Face-to-face Assembly Strategy of Au Nanocubes: Induced Generation of Broad Hotspot Regions for SERS-Fluorescence Dual-Signal Detection of Intracellular miRNAs.

While designing anisotropic noble metal nanoparticles (NPs) can enhance the signal intensity of Raman dyes, more sensitive surface-enhanced Raman scattering (SERS) probes can be designed by oriented self-assembly of noble metal nanomaterials into dimers or higher-order nanoclusters. In this study, we engineered a self-assembly strategy in living cells for real-time fluorescence and SERS dual-channel detection of intracellular microRNAs (miRNAs), using Mg2+-dependent 8-17E DNAzyme sequences as the driving motors, gold nanocubes (AuNCs) as the driver components, and three-branched double-stranded DNA as the linking tool. The assembly selects adenine in DNA as a reporter molecule, simplifying the labeling process of Raman reporter molecules and reducing the synthesis process. In addition, adenine is stably distributed between the faces of AuNCs and the wide hotspot region gives good reproducibility of the adenine SERS signal. In this strategy, the SERS channel was consistently stable and more sensitive compared to the fluorescence channel. Among them, the detection limit of the SERS channel was 2.1 pM and the coefficient of variation was 1.26% in the in vitro liquid phase and 1.49% in MCF-7 cells. The strategy successfully achieved accurate tracking and quantification of miRNA-21 in cancer cells, showing good reproducibility in complex samples as well as cells. The reported strategy provides ideas for exploring intracellular specific triggering of nanoparticles for precise control of self-assembly.

Wine- and stir-frying processing of Cuscutae Semen enhance its ability to alleviate oxidative stress and apoptosis via the Keap 1-Nrf2/HO-1 and PI3K/AKT pathways in H2O2-challenged KGN human granulosa cell line.

BACKGROUND: Cuscutae Semen (CS) has been prescribed in traditional Chinese medicine (TCM) for millennia as an aging inhibitor, an anti-inflammatory agent, a pain reliever, and an aphrodisiac. Its three main forms include crude Cuscutae Semen (CCS), wine-processed CS (WCS), and stir-frying-processed CS (SFCS). Premature ovarian insufficiency (POI) is a globally occurring medical condition. The present work sought a highly efficacious multi-target therapeutic approach against POI with minimal side effects. Finally, it analyzed the relative differences among CCS, WCS and SFCS in terms of their therapeutic efficacy and modes of action against H2O2-challenged KGN human granulosa cell line. METHODS: In this study, ultrahigh-performance liquid chromatography (UPLC)-Q-ExactiveTM Orbitrap-mass spectrometry (MS), oxidative stress indices, reactive oxygen species (ROS), Mitochondrial membrane potential (MMP), real-time PCR, Western blotting, and molecular docking were used to investigate the protective effect of CCS, WCS and SFCS on KGN cells oxidative stress and apoptosis mechanisms. RESULTS: The results confirmed that pretreatment with CCS, WCS and SFCS reduced H2O2-induced oxidative damage, accompanied by declining ROS levels and malondialdehyde (MDA) accumulation in the KGN cells. CCS, WCS and SFCS upregulated the expression of antioxidative levels (GSH, GSH/GSSG ratio, SOD, T-AOC),mitochondrial membrane potential (MMP) and the relative mRNA(Nrf2, Keap1, NQO-1, HO-1, SOD-1, CAT). They inhibited apoptosis by upregulating Bcl-2, downregulating Bax, cleaved caspase-9, and cleaved caspase-3, and lowering the Bax/Bcl-2 ratio. They also exerted antioxidant efficacy by partially activating the PI3K/Akt and Keap1-Nrf2/HO-1 signaling pathways. CONCLUSIONS: The results of the present work demonstrated the inhibitory efficacy of CCS, WCS and SFCS against H2O2-induced oxidative stress and apoptosis in KGN cells and showed that the associated mechanisms included Keap1-Nrf2/HO-1 activation, P-PI3K upregulation, and P-Akt-mediated PI3K-Akt pathway induction.

Multielement simultaneous quantitative analysis of trace elements in stainless steel via full spectrum laser-induced breakdown spectroscopy.

Laser-Induced Breakdown Spectroscopy (LIBS) instruments are increasingly recognized as valuable tools for detecting trace metal elements due to their simplicity, rapid detection, and ability to perform simultaneous multi-element analysis. Traditional LIBS modeling often relies on empirical or machine learning-based feature band selection to establish quantitative models. In this study, we introduce a novel approach-simultaneous multi-element quantitative analysis based on the entire spectrum, which enhances model establishment efficiency and leverages the advantages of LIBS. By logarithmically processing the spectra and quantifying the cognitive uncertainty of the model, we achieved remarkable predictive performance (R2) for trace elements Mn, Mo, Cr, and Cu (0.9876, 0.9879, 0.9891, and 0.9841, respectively) in stainless steel. Our multi-element model shares features and parameters during the learning process, effectively mitigating the impact of matrix effects and self-absorption. Additionally, we introduce a cognitive error term to quantify the cognitive uncertainty of the model. The results suggest that our approach has significant potential in the quantitative analysis of trace elements, providing a reliable data processing method for efficient and accurate multi-task analysis in LIBS. This methodology holds promising applications in the field of LIBS quantitative analysis.

l-arginine and l-lysine supplementation to NaCl tenderizes porcine meat by promoting myosin extraction and actomyosin dissociation.

This study investigated the individual and combined effects of l-arginine, l-lysine, and NaCl on the ultrastructure of porcine myofibrils to uncover the mechanism underlying meat tenderization. Arg or Lys alone shortened A-bands and damaged M-lines, while NaCl alone destroyed M- and Z-lines. Overall, Arg and Lys cooperated with NaCl to destroy the myofibrillar ultrastructure. Moreover, these two amino acids conjoined with NaCl to increase myosin solubility, actin band intensity, and the protein concentration of the actomyosin supernatant. However, they decreased the turbidity and particle size of both myosin and actomyosin solutions, and the remaining activities of Ca2+- and Mg2+-ATPase. The current results revealed that Arg/Lys combined with NaCl to extract myosin and dissociate actomyosin, thereby aggravating the destruction of the myofibrillar ultrastructure. The present results provide a good explanation for the previous phenomenon that Arg and Lys cooperated with NaCl to improve meat tenderness.

Density Functional Theory and Raman Spectroscopy Studies of Adsorption Sites of Au Nanoparticles with Alectinib.

Alectinib is an ALK tyrosine kinase inhibitor, which is mainly used in patients with crizotinib-resistant nonsmall cell lung cancer. Alectinib has attracted much clinical attention for its longest progression-free survival time and the best therapeutic effect. The chemical adsorption of Au nanoclusters (AuNPs) with alectinib molecules is studied by density functional theory (DFT) and surface-enhanced Raman scattering spectroscopy (SERS) experiments. DFT/B3LYP-D3/6-311G** was used for optimization and vibration analysis of alectinib-Au6 complexes, as well as molecular electrostatic potential, frontier molecular orbital, and electro-optic-based charge transfer descriptors. Comparing the results of the DFT theory and SERS experiment, alectinib and AuNPs can form Au-N6 bonds primarily through chemical adsorption of N6 atoms, and the experimental results showed that the enhancement factor (EFCHEM) could reach 4.27. The results provide a theoretical basis for exploring the mechanism of chemical enhancement between AuNPs and alectinib.

Novel insights into IL-37: an anti-inflammatory cytokine with emerging roles in anti-cancer process.

Interleukin-37 (IL-37) is a newly discovered member of IL-1 family. The cytokine was proved to have extensive protective effects in infectious diseases, allergic diseases, metabolic diseases, autoimmune diseases and tumors since its discovery. IL-37 was mainly produced by immune and some non-immune cells in response to inflammatory stimulus. The IL-37 precursors can convert into the mature forms after caspase-1 cleavage and activation intracellularly, and then bind to Smad-3 and transfer to the nucleus to inhibit the production and functions of proinflammatory cytokines; extracellularly, IL-37 binds to cell surface receptors to form IL-37/IL-18Rα/IL-1R8 complex to exert immunosuppressive function via inhibiting/activating multiple signal pathways. In addition, IL-37 can attenuate the pro-inflammatory effect of IL-18 through directly or forming an IL-37/IL-18BP/IL-18Rß complex. Therefore, IL-37 has the ability to suppress innate and acquired immunity of the host, and effectively control inflammatory stimulation, which was considered as a new hallmark of cancer. Specifically, it is concluded that IL-37 can inhibit the growth and migration of tumor cells, prohibit angiogenesis and mediate the immunoregulation in tumor microenvironment, so as to exert effective anti-tumor effects. Importantly, latest studies also showed that IL-37 may be a novel therapeutic target for cancer monitoring. In this review, we summarize the immunoregulation roles and mechanisms of IL-37 in anti-tumor process, and discuss its progress so far and potential as tumor immunotherapy.

Small-sample stacking model for qualitative analysis of aluminum alloys based on femtosecond laser-induced breakdown spectroscopy.

Material characterization using laser-induced breakdown spectroscopy (LIBS) often relies on extensive data for effective analysis. However, data acquisition can be challenging, and the high dimensionality of raw spectral data combined with a large-scale sample dataset can strain computational resources. In this study, we propose a small sample size stacking model based on femtosecond LIBS to achieve accurate qualitative analysis of aluminum alloys. The proposed three-layer stacking algorithm performs data reconstruction and feature extraction to enhance the analysis. In the first layer, random forest spectral feature selection and specific spectral line spreading are employed to reconstruct the data. The second layer utilizes three heterogeneous classifiers to extract features from the reconstructed spectra in different feature spaces, generating second-level reconstructed data. Finally, the third layer utilizes the reconstructed dataset for qualitative prediction. Results indicate that the Stacking algorithm outperforms traditional methods such as k-nearest neighbors (KNN), support vector machine (SVM), and random forest (RF), including those combined with principal component analysis (PCA). The Stacking algorithm achieves an impressive 100% recognition rate in classification, with Accuracy, precision, recall, and F1 scores reaching 1.0. Moreover, as the number of samples decreases, the gap between the recognition accuracy of the Stacking algorithm and traditional approaches widens. For instance, using only 15 spectra for training, the Stacking algorithm achieves a recognition accuracy of 96.47%, significantly surpassing the improved RF's accuracy of 71.76%. Notably, the model demonstrates strong robustness compared to traditional modeling approaches, and the qualitative prediction error remains consistently below 5%. These findings underscore the model's enhanced generalization ability and higher prediction accuracy in small sample machine learning. This research contributes significantly to improving the applicability of the LIBS technique for fast detection and analysis of small samples. It provides valuable insights into the development of effective methodologies for material characterization, paving the way for advancements in the field.

A new compact adenine base editor generated through deletion of HNH and REC2 domain of SpCas9.

BACKGROUND: Adenine base editors (ABEs) are promising therapeutic gene editing tools that can efficiently convert targeted A•T to G•C base pairs in the genome. However, the large size of commonly used ABEs based on SpCas9 hinders its delivery in vivo using certain vectors such as adeno-associated virus (AAV) during preclinical applications. Despite a number of approaches having previously been attempted to overcome that challenge, including split Cas9-derived and numerous domain-deleted versions of editors, whether base editor (BE) and prime editor (PE) systems can also allow deletion of those domains remains to be proven. In this study, we present a new small ABE (sABE) with significantly reduced size. RESULTS: We discovered that ABE8e can tolerate large single deletions in the REC2 (Δ174-296) and HNH (Δ786-855) domains of SpCas9, and these deletions can be stacked together to create a new sABE. The sABE showed higher precision than the original ABE8e, with proximally shifted protospacer adjacent motif (PAM) editing windows (A3- A15), and comparable editing efficiencies to 8e-SaCas9-KKH. The sABE system efficiently generated A-G mutations at disease-relevant loci (T1214C in GAA and A494G in MFN2) in HEK293T cells and several canonical Pcsk9 splice sites in N2a cells. Moreover, the sABE enabled in vivo delivery in a single adeno-associated virus (AAV) vector with slight efficiency. Furthermore, we also successfully edited the genome of mouse embryos by microinjecting mRNA and sgRNA of sABE system into zygotes. CONCLUSIONS: We have developed a substantially smaller sABE system that expands the targeting scope and offers higher precision of genome editing. Our findings suggest that the sABE system holds great therapeutic potential in preclinical applications.

Natural epidithiodiketopiperazine alkaloids as potential anticancer agents: Recent mechanisms of action, structural modification, and synthetic strategies.

Cancer has become a grave health crisis that threatens the lives of millions of people worldwide. Because of the drawbacks of the available anticancer drugs, the development of novel and efficient anticancer agents should be encouraged. Epidithiodiketopiperazine (ETP) alkaloids with a 2,5-diketopiperazine (DKP) ring equipped with transannular disulfide or polysulfide bridges or S-methyl moieties constitute a special subclass of fungal natural products. Owing to their privileged sulfur units and intriguing architectural structures, ETP alkaloids exhibit excellent anticancer activities by regulating multiple cancer proteins/signaling pathways, including HIF-1, NF-κB, NOTCH, Wnt, and PI3K/AKT/mTOR, or by inducing cell-cycle arrest, apoptosis, and autophagy. Furthermore, a series of ETP alkaloid derivatives obtained via structural modification showed more potent anticancer activity than natural ETP alkaloids. To solve supply difficulties from natural resources, the total synthetic routes for several ETP alkaloids have been designed. In this review, we summarized several ETP alkaloids with anticancer properties with particular emphasis on their underlying mechanisms of action, structural modifications, and synthetic strategies, which will offer guidance to design and innovate potential anticancer drugs.

Effect of different concentrations of gellan gum with/without 0.50% basil essential oil on the physicochemical properties of gellan gum-rice bran oil coating emulsions and their application in egg preservation.

This work investigated the effects of different concentrations (0.10 %, 0.15 % or 0.20 %, w/v) of gellan gum (GG) with/without 0.50 % (v/v) basil essential oil (BEO) on physicochemical properties of gellan gum-rice bran oil (GG-RBO) emulsions. The results showed that GG-RBO emulsions with 0.15 % or 0.20 % GG were more stable than GG-RBO emulsion with 0.10 % GG (as evidenced by higher apparent viscosity and absolute zeta potential, but smaller average particle size and lower turbidity), thus displaying better coating performances (as evidenced by bigger contact angle but lower moisture content). The presence of BEO further improved their stability and coating performances. Coating with GG-BRO or GG-RBO-BEO emulsion with 0.15 % GG significantly delayed the increase in weight loss, and the decrease in haugh unit, yolk index and albumen pH of eggs during 42 days storage; moreover, GG-RBO-BEO emulsion caused lower total aerobic plate count. Therefore, GG-RBO, especially GG-RBO-BEO emulsion has potential in egg preservation.

Dynamic changes in marker components during the stir-frying of Pharbitidis Semen, and network analysis of its potential effects on nephritis.

Introduction: Pharbitidis Semen (PS) has been widely used in traditional Chinese medicine to treat several diseases such as nephritis. PS is usually stir-fried to enhance its therapeutic efficacy before use in clinical practice. However, the changes in phenolic acids during stir-frying and the mechanisms of their therapeutic effects on nephritis are still unclear. Methods: Here, we studied the processing-induced chemical changes and elucidated the mechanism of PS in the treatment of nephritis. We determined the levels of the 7 phenolic acids in raw PS (RPS) and stir-fried PS (SPS) using high-performance liquid chromatography, analyzed the dynamic compositional changes during stir-frying, and used network analysis and molecular docking to predict and verify compound targets and pathways corresponding to nephritis. Results: The dynamic changes in the 7 phenolic acids in PS during stir-frying are suggestive of a transesterification reaction. Pathway analysis revealed that the targets of nephritis were mainly enriched in the AGE-RAGE, hypoxia-inducible factor-1, interleukin-17, and tumor necrosis factor signaling pathways among others. Molecular docking results showed that the 7 phenolic acids had good binding ability with the key nephritic targets. Discussion: The potential pharmaceutical basis, targets, and mechanisms of PS in treating nephritis were explored. Our findings provide a scientific basis for the clinical use of PS in treating nephritis.

Recent progress in chemistry and bioactivity of monoterpenoid indole alkaloids from the genus gelsemium: a comprehensive review.

Monoterpenoid indole alkaloids (MIAs) represent a major class of active ingredients from the plants of the genus Gelsemium. Gelsemium MIAs with diverse chemical structures can be divided into six categories: gelsedine-, gelsemine-, humantenine-, koumine-, sarpagine- and yohimbane-type. Additionally, gelsemium MIAs exert a wide range of bioactivities, including anti-tumour, immunosuppression, anti-anxiety, analgesia, and so on. Owing to their fascinating structures and potent pharmaceutical properties, these gelsemium MIAs arouse significant organic chemists' interest to design state-of-the-art synthetic strategies for their total synthesis. In this review, we comprehensively summarised recently reported novel gelsemium MIAs, potential pharmacological activities of some active molecules, and total synthetic strategies covering the period from 2013 to 2022. It is expected that this study may open the window to timely illuminate and guide further study and development of gelsemium MIAs and their derivatives in clinical practice.

The Extracts of Dendrobium Alleviate Dry Eye Disease in Rat Model by Regulating Aquaporin Expression and MAPKs/NF-κB Signalling.

Dry eye is one of the most common ocular surface diseases caused by tear film instability and ocular surface damage due to an abnormal quality or quantity of tears. Inflammatory factors can initiate relevant transduction signalling pathways and trigger the inflammatory cascade response, resulting in ocular surface inflammation. It has been shown that the active ingredients in Dendrobium, such as polysaccharides, alkaloids and phenols, have anti-inflammatory, anti-tumour and immunity-boosting effects, and Dendrobium officinale extract can improve glandular secretion function, increase salivary secretion and increase the expression level of water channel protein in salivary glands in patients with dry eye syndromes. We investigated the in vitro cytoprotective effect of Dendrobium extracts in sodium chloride induced hyperosmotic conditions in human cornea keratocytes (HKs). Results showed that Dendrobium officinale Kimura et Migo water extract (DOW) and Dendrobium loddigesii Rolfe water extract (DLW) could upregulate the expression of aquaporins (AQP)5 protein, thus exerting a repairing effect by promoting cell migration. Furthermore, oral administration of DOW and DLW enhanced tear production in rats and exerted a protective effect on ocular surface damage. DOW and DLW could upregulate the expression of AQP5 and mucin (muc)5ac proteins in the lacrimal gland and reduce the inflammatory response. DOW and DLW inhibited the activation of the corresponding mitogen-activated protein kinases (MAPK) and NF-KB pathway, thereby playing a role in improving dry eye symptoms. This study provides a new perspective on dry eye treatment, and DOW and DLW may be potential therapeutic agents for dry eye.

Establishing a UHPLC-MS/MS method for evaluation of the influence of stir-frying on the pharmacokinetics of seven compounds in Arctii Fructus.

At a fundamental level, the broad application of raw and stir-fried Arctii Fructus products as anti-tumor and anti-inflammatory agents is commonly recognized. In order to understand some of the discrepancies pertaining to their therapeutic functions, an associated study of pharmacokinetics is required. In this study, a reliable ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was initially developed for the concurrent determination of seven compounds from Arctii Fructus in plasma. By virtue of its acceptable performance, the developed method was incorporated in assessing the pharmacokinetic differences of the compounds following the oral administration of raw and stir-fried Arctii Fructus. Subsequently, the results highlighted potential improvements to the exposure of the seven compounds, and the enriched bioavailability of arctiin through the process of stir-frying, which are deemed essential constituents of Arctii Fructus. This study represents the initial attempt at assessing the influence of stir-frying on the pharmacokinetic behaviors of the primary Arctii Fructus composition. Furthermore, the results could be instrumental in expanding the clinical applications of diverse Arctii Fructus products, and reveal the inherent processing mechanism.

The chemical adsorption effect of surface enhanced Raman spectroscopy of nitrobenzene and aniline using the density functional theory.

Nitrobenzene and Aniline are representatives of the nitro or amino compounds of benzene, mainly used in the manufacture of dyes, spices, medicines, and so on. Extensive use of Nitrobenzene and Aniline may cause pesticide residue pollution and have carcinogenic effects on organisms. In this paper, the Nitrobenzene and Aniline single molecules and their complexes with gold nanoparticles are studied theoretically by Raman spectroscopy, the surface-enhanced Raman spectroscopy (SERS) and the density functional theory (DFT) simulations. Selective binding of gold nanoparticles (AuNPs) to the analyte was used to study the molecular electrostatic potential (MEP), frontier molecular orbital (FMO) and the Raman activity spectra of Nitrobenzene and Aniline, as well as the Raman activity spectrum of the complexes. The most electronegative sites of Nitrobenzene and Aniline are found in the MEP and the hypothesis that these sites might be the adsorption sites of Nitrobenzene/Aniline molecules at the gold surface. At the same time, the MEP of the Nitrobenzene/Aniline complexes also prove the existence of the charge transfer effect between Nitrobenzene/Aniline and Au. The FMO energy gap of Nitrobenzene/Aniline is 0.18983 eV and 0.18953 eV, respectively, and which, after adding the Au3 clusters, change to 0.03376 eV and 0.0797 eV, respectively, indicating that the Nitrobenzene/Aniline-Au3 complexes have stronger chemical activities and are more prone to the charge transfer effects. The electrophilic indices of Nitrobenzene (0.17921 eV) and Aniline (0.05635 eV) are calculated and analyzed, as well as that of Nitrobenzene/Aniline-Au3 complexes after adding the Au3 atomic clusters, 0.80819 eV and 0.19819 eV, respectively. The obvious increasing trend in the electrophilic indices of the Nitrobenzene/Aniline-Au3 complexes indicate their stronger biological activities and more prone to chemical reactions. The chemisorption of Nitrobenzene/Aniline and gold nanoparticles complexes is studied by the SERS, and the Raman formation of the complexes at different binding sites of Nitrobenzene/Aniline and Nitrobenzene/Aniline-Au3 is well explained by the surface selection rule. The reason for the selective enhancement of the spectral peaks presented in the Raman activity spectrum is calculated, and the enhancement factor of the chemical enhancement due to the charge transfer effect is calculated as well. The reason for the peak offset in the SERS spectrum to the conventional Raman spectrum is explained.

Detection of hypokalemia disorder and its relation with hypercalcemia in blood serum using LIBS technique for patients of colorectal cancer grade I and grade II.

Cancer continues to be the most dangerous disease around the world; it causes electrolyte imbalance as well as metabolic changes. There is a complicated relationship between electrolyte disorder and cancer. Cancer patients commonly pass with abnormalities in serum electrolyte levels such as hypokalemia, hyperkalemia, hyponatremia, and hypercalcemia. So, these electrolyte imbalances indicate the existence of paraneoplastic processes and help come to a more informed prognosis. Hypokalemia is defined as a serum potassium concentration below 3.5 mmol/L and it is the second common electrolyte imbalance seen in patients with malignant diseases. In this paper, the contribution of serum potassium concentration to tumor progression was studied by applying a promising and non-invasive technique called laser-induced breakdown spectroscopy (LIBS). It was found that there is a correlation between hypokalemia and the colorectal cancer problem. Also, significant serum potassium concentration differences were detected among two different stages of the same cancer and also between two groups of the same stage of a cancer held in common but one of them suffers from hypercalcemia. In addition, the optimum conditions of LIBS setup were arranged such that it will be suitable to work with serum samples on glass substrate.

Chemical Enhancement Effect of Icotinib-Au Complex Studied by Combined Density Functional Theory and Surface-Enhanced Raman Scattering.

Icotinib is an epidermal growth factor receptor tyrosine kinase inhibitor used in the treatment of non-small cell lung cancer. The charge transfer effect between gold nanoparticles (AuNPs) and icotinib molecules can be used as a model to study the adsorption mechanism between molecules and metal. The adsorption of icotinib on the AuNP surface was confirmed by UV-vis and transmission electron microscopy (TEM) experiments. To explain the nature of chemisorption between icotinib and AuNPs from a theoretical perspective, the molecular correlation properties of the complex model of icotinib-Au6 were studied by the density functional theory method. By studying the molecular electrostatic potential of an icotinib molecule, four potential binding sites of the icotinib molecule were predicted. The calculation results of binding energy showed that the complex formed by chemisorption of icotinib through acetylene group and Au6 was the most stable one. The molecular frontier orbitals of icotinib and icotinib-Au6 confirmed that the charge transfer effect occurred on the acetylene group, benzene ring, and quinazoline ring of the icotinib molecule. The Herzberg-Teller surface selection rule was used to explain selective enhancement in the theoretically calculated Raman spectra. By comparing the spectra of theory and experiment, the cause of spectral peak shift and broadening that appeared in the surface-enhanced Raman scattering spectrum compared with the normal Raman spectrum was explained as well. This work would contribute to the development and application of the icotinib-Au drug carrier system.

The characteristics of Raman spectroscopy of fenbendazole-gold nanoparticles based on the chemical adsorption effect.

Fenbendazole, a benzimidazole derivative with anti-tubulin polymerization properties, has been widely used in the treatment of parasitic infections. Because of its anticancer activity similar to that of many anticancer drugs, low cost and few side effects, fenbendazole has attracted wide research attention. The chemical adsorption of fenbendazole and gold nanoparticles are studied by the UV-Vis spectrophotometry, density functional method, Raman spectroscopy and surface-enhanced Raman spectroscopy. By comparing and analyzing the theoretical and experimental Raman spectra, this paper explains the reasons for the difference between the theoretical and experimental Raman spectra. Meanwhile, it is also found that the frequencies at 851 cm-1, 1222 cm-1, 1425 cm-1 and 1566 cm-1 are greatly enhanced. It is found that imidazole is adsorbed vertically to the surface of the substrate. It is concluded that Fenbendazole is vertically adsorbed on the surface of AuNPs through imidazole.

Interleukin-38 ameliorates poly(I:C) induced lung inflammation: therapeutic implications in respiratory viral infections.

Interleukin-38 has recently been shown to have anti-inflammatory properties in lung inflammatory diseases. However, the effects of IL-38 in viral pneumonia remains unknown. In the present study, we demonstrate that circulating IL-38 concentrations together with IL-36α increased significantly in influenza and COVID-19 patients, and the level of IL-38 and IL-36α correlated negatively and positively with disease severity and inflammation, respectively. In the co-cultured human respiratory epithelial cells with macrophages to mimic lung microenvironment in vitro, IL-38 was able to alleviate inflammatory responses by inhibiting poly(I:C)-induced overproduction of pro-inflammatory cytokines and chemokines through intracellular STAT1, STAT3, p38 MAPK, ERK1/2, MEK, and NF-κB signaling pathways. Intriguingly, transcriptomic profiling revealed that IL-38 targeted genes were associated with the host innate immune response to virus. We also found that IL-38 counteracts the biological processes induced by IL-36α in the co-culture. Furthermore, the administration of recombinant IL-38 could mitigate poly I:C-induced lung injury, with reduced early accumulation of neutrophils and macrophages in bronchoalveolar lavage fluid, activation of lymphocytes, production of pro-inflammatory cytokines and chemokines and permeability of the alveolar-epithelial barrier. Taken together, our study indicates that IL-38 plays a crucial role in protection from exaggerated pulmonary inflammation during poly(I:C)-induced pneumonia, thereby providing the basis of a novel therapeutic target for respiratory viral infections.

Comprehensive identification, fragmentation pattern, and metabolic pathways of gefitinib metabolites via UHPLC-Q-TOF-MS/MS: in vivo study of rat plasma, urine, bile, and faeces.

Gefitinib, the first approved inhibitor for oral epidermal growth factor receptor (EGFR), has been proved to be effective in non-small cell lung cancer with EGFR mutation. However, there are many metabolites of gefitinib that have not been identified in vivo. This study aims to identify the metabolites of gefitinib and its metabolic pathways in rats using ultra-high-performance liquid chromatography coupled with a quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) detector. Protein precipitation, solid-phase and ultrasonic extraction were used for the pre-treatment of plasma, urine, bile and faeces samples. In this study, a total of 28 compounds were identified in rat plasma, 29 in bile, 20 in urine and 16 in faeces. 20 new compounds were firstly reported as metabolites of gefitinib. Reduction, hydroxylation, dealkylation and dehalogenation were the major metabolic pathways in phase I. For phase II, the main pathways were sulphate and glucuronide conjugation. The fragment ions of gefitinib and its metabolites were usually generated via the fracture of C1-O bond of propoxy on the C6 position of aniline quinazoline ring. The results may be valuable and important for understanding the metabolic process of gefitinib in clinical application and drug safety.