Enantioselective Conjugate Addition of Boronic Acids to α,ß-Unsaturated 2-Acyl Imidazoles Catalyzed by Chiral Diols.

Herein, we report the enantioselective conjugate addition of organic boronic acids to α,ß-unsaturated 2-acyl imidazoles using (R)-3,3'-I2-BINOL as the catalyst. The catalytic system shows high efficiency and tolerance to alkenylboronic acids and heteroarylboronic acids. The corresponding Michael addition products were obtained in moderate to excellent yields and with moderate to excellent enantioselectivities (up to 97% ee). A gram-scale reaction was also conducted, and the desired product was obtained in high yield with no erosion in enantioselectivity. Finally, the synthetic utility of the methodology was demonstrated by transforming the 2-acyl imidazole moiety to the corresponding aldehyde, carboxylic acid, ester, and amide derivatives.

Neutrophilic granulocyte percentage is associated with anxiety in Chinese hospitalized heart failure patients.

BACKGROUND: In patients with heart failure, anxiety disorder is common and associated with adverse prognosis. This study intended to find more confounding factors of Chinese heart failure patients. METHODS: We enrolled 284 hospitalized heart failure patients, whose New York Heart Association (NYHA) classed as II-IV and left ventricular ejection fraction (LVEF) ≤ 45%. All the patients were scaled in Hamilton Rating Scale for Anxiety (14-items) (HAM-A14). Ordinal logistic regression analysis was performed to examine the association of correlated factors with anxiety disorder. RESULTS: There were 184 patients had anxiety accounting for 64.8% of all 284 hospitalized heart failure patients. The neutrophilic granulocyte percentage, urea nitrogen, total bilirubin and brain natriuretic peptide were positively associated with HAM-A14 score, meanwhile, the hemoglobin, red blood cells counts, albumin and LVEF were negatively associated with HAM-A14 score (All P < 0.05). After the adjustments of sex, hemoglobin, urea nitrogen, total bilirubin, albumin and brain natriuretic peptide, the neutrophilic granulocyte percentage was significantly associated with anxiety (OR = 43.265, P = 0.012). The neutrophilic granulocyte percentage was 0.616 ± 0.111, 0.640 ± 0.102, 0.681 ± 0.106 and 0.683 ± 0.113 in heart failure patients with no anxiety, possible anxiety, confirmed anxiety and obvious anxiety, respectively. CONCLUSIONS: Neutrophilic granulocyte percentage as well as the traditional risk factors such as sex, urea nitrogen and brain natriuretic peptide is associated with anxiety in hospitalized heart failure patients.

Organocatalyzed Enantioselective Conjugate Addition of Boronic Acids to ß,γ-Unsaturated α-Ketoesters.

We report herein the (R)-3,3'-Br2-BINOL-catalyzed enantioselective conjugate addition of organic boronic acids to ß,γ-unsaturated α-ketoesters to generate the corresponding Michael addition products in moderate to high yields and with moderate to excellent enantioselectivities (up to 99% ee). This catalytic system features characteristics of mild reaction conditions, high efficiency, and tolerance to alkenylboronic acids and heteroarylboronic acids.

A Multi-Layer Device for Light-Triggered Hydrogen Production from Alkaline Methanol.

It usually requires high temperature and high pressure to reform methanol with water to hydrogen with high turnover frequency (TOF). Here we show that hydrogen can be produced from alkaline methanol on a light-triggered multi-layer system with a very high hydrogen evolution rate up to ca. 1 µmol s-1 under the illumination of a standard Pt-decorated carbon nitride. The system can achieve a remarkable TOF up to 1.8×106  moles of hydrogen per mole of Pt per hour under mild conditions. The total turnover number (TTN) of 470 000 measured over 38 hours is among the highest reported. The system does not lead to any COx emissions, hence it could feed clean hydrogen to fuel cells. In contrast to a slurry system, the proposed multi-layer system avoids particle aggregation and effectively uses light and Pt active sites. The performance is also attributed to the light-triggered reforming of alkaline methanol. This notable performance is a promising step toward practical light-driven hydrogen generation.

Spontaneous Crystallization of Perovskite Nanocrystals in Nonpolar Organic Solvents: A Versatile Approach for their Shape-Controlled Synthesis.

The growing demand for perovskite nanocrystals (NCs) for various applications has stimulated the development of facile synthetic methods. Perovskite NCs have often been synthesized by either ligand-assisted reprecipitation (LARP) at room temperature or by hot-injection at high temperatures and inert atmosphere. However, the use of polar solvents in LARP affects their stability. Herein, we report on the spontaneous crystallization of perovskite NCs in nonpolar organic media at ambient conditions by simple mixing of precursor-ligand complexes without application of any external stimuli. The shape of the NCs can be controlled from nanocubes to nanoplatelets by varying the ratio of monovalent (e.g. formamidinium+ (FA+ ) and Cs+ ) to divalent (Pb2+ ) cation-ligand complexes. The precursor-ligand complexes are stable for months, and thus perovskite NCs can be readily prepared prior to use. Moreover, we show that this versatile synthetic process is scalable and generally applicable for perovskite NCs of different compositions.

Carbon Quantum Dots/TiOx Electron Transport Layer Boosts Efficiency of Planar Heterojunction Perovskite Solar Cells to 19.

In planar n-i-p heterojunction perovskite solar cells, the electron transport layer (ETL) plays important roles in charge extraction and determine the morphology of the perovskite film. Here, we report a solution-processed carbon quantum dots (CQDs)/TiO2 composite that has negligible absorption in the visible spectral range, a very attractive feature for perovskite solar cells. Using this novel CQDs/TiO2 ETL in conjunction with a planar n-i-p heterojunction, we achieved an unprecedented efficiency of ∼19% under standard illumination test conditions. It was found that a CQDs/TiO2 combination increases both the open circuit voltage and short-circuits current density as compared to using TiO2 alone. Various advanced spectroscopic characterizations including ultrafast spectroscopy, ultraviolet photoelectron spectroscopy, and electronic impedance spectroscopy elucidate that the CQDs increases the electronic coupling between the CH3NH3PbI3-xClx and TiO2 ETL interface as well as energy levers that contribute to electron extraction.

Guanidinium: A Route to Enhanced Carrier Lifetime and Open-Circuit Voltage in Hybrid Perovskite Solar Cells.

Hybrid perovskites have shown astonishing power conversion efficiencies owed to their remarkable absorber characteristics including long carrier lifetimes, and a relatively substantial defect tolerance for solution-processed polycrystalline films. However, nonradiative charge carrier recombination at grain boundaries limits open circuit voltages and consequent performance improvements of perovskite solar cells. Here we address such recombination pathways and demonstrate a passivation effect through guanidinium-based additives to achieve extraordinarily enhanced carrier lifetimes and higher obtainable open circuit voltages. Time-resolved photoluminescence measurements yield carrier lifetimes in guanidinium-based films an order of magnitude greater than pure-methylammonium counterparts, giving rise to higher device open circuit voltages and power conversion efficiencies exceeding 17%. A reduction in defect activation energy of over 30% calculated via admittance spectroscopy and confocal fluorescence intensity mapping indicates successful passivation of recombination/trap centers at grain boundaries. We speculate that guanidinium ions serve to suppress formation of iodide vacancies and passivate under-coordinated iodine species at grain boundaries and within the bulk through their hydrogen bonding capability. These results present a simple method for suppressing nonradiative carrier loss in hybrid perovskites to further improve performances toward highly efficient solar cells.

Elevated Homocysteine Level Related to Poor Outcome After Thrombolysis in Acute Ischemic Stroke.

BACKGROUND Hyperhomocysteinemia (HHcy) is a well-known risk factor for ischemic stroke. However, whether HHcy can influence the treatment outcome of acute ischemic stroke (AIS) patients has yet to be fully determined. In this study, we investigated the relationship between serum homocysteine (Hcy) level and prognosis in AIS patients who received tissue plasminogen activator (tPA) treatment. MATERIAL AND METHODS Patients were recruited according to the research criteria and grouped by their serum Hcy levels. Neurological outcome was evaluated by National Institute of Health Stroke Scale (NIHSS) score system before and 1 week after treatment, and functional outcome was evaluated by modified Rankin Scale (MRS) score system after 3 months. All patients took CT/MRI examination to detect cerebral hemorrhage in 24 hours after tPA treatment. Receiver operating characteristic curve (ROC) was employed to assess if serum homocysteine level can be used as an index to predict the outcome after tPA treatment. RESULTS The mean (±SD) serum Hcy level of 194 patients was 22.62±21.23 µmol/L. After 1-week tPA treatment, the NIHSS scores of high Hcy level group were significantly higher than those of low level group (p<0.05), meantime the high Hcy group showed obvious symptomatic intracerebral hemorrhage risk after 24 hours (p<0.05). Poor outcome was presented in mRS score results after 3 months in high Hcy level group, which compared with low Hcy level group (p<0.01). The ROC showed that Hcy level was a moderately sensitive and specific index to predict the prognosis with an optimal cut-off value at 19.95 µmol/L (sensitivity [58.2%], specificity [80.3%]). CONCLUSIONS High serum homocysteine level could potentially predict poor prognosis in acute ischemic stroke patients after tPA treatment.

An investigation of organic photovoltaics improvement via extension of the exciton lifetime.

The phosphorescent material tris(phenylpyrazole)iridium (Ir(ppz)3) was doped into the bulk heterojunction (BHJ) layer of a 3-hexylthiophene-2,5-diyl and indene-C60 bisadduct blend to form more excitons in the triplet state. Triplet-state excitons have longer lifetimes than singlet-state excitons. Surface phase separation was determined via atomic force microscopy and the vertical distribution of various molecules was analyzed via secondary ion mass spectroscopy. Several annealing processes were applied to the BHJ layer doped with Ir(ppz)3 to investigate the thermal stability of the film. The exciton lifetime in the BHJ film was characterized using femtosecond time-reserved photoluminescence.

Chiral-Boron-Complex-Catalyzed Asymmetric [3 + 2] Cycloaddition of 2'-Hydroxychalcones with N,N'-Cyclic Azomethine Imines.

We report the (R)-3,3'-I2-BINOL-boron-complex-catalyzed asymmetric 1,3-dipolar cycloaddition of 2'-hydroxychalcones with N,N'-cyclic azomethine imines, providing the corresponding N,N'-bicyclic pyrazolidine derivatives with three contiguous tertiary stereocenters in high yields with excellent diastereo- and enantioselectivities (up to >99:1 diastereomeric ratio and >99% enantiomeric excess). This catalytic system exhibits advantages of mild reaction conditions, high efficiency, and broad substrate scopes.

One-Step Reductive Amination of 5-Hydroxymethylfurfural into 2,5-Bis(aminomethyl)furan over Raney Ni.

Simultaneous reductive amination of C=O and C-OH in 5-hydroxymethylfurfural (HMF) into C-NH2 in 2,5-bis(aminomethyl)furan (BAMF) is challenging. In this work, reductive amination of C=O in HMF was firstly studied, in which HMF can be converted into 5-hydroxymethyl furfurylamine (HMFA) with a 99.5 % yield over Raney Co catalyst. BAMF was then directly synthesized with 82.3 % yield from HMF over Raney Ni catalyst at 160 °C for 12 h. An even higher yield of 88.3 % could be obtained through a stepwise reductive amination process, in which the reaction started at 120 °C for the first 2 h over Raney Co mainly for amination of C=O and then continued at 160 °C for another 10 h over Raney Ni mainly for amination of C-OH. Under optimized reaction conditions, the catalyst could be reused four times without obvious loss in catalytic performance. XRD and XPS characterization of the reused catalyst indicated that the formation of Ni3 N and the adsorption of alkyl amines could be the main reasons for the deactivation of the catalyst. Moreover, plausible reaction pathways were proposed to originate the detected by-products according to the kinetic profiles.

Morin exerts protective effects on encephalopathy and sepsis-associated cognitive functions in a murine sepsis model.

Sepsis-associated encephalopathy (SAE) often leads to cognitive impairments in the rest life of septic survivors. The potential pathological changes of SAE are complicated and have not been fully understood. Morin, a flavone compound exhibiting neuroprotective activity and anti-inflammation effect, was employed to treat with CLP-induced septic mice in our study. The data from a novel object recognition test and tail suspension test indicated that morin treatment reversed cognitive dysfunction and relieved depressive-like behaviors in septic mice. Morin down-regulated the expressions of IL-6, MCP-1, TNF-α and IL-10 in serum and diminished microglia activation in septic mice. Additionally, Western blot results showed that morin reduced the phosphokinase GSK3ß activity and elevated the phosphatase PP2A activity, which led to lower tau phosphorylation. Morin reduced Aß deposition and protected the synapse integrity, which might be the possible mechanism of protecting cognitive functions in septic mice. In conclusion, we identified that morin exerted anti-inflammation and anti-neurodegeneration effects in septic mice, and prevented further cognitive impairments.

Complement 3 activates the KLF5 gene in rat vascular smooth muscle cells.

We have shown that spontaneously hypertensive rat (SHR)-derived vascular smooth muscle cells (VSMCs) change to the synthetic phenotype and show increased expression of complement 3 (C3) and that C3 plays a role in the change to the synthetic phenotype. To determine the mechanisms underlying the effects of C3 on this phenotypic change, we examined the effects of C3a on transcription factors involved in VSMC phenotype and found that C3a increased the expression of Krüppel-like zinc-finger transcription factor 5 (KLF5) mRNA. C3a increased KLF5 promoter activity in a concentration-dependent manner. Deletion analysis of the promoter region of the KLF5 gene revealed that the region between nucleotides-991 and -699 contains the transcriptional regulatory element stimulated by C3a. C3a induced extracellular signal-regulated kinase (ERK) phosphorylation, and C3a-increased KLF5 promoter activity was completely inhibited by the MEK inhibitor U0126. These findings suggest that C3 increases KLF5 promoter activity and gene expression via ERK signaling.

Effects of the antioxidative beta-blocker celiprolol on endothelial progenitor cells in hypertensive rats.

BACKGROUND: Endothelial progenitor cells (EPCs) derived from bone marrow migrate to areas of endothelial damage and repair them. EPC function is impaired by oxidative stress. We examined the effects of an antioxidative beta1-adrenoceptor blocker on the number and function of EPCs in hypertensive rats. METHODS: Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats were fed diets loaded with high salt. The SHRs were treated with celiprolol or atenolol for 2 weeks. Peripheral blood mononuclear cells (MNCs) were separated, subjected to flow cytometric analysis to determine the number of circulating EPCs, and cultured to quantify EPC colony formation. EPC migration was evaluated in migration assay chambers. EPC senescence was evaluated using beta-galactosidase assay. Oxidative stress of EPCs was evaluated using thiobarbituric acid-reactive substance (TBARS) assay. The expression of nicotinamine adenine dinucleotide phosphate (NAD(P)H) oxidase component mRNAs in the renal cortex, aorta, and heart were evaluated by real-time PCR. RESULTS: The number, colony formation, and migration of EPCs in SHRs were significantly lower than those in WKY rats. TBARS scores in EPCs from SHRs were significantly higher than those from WKY rats. Celiprolol increased the number of circulating EPCs and stimulated EPC colony formation and migration, while decreasing EPC senescence. Celiprolol inhibited oxidation in EPCs from SHRs, and decreased the expression of NAD(P)H oxidase component mRNAs in the renal cortex, aorta, and heart. CONCLUSION: EPCs are impaired in SHRs in response to oxidative stress. Celiprolol decreases oxidative stress in hypertension in vivo and improves EPC numbers and function. It appears, therefore, that celiprolol may exert beneficial cardiovascular effects through its antioxidative properties.

Effects of an ARB on endothelial progenitor cell function and cardiovascular oxidation in hypertension.

BACKGROUND: Angiotensin II (Ang II) receptor blocker (ARB) has been reported to have protective effects on the cardiovascular system independent of blood pressure reduction. Endothelial progenitor cells (EPCs) play a significant role in neovascularization of ischemic tissue. The average lifespan of EPCs was recently reported to be shortened by oxidative stress and regulated by anti-oxidative mechanisms. It has been reported that EPCs are present in peripheral blood and have the ability to repair cardiovascular damage. We investigated the effects of an ARB, candesartan, on EPC function and cardiovascular oxidation in salt-loaded, stroke-prone, spontaneously hypertensive rats (SHR-SP) in vivo. METHODS: Salt-loaded SHR-SP were treated with candesartan (1 mg/kg/day), a diuretic (trichlormethiazide, TCM, 1.6 mg/kg/day), or an antioxidant (tempol, 5 mg/kg/day) for 2 weeks. Peripheral blood mononuclear cells (MNCs) were isolated and cultured to assay EPC colony formation and migration. Oxidative stress in EPCs was evaluated by thiobarbituric acid reactive substance (TBARS) assay. We evaluated messenger RNA (mRNA) expression of c-kit in the heart, the renin-angiotensin system (RAS) in EPC colonies, and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit in cardiovascular organs. RESULTS: Candesartan and tempol, but not TCM, markedly increased EPC colony number in SHR-SP and reduced TBARS. Candesartan also significantly decreased mRNA expression of NADPH oxidase subunits in cardiovascular organs and increased cardiac c-kit mRNA expression. EPCs expressed mRNAs of renin, cathepsin D, chymase, and Ang II type 1 and type 2 receptors. CONCLUSIONS: Candesartan, an ARB, improves EPC dysfunction and increases cardiac c-kit expression through the anti-oxidative mechanism in hypertension. The local RAS induces oxidative stress and regulates the EPC functions.

Cardiovascular remodeling and metabolic abnormalities in SHRSP.Z-Lepr(fa)/IzmDmcr rats as a new model of metabolic syndrome.

The purpose of this study was to evaluate whether the spontaneously hypertensive rat SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP fatty) is a useful animal model to clarify molecular mechanisms that underlie metabolic syndrome. We investigated histopathologic changes in the cardiovascular organs and metabolic characteristics of SHRSP fatty rats, which are congenic rats from a cross between SHRSP and Zucker fatty (ZF) rats. The aortic wall and cardiac, carotid, and renal arteries from SHRSP and SHRSP fatty rats were thicker than those of ZF rats. The renal cortex in SHRSP and SHRSP fatty rats showed severe glomerulosclerosis. Pancreatic islands in SHRSP fatty and ZF rats showed marked hyperplasia. Steady-state plasma glucose concentrations were higher in SHRSP fatty than in ZF rats. Non-fasting triglyceride levels in SHRSP fatty rats were higher than in ZF rats. DNA synthesis in cultured vascular smooth muscle cells (VSMCs) from SHRSP fatty and SHRSP rats was significantly higher than that in VSMCs from Wistar-Kyoto (WKY) or ZF rats. Levels of platelet-derived growth factor A-chain and transforming growth factor-beta1 mRNAs were higher in VSMCs from SHRSP fatty and SHRSP than from ZF rats. Microarray analysis identified five genes that were significantly upregulated and four genes that were significantly downregulated in visceral adipose tissue of SHRSP fatty rats compared with levels in control strains (SHRSP and ZF rats). These findings suggest that the combination of hypertension and obesity accelerates vascular remodeling, dyslipidemia, and insulin resistance in metabolic syndrome. The phenotype of SHRSP fatty is similar to that of human metabolic syndrome, and therefore, studies of these rats may help clarify the molecular mechanisms that underlie metabolic syndrome in humans.

[Comparative genomic hybridization: the profile of chromosomal imbalances in rhabdomyosarcoma].

OBJECTIVE: To characterize the profile of chromosomal imbalances of rhabdomyosarcoma(RMS). METHODS: Comparative genomic hybridization (CGH) was used to investigate genomic imbalances in 25 cases of primary RMS including 10 cases of alveolar rhabdomyosarcoma (ARM), 12 cases of embryonic rhabdomyosarcoma (ERMS), 3 cases of polymorphic rhabdomyosarcoma (PRMS) and 2 RMS cell lines (A240 originated from ARMS and RD from PRMS), with correlation to histological type, pathologic grading, clinical staging, gender and age, respectively. RESULTS: All twenty-five rhabdomyosarcomas showed evidence of increased or decreased DNA sequence copy numbers involving one or more regions of the genome. (1) The frequently gained chromosome regions in RMS were 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q, 18q, and the frequently lost chromosome regions were 3p, 11p, 6p. (2) The frequently gained chromosome arms in ARMS were 12q, 2p, 6, 2q, 4q, 10q, 15q. The frequently lost chromosome arms were 3p, 6p, 1q, 5q. The frequently gained chromosome regions in ERMS were 7p, 9q, 2p, 18q, 1p, 8q. The frequently lost chromosome arms in ERMS were 11p. (3) The frequently gained chromosome arms in translocation associated RMS were 12q, 2, 6, 10q, 4q and 15q (> 30%), 3p, 6p, 5q (> 30%) were the frequently loss chromosome arms. The frequently gained chromosome regions in non-translocation associated RMS were 2p, 9q, 18q (> 30%), and 11p, 14q (> 30%) were the frequently loss chromosome regions. Gain of 12q was significantly correlated with the translocation-associated tumors (P < 0.05). (4) Gains of 9q was significantly correlated with clinical staging (P < 0.05). CONCLUSIONS: Gain of 2p, 12q, 6p, 9q, 10q, 1p, 2q, 6q, 8q, 15q, 18q and loss of 3p, 11p, 6p may be involved in the tumorigenesis of RMS. Gains of 12q may be correlated with gene fusion/chromosomal translocation in ARMS. Gains of 9q may be correlated with an early tumor stage of RMS.

Resonantly enhanced multiple exciton generation through below-band-gap multi-photon absorption in perovskite nanocrystals.

Multi-photon absorption and multiple exciton generation represent two separate strategies for enhancing the conversion efficiency of light into usable electric power. Targeting below-band-gap and above-band-gap energies, respectively, to date these processes have only been demonstrated independently. Here we report the combined interaction of both nonlinear processes in CsPbBr3 perovskite nanocrystals. We demonstrate nonlinear absorption over a wide range of below-band-gap excitation energies (0.5-0.8 Eg). Interestingly, we discover high-order absorption processes, deviating from the typical two-photon absorption, at specific energetic positions. These energies are associated with a strong enhancement of the photoluminescence intensity by up to 105. The analysis of the corresponding energy levels reveals that the observed phenomena can be ascribed to the resonant creation of multiple excitons via the absorption of multiple below-band-gap photons. This effect may open new pathways for the efficient conversion of optical energy, potentially also in other semiconducting materials.

High-performance perovskite/Cu(In,Ga)Se2 monolithic tandem solar cells.

The combination of hybrid perovskite and Cu(In,Ga)Se2 (CIGS) has the potential for realizing high-efficiency thin-film tandem solar cells because of the complementary tunable bandgaps and excellent photovoltaic properties of these materials. In tandem solar device architectures, the interconnecting layer plays a critical role in determining the overall cell performance, requiring both an effective electrical connection and high optical transparency. We used nanoscale interface engineering of the CIGS surface and a heavily doped poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine] (PTAA) hole transport layer between the subcells that preserves open-circuit voltage and enhances both the fill factor and short-circuit current. A monolithic perovskite/CIGS tandem solar cell achieved a 22.43% efficiency, and unencapsulated devices under ambient conditions maintained 88% of their initial efficiency after 500 hours of aging under continuous 1-sun illumination.

Spontaneous Self-Assembly of Perovskite Nanocrystals into Electronically Coupled Supercrystals: Toward Filling the Green Gap.

Self-assembly of nanoscale building blocks into ordered nanoarchitectures has emerged as a simple and powerful approach for tailoring the nanoscale properties and the opportunities of using these properties for the development of novel optoelectronic nanodevices. Here, the one-pot synthesis of CsPbBr3 perovskite supercrystals (SCs) in a colloidal dispersion by ultrasonication is reported. The growth of the SCs occurs through the spontaneous self-assembly of individual nanocrystals (NCs), which form in highly concentrated solutions of precursor powders. The SCs retain the high photoluminescence (PL) efficiency of their NC subunits, however also exhibit a redshifted emission wavelength compared to that of the individual nanocubes due to interparticle electronic coupling. This redshift makes the SCs pure green emitters with PL maxima at ≈530-535 nm, while the individual nanocubes emit a cyan-green color (≈512 nm). The SCs can be used as an emissive layer in the fabrication of pure green light-emitting devices on rigid or flexible substrates. Moreover, the PL emission color is tunable across the visible range by employing a well-established halide ion exchange reaction on the obtained CsPbBr3 SCs. These results highlight the promise of perovskite SCs for light emitting applications, while providing insight into their collective optical properties.