Search

Macrophages play a key role in the development of sepsis-induced acute respiratory distress syndrome (ARDS). Recent evidence has proved that glycolysis plays an important role in regulating macrophage polarization through metabolic reprogramming. Bone marrow mesenchymal stem cells (BMSCs) can alleviate sepsis-induced lung injury and possess potent immunomodulatory and immunosuppressive properties via secreting exosomes. However, it is unknown whether BMSCs-derived exosomes exert their therapeutic effect against sepsis-induced lung injury by inhibiting glycolysis in macrophages. Therefore, the present study aimed to evaluate the anti-inflammatory effects of exosomes released from BMSCs on acute lung injury induced by lipopolysaccharide (LPS) in mice and explored the possible underlying mechanisms in vitro and in vivo. We found that BMSCs inhibited M1 polarization and promoted M2 polarization in MH-S cells (a murine alveolar macrophage cell line) by releasing exosomes. Further experiments showed that exosomes secreted by BMSCs modulated LPS-treated MH-S cells polarization by inhibiting cellular glycolysis. Moreover, our results showed that BMSCs-derived exosomes down-regulated the expression of several essential proteins of glycolysis via inhibition of hypoxia-inducible factor 1 (HIF-1)α. Finally, a model of LPS-induced ARDS in mice was established, we found that BMSCs-derived exosomes ameliorated the LPS-induced inflammation and lung pathological damage. Meanwhile, we found that intratracheal delivery of BMSCs-derived exosomes effectively down-regulated LPS-induced glycolysis in mice lung tissue. These findings reveal new mechanisms of BMSCs-derived exosomes in regulating macrophage polarization which may provide novel strategies for the prevention and treatment of LPS-induced ARDS.

The epoxidation of styrene was studied over three ternary catalysts M0.5Cu0.5Co2Ox (M=Ca, Ni and Cr) using tert-butyl hydroperoxide (TBHP) as an oxidant. Cr3+ was incorporated into the lattice of C...

As tissue-resident cells in the lung, alveolar macrophages display remarkable heterogeneity and play a crucial role in the development and control of septic acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Recent evidence suggests that α-ketoglutarate (α-KG) plays an important role in alternative activation of macrophage (M2) through metabolic and epigenetic reprogramming, and thus possesses anti-inflammatory properties. However, the underlying mechanisms of α-KG's effect on alveolar macrophage polarization and the potential effects of α-KG in ALI/ARDS remain unclear. Here, we examined the effects and mechanisms of α-KG on alveolar macrophage polarization, and investigated the possible effects of α-KG on lipopolysaccharide (LPS)-induced ALI/ARDS in a mouse model. We found that α-KG inhibited M1 macrophage polarization and promoted IL-4-induced M2 macrophage polarization in MH-S cells (a murine alveolar macrophage cell line). Further experiments showed that α-KG down-regulated the expression of M1-polarized marker genes and inhibited the activities of mammalian target of rapamycin complex 1 (mTORC1)/p70 ribosomal protein S6 kinase (p70S6K) signaling pathway in M1-polarized MH-S cells. Moreover, our results showed that α-KG promoted IL-4-induced M2 polarization of MH-S cells by augmenting nuclear translocation of peroxisome proliferator-activated receptor γ (PPARγ) and increasing expression of relevant fatty acid metabolic genes. Finally, using an LPS-induced ALI/ARDS mouse model, we found that α-KG ameliorated the LPS-induced inflammation and lung pathological damage, as well as α-KG pretreated mice had better clinical scores compared with the LPS group. These findings reveal new mechanisms of α-KG in regulating macrophage polarization which may provide novel strategies for the prevention and treatment of inflammatory diseases, including sepsis and septic ALI/ARDS.

Single-atom catalysts (SACs) have sparked intense interest in heterogeneous catalysis lately, but insufficient accessibility of active sites restricts their further applications. Herein, a hydrangea-like carbon nanoparticle possessing highly open nanospaces and enhanced external surface area that fully exposes the catalytic sites is reported. By introducing mesoporous silica nanoparticles (MSNs), Fe-doping zeolitic imidazolate framework-8 (ZIF-8) precursors are assembled into a flower-like superstructure interlaced by porous nanosheets, which expand from inside out constructing an open and interconnected architecture. This unique structure can substantially liberate the densely dispersed but deeply buried Fe-N4 sites inside carbon nanoparticles and accelerate mass transfer in the catalyst layer that increases active-site utilization. Furthermore, the physical and chemical properties of the assembled catalysts can be adjusted by the diameter (200, 300, and 500 nm) of MSNs. When the diameter was 500 nm, the optimal FeNC-F3 catalyst exhibited large specific surface area, maximum metal centers utilization, high oxygen reduction reaction efficiency, and excellent stability. The novel cathodic electrocatalyst achieved high power density of 0.32 mW cm−2 in microbial fuel cell and 288 mW cm−2 in Zn-air battery. This work established a realistic strategy for promoting the practical development of fuel cell catalysts.

The transcription factor nuclear factor E2-related factor 2 (Nrf2) is known to control the expression of antioxidant response elements and cytoprotective genes and modulate inflammatory response, helping to ameliorate damage in many diseases. Exactly how Nrf2 regulates innate inflammatory homeostasis remains unclear. In this study, we provide in vitro and in vivo evidence that Nrf2 plays a crucial role in macrophage polarization and acute respiratory distress syndrome (ARDS). We conducted in vitro experiments using a mouse alveolar macrophage cell line as well as primary cultures of macrophages in which cells were exposed to lipopolysaccharide (LPS) or interferon-γ in order to mimic ARDS, in the presence or absence of the Nrf2 activator tert-butylhydroquinone (tBHQ). Using siRNA-mediated Nrf2 knockdown, we showed that Nrf2 inhibited the inflammatory response by promoting M2 macrophage polarization and inhibiting M1 macrophage polarization. At the same time, tBHQ activated Nrf2-mediated inhibition of the p65 nuclear factor-κB pathway and activation of peroxisome proliferator-activated receptor-γ, which play important roles in regulating macrophage polarization. We also conducted in vivo experiments in which mice were given tBHQ with or without intratracheal LPS, then their survival was monitored, lung injury was assessed using histology, and levels of pro- and anti-inflammatory cytokines were assayed in the lungs and serum. Activation of Nrf2 with tBHQ dramatically reduced LPS-induced mortality and lung injury, down-regulated pro-inflammatory mediators and up-regulated anti-inflammatory mediators. These results suggest that Nrf2 can help prevent ARDS progression by promoting M2 polarization of macrophages. Interfering with Nrf2 may be an effective strategy for reprogramming macrophage polarization in order to treat ARDS.

Magnetically recyclable catalysts with high activity are highly desired in heterogeneous catalysis, as their magnetic nature allows the facile and efficient separation under an external magnetic field. We developed a facile method to fabricate a new type of recyclable nanocatalyst based on double-shelled hollow nanospheres (HNSs) supported Pd nanoparticles (NPs), in which magnetic Fe species were served as inner shell and nitrogen doped carbon (NC) as outer shell. The resultant Fe@NC@Pd HNSs possess unique hollow structure and mesoporous shells for facile mass transportation, magnetic inner shell for easy recycling and well dispersed Pd NPs for high-density of catalytic sites. The magnetic Fe-based inner shell, catalytically active outer NC shell combined with ultrafine Pd NPs synergistically enhanced the catalytic activity and recyclability in organocatalysis. In 4-nitrophenol reduction reaction, the turnover frequency (TOF) of Fe@NC@Pd catalyst is up to 370.3 min−1, which is one of the highest efficiencies ever reported. Furthermore, Fe@NC@Pd can also be applied for Suzuki coupling reaction with the TOF as high as 52.7 min−1.

The use of oil recovery technologies has resulted in the weakening of interfacial tension between oil and water in oilfield wastewater due to a large amount of polymer present. This leads to the formation of stable emulsified colloidal systems and increases the difficulty of oilfield wastewater treatment. This study investigated hydrophobically-modified polyaluminium silicate sulphate (PASS-C) as a coagulant for oilfield wastewater treatment. PASS-C was prepared by the condensation polymerisation of Al2(SO4)3·18H2O with dialysed and hydrolysed KH570 [3-(trimethoxysilyl)propyl methacrylate] under titration with NaAlO2 and water glass at low temperature. The zeta potential of PASS-C showed that the introduction of hydrophobic groups increased its charge neutralisation ability. Additionally, compared with conventional PASS, PASS-C showed a satisfactory oil removal rate from simulated polymer flooding oily wastewater. When the hydrophobic group content was 1% and the dosage of PASS-C was 140 mg·L–1, the optimal oil removal rate and turbidity removal rate was 95% and 98%, respectively. The particle size and morphology of the coagulated flocs were characterised by laser particle size analysis and SEM. Compared with PASS, PASS-C formed a larger and more compact floc. These findings indicated that the good flocculability of PASS-C for crude oil wastewater was attributable to the synergistic effects of charge neutralisation, hydrophobic associations and adsorption bridging.

In this paper, a rapid and sensitive flow injection-chemiluminescence (FI-CL) method is proposed for the quantitative determination of rutin based on the inhibitory effect of rutin on the chemiluminescence intensity from the luminol–chymotrypsin (CT) system. The decrease of CL intensity was found to be proportional to the logarithm of rutin concentration in the range 0.1–30.0 ng/mL. A method for the quantification of rutin is proposed, with the limit of detection (LOD) of 0.03 ng/mL (3σ). A complete analytical process including sampling and washing for rutin determination, which was conducted at a flow rate of 2.0 mL/min, could be performed completely within 30 s, yielding a sample efficiency of 120 h−1. The proposed procedure was successfully applied for the determination of rutin in human urine after oral intake, with recoveries varying from 93.9 to 108.1% and relative standard derivation

A novel composite material consisting of multi-walled carbon nanotube (MWNTs)-molecularly imprinted polymers (MIPs) for a tartrazine assay was synthesized by a surface molecular imprinting technique. The molecularly imprinted polymers were prepared with beta-cyclodextrins and [2-(methacryloyloxy) ethyl]trimethylammonium chloride (DMC) as bifunctional monomers. The MWNTs-MIPs were characterized using transmission electron microscopy (TEM) and Fourier transform infrared spectroscopy (FT-IR). Adsorption experiments showed that the MWNTs-MIPs exhibited a high capacity and favourable selectivity toward tartrazine, and the maximum adsorption capacity, qm, and distribution coefficient, kd, were estimated to be 135.15 mg g−1 and 14.72, respectively. A SPE-HPLC analytical method was developed and used to assay tartrazine in five drinks. The recoveries were in the range from 88.6–102.4% with a relative standard deviation below 5.0%. The tartrazine content was lower in all samples than the permitted maximum limit set by the European Commission and Ministry of Health of the People’s Republic of China. A t test demonstrated that this method had no significant difference to the Chinese standard method of GB/T 5009.35-2003 at P = 0.95.

Mannich addition reactions between in situ generated α,α-difluoroenolates and various N -sulfonyl imines readily occur with exceptionally high reaction rates at ambient temperature. The method features remarkable generality and enjoys operationally convenient conditions underscoring its practicality and methodological importance for preparation of sulfonamides bearing β-amino-α,α-difluoro ketone moiety.

A Cu-catalyzed asymmetric detrifluoroacetylative aldol addition reaction of 2-fluoro-1,3-diketones/hydrates to aldehydes in the presence of base and chiral bidentate ligand was developed. The reaction was carried out under convenient conditions and tolerated a wide range of substrates, resulting in fluorinated quaternary stereogenic α-fluoro-β-hydroxy ketone products with good chemical yields, diastereo- and enantioselectivities. This catalytic asymmetric detrifluoroacetylative aldol addition reaction provides a new approach for the preparation of biologically relevant products containing C-F quaternary stereogenic centers.

This work describes an asymmetric functionalization of the pyrrole ring of an indole structure with (2,2,2-trifluoro)ethylamine moiety allowing for general access to two novel classes of trifluoromethyl-containing indoles. We found that under the Friedel–Crafts reaction conditions (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimine (1) easily reacts with indole derivatives affording the target 3-substituted products, while LDA-promoted reactions proceed exclusively at the 2-position. We demonstrate that both approaches feature wide substrate scope, high chemical yields and diastereoselectivities, which render these reactions readily applicable for straightforward preparation of biologically interesting compounds containing chiral CF3 CH(NH2) and indole groups. The mechanistic rationales accounting for the observed mode of stereochemical preferences are proposed.

The reactions between lithium-benzothiazoles and (S)-N-tert-butanesulfinylketimines have been found to be of general synthetic importance for asymmetric preparation of previously unknown type of amino-benzothiazol derivatives of high pharmaceutical potential. In most cases, the reactions proceed with excellent diastereoselectivities and good isolated yields of the target compounds rendering the developed procedure of high synthetic value and immediate practical use.

This paper presents the first study of the addition reactions between amide-derived nucleophiles and chiral CF3-containing N-sulfinyl-imines. We demonstrate that enolates of 1-(alkyl)-indolin-2-ones cleanly react with (S)-N-t-butylsulfinyl-3,3,3-trifluoroacetaldimine affording 3-(1-amino-2,2,2-trifluoroethyl)-1-(alkyl)-indolin-2-ones of (3S,1'S) absolute configuration as the major reaction products with synthetically meaningful diastereoselectivity and chemical yields. The reactions were shown to be of general practical application for preparation of various oxindole derivatives in a diastereomerically pure form.

Here we describe the first attempts to scale up five addition reactions between (SS)-N-tert-butanesulfinyl-(3,3,3)-trifluoroacetaldimine 6 with C-nucleophiles derived from ketones (two examples), glycine Schiff base and heterocycles (two examples). In all cases studied, the observed stereochemical outcome of the scaled up (5.0–25.0 mmol) reactions was lower as compared with the original 0.5 mmol scale. However, the observed worsening of yields and diastereoselectivity was not identical and depended on the reaction conditions and reaction mechanisms. In general, scaling up of the reactions conducted at ambient temperatures presented no problems while the low-temperature (−78 °C) processes would require special equipment to provide strict maintenance of the reaction temperature to obtain the desirable outcome. Importantly, using procedures described here, series of biologically relevant compounds containing 2,2,2-trifluoro-1-(amino)ethyl [CF3 CH(NH2)-] pharmacophore unit can be prepared in enantiomerically pure form on up to 5 g scale, allowing their systematic biological studies.

This study describes the anomalous outcome of the Mannich-type reaction of N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimine and Li derivatives of benzo[d]thiazoles, which offers a convenient and generalized method for the synthesis of biologically relevant (E)-1,2-bis(2-benzothiazolyl)ethanes. The mechanism, scope, and scalability of this new reaction are discussed.

A variety of chiral N-phosphinyl α-imino esters have been synthesized for the first time from ketoesters and phosphinylamide, which were then reduced by L-selectride to give the corresponding N-phosphinyl-protected α-amino esters. The reduction proceeded very well with excellent chemical yields (88–98%) as well as high diastereoselectivities (96:4 to 99:1). Some of these products could be obtained without column chromatography and recrystallization. The chiral phosphinyl auxiliary could be easily cleaved under acidic conditions.

We demonstrate that reactions between various 1-indanones and (SS)-N-tert-butanesulfinyl-(3,3,3)-trifluoroacetaldimine, conducted in the presence of catalytic amounts of LDA, occur with virtually complete stereochemical outcome, offering reliable and generalized access to biologically relevant β-trifluoromethyl-β-amino indanone derivatives. The products can be isolated in diastereomerically pure form simply by washing the crude reaction mixture with hexanes, underscoring practicality of the present method.

(S)-N-(tert-Butylsulfinyl)-3,3,3-trifluoroacetaldimine underwent reactions with enolates of glycine esters with quite remarkable stereochemical results, that is, with virtually complete (>99 % de) diastereoselectivity and excellent (>98 %) yields. Furthermore, the reactions are conducted under operationally convenient conditions (Cs2CO3-catalyzed, ambient temperature) to provide the most advanced, general, and scalable access to biologically important β-trifluoromethylated α,β-diamino acids.

We report here that the reactions of in situ generated unprotected α,α-difluoroenolates with various N-sulfonyl imines take place under operationally convenient conditions affording a novel type of fluorinated sulfonamides of high pharmaceutical potential. The reactions feature structural generality, excellent yields and can be easily scaled up for practical preparation of the target fluorine-containing sulfonamides.

Reaction of 2-fluoro-1,3-diketone hydrates (I), (IV), and (VI) with aldehydes proceeds through a detrifluoroacetylative aldol addition mechanism to yield fluorinated aldol products in good stereoselectivities.

Herein is reported a study of asymmetric decarboxylative Mannich addition reactions between (Ss)-N-t-butylsulfinyl-3,3,3-trifluoroacetaldimine and Schiff bases derived from various aldehydes and lithium 2,2-diphenylglycinate. These reactions proceed with excellent diastereoselectivities and good chemical yields, providing a practical method for preparation of trifluoromethyl-containing vicinal diamines. The procedures can be conducted under convenient conditions, rendering this approach of high synthetic value.

Functionalization of the pyrrole ring using imine (II) as reagent takes place at position 3 of indoles (I) under Friedel—Crafts conditions, whereas position 2 of N-protected indoles (IV) is substituted in the presence of LDA.

A highly diastereoselective synthesis of a previously unknown type of aminobenzothiazol derivatives of high pharmaceutical potential is given.

The synthesis of a novel type of fluorinated sulfonamides with high pharmaceutical potential can be scaled up.

Enolates of indolin-2-ones react cleanly with the chiral imine (II) to afford adducts (III) and (V) in good diastereoselectivity.

Herein is reported a study of asymmetric decarboxylative Mannich addition reactions between (Ss)-N-t-butylsulfinyl-3,3,3-trifluoroacetaldimine and Schiff bases derived from various aldehydes and lithium 2,2-diphenylglycinate. These reactions proceed with excellent diastereoselectivities and good chemical yields, providing a practical method for preparation of trifluoromethyl-containing vicinal diamines. The procedures can be conducted under convenient conditions, rendering this approach of high synthetic value.

CF3-containing chiral imines readily react with α,α-difluoroenolates affording a novel type of β-keto-amino compounds featuring the R-CO-CF2-CH(NH2)-CF3 moiety. The reactions feature exceptional generality allowing preparation of various aromatic, hetero-aromatic and aliphatic derivatives in high yields and diastereoselectivity. The products are configurationally stable and can be transformed to more functionalized complex compounds.

Here we describe the first attempts to scale up five addition reactions between (SS)-N-tert-butanesulfinyl-(3,3,3)-trifluoroacetaldimine 6 with C-nucleophiles derived from ketones (two examples), glycine Schiff base and heterocycles (two examples). In all cases studied, the observed stereochemical outcome of the scaled up (5.0–25.0 mmol) reactions was lower as compared with the original 0.5 mmol scale. However, the observed worsening of yields and diastereoselectivity was not identical and depended on the reaction conditions and reaction mechanisms. In general, scaling up of the reactions conducted at ambient temperatures presented no problems while the low-temperature (−78 °C) processes would require special equipment to provide strict maintenance of the reaction temperature to obtain the desirable outcome. Importantly, using procedures described here, series of biologically relevant compounds containing 2,2,2-trifluoro-1-(amino)ethyl [CF3 CH(NH2)-] pharmacophore unit can be prepared in enantiomerically pure form on up to 5 g scale, allowing their systematic biological studies.

The main feature of the synthesis of unexpected bis(benzothiazolyl)ethanes is the unusual role of CF3-imine, which serves as a precursor to the bridging ethylene moiety.

Compound (IIIa) can be further transformed to the corresponding β-amino alcohol by stereoselective reduction of its ketone moiety.

We demonstrate that reactions between various 1-indanones and (SS)-N-tert-butanesulfinyl-(3,3,3)-trifluoroacetaldimine, conducted in the presence of catalytic amounts of LDA, occur with virtually complete stereochemical outcome, offering reliable and generalized access to biologically relevant β-trifluoromethyl-β-amino indanone derivatives. The products can be isolated in diastereomerically pure form simply by washing the crude reaction mixture with hexanes, underscoring practicality of the present method.

We have demonstrated that 3,3,3-trifluoroacetaldimine (S)-1 easily reacts with indole derivatives under Friedel–Crafts reactions to provide reliable and generalized access to biologically interesting compounds containing the CF3CH(NH2)– pharmacophoric group. The reactions proceed with high rates and generally excellent yields (>90%) and stereochemical outcomes (99:1 dr).

Here we report that, unlike other ketones, 1-indanone and acetophenone derived enolates undergo Mannich-type addition reactions with N-tert-butanesulfinyl ketimines with excellent yields (up to 98%) and diastereoselectivity (>99/1). The resulting compounds represent a new type of biologically relevant β-aminoketone derivative bearing quaternary stereogenic carbon, which could be further converted into the corresponding β-amino ketones and β-amino alcohols, possessing three consecutive stereogenic centres.

In the title reaction, the N-tert-butylsulfinyl group serves not only as an efficient chiral auxiliary, but also as an amine protecting group.

Asymmetric Mannich reactions of imidazo[2,1-b]thiazole-derived nucleophiles with (SS)-N-tert-butanesulfinyl (3,3,3)-trifluoroacetaldimine were found to proceed with reasonably good yields (55%–79%) and exceptionally high stereoselectivity (>99 : 1 dr). This method presents a general approach for the preparation of a new type of biologically relevant compounds containing pharmacophoric imidazo[2,1-b]thiazole and (trifluoro)ethylamine groups.