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Every late autumn, fluttering poplar leaves scatter throughout the campus and city streets. In this work, poplar leaves were used as the raw material, while H[sub.3]PO[sub.4] and KOH were used as activators and urea was used as the nitrogen source to prepare biomass based-activated carbons (ACs) to capture CO[sub.2]. The pore structures, functional groups and morphology, and desorption performance of the prepared ACs were characterized; the CO[sub.2] adsorption, regeneration, and kinetics were also evaluated. The results showed that H[sub.3]PO[sub.4] and urea obviously promoted the development of pore structures and pyrrole nitrogen (N–5), while KOH and urea were more conductive to the formation of hydroxyl (–OH) and ether (C–O) functional groups. At optimal operating conditions, the CO[sub.2] adsorption capacity of H[sub.3]PO[sub.4]– and KOH–activated poplar leaves after urea treatment reached 4.07 and 3.85 mmol/g, respectively, at room temperature; both showed stable regenerative behaviour after ten adsorption–desorption cycles.

Among patients with heart failure and a reduced ejection fraction, those who received the cardiac myosin activator omecamtiv mecarbil had a lower incidence of a composite of heart-failure events or cardiovascular death at a median of 22 months than those who received placebo.

Information on the homogeneity and distribution of .sup.13 carbon (.sup.13 C) and nitrogen (.sup.15 N) labeling in winter wheat (Triticum aestivum L.) is limited. We conducted a dual labeling experiment to evaluate the variability of .sup.13 C and .sup.15 N enrichment in aboveground parts of labeled winter wheat plants. Labeling with .sup.13 C and .sup.15 N was performed on non-nitrogen fertilized (-N) and nitrogen fertilized (+N, 250 kg N ha.sup.-1 ) plants at the elongation and grain filling stages. Aboveground parts of wheat were destructively sampled at 28 days after labeling. As winter wheat growth progressed, [delta].sup.13 C values of wheat ears increased significantly, whereas those of leaves and stems decreased significantly. At the elongation stage, N addition tended to reduce the aboveground [delta].sup.13 C values through dilution of C uptake. At the two stages, upper (newly developed) leaves were more highly enriched with .sup.13 C compared with that of lower (aged) leaves. Variability between individual wheat plants and among pots at the grain filling stage was smaller than that at the elongation stage, especially for the -N treatment. Compared with those of .sup.13 C labeling, differences in .sup.15 N excess between aboveground components (leaves and stems) under .sup.15 N labeling conditions were much smaller. We conclude that non-N fertilization and labeling at the grain filling stage may produce more uniformly .sup.13 C-labeled wheat materials, whereas the materials were more highly .sup.13 C-enriched at the elongation stage, although the [delta].sup.13 C values were more variable. The .sup.15 N-enriched straw tissues via urea fertilization were more uniformly labeled at the grain filling stage compared with that at the elongation stage.

The urea cycle is a metabolic pathway for the disposal of excess nitrogen, which arises primarily as ammonia. Nitrogen is essential for growth and life-maintenance, but excessive ammonia leads to life-threatening conditions. The urea cycle disorders (UCDs) comprise diseases presenting with hyperammonemia that arise in either the neonatal period (about 50% of cases) or later. Congenital defects of the enzymes or transporters of the urea cycle cause the disease. This cycle utilizes five enzymes, two of which, carbamoylphosphate synthetase 1 and ornithine transcarbamylase are present in the mitochondrial matrix, whereas the others (argininosuccinate synthetase, argininosuccinate lyase and arginase 1) are present in the cytoplasm. In addition, N-acetylglutamate synthase and at least two transporter proteins are essential to urea cycle function. Severity and age of onset depend on residual enzyme or transporter function and are related to the respective gene mutations. The strategy for therapy is to prevent the irreversible toxicity of high-ammonia exposure to the brain. The pathogenesis and natural course are poorly understood because of the rarity of the disease, so an international registry system and novel clinical trials are much needed. We review here the current concepts of the pathogenesis, diagnostics, including genetics and treatment of UCDs.

Morphine is an alkaloid from the opium poppy used to treat pain. The potentially lethal side effects of morphine and related opioids—which include fatal respiratory depression—are thought to be mediated by μ-opioid-receptor (μOR) signalling through the β-arrestin pathway or by actions at other receptors. Conversely, G-protein μOR signalling is thought to confer analgesia. Here we computationally dock over 3 million molecules against the μOR structure and identify new scaffolds unrelated to known opioids. Structure-based optimization yields PZM21—a potent G i activator with exceptional selectivity for μOR and minimal β-arrestin-2 recruitment. Unlike morphine, PZM21 is more efficacious for the affective component of analgesia versus the reflexive component and is devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses. PZM21 thus serves as both a probe to disentangle μOR signalling and a therapeutic lead that is devoid of many of the side effects of current opioids. Computational docking to the the μ-opioid-receptor identifies PZM21, a novel selective biased agonist that generates substantial affective analgesia in mice without altering respiration or inducing drug reinforcement. Designer opioids to target pain Morphine and other alkaloids from the opium poppy are μ-opioid receptor agonists that have been used to treat pain for many centuries. These authors used a computational approach to dock over three million small molecules to the μ-opioid receptor. Structure-based optimization of the most promising structures led to the identification of a potent agonist, PZM21, with exceptional subtype selectivity for the μ-opioid receptor. In mice, PZM21 generates substantial analgesia, which is fully ablated in μ-opioid receptor knockout animals. This small molecule seems to reduce the affective component of pain, without detectably altering reflexive behaviours, and has little effect on respiration.

In the presence of CuOAc, a series of unsymmetric ureas can be generated in moderate to good yields under mild reaction conditions (10 mol% of CuOAc, 2 equiv t-BuONa or PhONa, 30 °C), using aryl isocyanides and O-benzoyl hydroxylamines as the readily accessible starting materials. The reactions might undergo a cascade process involving isocyanide insertion into the N-O bond and Mumm-type rearrangement. This work represents a rare example of isocyanide insertion into N-O bonds, which would extend isocyanide insertion chemistry.

Background Urea cycle disorders (UCDs) are a group of rare genetic metabolic disorders characterized by hyperammonemia, which can lead to neurological damage, systemic complications, and even death. Understanding UCDs’ clinical features and progression in the Chinese population will fill research gaps and benefit patients globally. Methods This retrospective study evaluated the clinical, biochemical, genetic characteristics, and long-term outcomes in 101 Chinese patients with six subtypes of UCDs between 2007 and 2024. Data were collected from medical records and analyzed. Results The overall survival rate was 93.0% among UCD patients. An equal gender ratio was observed in ornithine transcarbamylase deficiency. Newborn screening (NBS) was conducted in this cohort, and 57.0% of patients were diagnosed through NBS. Neurological and gastrointestinal symptoms were the most common. Symptoms often appeared within the first year, especially in the first month. Arginine was the most frequently used treatment, with glycerol phenylbutyrate often used as a nitrogen scavenger in severe cases. Biochemical analysis showed subtype-specific differences, including notable declines in leucine and glycine on low-protein diets. Genetic analysis revealed a wide distribution of mutations, with few hotspots and 17 newly identified mutations. Clinically diagnosed patients had worse outcomes than those diagnosed via newborn screening. Conclusion This study is the first to describe the clinical features and long-term outcomes of UCDs in a large sample of Chinese patients, highlighting the importance of newborn screening for early diagnosis and improved treatment outcomes.

In order to inhibit the serious damage of pore structure of silica template during the conventional hydrothermal method to prepare Ni-phyllosilicate material, a solvothermal method using double solvent, a small amount of water and a large amount of hydrophobic n-pentane, was proposed to synthesize FDU-12 derived Ni-phyllosilicate in this work. Water can infiltrate the inside channels of FDU-12 owing to more hydrophilic silica hydroxyl groups, and the hydrophobic n-pentane tends to surround the outside of FDU-12. The growth of Ni-phyllosilicate occured only inside channels rather than surface, and the addition of urea could improve its formation at 180 °C in 12 h. As a result, the optimal catalyst retained the pore structure of FDU-12 and obtained fine Ni particle size of 1.5 nm after 750 °C reduction in H.sub.2 flow, which exhibited CO.sub.2 conversion of 77.0% and CH.sub.4 selectivity of 94.7% at 450 °C, 60 L·g.sup.-1·h.sup.-1. In addition, this catalyst showed high long-term stability in a 100 h-lifetime test with high anti-sintering property derived from Ni-phyllosilicate. Graphic

Many patients with heart failure remain symptomatic and have a poor prognosis despite existing treatments. Decreases in myocardial contractility and shortening of ventricular systole are characteristic of systolic heart failure and might be improved by a new therapeutic class, cardiac myosin activators. We report the first study of the cardiac myosin activator, omecamtiv mecarbil, in patients with systolic heart failure. We undertook a double-blind, placebo-controlled, crossover, dose-ranging, phase 2 trial investigating the effects of omecamtiv mecarbil (formerly CK-1827452), given intravenously for 2, 24, or 72 h to patients with stable heart failure and left ventricular systolic dysfunction receiving guideline-indicated treatment. Clinical assessment (including vital signs, echocardiograms, and electrocardiographs) and testing of plasma drug concentrations took place during and after completion of each infusion. The primary aim was to assess safety and tolerability of omecamtiv mecarbil. This study is registered at ClinicalTrials.gov, NCT00624442. 45 patients received 151 infusions of active drug or placebo. Placebo-corrected, concentration-dependent increases in left ventricular ejection time (up to an 80 ms increase from baseline) and stroke volume (up to 9·7 mL) were recorded, associated with a small reduction in heart rate (up to 2·7 beats per min; p<0·0001 for all three measures). Higher plasma concentrations were also associated with reductions in end-systolic (decrease of 15 mL at >500 ng/mL, p=0·0026) and end-diastolic volumes (16 mL, p=0·0096) that might have been more pronounced with increased duration of infusion. Cardiac ischaemia emerged at high plasma concentrations (two patients, plasma concentrations roughly 1750 ng/mL and 1350 ng/mL). For patients tolerant of all study drug infusions, no consistent pattern of adverse events with either dose or duration emerged. Omecamtiv mecarbil improved cardiac function in patients with heart failure caused by left ventricular dysfunction and could be the first in class of a new therapeutic agent. Cytokinetics Inc.