Arabidopsis Serine Decarboxylase Mutants Implicate the Roles of Ethanolamine in Plant Growth and Development

Ethanolamine is important for synthesis of choline, phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in plants. The latter two phospholipids are the major phospholipids in eukaryotic membranes. In plants, ethanolamine is mainly synthesized directly from serine by serine decarboxylase. Serine decarboxylase is unique to plants and was previously shown to have highly specific activity to l-serine. While serine decarboxylase was biochemically characterized, its functions and importance in plants were not biologically elucidated due to the lack of serine decarboxylase mutants. Here we characterized an Arabidopsis mutant defective in serine decarboxylase, named atsdc-1 (Arabidopsis thaliana serine decarboxylase-1). The atsdc-1 mutants showed necrotic lesions in leaves, multiple inflorescences, sterility in flower, and early flowering in short day conditions. These defects were rescued by ethanolamine application to atsdc-1, suggesting the roles of ethanolamine as well as serine decarboxylase in plant development. In addition, molecular analysis of serine decarboxylase suggests that Arabidopsis serine decarboxylase is cytosol-localized and expressed in all tissue

Safety and Efficacy of Second-Generation Everolimus-Eluting Xience V Stents Versus Zotarolimus-Eluting Resolute Stents in Real-World Practice Patient-Related and Stent-Related Outcomes From the Multicenter Prospective EXCELLENT and RESOLUTE-Korea Registries

ObjectivesThis study sought to compare the safety and efficacy of the Xience V/Promus everolimus-eluting stent (EES) (Abbott Vascular, Temecula, California) with the Endeavor Resolute zotarolimus-eluting stent (ZES-R) (Medtronic Cardiovascular, Santa Rosa, California) in “all-comer” cohorts.BackgroundOnly 2 randomized controlled trials have compared these stents.MethodsThe EXCELLENT (Efficacy of Xience/Promus Versus Cypher to Reduce Late Loss After Stenting) and RESOLUTE-Korea registries prospectively enrolled 3,056 patients treated with the EES and 1,998 patients treated with the ZES-R, respectively, without exclusions. Stent-related composite outcomes (target lesion failure [TLF]) and patient-related composite outcomes were compared in crude and propensity score-matched analyses.ResultsOf 5,054 patients, 3,830 (75.8%) had off-label indication (2,217 treated with EES and 1,613 treated with ZES-R). The stent-related outcome (82 [2.7%] vs. 58 [2.9%], p = 0.662) and the patient-related outcome (225 [7.4%] vs. 153 [7.7%], p = 0.702) did not differ between EES and ZES-R, respectively, at 1 year, which was corroborated by similar results from the propensity score-matched cohort. The rate of definite or probable stent thrombosis (18 [0.6%] vs. 7 [0.4%], p = 0.306) also was similar. In multivariate analysis, off-label indication was the strongest predictor of TLF (adjusted hazard ratio: 2.882; 95% confidence interval: 1.226 to 6.779; p = 0.015).ConclusionsIn this robust real-world registry with unrestricted use of EES and ZES-R, both stents showed comparable safety and efficacy at 1-year follow-up. Overall incidences of TLF and definite stent thrombosis were low, even in the patients with off-label indication, suggesting excellent safety and efficacy of both types of second-generation drug-eluting stents

Depression and quality of life among Macau residents in the 2022 COVID-19 pandemic wave from the perspective of network analysis

BackgroundIn the summer of 2022, Macau experienced a surge of COVID-19 infections (the 618 COVID-19 wave), which had serious effects on mental health and quality of life (QoL). However, there is scant research on mental health problems and QoL among Macau residents during the 618 COVID-19 wave. This study examined the network structure of depressive symptoms (hereafter depression), and the interconnection between different depressive symptoms and QoL among Macau residents during this period.MethodA cross-sectional study was conducted between 26th July and 9th September 2022. Depressive symptoms were measured with the 9-item Patient Health Questionnaire (PHQ-9), while the global QoL was measured with the two items of the World Health Organization Quality of Life-brief version (WHOQOL-BREF). Correlates of depression were explored using univariate and multivariate analyses. The association between depression and QoL was investigated using analysis of covariance (ANCOVA). Network analysis was used to evaluate the structure of depression. The centrality index “Expected Influence” (EI) was used to identify the most central symptoms and the flow function was used to identify depressive symptoms that had a direct bearing on QoL.ResultsA total 1,008 participants were included in this study. The overall prevalence of depression was 62.5% (n = 630; 95% CI = 60.00–65.00%). Having depression was significantly associated with younger age (OR = 0.970; p < 0.001), anxiety (OR = 1.515; p < 0.001), fatigue (OR = 1.338; p < 0.001), and economic loss (OR = 1.933; p = 0.026). Participants with depression had lower QoL F (1, 1,008) =5.538, p = 0.019). The most central symptoms included PHQ2 (“Sad Mood”) (EI: 1.044), PHQ4 (“Fatigue”) (EI: 1.016), and PHQ6 (“Guilt”) (EI: 0.975) in the depression network model, while PHQ4 (“Fatigue”), PHQ9 (“Suicide”), and PHQ6 (“Guilt”) had strong negative associations with QoL.ConclusionDepression was common among Macao residents during the 618 COVID-19 wave. Given the negative impact of depression on QoL, interventions targeting central symptoms identified in the network model (e.g., cognitive behavioral therapy) should be developed and implemented for Macau residents with depression

High-performance silicon-based multicomponent battery anodes produced via synergistic coupling of multifunctional coating layers

Nanostructured Si-based materials are key building blocks for next-generation energy storage devices. To meet the requirements of practical energy storage devices, Si-based materials should exhibit high-power, low volume change, and high tap density. So far, there have been no reliable materials reported satisfying all of these requirements. Here, we report a novel Si-based multicomponent design, in which the Si core is covered with multifunctional shell layers. The synergistic coupling of Si with the multifunctional shell provides vital clues for satisfying all Si anode requirements for practical batteries. The Si-based multicomponent anode delivers a high capacity of similar to 1000 mA h g(-1), a highly stable cycling retention (similar to 65% after 1000 cycles at 1 C), an excellent rate capability (similar to 800 mA h g(-1) at 10 C), and a remarkably suppressed volume expansion (12% after 100 cycles). Our synthetic process is simple, low-cost, and safe, facilitating new methods for developing electrode materials for practical energy storage.open0

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

Anesthetic Propofol Reduces Endotoxic Inflammation by Inhibiting Reactive Oxygen Species-regulated Akt/IKKβ/NF-κB Signaling

BACKGROUND: Anesthetic propofol has immunomodulatory effects, particularly in the area of anti-inflammation. Bacterial endotoxin lipopolysaccharide (LPS) induces inflammation through toll-like receptor (TLR) 4 signaling. We investigated the molecular actions of propofol against LPS/TLR4-induced inflammatory activation in murine RAW264.7 macrophages. METHODOLOGY/PRINCIPAL FINDINGS: Non-cytotoxic levels of propofol reduced LPS-induced inducible nitric oxide synthase (iNOS) and NO as determined by western blotting and the Griess reaction, respectively. Propofol also reduced the production of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-10 as detected by enzyme-linked immunosorbent assays. Western blot analysis showed propofol inhibited LPS-induced activation and phosphorylation of IKKβ (Ser180) and nuclear factor (NF)-κB (Ser536); the subsequent nuclear translocation of NF-κB p65 was also reduced. Additionally, propofol inhibited LPS-induced Akt activation and phosphorylation (Ser473) partly by reducing reactive oxygen species (ROS) generation; inter-regulation that ROS regulated Akt followed by NF-κB activation was found to be crucial for LPS-induced inflammatory responses in macrophages. An in vivo study using C57BL/6 mice also demonstrated the anti-inflammatory properties against LPS in peritoneal macrophages. CONCLUSIONS/SIGNIFICANCE: These results suggest that propofol reduces LPS-induced inflammatory responses in macrophages by inhibiting the interconnected ROS/Akt/IKKβ/NF-κB signaling pathways

Fluorescence imaging through dynamic scattering media with speckle-encoded ultrasound-modulated light correlation

Fluorescence imaging is indispensable to biomedical research, and yet it remains challenging to image through dynamic scattering samples. Techniques that combine ultrasound and light as exemplified by ultrasound-assisted wavefront shaping have enabled fluorescence imaging through scattering media. However, the translation of these techniques into in vivo applications has been hindered by the lack of high-speed solutions to counter the fast speckle decorrelation of dynamic tissue. Here, we report an ultrasound-enabled optical imaging method that instead leverages the dynamic nature to perform imaging. The method utilizes the correlation between the dynamic speckle-encoded fluorescence and ultrasound-modulated light signal that originate from the same location within a sample. We image fluorescent targets with an improved resolution of ≤75 µm (versus a resolution of 1.3 mm with direct optical imaging) within a scattering medium with 17 ms decorrelation time. This new imaging modality paves the way for fluorescence imaging in highly scattering tissue in vivo