Although substantial progress has been made in cancer biology and treatment, clinical outcomes of bladder carcinoma (BC) patients are still not satisfactory. The tumor microenvironment (TME) is a ...potential target. Here, by single-cell RNA sequencing on 8 BC tumor samples and 3 para tumor samples, we identify 19 different cell types in the BC microenvironment, indicating high intra-tumoral heterogeneity. We find that tumor cells down regulated MHC-II molecules, suggesting that the downregulated immunogenicity of cancer cells may contribute to the formation of an immunosuppressive microenvironment. We also find that monocytes undergo M2 polarization in the tumor region and differentiate. Furthermore, the LAMP3 + DC subgroup may be able to recruit regulatory T cells, potentially taking part in the formation of an immunosuppressive TME. Through correlation analysis using public datasets containing over 3000 BC samples, we identify a role for inflammatory cancer-associated fibroblasts (iCAFs) in tumor progression, which is significantly related to poor prognosis. Additionally, we characterize a regulatory network depending on iCAFs. These results could help elucidate the protumor mechanisms of iCAFs. Our results provide deep insight into cancer immunology and provide an essential resource for drug discovery in the future.
Asthma is a common chronic respiratory disease in children. In addition to medications, physical therapy is considered as a treatment strategy for asthma. We conducted this study to investigate the ...effects of physical therapy on lung function in children with asthma.
Three databases were searched. We conducted the meta-analysis for the forced expiratory volume in the first second in percent predicted values FEV1(%pred), the forced vital capacity in percent predicted values FVC(%pred), and the peak expiratory flow in percent predicted values PEF(%pred) by using a random effect model.
Of the 6474 identified studies, 18 studies (16 in physical training, 2 in breathing exercise or inspiratory muscle training) were included in the systematic review and 11 studies (all in physical training) were included in the meta-analysis. The meta-analysis showed a significantly improved FVC(%pred) in the experimental group.
Physical training improved FVC(%pred) significantly in children with asthma. Further study is needed, especially on the effects of breathing exercise and inspiratory muscle training in children with asthma.
Our study reviewed the physical therapies for children with asthma and clarified whether and how these therapies affect them. Our study found that physical training improved the forced vital capacity in percent predicted values FVC(%pred) significantly in asthmatic children. Our study provided evidence that physical training could improve lung function in children with asthma, which is not identical to the Global Initiative for Asthma (GINA) guidelines.
Reanalysis products have been applied to calculate the tropospheric delay for Global Navigation Satellite System (GNSS) positioning purposes widely. It is necessary to obtain high-precision ...tropospheric delay information from GNSS users with a high-precision tropospheric vertical stratification model because the height of the grids of the atmospheric reanalysis data is inconsistent with that of GNSS users, especially in regions with high terrains. In addition, the variation of the tropospheric delay in the vertical direction is much higher than that in the horizontal direction. The zenith total delay (ZTD) vertical stratification model is also key to the development of real-time and high-precision ZTD models. A new approach, the sliding window algorithm, is proposed to develop a ZTD vertical stratification model. In this work, a ZTD vertical stratification model considering spatiotemporal factors is developed based on the second Modern-Era Retrospective analysis for Research and Applications (MERRA-2) data, which is named the GZTD-H model. Radiosonde and International GNSS Service (IGS) data are treated as reference values to evaluate the performance of the GZTD-H model, which is compared to the model GPT2w. The results show that the GZTD-H model realizes the highest performance in ZTD layered vertical interpolation against ZTD layered profiles obtained at radiosonde sites, which achieves an improvement of 10% over the model GPT2w. Compared to model GPT2w, the GZTD-H model attains a spatial interpolation improvement of 8% for the Global Geodetic Observing System (GGOS) Atmosphere gridded ZTD over the surface ZTD calculated from radiosonde profiles. Furthermore, compared to model GPT2w, the model GZTD-H also attains improvements of 11% over the precise ZTD products acquired at IGS sites. In terms of model parameters, the GZTD-H model is greatly reduced and optimized over model GPT2w. Hence, the applicability of this model is enhanced in terms of GNSS atmospheric sounding and precise GNSS positioning.
Clear-cell renal cell carcinoma (ccRCC) is the most common histological type of RCC. To investigate the intratumoral heterogeneity of ccRCC, we analyzed single-cell RNA-sequencing data and identified ...15 major cell types, along with 39 subgroups of cells derived from tumor or non-malignant tissues, and confirmed their presence by immunofluorescence staining in tissue chips. In this study, we verified that T cell exhaustion was the key factor responsible for the immunosuppressive property of ccRCC tissues, which was significantly related to poor prognosis. We also found that abnormal metabolic patterns occurred not only in cancer cells, but also in tumor-infiltrating stromal cells. Based on the fraction of each cell cluster detected by CIBERSORTx, 533 patients from The Cancer Genome Atlas (TCGA) KIRC dataset were divided into three groups. One group, which showed a lesser proportion of activated CD8+ cells and greater proportion of exhausted CD8+ cells, was associated with a poor prognosis. Hence, the blockade of immunosuppressive checkpoints, not only PD-1, but also LAG3, TIM-3, and other inhibitory checkpoints, could serve as a potential target for ccRCC immunotherapy. Our work will further the understanding of the heterogeneity among ccRCC tissues and provide novel strategies for treating ccRCC.
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Via single-cell transcriptome analysis, we investigated the intra-tumoral heterogeneity of clear-cell renal cell carcinoma (ccRCC) and identified the composition inside tumor tissues. With a computational pipeline, we revealed the clinical significance of tumor-infiltrating cells and provided novel strategies for treating ccRCC.
Immune checkpoint inhibitor-related cardiotoxicity is one of the most lethal adverse effects, and thus, the identification of underlying mechanisms for developing strategies to overcome it has ...clinical importance. This study aimed to investigate whether microbiota-host interactions contribute to PD-1/PD-L1 inhibitor-related cardiotoxicity.
A mouse model of immune checkpoint inhibitor-related cardiotoxicity was constructed by PD-1/PD-L1 inhibitor BMS-1 (5 and 10 mg/kg), and cardiomyocyte apoptosis and cardiotoxicity were determined by hematoxylin and eosin, Masson's trichome and TUNEL assays. 16S rRNA sequencing was used to define the gut microbiota composition. Gut microbiota metabolites short-chain fatty acids (SCFAs) were determined by HPLC. The serum levels of myocardial enzymes (creatine kinase, aspartate transaminase, creatine kinase-MB and lactate dehydrogenase) and the production of M1 factors (TNF-α and IL-1β) were measured by ELISA. The colonic macrophage phenotype was measured by mmunofluorescence and qPCR. The expression of Claudin-1, Occludin, ZO-1 and p-p65 was measured by western blot. The gene expression of peroxisome proliferator-activated receptor α (PPARα) and cytochrome P450 (CYP) 4X1 was determined using qPCR. Statistical analyses were performed using Student's t-test for two-group comparisons, and one-way ANOVA followed by Student-Newman-Keul test for multiple-group comparisons.
We observed intestinal barrier injury and gut microbiota dysbiosis characterized by Prevotellaceae and Rikenellaceae genus depletion and Escherichia-Shigella and Ruminococcaceae genus enrichment, accompanied by low butyrate production and M1-like polarization of colonic macrophages in BMS-1 (5 and 10 mg/kg)-induced cardiotoxicity. Fecal microbiota transplantation mirrored the effect of BMS-1 on cardiomyocyte apoptosis and cardiotoxicity, while macrophage depletion and neutralization of TNF-α and IL-1β greatly attenuated BMS-1-induced cardiotoxicity. Importantly, Prevotella loescheii recolonization and butyrate supplementation alleviated PD-1/PD-L1 inhibitor-related cardiotoxicity. Mechanistically, gut microbiota dysbiosis promoted M1-like polarization of colonic macrophages and the production of proinflammatory factors TNF-α and IL-1β through downregulation of PPARα-CYP4X1 axis.
Intestinal barrier dysfunction amplifies PD-1/PD-L1 inhibitor-related cardiotoxicity by upregulating proinflammatory factors TNF-α and IL-1β in colonic macrophages via downregulation of butyrate-PPARα-CYP4X1 axis. Thus, targeting gut microbiota to polarize colonic macrophages away from the M1-like phenotype could provide a potential therapeutic strategy for PD-1/PD-L1 inhibitor-related cardiotoxicity.
Single-cell sequencing technologies have noteworthily improved our understanding of the genetic map and molecular characteristics of bladder cancer (BC). Here we identify CD39 as a potential ...therapeutic target for BC via single-cell transcriptome analysis. In a subcutaneous tumor model and orthotopic bladder cancer model, inhibition of CD39 (CD39i) by sodium polyoxotungstate is able to limit the growth of BC and improve the overall survival of tumor-bearing mice. Via single cell RNA sequencing, we find that CD39i increase the intratumor NK cells, conventional type 1 dendritic cells (cDC1) and CD8 + T cells and decrease the Treg abundance. The antitumor effect and reprogramming of the tumor microenvironment are blockaded in both the NK cells depletion model and the cDC1-deficient Batf3
model. In addition, a significant synergistic effect is observed between CD39i and cisplatin, but the CD39i + anti-PD-L1 (or anti-PD1) strategy does not show any synergistic effects in the BC model. Our results confirm that CD39 is a potential target for the immune therapy of BC.
In this study, a new vegetation observable derived from spaceborne Global Navigation Satellite System-Reflectometry (GNSS-R) was developed. Firstly, a linear relationship between the Cyclone Global ...Navigation Satellite System (CYGNSS) reflectivity and soil moisture was derived based on the tau-omega (τ−w) model. The intercept and slope of this linear function were associated with the vegetation properties. Moreover, the intercept is not affected by soil moisture and depends only on vegetation properties. Secondly, to validate the new observable, the intercept demonstrated a significant correlation with vegetation water content (VWC), with the highest correlation coefficient of 0.742. Based on the intercept and slope, a linear model and an artificial neural network (ANN) model were established to retrieve VWC by combining geographical location and land cover information. The correlation coefficient and root-mean-square error (RMSE) of VWC retrieval based on the linear model were 0.795 and 2.155 kg/m2, respectively. The correlation coefficient and RMSE for the ANN model were 0.940 and 1.392 kg/m2, respectively. Compared with the linear model, the ANN model greatly improves the global VWC retrieval in accuracy, especially in areas with poor linear model retrieval results. Therefore, compared with conventional remote sensing techniques, the spaceborne GNSS-R can provide a new and effective approach to global VWC monitoring.
The aim of this study was to uncover the molecular mechanism through which fungicide resistance develops in Podosphaera xanthii, a fungi that causes powdery mildew in hull-less pumpkin. Treatments of ...inoculated P. xanthii were carried out on leaves of hull-less pumpkin and subsequently treated with kinds of triazole fungicide for seven generations. Resistant strains of P. xanthii thus obtained were evaluated for their resistance levels. The resistance levels of the fungi to four fungicides of were high except that of the propiconazole-resistant strain, which showed moderate resistance. The F7 generations of five resistant strains thus obtained were cultured continuously for five generations without fungicide induction, and their resistance level were found to be relatively stable. The DNA of the sensitive strain and the five kinds of resistant strains were extracted by the sodium dodecyl sulfate (SDS) method and its internal transcribed spacer (ITS) region was amplified by using ITS1/ITS4 primer and specific primer F/R and they were sequenced respectively. The DNA sequence comparison of resistant and sensitive strains showed that the base pairs of tebuconazole-resistant strains and flusilazole-resistant strains were mutated, with mutation rates of 4.8% and 1.6%, respectively. The base pairs of the other three resistant strains did not change.
Snow is not only a critical storage component in the hydrologic cycle but also an important data for climate research; however, snowfall observations are only sparsely available. Signal-to-noise ...ratio (SNR) has recently been applied for sensing snow depths. Most studies only consider either global positioning system (GPS) L1 or L2 SNR data. In the current study, a new snow depth estimation approach is proposed using multipath reflectometry and SNR combination of GPS triple frequency (i.e. L1, L2 and L5) signals. The SNR combination method describes the relationship between antenna height variation and spectral peak frequency. Snow depths are retrieved from the SNR combination data at YEL2 and KIRU sites and validated by comparing it with in situ observations. The elevation angle ranges from 5° to 25°. The correlations for the two sites are 0.99 and 0.97. The performance of the new approach is assessed by comparing it with existing models. The proposed approach presents a high correlation of 0.95 and an accuracy (in terms of Root Mean Square Error) improvement of over 30%. Findings indicate that the new approach could potentially be applied to monitor snow depths and may serve as a reference for building multi-system and multi-frequency global navigation satellite system reflectometry models.
•Huixian Karst National Wetland is currently the most representative karst wetland in China.•Optimized RF outperforms fused SegNet classifier in coarse classification of vegetation.•RF-based ...classifications have significant differences from SegNet classifier using UAV images.•RF-DT algorithm achieved over 0.878 overall accuracy of karst vegetation communities.•Statistical analysis of variables’ importance for classifying karst vegetation communities.
Karst wetlands have the characteristics of small scale and poor stability. At present, the wetland is being severely damaged and its area is seriously degraded, and the accurate identification of vegetation communities is very important for the rapid assessment and management of karst wetland. In this paper, Huixian Karst National Wetland Park, located in Guilin city, China, was taken as the study area, the digital orthophoto map (DOM) and digital surface model (DSM) of UAV images were selected as the data sources, and the vegetation communities of karst wetland were classified by using the object-based Random Forest (RF)-Decision Tree (DT) algorithm and SegNet algorithm. When the object-based RF algorithm and SegNet algorithm were used for coarse classification of karst vegetation, the parameters (mtry, ntree) of the object-based RF algorithm were optimized, and the data dimensionality reduction and RFE variable selection algorithm were used for selecting feature, and the single-class SegNet model was integrated based on the soft voting method to improve the applicability of vegetation classification in karst wetlands. In the classification of vegetation communities in karst wetlands, the optimized object-based RF-DT algorithm were used to extract the vegetation communities in the Areas A, B, and C. The statistical analysis of the importance of the feature variables (spectral features, texture features, geometric features, and position features) of various types of land cover in the three areas was carried out to explore the optimal classification variables of various types of vegetation. The results showed that: (1) the optimized object-based RF algorithm performed better than the SegNet algorithm in classifying karst vegetation at 95% confidence level during the coarse classification. The average accuracy of wetland vegetation was improved by 1.06–13.58%; (2) the object-based RF-DT algorithm had high classification ability for the karst wetland vegetation community, with overall accuracy and kappa coefficient above 0.85; and that (3) although geometric features accounted for the largest proportion (52.2%) in the classification of bermudagrass, water hyacinth, lotus, linden and other vegetation, texture features accounted for the highest proportion of 56.3% in the classification of vegetation whose importance was more than 90.
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