GRAS gene family in rye (Secale cereale L.): genome-wide identification, phylogeny, evolutionary expansion and expression analyses.

BACKGROUND: The GRAS transcription factor family plays a crucial role in various biological processes in different plants, such as tissue development, fruit maturation, and environmental stress. However, the GRAS family in rye has not been systematically analyzed yet. RESULTS: In this study, 67 GRAS genes in S. cereale were identified and named based on the chromosomal location. The gene structures, conserved motifs, cis-acting elements, gene replications, and expression patterns were further analyzed. These 67 ScGRAS members are divided into 13 subfamilies. All members include the LHR I, VHIID, LHR II, PFYRE, and SAW domains, and some nonpolar hydrophobic amino acid residues may undergo cross-substitution in the VHIID region. Interested, tandem duplications may have a more important contribution, which distinguishes them from other monocotyledonous plants. To further investigate the evolutionary relationship of the GRAS family, we constructed six comparative genomic maps of homologous genes between rye and different representative monocotyledonous and dicotyledonous plants. The response characteristics of 19 ScGRAS members from different subfamilies to different tissues, grains at filling stages, and different abiotic stresses of rye were systematically analyzed. Paclobutrazol, a triazole-based plant growth regulator, controls plant tissue and grain development by inhibiting gibberellic acid (GA) biosynthesis through the regulation of DELLA proteins. Exogenous spraying of paclobutrazol significantly reduced the plant height but was beneficial for increasing the weight of 1000 grains of rye. Treatment with paclobutrazol, significantly reduced gibberellin levels in grain in the filling period, caused significant alteration in the expression of the DELLA subfamily gene members. Furthermore, our findings with respect to genes, ScGRAS46 and ScGRAS60, suggest that these two family members could be further used for functional characterization studies in basic research and in breeding programmes for crop improvement. CONCLUSIONS: We identified 67 ScGRAS genes in rye and further analysed the evolution and expression patterns of the encoded proteins. This study will be helpful for further analysing the functional characteristics of ScGRAS genes.

A longitudinal analysis of the impact of the local tobacco retail availability and neighbourhood deprivation on male smoking behaviours in Shanghai, China.

Some evidence from Western high-income countries suggests local tobacco retail availability and neighbourhood deprivation may influence smoking behaviours. However, this assertion has not been considered in China, where 44% of males continue to smoke. Data were analysed from Chinese males (n = 2054) who participated in Waves 3-5 (2009-2015) of the International Tobacco Control (ITC) China Survey by linking information on tobacco retail availability (estimated through population weighted Kernel Density of tobacco retailers in 2019) and neighbourhood deprivation (calculated as a composite score derived from the 2010 Chinese census) across Shanghai. Generalised Estimating Equation models were fitted to examine the impacts of local tobacco availability and neighbourhood deprivation on smoking behaviours (current smoking versus current non-smoking, quitting versus current smoking, longer durations of smoking abstinence versus current smoking) using the longitudinal data. Examining the impacts separately, participants living in neighbourhoods with greater availability and higher levels of deprivation were less likely to maintain longer durations of smoking abstinence in both unadjusted and adjusted models. Neighbourhood deprivation, but not availability, was found to be associated with higher odds of being a current smoker. Examining the impacts jointly, neighbourhood deprivation was still positively associated with current smoking and negatively associated with longer durations of smoking abstinence, but the negative association between availability and longer durations of smoking abstinence disappeared. The findings offer some evidence that greater tobacco retail availability and deprivation are obstacles on prolonged smoking cessation among males in Shanghai, China. Policymakers should consider small-area level place-based restrictions in China, such as reducing the availability of tobacco, as part of a comprehensive tobacco control strategy aimed at addressing the high prevalence of smoking.

Asymmetric Solvents Regulated Crystallization-Limited Electrolytes for All-Climate Lithium Metal Batteries.

Electrolytes that can keep liquid state are one of the most important physical metrics to ensure the ions transfer with stable operation of rechargeable lithium-based batteries at a wide temperature window. It is generally accepted that strong polar solvents with high melting points favor the safe operation of batteries above room temperatures but are susceptible to crystallization at low temperatures (≤-40 °C). Here, a crystallization limitation strategy was proposed to handle this issue. We demonstrate that, although the high melting points of ethylene sulfite (ES, -17 °C) and fluoroethylene carbonate (FEC, ≈23 °C), their mixtures can avoid crystallization at low temperatures, which can be attributed to low intermolecular interactions and altered molecular motion dynamics. A suitable ES/FEC ratio (10 % FEC) can balance the bulk and interface transport of ions, enabling LiNi0.8 Mn0.1 Co0.1 O2 ||lithium (NCM811||Li) full cells to deliver excellent temperature resilience and cycling stability over a wide temperature range from -50 °C to +70 °C. More than 66 % of the capacity retention was achieved at -50 °C compared to room temperature. The NCM811||Li pouch cells exhibit high cycling stability under realistic conditions (electrolyte weight to cathode capacity ratio (E/C)≤3.5 g Ah-1 , negative to positive electrode capacity ratio (N/P)≤1.09) at different temperatures.

Food Intake Suppresses ApoB Secretion and Fractional Catabolic Rates in Humans.

BACKGROUND: Humans spend much of the day in the postprandial state. However, most research and clinical guidelines on plasma lipids pertain to blood drawn after a 12-hour fast. We aimed to study the metabolic differences of apoB lipoproteins between the fasting and postprandial states. METHODS: We investigated plasma apoB metabolism using stable isotope tracers in 12 adult volunteers under fasting and continuous postprandial conditions in a randomized crossover study. We determined the metabolism of apoB in multiple lipoprotein subfractions, including light and dense VLDLs (very-low-density lipoproteins), IDLs (intermediate-density lipoproteins), and light and dense LDLs (low-density lipoproteins) that do or do not contain apoE or apoC3. RESULTS: A major feature of the postprandial state is 50% lower secretion rate of triglyceride-rich lipoproteins and concurrent slowdown of their catabolism in circulation, as shown by 34% to 55% lower rate constants for the metabolic pathways of conversion by lipolysis from larger to smaller lipoproteins and direct clearance of lipoproteins from the circulation. In addition, the secretion pattern of apoB lipoprotein phenotypes was shifted from particles containing apoE and apoC3 in the fasting state to those without either protein in the postprandial state. CONCLUSIONS: Overall, during the fasting state, hepatic apoB lipoprotein metabolism is activated, characterized by increased production, transport, and clearance. After food intake, endogenous apoB lipoprotein metabolism is globally reduced as appropriate to balance dietary input to maintain the supply of energy to peripheral tissues.

Impact of individual, household, and area characteristics on health and social care outcomes for people with multimorbidity: Protocol for a multilevel analysis.

BACKGROUND: Multimorbidity is one of the greatest challenges facing health and social care systems globally. It is associated with high rates of health service use, adverse healthcare events, and premature death. Despite its importance, little is known about the effects of contextual determinants such as household and area characteristics on health and care outcomes for people with multimorbidity. This study protocol presents a plan for the examination of associations between individual, household, and area characteristics with important health and social care outcomes. METHODS: The study will use a cross-section of data from the SAIL Databank on 01 January 2019 and include all people alive and registered with a Welsh GP. The cohort will be stratified according to the presence or absence of multimorbidity, defined as two or more long-term conditions. Multilevel models will be used to examine covariates measured for individuals, households, and areas to account for social processes operating at different levels. The intra-class correlation coefficient will be calculated to determine the strength of association at each level of the hierarchy. Model outcomes will be any emergency department attendance, emergency hospital or care home admission, or mortality, within the study follow-up period. DISCUSSION: Household and area characteristics might act as protective or risk factors for health and care outcomes for people with multimorbidity, in which case results of the analyses can be used to guide clinical and policy responses for effective targeting of limited resources.

bHLH transcription factor family identification, phylogeny, and its response to abiotic stress in Chenopodium quinoa.

The second-largest transcription factor superfamily in plants is that of the basic helix-loop-helix (bHLH) family, which plays an important complex physiological role in plant growth, tissue development, and environmental adaptation. Systematic research on the Chenopodium quinoa bHLH family will enable a better understanding of this species. Herein, authors used a variety of bioinformatics methods and quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) to explore the evolution and function of the 218 CqbHLH genes identified. A total of 218 CqbHLH transcription factor genes were identified in the whole genome, located on 18 chromosomes. A phylogenetic tree was constructed using the CqbHLH and AtbHLH proteins to determine their homology, and the members were divided into 20 subgroups and one unclustered gene. Authors also analyzed 218 CqbHLH genes, conservative motifs, chromosome diffusion, and gene replication. The author constructed one Neighbor-Joining (NJ) tree and a collinearity analysis map of the bHLH family in C. quinoa and six other plant species to study the evolutionary relationship and homology among multiple species. In addition, the expression levels of 20 CqbHLH members from different subgroups in various tissues, different fruit developmental stages, and six abiotic stresses were analyzed. Authors identified 218 CqbHLH genes and studied their biological functions, providing a basis for better understanding and further studying the bHLH family in quinoa.

UV-excited single-component white phosphor of Lu2WO6 with broad-band emission for pc-WLED.

Obtaining white light from a single-component phosphor is still a significant challenge due to the complex energy transfer between multiple luminescent centers. Herein, white light emission is obtained in a single-component lutetium tungstate without any doping elements. By tuning the pH values during the hydrothermal synthesis, the orthorhombic Lu2W3O12 transformed into monocline Lu6WO12 and rhombohedra Lu6WO12. Only the monoclinic Lu2WO6 phase emitted light, whereas the other two phases did not. The main reason was that the exciton binding energy of Lu2WO6 was larger than that of Lu2W3O12 and Lu6WO12. Except for the 480 nm intrinsic emission of Lu2WO6, new long-wavelength excitation and emission bands were observed with the center at 340 nm and 520 nm. Based on the first-principle calculation, this new photoluminescence band comes from the electron transition between the local states of oxygen vacancies and valence band. Owing to this new broad-band emission, the white light LED lamp is fabricated by combining Lu2WO6 phosphor synthesized at pH values of 4.5 and 6 and 365 nm LED chips. The CIE coordinates of the pc-WLEDs are (0.346, 0.359) and (0.380, 0.380), respectively, and both are located in the white light region. Our research demonstrated a facile way to obtain a single-component white light emission phosphor without any doping components for pc-WLED applications.

Potential impacts of spatial restrictions on tobacco retail availability in China: a simulation study in Shanghai.

OBJECTIVES: Regulating tobacco retail availability provides promising new opportunities for effective tobacco control. This study simulates the potential impacts of introducing spatial restrictions on the availability of tobacco in Shanghai, the largest city in China. METHODS: Twelve stakeholder-informed simulation scenarios under four types of spatial restrictions were considered: (1) capping, (2) ban of sales, (3) minimum spacing and (4) school-buffer exclusion zone. Tobacco retailer data for Shanghai (n=19 413) were used. The main outcome was per cent reduction in retail availability measured by population-weighted kernel density estimation across neighbourhoods, and impacts on social inequality in availability were estimated using the Kruskal-Wallis test and effect size estimation. All analyses were further stratified by three levels of urbanity to examine geographical disparities in overall effectiveness and equity of the simulation scenarios. RESULTS: All simulation scenarios have the potential to reduce availability, with overall reductions ranging from 8.60% to 85.45%. Compared with the baseline, the effect size regarding the association between availability and neighbourhood deprivation quintiles suggests that the most effective scenario, '500 m minimum spacing' between retailers, increased the social inequality in availability (p<0.001). Conversely, school-buffer scenarios were both effective and equitable. Additionally, the effectiveness and the equity impact of scenarios varied by urbanity level. CONCLUSION: Spatial restrictions offer potential new policy opportunities to reduce retail availability, but some may increase social inequality in accessing tobacco. For effective tobacco control, policymakers should consider the overall and equity impacts of spatial restrictions when developing comprehensive tobacco retail regulations.

GEospatial aNalysis of ExtRacorporeal membrane oxygenATion in Europe (GENERATE).

INTRODUCTION: A cross-sectional survey GENERATE (GEospatial aNalysis of ExtRacorporeal membrane oxygenATion in Europe) initiated on behalf of the European chapter of the Extracorporeal Life Support Organization (EuroELSO), aims to provide a systematic, detailed description of contemporary Extracorporeal Life Support (ECLS) provision in Europe, map the spatial distribution of ECLS centers, and the accessibility of ECLS. METHODS: Structured data collection forms were used to create a narrative description of ECLS provision in EuroELSO affiliated countries. This consisted of both center-specific data and relevant national infrastructure. Data was provided by a network of local and national representatives. Spatial accessibility analysis was conducted where appropriate geographical data were available. RESULTS: 281 centers from 37 countries affiliated to EuroELSO were included in the geospatial analysis and demonstrate heterogeneous patterns of ECLS provision. Accessibility of ECLS services within 1 hour of drive-time is available for 50% of the adult population in 8 of 37 countries (21.6%). This proportion is reached within 2 hours in 21 of 37 countries (56.8%) and within 3 hours in 24 of 37 countries (64.9%). For pediatric centers, accessibility is similar with 9 of 37 countries (24.3%) reached the covering of 50% of the population aged 0-14 within 1 hour and 23 of 37 countries (62.2%) within 2 hours and 3 hours. CONCLUSIONS: ECLS services are accessible in most of the European countries, but their provision differs across the continent. There is still no solid evidence given regarding the optimal ECLS provision model. The spatial disparity in ECLS provision demonstrated in our analysis requires governments, healthcare professionals and policy makers to consider how to develop existing provision to accommodate the anticipated increase in need for time critical access to this advanced support modality.

A Cross-sectional Analysis of Socio-spatial Patterning of Tobacco Retail in Shanghai, China.

INTRODUCTION: International evidence from high-income countries demonstrates that the availability of tobacco tends to be greater in more urban and more deprived neighborhoods. However, little is known about the socio-spatial disparities in other settings, including megacities in China. This study investigated the patterning of tobacco retailers across Shanghai by types of tobacco retailers, including the relationship with levels of urbanity and neighborhood deprivation. AIMS AND METHODS: Tobacco retailer data (n = 19 413) was extracted from a web-scraped Points-of-Interest database. For all communities (n = 5432) across Shanghai, neighborhood tobacco retail availability was calculated using population-weighted kernel density estimation and grouped by quintiles of neighborhood deprivation and a 3-level urban classification. Associations were analyzed using the Kruskal-Wallis tests and epsilon squared. RESULTS: Across Shanghai, tobacco retail availability decreased from more urbanized areas to less urbanized areas. There was a statistical difference (p < .001) in the availability of tobacco retail across quintiles of deprivation, with the highest availability in the less deprived neighborhoods, and the lowest availability in the most deprived neighborhoods. However, this trend was reversed in the urban center, where retail availability was greatest in the most deprived areas. Convenience stores were the most common type of tobacco retailer across the city, while tobacco-only outlets were most strongly associated with levels of neighborhood deprivation. CONCLUSIONS: The results show an association between tobacco retail availability and neighborhood deprivation, which varied with levels of urbanity and types of tobacco retailers. These findings provide supportive evidence for further interventions that target reducing inequalities in exposure to tobacco retail. IMPLICATIONS: This is the first study to examine the relationship between tobacco retail availability and neighborhood deprivation in the context of Chinese megacities. Using data from Shanghai, China, we found a significant non-linear association between tobacco retail availability and neighborhood deprivation across the city. It is plausible that the socio-spatial disparities in tobacco retail availability at the neighborhood level may be a key factor explaining differences in smoking behaviors between sociodemographic groups. The findings emphasize the need for greater efforts in regulating neighborhood-level tobacco retailing in China.

Retrospective Analysis of Clinicopathological Features and Prognosis of Gynecological Small-Cell Carcinoma.

PURPOSE: Although rare, small-cell neuroendocrine carcinoma of the gynecologic tract (SCNCGT) is associated with poor prognosis. We analyzed the clinical characteristics, pathological features, treatment strategies, and prognosis in patients with SCNCGT. PATIENTS AND METHODS: We performed a retrospective data analysis of 34 patients with SCNCGT diagnosed and treated at our hospital between 2006 and 2018. Medical records were reviewed for pathological features, treatment methods, and outcomes of this disease. RESULTS: We included 34 patients who had small-cell neuroendocrine carcinoma of the endometrium (SCNCE; 7), ovary (SCNCO; 7), and cervix (SCNCC; 20). All patients with SCNCE underwent comprehensive surgery and six received postoperative chemotherapy. All patients with SCNCO received chemotherapy after surgery; six underwent comprehensive surgery and one underwent treatment only in the pelvic cavity. Sixteen patients with SCNCC underwent radical surgery and received chemotherapy, two of whom received simultaneous radiotherapy. The remaining four patients with SCNCC underwent comprehensive chemotherapy and radiation therapy. Among the 34 patients, 11 had vascular metastases, 15 had lymph node metastases, and seven exhibited positive margins. The median overall survival time among all patients was 23.18 months (range: 3-66 months). Death occurred in 18 cases (52.94%). Recurrence was observed in 13 cases (38.24%). The average time to recurrence was 15.78 months following treatment (range: 2-30 months). All 34 patients were evaluated for neuroendocrine markers. The immunohistochemical positive rates of synaptophysin, CD56, and chromogranin A were 73.5%, 64.7%, and 55.9%, respectively. CONCLUSION: The rates of metastasis and recurrence are high, and prognosis remains poor, even among patients with early-stage SCNCGT. Our data may aid in the development of reference standards for diagnosis and treatment.

Photogenerated charge separation and recombination path modification in monocline Lu2WO6via lattice transition and Bi-O antibonding states.

Monoclinic Lu2WO6 undergoes diphase-to-perovskite BiLuWO6 transition via selective occupancy of Bi in three Lu sites. The transformation mechanism, process, and structure stabilities are revealed by variable cell nudged elastic band method, video, and phonon spectrum. Lattice transition brings about photogenerated charge separation in BiLuWO6. This is verified by indirect band gap transition, high electron migration rate, weak exciton binding energy, large photocurrent response, and small impedance. The electron-hole life time is elongated to produce abundant superoxide and hydroxyl radicals for the degradation of rhodamine B and phenol molecules. Bi-O antibonding states serve as immediate energy levels to change the recombination path, inducing 340 nm excitation band and 510 nm green light emission of Lu2WO6. Furthermore, multicolor emission of 1 at% Bi3+ + RE3+ (RE = Sm/Eu/Dy)-codoped Lu2WO6 is acquired via synergistic modification of the Bi-O antibonding state and RE3+ 4f states. Thus, the photogenerated charge motion in Lu2WO6 is tuned to expand application fields.

Intrahippocampal miR-342-3p inhibition reduces ß-amyloid plaques and ameliorates learning and memory in Alzheimer's disease.

Accumulation of extracellular amyloid-ß (Aß) in hippocampal subregions is a hallmark of Alzheimer's disease (AD), which promotes neuronal apoptosis, potentiates cognitive decline and play a causative role in AD pathogenesis. However, whether this process is controlled by distinct miRNAs at the posttranscriptional level remain fascinating but poorly understood. Using post mortem hippocampal samples from human AD patients and 3xTg-AD mouse, we demonstrate that miR-342-3p expression was significantly induced during the AD development. With the aid of intrahippocampal injection of miR-342-3p antagomir, we further show that in vivo miR-342-3p inhibition synergistically improved cognitive deficits in 3xTg-AD mice. The hippocampal Aß-plaque burden in 3xTg-AD mice, as revealed by immunohistochemical analysis with 4G8 antibody, was attenuated also. Mechanistically, the upregulation of neuronal miR-342-3p is linked to an increase in the activation of the stress kinase c-Jun N-terminal kinase with the subsequent death of the neurons in Aß-challenged HT22 hippocampal neuronal cells. These findings support the model that derangement of hippocampus signal transduction and subsequent neuronal apoptosis in AD arises as a consequence of increased Aß burden and chronic activation of the JNK MAPK cascade in a miR-342-3p-dependent manner. Overall, we described for the first time the regulatory activity of miR-342-3p on relevant Aß metabolism pathways in Alzheimer's disease.

Responses of soil hydrolytic enzymes, ammonia-oxidizing bacteria and archaea to nitrogen applications in a temperate grassland in Inner Mongolia.

We used a seven-year urea gradient applied field experiment to investigate the effects of nitrogen (N) applications on soil N hydrolytic enzyme activity and ammonia-oxidizing microbial abundance in a typical steppe ecosystem in Inner Mongolia. The results showed that N additions inhibited the soil N-related hydrolytic enzyme activities, especially in 392 kg N ha(-1 )yr(-1) treatment. As N additions increased, the amoA gene copy ratios of ammonia-oxidizing archaea (AOA) to ammonia-oxidizing bacteria (AOB) decreased from 1.13 to 0.65. Pearson correlation analysis showed that the AOA gene copies were negatively related with NH4(+)-N content. However, the AOB gene copies were positively correlated with NO3(-)-N content. Moderate N application rates (56-224 kg N ha(-1 )yr(-1)) accompanied by P additions are beneficial to maintaining the abundance of AOB, as opposed to the inhibition of highest N application rate (392 kg N ha(-1 )yr(-1)) on the abundance of AOB. This study suggests that the abundance of AOB and AOA would not decrease unless N applications exceed 224 kg N ha(-1 )yr(-1) in temperate grasslands in Inner Mongolia.

[Clinical value of viral detection of liquid chip method in community-acquired pneumonia].

OBJECTIVE: To evaluate the clinical value of viral detection of liquid chip method in community-acquired pneumonia (CAP). METHODS: A total of 342 swabs were collected from 171 patients of community-acquired pneumonia from October 2013 to September 2014. The methods of xTAG(RVP) and Seeplex RV15 ACE were employed to detect respiratory viruses. And traditional methods of indirect immunofluorescence and specific antigen were used for comparison. All results were validated by realtime-PCR and statistically analyzed. RESULTS: Of 171 CAP patients with an average age of 49.17 years, 35.7% (61/171) were virus positive.Influenza A (FluA), influenza B (FluB), respiratory syncytial virus (RSV), human rhinovirus (HRV) and human metapneumovirus (hMPV) accounted for 90.5% of all detected viruses. The detection rates of mouth swabs and nasopharyngeal swabs were 31.6% and 33.9% respectively. Two specimen types showed no significant differences (Kappa = 0.714, P < 0.001; McNemar χ(2) = 0, P = 1.000). The positive rates of viral detection by xTAG(RVP) and Seeplex RV15 were 32.5% and 29.5% respectively. And the consistence rate of results was up to 85.4% (292/342) (Kappa = 0.66). The positive rate of traditional methods was 14.0%.However, xTAG(RVP) had a higher sensitivity (93.3%), higher consistence rate (92.4%) and negative predictive value (96.9%) compared with Seeplex RV15 and traditional methods. Also xTAG(RVP) had a high consistent rate of realtime-PCR (Kappa = 0.83). CONCLUSIONS: Liquid chip is superior to other detection methods. And it may be used routinely for viral detection of CAP.

Selective cathepsin S inhibition attenuates atherosclerosis in apolipoprotein E-deficient mice with chronic renal disease.

Chronic renal disease (CRD) accelerates the development of atherosclerosis. The potent protease cathepsin S cleaves elastin and generates bioactive elastin peptides, thus promoting vascular inflammation and calcification. We hypothesized that selective cathepsin S inhibition attenuates atherogenesis in hypercholesterolemic mice with CRD. CRD was induced by 5/6 nephrectomy in high-fat high-cholesterol fed apolipoprotein E-deficient mice. CRD mice received a diet admixed with 6.6 or 60 mg/kg of the potent and selective cathepsin S inhibitor RO5444101 or a control diet. CRD mice had significantly higher plasma levels of osteopontin, osteocalcin, and osteoprotegerin (204%, 148%, and 55%, respectively; P < 0.05), which were inhibited by RO5444101 (60%, 40%, and 36%, respectively; P < 0.05). Near-infrared fluorescence molecular imaging revealed a significant reduction in cathepsin activity in treated mice. RO5444101 decreased osteogenic activity. Histologic assessment in atherosclerotic plaque demonstrated that RO5444101 reduced immunoreactive cathepsin S (P < 0.05), elastin degradation (P = 0.01), plaque size (P = 0.01), macrophage accumulation (P < 0.01), growth differentiation factor-15 (P = 0.0001), and calcification (alkaline phosphatase activity, P < 0.01; osteocalcin, P < 0.05). Furthermore, cathepsin S inhibitor or siRNA significantly decreased expression of growth differentiation factor-15 and monocyte chemotactic protein-1 in a murine macrophage cell line and human primary macrophages. Systemic inhibition of cathepsin S attenuates the progression of atherosclerotic lesions in 5/6 nephrectomized mice, serving as a potential treatment for atherosclerosis in patients with CRD.

Updates on apolipoprotein CIII: fulfilling promise as a therapeutic target for hypertriglyceridemia and cardiovascular disease.

PURPOSE OF REVIEW: The lipid hypothesis of atherosclerosis is mainly predicated on the function of apolipoprotein (apo)B lipoproteins, which promote atherosclerosis, and apoA lipoproteins, which prevent it. However, accumulating evidence suggests causal roles of other apolipoproteins, abundant surface components of apoB and apoA lipoprotein, in promoting atherosclerosis and other metabolic diseases. This article reviews recent literature on one such apolipoprotein: apoCIII. RECENT FINDINGS: Population studies have consistently demonstrated that plasma apoCIII strongly predicts cardiovascular disease. ApoCIII's atherogenicity was traditionally attributed to hypertriglyceridemia because of its inhibition on the lipolysis of triglyceride-rich lipoproteins. Recent evidence expands this function and reveals apoCIII's key role in hepatic assembly and secretion of triglyceride-rich lipoproteins. In addition to these indirect atherogenic functions mediated through dyslipidemia, recent research discovers that apoCIII directly provoke proinflammatory responses in vascular cells, including monocytes and endothelial cells. These direct atherogenic effects are dependent on apoCIII. ApoCIII is also involved in pancreatic beta-cell biology and contributes to type I diabetes. SUMMARY: Recent data further strengthen the theory that apoCIII exerts strong atherogenic functions through both indirect and direct mechanisms. Encouraging results from early stage clinical trials demonstrate that modulating apoCIII per se is a novel and potent therapeutic approach to managing dyslipidemia and cardiovascular disease risk.

Characterization of the major capsid genes (g23) of T4-type bacteriophages in the wetlands of northeast China.

To obtain genetic information and to evaluate the composition of T4-type bacteriophage (phage) communities in wetlands, environmental soil and water DNAs were obtained from two natural wetlands dominated by Carex lasiocarpa and Deyeuxia angustifolia plant species, and a neighboring paddy field in Sanjiang plain of northeast China. The biomarker gene of g23, which encodes the major capsid protein of T4-type phages, was amplified with primers MZIA1bis and MZIA6, and the PCR products were cloned and sequenced. In total, 96 and 50 different g23 clones were obtained from natural wetlands and a paddy field, respectively. A larger number of clones with low levels of identity to known sequences were found in water than in soil both in the natural wetlands and the paddy field, suggesting that many of T4-type phages in wetland water and paddy floodwater in Sanjiang plain are uncharacterized. Phylogenetic analyses showed that the g23 clones in natural wetlands, irrespective of water and soil, were distinctly different from those in marine waters, lake waters, and upland black soils, but were similar to those in paddy fields. The UniFrac analysis of g23 assemblages indicated that T4-type phage community compositions were different between soils and waters, and also were different between the natural wetlands and the paddy field. In general, the global analysis of g23 clone assemblages demonstrated that T4-type phage community compositions were different among natural wetlands, marines, lakes, paddy fields, and upland black soils.

Statins suppress apolipoprotein CIII-induced vascular endothelial cell activation and monocyte adhesion.

AIMS: Activation of vascular endothelial cells (ECs) contributes importantly to inflammation and atherogenesis. We previously reported that apolipoprotein CIII (apoCIII), found abundantly on circulating triglyceride-rich lipoproteins, enhances adhesion of human monocytes to ECs in vitro. Statins may exert lipid-independent anti-inflammatory effects. The present study examined whether statins suppress apoCIII-induced EC activation in vitro and in vivo. METHODS AND RESULTS: Physiologically relevant concentrations of purified human apoCIII enhanced attachment of the monocyte-like cell line THP-1 to human saphenous vein ECs (HSVECs) or human coronary artery ECs (HCAECs) under both static and laminar shear stress conditions. This process mainly depends on vascular cell adhesion molecule-1 (VCAM-1), as a blocking VCAM-1 antibody abolished apoCIII-induced monocyte adhesion. ApoCIII significantly increased VCAM-1 expression in HSVECs and HCAECs. Pre-treatment with statins suppressed apoCIII-induced VCAM-1 expression and monocyte adhesion, with two lipophilic statins (pitavastatin and atorvastatin) exhibiting inhibitory effects at lower concentration than those of hydrophilic pravastatin. Nuclear factor κB (NF-κB) mediated apoCIII-induced VCAM-1 expression, as demonstrated via loss-of-function experiments, and pitavastatin treatment suppressed NF-κB activation. Furthermore, in the aorta of hypercholesterolaemic Ldlr(-/-) mice, pitavastatin administration in vivo suppressed VCAM-1 mRNA and protein, induced by apoCIII bolus injection. Similarly, in a subcutaneous dorsal air pouch mouse model of leucocyte recruitment, apoCIII injection induced F4/80+ monocyte and macrophage accumulation, whereas pitavastatin administration reduced this effect. CONCLUSIONS: These findings further establish the direct role of apoCIII in atherogenesis and suggest that anti-inflammatory effects of statins could improve vascular disease in the population with elevated plasma apoCIII.