Early structural cardiovascular changes on neonatal echocardiography after adverse intrauterine circumstances in identical twins
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Severity of neonatal influenza infection is driven by type I interferon and oxidative stress
Neonates exhibit increased susceptibility to respiratory viral infections, attributed to inflammation at the developing pulmonary air-blood interface. IFN I are antiviral cytokines critical to control viral replication, but also promote inflammation. Previously, we established a neonatal murine influenza virus (IV) model, which demonstrates increased mortality. Here, we sought to determine the role of IFN I in this increased mortality. We found that three-day-old IFNAR-deficient mice are highly protected from IV-induced mortality. In addition, exposure to IFNβ 24 h post IV infection accelerated death in WT neonatal animals but did not impact adult mortality. In contrast, IFN IIIs are protective to neonatal mice. IFNβ induced an oxidative stress imbalance specifically in primary neonatal IV-infected pulmonary type II epithelial cells (TIIEC), not in adult TIIECs. Moreover, neonates did not have an infection-induced increase in antioxidants, including a key antioxidant, superoxide dismutase 3, as compared to adults. Importantly, antioxidant treatment rescued IV-infected neonatal mice, but had no impact on adult morbidity. We propose that IFN I exacerbate an oxidative stress imbalance in the neonate because of IFN I-induced pulmonary TIIEC ROS production coupled with developmentally regulated, defective antioxidant production in response to IV infection. This age-specific imbalance contributes to mortality after respiratory infections in this vulnerable population.
The biomechanical evolution of the uterus and cervix and fetal growth in human pregnancy
The coordinated biomechanical performance of maternal tissues facilitates healthy pregnancy. Quantifying uterine and cervical biomechanical function has been challenging due to minimal data on the anatomy’s shape, size, and material properties across gestation. Addressing this challenge, this study quantifies structural features of human pregnancy by assessing maternal reproductive tissues and estimated fetal weight in 47 low-risk pregnancies at four gestation times. Uterocervical size and estimated fetal weight were measured via ultrasound, and cervical stiffness was measured via mechanical aspiration. Patient-specific uterocervical solid models were built for each time point, and uterocervical dimensions and cervical stiffness rate changes were assessed between time points. We found that uterine growth rates are time- and direction-dependent, with cervical softening occurring fastest in early gestation and cervical shortening fastest in late gestation. In conclusion, this work enables computational modeling platforms (i.e., digital twins) to explore the structural performance of the uterus and cervix in pregnancy.
Modulating cytokine microenvironment during T cell activation induces protective RSV-specific lung resident memory T cells in early life in mice
Maternal immunisation against respiratory viruses provides protection in early life, but as antibodies wane, there can be a gap in coverage. This immunity gap might be filled by inducing pathogen-specific lung tissue-resident T cells (TRM). However, the neonatal mouse lung has a different inflammatory environment to the adult lung which affects T cell recruitment. We compared the factors affecting viral-specific TRM recruitment in the lungs of adult or neonatal mice. In contrast to adulthood, we demonstrated that RSV or influenza infection in neonatal mice recruited fewer TRM to the lungs. This was associated with reduced lung levels of CCL5 and CXCL10. Co-administration of CCL5 or CXCL10 at the time of primary T cell activation significantly increased RSV-specific TRM in the lung, protecting mice upon reinfection. These chemokine differences were reflected in responses to infection in human cord blood. Here we show a critical role for CCL5 and CXCL10 in the induction of lung TRM and a possible strategy for boosting responses.
Energy metabolism in health and diseases
Energy metabolism is indispensable for sustaining physiological functions in living organisms and assumes a pivotal role across physiological and pathological conditions. This review provides an extensive overview of advancements in energy metabolism research, elucidating critical pathways such as glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism, along with their intricate regulatory mechanisms. The homeostatic balance of these processes is crucial; however, in pathological states such as neurodegenerative diseases, autoimmune disorders, and cancer, extensive metabolic reprogramming occurs, resulting in impaired glucose metabolism and mitochondrial dysfunction, which accelerate disease progression. Recent investigations into key regulatory pathways, including mechanistic target of rapamycin, sirtuins, and adenosine monophosphate-activated protein kinase, have considerably deepened our understanding of metabolic dysregulation and opened new avenues for therapeutic innovation. Emerging technologies, such as fluorescent probes, nano-biomaterials, and metabolomic analyses, promise substantial improvements in diagnostic precision. This review critically examines recent advancements and ongoing challenges in metabolism research, emphasizing its potential for precision diagnostics and personalized therapeutic interventions. Future studies should prioritize unraveling the regulatory mechanisms of energy metabolism and the dynamics of intercellular energy interactions. Integrating cutting-edge gene-editing technologies and multi-omics approaches, the development of multi-target pharmaceuticals in synergy with existing therapies such as immunotherapy and dietary interventions could enhance therapeutic efficacy. Personalized metabolic analysis is indispensable for crafting tailored treatment protocols, ultimately providing more accurate medical solutions for patients. This review aims to deepen the understanding and improve the application of energy metabolism to drive innovative diagnostic and therapeutic strategies.
Functional brain connectivity in early adolescence after hypothermia-treated neonatal hypoxic-ischemic encephalopathy
Neonatal hypoxic-ischemic encephalopathy (HIE) injures the infant brain during the basic formation of the developing functional connectome. This study aimed to investigate long-term changes in the functional connectivity (FC) networks of the adolescent brain following neonatal HIE treated with therapeutic hypothermia (TH).
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