Coordinating single-cell and bulk RNA-seq in deciphering the intratumoral immune landscape and prognostic stratification of prostate cancer patients.

INTRODUCTION: Prostate cancer is a common cancer among male population. The aberrant expression of histone modifiers has been identified as a potential driving force in numerous cancer types. However, the mechanism of histone modifiers in the development of prostate cancer remains unknown. METHODS: Expression profiles and clinical data were obtained from GSE70769, GSE46602, and GSE67980. Seruat R package was utilized to calculate the gene set enrichment of the histone modification pathway and obtain the Histone score. Least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were employed to identify marker genes with prognostic value. Kaplan-Meier survival analysis was conducted to assess the efficacy of the prognostic model. In addition, microenvironment cell populations counter (MCPcounter), single-sample gene set enrichment analysis (ssGSEA), and xCell algorithms were employed for immune infiltration analysis. Drug sensitivity prediction was performed using oncoPredict R package. RESULTS: We screened differentially expressed genes (DEGs) between Histone-high score (Histone-H) and Histone-low score (Histone-L) groups, which were enriched in RNA splicing and DNA-binding transcription factor binding pathways. We retained four prognostic marker genes, including TACC3, YWHAH, TAF1C and TTLL5. The risk model showed significant efficacy in stratification of the prognosis of prostate cancer patients in both internal and external cohorts (p < .0001 and p = .032, respectively). In addition, prognostic gene YWHAH was infiltrated in abundance of fibroblasts and highly correlated with Entinostat_1593 drug sensitivity score and the value of risk score. CONCLUSION: We innovatively developed a histone modification-related prognostic model with high prognostic potency and identified YWHAH as possible diagnostic and therapeutic biomarkers for prostate cancer. It provides novel insights to address prostate cancer and enhance clinical outcomes, thereby opening up a new avenue for customized treatment alternatives.

Investigating the prognostic role of lncRNAs associated with disulfidptosis-related genes in clear cell renal cell carcinoma.

INTRODUCTION: Renal cell carcinoma (RCC) is a grave malignancy that poses a significant global health burden with over 400,000 new cases annually. Disulfidptosis, a newly discovered programmed cell death process, is linked to the actin cytoskeleton, which plays a vital role in maintaining cell shape and survival. The role of disulfidptosis is poorly depicted in the clear cell histologic variant of RCC (ccRCC). METHODS: Three sets of ccRCC cohorts, ICGC_RECA-EU (n = 91), GSE76207 (n = 32) and TCGA-KIRC (n = 607), were included in our study, the batch effect of which was removed using the "combat" function. Correlation was calculated using the "rcorr" function of the "Hmisc" package for Pearson analysis, which was visualized using the "pheatmap" package. Principal component analysis was performed by the "vegan" package, visualized using the "scatterplot3d" package. Long non-coding RNAs (lncRNAs) associated with disulfidptosis were screened out using least absolute shrinkage and selection operator (LASSO) and COX analysis. Tumor mutation, immune landscaping and immunotherapy prediction were performed for further characterization of two risk groups. RESULTS: A total of 1822 disulfidptosis-related lncRNAs was selected, among which 308 lncRNAs were found to be significantly associated with the clinical outcome of ccRCC patients. We retained 11 disulfidptosis-related lncRNAs, namely, AP000439.3, RP11-417E7.1, RP11-119D9.1, LINC01510, SNHG3, AC156455.1, RP11-291B21.2, EMX2OS, AC093850.2, HAGLR and RP11-389C8.2, through LASSO and COX analysis for prognosis model construction, which displayed satisfactory accuracy (area under the curve, AUC, values all above 0.6 in multiple cohorts) in stratification of ccRCC prognosis. A nomogram model was constructed by integrating clinical factors with risk score, which further enhanced the prediction efficacy (AUC values all above 0.7 in multiple cohorts). We found that patients of male gender, higher clinical stages and advanced pathological T stage were inclined to have higher risk score values. Dactinomycin_1911, Vinblastine_1004, Daporinad_1248 and Vinorelbine_2048 were identified as promising candidate drugs for treating ccRCC patients of higher risk score value. Moreover, patients of higher risk value were prone to be resistant to immunotherapy. CONCLUSION: We developed a prognosis predicting model based on 11 selected disulfidptosis-related lncRNAs, the efficacy of which was verified in different cohorts. Furthermore, we delineated an intricate portrait of tumor mutation, immune topography and pharmacosensitivity evaluations within disparate risk stratifications.

Carbon footprints: Uncovering multilevel spatiotemporal changes of ship emissions during 2019-2021 in the U.S.

Quantifying and understanding changes in carbon emissions is essential for the U.S. shipping industry to reduce carbon emissions, especially after its return to the Paris Agreement. We estimated carbon emissions from 48,321 ships in the U.S. Exclusive Economic Zone (EEZ) using the power-based method based on 3.6 billion Automatic Identification System (AIS) reports. We explored the characterization of carbon emissions from the national, regional, and port levels during 2019-2021 by allocating emissions on a 1 km*1 km grid through an activity-weighted method. The results show: (1) Due to the COVID-19 pandemic, emissions within the EEZ show a temporal trend of decreased and then rebound, specifically from 32.628 Tg in 2019 to 30.741 Tg in 2020 and then bounced to 31.786 Tg in 2021. The spatial differences in emissions show significant heterogeneity; (2) There are significant differences in emissions by vessel type, flag, and operational mode for the four regions of the U.S. (Great Lakes, Gulf Coast, Pacific Coast, and Atlantic Coast). Thus, emissions in these regions show different variability patterns over three years. Notably, "port congestion" led to record high emissions on the Pacific Coast; (3) Containerized cargo contributes the most to port core area emissions, so most ports with higher throughputs have higher emissions, with Long Beach and Los Angeles having the highest. Emissions from coastal ports are high and volatile, while inland ports are low and stable. This study provides the U.S. with a high spatiotemporal resolution inventory of carbon emissions from ships, and the findings are expected to provide some reference for controlling ship emissions.

Spatiotemporal characteristic analysis of PM2.5 in central China and modeling of driving factors based on MGWR: a case study of Henan Province.

Since the start of the twenty-first century, China's economy has grown at a high or moderate rate, and air pollution has become increasingly severe. The study was conducted using data from remote sensing observations between 1998 and 2019, employing the standard deviation ellipse model and spatial autocorrelation analysis, to explore the spatiotemporal distribution characteristics of PM2.5 in Henan Province. Additionally, a multiscale geographically weighted regression model (MGWR) was applied to explore the impact of 12 driving factors (e.g., mean surface temperature and CO2 emissions) on PM2.5 concentration. The research revealed that (1) Over a period of 22 years, the yearly mean PM2.5 concentrations in Henan Province demonstrated a trend resembling the shape of the letter "M", and the general trend observed in Henan Province demonstrated that the spatial center of gravity of PM2.5 concentrations shifted toward the north. (2) Distinct spatial clustering patterns of PM2.5 were observed in Henan Province, with the northern region showing a primary concentration of spatial hot spots, while the western and southern areas were predominantly characterized as cold spots. (3) MGWR is more effective than GWR in unveiling the spatial heterogeneity of influencing factors at various scales, thereby making it a more appropriate approach for investigating the driving mechanisms behind PM2.5 concentration. (4) The results acquired from the MGWR model indicate that there are varying degrees of spatial heterogeneity in the effects of various factors on PM2.5 concentration. To summarize the above conclusions, the management of the atmospheric environment in Henan Province still has a long way to go, and the formulation of relevant policies should be adapted to local conditions, taking into account the spatial scale effect of the impact of different influencing factors on PM2.5.

Exploring oncogenes for renal clear cell carcinoma based on G protein-coupled receptor-associated genes.

G protein-coupled receptors (GPCRs) are a class of receptors on cell membranes that regulate various biological processes in cells, such as cell proliferation, differentiation, migration, apoptosis, and metabolism, by interacting with G proteins. However, the role of G protein-coupled receptors in predicting the prognosis of renal clear cell carcinoma is still unknown. The transcriptome data and clinical profiles of renal clear cell carcinoma patients, were downloaded from TCGA databases, and the validation group data were downloaded from number GSE167573, including 63 tumor samples and 14 normal samples. Single-cell RNA sequencing data were downloaded from the GEO database, No. GSE152938 and selected samples were used for GSEA enrichment analysis, WGCNA subgroup analysis, single-cell data analysis, and mutation analysis to explore the role of G protein-coupled receptor-related genes in the diagnosis and prognosis of renal clear cell carcinoma and to verify their reliability with cellular experiments. Finally, this study establishes a disease model based on G protein-coupled receptor-related genes, which may help to propose targeted therapeutic regimens in different strata of renal cell carcinoma patients.Author names: Please confirm if the author names are presented accurately and in the correct sequence (given name, middle name/initial, family name). Author: Given name [Lisa Jia] Last name [Tran].It's ok!

Single-cell transcriptome analysis revealing the intratumoral heterogeneity of ccRCC and validation of MT2A in pathogenesis.

Clear-cell renal cell carcinoma (ccRCC) appears as the most common type of kidney cancer, the carcinogenesis of which has not been fully elucidated. Tumor heterogeneity plays a crucial role in cancer progression, which could be largely deciphered by the implement of scRNA-seq. The bulk and single-cell RNA expression profile is obtained from TCGA and study conducted by Young et al. We utilized UMAP, TSNE, and clustering algorithm Louvain for dimensionality reduction and FindAllMarkers function for determining the DEGs. Monocle2 was utilized to perform pseudo-time series analysis. SCENIC was implemented for transcription factor analysis of each cell subgroup. A series of WB, CFA, CCK-8, and EDU analysis was utilized for the validation of the role of MT2A in ccRCC carcinogenesis. We observed higher infiltration of T/NK and B cells in tumorous tissues, indicating the role of immune cells in ccRCC carcinogenesis. Transcription factor analysis revealed the activation of EOMES and ETS1 in CD8 + T cells, while CAFs were divided into myo-CAFs and i-CAFs, with i-CAFs showing distinct enrichment of ATF3, JUND, JUNB, EGR1, and XBP1. Through cell trajectory analysis, we discerned three distinct stages of cellular evolution, where State2 symbolizes normal renal tubular cells that underwent transitions into State1 and State3 as the CNV score ascended. Functional enrichment examination revealed an amplification of interferon gamma and inflammatory response pathways within tumor cells. The consensus clustering algorithm yielded two molecular subtypes, with cluster 2 being associated with advanced tumor stages and an abundance of infiltrated immune cells. We identified 17 prognostic genes through Cox and LASSO regression models and used them to construct a prognostic model, the efficacy of which was verified in multiple cohorts. Furthermore, we investigated the role of MT2A, one of our hub genes, in ccRCC carcinogenesis, and found it to regulate proliferation and migration of malignant cells. We depicted a detailed single-cell landscape of ccRCC, with special focus on CAFs, endothelial cells, and renal tubular cells. A prognostic model of high stability and accuracy was constructed based on the DEGs. MT2A was found to be actively implicated in ccRCC carcinogenesis, regulating proliferation and migration of the malignant cells.

Driving Forces of Meteorology and Emission Changes on Surface Ozone in the Huaihe River Basin, China.

Surface ozone (O3) pollution in China has become a serious environmental problem in recent years. In the present study, we targeted the HRB, a large region located in China's north-south border zone, to assess the driving forces of meteorology and emission changes on surface ozone. A Kolmogorov-Zurbenko (KZ) filter method was performed on the maximum daily average 8-h (MDA8) concentrations of ozone in the HRB during 2015-2020 to decompose the original time series. The findings demonstrated that the short-term (O3ST), seasonal (O3SN), and long-term components (O3LT) of MDA8 O3 variations accounted for 34.2%, 56.1%, and 2.9% of the total variance, respectively. O3SN has the greatest influence on the daily variation in MDA8 O3, followed by O3ST. In coastal cities, the influence of O3ST was enhanced. The influence of O3SN was stronger in the northwestern HRB. Air temperature is the prevailing variable that influences the photochemical formation of ozone. A clear phase lag (7-34 days) of the baseline component between MDA8 O3 and the atmospheric temperature was found in the HRB. Using multiple linear regression, the effect of temperature on ozone was removed. We estimated that the increase in ozone concentration in the HRB was mainly caused by the emission changes (79.4%), and the meteorological conditions made a small contribution (20.6%). This study suggests that reductions in volatile organic compounds (VOCs) will play an important role in further ozone pollution reduction in the HRB. Supplementary Information: The online version contains supplementary material available at 10.1007/s11270-023-06345-1.

Modeling of spatial pattern and influencing factors of cultivated land quality in Henan Province based on spatial big data.

The quality of cultivated land determines the production capacity of cultivated land and the level of regional development, and also directly affects the food security and ecological safety of the country. This paper starts from the perspective of spatial pattern of cultivated land quality and uses spatial autocorrelation analysis to study the spatial aggregation characteristics and differences of cultivated land quality in Henan Province at the county level scale, and also uses bivariate spatial autocorrelation to analyze the influence of neighboring influences on the quality of cultivated land in the target area. The spatial autoregressive model was used to further analyze the driving factors affecting the quality of cultivated land, and the influence of cultivated land area index was coupled in the process of rating analysis, which was finally used as a basis to propose more precise measures for the protection of cultivated land zoning. The results show that: (1) The quality of cultivated land in Henan Province has a strong spatial correlation (global Moran's I≈0.710) and shows an obvious aggregation pattern in spatial distribution; positive correlation types (high-high and low-low) are concentrated in north-central and western mountainous areas of Henan Province, respectively; negative correlation types are discrete. The negative correlation types are distributed in a discrete manner. (2) The bivariate spatial autocorrelation results show that Slope (Moran's I≈-0.505), Irrigation guarantee rate (IGR, 0.354), Urbanization rate (-0.255), Total agricultural machinery power (TAMP, 0.331) and Pesticide use (0.214) are the main influencing factors. (3) According to the absolute values of the regression coefficients, it can be seen that the magnitude of the influence of different factors on the quality of cultivated land is: Slope (0.089) >IGR (0.025) > Urbanization rate (0.002) > TAMP (0.001) > Pesticide use (1.96e-006). (4) Based on the spatial pattern presented by the spatial autocorrelation results, we proposed corresponding protection zoning measures to provide more scientific reference decisions and technical support for the implementation of refined cultivated land management in Henan Province.

Evaluating Ecosystem Services Supply and Demand Dynamics and Ecological Zoning Management in Wuhan, China.

The concept of ecosystem services (ES) supply and demand has attracted increasing attention in science and policy making because it effectively links ecosystem services to human well-being. The imbalance of ES supply and demand in urban areas has become a key issue in regional sustainable development. In this context, we calculated ES supply and demand for Wuhan City, China, using the ES supply and demand ratio (ESDR) and the comprehensive ES supply-demand ratio (CESDR) to express the relationship between ES supply and demand. Ecological zoning was proposed according to the spatial differentiation of the ES supply-demand relationship, and policy recommendations are made. The results show that from the perspective of total ES supply and demand, the water yield supply (SWY), grain yield supply (SGY), and recreation services supply (SRS) are greater than the water yield demand (DWY), grain yield demand (DGY), and recreation services demand (DRS), and that the climate regulation supply (SCR) is less than the climate regulation demand (DCR). From a spatial perspective, there are imbalances and mismatches in ES supply and demand, especially in urban central areas. The values of SWY, SGY, SCS, and SRS per unit area are less than their respective demand values, and the area of mismatch has expanded with the gradual increase of the built-up area. The spatial pattern of ES supply and demand is circular, with the form of "deficit zone-relative equilibrium zone-surplus zone", which corresponds to "urban central area-near suburbs-distant suburbs and rural areas".

Numerical calculation of boundary layers and wake characteristics of high-speed trains with different lengths.

Trains with different numbers of cars running in the open air were simulated using the delayed detached-eddy simulation (DDES). The numbers of cars included in the simulation are 3, 4, 5 and 8. The aim of this study was to investigate how train length influences the boundary layer, the wake flow, the surface pressure, the aerodynamic drag and the friction drag. To certify the accuracy of the mesh and methods, the drag coefficients from numerical simulation of trains with 3 cars were compared with those from the wind tunnel test, and agreement was obtained. The results show that the boundary layer is thicker and the wake vortices are less symmetric as the train length increases. As a result, train length greatly affects pressure. The upper surface pressure of the tail car reduced by 2.9%, the side surface pressure of the tail car reduced by 8.3% and the underneath surface pressure of the tail car reduced by 19.7% in trains that included 3 cars to those including 8 cars. In addition, train length also has a significant effect on the friction drag coefficient and the drag coefficient. The friction drag coefficient of each car in a configuration decreases along the length of the train. In a comparison between trains consisting of 3 cars to those consisting of 8 cars, the friction drag coefficient of the tail car reduced by 8.6% and the drag coefficient of the tail car reduced by 3.7%.

Influence of induced-charge electrokinetic phenomena on the dielectrophoretic assembly of gold nanoparticles in a conductive-island-based microelectrode system.

Metal nanoparticles in a liquid suspension can be assembled dielectrophoretically (DEP) into nanoparticle chains, which can serve as electrical functional microwires connecting isolated and conductive elements to an electrode pair, as used in wet electronics, bioelectronics, and biochemical sensors. The frequency-dependent morphology of these nanoparticle chains assembled between an electrode pair has even been attributed to the decreasing magnitude of alternating current electroosmosis (ACEO) flow velocity with driving frequency. For instance, highly oriented nanoparticle nanowires can be generated by DEP assembly only at a high frequency, which induces a negligible small ACEO above the electrode surface, corresponding to fewer nanoparticles transported to the assembly region. In this study, attention is focused on the formation of nanoparticle chains in a conductive-island-based microelectrode system. It is worth noting that the intrusion of an island entity can bring about further double-layer polarization and induced charge electroosmosis flow (ICEO) around this conductive object, which exerts a significant influence on DEP assembly. In our experiments, the ends of nanoparticle chains are always extended onto the metal surfaces at 50 kHz, and their central parts become slender at 150 kHz. Meanwhile, wire-shaped particle clusters aligned along the direction of local field lines are more densely distributed at the island rims than that growing from the electrode edges. Consequently, a series of numerical modeling based on the theory of induced charge electrokinetic phenomena are introduced to account for these regular experimental results, including the double-layer charging effect at the metal/electrolyte interface, ACEO, ICEO, and electrothermal flow. Mutual DEP is also treated as an important factor affecting DEP behavior when neighboring particles are approaching one another. The results from the theoretical study are in good agreement with the experimental observations.