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An unprecedented photoredox-catalyzed phosphine-mediated deoxygenation of hexafluoroacetone hydrate was established to accomplish the hydroxylpolyfluoroalkylation of electron-deficient alkenes. A range of bis(trifluoromethyl)carbinols were facilely accessed by using readily available hexafluoroacetone hydrate, instead of toxic gaseous hexafluoroacetone. A range of electron-deficient alkenes are tolerated, giving the corresponding hydro-hydroxylpolyfluoroalkylated products in moderate to high yields. Remarkable features of this synthetic strategy include operational simplicity, mild reaction conditions, excellent regioselectivity, and broad functional group tolerance. The success of this strategy relies on the delicate utilization of aldehyde/ketone-gem-diol intrinsic equilibrium, which offers an innovated open-shell pathway for the assembly of synthetically challenging polyfluoroalkylated scaffolds.

A metal-free photosensitized protocol for regioselective diamination of alkene feedstocks over a single step was developed based on the rationally designed bifunctional diamination reagent, thus affording a range of differentially protected 1,2-diamines in moderate to high yields. Mechanistic studies reveal that the reaction is initiated with a triplet-triplet energy transfer between thioxanthone catalyst and diamination reagent, followed by fragmentation to simultaneously generate long-lived iminyl radical and transient amidyl radical. The excellent regioselectivity presumably stems from the large reactivity difference between two different N-centered radical species. This protocol is characterized by excellent regioselectivity, broad functional group tolerance, and mild reaction conditions, which would enrich the diversity and versatility of facilitate the diversity-oriented synthesis of 1,2-diamine-containing complex molecule scaffolds.

1,2-Bisphosphines have been identified as one class of important and powerful chiral ligands in asymmetric catalysis with transition metals. Herein, a copper(I)-catalyzed asymmetric hydrophosphination of α,β-unsaturated phosphine sulfides was developed with the assistance of "soft-soft" interaction between copper(I)-catalyst and the phosphine sulfide moiety, which afforded 1,2-bisphosphine derivatives with diversified electronic nature and steric hindrance in high to excellent yields with high to excellent enantioselectivity. Moreover, the challenging catalytic asymmetric hydrophosphination/protonation reaction was achieved with excellent enantioselectivity. Strikingly, the dynamic kinetic resolution of racemic diarylphosphines was also successfully carried out with high to excellent diastereo- and enantioselectivities. Interestingly, the nucleophilic copper(I)-diphenylphosphide species was characterized by 31 P NMR spectrum and mass spectrum. At last, three products were transformed to chiral 1,2-bisphosphines, which were employed as ligands in Rh-catalyzed asymmetric hydrogenation of α-amino-α,β-unsaturated ester. The α-amino acid derivative was produced in high enantioselectivity, which demonstrated the utility of the present methodology.

Herein, a copper(I)-catalyzed reaction of diarylphosphines and O-benzoyl hydroxylamines is developed. In the cases of symmetrical diarylphosphines, a series of aminophosphinites is prepared in high yields. In the cases of unsymmetrical diarylphosphines, an array of P-chiral aminophosphinites is synthesized in high yields with high enantioselectivity by using a copper(I)-(R,R

A photoinduced SET process enables the direct B-H bond activation of NHC-boranes. In contrast to common hydrogen atom transfer (HAT) strategies, this photoinduced reaction simply takes advantage of the beneficial redox potentials of NHC-boranes, thus obviating the need for extra radical initiators. The resulting NHC-boryl radical was used for the borylation of a wide range of α-trifluoromethylalkenes and alkenes with diverse electronic and structural features, providing facile access to highly functionalized borylated molecules. Labeling and photoquenching experiments provide insight into the mechanism of this photoinduced SET pathway.

One-pot ring-opening/ring-closure process of combining methyleneindolinone with 3-aminooxindole has been developed in this work. Novel polycyclic spirooxindoles were efficiently assembled under mild conditions in high yields (up to 95 %) with moderate to good diastereoselectivities (up to >95:5 d.r.) through simple filtration.

Transient receptor potential canonical channel 3 (TRPC3) proteins function as non-voltage-gated Ca2+ -permeable channels and play divergent roles in many processes of pathophysiology. The purpose of this study was to determine the relationship between TRPC3 expression and airway hyperresponsiveness and remodeling in ovalbumin-induced asthmatic Kunming mice. Mice were sensitized and challenged by ovalbumin to establish asthmatic model. Hematoxylin-eosin staining, hydroxyproline assay, and isometric tracheal ring force measurement were used to evaluate airway remodeling and hyperresponsiveness in asthmatic mice. Western blot was performed to detect the expression of TRPC3 proteins. MTT assay was used to measure the proliferation of airway smooth muscle cells. TRPC3 protein expression increased in airway smooth muscle of asthmatic mice. GdCl3 , a nonspecific TRPC blocker, attenuated the contractile force of airway smooth muscle. Fetal bovine serum stimulated airway smooth muscle cells proliferation and augmented TRPC3 protein expression. Both TRPC3 blockade by GdCl3 or specific TRPC3 antibodies and gene silencing by siRNA inhibited the proliferation of airway smooth muscle cells. In contrast, the current drugs treatment for asthma such as Dexamethasone and Aminophylline had no effects on TRPC3 protein overexpression. Therefore, TRPC3 protein overexpression may be involved in airway smooth muscle hyperresponsiveness and remodeling in asthmatic mice, providing evidence for a new direction of asthma pathogenesis research and a new target for drug intervention.

An unusual ligand-to-palladium-ratio-dependent reversal of enantioselectivity was systematically observed in the asymmetric Pd-catalysed [3+3]-annulation of Morita-Baylis-Hillman acetate with 4-hydroxycoumarin or 1,3-cyclohexanedione. The absolute configurations of the annulation products can be readily inversed by simply modifying L/Pd ratio from 1:3 to 2:1.

The unprecedented aerobic oxidative ring-opening-initiated cascades of isatins with 1,2,3,4-tetrahydroisoquinoline were explored, in which the reaction sequence could be readily modulated by simply introducing a protecting group in the isatin. Consequently, quinazoline-2,4-diones and polycyclic 2,3-dihydro-4(1H)-quinazolinones with potential bioactivities were efficiently assembled in moderate chemical yields.

With the aid of the hydrogen-bond relay of (S)-camphorsulfonic acid, the enantioselective exo-Diels–Alder cycloaddition of cyclic enones and 2-vinyl-1H-indoles catalyzed by prolinosulfonamide was developed. The corresponding Diels–Alder cycloadducts were readily obtained by a single recrystallization, free of column chromatography. Consequently, tetracyclic tetrahydrocarbazole ring systems with three contiguous stereogenic centers were prepared in moderate yields with excellent diastereoselectivities (exo/endo up to >20:1) and enantioselectivities (up to > 99 % ee).

Summary Aims Anxiety disorders are characterized by a deficient extinction of fear memory. Evidence is growing that leptin influences numerous neuronal functions. The aims of this study were to investigate the effects and the mechanism of leptin on fear extinction. Methods and results Leptin (1 mg/kg, i.p) was applied to evaluate the anxiolytic effect in rat behavioral tests. Field potentials recording were used to investigate the changes in synaptic transmission in the thalamic-lateral amygadala (LA) pathway of rat. We found that leptin produced strong anxiolytic effects under basal condition and after acute stress. Systemic administration and intra-LA infusions of leptin facilitated extinction of conditioned fear responses. The antagonist of NMDA receptor, MK-801, blocked the effect of leptin on fear extinction completely. Furthermore, these effects of leptin on fear extinction were accompanied by a reversal of conditioning-induced synaptic potentiation in the LA. Leptin facilitated NMDA receptor-mediated synaptic transmission, and reversed amygdala long-term potentiation (LTP) in a dose-dependent manner in vitro, and this LTP depotentiation effect was mediated by NMDA receptor and MAPK signaling pathway. Conclusions These results identify a key role of leptin in dampening fear conditioning-induced synaptic potentiation in the LA through NMDA receptor and indicate a new strategy for treating anxiety disorders.

The enantioselective 1,3-dipolar cycloaddition of 2-cyclohexene-1-one and azomethine ylides generated in situ from isatins and amino esters was developed by employing prolinosulfonamides as the catalyst. Consequently, novel polycyclic spirooxindole scaffolds with three contiguous stereocenters were prepared in high yield (up to 95 %) with excellent diastereo- (>20:1 dr) and enantioselectivity (up to 99 % ee).

One of the major bottle-necks in current LC-MS-based metabolomic investigations is metabolite identification. An often-used approach is to first look up metabolites from databases through peak mass, followed by verification of the obtained putative identifications using MS/MS data. However, the mass-based search may provide inappropriate putative identifications when the observed peak is from isotopes, fragments, or adducts. In addition, a large fraction of peaks is often left with multiple putative identifications. To differentiate these putative identifications, manual verification of metabolites through comparison between biological samples and authentic compounds is necessary. However, such experiments are laborious, especially when multiple putative identifications are encountered. It is desirable to use computational approaches to obtain more reliable putative identifications and prioritize them before performing experimental verification of the metabolites. In this article, a computational pipeline is proposed to assist metabolite identification with improved metabolome coverage and prioritization capability. Multiple publicly available software tools and databases, along with in-house developed algorithms, are utilized to fully exploit the information acquired from LC-MS/MS experiments. The pipeline is successfully applied to identify metabolites on the basis of LC-MS as well as MS/MS data. Using accurate masses, retention time values, MS/MS spectra, and metabolic pathways/networks, more appropriate putative identifications are retrieved and prioritized to guide subsequent metabolite verification experiments.

The enantioselective DAR of cyclic enones with 2-vinylindoles is achieved with the aid of hydrogen-bond relay from (S)-camphorsulfonic acid.

The highly diastereoselective intramolecular [3+2] annulation via the ring-opening of a cyclopropane diester derivative has been developed to construct a dihydroquinolinone scaffold. A series of tricyclic dihydroquinolinones bearing one or two all-carbon quaternary stereogenic centers were obtained in good yields and excellent diastereoselectivities (up to 20 : 1 dr). Moreover, the amide-linking mode shows obviously beneficial effects on the ring-opening of cyclopropane.

A series of novel 2,3- or 2,5-dispirooxindole-piperazine ring systems were efficiently constructed through the acid-promoted self-1,3-dipolar [3+3] cyclizations of azomethine ylides derived from isatin with various primary or cyclic secondary amines. Interestingly, the regioselectivity of this self-[3+3] cyclization could be effectively tuned by varying the structural features of substrates. The unprecedented 2,5-dispirooxindole-piperazine skeleton was achieved in good diastereoselectivity by employing 1,2,3,4-tetrahydroisoquinoline, while using pyrrolidine or glycine methyl ester furnished the 2,3-dispirooxindole-piperazine scaffold in excellent diastereoselectivity (only a single isomer formed).

Amiodarone, an iodinated benzofuran derivative with predominantly class III anti-arrhythmic effects, is used to treat supraventricular and ventricular arrhythmias. The purpose of this study was to assess the potential of neferine, an effective anti-pulmonary fibrosis drug isolated from the embryo of Nelumbo nucifera Gaertner's seeds, to alter the pharmacokinetic profile of amiodarone. Experimental Sprague-Dawley rats were randomly divided into two groups. In groups 1 and 2, amiodarone was given to rats by intragastric and intravenous administration, respectively, while neferine was co-administratered by intragastric administration. Blood samples were collected from the orbital venous plexus at indicated time points and were analyzed for amiodarone concentration using RP-HPLC. The geometric mean ratio for C(max) and AUC(0-96) was calculated. There were no significant differences between the pharmacokinetics parameters of amiodarone administered intravenously or intragastrically and the control (without neferine) group (with ratios of 0.7-1.4 in all experimental groups), suggesting that neferine had no effect on amiodarone plasma pharmacokinetics. The dosage regimen of amiodarone does not need to be taken into consideration when combined with neferine.

Free second toe transfer has become a popular method for the management of thumb or finger reconstruction. However, this creates an obvious appearance defect. A new operating procedure has been used since 1999. To enlarge the perimeter of the reconstructed thumb, a composite tissue strip flap from the fibular of great toe pedicled with the fibular proper plantar digital artery, combined or not with the island dorsal index finger flap, was inlaid with the second toe at the same time before the reconstruction. A crescent double-winged dorsal metatarsus flap, connected with second toe, in combination with the partial metatarsal bone, was also used to reconstruct fingers. There were 36 patients in the study group with a follow-up time of 6 months to 3 years. The thumb and finger reconstructed in this way showed better appearance, with normal caliber and length and without obvious adverse affects. This method has ameliorated the embarrassing appearance of the reconstructed thumb with earlier methods and is a relatively ideal method for thumb or finger reconstruction.

In this study, in vitro and in vivo antiinflammatory activities of fruits from Lindera erythrocarpa Makino were evaluated. The ethyl acetate soluble fraction derived from the ethanol extract of L. erythrocarpa fruits inhibited significantly nitric oxide (NO) production in lipopolysaccharide (LPS) induced NO in the murine macrophage cell line (RAW264.7) assay, the EC(50) being 16.35 microg/mL. Four compounds, including lucidone (1), cis/trans-methylludicone (2), methyl linderone (3) and linderone (4) were identified from the active fraction based on the bioactivity-guided fractionation procedure. Of these lucidone possessed the strongest NO inhibitory activity with an EC(50) value of 4.22 microg/mL. Furthermore, results from the protein expression assay demonstrated that lucidone suppressed iNOS and COX-2 protein expression in a dose-dependent manner. Lucidone also provided antiinflammatory activity in the croton oil-induced ear edema assay. When it was applied topically at a dosage of 0.5 and 1 mg per ear, the percent edema reduction in treated mice was 44% and 25%, respectively. The results obtained in this study indicated that lucidone has a good potential to be developed as an antiinflammation agent.

An acid-promoted self-1,3-dipolar cycloaddition of ketimines derived from isatins and benzylamines was successfully developed to assemble unprecedented dispirooxindole–imidazolidine ring systems. Generally, excellent diastereoselectivities (only a single stereoisomer formed) and good yields (up to 94%) were obtained. Consequently, this self-1,3-dipolar cycloaddition protocol offers facile access to a novel dispiroheterocyclic skeleton.

A Michael-Michael-acetalization cascade between 4-(2-hydroxyphenyl)but-3-en-2-ones and α,β-unsaturated aldehydes via a novel dual activation mode promoted by pyrrolidine was successfully established. Consequently, various novel tetrahydro-6-hydroxyl-6H-benzo[c]chromen-9-one derivatives were prepared in excellent diastereoselectivities and moderate to good yields. Further diverse modification of the resulting tricyclic scaffolds provided a facile pathway to achieve a variety of tetrahydro-6-hydroxyl-6H-benzo[c]chromen-9-one analogs.

Title compounds are conveniently and efficiently synthesized with excellent diastereoselectivities under extremely mild conditions.

Novel prolinamides were prepared and applied as organocatalysts in the asymmetric aldol reaction. Stable imidazolidinones were formed between prolinamides and aromatic aldehydes in organic solvents. It was found that aqueous conditions can significantly suppress the formation of the unwanted imidazolidinone intermediate and improve the catalytic activity of the prolinamides. As a consequence, high chemical yields (up to 99%) and good diastereoselectivity (up to >20:1 dr) and enantioselectivity (up to 95% ee) were achieved in 2-Me-THF or brine. This strategy could serve as a general solution to enhance the performance of prolinamides as organocatalysts.

The 1,3-dipolar cycloaddition of in situ generated azomethine ylides and 2-cyclohexenone is studied in the presence of a chiral proline-sulfonamide catalyst.

The effects of exposure to atmospheric pressure argon plasma on the quality of edible oil were studied. Peanut oil was exposed to the plasma that was generated in voltages ranging from 150–170 V and the variations of peroxide value, iodine value, acid value, and brightness of the resultant products were monitored. Besides, the storage stability of the radiated peanut oil was investigated as well. Plasma treatment did not change the acid value, but reduced the iodine value and increased the peroxide value and brightness of peanut oil in a voltage-dependent manner. Compared with control, exposure to the plasma generated in 170 V significantly decreased the contents of oleic acid and linoleic acid by 2.14 and 2.99% respectively, but exhibited no effect on that of palmitic acid. Storage results revealed that the acid value of the treated peanut oils kept increasing in the 30-day storage period, but the peroxide and iodine values peaked on the 14th and 4th day respectively and then declined gradually. Besides, the voltage-dependent variation pattern was observed for all the three parameters monitored. Since the peroxide, iodine, and acid values of the treated peanut oil are still in the ranges allowed by the Codex Alimentarius standards, it is concluded that the atmospheric pressure argon plasma treatment does not deteriorate the quality of peanut oil and this technology has potential application in the edible oil industry. A total of 5 mL peanut oil is transferred to a weighing bottle (diameter 40 mm) and exposed to atmospheric pressure argon plasma at a flow rate of 0.5 L/h for 100 s. The voltage of the power supply is set to 150, 155, 160, 165, or 170 V to explore the effects of plasma density on peanut oil quality. Treatment by the plasma generated in voltages 0∼170 V shows no effect on the acid value, but significantly reduces the iodine value, increases the peroxide value, and brightness of peanut oil in a voltage-dependent manner. Exposure to the plasma generated in 170 V significantly reduces the contents of oleic acid and linoleic acid by 2.14 and 2.99%, respectively, but exhibits no effect on that of palmitic acid. Practical applications: Peanut oil is rich in oleic acid, linoleic acid and other polyunsaturated fatty acids, as well as vitamin E and other nutrients, it also has high nutritional value and pleasant, peculiar flavor. However, aflatoxin B1 (AFB1) which comes from contaminated peanuts is often detected in peanut oil. An alternative that has been presented for the prevention and control of AFs in food is plasma. The plasma is a quasineutral gas of charged and neutral particles which exhibits collective behavior. The domestic and international research indicates that low temperature plasma has a good restraint of tumor cells, the promotion of gene transfection, coagulation and many other aspects. To our knowledge, the report about atmospheric pressure plasma treatment of aflatoxin has not been found in literature. Atmospheric pressure plasma for degradating AFs has the advantages of good safety, high efficiency, environmental friendliness, and is the developing direction of AFs control. In recent years, the development of atmospheric pressure plasma technology have outpaced the traditional low pressure plasma technology because it does not require the use of vacuum equipment, and it shows its advantage of handling large areas of objects more suited to the practical production line. Accordingly, in this paper, acid value, iodine value, peroxide value, chromatic value, fatty acid content and composition, and storage stability are chosen as detection indexes, to study the effects of atmospheric pressure plasma with different voltage on peanut oil quality, in order to provide theoretical basis for the application of atmospheric pressure plasma technology in vegetable oil industry.

A series of novel dispirooxindole derivatives, 3-acetyl-5-phenyl-pyrrolo(spiro-[2.3′]-1′-benzyl-oxindole)-spiro-[4.3″]-1″-benzyl-oxindoles, were synthesized via 1,3-dipolar cycloaddition of the azomethine ylide with 3-acetonylideneoxindole in high regioselectivities and yields. An unusual regioselectivity was observed in this 1,3-dipolar cycloaddition, leading to the construction of novel dispirooxindole skeleton. The substituent effects on the regioselectivity were also investigated.

A convenient method using FeCl3 as oxidant to dehydrogenate symmetric hydrazo compounds is reported for the first time. The method is superior to other known methods for dehydrogenating ArNHNHAr. It needs only cheap and less toxic reagents, mild conditions and short reaction time. Eight symmetric azo compounds are prepared in good yields.

The preparation of bisaryl carbodiazone compounds from the aryl substituted carbazides with Ceric Ammonium Nitrate (CAN) has been reported for the first time in excellent yields (80-91%). This method only needs simple instruments and short reaction time. A possible mechanism has been suggested.

The selective synthesis of diaryl carbazone using K3Fe(CN)6 as oxidant under alkaline condition in solid state is reported for the first time. Eight diaryl carbazone have been synthesized in excellent yields, and this method only needs cheap reagents, and simple procedure under mild condition.