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Abstract Ferroptosis is a newly identified form of regulated cell death (RCD) characterized by the iron-dependent lipid reactive oxygen species (ROS) accumulation, but its mechanism in gliomas remains elusive. Acyl–coenzyme A (CoA) synthetase long-chain family member 4 (Acsl4), a pivotal enzyme in the regulation of lipid biosynthesis, benefits the initiation of ferroptosis, but its role in gliomas needs further clarification. Erastin, a classic inducer of ferroptosis, has recently been found to regulate lipid peroxidation by regulating Acsl4 other than glutathione peroxidase 4 (GPX4) in ferroptosis. In this study, we demonstrated that heat shock protein 90 (Hsp90) and dynamin-related protein 1 (Drp1) actively regulated and stabilized Acsl4 expression in erastin-induced ferroptosis in gliomas. Hsp90 overexpression and calcineurin (CN)–mediated Drp1 dephosphorylation at serine 637 (Ser637) promoted ferroptosis by altering mitochondrial morphology and increasing Acsl4-mediated lipid peroxidation. Importantly, promotion of the Hsp90–Acsl4 pathway augmented anticancer activity of erastin in vitro and in vivo. Our discovery reveals a novel and efficient approach to ferroptosis-mediated glioma therapy.

Although there has been a substantial body of research on the chemical stabilization of sewage sludge, most of these results are project-specific and relate mainly to the use of new binders and sewage sludge from specific sources. In this sense, much of the work to date is context-specific. At present, there is still no general framework for estimating the strength of the chemically treated sludge. This paper proposes one such general framework, based on data from some recent studies. An in-depth re-interpretation of the data is first conducted, leading to the observation that sludge, which has coarse, hard particulate inclusions, such as sand, premixed into it, gives significantly higher strength. This was attributed to the hard coarse particles that lower the void ratio of treated soil, are much less susceptible to volume collapse under pressure, and contribute to the strength through frictional contacts and interlocking. This motivates the postulation of a general framework, based on the premise that coarse, hard particulate inclusions in the sludge which do not react with the binders can nonetheless contribute to the strength of the treated soil. The overall void ratio, defined as the volume of voids in the cementitious matrix normalised by the overall volume, is proposed as a parameter for quantifying the combined effect of the coarse particulate inclusions and the cementitious matrix. The binder-sludge ratio is another parameter which quantifies the strength of the cementitious matrix, excluding the hard particulate inclusions. Back-analysis of the data suggests that the significance of the binder-sludge ratio may diminish as the content of hard particulate inclusions increases.

AGPATs (1-acylglycerol-3-phosphate O-acyltransferases) catalyze the acylation of lysophosphatidic acid to form phosphatidic acid (PA), a key step in the synthesis of all glycerolipids. Here, the authors show that AGPAT2 and CDP-DAG synthases (CDS1 and CDS2) form functional complexes that promote further conversion of PA along the CDP-DAG pathway of phospholipid synthesis.

Prokineticin-2 (Prok2) is a secreted protein involved in many physiological processes. Here, the authors show that Prok2 prevents neuronal cell ferroptosis after traumatic brain injury and its administration before cortical injury reduces neuronal degeneration, and motor and cognitive impairments.

Diheme-containing succinate:menaquinone oxidoreductases (Sdh) are members of the complex II superfamily. Here, the authors present the 2.8 Å cryo-EM structure of Mycobacterium smegmatis Sdh2, which reveals membrane-anchored SdhF as a component of the complex and they discuss the electron/proton transfer pathway in the Sdh2 trimer.

Abstract Background & aims Emerging evidence supports ambient fine particulate matter (PM2.5) exposure is associated with insulin resistance (IR) and hepatic lipid accumulation. In this study, we aimed to evaluate the sex-dependent vulnerability in response to PM2.5 exposure and investigate the underlying mechanism by which PM2.5 modulates hepatic lipid metabolism. Methods Both male and female C57BL/6 mice were randomly assigned to ambient PM2.5 or filtered air for 24 weeks via a whole body exposure system. High-coverage quantitative lipidomics approaches and liquid chromatography-mass spectrometry techniques were performed to measure hepatic metabolites and hormones in plasma. Metabolic studies, histological analyses, as well as gene expression levels and molecular signal transduction analysis were applied to examine the effects and mechanisms by which PM2.5 exposure-induced metabolic disorder. Results Female mice were more susceptible than their male counterparts to ambient PM2.5 exposure-induced IR and hepatic lipid accumulation. The hepatic lipid profile was changed in response to ambient PM2.5 exposure. Levels of hepatic triacylglycerols (TAGs), free fatty acids (FFAs) and cholesterol were only increased in female mice from PM group compared to control group. Plasmalogens were dysregulated in the liver from PM2.5-exposed mice as well. In addition, exposure to PM2.5 led to enhanced hepatic ApoB and microsomal triglyceride transport protein expression in female mice. Finally, PM2.5 exposure inhibited hypothalamus-pituitary-adrenal (HPA) axis and decreased glucocorticoids levels, which may contribute to the vulnerability in PM2.5-induced metabolic dysfunction. Conclusions Ambient PM2.5 exposure inhibited HPA axis and demonstrated sex-associated differences in its effects on IR and disorder of hepatic lipid metabolism. These findings provide new mechanistic evidence of hormone regulation in air pollution-mediated metabolic abnormalities of lipids and more personalized care should be considered in terms of sex-specific risk factors.

Flight loss has occurred numerous times in bird evolution. Here, the authors examine convergent sites in the exonic and intronic sequences of 48 bird genomes, finding amino-acid changes in two genes, ATGL and ACOT7, with potential implications for a change in metabolism rather than anatomy.

The Greater Bay Area of southern China has a population of over 71 million people. The area is well-connected with Hubei province, the epicenter of the COVID-19 outbreak. Macau, as the most densely populated city in the world, is very vulnerable to infectious disease outbreaks. Since its return to the sovereignty of China 20 years ago, the city has experienced outbreaks such as severe acute respiratory syndrome (SARS), Swine flu, and COVID-19. At the time of writing, 10 confirmed imported/local transmission cases were recorded. The government undertook measures to attain and then maintain 40 days without new cases. In this article, we report on the 10 confirmed cases and discuss the measures that the Macau Special Administrative Region (S.A.R.) government undertook during the COVID-19 pandemic.

Metabolic changes associated with diabetes are reported to lead to the onset of early-stage diabetic nephropathy (DN). Furthermore, lipotoxicity is implicated in renal dysfunction. Most studies of DN have focused on a single or limited number of lipids, and the lipidome of the kidney during early-stage DN remains to be elucidated. In the present study, we aimed to comprehensively identify lipid abnormalities during early-stage DN; to this end, we established an early-stage DN rat model by feeding a high-sucrose and high-fat diet combined with administration of low-dose streptozotocin. Using a high-coverage, targeted lipidomic approach, we established the lipid profile, comprising 437 lipid species and 25 lipid classes, of the kidney cortex in normal rats and the DN rat model. Our findings additionally confirmed that the DN rat model had been successfully established. We observed distinct lipidomic signatures in the DN kidney, with characteristic alterations in side chain composition and degree of unsaturation. Glyceride lipids, especially cholesteryl esters, showed a significant increase in the DN kidney cortex. The levels of most phospholipids exhibited a decline, except those of phospholipids with side chain of 36:1. Furthermore, the levels of lyso-phospholipids and sphingolipids, including ceramide and its derivatives, were dramatically elevated in the present DN rat model. Our findings, which provide a comprehensive lipidome of the kidney cortex in rats with DN, are expected to be useful for the identification of pathologically relevant lipid species in DN. Furthermore, the results represent novel insights into the mechanistic basis of DN.

We examined the incidence and predictors of threat perceptions toward people who oppose government action (i.e., protestors) following the Umbrella Movement in Hong Kong (September 28th to December 15th, 2014). A population-representative sample of 1,208 citizens (mean age = 46.89 years; 52.4% female) was recruited two months after the conclusion of the Movement using random digit dialing. Upon giving their informed consent, respondents reported sociodemographics, perceived threats of protestors to the prospects of democracy, ways of life, and the economy, anxiety symptoms (STAI), and depressive symptoms (PHQ-9). More than half disagreed that protestors threatened the prospects of democracy (54.7%, 95% CI = .52, .57), ways of life (52.2%, 95% CI = .49, .55), and the economy (51.4%, 95% CI = .49, .54). Regression analyses revealed that male sex was associated with lower odds of perceiving threats to the prospects of democracy and ways of life. Being unmarried was associated with lower odds of perceiving threats to the economy. Secondary education level and depressive symptoms were associated with higher odds of perceiving threats to ways of life and the economy, respectively. This is one of the first population-based studies that measured socioeconomic and mental health correlates of political attitudes immediately following pro-democracy movements.

The acetyltransferase Tip60 mediates signaling pathways by acetylating non-histone proteins. Here the authors show that fatty acids induce Tip60–dependent acetylation of phosphatidic acid phosphatase lipin1 which, then, translocates to the ER and generates diacylglycerols for triglyceride synthesis.

This study evaluates a short therapy schedule for bladder cancer using BCG Tokyo. BCG Tokyo was evaluated in vitro using bone marrow derived dendritic cells, neutrophils, RAW macrophages and the murine bladder cancer cell line, MB49PSA, and compared to other BCG strains. BCG Tokyo > BCG TICE at inducing cytokine production. In vivo, high dose (1 × 107 colony forming units (cfu)) and low dose (1 × 106 cfu) BCG Tokyo with and without cytokine genes (GMCSF + IFNα) were evaluated in C57BL/6J mice (n = 12–16 per group) with orthotopically implanted MB49PSA cells. Mice were treated with four instillations of cytokine gene therapy and BCG therapy. Both high dose BCG alone and low dose BCG combined with cytokine gene therapy were similarly effective. In the second part the responsive groups, mice (n = 27) were monitored by urinary PSA analysis for a further 7 weeks after therapy cessation. More mice were cured at day 84 than at day 42 confirming activation of the immune system. Cured mice resisted the re-challenge with subcutaneous tumors unlike naïve, age matched mice. Antigen specific T cells recognizing BCG, HY and PSA were identified. Thus, fewer intravesical instillations, with high dose BCG Tokyo or low dose BCG Tokyo with GMCSF + IFNα gene therapy, can induce effective systemic immunity.

Mechanistic basis governing the extreme longevity and developmental quiescence of dauer juvenile, a “non-ageing” developmental variant of Caenorhabditis elegans, has remained largely obscure. Using a lipidomic approach comprising multiple reaction monitoring transitions specific to distinct fatty acyl moieties, we demonstrated that in comparison to other developmental stages, the membrane phospholipids of dauer larva contain a unique enrichment of polyunsaturated fatty acids (PUFAs). Esterified PUFAs in phospholipids exhibited temporal accumulation throughout the course of dauer endurance, followed by sharp reductions prior to termination of diapause. Reductions in esterified PUFAs were accompanied by concomitant increases in unbound PUFAs, as well as their corresponding downstream oxidized derivatives (i.e. eicosanoids). Global phospholipidomics has unveiled that PUFA sequestration in membrane phospholipids denotes an essential aspect of dauer dormancy, principally via suppression of eicosanoid production; and a failure to upkeep membrane lipid homeostasis is associated with termination of dauer endurance. Keywords: Dauer larva, Phospholipids, Polyunsaturated fatty acids, Eicosanoids, Lipidomics, Caenorhabditis elegans

Dye wastewater management has been a challenging task for the textile industry. In this study, basidiomycetes fungi was explored for its ability to degrade dye. Isolate EL2, collected from the decaying woods around Kampar, Perak, Malaysia was selected for this purpose. The collected isolate was identified as Trametes ljubarskyi by using a molecular characterization method and morphological observation. Then, it was screened with solid agar supplemented with 2,2-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid, guaiacol and Remazol Brillant Blue R dye for laccase production. Four different nitrogen sources were involved in further liquid screening for optimization of laccase production in EL2. Based on the results obtained, urea is the best candidate, as it was able to produce maximal laccase activity of 50.82 U/(L·d), as compared to three other nitrogen sources (1.11–5.08 U/(L·d)). Besides, EL2 was able to significantly decolourize Reactive Violet 5 (97.92%) on day 7.

Summary: The relation between gut microbiota and the host has been suggested to benefit metabolic homeostasis. Brown adipose tissue (BAT) and beige adipocytes facilitate thermogenesis to maintain host core body temperature during cold exposure. However, the potential impact of gut microbiota on the thermogenic process is confused. Here, we evaluated how BAT and white adipose tissue (WAT) responded to temperature challenges in mice lacking gut microbiota. We found that microbiota depletion via treatment with different cocktails of antibiotics (ABX) or in germ-free (GF) mice impaired the thermogenic capacity of BAT by blunting the increase in the expression of uncoupling protein 1 (UCP1) and reducing the browning process of WAT. Gavage of the bacterial metabolite butyrate increased the thermogenic capacity of ABX-treated mice, reversing the deficit. Our results indicate that gut microbiota contributes to upregulated thermogenesis in the cold environment and that this may be partially mediated via butyrate. : Li et al. use different antibiotic recipes and germ-free mice to demonstrate the dependence of UCP1-dependent thermogenesis in the cold on the presence of a healthy gut microbiome. Gavage with butyrate partly rescues the effect, indicating a role for this molecule in normal thermogenic responses to low temperature. Keywords: brown adipose tissue, beige adipocytes, brite adipocytes, white adipose tissue, hermogenesis, UCP1, gut microbiota, butyrate, antibiotics, germ free mice, macrophage, IL-4

A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21616-3

Various species of globeflowers, belonging to the genus Trollius, have been extensively used in traditional Chinese medicine due to their anti-inflammatory, antimicrobial, and antiviral properties, which are mainly attributed to their high polyphenol content. Differences in polyphenol composition, and abundances, will lead to varying treatment efficacies of globeflowers. Herein, we employ a combination of targeted and untargeted mass spectrometry (MS) approaches to characterize and quantify a comprehensive array of polyphenols, mainly including flavonoids and phenolic acids in two globeflower species commonly used in Chinese medicine, Trollius chinensis Bunge and Trollius ledebouri Reichb. In addition, free radical scavenging activity was investigated to evaluate the association between polyphenol composition and antioxidation capacity. Liquid chromatography (LC)-based separation and multiple-reaction-monitoring (MRM) transitions were optimized using a library of 78 polyphenol reference compounds to achieve absolute quantification on triple quadrupoles MS (QqQ). The analytical method was further expanded via high-resolution MS to provide relative quantitation of an additional 104 endogenous polyphenols in globeflowers not included in our reference library. Our results revealed stark differences in polyphenol content between T. chinensis and T. ledebouri, emphasizing the need for systematic characterization of polyphenol composition to ensure treatment efficacy and consistency in standardizing the use of globeflowers in Chinese medicine.

Biofilms are communities of sessile microorganisms that grow and produce extrapolymeric substances on an abiotic or biotic surface. Although biofilms are often associated with negative impacts, the role of beneficial biofilms is wide and include applications in bioremediation, wastewater treatment and microbial fuel cells. Microbial adhesion to a surface, which is highly dependent on the physicochemical properties of the cells and surfaces, is an essential step in biofilm formation. Surface modification therefore represents an important way to modulate microbial attachment and ultimately biofilm formation by microorganisms. In this review different surface modification processes such as organosilane surface modification, plasma treatment, and chemical modification of carbon nanotubes, electro-oxidation and covalent-immobilization with neutral red and methylene blue molecules are outlined. The effectiveness of these modifications and their industrial applications are also discussed. There is inadequate literature on surface modification as a process to enhance beneficial biofilm formation. These methods need to be safe, economically viable, scalable and environmental friendly and their potential to fulfil these criteria for many applications has yet to be determined.

Lipids and lipid metabolites play important roles in plant-microbe interactions. Despite the extensive studies of lipases in lipid homeostasis and seed oil biosynthesis, the involvement of lipases in plant immunity remains largely unknown. In particular, GDSL esterases/lipases, characterized by the conserved GDSL motif, are a subfamily of lipolytic enzymes with broad substrate specificity. Here, we functionally identified two GDSL lipases, OsGLIP1 and OsGLIP2, in rice immune responses. Expression of OsGLIP1 and OsGLIP2 was suppressed by pathogen infection and salicylic acid (SA) treatment. OsGLIP1 was mainly expressed in leaf and leaf sheath, while OsGLIP2 showed high expression in elongating internodes. Biochemical assay demonstrated that OsGLIP1 and OsGLIP2 are functional lipases that could hydrolyze lipid substrates. Simultaneous down-regulation of OsGLIP1 and OsGLIP2 increased plant resistance to both bacterial and fungal pathogens, whereas disease resistance in OsGLIP1 and OsGLIP2 overexpression plants was significantly compromised, suggesting that both genes act as negative regulators of disease resistance. OsGLIP1 and OsGLIP2 proteins mainly localize to lipid droplets and the endoplasmic reticulum (ER) membrane. The proper cellular localization of OsGLIP proteins is indispensable for their functions in immunity. Comprehensive lipid profiling analysis indicated that the alteration of OsGLIP gene expression was associated with substantial changes of the levels of lipid species including monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG). We show that MGDG and DGDG feeding could attenuate disease resistance. Taken together, our study indicates that OsGLIP1 and OsGLIP2 negatively regulate rice defense by modulating lipid metabolism, thus providing new insights into the function of lipids in plant immunity.

The general transcription factor TBP (TATA-box binding protein) and its associated factors (TAFs) together form the TFIID complex, which directs transcription initiation. Through RNAi and mutant analysis, we identified a specific TBP family protein, TRF2, and a set of TAFs that regulate lipid droplet (LD) size in the Drosophila larval fat body. Among the three Drosophila TBP genes, trf2, tbp and trf1, only loss of function of trf2 results in increased LD size. Moreover, TRF2 and TAF9 regulate fatty acid composition of several classes of phospholipids. Through RNA profiling, we found that TRF2 and TAF9 affects the transcription of a common set of genes, including peroxisomal fatty acid β-oxidation-related genes that affect phospholipid fatty acid composition. We also found that knockdown of several TRF2 and TAF9 target genes results in large LDs, a phenotype which is similar to that of trf2 mutants. Together, these findings provide new insights into the specific role of the general transcription machinery in lipid homeostasis.

Objectives: This experiment was conducted to examine the toxicity of WCF (Water soluble Carthmi-Flos herbal acupuncture) by administering a single intramuscular dose of WCF in 6-week-old, male and female Sprague-Dawley rats and to find the lethality dose for WCF. Methods: The experiment was conducted at Biotoxtech according to Good Laboratory Practices under a request by the Korean Pharmacopuncture Institute. This experiment was performed based on the testing standards of “Toxicity Test Standards for Drugs” by the Ministry of Food and Drug Safety. Subjects were divided into 4 groups: 1 control group in which normal saline was administered and 3 test groups in which 0.1, 0.5 or 1.0 mL of WCF was administered; a single intramuscular dose was injected into 5 males and 5 females in each group. General symptoms and body weights were observed/measured for 14 days after injection. At the end of the observation period, hematological and clinical chemistry tests were performed, followed by necropsy and histopathological examinations of the injected sections. Results: No mortalities were observed in any group. Also, symptoms, body weight, hematology, clinical chemistry and necropsy were not affected. However, histopathological examination of the injected part in one female in the 1.0-mL group showed infiltration of mononuclear cells and a multi-nucleated giant cell around eosinophilic material. Conclusion: Administration of single intramuscular doses of WCF in 3 groups of rats showed that the approximate lethal dose of WCF for all rats was in excess of 1.0 mL, as no mortalities were observed for injections up to and including 1.0 mL.

Background: White adipose tissue (WAT) browning confers beneficial effects on metabolic diseases. However, visceral adipose tissue (VAT) is not as susceptible to browning as subcutaneous adipose tissue (SAT). Aim: Interpreting the heterogeneity of VAT and SAT in brown remodeling and provide promising lipid targets to promote WAT browning. Methods: We first investigated the effects of β3-adrenergic stimulation by CL316,243 on systemic metabolism. Then, high-coverage targeted lipidomics approach with multiple reaction monitoring (MRM) was utilized to provide extensive detection of lipid metabolites in VAT and SAT. Results: CL316,243 notably ameliorated the systemic metabolism and induced brown remodeling of SAT but browning resistance of VAT. Comprehensive lipidomics analysis revealed browning heterogeneity of VAT and SAT with more dramatic alteration of lipid classes and species in VAT rather than SAT, though VAT is resistant to browning. Adrenergic stimulation differentially affected glycerides content in VAT and SAT and boosted the abundance of more glycerophospholipids species in VAT than in SAT. Besides, CL316,243 increased sphingolipids in VAT without changes in SAT, meanwhile, elevated cardiolipin species more prominently in VAT than in SAT. Conclusions: We demonstrated the browning heterogeneity of WAT and identified potential lipid biomarkers which may provide lipid targets for overcoming VAT browning resistance.

Objectives: This study was performed to analyze the toxicity of the test substance, anti-inflammatory pharmacopuncture (AIP), when used as a single intramuscular-dose in 6-week-old, male and female Sprague-Dawley rats and to find the lethal dose. Methods: The experiment was conducted at Biotoxtech according to Good Laboratory Practices. Twenty (20) female and 20 male Spague-Dawley rats were divided into 4 groups of five 5 female and 5 male animals per group. The rats in the three experimental groups received single intramuscular injections with 0.1-㎖, 0.5-㎖ and 1.0-㎖/animal doses of AIP, Groups 2, 3, and 4, respectively, and the control group, Group 1, received a single intramuscular injection with a 1.0-㎖ dose of normal saline. Clinical signs were observed and body weight measurements were carried out for 14 days following the injections. At the end of the observation period, hematology, clinical chemistry, histopathological tests and necropsy were performed on the injected parts. Results: No deaths occurred in any of the groups. Also, histopathological tests showed that AIP had no effect on the injected parts in terms of clinical signs, body weight, hematology, clinical chemistry, and necropsy. Conclusions: As a result of single intramuscular-dose tests of the test substance AIP in 4 groups of rats, the lethal dose for both males and females exceeded 1.0㎖/animal. Therefore, AIP is a relatively safe pharmacopuncture that can be used for treatment, but further studies should be performed.

Seven-month-old infants possess the ability to extract and generalize abstract rules from unimodal sequences of auditory syllables such as ABA and ABB whereas five-month-old infants are facilitated in their learning of these rules by bimodal sequences. In the current study, we investigated whether bimodal stimuli could also help infants acquire what we consider a more difficult abstract rule: AAB. Nineteen 8- to 9-month-old infants were habituated to the AAB rule with simultaneous visual shapes and speech sounds. They were later tested on their ability to discriminate this sequence from ABA and ABB with their looking times measured after each stimulus presentation at test periods. There was no significant difference in looking times amongst the different sequences, suggesting infants were not able to formulate an AAB rule different from those for ABA and ABB. Older infants' inability to utilize extra sensory information to acquire an abstract rule in which younger ones were ready to learn from unimodal stimulus (speech) was unexpected. It is unclear what leads to the failure of rule learning from bimodal stimuli, but possible explanations including perceptual narrowing in the inter-sensory integration and the difference in sensory representation of abstract rules with different difficulties are discussed.

BACKGROUND: Non-human primates (NHP) are now being considered as models for investigating human metabolic diseases including diabetes. Analyses of cholesterol and triglycerides in plasma derived from NHPs can easily be achieved using methods employed in humans. Information pertaining to other lipid species in monkey plasma, however, is lacking and requires comprehensive experimental analysis. METHODOLOGIES/PRINCIPAL FINDINGS: We examined the plasma lipidome from 16 cynomolgus monkey, Macaca fascicularis, using liquid chromatography coupled with mass spectrometry (LC/MS). We established novel analytical approaches, which are based on a simple gradient elution, to quantify polar lipids in plasma including (i) glycerophospholipids (phosphatidylcholine, PC; phosphatidylethanolamine, PE; phosphatidylinositol, PI; phosphatidylglycerol, PG; phosphatidylserine, PS; phosphatidic acid, PA); (ii) sphingolipids (sphingomyelin, SM; ceramide, Cer; Glucocyl-ceramide, GluCer; ganglioside mannoside 3, GM3). Lipidomic analysis had revealed that the plasma of human and cynomolgus monkey were of similar compositions, with PC, SM, PE, LPC and PI constituting the major polar lipid species present. Human plasma contained significantly higher levels of plasmalogen PE species (p

Abstract In this community effort, we compare measurements between 34 laboratories from 19 countries, utilizing mixtures of labelled authentic synthetic standards, to quantify by mass spectrometry four clinically used ceramide species in the NIST (National Institute of Standards and Technology) human blood plasma Standard Reference Material (SRM) 1950, as well as a set of candidate plasma reference materials (RM 8231). Participants either utilized a provided validated method and/or their method of choice. Mean concentration values, and intra- and inter-laboratory coefficients of variation (CV) were calculated using single-point and multi-point calibrations, respectively. These results are the most precise (intra-laboratory CVs ≤ 4.2%) and concordant (inter-laboratory CVs < 14%) community-derived absolute concentration values reported to date for four clinically used ceramides in the commonly analyzed SRM 1950. We demonstrate that calibration using authentic labelled standards dramatically reduces data variability. Furthermore, we show how the use of shared RM can correct systematic quantitative biases and help in harmonizing lipidomics. Collectively, the results from the present study provide a significant knowledge base for translation of lipidomic technologies to future clinical applications that might require the determination of reference intervals (RIs) in various human populations or might need to estimate reference change values (RCV), when analytical variability is a key factor for recall during multiple testing of individuals.

Abstract Disruption of ciliary homeostasis in vascular endothelial cells has been implicated in the development of atherosclerosis. However, the molecular basis for the regulation of endothelial cilia during atherosclerosis remains poorly understood. Herein, we provide evidence in male mice that the accumulation of lipid droplets in vascular endothelial cells induces ciliary loss and contributes to atherosclerosis. Triglyceride accumulation in vascular endothelial cells differentially affects the abundance of free fatty acid species in the cytosol, leading to stimulated lipid droplet formation and suppressed protein S-palmitoylation. Reduced S-palmitoylation of ciliary proteins, including ADP ribosylation factor like GTPase 13B, results in the loss of cilia. Restoring palmitic acid availability, either through pharmacological inhibition of stearoyl-CoA desaturase 1 or a palmitic acid-enriched diet, significantly restores endothelial cilia and mitigates the progression of atherosclerosis. These findings thus uncover a previously unrecognized role of lipid droplets in regulating ciliary homeostasis and provide a feasible intervention strategy for preventing and treating atherosclerosis.

Abstract Infection by bacteria leads to tissue damage and inflammation, which need to be tightly controlled by host mechanisms to avoid deleterious consequences. It is previously reported that TMEM16F, a calcium‐activated lipid scramblase expressed in various immune cell types including T cells and neutrophils, is critical for the control of infection by bacterium Listeria monocytogenes (Lm) in vivo. This function correlated with the capacity of TMEM16F to repair the plasma membrane (PM) damage induced in T cells in vitro, by the Lm toxin listeriolysin O (LLO). However, whether the protective effect of TMEM16F on Lm infection in vivo is mediated by an impact in T cells, or in other cell types, is not determined. Herein, the immune cell types and mechanisms implicated in the protective effect of TMEM16F against Lm in vivo are elucidated. Cellular protective effects of TMEM16F correlated with its capacity of lipid scrambling and augment PM fluidity. Using cell type‐specific TMEM16F‐deficient mice, the indication is obtained that TMEM16F expressed in liver Kupffer cells (KCs), but not in T cells or B cells, is key for protection against Listeria in vivo. In the absence of TMEM16F, Listeria induced PM rupture and fragmentation of KCs in vivo. KC death associated with greater liver damage, inflammatory changes, and dysregulated liver metabolism. Overall, the results uncovered that TMEM16F expressed in Kupffer cells is crucial to protect the host against Listeria infection. This influence is associated with the capacity of Kupffer cell‐expressed TMEM16F to prevent excessive inflammation and abnormal liver metabolism.

This article has been withdrawn: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal).The authors reached out to the Publisher to alert the Publisher to incorrect text published in the article. After investigating the situation, the journal came to the conclusion that the wrong version of the file was sent by the authors to the production team during the proof stage and the misplaced text was not noticed by the authors when they approved the final version. After consulting with the Editor-in-Chief of the journal, the decision was made to withdraw the current version of the article.

The occurrence of hyperuricemia (HUA; elevated serum uric acid) in athletes is relatively high despite that exercise can potentially reduce the risk of developing this condition. Although recent studies have shown the beneficial properties of DAG in improving overall metabolic profiles, a comprehensive understanding of the effect of DAG in modulating HUA in athletes is still lacking. In this study, we leveraged combinatorial lipidomics and metabolomics to investigate the effect of replacing TAG with DAG in the diet of athletes with HUA. A total of 1,074 lipids and metabolites from 94 classes were quantitated in serum from 33 athletes, who were categorized into responders and non-responders based on whether serum uric acid levels returned to healthy levels after the DAG diet intervention. Lipidomics and metabolomics analyses revealed lower levels of xanthine and uric acid in responders, accompanied by elevated plasmalogen phosphatidylcholines and diminished acylcarnitine levels. Our results highlighted the mechanisms behind how the DAG diet circumvented the risk and effects associated with high uric acid via lowered triglycerides at baseline influencing the absorption of DAG resulting in a decline in ROS and uric acid production, increased phospholipid levels associated with reduced p-Cresol metabolism potentially impacting on intestinal excretion of uric acid as well as improved ammonia recycling contributing to decreased serum uric acid levels in responders. These observed alterations might be suggestive that successful implementation of the DAG diet can potentially minimize the likelihood of a potentially vicious cycle occurring in high uric acid, elevated ROS, and impaired mitochondrial metabolism environment.

Abstract Diabetes-related distress (DRD) refers to the psychological distress specific to living with diabetes. DRD can lead to negative clinical consequences such as poor self-management. By knowing the local prevalence and severity of DRD, primary care teams can improve the DRD evaluation in our daily practice. This was a cross-sectional study conducted in 3 General Out-patient Clinics (GOPCs) from 1 December 2021 to 31 May 2022. A random sample of adult Chinese subjects with T2DM, who regularly followed up in the selected clinic in the past 12 months, were included. DRD was measured by the validated 15-item Chinese version of the Diabetes Distress Scale (CDDS-15). An overall mean score ≥ 2.0 was considered clinically significant. The association of DRD with selected clinical and personal factors was investigated. The study recruited 362 subjects (mean age 64.2 years old, S.D. 9.5) with a variable duration of living with T2DM (median duration 7.0 years, IQR 10.0). The response rate was 90.6%. The median HbA1c was 6.9% (IQR 0.9). More than half (59.4%) of the subjects reported a clinically significant DRD. Younger subjects were more likely to have DRD (odds ratio of 0.965, 95% CI 0.937–0.994, p = 0.017). Patients with T2DM in GOPCs commonly experience clinically significant DRD, particularly in the younger age group. The primary care clinicians could consider integrating the evaluation of DRD as a part of comprehensive diabetes care.