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C-X-C motif chemokine ligand 12(CXCL12) is an essential chemokine for organ development and homeostasis in multiple tissues. Its receptor, C-X-C chemokine receptor type 4(CXCR4), is expressed on the surface of target cells. The chemokine and receptor are expressed almost ubiquitously in human tissues and cells throughout life, and abnormal expression of CXCL12 and CXCR4 is observed in pathological conditions, such as inflammation and cancer. CXCR4 is reportedly translated into five splicing variants of different lengths, which each have different amino acids in the N-terminus. As the N-terminus is the first recognition site for chemokines, CXCR4 variants may respond differently to CXCL12. Despite these differences, the molecular and functional properties of CXCR4 variants have not been thoroughly described or compared. Here, we explored the expression of CXCR4 variants in cell lines and analyzed their roles in cellular responses using biochemical approaches. RT-PCR revealed that most cell lines express more than one CXCR4 variant. When expressed in HEK293 cells, the CXCR4 variants differed in protein expression efficiency and cell surface localization. Although variant 2 demonstrated the strongest expression and cell surface localization, variants 1, 3, and 5 also mediated chemokine signaling and induced cellular responses. Our results demonstrate that the N-terminal sequences of each CXCR4 variant determine the expression of the receptor and affect ligand recognition. Functional analyses revealed that CXCR4 variants may also affect each other or interact during CXCL12-stimulated cellular responses. Altogether, our results suggest that CXCR4 variants may have distinct functional roles that warrant additional investigation and could contribute to future development of novel drug interventions.

Background Tachykinins and their cognate receptors, neurokinin receptors (NKs) including NK1, NK2, and NK3 play vital roles in regulating various physiological processes including neurotransmission, nociception, inflammation, smooth muscle contractility, and stimulation of endocrine and exocrine gland secretion. Their abnormal expression has been reported to be associated with neurological disorders, inflammation, and cancer. Even though NKs are expressed in the same cells with their expression being inversely correlated in some conditions, there is no direct evidence to prove their interaction. Understanding the functional crosstalk between NKs in mediated downstream signaling and cellular responses may elucidate the roles of each receptor in pathophysiology. Results In this study, we showed that NKs were co-expressed in some cells. However, different from NK3, which only forms homodimerization, we demonstrated a direct interaction between NK1 and NK2 at the protein level using co-immunoprecipitation and NanoBiT-based protein interaction analysis. Through heterodimerization, NK2 downregulated substance P-stimulated NK1 signals, such as intracellular Ca 2+ mobilization and ERK phosphorylation, by enhancing β-arrestin recruitment, even at the ligand concentration that could not activate NK2 itself or in the presence of NK1 specific antagonist, aprepitant. In A549 cells with receptors deleted and reconstituted, NK2 exerted a negative effect on substance P/NK1-mediated cell migration. Conclusion Our study has provided the first direct evidence of an interaction between NK1 and NK2, which highlights the functional relevance of their heterodimerization in cellular responses. Our findings demonstrated that through dimerization, NK2 exerts negative effects on downstream signaling and cellular response mediated by NK1. Moreover, this study has significant implications for understanding the complexity of GPCR dimerization and its effect on downstream signaling and cellular responses. Given the important roles of tachykinins and NKs in pathophysiology, these insights may provide clues for developing NKs-targeting drugs.

As food packaging materials are in direct contact with the food we eat and cook under heat or pressure, consumers are apprehensive of their adverse effects on the food products. Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are often used in food packaging because of their hydrophobic properties; however, some PFASs are carcinogens, thus prompting further studies on their effects. In this study, a pretreatment method of 31 PFASs in coffee was established using the QuEChERS extraction method and analyzed by liquid chromatography–tandem mass spectrometry. We brewed 32 types of capsule coffee distributed in Korea, analyzed them for PFASs, and evaluated their safety. The results show that perfluorooctanoic acid and 8:2 fluorotelomer sulfonate levels are higher in machine-brewed capsule coffee than in capsule coffees brewed manually through a paper filter. However, the hazard quotient and excess cancer risk for all coffee samples are lower than the World Health Organization standards, and therefore, these samples are considered safe. The results of this study may aid in expanding the existing literature on PFAS detection in relation to human health.

HighlightsInducing a localized crystalline iron pyrophosphate in amorphous iron phosphate overlayer.Enhanced photoelectrochemical water oxidation activity with long-term durability.The heterogeneous hybrid structure overcoming the energy barrier in water oxidation.A rational regulation of the solar water splitting reaction pathway by adjusting the surface composition and phase structure of catalysts is a substantial approach to ameliorate the sluggish reaction kinetics and improve the energy conversion efficiency. In this study, we demonstrate a nanocrystalline iron pyrophosphate (Fe4(P2O7)3, FePy)-regulated hybrid overlayer with amorphous iron phosphate (FePO4, FePi) on the surface of metal oxide nanostructure with boosted photoelectrochemical (PEC) water oxidation. By manipulating the facile electrochemical surface treatment followed by the phosphating process, nanocrystalline FePy is localized in the FePi amorphous overlayer to form a heterogeneous hybrid structure. The FePy-regulated hybrid overlayer (FePy@FePi) results in significantly enhanced PEC performance with long-term durability. Compared with the homogeneous FePi amorphous overlayer, FePy@FePi can improve the charge transfer efficiency more significantly, from 60% of FePi to 79% of FePy@FePi. Our density-functional theory calculations reveal that the coexistence of FePi and FePy phases on the surface of metal oxide results in much better oxygen evolution reaction kinetics, where the FePi was found to have a typical down-hill reaction for the conversion from OH* to O2, while FePy has a low free energy for the formation of OH*.

Acute respiratory viral infections (ARIs) represent a significant global health challenge, contributing heavily to worldwide morbidity and mortality rates. Recent efforts to combat ARIs have focused on developing nasal spray formulations that effectively target the nasal mucosa. However, challenges such as irritation, discomfort, and safety concerns highlight the need for natural, eco-friendly ingredients. In this study, we evaluated the efficacy of solubilized sturgeon oil (SSO), prepared as an oil-in-water nanoemulsion from Siberian sturgeon, as an eco-friendly preventive nasal spray agent against ARIs. Intranasal pre-treatment with SSO effectively inhibited respiratory infections caused by SARS-CoV-2, influenza A virus (IAV), and respiratory syncytial virus (RSV). Additionally, it suppressed viral replication in both nasal and lung tissues. This antiviral effect was linked to reduced pulmonary inflammation, characterized by decreased infiltration of Ly-6C+ monocytes and Ly-6G+ neutrophils, along with lower pro-inflammatory cytokine levels. Histopathological analyses confirmed that nasal SSO administration significantly mitigated lung inflammation progression caused by viral infections. Notably, the protective effects of SSO against SARS-CoV-2, IAV, and RSV persisted for at least six hours following nasal application. These findings highlight SSO as a promising eco-friendly and safe candidate for nasal spray formulations, providing a potential frontline defense against ARIs.