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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]

The purpose of this study was to determine if there are any genetic changes with whole-exome sequencing associated with distal vaginal atresia. This was a retrospective genetics study of 5 patients who presented with distal vaginal atresia who were recruited between 2017 and 2018. Whole-exome sequencing was performed in each subject with distal vaginal atresia. Sanger sequencing was used to confirm the potential causative genetic mutation. Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China. The main outcome measure was the rare mutations potentially associated with distal vaginal atresia in 5 patients. A truncating mutation c.266delC (p.P89Rfs*5) in the T-box transcription factor 6 (TBX6) gene, which is highly expressed in the human vagina, was identified in 1 patient using whole-exome sequencing. The deletion of the 16p11.2 region containing the TBX6 locus has also been reported previously to have the clinical feature of Müllerian agenesis. This mutation was paternally inherited by the patient. This truncating mutation was absent from all of the databases we checked, suggesting that the variant is rare and pathogenic. We showed, to our knowledge, for the first time, that the mutation in TBX6 might be associated with human distal vaginal atresia. [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]

The focus of this study is an intense heat episode that occurred on 9–13 July 2017 in Beijing, China, that resulted in severe impacts on natural and human variables, including record-setting daily electricity consumption levels. This event was observed and analyzed with a suite of local and mesoscale instruments, including a high-density automated weather station network, soil moisture sensors, and ground-based vertical instruments (e.g., a wind profiler, a ceilometer, and three radiometers) situated in and around the city, as well as electric power consumption data and analysis data from the U.S. National Centers for Environmental Prediction. The results show that the heat wave originated from dry adiabatic warming induced by the dynamic downslope and synoptic subsidence. The conditions were aggravated by the increased air humidity during subsequent days, which resulted in historically high records of the heat index (i.e., an index representing the apparent temperature that incorporates both air temperature and moisture). The increased thermal energy and decreased boundary layer height resulted in a highly energized urban boundary layer. The differences between urban and rural thermal conditions throughout almost the entire boundary layer were enhanced during the heat wave, and the canopy-layer urban heat island intensity (UHII) reached up to 8°C at a central urban station at 2300 local standard time 10 July. A double-peak pattern in the diurnal cycle of UHIIs occurred during the heat wave and differed from the single-peak pattern of the decadal average UHII cycles. Different spatial distributions of UHII values occurred during the day and night. [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]

Fourteen-month precipitation measurements from a second-generation PARSIVEL disdrometer deployed in Beijing, northern China, were analyzed to investigate the microphysical structure of raindrop size distribution and its implications on polarimetric radar applications. Rainfall types are classified and analyzed in the domain of median volume diameter D 0 and the normalized intercept parameter N w . The separation line between convective and stratiform rain is almost equivalent to rain rate at 8.6 mm h−1 and radar reflectivity at 36.8 dBZ. Convective rain in Beijing shows distinct seasonal variations in log 10 N w – D 0 domain. X-band dual-polarization variables are simulated using the T-matrix method to derive radar-based quantitative precipitation estimation (QPE) estimators, and rainfall products at hourly scale are evaluated for four radar QPE estimators using collocated but independent rain gauge observations. This study also combines the advantages of individual estimators based on the thresholds on polarimetric variables. Results show that the blended QPE estimator has better performance than others. The rainfall microphysical analysis presented in this study is expected to facilitate the development of a high-resolution X-band radar network for urban QPE applications. [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]

Regional raindrop size distribution (DSD) features are poorly understood due to the lack of observations. Here we investigate the regional variability of summertime DSD in Beijing, using the DSD observations from ten disdrometer sites from April to September 2017. The characteristics of DSD are analyzed for both convective and stratiform precipitation, mainly classified by rain rate (R). The shape (μ) and slope (λ) parameters follow a second-degree polynomial regression relationship for both stratiform and convective precipitation. On average, stratiform precipitation is found to have larger values of μ and λ than convective precipitation, whereas convective precipitation has a larger mass-weighted mean diameter (D m) and a generalized intercept parameter (N w). Interestingly, the north of Beijing has larger values of μ and λ , as opposed to D m and N w that exhibit greater values in the south, which could probably be attributed to terrain differences. The rain rate dependence on DSD is analyzed as well. In general, the D m -R and N w -R relationships follow a power-law distribution, and both D m and N w increase significantly with R. As the rain rate increases, D m keeps increasing to around 1.5 mm until an equilibrium state is reached. The findings obtained here could provide useful reference for better estimations of rainfall using the remote sensing techniques. • Raindrop size distribution is reported from a network of disdrometers in Beijing. • Convective DSDs have larger D m and N w as compared to stratiform DSDs. • DSDs show variablity over space and dependence on precipitation regimes. [ABSTRACT FROM AUTHOR]

Volatile organic compounds (VOCs) and odors are two important gaseous pollutants escaped from landfill, which are harmful to human health and the surrounding environment. In this study, biofilter was used to control VOCs and odors from an actual landfill. The operating efficiency and mechanism of biofilters on the sealing zone and leachate treatment zone were respectively analyzed and compared. The results found that components of gaseous pollutants from these two zones are different. Hydrogen sulfide (572.96 μg/m3), ammonia (479.28 μg/m3), and dimethyl sulfide (279.81 μg/m3) were mainly detected in sealing zone, and dichloromethane (3573.97 μg/m3), triethylamine (1818.21 μg/m3), benzene (1809.11 μg/m3), and chlorobenzene (1286.81 μg/m3) were main components of gaseous pollutants in leachate treatment zone. Although the types and concentrations of gaseous pollutants in these two zones were significantly different, the biofilters showed good removal efficiencies. The average removal rate of the total VOC (TVOC), sulfides, and amines in both biofilters exceeded 80%. The outlet concentrations meet the level-3 standard of the Emission standards for odor pollutants (GB 14544–93). This is mainly related to the evolution of bacterial population during the operation of biofilters. In the inoculums, the dominant bacterial genus is Brevibacillus (58.84%), and bacteria with Bacillus and Pseudomonas only occupied 2.67% and 1.77%. With the extension of operation time, the dominant bacteria of biofilter in the sealing zone gradually evolved into Mycobacterium (67.82%) and Bacillus (27.90%), while the dominant bacteria of biofilter in the leachate treatment zone evolved into Bacillus (72.69%) and Pseudomonas (21.59%). These results indicated that identification of gaseous pollutant components and design of appropriate treatment systems based on their components will further improve the operating efficiency of biofilters in the actual landfill. Image 1 • Treatment of volatile organic compounds (VOCs) and odors by biofilters was studied. • Two biofilters were constructed in an actual landfill in Beijing. • Variation in waste gas concentrations and bacterial populations were analyzed. • The biofilters showed good removal efficiencies. • Scientific basis for co-treatment of VOCs and odors in landfills by biofilters provided. [ABSTRACT FROM AUTHOR]

Based on total lightning location data from the Beijing Lightning Network (BLNET) and hailfall reports from 2015 to 2017 in Beijing, as well as S-band radar data from the Beijing Meteorological Observation Center, the total lightning activities for 148 hailfall events are analyzed with the identification method of strong convective cells (CCs) (similar to Thunderstorm Identification Tracking Analysis and Nowcasting, TITAN). Most of the hailstorms have a very high flash rate (FR), and a significant increase in FR is observed before hailfall events. The 2σ lightning jump (LJ) algorithm (with 4 and 10 flashes/min activation thresholds for different districts of Beijing) is tested as a hailfall nowcasting predictor. The average LJ lead time is 27.1 min. LJs precede 81.8% of all hailfall events, and 38.6% of LJs are not followed by hailfall reports within one hour. The merging of two adjacent strong CCs usually forms hail-bearing severe thunderstorms producing a sudden increase in total lightning. In addition, most hailfall events occurred at the boundary of strong CCs instead of at the cell centers. This study shows that the total LJ is a potentially useful predictor for hail nowcasts in the Beijing area. • Detailed analysis on operational feasibility of the 2σ lightning jump algorithm for the hail nowcast in Beijing. • Hails usually occur in the vertical convection decline stage with the maximum VCS intensity exceeding 55 dBZ. • Hailstones are usually generated after two cells merge, except for isolated storms. [ABSTRACT FROM AUTHOR]