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Background Following the outbreak of the COVID-19 pandemic, a change in the incidence and transmission of respiratory pathogens was observed. Here, we retrospectively analyzed the impact of COVID-19 on the epidemiologic characteristics of Mycoplasma pneumoniae infection among children in Chengdu, one of the largest cities of western China. Method M. pneumoniae infection was diagnosed in 33,345 pediatric patients with respiratory symptoms at the Chengdu Women’s & Children’s Central Hospital between January 2017 and December 2020, based on a serum antibody titer of ≥1:160 measured by the passive agglutination assay. Differences in infection rates were examined by sex, age, and temporal distribution. Results Two epidemic outbreaks occurred between October-December 2017 and April-December 2019, and two infection peaks were detected in the second and fourth quarters of 2017, 2018, and 2019. Due to the public health response to COVID-19, the number of positive M. pneumoniae cases significantly decreased in the second quarter of 2020. The number of M. pneumoniae infection among children aged 3–6 years was higher than that in other age groups. Conclusions Preschool children are more susceptible to M. pneumoniae infection and close contact appears to be the predominant factor favoring pathogen transmission. The public health response to COVID-19 can effectively control the transmission of M. pneumoniae .

In this study, we aim to provide a deep understanding of the tumor microenvironment (TME) and its metabolic characteristics in non-small cell lung cancer (NSCLC) through single-cell RNA sequencing (scRNAseq) data obtained from public databases. Given that lung cancer is a leading cause of cancer-related deaths globally and NSCLC accounts for the majority of lung cancer cases, understanding the relationship between TME and metabolic pathways in NSCLC is crucial for developing new treatment strategies. Finally, machine learning algorithms were employed to construct a risk signature with strong predictive power across multiple independent cohorts. After quality control, 29,053 cells were retained, and PCA along with UMAP techniques were used to distinguish 13 primary cell subpopulations. Four highly activated metabolic pathways were identified within malignant cell subpopulations, which were further divided into seven distinct subgroups showing significant differences in differentiation potential and metabolic activity. WGCNA was utilized to identify gene modules and hub genes closely associated with these four metabolic pathways. Our analysis showed that DEGs between tumor and normal tissues were predominantly enriched in immune response and cell adhesion pathways. The comprehensive examination of our model revealed substantial variations in clinical and pathological characteristics, enriched pathways, cancer hallmarks, and immune infiltration scores between high-risk and low-risk groups. Wet lab experiments validated the role of KRT6B in NSCLC, demonstrating that KRT6B expression is elevated and it stimulates the proliferation of cancer cells. These observations not only enhance our understanding of metabolic reprogramming and its biological functions in NSCLC but also provide new perspectives for early detection, prognostic evaluation, and targeted therapy. However, future research should further explore the specific mechanisms of these metabolic pathways and their application potentials in clinical practice.

Background: The Wilms’ tumor suppressor gene (WT1) is a critical regulator in kidney development and disease pathogenesis. With the identification of at least 36 isoforms in mammals, each potentially playing distinct roles, WT1’s complexity is becoming increasingly apparent. The −KTS and +KTS isoforms, in particular, have been implicated in DNA and RNA regulation, respectively. This review consolidates recent insights into WT1’s multifaceted role in renal morphogenesis and its implications in kidney diseases. Summary: Our review highlights WT1’s expression during embryonic kidney development and its maintenance in postnatal kidney function. We discuss the association of WT1 mutations with genetic nephropathies like Denys-Drash and Frasier syndromes, emphasizing its genetic significance. Additionally, we explore the implications of WT1 expression alterations in glomerular diseases, such as IgA nephropathy and lupus nephritis, where its role extends beyond a mere biomarker to a potential therapeutic target. Key Messages: The WT1 gene and its protein products are central to understanding kidney morphogenesis and the molecular basis of renal disorders. As our understanding of WT1’s regulatory mechanisms expands, so does the potential for developing targeted therapies for kidney diseases. This review calls for further research to elucidate the precise functions of WT1 isoforms and to explore the upstream regulators of WT1 that could offer novel treatment strategies for kidney pathologies. The significance of WT1 in intricate signaling pathways governing kidney health and disease is underscored, highlighting the need for continued investigation into this pivotal gene.

Glycosylphosphatidylinositol (GPI) acyltransferase is crucial for the synthesis of GPI-anchored proteins. Targeting the fungal glycosylphosphatidylinositol acyltransferase GWT1 by manogepix is a promising antifungal strategy. However, the inhibitory mechanism of manogepix remains unclear. Here, we present cryo-EM structures of yeast GWT1 bound to the substrate (palmitoyl-CoA) and inhibitor (manogepix) at 3.3 Å and 3.5 Å, respectively. GWT1 adopts a unique fold with 13 transmembrane (TM) helixes. The palmitoyl-CoA inserts into the chamber among TM4, 5, 6, 7, and 12. The crucial residues (D145 and K155) located on the loop between TM4 and TM5 potentially bind to the GPI precursor, contributing to substrate recognition and catalysis, respectively. The antifungal drug, manogepix, occupies the hydrophobic cavity of the palmitoyl-CoA binding site, suggesting a competitive inhibitory mechanism. Structural analysis of resistance mutations elucidates the drug specificity and selectivity. These findings pave the way for the development of potent and selective antifungal drugs targeting GWT1. Cryo-EM structures reveal how the first-in-class antifungal drug manogepix inhibits fungal GWT1, a key enzyme for GPI-anchored protein synthesis. The study uncovers manogepix’s competitive binding mechanism and explains drug resistance, offering insights for more effective antifungal therapies.

Background The absence of the pulmonary vein is a rare Congenital cardiovascular anomaly. It is most commonly diagnosed in infants, and diagnosis in adolescence is rare. Here, we report the case of an 11-year-old girl with absence of the right pulmonary vein, initially misdiagnosed with interstitial lung disease. Case presentation This patient presented with recurrent haemoptysis, recurrent respiratory infection and decreased activity tolerance. The radiological findings included bronchiectasis, septal thickening, a small right lung with hypoplasia of the ipsilateral pulmonary artery and ipsilateral mediastinal shift. CTA revealed the absence of the right pulmonary vein. Surgery was recommended. However, the patient opted for conservative treatment and outpatient follow-up. Conclusion This report emphasizes the epidemiological factors, clinical features, and imaging findings of unilateral pulmonary vein atresia to prevent confusion and facilitate accurate diagnosis in similar cases. Unilateral PVA diagnosis should be considered when patients exhibit characteristic imaging features such as septal thickening, hypoplasia of the ipsilateral pulmonary artery and lung, compensatory dilation of the contralateral pulmonary artery and emphysema of the contralateral lung, coupled with clinical hallmarks including recurrent respiratory infection, haemoptysis, and decreased activity tolerance.

Postnatal respiration requires bulk formation of alveoli that produces extensive surface area for gas diffusion from epithelium to the circulatory system. Alveolar morphogenesis initiates at late gestation or postnatal stage during mammalian development and is mediated by coordination among multiple cell types. Here we show that fibroblast-derived Heparan Sulfate Glycosaminoglycan (HS-GAG) is essential for maintaining a niche that supports alveolar formation by modulating both biophysical and biochemical cues. Gli1-CreER mediated deletion of HS synthase gene Ext1 in lung fibroblasts results in enlarged and simplified alveolar structures. Ablation of HS results in loss of a subset of PDGFRα hi αSMA + alveolar myofibroblasts residing in the distal alveolar region, which exhibit contractile properties and maintain WNT signaling activity to support normal proliferation and differentiation of alveolar epithelial cells. HS is essential for proliferation while preventing precocious apoptosis of alveolar myofibroblasts. We show that these processes are dependent upon FGF/MAPK signaling and forced activation of MAPK/ERK signaling partially corrected alveolar simplification and restored alveolar myofibroblast number and AT2 cell proliferation in HS deficient mice. These data reveal HS-dependent myofibroblast heterogeneity and function as an essential orchestrator for developing alveolar niche critical for the generation of gas exchange units. The alveoli of the lung are formed through the coordination of multiple cell types to yield a large surface area for gas exchange. Here they show that heparan sulfate plays essential roles in lung myofibroblasts to maintain MAPK signaling and the alveolar niche.

Background Neonatal respiratory distress syndrome (NRDS) is one of the most common respiratory diseases in the neonatal period and a major cause of neonatal mortality. Prolonged mechanical ventilation (MV) is associated with adverse outcomes in NRDS patients, highlighting the need for effective early risk stratification tools. The Neonatal Sequential Organ Failure Assessment (nSOFA) score has emerged as a potential predictor of adverse outcomes, but its association with prolonged MV remains unclear. Methods This retrospective cohort study utilized data from the Medical Information Mart for Intensive Care III (MIMIC-III) database, analyzing 642 NRDS infants admitted to the neonatal intensive care unit (NICU) between 2001 and 2012. Patients were divided into two groups based on MV duration: prolonged MV (> 96 h) and non-prolonged MV (≤ 96 h). The highest nSOFA score within 24 h of admission was the primary exposure variable. Covariates included demographic data, clinical characteristics, and laboratory results. A multivariable logistic regression model was used to assess the association between nSOFA scores and prolonged MV. The predictive ability of nSOFA was evaluated using the area under the receiver operating characteristic curve (AUC). Results Of the 642 NRDS infants, 192 (29.9%) required prolonged MV. Each 1-point increase in the nSOFA score was associated with a 29% higher risk of prolonged MV (odds ratio [OR]: 1.29; 95% confidence interval [CI]: 1.16–1.44; p  < 0.001). The nSOFA score demonstrated moderate predictive ability (AUC: 0.7245; 95% CI: 68.41%–76.49%), which was significantly better than its respiratory sub-score (AUC: 0.6936; p  < 0.001) and comparable to the SOFA score (AUC: 0.7218; p  = 0.89). Using an nSOFA cutoff of 3, the sensitivity and specificity for predicting prolonged MV were 64.06% and 70.22%, respectively. Conclusion The nSOFA score is an independent risk factor for prolonged MV in NRDS infants, with moderate predictive ability. Its simplicity and effectiveness make it a valuable tool for early risk stratification in NICUs. Future multicenter studies are needed to validate these findings and explore the potential of dynamic nSOFA monitoring in improving predictive accuracy.

Background This study aims to review the clinical characteristics, therapeutic response and outcome of idiopathic pulmonary hemosiderosis (IPH), and discover the risk factors for recurrence in children with IPH, which will be helpful for the early diagnosis and reasonable treatment of this disease. Methods Children with a diagnosis of IPH were enrolled in the study. Clinical data of the children were collected and analysed. Results A total of 32 patients with regular follow-up after diagnosis were included in this study. Anaemia, cough and haemoptysis constituted the most common initial symptoms of the disease, and the incidences were 90.6%, 75% and 56.2%, respectively. The mean gap between the onset of symptoms and diagnosis was 5 (0.25-36) months. Most of the children experienced remission (complete and partial remission) over the course of 6 months of treatment, but 19 of the children experienced relapse. The causes of disease recurrence included respiratory tract infection (37.5%), corticosteroid (CS) reduction (18.8%), and irregular medication (6.3%). Interestingly, we found that children with history of allergy (HR 4.255, 1.107–16.356) tended to experience disease recurrence ( p  = 0.01). Conclusions Cough and anaemia are the most common symptoms in children with IPH. The recurrence rate of this disease is high, and respiratory tract infection is the most common cause of its recurrence. High-dose CS impluse therapy cannot reduce the recurrence rate of the disease. Allergic history was an import factor associated with disease recurrence. Trial registration This study is a retrospective and observational study, which does not involve human specimens or clinical intervention. Therefore, clinical trial registration is not required, and there is no clinical trial number. However, the study was approved by the Institutional Review Board/Ethics Committee affiliated with West China Second University Hospital, Sichuan University (Ethics review number 2022074).

Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies. Drug exposure during pregnancy lacks sufficient fetal safety information world-widely. Here, the authors report the establishment a multi-center birth cohort to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes.

Background The main features of bronchopulmonary dysplasia (BPD) are alveolar simplification, pulmonary growth arrest, and abnormal lung function. Multiple studies have highlighted microRNA-29 (miR-29) as a potential biomarker for lung diseases and cancers. Upregulation of miR-29a has been known to downregulate GRB2-associated-binding protein 1 (GAB1), which is often highly expressed in the lung. The current study was designed to investigate the potential role of miR-29a in hyperoxia-induced BPD by targeting GAB1 in a neonatal mouse model. Methods The expression of miR-29a and GAB1 in lung tissues of neonatal mice with hyperoxia-induced BPD and mouse alveolar epithelial cells (MLE-12) was determined using RT-qPCR and western blot analysis. Subsequently, the relationship between miR-29a and GAB1 was verified using in silico analysis. In order to assess the effects of miR-29a or GAB1 on BPD, the pathological characteristics of alveoli, as well as proliferation and apoptosis of cells were measured through gain- and loss-of-function studies. Results Upregulation of miR-29a and downregulation of GAB1 were evident in both lung tissues and MLE-12 cells following BPD modeling. GAB1 was a direct target gene of miR-29a. Inhibition of miR-29a and overexpression of GAB1 were shown to alleviate lung injury, promote cell proliferation and inhibit apoptosis but reduce chord length in lung tissues of neonatal mice following hyperoxia-induced BPD modeling. Conclusion Altogether, down-regulation of miR-29a can potentially elevate GAB1 expression, reducing cell apoptosis and stimulating proliferation, ultimately retarding the development of BPD in mice. This study highlights the potential of a promising new target for preventing BPD.