Effect of ticagrelor versus clopidogrel after implantation of drug-eluting stents guided by either intravascular ultrasound or angiography in patients with acute coronary syndrome-propensity score matching analysis.

BACKGROUND: The effect of different dual antiplatelet therapies on thrombotic events on the background of intravascular ultrasound (IVUS) guidance is unclear. We investigated whether ticagrelor can provide any additional benefit to clopidogrel in reducing thrombotic events in acute coronary syndrome (ACS) treated with drug- eluting stent (DES), when guided by IVUS or not. METHODS: A total of 5,666 ACS patients who underwent DES implantation and who were discharged on dual antiplatelet therapy were enrolled and grouped according to the use of IVUS or not. Each group was subdivided into two subgroups according to the type of P2Y12 inhibitor used after discharge. Propensity score matching (PSM) was used between the IVUS and no-IVUS groups. Covariate adjustment of Cox proportional hazards model was used between the ticagrelor and clopidogrel groups. Thrombotic event at 12 months was compared in groups separately. RESULTS: After PSM, 12-month follow-up data were available for 1,174 patients. Major adverse cardiac events (MACE) were less frequent in the IVUS-guided group (2.2% vs. 4.3%, P = 0.081) with a trend toward statistical significance. Comparison of antiplatelet regimens revealed significantly fewer major adverse cardiac and cerebrovascular events (MACCE) with ticagrelor in the entire PSM cohort and angiography-guided subgroup (2.9% vs. 5.7%, P = 0.035; 3.1% vs. 6.4%, P = 0.020, respectively). Among patients in the IVUS-guided group the outcome was comparable (2.5% vs. 4.4%, P = 0.312). Ticagrelor was associated with increasing bleeding incidence in the entire PSM cohort (1.3% vs. 3.3%, P = 0.030), mainly due to Bleeding Academic Research Consortium type 2 bleeding (0.7% vs. 2.6%, P = 0.010). The results were consistent after covariate adjustment of Cox proportional hazards model. CONCLUSION: The comparison of ischemic benefit between ticagrelor and clopidogrel was similar in patients receiving IVUS guidance during stent implantation, probably due to the precise implantation of IVUS. Multicenter, randomized studies should be performed to validate this conclusion.

A review on processing methods and functions of wheat germ-derived bioactive peptides.

Wheat germ protein is a potential resource to produce bioactive peptides. As a cheap, safe, and healthy nutritional factor, wheat germ-derived bioactive peptides (WGBPs) provide benefits and great potential for biomedical applications. The objective of this review is to reveal the current research status of WGBPs, including their preparation methods and biological functions, such as antibacterial, anti-tumor, immune regulation, antioxidant, and anti-inflammatory properties, etc. We also reviewed the information in terms of the preventive ability of WGBPs to treat serious infectious diseases, to offer their reference to further research and application. Opinions on future research directions are also discussed. Through the review of previous research, we find that there are still some scientific issues in the basic research and industrialization process of WGBPs that deserve further exploration. Firstly, based on current complex enzymolysis, the preparation and production of WGBPs need to be combined with other advanced technology to achieve efficient and large-scale production. Secondly, studies on the bioavailability, biosafety, and mechanism against different diseases of WGBPs need to be carried out in different in vitro and in vivo models. More human experimental evidence is also required to support its industrial application as a functional food and nutritional supplement.HighlightsThe purification and identification of wheat germ-derived bioactive peptides.The main biological activities and potential mechanisms of wheat germ hydrolysates/peptides.Possible absorption and transport pathways of wheat germ hydrolysate/peptide.Wheat germ peptide shows a variety of health benefits according to its amino acid sequence.Current food applications and future perspectives of wheat germ protein hydrolysates/peptide.

Exploration of Antimicrobial Ingredients in Psoralea corylifolia L. Seed and Related Mechanism against Methicillin-Resistant Staphylococcus aureus.

With the abuse of antibiotics, bacterial antibiotic resistance is becoming a major public healthcare issue. Natural plants, especially traditional Chinese herbal medicines, which have antibacterial activity, are important sources for discovering potential bacteriostatic agents. This study aimed to develop a fast and reliable method for screening out antimicrobial compounds targeting the MRSA membrane from Psoralea corylifolia Linn. seed. A UPLC-MS/MS method was applied to identify the prenylated flavonoids in major fractions from the extracts of Psoralea corylifolia Linn. seed. The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of different fractions and compounds. The morphological and ultrastructural changes of MRSA were determined by scanning electron microscopy (SEM). The membrane-targeting mechanism of the active ingredients was explored by membrane integrity assays, membrane fluidity assays, membrane potential assays, ATP, and ROS determination. We identified eight prenylated flavonoids in Psoralea corylifolia Linn. seed. The antibacterial activity and mechanism studies showed that this type of compound has a unique destructive effect on MRSA cell membranes and does not result in drug resistance. The results revealed that prenylated flavonoids in Psoralea corylifolia Linn. seeds are promising candidates for the development of novel antibiotic agents to combat MRSA-associated infections.

Towards Quantitative Microbiome Community Profiling Using Internal Standards.

An inherent issue in high-throughput rRNA gene tag sequencing microbiome surveys is that they provide compositional data in relative abundances. This often leads to spurious correlations, making the interpretation of relationships to biogeochemical rates challenging. To overcome this issue, we quantitatively estimated the abundance of microorganisms by spiking in known amounts of internal DNA standards. Using a 3-year sample set of diverse microbial communities from the Western Antarctica Peninsula, we demonstrated that the internal standard method yielded community profiles and taxon cooccurrence patterns substantially different from those derived using relative abundances. We found that the method provided results consistent with the traditional CHEMTAX analysis of pigments and total bacterial counts by flow cytometry. Using the internal standard method, we also showed that chloroplast 16S rRNA gene data in microbial surveys can be used to estimate abundances of certain eukaryotic phototrophs such as cryptophytes and diatoms. In Phaeocystis, scatter in the 16S/18S rRNA gene ratio may be explained by physiological adaptation to environmental conditions. We conclude that the internal standard method, when applied to rRNA gene microbial community profiling, is quantitative and that its application will substantially improve our understanding of microbial ecosystems.IMPORTANCE High-throughput-sequencing-based marine microbiome profiling is rapidly expanding and changing how we study the oceans. Although powerful, the technique is not fully quantitative; it provides taxon counts only in relative abundances. In order to address this issue, we present a method to quantitatively estimate microbial abundances per unit volume of seawater filtered by spiking known amounts of internal DNA standards into each sample. We validated this method by comparing the calculated abundances to other independent estimates, including chemical markers (pigments) and total bacterial cell counts by flow cytometry. The internal standard approach allows us to quantitatively estimate and compare marine microbial community profiles, with important implications for linking environmental microbiomes to quantitative processes such as metabolic and biogeochemical rates.

Light-driven synchrony of Prochlorococcus growth and mortality in the subtropical Pacific gyre.

Theoretical studies predict that competition for limited resources reduces biodiversity to the point of ecological instability, whereas strong predator/prey interactions enhance the number of coexisting species and limit fluctuations in abundances. In open ocean ecosystems, competition for low availability of essential nutrients results in relatively few abundant microbial species. The remarkable stability in overall cell abundance of the dominant photosynthetic cyanobacterium Prochlorococcus is assumed to reflect a simple food web structure strongly controlled by grazers and/or viruses. This hypothesized link between stability and ecological interactions, however, has been difficult to test with open ocean microbes because sampling methods commonly have poor temporal and spatial resolution. Here we use continuous techniques on two different winter-time cruises to show that Prochlorococcus cell production and mortality rates are tightly synchronized to the day/night cycle across the subtropical Pacific Ocean. In warmer waters, we observed harmonic oscillations in cell production and mortality rates, with a peak in mortality rate consistently occurring ∼6 h after the peak in cell production. Essentially no cell mortality was observed during daylight. Our results are best explained as a synchronized two-component trophic interaction with the per-capita rates of Prochlorococcus consumption driven either directly by the day/night cycle or indirectly by Prochlorococcus cell production. Light-driven synchrony of food web dynamics in which most of the newly produced Prochlorococcus cells are consumed each night likely enforces ecosystem stability across vast expanses of the open ocean.

Deep learning for predicting 16S rRNA gene copy number.

Culture-independent 16S rRNA gene metabarcoding is a commonly used method for microbiome profiling. To achieve more quantitative cell fraction estimates, it is important to account for the 16S rRNA gene copy number (hereafter 16S GCN) of different community members. Currently, there are several bioinformatic tools available to estimate the 16S GCN values, either based on taxonomy assignment or phylogeny. Here we present a novel approach ANNA16, Artificial Neural Network Approximator for 16S rRNA gene copy number, a deep learning-based method that estimates the 16S GCN values directly from the 16S gene sequence strings. Based on 27,579 16S rRNA gene sequences and gene copy number data from the rrnDB database, we show that ANNA16 outperforms the commonly used 16S GCN prediction algorithms. Interestingly, Shapley Additive exPlanations (SHAP) shows that ANNA16 can identify unexpected informative positions in 16S rRNA gene sequences without any prior phylogenetic knowledge, which suggests potential applications beyond 16S GCN prediction.

Antimicrobial activities of lavandulylated flavonoids in Sophora flavences against methicillin-resistant Staphylococcus aureus via membrane disruption.

INTRODUCTION: The continuous emergence and rapid spread of multidrug-resistant bacteria have accelerated the demand for the discovery of alternative antibiotics. Natural plants contain a variety of antibacterial components, which is an important source for the discovery of antimicrobial agents. OBJECTIVE: To explore the antimicrobial activities and related mechanisms of two lavandulylated flavonoids, sophoraflavanone G and kurarinone in Sophora flavescens against methicillin-resistant Staphylococcus aureus. METHODS: The effects of sophoraflavanone G and kurarinone on methicillin-resistant Staphylococcus aureus were comprehensively investigated by a combination of proteomics and metabolomics studies. Bacterial morphology was observed by scanning electron microscopy. Membrane fluidity, membrane potential, and membrane integrity were determined using the fluorescent probes Laurdan, DiSC3(5), and propidium iodide, respectively. Adenosine triphosphate and reactive oxygen species levels were determined using the adenosine triphosphate kit and reactive oxygen species kit, respectively. The affinity activity of sophoraflavanone G to the cell membrane was determined by isothermal titration calorimetry assays. RESULTS: Sophoraflavanone G and kurarinone showed significant antibacterial activity and anti-multidrug resistance properties. Mechanistic studies mainly showed that they could target the bacterial membrane and cause the destruction of the membrane integrity and biosynthesis. They could inhibit cell wall synthesis, induce hydrolysis and prevent bacteria from synthesizing biofilms. In addition, they can interfere with the energy metabolism of methicillin-resistant Staphylococcus aureus and disrupt the normal physiological activities of the bacteria. In vivo studies have shown that they can significantly improve wound infection and promote wound healing. CONCLUSION: Kurarinone and sophoraflavanone G showed promising antimicrobial properties against methicillin-resistant Staphylococcus aureus, suggesting that they may be potential candidates for the development of new antibiotic agents against multidrug-resistant bacteria.

In situ activity of a dominant Prochlorococcus ecotype (eHL-II) from rRNA content and cell size.

In the open ocean genetically diverse clades of the unicellular cyanobacteria Prochlorococcus are biogeographically structured along environmental gradients, yet little is known about their in situ activity. To address this gap, here we use the numerically dominant Prochlorococcus clade eHL-II (eMIT9312) as a model organism to develop and apply a method to examine their in situ activity using rRNA content and cell size as metrics of cellular physiology. For two representative isolates (MIT9312 and MIT9215) rRNA cell(-1) increases linearly with specific growth rate but is anticorrelated with cell size indicated by flow cytometrically measured (SSC). Although each strain has a unique relationship between cellular rRNA (or cell size) and growth rate, both strains have the same strong positive correlation between rRNA cell(-1) SSC(-1) and growth rate. We field test this approach and observe distinct patterns of eHL-II clade specific activity (rRNA cell(-1) SSC(-1)) with depth that are consistent with patterns of photosynthetic rates. This molecular technique provides unique insight into the ecology of Prochlorococcus and could potentially be expanded to include other microbes to unravel the ecological and biogeochemical contributions of genetically distinct marine side scatter microbes.

Relationship between abundance and specific activity of bacterioplankton in open ocean surface waters.

Marine microbial communities are complex and dynamic, and their ecology impacts biogeochemical cycles in pelagic ecosystems. Yet, little is known about the relative activities of different microbial populations within genetically diverse communities. We used rRNA as a proxy for activity to quantify the relative specific activities (rRNA/ribosomal DNA [rDNA or rRNA genes]) of the eubacterial populations and to identify locations or clades for which there are uncouplings between specific activity and abundance. After analyzing 1.6 million sequences from 16S rDNA and rRNA (cDNA) libraries from two euphotic depths from a representative site in the Pacific Ocean, we show that although there is an overall positive relationship between the abundances (rDNAs) and activities (rRNAs) among populations of the bacterial community, for some populations these measures are uncoupled. Different ecological strategies are exemplified by the two numerically dominant clades at this site: the cyanobacterium Prochlorococcus is abundant but disproportionately more active, while the heterotrophic SAR11 is abundant but less active. Other rare populations, such as Alteromonas, have high specific activities in spite of their low abundances, suggesting intense population regulation. More detailed analyses using a complementary quantitative PCR (qPCR)-based approach of measuring relative specific activity for Prochlorococcus populations in the Pacific and Atlantic Oceans also show that specific activity, but not abundance, reflects the key drivers of light and nutrients in this system; our results also suggest substantial top-down regulation (e.g., grazing, viruses, or organismal interactions) or transport (e.g., mixing, immigration, or emigration) of these populations. Thus, we show here that abundance and specific activity can be uncoupled in open ocean systems and that describing both is critical to characterizing microbial communities and predicting marine ecosystem functioning and responses to change.

Hepatoma-targeting and reactive oxygen species-responsive chitosan-based polymeric micelles for delivery of celastrol.

A glycyrrhetinic acid-modified carboxymethyl chitosan-thioketal-rhein (GCTR) conjugate was designed and synthesized for the in vivo delivery of celastrol (Cela). Cela was encapsulated into polymeric micelles (PMs) formed by GCTR conjugates self-assembly in water to form Cela/GCTR PMs with high drug loading capacity and small particle size. Cela/GCTR PMs had a sustained-release characteristic in the blood environment and a rapid-release feature in the tumor microenvironment. Cela/GCTR PMs had a significant proliferation inhibitory effect on HepG2 and BEL-7402 cells, but a negligible impact on L-02 cells at low concentrations. Cela/GCTR PMs possessed reactive oxygen species (ROS)-responsive properties in vitro and in cells, could improve the bioavailability of Cela, and exert remarkable hepatoma-targeting properties. Cela/GCTR PMs could also effectively inhibit tumor growth with no apparent damage to different organs. In summary, GCTR PMs with good ROS-responsive and hepatoma-targeting properties are expected to be possible delivery carriers for hydrophobic antineoplastic drugs for hepatocellular carcinoma therapy.

Arterial stiffness is associated with cancer mortality: Insight from Kailuan study.

BACKGROUND: There is limited evidence on the association between arterial stenosis and the risk of all-cause mortality in cancer patients (ACMC). This study investigated whether the status of arterial function and structure measured by brachial-ankle pulse wave velocity (baPWV) is associated with ACMC. METHODS: A total of 43,943 Chinese adults underwent a baPWV examination. Cox proportional hazards model was used to assess the association between the baPWV values and ACMC. RESULTS: During a total follow-up duration of 3.81 ± 2.50 years, there were 157 deaths among 553 cancer cases diagnosed during the follow-up. Patients with baPWV ≥18 m/s showed an increased risk of ACMC compared to patients with ideal vascular function. In the multivariate-adjusted model, we observed a significant association between arterial stiffness severity and ACMC with a hazard ratio (HR) 2.72 (95% confidence interval [CI]: 1.55-4.80; p < 0.001) in those with baPWV ≥18 m/s. With a 1-SD increase in baPWV, the HR (95% CI) for ACMC in the entire cohort, men, and patients ≤60 years old were 1.20 (95% CI: 1.03-1.41; p < 0.05), 1.20 (95% CI: 1.01-1.43; p < 0.05), and 1.44 (95% CI: 1.10-1.44; p = 0.008), respectively. CONCLUSIONS: Increased arterial stiffness measured by baPWV is associated with ACMC. The association between high baPWV (≥18 m/s) and risk of all-cause mortality was prominent in men and those ≤60 years of age.

Wheat Germ-Derived Peptide Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice.

This study explores the protective properties and potential mechanisms of wheat-germ-derived peptide APEPEPAF (APE) against ulcerative colitis. Colitis mice induced by dextran sulfate sodium (DSS) were used as the animal model. The results showed that the APE peptide could alleviate colitis symptoms including weight loss, colon shortening, and histopathological changes. This peptide attenuated the generation of inflammatory cytokines by inhibiting the phosphorylation of protein kinase PKCζ (Thr410) and NF-κB transcriptional activity in DSS-induced mice, suggesting that APE ameliorates colitis inflammation by regulating the PKCζ/NF-κB signaling pathway. APE also preserved the barrier function of the colon by dose-dependently promoting the expression of tight junction proteins (claudin-1, zonula occluded-1, and occludin). In addition, APE significantly decreased the abundance of Bacteroides and increased the abundance of Dubosiella and Lachnospiraceae_UCG-006 to improve the intestinal flora imbalance in DSS-induced colitis mice. Therefore, wheat germ peptide APE can be used as a novel agent and dietary supplement to treat ulcerative colitis..

Open science resources from the Tara Pacific expedition across coral reef and surface ocean ecosystems.

The Tara Pacific expedition (2016-2018) sampled coral ecosystems around 32 islands in the Pacific Ocean and the ocean surface waters at 249 locations, resulting in the collection of nearly 58 000 samples. The expedition was designed to systematically study warm-water coral reefs and included the collection of corals, fish, plankton, and seawater samples for advanced biogeochemical, molecular, and imaging analysis. Here we provide a complete description of the sampling methodology, and we explain how to explore and access the different datasets generated by the expedition. Environmental context data were obtained from taxonomic registries, gazetteers, almanacs, climatologies, operational biogeochemical models, and satellite observations. The quality of the different environmental measures has been validated not only by various quality control steps, but also through a global analysis allowing the comparison with known environmental large-scale structures. Such publicly released datasets open the perspective to address a wide range of scientific questions.

The Association Between Physical Activity and Insulin Level Under Different Levels of Lipid Indices and Serum Uric Acid.

OBJECTIVES: Insulin resistance (IR) has been shown to play important role in the pathogenesis of type 2 diabetes mellitus (T2DM). There is an intricate interplay between IR, dyslipidemia, and serum uric acid (SUA) in people with and without diabetes. Physical activity has a positive impact on insulin sensitivity in insulin-resistant populations. However, the effect of different intensities of physical activity on insulin levels under different lipid indices and SUA levels is unclear. METHODS: To explore the association between physical activity and insulin, we enrolled 12,982 participants aged above 18 years from the National Health and Nutrition Examination Survey (NHANES) conducted between 2009 and 2018. Next, we conducted multivariate logistic regression analyses, generated fitted smoothing curves, and visualized the data using generalized additive models. RESULTS: Increased intensities of physical activity can significantly reduce insulin levels. The association between physical activity and insulin persisted even after adjusting for confounding factors, with ß value (95% CI) = -17.10 (-21.64, -12.56) in moderate group, ß value (95% CI) = -28.60 (-33.08, -24.11) in high group, respectively. High-intensity physical activity significantly lowered insulin levels in the lower and higher SUA tertiles, and three tertiles of LDL-c, HDL-c, and TG. Moreover, the link between physical activity and insulin was stronger in male individuals. CONCLUSION: This study shows that physical activity can significantly lower insulin levels, and high-intensity physical activity still has additional potential benefits for insulin levels, even in the condition of dyslipidemia and hyperuricemia.

A Retrospective Study of the Relationship Between the Triglyceride Glucose Index and Myocardial Revascularization for New-Onset Acute Coronary Syndromes.

Background: This study explored the relationship between the TyG index/serum uric acid (SUA) panel and myocardial revascularization (MRT) for new-onset acute coronary syndromes (ACS). Methods: Between January 2011 and July 2020, 13,271 new-onset ACS patients were enrolled. The logistic regression models and the odds ratios (ORs) were used to quantify the risk of TyG index/SUA and MRT. Then, interaction analyses of TyG index and SUA on MRT were applied. Results: Elevated TyG index was positively associated higher risks of MRT. However, SUA levels were negatively associated with MRT. Compared with those in the lowest quartile, the risk of MRT increased gradually among patients in Q1 of the SUA category (OR = 1.03, 1.11, and 1.28 for Q2, Q3, and Q4 of TyG index, respectively), Q2 of the SUA category (OR = 1.41, 1.68, and 2.18 for Q2, Q3, and Q4 of TyG index, respectively), Q3 of the SUA category (OR = 1.05, 1.45, and 1.45 for Q2, Q3, and Q4 of TyG index, respectively), and Q4 of the SUA category (OR = 1.20, 1.29, and 1.46 for Q2, Q3, and Q4 of TyG index, respectively). This pattern was observed in both male and female, as well as patients without type 2 diabetes mellitus. Conclusion: Patients with a higher TyG index have a higher proportion of MRT in new-onset ACS. This result also applies to patients with different levels of SUA during new-onset ACS.

Anthracycline-Induced Atrial Structural and Electrical Remodeling Characterizes Early Cardiotoxicity and Contributes to Atrial Conductive Instability and Dysfunction.

Aims: Cancer patients treated with anthracyclines are susceptible to atrial fibrillation (AF), while the mechanisms remain unclear. Due to sudden and unpredictable features, prediction of anthracycline-induced AF at early phase is difficult. Clinically, we tested whether anthracycline-induced early atrial remodeling in patients could be detected by echocardiography. Experimentally, we investigated the mechanisms of doxorubicin-induced atrial remodeling and AF in mice, and the protective effects of dexrazoxane and antioxidants. Methods and Results: Postsurgery breast cancer patients with an anthracycline-containing or anthracycline exclusion regimen were recruited for echocardiography before chemotherapy, and 3 and 6 months after chemotherapy. Mice were injected with doxorubicin or vehicle (5 mg/kg/week, 4 weeks), and left atrial diameter, electrical transmission, and AF inducibility were measured. Meanwhile, the level of reactive oxygen species (ROS), activity of antioxidant enzymes, cardiomyocyte size, vacuolization, inflammation, and fibrosis were also measured in mouse atria. The therapeutic effects of dexrazoxane and antioxidants on doxorubicin-induced changes in the aforementioned parameters were also determined. While ventricular parameters and functions were unchanged in cancer patients receiving anthracyclines before and after chemotherapy, left atrial reservoir and conduit function were decreased at 3 months postchemotherapy versus prechemotherapy. Doxorubicin-induced susceptibility to AF occurred in mice before onset of ventricular dysfunction. Doxorubicin-induced AF was via inducing structural remodeling (cardiomyocyte death, hypotrophy, and vacuolization) and electrical remodeling (reduction and redistribution of connexin 43) in atria, which was effectively prevented by dexrazoxane or antioxidants through inhibiting ROS generation or enhancing ROS elimination. Innovation and Conclusion: AF inducibility was induced after doxorubicin injection, which can be inhibited by repressing the ROS level. Antioxid. Redox Signal. 37, 19-39. The Clinical Trial Registration number is PJ-KS-KY-2019-73.

Protective Effect of Uric Acid on ox-LDL-Induced HUVECs Injury via Keap1-Nrf2-ARE Pathway.

Uric acid is an effective antioxidant. Oxidized low-density lipoprotein (ox-LDL) is derived from circulating LDL and promotes atherosclerosis. The Keap1-Nrf2-ARE pathway is a key body pathway involved in protection against internal and external oxidative damages. The role of uric acid on vascular endothelial function damaged by ox-LDL, and its effect on the Keap1-Nrf2-ARE pathway has not been fully explored. HUVECs were treated with different concentrations of uric acid and ox-LDL to explore the effect of uric acid in vitro. Cell phenotype was determined by cytometry and Western blot. Nuclear translocation of Nrf2 was determined by immunofluorescence. Coimmunoprecipitation was used to determine the level of Nrf2 ubiquitination. A microfluidic device was used to mimic the vascular environment in the body, and the level of mRNA levels of inflammatory factors was determined by RT-PCR. The findings of this study show that suitable uric acid can significantly reduce endothelial damage caused by ox-LDL, such as oxidative stress, inflammation, and increased adhesion. In addition, uric acid reduced Nrf2 ubiquitination and increased nuclear translocation of Nrf2 protein, thus activating the Keap1-Nrf2-ARE pathway and playing a protective role. Interestingly, the effects of UA were significantly inhibited by administration of Brusatol, an inhibitor of Nrf2. In summary, suitable concentrations of uric acid can alleviate the oxidative stress level of endothelial cells through Nrf2 nuclear translocation and further protect cells from damage.

The Relationship Between Serum Uric Acid at Different Concentrations of Lipid Indices and the Risk of Myocardial Revascularization in Patients With Acute Coronary Syndrome: A Retrospective Analysis.

Objective: Both serum uric acid (SUA) levels and lipid components, such as LDL, HDL, and Lp(a), have been reported to associate with CAD. However, the influence of SUA status at different concentrations of lipid indices for the risk of myocardial revascularization (MRT) in ACS patients is currently unknown. Methods: We retrospectively analyzed a hospital-based sample of 14,234 ACS patients with no previous history of percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) surgery. All patients went for coronary angiography. Binary logistic regression models were performed, and the odds ratios (OR) at 95% confidence interval (CIs) were used to approximate the associated risk of UA and lipid profile for myocardial revascularization, with the lowest quartile/tertile serving as the reference category. Results: Overall, 8,818 (61.9%) patients undergone MRT out of 14,234 patients. Elevated SUA and HDL were negatively associated with an increased likelihood of MRT during admission (P < 0.001). However, LDL and Lp(a) levels were positively associated with MRT among ACS patients. Furthermore, interaction analyses between SUA and lipid profiles, particularly LDL and Lp(a), compared with those in the lowest quartile of SUA levels, show that patients in higher SUA quartiles grouped by lipid components had a significantly lower chance of undergoing MRT, with the lowest OR (95%CI) for subjects being 0.222 (0.170-0.290), 0.478 (0.374-0.612), and 0.604 (0.468-0.780) in LDL tertiles, being 0.671(0.523-0.862), 0.316(0.242-0.413), and 0.410 (0.310-0.542) in Lp(a) tertiles, respectively. In the three tertiles of HDL levels, the incidence of MRT dropped steadily as SUA levels increased. Also, we further analyzed ACS patients without diabetes. Compared with the first quartile of SUA levels, the risks of MRT were significantly lower in different tertiles of lipids components [LDL, Lp(a), HDL]. Conclusion: An increase in SUA levels may decrease the chance of undergoing MRT in ACS patients, even in those with increased Lp(a) and LDL-c. Elevated serum uric acid may play a protective role during an acute stage of ACS.

Decline in plankton diversity and carbon flux with reduced sea ice extent along the Western Antarctic Peninsula.

Since the middle of the past century, the Western Antarctic Peninsula has warmed rapidly with a significant loss of sea ice but the impacts on plankton biodiversity and carbon cycling remain an open question. Here, using a 5-year dataset of eukaryotic plankton DNA metabarcoding, we assess changes in biodiversity and net community production in this region. Our results show that sea-ice extent is a dominant factor influencing eukaryotic plankton community composition, biodiversity, and net community production. Species richness and evenness decline with an increase in sea surface temperature (SST). In regions with low SST and shallow mixed layers, the community was dominated by a diverse assemblage of diatoms and dinoflagellates. Conversely, less diverse plankton assemblages were observed in waters with higher SST and/or deep mixed layers when sea ice extent was lower. A genetic programming machine-learning model explained up to 80% of the net community production variability at the Western Antarctic Peninsula. Among the biological explanatory variables, the sea-ice environment associated plankton assemblage is the best predictor of net community production. We conclude that eukaryotic plankton diversity and carbon cycling at the Western Antarctic Peninsula are strongly linked to sea-ice conditions.

Identification of important risk factors for all-cause mortality of acquired long QT syndrome patients using random survival forests and non-negative matrix factorization.

BACKGROUND: Acquired long QT syndrome (aLQTS) is often associated with poor clinical outcomes. OBJECTIVE: The purpose of this study was to examine the important predictors of all-cause mortality of aLQTS patients by applying both random survival forest (RSF) and non-negative matrix factorization (NMF) analyses. METHODS: Clinical characteristics and manually measured electrocardiographic (ECG) parameters were initially entered into the RSF model. Subsequently, latent variables identified using NMF were entered into the RSF as additional variables. The primary outcome was all-cause mortality. RESULTS: A total of 327 aLQTS patients were included. The RSF model identified 16 predictive factors with positive variable importance values: cancer, potassium, RR interval, calcium, age, JT interval, diabetes mellitus, QRS duration, QTp interval, chronic kidney disease, QTc interval, hypertension, QT interval, female, JTc interval, and cerebral hemorrhage. Increasing the number of latent features between ECG indices, which incorporated from n = 0 to n = 4 by NMF, maximally improved the prediction ability of the RSF-NMF model (C-statistic 0.77 vs 0.89). CONCLUSION: Cancer and serum potassium and calcium levels can predict all-cause mortality of aLQTS patients, as can ECG indicators including JTc and QRS. The present RSF-NMF model significantly improved mortality prediction.