Highly Regio- and Stereoselective Dehydration of Allylic Alcohols to Conjugated Dienes via 1,4-syn-Elimination with H2 Evolution.

Dehydration of alcohols is one of the most fundamental transformations in the organic chemistry class and one of the most widely used methods for producing alkenes in synthetic research. Numerous methods and reagents have been developed to control the regio- and stereoselectivity as well as the dehydration efficiency of normal alcohols. Despite these achievements, regio- and stereoselective and predictable dehydration of allylic alcohol has seldom been reported, except for limited substrates with a native preferred elimination position, as a result of the challenges that many potential dienes could be formed via 1,2- or 1,4-syn- or anti-elimination. Here, we report a tBuOK/potassium 2,2-difluoroacetate-mediated 1,4-syn-dehydration of allylic alcohol for the synthesis of regio- and stereodefined conjugated dienes via an in situ generated directing group strategy. This reaction exhibits a broad substrate scope and good functional group compatibility for primary-tertiary alcohols. The simple and scalable (up to 0.6 mol) procedure with readily available and inexpensive reagents makes it a practical method for conjugated diene synthesis. Mechanistic studies reveal that an acetate with tert-butoxide and allyloxide acetal moiety is formed as an intermediate, in which the acetate and the acetal act as the directing group for the base-promoted elimination. An unusual H2 evolution is also involved in the reaction.

The neural representations of valence transformation in indole processing.

Indole is often associated with a sweet and floral odor typical of jasmine flowers at low concentrations and an unpleasant, animal-like odor at high concentrations. However, the mechanism whereby the brain processes this opposite valence of indole is not fully understood yet. In this study, we aimed to investigate the neural mechanisms underlying indole valence encoding in conversion and nonconversion groups using the smelling task to arouse pleasantness. For this purpose, 12 conversion individuals and 15 nonconversion individuals participated in an event-related functional magnetic resonance imaging paradigm with low (low-indole) and high (high-indole) indole concentrations in which valence was manipulated independent of intensity. The results of this experiment showed that neural activity in the right amygdala, orbitofrontal cortex and insula was associated with valence independent of intensity. Furthermore, activation in the right orbitofrontal cortex in response to low-indole was positively associated with subjective pleasantness ratings. Conversely, activation in the right insula and amygdala in response to low-indole was positively correlated with anticipatory hedonic traits. Interestingly, while amygdala activation in response to high-indole also showed a positive correlation with these hedonic traits, such correlation was observed solely with right insula activation in response to high-indole. Additionally, activation in the right amygdala in response to low-indole was positively correlated with consummatory pleasure and hedonic traits. Regarding olfactory function, only activation in the right orbitofrontal cortex in response to high-indole was positively correlated with olfactory identification, whereas activation in the insula in response to low-indole was negatively correlated with the level of self-reported olfactory dysfunction. Based on these findings, valence transformation of indole processing in the right orbitofrontal cortex, insula, and amygdala may be associated with individual hedonic traits and perceptual differences.

Quinoline Bridging Hyperconjugated Covalent Organic Framework as Solid-Phase Microextraction Coating for Ultrasensitive Determination of Phthalate Esters in Water Samples.

Phthalate esters (PAEs) are widely distributed in the environment, and this has caused serious health and safety concerns. Development of rapid and ultrasensitive identification and analysis methods for phthalate esters is urgent and highly desirable. In this work, a novel nitrogen-rich covalent organic framework (N-TTI) derived quinoline bridging covalent organic framework (N-QTTI) was fabricated and used as a solid-phase microextraction (SPME) coating for the ultrasensitive determination of phthalate esters in water samples. The physical and chemical properties of N-QTTI were investigated sufficiently. The N-QTTI-coated fiber demonstrates a superior enrichment performance than either the N-TTI-coated fiber or commercial fibers under the optimized SPME conditions. For the first time, we propose a semi-immersion strategy for the extraction of PAEs from water samples based on N-QTTI-coated SPME fibers. Combined with gas chromatography-mass spectrometry (GC-MS), the developed method N-QTTI-SPME-GC-MS exhibits a wide linear range with a satisfactory linearity (R2 ≥ 0.995). The limits of detection (LOD, S/N = 3) and the limits of quantification (LOQs, S/N = 10) were 0.17-1.70 and 0.57-5.60 ng L-1, respectively. The repeatability of the new method was examined using relative standard deviations (RSDs) between intraday and interday data, which were 0.38-7.98% and 1.22-6.60%, respectively. The spiked recoveries at three levels of 10, 100, and 1000 ng L-1 were in the range of 90.0-106.2% with RSDs of less than 7.48%. The enrichment factors ranged from 291 to 17180. When compared to previously published works, the LODs of the newly established method were improved 5-5400 times, and the enrichment factors were increased by at least 8 times. The absorption mechanism was investigated by X-ray photoelectron spectroscopy and noncovalent interaction force analysis. The technique was successfully employed for detecting PAEs in water samples.

Thermal/Redox-triggered release of pyrazinic functional molecules by coordination polymers with luminescence monitoring ability.

Storage of volatile active molecules, along with the prolongation of their specific functions, requires the use of regulatable carriers. Pyrazine derivatives are highly volatile compounds with a broad application owing to their flavoring, pharmaceutical, antimicrobial, antiseptic, and insecticidal properties. In this study, pyrazines were stored by coordinating them with cuprous iodide to easily generate a series of luminescent coordination polymer (CP)-based carriers. The CPs could respond to thermal-redox stimuli and manipulate pyrazine release by breaking the labile Cu-N bonds when triggered by the two stimuli. Moreover, the release process could be visualized by decreased luminescence caused by the gradual decomposition of CP structures. The loading efficiencies ranged from 31% to 38%, and the controlled release behaviors accord with the zero-order kinetics. This work is the first to prove that CPs could function as dual stimuli-mediated delivery systems, which hold the potential to control the release and strengthen the usability of functional molecules.

A flexible electrochemical glucose sensing platform based on an electrospun PVA mat covered with in situ grown silver nanoparticles and a mixed self-assembled monolayer of glucose oxidase and ferrocene.

An electrochemical glucose sensor based on flexible materials is significant for wearable devices used for real-time health monitoring and diagnosis. However, applying flexible electrodes involves complex fabrication processes and might reduce detection sensitivity. To overcome these obstacles, we herein report a novel strategy for preparing a highly flexible enzyme electrode based on an electrospun poly(vinyl alcohol) (PVA) mat decorated with in situ grown silver nanoparticles (nano-Ag) for electrochemical glucose sensing. Ferrocene (Fc) was selected as an electron acceptor for glucose oxidase (GOD) in order to minimize the influence of oxygen. Electron transfer between GOD and Fc was facilitated by confining them within a mixed self-assembled monolayer (SAM) formed on a thin layer of gold deposited on top of the PVA/nano-Ag film. Nano-Ag was found to significantly increase the surface area of the electrode and improve the stability of electrode conductivity during tensile deformation. Electrochemical glucose detection was performed by chronoamperometry in the electroactivity domain of ferrocene, and good linearity (R2 = 0.993) was obtained in the range of 0.2-7 mM with a detection limit of 0.038 mM and a relative standard deviation (RSD) of 1.45% (n = 6). After being stuck to a bendable PDMS slice and bent, respectively, at 30° and 60° 50 times, the electrode showed slight changes in detection results (<4.78%), which remained within 8% when the bending angle increased to 90°. With its high flexibility, good detection performance, and convenient fabrication process, the proposed enzyme electrode showed good potential as a flexible platform for wearable glucose sensing systems.

Brain distribution and metabolic profiling of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in rats investigated by UHPLC-HRMS/MS following peripheral administration.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is known to be a tobacco-specific N-nitrosamine and has peripheral carcinogenic properties. It can also induce oxidative stress, glial cell activation, and neuronal damage in the brain. However, the distribution and metabolic characteristics of NNK in the central nervous system are still unclear. Here, a sensitive and effective UHPLC-HRMS/MS method was established to identify and investigate the metabolites of NNK and their distribution in the rat brain. In addition, the pharmacokinetic profiles were simultaneously investigated via blood-brain synchronous microdialysis. NNK and its seven metabolites were well quantified in the hippocampus, cortex, striatum, olfactory bulb, brain stem, cerebellum, and other regions of rat brain after peripheral exposure (5 mg/kg, i.p.). The average content of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in all brain regions was at least threefold higher than that of NNK, indicating a rapid carbonyl reduction of NNK in the brain. Lower concentrations of pyridine N-oxidation products in the cortex, olfactory bulb, hippocampus, and striatum might be related to the poor detoxification ability in these regions. Compared to α-methyl hydroxylation, NNK and NNAL were more inclined to the α-methylene hydroxylation pathway. Synchronous pharmacokinetic results indicated that the metabolic activity of NNK in the brain was different from that in the blood. The mean α-hydroxylation ratio in the brain and blood was 0.037 and 0.161, respectively, which indicated poor metabolic activity of NNK in the central nervous system.

Copper(I)-Iodide Clusters as Carriers for Regulating and Visualizing Release of Aroma Molecules.

Achieving the controlled release of functional substances is indispensable in many aspects of life. Especially for the aroma molecules, their effective delivery of flavor and fragrance is challenging. Here, selected pyridines, as highly volatile odorants, were individually coordinated with copper(I) iodide (CuII) via a straightforward one-pot synthesis method, rapidly forming pure or even crystalline CuII cluster-based profragrances at room temperature. The obtained profragrances enabled the stable and high loading of volatile fragrances under ambient conditions and guaranteed their long-lasting release during heating. Furthermore, the intrinsic emission luminescence of these solid-state profragrances decayed along with the aroma release, which can serve as an additional indicator for monitoring the delivery process. This research sets a precedent for using CuII clusters as dual-purpose release agents and greatly expands their potential applications.

Exosomes derived from mesenchymal stem cells regulate Treg/Th17 balance in aplastic anemia by transferring miR-23a-3p.

Imbalanced Th17/Treg ratio is implicated in the pathogenesis of aplastic anemia. Studies have indicated that bone marrow-derived mesenchymal stem cells-derived exosomes (BMSC-Exo) could correct imbalanced Th17/Treg in aplastic anemia, but the mechanism remains not fully understand. This study was designed to investigate whether BMSC-Exo regulates the Th17/Treg balance in aplastic anemia by transferring miR-23a-3p. Here, miR-23a-3p inhibitor was utilized to knockdown the expression of miR-23a-3p in BMSC-Exo. A co-culture system of CD4+ T cells from aplastic anemia patients and BMSC-Exo was used to explore the effects of BMSC-Exo on the Th17/Treg balance and the underlying mechanism in aplastic anemia. The patients with aplastic anemia exhibited Th17/Treg imbalance favoring the Th17 cells. BMSC-Exo could balance the percentage of Th17 and Treg cells in aplastic anemia, but the effects of BMSC-Exo can be eliminated when miR-23a-3p expression was silenced in BMSCs. IL-6 was a direct target of miR-23a-3p. IL-6 overexpression could abrogate BMSC-Exo-induced balance in Th17/Treg ratio. Overall, BMSC-Exo could balance Th17/Treg ratio in aplastic anemia via suppressing IL-6 expression by transferring miR-23a-3p at least in part. These data indicated miR-23a-3p may be a potential target for the treatment of aplastic anemia. Our study may provide a new idea for the therapy of the disease.

Covalent Functionalization of Graphene by Nucleophilic Addition Reaction: Synthesis and Optical-Limiting Properties.

Covalent functionalization of reduced graphene oxide (rGO) was performed by using conjugated polymers with different monomers through nucleophilic addition of nitrogen anions to rGO. Three conjugated polymers containing tetraphenylethylene, carbazole, and phenyl groups were used, and as a result of π-π interactions and the "polymer-wrapping" effect, the dispersion stability of rGO was improved. Even if the reaction site in the polymers was the same, there were great differences in the reactivities of the polymers, the dispersion stabilities of the resultant composites, and also the optical limiting (OL) performances of the resultant composites. The differences may be attributed to the π-conjugated structure and steric hindrance of the moiety in the polymer skeleton, which has scarcely been reported. Besides, the resultant rGO-P1 and rGO-P3 materials both showed excellent OL responses, even at 4 µJ. This behavior should enable their potential application in photonic and optoelectronic devices to protect human eyes or optical sensors from damage by intense laser irradiation.

Betaine inhibits toll-like receptor 4 expression in rats with ethanol-induced liver injury.

AIM: To test whether ethanol feeding could induce Toll-like receptor 4 (TLR4) responses, assess the hepatoprotective effect of betaine and its inhibitive effect on TLR4 in animal models of alcoholic liver injury. METHODS: Forty-eight female Sprague-Dawley rats were randomly divided into four groups as control, model, low and high dose betaine groups. Except control group, all rats were fed with high fat-containing diet plus ethanol and fish oil gavages for 8 wk. Betaine was administered intragastrically after exposure of ethanol for 4 wk. The changes of liver histology were examined. The expression of TLR4 mRNA and protein was detected by RT-PCR and Western blot, respectively. The serum aminotransferase activity [alanine transarninase (ALT), aspartate aminotransferase (AST)], serum endotoxin, and liver inflammatory factors [tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin-18 (IL-18)] were also assayed. RESULTS: Compared with control group, rats of model group developed marked liver injury, accompanied by an increase of ALT (159.41 +/- 7.74 U/L vs 59.47 +/- 2.34 U/L, P < 0.0001), AST (248.25 +/- 1.40 U/L vs 116.89 +/- 3.48 U/L, P < 0.0001), endotoxin (135.37 +/- 30.17 ng/L vs 44.15 +/- 7.54 ng/L, P < 0.0001), TNF-alpha (20.81 +/- 8.58 pg/mL vs 9.34 +/- 2.57 pg/mL, P = 0.0003), IFN-gamma (30.18 +/- 7.60 pg/mL vs 16.86 +/- 9.49 pg/mL, P = 0.0039) and IL-18 (40.99 +/- 8.25 pg/mL vs 19.73 +/- 9.31 pg/mL, P = 0.0001). At the same time, the expression of TLR4 mRNA and protein was markedly induced in the liver after chronic ethanol consumption (1.45 +/- 0.07 vs 0.44 +/- 0.04, P < 0.0001; 1.83 +/- 0.13 vs 0.56 +/- 0.08, P < 0.0001). Compared with model group, betaine feeding resulted in significant decreases of ALT (64.93 +/- 6.06 U/L vs 159.41 +/- 7.74 U/L, P < 0.0001), AST (188.73 +/- 1.11 U/L vs 248.25 +/- 1.40 U/L, P < 0.0001), endotoxin (61.80 +/- 12.56 ng/L vs 135.37 +/- 30.17 ng/L, P < 0.0001), TNF-alpha (9.79 +/- 1.32 pg/mL vs 20.81 +/- 8.58 pg/mL, P = 0.0003), IFN-gamma (18.02 +/- 5.96 pg/mL vs 30.18 +/- 7.60 pg/mL, P = 0.0008) and IL-18 (18.23 +/- 7.01 pg/mL vs 40.99 +/- 8.25 pg/mL, P < 0.0001). Betaine also improved liver steatosis. The expression levels of TLR4 mRNA or protein in liver tissues were significantly lowered (0.62 +/- 0.04 vs 1.45 +/- 0.07, P < 0.0001; and 0.65 +/- 0.06 vs 1.83 +/- 0.13, P < 0.0001). There was a statistical difference of TLR4 mRNA and protein expression between high- and low-dose betaine groups (0.62 +/- 0.04 vs 0.73 +/- 0.05, P < 0.0001, and 0.65 +/- 0.06 vs 0.81 +/- 0.09, P < 0.0001). CONCLUSION: Betaine can prevent the alcohol-induced liver injury effectively and improve the liver function. The expression of TLR4 increases significantly in ethanol-fed rats and betaine administration can inhibit TLR4 expression.

[Hematopoietic reconstitution of recipient mice after mFasL-cDNA transfected hematopoietic cell transplantation].

OBJECTIVE: The study was designed to explore the influence of transfected bone marrow mononuclear cells (BMMNC) transplantation on the hematopoietic cells activity and the recipient mice hematopoietic reconstitution. METHODS: The exogenous mFasL-cDNA gene was transferred to Balb/C mouse BMMNC by liposomes. Then the transferred BMMNC was co-cultured with BMMNC from BAC mouse (H-2d x b, male) at a ratio of 0.625 to 1 for 6 days. In the experimental group (the 3rd group), 1 x 10(7) (0.5 ml) mixed viable cells were injected into whole bodily irradiated ((60)Co-r) mice (6 to 8 week old female Balb/C) via the tail vein. The following grafted mice were simultaneously used in the study, the mice transplanted with 0.5 ml of culture medium, the mice transplanted with the mixture of untransferred Balb/C mouse BMMNC and BAC mouse BMMNC, the mice transplanted with the mixture of transferred Balb/C mouse BMMNC and BAC mouse BMMNC and the mice transplanted with Balb/C mouse BMMNC. The hematopoietic reconstitution, the origin of bone marrow cells responsible for the reconstitution, the graft versus host disease (GVHD), the survival rate for the recipient mice were observed after bone marrow transplantation (BMT). RESULTS: The counts of leukocytes and platelets in recipient blood of group four on +10 d and +20 d after BMT were higher than those in group three and group two (P < 0.01), but on +30 d after BMT the counts of leukocytes and platelets in recipient blood of group two, group three and group four were at their normal levels. The Y chromosome from donor mice was discovered in BMMNC of recipient mice having survived for over two months after BMT in group two and group three. The survival rate of the recipient mice two mouths after BMT in all groups were 0% for group one, 30% for group two, 80% for group three, and 100% for group four, respectively. The total survival rate of recipient mice in the experimental group was obviously higher than that of group two (P < 0.01). Grade II to III GVHD signs were found on the histology from dead mice after BMT in group three and group two, and the mice having survived for over two months in the group two. Grade I GVHD signs were found on histology from 7 out of 8 mice which survived for over two months after BMT in group three. CONCLUSIONS: The transplantation of mixed cells into recipient mice made the recipient mice achieve hematopoietic reconstitution from donor BMMNC.