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Cancer-associated fibroblasts (CAFs), as a central component of the tumor microenvironment in primary and metastatic tumors, profoundly influence the behavior of cancer cells and are involved in cancer progression through extensive interactions with cancer cells and other stromal cells. Furthermore, the innate versatility and plasticity of CAFs allow their education by cancer cells, resulting in dynamic alterations in stromal fibroblast populations in a context-dependent manner, which highlights the importance of precise assessment of CAF phenotypical and functional heterogeneity. In this review, we summarize the proposed origins and heterogeneity of CAFs as well as the molecular mechanisms regulating the diversity of CAF subpopulations. We also discuss current strategies to selectively target tumor-promoting CAFs, providing insights and perspectives for future research and clinical studies involving stromal targeting. Cancer: Reprogramming cells that support tumors Tumors reprogram nearby wound-healing cells into cancer-associated fibroblasts (CAFs) to support their metabolism, escape the immune response and develop resistance to chemotherapy; targeting CAFs may provide therapeutic opportunities. CAFs are very diverse, and their origins and specific roles are not well understood. New genetic tools allow precise profiling of CAFs and their functions, and Dakai Yang at Jiangsu University in Zhenjiang, China, and co-workers have reviewed CAF diversity and the mechanisms by which they are generated. Although most CAFs support tumors, some CAFs fight tumors, and they can potentially be converted from one form to another. Improving our understanding of the variety of CAFs, their functions, and how they interact with tumor cells may help in identifying tumor-suppressing CAFs and in developing precision medicine treatments for various types of cancer.

Nitrate pollution is widespread environmental concern in most shallow groundwater systems. This study conducts a comprehensive investigation of shallow groundwater, deep groundwater, and surface water in a region of the Chinese Loess Plateau. Nitrate pollution in this area is severe with more than half of the shallow groundwater samples exceeding the limit of nitrate for drinking water (50 mg/L). Temporal variation of nitrate reveals a continued increase of nitrate in shallow groundwater, although the fertilizer use has been reduced, recently. Spatially, deep groundwater nitrate is much lower than that in shallow groundwater, supporting the anthropogenic origin of nitrate from surface. The intrinsic vulnerability index indicates less susceptibility of loess aquifer to pollution in comparison to alluvial aquifer. However, high levels of nitrate are observed in both alluvial and loess aquifers. The pollution risk assessment combined with anthropogenic loads explains the occurrence of nitrate more precisely. Agricultural inputs and release of sewage-effluents are the major contributions of nitrate from hydrogeochemical evidence. The high nitrate in loess aquifer, which is supposed to be less susceptible to contamination, indicates anthropogenic loads to be a non-negligible factor. Control of nitrate pollution in loess area is long-standing issue and will require sustained monitoring.

A feature of arbuscular mycorrhiza is enhanced drought tolerance of host plants, although it is unclear whether host H + -ATPase activity and gene expression are involved in the physiological process. The present study aimed to investigate the effects of an arbuscular mycorrhizal fungus (AMF), Funneliformis mosseae , on H + -ATPase activity, and gene expression of trifoliate orange ( Poncirus trifoliata ) seedlings subjected to well-watered (WW) and drought stress (DS), together with the changes in leaf gas exchange, root morphology, soil pH value, and ammonium content. Soil drought treatment dramatically increased H + -ATPase activity of leaf and root, and AMF inoculation further strengthened the increased effect. A plasma membrane (PM) H + -ATPase gene of trifoliate orange, PtAHA2 (MW239123), was cloned. The PtAHA2 expression was induced by mycorrhization in leaves and roots and also up-regulated by drought treatment in leaves of AMF-inoculated seedlings and in roots of AMF- and non-AMF-inoculated seedlings. And, the induced expression of PtAHA2 under mycorrhization was more prominent under DS than under WW. Mycorrhizal plants also showed greater photosynthetic rate, stomatal conductance, intercellular CO 2 concentration, and transpiration rate and better root volume and diameter than non-mycorrhizal plants under DS. AMF inoculation significantly increased leaf and root ammonium content, especially under DS, whereas it dramatically reduced soil pH value. In addition, H + -ATPase activity was significantly positively correlated with ammonium contents in leaves and roots, and root H + -ATPase activity was significantly negatively correlated with soil pH value. Our results concluded that AMF stimulated H + -ATPase activity and PtAHA2 gene expression in response to DS, which resulted in great nutrient (e.g., ammonium) uptake and root growth, as well as low soil pH microenvironment.

Exosomal circRNA serves a novel genetic information molecule, facilitating communication between tumor cells and microenvironmental cells, such as immune cells, fibroblasts, and other components, thereby regulating critical aspects of cancer progression including immune escape, tumor angiogenesis, metabolism, drug resistance, proliferation and metastasis. Interestingly, microenvironment cells have new findings in influencing tumor progression and immune escape mediated by the release of exosomal circRNA. Given the intrinsic stability, abundance, and broad distribution of exosomal circRNAs, they represent excellent diagnostic and prognostic biomarkers for liquid biopsy. Moreover, artificially synthesized circRNAs may open up new possibilities for cancer therapy, potentially bolstered by nanoparticles or plant exosome delivery strategies. In this review, we summarize the functions and underlying mechanisms of tumor cell and non-tumor cell-derived exosomal circRNAs in cancer progression, with a special focus on their roles in tumor immunity and metabolism. Finally, we examine the potential application of exosomal circRNAs as diagnostic biomarkers and therapeutic targets, highlighting their promise for clinical use.

Background Exosomes are extracellular vesicles that mediate cellular communication in health and diseases. Neutrophils could be polarized to a pro-tumor phenotype by tumor. The function of tumor-derived exosomes in neutrophil regulation remains unclear. Methods We investigated the effects of gastric cancer cell-derived exosomes (GC-Ex) on the pro-tumor activation of neutrophils and elucidated the underlying mechanisms. Results GC-Ex prolonged neutrophil survival and induced expression of inflammatory factors in neutrophils. GC-Ex-activated neutrophils, in turn, promoted gastric cancer cell migration. GC-Ex transported high mobility group box-1 (HMGB1) that activated NF-κB pathway through interaction with TLR4, resulting in an increased autophagic response in neutrophils. Blocking HMGB1/TLR4 interaction, NF-κB pathway, and autophagy reversed GC-Ex-induced neutrophil activation. Silencing HMGB1 in gastric cancer cells confirmed HMGB1 as a key factor for GC-Ex-mediated neutrophil activation. Furthermore, HMGB1 expression was upregulated in gastric cancer tissues. Increased HMGB1 expression was associated with poor prognosis in patients with gastric cancer. Finally, gastric cancer tissue-derived exosomes acted similarly as exosomes derived from gastric cancer cell lines in neutrophil activation. Conclusion We demonstrate that gastric cancer cell-derived exosomes induce autophagy and pro-tumor activation of neutrophils via HMGB1/TLR4/NF-κB signaling, which provides new insights into mechanisms for neutrophil regulation in cancer and sheds lights on the multifaceted role of exosomes in reshaping tumor microenvironment.

Groundwater is the major water resource for the agricultural development of the Guanzhong Basin, China. In this study, a total of 97 groundwater samples (51 from the North Bank of the Wei River (NBWR) and 46 from the South Bank of the Wei River (SBWR)) were collected from the central-western Guanzhong Basin. The aim of this study was to investigate the hydrogeochemical characteristics of the basin and to determine the suitability of shallow groundwater for irrigation. The groundwater of the entire study area is alkaline. The groundwater of the SBWR is fresh water, and the NBWR groundwater is either freshwater or brackish water. The average concentration of ions (except for Ca2+) in SBWR samples is lower than in NBWR samples. HCO3− is dominant in the groundwater of the study area. Ca2+ is dominant in the SBWR while Na+ is dominant in the NBWR. The SBWR groundwater is mainly of the HCO3-Ca·Mg type, and has undergone the main hydrogeochemical processes of rock weathering-leaching. The hydrochemical facies of the majority of the NBWR groundwater samples are the HCO3-Na type with several minor hydrochemical facies of the HCO3-Ca·Mg, SO4·Cl-Na, and SO4·Cl-Ca·Mg types. Its chemistry is mainly controlled by rock weathering, cation exchange, and evaporation. Salinity hazard, sodium percentage, sodium adsorption ratio, residual sodium carbonate, magnesium hazard, permeability index, Kelley’s ratio, potential salinity, synthetic harmful coefficient, and irrigation coefficient were assessed to evaluate the irrigation quality of groundwater. The results of the comprehensive consideration of these indicators indicate that the percentage of NBWR water samples suitable for irrigation purposes ranges between 15.7% and 100% at an average level of 56.7%. Of the SBWR water samples suitable for irrigation, the percentage ranges from 78.3% to 100% with an average of 91.8%. Land irrigated with such water will not be exposed to any alkali hazard, but will suffer from a salinity hazard, which is more severe in the NBWR. Thus, most of the water in the NBWR can be used for soils with good drainage conditions which control salinity.

Good quality drinking water is of utmost importance for the survival and development of human society in this modern era of contamination of groundwater throughout the world. However, the problem is enormous in many countries, especially in arid and semi-arid regions of the globe, where a vast number of people purely rely on groundwater for their daily uses including drinking, household, and irrigation purposes. This thematic issue of Environmental Earth Sciences was initiated to comprehensively comprehend the groundwater quality and its contamination process using various scientifically profound methods, so that considerable strategic steps can be implemented to mitigate the sources of pollution as well as revamp the groundwater quality scenarios and also improve the safety and securing the supply of drinking water in many regions. Specifically, studies reported in this thematic issue precisely emphasized on groundwater quality and contamination of anthropogenic and geogenic sources disseminated over an extensive geographic regions including China, India, Pakistan, Korea, Mexico, Iran, South Africa, Ghana, Nigeria, Ukraine, Kuwait, Turkey, and Brazil. The papers which were published in this thematic issue were remarkable and also covered a wide range of topics related to the main theme of the thematic issue/research topic, and these articles will have a broad impact on the sustainable protection of groundwater quality. However, the significant outcome of each contribution in this thematic issue was plainly recapitulated in this article, and more importantly, a few fruitful research directions were also recommended to promote further studies on groundwater contamination and evaluate the suitability of groundwater for various purposes.

Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

Loess is mainly distributed in arid and semiarid areas of the world, and water is essential and precious in the loess areas. Water is also an important factor inducing various geohazards and soil erosion in the loess areas. The thematic issue of Environmental Earth Sciences was edited to reflect the latest research on water and water-related themes in the loess areas of the world, especially on the Chinese Loess Plateau. This editorial introduced the background and initiative of editing this thematic issue, and it also introduced briefly the water environment projects currently underway on the Chinese Loess Plateau such as the grain for green project, the huge land creation project, and the sponge city project. The papers included in the thematic issue were also introduced to give readers a general understanding of their main research points. Finally, some suggestions to boost further water environment research in the loess areas were put forward. All the papers included in the thematic issue will scientifically support the sustainable socio-economic development in the loess areas of the world.

Recently, many studies explored the role of inflammation parameters such as neutrophil-to-lymphocyte ratio (NLR) in the prognosis of urinary cancers, but the results were not consistent. We carried out a meta-analysis of published studies to assess the prognostic value of NLR in patients with urinary cancers. Hazard ratio (OR) with 95% confidence interval (CI) was used to assess the association of NLR and OS and RFS/CSS. The pooled results showed that high NLR was a poor predictor for OS with HR of 1.81 (95%CI: 1.48-2.21; Pheterogeneity = 0.005) and RFS/CSS (HR = 2.07, 95% CI: 1.65-2.6; Pheterogeneity = 0.849). Subgroup analyses revealed that high NLR yielded a worse OS in RCC (HR = 1.9, 95%CI: 1.47-2.45; Pheterogeneity = 0.003) and a poor RFS/CSS in RCC (HR = 1.83, 95%CI: 1.35-2.48; Pheterogeneity = 0.709), bladder cancer (HR = 2.2, 95%CI: 1.27-3.8; Pheterogeneity = 0.447) and urothelial carcinoma (HR = 2.58, 95%CI: 1.66-4.01; Pheterogeneity = 0.784). Our results showed that NLR could act as a significant biomarker in the prognosis of urinary cancers.