Selective Hydrogenation of Aldehydes under Syngas Using CeO2-Supported Au Nanoparticle Catalyst.

Chemoselective hydrogenation of aldehydes to alcohols is of importance in synthetic chemistry. Here, we report a reusable CeO2-supported Au nanoparticle catalyst for the selective hydrogenation of aldehydes using syngas as the hydrogen source for which CO in syngas works as a site blocker to prevent side reactions. In particular, the hydrogenation of aldehydes with an easily reducible alkene, alkyne, or halogen moiety under syngas gave the corresponding alcohols with high selectivity, while the hydrogenation under pure hydrogen resulted in overreduction or dehalogenation. Of particular interest is that CO works as a site blocker but does not affect the hydrogenation rate significantly. A potential application of the present catalyst system was demonstrated by the conversion of terminal alkenes to alcohols via a one-pot hydroformylation/hydrogenation sequence.

Hydrogen-Induced Formation of Surface Acid Sites on Pt/Al(PO3)3 Enables Remarkably Efficient Hydrogenolysis of C-O Bonds in Alcohols and Ethers.

The hydrogenolysis of oxygenates such as alcohols and ethers is central to the biomass valorization and also a valuable transformation in organic synthesis. However, a mild and efficient catalyst system for the hydrogenolysis of a large variety of alcohols and ethers with various functional groups is still underdeveloped. Here, we report an aluminum metaphosphate-supported Pt nanoparticles (Pt/Al(PO3)3) for the hydrogenolysis of a wide variety of primary, secondary, and tertiary alkyl and benzylic alcohols, and dialkyl, aryl alkyl, and diaryl ethers, including biomass-derived furanic compounds, under mild conditions (0.1-1 atm of H2, as low as 70 °C). Mechanistic studies suggested that H2 induces formation of the surface Brønsted acid sites via its cleavage by supported Pt nanoparticles. Accordingly, the high efficiency and the wide applicability of the catalyst system are attributed to the activation and cleavage of C-O bonds by the hydrogen-induced Brønsted acid sites with the assistance of Lewis acidic Al sites on the catalyst surface. The high efficiency of the catalyst implies its potential application in energy-efficient biomass valorization or fine chemical synthesis.

Multifunctional WO3-ZrO2-Supported Platinum Catalyst for Remarkably Efficient Hydrogenolysis of Esters to Alkanes.

The hydrogenolysis of esters to alkanes is a key protocol for the synthesis of high-quality hydrocarbon fuels from renewable plant oils or fats. However, performing this process under mild energy-efficient conditions is challenging. Herein, we report a robust tungsten- and zirconium-oxide-supported platinum catalyst (Pt/WO3-ZrO2) for the hydrogenolysis of esters to alkanes at low temperatures (as low as 70 °C) and under ambient pressure (1 atm) of H2. For example, tristearin undergoes a complete conversion at 130 °C with more than 95% selectivity for the corresponding alkanes without carbon loss. In addition, the heterogeneous nature of the catalyst system reported herein permits multiple reuse of the catalyst without any significant loss of its high activity and selectivity. Mechanistic studies suggest that the multifunctional nature (acid and redox properties) of the WO3-ZrO2 support plays an important role in the high activity of the catalyst.

Dusp26 phosphatase regulates mitochondrial respiration and oxidative stress and protects neuronal cell death.

The dual specificity protein phosphatases (Dusps) control dephosphorylation of mitogen-activated protein kinases (MAPKs) as well as other substrates. Here, we report that Dusp26, which is highly expressed in neuroblastoma cells and primary neurons is targeted to the mitochondrial outer membrane via its NH2-terminal mitochondrial targeting sequence. Loss of Dusp26 has a significant impact on mitochondrial function that is associated with increased levels of reactive oxygen species (ROS), reduction in ATP generation, reduction in mitochondria motility and release of mitochondrial HtrA2 protease into the cytoplasm. The mitochondrial dysregulation in dusp26-deficient neuroblastoma cells leads to the inhibition of cell proliferation and cell death. In vivo, Dusp26 is highly expressed in neurons in different brain regions, including cortex and midbrain (MB). Ablation of Dusp26 in mouse model leads to dopaminergic (DA) neuronal cell loss in the substantia nigra par compacta (SNpc), inflammatory response in MB and striatum, and phenotypes that are normally associated with Neurodegenerative diseases. Consistent with the data from our mouse model, Dusp26 expressing cells are significantly reduced in the SNpc of Parkinson's Disease patients. The underlying mechanism of DA neuronal death is that loss of Dusp26 in neurons increases mitochondrial ROS and concurrent activation of MAPK/p38 signaling pathway and inflammatory response. Our results suggest that regulation of mitochondrial-associated protein phosphorylation is essential for the maintenance of mitochondrial homeostasis and dysregulation of this process may contribute to the initiation and development of neurodegenerative diseases.

TEMPO as a Hydrogen Atom Transfer Catalyst for Aerobic Dehydrogenation of Activated Alkanes to Alkenes.

2,2,6,6-Tetramethylpiperidine-N-oxyl (TEMPO) has been extensively utilized as a radical scavenger or an oxidation catalyst. In contrast, TEMPO as a hydrogen atom transfer (HAT) catalyst has rarely been studied. Here, we report that TEMPO, as the HAT catalyst, homolytically cleaves benzylic or allylic C-H bonds to give the corresponding alkyl radicals. Benefiting from the dual roles played by TEMPO as the HAT catalyst and the radical scavenger, the highly challenging aerobic dehydrogenation of activated alkanes to alkenes is successfully developed.

Increased Circulating Cathepsin L in Patients with Coronary Artery Disease.

Cathepsin L (CatL) is a potent collagenase involved in atherosclerotic vascular remodeling and dysfunction in animals and humans. This study investigated the hypothesis that plasma CatL is associated with the prevalence of coronary artery disease (CAD). Between February May 2011 and January 2013, 206 consecutive subjects were enrolled from among patients who underwent coronary angiography and percutaneous coronary intervention treatment. Age-matched subjects (n = 215) served as controls. Plasma CatL and high-sensitive C-reactive protein (hs-CRP) and high-density lipoprotein cholesterol were measured. The patients with CAD had significantly higher plasma CatL levels compared to the controls (1.4 ± 0.4 versus 0.4 ± 0.2 ng/mL, P < 0.001), and the patients with acute coronary syndrome had significantly higher plasma CatL levels compared to those with stable angina pectoris (1.7 ± 0.7 versus 0.8 ± 0.4 ng/mL, P < 0.01). Linear regression analysis showed that overall, the plasma CatL levels were inversely correlated with the high-density lipoprotein levels (r = -0.32, P < 0.01) and positively with hs-CRP levels (r = 0.35, P < 0.01). Multiple logistic regression analyses shows that cathepsin L levels were independent predictors of CAD (add ratio, 1.8; 95% CI, 1.2 to 2.1; P < 0.01). These data demonstrated that increased levels of plasma CatL are closely associated with the presence of CAD and that circulating CatL serves as a useful biomarker for CAD.

Immune Disorder in Atherosclerotic Cardiovascular Disease　- Clinical Implications of Using Circulating T-Cell Subsets as Biomarkers.

Atherosclerotic cardiovascular disease (ACVD) is an inflammatory phenomenon that leads to structural abnormality in the vascular lumen due to the formation of atheroma by the deposition of lipid particles and inflammatory cytokines. There is a close interaction between innate immune cells (neutrophils, monocyte, macrophages, dendritic cells) and adaptive immune cells (T and B lymphocytes) in the initiation and progression of atherosclerosis. According to novel insights into the role of adaptive immunity in atherosclerosis, the activation of CD4+T cells in response to oxidized low-density lipoprotein-antigen initiates the formation and facilitates the propagation of atheroma, whereas CD8+T cells cause the rupture of a developed atheroma by their cytotoxic nature. Peripheral CD4+and CD8+T-cell counts were altered in patients with other cardiovascular risk factors. Furthermore, on evaluation of the feasibility of immune cells as a diagnostic tool, the blood CD4+(helper), CD8+(cytotoxic), and CD4+CD25+Foxp3+(regulatory) T cells and the ratio of CD4 to CD8 cells hold promise as biomarkers of coronary artery disease and their subtypes. T cells also could be a therapeutic target for cardiovascular diseases. The goal of this review was therefore to summarize the available information regarding immune disorders in ACVD with a special focus on the clinical implications of circulating T-cell subsets as biomarkers.

Selective Synthesis of Primary Anilines from NH3 and Cyclohexanones by Utilizing Preferential Adsorption of Styrene on the Pd Nanoparticle Surface.

Dehydrogenative aromatization is one of the attractive alternative methods for directly synthesizing primary anilines from NH3 and cyclohexanones. However, the selective synthesis of primary anilines is quite difficult because the desired primary aniline products and the cyclohexanone substrates readily undergo condensation affording the corresponding imines (i.e., N-cyclohexylidene-anilines), followed by hydrogenation to produce N-cyclohexylanilines as the major products. In this study, primary anilines were selectively synthesized in the presence of supported Pd nanoparticle catalysts (e.g., Pd/HAP, HAP=hydroxyapatite, Ca10 (PO4 )6 (OH)2 ) by utilizing competitive adsorption unique to heterogeneous catalysis; in other words, when styrene was used as a hydrogen acceptor, which preferentially adsorbs on the Pd nanoparticle surface in the presence of N-cyclohexylidene-anilines, various structurally diverse primary anilines were selectively synthesized from readily accessible NH3 and cyclohexanones. The Pd/HAP catalyst was reused several times though its catalytic performance gradually declined.

WITHDRAWN: Abrogation of heat shock factor 1 (Hsf1) phosphorylation deregulates its activity and lowers activation threshold, leading to obesity in mice.

This article has been withdrawn by the authors. During preparation of this manuscript, a number of errors occurred in the preparation/assembly of Figs 2D, 2E, S1C, S1E, and S4. The authors apologize for not acknowledging that Fig. 6E and 6J represented the same samples and therefore the ß-actin immunoblot was reused. These presentation errors do not impact the underlying scientific findings of the article and the article is being withdrawn so that a corrected manuscript can be submitted for publication. We are sorry for any problems or issues that this may have caused the scientific community.

Selective Synthesis of Primary Anilines from Cyclohexanone Oximes by the Concerted Catalysis of a Mg-Al Layered Double Hydroxide Supported Pd Catalyst.

Although the selective conversion of cyclohexanone oximes to primary anilines would be a good complement to the classical synthetic methods for primary anilines, which utilize arenes as the starting materials, there have been no general and efficient methods for the conversion of cyclohexanone oximes to primary anilines until now. In this study, we have successfully realized the efficient conversion of cyclohexanone oximes to primary anilines by utilizing a Mg-Al layered double hydroxide supported Pd catalyst (Pd(OH)x/LDH) under ligand-, additive-, and hydrogen-acceptor-free conditions. The substrate scope was very broad with respect to both cyclohexanone oximes and cyclohexenone oximes, which gave the corresponding primary anilines in high yields with high selectivities (17 examples, 75% to >99% yields). The reaction could be scaled up (gram-scale) with a reduced amount of the catalyst (0.2 mol %). Furthermore, the one-pot synthesis of primary anilines directly from cyclohexanones and hydroxylamine was also successful (five examples, 66-99% yields). The catalysis was intrinsically heterogeneous, and the catalyst could be reused for the conversion of cyclohexanone oxime to aniline at least five times with keeping its high catalytic performance. Kinetic studies and several control experiments showed that the high activity and selectivity of the present catalyst system were attributed to the concerted catalysis of the basic LDH support and the active Pd species on LDH. The present transformation of cyclohexanone oximes to primary anilines proceeds through a dehydration/dehydrogenation sequence, and herein the plausible reaction mechanism is proposed on the basis of several pieces of experimental evidence.

Impact of Age on the Functional Significance of Intermediate Epicardial Artery Disease.

BACKGROUND: The functional significance of an intermediate coronary lesion is crucial for determining the treatment strategy, but age-related changes in cardiovascular function could affect the functional significance of an epicardial stenosis. The aim of this study was therefore to investigate the impact of age on fractional flow reserve (FFR) measurements in patients with intermediate coronary artery disease (CAD). METHODS AND RESULTS: Intracoronary pressure measurements and intravascular ultrasound (IVUS) were performed in 178 left anterior descending coronary arteries with intermediate stenosis. The morphological characteristics and FFR of 91 lesions in patients <65 years old were compared with those of 87 patients ≥65 years old. There was no difference in lesion location, diameter stenosis, minimum lumen area, plaque burden, or lesion length between the 2 age groups. Elderly patients had higher FFR (0.81±0.06 vs. 0.79±0.06, P=0.004) and lower ∆FFR, defined as the difference between resting Pd/Pa and FFR (0.13±0.05 vs. 0.15±0.05, P=0.014). Age, along with the location and degree of stenosis, was independently associated with FFR and ∆FFR (ß=0.162, P=0.008; ß=-0.131, P=0.043, respectively). CONCLUSIONS: Elderly patients with intermediate CAD are more likely to have higher FFR and lower ∆FFR, despite a similar degree of epicardial stenosis, compared with younger patients. (Circ J 2016; 80: 1583-1589).

Supported Gold Nanoparticles for Efficient α-Oxygenation of Secondary and Tertiary Amines into Amides.

Although the α-oxygenation of amines is a highly attractive method for the synthesis of amides, efficient catalysts suited to a wide range of secondary and tertiary alkyl amines using O2 as the terminal oxidant have no precedent. This report describes a novel, green α-oxygenation of a wide range of linear and cyclic secondary and tertiary amines mediated by gold nanoparticles supported on alumina (Au/Al2 O3 ). The observed catalysis was truly heterogeneous, and the catalyst could be reused. The present α-oxygenation utilizes O2 as the terminal oxidant and water as the oxygen atom source of amides. The method generates water as the only theoretical by-product, which highlights the environmentally benign nature of the present reaction. Additionally, the present α-oxygenation provides a convenient method for the synthesis of (18) O-labeled amides using H2 (18) O as the oxygen source.

Gold Nanoparticles Supported on a Layered Double Hydroxide as Efficient Catalysts for the One-Pot Synthesis of Flavones.

Flavones are a class of natural products with diverse biological activities and have frequently been synthesized by step-by-step procedures using stoichiometric amounts of reagents. Herein, a catalytic one-pot procedure for the synthesis of flavone and its derivatives is developed. In the presence of gold nanoparticles supported on a Mg-Al layered double hydroxide (Au/LDH), various kinds of flavones can be synthesized starting from 2'-hydroxyacetophenones and benzaldehydes (or benzyl alcohols). The present one-pot procedure consists of a sequence of several reactions, and Au/LDH can catalyze all these different types of reactions. The catalysis is shown to be truly heterogeneous, and Au/LDH can be readily recovered and reused.

Oxidative nucleophilic strategy for synthesis of thiocyanates and trifluoromethyl sulfides from thiols.

Thiocyanates and trifluoromethyl sulfides are important compounds and have classically been synthesized via multistep procedures together with the formation of significant amounts of byproducts. Herein, we demonstrate an oxidative nucleophilic strategy for the synthesis of thiocyanates and trifluoromethyl sulfides from thiol starting materials using nucleophilic reagents such as TMSCN and TMSCF3 (TMS = trimethylsilyl). In the presence of a 2 × 2 manganese oxide-based octahedral molecular sieve (OMS-2) and potassium fluoride (KF), various structurally diverse thiocyanates and trifluoromethyl sulfides could be synthesized in almost quantitative yields (typically >90%). The presented cyanation and trifluoromethylation reactions proceed through the OMS-2-catalyzed oxidative homocoupling of thiols to give disulfides followed by nucleophilic bond cleavage to produce the desired compounds and thiolate species (herein S-trimethylsilylated thiols). OMS-2 can catalyze oxidative homocoupling of the thiolate species, thus resulting formally in the quantitative production of thiocyanates and trifluoromethyl sulfides from thiols.

Gold-catalyzed heterogeneous aerobic dehydrogenative amination of α,ß-unsaturated aldehydes to enaminals.

Although enaminals (ß-enaminals) are very important compounds and have been utilized as useful synthons for various important compounds, they have been synthesized through non-green and/or limited procedures until now. Herein, we have successfully developed a green synthetic procedure using a heterogeneous catalyst. In the presence of gold nanoparticles supported on manganese-oxide-based octahedral molecular sieves OMS-2 (Au/OMS-2), dehydrogenative amination of α,ß-unsaturated aldehydes with amines proceeded efficiently, with the corresponding enaminals isolated in moderate to high yields (50-97 %). The catalysis was truly heterogeneous, and Au/OMS-2 could be reused. Furthermore, the formal Wacker-type oxidation of α,ß-unsaturated aldehydes to enaminones has been realized.

Targeted Replacement of HSF1 Phosphorylation Sites at S303/S307 with Alanine Residues in Mice Increases Cell Proliferation and Drug Resistance.

Mammalian heat shock factor HSF1 transcriptional activity is controlled by a multitude of phosphorylations that occur under physiological conditions or following exposure of cells to a variety of stresses. One set of HSF1 phosphorylation is on serine 303 and serine 307 (S303/S307). These HSF1 phosphorylation sites are known to repress its transcriptional activity. Here, we describe a knock-in mouse model where these two serine residues were replaced by alanine residues and have determined the impact of these mutations on cellular proliferation and drug resistance. Our previous study using this mouse model indicated the susceptibility of the mutant mice to become obese with age due to an increase in basal levels of heat shock proteins (HSPs) and chronic inflammation. Since HSF1 transcriptional activity is increased in many tumor types, this mouse model may be a useful tool for studies related to cellular transformation and cancer.

Circadian and seasonal variation in onset of acute myocardial infarction.

The aim was to investigate the circadian and seasonal variation of acute myocardial infarction (AMI). Clinical data of 3867 AMI patients hospitalized from November 2010 to October 2019 in the Border Yanbian Minority Autonomous Prefecture, China were collected, and 3158 patients with definite AMI onset times were analyzed. The clinical data analyzed included the time of onset, nationality, age, laboratory data. We divided the patients into 4 groups based on the timepoint of their AMI onsets: 00:00-05:59, 06:00-11:59, 12:00-17:59, and 18:00-23:59. We also divided the patients based on nationality: Chinese Korean and Han groups. We observed that there is a circadian rhythm in the incidence of AMI, and the peak of AMI is in the morning (7:00-9:00). Unexpectedly, the incidence of AMI was significantly lower in the cold winter than that of other 3 warm seasons (P < 0.01) and the peak of AMI presented at the months of the large contrast between day and night temperature difference (over 20°C) like May of Spring and October of Fall. Finally, there was no difference in circadian rhythm between Chinese Korean and Han, although these groups differed in age, body mass index, and the inflammatory cell level. These findings have shown a different seasonal and circadian variation in onset of AMI. Further studies are required to determine the pathophysiological mechanism(s) underlying these differences and to guide prevention of AMI for reducing its mortality and disability.

Heterogeneously catalyzed efficient hydration of alkynes to ketones by tin-tungsten mixed oxides.

The Sn-W mixed oxide prepared by calcination of the Sn-W mixed hydroxide precursor with a Sn/W molar ratio of 2:1 at 800 °C (SnW2-800) acts as an efficient heterogeneous catalyst for the hydration of alkynes. Structurally diverse terminal and internal alkynes, including aromatic, aliphatic, and double-bond-containing ones, can be converted into the corresponding ketones in moderate to high yields. The catalytic activity of SnW2-800 is much higher than those of previously reported heterogeneous catalysts and commonly utilized acid catalysts. The observed catalysis was truly heterogeneous, and the retrieved catalyst can be reused at least three times with retention of its high catalytic performance. The reaction rate for the SnW2-800-catalyzed hydration was decreased by addition of 2,6-lutidine and the hydration hardly proceeded in the presence of an equimolar amount of this compound with respect to that of the Brønsted acid sites in SnW2-800. Therefore, the present hydration is mainly promoted by the Brønsted acid sites in SnW2-800.

Synthesis of unsymmetrically substituted triarylamines via acceptorless dehydrogenative aromatization using a Pd/C and p-toluenesulfonic acid hybrid relay catalyst.

An efficient and convenient procedure for synthesizing triarylamines based on a dehydrogenative aromatization strategy has been developed. A hybrid relay catalyst comprising carbon-supported Pd (Pd/C) and p-toluenesulfonic acid (TsOH) was found to be effective for synthesizing a variety of triarylamines bearing different aryl groups starting from arylamines (diarylamines or anilines), using cyclohexanones as the arylation sources under acceptorless conditions with the release of gaseous H2. The proposed reaction comprises the following relay steps: condensation of arylamines and cyclohexanones to produce imines or enamines, dehydrogenative aromatization of the imines or enamines over Pd nanoparticles (NPs), and elimination of H2 from the Pd NPs. In this study, an interesting finding was obtained indicating that TsOH may promote the dehydrogenation.

HSF1-Mediated Control of Cellular Energy Metabolism and mTORC1 Activation Drive Acute T-Cell Lymphoblastic Leukemia Progression.

Deregulated oncogenic signaling linked to PI3K/AKT and mTORC1 pathway activation is a hallmark of human T-cell acute leukemia (T-ALL) pathogenesis and contributes to leukemic cell resistance and adverse prognosis. Notably, although the multiagent chemotherapy of leukemia leads to a high rate of complete remission, options for salvage therapy for relapsed/refractory disease are limited due to the serious side effects of augmenting cytotoxic chemotherapy. We report that ablation of HSF1, a key transcriptional regulator of the chaperone response and cellular bioenergetics, from mouse T-ALL tumors driven by PTEN loss or human T-ALL cell lines, has significant therapeutic effects in reducing tumor burden and sensitizing malignant cell death. From a mechanistic perspective, the enhanced sensitivity of T-ALLs to HSF1 depletion resides in the reduced MAPK-ERK signaling and metabolic and ATP-producing capacity of malignant cells lacking HSF1 activity. Impaired mitochondrial ATP production and decreased intracellular amino acid content in HSF1-deficient T-ALL cells trigger an energy-saving adaptive response featured by attenuation of the mTORC1 activity, which is coregulated by ATP, and its downstream target proteins (p70S6K and 4E-BP). This leads to protein translation attenuation that diminishes oncogenic signals and malignant cell growth. Collectively, these metabolic alterations in the absence of HSF1 activity reveal cancer cell liabilities and have a profound negative impact on T-ALL progression. IMPLICATIONS: Targeting HSF1 and HSF1-dependent cancer-specific anabolic and protein homeostasis programs has a significant therapeutic potential for T-ALL and may prevent progression of relapsed/refractory disease.