Deciphering the role of CX3CL1-CX3CR1 in aortic aneurysm pathogenesis: insights from Mendelian randomization and transcriptomic analyses.

Background: The crucial role of inflammation in aortic aneurysm (AA) is gaining prominence, while there is still a lack of key cytokines or targets for effective clinical translation. Methods: Mendelian randomization (MR) analysis was performed to identify the causal relationship between 91 circulating inflammatory proteins and AA and between 731 immune traits and AA. Bulk RNA sequencing data was utilized to demonstrate the expression profile of the paired ligand-receptor. Gene enrichment analysis, Immune infiltration, and correlation analysis were employed to deduce the potential role of CX3CR1. We used single-cell RNA sequencing data to pinpoint the localization of CX3CL1 and CX3CR1, which was further validated by multiplex immunofluorescence staining. Cellchat analysis was utilized to infer the CX3C signaling pathway. Trajectory analysis and the Cytosig database were exploited to determine the downstream effect of CX3CL1-CX3CR1. Results: We identified 4 candidates (FGF5, CX3CL1, IL20RA, and SCF) in multiple two-sample MR analyses. Subsequent analysis of the expression profile of the paired receptor revealed the significant upregulation of CX3CR1 in AA and its positive correlation with pro-inflammatory macrophages. Two sample MR between immune cell traits and AA demonstrated the potential causality between intermediate monocytes and AA. We finally deciphered in single-cell sequencing data that CX3CL1 sent by endothelial cells (ECs) acted on CX3CR1 of intermediated monocytes, leading to its recruitment and pro-inflammatory responses. Conclusion: Our study presented a genetic insight into the pathogenetic role of CX3CL1-CX3CR1 in AA, and further deciphered the CX3C signaling pathway between ECs and intermediate monocytes.

Histone H3Y99sulf regulates hepatocellular carcinoma responding to hypoxia.

Histone H3 tyrosine-99 sulfation (H3Y99sulf) is a recently identified histone mark that can cross-talk with H4R3me2a to regulate gene transcription, but its role in cancer biology is less studied. Here, we report that H3Y99sulf is a cancer-associated histone mark that can mediate hepatocellular carcinoma (HCC) cells responding to hypoxia. Hypoxia-stimulated SNAIL pathway elevates the expression of PAPSS2, which serves as a source of adenosine 3'-phosphate 5'-phos-phosulfate for histone sulfation and results in upregulation of H3Y99sulf. The transcription factor TDRD3 is the downstream effector of H3Y99sulf-H4R3me2a axis in HCC. It reads and co-localizes with the H3Y99sulf-H4R3me2a dual mark in the promoter regions of HIF1A and PDK1 to regulate gene transcription. Depletion of SULT1B1 can effectively reduce the occurrence of H3Y99sulf-H4R3me2a-TDRD3 axis in gene promoter regions and lead to downregulation of targeted gene transcription. Hypoxia-inducible factor 1-alpha and PDK1 are master regulators for hypoxic responses and cancer metabolism. Disruption of the H3Y99sulf-H4R3me2a-TDRD3 axis can inhibit the expression and functions of hypoxia-inducible factor 1-alpha and PDK1, resulting in suppressed proliferation, tumor growth, and survival of HCC cells suffering hypoxia stress. The present study extends the regulatory and functional mechanisms of H3Y99sulf and improves our understanding of its role in cancer biology.

[Analysis of volatile and semivolatile components of burley tobacco before and after baking by headspace solid-phase microextraction gas chromatography/mass spectrometry with chemometrics].

The volatile and semivolatile components in burley tobacco leaves were analyzed by headspace solid-phase microextraction gas chromatography/mass spectrometry (HS-SPME-GC/MS). Twenty milligrams of tobacco powder was incubated at 60 ℃ for 8 min and then extracted using 65 µm polydimethylsiloxane/divinylbenzene (PDMS/DVB) fiber for 40 min. Finally, the fiber was desorbed at 250 ℃ for 3 min. One hundred twenty two kinds of volatile and semivolatile components in the burley tobacco leaves were tentatively identified by comparing with standard products and mass spectrometry databases, and these compounds were semi-quantitatively analyzed by the internal standard method. The differences between the volatile and semivolatile components for the burley tobacco leaves before and after baking were discriminated and visualized by principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA). This method has the advantages of small sample size, simple pretreatment, and high sensitivity. In combination with chemometrics, the HS-SPME-GC/MS method is suitable for discriminating changes in the chemical composition of burley tobacco before and after baking, and hence has broad prospective application in the optimization of the baking conditions used for burley tobacco.

Confinement Induced Preferential Orientation of Crystals and Enhancement of Properties in Ferroelectric Polymer Nanowires.

The physical properties of polymers strongly depend on the molecular or supermolecular order and orientation. Here we demonstrate the preferential orientation of lamellar crystals and the enhancement of ferro/piezoelectric properties in individual poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) nanowires fabricated from anodic alumina oxide (AAO) templates. The crystallographic a axis of P(VDF-TrFE) was found to be aligned along the long axis of nanowires due to geometrical confinement and grapho-expitaxial crystals growth. The alignment of lamellar crystals in P(VDF-TrFE) nanowires and enhancement of crystallization translated into improved ferro/piezoelectric properties such as lower coercive field and higher piezoelectric coefficient, testified by piezoresponse force microscopy images and piezoresponse hysteresis loops.