Lipid biomarkers that reflect postoperative recurrence risk in lung cancer patients who smoke: a case-control study.

BACKGROUND: The risk of postoperative recurrence is higher in lung cancer patients who smoke than non-smokers. However, objective evaluation of the postoperative recurrence risk is difficult using conventional pathological prognostic factors because of their lack of reproducibility. Consequently, novel objective biomarkers that reflect postoperative risk in lung cancer patients who smoke must be identified. Because cigarette smoking and oncogenesis alter lipid metabolism in lung tissue, we hypothesized that the lipid profiles in lung cancer tissues are influenced by cigarette smoking and can reflect the postoperative recurrence risk in smoking lung cancer patients. This study aimed to identify lipid biomarkers that reflect the smoking status and the postoperative recurrence risk. METHODS: Primary tumor tissues of lung adenocarcinoma (ADC) (n = 26) and squamous cell carcinoma (SQCC) (n = 18) obtained from surgery were assigned to subgroups according to the patient's smoking status. The ADC cohort was divided into never smoker and smoker groups, while the SQCC cohort was divided into moderate smoker and heavy smoker groups. Extracted lipids from the tumor tissues were subjected to liquid chromatography-tandem mass spectrometry analysis. Lipids that were influenced by smoking status and reflected postoperative recurrence and pathological prognostic factors were screened. RESULTS: Two and 12 lipid peaks in the ADC and SQCC cohorts showed a significant positive correlation with the Brinkman index, respectively. Among them, in the ADC cohort, a higher lipid level consisted of three phosphatidylcholine (PC) isomers, PC (14:0_18:2), PC (16:1_16:1), and PC (16:0_16:2), was associated with a shorter recurrence free period (RFP) and a greater likelihoods of progressed T-factor (≥ pT2) and pleural invasion. In the SQCC cohort, a lower m/z 736.5276 level was associated with shorter RFP and greater likelihood of recurrence. CONCLUSIONS: From our data, we propose three PC isomers, PC (14:0_18:2), PC (16:1_16:1), and PC (16:0_16:2), and a lipid peak of m/z 736.5276 as novel candidate biomarkers for postoperative recurrence risk in lung ADC and SQCC patients who are smokers.

Tandem Mass Spectrometry Imaging Enables High Definition for Mapping Lipids in Tissues.

Mass spectrometry imaging (MSI) of lipids in biological tissues is useful for correlating molecular distribution with pathological results, which could provide useful information for both biological research and disease diagnosis. It is well understood that the lipidome could not be clearly deciphered without tandem mass spectrometry analysis, but this is challenging to achieve in MSI due to the limitation in sample amount at each image spot. Here we develop a multiplexed MS2 imaging (MS2 I) method that can provide MS2 images for 10 lipid species or more for each sampling spot, providing spatial structural lipidomic information. Coupling with on-tissue photochemical derivatization, imaging of 20 phospholipid C=C location isomers is also realized, showing enhanced molecular images with high definition in structure for mouse brain and human liver cancer tissue sections. Spatially mapped t-distributed stochastic neighbor embedding has also been adopted to visualize the tumor margin with enhancement by structural lipidomic information.

Plasma lipidomics analysis reveals altered lipids signature in patients with osteonecrosis of the femoral head.

INTRODUCTION: Although studies have established a link between lipid metabolism disorder and osteonecrosis of the femoral head (ONFH), the characteristics of the circulating lipidome signature of ONFH have not yet been investigated and need to be explored. OBJECTIVES: We aimed to explore the plasma lipidome signatures in patients with ONFH, and to identify specific lipid biomarkers of ONFH. METHODS: In this study, a comprehensive detection and analysis of plasma lipidomics was conducted in clinical human cohort, including 32 healthy normal control (NC) subjects and 91 ONFH patients in different subgroups [alcohol-induced ONFH (AONFH), steroid-induced ONFH (SONFH), and traumatic-induced ONFH (TONFH)] or at different disease stages (stage I, II, III and IV of ONFH) using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). RESULTS: Overall, the plasma lipidome profile differs between ONFH and NC samples. Lipidome signature including 22 common differentially expressed lipids (DELs) in all three subgroups (variable importance in projection > 1, P < 0.05, fold change > 1.5 or < 0.67, compared to the NC group) was identified. Besides, the subtype-specific lipidome profiles for each ONFH subgroup were also analyzed. Generally, the AONFH subgroup has the largest number of DELs, and the plasma levels of triacylglycerol lipid compounds increased obviously in the AONFH samples. In the subgroup of SONFH, the relative abundance of lipid 4-Aminobenzoic acid increased significantly with changes in the expression of several of its interactive genes. We have identified that 9 stage-positive and 2 stage-negative lipids may function as novel biomarkers predicting the progression of ONFH. CONCLUSION: Our study presents an overview of the phenotype-related plasma lipidome signature of patients with ONFH. The results will provide insight into the mechanisms underlying the metabolism of lipids in the pathogenesis and progression of ONFH and help identify novel lipids biomarkers or disease diagnosis and treatment targets.

Warming and elevated CO2 promote rapid incorporation and degradation of plant-derived organic matter in an ombrotrophic peatland.

Rising temperatures have the potential to directly affect carbon cycling in peatlands by enhancing organic matter (OM) decomposition, contributing to the release of CO2 and CH4 to the atmosphere. In turn, increasing atmospheric CO2 concentration may stimulate photosynthesis, potentially increasing plant litter inputs belowground and transferring carbon from the atmosphere into terrestrial ecosystems. Key questions remain about the magnitude and rate of these interacting and opposing environmental change drivers. Here, we assess the incorporation and degradation of plant- and microbe-derived OM in an ombrotrophic peatland after 4 years of whole-ecosystem warming (+0, +2.25, +4.5, +6.75 and +9°C) and two years of elevated CO2  manipulation (500 ppm above ambient). We show that OM molecular composition was substantially altered in the aerobic acrotelm, highlighting the sensitivity of acrotelm carbon to rising temperatures and atmospheric CO2 concentration. While warming accelerated OM decomposition under ambient CO2 , new carbon incorporation into peat increased in warming × elevated CO2 treatments for both plant- and microbe-derived OM. Using the isotopic signature of the applied CO2 enrichment as a label for recently photosynthesized OM, our data demonstrate that new plant inputs have been rapidly incorporated into peat carbon. Our results suggest that under current hydrological conditions, rising temperatures and atmospheric CO2  levels will likely offset each other in boreal peatlands.

Effect of synbiotic yogurt fortified with monk fruit extract on hepatic lipid biomarkers and metabolism in rats with type 2 diabetes.

Monk fruit extract (MFE) is widely used as a sweetener in foods. In this study, the effects of the consumption of MFE-sweetened synbiotic yogurt on the lipid biomarkers and metabolism in the livers of type 2 diabetic rats were evaluated. The results revealed that the MFE-sweetened symbiotic yogurt affected the phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerol, lysophosphatidic acids, lysophosphatidylcholines, lysophosphatidylethanolamines, lysophosphatidylglycerols, lysophosphatidylinositols, lysophosphatidylserines, and fatty acid-hydroxy fatty acids biomarkers in the livers of type 2 diabetic rats. In addition, the consumption of the MFE-sweetened synbiotic yogurt significantly altered 12 hepatic metabolites, which are involved in phenylalanine metabolism, sphingolipid metabolism, bile secretion, and glyoxylate and dicarboxylate metabolism in the liver. Furthermore, a multiomics (metabolomic and transcriptomic) association study revealed that there was a significant correlation between the MFE-sweetened synbiotic yogurt and the metabolites and genes involved in fatty acid biosynthesis, bile secretion, and glyoxylate and dicarboxylate metabolism. The findings of this study will provide new insights on exploring the function of sweeteners for improving type 2 diabetes mellitus liver lipid biomarkers.

Liver CPT1A gene therapy reduces diet-induced hepatic steatosis in mice and highlights potential lipid biomarkers for human NAFLD.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased drastically due to the global obesity pandemic but at present there are no approved therapies. Here, we aimed to revert high-fat diet (HFD)-induced obesity and NAFLD in mice by enhancing liver fatty acid oxidation (FAO). Moreover, we searched for potential new lipid biomarkers for monitoring liver steatosis in humans. We used adeno-associated virus (AAV) to deliver a permanently active mutant form of human carnitine palmitoyltransferase 1A (hCPT1AM), the key enzyme in FAO, in the liver of a mouse model of HFD-induced obesity and NAFLD. Expression of hCPT1AM enhanced hepatic FAO and autophagy, reduced liver steatosis, and improved glucose homeostasis. Lipidomic analysis in mice and humans before and after therapeutic interventions, such as hepatic AAV9-hCPT1AM administration and RYGB surgery, respectively, led to the identification of specific triacylglyceride (TAG) specie (C50:1) as a potential biomarker to monitor NAFFLD disease. To sum up, here we show for the first time that liver hCPT1AM gene therapy in a mouse model of established obesity, diabetes, and NAFLD can reduce HFD-induced derangements. Moreover, our study highlights TAG (C50:1) as a potential noninvasive biomarker that might be useful to monitor NAFLD in mice and humans.

Revealing potential lipid biomarkers in clear cell renal cell carcinoma using targeted quantitative lipidomics.

BACKGROUND: The high drug resistance and metabolic reprogramming of clear cell renal cell carcinoma (ccRCC) are considered responsible for poor prognosis. In-depth research at multiple levels is urgently warranted to illustrate the lipid composition, distribution, and metabolic pathways of clinical ccRCC specimens. METHODS: In this project, a leading-edge targeted quantitative lipidomic study was conducted using 10 pairs of cancerous and adjacent normal tissues obtained from ccRCC patients. Accurate lipid quantification was performed according to a linear equation calculated using internal standards. Qualitative and quantitative analyses of lipids were performed with multiple reaction monitoring analysis based on ultra-performance liquid chromatography (UPLC) and mass spectrometry (MS). Additionally, a multivariate statistical analysis was performed using data obtained on lipids. RESULTS: A total of 28 lipid classes were identified. Among them, the most abundant were triacylglycerol (TG), diacylglycerol (DG), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Cholesteryl ester (CE) was the lipid exhibiting the most considerable difference between normal samples and tumor samples. Lipid content, chain length, and chain unsaturation of acylcarnitine (CAR), CE, and DG were found to be significantly increased. Based on screening for variable importance in projection scores ≥1, as well as fold change limits between 0.5 and 2, 160 differentially expressed lipids were identified. CE was found to be the most significantly upregulated lipid, while TG was observed to be the most significantly downregulated lipid. CONCLUSION: Based on the absolute quantitative analysis of lipids in ccRCC specimens, it was observed that the content and change trends varied in different lipid classes. Upregulation of CAR, CE, and DG was observed, and analysis of changes in the distribution helped clarify the causes of lipid accumulation in ccRCC and possible carcinogenic molecular mechanisms. The results and methods described herein provide a comprehensive analysis of ccRCC lipid metabolism and lay a theoretical foundation for cancer treatment.

A UHPLC-Mass Spectrometry View of Human Melanocytic Cells Uncovers Potential Lipid Biomarkers of Melanoma.

Melanoma is the deadliest form of skin cancer due to its ability to colonize distant sites and initiate metastasis. Although these processes largely depend on the lipid-based cell membrane scaffold, our understanding of the melanoma lipid phenotype lags behind most other aspects of this tumor cell. Here, we examined a panel of normal human epidermal and nevus melanocytes and primary and metastatic melanoma cell lines to determine whether distinctive cell-intrinsic lipidomes can discern non-neoplastic from neoplastic melanocytes and define their metastatic potential. Lipidome profiles were obtained by UHPLC-ESI mass-spectrometry, and differences in the signatures were analyzed by multivariate statistical analyses. Significant and highly specific changes in more than 30 lipid species were annotated in the initiation of melanoma, whereas less numerous changes were associated with melanoma progression and the non-malignant transformation of nevus melanocytes. Notably, the "malignancy lipid signature" features marked drops in pivotal membrane lipids, like sphingomyelins, and aberrant elevation of ether-type lipids and phosphatidylglycerol and phosphatidylinositol variants, suggesting a previously undefined remodeling of sphingolipid and glycerophospholipid metabolism. Besides broadening the molecular definition of this neoplasm, the different lipid profiles identified may help improve the clinical diagnosis/prognosis and facilitate therapeutic interventions for cutaneous melanoma.

Atlantic walrus signal latitudinal differences in the long-term decline of sea ice-derived carbon to benthic fauna in the Canadian Arctic.

Climate change is altering the biogeochemical and physical characteristics of the Arctic marine environment, which impacts sea ice algal and phytoplankton bloom dynamics and the vertical transport of these carbon sources to benthic communities. Little is known about whether the contribution of sea ice-derived carbon to benthic fauna and nitrogen cycling has changed over multiple decades in concert with receding sea ice. We combined compound-specific stable isotope analysis of amino acids with highly branched isoprenoid diatom lipid biomarkers using archived (1982-2016) tissue of benthivorous Atlantic walrus to examine temporal trends of sea ice-derived carbon, nitrogen isotope baseline and trophic position of Atlantic walrus at high- and mid-latitudes in the Canadian Arctic. Associated with an 18% sea ice decline in the mid-Arctic, sea ice-derived carbon contribution to Atlantic walrus decreased by 75% suggesting a strong decoupling of sea ice-benthic habitats. By contrast, a nearly exclusive amount of sea ice-derived carbon was maintained in high-Arctic Atlantic walrus (98% in 1996 and 89% in 2006) despite a similar percentage in sea ice reduction. Nitrogen isotope baseline or the trophic position of Atlantic walrus did not change over time at either location. These findings indicate latitudinal differences in the restructuring of carbon energy sources used by Atlantic walrus and their benthic prey, and in turn a change in Arctic marine ecosystem functioning between sea ice-pelagic-benthic habitats.

Associations Among Fatty Acids, Desaturase and Elongase, and Insulin Resistance in Children.

OBJECTIVES: Fatty acid profiles and desaturase (SCD-16, SCD018, D5D, D6D) and elongase (ELOVL6) enzyme activity have been associated with adiposity and metabolic disease. While this has been studied in adults, few studies have included children. The objective of this study was to evaluate these markers in children and identify relationships with markers of metabolic health. It was hypothesized that these lipid markers would be correlated to adiposity and metabolic disease. METHODS: This study was a cross-sectional analysis of fourth- and fifth-grade children (n = 86, aged 9-12) participating in a comprehensive nutrition program. Any student enrolled in the program was eligible for inclusion in this study. Fasting plasma was collected and analyzed for total fatty acids, glucose, insulin, and full lipid panels. Insulin resistance was estimated using calculated homeostatic model assessment for insulin resistance (HOMA-IR) values. RESULTS: There were no differences in lipid markers, glucose, insulin, or HOMA-IR among children classified as normal weight, overweight, or obese. SCD-16, D5D, and ELOVL6 activity was significantly correlated to HOMA-IR values (r = 0.39, p = 0.001; r = -0.33, p = 0.006; r = -0.37, p = 0.005, respectively). In regression analysis, body mass index for age percentile, D6D activity, ELOVL6 activity, and systolic blood pressure were the most significant predictors of HOMA-IR values (adjusted r2 = 0.39, p ≤ 0.001). CONCLUSIONS: There was no relationship between these lipid markers and adiposity in this population; however, there were correlations with HOMA-IR. Regardless of adiposity, there may be underlying changes in fatty acid and lipid metabolism associated with the development of metabolic diseases.

Dynamic analysis of phospholipid metabolism of mouse macrophages treated with common non-steroidal anti-inflammatory drugs.

Through studying the changes of the total phospholipid components in mouse macrophages under the inflammatory status and the drug intervention status, we found the targets of non-steroidal anti-inflammatory drugs on phospholipids, thus providing the basis for the targets of in vitro anti-inflammatory effects of non-steroidal anti-inflammatory drugs. After RAW264.7 cells were pretreated with common non-steroidal anti-inflammatory drugs (aspirin and ibuprofen) and, respectively, stimulated with KLA for various periods (0.5, 4, 12, 16, and 24 h), the phospholipids were extracted. The dynamic changes of phospholipids in cells under various stimulations were analyzed with UPLC-Q-TOF-MS technique. Through the statistical analysis of Simca-P, we explored the potential targets of non-steroidal anti-inflammatory drugs on phospholipids. Through the dynamic analysis of phospholipids, we found two biomarkers (PC(17:1/18:1), PA(18:0/18:4)) which might be in vitro intervention inflammatory response targets of non-steroidal anti-inflammatory drugs. The analysis results show that in anti-inflammatory effects, non-steroidal anti-inflammatory drugs can inhibit COX, induce the cellular fatty acid desaturation and the changes of phospholipid components, stimulate free fatty acids, activate calcium ion channels of endoplasmic reticulum, and promote cell endocytosis, thus controlling inflammation and activating cells. Non-steroidal anti-inflammatory drugs can promote endocytosis, alter cell inflammatory response, and activate the process cells, thus realizing the anti-inflammatory effects.

Weight gain during nutritional rehabilitation post-childhood malnutrition may influence the associations between adulthood desaturases activity and anthro-cardiometabolic risk factors.

BACKGROUNDS & AIMS: Childhood malnutrition is a major global health problem with long-term sequelae, including non-communicable diseases (NCDs). Mechanisms are unknown but may involve metabolic programming, resulting from "short-term" solutions to optimise survival by compromising non-priority organs. As key players in lipid metabolism, desaturases have been shown to be predictive of NCDs. We hypothesised that the association between specific desaturase activities and NCD risk determinants (including body composition, serum glucose, insulin levels, and blood pressure) are influenced by childhood post-malnutrition weight gain. METHODS: 278 Afro-Caribbean adults with well-documented clinical history of severe malnutrition in childhood were studied. Extensive metabolic analyses including body composition (DXA), fasting serum glucose and lipidomics (n = 101), and fasting serum insulin (n = 83) were performed in malnutrition survivors and matched community controls (n = 90). Established lipid ratios were used as proxies of desaturase activities: CE 16:1/CE 16:0 for stearoyl-CoA desaturase (SCD1), LysoPC 20:4/20:3 for fatty acid desaturase 1 (FADS1), and LysoPC 20:3/18:2 for FADS2. RESULTS: Compared to community controls, adult malnutrition survivors (mean ± SD) age 28.3 ± 7.8 and BMI 23.6 ± 5.2 had higher SCD1 and FADS1 activity, (B ± SE) 0.07 ± 0.02 and 0.7 ± 0.08, respectively, but lower FADS2 activities (B ± SE) -0.05 ± 0.01, adjusted for sex and age (p < 0.0005). SCD1 was positively associated with adult BMI and body fat percentage, and negatively associated with lean mass and height. Stratification based on weight gain during nutritional rehabilitation among malnutrition survivors might signal the potential associations between weight gain during that critical period, desaturase activities, and some of adult metabolic parameters, with the lowest tertiles (slowest catch-up weight gain) performing more similarly to controls. CONCLUSIONS: In adult survivors of early-life severe acute malnutrition, desaturase activity is associated with markers of NCD risk, especially adiposity. These associations seem to be strengthened by faster weight gain during nutritional rehabilitation.

Lipid biomarkers recording marine microbial community structure changes through the Frasnian-Famennian mass extinction event.

Studying the response and recovery of marine microbial communities during mass extinction events provides an evolutionary window through which to understand the adaptation and resilience of the marine ecosystem in the face of significant environmental disturbances. The goal of this study is to reconstruct changes in the marine microbial community structure through the Late Devonian Frasnian-Famennian (F-F) transition. We performed a multiproxy investigation on a drill core of the Upper Devonian New Albany Shale from the Illinois Basin (western Kentucky, USA). Aryl isoprenoids show green sulfur bacteria expansion and associated photic zone euxinia (PZE) enhancement during the F-F interval. These changes can be attributed to augmented terrigenous influxes, as recorded collectively by the long-chain/short-chain normal alkane ratio, carbon preference index, C30 moretane/C30 hopane, and diahopane index. Hopane/sterane ratios reveal a more pronounced dominance of eukaryotic over prokaryotic production during the mass extinction interval. Sterane distributions indicate that the microalgal community was primarily composed of green algae clades, and their dominance became more pronounced during the F-F interval and continued to rise in the subsequent periods. The 2α-methylhopane index values do not show an evident shift during the mass extinction interval, whereas the 3ß-methylhopane index values record a greater abundance of methanotrophic bacteria during the extinction interval, suggesting enhanced methane cycling due to intensified oxygen depletion. Overall, the Illinois Basin during the F-F extinction experienced heightened algal productivity due to intensified terrigenous influxes, exhibiting similarities to contemporary coastal oceans that are currently undergoing globalized cultural eutrophication. The observed microbial community shifts associated with the F-F environmental disturbances were largely restricted to the extinction interval, which suggests a relatively stable, resilient marine microbial ecosystem during the Late Devonian.

A carbonate corrosion experiment at a marine methane seep: The role of aerobic methanotrophic bacteria.

Methane seeps are typified by the formation of authigenic carbonates, many of which exhibit corrosion surfaces and secondary porosity believed to be caused by microbial carbonate dissolution. Aerobic methane oxidation and sulfur oxidation are two processes capable of inducing carbonate corrosion at methane seeps. Although the potential of aerobic methanotrophy to dissolve carbonate was confirmed in laboratory experiments, this process has not been studied in the environment to date. Here, we report on a carbonate corrosion experiment carried out in the REGAB Pockmark, Gabon-Congo-Angola passive margin, in which marble cubes were deployed for 2.5 years at two sites (CAB-B and CAB-C) with apparent active methane seepage and one site (CAB-D) without methane seepage. Marble cubes exposed to active seepage (experiment CAB-C) were found to be affected by a new type of microbioerosion. Based on 16S rRNA gene analysis, the biofilms adhering to the bioeroded marble mostly consisted of aerobic methanotrophic bacteria, predominantly belonging to the uncultured Hyd24-01 clade. The presence of abundant 13 C-depleted lipid biomarkers including fatty acids (n-C16:1ω8c , n-C18:1ω8c , n-C16:1ω5t ), various 4-mono- and 4,4-dimethyl sterols, and diplopterol agrees with the dominance of aerobic methanotrophs in the CAB-C biofilms. Among the lipids of aerobic methanotrophs, the uncommon 4α-methylcholest-8(14)-en-3ß,25-diol is interpreted to be a specific biomarker for the Hyd24-01 clade. The combination of textural, genetic, and organic geochemical evidence suggests that aerobic methanotrophs are the main drivers of carbonate dissolution observed in the CAB-C experiment at the REGAB pockmark.

Sediment geochemical records of water quality deterioration in lake Jiren, a remote alpine lake on the southeastern margin of the Tibetan Plateau.

Limited human activities in catchments make remote alpine lakes valuable sites for studying the evolution of lake environments in response to climate change and atmospheric deposition; however, this issue remains rarely studied owing to the scarcity of monitoring data. In this study, water quality evolution in Lake Jiren, a remote alpine lake on the southeastern margin of the Tibetan Plateau, over the past two centuries was reconstructed through geochemical analyses of aliphatic hydrocarbons, major and trace elements, and organic matter (OM) pyrolysis products in a dated sediment core, and the associated drivers were identified by temporally comparing the geochemical results with document records. All geochemical data demonstrated that the lake water remained relatively pure until 1947, after which the n-alkane and αß-hopane proxies indicated eutrophication and petroleum contamination. The OM pyrolysis proxy hydrocarbon index indicated more eutrophic conditions after 1957. Concurrently, hypolimnetic deoxygenation increased, as indicated by redox-sensitive proxies, such as the enrichment factors (EFs) of molybdenum (Mo). These proxies recorded further intensification of deoxygenation after 1976. The EFs for other trace elements indicated cadmium contamination after 1967. The greater anthropogenic emissions of reactive nitrogen, petroleum products, and heavy metals in East and South Asia since approximately 1950 and the subsequent atmospheric transport of these materials to the lake might be the basic driver of water quality deterioration. Eutrophication induced by nitrogen deposition was responsible for increased hypolimnetic deoxygenation by enhancing phytoplankton productivity and OM input. The further intensification of deoxygenation was attributed to climate warming since the 1970s, as prolonged water column stratification under this condition decreased oxygen input from the epilimnion to the lake bottom. These findings may be beneficial for understanding the natural and anthropogenic effects on the water quality of alpine lakes and help in the environmental management of Lake Jiren and other alpine lakes.

An Overview of Lipid Biomarkers in Terrestrial Extreme Environments with Relevance for Mars Exploration.

Lipid molecules are organic compounds, insoluble in water, and based on carbon-carbon chains that form an integral part of biological cell membranes. As such, lipids are ubiquitous in life on Earth, which is why they are considered useful biomarkers for life detection in terrestrial environments. These molecules display effective membrane-forming properties even under geochemically hostile conditions that challenge most of microbial life, which grants lipids a universal biomarker character suitable for life detection beyond Earth, where a putative biological membrane would also be required. What discriminates lipids from nucleic acids or proteins is their capacity to retain diagnostic information about their biological source in their recalcitrant hydrocarbon skeletons for thousands of millions of years, which is indispensable in the field of astrobiology given the time span that the geological ages of planetary bodies encompass. This work gathers studies that have employed lipid biomarker approaches for paleoenvironmental surveys and life detection purposes in terrestrial environments with extreme conditions: hydrothermal, hyperarid, hypersaline, and highly acidic, among others; all of which are analogous to current or past conditions on Mars. Although some of the compounds discussed in this review may be abiotically synthesized, we focus on those with a biological origin, namely lipid biomarkers. Therefore, along with appropriate complementary techniques such as bulk and compound-specific stable carbon isotope analysis, this work recapitulates and reevaluates the potential of lipid biomarkers as an additional, powerful tool to interrogate whether there is life on Mars, or if there ever was.

Integrating Widely Targeted Lipidomics and Transcriptomics Unravels Aberrant Lipid Metabolism and Identifies Potential Biomarkers of Food Allergies in Rats.

SCOPE: Oral food challenges (OFCs) are currently the gold standard for determining the clinical reactivity of food allergy (FA) but are time-consuming, expensive, and risky. To screen novel peripheral biomarkers of FA and characterize the aberrant lipid metabolism in serum, 24 rats are divided into four groups: peanut, milk, and shrimp allergy (PA, MA, and SA, respectively) and control groups, with six rats in each group, and used for widely targeted lipidomics and transcriptomics analysis. METHODS AND RESULTS: Widely targeted lipidomics reveal 144, 162, and 206 differentially accumulated lipids in PA, MA, and SA groups, respectively. The study integrates widely targeted lipidomics and transcriptomics and identifies abnormal lipid metabolism correlated with widespread differential accumulation of diverse lipids (including triacylglycerol, diacylglycerol, sphingolipid, and glycerophospholipid) in PA, MA, and SA. Simplified random forest classifier is constructed through five repetitions of 10-fold cross-validation to distinguish allergy from control. A subset of 15 lipids as potential biomarkers allows for more reliable and more accurate prediction of FA. Independent replication validates the reproducibility of potential biomarkers. CONCLUSION: The results reveal the major abnormalities in lipid metabolism and suggest the potential role of lipids as novel molecular signatures for FA.

Lipid Alterations in Glioma: A Systematic Review.

Gliomas are highly lethal tumours characterised by heterogeneous molecular features, producing various metabolic phenotypes leading to therapeutic resistance. Lipid metabolism reprogramming is predominant and has contributed to the metabolic plasticity in glioma. This systematic review aims to discover lipids alteration and their biological roles in glioma and the identification of potential lipids biomarker. This systematic review was conducted using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Extensive research articles search for the last 10 years, from 2011 to 2021, were conducted using four electronic databases, including PubMed, Web of Science, CINAHL and ScienceDirect. A total of 158 research articles were included in this study. All studies reported significant lipid alteration between glioma and control groups, impacting glioma cell growth, proliferation, drug resistance, patients' survival and metastasis. Different lipids demonstrated different biological roles, either beneficial or detrimental effects on glioma. Notably, prostaglandin (PGE2), triacylglycerol (TG), phosphatidylcholine (PC), and sphingosine-1-phosphate play significant roles in glioma development. Conversely, the most prominent anti-carcinogenic lipids include docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and vitamin D3 have been reported to have detrimental effects on glioma cells. Furthermore, high lipid signals were detected at 0.9 and 1.3 ppm in high-grade glioma relative to low-grade glioma. This evidence shows that lipid metabolisms were significantly dysregulated in glioma. Concurrent with this knowledge, the discovery of specific lipid classes altered in glioma will accelerate the development of potential lipid biomarkers and enhance future glioma therapeutics.

Shotgun mass spectrometry-based lipid profiling identifies and distinguishes between chronic inflammatory diseases.

BACKGROUND: Localized stress and cell death in chronic inflammatory diseases may release tissue-specific lipids into the circulation causing the blood plasma lipidome to reflect the type of inflammation. However, deep lipid profiles of major chronic inflammatory diseases have not been compared. METHODS: Plasma lipidomes of patients suffering from two etiologically distinct chronic inflammatory diseases, atherosclerosis-related vascular disease, including cardiovascular (CVD) and ischemic stroke (IS), and systemic lupus erythematosus (SLE), were screened by a top-down shotgun mass spectrometry-based analysis without liquid chromatographic separation and compared to each other and to age-matched controls. Lipid profiling of 596 lipids was performed on a cohort of 427 individuals. Machine learning classifiers based on the plasma lipidomes were used to distinguish the two chronic inflammatory diseases from each other and from the controls. FINDINGS: Analysis of the lipidomes enabled separation of the studied chronic inflammatory diseases from controls based on independent validation test set classification performance (CVD vs control - Sensitivity: 0.94, Specificity: 0.88; IS vs control - Sensitivity: 1.0, Specificity: 1.0; SLE vs control - Sensitivity: 1, Specificity: 0.93) and from each other (SLE vs CVD ‒ Sensitivity: 0.91, Specificity: 1; IS vs SLE - Sensitivity: 1, Specificity: 0.82). Preliminary linear discriminant analysis plots using all data clearly separated the clinical groups from each other and from the controls, and partially separated CVD severities, as classified into five clinical groups. Dysregulated lipids are partially but not fully counterbalanced by statin treatment. INTERPRETATION: Dysregulation of the plasma lipidome is characteristic of chronic inflammatory diseases. Lipid profiling accurately identifies the diseases and in the case of CVD also identifies sub-classes. FUNDING: Full list of funding sources at the end of the manuscript.

Biosulfidogenesis Mediates Natural Attenuation in Acidic Mine Pit Lakes.

Acidic pit lakes are abandoned open pit mines filled with acid mine drainage (AMD)-highly acidic, metalliferous waters that pose a severe threat to the environment and are rarely properly remediated. Here, we investigated two meromictic, oligotrophic acidic mine pit lakes in the Iberian Pyrite Belt (IPB), Filón Centro (Tharsis) (FC) and La Zarza (LZ). We observed a natural attenuation of acidity and toxic metal concentrations towards the lake bottom, which was more pronounced in FC. The detection of Cu and Zn sulfides in the monimolimnion of FC suggests precipitation of dissolved metals as metal sulfides, pointing to biogenic sulfide formation. This was supported by microbial diversity analysis via 16S rRNA gene amplicon sequencing of samples from the water column, which showed the presence of sulfidogenic microbial taxa in FC and LZ. In the monimolimnion of FC, sequences affiliated with the putative sulfate-reducing genus Desulfomonile were dominant (58%), whereas in the more acidic and metal-enriched LZ, elemental sulfur-reducing Acidianus and Thermoplasma spp., and disproportionating Desulfocapsa spp. were more abundant. Furthermore, the detection of reads classified as methanogens and Desulfosporosinus spp., although at low relative abundance, represents one of the lowest pH values (2.9 in LZ) at which these taxa have been reported, to our knowledge. Analysis of potential biomarker lipids provided evidence that high levels of phosphocholine lipids with mixed acyl/ether glycerol core structures were associated with Desulfomonile, while ceramide lipids were characteristic of Microbacter in these environments. We propose that FC and LZ function as natural bioremediation reactors where metal sulfide precipitation is mediated by biosulfidogenesis starting from elemental sulfur reduction and disproportionation at an early stage (LZ), followed by sulfate reduction at a later stage (FC).