Effect of Linkage Bond between Backbone and Side Chain in Comb-Like Copolymer Dispersants on Early Properties of Concentrated Cement Suspensions

AbstractComb-like copolymer, consists of backbone with ionizable group and charge neutral poly(ethylene oxide)-based “teeth” side chain grafted onto the backbone at frequent intervals, has been widely used as superplasticizer in concrete industry due to its unique properties compared to traditional polyelectrolyte dispersants, such as lower dosages, outstanding water reduction, excellent workability retention and lower shrinkage. It is easy to modify and adapt this molecular structure in order to maximize the targeted properties and also meet specific properties for different applications. However, modification attempts usually focused on the side-chain length and charge density. In fact, the linkage bond between backbone and side chain has greatly influence on the early behavior of cement suspensions due to copolymers with different linkage bond have different structure stability under the strong basic environment. In this study, two comb-like copolymer dispersants with different linkage group (ester and ether) were produced. The effects of the type of linkage bond in comb-like copolymers on the adsorption characteristics and hydration behavior of concentrated cement suspensions, were investigated by means of Total organic carbon analyzer(TOC),DSC-TG and calorimetric device and Environmental Scanning Electron Microscope(ESEM). Test results showed that the comb-like copolymer with ester linkage bond, has lower initial adsorbed amount, and thus not only accelerate the hydration rate, but also change its crystal shape of hydrated cement. This will help in the understanding of the structure-property relationship of comb-like copolymer and in the designing the molecular structure of new functional superplasticizer

Arctigenin-induced reversal of drug resistance in cisplastin-resistant cell line A549/DDP, and the mechanism involved

Purpose: To investigate the drug resistance reversal effect of arctigenin (ARG) on cisplatin-insensitive A549/DDP cancer cells, and to elucidate the underlying mechanism(s). Methods: Four groups of cells: control, DDP, ARG and ADP were used. The degrees of inhibition of proliferation, drug resistance and apoptotic changes were measured using MTT assay, CCK-8 assay and flow cytometry, respectively. Expressions of PTEN and STAT3 proteins were determined by Western blotting. Results: At ARG concentration of 5 μmol/L, A549/DDP cells were significantly inhibited (p < 0.05). The combination therapy was more effective in reversing A549/DDP cells resistance than the single therapy. The expression level of PTEN protein increased with increase in ARG concentration, while STAT3 protein expression decreased with increase in ARG concentration. ADP group up-regulated PTEN but decreased STAT3 expression levels. Conclusion: ARG regulates drug resistance in A549/DDP cells, possibly via a mechanism involving reduction of A549/DDP cell sensitivity to DDP, thereby regulating the stress pathways associated with PTEN and STAT3. The combination of ARG and DDP effectively reduces A549/DDP cells resistance

Affinity of Tau antibodies for solubilized pathological Tau species but not their immunogen or insoluble Tau aggregates predicts in vivo and ex vivo efficacy

BACKGROUND: A few tau immunotherapies are now in clinical trials with several more likely to be initiated in the near future. A priori, it can be anticipated that an antibody which broadly recognizes various pathological tau aggregates with high affinity would have the ideal therapeutic properties. Tau antibodies 4E6 and 6B2, raised against the same epitope region but of varying specificity and affinity, were tested for acutely improving cognition and reducing tau pathology in transgenic tauopathy mice and neuronal cultures. RESULTS: Surprisingly, we here show that one antibody, 4E6, which has low affinity for most forms of tau acutely improved cognition and reduced soluble phospho-tau, whereas another antibody, 6B2, which has high affinity for various tau species was ineffective. Concurrently, we confirmed and clarified these efficacy differences in an ex vivo model of tauopathy. Alzheimer’s paired helical filaments (PHF) were toxic to the neurons and increased tau levels in remaining neurons. Both toxicity and tau seeding were prevented by 4E6 but not by 6B2. Furthermore, 4E6 reduced PHF spreading between neurons. Interestingly, 4E6’s efficacy relates to its high affinity binding to solubilized PHF, whereas the ineffective 6B2 binds mainly to aggregated PHF. Blocking 4E6's uptake into neurons prevented its protective effects if the antibody was administered after PHF had been internalized. When 4E6 and PHF were administered at the same time, the antibody was protective extracellularly. CONCLUSIONS: Overall, these findings indicate that high antibody affinity for solubilized PHF predicts efficacy, and that acute antibody-mediated improvement in cognition relates to clearance of soluble phospho-tau. Importantly, both intra- and extracellular clearance pathways are in play. Together, these results have major implications for understanding the pathogenesis of tauopathies and for development of immunotherapies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13024-016-0126-z) contains supplementary material, which is available to authorized users

Toward Building a Physical Proxy for Gas-Phase Sulfuric Acid Concentration Based on Its Budget Analysis in Polluted Yangtze River Delta, East China

Gaseous sulfuric acid (H2SO4) is a crucial precursor for secondary aerosol formation, particularly for new particle formation (NPF) that plays an essential role in the global number budget of aerosol particles and cloud condensation nuclei. Due to technology challenges, global-wide and long-term measurements of gaseous H2SO4 are currently very challenging. Empirical proxies for H2SO4 have been derived mainly based on short-term intensive campaigns. In this work, we performed comprehensive measurements of H2SO4 and related parameters in the polluted Yangtze River Delta in East China during four seasons and developed a physical proxy based on the budget analysis of gaseous H2SO4. Besides the photo-oxidation of SO2, we found that primary emissions can contribute considerably, particularly at night. Dry deposition has the potential to be a non-negligible sink, in addition to condensation onto particle surfaces. Compared with the empirical proxies, the newly developed physical proxy demonstrates extraordinary stability in all the seasons and has the potential to be widely used to improve the understanding of global NPF fundamentally.Peer reviewe

Development, validation, and evaluation of a risk assessment tool for personalized screening of gastric cancer in Chinese populations

Background Effective risk prediction models are lacking for personalized endoscopic screening of gastric cancer (GC). We aimed to develop, validate, and evaluate a questionnaire-based GC risk assessment tool for risk prediction and stratification in the Chinese population. Methods In this three-stage multicenter study, we first selected eligible variables by Cox regression models and constructed a GC risk score (GCRS) based on regression coefficients in 416,343 subjects (aged 40–75 years) from the China Kadoorie Biobank (CKB, development cohort). In the same age range, we validated the GCRS effectiveness in 13,982 subjects from another independent Changzhou cohort (validation cohort) as well as in 5348 subjects from an endoscopy screening program in Yangzhou. Finally, we categorized participants into low (bottom 20%), intermediate (20–80%), and high risk (top 20%) groups by the GCRS distribution in the development cohort. Results The GCRS using 11 questionnaire-based variables demonstrated a Harrell’s C-index of 0.754 (95% CI, 0.745–0.762) and 0.736 (95% CI, 0.710–0.761) in the two cohorts, respectively. In the validation cohort, the 10-year risk was 0.34%, 1.05%, and 4.32% for individuals with a low (≤ 13.6), intermediate (13.7~30.6), and high (≥ 30.7) GCRS, respectively. In the endoscopic screening program, the detection rate of GC varied from 0.00% in low-GCRS individuals, 0.27% with intermediate GCRS, to 2.59% with high GCRS. A proportion of 81.6% of all GC cases was identified from the high-GCRS group, which represented 28.9% of all the screened participants. Conclusions The GCRS can be an effective risk assessment tool for tailored endoscopic screening of GC in China. Risk Evaluation for Stomach Cancer by Yourself (RESCUE), an online tool was developed to aid the use of GCRS

Time to full enteral feeding for very low-birth-weight infants varies markedly among hospitals worldwide but may not be associated with incidence of necrotizing enterocolitis:The NEOMUNE-NeoNutriNet Cohort Study

Background: Transition to enteral feeding is difficult for very low-birth-weight (VLBW; ≤1500 g) infants, and optimal nutrition is important for clinical outcomes. Method: Data on feeding practices and short-term clinical outcomes (growth, necrotizing enterocolitis [NEC], mortality) in VLBW infants were collected from 13 neonatal intensive care units (NICUs) in 5 continents (n = 2947). Specifically, 5 NICUs in Guangdong province in China (GD), mainly using formula feeding and slow feeding advancement (n = 1366), were compared with the remaining NICUs (non-GD, n = 1581, Oceania, Europe, United States, Taiwan, Africa) using mainly human milk with faster advancement rates. Results: Across NICUs, large differences were observed for time to reach full enteral feeding (TFF; 8–33 days), weight gain (5.0–14.6 g/kg/day), ∆z-scores (−0.54 to −1.64), incidence of NEC (1%–13%), and mortality (1%–18%). Adjusted for gestational age, GD units had longer TFF (26 vs 11 days), lower weight gain (8.7 vs 10.9 g/kg/day), and more days on antibiotics (17 vs 11 days; all P <.001) than non-GD units, but NEC incidence and mortality were similar. Conclusion: Feeding practices for VLBW infants vary markedly around the world. Use of formula and long TFF in South China was associated with more use of antibiotics and slower weight gain, but apparently not with more NEC or higher mortality. Both infant- and hospital-related factors influence feeding practices for preterm infants. Multicenter, randomized controlled trials are required to identify the optimal feeding strategy during the first weeks of life

Ultrasensitive electrocatalytic detection of COX-2 rs20417: relying on 3D interconnected architecture of Pt-LSSUs@PAA nanostructures for sensor interface modification

Mutated COX-2 has become the new molecular marker of aspirin resistance. However, there is still a technical ‘bottleneck’ for direct and sensitive detection of circulating COX-2 mutant gene. In this work, we reported a simple and ultrasensitive electrochemical method for COX-2–765G/C (rs20417) detection for the first time. Polyallylamine (PAA) functionalised Pt nanostructures with long-spined sea urchin-like morphology (Pt-LSSUs@PAA) was synthesised by a simple chemical method for the construction of nano-sensing interface. Ru(NH3)63+ is used as a primary electron acceptor that is electrostatically attracted to peptide nucleic acid modified electrodes and Fe(CN)63− is introduced into the redox system as secondary electron acceptor to regenerate Ru3+ after electrochemical reduction for multiple redox cycles. Different pulse voltammetry was applied to record the electrochemical signals. Under optimal conditions, the DNA sensors showed a wide linear relationship, from 10 fM to 1 nM, with detection limits of 3.3 fM (S/N = 3). This study will provide the basis for the precise use of aspirin, and it has important guiding value for individual drug testing of cardiovascular disease

Dynamic assessment of tau immunotherapies in the brains of live animals by two-photon imagingResearch in context

Our original findings, showing the effectiveness of active and passive tau immunizations in mouse models, have now been confirmed and extended by many groups, with several clinical trials underway in Alzheimer's disease and progressive supranuclear palsy. Here, we report on a unique and sensitive two-photon imaging approach to concurrently study the dynamics of brain and neuronal uptake and clearance of tau antibodies as well as the acute removal of their pathological target in live animals. This in vivo technique is more sensitive to detect clearance of pathological tau protein than western blot tau analysis of brain tissue. In addition to providing an insight into the mechanisms involved, it allows for an efficient in vivo assessment of the therapeutic potential of tau antibodies, and may be applied to related protein misfolding diseases. Keywords: Tau protein, Alzheimer's disease, Tauopathy, Antibody, Immunotherapy, Two-photon imagin