Abstract Background Anomalous aortic origin of a coronary artery from the inappropriate sinus of Valsalva (AAOCA) is a rare congenital heart lesion. It is uncommon for patients with AAOCA to present ...with severe symptoms at a very young age. Case presentation We describe a very rare but critical presentation in a young infant with AAOCA that requires surgical repair and pacemaker placement. A three-month-old infant was referred because of syncope. Cardiac arrest occurred shortly after admission. The electrocardiogram indicated a complete atrioventricular block and a transvenous temporary pacemaker was implanted. A further coronary computed tomographic angiography (CTA) showed the anomalous origin of the right coronary artery from the left sinus of Valsalva. Coronary artery unroofing was performed due to an interarterial course with the intramural component, and a permanent epicardial pacemaker was implanted. The postoperative recovery was uneventful, and this patient was thriving and asymptomatic at the nine-month follow-up. However, the electrocardiogram still indicated a complete pacing rhythm. Conclusions By timely diagnosis and treatment, this patient is successfully rescued. Although rare, AAOCA may be fatal even in infants.
Introduction: It has been shown that polystyrene nanoplastic (PS-NP) exposure induces toxicity in the lungs. Objectives: This study aims to provide foundational evidence to corroborate that ...ferroptosis and abnormal HIF-1α activity are the main factors contributing to pulmonary dysfunction induced by PS-NP exposure. Methods: Fifty male and female C57BL/6 mice were exposed to distilled water or 100 nm or 200 nm PS-NPs via intratracheal instillation for 7 consecutive days. Hematoxylin and eosin (H&E) and Masson trichrome staining were performed to observe the histomorphological changes in the lungs. To clarify the mechanisms of PS-NP-induced lung injury, we used 100 μg/ml, 200 μg/ml and 400 μg/ml 100 or 200 nm PS-NPs to treat the human lung bronchial epithelial cell line BEAS-2B for 24 h. RNA sequencing (RNA-seq) of BEAS-2B cells was performed following exposure. The levels of glutathione, malondialdehyde, ferrous iron (Fe2+), and reactive oxygen species (ROS) were measured. The expression levels of ferroptotic proteins were detected in BEAS-2B cells and lung tissues by Western blotting. Western blotting, immunohistochemistry, and immunofluorescence were used to evaluate the HIF-1α/HO-1 signaling pathway activity. Results: H&E staining revealed substantial perivascular lymphocytic inflammation in a bronchiolocentric pattern, and Masson trichrome staining demonstrated critical collagen deposits in the lungs after PS-NP exposure. RNA-seq revealed that the differentially expressed genes in PS-NP-exposed BEAS-2B cells were enriched in lipid metabolism and iron ion binding processes. After PS-NP exposure, the levels of malondialdehyde, Fe2+, and ROS were increased, but glutathione level was decreased. The expression levels of ferroptotic proteins were altered significantly. These results verified that PS-NP exposure led to pulmonary injury through ferroptosis. Finally, we discovered that the HIF-1α/HO-1 signaling pathway played an important role in regulating ferroptosis in the PS-NP-exposed lung injury. Conclusion: PS-NP exposure caused ferroptosis in bronchial epithelial cells by activating the HIF-1α/HO-1 signaling pathway, and eventually led to lung injury.
Tuberculous meningitis (TBM) is a devastating form of tuberculosis (TB) causing high mortality and disability. TBM arises due to immune dysregulation, but the underlying immune mechanisms are ...unclear.
We performed single-cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) and cerebrospinal fluid (CSF) cells isolated from children (n=6) with TBM using 10 xGenomics platform. We used unsupervised clustering of cells and cluster visualization based on the gene expression profiles, and validated the protein and cytokines by ELISA analysis.
We revealed for the first time 33 monocyte populations across the CSF cells and PBMCs of children with TBM. Within these populations, we saw that CD4_C04 cells with Th17 and Th1 phenotypes and Macro_C01 cells with a microglia phenotype, were enriched in the CSF. Lineage tracking analysis of monocyte populations revealed myeloid cell populations, as well as subsets of CD4 and CD8 T-cell populations with distinct effector functions. Importantly, we discovered that complement-activated microglial Macro_C01 cells are associated with a neuroinflammatory response that leads to persistent meningitis. Consistently, we saw an increase in complement protein (C1Q), inflammatory markers (CRP) and inflammatory factor (TNF-α and IL-6) in CSF cells but not blood. Finally, we inferred that Macro_C01 cells recruit CD4_C04 cells through CXCL16/CXCR6.
We proposed that the microglial Macro_C01 subset activates complement and interacts with the CD4_C04 cell subset to amplify inflammatory signals, which could potentially contribute to augment inflammatory signals, resulting in hyperinflammation and an immune response elicited by
-infected tissues.
Background
Respiratory syncytial virus (RSV) is the leading cause of mortality and morbidity in children under the age of five. Despite this, there is still a lack of safe and effective vaccines and ...antiviral agents for clinical use. Andrographolide exerts antiviral functions against a variety of viruses, but whether (and how) it exerts antiviral effects on RSV remains unclear.
Methods and results
In vitro RSV infection models using A549 and 16HBE cell lines were established, and the effects of andrographolide on RSV were analyzed via RSV N gene load and proinflammatory cytokine levels. The RNA transcriptome was sequenced, and data were analyzed by R software. Andrographolide-related target genes were extracted via network pharmacology using online databases. Lentiviral transfection was applied to knockdown the heme oxygenase-1 gene (
Hmox1
,
HO-1
). Results showed that andrographolide suppressed RSV replication and attenuated subsequent inflammation. Network pharmacology and RNA sequencing analysis indicated that the hub gene
HO-1
may play a pivotal role in the anti-RSV effects of andrographolide. Furthermore, andrographolide exerted antiviral effects against RSV partially by inducing
HO-1
but did not activate the antiviral interferon response.
Conclusion
Our findings demonstrated that andrographolide exerted anti-RSV activity by up-regulating
HO-1
expression in human airway epithelial cells, providing novel insights into potential therapeutic targets and drug repurposing in RSV infection.
—Respiratory syncytial virus (RSV) is a pivotal virus leading to acute lower respiratory tract infections in children under 5 years old. This study aimed to explore the correlation between p53 and ...Toll-like receptors (TLRs) post RSV infection. p53 levels exhibited a substantial decrease in nasopharyngeal aspirates (NPAs) from infants with RSV infection compared to control group. Manipulating p53 expression had no significant impact on RSV replication or interferon signaling pathway. Suppression of p53 expression led to heightened inflammation following RSV infection in A549 cells or airways of BALB/c mice. while stabilizing p53 expression using Nutlin-3a mitigated the inflammatory response in A549 cells. Additionally, Inhibiting p53 expression significantly increased Toll-like receptor 2 (TLR2) expression in RSV-infected epithelial cells and BALB/c mice. Furthermore, the TLR2 inhibitor, C29, effectively reduced inflammation mediated by p53 in A549 cells. Collectively, our results indicate that p53 modulates the inflammatory response after RSV infection through TLR2.
•p53 protein exhibited a notable decrease in infants with RSV infection.•Reduced p53 levels heightened the inflammatory response induced by RSV.•p53 suppressed the expression of TLR2 to alleviate inflammation.
Display omitted
•The specific mechanisms of PS-NP-induced pulmonary injury are unclear.•A mouse model of lung injury is created based on the real-world NP exposure in human.•PS-NP exposure induces ...ferroptosis in lung tissues and bronchial epithelial cells.•HIF-1α inhibition rescues PS-NP-induced ferroptosis in bronchial epithelial cells.•PS-NP exposure induces ferroptosis via the HIF-1α/HO-1signaling pathway in lungs.
It has been shown that polystyrenenanoplastic (PS-NP) exposure induces toxicity in the lungs.
This study aims to provide foundational evidence to corroborate that ferroptosis and abnormal HIF-1α activity are the main factors contributing to pulmonary dysfunction induced by PS-NP exposure.
Fifty male and female C57BL/6 mice were exposed to distilled water or 100 nm or 200 nm PS-NPs via intratracheal instillation for 7 consecutive days. Hematoxylin and eosin (H&E) and Masson trichrome staining were performed to observe the histomorphological changes in the lungs. To clarify the mechanisms of PS-NP-induced lung injury, we used 100 μg/ml, 200 μg/ml and 400 μg/ml 100 or 200 nm PS-NPs to treat the human lung bronchial epithelial cell line BEAS-2B for 24 h. RNA sequencing (RNA-seq) of BEAS-2B cells was performed following exposure. The levels of glutathione, malondialdehyde, ferrous iron (Fe2+), and reactive oxygen species (ROS) were measured. The expression levels of ferroptotic proteins were detected in BEAS-2B cells and lung tissues by Western blotting. Western blotting, immunohistochemistry, and immunofluorescence were used to evaluate the HIF-1α/HO-1 signaling pathway activity.
H&E staining revealed substantial perivascular lymphocytic inflammation in a bronchiolocentric pattern, and Masson trichrome staining demonstrated critical collagen deposits in the lungs after PS-NP exposure. RNA-seq revealed that the differentially expressed genes in PS-NP-exposed BEAS-2B cells were enriched in lipid metabolism and iron ion binding processes. After PS-NP exposure, the levels of malondialdehyde, Fe2+, and ROS were increased, but glutathione level was decreased. The expression levels of ferroptotic proteins were altered significantly. These results verified that PS-NP exposure led to pulmonary injury through ferroptosis. Finally, we discovered that the HIF-1α/HO-1 signaling pathway played an important role in regulating ferroptosis in the PS-NP-exposed lung injury.
PS-NP exposure caused ferroptosis in bronchial epithelial cells by activating the HIF-1α/HO-1 signaling pathway, and eventually led to lung injury.
Mercury pollution control has become a global goal. The accurate estimate of long-term mercury emissions in China is critical to evaluate the global mercury budget and the emission reduction ...potentials. In this study, we used a technology-based approach to compile a consistent series of China's atmospheric mercury emissions at provincial level from 1978 to 2014. China totally emitted 13 294 t of anthropogenic mercury to air during 1978-2014, in which gaseous elemental mercury, gaseous oxidized mercury, and particulate-bound mercury accounted for 58.2%, 37.1%, and 4.7%, respectively. The mercury removed during this period were 2085 t in coal-fired power plants (counting 49% of mercury input), 7259 t in Zn smelting (79%), 771 t in coal-fired industrial boilers (25%), and 658 t in cement production plants (27%), respectively. Annual mercury emissions increased from 147 t in 1978 to 530 t in 2014. Both sectoral and spatial emissions of atmospheric mercury experienced significant changes. The largest mercury emission source evolved from coal-fired industrial boilers before 1998, to zinc smelting during 1999-2004, coal-fired power plants during 2005-2008, finally to cement production after 2009. Coal-fired industrial boilers and cement production have become critical hotpots for China's mercury pollution control.
