Health impact assessment of the surface water pollution in China.

China suffers from severe surface water pollution. Health impact assessment could provide a novel and quantifiable metric for the health burden attributed to surface water pollution. This study establishes a health impact assessment method for surface water pollution based on classic frameworks, integrating the multi-pollutant city water quality index (CWQI), informative epidemiological findings, and benchmark public health information. A relative risk level assignment approach is proposed based on the CWQI, innovatively addressing the challenge in surface water-human exposure risk assessment. A case study assesses the surface water pollution-related health impact in 336 Chinese cities. The results show (1) between 2015 and 2022, total health impact decreased from 3980.42 thousand disability-adjusted life years (DALYs) (95 % Confidence Interval: 3242.67-4339.29) to 3260.10 thousand DALYs (95 % CI: 2475.88-3641.35), measured by total cancer. (2) The annual average health impacts of oesophageal, stomach, colorectal, gallbladder, and pancreatic cancers added up to 2621.20 thousand DALYs (95 % CI: 2095.58-3091.10), revealing the significant health impact of surface water pollution on digestive cancer. (3) In 2022, health impacts in the Beijing-Tianjin-Hebei and surroundings, the Yangtze River Delta, and the middle reaches of the Yangtze River added up to 1893.06 thousand DALYs (95 % CI: 1471.82-2097.88), showing a regional aggregating trend. (4) Surface water pollution control has been the primary driving factor to health impact improvement, contributing -3.49 % to the health impact change from 2015 to 2022. It is the first city-level health impact map for China's surface water pollution. The methods and findings will support the water management policymaking in China and other countries suffering from water pollution.

Characterizing the water resource-environment-ecology system harmony in Chinese cities using integrated datasets: A Beautiful China perspective assessment.

Integrated management and synergistic improvement of the water system is a topic of widespread concern. This study innovatively integrates three functions of quality assessment, synergy evaluation, and driving influence determination to establish a systematic framework assessing water system harmony. A case study of 336 Chinese cities is further performed by combining multi-scale and multi-source datasets. The results show China's water system quality has improved from 2015 to 2022. Development in the water resource, environment, and ecology subsystems have been differentiated, with 0.05 %, 4.33 %, and -1.64 % changes, respectively. The degradation of water ecology and the weak synergy with the other two subsystems have limited China's water system harmony. Water environment improvement played a contributive role in improving the water system quality. The contribution structure of water resources, environment, and ecology has shifted towards equilibrium in recent years. We found and highlighted the north-south differentiation of water system harmony in Chinese cities. The Beijing-Tianjin-Hebei and its surroundings, the Yangtze River Delta, and the middle reaches of the Yangtze River are identified as priority regions for water system harmony improvement. The primary contribution of this study is to propose an assessing concept of water resource-environment-ecology system harmony, establish well-structured assessment methods, and integrate the multiple data sources. The novel methods and findings, including the indicator system, application of data mining and decomposing methods, and the city-level water system harmony map, deconstruct and quantify the complex and diverse water system, supporting clearer and more efficient water management policymaking.

Integrated analysis identities Rho GTPases related molecular map in patients with gastric carcinoma.

The intricate involvement of Rho GTPases in a multitude of human malignancies and their diverse array of biological functions has garnered substantial attention within the scientific community. However, their expression pattern and potential role in gastric cancer (GC) remain unclear. In this study, we successfully identified two distinct subtypes associated with Rho GTPase-related gene (RGG) through consensus clustering analysis, which exhibited significant disparities in overall survival and the tumor microenvironment. Subsequently, an extensively validated risk model termed RGGscore was meticulously constructed to prognosticate the outcomes of GC patients. This model was further assessed and validated using an external cohort. Notably, the high RGGscore group was indicative of a poorer prognosis. Univariate and multivariate Cox regression analyses unveiled the RGGscore as an autonomous prognostic indicator for GC patients. Subsequent external validation, utilizing two cohorts of patients who underwent immunotherapy, demonstrated a significant correlation between a low RGGscore and improved response to immunotherapy. Additionally, the expression levels of three genes associated with RGGscore were examined using qRT-PCR. Taken together, a pioneering RGGscore model has been successfully established, showcasing its potential efficacy in offering valuable therapeutic guidance for GC.

A novel and robust pyroptosis-related prognostic signature predicts prognosis and response to immunotherapy in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a highly malignant gastrointestinal tumor, has a poor prognosis and high mortality rate. Pyroptosis could regulate tumor cell proliferation, invasion, and metastasis, thereby affecting the prognosis of cancer patients. However, the role of pyroptosis-related genes (PRGs) in ESCC remains unclear. This study selected 33 PRGs, and finally identified 29 PRGs that were differentially expressed between ESCC and normal esophageal tissues. The genetic mutation variation landscape of PRG in ESCC was also summarised. Based on consensus clustering for the 33 PRGs, all ESCC patients could be divided into two subtypes. Functional enrichment analysis revealed that these 33 PRGs were mainly involved in cytokine production, interleukin-1 production, and the NOD-like receptor signalling pathway. We created a prognostic PRG signature based on least absolute shrinkage and selection operator regression and Cox regression analysis with good survival prediction ability in both GEO and TCGA cohorts. Combined with the clinical characteristics, signature-based risk score was found to be an independent factor for predicting the OS of ESCC patients. A nomogram with enhanced precision for forecasting ESCC was established based on various independent prognostic elements. Significant correlation was observed between prognostic PRGs and immune-cell infiltration, tumor mutation burden, microsatellite instability, immune checkpoint, and drug sensitivity. Finally, we validated the expression of four PRGs in ESCC cell lines and tissues samples. In conclusion, the PRGs exerted significant effects on tumor immunity and prognosis of ESCC.

Assessing the health impacts of PM2.5 and ozone pollution and their comprehensive correlation in Chinese cities based on extended correlation coefficient.

The coordinated control of PM2.5 and ozone pollution is becoming more and more important in the current and next stage of Chinese environmental pollution control. Existing studies are unable to provide sufficient quantitative assessments of the correlation of PM2.5 and ozone pollution to support the coordinated control of the two air pollutants. This study develops a systematic method to comprehensively assess the correlation between PM2.5 and ozone pollution, including the evaluation of the impact of two air pollutants on human health and the extended correlation coefficient (ECC) for assessing the bivariate correlation index of PM2.5-ozone pollution in Chinese cities. According to the latest studies on epidemiology conducted in China, we take cardiovascular and cerebrovascular diseases and respiratory diseases as the ozone pollution's health burden when evaluating the health impact of ozone pollution. The results show that the health impact of PM2.5 in China decreases by 25.9 % from 2015 to 2021, while the health impact of ozone increases by 11.8 %. The ECC of 335 cities in China shows an increasing-decreasing trend but has generally increased from 2015 to 2021. The study provides important support for an in-depth understanding of the correlation and development trend of Chinese PM2.5 and ozone pollution by classifying the comprehensive PM2.5-ozone correlation performances of Chinese cities into four types. China or other countries will get better environmental benefits by implementing different coordinated management approaches for different correlative types of regions based on the assessment method in this study.

A stratification system of ferroptosis and iron-metabolism related LncRNAs guides the prediction of the survival of patients with esophageal squamous cell carcinoma.

Ferroptosis and iron-metabolism have been widely reported to play an important role in cancer. Long non-coding RNAs (lncRNAs) are increasingly recognized as the crucial mediators in the regulation of ferroptosis and iron metabolism. A systematic understanding of ferroptosis and iron-metabolism related lncRNAs (FIRLs) in esophageal squamous cell carcinoma (ESCC) is essential for prognosis prediction. Herein, Pearson's correlation analysis was carried out between ferroptosis and iron-metabolism-related genes (FIRGs) and all lncRNAs to derive the FIRLs. Based on weighted gene co-expression network exploration (WCGNA), least absolute shrinkage and selection operator (LASSO) regression and Cox regression analysis, a risk stratification system, including 3 FIRLs (LINC01068, TMEM92-AS1, AC243967.2), was established. According to Kaplan-Meier analysis, receiver operating characteristic (ROC) curve analysis, and univariate and multivariate Cox regression analyses, the risk stratification system had excellent predictive ability and clinical relevance. The validity of the established prognostic signature was further examined in TCGA (training set) and GEO (validation set) cohorts. A nomogram with enhanced precision for forecasting OS was set up on basis of the independent prognostic elements. Functional enrichment analysis revealed that three FIRLs took part in various cellular functions and signaling pathways, and the immune status was varied in the high-risk and low-risk groups. In the end, the oncogenic effects of LINC01068 was explored using in vitro researches. Overall, a risk stratification system of three FIRLs was found to have significant prognostic value for ESCC and may serve as a ferroptosis-associated therapeutic target in the clinic.

Pro-Angiogenesis Role of LINC00662 From Esophageal Squamous Cell Carcinoma Cells-Derived Extracellular Vehicles.

Objective: LINC00662 is oncogenic in some human cancers, but no much was revealed concerning to its specific action in tumor angiogenesis. Given that, our study investigated the role of LINC00662 from esophageal squamous cell carcinoma (ESCC) cells-derived extracellular vehicles (EVs) in angiogenesis through microRNA (miR)-195-5p/vascular endothelial growth factor A (VEGFA) axis. Methods: Clinical tissue samples were collected from patients with ESCC, in which LINC00662, miR-195-5p and VEGFA expression was analyzed. ESCC cells were transfected, from which EVs were isolated. Human umbilical vein endothelial cells (HUVECs) were co-cultured with the pretreated EVs. After that, viability, colony formation ability, invasion, migration and tube formation ability of HUVECs were observed. Tumor xenograft in nude mice was performed to detect the effect of LINC00662, miR-195-5p or EV specific inhibitor GW4869 on tumor development. Results: LINC00662 and VEGFA were upregulated while miR-195-5p was downregulated in the cancer tissue of patients with ESCC. EVs derived from ESCC cells promoted viability, colony formation ability, invasion and tube formation ability of HUVECs. Downregulation of LINC00662 or upregulation of miR-195-5p reversed the promotion of EVs derived from ESCC cells on the viability, colony formation ability, invasion and tube formation ability of HUVECs in vitro and in vivo. VEGFA overexpression reversed EVs carrying restored miR-195-5p induced effects on HUVECs in vitro. Conclusion: In summary, elevated LINC00662 transferred by ESCC cells-derived EVs induces angiogenesis through downregulating miR-195-5p and upregulating VEGFA.

Comprehensive Analysis of TRP Channel-Related Genes for Estimating the Immune Microenvironment, Prognosis, and Therapeutic Effect in Patients With Esophageal Squamous Cell Carcinoma.

The Nobel Prize in Physiology or Medicine for the year 2021 was awarded to Ardem Patapoutian and David Julius for their discoveries of temperature-sensitive receptors (TRP channels) and tactile receptors (Piezo channels), both of which were previously unknown. TRP channels are at the heart of the human ability to detect temperature, and they also play crucial regulatory functions in the occurrence and progression of cancer. Despite this, there have been no research conducted on the prognostic significance of TRP channels in individuals with esophageal squamous cell carcinoma (ESCC). In GEO and TCGA cohorts, unsupervised clustering was first conducted based on 18 TRP channel-associated differentially expressed genes (DEGs) extracted from MSigDB database and KEGG database. Two TRP subtypes were identified and patients in subtype B had the best prognosis among the two subtypes. Significant differences in staging and grading existed among the different subtypes. In GEO cohort, univariate Cox analysis were performed to screen prognosis related genes. A TRP channel-related prognostic signature, which included 7 signature-related genes, was constructed by the least absolute shrinkage and selection operator (LASSO) Cox regression. Patients were divided into a high-risk group and low-risk group by the median risk score. In GEO and TCGA cohorts, Receiver operating characteristic (ROC) curves, principal component analysis (PCA), and univariate and multivariate Cox regression were performed to confirm the validity of signature. Following a more in-depth study of the TME based on the risk signature, it was discovered that the high-risk group had higher immune cell infiltration and lower tumor purity, indicating a bad prognosis. Patients with high risk scores also had increased immune checkpoint expression, indicating that these patients may be more likely to benefit from immunotherapy than other patients. We also found that paclitaxel, cisplatin, and 5-fluorouracil displayed a better response in treating the low-risk score ESCC patients. This study also adopted GTEx and qRT-PCR to perform experimental verification processes. In summary, we identified a TRP channel-associated prognostic signature. This signature can predict prognosis and immune microenvironment in ESCC.

miR-493 by regulating of c-Jun targets Wnt5a/PD-L1-inducing esophageal cancer cell development.

BACKGROUND: Esophageal cancer is one of the most common cancers across the globe; the 5-year survival of esophageal cancer patients is still low. MicroRNA (miRNA) dysregulation has been implicated in cancer development, and the miRNAs play a pivotal role in esophageal cancer pathogenesis. It is urgently needed to find out how miRNA dysregulation was involved in esophageal cancer (EC) development. METHODS: Through experiments in vivo and in vitro, we explored potential signaling pathways, miR-493/Wnt5A/c-JUN loop, in EC. Their mechanistic roles in EC cell proliferation, migration, and invasion were investigated through multiple validation steps in EC9706 and TE13 cell lines and EC specimens. RESULTS: Overexpression of miR-493 attenuates esophageal cancer cell proliferation, migration, and invasion in vivo and in vitro. Moreover, miR-493 downregulation is an unfavorable factor in EC and negatively correlated with Wnt5A. The existence of miR-493 is also an important attribute of metabolism. Based on mechanism analyses, we show that miR-493 inhibits the activity of c-JUN and p-PI3K/p-AKT with enhanced p21 and directly regulates Wnt5A expression and function, whereas c-JUN binds the promoter region of miR-493 and suppressed the expression of miR-493, forming a negative feedback loop. CONCLUSIONS: The miR-493/Wnt5A/c-JUN loop is a molecular feedback loop that refers to the development of esophageal cancer cells and a potential target for the treatment of esophageal cancer.

Mir-192 suppresses apoptosis and promotes proliferation in esophageal aquamous cell caicinoma by targeting Bim.

MicroRNAs (miRNAs) are small, non-coding RNAs of endogenous origin. Accumulating studies have shown aberrant miRNA expression plays an important role in many tumor types. However, the mechanisms by which miRNAs regulate esophageal squamous cell carcinoma (ESCC) development remain poorly understood. In the present study, we assayed expression level of miR-192 in ESCC tissues and cell lines by real-time PCR, and defined the target gene and biological function by luciferase reporter assay, Western blot and apoptosis assay. We first verified that the expression level of miR-192 was significantly increased in ESCC tissues and cancer cells. Moreover, miR-192 over-expression inhibited cells apoptosis and promoted ESCC cells proliferation. We further demonstrated that miR-192 directly targeted 3'-UTR of Bim gene, and inhibited its protein expression. Importantly, Bim could reduce ESCC cells apoptosis ability induced by miR-192. These data suggest an important role of miR-192 in the molecular etiology of ESCC and implicate the potential application of miR-192 in ESCC therapy.

MiR-133a suppresses the migration and invasion of esophageal cancer cells by targeting the EMT regulator SOX4.

MicroRNAs (miRNAs) are small, non-coding RNAs which can function as oncogenes or tumor suppressor genes in human cancers. In the present study, we demonstrated that the expression ofmiR-133a was dramatically decreased in examined esophageal squamous cell carcinoma (ESCC) cell lines and clinical ESCC tissue samples. Additionally, miR-133a expression was inversely correlated with tumor progression in ESCCs. We have found that over-expression of miR-133a significantly suppressed the proliferation, migration and invasion of ESCC cells in vitro. miR-133a over-expression also significantly suppressed the aggressive phenotype of ESCC in vivo, suggesting that miR-133a may function as a novel tumor suppressor. Further studies indicated that the EMT-related transcription factor Sox4 was a direct target gene of miR-133a, evidenced by the direct binding of miR-133a with the 3'UTR of Sox4. Notably, the EMT marker E-cadherin or vimentin, a downstream of Sox4, was also down-regulated or upregulated upon miR-133a treatment. We have also shown that over-expressing or silencing Sox4 was able to elevate or inhibit the migration and invasion of ESCC cells, similar to the effect of miR-133a on the ESCC cells. Moreover, knockdown of Sox4 reversed the enhanced migration and invasion mediated by anti-miR-133a. These results demonstrate that miR-133a acts as a tumor suppressor in ESCC through targeting Sox4 and the EMT process. miR-133a may serve as a potential target in the treatment of human esophageal cancer.