Daily Respiratory Research Analysis

Early-stage lung adenocarcinoma generally has a favorable prognosis. However, more than 30% of early-stage lung adenocarcinoma cases relapse within 5 years of initial treatment, even after complete removal of the primary tumor. Identification of the factors contributing to early-stage lung adenocarcinoma metastasis is needed to develop effective prevention and treatment strategies. In this study, we found upregulation of xylosyltransferase 1 (XYLT1), a glycosyltransferase that initiates the biosynthesis of sulfated glycosaminoglycan (sGAG) chains, in metastatic recurrent lesions of early-stage lung adenocarcinoma, which correlated with poor prognosis. In vitro and in vivo experiments showed that XYLT1 promoted lung adenocarcinoma cell survival and metastasis by activating the NF-κB pathway. Mechanistically, XYLT1 interacted with IκBα and facilitated the biosynthesis of sGAG-conjugated IκBα, which enhanced the interaction between IκBα and IKKs to promote the proteasomal degradation of IκBα. These results illustrate that proteoglycan modification-mediated activation of NF-κB signaling is a driver of early-stage lung adenocarcinoma metastasis, providing a possibility for the detection and intervention of early lung adenocarcinoma metastasis. Significance: XYLT1 promotes metastatic recurrence of early-stage lung adenocarcinoma by facilitating sulfated glycosaminoglycan conjugation and proteasomal degradation of IκBα to activate NF-κB, providing potential biomarker and treatment strategies for lung cancer metastasis.

Recent avian-origin H3N8 influenza A virus (IAV) that have infected humans pose a potential public health concern. Alterations in the viral surface glycoprotein, hemagglutinin (HA), are typically required for IAVs to cross the species barrier for adaptation to a new host, but whether H3N8 has adapted to infect humans remains elusive. The observation of a degenerative codon in position 228 of HA in human H3N8 A/Henan/4-10/2022 protein sequence, which could be residue G or S, suggests a dynamic viral adaptation for human infection. Previously, we found this human-isolated virus has shown the ability to transmit between ferrets via respiratory droplets, with the HA-G228S substitution mutation emerging as a critical determinant for the airborne transmission of the virus in ferrets. Here, we investigated the receptor-binding properties of these two H3N8 HAs. Our results showed H3N8 HAs have dual receptor-binding properties with a preference for avian receptor binding, and G228S slightly increased binding to human receptors. Cryo-electron microscopy structures of the two H3N8 HAs with avian and human receptor analogs revealed the basis for dual receptor binding. Mutagenesis studies reveal that the Q226L mutation shifts H3N8 HA's receptor preference from avian to human, while the G228S substitution enhances binding to both receptor types. H3N8 exhibits distinct antigenic sites compared to H3N2, prompting concerns regarding vaccine efficacy. These findings suggest that the current H3N8 human isolates are yet to adapt for efficient human-to-human transmission and further continuous surveillance should be implemented.IMPORTANCEInfluenza virus transmission remains a public health concern currently. H3N8 subtype influenza A viruses infect humans and their HAs acquire the ability to bind to both human and avian receptors, posing a threat to human health. We have solved and analyzed the structural basis of dual receptor binding of recently human-infecting H3N8 HA, and we demonstrate that the G228S enhances human receptor binding and adaptation. We also found that HN/4-10 H3N8 HA has distinct antigenic sites, which challenges vaccine efficacy. Taken together, our work is critical to the prevention and control of human H3 influenza virus infection.

BACKGROUND: Respiratory distress is the main reason for the admission of infants to the neonatal intensive care unit (NICU). Rapid identification of the causes of respiratory distress and selection of appropriate and effective treatment strategies are important to optimise favourable short- and long-term patient outcomes. Lung ultrasound (LUS) technology has become increasingly important in this field. According to the scientific literature, LUS has high sensitivity (92-99%) and specificity (95-97%) in diagnosing neonatal respiratory distress syndrome. This diagnostic power helps guide timely interventions, such as surfactant therapy and mechanical ventilation. METHODS: Our objective was to outline consensus guidelines among an international panel of experts on the use of LUS to support the decision-making process in managing respiratory distress in the NICU. We used a three-round Delphi process. In each Delphi round, 28 panellists rated their level of agreement with each statement using a four-point Likert scale. RESULTS: In round 1, the panellists reviewed 30 initially proposed statements. In rounds 2 and 3, the statements were redeveloped based on the reviewers' comments, leading to the final approval of 18 statements. Among the 18 consensus statements, grade A was assigned a value of 10, grade B was assigned a value of 7, and grade C was assigned a value of 1. CONCLUSIONS: A panel of experts agreed on 18 statements regarding managing infants with respiratory distress. Using LUS may help design future interventional studies and improve the benchmarking of respiratory care outcomes.