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Few studies on anti-inflammatory drugs with indole groups have been published. This is the first study that demonstrates the anti-inflammatory effects of indole derivative XCR-5a in vitro and in vivo. This study aimed to discover more anti-inflammatory drugs with indole groups and investigate their anti-inflammatory mechanisms. First, a series of indole derivatives was synthesized, then screened for XCR-5a, a compound with anti-inflammatory effects. Second, the in vitro production of IL-1β, IL-6, TNF-α, inducible nitric oxide synthase (iNOS), and cyclo-oxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced primary cells of mice pretreated with XCR-5a was determined using qPCR and ELISA. Finally, the effect of XCR-5a on LPS-induced NF-κB signaling activation was determined by Western blotting. An in vivo mouse sepsis model was established. In mouse lung tissue, the production of IL-1β, IL-6, and TNF-α was determined and H&E staining was performed. Our findings showed that XCR-5a could suppress the production of LPS-induced IL-1β, IL-6, and TNF-α, as well as mRNA expression of iNOS and COX-2. Pretreatment with XCR-5a inhibited the LPS-induced inflammatory response in septic mice in vivo by decreasing pro-inflammatory cytokines production in serum and reducing immune cell infiltration. Mechanistically, XCR-5a suppressed LPS-induced activation of the NF-κB signaling pathway. XCR-5a has anti-inflammatory effects in vitro and in vivo. Therefore, XCR-5a could be a potential drug candidate for the treatment of inflammatory diseases. [ABSTRACT FROM AUTHOR]

This study employs first-principles calculation to investigate the MoSi 2 N 4 /SiC heterojunction. It aims to determine the structure, electronic, and optical properties of the heterojunction and assess the impact of varying vertical electric fields and biaxial strains on these properties. The results show that the MoSi 2 N 4 /SiC heterojunction is a direct bandgap semiconductor, exhibiting a band gap of 0.31 eV. This heterojunction benefits from a built-in electric field originating from the SiC layer and extending to the MoSi 2 N 4 layer. The optical absorption peaks in the ultraviolet region are significantly more intense than those in MoSi 2 N 4 and SiC monolayers, particularly at a wavelength of 172 nm, where the intensity reaches 1.99 × 106 cm−1. The study also shows that an increasing positive vertical electric field leads to a rising band gap. On the other hand, increasing tensile or compressive strain causes a gradual decline in the band gap. Specifically, at a strain of −8 %, the absorption peak intensity reaches 3.4 × 106 cm−1 at 172 nm, and the absorption spectrum broadens to 722 nm at an 8 % strain. In conclusion, the MoSi 2 N 4 /SiC heterojunction shows promise for enhancing the optical properties of two-dimensional materials and offers valuable insights for the development of efficient new ultraviolet devices. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD), which affects approximately one-third of the general population, has become a global health problem. Thus, more effective treatments for NAFLD are urgently required. In the present study, high levels of C-C motif ligand 19 (CCL19), signaling pathways such as Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB), and proinflammatory factors including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected in NAFLD patients, thereby indicating that there may be an association between CCL19 and these factors in NAFLD progression. Using a high-fat diet (HFD), the present study generated a Sprague-Dawley rat model of NAFLD, which displayed dyslipidemia with increased levels of plasma aspartate aminotransferase, alanine aminotransferase, total cholesterol and triglyceride. Dyslipidemia, liver histopathology and gene expression analyses indicated that the NAFLD model was successfully induced by HFD, and metformin and berberine (BBR) were effective treatments for NAFLD. HFD-induced CCL19 levels and associated factors were markedly reduced by the two drug treatments. In addition, metformin or BBR alone significantly promoted adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, which was inhibited by HFD. These results demonstrated that metformin and BBR could improve NAFLD, which may be via the activation of AMPK signaling, and the high expression of CCL19 in NAFLD was significantly reduced by metformin and BBR. It could be inferred that inhibition of CCL19 may be an effective treatment for NAFLD. [ABSTRACT FROM AUTHOR]

Fe 3+ doping is used to enhance the capacity of polythiophene as supercapacitor electrode and the flexible Fe 3+ doped PTh electrode on carbon cloth is prepared with an electrochemical deposition method. The successful doping of Fe 3+ is confirmed by IR, XPS, and EDS measurements. The electrochemical performance of the PTh electrode is evaluated using cyclic voltammetry, galvanostatic charge-discharge technique, and electrochemical impedance spectroscopy in acidic aqueous electrolyte. The pristine PTh exhibits specific capacitance of 77.2 F g −1 at a current density of 0.5 A g −1 . After Fe 3+ doping, the specific capacitance is improved to 108.1 F g −1 and the retention rate also improved from 7.8% to 21.2% after 1000 charge-discharge circles. [ABSTRACT FROM AUTHOR]

Macromolecular crowding and confinement are two factors that potentially affect protein structure and function in a complex cellular environment. The confinement effect on the structure and function of holoCaM [Ca2+-loaded calmodulin (CaM)], a two-domain protein involved in many calcium-mediated signaling pathways, has been investigated previously. However, little is known about how macromolecular crowding affects holoCaM structure and function. Here, the structure-function correlations of holoCaM are investigated in macromolecular crowded environments. It was found that macromolecular crowding impacts its structure and function mildly. The major conformational states are still extended conformation with inter-domain separation in crowded environment as well as those in dilute solution, but the population of transiently compact conformation increases compared to dilute solution. Furthermore, macromolecular crowding facilitates the binding of CaM with AcN19 peptide (CaM-bind domain of α- syn). This study provides a direct comparison for macromolecular crowding and confinement effects on protein structure and function, which helps to understand chemistry regulation in living cells. [ABSTRACT FROM AUTHOR]

In this study, a novel three-dimensional semi-rigid steel joint with a channel steel component is proposed, in which the channel steel component is connected to the column flange through a hybrid connection of bolts and welds along the minor axis. The design of the minor axis connection in this study had no weakening effect on the column web, and it was more convenient and easier to attach the additional channel steel component than the additional plates to the column flanges by welding. In order to investigate the static behaviour and seismic performance of the proposed novel three-dimensional semi-rigid steel joint with a channel steel component and to evaluate the interaction between both axes, numerical analyses were conducted systematically. The finite element (FE) models are firstly calibrated against the experimental results in order to get accurate results, and then the rotating characteristics, joint moment capacity, joint stiffness, ductility and energy dissipation capacity of the proposed novel semi-rigid steel joints were analysed under ten loading cases along the major and minor axes. The results indicate that the proposed novel semi-rigid steel joint has good energy dissipation capacity and deformation performance. Loading in the major-axis direction has almost no influence on the ultimate joint moment capacity but has some influence on the initial stiffness, ductility, stiffness degradation and energy dissipation ability of the proposed novel semi-rigid steel joint along the minor axis. In addition, the modified moment-rotation (M - θ) hysteretic model for the proposed novel semi-rigid steel joint is capable of effectively characterising its hysteretic behaviours, which can provide a reference for practical applications. • A novel 3D semi-rigid steel joint with channel steel component is proposed. • It is simpler and easier to attach channel steel component in minor-axis direction. • The novel joint has a good energy dissipation capacity and deformation performance. • Loading in major axis has some influence on the mechanical behaviours in minor axis. • The modified M - θ hysteretic model for the proposed novel joint is proposed. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, waste sawdust was functionalized by monosodium glutamate for improving its cationic sorption capacity. The functionalized sawdust (FS) and crude sawdust (CS) were compared for their malachite green (MG) sorption behaviors with a batch system. The effects of various experimental parameters (e.g. initial pH, sorbent dose, dye concentration, contact time, and temperature etc.) were investigated and the sorption kinetic and thermodynamic characteristics were understood. The MG removal ratios on FS and on CS increased with increasing initial pH and came up to the maximum value beyond pH 6 for FS and pH 8 for CS, respectively. The ratio of sorbed MG kept above 95% for 250mg/l of MG solution when 2.0g/l or more of FS was used. The MG removal percentage decreased more on CS than on FS with increasing initial MG concentration. The isothermal data of MG sorbed on FS and on CS followed the Langmuir model. By functionalizing, the sorption capacity (Q m) of sawdust for MG was increased from 85.47 to 196.08mg/g and the sorption equilibrium time of MG was shortened from 23 to 4.5h. The MG sorption processes on FS and on CS followed the pseudo-second-order rate kinetics. The sorptions of MG on FS and on CS were spontaneous and exothermic processes and lower temperatures were favorable for the sorption processes. [Copyright &y& Elsevier]

Background: Isatidis Radix, the root of Isatis indigotica Fort. (Chinese woad) can produce a variety of efficacious compound with medicinal properties. The tetraploid I. indigotica plants exhibit superior phenotypic traits, such as greater yield, higher bioactive compounds accumulation and enhanced stress tolerance. In this study, a comparative transcriptomic and metabolomic study on Isatidis Radix autotetraploid and its progenitor was performed. Results: Through the targeted metabolic profiling, 283 metabolites were identified in Isatidis Radix, and 70 polyploidization-altered metabolites were obtained. Moreover, the production of lignans was significantly increased post polyploidization, which implied that polyploidization-modulated changes in lignan biosynthesis. Regarding the transcriptomic shift, 2065 differentially expressed genes (DEGs) were identified as being polyploidy-responsive genes, and the polyploidization-altered DEGs were enriched in phenylpropanoid biosynthesis and plant hormone signal transduction. The further integrative analysis of polyploidy-responsive metabolome and transcriptome showed that 1584 DEGs were highly correlated with the 70 polyploidization-altered metabolites, and the transcriptional factors TFs-lignans network highlighted 10 polyploidy-altered TFs and 17 fluctuated phenylpropanoid pathway compounds. Conclusions: These results collectively indicated that polyploidization contributed to the high content of active compounds in autotetraploid roots, and the gene–lignan pathway network analysis highlighted polyploidy–responsive key functional genes and regulators. [ABSTRACT FROM AUTHOR]

Saffron, the dried stigma of Crocus sativus L., has a long history of use in the treatment of depression in traditional Chinese medicine and Islamic medicine. The unique aroma of saffron, primarily derived from its volatile oil, has been widely used by folk to mitigate anxiety and depression via sniffing because the aroma of saffron has a pleasant and invigorating effect. Aim of the study : This study aimed to investigate the antidepressant effect and the underlying mechanism of saffron essential oil (SEO) in mice exposed to chronic unpredictable mild stress (CUMS). In this study, compounds of SEO were identified using gas chromatography-mass spectrometry analysis, while network pharmacology was used to predict potential active compounds, antidepressant targets, and related signaling pathways of SEO. The CUMS depression model was further used to explore the therapeutic effect and possible mechanism of SEO. During the modeling period, mice were regularly administered fluoxetine (3.6 mg/kg, i.g.) or diluted SEO (2%, 4%, and 6% SEO, inhalation). The antidepressant and neuroprotective effects of SEO were evaluated by behavior tests (the open field test, the sucrose preference test, the tail suspension test, and the forced swimming test), hematoxylin-eosin staining, and Nissl staining. The enzyme-linked immunosorbent assay kits were used to measure dopamine (DA), 5-serotonin (5-HT), brain-derived neurotrophic factor (BDNF), and γ-aminobutyric acid (GABA) levels in serum. The relative abundance of Raf1, MEK1, P-ERK1/2/ERK1/2, P-CREB1/CREB1, BDNF, and P-Trk B/Trk B in the hippocampus was determined using western blot (WB). According to the network pharmacology analysis, seven active SEO compounds mediated 113 targets related to depression treatment, most of which were enriched in the 5-HT synapse, calcium signaling pathway, and cAMP signaling pathway. In vivo experiments indicated that fluoxetine and SEO improved depression-like behaviors in depressed mice. The levels of 5-HT, DA, BDNF, and GABA in serum increased significantly. Histopathological examinations revealed that fluoxetine and SEO ameliorated neuronal damage in the hippocampus. WB analysis showed that the relative expressions of Raf1, MEK1, P-ERK1/2/ERK1/2, P-CREB1/CREB1, BDNF, and P-Trk B/Trk B were significantly higher in the fluoxetine and SEO groups than in the CUMS group. Overall, these findings suggest that SEO significantly alleviates the depressive symptoms in CUMS exposed mice and partially restores hippocampal neuronal damage. Meanwhile, the best efficacy was observed in 4% SEO. Furthermore, the antidepressant mechanism of SEO is primarily dependent on the regulation of the MAPK-CREB1-BDNF signaling pathway. [Display omitted] • Saffron essential oil can ameliorate depressive behaviors in mice • Saffron essential oil can affect the release of neurotransmitters • Saffron essential oil inhalation can improve hippocampal neuron damage • The MAPK-CREB1-BDNF signaling pathway plays an important role in the antidepressant effects of SEO [ABSTRACT FROM AUTHOR]

Inflammation is a biological process closely related to different kinds of diseases, such as cancer and metabolic diseases. Therefore, effective control of the occurrence and development of inflammation is of great significance for disease prevention and control. Recently, 2-substituted indoles have gradually become a research hotspot because of their stability and pharmacological activity. Here we synthesized a series of compound containing 2-substituted indoles and investigated XCR-7a's role in inflammatory response. Our data show that XCR-7a can inhibit the production of inflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6) and inflammatory mediator cyclooxygenase-2 (COX-2) induced by lipopolysaccharide (LPS) in mouse peritoneal macrophages. Also, XCR-7a has a protective effect on LPS-induced inflammatory response in mice. Mechanically, we found that XCR-7a could inhibit the phosphorylation of c-Fos induced by LPS, which suggested that the protective effect of XCR-7a on inflammation was related to its negative regulation to phosphorylation of c-Fos. Briefly, our results demonstrated that XCR-7a could be expected to be a potential drug for controlling inflammation. XCR-7a had anti-inflammatory activities in vitro and in vivo, and might be a potential therapeutic candidate for LPS-induced sepsis. [Display omitted] • XCR-7a inhibits LPS-induced inflammatory cytokines in mouse peritoneal macrophages. • XCR-7a relieves LPS-induced sepsis in mice. • XCR-7a suppresses LPS-induced c-Fos phosphorylation. [ABSTRACT FROM AUTHOR]

A deterministic Extreme Value Analysis method is of particular importance in an engineering-oriented context. In this paper, three extreme value analysis (EVA) methods, in which annual maxima, monthly maxima or the Peaks-Over-Threshold are fitted into Generalized Extreme Value distribution (GEV) function or Generalized Pareto distribution (GP) function, are used to estimate return values of significant wave height. Sensitivity of return levels on water depth and sampling length is vigorously investigated, based on a 40-year long and high-resolution wave hindcast for the South Yellow Sea (SYS). A spatially-and-temporally varied POT sampling method combined with GP function produces most conservative and confident estimates of return levels for a large return period, but produces wider confidence level than the other two EVA approaches based on GEV function for short return period. In the SYS, the return level estimates are significantly reduced with a longer sample length. However, we find that the reduction is closely related to the long-term trend in extreme wave heights, rather than due to the sampling effect. From deep to shallow waters, spatial inhomogeneity of return levels increases, which should be considered in the engineering practice. • A sophisticated investigation was conducted on the dependence of the return level of extreme wave heights in the SYS to the epistemic and intrinsic factors. • GEV distribution model is more confident in short-term return level estimates, whilst GP distribution model is more confident for long-term return level estimates. • The inter-tidal region although is least sensitive to sampling length for the return level estunates, whilst contains the largest spatial inhomogeneity of extreme wave heights. • A temporal negative long-term trend was found in the return levels of extreme wave height in the SYS. [ABSTRACT FROM AUTHOR]