Flame-Retardant GF-PSB/DOPO-POSS Composite with Low Dk/Df and High Thermal Stability for High-Frequency Copper Clad Applications.

In the field of high-frequency communications devices, there is an urgent need to develop high-performance copper clad laminates (CCLs) with low dielectric loss (Df) plus good flame retardancy and thermal stability. The hydrocarbon resin styrene-butadiene block copolymer (PSB) was modified with the flame-retardant 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide/polyhedral oligomeric silsesquioxanes (DOPO-POSS) to meet the demands of high-frequency and high-speed applications. The resulting DOPO-POSS-modified PSB was used as the resin matrix along with other additives to fabricate PSB/DOPO-POSS laminates. At a high-frequency of 10 GHz, the laminates containing 20 wt.% of DOPO-POSS and with a thickness of 0.09 mm exhibited a Df of 0.00328, which is much lower compared with the commercial PSB/PX-200 composite (Df: 0.00498) and the PSB without flame retardancy (Df: 0.00453). Afterwards, glass fiber cloth (GF) was used as a reinforcing material to manufacture GF-PSB/DOPO-POSS composite laminates with a thickness of 0.25 mm. The flame retardancy of GF-PSB/DOPO-POSS composite laminate reached vertical burning (UL-94) V-1 grade, and GF-PSB/DOPO-POSS exhibited higher thermal and dynamic mechanical properties than GF-PSB/PX-200. The results of a limited oxygen index (LOI) and self-extinguishing time tests also demonstrated the superior flame-retardant performance of DOPO-POSS compared with PX-200. The investigation indicates that GF-PSB/DOPO-POSS composite laminates have significant potential for use in fabricating a printed circuit board (PCB) for high-frequency and high-speed applications.

Singlet oxygen dominance for phenolic degradation mediated by mixed-valence FeOx nanospheres.

In this investigation, we successfully synthesized magnetic FeOx nanosphere catalysts with mixed-valence and high operational stability through the pyrolysis of a hybrid material containing polyferrocenlyphosphazene with coordinating heteroatoms (N, P, O). We evaluated the degradation performance of these catalysts using the peroxymonosulfate (PMS) activation process against four different phenolic compounds, namely phenol, 4-nitrophenol, 2,4-dinitrophenol, and 2,4,5-trinitrophenol. Our results demonstrate the significant role of FeOx in the degradation process. The presence of mixed iron species, such as ferric iron, zero-valent iron, and iron oxides, activated PMS to generate radicals. Additionally, the heteroatoms facilitated the anchoring and dispersion of FeOx nanospheres while also breaking the inertness of the carbon structure. Notably, the FeOx-800 catalyst exhibited a maximum degradation activity of 98% for phenol, surpassing its counterparts. Electron paramagnetic resonance and free radical scavenging experiments confirmed that singlet oxygen (1O2) is the principal reactive oxygen species (ROS) that leads to the oxidative breakdown of phenolic compounds. This study introduces new concepts for designing Fenton-like catalysts incorporating heteroatoms into the carbon matrix. Due to their low cost and non-toxicity, these catalysts have recently received a great deal of attention for peroxymonosulfate (PMS) activation and environmental remediation.

Soot Erased: Catalysts and Their Mechanistic Chemistry.

Soot formation is an inevitable consequence of the combustion of carbonaceous fuels in environments rich in reducing agents. Efficient management of pollution in various contexts, such as industrial fires, vehicle engines, and similar applications, relies heavily on the subsequent oxidation of soot particles. Among the oxidizing agents employed for this purpose, oxygen, carbon dioxide, water vapor, and nitrogen dioxide have all demonstrated effectiveness. The scientific framework of this research can be elucidated through the following key aspects: (i) This review situates itself within the broader context of pollution management, emphasizing the importance of effective soot oxidation in reducing emissions and mitigating environmental impacts. (ii) The central research question of this study pertains to the identification and evaluation of catalysts for soot oxidation, with a specific emphasis on ceria-based catalysts. The formulation of this research question arises from the need to enhance our understanding of catalytic mechanisms and their application in environmental remediation. This question serves as the guiding principle that directs the research methodology. (iii) This review seeks to investigate the catalytic mechanisms involved in soot oxidation. (iv) This review highlights the efficacy of ceria-based catalysts as well as other types of catalysts in soot oxidation and elucidate the underlying mechanistic strategies. The significance of these findings is discussed in the context of pollution management and environmental sustainability. This study contributes to the advancement of knowledge in the field of catalysis and provides valuable insights for the development of effective strategies to combat air pollution, ultimately promoting a cleaner and healthier environment.

Turning precious metal-loaded e-waste to useful catalysts: Investigation into supercilious recovery and catalyst viability for peroxymonosulfate activation.

Here, the key tasks to be accomplished are selective precious metal recovery from e-wastewater and their conversion into valuable catalysts for peroxymonosulfate (PMS) activation. In this regard, we developed a hybrid material using 3D functional graphene foam and copper para-phenylenedithol (Cu-pPDT) MOF. The prepared hybrid showed a supercilious recovery of 92-95% even up to five cycles for Au(III) and Pd(II), which can be viewed as a reference for both the 2D graphene and the MOFs family. The outstanding performance has been attributed principally to the impact of diverse functionality as well as the unique morphology of 3D graphene foam, which provided a wide range of surface area and additional active sites in the hybrid frameworks. To prepare the surface-loaded metal nanoparticle catalysts, the sorbed samples recovered after precious metal extraction were calcined at 800 °C. The viability of the developed catalysts for the breakdown of 4-nitrophenol (4-NP) via PMS activation was investigated. Electron paramagnetic resonance spectroscopy (EPR) and experiments with radical scavengers suggest that sulfate and hydroxyl radicals are the main reactive species involved in the breakdown of 4-NP. This is because the active graphitic carbon matrix and the exposed precious metal and copper active sites work together in a way that is more effective.

Fasudil compensates podocyte injury via CaMK4/Rho GTPases signal and actin cytoskeleton-dependent activation of YAP in MRL/lpr mice.

Deposition of immune complexes in the glomerulus leads to irreversible renal damage in lupus nephritis (LN), of which podocyte malfunction arises earlier. Fasudil, the only Rho GTPases inhibitor approved in clinical settings, possesses well-established renoprotective actions; yet, no studies addressed the amelioration derived from fasudil in LN. To clarify, we investigated whether fasudil exerted renal remission in lupus-prone mice. In this study, fasudil (20 mg/kg) was intraperitoneally administered to female MRL/lpr mice for 10 weeks. We report that fasudil administration swept antibodies (anti-dsDNA) and attenuated systemic inflammatory response in MRL/lpr mice, accompanied by preserving podocyte ultrastructure and averting immune complex deposition. Mechanistically, it repressed the expression of CaMK4 in glomerulopathy by preserving nephrin and synaptopodin expression. And fasudil further blocked cytoskeletal breakage in the Rho GTPases-dependent action. Further analyses showed that beneficial actions of fasudil on the podocytes required intra-nuclear YAP activation underlying actin dynamics. In addition, in vitro assays revealed that fasudil normalized the motile imbalance by suppressing intracellular calcium enrichment, thereby contributing to the resistance of apoptosis in podocytes. Altogether, our findings suggest that the precise manners of crosstalks between cytoskeletal assembly and YAP activation underlying the upstream CaMK4/Rho GTPases signal in podocytes is a reliable target for podocytopathies treatment, and fasudil might serve as a promising therapeutic agent to compensate for the podocyte injury in LN.

A Novel POP-Ni Catalyst Derived from PBTP for Ambient Fixation of CO2 into Cyclic Carbonates.

The immobilization of homogeneous catalysts has always been a hot issue in the field of catalysis. In this paper, in an attempt to immobilize the homogeneous [Ni(Me6Tren)X]X (X = I, Br, Cl)-type catalyst with porous organic polymer (POP), the heterogeneous catalyst PBTP-Me6Tren(Ni) (POP-Ni) was designed and constructed by quaternization of the porous bromomethyl benzene polymer (PBTP) with tri[2-(dimethylamino)ethyl]amine (Me6Tren) followed by coordination of the Ni(II) Lewis acidic center. Evaluation of the performance of the POP-Ni catalyst found it was able to catalyze the CO2 cycloaddition with epichlorohydrin in N,N-dimethylformamide (DMF), affording 97.5% yield with 99% selectivity of chloropropylene carbonate under ambient conditions (80 °C, CO2 balloon). The excellent catalytic performance of POP-Ni could be attributed to its porous properties, the intramolecular synergy between Lewis acid Ni(II) and nucleophilic Br anion, and the efficient adsorption of CO2 by the multiamines Me6Tren. In addition, POP-Ni can be conveniently recovered through simple centrifugation, and up to 91.8% yield can be obtained on the sixth run. This research provided a facile approach to multifunctional POP-supported Ni(II) catalysts and may find promising application for sustainable and green synthesis of cyclic carbonates.

Pharmacological Mechanism of Sancao Yuyang Decoction in the Treatment of Oral Mucositis Based on Network Pharmacology and Experimental Validation.

Purpose: The network pharmacology analysis, molecular docking and experimental verification were performed to explore the pharmacological mechanisms of Sancao Yuyang Decoction (SCYYD) in the treatment of oral mucositis (OM). Methods: Active ingredients in SCYYD and their potential targets, as well as OM-related targets were screened from public databases. The core targets and signaling pathways of SCYYD against OM were determined by protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The ingredient-target-disease network and target-pathway network were constructed. Subsequently, molecular docking was carried out to predict the binding activity between active ingredients and key targets. Moreover, in vivo experiment was conducted to further verify the core targets predicted by network pharmacology analysis. Results: A total of 119 bioactive ingredients were screened from the corresponding databases. One hundred and eighty-six putative targets were retrieved and bioinformatics analysis was performed to reveal the top 5 potential candidate agents and 10 core targets. GO and KEGG enrichment analysis showed that SCYYD exerted excellent therapeutic effects on OM through several pathways, such as HIF-1 and Ras signaling pathway. Subsequently, molecular docking showed that main ingredients in SCYYD had optimal binding activities to the key protein targets. Moreover, the result of in vivo experiment indicated that SCYYD not only inhibited inflammation response and promoted wound healing of oral mucosa in OM rats, but also reversed high expressions of SRC, HSP90AA1, STAT3, HIF1α, mTOR, TLR4, MMP9, and low expression of ESR1. Conclusion: This study preliminarily uncovered the multiple compounds and multiple targets of SCYYD against OM using network pharmacology, molecular docking and in vivo verification, which provided a new insight of the pharmacological mechanisms of SCYYD in treatment of OM.

Cobalt Encapsulated in Nitrogen-Doped Graphite-like Shells as Efficient Catalyst for Selective Oxidation of Arylalkanes.

Selective oxidation of ethylbenzene to acetophenne is an important process in both organic synthesis and fine chemicals diligence. The cobalt-based catalysts combined with nitrogen-doped carbon have received great attention in ethylbenzene (EB) oxidation. Here, a series of cobalt catalysts with metallic cobalt nanoparticles (NPs) encapsulated in nitrogen-doped graphite-like carbon shells (Co@NC) have been constructed through the one-pot pyrolysis method in the presence of different nitrogen-containing compounds (urea, dicyandiamide and melamine), and their catalytic performance in solvent-free oxidation of EB with tert-butyl hydrogen peroxide (TBHP) as an oxidant was investigated. Under optimized conditions, the UCo@NC (urea as nitrogen source) could afford 95.2% conversion of EB and 96.0% selectivity to acetophenone, and the substrate scalability was remarkable. Kinetics show that UCo@NC contributes to EB oxidation with an apparent activation energy of 32.3 kJ/mol. The synergistic effect between metallic cobalt NPs and nitrogen-doped graphite-like carbon layers was obviously observed and, especially, the graphitic N species plays a key role during the oxidation reaction. The structure-performance relationship illustrated that EB oxidation was a free radical reaction through 1-phenylethanol as an intermediate, and the possible reaction mechanistic has been proposed.

Paeoniflorin Inhibits LPS-Induced Activation of Splenic CD4+ T Lymphocytes and Relieves Pathological Symptoms in MRL/lpr Mice by Suppressing IRAK1 Signaling.

Interleukin-1receptor-associated kinase 1 (IRAK1) plays a critical role in systemic lupus erythematosus (SLE). It was reported that SLE was associated with an inflammatory response mediated by defective immune tolerance, including overproduction of autoantibodies, chronic inflammation, and organ damage. Previous reports stated paeoniflorin (PF) had an immunosuppressive effect. The purpose of this study was to determine the anti-inflammatory effect of PF in SLE and its underlying mechanisms. Followed by induced with lipopolysaccharide (LPS), the splenocytes and the isolated CD4+ T lymphocytes of MRL/lpr mice were divided into three groups: control group, LPS group, and LPS + PF group, respectively. MRL/MP mice were used as the control group (treated with distilled water). The MRL/lpr mice were randomly divided into three groups: the model group (treated with distilled water), the prednisone group, and the PF group. The MRL/lpr mice were treated with prednisone acetate (5 mg/kg) and PF (25, 50, and 75 mg/kg) for eight weeks. Subsequently, ELISA, qRT-PCR, western blotting, HE, and Masson staining were performed to detect various indicators. The results of Cell Counting Kit-8 (CCK-8) showed that 10 µg/mL of LPS had the optimum effect on cell viability, and 50 µmol/L of PF had no obvious cytotoxicity to LPS-treated cells. PF reduced the expression level of IRAK1-nuclearfactor-κB (NF-κB) and its downstream inflammatory cytokines in the splenocytes and CD4+ T lymphocytes of MRL/lpr mice stimulated by LPS, especially in the latter. The serum antibody contents in the PF group mice were reduced, and the kidney damage was also alleviated accordingly. Moreover, the IRAK1/inhibitor of the nuclear factor-κB kinase (IKK)/NF-κB inhibitor (IκB)/NF-κB pathways was found to be involved in the anti-inflammation effect of PF in the kidney and spleen. In conclusion, it is thought that PF may have the potential to be used as a therapeutic agent to reduce the inflammatory activity of SLE. Inhibition of the IRAK1-NF-κB pathway may help formulate novel therapeutic tactics for SLE.

Integrating Network Pharmacology and Experimental Verification to Explore the Pharmacological Mechanisms of Aloin Against Gastric Cancer.

Purpose: This study was designed to evaluate the pharmacological mechanisms of Aloin against gastric cancer (GC) via network pharmacology analysis combined with experimental verification. Methods: Using network pharmacology methods, the potential targets of Aloin and targets related to GC were screened from public databases. The protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the core targets and pathways of Aloin against GC. The expressions of major targets predicted by network pharmacology in normal stomach tissues and GC tissues and their relationships with overall survival of GC were searched in GEPIA, HPA and DriverDBv3 database. The results of network pharmacology analysis were verified by in vitro experiments. Results: A total of 129 potential targets were retrieved by searching the intersection of Aloin and GC targets. PPI network analysis indicated that 10 targets, including AKT1 and CASP3, were hub genes. GO enrichment analysis involved 93 biological processes, 19 cellular components, and 37 molecular functions. KEGG enrichment analysis indicated that the anti-cancer effect of Aloin was mediated through multiple pathways, such as PI3K-AKT, FoxO and Ras signaling pathway. Among them, the PI3K-AKT signaling pathway, which contained the largest number of enriched genes, may play a greater role in the treatment of GC. The validation of key targets in GEPIA, HPA and DriverDBv3 database showed that the verification results for most core genes were consistent with this study. Then, the results of in vitro experiment indicated that Aloin could inhibit proliferation of NCI-N87 cells and induce cell apoptosis. The results also showed that Aloin could decrease the mRNA and protein expressions of PI3K and AKT, suggesting that Aloin can treat GC by inducing cell apoptosis and regulating the PI3K-AKT signaling pathway. Conclusion: This study identified the potential targets of Aloin against GC using network pharmacology and in vitro verification, which provided a new understanding of the pharmacological mechanisms of Aloin in treatment of GC.

Lipidomics Revealed Aberrant Lipid Metabolism Caused by Inflammation in Cardiac Tissue in the Early Stage of Systemic Lupus Erythematosus in a Murine Model.

Cardiac involvement, displayed as premature cardiovascular disease (CVD), is one of common clinical symptoms of patients with systemic lupus erythematosus (SLE), contributing to mortality of the disease. The precise underlying pathological mechanism(s) for the cardiac involvement in lupus remains poorly understood. Lipids and their metabolites are directly involved in atherosclerosis development, oxidative stress, and inflammation, which are closely related to the development of CVD. In the study, shotgun lipidomics was exploited to quantitatively analyze cellular lipidomes in the cardiac tissue of MRL/lpr mice at two different time points (i.e., pre-lupus and lupus state) with/without treatment with glucocorticoids (GCs). Urine protein, spleen index, and renal histopathological evaluation of the mice were also performed for assessment of SLE onset and/or outcome. Lipidomics analysis revealed that the deposition of cholesterol and the aberrant metabolism of lipids caused by the increased energy metabolism and the enhanced activation of phospholipases, both of which were originally induced by inflammation, were already present in cardiac tissues from lupus-prone mice even at pre-lupus state. These lipid alterations could further induce inflammation and autoimmune responses, accelerating the process of CVD. In addition, the present study also demonstrated that GCs therapy could not only delay the progression of SLE, but also partially corrected these alterations of lipid species in cardiac tissue due to their anti-inflammatory effect. Thus, the medications with better anti-inflammatory effect might be a useful therapeutic method for premature CVD of SLE.

Jieduquyuzishen Prescription Attenuates Renal Fibrosis in MRL/lpr Mice via Inhibiting EMT and TGF-ß1/Smad2/3 Pathway.

Jieduquyuziyin prescription (JP) has been used to treat lupus nephritis (LN) and its effectiveness in the treatment of LN has been clinically proven, but the underlying mechanisms have yet to be completely understood. This aim of this study was to clarify the efficacy of JP on the epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells and the molecular mechanisms of JP in MRL/lpr mice. In vivo, we observed the therapeutic actions of JP in MRL/lpr mice as well as its antifibrosis effect and potential mechanism. In vitro, we evaluated the role of JP in EMT and its possible mechanism through the EMT of human renal proximal tubular epithelial cells (HK-2) induced by transforming growth factor-beta 1 (TGF-ß1) and M2c macrophages. HK-2 cells were treated with JP-treated serum, and MRL/lpr mice were treated by JP for 8 weeks. The results showed that JP alleviated disease activity, improved renal function, decreased proteinuria, and improved renal injury and fibrosis in MRL/lpr mice. Furthermore, JP suppressed the activation of the TGF-ß1/Smad2/3 signaling pathway, upregulated the E-cadherin levels, and downregulated the Vimentin and mesenchymal α-smooth muscle actin (α-SMA) levels in the kidney of MRL/lpr mice. JP was further found to prevent the TGF-ß1 and M2c macrophages-induced EMT of HK-2 cells. Collectively, JP could alleviate the disease activity of MRL/lpr mice, improve renal function, and attenuate renal fibrosis, and its underlying mechanisms may be related to the inhibition of EMT and TGF-ß1/Smad2/3 signaling pathway.

Jieduquyuziyin Prescription alleviates hepatic gluconeogenesis via PI3K/Akt/PGC-1α pathway in glucocorticoid-induced MRL/lpr mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Jieduquyuziyin prescription (JP) is a traditional Chinese medicine (TCM) formula. According to both TCM theory and more than a decade of clinical practice, JP has been testified to be effective for systemic lupus erythematosus (SLE) treatment as an approved hospital prescription in China. AIM OF THE STUDY: To determine the effect of JP on the treatment of SLE by glucocorticoid (GC) and to further examine the molecular mechanisms. MATERIALS AND METHODS: We conducted in vivo experiments to estimate the effect of JP on hepatic gluconeogenesis in MRL/lpr mice treated with GC. Additionally, isoproterenol (ISO) induced hepatic gluconeogenesis model and GC-treated MRL/lpr mouse hepatocytes were carried out in vitro experiments to verify the effect of JP on gluconeogenesis. RESULTS: The results showed that JP combined with GC could effectively alleviate the lupus symptoms in MRL/lpr mice and improve the pathological changes of the kidney and liver. And the combination of JP reduced the side effects caused by GC, which was related to the inhibition of GC-induced hepatic gluconeogenesis in MRL/lpr mice. Specifically, JP up-regulated the expression of glucocorticoid receptor (GR) α, phosphoinositide-3-kinase (PI3K) and Akt restrained by GC to reduce the production of forkhead box O1 (FoxO1), peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), and the gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). In vivo, the use of JP either alone or with GC could reduce spleen enlargement, high levels of serum antibodies, aggravated urine protein and renal pathological damage in MRL/lpr mice. Furthermore, the glucose content was reduced in the liver of MRL/lpr mice treated with JP, and the liver damage and steatosis were also alleviated. In vitro, the expressions of PI3K and Akt increased and the expressions of FoxO1, PGC-1α, PEPCK and G6Pase decreased after JP treatment in ISO-treated hepatocytes. Compared with MRL/MP mice, we found that JP could significantly inhibit the expression of gluconeogenesis in the hepatocytes of MRL/lpr mice induced by GC to a greater extent. CONCLUSIONS: The therapeutic effect of JP on GC-induced is likely related to hepatic gluconeogenesis, which provides a new perspective to reveal the positive role of JP in SLE.

Azo-Functionalized Zirconium-Based Metal-Organic Polyhedron as an Efficient Catalyst for CO2 Fixation with Epoxides.

Chemical fixation of CO2 as C1 source at ambient temperature and low pressure is an energy-saving way to make use of the green-house gas, but it still remains a challenge since efficient catalyst with high catalytic active sites is required. Here, a novel monoclinic azo-functionalized Zr-based metal-organic polyhedron (Zr-AZDA) has been prepared and applied in CO2 fixation with epoxides. The inherent azo groups not only endow Zr-AZDA with good solubilization, but also act as basic sites to enrich CO2 showing efficient synergistic catalysis as confirmed by TPD-CO2 analysis. XPS results demonstrate that the Zr active sites in Zr-AZDA possess suitable Lewis acidity, which satisfies both substrates activation and products desorption. DFT calculation indicates the energy barrier of the rate-determining step in CO2 cycloaddition could be reduced remarkably (by ca. 60.9 %) in the presence of Zr-AZDA, which may rationalize the mild and efficient reaction condition employed (80 °C and 1 atm of CO2 ). The work provides an effective multi-functional cooperative method for improvement of CO2 cycloaddition.

Metabolic Disturbance and Th17/Treg Imbalance Are Associated With Progression of Gingivitis.

Objective: This study sought to explore the role of metabolic disturbance in immunoregulation of gingivitis targeting T helper 17 cells (Th17)/regulatory T cell (Treg). Materials and Methods: A total of 20 gingivitis patients and 19 healthy volunteers were recruited. Quantitative real time polymerase chain reaction (qRT-PCR) was used to evaluate expression patterns of Forkhead box protein P3 (Foxp3), transforming growth factor-ß (TGF-ß), retinoid-related orphan receptor-gammat (RORγt) and interleukin 17A (IL-17A) in the peripheral blood lymphocytes of subjects across the two groups. Moreover, the enzyme-linked immunosorbent assay (ELISA) technique was used to detect levels of TGF-ß, IL-4, IL-6,TL-10 and L-17A secreted in the plasma as well as the SIgA secreted in saliva. Flow cytometry was used to detect the percentage of CD4+CD25+ Foxp3+Treg cells and the percentage of CD4+IL-17A+ Th17 cells in whole blood of subjects in both groups. Gas chromatography-mass spectrometry (GC-MS) was employed to analyze the plasma metabolites in the gingivitis patient group. Statistical analysis was applied to determine whether the plasma metabolites and related metabolic pathways significantly differed between gingivitis patients and healthy controls. Ingenuity pathway analysis (IPA) was employed to identify the potential relation between the metabolites and the Th17 and Treg related pathway. Results: The percentages of CD4+IL17A+Th17 cells and IL-17 significantly increased in the peripheral blood in the gingivitis group. Moreover, the upregulation of IL-17A mRNA and RORγt mRNA were also found in the gingivitis group. However, the percentage of CD4+CD25+ Foxp3+Treg cells and Foxp3 mRNA in the whole blood did not significantly change. However, TGF-ß mRNA as well as TGF-ß, IL-4, IL-6, IL-10 in the periperial blood and SIgA in the saliva were higher in the gingivitis group. Notably, that the ratio of Th17/Treg cells was significantly increased during peripheral circulation. Furthermore, we identified 18 different metabolites which were differentially expressed in plasma between the gingivitis and healthy control groups. Notably, the levels of cholesterol, glycerol 1-octadecanoate, d-glucose, uric acid, cyclohexaneacetic acid, 3-pyridine, tryptophan, and undecane 2,4-dimethyl were significantly up-regulated. whereas the levels of lactic acid, glycine, linoleic acid, monopalmitic acid, glycerol, palmitic acid, pyruvate, 1-(3-methylbutyl)-2,3,4,6-tetramethylbenzene, 1 5-anhydro d-altrol, and boric acid were down-regulated in the gingivitis group, relative to healthy controls. IPA showed that these metabolites are connected to IL17 signaling, TGF-B signaling, and IL10 signaling, which are related closely to Th17 and Treg pathway. Conclusion: Overall, these results showed that disturbance to glycolysis as well as amino and fatty acid metabolism are associated with Th17/Treg balance in gingivitis. Impaired immunometabolism may influence some periodontally involved systemic diseases, hence it is a promising strategy in targeted development of treatment therapies.

Altered oral microbiota composition associated with recurrent aphthous stomatitis in young females.

ABSTRACT: Oral microbiota has been implicated in pathogenesis of recurrent aphthous stomatitis (RAS), which is a common mucosal disorder with unclear etiology. This study has explored the association between oral microbiota disorder and RAS in high-risk young female population.Forty-five young females were enrolled, including 24 RAS patients and 21 healthy individuals. Oral microbiome was analyzed by Illumina Miseq sequencing.Oral microbiota associated with RAS was characterized by the lower alpha-diversity indices (Chao1 and ACE). Several infectious pathogens increased in RAS, such as genera Actinobacillus, Haemophilus, Prevotella and Vibrio. The PICRUSt analysis indicated that the oral microbiota might be related with the up-regulation of genes involving infectious and neurodegenerative diseases, environmental adaptation, the down-regulation of genes involving basal metabolism, such as carbohydrate, energy, and amino acid metabolism.This study indicated that oral microbiota may play a significant role in RAS development.

Epigallocatechin Gallate Protects against MNNG-Induced Precancerous Lesions of Gastric Carcinoma in Rats via PI3K/Akt/mTOR Pathway.

OBJECTIVE: To evaluate the therapeutic effect of epigallocatechin gallate (EGCG) on precancerous lesions of gastric carcinoma (PLGC) and to determine whether EGCG protects against PLGC by regulating PI3K/Akt/mTOR pathway. METHODS: Twenty-four male Wistar rats were randomly divided into 3 groups: normal control group (NC), PLGC model group (MC), and group of PLGC rats treated with EGCG (MC + EGCG). 1-Methyl-3-nitro-1-nitrosoguanidine (MNNG) and sodium salicylate were combined and used to establish the PLGC rat animal model. The therapeutic effect of EGCG on PLGC was evaluated by body weight and pathological lesions of gastric mucosa in PLGC rats. Quantitative polymerase chain reaction (qPCR) was applied to measure the mRNA expressions of PI3K, Akt, and mTOR. The protein expressions of cleaved caspase-3, PTEN, PI3K, p-PI3K, Akt, p-Akt, p-mTOR, and mTOR were determined by automated western immunoblotting. RESULTS: The body weight decreased in PLGC rats while EGCG significantly increased body weight. The gastric mucosa of PLGC rats exhibited the pathological lesions of atrophy, intestinal metaplasia, and atypical hyperplasia while EGCG could ameliorate the pathological lesions. EGCG could upregulate the expressions of cleaved caspase-3 and PTEN and reduce the expressions of PI3K, Akt, and mTOR. CONCLUSIONS: EGCG ameliorated pathological lesions of PLGC and exerted the effect of apoptosis promotion in PLGC rats. The apoptotic pathway triggered by EGCG may be related to inhibition of PI3K/Akt/mTOR pathway. It provided a theoretical basis for the PLGC treatment and gastric cancer prevention.

Oxidative stress-induced aberrant lipid metabolism is an important causal factor for dysfunction of immunocytes from patients with systemic lupus erythematosus.

There exist close relationships among oxidative stress, dyslipidaemia, inflammation, and autoimmune response in patients with systemic lupus erythematosus (SLE). Dysfunction and/or dysregulation of immunocytes is one of the major characteristics of SLE pathogenesis. Lipids play many important roles in biological processes and cellular functions. We hypothesized that oxidative stress-induced aberrant lipid metabolism and integrity presented in immunocytes is one of the early events in patients, thereby leading to enhanced production of IgG autoantibodies and cytokines. Herein, shotgun lipidomics was employed for quantitative analysis of cellular lipidomes in peripheral blood mononuclear cells (PBMC) both freshly isolated from SLE patients and cultured with treatment. The levels of IgG autoantibodies and cytokines in cell culture media and serum samples from lupus-prone mice treated with a natural, powerful antioxidant isotonix OPC-3 were measured by ELISA kits. IgG antibody deposition in glomeruli of the mice was determined by immunofluorescence analysis. Lipidomics analysis of PBMC from 33 SLE patients and 28 healthy controls revealed aberrant lipid metabolism in PBMC from the patients. The changes included significantly reduced plasmalogens, markedly increased lysophospholipids, altered phosphatidylserines, and accumulated 4-hydroxyalkenals. These alterations of lipids in SLE PBMC could be significantly corrected after cultured with the antioxidant in vitro. Parallel to the IgG antibody deposition in glomeruli, the concentrations of cytokines (i.e., IL-10, IL-6, and TNF-α) and autoantibodies (e.g., IgG antiphospholipid and anti-dsDNA antibodies) in culture medium and serum samples from the mice after treatment with the antioxidant were also significantly reduced compared with those of the SLE group. The results clearly demonstrated that correction of the aberrant lipid metabolism led to inhibition of the autoimmune reactions of PBMC after reduction of the increased oxidative stress. The current study also revealed potential drug treatment of SLE with lesser adverse effects through reducing the aberrant lipid metabolism with an effective antioxidant.

Herpes simplex virus type I-infected disorders alter the balance between Treg and Th17 cells in recurrent herpes labialis patients.

Recurrent herpes labialis (RHL) is a common skin disease that is often caused by herpes simplex virus type I (HSV-1), but its immunology and pathogenesis remain unclear. The balance of Th17/Treg cells is crucial for maintaining immune homeostasis. This study aimed to investigate whether the balance of Th17/Treg cells and related cytokines may be a determinant occurrence in patients with RHL. This is a clinical experimental research based on clinical observation and analysis. We collected RHL patients from the outpatient clinic of the Department of Dermatology of Zhejiang Chinese Medical University (Hangzhou, China) in 2017, conducted questionnaire survey and signed informed consent. Peripheral blood was collected from 30 patients with RHL and 30 healthy volunteers. Flow cytometry was used to detect the percentages of Treg cells and Th17 cells. Protein microarrays coated with 20 cytokines related to T-cell subsets were performed. Enzyme-linked immunosorbent assay (ELISA) assay was conducted to further verify the expression levels of the cytokines that were screened by protein microarrays. Percentages of Th17/Treg cells in peripheral blood of RHL patients were significantly increased compared to those in healthy volunteers. The fold changes of GM-CSF, IL-4, TGF-ß, IL-12, IL-10, IL-17F, and TNF-α were significantly increased compared with healthy volunteers. In addition, the expression of IL-4, IL-10, and TGF-ß in the serum of RHL patients increased significantly. Our results indicated an imbalance of Th17/Treg cells in RHL, and this imbalance is probably an important factor in the occurrence, development, and recovery of RHL.

Metal-free synthesis of phosphinoylchroman-4-ones via a radical phosphinoylation-cyclization cascade mediated by K2S2O8.

A variety of chroman-4-ones bearing phosphine oxide motifs were conveniently synthesized from readily available diphenylphosphine oxides and alkenyl aldehydes via a metal-free tandem phosphinoylation/cyclization protocol. The reaction utilizes K2S2O8 as oxidant and proceeds in DMSO/H2O at environmentally benign conditions with a broad substrate scope and afforded the title compounds in moderate yields.