Mechanistic Insight into the Enantioselective Degradation of Esterase QeH to ()/()-Quizalofop-Ethyl with Molecular Dynamics Simulation Using a Residue-Specific Force Field.

The enantioselective mechanism of the esterase QeH against the two enantiomers of quizalofop-ethyl (QE) has been primitively studied using computational and experimental approaches. However, it is still unclear how the esterase QeH adjusts its conformation to adapt to substrate binding and promote enzymrate interactions and catalytic dynamics were reproduced by performing independent molecular dynamics (MD) runs on the QeH-()/()-QE complexes with a newly developed residue-specific force field (RSFF2C). Our results indicated that the benzene ring of the ()-QE structure can simultaneously form anion-π and cation-π interactions with the side-chain group of Glu328 and Arg384 in the binding cavity of the QeH-()-QE complex, resulting in ()-QE being closer to its catalytic triplet system (Ser78-Lys81-Tyr189) with the distances measured for the hydroxyl oxygen atom of the catalytic Ser78 of QeH and the carbonyl carbon atom of ()-QE of 7.

Coactivation of Hydrogen Peroxide Using Pyrogenic Carbon and Magnetite for Sustainable Oxidation of Organic Pollutants.

Pyrogenic carbon and magnetite (FeO) were mixed together for the activation of hydrogen peroxide (HO), aiming to enhance the oxidation of refractory pollutants in a sustainable way. The experimental results indicated that the straw-derived carbon obtained by pyrolysis at 500-800 °C was efficient on coactivation of HO, and the most efficient one was that prepared at 700 °C (C700) featured with abundant defects. Specifically, the reaction rate constant () for removal of an antibiotic ciprofloxacin in the coactivation system (C700/FeO/HO) is 12.

N,S-codoped biochar outperformed N-doped biochar on co-activation of HO with trace dissolved Fe(Ⅲ) for enhanced oxidation of organic pollutants.

Co-activation of HO with biochar and iron sources together provides an attractive strategy for efficient removal of refractory pollutants, because it can solve the problems of slow Fe(Ⅱ) regeneration in Fenton/Fenton-like processes and of low OH yield in biochar-activated process. In this study, a wood-derived biochar (WB) was modified by heteroatom doping for the objective of enhancing its reactivity toward co-activation of HO. The performance of the co-activated system using doped biochars and trace dissolved Fe(Ⅲ) on oxidation of organic pollutants was evaluated for the first time.

Experimental and computational approaches to characterize a novel amidase that initiates the biodegradation of the herbicide propanil in Bosea sp. P5.

The herbicide propanil and its major metabolite 3,4-dichloroaniline (3,4-DCA) are difficult to biodegrade and pose great health and environmental risks. However, studies on the sole or synergistic mineralization of propanil by pure cultured strains are limited. A two-strain consortium (Comamonas sp.

Structure Based Affinity Maturation and Characterizing of SARS-CoV Antibody CR3022 against SARS-CoV-2 by Computational and Experimental Approaches.

The COVID-19 epidemic is raging around the world. Neutralizing antibodies are powerful tools for the prevention and treatment of SARS-CoV-2 infection. Antibody CR3022, a SARS-CoV neutralizing antibody, was found to cross-react with SARS-CoV-2, but its affinity was lower than that of its binding with SARS-CoV, which greatly limited the further development of CR3022 against SARS-CoV-2.

Root-Bacteria Associations Boost Rhizosheath Formation in Moderately Dry Soil through Ethylene Responses.

The rhizosheath is a layer of soil around the root that provides a favorable environment for soil microbe enrichment and root growth. Rice () roots form rhizosheaths under moderate soil drying (MSD) conditions, but how the rhizosheath forms associations with microbes is unclear. To investigate rice rhizosheath formation under MSD, we employed a multiphasic approach, integrating data from high-throughput sequencing and root-bacteria interactions.

Moderate water stress in rice induces rhizosheath formation associated with abscisic acid and auxin responses.

The rhizosheath is known to be beneficial for drought resistance in many plants, but the regulation of rhizosheath formation in rice plants is unclear. Here, we investigate rhizosheath formation in different rice varieties and root hair mutants. Our results showed that moderate water stress in rice induced rhizosheath formation.

Combining Irrigation Scheme and Phosphorous Application Levels for Grain Yield and Their Impacts on Rhizosphere Microbial Communities of Two Rice Varieties in a Field Trial.

Root and rhizosphere is important for phosphorus (P) uptake in rice plants. However, little is known about the detailed regulation of irrigation regimes, especially frequently alternate wetting and drying (FAWD), on P usage of rice plants. Here, we found that compared with normal water and P dose, FAWD with a reduced P dose maintained the grain yield in two rice varieties.

Discovery of AG-120 (Ivosidenib): A First-in-Class Mutant IDH1 Inhibitor for the Treatment of IDH1 Mutant Cancers.

Somatic point mutations at a key arginine residue (R132) within the active site of the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) confer a novel gain of function in cancer cells, resulting in the production of d-2-hydroxyglutarate (2-HG), an oncometabolite. Elevated 2-HG levels are implicated in epigenetic alterations and impaired cellular differentiation. IDH1 mutations have been described in an array of hematologic malignancies and solid tumors.

AG-348 enhances pyruvate kinase activity in red blood cells from patients with pyruvate kinase deficiency.

Pyruvate kinase (PK) deficiency is a rare genetic disease that causes chronic hemolytic anemia. There are currently no targeted therapies for PK deficiency. Here, we describe the identification and characterization of AG-348, an allosteric activator of PK that is currently in clinical trials for the treatment of PK deficiency.

Decreased anxiety-like behavior and Gαq/11-dependent responses in the amygdala of mice lacking TRPC4 channels.

Transient receptor potential (TRP) channels are abundant in the brain where they regulate transmission of sensory signals. The expression patterns of different TRPC subunits (TRPC1, 4, and 5) are consistent with their potential role in fear-related behaviors. Accordingly, we found recently that mutant mice lacking a specific TRP channel subunit, TRPC5, exhibited decreased innate fear responses.

Doxycycline stabilizes vulnerable plaque via inhibiting matrix metalloproteinases and attenuating inflammation in rabbits.

Enhanced matrix metalloproteinases (MMPs) activity is implicated in the process of atherosclerotic plaque instability. We hypothesized that doxycycline, a broad MMPs inhibitor, was as effective as simvastatin in reducing the incidence of plaque disruption. Thirty rabbits underwent aortic balloon injury and were fed a high-fat diet for 20 weeks.

Gax gene transfer inhibits vascular remodeling induced by adventitial inflammation in rabbits.

Aims: Adventitial fibroblasts (AFs) and inflammation play an important role in neointimal formation and vascular remodeling. The present study was aimed to investigate the therapeutic effects and underlying mechanisms of transcriptional regulator Gax gene transfection in aortic remodeling induced by adventitial inflammation.

Methods And Results: Fifty rabbits fed a chow diet were randomly divided into a normal control group (n=10) and experimental group (n=40).

Essential role for TRPC5 in amygdala function and fear-related behavior.

The transient receptor potential channel 5 (TRPC5) is predominantly expressed in the brain where it can form heterotetrameric complexes with TRPC1 and TRPC4 channel subunits. These excitatory, nonselective cationic channels are regulated by G protein, phospholipase C-coupled receptors. Here, we show that TRPC5(-/-) mice exhibit diminished innate fear levels in response to innately aversive stimuli.

Plaque volume compression ratio, a novel biomechanical index, is independently associated with ischemic cerebrovascular events.

Objective: The purpose of this study was to develop a new biomechanical index for assessing the elastic characteristics of carotid plaques and to test the association between carotid plaque elasticity and ischemic cerebrovascular events (ICEs).

Methods: One hundred and eighteen carotid plaques were detected with real-time three-dimensional ultrasonography in 104 patients. All patients received MRI and were divided into two groups according to the history of ICEs: patients with ICEs (n=58, including 20 patients with transient ischemic attack and 38 with ischemic stroke) and patients without ICEs (n=46).

Usefulness of left ventricular conic index measured by real-time three-dimensional echocardiography to predict left ventricular remodeling after acute myocardial infarction.

Early identification of left ventricular (LV) remodeling after acute myocardial infarction (AMI) is of clinical importance. The predictive value of real-time 3-dimensional echocardiography (RT-3DE) for LV remodeling after AMI is unknown. We prospectively studied 62 patients with AMI who underwent RT-3DE at baseline (72 +/- 5 hours) and 1 month and 6 months after AMI.

[Expression of amphiregulin in human endometrium during the menstrual cycle].

Objective: To investigate the expression of amphiregulin in human endometrium during the menstrual cycle.

Methods: Endometrial tissues were collected from the patients undergoing hysterectomy or endometrial biopsy. Real-time RT-PCR, in situ hybridization and immunohistochemistry were used to detect the expression characteristics of amphiregulin in human endometrium in proliferative and secretory phases.

Dominant-negative mutation of monocyte chemoattractant protein-1 prevents vulnerable plaques from rupture in rabbits independent of serum lipid levels.

Active inflammation is an important feature of vulnerable plaques, and monocyte chemoattractant protein-1 (MCP-1) is a key chemokine that promotes monocyte-endothelium binding and initiates inflammation. We aimed to determine whether dominant-negative mutation of MCP-1 could reverse atherosclerotic lesion progression and prevent vulnerable plaques from rupture regardless of serum lipid levels. The mutant MCP-1 was produced by deletion of the N-terminal amino acids 2 to 8 (7ND), and a eukaryotic expression vector plRES-EGFP-7ND was constructed.

Impact of the number of image planes of real-time three-dimensional echocardiography on the accuracy of left atrial and ventricular volume measurements.

Real-time three-dimensional (3D) echocardiography (RT-3DE) has emerged as a new technique in measuring left atrial and ventricular volume. However, the impact of cutting planes of RT-3DE on the accuracy of volume measurement in patients with a normal or enlarged heart is still unknown. We enrolled 30 normal subjects (control group) and 30 patients with heart failure (patient group).

Prediction of atherosclerotic plaque ruptures with high-frequency ultrasound imaging and serum inflammatory markers.

Atherosclerotic plaque rupture and thrombosis are the main causes of acute coronary syndrome. In the present study, we investigated whether ultrasound imaging and inflammatory parameters are predictive of plaque rupture in a newly established animal model. We developed a rabbit model for plaque rupture by locally delivering recombinant p53 adenovirus to plaques in rabbits fed a high-cholesterol diet for 10 wk, and plaque rupture was triggered using Chinese Russell's viper venom and histamine.

Mechanism of spontaneous firing in dorsomedial suprachiasmatic nucleus neurons.

We studied acutely dissociated neurons from the dorsomedial (shell) region of the rat suprachiasmatic nucleus (SCN) with the aim of determining the ionic conductances that underlie spontaneous firing. Most isolated neurons were spontaneously active, firing rhythmically at an average frequency of 8 +/- 4 Hz. After application of TTX, oscillatory activity generally continued, but more slowly and at more depolarized voltages; these oscillations were usually blocked by 2 microm nimodipine.