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Trimethylamine N-oxide (TMAO) is a gut microbiota metabolite derived from trimethylamine- containing nutrient precursors such as choline, L-carnitine, and betaine, which are rich in many vegetables, fruits, nuts, dairy products, and meats. An increasing number of clinical studies have demonstrated a strong relationship between elevated plasma TMAO levels and adverse cardiovascular events. It is commonly agreed that TMAO acts as an independent risk factor and a prognostic index for patients with cardiovascular disease. Although most animal (mainly rodent) data support the clinical findings, the mechanisms by which TMAO modulates the cardiovascular system are still not well understood. In this context, we provide an overview of the potential mechanisms underlying TMAO-induced cardiovascular diseases at the cellular and molecular levels, with a focus on atherosclerosis. We also address the direct effects of TMAO on cardiomyocytes (a new and under-researched area) and finally propose TMAO as a potential biomarker and/or therapeutic target for diagnosis and treatment of patients with cardiovascular disease.

Luteolin (LUT) possesses multiple biologic functions and has beneficial effects for cardiovascular and cerebral vascular diseases. Here, we investigated the protective effects of LUT against subarachnoid hemorrhage (SAH) and the involvement of underlying molecular mechanisms. In a rat model of SAH, LUT significantly inhibited SAH-induced neuroinflammation as evidenced by reduced microglia activation, decreased neutrophil infiltration, and suppressed proinflammatory cytokine release. In addition, LUT markedly ameliorated SAH-induced oxidative damage and restored the endogenous antioxidant systems. Concomitant with the suppressed oxidative stress and neuroinflammation, LUT significantly improved neurologic function and reduced neuronal cell death after SAH. Mechanistically, LUT treatment significantly enhanced the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), while it downregulated nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome activation. Inhibition of Nrf2 by ML385 dramatically abrogated LUT-induced Nrf2 activation and NLRP3 suppression and reversed the beneficial effects of LUT against SAH. In neurons and microglia coculture system, LUT also mitigated oxidative stress, inflammatory response, and neuronal degeneration. These beneficial effects were associated with activation of the Nrf2 and inhibitory effects on NLRP3 inflammasome and were reversed by ML385 treatment. Taken together, this present study reveals that LUT confers protection against SAH by inhibiting NLRP3 inflammasome signaling pathway, which may be modulated by Nrf2 activation.

Introduction Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swept rapidly throughout the world. So far, no therapeutics have yet proven to be effective. Ribavirin was recommended for the treatment of COVID-19 in China because of its in vitro activity. However, evidence supporting its clinical use with good efficacy is still lacking. Methods A total of 208 confirmed severe COVID-19 patients who were hospitalized in Wuhan Union West Campus between 1 February 2020 and 10 March 2020 were enrolled in the retrospective study. Patients were divided into two groups based on the use of ribavirin. The primary endpoint was the time to clinical improvement. The secondary endpoints included mortality, survival time, time to throat swab SARS-CoV-2 nucleic acid negative conversion, and the length of hospital stay. Results 68 patients were treated with ribavirin while 140 not. There were no significant between-group differences in demographic characteristics, baseline laboratory test results, treatment, and distribution of ordinal scale scores at enrollment, except for coexisting diseases especially cancer (ribavirin group vs no ribavirin group, P = 0.01). Treatment with ribavirin was not associated with a difference in the time to clinical improvement (P = 0.48, HR = 0.88, 95% CI = 0.63–1.25). There were also no significant differences between-group in SARS-CoV-2 nucleic acid negative conversion, mortality, survival time, and the length of hospital stay. Conclusions In hospitalized adult patients with severe COVID-19, no significant benefit was observed with ribavirin treatment.

Borylated aza-arenes are of great importance in the area of organic synthesis. A radical borylative cyclization of isocyanoarenes with N-heterocyclic carbene borane (NHC-BH3) under metal-free conditions was developed. The reaction allows the efficient assembly of several types of borylated aza-arenes (phenanthridines, benzothiazoles, etc.), which are difficult to access using alternative methods. Mild reaction conditions, a good functional-group tolerance, and generally good efficiencies were observed. The utility of these products is demonstrated, and the mechanism is discussed.

A mild and selective Cp*Ir(III)- and Cp*Rh(III)-catalyzed direct C(sp2)–H amination of arenes and three types of nitrene precursor reagents is reported, with the assistance of a thioether directing group. This redox-neutral protocol proceeds under mild reaction conditions, has a broad substrate scope and high functional-group compatibility and generates the desired aminated products in moderate to excellent yields. The reaction represents the first example of a thioether-directed Cp*Ir(III)- and Cp*Rh(III)-catalyzed C(sp2)–H direct amination reaction. Moreover, azide compounds were employed as a diverse and robust aminating reagent for the first time in a thioether-directed C–H functionalization reaction.

A novel approach to prepare a HAu(Cys)2 compound via a ligand exchange reaction in an aqueous solution is introduced. The prepared HAu(Cys)2 compound is shown as a very good main salt for environme...

This study explored the influence of ferrous iron (Fe2+) addition on ammonium nitrogen (NH4-N) removal and microbial communities in horizontal subsurface flow constructed wetlands (HSSFs) at different carbon/nitrogen (C/N) ratios. Fe2+ addition could improve NH4-N removal under the C/N ratio of 2.1 and alter the microbial community structure. The microbial diversity and functional genes at the C/N ratio of 2.1 were enhanced by the addition of 50 mg/L Fe2+, with the increases observed in NH4-N and total nitrogen (TN) removal. This indicates the enhancement of nitrogen removal by Fe2+ addition with the presence of high organic matter. However, the enhancement of Fe2+ on chemical oxygen demand removal was not obvious overall. The relative abundance of functional genes and those related to energy metabolism, xenobiotic biodegradation, and metabolism decreased significantly in HSSFs with Fe2+ at C/N ratio of 1.1, whereas they increased in HSSFs with the addition of 50 mg/L Fe2+ at C/N ratio of 2.1.

Strain C was isolated from chicken manure, and its phenotypic characteristics were gram-stain negative, yellow-pigmented, aerobic bacterium, heterotrophic, non-motile, chemoorganotrophic, non-gliding as well as non-spore-forming. A 16S rRNA gene sequence analysis showed that strain C occupied a distinct lineage within the family of the genus Chryseobacterium, and it shared highest sequence similarity with Chryseobacterium solincola strain 1YB-R12 (80%). The new isolate has been studied for removing ammonium-nitrogen (NH4-N) and the optimization of suitable conditions. The strain C was able to degrade over 42.8% of NH4-N during its active growth cycle. Experimental study of the effect of temperature and pH on NH4-N removal showed that the temperature and pH optima for NH4-N removal were 30–35℃ and 4–8, respectively. The results indicated that strain C shows a potential application for wastewater treatment.

Solid/liquid interfacial structure occupies great importance in chemistry, biology, and materials. In this paper, by combining EC-SERS study and DFT calculation, we reveal the adsorption and dimerization of sulfite (SO32-) at a gold electrode/water solution interface, and establish an adsorption displacement strategy to suppress the dimerization of sulfite. At the gold electrode/sodium sulfite solution interface, at least two layers of SO32- anions are adsorbed on the electrode surface. As the applied potential shifts negatively, the adsorption strength of the first SO32- layer is weakened gradually and then is dimerized with the second orientated SO32- layer to form S2O52-, and S2O52- is further reduced to S2O32-. After hydroxyethylene disphosphonic acid (HEDP) is introduced to the gold electrode/sodium sulfite solution interface, the second oriented SO32- layer is replaced by a HEDP coadsorption layer. This results in the first layer of SO32- being desorbed directly without any structural transformation or chemical reaction as the potential shifts negatively. The suppression of sulfite dimerization by HEDP is more clear at the gold electrode/gold sulfite solution interface owing to the electroreduction of gold ions. Furthermore, the electrochemical studies and electrodeposition experiments show that as the sulfite dimerization reaction is suppressed, the electroreduction of gold ions is accelerated, and the deposited gold coating is bright and dense with finer grains.

Nuclear factor (NF)-κB–ty -50mediated neuroinflammation plays a crucial role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). As an important negative feedback regulator of NF-κB, A20 is essential for inflammatory homeostasis. Herein, we tested the hypothesis that A20 attenuates EBI by establishing NF-κB–associated negative feedback after experimental SAH. In vivo and in vitro models of SAH were established. TPCA-1 and lentivirus were used for NF-κB inhibition and A20 silencing/overexpression, respectively. Cellular localization of A20 in the brain was determined via immunofluorescence. Western blotting and enzyme-linked immunosorbent assays were applied to observe the expression of members of the A20/tumor necrosis factor receptor-associated factor 6 (TRAF6)/NF-κB pathway and inflammatory cytokines (IL-6, IL-1β, TNF-α). Evans blue staining, TUNEL staining, Nissl staining, brain water content, and modified Garcia score were performed to evaluate the neuroprotective effect of A20. A20 expression by astrocytes, microglia, and neurons was increased at 24 h after SAH. A20 and inflammatory cytokine levels were decreased while TRAF6 expression was elevated after NF-κB inhibition. TRAF6, NF-κB, and inflammatory cytokine levels were increased after A20 silencing but suppressed with A20 overexpression. Also, Bcl-2, Bax, MMP-9, ZO-1 protein levels; Evans blue, TUNEL, and Nissl staining; brain water content; and modified Garcia score showed that A20 exerted a neuroprotective effect after SAH. A20 expression was regulated by NF-κB. In turn, increased A20 expression inhibited TRAF6 and NF-κB to reduce the subsequent inflammatory response. Our data also suggest that negative feedback regulation mechanism of the A20/TRAF6/NF-κB pathway and the neuroprotective role of A20 to attenuate EBI after SAH.

Fifteen chalcone derivatives 3a-3o were synthesized, and evaluated as multifunctional agents against Alzheimer's disease. In vitro studies revealed that these compounds inhibited self-induced Aβ1-42 aggregation effectively ranged from 45.9-94.5 % at 20 μM, and acted as potential antioxidants. Their structure-activity relationships were summarized. In particular, (2E)-3-[4-(dimethylamino)phenyl]-1-(pyridin-2-yl)prop-2-en-1-one (3g) exhibited an excellent inhibitory activity of 94.5 % at 20 μM, and it could disassemble the self-induced Aβ1-42 aggregation fibrils with ratio of 57.1 % at 20 μM concentration. In addition, compound 3g displayed good chelating ability for Cu2+ , and could effectively inhibit and disaggregate Cu2+ -induced Aβ aggregation. Moreover, compound 3g exerted low cytotoxicity, significantly reversed Aβ1-42 -induced SH-SY5Y cell damage. More importantly, compound 3g remarkably ameliorated scopolamine-induced memory impairment in mice. In summary, all the results revealed compound 3g was a potential multifunctional agent for AD therapy.

Chronic myelogenous leukemia (CML) typically results from a reciprocal translocation between chromosomes 9 and 22 to produce the bcr-abl oncogene that when translated, yields the p210 BCR-ABL protein in more than 90% of all CML patients. This protein has constitutive tyrosine kinase activity that activates numerous downstream pathways that ultimately produces uncontrolled myeloid proliferation. Although the use of the BCR-ABL tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, dasatinib, bosutinib, and ponatinib have increased the overall survival of CML patients, their use is limited by drug resistance and severe adverse effects. Therefore, there is the need to develop novel compounds that can overcome these problems that limit the use of these drugs. Therefore, in this study, we sought to find novel compounds using Hypogen and Hiphip pharmacophore models based on the structures of clinically approved BCR-ABL TKIs. We also used optimal pharmacophore models such as three-dimensional queries to screen the ZINC database to search for potential BCR-ABL inhibitors. The hit compounds were further screened using Lipinski’s rule of five, ADMET and molecular docking, and the efficacy of the hit compounds was evaluated. Our in vitro results indicated that compound ZINC21710815 significantly inhibited the proliferation of K562, BaF3/WT, and BaF3/T315I leukemia cells by inducing cell cycle arrest. The compound ZINC21710815 decreased the expression of p-BCR-ABL, STAT5, and Crkl and produced apoptosis and autophagy. Our results suggest that ZINC21710815 may be a potential BCR-ABL inhibitor that should undergo in vivo evaluation.

Lanthanide coordination polymers (Ln-CPs) {[Ln(HL)2(H2O)3]·(H2O)4·Cl}n (Ln = Dy, 1; Eu, 2; Sm, 3) and [Ln0.18(HL)0.18(CH3COO)0.36(H2O)0.54]n (Ln = La, 4; H2L = 2-(hydroxymethyl)-1H-benzo[d]imidazole-5-carboxylic acid) have been successfully assembled by Ln3+ ions and asymmetric carboxylic acid ligand under solvothermal conditions. The structures of the complexes 1–4 were determined by single crystal X-ray diffraction and further characterized by elemental analyses, IR spectroscopy, powder X-ray diffraction (PXRD) and thermogravimetric analysis (TGA). The structure analysis display that complexes 1–3 are isostructural three-dimensional (3D) supramolecular network. Complexes 1–4 were constructed by hydrogen bonding interactions between the coordinated water molecules and the O atoms of the hydroxy group or free chloride ions. Furthermore, luminescence properties of complexes 1–4 have been measured in the solid state at room temperature. Complex 2 exhibits a strong red luminescence upon excitation at 283 nm and its lifetimes is 33.554 ns. In addition, magnetic studies reveal that complex 1 has a weak antiferromagnetic interaction.

The flexible synthesis of tetra- and triarylethenes bearing different aryl groups has been a long-standing challenge in organic synthesis. Here we report a palladium-catalysed syn-diarylation of arylethynyl N-methyliminodiacetyl (MIDA) boronates. The products, triarylalkenyl N-methyliminodiacetyl boronates, allow a step-economic and modular synthesis of tetra- or triarylethenes via a subsequent stereospecific Suzuki-Miyaura coupling reaction or base-promoted protodeborylation, respectively. Use of the sp3-B(MIDA) masked aryl alkyne is the key factor for success by offering an exceptionally good regioselectivity for the boron-retentive coupling. The unusual regioselectivity is believed to arise from the stabilization due to the strong electron donation from the C−Pd σ bond to the p-orbital of boron in the transition state of migratory insertion. A broad range of differently substituted tetra- and triarylethenes are constructed in good yields and geometrical control. Synthetic manipulation of the C-B bond also enables the facile construction of several other types of tetra-substituted alkenes. The synthesis of tri- and tetra-aryl alkenes is limited by poor regio- and stereoselectivity. Here MIDA boronate-substituted aryl alkynes are used to achieve regioselective three-component diarylation of the alkyne and to provide a cross-coupling handle for subsequent elaboration to tri- or tetra-substituted products.

Six new coordination polymers(CPs) {[Cd(L1)(CHDA)]·H2O}n (1), [Zn3(L1)2(1,2,4-BTC)2(H2O)4]n (2), [Zn(L2)(D-CAM)(H2O)]n (3), [Zn3(L2)(1,2,4-BTC)2(H2O)4]n (4), [Cd(L2)(1,3,5-HBTC)]n (5) and {[Zn(L2)(4,4´-BOA)]·H2O}n (6) (L1 = 3,6-bis(imidazol-1-yl)pyridazine, L2 = 3,6-bis(benzimidazol-1-yl)pyridazine, 1,4-H2CHDA = (1 S,4 S)-cyclohexane-1,4-dicarboxylic acid, 1,2,4-H3BTC = benzene-1,2,4-tricarboxylic acid, D-CAM = (1 R,3 S)-1,2,2-trimethylcyclopentane-1,3-dicarboxylic acid, 1,3,5-H3BTC = benzene-1,3,5-tricarboxylic acid, 4,4´-H2OBA = 4,4´-oxydibenzoic acid) were achieved by reactions of the corresponding metal salt with mixed organic ligands. Their structures were determined by single-crystal X-ray diffraction, IR spectra, elemental analysis, powder X-ray diffraction and thermogravimetric analysis. They exhibit varied structures, complexes 4 and 5 are porous three-dimensional (3D) frameworks, while 2 and 3 are 3D supermolecule structure formed by hydrogen-bonding interactions, and 1 is a two-dimensional (2D) network and 6 is an infinite one-dimensional (1D) chain. In addition, the fluorescent emission, fluorescence lifetimes of L1, L2 and 1–6 have been investigated and discussed.

Three new coordination polymers [Co(L)(1,2,4,5-BTC)0.5(H2O)]n (1), {[Ni(L)(1,2-BDC)(H2O)3]·H2O}n (2) and {[Zn3(L)2(1,3,5-BTC)2(H2O)2]·3H2O}n (3) [L = 3,6-bis(imidazole-1-yl)pyridazine, H4BTC = 1,2,4,5-Benzenetetracarboxylic acid, H2BDC = 1,2-Benzenedicarboxylic acid, H3BTC = 1,3,5-Benzenetricarboxylic acid] were synthesized based on a rigid ligand L and different aromatic carboxylic acid ligands under solvothermal conditions. The structures of the complexes 1–3 were determined by single crystal X-ray diffraction and further characterized by elemental analyses, IR spectroscopy, powder X-ray diffraction (PXRD), and thermogravimetric analysis (TGA). In addition, UV–vis diffuse-reflectance spectra demonstrate wide band gaps. The structural analysis reveals that complex 1 features a two-dimensional (2D) layer structure with a 6-connected sql topological net. Complex 2 shows a one-dimensional (1D) zigzag chain, while complex 3 displays a three-dimensional (3D) coordination network which exhibits an intriguing (5,5,6)-connected novel topological net with the point symbol of {32·42·53·63}2{32·44·54·63·72}. Moreover, the luminescence property and lifetimes of complex 3 has been measured at room temperature. Furthermore, in the complex-catalyzed homocoupling reaction of 4-substituted aryl iodides, the catalytic activities of complexes 1–3 have also been studied and discussed.

A hydrothermal procedure has been developed to produce azine-linked COFs by conducting condensation reactions of hydrazine with hydroxy-substituted 1,3,5-triformylbenzene in water. The synthesis of one representative COF was drastically promoted by water in comparison with the traditional solvothermal reactions in organic solvents. This synthesis has advantages of large-scale production, catalyst-free reaction, short reaction time, and the obtained COF exhibits higher crystallinity and surface area.

Benzofused nitrogen heterocycles are prevalent as key core structural motifs in functional molecules. Major syntheses of benzofused nitrogen heterocycles focus on construction of the heterocyclic ring starting from (poly)substituted benzene derivatives. Given that polysubstituted benzene derivatives are not always easily available, the flexibility of these methods may be problematic. The direct benzannulation reactions of simple N-heterocycles thus provide a complementary and valuable strategy. However, this approach has been far less explored, especially when nonprefunctionalized N-heterocycles are used as starting materials. In recent years, the metal-catalyzed direct functionalization of an inert C–H bond has become a powerful tool to construct (hetero)aromatics. In the C–H benzannulation reactions, alkynes, activated alkenes, enaldiazo compounds, and biaryl compounds were previously utilized as efficient coupling partners. Reported herein is a de novo synthesis of a benzene ring through the rhodium-ca...

For the first time, we present an original sensing strategy with an ultra-wide detection window from 17 nM to 20 mM to detect SCN- ions. Initially, we investigated the clustering and optical properties of noble metal sol nanoparticles (NPs) due to the competitive interaction of thiocyanate ions (SCN-) and cetyltrimethylammonium bromide (CTAB) under weak acidic conditions, and found that different dimensions and scales of nanoclusters containing the alkyne-embedded Au@Ag NPs and relatively small Ag NPs could be achieved by the mediation of CTAB through electrostatic forces and hydrophobic interaction, in which SCN- could be covalently bonded with the silver surface of NPs to form a compact molecular layer (-Ag-S-C[triple bond, length as m-dash]N), and CTAB could only occupy remaining sites. In this process, we found that SCN- always runs counter to CTAB and tends to dissolve nanoclusters, so that they occupy the exposed surface of NPs in nanoclusters rather than the binding sites of one another. Remarkably, when the concentration of SCN- initially increased, two highly recognizable SERS emissions, which were assigned to alkyne reporter molecules (2208 cm-1) and C[triple bond, length as m-dash]N of SCN- (2110 cm-1), respectively, were rapidly detected, and their ratios (I2110/I2208) increased linearly proportional to the concentration of SCN- over a range of 17 nM to 172 μM, with a limit of detection (LOD) of 10 nM. With the further increase of SCN-, small Ag NPs started to desorb from the surface of individual Au@Ag NPs and dissociated in the solution but did not contribute to SERS signals. Instead, the surface plasmon resonance (SPR) peak of pure silver NPs at 385 nm increased gradually in the range from 0.5 to 20 mM with an LOD of 0.2 mM. Of particular significance, this simple sensor in conjunction with surface-enhanced Raman-extinction spectroscopy can be used for the rapid detection of extensive samples with an ultra-wide detection window, such as body fluids (saliva, urine, and serum) and food (milk powder and brassica vegetables), which is far superior to that of ion chromatography (IC).

BACKGROUND Lactoferrin (LF) has been shown to promote bone anabolism, and the vitamin D receptor (VDR) mediates the effects of vitamin D on bone. We hypothesized that LF improves bone health by increasing VDR expression. OBJECTIVES We sought to determine the role of VDR activation in LF-induced osteogenic activity in vivo and in vitro and the underlying molecular mechanisms. METHODS Sixty male C57BL/6J mice (aged 4 wk) were randomly assigned into 6 groups and fed vitamin D-deficient (VDD; 0 IU/kg) or vitamin D-normal diet (VDN; 1000 IU cholecalciferol/kg) and administered placebo or LF (100 or 1000 mg/kg body weight) by gavage for 24 wk. Trabecular bone structure was analyzed using micro-CT, and VDR expression was assessed by immunohistochemistry. In vitro, MC3T3-E1 cells were treated with 100 μg LF/mL to evaluate its effect on VDR expression. Finally, the direct recruitment of LF to the Vdr promoter was confirmed by chromatin immunoprecipitation assay. In addition, cells were transfected with pGL3-basic Vdr vector for monitoring Vdr promoter activation using luciferase assays. RESULTS LF supplementation at 100 and 1000 mg/kg revealed an ∼6.5% (P

Background: Coronavirus disease-2019 (COVID-19) spreads rapidly throughout the world. So far, no therapeutics have yet been proven to be effective. Ribavirin was recommended for the treatment of COVID-19 because of its in vitro activity. However, evidence supporting its clinical use with good efficacy is still lacking.Methods: A total of 208 confirmed severe or critical COVID-19 patients who were hospitalized in Wuhan Union West Campus between 1 February 2020 and 10 March 2020 were enrolled in the retrospective study. Patients were divided into two groups based on the use of ribavirin. The primary endpoint was the time to clinical improvement. The secondary endpoints included mortality, survival time, time to throat swab SARS-CoV-2 nucleic acid negative conversion, and hospital duration.Results: 68 patients were treated with ribavirin while 140 not. There were no significant between-group differences in demographic characteristics, baseline laboratory test results, treatment, and distribution of ordinal scale scores at enrollment, except coexisting diseases especially cancer (ribavirin group vs no ribavirin group, P = 0.014). Treatment with ribavirin was not associated with a difference in the time to clinical improvement (P = 0.483, HR = 0.884, 95% CI = 0.627-1.247). There were also no significant differences between-group in the number of patients with SARS-CoV-2 nucleic acid negative conversion, mortality, survival time, and hospital duration. Conclusion: In hospitalized adult patients with severe or critical COVID-19, no significant benefit was observed with ribavirin treatment.

Selenoprotein V (SELENOV) contains a thioredoxin-like fold and a conserved CxxU motif with a potential redox function. This study was to assess its in vivo and in vitro roles and mechanisms in coping with different oxidant insults. In Experiment (Expt.)1, SELENOV knockout (KO) and wild type (WT) mice (male, 8-wk old) were given an ip injection of saline, diquat (DQ, 12.5 mg/kg), or N-acetyl-para-aminophenol (APAP, 300 mg/kg) (n = 10), and killed 5 h after the injection. In Expt. 2, primary hepatocytes of WT and KO were treated with DQ (0–0.75 mM) or APAP (0–6 mM) for 12 h. In Expt. 3, 293 T cells overexpressing Selenov gene (OE) were treated with APAP (0–4 mM) for 24 h or H2O2 (0–0.4 mM) for 12 h. Compared with the WT, the DQ- and APAP-injected KO mice had higher (P

OBJECTIVES: Selenoprotein V (SELENOV) contains a thioredoxin-like fold and a conserved CxxU motif with a potential redox function. Three experiments were performed to assess its in vivo and in vitro roles and mechanisms in coping with different oxidant insults. METHODS: In Expt.1, SELENOV knockout (KO) and wildtype (WT) mice (male, 8-wk old) were given an IP injection of saline, diquat (DQ, 12.5 mg/kg), or acetaminophen (APAP, 300 mg/kg) (n = 10), and killed 5 h after the injection to collect liver and blood. In Expt. 2, primary hepatocytes were isolated from the 2 genotypes, cultured in complete Williams's medium E, and treated with DQ (0, 0.25 and 0.75 mM) and APAP (0, 1, 3, and 6 mM) for 12 h. In Expt. 3, 293 T cells were transfected with a control plasmid (GFP) or the plasmid containing Selenov gene (full length, OE) and treated with APAP (0, 1, 2, and 4 mM) for 24 h or H(2)O(2) (0.1, 0.2, and 0.4 mM) for 12 h. RESULTS: In Expt. 1, the DQ and APAP injections caused greater (P

A novel lactate dehydrogenase gene, named lrldh, was cloned from Lactobacillus rossiae and heterologously expressed in Escherichia coli. The lactate dehydrogenase LrLDH is NADH-dependent with a molecular weight of approximately 39 kDa. It is active at 40 °C and pH 6.5 and stable in a neutral to alkaline environment below 35 °C. The kinetic constants, including maximal reaction rate (Vmax), apparent Michaelis–Menten constant (Km), turnover number (Kcat) and catalytic efficiency (Kcat/Km) for phenylpyruvic acid were 1.95 U mg−1, 2.83 mM, 12.29 s−1, and 4.34 mM−1 s−1, respectively. Using whole cells of recombinant E. coli/pET28a-lrldh, without coexpression of a cofactor regeneration system, 20.5 g l−1 d-phenyllactic acid with ee above 99% was produced from phenylpyruvic acid in a fed-batch biotransformation process, with a productivity of 49.2 g l−1 d−1. Moreover, LrLDH has broad substrate specificity to a range of ketones, keto acids and ketonic esters. Taken together, LrLDH is a promising biocatalyst for the efficient synthesis of d-phenyllactic acid and other fine chemicals.

Secondary brain injury following subarachnoid hemorrhage (SAH) is the critical contributor to the mortality of SAH patients. The underlying mechanisms are poorly understood. In this study, we utilized a mice model of SAH to investigate whether FoxO4 is related to the brain injury after SAH and identified its upstream regulator Akt. Experimental SAH was induced in adult male mice by prechiasmatic cistern injection. Brain FoxO4 protein levels in cytoplasm and nucleaus were examined in the sham-operated controls, and in mice 1h, 6h, 12h, 24h, 3d, and 5d after SAH induction. The Akt inhibitor LY294002 was administered by intracerebroventricular infusion to determine its effects on FoxO4. Moreover, the expression of FoxO4 was also investigated in neurons incubated with hemoglobin in vitro, which was also dertermined after inhibition of Akt. FoxO4 protein expression in the nuclei increased remarkably after SAH. The Akt inhibitor LY294002 induced more FoxO4 nuclear localization after SAH in vivo and in vitro. Our results suggest the activation of FoxO4 after SAH and which was inhibited by the increased phosphorylated Akt (p-Akt).

Four new complexes [Ni3(L1)3(H2O)10] (1), [Zn3(L2)3(H2O)]n (2), [Cd(L2)(H2O)]n (3) and [Cd2(HL2)4(H2O)4] (4) have been synthesized by the reaction of 4-(1H-tetrazol-5-yl)phenol (H2L1) and 2-(1H-tetrazol-5-yl)phenol (H2L2) with nickel, zinc, cadmium salts. Complex 1 was synthesized by H2L1 ligand at room temperature conditions, 2 and 3 are synthesized by H2L2 ligand in situ reaction under hydrothermal conditions, 4 is synthesized by H2L2 ligand at room temperature reflux conditions. All of them were characterized by elemental analysis and single-crystal X-ray diffraction, infrared spectrosopy, powder X-ray diffraction and thermogravimetric analysis (TGA). Complexes 1 and 4 are the small-size clusters, the structure of complexes 2 and 3 reveal 2D coordination network. Topologically, complexes 2 and 3 show that binodal networks with a 4-connected and the point symbol of (44·62). In addition, magnetic, fluorescence, and UV–Vis properties of these complexes have been studied.

We report the synthesis and characterization of five transition metal coordination polymers (CPs) based on M(II) (M: Co, Ni and Cu), 2-(hydroxymethyl)-1H-benzo[d]imidazole-5-carboxylic acid (H2L) ligand. They are formulated as {[Co2(HL)2(H2O)3(SO4)]·H2O}n (1), {[Co2(HL)2(H2O)2]·SiF6}n (2), {[Ni2(HL)2(H2O)3(SO4)]·2H2O}n (3), {[Ni2(HL)2(H2O)4]·H2O·SiF6}n (4), {[Cu2(HL)2(H2O)2]·SiF6}n (5). The complexes 1–5 structure were characterized by single-crystal X-ray diffraction, elemental analyses, infrared spectroscopy (IR), powder X-ray diffraction (PXRD), and thermogravimetric analyses (TGA). Complexes 1–5 are two-dimensional (2D) network type coordination polymers that 1–3, 5 crystallize in monoclinic system within the centrosymmetric space group P2(1)/c, and 4 in triclinic system P-1 space group, they show the same coordination modes (κ1-κ1)-(κ1)-(κ1)-μ3 in coordination polymers. Complexes 1 and 3 expand to three-dimensional framework by means of hydrogen bond interactions, and can be rationalized to be three-connected {63} topological network, while 2, 4, 5 exhibit the topological network with a four-connected {44·62} topological sql network. The luminescent properties (for complexes 1, 2) and UV diffuse reflectance (for complexes 1–5) in the solid state at room temperature were also investigated and discussed. Complexes 1–5 act as effective heterogeneous catalysts, under mild conditions, for the homocoupling reaction of 4-substituted aryl iodides bearing electron-donating groups (-CH3, -OCH3).

A series of indole-based [1,2,4]triazolo [4,3-a]pyridine derivatives was designed and synthesized as novel microtubulin polymerization inhibitors by using a conformational restriction strategy. These compounds exhibited moderate to potent anti-proliferative activities against a panel of cancer cell lines (HeLa, A549, MCF-7 and HCT116). Among them, compound 12d featuring a N-methyl-5-indolyl substituent at the C-6 position of the [1,2,4]triazolo [4,3-a]pyridine core exhibited the highest antiproliferative activity with the IC50 values ranging from 15 to 69 nM, and remarkable inhibitory effect on tubulin polymerization with an IC50 value of 1.64 μM. Mechanistic studies revealed that compound 12d induced cellular apoptosis and cell cycle arrest at the G2/M phase in a dose-dependent fashion. Moreover, compound 12d significantly suppressed wound closure and disturbed microtubule networks.

In the process of global transition to a sustainable low-carbon economy, the two major low-carbon energy technologies, namely, methane (CH4) storage and methane capture face the same challenge, that is, the lack of efficient adsorbents. Metal-organic framework (MOF) materials have potential value in the field of gas adsorption storage because of their high specific surface area, good porosity, and adjustable pore structure. In this study, the structural design and synthesis methods of MOFs are introduced, and the research progress and problems associated with MOF materials in methane storage and capture are reviewed. The current research status of methane storage at high pressure is introduced in terms of volumetric and gravimetric uptake. For methane capture at atmospheric pressure, emphasis is placed on CH4/N2 and CO2/CH4 separation and methane capture technologies. Finally, the problems and challenges of using MOF materials to achieve efficient methane storage and capture are analyzed and future prospects are presented.

We study experimentally the resistive behaviors of a niobium nitride superconducting hot-electron bolometer (HEB) device driven by magnetic field and terahertz radiation. We find that the resistance of the superconducting HEB device emerges due to time-dependent changes of the macroscopic quantum phase by flux-flow events. The flux-flow resistance is found to be increased linearly with magnetic field at low vortex velocities and is enhanced by terahertz radiation. At high vortex velocities, there is an obvious non-linear change, which can be well interpreted by viscous flux-flow instability predicted by the Larkin and Ovchinnikov theory. In addition, we demonstrate a technique taking use of the device resistance dependence on magnetic field to stabilize the superconducting HEB device.

Calligonum caput-medusae is known to grow well when irrigated with water containing NaCl. The aim of this study was to investigate ecophysiological responses of C. caput-medusae to different NaCl concentrations. In our study, we examined the effect of 0, 50, 100, 200, and 400 mM NaCl. Our results demonstrated that maximum seedling growth occurred at 50 mM NaCl. Photosynthetic parameters, such as the photosynthetic pigment content and gas exchange parameters, correlated with growth response. High salinity (≥ 100 mM NaCl) resulted in a significant reduction of the plant growth. Similarly, marked declines in the pigment content, maximal efficiency of PSII photochemistry, net photosynthetic rate, transpiration rate, and stomatal conductance were also detected. However, intercellular CO2 concentration showed a biphasic response, decreasing with water containing less than 200 mM NaCl and increasing with NaCl concentration up to 400 mM. Water-use efficiency and intrinsic water-use efficiency exhibited the opposite response. The reduction of photosynthesis at the high NaCl concentration could be caused by nonstomatal factors. High salinity led also to a decrease in the relative water content and water potential. Correspondingly, an accumulation of soluble sugars and proline was also observed. Na+ and Cl− concentrations increased in all tissues and K+ concentrations were maintained high during exposure to NaCl compared with the control. High salinity caused oxidative stress, which was evidenced by high malondialdehyde and hydrogen peroxide contents. In order to cope with oxidative stress, the activity of antioxidative enzymes increased to maximum after 50 mM NaCl treatment. The data reported in this study indicate that C. caput-medusae can be utilized in mild salinity-prone environments.

Fluorinated heterocycles play an important role in pharmaceutical and agrochemical industries. Herein, we report on the synthesis of four types of fluorinated heterocycles via rhodium(III)-catalyzed C-H activation of arenes/alkenes and versatile coupling with 2,2-difluorovinyl tosylate. With N-OMe benzamide being a directing group (DG), the reaction delivered a monofluorinated alkene with the retention of the tosylate functionality. Subsequent one-pot acid treatment allowed the efficient synthesis of 4-fluoroisoquinolin-1(2H)-ones and 5-fluoropyridin-2(1H)-ones. When N-OPiv benzamides were used, however, [4 + 2] cyclization occurred to provide gem-difluorinated dihydroisoquinolin-1(2H)-ones. Synthetic applications have been demonstrated and the ready availability of both the arene and the coupling partner highlighted the synthetic potentials of these protocols. Mechanistically, these two processes share a common process involving N-H deprotonation, C-H activation, and olefin insertion to form a 7-membered rhodacycle. Thereafter, different reaction pathways featuring β-F elimination and C-N bond formation are followed on the basis of density functional theory (DFT) studies. These two pathways are DG-dependent and led to the open chain and cyclization products, respectively. The mechanistic rationale was supported by detailed DFT studies. In particular, the origins of the intriguing selectivity in the competing β-F elimination versus C-N bond formation were elucidated. It was found that β-F elimination is a facile event and proceeds via a syn-coplanar transition state with a low energy barrier. The C-N bond formation proceeds via a facile migratory insertion of the Rh-C(alkyl) into the Rh(V) amido species. In both reactions, the migratory insertion of the alkene is turnover-limiting, which stays in good agreement with the experimental studies.

Magnetic microspheres (Fe3O4@PVIM@Zn(II)) composed of a high magnetic-response Fe3O4 core and a Zn(II)-immobilized cross-linked polyvinyl imidazole (PVIM) shell via reflux-precipitation polymerization and metal-ion affinity strategy were fabricated. Integrating the advantages of specific uptake and fast separation, Fe3O4@PVIM@Zn(II) was adopted as an ideal pathway for luteolin (LTL) recognition. As-prepared Fe3O4@PVIM@Zn(II) possessed core–shell structure, uniform size (200 nm), high magnetic responsiveness (32.6 emu g−1), and a very easy synthesis process. X-ray photoelectron spectroscopy (XPS) suggested a strong interaction between the nitrogen heterocyclic ring of PVIM and Zn(II), which produced abundant binding sites for LTL. The batch mode experiments can be well described by pseudo-first-order kinetic models and a Langmuir isotherm. A rapid binding equilibrium (within 45 min) and large monolayer adsorption capacity (23.92 mg g−1) at 298 K were also observed. In addition, Fe3O4@PVIM@Zn(II) displayed remarkable selectivity to LTL; the purification process using Fe3O4@PVIM@Zn(II) can make purified LTL from approximately 85% to 94.26%. The antibacterial activity of purified LTL was outstanding by means of a Staphylococcus aureus (ATCC29213) resistance experiment. Considering its multiple merits, Fe3O4@PVIM@Zn(II) exhibited great potential for specific binding with natural products, such as flavonoids.

As the most important starting material and degradation product of peroxide explosives, H2O2 is considered as a signature compound for peroxide-based explosives. A new probe, (2-(2,6-bis((E)-2-(10-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anthracen-9-yl)vinyl)-4H-pyran-4-ylidene)malononitrile) (AVPM), for both chromophoric/fluorometric detection of H2O2 was designed and synthesized. AVPM emitted a long wavelength emission from its intramolecular charge transfer (ICT) and hence its absorption was expanded to the visible region. The response rate and sensitivity of AVPM for H2O2 detection were tremendously improved (91% of the fluorescence was quenched within 2 min for H2O2) by adding triethylamine (TEA) into the probe solution. And the solution color changed from yellow to blue. A detection limit down to 17.58 nM is remarkably achieved. These features lead to a new chromophoric/fluorometric probe for H2O2 detection and make it an ideal candidate for chemical detection and analysis in public safety and environmental monitoring.

Being lightweight, broadband, thin and highly efficient are the key desirable properties for microwave absorbers. We have successfully prepared reduced graphene oxide (rGO) coated with barium titanate (BT) using a simple method and a series of measurements were carried out to determine its morphology and structure. The composites of rGO@BT/poly(vinylidene fluoride) (PVDF) with filler amounts of 10, 15, 20 and 25 wt% exhibit broad frequency bands (

Summary Blueberry anthocyanins are the major active ingredients of blueberry with a variety of biological activities. The scale extraction and separation of blueberry anthocyanins could contribute to their application in drugs, cosmetics, food additives and so on. In this study, using combined technologies to high-efficient extraction and separation of blueberry anthocyanins was developed. Under the optimum extraction conditions of first 0.3% cellulose and pectinase with 2:1 (m/m) at 37 °C for 4 h and then 1% citric acid-acidified 75% (v/v) ethanol at 37 °C for 6 h, as high as 25% extraction rate of blueberry anthocyanins was obtained. By ethyl acetate extraction in triplicate and then D101 resin column chromatography, up to 49.6% purity of blueberry anthocyanins was obtained based on UV–vis analysis. The scale-up extraction and separation of blueberry anthocyanins were carried out. This method was simple but effective, and easy scalable at industrial purpose.

Reduced graphene oxides (rGO)@MoS2 composites with loose structure were prepared and added into poly(vinylidene fluoride) (PVDF) to form the composites show superior microwave absorption and excellent electromagnetic interference shielding performances. The maximum reflection loss of the rGO@MoS2/PVDF composites with a low filling rate (only 5.0 wt%) can reach -43.1 dB at 14.48 GHz, and the frequency bandwidth less than -10 dB is from 3.6 to 17.8 GHz (in the frequency range of 2~18 GHz) with the thickness of 1-5 mm. Furthermore, the rGO@MoS2/PVDF composites with a higher filling rate (25 wt%) also exhibit outstanding electromagnetic interference (EMI) shielding effectiveness (SE) reaching a maximum at 27.9 dB. The mechanism of enhanced absorption and electromagnetic interference shielding performances were also studied in detail.

The three-dimensional (3D) MoS2 hierarchical nanospheres which assembled spontaneously by two-dimensional (2D) lamina have been successfully designed and fabricated in large scale via a simple hydrothermal process. Subsequently, the electromagnetic wave absorption properties of hierarchical MoS2 nanospheres compounded with polyvinylidene fluoride (PVDF) were investigated in a broad frequency range of 2–40 GHz. The results indicated that the MoS2/PVDF nanocomposites possess adjustable and enhanced wave absorption performance. Furthermore, the MA performance can be effectively tuned by the absorber’s thickness and filler content. In addition, the peculiar hierarchical nanostructure of MoS2 is beneficial to microwave absorption property compared with the bulk MoS2 and micrometer-sized MoS2. Moreover, the main microwave absorption mechanism including various polarization, destructive interference theory, and multiple reflection has been described in detail.

Objective The gut microbiota regulates thermogenesis to benefit metabolic homeostasis at least partially via its metabolite butyrate, and the underlying mechanisms of this regulation are still unclear. In this study, we aim to investigate the role of lysine specific demethylase (LSD1), a histone demethylase and important regulator of thermogenesis, in mediating gut microbial metabolite butyrate regulation of thermogenesis. Methods The antibiotic cocktail (ABX) was administrated to deplete gut microbiota. Adipose-specific LSD1 knockout mice (LSD1 aKO) were generated by crossing LSD1-lox/lox with adiponectin-cre mice and sodium butyrate and dietary fiber inulin was administrated through oral-gavage. Primary stromal vascular cells were isolated from adipose tissues and differentiated to adipocytes for studying butyrate effects on adipocyte thermogenesis. Results The antibiotic cocktail (ABX)-mediated depletion of the gut microbiota in mice downregulated the expression of LSD1 in both brown adipose tissue (BAT) and subcutaneous white adipose tissue (scWAT) in addition to uncoupling protein 1 (UCP1) and body temperature. Gavage of the microbial metabolite butyrate in ABX-treated mice reversed the thermogenic functional impairment and LSD1 expression. The adipose-specific ablation of LSD1 in mice attenuated the butyrate-mediated induction of thermogenesis and energy expenditure. Notably, our results showed that butyrate directly increased the expression of LSD1 and UCP1 as well as butyrate transporter monocarboxylate transporter 1 (MCT1) and catabolic enzyme acyl-CoA medium-chain synthetase 3 (ACSM3) in ex vivo cultured adipocytes. The inhibition of MCT1 blocked the effects of butyrate in adipocytes. Furthermore, the butyrate-mediated prevention of diet-induced obesity (DIO) through increased thermogenesis was attenuated in LSD1 aKO mice. Moreover, after gavaging HFD-fed mice with the dietary fiber inulin, a substrate of microbial fermentation that rapidly produces butyrate, thermogenesis in both BAT and scWAT was increased, and DIO was decreased; however, these beneficial metabolic effects were blocked in LSD1 aKO mice. Conclusions Together, our results indicate that the microbial metabolite butyrate regulates thermogenesis in BAT and scWAT through the activation of LSD1.

A general and efficient synthetic methodology for the preparation of enantio- and diastereopure [6]-, and [7]helicenes is developed. Commercially available chiral binaphthanols are utilized to generate the arylene-vinylene precursors, which undergo helical folding via photocyclization to give enantio- and diastereopure [6]-, and [7]helicenes. These optically pure helicenes could be easily obtained via silica gel column chromatography without the use of expensive HPLC or chiral resolution reagents. The configurations and structures of these helicenes are confirmed by CD spectra and X-ray crystallographic analysis. This work provides a new method for preparation of enantiopure helicenes.

Selenium (Se) is an essential nutrient for humans and all food-producing animal species. Nutritional deficiencies of Se and (or) vitamin E induce exudative diathesis, nutritional pancreatic atrophy, and nutritional muscular dystrophy in chicks. Although these diseases are presumably associated with the need of Se for the synthesis of the 21st amino acid, selenocysteine (Sec, U) in selenoproteins, metabolic functions of the 25 selenoproteins identified in avian species remain largely unknown. This paper reviews regulations of the whole selenogenome and selected selenoproteins by different concentrations and chemical forms of dietary Se and (or) vitamin E in various affected tissues. The avian selenogenome may be divided into 2 groups: responders and non-responders, based on its response to dietary Se and vitamin E changes. Mechanisms for the gene-, tissue-, and age-dependent responses and the correlation with the stress and cell death signaling are explored. Overall, this review intends to link the novel regulation and function of avian selenogenome to the protection by Se against oxidative insults associated with the classical Se/vitamin E deficiency diseases in chicks.

In this paper, the effects of complexing agents (oxalic acid and glycine) and Fe(II) ions on the electro-reduction of Cr(III) ions are studied carefully. Based on the electrochemical analyses, both the complexing agents and Fe(II) ions can obviously decrease the cathodic polarization in the electro-reduction of Cr(III) ions, and the Fe(II) ions can also be co-deposited with Cr(III) ions. One water molecule in [Cr(III)(H2O)6]3+ ion is substituted by one oxalic acid or glycine to form an electrochemically active penta-aqua-Cr(III) coordination ion. In situ infrared spectroscopy and energy dispersive spectroscopy reveal the typical induced-deposition mechanism of ferrochrome alloy. Fe(II) ions are firstly reduced to Fe crystal nuclei, then Cr and Fe atoms grow on the Fe nuclei to form ferrochrome alloy.

Background and purpose Early brain injury is an essential pathological process after subarachnoid hemorrhage (SAH), with many cell death modalities. Ferroptosis is a newly discovered regulated cell death caused by the iron-dependent accumulation of lipid peroxidation, which can be prevented by glutathione peroxidase 4 (GPX4). Our study aimed to investigate the role of GPX4 in neuronal cell death after experimental SAH. Methods In vivo experimental SAH was induced by injecting autologous arterial blood into the prechiasmatic cistern in male Sprague-Dawley rats. Meanwhile, the in vitro SAH model was performed with primary rat cortical neurons cultured in medium containing hemoglobin (Hb). Adenovirus was used to overexpress GPX4 before experimental SAH. GPX4 expression was detected by western blot and immunofluorescence experiments. Malondialdehyde (MDA) was measured to evaluate the level of lipid peroxidation. Nissl staining was employed to assess cell death in vivo, whereas lactate dehydrogenase (LDH) release was used to evaluate cell damage in vitro. The brain water content and neurological deficits were evaluated to determine brain injury. Results Endogenous GPX4 was mainly expressed in neurons, and its expression decreased at 24 h after experimental SAH. Overexpression of GPX4 significantly reduced lipid peroxidation and cell death in the experimental SAH models both in vivo and in vitro. Moreover, overexpression of GPX4 ameliorated brain edema and neurological deficits at 24 h after SAH. Conclusions The decrease of GPX4 expression potentially plays an important role in ferroptosis during early brain injury after SAH. Overexpression of GPX4 has a neuroprotective effect after SAH.

Nine types of diversely fused heterocyclic quaternary ammonium salts were constructed through an oxidative CH annulation reaction. Both high-valent pentamethylcyclopentadienylcobalt(III) and pentamethylcyclopentadienyliridium(III) were found to be effective as catalyst for this reaction. Broad substrate scope and good functional group tolerance were observed.

A synthetic method for isoquinoline synthesis via a [4+2] annulation of NH imines with alkynes using the high-valent (pentamethylcyclopentadienyl)cobalt(III) [Cp*Co(III)] catalyst is described. Cerium(IV) sulfate was found to be an efficient oxidant in lieu of the commonly used copper or silver salts. Broad substrate scope, high functional group tolerance, and generally good yields were observed.

In this paper, different SBA-15 molecular sieves were prepared in a facile sol-gel method by using a low-cost sodium silicate as silicon source at different ripening temperature. The materials were characterized by small-angle XRD, TEM, nitrogen adsorption–desorption test. The results showed that ripening temperature can affect the pore size and mesostructure of SBA-15. High surface area SBA-15 can be obtained at low ripening temperature, and plugged mesostructure can be prepared at high temperature. The gravimetric humidity sensing property of the materials were tested based on a transducer of quartz crystal microbalance. The test results revealed that all the samples showed high response in the wide range of relative humidity. The sensors based on that prepared at 35°C show a good stability and linearity in the range of 11.3%RH to 98%RRH along with fast response (12s) and recovery time (8s), ultrahigh sensitivity and low hysteresis, implying that has a great potential for humidity detection.

Nitrites (NO2(-) ions) in food and drink play an important role in human health but require complicated operations before detection. Herein, we present a rationally designed SERS-enabled micro-chamber that comprised a drawn glass capillary with a tiny orifice (∼50 μm) at the distal tip, wherein the gold nanoparticles (Au NPs) are compactly coated on the inner wall surface. In this chamber, nitrites specifically trigger a pH and laser irradiance-dependent diazotization starting from p-aminothiophenol (PATP) absorbed onto the surface of Au NPs to form p,p'-dimercaptoazobenzene (DMAB) molecules, in which the presence of NO2(-) ions above 30.7 μM (1.38 ppm) in the siphoned liquid sample can be identified relying on SERS peak (1141 cm(-1)) intensity of the emerging azo moiety. Except for pH conditions, laser irradiance is more important but easily neglected in previous studies, which is capable of preventing generation of errors when the detection sensitivity was pursued through increasing the laser power. In this case, several real samples (rather than simple water samples), including honey, pickled vegetable and fermented bean curd, had been successfully detected accurately through such a convenient sampling micro-chamber. The SERS-enabled device could potentially be facilely incorporated with portable Raman instruments for a special application of food inspection in rapid and field analysis of NO2(-) ions.

Integrative pharmacology has been used to identify the key active constituents (KACs) of Buchang Naoxintong capsules (BNCs), a traditional Chinese medical preparation; this approach involves the evaluation of the content profiles and drug-like properties of the BNC constituents and development of an ingredient-target network. In this study, we used a sensitive analytical method to simultaneously identify and quantify 16 constituents of BNCs. Metabolism of these constituents by gut microbiota and human oral bioavailability were predicted using an in silico approach, followed by construction of networks to analyze the interactions between BNC constituents, their molecular targets, and proteins known to be the molecular targets for Food and Drug Administration-approved colitis medication. Finally, an animal model of ischemic stroke was used to verify the therapeutic effects of the KACs of BNCs. Amygdalin and paeoniflorin were identified as the KACs because they were the 2 most abundant BNC constituents, having appropriate drug-like properties, and produced therapeutic effects against cerebral ischemia. Amygdalin produced an anti-cerebral ischemia effect, likely by interacting with the glucocorticoid receptor (NR3C1) and serpin peptidase inhibitor, clade C (antithrombin), member 1 (SERPINC1). These results form the basis for conducting studies to identify KACs in traditional medicinal preparations; such studies might improve quality control and allow the in vivo evaluation of synergistic interactions between the complex mixtures of compounds.