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Publication
Journal: Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases
February/15/2020
Abstract
Severe acute respiratory infection (SARI) diseases (such as SARS, MERS, pH1N1) can rapidly progress to acute respiratory failure with high lethality. The outbreak of a novel coronavirus infection can lead to 15% ~ 30% patients developing into acute respiratory distress syndrome (ARDS). Respiratory support is the most important therapy for SARI patients with respiratory failure. However, respiratory support is a high skilled technology, which means inappropriate application may bring related complications and cross infection of SARI pathogens among medical staff and non-medical personnel in hospital. Therefore, it is meaningful to established a standardized indication of respiratory support and to prevent related nosocomial transmission in SARI patients.
Publication
Journal: Rapid communications in mass spectrometry : RCM
February/15/2020
Abstract
Orientin and isoorientin are C-glycosidic flavonoids, considered as markers of some plant species as Passiflora edulis var. flavicarpa Degener and reported in the literature to have pharmacological properties. In order to evaluate and characterize the in vitro metabolism of flavonoids, phase I biotransformation reactions were simulated using Salen complexes.These flavonoids were oxidized separately in biomimetic reaction in different proportions, using one oxidant, m-chloroperbenzoic acid (m-CPBA) or iodozylbenzen (PhIO), and one catalyst, the Jacobsen catalyst or [Mn(3-MeOSalen)Cl]. The [Mn(3-MeOSalen)Cl] was synthesized and characterized by spectrometric techniques. The oxidation potentials of the catalysts were compared. All reactions were monitored and analyzed by UPLC-DAD and HPLC/MS/MS.The analysis by UPLC-DAD and HPLC/MS/MS showed that isoorientin produces more products than orientin and that the [Mn(3-MeOSalen)CI] produces more products than the Jacobsen catalyst. In addition, the [Mn(3-MeOSalen)CI] catalyst, which has a higher oxidation potential, formed products with an addition of one or two atoms of oxygen, while the Jacobsen catalyst formed compounds with only one added oxygen atom. The products with the addition of one oxygen were mainly epoxides, while those with two added oxygens formed an epoxide in the C-ring and incorporated the other oxygen into the glycosidic moiety.The formation of epoxides is common in biomimetic reactions and they may represent a safety risk in medicinal products due to their high reactivity. This study may serve as a basis for subsequent pharmacological and toxicological studies that investigate the presence of these compounds as phase I metabolites, and ensure the safe use of plant products containing orientin as a chemical marker.
Publication
Journal: Physiological reports
February/15/2020
Abstract
In the present study, we hypothesized that habitual cigarette smoking attenuates endothelial function in the cerebral circulation as well as that of the peripheral circulation in young adults. To test this hypothesis, we measured cerebrovascular and peripheral flow-mediated dilation (FMD) in young smokers and nonsmokers in the present study. Ten healthy nonsmokers and 10 smokers participated in the study. We measured blood velocity and diameter in the brachial artery and internal carotid artery (ICA) using Doppler ultrasound. We identified shear-mediated dilation in the brachial artery and ICA by the percentage change in peak diameter during hyperemia stimulation (reactive hyperemia and hypercapnia). We measured the baseline diameter and the shear rate area under the curve from the onset of hyperemia to peak dilation in the brachial artery and ICA, finding the measurements of the smokers and those of the nonsmokers did not differ (p > .05). In contrast to brachial FMD (5.07 ± 1.79% vs. 7.92 ± 3.01%; smokers vs. nonsmokers, p = .019), FMD in the ICA was not attenuated in the smokers compared with that of the nonsmokers (5.46 ± 2.32% vs. 4.57 ± 2.70%; p = .442). These findings indicate that in young healthy smokers, cerebral endothelial function was preserved, and the response of cerebral endothelial function to smoking was different from that of peripheral vasculature.
Publication
Journal: Proteomics
February/15/2020
Abstract
Transgelin is a protein reported to be a marker of several cancers. However, previous studies have shown both up- and down-regulation of transgelin in tumors when compared with non-tumor tissues and the mechanisms whereby transgelin may affect the development of cancer remain largely unknown. Transgelin is especially abundant in smooth muscle cells and is associated with actin stress fibers. These contractile structures participate in cell motility, adhesion, and the maintenance of cell morphology. Here, we focused on the role of transgelin in breast cancer. Initially, we studied the effects of transgelin on cell migration using the breast cancer cell lines, BT 549 and PMC 42. Using the xCELLigence system, we found opposite results in the two cell lines. Transgelin silencing increased the migration of PMC 42 cells, but decreased the migration of BT 549 cells. To further clarify these contradictory results, we performed an experiment to quantify the changes in protein expression after transgelin silencing in these two cell lines, using quantitative proteomics (iTRAQ-2DLC-MS/MS). Our results confirmed the role of transgelin in the migration of BT 549 cells and suggested the involvement of transgelin in apoptosis and small molecule biochemistry in PMC 42 cells. The context-dependent function of transgelin reflects the different molecular backgrounds of these cell lines, which differ in karyotypes, mutation statuses, and proteome profiles. This article is protected by copyright. All rights reserved.
Publication
Journal: Pediatric research
February/15/2020
Abstract
To assess the growth outcomes at 18 months corrected age in very low birth weight (VLBW) infants compared to standardized norms, and in VLBW infants with and without bronchopulmonary dysplasia (BPD) or fetal growth restriction (FGR).In all, 1149 VLBW infants completed anthropometrics at 18 months corrected age. To derive weight, height, and body mass index (BMI) percentiles and z-scores at 18 months, we used the SAS macro from the Centers for Disease Control and Prevention (CDC). z-scores for a child's sex and age are based on the World Health Organization's growth charts for children <24 months of age.Female and male VLBW infants had higher body-mass-index (BMI)-for-age z-scores compared to normative data (0.82 and 1.77 respectively). No significant difference was found in BMI-for-age z-scores in BPD and non-BPD (1.76 vs. 2.3; p = 0.4), nor in FGR and non-FGR (1.24 vs. 2.16; p = 0.2).At 18 months corrected age, VLBW infants, including those with BPD or FGR, had BMI-for-age z-scores higher than reference standards. No significant difference was seen comparing BMI-for-age z-scores in the BPD/non-BPD and FGR/non-FGR groups.
Publication
Journal: European eating disorders review : the journal of the Eating Disorders Association
February/15/2020
Abstract
This study aimed to provide updated lifetime prevalence estimates of eating disorders, specifically bulimia nervosa (BN) and binge eating disorder (BED) and investigate changes over time in lifetime prevalence by age.Two thousand nine hundred seventy-seven participants from South Australia were interviewed in the Health Omnibus Survey. DSM-5 criteria were used for current and broad (in accord with the International Statistical Classification of Diseases and Related Health Problems-11 [ICD-11]) criteria for lifetime prevalence of BED.This study found that the lifetime prevalence of BN was 1.21% (95% CI [0.87, 1.67]) and 2.59% (95% CI [2.07, 3.22]) for males and females, respectively, and that lifetime prevalence for BED-broad was 0.74% (95% CI [0.49, 1.11]) and 1.85% (95% CI [1.42, 2.40]) for males and females, respectively, which is higher than reported in previous research. Current prevalence (past 3 months) of BN was 0.40% (95% CI [0.23, 0.70]) and 0.81% (95% CI [0.54, 1.20]) for males and females, respectively, and current prevalence for BED was found to be 0.03 (95% CI [0.01, 0.04]) and 0.20% (95% CI [0.09, 0.44]) for males and females, respectively.The current study confirmed the moderate community prevalence of BN and BED. BED was found to be less prevalent than BN in the present study, and a significant lifetime prevalence by age effect was found for both. Lifetime prevalence by age indicated that past increases in prevalence may be waning in this century and that overall BN and BED are not increasing in Australia.
Publication
Journal: Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases
February/15/2020
Abstract
The novel coronavirus 2019 (COVID-19) infected patients by binding human ACE2, leading to severe pneumonia and highly mortality rate in patients. At present, there is no definite and effective treatment for COVID-19. ACE2 plays an important role in the RAS, and the imbalance between ACE/Ang II/AT1R pathway and ACE2/Ang (1-7)/Mas receptor pathway in the RAS system will lead to multi-system inflammation. Increased ACE and Ang II are poor prognostic factors for severe pneumonia. Animal studies have shown that RAS inhibitors could effectively relieve symptoms of acute severe pneumonia and respiratory failure. The binding of COVID-19 and ACE2 resulted in the exhaustion of ACE2, and then ACE2/Ang (1-7)/Mas receptor pathway was inhibited. The balance of the RAS system was broken, and this would lead to the exacerbation of acute severe pneumonia. Therefore, we speculate that ACEI and AT1R inhibitors could be used in patients with COVID-19 pneumonia under the condition of controlling blood pressure, and might reduce the pulmonary inflammatory response and mortality.
Publication
Journal: Pediatric research
February/15/2020
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Publication
Journal: Physiological reports
February/15/2020
Abstract
Overlap syndrome (OVS) is the concurrence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA), and is associated with poor outcomes. We hypothesized that physiological changes in COPD may affect the pathogenesis of OSA in important ways. We therefore sought to measure the anatomical and nonanatomical OSA traits in individuals with OVS and compare to those with OSA alone. Patients with established OVS were recruited, along with age, gender, and BMI matched OSA only controls. Smoking and relevant comorbidities or medications were excluded. Subjects underwent baseline polysomnography followed by an overnight physiological research study to measure the OSA traits (Veupnea , Varousal , Vpassive , Vactive , and loop gain). Fifteen subjects with OVS and 15 matched controls with OSA alone were studied (overall 66 ± 8 years, 20% women, BMI 31 ± 4 kg/m2 , apnea-hypopnea index 49 ± 36/hr). Mixed-modeling was used to incorporate each measurement (range 52-270 measures/trait), and account for age, gender, and BMI. There were no significant differences in the traits between OVS and OSA subjects, although OVS subjects potentially tolerated a lower ventilation before arousal (i.e., harder to wake; p = .06). Worsened lung function was significantly associated with worsened upper airway response and more unstable breathing (p < .05 for all). Consistent differences in key OSA traits were not observed between OVS and OSA alone. However, worse lung function does appear to exert an influence on several OSA traits. These findings indicate that a diagnosis of OVS should not generally influence the approach to OSA, but that lung function might be considered if utilizing OSA trait-specific treatment.
Publication
Journal: Molecular plant pathology
February/15/2020
Abstract
Fungal effector proteins facilitate host-plant colonization and have generally been characterized as small secreted proteins (SSPs). We classified and functionally tested SSPs from the secretomes of three closely related necrotrophic phytopathogens: Ciborinia camelliae, Botrytis cinerea, and Sclerotinia sclerotiorum. Alignment of predicted SSPs identified a large protein family that share greater than 41% amino acid identity and that have key characteristics of previously described microbe-associated molecular patterns (MAMPs). Strikingly, 73 of the 75 SSP family members were predicted within the secretome of the host-specialist C. camelliae with single-copy homologs identified in the secretomes of the host generalists S. sclerotiorum and B. cinerea. To explore the potential function of this family of SSPs, 10 of the 73 C. camelliae proteins, together with the single-copy homologs from S. sclerotiorum (SsSSP3) and B. cinerea (BcSSP2), were cloned and expressed as recombinant proteins. Infiltration of SsSSP3 and BcSSP2 into host tissue induced rapid necrosis. In contrast, only one of the 10 tested C. camelliae SSPs was able to induce a limited amount of necrosis. Analysis of chimeric proteins consisting of domains from both a necrosis-inducing and a non-necrosis-inducing SSP demonstrated that the C-terminus of the S. sclerotiorum SSP is essential for necrosis-inducing function. Deletion of the BcSSP2 homolog from B. cinerea did not affect growth or pathogenesis. Thus, this research uncovered a family of highly conserved SSPs present in diverse ascomycetes that exhibit contrasting necrosis-inducing functions.
Publication
Journal: Journal of applied toxicology : JAT
February/15/2020
Abstract
Small-molecule inhibitors of transforming growth factor beta receptor 1 (TGFβRI) have a history of significant class-based toxicities (eg, cardiac valvulopathy) in preclinical species that have limited their development as new medicines. Nevertheless, some TGFβRI inhibitors have entered into clinical trials using intermittent-dosing schedules and exposure limits in an attempt to avoid these toxicities. This report describes the toxicity profile of the small-molecule TGFβRI inhibitor, BMS-986260, in rats and dogs. Daily oral dosing for 10 days resulted in valvulopathy and/or aortic pathology at systemic exposures that would have been targeted clinically, preventing further development with this dosing schedule. These toxicities were not observed in either species in 1-month studies using the same doses on an intermittent-dosing schedule of 3 days on and 4 days off (QDx3 once weekly). Subsequently, 3-month studies were conducted (QDx3 once weekly), and while there were no cardiovascular findings in dogs, valvulopathy and mortality occurred early in rats. The only difference compared to the 1-month study was that the rats in the 3-month study were 2 weeks younger at the start of dosing. Therefore, a follow-up 1-month study was conducted to evaluate whether the age of rats influences sensitivity to target-mediated toxicity. Using the same dosing schedule and similar doses as in the 3-month study, there was no difference in the toxicity of BMS-986260 in young (8 weeks) or adult (8 months) rats. In summary, an intermittent-dosing schedule mitigated target-based cardiovascular toxicity in dogs but did not prevent valvulopathy in rats, and thus the development of BMS-986260 was terminated.
Publication
Journal: Physiological reports
February/15/2020
Abstract
The immunologic responses that occur early in the acute respiratory distress syndrome (ARDS) elicit immune-mediated damage. The mechanisms underlying the resolution of ARDS, particularly the role of signaling molecules in regulating immune cell kinetics, remain important questions. Th1-mediated responses can contribute to the pathogenesis of acute lung injury (ALI). Interferon-gamma (IFN-γ) orchestrates early inflammatory events, enhancing immune-mediated damage. The current study investigated IFN-γ during resolution in several experimental models of ALI. The absence of IFN-γ resulted in altered kinetics of lymphocyte and macrophage responses, suggesting that IFN-γ present in this microenvironment is influential in ALI resolution. Genetic deficiency of IFN-γ or administering neutralizing IFN-γ antibodies accelerated the pace of resolution. Neutralizing IFN-γ decreased the numbers of interstitial and inflammatory macrophages and increased alveolar macrophage numbers during resolution. Our results underline the complexity of lung injury resolution and provide insight into the effects through which altered IFN-γ concentrations affect immune cell kinetics and the rate of resolution. These findings suggest that therapies that spatially or temporally control IFN-γ signaling may promote ALI resolution. Identifying and elucidating the mechanisms critical to ALI resolution will allow the development of therapeutic approaches to minimize collateral tissue damage without adversely altering the response to injury.
Publication
Journal: Physiotherapy research international : the journal for researchers and clinicians in physical therapy
February/15/2020
Abstract
The purpose of this study was to determine the relationship between objective and subjective findings of motor function measures in older adults following a 12-week adapted tango intervention.A quasi-experimental repeated-measures design was used. Secondary analysis of the experimental group (Tango) data is reported here. The study took place in diverse senior independent living communities in an urban metropolitan area. Sixty-two older adults participated (n = 62, age: M = 82.3, SD = 8.8 years). Participants were assigned to 20 sessions of 90-min tango classes over 12 weeks. Motor function, depression, mental, and physical quality of life were measured before and after intervention. At post-test, satisfaction and subjective measures of motor function were assessed by participants indicating their level of agreement with statements that they improved in objective domains of motor function. Correlations were performed between subjectively rated agreement and changes in motor function, depression, and quality of life.A strong negative correlation was found between subjective ratings and empirically observed improvements in balance (r = -.423) and endurance (r = -.241), although participant ratings correlated moderately with manual dual tasking (r = .319) and weakly correlated with lower body strength (r = .188). Decreased depression was correlated with subjectively improved lower body strength (r = .271) and endurance (r = .254). Improved mental quality of life was strongly (r = .423) correlated with subjectively improved balance and moderately correlated with improved manual dual tasking (r = .306).After rehabilitation, even with improved depression and quality of life, older adults may not perceive empirically observed motor function improvements, particularly in balance and lower body strength. This study informs clinicians on the importance of assessing subjective data during rehabilitation to provide older adults with person-centred care.
Publication
Journal: Angewandte Chemie (International ed. in English)
February/15/2020
Abstract
While poly(acyclic orthoesters) (PAOEs) have many appealing features for drug delivery, their application is significantly hindered by a lack of facile synthetic method. Here we report a simple method for synthesizing acyclic diketene acetal monomers from diols and vinyl ether, and their polymerization with a diol to first synthesize PAOEs. The PAOEs rapidly hydrolyzed at lysosomal pH. With the help of a cationic lipid, ovalbumin, a model vaccine antigen, was efficiently loaded into PAOEs nanoparticles using a double emulsion method. These nanoparticles efficiently delivered ovalbumin into the cytosol of dendritic cells and demonstrated enhanced antigen presentation over PLGA nanoparticles. PAOEs are promising vehicles for intracellular delivery of biopharmaceuticals and could increase the utility of poly(orthoesters) in biomedical research.
Publication
Journal: Phytotherapy research : PTR
February/15/2020
Abstract
Natural polyphenols are being tested both in preclinical and clinical settings for the treatment of different neurological disorders. The article describes the outcome of three polyphenols, resveratrol, epigallocatechin gallate, and quercetin, in preclinical animal models of epilepsy (both acute and chronic) and epileptogenesis. In theory, the antioxidant and neuroprotective properties of these natural polyphenols might be valuable in the management of acute seizures and the prevention of epileptogenesis. It is fascinating to observe that these polyphenols have a capacity to alter various signaling processes involved in the pathogenesis of epilepsy. The antiepileptic or antiseizure potential with these molecules delivers a mixed outcome. Some studies have demonstrated the usefulness of these molecules in preclinical models of epilepsy; however, contrary to the findings also exist. These molecules have poor bioavailability that may remain as the limiting factor in their clinical effects. The use of nanotechnology and other techniques have been tested to enhance bioavailability and brain penetration. There are no randomized double-blinded clinical studies establishing their antiepileptic effects in humans. It is concluded that more preclinical mechanism-based studies are needed to deliver a more certain picture regarding the use of natural polyphenols in the treatment of epilepsy.
Publication
Journal: Pharmaceutical statistics
February/15/2020
Abstract
Phase II clinical trials designed for evaluating a drug's treatment effect can be either single-arm or double-arm. A single-arm design tests the null hypothesis that the response rate of a new drug is lower than a fixed threshold, whereas a double-arm scheme takes a more objective comparison of the response rate between the new treatment and the standard of care through randomization. Although the randomized design is the gold standard for efficacy assessment, various situations may arise where a single-arm pilot study prior to a randomized trial is necessary. To combine the single- and double-arm phases and pool the information together for better decision making, we propose a Single-To-double ARm Transition design (START) with switching hypotheses tests, where the first stage compares the new drug's response rate with a minimum required level and imposes a continuation criterion, and the second stage utilizes randomization to determine the treatment's superiority. We develop a software package in R to calibrate the frequentist error rates and perform simulation studies to assess the trial characteristics. Finally, a metastatic pancreatic cancer trial is used for illustrating the decision rules under the proposed START design.
Publication
Journal: Proteomics
February/15/2020
Publication
Journal: Physiological reports
February/15/2020
Abstract
Moderate-intensity exercise sessions are incorporated into heat-acclimation and hypoxic-training protocols to improve performance in hot and hypoxic environments, respectively. Consequently, a training effect might contribute to aerobic performance gains, at least in less fit participants. To explore the interaction between fitness level and a training stimulus commonly applied during acclimation protocols, we recruited 10 young males of a higher (more fit-MF, peak aerobic power [VO2peak ]: 57.9 [6.2] ml·kg-1 ·min-1 ) and 10 of a lower (less fit-LF, VO2peak : 41.7 [5.0] ml·kg-1 ·min-1 ) fitness level. They underwent 10 daily exercise sessions (60 min@50% peak power output [Wpeak ]) in thermoneutral conditions. The participants performed exercise testing on a cycle ergometer before and after the training period in normoxic (NOR), hypoxic (13.5% Fi O2 ; HYP), and hot (35°C, 50% RH; HE) conditions in a randomized and counterbalanced order. Each test consisted of two stages; a steady-state exercise (30 min@40% NOR Wpeak to evaluate thermoregulatory function) followed by incremental exercise to exhaustion. VO2peak increased by 9.2 (8.5)% (p = .024) and 10.2 (15.4)% (p = .037) only in the LF group in NOR and HE, respectively. Wpeak increases were correlated with baseline values in NOR (r = -.58, p = .010) and HYP (r = -.52, p = .018). MF individuals improved gross mechanical efficiency in HYP. Peak sweat rate increased in both groups in HE, whereas MF participants activated the forehead sweating response at lower rectal temperatures post-training. In conclusion, an increase in VO2peak but not mechanical efficiency seems probable in LF males after a 10-day moderate-exercise training protocol.
Publication
Journal: Addiction (Abingdon, England)
February/15/2020
Abstract
Many addictive substances, such as tobacco and alcohol, influence atherosclerosis development. Whether tobacco's pro-atherosclerotic effect is influenced by alcohol consumption is unknown. We aimed to estimate the impact of alcohol intake on the presence of subclinical atherosclerosis in femoral arteries in smoking and non-smoking middle-aged men.Cross-sectional analysis of a subset of the Aragon Workers Health Study (AWHS), comprising 2099 men with mean age 50.9 years without previous cardiovascular disease.The presence of plaques in femoral arteries was assessed by high-resolution sonography. Self-reported alcohol consumption over the previous year was measured with a food frequency questionnaire. The sample was divided into four groups according to their daily grams of alcohol consumption ≤1 (abstainers), ≥2 to <30, ≥30 to <60, and ≥60 g/day. Participants were divided on ever-smoking (current and former), versus never-smoking strata in the main analysis.We did not find a significant association between the different levels of alcohol intake and the likelihood of developing femoral artery atherosclerosis in never-smokers. Ever-smoking was positively associated with femoral atherosclerosis overall (OR=3.00; 95%CI:2.40,3.74; p<0.001) and within each level of alcohol consumption. Atherosclerosis was lower in ever-smokers who consumed 2g/day or more but less than 30g/day with respect to those ever-smokers who were abstainers (OR=0.70; 95%CI:0.49,0.99; p<0.05). However, among them, atherosclerosis prevalence was still higher than among never-smokers who consumed alcohol in the same amount (2g/day or more but less than 30g/day) (OR=2.73; 95%CI:2.07,3.61; p<0.001).Among middle-aged men, moderate alcohol consumption appears to be associated with lower prevalence of femoral artery subclinical atherosclerosis compared with alcohol abstinence only in ever-smokers.
Publication
Journal: Physiological reports
February/15/2020
Abstract
The liver is the primary metabolic organ involved in the endogenous production of glucose through glycogenolysis and gluconeogenesis. Hepatic glucose production (HGP) is increased via neural-hormonal mechanisms such as increases in catecholamines. To date, the effects of prior exercise training on the hepatic response to epinephrine have not been fully elucidated. To examine the role of epinephrine signaling on indices of HGP in trained mice, male C57BL/6 mice were either subjected to 12 days of voluntary wheel running or remained sedentary. Epinephrine, or vehicle control, was injected intraperitoneally on day 12 prior to sacrifice with blood glucose being measured 15 min postinjection. Epinephrine caused a larger glucose response in sedentary mice and this was paralleled by a greater reduction in liver glycogen in sedentary compared to trained mice. There was a main effect of epinephrine to increase the phosphorylation of protein kinase-A (p-PKA) substrates in the liver, which was driven by increases in the sedentary, but not trained, mice. Similarly, epinephrine-induced increases in the mRNA expression of hepatic adrenergic receptors (Adra1/2a, Adrb1), and glucose-6-phosphatase (G6pc) were greater in sedentary compared to trained mice. The mRNA expression of cAMP-degrading enzymes phosphodiesterase 3B and 4B (Pde3b, Pde4b) was greater in trained compared to sedentary mice. Taken together, our data suggest that prior exercise training reduces the liver's response to epinephrine. This could be beneficial in the context of training-induced glycogen sparing during exercise.
Publication
Journal: Journal of tissue engineering and regenerative medicine
February/15/2020
Abstract
Enhancement of cell-matrix adhesion is preferable and crucial in various fields of tissue engineering. Integrins are important receptors that facilitate cell-matrix adhesion, mediated by intracellular molecules and crosstalk with the cadherin adhesion pathway, which mainly facilitates cell-cell adhesion. PTP1B has emerged as a pivot in the crosstalk between the cadherin adhesion pathway and the integrin adhesion pathway. The phosphorylation state of PTP1B tyrosine-152 (Y152) plays a central role in balancing the two different cell adhesion forms. In this study, a PTP1B Y152 region mimicking (152RM) peptide was designed to decrease the phosphorylation of PTP1B Y152 via competitive inhibition. As a result, the dissociation of cadherin complexes and the release of PTP1B from cadherin had sharply increased, and Src, an important intracellular component of integrin, was activated, indicating the cadherin adhesion pathway was inhibited while the integrin adhesion pathway was enhanced. Moreover, upon treatment with the 152RM peptide, we observed that the early adhesion of human bone marrow-derived mesenchymal stem cells (MSCs) was accelerated and the anchoring of MSCs on the surface of integrin ligands was enhanced by an enhanced matrix adhesion ability of MSCs themselves. Importantly, the 152RM peptide significantly promoted the adhesion efficiency of MSCs in the selective cell retention technology, which fabricates instant bone implants in clinical settings, to stimulate osteogenesis in vivo.
Publication
Journal: Yeast (Chichester, England)
February/15/2020
Abstract
The Wickerhamiella and Starmerella genera form a clade (W/S clade) that branches close to Yarrowia lipolytica in the Saccharomycotina species tree. It comprises approximately 90 recognized species and 50 putative new species not formally described yet. The large majority of the members of the W/S clade are ecologically associated with flowers and floricolous insects. Many species exhibit unusual metabolic traits, like fructophily and the production of sophorolipids, which are glycolipids that can be used as environmentally friendly biosurfactants. Genomic data have not only firmly established the W/S clade but have also revealed a tumultuous evolution of metabolism marked by losses and gains of important metabolic pathways, among which alcoholic fermentation. Possibly the most surprising finding brought to light by comparative genomics concerned the large number of genes acquired by some species of the W/S clade from bacteria through horizontal gene transfer, many of which were shown to be functional in their new setting. This was facilitated by the genetic tractability of one species in the clade, Starmerella bombicola, which is used for the industrial production of sophorolipids. We suggest that high-density coverage of genome sequencing in this clade, combined with the possibility to conduct molecular genetics experiments in at least one species has the potential to set the stage for yet more exciting discoveries concerning the evolution of yeast metabolism.
Publication
Journal: ChemSusChem
February/15/2020
Abstract
The hydrogenation of organic carbonates to methanol is a relevant transformation to realize flexible processes for the recycling of waste CO2 with renewable H2 mediated by condensed CO2 surrogates. Oxide-supported copper nanoparticles (NPs) are promising solid catalysts for this selective hydrogenation. However, essential for their optimization is to rationalize the prominent impact of the oxide support on performance. Herein, the role of Lewis acid centers, exposed on the oxide support at the periphery of the Cu NPs is systematically assessed. For the hydrogenation of propylene carbonate, as a model cyclic carbonate, the conversion rate, the apparent activation energy as well as the selectivity to methanol correlate with the Lewis acidity of the coordinatively unsaturared cationic sites (cus) exposed on the oxide carrier. Lewis sites of markedly low and high electron withdrawing character promote decarbonylation and decarboxylation unselective reaction pathways, respectively. Supports exposing Lewis sites of intermediate acidity maximize the selectivity to methanol while inhibiting secondary, acid-catalyzed reactions of the propanediol product, enabling its recovery in cyclic processes of CO2 hydrogenation mediated by condensed carbonate derivatives. These findings help rationalize metal-support promotion effects which determine the performance of supported metal NPs in this and other selective hydrogenations of significance in the context of sustainable chemistry.
Publication
Journal: Angewandte Chemie (International ed. in English)
February/15/2020
Abstract
Biocompatible and proteolysis-resistant poly-β-peptides have broad applications and are dominantly synthesized via the harsh and water sensitive ring-opening polymerization of β-lactams in the glovebox or using a Schlenk line, catalyzed by strong base LiN(SiMe 3 ) 2 . We developed a controllable and water insensitive ring opening polymerization of β-amino acid N-thiocarboxyanhydrides (β-NTAs) that can be operated in open vessels to prepare poly-β-peptides in high yields, with diverse functional groups, variable chain length, narrow dispersity and defined architecture. These merits imply wide applications of β-NTA polymerization and resulting poly-β-peptides, which is validated by the find of a HDP mimicking poly-β-peptide with potent antimicrobial activities. The living β-NTA polymerization enables the controllable synthesis of random, block copolymers and easy tuning of both terminal groups of polypeptides, which facilitated unravelling the antibacterial mechanism using the fluorophore-labelled poly-β-peptide.
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