Background: Evidence remains limited about the association of maternal exposure to ambient fine particulate matter (airborne particles with an aerodynamic diameter ≤2.5 µm [PM _2.5 ]) with fetal congenital heart defects (CHDs) in highly polluted regions, and few studies have focused on preconception exposure. Methods: Using a nationwide surveillance-based case-control design in China, we examined the association between maternal exposure to PM _2.5 during periconception (defined as 3 months before conception until 3 months into pregnancy) and risk of CHD in offspring. The study included 1 434 998 births involving 7335 CHDs from 2014 through 2017 on the basis of the National Population-Based Birth Defects Surveillance System, covering 30 provinces, municipalities, or municipal districts in China. We assigned maternal PM _2.5 exposure during the periconception period to each participant using satellite-based PM _2.5 concentrations at 1-km spatial resolution. Multilevel logistic regression models were used to calculate the multivariable-adjusted odds ratio and 95% CI for CHDs in offspring associated with maternal PM _2.5 exposure, and the exposure–response association was investigated using restricted cubic spline analysis. Subgroup or sensitivity analyses were conducted to identify factors that may modify the association. Results: The average maternal exposure to PM _2.5 levels across all participants was 56.51 μg/m ³ (range, 10.95 to 182.13 μg/m ³ ). For each 10 μg/m³ increase in maternal PM _2.5 exposure, the risk of CHDs in offspring was increased by 2% (odds ratio, 1.02 [95% CI, 1.00 to 1.05]), and septal defect was the most influenced subtype (odds ratio, 1.04 [95% CI, 1.01 to 1.08]). The effect of PM _2.5 on CHD risk was more pronounced during the preconception period. Mothers <35 years of age, those living in northern China, and those living in low-income areas were more susceptible to PM _2.5 exposure than their counterparts (all P <0.05). PM _2.5 exposure showed a linear association with total CHDs or specific CHD types. Conclusions: High maternal PM _2.5 exposure, especially during the preconception period, increases risk of certain types of CHD in offspring. These findings are useful for CHD prevention and highlight the public health benefits of improving air quality in China and other highly polluted regions.

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.

Gastrointestinal and respiratory tract diseases often occur together. There are many overlapping pathologies, leading to the concept of the ‘gut–lung axis’ in which stimulation on one side triggers a response on the other side. This axis appears to be implicated in infections involving severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which has triggered the global coronavirus disease 2019 (COVID-19) pandemic, in which respiratory symptoms of fever, cough and dyspnoea often occur together with gastrointestinal symptoms such as nausea, vomiting, abdominal pain and diarrhoea. Besides the gut–lung axis, it should be noted that the gut participates in numerous axes which may affect lung function, and consequently the severity of COVID-19, through several pathways. This article focuses on the latest evidence and the mechanisms that drive the operation of the gut–lung axis, and discusses the interaction between the gut–lung axis and its possible involvement in COVID-19 from the perspective of microbiota, microbiota metabolites, microbial dysbiosis, common mucosal immunity and angiotensin-converting enzyme II, raising hypotheses and providing methods to guide future research on this new disease and its treatments.

Hypoxia is a hallmark of the tumor microenvironment (TME), and it plays a crucial role in the occurrence and progression in vascular tumors. Under hypoxic conditions, hypoxia-inducible factor 1-alpha (HIF-1α) is stabilized, inducing changes in the expression of various target genes involved in angiogenesis, metabolism, and cell survival. This includes the upregulation of pro-angiogenic factors like VEGF, which promotes the formation of dysfunctional blood vessels, contributing to the worsening of the hypoxic microenvironment. At the same time, hypoxia induces a metabolic shift toward glycolysis, even in the presence of oxygen, supporting tumor cell survival and proliferation by providing necessary energy and biosynthetic precursors. This review discusses the molecular mechanisms by which hypoxia regulates angiogenesis and metabolic reprogramming in vascular tumors, highlighting the intricate link between these processes, and explores potential therapeutic strategies to target these pathways in order to develop effective treatment strategies for patients.

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.

Pulmonary hypertension is characterized by pulmonary arterial remodeling that results in increased pulmonary vascular resistance, right ventricular failure, and premature death. It is a threat to public health globally. Autophagy, as a highly conserved self-digestion process, plays crucial roles with autophagy-related (ATG) proteins in various diseases. The components of autophagy in the cytoplasm have been studied for decades and multiple studies have provided evidence of the importance of autophagic dysfunction in pulmonary hypertension. The status of autophagy plays a dynamic suppressive or promotive role in different contexts and stages of pulmonary hypertension development. Although the components of autophagy have been well studied, the molecular basis for the epigenetic regulation of autophagy is less understood and has drawn increasing attention in recent years. Epigenetic mechanisms include histone modifications, chromatin modifications, DNA methylation, RNA alternative splicing, and non-coding RNAs, which control gene activity and the development of an organism. In this review, we summarize the current research progress on epigenetic modifications in the autophagic process, which have the potential to be crucial and powerful therapeutic targets against the autophagic process in pulmonary hypertension development.