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• Androgen receptor mutations were identified in women with Müllerian duct anomalies. • In silico analysis and ACMG guidelines classified the variants' pathogenicity. • Androgen receptor mutations resulted in conformational changes of the native protein. Müllerian duct anomalies (MDAs) are congenital developmental disorders exhibiting as a variety of malformations of female reproductive tract. The identified etiology of MDAs is limited. The present study aimed to unravel the underlying genetic causes of MDAs. Rare variants in androgen receptor (AR) were called from the cohort consists of patients with MDAs and underwent whole exome sequencing (WES) at Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. Sanger sequencing was used to confirm the causative genetic mutations. In silico analysis were used to classify the pathogenicity of each variant. Molecular modeling and simulations were conducted to investigate the conformational changes between the wild-type (WT) and mutant proteins. A total of 3 rare heterozygous variants in AR from the MDAs cohort in our institution were identified, with unknown effects. All variants were missense mutations, including c.173A > T, c.558C > A and c.1208C > T, and were absent or rare in East Asian populations in Genome Aggregation Database and the Exome Aggregation Consortium Database. According to the American College of Medical Genetics and Genomics guidelines, c.1208C > T variant was classified as likely pathogenic, while the other two were variants of uncertain significance. During molecular dynamics simulations, WT and mutant proteins all reached stable status according to root-mean-square variance. Values of radius of gyration showed that Q58L and S186R protein would be more compact than WT, while the structure of A403V became looser. Despite, in comparison with WT, the number of hydrogen bonds increased in Q58L, while decreased in the other two variants. Furthermore, the solvent-accessible surface area diminished in Q58L and A403V while enlarged in S186R proteins, when compared with WT. To our knowledge, this is the first report regarding the association of AR mutation and MDAs. The identification of these variants, predicted to damage the structure and function of AR protein, not only expanded the mutational spectrum of causative genes of MDAs, but provide novel molecular genetic reference for future studies. [ABSTRACT FROM AUTHOR]

Purpose: Older patients with cancer are underrepresented in pivotal trials of immune checkpoint inhibitors (ICIs). This study aimed to investigate immune-related adverse events (irAEs) that occur in older patients with lung cancer treated with ICIs, and explore predictors of the occurrence of irAEs. Methods: A prospective analysis was performed on older patients with lung cancer aged ≥ 65 years who were treated with anti-programmed cell death-1/-ligand 1 (PD-1/PD-L1) inhibitors in Beijing Hospital from January 2018 to December 2022. The incidence and risk factors of irAEs were estimated by the Chi-square test or Wilcoxon rank-sum tests. The predictive power of Geriatric-8 (G-8) for irAEs was tested by receiver operating characteristic (ROC) curve analysis. Lymphocyte counts were measured by flow cytometry. Cytokine levels were tested by Enzyme-linked immunosorbent assay, respectively. Kaplan–Meier method was used to calculated progression-free survival (PFS) curves, and the log-rank test was used to evaluate differences. Results: A total of 201 older patients aged ≥ 65 years with lung cancer were enrolled in this study. The most common irAEs were interstitial pneumonia, dermatological toxicity and hypothyroidism, with rates of 17.2%, 16.1% and 5.6%, respectively. ROC showed that G-8 could predict the occurrence of irAEs in patients aged 65–71 years (≥ G2 irAEs: AUC = 0.757, p < 0.001; ≥ G3 irAEs: AUC = 0.862, p < 0.001), but not for patients aged ≥ 71 years. NLR, LMR, PNI, hypertension and diabetes were associated with irAEs. Lower CD4 + T cells and B cells, and lower levels of IL-10 were associated with the development of irAEs. Conclusion: Our study confirmed the accuracy of G-8 for predicting irAEs in older patients. We also identified several predictors of irAEs in older patients with lung cancer. [ABSTRACT FROM AUTHOR]

With the acceleration of urbanization, road dust poses a significant threat to ecological systems. To explore the source and ecological risks associated with heavy metals in surface dust, 36 road dust samples were collected in Beijing in May, August, and November 2018, and February 2019. The results indicated that the concentrations of Cd, Cr, Cu, Hg, Ni, Pb, and Zn exceeded their background values, and the mean concentration of Cd was nearly 10 times the background value. Three main sources were identified by Principal Component Analysis (PCA): industrial emissions, fuel combustion, and traffic exhaust. According to the Genetic Algorithm optimized Back Propagation (GA-BP) neural network, heavy metals from industrial sources and fuel combustion originate from suburban districts, while heavy metals from traffic exhaust originate from the city center. After careful screening of species and corresponding toxicity data, the concentration of pollutants corresponding to a 5% cumulative probability on the curve (HC5) of eight heavy metals was calculated by species sensitivity distribution (SSD), and the results indicate that most HC5 values are consistent with national standards. However, the HC5 values of Ni, Cu, and As differed from the national standards, which can be used to supplement existing standards. From the risk analysis based on HC5 values, the high-risk area of Ni (12.70–30.97%) was much larger than that of As (1.55–4.95%), and the proportions of high-risk areas of Ni and As reached their highest values in spring and autumn, respectively. Uncertainty existed between different geostatistical methods. The areas of uncertainty of Ni and As were small (less than 5.58%). The heavy metals in the surface dust in Beijing had potential ecological risks that vary with seasons and regions. Therefore, it is critical to implement targeted management measures based on pollution sources and risk distribution. [ABSTRACT FROM AUTHOR]

This study presents a comprehensive approach to renovating and optimizing balconies in old residential buildings in Beijing. Firstly, it explores residential balconies' evolution, characteristics, and development trends to identify various sample types and understand the associated problems and residents' needs related to balconies through investigation. Secondly, the Rhino/Grasshopper parametric platform is employed to simulate the performance and analyze data from standard balcony types, resulting in five qualitative and four quantitative renovation strategies and methods. Subsequently, these comprehensive renovation and optimization design strategies are implemented in the renovation process, and their performance is simulated. The daylight autonomy (DA), universal daylight indicator (UDI), and spatial daylight autonomy (sDA) metrics experienced significant increases of 16.56, 20.12, and 0.13, respectively, indicating improved light environment and functionality. Notably, the proposed strategies maintain consistent energy consumption and thermal comfort levels. Both PMV and PPD have improved, but the improvement is not significant, only by 0.01. The window-to-wall ratio has been increased by 0.1, and insulation has been added. The overall thermal comfort value is stable. These findings validate the practicality and effectiveness of the proposed approach and methods. This study provides valuable references for renovating and optimizing balconies in old residential buildings, contributing to problem-solving efforts and enhancing living quality. [ABSTRACT FROM AUTHOR]

In studying the spatial, temporal, and particle size variations heavy metal sources, a source apportionment model for a four-way array of data is required. In this study, referencing two-way and three-way models, a four-way (particle fractions, elements, sites, and time) source apportionment model (FEST) was developed. Errors in the three-way models solving four-way problems verified the necessity of developing the FEST model. The results showed that the FEST model had a higher accuracy than the existing models, which was probably because of more constraints and input data in the FEST model. Based on the sampled data in Beijing, sources were apportioned for the four-way array of data using the FEST model, and the spatial, temporal, and particle size variations of sources were evaluated. The main sources of heavy metals were similar to those in our prior studies, whereas the contributions of sources to specific heavy metals differed. Traffic exhaust and fuel combustion contributed more to fine particles than coarse particles, indicating that the two should be controlled preferentially among all sources. The management of traffic exhaust should be focused on the central and northern areas in each season, and the control of fuel combustion should be strengthened in the southern area in winter. [Display omitted] • A four-way source apportionment model (FEST) was developed for the first time. • Accuracy of the FEST model was higher than that of existing models. • Tempo–spatial and particle size changes of sources were analyzed using the FEST model. • Traffic exhaust and fuel combustion impacted larger on fine particles than coarse particles. [ABSTRACT FROM AUTHOR]