Omic-Scale High-Throughput Quantitative LC-MS/MS Approach for Circulatory Lipid Phenotyping in Clinical Research.

Lipid analysis at the molecular species level represents a valuable opportunity for clinical applications due to the essential roles that lipids play in metabolic health. However, a comprehensive and high-throughput lipid profiling remains challenging given the lipid structural complexity and exceptional diversity. Herein, we present an 'omic-scale targeted LC-MS/MS approach for the straightforward and high-throughput quantification of a broad panel of complex lipid species across 26 lipid (sub)classes. The workflow involves an automated single-step extraction with 2-propanol, followed by lipid analysis using hydrophilic interaction liquid chromatography in a dual-column setup coupled to tandem mass spectrometry with data acquisition in the timed-selective reaction monitoring mode (12 min total run time). The analysis pipeline consists of an initial screen of 1903 lipid species, followed by high-throughput quantification of robustly detected species. Lipid quantification is achieved by a single-point calibration with 75 isotopically labeled standards representative of different lipid classes, covering lipid species with diverse acyl/alkyl chain lengths and unsaturation degrees. When applied to human plasma, 795 lipid species were measured with median intra- and inter-day precisions of 8.5 and 10.9%, respectively, evaluated within a single and across multiple batches. The concentration ranges measured in NIST plasma were in accordance with the consensus intervals determined in previous ring-trials. Finally, to benchmark our workflow, we characterized NIST plasma materials with different clinical and ethnic backgrounds and analyzed a sub-set of sera (n = 81) from a clinically healthy elderly population. Our quantitative lipidomic platform allowed for a clear distinction between different NIST materials and revealed the sex-specificity of the serum lipidome, highlighting numerous statistically significant sex differences.

Effects of Multi-Dimensional Nursing Based on HAPA Theory on Self-Care Ability and Cardiac Function in Patients with Coronary Heart Failure and Heart Failure.

Objective: This study aimed to investigate the effects of multi-dimensional nursing based on the Health Action Process Approach (HAPA) theory on self-care ability and cardiac function in patients with coronary heart disease (CHD) and heart failure. To explore the effects of multi-dimensional nursing based on the health action process approach (HAPA) theory on self-care ability and cardiac function in patients with coronary heart disease (CHD) and heart failure. Methods: A total of 94 patients with CHD and heart failure admitted to the hospital were enrolled between January 2021 and October 2022. The random number table method divided them into a control group (47 cases, routine nursing in cardiology department) and observation group (47 cases, multi-dimensional nursing based on HAPA theory, which is a mental model used to explain and predict the health behavior of individuals). Before and after the intervention, self-care ability, negative emotions, cardiac function and quality of life in both groups were evaluated by the exercise of self-care agency scale (ESCA), self-rating anxiety scale (SAS), self-rating depression scale (SDS), 6-minute walking test, left ventricular ejection fraction (LVEF) and Minnesota living with heart failure questionnaire (MLWHFQ). Results: During the study period, at discharge, self-care ability in both groups was improved, which was better in the observation group than the control group (P < .05). At discharge, SAS and SDS scores in both groups were decreased, which were lower in the observation group than control group (P < .05). At 6 weeks after discharge, cardiac function (LVEF, 6 min walking distance) in both groups was improved, and the improvement effect was better in the observation group than control group (P < .05). There was no significant difference in the quality of life at discharge and 6 weeks after discharge in the observation group (P > .05), but it was worse in the control group at 6 weeks after discharge (P < .05). Conclusions: Multi-dimensional nursing based on HAPA theory can significantly improve self-care ability, improve cardiac function, and quality of life in patients with CHD and heart failure.

Wastewater treatment: A universal, scalable and recyclable catalyst with adjustable activity for diverse dyes degradation.

The growing concern over water shortage and pollution is propelling and accelerating the development of sewage treatment technologies. Among them, the catalytic hydrogenation method is highly recommended from a sustainable perspective, because it can turn toxic pollutants into valuable raw materials. The catalyst with excellent activity and stability plays a critical role in this "trash to treasure" approach. Herein, we proposed a novel economical, scalable and recyclable candidate catalyst, i.e., the copper nanoparticles supported on zinc oxide nanowire array (Cu-ZnO NWA), for realizing efficient and stable dye wastewater treatment. The salix argyracea-shaped Cu-ZnO NWA displays very outstanding universality and controllability towards the catalytic hydrogenation reactions of diverse dyes, owing to the fact that ZnO nanowire array not only offers a platform to realize stable and homogeneous dispersion of Cu nanoparticles, but also provides a large quantity of catalytically active sites. More attractively, its synthetic method can be facilely extended to various conductive substrates through combined electrodeposition and hydrothermal technique, showing its general applicability for the surface assembly of sewage treatment facilities. Benefiting from above advantages, this proposal offers an attractive approach for large-scale and continuous decolorization of dye wastewater, and presents a broad application prospect in the textile printing industry.

Population-based plasma lipidomics reveals developmental changes in metabolism and signatures of obesity risk: a mother-offspring cohort study.

BACKGROUND: Lipids play a vital role in health and disease, but changes to their circulating levels and the link with obesity remain poorly characterized in expecting mothers and their offspring in early childhood. METHODS: LC-MS/MS-based quantitation of 480 lipid species was performed on 2491 plasma samples collected at 4 time points in the mother-offspring Asian cohort GUSTO (Growing Up in Singapore Towards healthy Outcomes). These 4 time points constituted samples collected from mothers at 26-28 weeks of gestation (n=752) and 4-5 years postpartum (n=650), and their offspring at birth (n=751) and 6 years of age (n=338). Linear regression models were used to identify the pregnancy and developmental age-specific variations in the plasma lipidomic profiles, and their association with obesity risk. An independent birth cohort (n=1935), the Barwon Infant Study (BIS), comprising mother-offspring dyads of Caucasian origin was used for validation. RESULTS: Levels of 36% of the profiled lipids were significantly higher (absolute fold change > 1.5 and Padj < 0.05) in antenatal maternal circulation as compared to the postnatal phase, with phosphatidylethanolamine levels changing the most. Compared to antenatal maternal lipids, cord blood showed lower concentrations of most lipid species (79%) except lysophospholipids and acylcarnitines. Changes in lipid concentrations from birth to 6 years of age were much higher in magnitude (log2FC=-2.10 to 6.25) than the changes observed between a 6-year-old child and an adult (postnatal mother) (log2FC=-0.68 to 1.18). Associations of cord blood lipidomic profiles with birth weight displayed distinct trends compared to the lipidomic profiles associated with child BMI at 6 years. Comparison of the results between the child and adult BMI identified similarities in association with consistent trends (R2=0.75). However, large number of lipids were associated with BMI in adults (67%) compared to the children (29%). Pre-pregnancy BMI was specifically associated with decrease in the levels of phospholipids, sphingomyelin, and several triacylglycerol species in pregnancy. CONCLUSIONS: In summary, our study provides a detailed landscape of the in utero lipid environment provided by the gestating mother to the growing fetus, and the magnitude of changes in plasma lipidomic profiles from birth to early childhood. We identified the effects of adiposity on the circulating lipid levels in pregnant and non-pregnant women as well as offspring at birth and at 6 years of age. Additionally, the pediatric vs maternal overlap of the circulating lipid phenotype of obesity risk provides intergenerational insights and early opportunities to track and intervene the onset of metabolic adversities. CLINICAL TRIAL REGISTRATION: This birth cohort is a prospective observational study, which was registered on 1 July 2010 under the identifier NCT01174875 .

LICAR: An Application for Isotopic Correction of Targeted Lipidomic Data Acquired with Class-Based Chromatographic Separations Using Multiple Reaction Monitoring.

Lipidomics is developing as an important area in biomedical and clinical research. Reliable quantification of lipid species is required for clinical translation of lipidomic studies. Hydrophilic interaction chromatography (HILIC), normal-phase liquid chromatography (NPLC), and supercritical fluid chromatography (SFC) are commonly used techniques in lipidomics and provide class-based separation of lipids. While co-elution of lipid species and their internal standards is an advantage for accurate quantification, it leads to isotopic overlap between species of the same lipid class. In shotgun lipidomics, isotopic correction is typically done based on elemental formulas of precursor ions. In multiple reaction monitoring (MRM) analyses, however, this approach should not be used, as the overall contribution of heavy isotopes to the MRM transitions' intensities depends on their location in the molecule with respect to the fragmentation pattern. We present an algorithm, provided in the R programming language, for isotopic correction in class-based separation using MRM, extracting relevant structural information from MRM transitions to apply adequate isotopic correction factors. Using standards, we show that our algorithm accurately estimates the isotopic contribution of isotopologues to MRM transitions' measured intensities. Using human plasma as an example, we demonstrate the necessity of adequate isotopic correction for accurate quantitation of lipids measured by MRM with class-based chromatographic separation. We show that over a third of the measured phosphatidylcholine species had their intensity corrected by more than 10%. This isotopic correction algorithm and R-implemented application enable a more accurate quantification of lipids in class-based separation-MRM, a prerequisite for successful translation of lipidomic applications.

Pharmacokinetics of Prenylflavonoids following Oral Ingestion of Standardized Epimedium Extract in Humans.

Leaves of the Epimedium plant are traditionally consumed for bone health and other indications. The aim of this study was to establish the safety and pharmacokinetics of the metabolites of prenylflavonoids (icariin, icariside I, icariside II, icaritin, and desmethylicaritin) following single doses of a defined Epimedium prenylflavonoid extract in humans. A single oral dose of 370, 740, or 1110 mg of a standardized Epimedium prenylflavonoid extract was administered to 30 healthy male subjects in a randomized, placebo-controlled trial. Serum samples were collected over a 48-h period and analyzed by liquid chromatography-tandem mass spectrometry and non-compartmental pharmacokinetic modelling. Epimedium prenylflavonoid extracts were well tolerated and no adverse effects were observed. The principle metabolites detected in the serum were icariside II and desmethylicaritin. Icariside II had a T max of between 4.1 - 4.3 h, reaching a maximum AUC0→∞ of 23.0 (17.5, 29.9) h×ng/mL (median [IQR: interquartile range]) with the highest dose of the Epimedium prenylflavonoid. On the other hand, desmethylicaritin had a delayed T max of 24.1 - 24.4 h and reached a maximum AUC0→∞ of 126.1 (62.4, 202.9) h×ng/mL. The median maximum plasma concentration and AUC0→∞ of desmethyliciaritin showed an increase with higher doses of the Epimedium prenylflavonoid (p < 0.05). Icariin, icariside I, and icaritin levels were below detection limits. Levels of Epimedium prenylflavonoid metabolites observed in this study were consistent with levels demonstrated to have anti-osteoporotic effects in cellular and animal studies. Coupled with the favorable safety profile of the extract observed, further studies are required to explore the utility of Epimedium prenylflavonoid extracts to prevent osteoporosis in postmenopausal women.

Association between serum galectin-3 and chronic obstructive pulmonary disease: A meta-analysis.

Chronic obstructive pulmonary disease (COPD) is a significant public health issue characterized by progressive and irreversible airflow limitation. The aim of this meta-analysis was to determine the association between changes in serum galectin-3 levels and COPD and to assess the relationship between serum galectin-3 levels and acute exacerbations of COPD (AECOPD). Relevant observational studies were retrieved from electronic databases, including PubMed, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI). A random-effects model was used to combine the data, incorporating the influence of between-study heterogeneity. Twelve case-control studies were included. The pooled results showed a significantly higher serum level of galectin-3 in patients with COPD compared to controls (standardized mean difference [SMD] 0.60; 95% confidence interval [CI] 0.40 - 0.80; P < 0.001; I2 = 68%). Further meta-analysis suggested higher levels of serum galectin-3 in patients with AECOPD compared to those with stable COPD (SMD 0.33; 95% CI 0.20 - 0.46; P < 0.001; I2 = 0%). Subgroup analyses according to the mean age of the participants, the proportion of males, and study quality scores did not significantly change the results (P for subgroup differences all > 0.05). In conclusion, patients with COPD were found to have higher serum levels of galectin-3, with levels further elevated in patients with AECOPD compared to those with stable COPD.

Size-Effect-Based Dimension Compensations in Wet Etching for Micromachined Quartz Crystal Microstructures.

Microfabrication technology with quartz crystals is gaining importance as the miniaturization of quartz MEMS devices is essential to ensure the development of portable and wearable electronics. However, until now, there have been no reports of dimension compensation for quartz device fabrication. Therefore, this paper studied the wet etching process of Z-cut quartz crystal substrates for making deep trench patterns using Au/Cr metal hard masks and proposed the first quartz fabrication dimension compensation strategy. The size effect of various sizes of hard mask patterns on the undercut developed in wet etching was experimentally investigated. Quartz wafers masked with initial vias ranging from 3 µm to 80 µm in width were etched in a buffered oxide etch solution (BOE, HF:NH4F = 3:2) at 80 °C for prolonged etching (>95 min). It was found that a larger hard mask width resulted in a smaller undercut, and a 30 µm difference in hard mask width would result in a 17.2% increase in undercut. In particular, the undercuts were mainly formed in the first 5 min of etching with a relatively high etching rate of 0.7 µm/min (max). Then, the etching rate decreased rapidly to 27%. Furthermore, based on the etching width compensation and etching position compensation, new solutions were proposed for quartz crystal device fabrication. And these two kinds of compensation solutions were used in the fabrication of an ultra-small quartz crystal tuning fork with a resonant frequency of 32.768 kHz. With these approaches, the actual etched size of critical parts of the device only deviated from the designed size by 0.7%. And the pattern position symmetry of the secondary lithography etching process was improved by 96.3% compared to the uncompensated one. It demonstrated significant potential for improving the fabrication accuracy of quartz crystal devices.

Pseudogene CSPG4P12 inhibits colorectal cancer progression by attenuating epithelial-mesenchymal transition.

Colorectal cancer is one of the most common malignant cancers. Pseudogenes have been identified as oncogenes or tumor suppressor genes in the development of various cancers. However, the function of pseudogene CSPG4P12 in colorectal cancer remains unclear. Therefore, the aim of this study was to investigate the potential role of CSPG4P12 in colorectal cancer and explore the possible underlying mechanism. The difference of CSPG4P12 expression between colorectal cancer tissues and adjacent normal tissues was analyzed using the online Gene Expression Profiling Interactive Analysis 2 (GEPIA2) database. Cell viability and colony formation assays were conducted to evaluate cell viability. Transwell and wound healing assays were performed to assess cell migration and invasion capacities. Western blot was used to measure the expression levels of epithelial-mesenchymal transition-related proteins. Colorectal cancer tissues had lower CSPG4P12 expression than adjacent normal tissues. The overexpression of CSPG4P12 inhibited cell proliferation, invasion, and migration in colorectal cancer cells. Overexpressed CSPG4P12 promoted the expression of E-cadherin, whereas it inhibited the expression of vimentin, N-cadherin, and MMP9. These findings suggested that CSPG4P12 inhibits colorectal cancer development and may serve as a new potential target for colorectal cancer.

The Characteristics of Coronary Artery Lesions in COVID-19 Infected Patients With Coronary Artery Disease: An Optical Coherence Tomography Study.

COVID-19 may predispose patients to cardiac injuries but whether COVID-19 infection affects the morphological features of coronary plaques to potentially influence the outcome of patients with coronary artery disease (CAD) remains unknown. By using optical coherence tomography (OCT), this study compared the characteristics of coronary plaque in patients with CAD with/without COVID-19 infection. The 206 patients were divided into 2 groups. The COVID-19 group had 113 patients between December 7, 2022, and March 31, 2023, who received OCT assessment after China decided to lift the restriction on COVID-19 and had a history of COVID-19 infection. The non-COVID-19 group had 93 patients without COVID-19 infection who underwent OCT before December 7, 2022. The COVID-19 group demonstrated a higher incidence of plaque ruptures (53.1% vs 38.7%, p = 0.039), erosions (28.3% vs 11.8%, p = 0.004), fibrous (96.5% vs 89.2%, p = 0.041) and diffuse lesions (73.5% vs 50.5%, p <0.001) compared with the non-COVID-19 group, whereas non-COVID-19 group exhibited a higher frequency of cholesterol crystals (83.9% vs 70.8%, p = 0.027), deep calcifications (65.6% vs 51.3%, p = 0.039) and solitary lesions (57.0% vs 34.5%, p = 0.001). Kaplan-Meier survival analysis revealed a significantly lower major adverse cardiac events-free probability in the COVID-19 group (91.6% vs 95.5%, p = 0.006) than in the non-COVID-19 group. In conclusion, OCT demonstrated that COVID-19 infection is associated with coronary pathological changes such as more plaque ruptures, erosions, fibrosis, and diffuse lesions. Further, COVID-19 infection is associated with a higher propensity for acute coronary events and a higher risk of major adverse cardiac events in patients with CAD.

LINC00511 promotes melanoma progression by targeting miR-610/NUCB2.

Long intergenic noncoding RNA 00511 (LINC00511) predicts poor prognosis in various malignancies and functions as an oncogene in distinct malignant tumors. The role of LINC00511 in melanoma progression was assessed. In our research, expression of LINC00511 in melanoma cells was detected by quantitative reverse transcription PCR. Colony formation and CCK8 assays were used to detect cell proliferation. Cell metastasis was evaluated by transwell and wound healing assays. Downstream target of LINC00511 was investigated by luciferase activity assay. As a results, LINC00511 was elevated in melanoma cells and tissues. Loss of LINC00511 decreased cell viability, reduced proliferation, invasion, and migration of melanoma. miR-610 was target of LINC00511, and miR-610 binds to 3'UTR of nucleobindin-2 (NUCB2). Inhibition of miR-610 attenuated LINC00511 deficiency-induced decrease of NUCB2 in melanoma cells. Loss of miR-610 weakened LINC00511 deficiency-induced decrease of cell viability, proliferation, invasion, and migration of melanoma. In conclusion, silence of LINC00511 reduced cell proliferation and metastasis of melanoma through down-regulation of miR-610-mediated NUCB2.

Synthesis of a ZnO nanowire array within minutes.

A ZnO nanowire array was successfully synthesized within 10 minutes, for the first time, through electrodeposition of a Zn nanocrystal coating followed by a microwave hydrothermal treatment, representing the cheapest and fastest route from aqueous solutions so far. This simple, economical, efficient, flexible and scalable method shows attractive prospects for industrial application.

miRNA-633 and KAI1 as Potential Biomarkers of Malignant Melanoma with Gastric Cancer.

OBJECTIVE: Malignant melanoma with gastric cancer is one of the most malignant tumors. However, there have been no reports on the effects of KAI1 and miRNA-633 on the survival and prognosis of patients with malignant melanoma with gastric cancer. METHODS: Fifty patients with malignant melanoma and gastric cancer were collected from October 2017 to December 2019. The clinical parameters included clinical information, such as sex, age, tumor size, and tumor staging. RT-qPCR was used to detect the expression of KAI1 and miRNA- 633. The role of KAI1 and miRNA-633 on the overall survival of melanoma was explored by the Pearson chi-square test, Spearman-rho correlation test, Univariate and multivariate cox regression analyses, and Kaplan-Meier method. Furthermore, the bioinformatic analysis was used to verify the role of KAI1 and miRNA-633 on malignant melanoma with gastric cancer. RESULTS: The expression of KAI1 and miRNA-633 was significantly related with the tumor size and staging of tumor (p<0.05) based on the Pearson chi-square test. Spearman's correlation coefficient displayed that KAI1 was significantly correlated with the miRNA-633 (ρ=-0.439, p=0.001). The result of multivariate cox proportional regression analysis showed that KAI1 (HR =0.109, 95% CI: 0.031-0.375, p< 0.001), and miRNA-633 (HR = 13.315, 95% CI: 3.844-46.119, p<0.001) were significantly associated with overall survival. CONCLUSION: The low expression level of KAI1 and high expression of miRNA-633 are significantly correlated with the poor overall survival prognosis of malignant melanoma with gastric cancer, to provide a basis for KAI1 and miRNA-633 to become novel molecular targets for malignant melanoma with gastric cancer.

A Comparison Study on the Therapeutic Effect of High Protein Diets Based on Pork Protein versus Soybean Protein on Obese Mice.

In this study, an obese C57BL/6J mice model was induced to compare the effect of different high protein diets (soybean protein and pork protein) on obesity. The obese mice were randomly divided into four groups: natural recovery (NR), high-fat diet (HF), high soybean protein diet (HSP), and high pork protein diet (HPP) groups. After 12 weeks of dietary intervention, the obesity-related indexes of mice were measured, such as body weight, fat coefficients, blood lipid indexes and so on. Results showed that HSP and HPP decreased the weight and fat coefficients of mice, the levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and leptin (p < 0.05). Soybean protein was shown to be more effective in reducing the weight and fat mass of obese mice, although pork protein seemed to have a better effect on regulating serum triglyceride (TG). In addition, the two high protein diets both alleviated hepatic fat deposition effectively. Furthermore, HPP and HSP decreased the expression of hepatic peroxisome proliferator-activated receptor-γ (PPAR-γ) and increased the protein expression of phosphorylated AMP-activated protein kinase (pAMPK), phosphorylated acetyl CoA carboxylase (pACC), and uncoupling protein 2 (UCP2) (p < 0.05). In conclusion, the study shows that high protein diets based on both pork protein and soybean protein alleviated abdominal obesity in mice effectively by regulating lipid metabolism, probably via the UCP2-AMPK-ACC signaling pathway.

The genetic and epigenetic regulation of CD55 and its pathway analysis in colon cancer.

Background: CD55 plays an important role in the development of colon cancer. This study aims to evaluate the expression of CD55 in colon cancer and discover how it is regulated by transcriptional factors and miRNA. Methods: The expression of CD55 was explored by TIMER2.0, UALCAN, and Human Protein Atlas (HPA) databases. TRANSFAC and Contra v3 were used to predict the potential binding sites of transcription factors in the CD55 promoter. TargetScan and starBase v2.0 were used to predict the potential binding ability of miRNAs to the 3' untranslated region (3'UTR) of CD55. SurvivalMeth was used to explore the differentially methylated sites in the CD55 promoter. Western blotting was used to detect the expression of TFCP2 and CD55. Dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were performed to determine the targeting relationship of TFCP2, NF-κB, or miR-27a-3p with CD55. CD55-related genes were explored by constructing a protein-protein interaction (PPI) network and performing pathway analysis by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: CD55 was highly expressed in colon cancer tissues. The mRNA and protein expression levels of TFCP2 were reduced by si-TFCP2. NF-κB mRNA was obviously reduced by NF-κB inhibitor and increased by NF-κB activator. CD55 protein was also inhibited by miR-27a-3p. Dual-luciferase reporter assays showed that after knocking down TFCP2 or inhibiting NF-κB, the promoter activity of CD55 was decreased by 21% and 70%, respectively; after activating NF-κB, the promoter activity of CD55 increased by 2.3 times. As TFCP2 or NF-κB binding site was mutated, the transcriptional activity of CD55 was significantly decreased. ChIP assay showed that TFCP2 and NF-κB combined to the promoter of CD55. The luciferase activity of CD55 3'UTR decreased after being co-transfected with miR-27a-3p mimics and increased by miR-27a-3p antagomir. As the miR-27a-3p binding site was mutated, we did not find any significant effect of miR-27a-3p on reporter activity. PPI network assay revealed a set of CD55-related genes, which included CFP, CFB, C4A, and C4B. GO and KEGG analyses revealed that the target genes occur more frequently in immune-related pathways. Conclusion: Our results indicated that CD55 is regulated by TFCP2, NF-κB, miR-27a-3p, and several immune-related genes, which in turn affects colon cancer.

Immunolipidomics Reveals a Globoside Network During the Resolution of Pro-Inflammatory Response in Human Macrophages.

Toll-like receptor 4 (TLR4)-mediated changes in macrophages reshape intracellular lipid pools to coordinate an effective innate immune response. Although this has been previously well-studied in different model systems, it remains incompletely understood in primary human macrophages. Here we report time-dependent lipidomic and transcriptomic responses to lipopolysaccharide (LPS) in primary human macrophages from healthy donors. We grouped the variation of ~200 individual lipid species measured by LC-MS/MS into eight temporal clusters. Among all other lipids, glycosphingolipids (glycoSP) and cholesteryl esters (CE) showed a sharp increase during the resolution phase (between 8h or 16h post LPS). GlycoSP, belonging to the globoside family (Gb3 and Gb4), showed the greatest inter-individual variability among all lipids quantified. Integrative network analysis between GlycoSP/CE levels and genome-wide transcripts, identified Gb4 d18:1/16:0 and CE 20:4 association with subnetworks enriched for T cell receptor signaling (PDCD1, CD86, PTPRC, CD247, IFNG) and DC-SIGN signaling (RAF1, CD209), respectively. Our findings reveal Gb3 and Gb4 globosides as sphingolipids associated with the resolution phase of inflammatory response in human macrophages.

Understanding the systemic burden of disease in hidradenitis suppurativa from plasma lipidomic analysis.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory skin condition that is often considered a systemic disease due to its association with metabolic comorbidity. OBJECTIVE: In this study, we aimed to identify differences in plasma lipidomic profiles between HS patients and control subjects. METHODS: HS patients were recruited from a tertiary dermatological centre and demographic and comorbidity matched controls from the general population. A targeted lipidomic approach was performed to characterize over 700 lipid species representing 35 lipid classes/sub-classes. Linear regression models adjusted for confounding factors were used to compare the plasma lipidomic profiles of HS patients to controls. Ordinal regression models were used to study the association of lipids with disease activity and severity scores. RESULTS: 60 HS patients and 73 control subjects were recruited. Differential levels (p < 0.05) of 32 lipid species in HS patients compared to controls were observed, including a decrease in the long chain base d19:1 containing ceramides, and elevation of hydroxyeicosatetraenoic acid (HETE) and dihydroxyeicosatrienoic acid (DHET) oxylipins. These lipids along with several other molecules showed associations with Hurley, HS-PGA and disease activity scores. CONCLUSION: This study found mild changes in plasma lipidomic profiles, consistent with previous studies showing attenuated metabolomic changes in plasma as opposed to lesional skin. However, a number of lipid species were associated with increasing activity and severity of the disease. Further, the significant lipid species within the same class showed consistent trends of increase or decrease in HS as compared to controls.

Transient Complexity of E. coli Lipidome Is Explained by Fatty Acyl Synthesis and Cyclopropanation.

In the case of many bacteria, such as Escherichia coli, the composition of lipid molecules, termed the lipidome, temporally adapts to different environmental conditions and thus modifies membrane properties to permit growth and survival. Details of the relationship between the environment and lipidome composition are lacking, particularly for growing cultures under either favourable or under stress conditions. Here, we highlight compositional lipidome changes by describing the dynamics of molecular species throughout culture-growth phases. We show a steady cyclopropanation of fatty acyl chains, which acts as a driver for lipid diversity. There is a bias for the cyclopropanation of shorter fatty acyl chains (FA 16:1) over longer ones (FA 18:1), which likely reflects a thermodynamic phenomenon. Additionally, we observe a nearly two-fold increase in saturated fatty acyl chains in response to the presence of ampicillin and chloramphenicol, with consequences for membrane fluidity and elasticity, and ultimately bacterial stress tolerance. Our study provides the detailed quantitative lipidome composition of three E. coli strains across culture-growth phases and at the level of the fatty acyl chains and provides a general reference for phospholipid composition changes in response to perturbations. Thus, lipidome diversity is largely transient and the consequence of lipid synthesis and cyclopropanation.

Predictors of circulating vitamin D levels in healthy mid-life Singaporean women.

Vitamin D levels were lowest in Indian and Malay compared to Chinese women, and in younger and employed women. The main reason for hypovitaminosis D in study women was deficient cutaneous production. Supplementation in regions with abundant sunshine should consider ethnicity and opportunities for exposure to sunlight. INTRODUCTION: Little is known about variations in circulating vitamin D levels in multiethnic mid-life women living in communities with year-round sunlight. Our study describes the circulating vitamin D levels and their sociodemographic predictors in mid-life Singaporean women. METHODS: Prospective cross-sectional study of healthy Singaporean women, age 45-69 years, who were not consuming vitamin D supplements. Total 25-hydroxyvitaminD [25(OH)D], the sum of 25(OH)D2 and 25(OH)D3, was measured by liquid chromatography-tandem mass spectrometry. RESULTS: The analytic cohort of 721 women, mean age 55.2±6.0 (±SD) years, was of Chinese (82%), Indian (11%), and Malay (7%) ethnicity. Their mean 25(OH)D level was 24.8±7.8ng/mL. One-third (32.6%) of the women had deficient 25(OH)D (≤20ng/mL) and 3.5% were severely deficient (<12ng/mL). 25(OH)D3 comprised 98% of the total circulating 25(OH)D level. Adjusted mean total 25(OH)D levels were significantly lower for women of Indian and Malay (vs Chinese) ethnicity, who were premenopausal or working outside the home. Indian and Malay women had higher odds (adjusted OR 5.58 (95% CI 3.22, 9.87) and 3.83 (95% CI 1.97, 7.57), respectively) of low 25(OH)D compared to Chinese women. Obesity was not an independent predictor of low 25(OH)D, as its strong crude association was confounded by ethnicity. The adjusted odds of low 25(OH)D was reduced in women ≥65 years (adjusted OR 0.37 (95% CI 0.14, 0.87)) compared to those aged 45-55 years. CONCLUSION: One-third of mid-life Singaporean women were 25(OH)D deficient, and the major independent predictors of deficiency were Indian or Malay ethnicity and younger age. Vitamin D supplementation in mid-life women should be targeted to those with documented deficiency or limited cutaneous production.

A reference map of sphingolipids in murine tissues.

Sphingolipids (SPs) have both a structural role in the cell membranes and a signaling function that regulates many cellular processes. The enormous structural diversity and low abundance of many SPs pose a challenge for their identification and quantification. Recent advances in lipidomics, in particular liquid chromatography (LC) coupled with mass spectrometry (MS), provide methods to detect and quantify many low-abundant SP species reliably. Here we use LC-MS to compile a "murine sphingolipid atlas," containing the qualitative and quantitative distribution of 114 SPs in 21 tissues of a widely utilized wild-type laboratory mouse strain (C57BL/6). We report tissue-specific SP fingerprints, as well as sex-specific differences in the same tissue. This is a comprehensive, quantitative sphingolipidomic map of mammalian tissues collected in a systematic fashion. It will complement other tissue compendia for interrogation into the role of SP in mammalian health and disease.