A novel aerobic, Gram-stain-positive, non-motile, non-spore-forming, short rod-shaped strain X10-3T, was isolated from Daihai Lake, Inner Mongolia, China. The strain formed circular, smooth, transparent, orange-colored colonies with convex elevation and entire margins, which measured approximately 1.0-4.0mm in diameter after 48h of incubation on Luria-Bertani agar at 32°C. The strain was able to grow at pH levels between 6.5 and 9.0 (optimal at 7.5-8.0), temperatures from 4 to 40°C (optimal at 37°C), and in 0-13% (optimal at 2-3%, w/v) NaCl. The complete genome of strain X10-3T comprises 3,244,194bp with a DNA G + C content of 45.9%. Phylogenetic analysis revealed the closest relationship to members of the genus Planococcus, showing 16S rRNA gene sequence similarities of 99.2% with P. salinarum DSM 23820T, 98.8% with P. wigleyi Sa1BUA13T, 98.6% with P. koreense JG07T, and 98.6% with P. halotolerans SCU63T. The average nucleotide identity between strain X10-3T and the species within the genus Planococcus fell below the species delineation thresholds of 95%, and the digital DNA-DNA hybridization values were lower than 70%. Chemotaxonomic analysis revealed that the predominant cellular fatty acids of strain X10-3T were anteiso-C15:0 and C16:1 ω7c alcohol. The primary cellular polar lipids included phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol, while the predominant isoprenoid quinones were menaquinone-8 and menaquinone-7. Based on these comprehensive analyses, strain X10-3T represents a new species of the genus Planococcus, for which the name Planococcus daihaiensis sp. nov. is proposed. The type strain is X10-3T (= CGMCC 1.60163T = KCTC 43688T).

Imidacloprid Exposure at Population-Relevant Doses Induces Hepatic Lipid Dysregulation: Exploring the Role of cGAS-STING Pathway-Mediated Hepatocyte Senescence.

Viruses remodel metabolic processes and utilize host lipids for different stages of their life cycle. Our earlier studies have shown that the flavivirus Japanese encephalitis virus (JEV) downmodulates several key proteins involved in sterol and lipid biosynthesis. Through a lipidome analysis, we report that virus infection dysregulates nearly 41% of the cellular lipids in mouse embryonic fibroblasts (MEFs). This manifests as down-modulation of cholesterol, cholesterol esters, and glycerolipids and upregulation of ceramides and several phospholipids. Significant transcriptional downregulation of cholesterol biosynthetic pathway genes was observed in JEV-infected MEFs and mouse bone marrow-derived macrophages (BMDMs). This effect was dependent upon an active interferon (IFN) signaling node. Both knockdown and pharmacological inhibition of 7-dehydrocholesterol reductase (Dhcr7), a key regulator of the cholesterol biosynthesis pathway, exerted potent antiviral effects by blocking viral replication and enhancing IFN signaling. Direct supplementation with the Dhcr7 substrate, 7-dehydrocholesterol (7DHC), showed similar antiviral effects. A partial inhibition of virus replication was also observed in cells deficient for IFN signaling, highlighting an IFN-independent antiviral role of Dhcr7 inhibition. Overall, these findings underscore the potential of cholesterol biosynthetic pathway inhibition as an antiviral strategy for JEV.IMPORTANCEJEV, a mosquito-borne virus, is a leading global cause of virus-induced encephalitis with a significant disease burden in Southeast Asia. In this study, we observe that the cellular lipid composition changes in virus-infected cells, with lower levels of cholesterol and cholesterol esters. We also observe that specific genes of the cholesterol biosynthesis pathway are decreased, and this depends on the activation of the antiviral interferon (IFN) response. We have characterized one specific downregulated gene Dhcr7, which catalyzes the conversion of 7-dehydrocholesterol (7DHC) to cholesterol. Depletion of the Dhcr7-specific mRNA, inhibition through drugs, or adding the substrate 7DHC further enhanced the IFN response and blocked virus replication. Our study highlights that downregulation of the cholesterol biosynthetic pathway has the potential to be developed into an antiviral strategy. .

The adiponectin receptor agonist AdipoRon alleviates lipotoxic injury in LMH cells.

High-fat diet mediates the formation of nonalcoholic fatty liver by modulating the AhR/miR-132/SIRT1 axis.

Acetyl tributyl citrate induces intestinal toxicity by regulating the IDH2/NF-κB pathway and lipid peroxidation.

A multi-omics investigation reveals the hepatic response to salinity stress in grass carp (Ctenopharyngodon idella).

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is now recognized as the leading cause of chronic liver disease worldwide. MASLD spans a spectrum ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and is linked to progressive fibrosis and ultimately hepatocellular carcinoma (HCC). Growing evidence implicates cellular senescence (CS) and lipid droplets (LDs) as key drivers of disease progression, although their interaction remains poorly characterized. This review provides an integrative and stage-dependent synthesis of current mechanistic insights into how bidirectional crosstalk between CS and LD regulation shapes the transition from steatosis to MASH. Senescent hepatocytes display altered lipid metabolism, including upregulation of receptors such as cluster of differentiation (CD) 36, enhancing lipid uptake to meet increased energy demands. Initially, elevated free fatty acid influx can activate peroxisome-proliferator-activated receptor alpha (PPARα), promoting fatty acid oxidation (FAO) as a compensatory response. Over time, persistent CS under steatotic conditions leads to mitochondrial dysfunction and suppression of fatty acid oxidation (FAO), while the senescence-associated secretory phenotype (SASP), largely driven by nuclear factor-kappa B (NF-κB) signaling, promotes chronic hepatic inflammation. By framing LDs as active modulators of senescence-associated signaling rather than passive lipid stores, this review highlights how disruption of senescence-lipid feedback loops may represent a disease-modifying opportunity in MASLD progression.

FOXOs constitute a class of evolutionarily conserved transcription factors that play pivotal roles in diverse cellular processes, including glucose and lipid metabolism, energy homeostasis, oxidative stress response, and autophagy. They are recognized as central regulators of longevity. This review details the mechanisms linking FOXO to aging. FOXO activity is regulated via nucleocytoplasmic shuttling, a process controlled by phosphorylation and dephosphorylation through the insulin/insulin-like growth factor (IIS) signaling pathway. This shuttling influences the expression of aging-related genes, thereby modulating aging-related phenotypes in tissues such as muscle and liver. Furthermore, FOXO can also regulate the autophagy pathway through multiple mechanisms: On one hand, it transcriptionally activates core autophagy genes such as Ulk2 and Becn1; on the other hand, it enhances autophagic activity by modulating miRNAs or epigenetic modifications, thereby promoting the elimination of damaged cellular components, and ultimately delaying organismal aging. Moreover, as a key sensor of oxidative stress, FOXO is activated by reactive oxygen species (ROS), thereby inducing the expression of antioxidant enzymes that mitigate oxidative damage and delay cellular aging. This review provides an in-depth exploration of the dual roles of FOXO in various aging-related diseases. This includes neurodegenerative diseases (such as Huntington's disease, Parkinson's disease, and Alzheimer's disease), metabolic disorders (such as type 2 diabetes), and various cancers. Meanwhile, this review also discusses drugs targeting the FOXO pathway in recent years (such as canagliflozin, metformin, resveratrol, and berberine). These FOXO-targeting compounds demonstrate great potential in improving metabolic disorders and delaying the onset of aging phenotypes.

Lipidomic profiling of Arabidopsis chloroplast protein phosphatase SLP1 mutants reveals altered diurnal lipid remodeling

Lipid disorder is an independent risk factor of diabetic kidney disease (DKD). Excess accumulation of lipid in podocytes can cause cell dysfunction and cell death. Chaperone-mediated autophagy (CMA) serves as a critical role in regulating lipid metabolism. However, the exact role of CMA in the podocytes of DKD with dyslipidemia is still uncertain. Herein, we aimed to explore the role of CMA in hyperlipidemia-induced lipid accumulation and apoptosis in podocytes. In the present study, we showed that palmitic acid (PA) treatment induced the activation of CMA, increased lipid accumulation and apoptosis in podocytes. We further found that blocking CMA with inhibitor VER155008 or LAMP-2A siRNA significantly upregulated PA-induced increased expression of PLIN2, exacerbated PA-induced lipid accumulation and apoptosis, whereas promoting CMA with Torin1 downregulated the expression of PLIN2, ameliorated lipid accumulation and apoptosis in PA-induced podocytes. Moreover, we also observed the activation of CMA and increased lipid accumulation in the kidney tissue of DKD mice. Taken together, these results suggest that CMA plays a protective role in PA-induced podocytes apoptosis and that the potential protective mechanism of CMA is involved in reducing cellular lipid accumulation through mediating the degradation of PLIN2.

High-yield influenza virus production is essential for efficient vaccine manufacturing to support global demands. Using Madin-Darby canine kidney (MDCK) cells to produce influenza viruses is an attractive alternative to the conventional method of manufacturing vaccines using embryonated eggs. MDCK cells exhibit heterogeneity which can impact viral yields. However, the factors driving the variation between MDCK cells are not fully understood. Utilizing an untargeted liquid chromatography-mass spectrometry lipidomic approach, we investigated two proprietary MDCK clones (C59 and C113) provided by Sartorius (Germany) that differ in biochemical and viral production properties and examined their lipid profiles and dynamics upon influenza A virus (IAV) infection between 24 and 72 h. C113, a high-yield clone, displayed elevated levels across all lipid classes, aside from ether lipids compared to C59, a clone with superior growth properties. IAV infection in clone C59 and C113 displayed key differences, specifically triacylglycerols. Analysis of progeny virions from C59 and C113 clones revealed subtle differences with a positive correlation in lipid profile (R2 = 0.77), suggesting similar lipid raft domains between clones. Overall, these findings highlight specific cellular lipid signatures associated with high-yield production and demonstrate the value of integrating lipidomics methods into biomanufacturing pipelines, providing complimentary quality assurance markers.Supplementary InformationThe online version contains supplementary material available at 10.1038/s41598-025-33499-1.

Cellular lipid metabolism is subject to strong homeostatic regulation, but the players involved in and mechanisms underlying these pathways remain largely uncharacterized. Here we develop a 'feeding-fishing' approach coupling membrane editing using optogenetic lipid-modifying enzymes (feeding) with organelle membrane proteomics through proximity labeling (fishing) to elucidate molecular players and pathways involved in the homeostasis of phosphatidic acid (PA), a multifunctional lipid central to glycerolipid metabolism. This approach identified several PA-metabolizing enzymes and lipid transfer proteins enriched in and depleted from PA-fed membranes. Mechanistic analysis revealed that PA homeostasis in the cytosolic leaflets of the plasma membrane and lysosomes is mediated by both local PA metabolism and the action of lipid transfer proteins that carry out interorganelle lipid transport before subsequent metabolism. More broadly, the interfacing of membrane editing to controllably modify membrane lipid composition with organelle membrane proteomics using proximity labeling represents a strategy for revealing mechanisms governing lipid homeostasis.

Abstract Introduction and aims Keloids are a type of fibroproliferative scar that progressively grow beyond the original wound site. Currently, there are no treatments to halt or revert keloid scarring, emphasizing an unmet clinical need. Fibroblasts are presumed to be one of the main cells involved in keloid, due to their role in depositing and remodelling extracellular matrix. In normal tissue repair fibroblasts enter a resolution phase, which we hypothesize fails in keloid. Therefore, this study investigates the chromatin and transcriptional landscape of keloid fibroblasts, questioning whether manipulation of the epigenome can reverse their locked profibrotic state. Methods We performed ATAC sequencing (ATACseq) and RNA sequencing on a patient-matched pair of keloid and nonlesional fibroblasts. Bioinformatic analysis revealed differential accessible regions with multiple transcription factors and regulatory elements which we correlated to gene expression changes. Identified key candidates were manipulated in two-dimensional cell culture models and validated in keloid scar tissue. Results ATACseq analysis revealed a more accessible chromatin structure in keloid fibroblasts in areas regulating developmental, growth factor signalling and profibrotic gene signatures. This was confirmed in vitro with increased histone acetylation and methylation marks, associated with open chromatin and higher transcriptional activation. The most accessible chromatin regions in keloid fibroblasts were around the FGFR2 and TGFβR3 gene loci. Stimulation of cells with these growth factors increased signalling responsiveness in proliferation in keloid fibroblasts. Additionally, keloid cells had shown a more reticular-like cellular membrane lipid composition which can be altered in response to fibroblast growth factor 2 and transforming growth factor β stimulation. Treatment with chromatin-modifying drugs such as trichostatin A actively modulated the fibrotic morphology of keloid fibroblasts. Conclusions Keloids have a more open chromatin that is anticipated to play an active role in maintaining profibrotic signalling pathways and cell behaviours. We are currently exploring the therapeutic potential of manipulating the chromatin in keloid fibroblasts to reduce scarring.

Lipid droplets (LDs) are central to cellular energy homeostasis and lipid metabolism. While LD-associated proteins are known to regulate LD dynamics and function, their roles in LD transport and their broader cellular significance remain poorly understood. In this study, we identify lipid droplet-localized spindle apparatus coiled-coil protein 1 (SPDL1-L) as a key regulator of intracellular LD transport. SPDL1-L localizes to LDs through the synergistic action of its hydrophobic region and nearby basic residues. SPDL1-L expression promotes LD clustering at the microtubule-organizing center (MTOC) and the formation of donut-shaped (toroidal) nuclei during cell division. SPDL1-L-mediated LD clustering is likely through dynein-mediated minus end transport. LD clustering activity is diminished when the LD targeting or dynein binding function of SPDL1-L is impaired. Together, our findings provide new insights into the mechanisms governing LD dynamics and their impact on cellular organization.

IL-17D promotes ferroptosis resistance in lung cancer via activating PPARγ pathway.

Ferroptosis, an instance of iron-dependent programmable cell death that results from oxidative stress & lipid peroxidation, has garnered interest due to its associations with cardiovascular diseases, such as atherosclerosis, myocardial infarction, as well as heart failure. Unlike necrosis or apoptosis, ferroptosis involves unique metabolic pathways that disrupt cellular redox balance and lipid homeostasis, leading to substantial cell damage in cardiovascular tissues. It is becoming recognized that phytoconstituents-bioactive compounds derived from plants-can modify ferroptosis pathways and provide cardioprotective advantages. Compounds including curcumin, resveratrol, quercetin, tanshinone IIA, and epigallocatechin gallate (EGCG) have shown potential in preclinical studies by concentrating on significant ferroptotic processes. Finally, by controlling iron homeostasis, boosting antioxidant responses (such as Nrf2 pathway activation), and reducing lipid peroxidation, these phytochemicals may mitigate ferroptosisinduced cardiac cell death. In animal studies, these natural compounds have shown promise in reducing oxidative damage and improving heart function after injury. This article summarises the mechanisms via which a variety of phytoconstituents influence ferroptosis and discusses their potential as an adjuvant treatment for CVD. While these findings are encouraging, further research is needed to use them in clinical settings, with a focus on long-term safety in human populations, optimal dose, and absorption. The cardioprotective properties of phytoconstituents, which focus on ferroptosis, may provide a unique, plant-based therapeutic strategy for the treatment of CVDs.

Perfluorooctanoic acid (PFOA) exposure induced ferroptosis through the PPARα/FABP7 signaling pathway in the liver of spotted sea bass (Lateolabrax maculatus).

Current Therapeutic Targets for Alcohol-Associated Liver Disease.

Sigma Non-Opioid Intracellular Receptor 1 (SigmaR1) is a member of the sigma family of receptors that interacts with a variety of psychotomimetic drugs and is involved in a wide range of cellular and physiological functions. Despite its increasing importance in human physiology and disease, the subcellular localization of SigmaR1 and its molecular function remain poorly defined. Using endogenous tagging and cell fractionation, we show that SigmaR1 is a type II integral ER membrane protein that is specifically enriched at ER sheets. A short region at the N-terminus of SigmaR1 promotes its ER-sheet localization. Importantly, our biochemical studies demonstrate that SigmaR1 directly interacts with components of the translocon complex including TRAPα and Nicalin. In addition, we found that a β-barrel at the C-terminal of SigmaR1 binds phosphatidylcholine (PC), and the binding of PC strengthens the association of SigmaR1 with the translocon complex. SigmaR1 knockout systematically impaired cellular protein and lipid homeostasis, resulting in accumulation of lipid droplets in hepatocytes. Collectively, we propose that SigmaR1 is an auxiliary translocon factor that binds lipids to regulate protein and lipid droplet homeostasis, which may underlie the broad and vital roles of SigmaR1 in physiology and disease.