A brief exposure to systemic hypoxia (i.e., hypoxic preconditioning; HPC) prior to transient middle cerebral artery occlusion (tMCAo) reduces infarct volume, blood-brain barrier disruption, and ...leukocyte migration. CCL2 (MCP-1), typically regarded as a leukocyte-derived pro-inflammatory chemokine, can also be directly upregulated by hypoxia-induced transcription. We hypothesized that such a hypoxia-induced upregulation of CCL2 is required for HPC-induced ischemic tolerance.
Adult male SW/ND4, CCL2-null, and wild-type mice were used in these studies. Cortical CCL2/CCR2 message, protein, and cell-type specific immunoreactivity were determined following HPC (4 h, 8% O2) or room air control (21% O2) from 6 h through 2 weeks following HPC. Circulating leukocyte subsets were determined by multi-parameter flow cytometry in naïve mice and 12 h after HPC. CCL2-null and wild-type mice were exposed to HPC 2 days prior to tMCAo, with immunoneutralization of CCL2 during HPC achieved by a monoclonal CCL2 antibody.
Cortical CCL2 mRNA and protein expression peaked at 12 h after HPC (both p < 0.01), predominantly in cortical neurons, and returned to baseline by 2 days. A delayed cerebral endothelial CCL2 message expression (p < 0.05) occurred 2 days after HPC. The levels of circulating monocytes (p < 0.0001), T lymphocytes (p < 0.0001), and granulocytes were decreased 12 h after HPC, and those of B lymphocytes were increased (p < 0.0001), but the magnitude of these respective changes did not differ between wild-type and CCL2-null mice. HPC did decrease the number of circulating CCR2+ monocytes (p < 0.0001) in a CCL2-dependent manner, but immunohistochemical analyses at this 12 h timepoint indicated that this leukocyte subpopulation did not move into the CNS. While HPC reduced infarct volumes by 27% (p < 0.01) in wild-type mice, CCL2-null mice subjected to tMCAo were not protected by HPC. Moreover, administration of a CCL2 immunoneutralizing antibody prior to HPC completely blocked (p < 0.0001 vs. HPC-treated mice) the development of ischemic tolerance.
The early expression of CCL2 in neurons, the delayed expression of CCL2 in cerebral endothelial cells, and CCL2-mediated actions on circulating CCR2+ monocytes, appear to be required to establish ischemic tolerance to focal stroke in response to HPC, and thus represent a novel role for this chemokine in endogenous neurovascular protection.
To assess changes in the quality of primary care in two megacities following the introduction of health system reforms in China.
We conducted multistage stratified random face-to-face surveys of ...patients visiting community health centres in Shanghai in 2011 and 2013, and Shenzhen in 2012 and 2013. Quality of primary care was measured using an assessment tool. Difference-in-difference analyses based on multiple linear regressions were used to compare the changes over time, after controlling for potential confounders.
Most (2721) of the 3214 participants used a community health centre as their regular source of care and were included in our analyses. The mean total scores for quality of primary care were similar for Shanghai and Shenzhen at baseline. In Shenzhen, the mean total scores for all participants and those on low incomes had worsened by 0.922 (95% CI: 0.629 to 1.215) and 1.203 (95% CI: 0.397 to 2.009), respectively. In Shanghai, however, there were improvements in the mean total scores which included increases in the scores for first-contact utilization, continuity, coordination of information and comprehensiveness.
The quality of primary care improved in Shanghai but not in Shenzhen. This may be because, in Shanghai, beneficial long-term relationships between patients and general practitioners were supported by capitation payments and the provision of services tailored to the local health priorities.
Abstract
Differential rotation is the basis of the solar dynamo theory. Synoptic maps of He
I
intensity from Carrington rotations 2032–2135 are utilized to investigate the differential rotation of ...the solar chromosphere in the He
I
absorption line. The chromosphere is surprisingly found to rotate faster than the photosphere below it. The anomalous heating of the chromosphere and corona has been a big problem in modern astronomy. It is speculated that the small-scale magnetic elements with magnetic flux in the range of (2.9–32.0) × 10
18
Mx, which are anchored in the leptocline, heat the quiet chromosphere to present the anomalous temperature increase, causing it to rotate at the same rate as the leptocline. The differential of rotation rate in the chromosphere is found to be strengthened by strong magnetic fields, but in stark contrast, at the photosphere strong magnetic fields repress the differential of rotation rate. A plausible explanation is given for these findings.
Autologous bone marrow cells (BMCs) transplanted into ventricular scar tissue may differentiate into cardiomyocytes and restore myocardial function. This study evaluated cardiomyogenic ...differentiation of BMCs, their survival in myocardial scar tissue, and the effect of the implanted cells on heart function.
BMCs from adult rats were cultured in cell culture medium (control) and medium with 5-azacytidine (5-aza, 10 micromol/L), TGFbeta1 (10 ng/mL), or insulin (1 nmol/L) (n=6, each group). Only BMCs cultured with 5-aza formed myotubules which stained positively for troponin I and myosin heavy chain. In vivo studies: a cryoinjury-derived scar was formed in the left ventricular free wall. At 3 weeks after injury, fresh BMCs (n=9), cultured BMCs (n=9), 5-aza-induced BMCs (n=12), and medium (control, n=12) were autologously transplanted into the scar. Heart function was measured at 8 weeks after myocardial injury. Cardiac-like muscle cells which stained positively for myosin heavy chain and troponin I were observed in the scar tissue of the 3 groups of BMC transplanted hearts. Only the 5-aza-treated BMC transplanted hearts had systolic and developed pressures which were higher (P<0.05) than that of the control hearts. All transplanted BMCs induced angiogenesis in the scar.
Transplantation of BMCs induced angiogenesis. BMCs cultured with 5-aza differentiated into cardiac-like muscle cells in culture and in vivo in ventricular scar tissue and improved myocardial function.
The Formosan wild boar () is an endemic subspecies in Taiwan. Understanding the origins and spread of the Formosan wild boar could help clarify East Asian wild boar dispersion. Although in situ ...domestication of the wild boar occurred at a number of domestication centers across East Asia, corroborating archaeological and genetic evidence of pig domestication on Taiwan is lacking, leading to domestication being described as cryptic. This characterization applies to the Lanyu pig-a domestic pig breed found on Taiwan. To better understand pig domestication, this study examines the sympatric Formosan wild boar and domestic Lanyu pig to build a model of potential wild boar domestication on Taiwan and elucidate wild boar domestication patterns in the region. To this end, a comprehensive phylogenetic study of the Formosan wild boar and the Lanyu pig was conducted on animals sourced from Taiwan, Lanyu, and the Philippines. Phylogenetic analyses were conducted using full mitochondrial control-region sequences from 345 wild boars and domestic pigs. These were studied in concert with existing reports on 206 Asian wild boars. Genetic characteristics and Bayesian phylogenetic tree results identified 2 wild boar lineages of remote phylogenetic relationship. These were Formosan wild boar lineage (FWBL) and Formosan wild boar with Lanyu sign lineage (FWBLYL). Molecular clock analyses indicate that FWBLYL diverged earlier than other insular East Asia wild boars and show that FWBLYL and FWBL diverged approximately 0.60 million years ago. This result supports boars of FWBLYL being the earliest wild boars to have spread and become isolated in insular East Asia. In addition, the study proposes 6 Asian wild boar dispersion routes during glacial periods. At least 3 of these events occurred in insular East Asia with subsequent geographical isolation after glacial recession. This isolation potentially led to allopatric differentiation of wild boar subspecies. Also, the similar genetic signature and phylogenetic uniqueness of Lanyu pigs to wild boars of FWBLYL suggests such wild boars were the wild ancestor of domestic Lanyu pigs. This result indicates potential in situ domestication occurring on Taiwan. Finally, pigs possessing FWBLYL's genetic signatures were continuously distributed among Taiwan, Lanyu, and the Philippines. This pattern may signify human-mediated pig dispersal routes.
In this study, a new controlled sintering process has been proposed to improve the water permeation of asymmetric alumina hollow fibre membranes. In this process, polymer binder (PESf) in precursor ...fibres is purposely pre-treated in static air at selected temperatures (400–600°C) to have it partially removed, prior to be converted into carbon in a second sintering step (1450°C) under an oxygen free environment. During the second sintering step, proper bounding between ceramic particles takes place, while the growth of ceramic grains is effectively suppressed due to the presence of carbon. The carbon in the voids formed by particle packing also acts as a pore structure “stabilizer” and can be removed easily via subsequent thermal treatment in static air at 800°C. Compared to the membranes with the same asymmetric structure and sintered in static air only (i.e. normal sintering), the membranes sintered using the new controlled sintering process shows water permeation flux is approximately 13 times higher, together with comparable mechanical strength. Moreover, this original concept of using the polymer binder to design the pore structure of ceramic membranes can be transferred to other inorganic materials.
•A controlled sintering is proposed to improve characteristics of ceramic membranes.•It uses the polymer binder (PESf) in precursor fibres as a pore structure “stabilizer”.•Proper control of the polymer quantity allows less densification of the alumina membranes.•High water permeation together with comparable mechanical strength is achieved.•The new concept in designing ceramic membranes can be transferred to other inorganic materials.
To fully understand the cytotoxicity of after-degradation QDs, we synthesized CdS QDs and investigated its toxicity mechanism.
Biomimetic method was proposed to synthesize cadmium sulfide (CdS) QDs. ...Thereafter MTT (3-4,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide) assay was conducted to evaluate their cytotoxicity. To investigate the toxicity mechanism, we subsequently conducted intracellular reactive oxygen species (ROS) measurement with DCFH-DA, glutathione (GSH) measurement with DTNB, and cellular cadmium assay using atomic absorption spectrometer. Microsized CdS were simultaneously tested as a comparison.
MTT assay results indicated that CdS QDs are more toxic than microsized CdS especially at concentrations below 40
μg/ml. While microsized CdS did not trigger ROS elevation, CdS QDs increase ROS by 20–30% over control levels. However, they both deplete cellular GSH significantly at the medium concentration of 20
μg/ml. In the presence of NAC, cells are partially protected from CdS QDs, but not from microsized particles. Additionally, nearly 20% of cadmium was released from CdS nanoparticles within 24
h, which also accounts for QDs’ toxicity.
Intracellular ROS production, GSH depletion, and cadmium ions (Cd
2+) release are possible mechanisms for CdS QDs’ cytotoxicity. We also suggested that with QD concentration increasing, the principal toxicity mechanism changes from intracellular oxidative stress to Cd
2+ release.
The fundamental role of bacteria in global biogeochemical cycles warrants a thorough understanding of the factors controlling bacterial community structure. In this study, the integrated effect of ...seasonal differences and spatial distribution on bacterial community structure and diversity were investigated at the regional scale. We conducted a comprehensive bacterial survey, with 451 samples of the Scotian Shelf sector of the Northwest Atlantic Ocean during spring and fall of 2014 and 2016, to analyze the effects of physicochemical gradients on bacterial community structure. Throughout the region, Pelagibacteraceae and Rhodobacteraceae were the most common in the free-living fraction, while Flavobacteriia and Deltaproteobacteria were more abundant in the particle-associated fraction. Overall, there was strong covariation of the microbial community diversity from the two size fractions. This relationship existed despite the statistically significant difference in community structure between the free-living and particle-associated size fractions. In both size fractions, distribution patterns of bacterial taxa, and species within taxa, displayed temporal and spatial preferences. Distinct bacterial assemblages specific to season and depth in the water column were identified. These distinct assemblages, consistent for both 2014 and 2016, suggested replicable patterns in microbial communities for spring and fall in this region. Over all sites, temperature and oxygen values were highly correlated with community similarity, and salinity and oxygen values were the most strongly positively- and negatively correlated with alpha diversity, respectively. However, the strengths of these correlations depended on the depth and season sampled. The bathymetry of the Scotian Shelf, the abrupt shelf break to the Scotian Slope and the major ocean currents dominating in the region led to the formation of distinct on-shelf and off-shelf bacterial communities both in spring and fall. The highest species richness was observed at the shelf break, where water masses from the two major currents meet. Our study establishes the baseline for assessing future changes in the bacterial community of the Scotian Shelf waters, a rapidly changing sector of the Atlantic Ocean.
The MELD score was developed to predict survival after transjugular intrahepatic portosystemic shunt (TIPS) placement. Given changes in practice patterns and development of new prognostic tools in ...cirrhosis, we aimed to evaluate common models to predict mortality after TIPS placement.
Analysis of consecutive patients who underwent TIPS placement for ascites or bleeding. Performance to predict 90-day mortality was assessed by C statistic for six models (MELD, MELD-Na, CLIF-C ACLF, Child-Pugh, Platelet-Albumin-Bilirubin, and Emory score). Added predictive value to MELD score was assessed for univariate predictors of 90-day mortality. Stratified analysis by TIPS indication, emergent placement status, and TIPS stent type was performed.
413 patients were analyzed (248 with variceal bleeding, 165 with refractory ascites). 90-day mortality was 27% (113/413). Mean MELD score was 15 ± 7.9. MELD score best predicted mortality for all patients (c = 0.779), for variceal bleeding (c = 0.844), and for emergent TIPS (c = 0.817). CLIF-C ACLF score best predicted mortality for refractory ascites (c = 0.707). Addition of sodium to the MELD score did not improve predictive value across multiple strata. Addition of hemoglobin improved MELD score's predictive value in variceal bleeding. Addition of age improved MELD score's predictive value in refractory ascites.
MELD score best predicted 90-day mortality. Addition of sodium to the MELD score did not improve its performance, though mortality prediction was improved using Age-MELD for ascites and Hemoglobin-MELD for bleeding. An individualized risk stratification approach may be best when considering candidates for TIPS placement.
A new analytical model is developed for thermomechanical responses of multi-layered structures with an arbitrary number of layers and subjected to general thermal and mechanical loading. The ...formulation is based on an extended Bernoulli–Euler beam theory and a slip-interface model. The former includes Poisson’s effect and covers both the plane stress and plane strain deformations, and the latter allows slipping between two adjacent layers but no jump in the normal displacement or traction. An analytical solution for a multi-layered structure under general thermomechanical loading is derived by using a new approach that first determines one interfacial shear stress and the curvature of the deformed structure. To illustrate the newly developed model, three example problems for two-, three- and five-layer structures respectively are analytically solved by directly applying the new model. In all three cases, the solutions are obtained in closed-form expressions by considering both temperature changes and mechanical loads including body forces, distributed normal and shear stresses on the top and bottom surfaces, and normal forces, transverse shear forces and bending moments at the two ends, unlike existing ones. It is shown that the current solution for two-layer structures recovers an existing solution without considering Poisson’s effect and mechanical loading and the classical solution of Timoshenko for perfectly bonded bi-metal thermostats as two special cases. The closed-form solution for five-layer structures with imperfect interfaces is derived here for the first time. In addition, numerical results are provided for five- and seven-layer transistor stacks to quantitatively demonstrate the new model. It is found that the current results for the five-layer transistor stack agree well with those obtained by others, thereby further validating the new model.
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