A novel fluorescent probe based on a bisbinaphthyl structure has been designed and synthesized. This compound in combination with Zn­(II) has exhibited highly enantioselective fluorescence enhancement with 13 common free amino acids. For example, its enantiomeric fluorescent enhancement ratios (ef or ΔI L/ΔI D) in the presence of the following amino acids are extremely high: 177 for valine, 199 for methionine, 186 for phenylalanine, 118 for leucine, and 89 for alanine. The observed high enantioselectivity and the extent of the substrate scope are unprecedented in the fluorescent recognition of free amino acids. This fluorescent probe can be applied to determine the enantiomeric composition of the structurally diverse chiral amino acids. NMR and mass spectroscopic investigations have provided clues to elucidate the observed high enantioselectivity.

Although most treatment research on bipolar disorder has focused on mania, depressive episodes occur more frequently among patients with bipolar disorder. Here, we report the results of 2 identically designed, 8-week, multicenter, randomized, double-blind, placebo-controlled studies (CN138-096 and CN138-146) to evaluate the efficacy and safety of aripiprazole monotherapy in outpatients with bipolar I disorder experiencing a major depressive episode without psychotic features. Patients were randomized to placebo or aripiprazole (initiated at 10 mg/d, then flexibly dosed at 5-30 mg/d based on clinical effect and tolerability). The primary end point was mean change from baseline to Week 8 (last observation carried forward) in the Montgomery-Asberg Depression Rating Scale total score. In Studies 1 and 2, respectively, 186 and 187 patients were randomized to aripiprazole, and 188 and 188 to placebo. Although statistically significant differences were observed during Weeks 1 to 6, aripiprazole did not achieve statistical significance versus placebo at Week 8 in either study in the change in Montgomery-Asberg Depression Rating Scale total (primary end point). In addition, despite early statistical separation on the Clinical Global Impressions Bipolar Version Severity of Illness-Depression score (key secondary end point), aripiprazole was not superior to placebo at end point. Aripiprazole was associated with a higher incidence of akathisia, insomnia, nausea, fatigue, restlessness, and dry mouth versus placebo. More patients discontinued with aripiprazole versus placebo in Study 1 (46.8% vs 35.1%) and Study 2 (41.2% vs 29.8%). Aripiprazole monotherapy-as dosed in this study design-was not significantly more effective than placebo in the treatment of bipolar depression at end point (Week 8).

A novel perfluoroalkyl-BINOL-based chiral diketone is found to be the first highly enantioselective fluorescent sensor in the fluorous phase. One enantiomer of a chiral amino alcohol or diamine at a concentration greater than 1 mM can cause an up to 1200-2000-fold fluorescent enhancement of the sensor (0.08 mM), while the other enantiomer gives only a 10-50-fold enhancement. The fluorous-phase-based sensor is found to enhance the reactivity of the previously reported fluorous insoluble sensor with amino alcohols and expand its chiral recognition ability. Dynamic light scattering studies show the formation of aggregates of very different particle sizes when two enantiomers of a substrate interact with the sensor in perfluorohexane (FC-12). This substantial difference enables easy discrimination of the enantiomers with UV-lamps or even the naked eye. NMR, IR, and mass spectroscopic studies indicate that the fluorescent enhancement and enantioselectivity should originate from the fluorous solvent-promoted nucleophilic addition of the amino alcohols to the carbonyl groups of the sensor.

A novel BINOL-based near-IR fluorescent probe was designed and synthesized by incorporating a rhodamine-like dye. In the presence of Zn­(II), this compound was found to exhibit highly enantioselective fluorescence enhancement at λemi > 730 nm and λexc = 690 nm when treated with 14 common amino acids in aqueous solution. An enantioselective fluorescence enhancement ratio up to 163 was observed. The mechanism of the fluorescence response of this probe was investigated by various spectroscopic methods.

A unique supramolecular two-component gelation system was constructed from amphiphilic shape-persistent cyclo[6]aramides and diethylammonium chloride (or triethylammonium chloride). This system has the ability to discriminate native arginine from 19 other amino acids in a specific fashion. Cyclo[6]aramides show preferential binding for the guanidinium residue over ammonium groups. This specificity was confirmed by both experimental results and theoretical simulations. These results demonstrated a new modular displacement strategy, exploring the use of species-binding hydrogen-bonded macrocyclic foldamers for the construction of two-component gelation systems for selective recognition of native amino acids by competitive host-guest interactions. This strategy may be amenable to developing a variety of functional two-component gelators for specific recognition of various targeted organic molecular species.

The aim of this study was to investigate the effects of osteocalcin ( OCN ) on fatty liver hemorrhagic syndrome ( FLHS ) in aged laying hens. Thirty 68-week-old White Plymouth laying hens were randomly assigned into conventional single-bird cages, and the cages were randomly allocated into one of 3 treatments (n = 10): normal diet (ND + vehicle, ND + V ), high-fat diet (HFD + vehicle, HFD + V ), and HFD + OCN (3 μg/bird, 1 time/2 d, i.m.) for 40 d. At day 30, oral glucose tolerance tests ( OGTT ) and insulin tolerance tests ( ITT ) were performed. At the end of experiment, the hens were euthanized followed by blood collection. The plasma aspartate transaminase ( AST ), alkaline phosphatase ( ALP ), total cholesterol ( TC ), triglyceride ( TG ), low-density lipoprotein cholesterol ( LDL-C ), and high-density lipoprotein cholesterol ( HDL-C ) were measured using an automatic biochemistry analyzer. Pathological changes in the liver were examined under both light and transmission electron microscopes. The plasma inflammatory factors including interleukin-1 ( IL-1 ), IL-6, and tumor necrosis factor-alpha ( TNF-α ) were analyzed by ELISA, and the gene expressions of these inflammatory factors in the liver were analyzed by real-time PCR. The level of oxidative stress was evaluated using malondialdehyde ( MDA ) and glutathione peroxidase ( GSH-Px ) assay kits, respectively. The results showed that HFD + V hens had more severe liver hemorrhage and fibrosis than ND + V hens ( P < 0.05). The ultramicrostructural examination showed that hepatocytes of HFD + V hens exhibited necrotic pyknosis showing great intracellular electron, mitochondrial swelling, shrunk nucleus, and absence of autolysosomes. Osteocalcin mitigated HFD + V–induced pathological changes in aged laying hens. High-fat diet + OCN hens had higher insulin sensitivity; lower liver concentrations of MDA ( P = 0.12) but higher GSH-Px ( P < 0.05); and lower blood TNF-α concentrations ( P < 0.05) and mRNA expressions ( P < 0.05) than HFD + V hens. These results suggest OCN functions in preventing the FLHS process in old laying hens through inhibiting excessive energy diet-induced metabolic disorder, oxidative stress, and related pathological damage.

Af luorophilic fluorescent probe based on ap erfluoroalkyl-substituted bis(binaphthyl) compound wasd esigned and synthesized.I td isplayed ah ighly enantioselective fluorescencer esponse towards tructurally diverse amino acids in ab iphasic fluorous/aqueous system with enantiomeric fluorescent enhancementr atio (ef; DI D /DI L )v alues up to 45.2 (histidine). It can be used to determinet he enantiomeric compositions of amino acids and also allows the amino acid enantiomerst ob ev isually discriminated. NMR and mass-spectroscopic investigations provided insights into the observedh igh enantioselectivity.T his biphasic fluorescent recognition was used to determine the enantiomeric composition of the crude phenylalanine products generated by an enzyme-catalyzed asymmetrichydrolysis under various reactionc onditions. The fluorous-phase-based fluorescence measurement under the biphasic conditions wasa ble to minimize the interference of other reaction componentsa nd thus has potential in asymmetricreactionscreening.[a] Dr.Y .-Y.Zhu SchoolofC hemistry and EnvironmentalE ngineering Wuhan Institute of Technology, Wuhan4 30205 (P.R.C hina)[b] Dr.

An easily available BINOL-Ti(O(i)Pr)4 catalyst system is found to activate the reaction of Zn powder with EtI for the asymmetric alkyne addition to aldehydes at room temperature. It allows the synthesis of a number of synthetically useful chiral propargylic alcohols with both high yields and high enantioselectivity (up to >96% ee).