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• The high level N-doped Co@NCNTs composites via one-step pyrolysis derived from adenine-based MOFs. • Adenine as an endogenous nitrogen source to apparently increase the N content of the material. • The prepared magnetic Co-based catalysts imply excellent catalytic activity and reusability even after five cycles. Nitrogen-doped porous Co@NCNT-1/11 catalysts with Co nanoparticles encapsulated in the nitrogen-rich carbon materials in situ grown CNTs were successfully synthesized through a one-step pyrolysis method for the reduction of aromatic nitro organics. ga1 A rational and convenient strategy was designed to synthesize high level N-doped Co@NCNTs composites derived from adenine-based AD-MOF-1 and Bio-MOF-11 via one-step pyrolysis method. Adenine can be used as an endogenous nitrogen source to apparently increase the N content of the materials. N-rich CNTs form a protecting layer for Co nanoparticles to avoid the aggregation of metal nanoparticles. The abundant nitrogen content can enhance electronic conductivity and bring additional active sites. The prepared Co@NCNTs display high catalytic efficiency for various nitro aromatics reduction in aqueous solution. The Co@NCNT-1-800 implies outstanding catalytic efficiency of 96% for the reduction of 4-NP. A mechanistic analysis revealed the abundant Co catalytic sites on the surface of catalysts to promote electron transfer efficiency and improve catalytic performance significantly. Moreover, the magnetic Co-based catalysts remained excellent catalytic activity and reusability even after five cycles. [ABSTRACT FROM AUTHOR]

Aims: The aim of the study was to evaluate the suitability of the current caffeine dosing regimen for the Chinese population using modelling and simulation approach. Methods: Pharmacokinetic samples were collected from 99 Chinese newborns with premature apnoea. The median (range) of gestational age and postmenstrual age were 28.3 (25.0–33.4) weeks and 31.1 (26.4–38.0) weeks, respectively. Newborns were receiving caffeine citrate at a loading dose of 20 mg/kg/d and a maintenance dose of 5–10 mg/kg/d. Caffeine concentrations and CYP1A2 polymorphisms were investigated. Population pharmacokinetic modelling of caffeine in Chinese preterm newborn on a population‐wide scale was conducted using NONMEM. Results: A 1‐compartment model with first‐order elimination was used to describe population pharmacokinetic. With current weight implemented using 0.75 allometric scaling, clearance (CL) was positively related to current weight and postmenstrual age, but a negative relationship was observed with serum creatinine concentration. Eight genotypes of CYP1A2 were tested and none of them had a significant impact on caffeine pharmacokinetic parameters. Interindividual variability of CL and volume of distribution was 7.70 and 65.9%. The median (range) of 95% confidence intervals of CL were 0.0128 (0.0128–0.0131) L/h/kg. Monte Carlo simulation demonstrated that 80% (loading dose) and 98% (maintenance dose) of premature infants treated with a labelled dosing regimen attained the concentration target range of 5–20 mg/L. Conclusion: A population PK model of caffeine was developed in Chinese newborns. Body weight‐implemented allometric scaling, postmenstrual age and serum creatinine concentration markedly affected caffeine clearance. The labelled dosing regimen is suitable for Chinese premature infants. [ABSTRACT FROM AUTHOR]

Background: Variants in the GJB2 gene encoding the gap junction protein connexin‐26 (Cx26) can cause autosomal recessive nonsyndromic hearing loss or a variety of phenotypically variable autosomal dominant disorders that effect skin and hearing, such as palmoplantar keratoderma (PPK) with deafness and keratitis–ichthyosis–deafness (KID) syndrome. Here, we report a patient with chronic mucocutaneous candidiasis, hyperkeratosis with resorption of the finger tips, profound bilateral sensorineural hearing loss, and normal hair and ocular examination. Exome analysis identified a novel missense variant in GJB2 (NM_004004.5:c.101T>A, p.Met34Lys) that was inherited from a mosaic unaffected parent in the setting of a well‐reported GJB2 loss of function variant (NM_004004.5:c.35delG, p.Gly12Valfs*2) on the other allele. Method: Rat epidermal keratinocytes were transfected with cDNA encoding wildtype Cx26 and/or the Met34Lys mutant of Cx26. Fixed cells were immunolabeled in order to assess the subcellular location of the Cx26 mutant and cell images were captured. Results: Expression in rat epidermal keratinocytes revealed that the Met34Lys mutant was retained in the endoplasmic reticulum, unlike wildtype Cx26, and failed to reach the plasma membrane to form gap junctions. Additionally, the Met34Lys mutant acted dominantly to wildtype Cx26, restricting its delivery to the cell surface. Conclusion: Overall, we show the p.Met34Lys variant is a novel dominant acting variant causing PPK with deafness. The presence of a loss a function variant on the other allele creates a more severe clinical phenotype, with some features reminiscent of KID syndrome. [ABSTRACT FROM AUTHOR]

Background: Lean management has been successfully employed in healthcare to improve outcomes and efficiencies. Facilitation is increasingly being used to support evidence-based practice uptake in healthcare. However, while both Lean and Facilitation are used in healthcare quality improvement, limited research has explored their integration and the sustainability of their combined effects. Objective: To improve hepatitis C virus (HCV) screening rates among persons born between 1945 and 1965 through the design and evaluation of a multi-modal Lean-Facilitation intervention (LFI) for Department of Veterans Affairs primary care community clinics. Design: We conducted a mixed methods quasi-experimental evaluation in eight clinics, guided by the integrated Promoting Action on Research Implementation in Health Services framework. Participants: We engaged regional and local leadership (N = 9), implemented our LFI with clinicians and staff (N = 68), and conducted summative interviews with participants (N = 13). Intervention: The LFI included six implementation strategies: (1) external facilitation, (2) stakeholder engagement, (3) champion activation, (4) rapid process improvement sessions, (5) Plan-Do-Study-Act cycles, and (6) audit-feedback. Measures: The primary outcome was rate of new HCV screening among previously untested patients with a primary care visit. Using interrupted time series, we analyzed intervention and time effects on HCV testing rates, and administered organizational readiness surveys, conducted summative qualitative interviews, and tracked facilitation events. Results: The LFI was associated with significant, immediate, and sustained increases in HCV testing. No change was detected at matched comparison clinics. Staff accepted the LFI and the philosophy of "bottom-up" solution development yet had mixed feedback on its appropriateness and feasibility. Enablers of implementation and early sustainment included lower satisfaction with baseline HCV testing processes and staff culture, while later sustainment was related to implementation climate support, measurement, and evaluation. Conclusions: High-reach and relatively low effort, but persistent intervention led to significant improvement in guideline-concordant HCV testing rates which were sustained. Trial Registration: ClinicalTrials.gov Identifier: NCT02936648 [ABSTRACT FROM AUTHOR]

Traditionally, Clematis tangutica Korsh. (Ranunculaceae) is used as a Tibetan herb for treating indigestion and blood stasis in China. Recently, a flavonoid glycoside, apigenin-7-O-β-d-(6″-p-coumaroyl)-glucopyranoside (APG), was isolated from the whole plant of C. tangutica. To investigate the cardioprotective effects of APG against myocardial ischaemia/reperfusion injury (MI/RI) and the possible mechanism. Animals were subjected to 30 min/3 h MI/RI model. At the end of reperfusion, infarct size (IS), histopathology, serum levels CK-MB, LDH, TNF-α, IL-6 and MPO activities were detected. Phospho-IκB-α, ICAM-1 and NF-κB were assessed in vivo. Neonatal rat cardiomyocytes were pre-treated with or without APG, followed by stimulation with 8 h/2 h oxygen and glucose deprived/reoxygenation (OGD/R) model. Cell viability, LDH and cardiomyocyte apoptosis were assessed. The expression levels of phospho-IκB-α and NF-κB were measured in vitro. Treatment with APG significantly reduced the following indicators in vivo (p < 0.05): (1) the IS (16.2%); (2) morphology score (1.67); (3) myocardial injury enzymes: CK-MB (26.2 ng/mL) and LDH (688 U/L); (4) pro-inflammatory cytokines: TNF-α (31.5 pg/mL) and IL-6 (163.8 pg/mL); (5) MPO activity (2.75 U/mg); (6) expression levels of phospho-IκB-α (0.47), NF-κB (2.87) and ICAM-1 (10.2). Moreover, treatment with APG also remarkably (p < 0.05) attenuated the following indicators in vitro: (1) LDH level (206 U/L); (2) cardiomyocyte apoptosis; (3) phospho-IκB-α (1.37) and NF-κB (2.50). APG possesses protective effects against MI/RI injury in rats and OGD/R-induced injury in cardiomyocytes by suppressing translocation of NF-κB and reducing inflammatory response; consequently, APG is helpful for treatment of ischaemic heart disease. [ABSTRACT FROM AUTHOR]

Peptide co-assembly is attractive for creating biomaterials with new forms and functions. Emergence of these properties depends on the peptide content of the final assembled structure, which is difficult to predict in multicomponent systems. Here using experiments and simulations we show that charge governs content by affecting propensity for self- and co-association in binary CATCH(+/−) peptide systems. Equimolar mixtures of CATCH(2+/2−), CATCH(4+/4−), and CATCH(6+/6−) formed two-component β-sheets. Solid-state NMR suggested the cationic peptide predominated in the final assemblies. The cationic-to-anionic peptide ratio decreased with increasing charge. CATCH(2+) formed β-sheets when alone, whereas the other peptides remained unassembled. Fibrillization rate increased with peptide charge. The zwitterionic CATCH parent peptide, "Q11", assembled slowly and only at decreased simulation temperature. These results demonstrate that increasing charge draws complementary peptides together faster, favoring co-assembly, while like-charged molecules repel. We foresee these insights enabling development of co-assembled peptide biomaterials with defined content and predictable properties. Co-assembly of peptide mixtures can yield interesting materials, but predictive understanding of assembly pathways is lacking. Here the self- and co-assembly preferences of oppositely-charged peptides are systematically studied experimentally and by molecular dynamics simulations. [ABSTRACT FROM AUTHOR]

Background & aims: Given ongoing challenges in non-invasive non-alcoholic liver disease (NAFLD) diagnosis, we sought to validate an ALT-based NAFLD phenotype using measures readily available in electronic health records (EHRs) and population-based studies by leveraging the clinical and genetic data in the Million Veteran Program (MVP), a multi-ethnic mega-biobank of US Veterans. Methods: MVP participants with alanine aminotransferases (ALT) >40 units/L for men and >30 units/L for women without other causes of liver disease were compared to controls with normal ALT. Genetic variants spanning eight NAFLD risk or ALT-associated loci (LYPLAL1, GCKR, HSD17B13, TRIB1, PPP1R3B, ERLIN1, TM6SF2, PNPLA3) were tested for NAFLD associations with sensitivity analyses adjusting for metabolic risk factors and alcohol consumption. A manual EHR review assessed performance characteristics of the NAFLD phenotype with imaging and biopsy data as gold standards. Genetic associations with advanced fibrosis were explored using FIB4, NAFLD Fibrosis Score and platelet counts. Results: Among 322,259 MVP participants, 19% met non-invasive criteria for NAFLD. Trans-ethnic meta-analysis replicated associations with previously reported genetic variants in all but LYPLAL1 and GCKR loci (P<6x10-3), without attenuation when adjusted for metabolic risk factors and alcohol consumption. At the previously reported LYPLAL1 locus, the established genetic variant did not appear to be associated with NAFLD, however the regional association plot showed a significant association with NAFLD 279kb downstream. In the EHR validation, the ALT-based NAFLD phenotype yielded a positive predictive value 0.89 and 0.84 for liver biopsy and abdominal imaging, respectively (inter-rater reliability (Cohen's kappa = 0.98)). HSD17B13 and PNPLA3 loci were associated with advanced fibrosis. Conclusions: We validate a simple, non-invasive ALT-based NAFLD phenotype using EHR data by leveraging previously established NAFLD risk-associated genetic polymorphisms. [ABSTRACT FROM AUTHOR]

• Ce (Mn) incorporation improved the activity and hydrothermal stability of Cu-SSZ-39. • More active CuO crystallites and stronger acidity contribute high activity after Ce/Mn addition. • Stable structure, acidity and less large Cu oxides promote MnCu-SSZ-39 hydrothermally stable. • Cu2+ ion re-distribution to ion exchange sites during hydrothermal process over MnCu-SSZ-39. • NH 3 -SCR reaction over MnCu-SSZ-39 follows L–H", E–R, and "Fast SCR" mechanisms. In this work, Ce and Mn were added to Cu-SSZ-39 zeolites by ion-exchange process, and their activity performance for selective catalytic reduction of NO x with ammonia (NH 3 -SCR), especially hydrothermal stability (hydrothermal aging at 750, 800, 850 °C) was investigated systematically. It is found that the addition of Ce and Mn, Mn more evidently, both can greatly improve the activity of Cu-SSZ-39 catalyst. Moreover, MnCu-SSZ-39 catalyst have shown superior hydrothermal stability compared with Cu-SSZ-39 catalyst, and outstandingly its activity is not only not decreased significantly like Cu-SSZ-39 but improved obviously after hydrothermal aging at as high as 850 °C. The high and improved activity of Ce and Mn added Cu-SSZ-39 is ascribed to more active CuO crystallites formation in the inner channel and higher acidity strength. The superior hydrothermal stability of MnCu-SSZ-39 may be due to its well-preserved structure and acid density even after hydrothermal aging at as high as 850 °C. Moreover, during the hydrothermal aging process, not only Cu oxides aggregation is inhibited, but also more Cu2+ ion species are induced to ion exchange sites in MnCu-SSZ-39, which may account for its excellent hydrothermal stability (even higher than the activity of fresh samples). The mechanism analysis has shown NH 3 -SCR reaction over Cu-SSZ-39 and CeCu-SSZ-39 samples follow the "Langmuir–Hinshelwood" (L-H) mechanism, while on MnCu-SSZ-39, it follows both "L–H" and "Eley–Rideal" (E–R) mechanisms, which may also be another reason for its excellent activity and hydrothermal stability. Moreover, "Fast SCR" mechanisms also occur and contribute over hydrothermal aged A-MnCu-SSZ-39 sample, in addition to "L-H" and "E-R" mechanisms. Thus, the easily prepared MnCu-SSZ-39 catalyst has shown the excellent activity and super hydrothermal stability, with 90% NO conversion at 245 °C and broader temperature window of 245 °C to 550 °C, even after hydrothermal aging at 850 °C, therefore indicate great potential for future application in NO x purifying from diesel engine exhaust. [ABSTRACT FROM AUTHOR]

Against non-caspase-dependent apoptosis in mice hippocampal neurons following MCAO To determine the protein expressions of AIF, Endo G and BNIP3 in the mitochondria of Table 1 Effects of 2-AG on apoptosis rate of hippocampal neurons, the expression of AIF, Endo G and BNIP3 in mice (± s) Induced mitochondria-mediated apoptosis involving AIF, Endo-G. [Extracted from the article]

Introduction: Standard bi‐level non‐invasive ventilation with fixed‐level pressure support (PS) delivery may not maintain ventilation during the changes in pulmonary mechanics that occur throughout day and night, so average volume‐assured pressure support (AVAPS) modes that target a preset volume by adjustment of PS may be effective. Objective: Our meta‐analysis wants to compare AVAPS and pressure support non‐invasive ventilation (PS‐NIV) regarding arterial blood gases (ABGs), sleep efficiency and compliance. Method: Relevant publications indexed in PubMed, Cochrane Library, Embase, Web of Science, Wanfang Data, China National Knowledge Infrastructure and VIPI were identified. Appropriate articles identified from the reference lists of the above searches were also reviewed. We included randomized controlled trials involved the use of AVAPS and PS‐NIV ventilation for chronic respiratory failure. Each included study weighted mean differences, and 95% confidence intervals (CI) were calculated for continuous outcomes. Statistical heterogeneity was assessed using the I2 value ≤ 50% were considered as no statistical heterogeneity and used fixed effects model. Otherwise, a random effects model was used. Results: Eight trials were eligible. No significant difference was observed between AVAPS and PS‐NIV groups to compare PaCO2 (OR −0.97, CI‐2.54‐0.61, P = 0.23) and PaO2 (OR −1.81, CI‐4.29‐0.67, P = 0.15) in ABGs. There was no significant difference between the two groups with sleep efficiency (OR −3.31, CI‐7.58‐0.95, P = 0.13) and visual analog scale (OR 0.32, CI‐6.97‐7.61, P = 0.93). Conclusions: The evidence shows there is no significant difference in clinical outcomes when comparing AVAPS and PS‐NIV used for chronic respiratory failure patients. [ABSTRACT FROM AUTHOR]

Aims: Increasing evidence indicates that neuroinflammatory and oxidative stress play two pivotal roles in cognitive impairment after surgery. Honokiol (HNK), as an activator of Sirtuin3 (SIRT3), has potential multiple biological functions. The aim of these experiments is to evaluate the effects of HNK on surgery/anesthesia‐induced cognitive decline in mice. Methods: Adult C57BL/6 mice received a laparotomy under sevoflurane anesthesia and HNK or SIRT3 inhibitor (3‐TYP) treatment. Cognitive function and locomotor activity of mice were evaluated using fear conditioning test and open field test on postoperative 1 and 3 days. Neuronal apoptosis in CA1 and CA3 area of hippocampus was examined using TUNEL assay. And Western blot was applied to measure the expression of pro‐inflammatory cytokines and SIRT3/SOD2 signaling‐associated proteins in hippocampus. Meanwhile, SIRT3 positive cells were calculated by immunohistochemistry. The mitochondrial membrane potential, malondialdehyde (MDA), and mitochondrial radical oxygen species (mtROS) were detected using standard methods. Results: Honokiol attenuated surgery‐induced memory loss and neuronal apoptosis, decreased neuroinflammatory response, and ameliorated oxidative damage in hippocampus. Notably, surgery/anesthesia induced an obviously decrease in hippocampal SIRT3 expression, whereas the HNK increased SIRT3 expression and thus decreased the acetylation of superoxide dismutase 2 (SOD2). However, 3‐TYP treatment inhibited the HNK's rescuing effects. Conclusions: These results suggested that activation of SIRT3 by honokiol may attenuate surgery/anesthesia‐induced cognitive impairment in mice through regulation of oxidative stress and neuroinflammatory in hippocampus. [ABSTRACT FROM AUTHOR]

Flower of Abelmoschus manihot (FAM) is clinically effective to treat chronic kidney disease (CKD) with a relatively high dosage. To improve the efficacy and the compliance of patients, macroporous resins were adopted to enrich and purify flavonoids from FAM, which are thought to be the major renal protective constituents in FAM. After screening six different kinds of macroporous resins, HPD-100 was selected for its great adsorption and desorption capacity. Then, orthogonal design tests were used to optimize parameters in the processes of impurity removal and flavonoids of FAM desorption on column chromatogram. Moreover, process scale-up was performed, and purification effects maintained after amplification. After purification, the content of seven main flavonoids in the product increased from 8.29% to 51.43%. Protective and anti-inflammatory effects of crude extract and the flavonoid component of FAM after purification were investigated on the adriamycin-damaged HK-2 cells and lipopolysaccharide-stimulated Raw 264.7 cells models. Both bioactivities were improved greatly after purification for these two cell models. Therefore, the purification process had enriched the main bioactive constituents with potential alleviating kidney injury activities. The flavonoid component of FAM is worthy of being developed as an improved remedy for CKD with better patients' compliance. [ABSTRACT FROM AUTHOR]

[Display omitted] • Persulfate is synergistically activated by hybrid homogeneous-heterogeneous process. • SO 4 •−, •OH and Fe(IV) made concerted efforts to phenol degradation. • A new formation path of aqueous Fe(IV) in Fe2+/persulfate system was proposed. • The effect of Fe(IV) on phenol degradation was disclosed from a DFT perspective. • Various phenolic compounds were effectively degraded in FeO/persulfate system. This study presents new findings on persulfate (PDS) activation by iron(II) oxide (FeO). PDS was activated through both homogeneous and heterogeneous approaches, while the latter played a dominant role. The species responsible for phenol oxidation were identified as SO 4 −, OH, and high-valent Fe(IV). A new possible formation pathway of aqueous Fe(IV) is proposed, involving electron transfer between SO 4 −/OH and Fe(III)–OH complex. Density functional theory calculations support that Fe(IV) is apt to attack phenol by electrophilic addition on the benzene ring and hydrogen atom abstraction on the phenolic hydroxyl group. Phenol removal was accelerated at a higher catalyst dosage or PDS concentration but inhibited at higher pH. The coexistence of inorganic anions (e.g., PO 4 3−, SO 4 2−, NO 3 −, and Cl−) and fulvic acid have different effects on this system. Phenol degradation mainly occurred through hydroxylation and eventual ring-opening. In addition, the FeO/PDS system has not only achieved a high removal effect on other phenolic compounds but has also exhibited high performance in actual water. Thus, this system is anticipated to be a promising treatment technique for phenolic-polluted water. [ABSTRACT FROM AUTHOR]

The solid solution alloys containing short-range order (SRO) structure, such as CuNi alloys, are not well structurally described using conventional quasi-disordered models. Based on the first-principles calculations, the optimal cluster-plus-glue-atom (CPGA) models of six typical solid solution CuNi alloys were demonstrated. These CPGA models are better to be used to describe the microstructure of the six CuNi alloys at the atomic scale from the viewpoint of energy. Our further study shown that the stabilities of CPGA models are highly related to the symmetry of initial CPGA models and the aggregation degree of solute atoms in CPGA models. In the condition of low solute Ni concentration, the stability of CPGA model is mostly determined by the symmetry of initial CPGA model, the CPGA model with high symmetry is more stable. As the concentration of solute Ni increasing, the aggregation degree of solute Ni atoms in CPGA models plays more and more important role. The CPGA model with higher aggregation degree of solute Ni is more stable. The simple selection method of optimal CPGA models, therefore is proposed, and which can be extended to other bielement solid solution AB alloys with positive mixing enthalpy of A-B. Using the selected CPGA models, we found the third additive atoms having negative mixing enthalpy with solvent and solute atoms prefer to reside the central site of characteristic principal cluster (CPC) of CPGA, and thereby enhancing the stability of alloys. Our studies provide a distinctive perspective to select the optimal CPGA models of solid solution alloys containing SRO structure and design alloy using the optimal CPGA model. [ABSTRACT FROM AUTHOR]

Aims: Because of concerns about the safety of aliskiren in patients with diabetes, study treatment was stopped prematurely in the Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failuRE (ATMOSPHERE). We examined outcomes and treatment effect in these patients compared with those without diabetes.Methods and Results: ATMOSPHERE included 7016 patients with heart failure and a reduced ejection fraction (HFrEF) randomly assigned to enalapril plus aliskiren, aliskiren alone, or enalapril. At baseline, 1944 (27.7%) patients had diabetes. Median follow-up was shorter in patients with diabetes compared with those without (24 months vs. 46 months). Among patients with diabetes, the primary endpoint of cardiovascular death or hospitalization for heart failure occurred in 216 patients (33.1%) in the enalapril group (reference), 172 (27.4%) in the aliskiren group [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.67-1.00; P = 0.053], and 196 (29.5%) in the combination group (HR 0.86, 95% CI 0.71-1.04; P = 0.13). The effects of the treatments studied did not differ significantly compared with patients without diabetes. In patients with diabetes, aliskiren monotherapy was associated with a lower risk of symptomatic hypotension compared to enalapril [42 (6.7%) vs. 65 (10.0%); P = 0.04], whereas other adverse events were generally balanced between the three groups.Conclusion: In patients with HFrEF and diabetes, there was no signal of harm and a trend towards benefit when direct renin inhibition monotherapy was compared with an angiotensin-converting enzyme inhibitor, whereas combined aliskiren and enalapril treatment led to more adverse events with no improvement in outcomes. Treatment effects did not differ in patients with diabetes compared with those without. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00853658. [ABSTRACT FROM AUTHOR]

Background/Aims: Trastuzumab is an important treatment used for patients with Her-2-positive breast cancer, but an increasing incidence of trastuzumab resistance has been observed clinically during the past decade. Aberrant microRNA (miR) expression levels are correlated with prognosis and response to trastuzumab in breast cancer. MiR-129-5p is downregulated in trastuzumab-resistant human breast cancer cells (JIMT-1), but its potential function and underlying mechanism remain unclear. Methods: Quantitative RT-PCR (qRT-PCR) was used to determine the expression levels of miR-129-5p and its potential target genes. The effects of miR-129-5p on cell responses to trastuzumab were analyzed by CCK-8 and flow cytometry assays in Her-2-positive breast cancer cells (SKBR-3 and JIMT-1). Bio-informatics analyses were performed to predict target genes of miR-129-5p, and luciferase assays were carried out to confirm the binding of miR-129-5p and rpS6. Results: MiR-129-5p, which was downregulated and predicted to target rpS6 in trastuzumab-resistant breast cancer cells, enhanced the sensitivity of breast cancer cells to trastuzumab by reducing the expression of rpS6. Moreover, the overexpression of rpS6 reversed the sensitivity of cells to trastuzumab induced by miR-129-5p. Conclusions: MiR-129-5p sensitized Her-2-positive breast cancer to trastuzumab by downregulating rpS6. These findings provide novel insights into the common role of rpS6 and its related molecular mechanisms in mediating trastuzumab-resistance in Her-2-positive breast cancers. [ABSTRACT FROM AUTHOR]

A primary factor regulating the composition of the microbial community in the rhizosphere is carbon (C) efflux from root systems, which fundamentally influences microbial functions in the rhizosphere, such as biodegradation, plant growth, and rhizosphere signalling. However, information regarding the incorporation of plant-C by the bacterial community in the rhizosphere is limited, particularly in soybean. Soybean plants were grown in rhizo-boxes containing low- or high-organic C (C org ) Mollisols and labelled with 13 CO 2 at the flowering stage. After soil DNA was extracted from the rhizosphere, 13 C-DNA was separated from 12 C-DNA using the stable isotope probing method, followed by pyrosequencing analysis. Between soils, significant differences in the abundance of genera incorporating 13 C in the rhizosphere were observed, with Aquincola , Dechloromonas , Massilia , Amycolatopsis , Delftia , Magnetospirillum , Psychrobacter , Ochrobactrum , Pseudoxanthomonas and Niastella showing greater relative abundances in low-C org soil ( p < 0.05) compared to high-C org soil. However, the opposite trend was observed for Enhydrobacter , Flavisolibacter , Propionibacterium and Staphylococcus. Correspondingly, the number of operational taxonomic units in each genus varied between soils. Soil type greatly affected the flow of plant-C into rhizospheric bacterial community. The plant-C metabolizing bacteria may contribute to the transformation of rhizodeposits in the soil and soil C sequestration. [ABSTRACT FROM AUTHOR]

Solvent innovation has become a central task for improving the sustainability of chemical processes1. Deep eutectic solvents (DESs) emerge as environmentally friendly alternatives to toxic and volatile organic solvents. One appealing aspect for DESs is that they can be synthesized using naturally occurring compounds from biomass. Herein, we prepared novel hydrophobic DESs based on lignin derivatives and characterized their physicochemical properties including density, viscosity, and thermal behavior. The results showed that five lignin-derived hydrophobic DESs made from menthol, thymol, and 2,6-dimethoxyphenol were promising as green solvents due to their low viscosities and environmentally friendly constituents. To evaluate the potential application of these DESs, liquid-liquid extraction was performed to recover the typical biofuel fermentation products including acetone, ethanol, n -butanol, and isopentanol from aqueous solutions. High distribution coefficients, selectivity, and recovery rates for acetone, n -butanol, and isopentanol were achieved with the thymol: 2,6-dimethoxyphenol DESs. Moreover, molecular dynamic simulations were conducted to investigate the DES molecular interactions and formation mechanism. This work demonstrates the potential of lignin derived hydrophobic DESs for applications as sustainable extraction media. Hydrophobic deep eutectic solvents were prepared using lignin derivatives, which possess the potential as sustainable extractants. [Display omitted] • Novel lignin based hydrophobic deep eutectic solvents (DESs) were developed. • The DESs showed low viscosity and tolerance to low temperatures (as low as −75 °C). • The molecular interactions within the DES contributed to its properties. • The DESs can be applied as extractants for liquid-liquid extractions. • The lignin based hydrophobic DESs hold great promise as sustainable solvents. [ABSTRACT FROM AUTHOR]

Background: The Y-chromosome haplogroup Q has three major branches: Q1, Q2, and Q3. Q1 is found in both Asia and the Americas where it accounts for about 90% of indigenous Native American Y-chromosomes; Q2 is found in North and Central Asia; but little is known about the third branch, Q3, also named Q1b-L275. Here, we combined the efforts of population geneticists and genetic genealogists to use the potential of full Y-chromosome sequencing for reconstructing haplogroup Q3 phylogeography and suggest possible linkages to events in population history. Results: We analyzed 47 fully sequenced Y-chromosomes and reconstructed the haplogroup Q3 phylogenetic tree in detail. Haplogroup Q3-L275, derived from the oldest known split within Eurasian/American haplogroup Q, most likely occurred in West or Central Asia in the Upper Paleolithic period. During the Mesolithic and Neolithic epochs, Q3 remained a minor component of the West Asian Y-chromosome pool and gave rise to five branches (Q3a to Q3e), which spread across West, Central and parts of South Asia. Around 3-4 millennia ago (Bronze Age), the Q3a branch underwent a rapid expansion, splitting into seven branches, some of which entered Europe. One of these branches, Q3a1, was acquired by a population ancestral to Ashkenazi Jews and grew within this population during the 1st millennium AD, reaching up to 5% in present day Ashkenazi. Conclusions: This study dataset was generated by a massive Y-chromosome genotyping effort in the genetic genealogy community, and phylogeographic patterns were revealed by a collaboration of population geneticists and genetic genealogists. This positive experience of collaboration between academic and citizen science provides a model for further joint projects. Merging data and skills of academic and citizen science promises to combine, respectively, quality and quantity, generalization and specialization, and achieve a well-balanced and careful interpretation of the paternal-side history of human populations. [ABSTRACT FROM AUTHOR]

Anti-inflammatory compounds were investigated from the ethanol extract of the roots and rhizomes of Asarum heterotropoides var. mandshuricum, a traditional Chinese medicine called Xixin and used for pain and inflammatory. Nine new compounds were isolated, including six new lignans, neoasarinin A–C (1–3), neoasarininoside A and B (4 and 5), and asarinin B (7), and one new monoterpene, asarincin A (8), two new amides, asaramid II and III (10 and 11), and one new natural monoterpene, asaricin B (9), along with 37 known compounds (6, 12–47). Their structures and absolute configurations were elucidated on the basis of spectroscopic methods and chemical analyses. This is the first report of the absolute configuration of asarinin A (6). The 8-O-4′ neolignans (1–5) were reported in the genus Asarum for the first time. The 15 compounds 17, 19, 22–25, 28, 31, 36, 40, 42, 43, 45–47 were isolated from the genus Asarum, and compounds 16, 32, 33, 37 and 39 were isolated from A. heterotropoides var. mandshuricum for the first time. Thirty-seven of the isolates were evaluated for anti-inflammatory activity against the release of β-glucuronidase in polymorphonuclear leukocytes (PMNs) induced by the platelet-activating factor (PAF), and compounds 1, 4, 7, 8, 14, 17–19, 22, 24, 25, 29, 30, 32, 33, 40–43, 45, and 46 showed potent anti-inflammatory activities in vitro, with 27.9%–72.6% inhibitions at 10-5 mol/L. The results of anti-inflammatory assay suggested that lignans obtained from the CHCl3 extract might be the main active components of Xixin. [ABSTRACT FROM AUTHOR]

Taxifolin is a ubiquitous bioactive constituent of foods and herbs. To thoroughly explore its metabolism in vivo, an HPLC-ESI-IT-TOF-MSn method combined with specific metabolite detection strategy was used to detect and identify the metabolites of taxifolin in rats. Of the 191 metabolites tentatively identified, 154 were new metabolites, 69 were new compounds and 32 were dimers. This is the first report of the in vivo biotransformation of a single compound into more than 100 metabolites. Furthermore, acetylamination and pyroglutamic acid conjugation were identified as new metabolic reactions. Seventeen metabolites were found to have various taxifolin-related bioactivities. The potential targets of taxifolin and 63 metabolites were predicted using PharmMapper, with results showing that more than 60 metabolites have the same five targets. Metabolites with the same fragment pattern may have the same pharmacophore. Thus these metabolites may exert the same pharmacological effects as taxifolin through an additive effect on the same drug targets. This observation indicates that taxifolin is bioactive not only in the parent form, but also through its metabolites. These findings enhance understanding of the metabolism and effective forms of taxifolin and may provide further insight of the beneficial effects of taxifolin and its derivatives. [ABSTRACT FROM AUTHOR]

The grain boundary (GB) is critical to the mechanical properties of NiAl. The addition of B in NiAl can lead to the increase of yield strength due to its segregation in GB. To elucidate the B-induced enhancement of GB, we investigate the segregation state and its strengthening mechanism of the additive B in the typical ∑5(3 1 0)[0 0 1] GB of NiAl at atomic scale using the first-principles method. Our calculations shown that the additive B atom prefers to segregate at the interstitial I 1 site of GB, in which case it is surrounded by four first-nearest-neighboring (1NN) and two second-nearest-neighboring (2NN) Ni atoms. It is found the segregated B prefers to bond with its neighboring Ni instead of Al atoms. Our calculations further shown not only the intergranular cohesion is improved by the covalent bonding between the segregated B and its four 1NN Ni atoms, but also the intra-planar cohesion of GB is enhanced by the covalent bonding between the segregated B and its two 2NN Ni atoms. The covalent bonding between B and Ni atoms mainly stem from the contribution of B- p and Ni- d states, partly from the weak interactions of B- s and Ni- s states. Our first-principles tensile test shown that the yield stress and ductility of NiAl are indeed improved due to the segregation of B in GB. [ABSTRACT FROM AUTHOR]

Extracellular matrix proteins of hard tissues are thought to play a key role in biomineralization, but whether other types of protein-derived biomolecules can promote the formation of mineralized crystals remains to be explored. Recent studies have shown that functional ultrashort peptides, which are less than seven amino acids in length, can partially replace the function of proteins and show unique physiological advantages. In this study, for the first time, we designed ultrashort peptides composed of several acid amino acids (serine and glutamic acid) based on the intrinsically disordered extracellular matrix proteins predicted by AlphaFold2 to explore new ideas for promoting the formation of hydroxyapatite crystals. We synthesized several ultrashort peptides with different amino acid combinations and lengths, such as SE and SESSE to evaluate the correlation between the sequence characteristics and biomineralization ability. The morphological characteristics of the crystals, cell adhesion with ultrashort peptides, and their role in tooth remineralization and bone formation were examined. In conclusion, ultrashort peptides can play an active role in the biomineralization in vivo and in vitro , which provides new insights into novel molecules that induce biomineralization and explores new therapeutic strategies for mineral loss. [Display omitted] • Novel IDR-based strategies were used to identify ultrashort peptide molecules. • S + E combination ultrashort peptide could induce hydroxyapatite mineralization. • Ultrashort peptide SESSE promoted dentin remineralization and bone formation. • Ultrashort peptide had dual mechanisms in biomineralization. [ABSTRACT FROM AUTHOR]

[Display omitted] • FeO was first used as a ferrous source for sulfite (S(IV)) activation. • DFT and electrochemical analyses confirm the little role of interface catalysis. • The Fe(II/III)–S(IV) complex geometry was determined from thermodynamics. • The RSE decreased with the increase of S(IV) concentration. • The FeO/S(IV) process has an advantage over FeO/persulfate and FeO/peroxymonosulfate. In this study, we constructed an advanced oxidation process using FeO for sulfite (S(IV)) activation. By selecting antidepressant fluoxetine (FLX) as the target, the FeO/S(IV) system's performance was investigated. Up to 84.4% of FLX could be rapidly eliminated in 17.5 min under optimal reaction conditions. The results confirmed that the S(IV) activation was dominantly attributed to the released Fe2+ from FeO, rather than an interface reaction, supported by theoretical calculations and electrochemical characterization. Besides, the Fe–S(IV) complex geometry was determined using density functional theory (DFT), indicating a Fe–O–S ligand form. Energy files demonstrate the decomposition of FeSO 3 + complex might be endothermic. These findings provide new insight into the Fe(II)/S(IV) mechanism. The generated SO 4 •− primarily caused FLX removal, where 23 product types were detected. The degradation pathway was proposed, mostly containing hydroxylation and ring-opening, which decreased the toxicity of FLX. Furthermore, the FeO/S(IV) system had good reusability and applicability, maintaining high efficiency in real water. Compared to peroxydisulfate and peroxymonosulfate, S(IV) had obvious advantages in FeO-induced activation. This research discloses a promising technology for the FeO/S(IV) water treatment system. [ABSTRACT FROM AUTHOR]

Ginseng, Panax ginseng C. A. Meyer, is an industrial crop in China and Korea. The functional components in ginseng roots and rhizomes are characteristic ginsenosides. This work developed a new high-performance liquid chromatography coupled with electrospray ionization ion trap time-of-flight multistage mass spectrometry (LC–ESI-IT-TOF-MSn) method to identify the triterpenoids. Sixty compounds (1–60) including 58 triterpenoids were identified from the ginseng cultivated in China. Substances 1, 2, 7, 15–20, 35, 39, 45–47, 49, 55–57, 59, and 60 were identified for the first time. To evaluate the quality of ginseng cultivated in Northeast China, this paper developed a practical liquid chromatography–diode array detection (LC–DAD) method to simultaneously quantify 14 interesting ginsenosides in ginseng collected from 66 different producing areas for the first time. The results showed the quality of ginseng roots and rhizomes from different sources was different due to growing environment, cultivation technology, and so on. The developed LC–ESI-IT-TOF-MSn method can be used to identify many more ginsenosides and the LC–DAD method can be used not only to assess the quality of ginseng, but also to optimize the cultivation conditions for the production of ginsenosides. [ABSTRACT FROM AUTHOR]

Siamenoside I is the sweetest mogroside that has several kinds of bioactivities, and it is also a constituent of Siraitiae Fructus, a fruit and herb in China. Hitherto the metabolism of siamenoside I in human or animals remains unclear. To reveal its metabolic pathways, a high-performance liquid chromatography-electrospray ionization-ion trap-time of flight-multistage mass spectrometry (HPLC-ESI-IT-TOF-MSn) method was used to profile and identify its metabolites in rats. Altogether, 86 new metabolites were identified or tentatively identified, and 23 of them were also new metabolites of mogrosides. In rats, siamenoside I was found to undergo deglycosylation, hydroxylation, dehydrogenation, deoxygenation, isomerization, and glycosylation reactions. Among them, deoxygenation, pentahydroxylation, and didehydrogenation were novel metabolic reactions of mogrosides. The distributions of siamenoside I and its 86 metabolites in rat organs were firstly reported, and they were mainly distributed to intestine, stomach, kidney, and brain. The most widely distributed metabolite was mogroside IIIE. In addition, eight metabolites were bioactive according to literature. These findings would help to understand the metabolism and effective forms of siamenoside I and other mogrosides in vivo. [ABSTRACT FROM AUTHOR]

Background: The human heart consists of several cell types with distinct lineage origins. Interactions between these cardiac progenitors are very important for heart formation. The muscle segment homeobox gene family plays a key role in the cell morphogenesis and growth, controlled cellular proliferation, differentiation, and apoptosis, but the relationships between the genetic abnormalities and CHD phenotypes still remain largely unknown. The aim of this work was to evaluate variations in MSX1 and MSX2 for their possible associations with CHD. Methods: We sequenced the MSX1 and MSX2 genes for 300 Chinese Han CHD patients and 400 normal controls and identified the variations. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 19.0). The Hardy-Weinberg equilibrium test of the population was carried out using the online software OEGE. Results: Six variations rs4647952, rs2048152, rs4242182, rs61739543, rs111542301 and rs3087539 were identified in the MSX2 gene, but the genetic heterozygosity of those SNPs was very low. In contrast, the genetic heterozygosity of two variations rs3821949 near the 5’UTR and rs12532 within 3’UTR of the MSX1 gene was considerably high. Statistical analyses showed that rs3821949 and rs12532 were associated with the risk of CHD (specifically VSD). Conclusions: The SNPs rs3821949 and rs12532 in the MSX1 gene were associated with CHD in Chinese Han populations. [ABSTRACT FROM AUTHOR]

The House of Aisin Gioro is the imperial family of the last dynasty in Chinese history-Qing dynasty (1644-1911). The Aisin Gioro family originated from Jurchen tribes and founded the Manchu people before they conquered China. By investigating the Y chromosomal short tandem repeats (STRs) of seven modern male individuals who claim to belong to the Aisin Gioro family (three of which have full records of pedigree), we found that three of them (two of which having full pedigree, whose most recent common ancestor is Nurgaci) showed very close relationship (1-2 steps of differences in 17 STRs) and possessed a rare haplotype. We therefore conclude that this haplotype is the Y chromosome of the House of Aisin Gioro. Further tests of single-nucleotide polymorphisms indicate that they belong to haplogroup C3b2b1*-M401(xF5483), although their Y-STR results indicate that they are not a part of the 'star cluster' (once linked to Genghis Khan), which belongs to the same haplogroup. This study forms the base for the pedigree research of the imperial family of Qing dynasty by means of genetics. [ABSTRACT FROM AUTHOR]

Seven new diterpenes, named ovoideal A (1), B (2), C (3), D (4), E (5), F (6) and G (7), have been isolated along with eleven known diterpenes 8-18 from the petroleum ether soluble fraction of an ethanol extract of the aerial parts of Tirpitzia ovoidea. The structures of the new compounds were elucidated primarily by 1D and 2D NMR spectroscopy, as well as by the HR-ESI-MS spectrometry. All compounds were isolated from the Linaceae family for the first time. The in vitro cytotoxic activity of compounds 1, 3-5, 8-18 was evaluated against the Hela, HepG2 and K562 cell lines. Among them, compounds 3, 9, 11, 12, 13, 14, 15, 17, 18 showed moderate inhibitory activities. [ABSTRACT FROM AUTHOR]

Thirty-three Phylostachys edulis germplasms from 11 provenances in Guangxi were analyzed by AFLP markers Five pairs of primer combination were used to amplify the genomic DNA. A total of 198 AFLP bands were obtained, 47 (23.74%) of them were polymorphic The genetic distance between the 11 provenance ranged from 0.006 to 0.136 9. The tested gemplasms can be divided into 4 categories by UPGMA cl ustering analysis Nandan and Zhaoping provenances were clustered into two categories respectively They were distinct to other two categories PCA analysis results were consistent with the results of cluster analysis Mantel test results showed that the corela tions between genetic distance and geographic distance in P. edulis provenance sources were significant (r = 0.555 8, P = 0.555 8), and AFLP was an effective marker to identify germplasm of P. edulis. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cu 2 (OH) 2 CO 3 was firstly used to activate sulfite as a new advanced oxidation process. • Sulfite is synergistically activated by homogeneous and heterogeneous approaches. • SO 4 − and SO 5 − are mainly responsible for the oxidation of As(III) to As(V). • DFT calculations were performed to help understand the activation mechanism. • The toxicity of the Cu 2 (OH) 2 CO 3 /sulfite system decreased as the reaction proceeded. Arsenic is categorized as a class I carcinogen due to its strong biological toxicity. In this study, a novel treatment process with Cu 2 (OH) 2 CO 3 as catalyst is proposed, whereby As(III) in water is oxidized by activating sulfite to generate SO 4 − and SO 5 − radicals. Under conditions of [Cu 2 (OH) 2 CO 3 ] 0 = 0.01 g·L−1, [sulfite] 0 = 0.3 mmol·L−1, and initial pH 8.0, 94% of As(III) was converted into As(V) within 20 min, whereby dissolved oxygen had a pivotal impact on the reaction. However, HCO 3 −, humic acid, and fulvic acid all significantly inhibited the oxidation. Heterogeneous electron transfer on the catalyst surface and homogeneous dissolved Cu2+ jointly activated sulfite in the Cu 2 (OH) 2 CO 3 /sulfite system, with the heterogeneous process predominating. Density functional theory (DFT) calculations disclose a dominate physical adsorption of sulfite on Cu 2 (OH) 2 CO 3 surface with 1.74 electrons transferred. >90% of As(III) was still oxidized after recycling the material five times, indicating excellent reusability. Overall, it shows good potential for application in the removal of As(III) from real water samples. [ABSTRACT FROM AUTHOR]

Glomerular matrix accumulation is a hallmark of diabetic renal disease. Serine/threonine kinase PKC-β1 mediates glucose-induced Akt S473 phosphorylation, RhoA activation, and transforming growth factor (TGF)-β1 upregulation and finally leads to matrix upregulation in mesangial cells (MCs). It has been reported that glucose-induced PKC-β1 activation is dependent on caveolin-1 and the presence of intact caveolae in MCs; however, whether activated PKC-β1 regulates caveolin-1 expression and phosphorylation are unknown. Here, we showed that, although the caveolin-1 protein level had no significant change, the PKC-β-specific inhibitor LY-333531 blocked caveolin-1 Y14 phosphorylation in high glucose (HG)-treated MCs and in the renal cortex of diabetic rats. The Src-specific inhibitor SU-6656 prevented the HG-induced association between PKC-β1 and caveolin-1 and PKC-β1 membrane translocation, whereas PKC-β1 small interfering RNA failed to block Src activation, indicating that Src kinase is upstream of PKC-β1 activation. Although LY-333531 blocked PKC-β1 membrane translocation, it had no effect on the PKC-β1/caveolin-1 association, suggesting that PKC-β1 activation requires the interaction of caveolin-1 and PKC-β1. PKC-β1-mediated Akt S473 phosphorylation, RhoA activation, and fibronectin upregulation in response to HG were prevented by SU-6656 and nonphosphorylatable mutant caveolin-1 Y14A. In conclusion, Src activation by HG mediates the PKC-β1/caveolin-1 association and PKC-β1 activation, which assists in caveolin-1 Y14 phosphorylation by Src kinase. The downstream effects, including Akt S473 phosphorylation, RhoA activation, and fibronectin upregulation, require caveolin-1 Y14 phosphorylation. Caveolin-1 is thus an important mediator of the profibrogenic process in diabetic renal disease. [ABSTRACT FROM AUTHOR]

The aim of the present study was to explore the feasibility of enhancing green fluorescent protein (EGFP) gene transfection into the synovial joint tissues of rats with rheumatoid arthritis (RA) by ultrasound-mediated micro-bubble destruction. An optimal SonoVue dose was determined using 40 normal rats categorized into five groups according to the various doses of microbubbles used. At 1 week after ultrasound irradiation, the rats were sacrificed. Damage to the joint synovial tissues was observed with hematoxylin and eosin histopathological staining under a microscope. A further 44 normal rats were used to establish a rat model of RA, and were then categorized into four groups: EGFP, ultrasound + EGFP, microbubbles + EGFP and ultrasound + microbubbles + EGFP. The last group was irradiated with ultrasound for 10 min following the injection of 300 μl SonoVue and 10 μg EGFP into the joint cavity. Rats were sacrificed after 3 days and synovial tissue was collected from the knee joints for observation of EGFP with fluorescence microscopy and analysis by quantitative polymerase chain reaction. EGFP expression was observed in the synovial tissues of all groups. However, high EGFP expression levels were observed in the ultrasound + microbubbles + EGFP group. No statistically significant differences (P>0.05) were observed in the EGFP expression levels between the EGFP, ultrasound + EGFP and microbubbles + EGFP groups. However, EGFP expression levels in the EGFP, ultrasound + EGFP and microbubbles + EGFP groups significantly differed (P<0.05) from that in the ultrasound + microbubbles + EGFP group. Therefore, ultrasound-mediated microbubble destruction improved EGFP transfection efficiency into the joint synovial tissues of rats with RA. [ABSTRACT FROM AUTHOR]

Abstract: The biomedical applications of current self-healing materials are largely impeded by their healing conditions, which usually require heating, UV exposure or harsh pH environments. At the same time, for very few existing spontaneously self-healing materials, healing can only be achieved immediately after rupture occurs. Here, we developed a spontaneously healing material, driven by a new mechanism, “zwitterionic fusion”, which is repairable independent of time after damage under physiological conditions. We also tested the anti-fatigue property of this zwitterionic hydrogel. Furthermore, we utilized this zwitterionic fusion to link different cell-hydrogel constructs together. [Copyright &y& Elsevier]

Connexin 30 (Cx30), a member of the large gap-junction protein family, plays a role in the homeostasis of the epidermis and inner ear through gap junctional intercellular communication (GJIC). Here, we investigate the underlying mechanisms of four autosomal dominant Cx30 gene mutations that are linked to hearing loss and/or various skin diseases. First, the T5M mutant linked to non-syndromic hearing loss formed functional gap junction channels and hemichannels, similar to wild-type Cx30. The loss-of-function V37E mutant associated with Clouston syndrome or keratitis-ichthyosis-deafness syndrome was retained in the endoplasmic reticulum and significantly induced apoptosis. The G59R mutant linked to the Vohwinkel and Bart-Pumphrey syndromes was retained primarily in the Golgi apparatus and exhibited loss of gap junction channel and hemichannel function but did not cause cell death. Lastly, the A88V mutant, which is linked to the development of Clouston syndrome, also significantly induced apoptosis but through an endoplasmic-reticulum-independent mechanism. Collectively, we discovered that four unique Cx30 mutants might cause disease through different mechanisms that also likely include their selective trans-dominant effects on coexpressed connexins, highlighting the overall complexity of connexin-linked diseases and the importance of GJIC in disease prevention. [ABSTRACT FROM AUTHOR]

Traditional Chinese Medicine (TCM) nasal therapy has been utilized to treat numerous diseases for over two millennia. It has many advantages compared with other routes. In this article, headspace-solid phase microextraction-gas chromatography-mass spectrometry and high performance liquid chromatography-atmospheric pressure chemical ionization-ion trap-time of flight-multistage mass spectrometry were applied for the first time to analyze the absorbed constituents in rabbit plasma and cerebrospinal fluid (CSF) after intranasal administration of Asari Radix et Rhizoma (AR). In total, 47 absorbed AR constituents including 14 monoterpenes, 10 phenylpropanoids, four benzene derivatives, two alkanes, nine N-alkylamides and eight lignans were tentatively identified in the rabbit plasma and CSF. Thirty-three absorbed constituents are found to have different bioactivities related to the pharmacological actions of AR through bibliography data retrieval. These indicated that many types of constituents of TCM can be absorbed at the nasal cavity into both rabbit blood and CSF. This is the first study to explore the absorption of AR, and comprehensively analyze the absorbed constituents after intranasal administration of TCM. These findings extend our understanding of the effective substances of AR, and inspire us to make a hypothesis on the mechanism of additive effect of multiple constituents of TCMs, which is very worthy of further investigation. [ABSTRACT FROM AUTHOR]

Ginsenoside Rb1 (RB1), the most clinically effective constituent of ginseng, possesses a variety of biological activities. The objectives of this study were to investigate the protective effects of RB1 and its underlying mechanism on renal injury induced by intestinal ischemia-reperfusion (IIR) in mice. RB1 was administered prior to inducing IIR achieved by occluding the superior mesenteric artery for 45 min followed by 120 min of reperfusion. All-trans-retinoic acid (ATRA) was used as an inhibitor of NF-E2-related factor-2 (Nrf2) signaling. Adult male C57BL/6J mice were randomly divided into six groups: (1) sham group, (2) IIR group, (3) RB1 group, (4) sham + ATRA group, (5) IIR + ATRA group, and (6) RB1 + ATRA group. Intestinal histology and pathological injury score were observed. Intestinal mucosal injury was also evaluated by measuring serum diamine oxidase (DAO). Renal injury induced by IIR was characterized by increased levels of histological severity score, blood urea nitrogen (BUN), serum creatinine (Scr) and neutrophil gelatinase-associated lipocalin (NGAL), which was accompanied with elevated renal TUNEL-positive cells and the Bcl-2/Bax expression ratio. RB1 significantly reduced renal injury and apoptosis as compared with IIR group, which was reversed by ATRA treatment. Immunohistochemistry and Western blot analysis demonstrated that RB1 significantly upregulated the protein expression of heme oxygenase-1 (HO-1) and Nrf2, which were attenuated by ATRA treatment. Taken together, these results suggest that the protective effects of RB1 pretreatment against renal injury induced by IIR are associated with activation of the Nrf2/ anti-oxidant response element (ARE) pathway. [ABSTRACT FROM AUTHOR]

Chargedamino acids are the most common on surfaces of proteinsand understanding the interactions between these charged amino acids,salt bridging, is crucial for understanding protein–proteininteractions. Previous simulations have been limited to implicit solventor fixed binding geometry due to the sampling required for convergedfree energies. Using well-tempered metadynamics, we have calculatedsalt bridge free energy surfaces in water and confirmed the resultswith NMR experiments. The simulations give binding free energies,quantitative ranking of salt bridging strength, and insights intothe hydration of the salt bridges. The arginine–aspartate saltbridge was found to be the weakest and arginine-glutamate the strongest,showing that arginine can discriminate between aspartate and glutamate,whereas the salt bridges with lysine are indistinguishable in theirfree energy. The salt bridging hydration is found to be complementaryto salt bridge orientation with arginine having specific orientations. [ABSTRACT FROM AUTHOR]

Six new phenolic compounds, named smiglabrone A (1), smiglabrone B (2), smilachromanone (3), smiglastilbene (4), smiglactone (5), smiglabrol (6), together with fifty-seven known ones 7-63 were isolated from the rhizomes of Smilax glabra. Their structures were elucidated on the basis of extensive spectroscopic analyses, as well as by comparison with literature data. Twenty-seven of these compounds were obtained from and identified in the genus Smilax for the first time. The absolute configuration of (2S)-1,2-Odi- trans-p-coumaroylglycerol (43) was determined for the first time using the excitoncoupled circular dichroism (ECCD) method. Thirty isolated compounds were evaluated for their antimicrobial activity against three Gram-negative bacteria, three Gram-positive bacteria and one fungus, and the corresponding structure-activity relationships were also discussed. Eighteen compounds were found to be antimicrobial against the microorganisms tested and the minimum inhibitory concentrations (MIC) were in the range of 0.0794-3.09 mM. Among them, compound 1 showed antimicrobial activity against Canidia albicans with MIC value of 0.146 mM, which was stronger than cinchonain Ia with an MIC of 0.332 mM. Compounds 3 and 4 exhibited inhibitory activity against Staphylococcus aureus with MIC values of 0.303 and 0.205 mM, respectively. The results indicated that these antimicrobial constituents of this crude drug might be responsible for its clinical antimicrobial effect. [ABSTRACT FROM AUTHOR]

Nine standard coal samples from different coalbeds of Zhongliangshan southern coal mine in Huayingshan coalfield were tested using the low-temperature nitrogen adsorption method to study the fractal characteristics of adsorption pores (pore diameter <100 nanometers) and the relationship between fractal dimension and the gas adsorption capacity of tectonic coal. The results of both the low-temperature nitrogen adsorption and desorption show that different deformed coal has different adsorption characteristics under relative pressures between 0.5-1.0. Based on the results, the fractal dimension D of tectonic coal was studied using the fractal Frenkel-Halsey-Hill (FHH) method. The results demonstrate that the fractal dimension D can represent the variation characteristics of pore structure and pore surface area of tectonic coal. The higher fractal dimension D, the more micropores, the more irregular specific coal surface, and the higher heterogeneity of pore structure. The gas storage capacity of coal can be represented by the fractal dimension D, and the gas adsorption capacity of coal increases with the increasing of fractal dimension D. Therefore, the higher fractal dimension and the more homogeneous pore structure resulting from strong tectonic deformation, indicate that the coal has a higher gas adsorption capacity. [ABSTRACT FROM AUTHOR]

It has been suggested that the mitochondrial chimeric gene orfH79 is the cause for abortion of microspores in Honglian cytoplasmic male sterile rice, yet little is known regarding its mechanism of action. In this study, we used a mass spectrometry- based quantitative proteomics strategy to compare the mitochondrial proteome between the sterile line Yuetai A and its fertile near-isogenic line Yuetai B. We discovered a reduced quantity of specific proteins in mitochondrial complexes in Yuetai A compared with Yuetai B, indicating a defect in mitochondrial complex assembly in the sterile line. Western blotting showed that ORFH79 protein and ATP1 protein, an F1 sector component of complex V, are both associated with large protein complexes of similar size. Respiratory complex activity assays and transmission electron microscopy revealed functional and morphological defects in the mitochondria of Yuetai A when compared with Yuetai B. In addition, we identified one sex determination TASSELSEED2-like protein increased in Yuetai A, leading to the discovery of an aberrant variation of the jasmonic acid pathway during the development of microspores. [ABSTRACT FROM AUTHOR]

Electrostatic interactions play an important role insetting theaqueous two-phase separation behaviors of mixtures of oppositely chargedsurfactants. The aqueous mixture of cetyltrimethylammonium bromide(CTAB) and sodium dodecylsulfonate (AS) is actually a five-componentsystem, comprised of CTAB, AS, complex salt (cetyltrimethylammoniumdodecylsulfonate, abbreviated as CTA–), NaBr, and water. In the three-dimensional pyramid phase diagram,the aqueous two-phase region with excess AS or with excess CTAB extendssuccessively from the region very near to the NaBr–H2O line through the CTAB–AS–H2O conventionalmixing plane to the CTA––AS–H2O side plane or to the CTA––CTAB–H2O side plane, respectively. Largeor small molar ratios between the counterions and their correspondingsurfactant ions for oppositely charged surfactants located in theNaBr side or the CTA–side of thepyramid imply strong or weak electrostatic screening. Electrostaticscreening of counterions alters the electrostatic attractions betweenthe oppositely charged head groups or the electrostatic repulsionsbetween the like-charged head groups in excess, and the electrostaticfree energy of aggregation thus affects the aqueous two-phase separationmodes. Composition analysis, rheological property investigation, andTEM images suggest that there are two kinds of aqueous two-phase systems(ATPSs). On the basis of these experimental results and Kaler’scell model, two kinds of phase separation modes were proposed. Experimentalresults also indicate that all of the top phases are surfactant-rich,and all of the bottom phases are surfactant-poor; the density differencebetween the top phase and the bottom phase in one ATPS is very small;the interfacial tension (σ) of the ATPS is ultralow. [ABSTRACT FROM AUTHOR]

Background. Aristolochic acid nephropathy (AAN) is a worldwide problem and one of the common causes of chronic kidney disease (CKD) in China. Methods. Three hundred patients diagnosed as AAN from 1997 to 2006 were enrolled. Medical histories of Chinese herb ingestion, clinical–pathological features and risk factors for renal failure were recorded. Patients were followed up for 2–156 months. Factors involved in the prognosis of AAN were investigated. Results. The 300 patients with AAN manifested three clinical subtypes, including acute kidney injury (acute AAN) in 13 patients, abrupt tubular dysfunction with normal serum creatinine (Scr) levels in seven cases and chronic tubulointerstitial nephropathy with decreased estimated glomerular filtration rate (eGFR) (chronic AAN) in 280 cases. The acute AAN cases had the highest aristolochic acid (AA)-I intake per day and developed progressive kidney failure during 1–7 years follow-up. The tubular dysfunction AAN patients had the lowest cumulative AA-I intake and were able to keep normal Scr levels during 2–8 years follow-up. The chronic AAN patients took the lowest AA-I dose per day but with the longest period and the highest cumulative dosage and exhibited a very large range of eGFR changing rate (from −21.6 to 5.2, median −3.5 mL/min/year). The cumulative AA-I intake (r = 0.330, P = 0.045) and the time course from the termination of AA medication to the start of follow-up (r = −0.430, P = 0.009) were found to be independent factors correlated with the decrease rate of eGFR in the chronic AAN patients. AA and the metabolites could be detected in a high frequency in patients who had stopped herbal medication for 1 year, which indicates a rather long washout time for these chemicals. Conclusions. AAN has variant phenotypes with distinct prognosis, which is determined by the variable AA medications. With better understanding of toxic and environmental causes for kidney injury, there would be a better chance to uncover the causal factors of cases of ‘CKD without known causes’ which is crucial for improving the disease outcomes. [ABSTRACT FROM PUBLISHER]

Progestin supplementation appears to be a promising approach to both preventing initiation of preterm labor and treating it once it is already established, given the role of progesterone in maintaining pregnancy, as well as support from basic and clinical research. Progesterone and 17α-hydroxyprogesterone acetate slow the process of cervical ripening, and this is the rationale for prophylactic long-term progestin supplementation mostly studied so far. However, progesterone (but not 17α-hydroxyprogesterone acetate) also inhibits myometrial activity even after the cervix has already ripened. Moreover, these effects depend greatly on the vehicle used and the route of administration. Understanding different mechanisms of action, as well as the importance of progestin formulation, vehicle and route of administration, is the key to finding the optimal progestin treatment for prevention of preterm birth. [ABSTRACT FROM AUTHOR]

Current methodologies to assess the process of labor, such as tocodynamometry or intrauterine pressure catheters, fetal fibronectin, cervical length measurement and digital cervical examination, have several major drawbacks. They only measure the onset of labor indirectly and do not detect cellular changes characteristic of true labor. Consequently, their predictive values for term or preterm delivery are poor. Uterine contractions are a result of the electrical activity within the myometrium. Measurement of uterine electromyography (EMG) has been shown to detect contractions as accurately as the currently used methods. In addition, changes in cell excitability and coupling required for effective contractions that lead to delivery are reflected in changes of several EMG parameters. Use of uterine EMG can help to identify patients in true labor better than any other method presently employed in the clinic. [ABSTRACT FROM AUTHOR]

Abstract: Marfan syndrome (MFS) is an autosomal dominant condition with pleiotropic manifestations involving the skeletal, ocular, and cardiovascular systems. The diagnosis is based primarily on clinical involvement of these and other systems, referred to as the Ghent criteria. We have identified three Hispanic families from Mexico with cardiovascular and ocular manifestations due to novel FBN1 mutations but with paucity of skeletal features. The largest family, hMFS001, had a frameshift mutation in exon 24 (3075delC) identified as the cause of aortic disease in the family. Assessment of eight affected adults revealed no major skeletal manifestation of MFS. Family hMFS002 had a missense mutation (R1530C) in exon 37. Four members fulfilled the criteria for ocular and cardiovascular phenotype but lacked skeletal manifestations. Family hMFS003 had two consecutive missense FBN1 mutations (C515W and R516G) in exon 12. Eight members fulfilled the ocular criteria for MFS and two members had major cardiovascular manifestations, however none of them met criteria for skeletal system. These data suggest that individuals of Hispanic descent with FBN1 mutations may not manifest skeletal features of the MFS to the same extent as Caucasians. We recommend that echocardiogram, ocular examination and FBN1 molecular testing be considered for any patients with possible MFS even in the absence of skeletal features, including Hispanic patients. [Copyright &y& Elsevier]

Background: The effects of enterolignans, e.g., enterodiol (END) and particularly its oxidation product, enterolactone (ENL), on prevention of hormone-dependent diseases, such as osteoporosis, cardiovascular diseases, hyperlipemia, breast cancer, colon cancer, prostate cancer and menopausal syndrome, have attracted much attention. To date, the main way to obtain END and ENL is chemical synthesis, which is expensive and inevitably leads to environmental pollution. To explore a more economic and eco-friendly production method, we explored biotransformation of enterolignans from precursors contained in defatted flaxseeds by human intestinal bacteria. Results: We cultured fecal specimens from healthy young adults in media containing defatted flaxseeds and detected END from the culture supernatant. Following selection through successive subcultures of the fecal microbiota with defatted flaxseeds as the only carbon source, we obtained a bacterial consortium, designated as END-49, which contained the smallest number of bacterial types still capable of metabolizing defatted flaxseeds to produce END. Based on analysis with pulsed field gel electrophoresis, END-49 was found to consist of five genomically distinct bacterial lineages, designated Group I-V, with Group I strains dominating the culture. None of the individual Group I-V strains produced END, demonstrating that the biotransformation of substrates in defatted flaxseeds into END is a joint work by different members of the END-49 bacterial consortium. Interestingly, Group I strains produced secoisolariciresinol, an important intermediate of END production; 16S rRNA analysis of one Group I strain established its close relatedness with Klebsiella. Genomic analysis is under way to identify all members in END-49 involved in the biotransformation and the actual pathway leading to END-production. Conclusion: Biotransformation is a very economic, efficient and environmentally friendly way of mass-producing enterodiol from defatted flaxseeds. [ABSTRACT FROM AUTHOR]

Abstract: The effect of large range Be addition (0–20.83at.% Be) on the lattice distortion as well as dislocation mobility in TiAl was examined by density functional theory (DFT) calculations. The calculation of the formation energy showed that Be obviously decreases the phase stability. The shearing energy barrier of the TiAl alloys with Be solute is weakened by stages during the static shear deformation process. Further analysis of the partial density of states reveals that the physical origin is closely related with the content and atomic configuration of Be. The weakening effect of shearing energy barrier at the first stage occurs because of the decrement in the phase stability, which is induced by low Be addition related long-range alloying effect. The notable weakening effect at the second stage originates from the reduced p–d and enhanced p–p bonding, which is induced by large Be addition related short-range alloying interaction. [Copyright &y& Elsevier]