Search

The extensive deposits of calcium carbonate (CaCO 3 ) generated by marine organisms constitute the largest and oldest carbon dioxide (CO 2 ) reservoir. These organisms utilize macromolecules like peptides and proteins to facilitate the nucleation and growth of carbonate minerals, serving as an effective method for CO 2 sequestration. However, the precise mechanisms behind this process remain elusive. In this study, we report the use of sequence-defined peptoids, a class of peptidomimetics, to achieve the accelerated calcite step growth kinetics with the molecular level mechanistic understanding. By designing peptoids with hydrophilic and hydrophobic blocks, we systematically investigated the acceleration in step growth rate of calcite crystals using in situ atomic force microscopy (AFM), varying peptoid sequences and concentrations, CaCO 3 supersaturations, and the ratio of Ca 2+ / HCO 3 - . Mechanistic studies using NMR, three-dimensional fast force mapping (3D FFM), and isothermal titration calorimetry (ITC) were conducted to reveal the interactions of peptoids with Ca 2+ and HCO 3 - ions in solution, as well as the effect of peptoids on solvation and energetics of calcite crystal surface. Our results indicate the multiple roles of peptoid in facilitating HCO 3 - deprotonation, Ca 2+ desolvation, and the disruption of interfacial hydration layers of the calcite surface, which collectively contribute to a peptoid-induced acceleration of calcite growth. These findings provide guidelines for future design of sequence-specific biomimetic polymers as crystallization promoters, offering potential applications in environmental remediation (such as CO 2 sequestration), biomedical engineering, and energy storage where fast crystallization is preferred., Competing Interests: Competing interests statement:The authors declare no competing interest.

Introduction and Objectives: Percutaneous left atrial appendage closure (LAAC) has emerged as a nonpharmacological alternative for the prevention of thromboembolic events in patients with nonvalvular atrial fibrillation. However, there are few data on readmissions after LACC. The aim of this study was to determine the rate of early (≤ 30 days) and late (31-365 days) readmission after LAAC, and to assess the predictors and clinical impact of rehospitalization., Methods: This multicenter study included 1419 consecutive patients who underwent LAAC. The median follow-up was 33 [17-55] months, and follow-up was complete in all but 54 (3.8%) patients. The primary endpoint was readmissions for any cause. Logistic regression and Cox regression analysis were performed to determine the predictors of readmission and its clinical impact., Results: A total of 257 (18.1%) patients were readmitted within the first year after LAAC (3.2% early, 14.9% late). The most common causes of readmission were bleeding (24.5%) and heart failure (20.6%). A previous gastrointestinal bleeding event was associated with a higher risk of early readmission (OR, 2.65; 95%CI, 1.23-5.71). The factors associated with a higher risk of late readmission were a lower body mass index (HR, 0.96-95%CI, 0.93-0.99), diabetes (HR, 1.38-95%CI, 1.02-1.86), chronic kidney disease (HR, 1.60; 95%CI, 1.21-2.13), and previous heart failure (HR, 1.69; 95%CI, 1.26-2.27). Both early (HR, 2.12-95%CI, 1.22-3.70) and late (HR, 1.75; 95%CI, 1.41-2.17) readmissions were associated with a higher risk of 2-year mortality., Conclusions: Readmissions within the first year after LAAC were common, mainly related to bleeding and heart failure events, and associated with patients' comorbidity burden. Readmission after LAAC confered a higher risk of mortality during the first 2 years after the procedure., (Copyright © 2024 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: To compare tidal volume (V T ) delivery with compliance at 0.5 and 1.5 mL/cmH 2 O using four different ventilation (PPV) devices (i.e., self-inflating bag (SIB), T-Piece resuscitator, Next Step (a novel Neonatal Resuscitator), and Fabian ventilator (conventional neonatal ventilator) using a neonatal piglet model., Design/methods: Randomized experimental animal study using 10 mixed-breed neonatal piglets (1-3 days; 1.8-2.4 kg). Piglets were anesthetized, intubated, instrumented, and randomized to receive positive pressure ventilation (PPV) for one minute with a SIB with or without a respiratory function monitor (RFM), T-Piece resuscitator with or without an RFM, Next Step, and Fabian Ventilator with both compliance levels. Compliance changes were achieved by placing a wrap around the piglets' chest and tightened it. Our primary outcome was targeted V T delivery of 5 mL/kg at 0.5 and 1.5 mL/cmH 2 O lung compliance., Results: At 0.5 mL/cmH 2 O compliance, the mean(SD) expired V T with the Next Step was 5.1(0.2) mL/kg compared to the Fabian 4.8(0.5) mL/kg, SIB 8.9(3.6) mL/kg, SIB + RFM 4.5(1.8) mL/kg, T-Piece 7.4(4.3) mL/kg, and T-Piece+RFM 6.4(3.1) mL/kg. At 1.5 mL/cmH 2 O compliance, the mean(SD) expired V T with the Next Step was 5.2(0.6) mL/kg compared to the Fabian 4.4(0.7) mL/kg, SIB 12.1(5.3) mL/kg, SIB + RFM 9.4(3.9) mL/kg, T-Piece 8.6(1.5) mL/kg, and T-Piece+RFM 6.5 (1.6) mL/kg., Conclusion: The Next Step provides consistent V T during PPV, which is comparable to a mechanical ventilator., Impact: Current guidelines recommend fixed peak inflation pressure in resuscitation, linked to lung and brain injury. The Next Step Neonatal Resuscitator, a cost-effective device, offers volume-targeted positive pressure ventilation with consistent tidal volumes. With two different compliances, the Next Step Neonatal Resuscitator delivered a consistent tidal volume which was similar to a mechanical ventilator. The Next Step Neonatal Resuscitator outperformed self-inflating bags and T-Pieces in delivering targeted tidal volumes. The Next Step Neonatal Resuscitator could be an alternative ventilation device for neonatal resuscitation., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Hierarchical self-assembly represents a powerful strategy for the fabrication of functional materials across various length scales. However, achieving precise formation of functional hierarchical assemblies remains a significant challenge and requires a profound understanding of molecular assembly interactions. In this study, we present a molecular-level understanding of the hierarchical assembly of sequence-defined peptoids into multidimensional functional materials, including twisted nanotube bundles serving as a highly efficient artificial light harvesting system. By employing synchrotron-based powder X-ray diffraction and analyzing single crystal structures of model compounds, we elucidated the molecular packing and mechanisms underlying the assembly of peptoids into multidimensional nanostructures. Our findings demonstrate that incorporating aromatic functional groups, such as tetraphenyl ethylene (TPE), at the termini of assembling peptoid sequences promotes the formation of twisted bundles of nanotubes and nanosheets, thus enabling the creation of a highly efficient artificial light harvesting system. This research exemplifies the potential of leveraging sequence-defined synthetic polymers to translate microscopic molecular structures into macroscopic assemblies. It holds promise for the development of functional materials with precisely controlled hierarchical structures and designed functions., (© 2024 Battelle Memorial Institute and The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

The detoxification of lethal organophosphate (OP) residues in the environment is crucial to prevent human exposure and protect modern society. Despite serving as excellent catalysts for OP degradation, natural enzymes require costly preparation and readily deactivate upon exposure to environmental conditions. Herein, we designed and prepared a series of phosphotriesterase mimics based on stable, self-assembled peptoid membranes to overcome these limitations of the enzymes and effectively catalyze the hydrolysis of dimethyl p -nitrophenyl phosphate (DMNP)─a nerve agent simulant. By covalently attaching metal-binding ligands to peptoid N-termini, we attained enzyme mimetics in the form of surface-functionalized crystalline nanomembranes. These nanomembranes display a precisely controlled arrangement of coordinated metal ions, which resemble the active sites found in phosphotriesterases to promote DMNP hydrolysis. Moreover, using these highly programmable peptoid nanomembranes allows for tuning the local chemical environment of the coordinated metal ion to achieve enhanced hydrolysis activity. Among the crystalline membranes that are active for DMNP degradation, those assembled from peptoids containing bis-quinoline ligands with an adjacent phenyl side chain showed the highest hydrolytic activity with a 219-fold rate acceleration over the background, demonstrating the important role of the hydrophobic environment in proximity to the active sites. Furthermore, these membranes exhibited remarkable stability and were able to retain their catalytic activity after heating to 60 °C and after multiple uses. This work provides insights into the principal features to construct a new class of biomimetic materials with high catalytic efficiency, cost-effectiveness, and reusability applied in nerve agent detoxification.

Several previous studies in the field of assisted reproduction have focused on the use of blood gel derivatives, such as platelet-rich fibrin (PRF), as a treatment for endometrial rehabilitation. However, the ability to release growth factors and the gel form of this product led to the evolution of platelet lysates. In this study, blood gel derivatives, including PRF lysate, which was in liquid form, and PRF gel, were collected and evaluated for growth factors. It was shown to be effective in endometrial wound healing and regeneration in mouse injured uterine tissue models through structure and function (pinopode expression, embryo implantation) evaluation. The results demonstrated that the concentrations of growth factors, including PDGF-AB and VEGF-A, were higher in the PRF lysate compared to the PRF gel ( p < 0.05). PRF lysate could release these growth factors for 8 days. Furthermore, both PRF gel and PRF lysate restored the morphology of injured endometrial tissues in terms of luminal and glandular epithelia, as well as uterine gland secretory activity. However, the presence of pinopodes and embryonic implantation were only observed in the PRF lysate group. It can be concluded that PRF lysate promotes wound healing in mouse injured tissue models in vitro, which can act as healing products in tissue repair.

Background: The updated Valve Academic Research Consortium (VARC) definition for bleeding events after transcatheter aortic valve replacement (TAVR) lacks of clinical validation., Objectives: The aim of this study was to determine the incidence, predictors, and clinical impact of bleeding events following TAVR as defined by recent VARC-3 criteria., Methods: A total of 2,384 consecutive patients with severe symptomatic aortic stenosis undergoing TAVR were included. Early (at index hospitalization) and late (after hospital discharge) bleeding complications were defined according to VARC-3 criteria as type 1, 2, 3, or 4. Baseline, procedural, and follow-up (24 [IQR: 12-43] months) data were prospectively collected., Results: Bleeding events occurred in 761 patients (31.9%): types 1, 2, 3, and 4 in 169 (22.2%), 399 (52.4%), 149 (19.6%), and 44 (5.8%) patients, respectively. The primary vascular access site and gastrointestinal locations were the most common bleeding sources among early and late bleeding events, respectively. Female sex, thoracotomy access, larger (14-F) sheath use, and dual antiplatelet therapy determined an increased risk of early bleeding events (P < 0.02 for all). The use of the radial artery for secondary access was associated with a significant risk reduction of early bleeding (P < 0.001). Type 2 and type 3 events were associated with an increased mortality risk at 30-day (HR: 2.94 [95% CI: 1.43-6.03; P = 0.003] and HR: 4.91 [95% CI: 2.19-11.03; P < 0.001], respectively) and 1-year (HR: 1.86 [95% CI: 1.28-2.69; P = 0.001] and HR: 2.28 [95% CI: 1.41-3.66; P = 0.001], respectively) follow-up. A similar prognostic pattern was observed when applying VARC-2 criteria but with a much lower global incidence of early bleeding events (19% vs 27%; P < 0.001)., Conclusions: Bleeding events after TAVR were associated with poorer short- and long-term survival. The magnitude of this correlation was proportional to bleeding severity defined according to VARC-3 criteria. Further studies on bleeding prevention following TAVR are warranted to improve procedural safety and patient prognosis., Competing Interests: Funding Support and Author Disclosures Dr Real is supported by the Fundacion Interhospitalaria Para la Investigación Cardiovascular (Madrid, Spain). Dr Nuche is a recipient of a grant from Fundación Alfonso Martín Escudero (Madrid, Spain). Dr Rodés-Cabau has received institutional research grants and speaker and consultant fees from Edwards Lifesciences and Medtronic, and holds the Research Chair “Fondation Famille Jacques Larivière” for the Development of Structural Heart Disease Interventions (Laval University, Quebec City, Canada). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: In patients undergoing percutaneous coronary intervention (PCI) in the work-up pre-transcatheter aortic valve replacement (TAVR), the incidence and clinical impact of late bleeding events (LBEs) remain largely unknown., Objectives: This study sought to determine the incidence, clinical characteristics, associated factors, and outcomes of LBEs in patients undergoing PCI in the work-up pre-TAVR., Methods: This was a multicenter study including 1,457 consecutive patients (mean age 81 ± 7 years; 41.5% women) who underwent TAVR and survived beyond 30 days. LBEs (>30 days post-TAVR) were defined according to the Valve Academic Research Consortium-2 criteria., Results: LBEs occurred in 116 (7.9%) patients after a median follow-up of 23 (IQR: 12-40) months. Late bleeding was minor, major, and life-threatening or disabling in 21 (18.1%), 63 (54.3%), and 32 (27.6%) patients, respectively. Periprocedural (<30 days post-TAVR) major bleeding and the combination of antiplatelet and anticoagulation therapy at discharge were independent factors associated with LBEs (P ≤ 0.02 for all). LBEs conveyed an increased mortality risk at 4-year follow-up compared with no bleeding (43.9% vs 36.0; P = 0.034). Also, LBE was identified as an independent predictor of all-cause mortality after TAVR (HR: 1.39; 95% CI: 1.05-1.83; P = 0.020)., Conclusions: In TAVR candidates with concomitant significant coronary artery disease requiring percutaneous treatment, LBEs after TAVR were frequent and associated with increased mortality. Combining antiplatelet and anticoagulation regimens and the occurrence of periprocedural bleeding determined an increased risk of LBEs. Preventive strategies should be pursued for preventing late bleeding after TAVR, and further studies are needed to provide more solid evidence on the most safe and effective antithrombotic regimen post-TAVR in this challenging group of patients., Competing Interests: Funding Support and Author Disclosures Dr Rodés-Cabau holds the Research Chair “Fondation Famille Jacques Larivière” for the Development of Structural Heart Disease Interventions (Laval University); and has received institutional research grants and speaker/consultant fees from Edwards Lifesciences and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Accurate 3D structures of membrane proteins are essential for comprehending their mechanisms of action and designing specific ligands to modulate their activities. However, these structures are still uncommon due to the involvement of detergents in the sample preparation. Recently, membrane-active polymers have emerged as an alternative to detergents, but their incompatibility with low pH and divalent cations has hindered their efficacy. Herein, we describe the design, synthesis, characterization, and application of a new class of pH-tunable membrane-active polymers, NCMNP2a- x . The results demonstrated that NCMNP2a- x could be used for high-resolution single-particle cryo-EM structural analysis of AcrB in various pH conditions and can effectively solubilize Bc TSPO with the function preserved. Molecular dynamic simulation is consistent with experimental data that shed great insights into the working mechanism of this class of polymers. These results demonstrated that NCMNP2a- x might have broad applications in membrane protein research., Competing Interests: Y. G. and T. K. H. T. are inventors of NCMNP2a-x (patent pending)., (This journal is © The Royal Society of Chemistry.)

Ca 2+ -ATPases are membrane pumps that transport calcium ions across the cell membrane and are dependent on ATP. The mechanism of Listeria monocytogenes Ca 2+ -ATPase (LMCA1) in its native environment remains incompletely understood. LMCA1 has been investigated biochemically and biophysically with detergents in the past. This study characterizes LMCA1 using the detergent-free Native Cell Membrane Nanoparticles (NCMNP) system. As demonstrated by ATPase activity assays, the NCMNP7-25 polymer is compatible with a broad pH range and Ca 2+ ions. This result suggests that NCMNP7-25 may have a wider array of applications in membrane protein research., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Youzhong Guo reports financial support was provided by National Institutes of Health. Youzhong Guo has patent pending to VCU. Thi Kim Hoang Trinh has patent pending to VCU., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: The Valve Academic Research Consortium (VARC)-3 definition for myocardial injury after transcatheter aortic valve replacement (TAVR) lacks of clinical validation., Objectives: This study sought to determine the incidence, predictors, and clinical impact of periprocedural myocardial injury (PPMI) following TAVR as defined by recent VARC-3 criteria., Methods: We included 1,394 consecutive patients who underwent TAVR with a new-generation transcatheter heart valve. High-sensitivity troponin levels were assessed at baseline and within 24 hours after the procedure. PPMI was defined according to VARC-3 criteria as an increase ≥70 times in troponin levels (vs ≥15 times according to the VARC-2 definition). Baseline, procedural, and follow-up data were prospectively collected., Results: PPMI was diagnosed in 193 (14.0%) patients. Female sex and peripheral artery disease were independent predictors of PPMI (P < 0.01 for both). PPMI was associated with a higher risk of mortality at 30-day (HR: 2.69, 95% CI: 1.50-4.82; P = 0.001) and 1-year (for all-cause mortality, HR: 1.54; 95% CI: 1.04-2.27; P = 0.032; for cardiovascular mortality, HR: 3.04; 95% CI: 1.68-5.50; P < 0.001) follow-up. PPMI according to VARC-2 criteria had no impact on mortality., Conclusions: About 1 out of 10 patients undergoing TAVR in the contemporary era had PPMI as defined by recent VARC-3 criteria, and baseline factors like female sex and peripheral artery disease determined an increased risk. PPMI had a negative impact on early and late survival. Further studies on the prevention of PPMI post-TAVR and implementing measures to improve outcomes in PPMI patients are warranted., Competing Interests: Funding Support and Author Disclosures Dr Real was funded by the Fundación Interhospitalaria para la Investigación Cardiovascular. Dr Nuche was the recipient of a grant from the Fundación Alfonso Martín Escudero (Madrid, Spain). Dr Rodés-Cabau has received institutional research grants and speaker/consultant fees from Edwards Lifesciences and Medtronic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Publicly available gene expression datasets were analyzed to develop a chromophobe and oncocytoma related gene signature (COGS) to distinguish chRCC from RO. The datasets GSE11151, GSE19982, GSE2109, GSE8271 and GSE11024 were combined into a discovery dataset. The transcriptomic differences were identified with unsupervised learning in the discovery dataset (97.8% accuracy) with density based UMAP (DBU). The top 30 genes were identified by univariate gene expression analysis and ROC analysis, to create a gene signature called COGS. COGS, combined with DBU, was able to differentiate chRCC from RO in the discovery dataset with an accuracy of 97.8%. The classification accuracy of COGS was validated in an independent meta-dataset consisting of TCGA-KICH and GSE12090, where COGS could differentiate chRCC from RO with 100% accuracy. The differentially expressed genes were involved in carbohydrate metabolism, transcriptomic regulation by TP53, beta-catenin-dependent Wnt signaling, and cytokine (IL-4 and IL-13) signaling highly active in cancer cells. Using multiple datasets and machine learning, we constructed and validated COGS as a tool that can differentiate chRCC from RO and complement histology in routine clinical practice to distinguish these two tumors.

Background: The substantial female hormone fluctuations associated with pregnancy and postpartum have been linked to a greater risk of developing depressive symptoms, particularly in high-risk women (HRW), i.e. those with histories of mood sensitivity to female hormone fluctuations. We have shown that glutamate (Glu) levels in the medial prefrontal cortex (MPFC) decrease during perimenopause, a period of increased risk of developing a major depressive episode. Our team has also demonstrated that percentage gray matter (%GM), another neural correlate of maternal brain health, decreases in the MPFC during pregnancy., Objective: To investigate MPFC Glu levels and %GM from late pregnancy up to 7 weeks postpartum in HRW and healthy pregnant women (HPW)., Methods: Single-voxel spectra were acquired from the MPFC of 41 HPW and 22 HRW using 3- Tesla in vivo proton magnetic resonance spectroscopy at five different time points., Results: We observed a statistically significant interaction between time and group for the metabolite Glu, with Glu levels being lower for HRW during pregnancy and early postpartum (p<0.05). MPFC %GM was initially lower during pregnancy and then significantly increased over time in both groups (p<0.01)., Conclusion: This investigation suggests that the vulnerability towards PPD is associated with unique fluctuations of MPFC Glu levels during pregnancy and early postpartum period. Our results also suggest that the decline in MPFC %GM associated with pregnancy seems to progressively recover over time. Further investigations are needed to determine the specific role that female hormones play on the physiological changes in %GM during pregnancy and postpartum., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Development of complications in type 1 diabetes patients can be reduced by modifying risk factors. We used a cross-sectional cohort of 1646 patients diagnosed with type 1 diabetes (T1D) to develop a clinical risk score for diabetic peripheral neuropathy (DPN), autonomic neuropathy (AN), retinopathy (DR), and nephropathy (DN). Of these patients, 199 (12.1%) had DPN, 63 (3.8%) had AN, 244 (14.9%) had DR, and 88 (5.4%) had DN. We selected five variables to include in each of the four microvascular complications risk models: age, age of T1D diagnosis, duration of T1D, and average systolic blood pressure and HbA1C over the last three clinic visits. These variables were selected for their strong evidence of association with diabetic complications in the literature and because they are modifiable risk factors. We found the optimism-corrected R2 and Harrell's C statistic were 0.39 and 0.87 for DPN, 0.24 and 0.86 for AN, 0.49 and 0.91 for DR, and 0.22 and 0.83 for DN, respectively. This tool was built to help inform patients of their current risk of microvascular complications and to motivate patients to control their HbA1c and systolic blood pressure in order to reduce their risk of these complications.

Chronic low-grade inflammation is involved in the pathogenesis of type-1 diabetes (T1D) and its complications. In this cross-section study design, we investigated association between serum levels of soluble cytokine receptors with presence of peripheral neuropathy in 694 type-1 diabetes patients. Sex, age, blood pressure, smoking, alcohol intake, HbA1c and lipid profile, presence of DPN (peripheral and autonomic), retinopathy and nephropathy was obtained from patient's chart. Measurement of soluble cytokine receptors, markers of systemic and vascular inflammation was done using multiplex immunoassays. Serum levels were elevated in in DPN patients, independent of gender, age and duration of diabetes. Crude odds ratios were significantly associated with presence of DPN for 15/22 proteins. The Odds ratio (OR) remained unchanged for sTNFRI (1.72, p=0.00001), sTNFRII (1.45, p=0.0027), sIL2Rα (1.40, p=0.0023), IGFBP6 (1.51, p=0.0032) and CRP (1.47, p=0.0046) after adjusting for confounding variables, HbA1C, hypertension and dyslipidemia. Further we showed risk of DPN is associated with increase in serum levels of sTNFRI (OR=11.2, p<10), sIL2Rα (8.69, p<10 -15 ), sNTFRII (4.8, p<10 -8 ) and MMP2 (4.5, p<10 -5 ). We combined the serum concentration using ridge regression, into a composite score, which can stratify the DPN patients into low, medium and high-risk groups. Our results here show activation of inflammatory pathway in DPN patients, and could be a potential clinical tool to identify T1D patients for therapeutic intervention of anti-inflammatory therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Purohit, Tran, Tran, Satter, He, Zhi, Bai, Hopkins, Gardiner, Wakade, Bryant, Bernard, Morgan, Bode, Reed and She.)

Complementary to hydrophobic five membered ring β-amino acids (e.g. ACPC), β-sugar amino acids (β-SAAs) have found increasing application as hydrophilic building blocks of foldamers and α/β chimeric peptides. Fmoc-protected β-SAAs [e.g. Fmoc-RibAFU(ip)-OH] are indeed useful Lego elements, ready to use for SPPS. The removal of 1,2-OH isopropylidene protecting group increasing the hydrophilicity of such SAA is presented here. We first used N 3 -RibAFU(ip)-OH model compound to optimize mild deprotection conditions. The formation of the 1,2-OH free product N 3 -RibAFU-OH and its methyl glycoside methyl ester, N 3 -RibAFU(Me)-OMe were monitored by RP-HPLC and found that either 50% TFA or 8 eqv. Amberlite IR-120 H + resin in MeOH are optimal reagents for the effective deprotection. These conditions were then successfully applied for the synthesis of chimeric oligopeptide: -GG-X-GG- [X=RibAFU(ip)]. We found the established conditions to be effective and-at the same time-sufficiently mild to remove 1,2-O-isopropylidene protection and thus, it is proposed to be used in the synthesis of oligo- and polypeptides of complex sequence combination.

This study was conducted to investigate the genetic diversity of porcine circovirus type 2 (PCV2) and its coinfecting pathogens in pigs with respiratory disease in Vietnam. Samples from 127 clinical cases were obtained from different southern provinces of Vietnam from January 2018 to January 2020 for PCR and sequence analysis. The infection rate of PCV2 was 78.8%, and the major pathogens found in coinfections with PCV2 were porcine reproductive and respiratory syndrome virus, Mycoplasma hyopneumoniae, and Haemophilus parasuis. Forty-three PCV2-positive clinical samples were selected for amplification and sequencing of the ORF2 region. Phylogenetic analysis of PCV2 ORF2 showed that five of the sequences belonged to PCV2b (11.6%) and 38 belonged to PCV2d (88.4%), indicating that PCV2d strains were predominant in southern provinces of Vietnam. Alignment of the predicted amino acid sequences of the PCV2 capsid protein revealed polymorphic sites in the antibody recognition regions. This study demonstrates the prevalence of the PCV2d genotype in southern Vietnam and presents a comprehensive overview of the coinfecting pathogens associated with PCV2 in young pigs with respiratory disease.

Gene expression profiling has been shown to be comparable to other molecular methods for glioma classification. We sought to validate a gene-expression based glioma classification method. Formalin-fixed paraffin embedded tissue and flash frozen tissue collected at the Augusta University (AU) Pathology Department between 2000-2019 were identified and 2 mm cores were taken. The RNA was extracted from these cores after deparaffinization and bead homogenization. One hundred sixty-eight genes were evaluated in the RNA samples on the nCounter instrument. Forty-eight gliomas were classified using a supervised learning algorithm trained by using data from The Cancer Genome Atlas. An ensemble of 1000 linear support vector models classified 30 glioma samples into TP1 with classification confidence of 0.99. Glioma patients in TP1 group have a poorer survival (HR (95% CI) = 4.5 (1.3-15.4), p = 0.005) with median survival time of 12.1 months, compared to non-TP1 groups. Network analysis revealed that cell cycle genes play an important role in distinguishing TP1 from non-TP1 cases and that these genes may play an important role in glioma survival. This could be a good clinical pipeline for molecular classification of gliomas.

Molecular biomarkers that can predict survival and therapeutic outcome are still lacking for cervical cancer. Here we measured a panel of 19 serum proteins in sera from 565 patients with stage II or III cervical cancer and identified 10 proteins that have an impact on disease specific survival (DSS) (Hazzard's ratio; HR = 1.51-2.1). Surprisingly, all ten proteins are implicated in senescence-associated secreted phenotype (SASP), a hallmark of cellular senescence. Machine learning using Ridge regression of these SASP proteins can robustly stratify patients with high SASP, which is associated with poor survival, and patients with low SASP associated with good survival (HR = 3.09-4.52). Furthermore, brachytherapy, an effective therapy for cervical cancer, greatly improves survival in SASP-high patients (HR = 3.3, p < 5 × 10 -5 ) but has little impact on survival of SASP-low patients (HR = 1.5, p = 0.31). These results demonstrate that cellular senescence is a major determining factor for survival and therapeutic response in cervical cancer and suggest that senescence reduction therapy may be an efficacious strategy to improve the therapeutic outcome of cervical cancer.

Protein-protein interactions in cell membrane systems play crucial roles in a wide range of biological processes- from cell-to-cell interactions to signal transduction; from sensing environmental signals to biological response; from metabolic regulation to developmental control. Accurate structural information of protein-protein interactions is crucial for understanding the molecular mechanisms of membrane protein complexes and for the design of highly specific molecules to modulate these proteins. Many in vivo and in vitro approaches have been developed for the detection and analysis of protein-protein interactions. Among them the structural biology approach is unique in that it can provide direct structural information of protein-protein interactions at the atomic level. However, current membrane protein structural biology is still largely limited to detergent-based methods. The major drawback of detergent-based methods is that they often dissociate or denature membrane protein complexes once their native lipid bilayer environment is removed by detergent molecules. We have been developing a native cell membrane nanoparticle system for membrane protein structural biology. Here, we demonstrate the use of this system in the analysis of protein-protein interactions on the cell membrane with a case study of the oligomeric state of AcrB.

Effective removal of organic contaminants in wastewater effluent poses a challenge to small communities worldwide, particularly in the Arctic due to infrastructure challenges and harsh climates. To understand better the efficacy of current treatment options and risks posed by pharmaceuticals and pesticides on receiving waters in the Arctic, four representative human communities in Nunavut, Canada were evaluated. Per- and polyfluorinated alkyl substances (PFASs) were also investigated in one community. These communities have treatment ranging from primary lagoons, engineered wetlands, and natural lakes. Pharmaceuticals and pesticides were measured using the organic diffusive gradients in thin film (o-DGT) passive sampler in summer 2018. Of the 34 compounds studied, seven pharmaceuticals were found at least once: atenolol, carbamazepine, metoprolol, naproxen, sulfapyridine, sulfamethoxazole, and trimethoprim. With the exception of 5210 ng naproxen/L in Iqaluit, most receiving waters showed negligible amounts of contamination. Iqaluit had the poorest overall system performance while Baker Lake had the best. Measured pharmaceutical concentrations do not appear to pose a significant acute hazard to receiving waters at this time, based on known toxicological endpoints. PFAS concentrations were found to be over 100-fold greater in Cambridge Bay wastewater than previously reported Arctic seawater. Results suggest that wastewater may be an important point source of PFASs in Arctic communities. The o-DGT passive samplers performed well in marine Arctic settings. We recommend further testing of wastewater efficiencies in Arctic communities along with evaluations of seasonal variations., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)

New Zealand uses more than a ton of pesticides each year; many of these are mobile, relatively persistent, and can make their way into waterways. While considerable effort goes into monitoring nutrients in agricultural streams and programs exist to monitor pesticides in groundwater, very little is known about pesticide detection frequencies, concentrations, or their potential impacts in New Zealand streams. We used the 'Polar Organic Chemical Integrative Sampler' (POCIS) approach and grab water sampling to survey pesticide concentrations in 36 agricultural streams in Waikato, Canterbury, Otago and Southland during a period of stable stream flows in Austral summer 2017/18. We employed a new approach for calculating site-specific POCIS sampling rates. We also tested two novel passive samplers designed to reduce the effects of hydrodynamic conditions on sampling rates: the 'Organic-Diffusive Gradients in Thin Films' (o-DGT) aquatic passive sampler and microporous polyethylene tubes (MPTs) filled with Strata-X sorbent. Multiple pesticides were found at most sites; two or more were detected at 78% of sites, three or more at 69% of sites, and four or more at 39% of sites. Chlorpyrifos concentrations were the highest, with a maximum concentration of 180 ng/L. Concentrations of the other pesticides were generally below 20 ng/L. Mean concentrations of individual pesticides were not correlated with in-stream nutrient concentrations. The majority of pesticides were detected most frequently in POCIS, presumably due to its higher sampling rate and the relatively low concentrations of these pesticides. In contrast, chlorpyrifos was most frequently detected in grab samples. Chlorpyrifos concentrations at two sites were above the 21-day chronic 'No Observable Effect Concentration' (NOEC) values for fish and another two sites had concentrations greater than 50% of the NOEC. Otherwise, concentrations were well-below NOEC values, but close to the New Zealand Environmental Exposure Limits in several cases., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Although metathesis photoinduced catalysis is now well established, there is little development in thin film preparation using photochemically activated ring-opening metathesis polymerization (ROMP). Herein, a N-heterocyclic carbene (NHC) photogenerator (1,3-bis(mesityl)imidazolium tetraphenylborate) is combined with an inactive metathesis catalyst ([RuCl 2 ( p -cymene)] 2 ) to generate under UV irradiation an active catalyst ( p -cymene)RuCl 2 (NHC), that is capable of producing in a single step cross-linked copolymer films by ROMP of norbornene with dicyclopentadiene. The study shows that the photoinitiated catalytic system can be optimized by increasing the yield of photogenerated NHC through a sensitizer (2-isopropylthioxanthone), and by choosing [RuI 2 ( p -cymene)] 2 as precatalyst to provide a long-term photolatency. The cross-linked polymer structure is investigated by a range of techniques including gel content measurement, FT-IR and solid-state 13 C NMR spectroscopy, TGA and DSC, which reveal a cross-linking mechanism proceeding through both metathesis and olefin coupling., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Although N-heterocyclic carbenes (NHCs) have brought profound changes in catalytic organic synthesis, their generation generally requires an inert atmosphere and harsh conditions. To overcome these limitations, an air-stable NHC photogenerator has been developed involving two mild components: 1,3-bis(mesityl)imidazolium tetraphenylborate (IMesH + BPh 4 - ) and electronically excited isopropylthioxanthone (ITX). In this study, the photochemical mechanism is investigated via the accurate identification of the transient species and photoproducts. Electron transfer reaction between the excited triplet state of ITX and BPh 4 - is demonstrated as being the primary photochemical step. Nanosecond laser spectroscopy shows an efficient quenching and the formation of the expected ITX radical anion. The oxidized borane species is not observed, suggesting that this short-lived species could dissociate very rapidly to give the phenyl radical - successfully identified using electron paramagnetic resonance - and triphenylborane. As regards the final photoproducts, 1 H and 13 C NMR spectroscopies support the formation of the targeted NHC, 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes), suggesting the occurrence of a subsequent proton transfer reaction between ITX radical anion and imidazolium cation (IMesH + ). Gas chromatography-mass spectrometry reveals three other products: biphenyl, isopropylthioxanthene and ITX. Their formation can be reconciled with a 2-step mechanism of photoinduced electron/proton transfer reactions. 11 B NMR spectroscopy demonstrates that the main organoboron photoproduct is diphenylborinic acid formed by oxidation of BPh 3 . Due to its Lewis acidity, Ph 2 BOH can react with IMes to yield an NHC-boron adduct.

In the search of smarter routes to control the conditions of N-heterocyclic carbene (NHCs) formation, a two-component air-stable NHC photogenerating system is reported. It relies on the irradiation at 365 nm of a mixture of 2-isopropylthioxanthone (ITX) with 1,3-bis(mesityl)imidazoli(ni)um tetraphenylborate. The photoinduced liberation of NHC is evidenced by reaction with a mesitoyl radical to form an NHC-radical adduct detectable by electron spin resonance spectroscopy. The NHC yield can be determined by 1 H NMR spectroscopy through the formation of a soluble and stable NHC-carbodiimide adduct. To deprotonate the azolium salt and liberate the NHC, a mechanism is proposed in which the role of base is played by ITX radical anion formed in situ by a primary photoinduced electron-transfer reaction between electronically excited ITX (oxidant) and BPh 4 - (reductant). An NHC yield as high as 70 % is achieved upon starting with a stoichiometric ratio of ITX and azolium salt. Three different photoNHC-mediated polymerizations are described: synthesis of polyurethane and polyester by organocatalyzed step-growth polymerization and ring-opening copolymerization, respectively, and generation of polynorbornene by ring-opening metathesis polymerization using an NHC-coordinated Ru catalyst formed in situ., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We report a method to generate the N-heterocyclic carbene (NHC) 1,3-dimesitylimidazol-2-ylidene (IMes) under UV-irradiation at 365 nm to characterize IMes and determine the corresponding photochemical mechanism. Then, we describe a protocol to perform ring-opening metathesis polymerization (ROMP) in solution and in miniemulsion using this NHC-photogenerating system. To photogenerate IMes, a system comprising 2-isopropylthioxanthone (ITX) as the sensitizer and 1,3-dimesitylimidazolium tetraphenylborate (IMesH + BPh4 - ) as the protected form of NHC is employed. IMesH + BPh4 - can be obtained in a single step by anion exchange between 1,3-dimesitylimidazolium chloride and sodium tetraphenylborate. A real-time steady-state photolysis setup is described, which hints that the photochemical reaction proceeds in two consecutive steps: 1) ITX triplet is photo-reduced by the borate anion and 2) subsequent proton transfer takes place from the imidazolium cation to produce the expected NHC IMes. Two separate characterization protocols are implemented. Firstly, CS2 is added to the reaction media to evidence the photogeneration of NHC through formation of the IMes-CS2 adduct. Secondly, the amount of NHC released in situ is quantified using acid-base titration. The use of this NHC photo-generating system for the ROMP of norbornene is also discussed. In solution, a photopolymerization experiment is conducted by mixing ITX, IMesH + BPh4 - , [RuCl2(p-cymene)]2 and norbornene in CH2Cl2, then irradiating the solution in a UV reactor. In a dispersed medium, a monomer miniemulsion is first formed then irradiated inside an annular reactor to produce a stable poly(norbornene) latex.

Although many studies have addressed the ability of subsurface filtration systems to remove emerging contaminants from wastewater at micro- and mesocosm-scale, little is known about their performance on full-scale wastewater treatment facilities. To understand better how effective these systems can be for municipal wastewater polishing, we assessed the ability of a full-scale lagoon-subsurface filter system located in Dunnottar, Manitoba, Canada, to attenuate regulatory wastewater parameters, nutrients, pharmaceuticals, and toxicity over the course of the discharge periods in 2015 and 2016 (June-October). Pharmaceuticals included β-blockers, anticonvulsant drugs, and macrolide and sulfonamide antibiotics. Out of six consistently detected pharmaceuticals, four were efficiently removed through lagoon treatment (e.g. clarithromycin, metoprolol, propranolol), while two persisted to a certain extent (e.g. carbamazepine, sulfamethoxazole), even after subsurface filtration. Attenuation was observed for nutrients with averages of 40% and 60% for ammonia and total phosphorus respectively within the filter, consistent with previous pilot-scale studies at this facility. Compliance with regulations for conventional wastewater parameters at the effluent was observed, as well as reduced acute toxicity (as determined by Microtox ® ) from the primary lagoon to the effluent, and little likelihood of acute toxicity in receiving waters. Our results suggest that first, the full-scale system has an overall similar performance when compared to the previously studied pilot-scale system; second, there was no apparent effect of acclimation on the attenuation of studied contaminants or toxicity; and finally, the concentrations of contaminants do not appear to pose an acute risk for aquatic species in the receiving environment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

1,3-Bis(mesityl)imidazolium tetraphenylborate (IMesH + BPh 4 - ) can be synthesized in one step by anion metathesis between the corresponding imidazolium chloride and sodium tetraphenylborate. In the presence of 2-isopropylthioxanthone (sensitizer), an IMes N-heterocyclic carbene (NHC) ligand can be photogenerated under irradiation at 365 nm through coupled electron/proton transfer reactions. By combining this tandem NHC photogenerator system with metathesis inactive [RuCl 2 (p-cymene)] 2 precatalyst, the highly active RuCl 2 (p-cymene)(IMes) complex can be formed in situ, enabling a complete ring-opening metathesis polymerization (ROMP) of norbornene in the matter of minutes at room temperature. To the best of our knowledge, this is the first example of a photogenerated NHC. Its exploitation in photoROMP has resulted in a simplified process compared to current photocatalysts, because only stable commercial or easily synthesized reagents are required., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The treatment of municipal wastewater in the Arctic is challenging due to a variety of financial, operational, climatic and technical issues. To better understand the efficacy of current wastewater treatment in this region and the hazard posed to receiving waters, we assessed the occurrence of nutrients and contaminants (i.e., pharmaceuticals, antibiotic resistance genes) as they moved through a lagoon-based treatment system in Cambridge Bay, Nunavut, Canada. Wastewater treatment in this community is performed by the use of a lagoon-tundra wetland system that is discharged into the marine environment and is representative of current common practices throughout the region. In 2014, samples were collected before and during lagoon discharge from two locations in the main lagoon, one location downstream from the lagoon effluent and three locations offshore. Grab samples were collected to measure nutrients (e.g., total nitrogen and phosphorus) and the presence of antibiotic resistance gene-bearing microbes, and Polar Organic Chemical Integrative Samplers (POCIS) were deployed to collect passively organic contaminants in all locations. A total of six pharmaceuticals were detected from a screen of twenty-eight analytes during the study: atenolol, carbamazepine, clarithromycin, metoprolol, sulfamethoxazole and trimethoprim. The greatest concentrations of nutrients, antibiotic resistance genes (ARGs), and pharmaceuticals were found in sampling locations within the treatment lagoon. Offshore of the release point, we observed limited to no detection of pharmaceuticals and ARGs, but no change in total nitrogen and phosphorus from pre-release. We conclude that the current concentrations of monitored pharmaceuticals do not pose a significant hazard at this time to aquatic organisms in Cambridge Bay., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Depression is one of the most frequently encountered psychiatric disease in the primary care setting, source of enormous suffering for the ill and for his/her entourage. Classical features of the disease in women are usually well known. This article's goal is to highlight the masculine specificities of depression, sometimes poorly known., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

This work consists of the adaptation of a non-additive hard sphere theory inspired by Malakhov and Volkov [Polym. Sci., Ser. A 49(6), 745-756 (2007)] to a square-well chain. Using the thermodynamic perturbation theory, an additional term is proposed that describes the effect of perturbing the chain of square well spheres by a non-additive parameter. In order to validate this development, NPT Monte Carlo simulations of thermodynamic and structural properties of the non-additive square well for a pure chain and a binary mixture of chains are performed. Good agreements are observed between the compressibility factors originating from the theory and those from molecular simulations.

Puffer fishes were collected from the central sea in Vietnam from spring to summer season. The eggs were incubated in MRS broth that was used to test the toxicity in mice and isolate the lactic acid bacteria community that could produce tetrodotoxin (TTX). Thin layer chromatography (TLC) and high performance lipid chromatography (HPLC) were used to detect and quantify TTX. As a result, Enterococcus faecium AD1 which was identified by biochemical test and 16S rRNA analysis could produce TTX 0.3 mg/mL when cultured in MRS broth. The bacterium was optimized for TTX production and gave 0.18 mg/mL, 0.07 mg/mL, and 0.15 mg/mL in media prepared from the meat-washing water of freshwater fishes (Pangasius bocourti, Oreochromis sp.) and sea fish (Auxis thazard), respectively, that are also hopeful to answer some poisoning cases related to eating fishes. Enterococcus faecium also showed the wide antimicrobial activities on yeast, Gram-negative and -positive bacteria. Extracted exopolysaccharide (EPS) that reacted with 2,2-diphenyl-1-picrylhydrazyl to give IC50 at 5 mg/mL equaled 11 mg/mL ascorbic acid which could show effects on Hela-6 and Hep G2 using sulforhodamine B test. Enterococcus faecium can be claimed as a promising source in tetrodotoxin and biological compounds.