Hasil untuk "Organic chemistry"

Ahmed Yameny

Cytokines are pivotal mediators of intercellular communication in immunity and inflammation, exerting their effects through tightly regulated signaling cascades that shape both innate and adaptive responses. Among them, interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) represent key biomarkers that orchestrate distinct yet interconnected phases of the inflammatory process. This review synthesizes current evidence on the molecular mechanisms, functional roles, and clinical significance of these four cytokines. IL-1β and TNF-α act as early pro-inflammatory mediators, initiating vascular activation, leukocyte recruitment, and febrile responses. IL-6 sustains acute-phase reactions and bridges innate and adaptive immunity, while IFN-γ enhances antimicrobial defenses and antigen presentation, shaping T-cell polarization. Advances in detection methods—including ELISA, multiplex immunoassays, high-sensitivity biosensors, and IFN-γ release assays—have enabled precise quantification, improving diagnostic accuracy, disease monitoring, and therapeutic decision-making across a broad spectrum of autoimmune, infectious, cardiovascular, and neoplastic disorders. Clinically, elevated cytokine levels serve as diagnostic discriminators, prognostic markers, and guides for targeted therapies such as anti-TNF and anti-IL-6 biologics. Conclusion: IL-1β, IL-6, TNF-α, and IFN-γ emerge as indispensable biomarkers whose measurement provides critical insights into disease pathogenesis and underpins the advancement of personalized medicine in inflammatory conditions.

Shuchi Goyal, Divya Thirumal, Jaya Rana et al.

Therapeutic tools in the biomedical field are increasingly utilizing nanoparticles (NPs) with a small size and large surface area. Chitosan (CS), a biotic polymeric carbohydrate found in shellfish, is a promising carrier for these diagnostic systems due to its biocompatibility, low toxic effects, and diverse shapes. CS-NPs are therapeutic transporters with properties such as bionomical, pH, and heat sensitivity, increased homogeneity, and potential to pass through the brain. These nanomaterials can detect and cure pathological conditions using curative instruments. CS-NPs slow down the movement and growth of anti-inflammatory colonies while encouraging the growth of cells causing inflammation. They could provide active substances for treating various medical conditions, such as auto-immune deformities, hyperglycemia, hypersensitivity, and cancer. Scientific resources are dedicated to improving the efficacy of CS-NP active agent compositions. Recent discoveries highlight the medicinal implications of CS-NPs preparations for drug delivery in managing severe inflammatory aberrations.

Wenhui Li, Shangci Yang, Jiulong An et al.

α-Amylase inhibitory peptides are used to treat diabetes, but few studies have statistically characterized their interaction with α-amylase. This study performed the molecular docking of α-amylase with inhibitory peptides from published papers. The key sites, side chain chargeability, and hydrogen bond distribution characteristics were analyzed. Molecular dynamics simulated the role of key sites in complex stability. Moreover, partial least squares regression (PLSR) was used to analyze the contribution of different amino acids in the peptides to inhibition. The results showed that, for the α-amylase molecule, His201 and Gln63, with the highest interaction numbers (INs, 15, 15) and hydrogen bond values (HBVs, 11.50, 10.33), are the key sites on α-amylase, and amino acids with positively charged side chains were important for inhibitory activity. For the inhibitory peptides, Asp and Arg had the highest HBVs, and amino acids with charged side chains were more likely to form hydrogen bonds and exert inhibitory activity. In molecular dynamics simulations, peptides involving key binding sites formed more stable complexes with α-amylase than α-amylase alone, suggesting enhanced inhibitory effects. Further, PLSR results showed that amino acids close to the N-terminus of the inhibitory peptide, located in the third and fifth positions, were significantly correlated with its inhibitory activity. In conclusion, this study provides a new approach to developing and screening α-amylase inhibitors.

Shaoxiong Zhou, Zheng Xiao, Junzheng Sun et al.

<i>Hypsizygus marmoreus</i> has abundant proteins and is a potential source for the development of bioactive peptides. However, currently, the research on the bioactive components of <i>H. marmoreus</i> mainly focuses on polysaccharides, and there is no relevant research on the preparation of bioactive peptides. In this article, an ultrasound-assisted extraction method was used to extract proteins from <i>H. marmoreus</i>, and then, four peptides with different molecular weight ranges were prepared through protease hydrolysis and molecular classification. The antioxidant and antibacterial activities were also studied. Under the optimal conditions, the extraction rate of <i>H. marmoreus</i> proteins was 53.6%. Trypsin exhibited the highest hydrolysis rate of <i>H. marmoreus</i> proteins. The optimal parameters for enzymatic hydrolysis were a substrate concentration of 3.7%, enzyme addition of 5700 U/g, pH value of 7, extraction temperature of 55 °C, and time of 3.3 h. Under these conditions, the peptide yield was 59.7%. The four types of <i>H. marmoreus</i> peptides were prepared by molecular weight grading. Among them, peptides with low molecular weight (<1 kDa) had stronger antioxidant and antibacterial activities. This study provides a theoretical basis for the efficient preparation of <i>H. marmoreus</i> peptides and the development of antioxidant and antibacterial peptide products.

Masashi Mamada, Sawako Yada, Masahiro Hayakawa et al.

Abstract Thermally activated delayed fluorescence (TADF) is a promising mechanism for harvesting triplet excitons in organic light-emitting diodes (OLEDs). The donor–acceptor (D–A) design is the most conventional strategy for developing efficient TADF emitters. A subsequently emerged approach, known as the multiple resonance (MR) effect, also employs electron-donating and electron-withdrawing functional groups. Thus, developing TADF materials has traditionally relied on ingenuity in selecting and combining two functional units. Here, we have realized a TADF molecule by utilizing only a carbazole donor moiety. This molecule is an unusual example in the family of TADF materials and offers better insight into the electronic structures in the excited states for luminescent materials.

Hong Soon Kang, Sara A. Grimm, Raja Jothi et al.

Abstract Background Loss of the transcription factor GLI-Similar 3 (GLIS3) function causes congenital hypothyroidism (CH) in both humans and mice due to decreased expression of several thyroid hormone (TH) biosynthetic genes in thyroid follicular cells. Whether and to what extent, GLIS3 regulates thyroid gene transcription in coordination with other thyroid transcriptional factors (TFs), such as PAX8, NKX2.1 and FOXE1, is poorly understood. Methods PAX8, NKX2.1, and FOXE1 ChIP-Seq analysis with mouse thyroid glands and rat thyrocyte PCCl3 cells was performed and compared to that of GLIS3 to analyze the co-regulation of gene transcription in thyroid follicular cells by these TFs. Results Analysis of the PAX8, NKX2.1, and FOXE1 cistromes identified extensive overlaps between these TF binding loci and those of GLIS3 indicating that GLIS3 shares many of the same regulatory regions with PAX8, NKX2.1, and FOXE1, particularly in genes associated with TH biosynthesis, induced by thyroid stimulating hormone (TSH), and suppressed in Glis3KO thyroid glands, including Slc5a5 (Nis), Slc26a4, Cdh16, and Adm2. ChIP-QPCR analysis showed that loss of GLIS3 did not significantly affect PAX8 or NKX2.1 binding and did not cause major alterations in H3K4me3 and H3K27me3 epigenetic signals. Conclusions Our study indicates that GLIS3 regulates transcription of TH biosynthetic and TSH-inducible genes in thyroid follicular cells in coordination with PAX8, NKX2.1, and FOXE1 by binding within the same regulatory hub. GLIS3 does not cause major changes in chromatin structure at these common regulatory regions. GLIS3 may induce transcriptional activation by enhancing the interaction of these regulatory regions with other enhancers and/or RNA Polymerase II (Pol II) complexes.

Alina Ciach, Andres De Virgiliis, Ariel Meyra et al.

Competing interactions between charged inclusions in membranes of living organisms or charged nanoparticles in near-critical mixtures can lead to self-assembly into various patterns. Motivated by these systems, we developed a simple triangular lattice model for binary mixtures of oppositely charged particles with additional short-range attraction or repulsion between like or different particles, respectively. We determined the ground state for the system in contact with a reservoir of the particles for the whole chemical potentials plane, and the structure of self-assembled conglomerates for fixed numbers of particles. Stability of the low-temperature ordered patterns was verified by Monte Carlo simulations. In addition, we performed molecular dynamics simulations for a continuous model with interactions having similar features, but a larger range and lower strength than in the lattice model. Interactions with and without symmetry between different components were assumed. We investigated both the conglomerate formed in the center of a thin slit with repulsive walls, and the structure of a monolayer adsorbed at an attractive substrate. Both models give the same patterns for large chemical potentials or densities. For low densities, more patterns occur in the lattice model. Different phases coexist with dilute gas on the lattice and in the continuum, leading to different patterns in self-assembled conglomerates (‘rafts’).

Timofei N. Zakharov, Pavel A. Sakharov, Mikhail S. Novikov et al.

An unprecedented oxidative cyclodimerization reaction of 2<i>H</i>-azirine-2-carboxylates to pyrimidine-4,6-dicarboxylates under heating with triethylamine in air is described. In this reaction, one azirine molecule undergoes formal cleavage across the C-C bond and another across the C=N bond. According to the experimental study and DFT calculations, the key steps of the reaction mechanism include nucleophilic addition of <i>N</i>,<i>N</i>-diethylhydroxylamine to an azirine to form an (aminooxy)aziridine, generation of an azomethine ylide, and its 1,3-dipolar cycloaddition to the second azirine molecule. The crucial condition for the synthesis of pyrimidines is generation of <i>N</i>,<i>N</i>-diethylhydroxylamine in the reaction mixture in a very low concentration, which is ensured by the slow oxidation of triethylamine with air oxygen. Addition of a radical initiator accelerated the reaction and resulted in higher yields of the pyrimidines. Under these conditions, the scope of the pyrimidine formation was elucidated, and a series of pyrimidines was synthesized.

Jisun Lee, Matthew C. Woodruff, Eui Ho Kim et al.

Abstract Since the discovery of messenger RNA (mRNA), there have been tremendous efforts to wield them in the development of therapeutics and vaccines. During the COVID-19 pandemic, two mRNA vaccines were developed and approved in record-breaking time, revolutionizing the vaccine development landscape. Although first-generation COVID-19 mRNA vaccines have demonstrated over 90% efficacy, alongside strong immunogenicity in humoral and cell-mediated immune responses, their durability has lagged compared to long-lived vaccines, such as the yellow fever vaccine. Although worldwide vaccination campaigns have saved lives estimated in the tens of millions, side effects, ranging from mild reactogenicity to rare severe diseases, have been reported. This review provides an overview and mechanistic insights into immune responses and adverse effects documented primarily for COVID-19 mRNA vaccines. Furthermore, we discuss the perspectives of this promising vaccine platform and the challenges in balancing immunogenicity and adverse effects.

Gianluca Veneziani, Diego L. García-González, Sonia Esposto et al.

In virgin olive oil industries, the technological choices of the production plant affect the biochemical activities that take place in the olives being processed throughout the entire process, thereby affecting the quality of the final product. The lipoxygenase pool enzymes that operated their activity during the first phases of the process need the best conditions to work, especially concerning temperature and oxygen availability. In this study, a system was equipped to supply oxygen in the crusher at a controllable concentration in an industrial olive oil mill at pilot plant scale, and four oxygen concentrations and two cultivars, Coratina and Ogliarola, were tested. The best concentration for oxygen supply was 0.2 L/min at the working capacity of 0.64 Ton/h. Further, using this addition of oxygen, it was possible to increase the compound’s concentration, which is responsible for the green, fruity aroma. The effect on volatile compounds was also confirmed by the sensory analyses. However, at the same time, it was possible to maintain the concentration of phenols in a good quality olive oil while also preserving all the antioxidant properties of the product due to the presence of phenols. This study corroborates the importance of controlling oxygen supply in the first step of the process for process management and quality improvement in virgin olive oil production.

Ragab E. Abouzeid, Ahmed Salama, Esmail M. El-Fakharany et al.

Bio sustainable hydrogels including tunable morphological and/or chemical cues currently offer a valid strategy of designing innovative systems to enhance healing/regeneration processes of damaged tissue areas. In this work, TEMPO-oxidized cellulose nanofibrils (T-CNFs) were embedded in alginate (Alg) and polyvinyl alcohol (PVA) solution to form a stable mineralized hydrogel. A calcium chloride reaction was optimized to trigger a crosslinking reaction of polymer chains and mutually promote in situ mineralization of calcium phosphates. FTIR, XRD, SEM/EDAX, and TEM were assessed to investigate the morphological, chemical, and physical properties of different mineralized hybrid hydrogels, confirming differences in the deposited crystalline nanostructures, i.e., dicalcium phosphate dehydrate (DCPDH) and hydroxyapatite, respectively, as a function of applied pH conditions (i.e., pH 4 or 8). Moreover, in vitro tests, in the presence of HFB-4 and HSF skin cells, confirmed a low cytotoxicity of the mineralized hybrid hydrogels, and also highlighted a significant increase in cell viability via MTT tests, preferentially, for the low concentration, crosslinked Alg/PVA/calcium phosphate hybrid materials (<1 mg/mL) in the presence of hydroxyapatite. These preliminary results suggest a promising use of mineralized hybrid hydrogels based on Alg/PVA/T-CNFs for bone and wound healing applications.

Yucen Li, Lingling Xia, Yiming Fan et al.

The synthesis of materials has been an important task throughout human history, and the ability to perform successful and efficient syntheses has been a factor in industrial revolutions and societal development. Recently, the rapid development of sophisticated techniques such as flow synthesis methods, artificial intelligence, information technology, and robotics, has facilitated the autonomous synthesis of chemicals with minimal effort and at little cost to the economy. This trend has influenced recent materials research and could potentially reduce the time from discovery of materials to their commercialization. In this short review, we focus on the autonomous synthesis of materials. We first discuss how autonomous synthesis could change materials research. Then, we provide some examples of autonomous syntheses in flow reactors. Finally, we present examples of autonomous syntheses using non-flow methods.

Carmela Maria Montone, Sara Elsa Aita, Anna Arnoldi et al.

This work describes an untargeted analytical approach for the screening, identification, and characterization of the trans-epithelial transport of green tea (<i>Camellia sinensis</i>) catechin extracts with in vitro inhibitory effect against the SARS-CoV-2 papain-like protease (PLpro) activity. After specific catechin extraction, a chromatographic separation obtained six fractions were carried out. The fractions were assessed in vitro against the PLpro target. Fraction 5 showed the highest inhibitory activity against the SARS-CoV-2 PLpro (IC₅₀ of 0.125 μg mL⁻¹). The untargeted characterization revealed that (−)-epicatechin-3-gallate (ECG) was the most abundant compound in the fraction and the primary molecule absorbed by differentiated Caco-2 cells. Results indicated that fraction 5 was approximately 10 times more active than ECG (IC₅₀ value equal to 11.62 ± 0.47 μg mL⁻¹) to inhibit the PLpro target. Overall, our findings highlight the synergistic effects of the various components of the crude extract compared to isolated ECG.

Sehrish Manan, Muhammad Wajid Ullah, Mazhar Ul-Islam et al.

Over the last couple of decades, the introduction of living systems to material science for the synthesis of functional materials from biological resources is receiving immense consideration. This is also in accordance with the need for green and sustainable development of new materials. For example, the growing concerns of the degradation of synthetic plastics are shifting the direction of materials-related research to the use of polymeric materials acquired from renewable resources. For example, the fungal mycelium-based materials are produced by growing the vegetative part of mushroom-forming fungi on different organic substrates. Such fungi are known for their ability to degrade agricultural wastes such as straws and sawdust. The mycelium-based composites having tailored structural, physical, chemical, mechanical, and biological properties are relying on the strain, feeding substrate, and the manufacturing process. The mycelium cell wall mainly contains the chitin, glucans, proteins, and lipids, whose concentrations depend upon the feeding substrate that ultimately defines the final properties of the synthesized materials. The mycelium-based functional materials with tunable properties are synthesized by selecting the desired components and the synthesis method. The pure and composites of stiff, elastic, porous, less dense, fast-growing, and low-cost mycelium-derived materials with efficient antimicrobial, antioxidant, and skin whitening properties pave their way in various applications such as construction, packaging, medicine, and cosmetics. This review describes the synthesis and structural organization of mycelium-based materials. It further discusses the effect of different factors on the material properties. Finally, it summarizes different applications of mycelium-based materials in medicine, cosmetics, packaging, and construction fields.

Bassam M. Ayoub, Haidy E. Michel, Shereen Mowaka et al.

The authors in the current work suggested the potential repurposing of omarigliptin (OMR) for neurodegenerative diseases based on three new findings that support the preliminary finding of crossing BBB after a single dose study in the literature. The first finding is the positive results of the docking study with the crystal structures of A_2A adenosine (A2AAR) and acetylcholine esterase (AChE) receptors. A2AAR is a member of non-dopaminergic GPCR superfamily receptor proteins and has essential role in regulation of glutamate and dopamine release in Parkinson’s disease while AChE plays a major role in Alzheimer’s disease as the primary enzyme responsible for the hydrolytic metabolism of the neurotransmitter acetylcholine into choline and acetate. Docking showed that OMR perfectly fits into A2AAR binding pocket forming a distinctive hydrogen bond with Threonine 256. Besides other non-polar interactions inside the pocket suggesting the future of the marketed anti-diabetic drug (that cross BBB) as a potential antiparkinsonian agent while OMR showed perfect fit inside AChE receptor binding site smoothly because of its optimum length and the two fluorine atoms that enables quite lean fitting. Moreover, a computational comparative study of OMR docking, other 12 DPP-4 inhibitors and 11 SGLT-2 inhibitors was carried out. Secondly, glucagon-like peptide-1 (GLP-1) concentration in rats’ brain tissue was determined by the authors using sandwich GLP-1 ELISA kit bio-analysis to ensure the effect of OMR after the multiple doses’ study. Brain GLP-1 concentration was elevated by 1.9-fold following oral multiple doses of OMR (5 mg/kg/day, p.o. for 28 days) as compared to the control group. The third finding is the enhanced BBB crossing of OMR after 28 days of multiple doses that had been studied using <i>LC</i>-MS/MS method with enhanced liquid–liquid extraction. A modified LC-MS/MS method was established for bioassay of OMR in rats’ plasma (10–3100 ng/mL) and rats’ brain tissue (15–2900 ng/mL) using liquid–liquid extraction. Alogliptin (ALP) was chosen as an internal standard (IS) due to its LogP value of 1.1, which is very close to the LogP of OMR. Extraction of OMR from samples of both rats’ plasma and rats’ brain tissue was effectively achieved with ethyl acetate as the extracting solvent after adding 1N sodium carbonate to enhance the drug migration, while choosing acetonitrile to be the diluent solvent for the IS to effectively decrease any emulsion between the layers in the stated method of extraction. Validation results were all pleasing including good stability studies with bias of value below 20%. Concentration of OMR in rats’ plasma were determined after 2 h of the latest dose from 28 days multiple doses, p.o, 5 mg/kg/day. It was found to be 1295.66 ± 684.63 ng/mL estimated from the bio-analysis regression equation. OMR passed through the BBB following oral administration and exhibited concentration of 543.56 ± 344.15 ng/g in brain tissue, taking in consideration the dilution factor of 10. The brain/plasma concentration ratio of 0.42 (543.56/1295.66) was used to illustrate the penetration power through the BBB after the multiple doses for 28 days. Results showed that OMR passed through the BBB more effectively in the multiple dose study as compared to the previously published single dose study by the authors. Thus, the present study suggests potential repositioning of OMR as antiparkinsonian agent that will be of interest for researchers interested in neurodegenerative diseases.

Barbara Lapinska, Magdalena Konieczka, Beata Zarzycka et al.

There is no consensus on the antibacterial activity of dentin bonding systems (DBS). Many study models have been used to evaluate the antimicrobial activity of dental materials. In this study, a novel detection method, flow cytometry, was introduced. It allows for evaluation of the antibacterial activity of DBS, based on assessment of the disruption of the bacterial physical membrane induced by DBS. The aim of the study was to evaluate the antibacterial properties of selected dentin bonding systems against <i>Streptococcus mutans</i>. The highest antibacterial activity against <i>S. mutans</i> was observed for Adhese Universal (99.68% dead cells) and was comparable to that of Prime&amp;Bond Universal, OptiBond Universal, or Clearfil Universal Bond Quick (<i>p</i> &gt; 0.05). The lowest activity of all tested systems was displayed by the multi-mode adhesive, Universal Bond (12.68% dead bacteria cells), followed by the self-etch adhesive, OptiBond FL (15.58% dead bacteria cells). The present study showed that in the case of two-component DBS, the primer exhibited higher antimicrobial activity than the adhesive (or bond) itself.

Jinyu Yang, Yanhao Zhang, Shuangzhi Zhao et al.

Pullulan, with its excellent characteristics of film-forming, water solubility, and biodegradability, is attracting more and more attention in agricultural products preservation. However, high pullulan production cost largely restricts its widely application due to its low production. In order to improve pullulan production by Aureobasidium pullulans NCPS2016, the medium was optimized using single factor experiment and response surface methodology. Based on the single factor experiments, the contents of soybean meal hydrolysates (SMHs), (NH4)2SO4, and K2HPO4&middot;3H2O were considered to be main factors influencing the extracellular polysaccharide (EPS) production, and were further optimized by Box&ndash;Behnken design. The optimal content of SMHs of 7.71 g/L, (NH4)2SO4 of 0.35 g/L, and K2HPO4&middot;3H2O of 8.83 g/L were defined. Finally, EPS production of 59.8 g/L was obtained, 39% higher in comparison with the production in the basal medium. The purified EPS produced by NCPS2016 was confirmed to be pullulan. This is the first time fructose is reported to be the optimal carbon source for pullulan production by Aureobasidium pullulans, which is of great significance for the further study of the mechanism of the synthesis of pullulan by NCPS2016. Also, the results here have laid a foundation for reducing the industrial production cost of pullulan.

R. H. H. Janssen, A. Pozzer

We present a new submodel for the Modular Earth Submodel System (MESSy): the MiXed Layer (MXL) model for the diurnal dynamics of the convective boundary layer, including explicit representations of entrainment and surface fluxes. This submodel is embedded in a new MESSy base model (VERTICO), which represents a single atmospheric column. With the implementation of MXL in MESSy, MXL can be used in combination with other MESSy submodels that represent processes related to atmospheric chemistry. For instance, the coupling of MXL with more advanced modules for gas-phase chemistry (such as the Mainz Isoprene Mechanism 2 (MIM2)), emissions, dry deposition and organic aerosol formation than in previous versions of the MXL code is possible. Since MXL is now integrated in the MESSy framework, it can take advantage of future developments of this framework, such as the inclusion of new process submodels. <br><br> The coupling of MXL with submodels that represent other processes relevant to chemistry in the atmospheric boundary layer (ABL) yields a computationally inexpensive tool that is ideally suited for the analysis of field data, for evaluating new parametrizations for 3-D models, and for performing systematic sensitivity analyses. A case study for the DOMINO campaign in southern Spain is shown to demonstrate the use and performance of MXL/MESSy in reproducing and analysing field observations.

Sudipta Pathak, Kamalesh Debnath, Animesh Pramanik

A convenient and efficient methodology for the synthesis of densely substituted pyrrole-fused isocoumarins, which employs solid-supported silica sulfuric acid (SSA) as catalyst, has been developed. When the mixture of ninhydrin adducts of acetylacetone/ethyl acetoacetate and primary amines was heated on the solid surface of SSA under solvent-free conditions, the pyrrole-fused isocoumarins were formed in good yields. This synthetic method has several advantages such as the employment of solvent-free reaction conditions without the use of any toxic reagents and metal catalysts, the ease of product isolation, the use of a recyclable catalyst, the low cost, the easy availability of the starting materials, and the excellent yields of products.