Enterovirus 71 (EV71) belongs to the family of Picornaviridae; it could cause a variety of illnesses and pose a great threat to public health worldwide. Currently, there is no specific drug treatment for this virus, and a better understanding of virus-host interaction is crucial for novel antiviral development. Here, we find that the class III phosphatidylinositol 3-kinase, VPS34, is an essential host factor for EV71 infection. VPS34 inhibition with either shRNA or specific chemical inhibitor significantly reduces EV71 infection. Meanwhile, EV71 infection upregulates phosphatidylinositol 3-phosphate (PI3P) production in viral replication organelles (ROs), while the depletion of PI3P by phosphatase overexpression inhibits EV71 infection. In addition, the PI3P-binding protein, double FYVE-containing protein 1 (DFCP1), is also required for an efficient replication of EV71. DFCP1 could interact with viral 2C protein and facilitate viral association with lipid droplets (LDs), which are important lipid sources for viral RO biogenesis. Taken together, these results indicate that EV71 virus exploits the VPS34-PI3P-DFCP1-LDs pathway to promote viral RO formation and viral infection, and they also illuminate novel targets for antiviral development.IMPORTANCEEnterovirus 71 (EV71) is a major pathogen that causes hand-foot-and-mouth disease (HFMD) and other serious complications, which are big threats to children under 5 years old. Unravelling the interactions between virus and the host cells will open new avenues in antiviral research. Here, we found the class III phosphatidylinositol 3-kinase, VPS34, and its effector, double FYVE-containing protein 1 (DFCP1), were essential for EV71 infection, both of which could support EV71 viral replication by enhancing the biogenesis of viral replication organelles (ROs). As DFCP1 localizes to lipid droplets, hijacking of these host factors will enable viral utilization of lipids from LDs for the generation of membrane structures during RO biogenesis. In addition, the VPS34 kinase inhibitor was found to be potent against EV71 infection; therefore, this study also brings up a novel target for future anti-EV71 drug development.

Several studies have indicated a potential causal relationship between plasma standard lipids, such as high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), and total cholesterol (TC), and psoriasis. However, few studies have offered causal evidence of lipid species beyond these standard lipids. We conducted an analysis using a genome-wide association study (GWAS) dataset comprising 179 lipid species, including 13 types across four major categories, to identify instrumental variables (IVs) associated with plasma lipids. We utilized two GWAS datasets from the IEU and Finngen for psoriasis vulgaris as the outcome. A two-sample Mendelian randomization (MR) analysis was used to explore the causal relationship between 179 lipid species and psoriasis vulgaris in two datasets. Lipid species showing causal association in both psoriasis datasets were compared for overlap. Our study identified potential causal relationships between six lipid species and psoriasis vulgaris: phosphatidylcholine (16:1_18:2), phosphatidylcholine (18:0_18:2), phosphatidylcholine (18:1_20:4), phosphatidylethanolamine (16:0_18:2), phosphatidylinositol (18:0_20:3), and triacylglycerol (50:1). In summary, elevated plasma levels of phosphatidylcholine (16:1_18:2), phosphatidylcholine (18:0_18:2), phosphatidylethanolamine (16:0_18:2), phosphatidylinositol (18:0_20:3), and triacylglycerol (50:1) may increase the risk of psoriasis vulgaris. Conversely, plasma phosphatidylcholine (18:1_20:4) may play a protective role against psoriasis vulgaris.

Interest in macropinocytosis has risen in recent years owing to its function in tumorigenesis, immune reaction, and viral infection. Cancer cells utilize macropinocytosis to acquire nutrients to support their uncontrolled proliferation and energy consumption. Macropinocytosis, a highly dynamic endocytic and vesicular process, is regulated by a series of cellular signaling pathways. The activation of small GTPases in conjunction with phosphoinositide signaling pivotally regulates the process of macropinocytosis. In this review, we summarize important findings about the regulation of macropinocytosis and provide information to increase our understanding of the regulatory mechanism underlying it.

The omega-3 fatty acid desaturase enzyme gene FAD3 is responsible for converting linoleic acid to linolenic acid in plant fatty acid synthesis. Despite limited knowledge of its role in cotton growth, our study focused on GhFAD3-4, a gene within the FAD3 family, which was found to promote fiber elongation and cell wall thickness in cotton. GhFAD3-4 was predominantly expressed in elongating fibers, and its suppression led to shorter fibers with reduced cell wall thickness and phosphoinositide (PI) and inositol triphosphate (IP3) levels. Transcriptome analysis of GhFAD3-4 knock-out mutants revealed significant impacts on genes involved in the phosphoinositol signaling pathway. Experimental evidence demonstrated that GhFAD3-4 positively regulated the expression of the GhBoGH3B and GhPIS genes, influencing cotton fiber development through the inositol signaling pathway. The application of PI and IP6 externally increased fiber length in GhFAD3-4 knock-out plants, while inhibiting PI led to a reduced fiber length in GhFAD3-4 overexpressing plants. These findings suggest that GhFAD3-4 plays a crucial role in enhancing fiber development by promoting PI and IP3 biosynthesis, offering the potential for breeding cotton varieties with superior fiber quality.

BACKGROUND: Alterations in the secretion and composition of skin surface lipids (SSL) are closely associated with the development of acne. Lipidomics is a useful tool to analyse the SSL of different types of acne. Our previous study found that phosphatidylserine and triacylglycerols dominate SSL changes in male acne and infantile acne, respectively. However, skin surface lipids as well as specific lipids in female acne patients remain to be investigated.
OBJECTIVE: To analyse and compare the SSL profile of acne women and healthy women and to discuss the involvement of differential lipids in acne development.
METHODS: Systematic lipidomics approach (high-throughput UPLC-QTOF-MS technology in combination with multivariate data analysis methods) was used to analyse the variations of SSL between acne and healthy groups.
RESULTS: Analysis revealed significant differences in lipid content and composition between the two groups. Further analysis showed that levels of 13 individual lipids were significantly different and followed the same trend as the main class and subclasses. The largest individual contributor to the subgroup was triglycerides (TG) and phosphatidylinositol (PI). In addition, female acne patients exhibited reduced ceramide chain length (CCL) and increased levels of unsaturated fatty acids (UFAs), The changes of CCL in female acne are identical to male acne.
CONCLUSIONS: There was a significantly higher level of TG and PI in the SSL of female acne patients. A reduction in CCL and an increase in UFAs content might contribute to the reduced skin barrier function in acne patients. The results suggest that female acne may have different pathogenesis than male acne.
BACKGROUND: Les altérations de la sécrétion et de la composition des lipides de la surface de la peau (SSL) sont étroitement associées au développement de l’acné. La lipidomique est un outil utile pour analyser les SSL de différents types d’acné. Notre précédente étude a révélé que la phosphatidylsérine et les triacylglycérols dominent les modifications de SSL dans l’acné masculine et l’acné infantile, respectivement. Cependant, les lipides de la surface de la peau ainsi que des lipides spécifiques chez les patients de sexe féminin souffrant d’acné restent à étudier.
OBJECTIVE: Analyser et comparer le profil des SSL des femmes atteintes d’acné et des femmes en bonne santé, et discuter de l’implication des lipides différentiels dans le développement de l’acné. MÉTHODES: Une approche lipidomique systématique (technologie UPLC‐QTOF‐MS à haut débit en association avec des méthodes d’analyse de données multivariées) a été utilisée pour analyser les variations des SSL entre les groupes de patients atteints d’acné et de patients en bonne santé. RÉSULTATS: L’analyse a révélé des différences significatives au niveau de la teneur en lipides et de la composition entre les deux groupes. Une analyse approfondie a montré que les taux de 13 lipides individuels étaient significativement différents et suivaient la même tendance que la classe principale et les sous‐classes. Le principal contributeur individuel au sous‐groupe était les triglycérides (TG) et le phosphatidylinositol (PI). En outre, les patientes atteintes d’acné ont présenté une réduction de la longueur de la chaîne céramide (CCL) et une augmentation des taux d’acides gras insaturés (UFA). Les variations de la CCL dans l’acné féminine sont identiques à celles observées chez les hommes.
CONCLUSIONS: Il y avait un taux significativement plus élevé de TG et de PI dans les SSL des patientes atteintes d’acné. Une réduction de la CCL et une augmentation de la teneur en UFA pourraient contribuer à réduire la fonction de barrière cutanée chez les patients atteints d’acné. Les résultats suggèrent que l’acné féminine peut avoir une pathogenèse différente de l’acné masculine.
背景: 皮肤表面脂质(SSL)的分泌和组成的改变与痤疮的发展密切相关。脂质组学是分析不同类型痤疮SSL的有用工具。我们之前的研究发现，磷脂酰丝氨酸和三酰基甘油分别主导了男性痤疮和婴儿痤疮的SSL变化。然而，女性痤疮患者的皮肤表面脂质以及特定的脂质仍有待研究. 目的: 分析和比较痤疮女性和健康女性的SSL特征，并讨论不同脂质在痤疮发展中的作用. 方法: 采用系统脂质组学方法(高通量UPLC‐QTOF‐MS技术结合多变量数据分析方法)分析痤疮组与健康组之间SSL的差异. 结果: 分析显示两组间的脂质含量和成分有显著性差异。进一步分析显示，13种个体脂质水平存在显著差异，与主要类和亚类遵循相同的趋势。该亚组中最大的个体贡献者是甘油三酯(TG)和磷脂酰肌醇(PI)。此外，女性痤疮患者的神经酰胺链长度(CCL)减少，不饱和脂肪酸(UFAs)水平升高，女性痤疮中CCL的变化与男性痤疮相同. 结论: 女性痤疮患者SSL中TG和PI水平显著升高。CCL的减少和UFAs含量的增加可能导致痤疮患者皮肤屏障功能的降低。结果表明，女性痤疮可能与男性痤疮有不同的发病机制.

As a member of the tumor necrosis factor-α-induced protein 8 (TNFAIP8/TIPE) family, TIPE1 has been found to be associated with many cellular signaling pathways in regulating apoptosis, autophagy, and tumorigenesis. However, the position of TIPE1 in the signaling network remains elusive. Here we present the crystal structure of zebrafish TIPE1 in complex with phosphatidylethanolamine (PE) at a resolution of 1.38 Å. By comparison with structures of other three TIPE family proteins, a universal phospholipid-binding mode was proposed. Namely, the hydrophobic cavity binds to fatty acid tails, while \'X-R-R\' triad nearby the entrance of cavity recognizes the phosphate group head. Using molecular dynamics (MD) simulations, we further elaborated the mechanism of how the lysine-rich N-terminal domain assisting TIPE1 to favorably bind to phosphatidylinositol (PI). Beside small molecule substrate, we identified Gαi3 as a direct-binding partner of TIPE1 using GST pull-down assay and size-exclusion chromatography. Analyses of key-residue mutations and predicted complex structure revealed that the binding mode of TIPE1 to Gαi3 could be non-canonical. In summary, our findings narrowed down TIPE1\'s position in Gαi3-related and PI-inducing signaling pathways.Communicated by Ramaswamy H. Sarma.

The process of fertilization includes sperm capacitation, hyperactivation, an acrosome reaction and the release of acrosome enzymes, membrane fusion and channel formation, the release of the sperm nucleus, and gamete fusion. This process is closely related to the shape and vitality of the sperm, acrosome enzyme release, and the zona pellucida structure of the egg, as well as the opening and closing of various ion (e.g., calcium) channels, the regulation of signaling pathways such as cyclic adenosine monophosphate-protein kinase A, the release of progesterone, and the coupling of G-proteins. The interaction among multiple factors and their precise regulation give rise to multiple cascading regulatory processes. Problems with any factor will affect the success rate of fertilization. Recent studies have shown that with rapid societal development, the incidence of male infertility is increasing and occurs at younger ages. According to World Health Organization statistics, 15% of couples of childbearing ages have infertility problems, of which 50% are caused by male factors. Additionally, the cause of infertility cannot be identified in as many as 60% to 75% of male infertility patients. In this article, we review the research progress on the microregulation of fertilization and mechanisms underlying this process to identify causes and develop novel prevention and treatment strategies for male infertility.

UNASSIGNED: Cardiac surgery with cardiopulmonary bypass (CPB) is considered to be one of the surgical types with the highest incidence of post-operative delirium (POD). POD has been associated with a prolonged intensive care and hospital stay, long-term neurocognitive deterioration, and increased mortality. However, the specific pathogenesis of POD is still unclear. Untargeted metabolomics techniques can be used to understand the changes of serum metabolites in early POD to discover the relationship between serum metabolites and disease.
UNASSIGNED: The present study recruited 58 elderly patients undergoing cardiac surgery with CPB. Serum was collected within the first 24 h after surgery. The Confusion Assessment Method (CAM) and ICU-CAM assessments were used to identify patients who experienced POD. All patients with normal post-operative cognitive assessment were included in the non-POD groups. Moreover, we collected serum from 20 healthy adult volunteers. We performed untargeted analyses of post-operative serum metabolites in all surgical groups, as well as serum metabolites in healthy non-surgical adults by using liquid chromatography mass spectrometry (LC/MS) and analyzed metabolic profiles and related metabolites.
UNASSIGNED: The probability of POD after cardiac surgery were 31%. There were statistically significant differences in post-operative mechanical ventilation time, ICU stay time and post-operative hospital stay between POD and non-POD group (P < 0.05). And ICU stay time was an independent risk factor for POD. The analysis revealed that a total of 51 differentially expressed metabolites (DEMs) were identified by comparing the POD and non-POD group, mostly lipids and lipid-like molecules. Three phosphatidylinositol (PI) were down-regulated in POD group, i.e., PI [18:0/18:2 (9Z, 12Z)], PI [20:4 (8Z, 11Z, 14Z, 17Z)/18:0], and PI [18:1 (9Z)/20:3 (8Z, 11Z, 14Z)]. The receiver operating characteristic (ROC) curve analysis showed that three kinds of PI metabolites had the highest area under the curve (AUC), which were 0.789, 0.781, and 0.715, respectively. Correlation analysis showed that the expression of three PIs was negatively correlated with the incidence of POD.
UNASSIGNED: Our findings suggest that lipid metabolism plays an important role in the serum metabolic profile of elderly patients with POD in the early post-operative period. Low serum lipid metabolic PI was associated with incidence of POD in elderly following cardiac bypass surgery, which may provide new insights into the pathogenesis of POD.

Genetic variants that increase the risk of fatty liver disease and cirrhosis have recently been identified in the proximity of membrane-bound O-acyltransferase domain-containing 7 (MBOAT7). To elucidate the link between these variants and fatty liver disease, we characterized Mboat7 liver-specific KO mice (Mboat7 LSKO). Chow-fed Mboat7 LSKO mice developed fatty livers and associated liver injury. Lipidomic analysis of liver using MS revealed a pronounced reduction in 20-carbon PUFA content in phosphatidylinositols (PIs) but not in other phospholipids. The change in fatty acid composition of PIs in these mice was associated with a marked increase in de novo lipogenesis because of activation of SREBP-1c, a transcription factor that coordinates the activation of genes encoding enzymes in the fatty acid biosynthesis pathway. Hepatic removal of both SREBP cleavage-activating protein (Scap) and Mboat7 normalized hepatic triglycerides relative to Scap-only hepatic KO, showing that increased SREBP-1c processing is required for Mboat7-induced steatosis. This study reveals a clear relationship between PI fatty acid composition and regulation of hepatic fat synthesis and delineates the mechanism by which mutations in MBOAT7 cause hepatic steatosis.

Phosphatidylglycerol (PG) and phosphatidylinositol (PI) are two essential classes of glycerophospholipids (GPs), playing versatile roles such as signalling messengers and lipid-protein interaction ligands in cell. Although a majority of PG and PI molecular species contain unsaturated fatty acyl chain(s), conventional tandem mass spectrometry (MS/MS) methods cannot discern isomers different in carbon-carbon double bond (CC) locations. In this work, we paired phosphate methylation with acetone Paternò-Büchi (PB) reaction, aiming to provide a solution for sensitive and structurally informative analysis of these two important classes of GPs down to the location of CC. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflow was established. Offline methylated PG or PI mixtures were subjected to hydrophilic interaction chromatographic separation, online acetone PB reaction, and MS/MS via collision-induced dissociation (CID) for CC location determination in positive ion mode. This method was sensitive, offering limit of identification at 5 nM for both PG and PI standards down to CC locations. On molecular species level, 49 PI and 31 PG were identified from bovine liver, while 61 PIs were identified from human plasma. This workflow also enabled ratiometric comparisons of CC location isomers (C18:1 Δ9 vs. Δ11) of a series of PIs from type 2 diabetes (T2D) plasma to that of normal plasma samples. PI 16:0_18:1 and PI 18:0_18:1 were found to exhibit significant changes in CC isomeric ratios between T2D and normal plasma samples. The above results demonstrate that the developed LC-PB-MS/MS workflow is applicable to different classes of lipids and compatible with other established lipid derivatization methods to achieve comprehensive lipid analysis.