied compounds., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The direct liquid-phase oxidative carbonylation of methane, utilizing abundant natural gas, offers a mild and straightforward alternative. However, most catalysts proposed for this process suffer from low acetic acid yields due to few active sites and rapid C1 oxygenate generation, impeding their industrial feasibility. Herein, we report a highly efficient 0.1Cu/Fe-HZSM-5-TF (TF denotes template-free synthesis) catalyst featuring exclusively mononuclear Fe and Cu anchored in the ZSM-5 channels. Under optimized conditions, the catalyst achieved an unprecedented acetic acid yield of 40.5 mmol g cat -1  h -1 at 50 °C, tripling the previous records of 12.0 mmol g cat -1  h -1 . Comprehensive characterization, isotope-labeled experiments and density functional theory (DFT) calculations reveal that the homogeneous mononuclear Fe sites are responsible for the activation and oxidation of methane, while the neighboring Cu sites play a key role in retarding the oxidation process, promoting C-C coupling for effective acetic acid synthesis. Furthermore, the methyl-group carbon in acetic acid originates solely from methane, while its carbonyl-group carbon is derived exclusively from CO, rather than the conversion of other C1 oxygenates. The proposed bimetallic catalyst design not only overcomes the limitations of current catalysts but also generalizes the oxidative carbonylation of other alkanes, demonstrating promising advancements in sustainable chemical synthesis., (© 2024 Wiley-VCH GmbH.)

Solution-processable poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) is an important polymeric conductor used extensively in organic flexible, wearable, and stretchable optoelectronics. However, further enhancing its conductivity and long-term stability while maintaining its superb mechanical properties remains challenging. Here, a novel post-treatment approach to enhance the electrical properties and stability of sub-20-nm-thin PEDOT:PSS films processed from solution is introduced. The approach involves a sequential post-treatment with HNO 3 and CsCl, resulting in a remarkable enhancement of the electrical conductivity of PEDOT:PSS films to over 5500 S cm -1 , along with improved carrier mobility. The post-treated films exhibit remarkable air stability, retaining over 85% of their initial conductivity even after 270 days of storage. Various characterization techniques, including X-ray photoelectron spectroscopy, atomic force microscopy, Raman spectroscopy, Hall effect measurements, and grazing incidence wide angle X-ray scattering, coupled with density functional theory calculations, provide insights into the structural changes and interactions responsible for these improvements. To demonstrate the potential for practical applications, the ultrathin PEDOT:PSS films are connected to an inorganic light-emitting diode with a battery, showcasing their suitability as transparent electrodes. This work presents a promising approach for enhancing the electrical conductivity of PEDOT:PSS while offering a comprehensive understanding of the underlying mechanisms that can guide further advances., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Climate changes threat global food security and food production. Soil salinization is one of the major issues of changing climate, causing adverse impacts on agricultural crops. Germination and seedlings establishment are damaged under these conditions, so seeds must be safeguard before planting. Here, we use recycled organic tree waste combined with cold (low-pressure) plasma treatment as grain coating to improve the ability of wheat seed cultivars (Misr-1 and Gemmeza-11) to survive, germinate and produce healthy seedlings. The seeds were coated with biofilms of lignin and hash carbon to form a protective extracellular polymeric matrix and then exposed them to low-pressure plasma for different periods of time. The effectiveness of the coating and plasma was evaluated by characterizing the physical and surface properties of coated seeds using X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), nuclear magnetic resonance (NMR) spectroscopy, and wettability testing. We also evaluated biological and physiological properties of coated seeds and plants they produced by studying germination and seedling vigor, as well as by characterizing fitness parameters of the plants derived from the seeds. The analysis revealed the optimal plasma exposure time to enhance germination and seedling growth. Taken together, our study suggests that combining the use of recycled organic tree waste and cold plasma may represent a viable strategy for improving crop seedlings performance, hence encouraging plants cultivation in stressed ecosystems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Elgendy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that causes atrophy of brain cells, leading to their death, and has become a leading cause of death in aging populations worldwide. AD is characterized by β-amyloid (Aβ) deposition and tau phosphorylation in neural tissues, but the precise pathophysiology of the disease is still obscure. Autophagy is an evolutionarily targeted mechanism that is necessary for the elimination of neuronal and glial misfolded proteins as well as proteins. It also plays an essential role in synaptic plasticity. The aberrant autophagy primarily influences the process of aging and neurodegeneration. Autophagy significantly influences how Aβ and tau function physiologically, therefore, atypical autophagy is expected to perform an important role in Aβ deposition and tau phosphorylation characteristic in the development of AD. Bioactive phytoconstituents could majorly contribute as a natural yet effective alternative approach to slow down the progression of neurodegeneration and promote the active aging process in elderly patients. Over the recent years, it is well evidenced that different secondary metabolites including polyphenols, alkaloids, terpenes, and phenols exhibited neuroprotective effects, and attenuated brain damage, and cognitive impairment in vitro as well as in vivo. Additionally, the underlying mechanism of action shared by them is the regulation of competent autophagy via the removal of aggregated protein and mitochondrial dysfunction. The present article is structured as a reference for researchers keen to investigate and assess the new natural compound-mediated therapeutic approach for AD treatment through the modulation of autophagy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

We present a series of newly developed donor-acceptor (D-A) polymers designed specifically for organic electrochemical transistors (OECTs) synthesized by a straightforward route. All polymers exhibited accumulation mode behavior in OECT devices, and tuning of the donor comonomer resulted in a three-order-of-magnitude increase in transconductance. The best polymer gFBT-g2T, exhibited normalized peak transconductance (g m,norm ) of 298±10.4 S cm -1 with a corresponding product of charge-carrier mobility and volumetric capacitance, μC*, of 847 F V -1  cm -1  s -1 and a μ of 5.76 cm 2  V -1  s -1 , amongst the highest reported to date. Furthermore, gFBT-g2T exhibited exceptional temperature stability, maintaining the outstanding electrochemical performance even after undergoing a standard (autoclave) high pressure steam sterilization procedure. Steam treatment was also found to promote film porosity, with the formation of circular 200-400 nm voids. These results demonstrate the potential of gFBT-g2T in p-type accumulation mode OECTs, and pave the way for the use in implantable bioelectronics for medical applications., (© 2024 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Lipids play crucial roles in human biology, serving as energy stores, cell membranes, hormone production, and signaling molecules. Accordingly, their study under lipidomics has advanced the study of living organisms. 1-Dimensional (D) and 2D NMR methods, particularly 1D 1 H and 2D 1 H- 1 H Total Correlation Spectroscopy (TOCSY), are commonly used in lipidomics for quantification and structural identification. However, these NMR methods suffer from low sensitivity, especially in cases of low concentrated molecules such as protons attached to hydroxy, esters, aliphatic, or aromatic unsaturated carbons. Such molecules are common in complex mixtures such as dairy products and plant oils. On the other hand, lipids have highly populated fractions of methyl and methylene groups that result in intense peaks that overwhelm lower peaks and cause inhomogeneities in 2D TOCSY spectra. In this study, we applied a method of suppression to suppress these intense peaks of methyl and methylene groups to detect weaker peaks. The suppression method was investigated on samples of cheese, butter, a mixture of lipids, coconut oil, and olive oil. A significant improvement in peak sensitivity and visibility of cross-peaks was observed, leading to enhanced comparative quantification and structural identification of a greater number of lipids. Additionally, the enhanced sensitivity reduced the time required for the qualitative and comparative quantification of other lipid compounds and components. This, in turn, enables faster and more reliable structural identification and comparative quantification of a greater number of lipids. Additionally, it reduces the time required for the qualitative, and comparative quantification due to the enhancement of sensitivity., Competing Interests: The authors declare that they have no conflicts of interest with the contents of this article., (This journal is © The Royal Society of Chemistry.)

Mixed tin-lead (Sn-Pb) halide perovskites stand out as promising materials for next-generation photovoltaics and near-infrared optoelectronics. However, their sensitivity to oxidative degradation remains a major hurdle toward their widespread deployment. A holistic understanding of their oxidation processes considering all their constituent ions is therefore essential to stabilize these materials. Herein, we reveal that A-site cation choice plays an inconspicuous yet crucial role in determining Sn-Pb perovskite stability toward oxidation. Comparing typical A-site compositions, we show that thin films and solar cells containing cesium are more resistant to oxidative stress relative to their methylammonium analogs. We identify degradation in these compositions to be closely linked to the presence of triiodide, a harmful species evolving from native I 2 oxidants. We find that hydrogen bonding between methylammonium and I 2 promotes triiodide formation, while the strong polarizing character of cesium limits this process by capturing I 2 . Inspired from these findings, we design two strategies to boost stability of sensitive methylammonium-based Sn-Pb perovskite films and devices against oxidation. Specifically, we modulate the polarizing character of surface A-sites in perovskite via CsI and RbI coatings, and we incorporate Na 2 S 2 O 3 as an I 2 scavenging additive. These crucial mechanistic insights will pave the way for the design of highly efficient and stable Sn-Pb perovskite optoelectronics.

Amylin is part of the endocrine pancreatic system that contributes to glycemic control, regulating blood glucose levels. However, human amylin has a high tendency to aggregate, forming isolated amylin deposits that are observed in patients with type 2 diabetes mellitus. In search of new inhibitors of amylin aggregation, we undertook the chemical analyses of five marine macroorganisms encountered in high populations in the Red Sea and selected a panel of 10 metabolites belonging to different chemical classes to evaluate their ability to inhibit the formation of amyloid deposits in the human amylin peptide. The thioflavin T assay was used to examine the kinetics of amyloid aggregation, and atomic force microscopy was employed to conduct a thorough morphological examination of the formed fibrils. The potential ability of these compounds to interact with the backbone of peptides and compete with β-sheet formation was analyzed by quantum calculations, and the interactions with the amylin peptide were computationally examined using molecular docking. Despite their structural similarity, it could be observed that the hydrophobic and hydrogen bond interactions of pyrrolidinones 9 and 10 with the protein sheets result in one case in a stable aggregation, while in the other, they cause distortion from aggregation.

The NF-κB pathway plays a pivotal role in impeding the diabetic wound healing process, contributing to prolonged inflammation, diminished angiogenesis, and reduced proliferation. In contrast to modern synthetic therapies, naturally occurring phytoconstituents are well-studied inhibitors of the NF-κB pathway that are now attracting increased attention in the context of diabetic wound healing because of lower toxicity, better safety and efficacy, and cost-effectiveness. This study explores recent research on phytoconstituent-based therapies and delve into their action mechanisms targeting the NF-κB pathway and potential for assisting effective healing of diabetic wounds. For this purpose, we have carried out surveys of recent literature and analyzed studies from prominent databases such as Science Direct, Scopus, PubMed, Google Scholar, EMBASE, and Web of Science. The classification of phytoconstituents into various categorie such as: alkaloids, triterpenoids, phenolics, polyphenols, flavonoids, monoterpene glycosides, naphthoquinones and tocopherols. Noteworthy phytoconstituents, including Neferine, Plumbagin, Boswellic acid, Genistein, Luteolin, Kirenol, Rutin, Vicenin-2, Gamma-tocopherol, Icariin, Resveratrol, Mangiferin, Betulinic acid, Berberine, Syringic acid, Gallocatechin, Curcumin, Loureirin-A, Loureirin-B, Lupeol, Paeoniflorin, and Puerarin emerge from these studies as promising agents for diabetic wound healing through the inhibition of the NF-κB pathway. Extensive research on various phytoconstituents has revealed how they modulate signalling pathways, including NF-κB, studies that demonstrate the potential for development of therapeutic phytoconstituents to assist healing of chronic diabetic wounds., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Human amylin (hIAPP) is found in the form of amyloid deposits within the pancreatic cells of nearly all patients diagnosed with type 2 diabetes mellitus (T2DM). However, rat amylin (rIAPP) and pramlintide - hIAPP analogs - are both non-toxic and non-amyloidogenic. Their primary sequences exhibit only slight variations in a few amino acid residues, primarily concentrated in the central region, spanning residues 20 to 29. This inspired us to study this fragment and investigate the impact on the aggregation properties of substituting residues within the central region of amylin and its analogs. Six fragments derived from amylin have undergone comprehensive testing against various metal ions by implementing a range of analytical techniques, including Nuclear Magnetic Resonance (NMR) spectroscopy, Thioflavin T (ThT) assays, Atomic Force Microscopy (AFM), and cytotoxicity assays. These methodologies serve to provide a thorough understanding of how the substitutions and interactions with metal ions impact the aggregation behavior of amylin and its analogs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alghrably, Bennici, Szczupaj, Alasmael, Qutub, Maatouk, Chandra, Nowakowski, Emwas and Jaremko.)

Rheumatoid arthritis (RA) is a chronic debilitating autoimmune disease, that causes joint damage, deformities, and decreased functionality. In addition, RA can also impact organs like the skin, lungs, eyes, and blood vessels. This autoimmune condition arises when the immune system erroneously targets the joint synovial membrane, resulting in synovitis, pannus formation, and cartilage damage. RA treatment is often holistic, integrating medication, physical therapy, and lifestyle modifications. Its main objective is to achieve remission or low disease activity by utilizing a "treat-to-target" approach that optimizes drug usage and dose adjustments based on clinical response and disease activity markers. The primary RA treatment uses disease-modifying antirheumatic drugs (DMARDs) that help to interrupt the inflammatory process. When there is an inadequate response, a combination of biologicals and DMARDs is recommended. Biological therapies target inflammatory pathways and have shown promising results in managing RA symptoms. Close monitoring for adverse effects and disease progression is critical to ensure optimal treatment outcomes. A deeper understanding of the pathways and mechanisms will allow new treatment strategies that minimize adverse effects and maintain quality of life. This review discusses the potential targets that can be used for designing and implementing precision medicine in RA treatment, spotlighting the latest breakthroughs in biologics, JAK inhibitors, IL-6 receptor antagonists, TNF blockers, and disease-modifying noncoding RNAs., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Colloidal quantum dots (CQDs) are emerging materials for short-wave infrared (SWIR, ≈1100-3000 nm) photodetectors, which are technologically important for a broad array of applications. Unfortunately, the most developed SWIR CQD systems are Pb and Hg chalcogenides; their toxicity and regulated compositions limit their applications. InSb CQD system is a potential environmentally friendly alternative, whose bandgap in theory, is tunable via quantum confinement across the SWIR spectrum. However, InSb CQDs are difficult to exploit, due to their complex syntheses and uncommon reactive precursors, which greatly hinder their application and study. Here, a one-pot synthesis strategy is reported using commercially available precursors to synthesize-under standard colloidal synthesis conditions-high-quality, size-tunable InSb CQDs. With this strategy, the large Bohr exciton radius of InSb can be exploited for tuning the bandgap of the CQDs over a wide range of wavelengths (≈1250-1860 nm) across the SWIR region. Furthermore, by changing the surface ligands of the CQDs from oleic acid (OA) to 1-dodecanthiol (DDT), a ≈20-fold lengthening in the excited-state lifetime, efficient carrier multiplication, and slower carrier annihilation are observed. The work opens a wide range of SWIR applications to a promising class of Pb- and Hg-free CQDs., (© 2023 Wiley‐VCH GmbH.)

In this work, a relatively new class of materials, rare earth (RE) based high entropy oxides (HEO) are discussed in terms of the evolution of the oxygen vacant sites (O v ) content in their structure as the composition changes from binary to HEO using both experimental and computational tools; the composition of HEO under focus is the CeLaPrSmGdO due to the importance of ceria-related (fluorite) materials to catalysis. To unveil key features of quinary HEO structure, ceria-based binary CePrO and CeLaO compositions as well as SiO 2 , the latter as representative nonreducible oxide, were used and compared as supports for Ru (6 wt % loading). The role of the O v in the HEO is highlighted for the ammonia production with particular emphasis on the N 2 dissociation step (N 2(ads) → N ads ) over a HEO; the latter step is considered the rate controlling one in the ammonia production. Density functional theory (DFT) calculations and 18 O 2 transient isotopic experiments were used to probe the energy of formation, the population, and the easiness of formation for the O v at 650 and 800 °C, whereas Synchrotron EXAFS, Raman, EPR, and XPS probed the Ce-O chemical environment at different length scales. In particular, it was found that the particular HEO composition eases the O v formation in bulk, in medium (Raman), and in short (localized) order (EPR); more O v population was found on the surface of the HEO compared to the binary reference oxide (CePrO). Additionally, HEO gives rise to smaller and less sharp faceted Ru particles, yet in stronger interaction with the HEO support and abundance of Ru-O-Ce entities (Raman and XPS). Ammonia production reaction at 400 °C and in the 10-50 bar range was performed over Ru/HEO, Ru/CePrO, Ru/CeLaO, and Ru/SiO 2 catalysts; the Ru/HEO had superior performance at 10 bar compared to the rest of catalysts. The best performing Ru/HEO catalyst was activated under different temperatures (650 vs 800 °C) so to adjust the O v population with the lower temperature maintaining better performance for the catalyst. DFT calculations showed that the HEO active site for N adsorption involves the O v site adjacent to the adsorption event.

Metabolomics, a recent addition to omics sciences, studies small molecules across plants, animals, humans, and marine organisms. Nuclear magnetic resonance (NMR) and gas chromatography-mass spectrometry (GC-MS) are widely used in those studies, including microalgae metabolomics. NMR is non-destructive and highly reproducible but has limited sensitivity, which could be supplemented by joining GC-MS analysis. Extracting metabolites from macromolecules requires optimization for trustworthy results. Different extraction methods yield distinct profiles, emphasizing the need for optimization. The results indicated that the optimized extraction procedure successfully identified NMR and GC-MS-based metabolites in MeOH, CHCl 3 , and H 2 O extraction solvents. The findings represented the spectral information related to carbohydrates, organic molecules, and amino acids from the water-soluble metabolites fraction and a series of fatty acid chains, lipids, and sterols from the lipid fraction. Our study underscores the benefit of combining NMR and GC-MS techniques to comprehensively understand microalgae metabolomes, including high and low metabolite concentrations and abundances.•In this study, we focused on optimizing the extraction procedure and combining NMR and GC-MS techniques to overcome the low NMR sensitivity and the different detected range limits of NMR and GC-MS.•We explored metabolome diversity in a tropical strain of the small cells' diatom Cheatoceros tenuissimus., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier B.V.)

Aims: The development of nanocomposites (NCs) of antitumor activity provides a new paradigm for fighting cancer. Here, a novel NC of green synthetic silver nanoparticles (AgNPs), graphene oxide (GO) and chitosan (Cs) NPs was developed. Materials & methods: The prepared GO/Cs/Ag NCs were analyzed using various techniques. Cytotoxicity of the NCs was evaluated against different cancer cell lines by Sulforhodamine B (SRB) assay. Results: GO/Cs/Ag NCs are novel and highly stable. UV-Vis showed two peaks at 227 and 469 nm, indicating the decoration of AgNPs on the surface of GO/Cs NPs. All tested cell lines were affected by GO/Cs NPs and GO/Cs/Ag NCs. Conclusion: The results indicate that GO/Cs/Ag NCs were present on tested cell lines and are a promising candidate for cancer therapy.

Efficiently capturing radioactive methyl iodide (CH 3 I), present at low concentrations in the high-temperature off-gas of nuclear facilities, poses a significant challenge. Here we present two strategies for CH 3 I adsorption at elevated temperatures using a unified azolate-based metal-organic framework, MFU-4l. The primary strategy leverages counter anions in MFU-4l as nucleophiles, engaging in metathesis reactions with CH 3 I. The results uncover a direct positive correlation between CH 3 I breakthrough uptakes and the nucleophilicity of the counter anions. Notably, the optimal variant featuring SCN - as the counter anion achieves a CH 3 I capacity of 0.41 g g -1 at 150 °C under 0.01 bar, surpassing all previously reported adsorbents evaluated under identical conditions. Moreover, this capacity can be easily restored through ion exchange. The secondary strategy incorporates coordinatively unsaturated Cu(I) sites into MFU-4l, enabling non-dissociative chemisorption for CH 3 I at 150 °C. This modified adsorbent outperforms traditional materials and can be regenerated with polar organic solvents. Beyond achieving a high CH 3 I adsorption capacity, our study offers profound insights into CH 3 I capture strategies viable for practically relevant high-temperature scenarios., (© 2024. The Author(s).)

Mitochondria are vital organelles found within living cells and have signalling, biosynthetic, and bioenergetic functions. Mitochondria play a crucial role in metabolic reprogramming, which is a characteristic of cancer cells and allows them to ensure a steady supply of proteins, nucleotides, and lipids to enable rapid proliferation and development. Their dysregulated activities have been associated with the growth and metastasis of different kinds of human cancer, particularly ovarian carcinoma. In this review, we briefly demonstrated the modified mitochondrial function in cancer, including mutations in mitochondrial DNA (mtDNA), reactive oxygen species (ROS) production, dynamics, apoptosis of cells, autophagy, and calcium excess to maintain cancer genesis, progression, and metastasis. Furthermore, the mitochondrial dysfunction pathway for some genomic, proteomic, and metabolomics modifications in ovarian cancer has been studied. Additionally, ovarian cancer has been linked to targeted therapies and biomarkers found through various alteration processes underlying mitochondrial dysfunction, notably targeting (ROS), metabolites, rewind metabolic pathways, and chemo-resistant ovarian carcinoma cells., (© 2024 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Lung cancer has the lowest survival rate due to its late-stage diagnosis, poor prognosis, and intra-tumoral heterogeneity. These factors decrease the effectiveness of treatment. They release chemokines and cytokines from the tumor microenvironment (TME). To improve the effectiveness of treatment, researchers emphasize personalized adjuvant therapies along with conventional ones. Targeted chemotherapeutic drug delivery systems and specific pathway-blocking agents using nanocarriers are a few of them. This study explored the nanocarrier roles and strategies to improve the treatment profile's effectiveness by striving for TME. A biofunctionalized nanocarrier stimulates biosystem interaction, cellular uptake, immune system escape, and vascular changes for penetration into the TME. Inorganic metal compounds scavenge reactive oxygen species (ROS) through their photothermal effect. Stroma, hypoxia, pH, and immunity-modulating agents conjugated or modified nanocarriers co-administered with pathway-blocking or condition-modulating agents can regulate extracellular matrix (ECM), Cancer-associated fibroblasts (CAF),Tyro3, Axl, and Mertk receptors (TAM) regulation, regulatory T-cell (Treg) inhibition, and myeloid-derived suppressor cells (MDSC) inhibition. Again, biomimetic conjugation or the surface modification of nanocarriers using ligands can enhance active targeting efficacy by bypassing the TME. A carrier system with biofunctionalized inorganic metal compounds and organic compound complex-loaded drugs is convenient for NSCLC-targeted therapy.

Diabetes is an emerging disorder in the world and is caused due to the imbalance of insulin production as well as serious effects on the body. In search of a better treatment for diabetes, we designed a novel class of 1,3,4-thiadiazole-bearing Schiff base analogues and assessed them for the α-glucosidase enzyme. In the series ( 1 - 12 ), compounds are synthesized and 3 analogues showed excellent inhibitory activity against α-glucosidase enzymes in the range of IC 50 values of 18.10 ± 0.20 to 1.10 ± 0.10 μM. In this series, analogues 4 , 8 , and 9 show remarkable inhibition profile IC 50 2.20 ± 0.10, 1.10 ± 0.10, and 1.30 ± 0.10 μM by using acarbose as a standard, whose IC 50 is 11.50 ± 0.30 μM. The structure of the synthesized compounds was confirmed through various spectroscopic techniques, such as NMR and HREI-MS. Additionally, molecular docking, pharmacokinetics, cytotoxic evaluation, and density functional theory study were performed to investigate their behavior., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Microtubule dynamics are critical for spindle assembly and chromosome segregation during cell division. Pharmacological inhibition of microtubule dynamics in cells causes prolonged mitotic arrest, resulting in apoptosis, an approach extensively employed in treating different types of cancers. The present study reports the synthesis of thirty-two novel bis-amides (SSE1901-SSE1932) and the evaluation of their antiproliferative activities. N-(1-oxo-3-phenyl-1-(phenylamino)propan-2-yl)benzamide (SSE1917) exhibited the most potent activity with GI 50 values of 0.331 ± 0.01 µM in HCT116 colorectal and 0.48 ± 0.27 µM in BT-549 breast cancer cells. SSE1917 stabilized microtubules in biochemical and cellular assays, bound to taxol site in docking studies, and caused aberrant mitosis and G 2 /M arrest in cells. Prolonged treatment of cells with the compound increased p53 expression and triggered apoptotic cell death. Furthermore, SSE1917 suppressed the growth of both mouse and patient-derived human colon cancer organoids, highlighting its potential therapeutic value as an anticancer agent., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rahman Shah Zaib Saleem reports financial support was provided by Higher Education Commission, Pakistan., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The steady increase in the use of electronic cigarettes (ECs) has reached an epidemic level, increasing mortality and morbidity, mainly due to pulmonary toxicity. Several mechanisms are involved in EC-induced toxicity, including oxidative stress and increased inflammation. Concurrently, the integrity of cellular metabolism is essential for cellular homeostasis and mitigation of toxic insults. However, the effects of EC on cellular metabolism remain largely unknown. In this study, we investigated the metabolic changes induced by EC in human lung epithelial cells (A549) using an untargeted metabolomics approach. A549 cells were exposed to increasing EC vapor extract concentrations, and cell viability, oxidative stress, and metabolomic changes were assessed. Our findings show that ECs induce cell death and increase oxidative stress in a concentration-dependent manner. Metabolomic studies demonstrated that ECs induce unique metabolic changes in key cellular metabolic pathways. Our results revealed that exposure to ECs induced clear segregation in metabolic responses which is driven significantly by number of essential metabolites such as aminoacids, fatty acids, glutathione, and pyruvate. Interstingly, our metabolomics results showed that each concentration of ECs induced unqiues pattern of metabolic changes, suggesting the complexity of ECs induced cytotoxcity. Disrupted metabolites were linked to essential cellular pathways, such as fatty acid biosynthesis, as well as glutathione, pyruvate, nicotinate and nicotinamide, and amino acid metabolisms. These results highlight the potential adverse effects of ECs on cellular metabolism and emphasize the need for further research to fully understand the long-term consequences of EC use. Overall, this study demonstrates that ECs not only induce cell death and oxidative stress but also disrupt cellular metabolism in A549 lung epithelial cells., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Aim: The indandione nucleus, is one of the most amazing nuclei in medicinal chemistry, is used to design new derivatives. Methods & materials: Novel indandione derivatives are prepared with different electrophilic and nucleophilic reagents to yield 3 , 4 , 8 , 11 , 14 , 16, 19, 20, 21, 22 and 23 . Compounds 8, 11, 16, 20 and 23 are investigated against OVCAR-3 and HeLa, using LLC-MK2 and cis -Pt as references. in silico and spectral studies were analyzed for the selected compounds. Results: Compounds 20 and 23 at 100 ns were the most potent compounds, so molecular dynamics studies were performed. Conclusion: Compound 23 was the most active toward the HeLa cervical cell line, and compound 20 was the most active toward the Ovcar-3 cell line.

Human immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS), a lethal disease that is prevalent worldwide. According to the Joint United Nations Programme on HIV/AIDS (UNAIDS) data, 38.4 million people worldwide were living with HIV in 2021. Viral reverse transcriptase (RT) is an excellent target for drug intervention. Nucleoside reverse transcriptase inhibitors (NRTIs) were the first class of approved antiretroviral drugs. Later, a new type of non-nucleoside reverse transcriptase inhibitors (NNRTIs) were approved as anti-HIV drugs. Zidovudine, didanosine, and stavudine are FDA-approved NRTIs, while nevirapine, efavirenz, and delavirdine are FDA-approved NNRTIs. Several agents are in clinical trials, including apricitabine, racivir, elvucitabine, doravirine, dapivirine, and elsulfavirine. This review addresses HIV-1 structure, replication cycle, reverse transcription, and HIV drug targets. This study focuses on NRTIs and NNRTIs, their binding sites, mechanisms of action, FDA-approved drugs and drugs in clinical trials, their resistance and adverse effects, their molecular docking studies, and highly active antiretroviral therapy (HAART)., (© 2023 John Wiley & Sons Ltd.)

Berberine-encapsulated polyelectrolyte nanocomposite (BR-PolyET-NC) gel was developed as a long-acting improved wound healing therapy. BR-PolyET-NC was developed using an ionic gelation/complexation method and thereafter loaded into Carbopol gel. Formulation was optimized using Design-Expert® software implementing a three-level, three-factor Box Behnken design (BBD). The concentrations of polymers, namely, chitosan and alginate, and calcium chloride were investigated based on particle size and %EE. Moreover, formulation characterized in vitro for biopharmaceutical performances and their wound healing potency was evaluated in vivo in adult BALB/c mice. The particle distribution analysis showed a nanocomposite size of 71 ± 3.5 nm, polydispersity index (PDI) of 0.45, ζ-potential of +22 mV, BR entrapment of 91 ± 1.6%, and loading efficiency of 12.5 ± 0.91%. Percentage drug release was recorded as 89.50 ± 6.9% with pH 6.8, thereby simulating the wound microenvironment. The in vitro investigation of the nanocomposite gel revealed uniform consistency, well spreadability, and extrudability, which are ideal for topical wound use. The analytical estimation executed using FT-IR, DSC, and X-ray diffraction (XRD) indicated successful formulation with no drug excipients and without the amorphous state. The colony count of microbes was greatly reduced in the BR-PolyET-NC treated group on the 15th day from up to 6 CFU compared to 20 CFU observed in the BR gel treated group. The numbers of monocytes and lymphocytes counts were significantly reduced following healing progression, which reached to a peak level and vanished on the 15th day. The observed experimental characterization and in vivo study indicated the effectiveness of the developed BR-PolyET-NC gel toward wound closure and healing process, and it was found that >99% of the wound closed by 15th day, stimulated via various anti-inflammatory and angiogenic factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Akhter, Al-Keridis, Saeed, Khalilullah, Rab, Aljadaan, Rahman, Jaremko, Emwas, Ahmad, Alam, Ali, Khan and Afzal.)

Introduction: Nuclear Magnetic Resonance (NMR) spectroscopy stands as a preeminent analytical tool in the field of metabolomics. Nevertheless, when it comes to identifying metabolites present in scant amounts within various types of complex mixtures such as plants, honey, milk, and biological fluids and tissues, NMR-based metabolomics presents a formidable challenge. This predicament arises primarily from the fact that the signals emanating from metabolites existing in low concentrations tend to be overshadowed by the signals of highly concentrated metabolites within NMR spectra., Objectives: The aim of this study is to tackle the issue of intense sugar signals overshadowing the desired metabolite signals, an optimal pulse sequence with band-selective excitation has been proposed for the suppression of sugar's moiety signals (SSMS). This sequence serves the crucial purpose of suppressing unwanted signals, with a particular emphasis on mitigating the interference caused by sugar moieties' signals., Methods: We have implemented this comprehensive approach to various NMR techniques, including 1D 1 H presaturation (presat), 2D J-resolved (RES), 2D 1 H- 1 H Total Correlation Spectroscopy (TOCSY), and 2D 1 H- 13 C Heteronuclear Single Quantum Coherence (HSQC) for the samples of dates-flesh, honey, a standard stock solution of glucose, and nine amino acids, and commercial fetal bovine serum (FBS)., Results: The outcomes of this approach were significant. The suppression of the high-intensity sugar signals has considerably enhanced the visibility and sensitivity of the signals emanating from the desired metabolites., Conclusion: This, in turn, enables the identification of a greater number of metabolites. Additionally, it streamlines the experimental process, reducing the time required for the comparative quantification of metabolites in statistical studies in the field of metabolomics., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Coral reef survival is threatened globally. One way to restore this delicate ecosystem is to enhance coral growth by the controlled propagation of coral fragments. To be sustainable, this technique requires the use of biocompatible underwater adhesives. Hydrogels based on rationally designed ultrashort self-assembling peptides (USP) are of great interest for various biological and environmental applications, due to their biocompatibility and tunable mechanical properties. Implementing superior adhesion properties to the USP hydrogel compounds is crucial in both water and high ionic strength solutions and is relevant in medical and marine environmental applications such as coral regeneration. Some marine animals secrete large quantities of the aminoacids dopa and lysine to enhance their adhesion to wet surfaces. Therefore, the addition of catechol moieties to the USP sequence containing lysine (IIZK) should improve the adhesive properties of USP hydrogels. However, it is challenging to place the catechol moiety (Do) within the USP sequence at an optimal position without compromising the hydrogel self-assembly process and mechanical properties. Here, we demonstrate that, among three USP hydrogels, DoIIZK is the least adhesive and that the adhesiveness of the IIZDoK hydrogel is compromised by its poor mechanical properties. The best adhesion outcome was achieved using the IIZKDo hydrogel, the only one to show equally sound adhesive and mechanical properties. A mechanistic understanding of this outcome is presented here. This property was confirmed by the successful gluing of coral fragments by means of IIZKDo hydrogel that are still thriving after more than three years since the deployment. The validated biocompatibility of this underwater hydrogel glue suggests that it could be advantageously implemented for other applications, such as surgical interventions.

InAs colloidal quantum dots (CQDs) have emerged as candidate lead- and mercury-free solution-processed semiconductors for infrared technology due to their appropriate bulk bandgap, which can be tuned by quantum confinement, and promising charge-carrier transport properties. However, the lack of suitable arsenic precursors and readily accessible synthesis conditions have limited InAs CQDs to smaller sizes (<7 nm), with bandgaps largely restricted to <1400 nm in the near-infrared spectral window. Conventional InAs CQD synthesis requires highly reactive, hazardous arsenic precursors, which are commercially scarce, making the synthesis hard to control and study. Here, we present a controlled synthesis strategy (using only readily available and less reactive precursors) to overcome the practical wavelength limitation of InAs CQDs, achieving monodisperse InAs nanorod CQDs with bandgaps tunable from ∼1200 to ∼1800 nm, thus crossing deep into the short-wave infrared (SWIR) region. By controlling the reactivity through in situ precursor complexation, we isolate the reaction mechanism, producing InAs nanorod CQDs that display narrow excitonic features and efficient carrier multiplication. Our work enables InAs CQDs for a wider range of SWIR applications.

Pyranopyrazole derivatives have a vital role in the class of organic compounds because of their broad spectrum of biological and pharmacological importance. Our current goal is the [3 + 3] cycloaddition of benzoyl isothiocyanate and pyrazolone 1 to undergo oxidation cyclization, producing pyrazoloxadiazine 3. The diol 5 was obtained as a condensation of two equivalents of 1 with thiophene-2-carboxaldehyde in acetic acid above the sodium acetate mixture. When the condensation was carried out in piperidine under fusion, unsaturated ketone 4 was obtained. The pyrazolo pyran derivative 11 resulted from the [3 + 3] cycloaddition of 1 and cinnamic acid, while the Pyrone derivative was prepared by acylation of 12 with two equivalents of acetic anhydride. Phthalic anhydride undergoes arylation using zinc chloride as a catalyst. The cyclic keto acid 23 was synthesized by the action of succinic anhydride on 12 in the acetic medium, while the latter reacted with cinnamic acid, leading to pyrazole derivative 24. All of these reactions were through the Michael reaction mechanism. All the tested compounds showed good antimicrobial activity against pathogenic microorganisms; newly synthesized compounds were also screened for their antioxidant activity. Rational studies were carried out by the ABTs method to allow a broader choice of activities. In addition, similar off-compounds were conducted. Molecular docking studies with the CB-Dock server and MD simulations were created with the default settings of the Solution Builder on the CHARMM-GUI server at 150 nm. A good correlation was obtained between the experimental results and the theoretical bioavailability predictions using POM theory., (© 2023. The Author(s).)

Autism spectrum disorders (ASD) represent a diverse group of neuropsychiatric conditions, and recent evidence has suggested a connection between ASD and microbial dysbiosis. Immune and gastrointestinal dysfunction are associated with dysbiosis, and there are indications that modulating the microbiota could improve ASD-related behaviors. Additionally, recent findings highlighted the significant impact of microbiota on the development of autoimmune liver diseases, and the occurrence of autoimmune liver disease in children with ASD is noteworthy. In the present study, we conducted both an in vivo study and a clinical study to explore the relationship between indomethacin-induced dysbiosis, autoimmune hepatitis (AIH), and the development of ASD. Our results revealed that indomethacin administration induced intestinal dysbiosis and bacterial translocation, confirmed by microbiological analysis showing positive bacterial translocation in blood cultures. Furthermore, indomethacin administration led to disturbed intestinal permeability, evidenced by the activation of the NLRP3 inflammasomes pathway and elevation of downstream biomarkers (TLR4, IL18, caspase 1). The histological analysis supported these findings, showing widened intestinal tight junctions, decreased mucosal thickness, inflammatory cell infiltrates, and collagen deposition. Additionally, the disturbance of intestinal permeability was associated with immune activation in liver tissue and the development of AIH, as indicated by altered liver function, elevated ASMA and ANA in serum, and histological markers of autoimmune hepatitis. These results indicate that NSAID-induced intestinal dysbiosis and AIH are robust triggers for ASD existence. These findings were further confirmed by conducting a clinical study that involved children with ASD, autoimmune hepatitis (AIH), and a history of NSAID intake. Children exposed to NSAIDs in early life and complicated by dysbiosis and AIH exhibited elevated serum levels of NLRP3, IL18, liver enzymes, ASMA, ANA, JAK1, and IL6. Further, the correlation analysis demonstrated a positive relationship between the measured parameters and the severity of ASD. Our findings suggest a potential link between NSAIDs, dysbiosis-induced AIH, and the development of ASD. The identified markers hold promise as indicators for early diagnosis and prognosis of ASD. This research highlights the importance of maintaining healthy gut microbiota and supports the necessity for further investigation into the role of dysbiosis and AIH in the etiology of ASD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mohamed, Abo Nahas, Elshaer, El-Waseef, El-Kharashi, Mohamed, Sabry, Almaimani, Almasmoum, Altamimi, Ibrahim, Alshawwa, Jaremko, Emwas and M. Saied.)

Since ancient times, the inhabitants of dry areas have depended on the date palm (Phoenix dactylifera L.) as a staple food and means of economic security. For example, dates have been a staple diet for the inhabitants of the Arabian Peninsula and Sahara Desert in North Africa for millennia and the local culture is rich in knowledge and experience with the benefits of dates, suggesting that dates contain many substances essential for the human body. Madinah dates are considered one of the most important types of dates in the Arabian Peninsula, with Ajwa being one of the most famous types and grown only in Madinah, Saudi Arabia. Date seeds are traditionally used for animal feed, seed oil production, cosmetics, and as a coffee substitute. Phytochemical compounds that have been detected in date fruits and date seeds include phenolic acids, carotenoids, and flavonoids. Phenolic acids are the most prevalent bioactive constituents that contribute to the antioxidant activity of date fruits. The bioactive properties of these phytochemicals are believed to promote human health by reducing the risk of diseases such as chronic inflammation. Ajwa dates especially are thought to have superior bioactivity properties. To investigate these claims, in this study, we compare the metabolic profiles of Ajwa with different types of dates collected from Saudi Arabia and Tunisia. We show by UHPLC-MS that date seeds contain several classes of flavonoids, phenolic acids, and amino acid derivatives, including citric acid, malic acid, lactic acid, and hydroxyadipic acid. Additionally, GC-MS profiling showed that date seeds are richer in metabolite classes, such as hydrocinnamic acids (caffeic, ferulic and sinapic acids), than flesh samples. Deglet N fruit extract (minimum inhibitory concentration: 27 MIC/μM) and Sukkari fruit extract (IC 50 : 479 ± 0.58μg /mL) have higher levels of antibacterial and antioxidative activity than Ajwa fruits. However, the seed analysis showed that seed extracts have better bioactivity effects than fruit extracts. Specifically, Ajwa extract showed the best MIC and strongest ABTS radical-scavenging activity among examined seed extracts (minimum inhibitory concentration: 20 μM; IC 50 : 54 ± 3.61μg /mL). Our assays are a starting point for more advanced in vitro antibacterial models and investigation into the specific molecules that are responsible for the antioxidative and anti-bacterial activities of dates., (© 2023. Kunming Institute of Botany, CAS.)

Berberine (BER) is an alkaloid obtained from berberis plant having broad biological activities including anticancer. BER-encapsulated alginate (ALG)/chitosan (CHS) nanoparticles (BER-ALG/CHS-NPs) were developed for long-acting improved treatment in breast cancer. The surface of the NPs was activated by a conjugation reaction, and thereafter, the BER-ALG/CHS-NP surface was grafted with folic acid (BER-ALG/CHS-NPs-F) for specific targeting in breast cancer. BER-ALG/CHS-NPs-F was optimized by applying the Box-Behnken design using Expert design software. Moreover, formulations are extensively evaluated in vitro for biopharmaceutical performances and tested for cell viability, cellular uptake, and antioxidant activity. The comparative pharmacokinetic study of formulation and free BER was carried out in animals for estimation of bioavailability. The particle size recorded for the diluted sample using a Malvern Zetasizer was 240 ± 5.6 nm. The ζ-potential and the predicted % entrapment efficiency versus (vs) observed were +18 mV and 83.25 ± 2.3% vs 85 ± 3.5%. The high % drug release from the NPs was recorded. The analytical studies executed using infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction expressed safe combinations of the components in the formulation and physical state of the drug revealed to be amorphous in the formulation. Cytotoxicity testing demonstrated that the formulation effectively lowered the cell viability and IC 50 of the tested cell line in comparison to a raw drug. The cellular uptake of BER-ALG/CHS-NPs-F was 5.5-fold higher than that of BER-suspension. The antioxidant capacities of BER-ALG/CHS-NPs-F vs BER-suspension by the DPPH assay were measured to be 62.3 ± 2.5% vs 30 ± 6%, indicating good radical scavenging power of folate-conjugated NPs. The developed formulation showed a 4.4-fold improved oral bioavailability compared to BER-suspension. The hemolytic assay intimated <2% destruction of erythrocytes by the developed formulation. The observed experimental characterization results such as cytotoxicity, cellular uptake, antioxidant activity, and improved absorption suggested the effectiveness of BER-ALG/CHS-NPs-F toward breast cancer., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Since its emergence in 2019, coronavirus infection (COVID-19) has become a global pandemic and killed several million people worldwide. Even though several types of vaccines are available against the COVID-19 virus, SARS-CoV-2, new strains are emerging that pose a constant danger to vaccine effectiveness. In this computational study, we identified and predicted potent allosteric inhibitors of the SARS-CoV-2 main protease (Mpro). Via molecular docking and simulations, more than 100 distinct flavonoids were docked with the allosteric site of Mpro. Docking experiments revealed four top hit compounds (Hesperidin, Schaftoside, Brickellin, and Marein) that bound strongly to the Mpro predicted allosteric site. Simulation analyses further revealed that these continually interacted with the enzyme's allosteric region throughout the simulation time. ADMET and Lipinski drug likenesses were calculated to indicate the therapeutic value of the top four hits: They were non-toxic and exhibited high human intestinal absorption concentrations. These novel allosteric site inhibitors provide a higher chance of drugging SARS-CoV2 Mpro due to the rapid mutation rate of the viral enzyme's active sites. Our findings provide a new avenue for developing novel allosteric inhibitors of SARS-CoV-2 Mpro.Communicated by Ramaswamy H. Sarma.

Microtubules are dynamic structures that form spindle fibers during cell division; pharmacological inhibition of microtubule dynamics arrests cells in mitosis, leading to apoptosis, and they have been extensively used to treat various cancers. However, the efficacy of such drugs is often limited by multidrug resistance. This study synthesized and evaluated 30 novel derivatives of podophyllotoxin, a natural antimitotic compound, for their antiproliferative activities. Compound SSE1806 exhibited the most potent antiproliferative activity with GI 50 values ranging from 1.29 ± 0.01 to 21.15 ± 2.1 μM in cancer cell lines of different origins; it directly inhibited microtubule polymerization, causing aberrant mitosis and G2/M arrest. Prolonged treatment with SSE1806 increased p53 expression, induced cell death in monolayer cultures, and reduced the growth of mouse- and patient-derived human colon cancer organoids. Importantly, SSE1806 overcame multidrug resistance in a cell line overexpressing MDR-1. Thus, SSE1806 represents a potential anticancer agent that can overcome multidrug resistance., Competing Interests: The authors declare no competing financial interest., (© 2023 American Chemical Society.)

New liquid crystalline hydrogen bonded 3- (or 4)- n -alkanoyloxy benzoic acids were synthesized and probed theoretically and experimentally. The molecular structures of these compounds were elucidated by proton NMR, carbon-13 NMR and elemental analyses. Differential scanning calorimetry (DSC) was used to investigate the thermal and mesomorphic properties of all the symmetrical dimers that bearing identical alkanoyloxy chains. Moreover, polarized optical microscopy (POM) was used to determine their mesophases. The findings show that all the designed symmetrical dimers exhibit the smectic mesophase with relative thermal stability that depends on the length of their terminal side chain. Additionally, the experimental findings of the mesomorphic behavior are further supported by DFT calculations. The alkanoyloxy benzoic acid para-derivatives ( I n) were shown to be more stable than their meta-substituted ( II n) analogues due to stronger hydrogen bonding interactions. The computed reactivity parameters showed that the position of ester moiety has a significant impact on the acids reactivity. The absorbance spectra of both the 3- (or 4)- n -alkanoyloxy benzoic acids revealed a blue shift with the increment of the of alkyl chain size; however, the energy band gaps of 3- n -alkanoyloxy benzoic derivatives were found to be slightly higher than those of the 4- n -alkanoyloxy benzoic acids. Moreover, the photoluminescence spectrum of the prepared materials is rather broad, and exhibited a red shift as the alkyl chain length increases. The fluorescence lifetime shown to rise as alkyl chain length grows longer, and 3- n -alkanoyloxy benzoic acids have slightly longer lifetime compared to their 4- n -alkanoyloxy benzoic analogues., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

In this work, the biological potency of nitazoxanide (NTZ) was enhanced through coordination with transition metal ions Cu(II), Ni(II), and Zn(II). Initially, complexes with a ligand-metal stoichiometry of 2:1 were successfully synthesized and characterized by spectroscopic techniques and thermogravimetric methods. Measurement of the infrared spectrum revealed the bidentate nature of the ligand and excluded the possibility of the metal ion-amide group interaction. Nuclear magnetic resonance spectra showed a reduction in the NH- intensity signal and integration, indicating the possibility of enolization and the formation of keto-enol tautomers. To interpret these results, density functional theory was utilized under B3LYP/6-311G** for the free ligand and B3LYP/LANL2DZ for the metal complexes. We used UV-Vis and fluorescence spectroscopy to understand the biological properties of the complexes. This showed stronger interactions of NTZ-Cu(II) and NTZ-Ni(II) with DNA molecules than the NTZ-Zn(II) compound, with a binding constant (K b ) for the copper complex of 7.00 × 10 5 M -1 . Both Cu(II)- and Ni(II)-NTZ had functional binding to the SARS-CoV-2 (6LU7) protease. Moreover, all metal complexes showed better antioxidation properties than the free ligand, with NTZ-Ni(II) having the best IC 50 value of 53.45 μg/mL. NTZ-Ni(II) was an effective antibacterial, with a mean inhibitory concentration of 6 μM, which is close to that of ampicillin (a reference drug). The metal complexes had moderated anticancer potencies, with NTZ-Cu(II) having IC 50 values of 24.5 and 21.5 against human breast cancer cells (MCF-7) and cancerous cervical tumor cells (HeLa), respectively. All obtained complexes exhibited high selectivity. Finally, the metal ions showed a practical role in improving the biological effectiveness of NTZ molecules.

MEK1/2 are critical components of the RAS-RAF-MEK-ERK or MAPK signalling pathway that regulates a variety of cellular functions including proliferation, survival, and differentiation. In 1997, a lung cancer cell line was first found to have a MEK mutation (encoding MEK2P298L). MEK is involved in various human cancers such as non-small cell lung cancer (NSCLC), spurious melanoma, and pancreatic, colorectal, basal, breast, and liver cancer. To date, 4 MEK inhibitors i.e. , trametinib, cobimetinib, selumetinib, and binimetinib have been approved by the FDA and several are under clinical trials. In this review, we have highlighted structural insights into the MEK1/2 proteins, such as the αC-helix, catalytic loop, P-loop, F-helix, hydrophobic pocket, and DFG motif. We have also discussed current issues with all FDA-approved MEK inhibitors or drugs under clinical trials and combination therapies to improve the efficacy of clinical drugs. Finally, this study addressed recent developments on synthetic MEK inhibitors (from their discovery in 1997 to 2022), their unique properties, and their relevance to MEK mutant inhibition., Competing Interests: The authors declare no competing interest., (This journal is © The Royal Society of Chemistry.)

Cells' interactions with their microenvironment influence their morphological features and regulate crucial cellular functions including proliferation, differentiation, metabolism, and gene expression. Most biological data available are based on in vitro two-dimensional (2D) cellular models, which fail to recapitulate the three-dimensional (3D) in vivo systems. This can be attributed to the lack of cell-matrix interaction and the limitless access to nutrients and oxygen, in contrast to in vivo systems. Despite the emergence of a plethora of 3D matrices to address this challenge, there are few reports offering a proper characterization of these matrices or studying how the cell-matrix interaction influences cellular metabolism in correlation with gene expression. In this study, two tetrameric ultrashort self-assembling peptide sequences, FFIK and FIIK, were used to create in vitro 3D models using well-described human dermal fibroblast cells. The peptide sequences are derived from naturally occurring amino acids that are capable of self-assembling into stable hydrogels without UV or chemical cross-linking. Our results showed that 2D cultured fibroblasts exhibited distinct metabolic and transcriptomic profiles compared to 3D cultured cells. The observed changes in the metabolomic and transcriptomic profiles were closely interconnected and influenced several important metabolic pathways including the TCA cycle, glycolysis, MAPK signaling cascades, and hemostasis. Data provided here may lead to clearer insights into the influence of the surrounding microenvironment on human dermal fibroblast metabolic patterns and molecular mechanisms, underscoring the importance of utilizing efficient 3D in vitro models to study such complex mechanisms.

Cancer is a progressive disease of multi-factorial origin that has risen worldwide, probably due to changes in lifestyle, food intake, and environmental changes as some of the reasons. Skin cancer can be classified into melanomas from melanocytes and nonmelanoma skin cancer (NMSC) from the epidermally-derived cell. Together it constitutes about 95% of skin cancer. Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (CSCC) are creditworthy of 99% of NMSC due to the limited accessibility of conventional formulations in skin cancer cells of having multiple obstacles in treatment reply to this therapeutic regime. Despite this, it often encounters erratic bioavailability and absorption to the target. Nanoparticles developed through nanotechnology platforms could be the better topical skin cancer therapy option. To improve the topical delivery, the nano-sized delivery system is appropriate as it fuses with the cutaneous layer and fluidized membrane; thus, the deeper penetration of therapeutics could be possible to reach the target spot. This review briefly outlooks the various nanoparticle preparations, i.e., liposomes, niosomes, ethosomes, transferosomes, transethosomes, nanoemulsions, and nanoparticles technologies tested into skin cancer and impede their progress tend to concentrate in the skin layers. Nanocarriers have proved that they can considerably boost medication bioavailability, lowering the frequency of dosage and reducing the toxicity associated with high doses of the medication.

The purpose of this study was to enhance the antimicrobial activity of bagasse paper by coating the paper with bismuth oxide (Bi 2 O 3 ) and using it to accelerate the process of wound healing. Paper sheets were prepared from sugarcane waste (bagasse). First, the paper sheets were coated with different Bi 2 O 3 concentrations to improve the antimicrobial activity of the paper. After that, the paper sheets were allowed to dry in an oven at 50 °C for 3 h. Then, in vitro antimicrobial activity was evaluated against different microbial species, including Gram-negative bacteria (i.e., Klebsiella pneumonia, Escherichia coli) and Gram-positive bacteria (i.e., Staphylococcus aureus, Streptococcus pyogenes). The obtained results showed that the paper coated with 25% and 100% Bi 2 O 3 had activity against all models of bacteria; however, the paper coated with 100% Bi 2 O 3 composite had the strongest inhibitory effect. Then, bagasse paper was coated with 100% Bi 2 O 3 and different antibiotics, to investigate their wound-healing potency in a wounded rat model for 14 days. Moreover, the paper coated with 100% Bi 2 O 3 inhibited the cellular migration in vitro. Conclusively, coating paper with Bi 2 O 3 enhances the wound-healing potential when applied to wounds. This impact could be ascribed to Bi 2 O 3 's broad antibacterial activity, which reduced infection and accelerated the healing process.

Serine/threonine-protein kinase B-Raf (BRAF; RAF = rapidly accelerated fibrosarcoma) plays an important role in the mitogen-activated protein kinase (MAPK) signaling cascade. Somatic mutations in the BRAF gene were first discovered in 2002 by Davies et al., which was a major breakthrough in cancer research. Subsequently, three different classes of BRAF mutants have been discovered. This class includes class I monomeric mutants (BRAF V600 ), class II BRAF homodimer mutants (non-V600), and class III BRAF heterodimers (non-V600). Cancers caused by these include melanoma, thyroid cancer, ovarian cancer, colorectal cancer, nonsmall cell lung cancer, and others. In this study, we have highlighted the major binding pockets in BRAF protein, their active and inactive conformations with inhibitors, and BRAF dimerization and its importance in paradoxical activation and BRAF mutation. We have discussed the first-, second-, and third-generation drugs approved by the Food and Drug Administration and drugs under clinical trials with all four different binding approaches with DFG-IN/OUT and αC-IN/OUT for BRAF protein. We have investigated particular aspects and difficulties with all three generations of inhibitors. Finally, this study has also covered recent developments in synthetic BRAF inhibitors (from their discovery in 2002 to 2022), their unique properties, and importance in inhibiting BRAF mutants., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Nanoemulgel (NEG) pharmaceutical formulations are gaining popularity because of their ability to serve both as a nanoemulsion and as a gel. These products are well-known for their ease of use, spreadability, controlled release, and ability to hydrate dry skin. Natural essential oils have been shown to promote the cutaneous permeability of topical formulations, enhancing medication safety and efficacy. Herein, we developed NEG for the enhanced permeation of ketoconazole against candidiasis using clove oil (clove-oil-NEG) or eucalyptus oil (eucalyptus-oil-NEG), using the gelling agents carbopol 943 and hydroxypropyl methylcellulose (HPMC). We tested various excipients to increase the solubility of ketoconazole and formulate a nanoemulsion (NE). We measured the NE droplet particle size, shape, entrapment efficiency, and drug release. Furthermore, the physicochemical properties of the optimized nanoemulsion formulation were characterized by techniques such as Fourier transform infrared (FT-IR) spectroscopy and X-ray diffraction (XRD) analysis. The NEs were loaded into gels to form NEGs. NEGs were characterized for drug content, homogeneity, rheology, spreadability, and antifungal activity against Candida albicans , both in vitro and in vivo . Optimized ketoconazole NEG preparations consisted of either 15% clove oil or 20% eucalyptus oil. Droplet sizes in the optimized NEs were <100 nm, and the polydispersity indexes were 0.24 and 0.26. The percentages of ketoconazole released after 24 h from the clove-oil-NEG and eucalyptus-oil-NEGs were 91 ± 4.5 and 89 ± 7%, respectively. Scanning electron microscopy (SEM) showed that the NEGs had a smooth, uniform, and consistent shape and internal structural organization. The drug contents in the clove-oil-NEG and eucalyptus-oil-NEG were 98.5 ± 2.2 and 98.8 ± 3.4%, respectively. Permeation values of ketoconazole from clove-oil-NEG and eucalyptus-oil-NEG were 117 ± 7 and 108.34 ± 6 μg cm -2 , respectively. The ketoconazole NEG formulations also had higher levels of fungal growth inhibition than a marketed formulation. Finally, in vivo studies showed that the NEGs do not irritate the skin. Ketoconazole NEG with either 15% clove oil or 20% eucalyptus oil is stable with better efficacy than ketoconazole alone due to excellent dispersion, drug dissolution, and permeability and thus might be recommended for the effective and safe treatment of candidiasis., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Glioma is a malignant form of brain cancer that is challenging to treat due to the progressive growth of glial cells. To target overexpressed folate receptors in glioma brain tumors, we designed and investigated doxorubicin-gefitinib nanoparticles (Dox-Gefit NPs) and folate conjugated Dox-Gefit NPs (Dox-Gefit NPs-F). Dox-Gefit NPs and Dox-Gefit NPs-F were characterized by multiple techniques including Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), proton nuclear magnetic resonance ( 1 H NMR), and transmission electron microscopy (TEM). In vitro release profiles were measured at both physiological and tumor endosomal pH. The cytotoxicity of the Dox-Gefit NP formulations was measured against C6 and U87 glioma cell lines. A hemolysis assay was performed to investigate biocompatibility of the formulations, and distribution of the drugs in different organs was also estimated. The Dox-Gefit NPs and Dox-Gefit NPs-F were 109.45 ± 7.26 and 120.35 ± 3.65 nm in size and had surface charges of -18.0 ± 3.27 and -20.0 ± 8.23 mV, respectively. Dox-Gefit NPs and Dox-Gefit NPs-F significantly reduced the growth of U87 cells, with IC 50 values of 9.9 and 3.2 μM. Similarly, growth of the C6 cell line was significantly reduced, with IC 50 values of 8.43 and 3.31 μM after a 24 h incubation, in Dox-Gefit NPs and Dox-Gefit NPs-F, respectively. The percentage drug releases of Dox and Gefit from Dox-Gefit NPs at pH 7.4 were 60.87 ± 0.59 and 68.23 ± 0.1%, respectively. Similarly, at pH 5.4, Dox and Gefit releases from NPs were 70.87 ± 0.28 and 69.24 ± 0.12%, respectively. Biodistribution analysis revealed that more Dox and Gefit were present in the brain than in the other organs. The functionalized NPs inhibited the growth of glioma cells due to high drug concentrations in the brain. Folate conjugated NPs of Dox-Gefit could be a treatment option in glioma therapy., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Proton activity in electrolytes plays a crucial role in deciding the electrochemical performance of aqueous batteries. On the one hand, it can influence the capacity and rate performance of host materials because of the high redox activity of protons. On the other hand, it can also cause a severe hydrogen evolution reaction (HER) when the protons are aggregated near the electrode/electrolyte interface. The HER dramatically limits the potential window and the cycling stability of the electrodes. Therefore, it is critical to clarify the impact of electrolyte proton activity on the battery macro-electrochemical performance. In this work, using an aza-based covalent organic framework (COF) as a representative host material, we studied the effect of electrolyte proton activity on the potential window, storage capacity, rate performance, and cycle stability in various electrolytes. A tradeoff relationship between proton redox reactions and the HER in the COF host is revealed by utilizing various in situ and ex situ characterizations. Moreover, the origin of proton activity in near-neutral electrolytes is discussed in detail and is confirmed to be related to the hydrated water molecules in the first solvation shell. A detailed analysis of the charge storage process in the COFs is presented. These understandings can be of importance for utilizing the electrolyte proton activity to build high-energy aqueous batteries.