Morus alba L. (Sangzhi) alkaloids alleviate diabetic nephropathy by suppressing endoplasmic reticulum stress and modulating AMPK-associated phosphatidylethanolamine content.

Lipidome mapping of natural rubber: Detailed investigation into the influence of geographical origin and treatment using liquid chromatography and high-resolution tandem mass spectrometry.

Dietary Ethanolamine Increases Hepatic Lipid Accumulation in Mice Fed a High-Fat Diet.

Integrative proteomics and metabolomics approach to elucidate the multi-organ developmental toxicity of decabromodiphenyl ethane in zebrafish larvae.

Elucidating the nature of the interactions of oseltamivir with the 2D model of influenza A virus lipid envelope.

Vibrio alginolyticus is an important antibiotic-resistant pathogen in aquaculture that can cause mortality in a wide range of aquatic animals and infect humans. It is urgently necessary to discover and develop effective antibiotic alternatives. Citral, a key antibacterial component of lemongrass oil, can be used as a food flavoring and additive. Although the antimicrobial activity and antibiofilm effect of citral against V. alginolyticus have been noted in our previous study, the potential lipidome influence of citral remains unclear. Accordingly, a non-targeted lipidomics approach was employed to investigate citral-induced lipidome disturbances and reveal potential regulated targets of citral against V. alginolyticus. We found that the citral exposure triggered substantial lipidome alterations (i.e., composition, contents, and structure) in V. alginolyticus. Specifically, the content of most phospholipids (e.g., phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), phosphatidylserines (PSs), phosphatidylinositols (PIs), and phosphatidylglycerols (PGs)) decreased with the increase in citral concentration, while ceramides (Cers) and lysophospholipids (LPLs) (e.g., lyso-PAs, lyso-PCs, lyso-PEs, and lyso-PGs) showed concentration-dependent accumulation under citral treatment. Notably, the critical lipid remodeling in response to citral exposure mainly involved the phospholipid and sphingolipid metabolic pathways. Collectively, our study reveals the bacterial lipidome response to citral exposure and highlights pivotal metabolic pathways, potentially offering a novel perspective for future investigations into lipid-centric antibacterial targets.

A Gram-stain-negative, aerobic, and rod-shaped bacterium, designated H14T, was isolated from a tidal flat in Zhoushan, Zhejiang Province, China. Colonies of strain H14T were yellow, round, smooth and convex after cultivating on marine agar at 37 ℃ for 72h. Cells were catalase-positive and oxidase-negative. Growth occurred at 16-40 ℃ (optimum, 37 ℃), pH 5.0-8.5 (optimum, pH 6.5) and with 0.5-10.0% (]/v) NaCl (optimum, 3.0%). Strain H14T showed highest 16S rRNA gene sequence similarity of 97.7% to Autumnicola tepida F363T. It contained menaquinone-6 (MK-6) as the sole respiratory quinone, iso-C15:0 and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c) as the major fatty acids. The main polar lipids were phosphatidylethanolamine (PE), three unidentified aminolipids (AL1-3) and four unidentified lipids (L1-4). The DNA G + C content was 39.6mol%. The average amino acid identity (AAI), average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain H14T and the current genome-sequenced Autumnicola type strains were 78.7-88.4%, 77.1-83.7%, and 17.1-45.8%, respectively. Based on the polyphasic taxonomic analysis, a novel member of the genusAutumnicola, named Autumnicola aciditolerans sp. nov., is proposed. The type strain is H14T (= MCCC 1K08336T = KCTC 82836T = CGMCC 1.61706T).

In silico design and evaluation of hybrid antimicrobial peptides for combating environmental multidrug-resistant bacteria.

During conjugation, plasmid DNA is transferred from donor to recipient bacteria via the plasmid-encoded mating pilus, formed as thin helical assemblies of polymerised pilin subunits. In the IncHI1 R27 plasmid-encoded pilus, the TrhA pilin undergoes cyclisation (via a peptide bond between Gly1 and Asp69), essential for conjugation. Gly1 and Asp69 are exposed on the pilus surface and conserved in all TrhA pilins in the Plascad database. Substituting Asp69 with Asn, Ala, Gly, or Arg does not prevent cyclisation or pilus formation, which remains structurally indistinguishable from the wild type. Conjugation efficiency of the Asp69 substitutions across multiple recipient species correlates with side chain size, in the order Asp69Asn > Asp69Ala > Asp69Gly. However, Asp69Arg, as well as Asp69Lys and Gly1Lys substitutions abolish conjugation, likely due to the positively charged pilus surface (opposite to the wild-type negative charge) forming unfavourable electrostatic interactions with the recipient outer membrane's inner leaflet, composed solely of zwitterionic phosphatidylethanolamine (PE). Consistently, conjugation is rescued in recipients lacking PE. These findings indicate strong selective pressure to maintain Gly1 and Asp69, as efficient DNA transfer depends on precise electrostatic and steric constraints of the pilus surface.

The ε4 allele of the APOE gene, encoding the E4 isoform of apolipoprotein E, is the leading genetic risk factor for late-onset Alzheimer's disease. While many potential mechanisms have been proposed to explain this risk, no dominant or unifying process has yet emerged. Here, we explore the primary function of apolipoprotein E in lipid transport and metabolism, by examining its lipid association properties, to establish whether they show isoform dependence and thereby could mediate Alzheimer's risk. We focus on ethanolamine plasmalogen, a phospholipid subclass known to be depleted in Alzheimer's disease brain. We purified apolipoprotein E from human cerebrospinal fluid by immunoprecipitation using an anti-pan-apolipoprotein E monoclonal antibody bound to magnetic beads, then conducted lipidomic and proteomic analyses of the precipitates by mass spectrometry. The cerebrospinal fluid samples were obtained from cognitively intact, relatively young individuals with no evidence of amyloid pathology and with known apolipoprotein E isoform status (E3E3, n = 5; E3E4, n = 4; E4E4, n = 5). The molar ratio of ethanolamine plasmalogen to apolipoprotein E was 29.5% lower for E4E4 than for E3E3 (P = 0.007) with a biological gradient: E3E3 > E3E4 > E4E4 (P = 0.03). No similar trends and differences were found for phosphatidyl ethanolamine, a chemically related lipid (P = 0.5). Compared to E3E3, the molar ratio of ethanolamine plasmalogen to phosphatidyl ethanolamine was significantly reduced for E3E4 (P = 0.0016) and E4E4 (P = 0.0001). The latter deficiency was similar in magnitude to that found in Alzheimer's disease brain relative to control. The finding that ethanolamine plasmalogen is depleted in apolipoprotein E4 relative to E3 strengthens the view that brain deficiency of this same lipid contributes to Alzheimer's disease causation, rather than being an effect of the neurodegeneration. Simultaneously, these results supply a potential mechanism for the risk of E4 versus E3, the former being less able to counteract the tissue defect. The apolipoprotein E4 lipid depletion cannot itself be a consequence of Alzheimer's disease, since cerebrospinal fluid samples were taken from individuals with no evidence of the condition. The biological gradient in ethanolamine plasmalogen deficiency mirrors the relationship of Alzheimer's disease risk (odds ratio) to E4 allelic dose. Ethanolamine plasmalogen deficiency could be linked to, or indeed drive, several metabolic pathways implicated in Alzheimer's pathogenesis, including amyloid-beta deposition and cholesterol dysregulation. Future studies should extend approaches to therapeutic intervention in Alzheimer's disease which attempt to reverse this lipid abnormality.

BamA is a highly conserved essential outer membrane chaperone of all Gram-negative bacteria. Our understanding of the BamA machinery remains incomplete, delaying knowledge-based antibacterial design. Here, we report the first detailed identification of molecular elements indispensable for BamA folding, stability, and function. BamA displays two unique transition state structures and folding pathways in phosphatidylethanolamine (PE)- and phosphatidylglycerol (PG)-containing membranes. PE retards BamA folding; once folded, PE lowers stability of the N-terminal β-strands. In interesting contrast, PG promotes directional folding of BamA, and rigidifies the protein structure by lowering its conformational sampling space. We demonstrate that BamA β5-L4-β8 is an obligatory late-assembly zone in both PE and PG. Thermodynamic free energy measurements show BamA as membrane-anchored at β11-β15 and destabilized at β2-β7 for its N-terminal gating function, with a C-terminal structural kink at β16. We show how BamA function links directly with (i) structures of PE-specific transition states, and (ii) zonal (de)stabilization hotspots at β5-L4-β8, β9-L5-β10, and β16-K808. We propose that these sites can now serve as novel hotspots for structure-based design of peptidomimetics to target multi-drug resistant Gram-negative pathogens.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are chronic liver diseases characterized by lipid accumulation and persistent inflammation, often progressing to fibrosis or hepatocellular carcinoma (HCC). Hepatitis C virus (HCV) infection shares overlapping pathological features, including chronic inflammation and fibrogenesis. Despite their prevalence, reproducible plasma-level molecular data that capture disease-associated systemic alterations remain limited. We conducted targeted proteomic and targeted lipidomic profiling of several hundred plasma samples from Japanese patients diagnosed with MASLD, MASH, or HCV infection. Targeted proteomics quantified 184 plasma proteins using the Olink Proximity Extension Assay, and targeted lipidomics quantified approximately 500 phospholipid and triglyceride species using LC/MS-based selected reaction monitoring. Reproducibility was assessed across three independent cohorts. Seven proteins (CASP-8, CCL20, CTSD, SCF, MMP-3, TRAIL, and TWEAK) consistently differed between MASLD and MASH across all cohorts, reflecting coordinated changes related to apoptosis, inflammation, and immune signaling. Similar alterations were observed in HCV (Hepatitis C virus), indicating shared immune dysregulation. Lipidomic analysis revealed reproducible remodeling characterized by decreased ether-linked phosphatidylethanolamine (PE), increased ester-linked PE, and elevated saturated sphingomyelin (SM) in MASH. Correlation analyses indicate coordinated relationships between selected protein and lipid alterations, including relationships between CTSD and PE and triglyceride (TG) species containing linoleic acid (18:2). The results of this research provide value to the field of proteomics as a large-scale, reproducible, and hypothesis-generating plasma dual-omics reference dataset. This study was not designed to establish diagnostic biomarkers, to assess clinical discriminative performance, or to imply causal mechanisms. Instead, by emphasizing reproduciblilty across independent cohorts, we provide a plasma dual-omics reference dataset that captures coordinated immune and lipid metabolic alterations associated with chronic liver disease severity. These data provide a framework and resource for future studies researching risk stratification, therapeutic monitoring, and mechanistic validation in chronic liver disease.

Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disorder with limited effective therapeutic options. Emerging lipidomic studies suggest that alterations in membrane-associated lipids contribute to MASH pathophysiology; however, nutritional interventions capable of modifying these lipid alterations remain poorly defined. This study aimed to investigate the effects of coenzyme Q10 (CoQ) supplementation on hepatic lipidomic remodeling in a methionine- and choline-deficient (MCD) diet-induced mouse model of MASH. Male C57BL/6J mice were fed a methionine- and choline-sufficient diet or an MCD diet for 4 weeks, with MCD-fed mice receiving vehicle or CoQ (100 mg/kg body weight/day). Hepatic lipid profiles were assessed using untargeted LC-MS-based lipidomics, and expression of genes involved in phospholipid and sphingolipid metabolism was quantified by quantitative real-time PCR. CoQ supplementation significantly attenuated liver injury induced by the MCD diet, as evidenced by reduced histological severity and decreased serum ALT and AST levels. Lipidomic analyses revealed marked alterations in hepatic phospholipid and sphingolipid profiles during MASH development. CoQ was associated with remodeling of phospholipid composition, increasing phosphatidylcholine (PC) species and reducing phosphatidylethanolamine (PE) species, resulting in an increased hepatic PC to PE ratio. This change was accompanied by upregulation of Pemt (phosphatidylethanolamine N-methyltransferase). In contrast, sphingolipid accumulation induced by the MCD diet remained largely unchanged by CoQ, and Smpd1 (sphingomyelin phosphodiesterase 1) expression was not altered. CoQ supplementation was associated with attenuation of MCD diet-induced MASH and modulation of hepatic phospholipid homeostasis, supporting its potential as a nutritional intervention targeting membrane lipid dysregulation in MASH.

Strain DSM 117947T was isolated from a Micromonospora matsumotoense co-culture originating from a water sample collected in Germany. The strain was subjected to a polyphasic taxonomic analysis. It exhibited 99.3% 16S rRNA gene sequence similarity with Nocardioides aurantiacus DSM 12652T. Digital DNA-DNA hybridization and average nucleotide identity values between the strain and its close phylogenetic neighbour were below the threshold of 70% and 95−96% for prokaryotic species demarcation, respectively. The strain had a polar lipid profile composed of diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylmethylethanolamine (PME), phosphatidylinositol (PI), glycophospholipid (GPL), and phospholipids (PLs). The predominant menaquinone (>20%) was MK-8(H4). The major fatty acids (>5%) were C16.0, C16:1 ω7c, and C18:1 ω9c. The genomic G + C content of the strain is 73%. The chemotaxonomic, biochemical, enzymatic, and genomic features distinguished the strain from its close relative, and justify its assignment to a novel species, for which the name Nocardioides aquaegermanicae sp. nov., is proposed, with strain DSM 117947T (WG_orangeT = KCTC 59414T) as the type strain.

Mitochondrial lipid metabolism is an emerging regulator of neuronal regeneration, yet its role remains poorly defined. We investigated the function of phosphatidylserine decarboxylase (PSD), a mitochondrial enzyme that converts phosphatidylserine to phosphatidylethanolamine (PE), in retinal ganglion cell (RGC) regeneration. Using human glaucomatous degenerating optic nerves, we found PE was aberrantly accumulated with an elevated PSD expression and activity. In contrast, transcriptomes of regenerating RGCs present downregulated PSD, implicating PSD as a potential negative regulator of axonal growth. Using AAV2-mediated gene modulation, we evaluated how PSD knockdown (PSDKD) and PSD overexpression (PSDOE) alter RGC neurite outgrowth in vitro while evaluating effects on mitochondrial morphology, membrane fluidity by C-Laurdan staining, and lipidomes by LC-MS analysis. PSDOE did not support RGC neurite outgrowth, fragmented mitochondria, and increased polyunsaturated triacylglycerols. PSDKD significantly enhanced RGC neurite outgrowth and increased somal membrane fluidity accompanied by decreased cholesterol and saturated triacylglycerols. Notably, Doxorubicin, which attenuates PSD activity, increased neurite growth in PSDOE RGCs, supporting PSD's activity as a negative role for growth. Using the optic nerve crush degenerative model in C57BL/6 mice, we confirm PSDKD RGCs have higher growth competency in vivo. These findings indicate PSDKD positions RGCs in a more growth-permissive state.

More insights from Abca4-/- mouse models of recessive Stargardt disease.

As a source of non-protein nitrogen, ammonium chloride (NH4Cl) is widely utilized in ruminant diets to reduce feed costs. However, the impact of its supplementation level on the flavor of sheep meat remains unclear, despite the known influence of fat on meat flavor. This study aimed to investigate the effects of dietary NH4Cl supplementation levels on the lipidome and flavor compounds of subcutaneous adipose tissue in Tibetan sheep, providing a scientific basis for dietary optimization in Tibetan sheep farming. Eighty 2-month-old early-weaned Tibetan lambs were selected and randomly allocated into four groups, fed diets supplemented with 0% (N0 group), 1.49% (N1 group), 2.24% (N2 group), and 3.01% (N3 group) NH4Cl for an experimental period of 105 days. The study conducted histomorphological observations, lipidomics analysis, and determination of flavor compounds. The results showed that NH4Cl supplementation significantly reduced (p < 0.05) the contents of various unsaturated fatty acids and n-3 polyunsaturated fatty acids (n-3 PUFA) in the subcutaneous adipose tissue of Tibetan sheep. Specifically, the total saturated fatty acid (total SFA) content in the N3 group was significantly higher than that in the other groups, while the total monounsaturated fatty acid (total MUFA) content was significantly lower than that in the N1 and N2 groups (p < 0.05). The absolute contents of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and the sum of triglycerides (TGs) and diglycerides (DGs) in the N3 group were significantly higher (p < 0.05) than those in the other groups. Regarding flavor compounds, the contents of ketone aroma compounds, such as 2-propanone and 2-butanone monomer, were significantly higher (p < 0.05) in the N0 group than in the other groups. The ammonia content in the N1 and N3 groups was significantly higher (p < 0.05) than that in the N0 and N2 groups, while the allyl sulfide content in the N2 group was significantly higher (p < 0.05) than that in the other groups. Correlation analysis revealed that the majority of TG and DG differential lipids were significantly positively correlated with allyl sulfide, and most differential lipids belonging to the PC, PE, and hexosylceramide (Hex1Cer) classes were significantly positively correlated with ammonia (|r| ≥ 0.80, p < 0.01). Conversely, PC (16:0_18:3) exhibited significant negative correlations with multiple beneficial aroma compounds (|r| ≥ 0.80, p < 0.01). The study indicates that dietary NH4Cl supplementation levels exceeding 2.24% are associated with alterations in lipid metabolism and reduced synthesis of unsaturated fatty acids and beneficial flavor compounds, such as 2-propanone and 2-butanone, in subcutaneous adipose tissue. This is also associated with the abnormal accumulation of phospholipids and ceramides, which correlate strongly with elevated ammonia concentrations in adipose tissue and the generation of oxidation products such as propanal, potentially compromising meat flavor quality.

Summary Mineral scale formation is a challenging issue in oil and gas production, causing economic losses and safety problems. Scale inhibitor is one of the most economical and effective methods to mitigate scale damage, and green scale inhibitors with better biodegradability, less bioaccumulation, and less toxicity are needed. Biomolecules, such as amino acids, polysaccharides, and phospholipids, exhibit potential as green scale inhibitors because of their prevalence in the biosphere. However, to the best of our knowledge, systematic study of the quantitative effects of biomolecules on mineral crystallization kinetics remains scarce, preventing their industrial applications. In this study, the induction time (tind) of calcium carbonate (CaCO3) with or without nine biomolecules, including four amino acids [L-aspartic acid (L-Asp), L-glutamic acid (L-Glu), L-histidine (L-His), and L-arginine (L-Arg)], three polysaccharides [pullulan (PL), xanthan gum (XG), and carboxymethyl cellulose (CMC)], and two phospholipids [phosphatidyl ethanolamine (PE) and phosphatidyl serine (PS)], was measured using a laser apparatus at conditions of a calcite saturation index (SIcalcite) from 1.00 to 1.90, pH from 7.78 to 8.05, temperature (T) from 25°C to 90°C, and biomolecule concentrations from 0 to 500 mg/kg water (H2O). The results showed that negatively charged amino acids (L-Asp, L-Glu) and polysaccharides (CMC) show inhibitive effects, while the positively charged amino acid (L-Arg) shows promotion effects, and the neutral biomolecules (L-His, PL, and XG) show negligible effects. However, the positively charged PE also shows inhibitive effects, while the negatively charged PS shows negligible effects. In addition, under conditions with elevated calcium ion (Ca2+) concentration and lower carbonate ion (CO32−) concentration at 25°C, the inhibition efficiencies of the negatively charged L-Asp and CMC are enhanced, while that of the positively charged PE remains unchanged. As a result, it is proposed that the interactions between aqueous ions, crystals (or nuclei), and the biomolecules are based not only on electrostatic interaction but also on competition between aqueous species and surface adsorption, governing CaCO3 crystallization kinetics. The morphology changes measured by scanning electron microscope showed that the biomolecules that inhibit CaCO3 crystallization (L-Asp, L-Glu, CMC, and PE) tend to precipitate near-spherical CaCO3 solids with smooth surfaces and edges, while the biomolecules promoting CaCO3 crystallization (L-Arg) are inclined to precipitate CaCO3 with better structured rhombohedral crystals, and biomolecules showing no impact (L-His, PL, and XG) on the crystallization have no effects on morphology. This study provides experimental data and theoretical support for the development of new green scale inhibitors from naturally present biomolecules.

Ketogenic diet impairs NK cell cytotoxic function in colorectal cancer liver metastasis by inducing ferroptosis via suppression of the p62-Keap1-Nrf2 pathway.

A liquid chromatography-mass spectrometry method for profiling global phospholipid methylation via Headgroup analysis revealing cell-type specificity.