Inhaled nitric oxide testing in predicting prognosis in pulmonary hypertension due to left-sided heart diseases.

AIMS: The pathophysiology of pulmonary hypertension (PH) due to left-sided heart disease (Group 2 PH) is distinct from that of other groups of PH, yet there are still no approved therapies that selectively target pulmonary circulation. The increase in pulmonary capillary pressure due to left-sided heart disease is a trigger event for physical and biological alterations of the pulmonary circulation, including the nitric oxide (NO)-soluble guanylate cyclase-cyclic guanosine monophosphate axis. This study investigated inhaled NO vasoreactivity tests for patients with Group 2 PH and hypothesized that these changes may have a prognostic impact. METHODS AND RESULTS: This was a single-centre, retrospective study with a median follow-up of 365 days. From January 2011 to December 2015, we studied 69 patients with Group 2 PH [age, 61.5 ± 13.0 (standard deviation) years; male:female, 49:20; left ventricular ejection fraction, 50.1 ± 20.4%; mean pulmonary arterial pressure, ≥25 mmHg; and pulmonary arterial wedge pressure (PAWP), >15 mmHg]. No adverse events were observed after NO inhalation. Thirty-four patients with Group 2 PH showed increased PAWP (ΔPAWP: 3.26 ± 2.22 mmHg), while the remaining 35 patients did not (ΔPAWP: -2.11 ± 2.29 mmHg). Multivariate analysis revealed that increased PAWP was the only significant predictor of all-cause death or hospitalization for heart failure (HF) after 1 year (hazard ratio 4.35; 95% confidence interval, 1.27-14.83; P = 0.019). The acute response of PAWP to NO differed between HF with preserved and reduced ejection fractions. CONCLUSIONS: Patients with Group 2 PH were tolerant of the inhaled NO test. NO-induced PAWP is a novel prognostic indicator.

Lipophilic N-Hydroxyimide Derivatives: Design, Synthesis, and Application to Aerobic Alkane Oxidation Under Neat Conditions.

This work reports the design and synthesis of a series of 5-membered and 6-membered N-hydroxyimides flanked by lipophilic alkyl groups adjacent to carbonyl groups, aiming to endow lipophilicity and tolerance toward ring opening degradation. Their solubility in cyclohexane was 5-20 times higher than those of unsubstituted N-hydroxyphthalimide (NHPI) and even 3-10 times higher than a formerly known lipophilic NHPI analog bearing a long alkyl ester. UV-Vis spectroscopy determined the rate constants of first-order decay of N-oxyls, which revealed enhanced stability of 3,5-di-tert-butyl-NHPI and N-hydroxyglutarimide flanked by spiro-cyclohexanes compared with that of NHPI. Their bond dissociation energies were assessed by EPR spectroscopy and DFT calculation, suggesting these lipophilic N-hydroxyimides catalyzed aerobic cyclohexane oxidation under neat conditions with up to 60 turnovers, which is the highest among hitherto reported reactions under neat conditions.

MYPT1-PP1ß phosphatase negatively regulates both chromatin landscape and co-activator recruitment for beige adipogenesis.

Protein kinase A promotes beige adipogenesis downstream from ß-adrenergic receptor signaling by phosphorylating proteins, including histone H3 lysine 9 (H3K9) demethylase JMJD1A. To ensure homeostasis, this process needs to be reversible however, this step is not well understood. We show that myosin phosphatase target subunit 1- protein phosphatase 1ß (MYPT1-PP1ß) phosphatase activity is inhibited via PKA-dependent phosphorylation, which increases phosphorylated JMJD1A and beige adipogenesis. Mechanistically, MYPT1-PP1ß depletion results in JMJD1A-mediated H3K9 demethylation and activation of the Ucp1 enhancer/promoter regions. Interestingly, MYPT1-PP1ß also dephosphorylates myosin light chain which regulates actomyosin tension-mediated activation of YAP/TAZ which directly stimulates Ucp1 gene expression. Pre-adipocyte specific Mypt1 deficiency increases cold tolerance with higher Ucp1 levels in subcutaneous white adipose tissues compared to control mice, confirming this regulatory mechanism in vivo. Thus, we have uncovered regulatory cross-talk involved in beige adipogenesis that coordinates epigenetic regulation with direct activation of the mechano-sensitive YAP/TAZ transcriptional co-activators.

An in vitro system for experimentally induced cryptorchidism.

Cryptorchidism is one of the most common abnormalities of male sexual development, and is characterized by the failure of the testis to descend into the scrotum. Despite extensive studies of cryptorchidism over the past century, the mechanisms for temperature-induced germ-cell loss are not well understood. All of the main cell types in the testis are believed to be affected by the elevated testis temperature induced by cryptorchidism. The cooler temperature in the special environment of the scrotum is required for maintaining optional conditions for normal spermatogenesis. Many studies reported that experimentally induced cryptorchidism caused germ cell apoptosis and suppressed spermatogenesis. However, other factors including hormones must also be examined for cryptorchidism. To explore the mechanism for cryptorchidism, in vitro cultures of testes have been used, but complete spermatogenesis using in vitro methods was not accomplished until 2011. In 2011, Sato et al. (Nature, 471, 504-507) reported the in vitro production of functional sperm in cultured neonatal mouse testes. Using this in vitro system, for the first time, we report that spermatogenesis was abrogated at 37 °C, in accordance with in vivo surgery-mediated cryptorchidism, while spermatogenesis proceeded at 34 °C in cultured testes. This result clearly showed that temperature is the sole determinant of cryptorchidism. Moreover, we found that spermatogenesis was arrested before early spermatocytes at 37 °C. In conclusion, using our in vitro system, we have demonstrated that (1) temperature is the determining factor for cryptorchidism, and (2) higher temperature (37 °C) suppresses DNA synthesis in spermatogenesis.

Three-dimensional CoM energetics, pelvis and lower limbs joint kinematics of uphill treadmill running at high speed.

The purpose of this study was to investigate the effects of slope on three-dimensional running kinematics at high speed. Thirteen male sprinters ran at high speed (7.5 m/s) on a motorised treadmill in each a level and a 5.0% slope condition. Three-dimensional motion analysis was conducted to compare centre of mass (CoM) energetics, pelvis segment and lower limb joints kinematics. We found that contact time was not affected by the slope, whereas flight time and step length were significantly shorter in uphill compared to level running. Uphill running reduced negative CoM work and increased positive CoM work compared to level running. Ankle, knee and hip joints were more flexed at initial ground contact, but only the knee was more extended at the end of stance in uphill compared to level running. Additionally, the hip joint was more abducted, and the free leg side of the pelvis was more elevated at the end of stance in uphill running. Our results demonstrate that joint motion must be developed from a more flexed/adducted position at initial contact through a greater range of motion compared to level running in order to meet the greater positive CoM work requirements in uphill running at high speed.

Electrodeposition of Large Area, Angle-Insensitive Multilayered Structural Colors.

We demonstrate structural colors produced by a simple, inexpensive, and nontoxic electrodeposition process. Asymmetric metal-dielectric-metal (MDM) multilayered structures were achieved by sequential electrodeposition of smooth gold, thin cuprous oxide, and finally thin gold on conductive substrates, forming an effective optical cavity with angle-insensitive characteristics. Different colors of high brightness were achieved by simply tuning the thickness of the electrodeposited middle cavity layer. This process is compatible with highly nonplanar substrates of arbitrary shape, size, and roughness. This work is the first demonstration of solution-processed, electrodeposited, MDM film stacks that are uniform over large areas and highlights the clear advantages of this approach over traditional deposition or assembly methods for preparing colored films.

Reactivity of a Tetra(o-tolyl)diborane(4) Dianion as a Diarylboryl Anion Equivalent.

Lithium and magnesium salts of tetra(o-tolyl)diborane(4) dianion, having B=B double bond character, were synthesized. It was clarified that the lithium salt of the dianion has a high-lying HOMO and a narrow HOMO-LUMO gap, which were perturbed by dissociation of Li+ cation, as judged by UV/Vis spectroscopy and DFT calculations. The lithium salt of the dianion reacted as two equivalents of a diarylboryl anion with CH2 Cl2 or S8 to give boryl-substituted products.

Plasmonic roller lithography.

Photo roller lithography systems can generate patterns continuously over large areas by employing flexible photomasks on rotating quartz cylinders. In comparison, plasmonic lithography systems can reach deep sub-wavelength resolution utilizing evanescent waves carrying high spatial frequency components. In this work, we demonstrate a plasmonic roller system by integrating a quartz mechanical roller with a specially designed photomask based on plasmonic waveguide lithography. Deep sub-wavelength uniform patterns with high aspect ratios were printed continuously over a moving substrate. The plasmonic roller system may find practical applications in the large-scale production of electronic and photonic devices in a cost-effective way.