Neuroendocrine tumors (NETs) are rare, heterogeneous, often indolent tumors that predominantly originate in the lungs and gastrointestinal tract. An understanding of the biology and tumor ...microenvironment of NETs has led to the development of molecularly targeted treatment options including somatostatin analogs, tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors and peptide receptor radionuclide therapy. Although increases in progression-free survival have been demonstrated, most currently approved NET therapies are limited by the development of tumor resistance. Surufatinib (HMPL-012, previously known as sulfatinib) is a new, oral, small-molecule tyrosine kinase inhibitor that potently inhibits vascular endothelial growth-factor receptor 1–3, fibroblast growth-factor receptor 1, and colony-stimulating-factor-1 receptor. This unique combination of molecular activities inhibits tumor angiogenesis, regulates tumor-immune evasion, and may decrease tumor resistance. Surufatinib demonstrated statistically significant, clinically meaningful antitumor activity, including tumor shrinkage, in two phase III studies recently completed in China in advanced pancreatic NETs and advanced extrapancreatic NETs. The safety profile of surufatinib in neuroendocrine tumors studies was consistent with previous surufatinib clinical studies. In an ongoing study in United States (US) patients with NETs of pancreatic origin and NETs of extrapancreatic origin previously treated with everolimus or sunitinib, surufatinib has also demonstrated promising efficacy. Furthermore, the pharmacokinetic and safety profile of surufatinib in US patients is similar to data collected in studies done in China. These positive phase III results support the efficacy of surufatinib in patients with advanced, progressive, well-differentiated NETs regardless of tumor origin.
There are global concerns about heavy metal (HM) contamination in soils, which in turn has produced an increased demand for soil remediation. Biochar has been widely documented to effectively ...immobilize metals in contaminated soils and has received increasing attention for use in soil remediation. Here, we review recent progresses in understanding metal-biochar interactions in soils, potential risks associated with biochar amendment, and application of biochar in soil remediation in China. These recent studies indicate that: (1) the remediation effect depends on the characteristics of both biochar and soil and their interactions; (2) biochar applications could decrease the mobility/bioavailability of HMs in soils and HM accumulation in plants; and (3) despite its advantages, biochar applications could pose ecological and health risks, e.g., by releasing toxic substances into soils or by inhalation of biochar dust. Research gaps still exist in the development of practical methods for preparing and applying different biochars that target specific HMs. In the future, the long term effects and security of biochar applications on soil remediation, soil organisms and plant growth need to be considered.
Display omitted
•The metal-biochar interactions and mechanisms in soils were reviewed.•Potential risks associated with biochar amendment were discussed.•Cases of biochar application in soils in China were summarized.•Long term effects of biochar on soil remediation need further investigation.
The remediation of heavy metal contaminated soils by biochar in China was reviewed, including metal-biochar interactions and mechanisms, its application risk and status.
Microplastics have a great potential to sorb organic pollutants from the adjacent environment. In this study, the sorption of tetracycline, a polar and ionizable antibiotic, on three types of ...microplastics (polyethylene (PE), polypropylene (PP) and polystyrene (PS)) were investigated in batch sorption experiments. The sorption isotherms were well fitted by the Langmuir model, indicating that not only hydrophobic interactions but also other interactions (e.g. electrostatic interactions) played important roles in the sorption process. PS had the maximum sorption capacity, following the order PS > PP > PE, which can be attributed to polar interactions and π-π interactions. The sorption of tetracycline on microplastics was significantly influenced by pH, with sorption capacity increasing gradually, peaking at pH 6.0 and then decreasing, likely due to the influence of tetracycline speciation with the change of pH. Fulvic acid was selected as representative dissolved organic matter (DOM) to examine the effect on sorption. The increasing concentration of fulvic acid inhibited the sorption of tetracycline on three microplastics, decreasing them by more than 90% at the fulvic acid concentration of 20 mg/L, which implied a greater affinity of tetracycline to fulvic acid than to microplastics. Increasing salinity from 0.05 to 3.5% had negligible effects on the sorption of tetracycline on the three microplastics. Our results highlight the importance of pH and DOM on the sorption of tetracycline on microplastics, and suggest the relatively minor role of microplastics in the fate and transport of tetracycline in the aquatic environment in the presence of DOM.
Display omitted
•The sorption isotherms of tetracycline were well fitted with the Langmuir model.•PS microplastics had the larger sorption capacity for tetracycline than PE and PP.•The sorption capacity of tetracycline peaked at pH 6.0 and then decreased.•Increasing dissolved organic matter decreased the sorption capacity of tetracycline.•Salinity had a negligible effect on the sorption of tetracycline.
Our findings highlight the importance of pH and dissolved organic matter to the sorption behavior of tetracycline on three types of microplastics.
This article reviews the molecular structure, expression pattern, physiological function, pathological roles and mo- lecular mechanisms of Twistl in development, genetic disease and cancer. Twistl is ...a basic helix-loop-helix domain- containing transcription factor. It forms homo- or hetero-dimers in order to bind the Ndel E-box element and acti- vate or repress its target genes. During development, Twistl is essential for mesoderm specification and differentia- tion. Heterozygous loss-of-function mutations of the human Twistl gene cause several diseases including the Saethre- Chotzen syndrome. The Twistl-null mouse embryos die with unclosed cranial neural tubes and defective head mesen- chyme, somites and limb buds. Twistl is expressed in breast, liver, prostate, gastric and other types of cancers, and its expression is usually associated with invasive and metastatic cancer phenotypes. In cancer cells, Twistl is upregulated by multiple factors including SRC-1, STAT3, MSX2, HIF-la, integrin-linked kinase and NF-κB. Twistl significantly enhances epithelial-mesenchymal transition （EMT） and cancer cell migration and invasion, hence promoting cancer metastasis. Twistl promotes EMT in part by directly repressing E-cadherin expression by recruiting the nucleosome remodeling and deacetylase complex for gene repression and by upregulating Bmil, AKT2, YB-1, etc. Emerging evi- dence also suggests that Twistl plays a role in expansion and chemotherapeutic resistance of cancer stem cells. Fur- ther understanding of the mechanisms by which Twistl promotes metastasis and identification of Twistl functional modulators may hold promise for developing new strategies to inhibit EMT and cancer metastasis.
Currently, environmental pollution by heavy metals is a global problem. Therefore, it is crucial to develop effective detection techniques to determine the levels of heavy metal contamination in ...various mediums. Voltammetry is a highly sensitive electrochemical method used for the in situ detection of heavy metal ions. This study investigates the current trends related to electrode modification, developments in materials, and optimization of the experimental parameters. We discuss the sensing performance of four kinds of nanomaterials capable of inorganic modification (metal nanoparticles, metal oxides, carbonaceous nanomaterials, and their nanocomposites). The impact of several important factors, such as the deposition potential and time, buffer solution types, and pH on the sensitivity, reproducibility, stability, and anti-interference ability of the detection process, especially with regard to the co-detection of several heavy metal ions, was reviewed. We noted that in addition to the application of voltammetry to water-related issues, it is suitable for rapid and simple identification and analyses of heavy metals in polluted soil and other mediums. Thus, it is important to conduct additional research on the application of voltammetry to this area.
Display omitted
•Basic principles of voltammetry for heavy metal detection were reviewed.•The sensing performance of inorganic nanomaterials modification were discussed.•The impact of several important experimental factors were emphasized.•The application of voltammetry involves in many mediums.
One of the important products of MERRA-2 (Modern-Era Retrospective Analysis for Research and Applications) developed by NASA (National Aeronautics and Space Administration) is the long-term global ...records of surface PM2.5 mass concentration since 1980s, providing the ability of studying the interactions between air pollution, weather and climate changes. In this study, the PM2.5 mass concentrations of MERRA-2 are firstly validated across China mainland by independent surface measurements collected by Ministry of Ecology and Environment of People's Republic of China from 2014 to 2018. The results show that MERRA-2 well captures the spatial distribution and seasonal variation of PM2.5 mass concentration in China mainland. The spatial and temporal evolution of large scale persistent PM2.5 pollution event is also generally reflected by MERRA-2 by case study based on the target object match method. However significant underestimation of the PM2.5 mass concentration in MEERA-2 is revealed across China mainland, especially in BTH region by 34.6 μg m−3, followed by 19.8 μg m−3 in YRD and 9.1 μg m−3 in PRD region. Such underestimation is most substantial in winter and autumn seasons. In addition, the discrepancy between MERRA-2 and observations increases significantly with the enhanced PM2.5 level, for example, ranging from 29.9 μg m−3 in clean days, while 66.1 μg m−3 in polluted days in BTH region. We highlight the downward trends of PM2.5 from 2014 to 2018 in China mainland estimated by MERRA-2 which is basically consistent in the observations, but with ~50% underestimation, indicating the potential applications of MERRA-2 for the future aerosol climatological studies. We suggest that the underestimations of both magnitude and variability of PM2.5 in MERRA-2 probably result from the uncertainty of the magnitude of emission inventory used in GOES model (lower intensity and weaker variations), and the absence of nitrate in PM2.5 constitution. A parameterized method for nitrate is proposed and evaluated by the sensitive study to improve MERRA-2 PM2.5 underestimation by 19.2–23.6% in BTH region. However, the more comprehensive validations are still required in future studies, especially by the aerosol composition measurements.
•The PM2.5 mass concentrations of MERRA-2 are firstly validated across China mainland from 2014 to 2018.•Significant underestimation of the PM2.5 concentration in MEERA-2 is revealed across China mainland.•A parameterized method for nitrate is proposed to improve MERRA-2 PM2.5 underestimation.
Heavy metal accumulation in agriculture soils is of particular concern in China, while the status and probabilistic health risks of metal contamination in Chinese agriculture soils have been rarely ...studied at the national scale. In this study, we compiled a database of heavy metal concentrations in Chinese agriculture soils and selected six heavy metals for pollution assessment and risk screening: arsenic (As), cadmium (Cd), chromium (Cr), nickel (Ni), lead (Pb) and Zinc (Zn). Monte Carlo simulation was employed to assess the probabilistic health risks, the associated uncertainties, as well as variations in toxicity parameters, ingestion rate and body weight. Results indicated that the concentrations of Cd were elevated above their reference standard and Cd had the highest mean geo-accumulation index (Igeo) of 1.79. Moreover, the mean hazard index (HI) through exposure to six heavy metals was 1.85E−01 and 2.87E−02 for children and adults, respectively, with 2.2% of non-cancer risks for children that exceeded the guideline value of 1. In contrast, 95.0% and 90.0% of the total cancer risks (TCR) through exposure to six heavy metals for children and adults, respectively, exceeded the guideline value of 1E−06. Six metals were ranked based on their percent of risk outputs exceeding the guideline values. Arsenic had the high exceedance of both cancer and non-cancer risks, while both Cr and Cd were metals with high concern that had high exceedance of cancer risk. Sensitivity analyses indicated that metal concentrations and ingestion rate of soil were the predominant contributors to total risk variance. Overall, the adverse health risks induced by exposure to heavy metals contaminated farmland were elevated. Results from this study may provide valuable implications for public health professionals and policy-makers to design effective strategy to manage nation-wide farmland and reduce heavy metal exposure.
Display omitted
•Pollution status and probabilistic health risk of heavy metal in agriculture soils across China was determined.•Chinese population face severe cancer risks of heavy metal exposure as their risk value exceeded the benchmark.•The spatial distribution of high-risk areas and that of cancer villages were correlated.•Priority metals and critical exposure factors for further risk control were identified.
Source apportionment can be an effective tool in mitigating soil pollution but its efficacy is often limited by a lack of information on the factors that influence the accumulation of pollutants at a ...site. In response to this limitation and focusing on a suite of heavy metals identified as priorities for pollution control, the study established a comprehensive pollution control framework using factor identification coupled with spatial agglomeration for agricultural soils in an industrialized part of Zhejiang Province, China. In addition to elucidating the key role of industrial and traffic activities on heavy metal accumulation through implementing a receptor model, specific influencing factors were identified using a random forest model. The distance from the soil sample location to the nearest likely industrial source was the most important factor in determining cadmium and copper concentrations, while distance to the nearest road was more important for lead and zinc pollution. Soil parent materials, pH, organic matter, and clay particle size were the key factors influencing accumulation of arsenic, chromium, and nickel. Spatial auto-correlation between levels of soil metal pollution and industrial agglomeration can enable a more targeted approach to pollution control measures. Overall, the approach and results provide a basis for improved accuracy in source apportionment, and thus improved soil pollution control, at the regional scale.
Display omitted
•Provision of a framework that links heavy metals in soils with their source.•Identification of environmental influence over heavy metal contamination of soils.•Spatially integrated industrial agglomerations and heavy metal-contaminated soils.•Basis for targeted measures aimed at mitigating pollution and health risks.
Long‐term elevated nitrogen (N) input from anthropogenic sources may cause soil acidification and decrease crop yield, yet the response of the belowground microbial community to long‐term N input ...alone or in combination with phosphorus (P) and potassium (K) is poorly understood. We explored the effect of long‐term N and NPK fertilization on soil bacterial diversity and community composition using meta‐analysis of a global dataset. Nitrogen fertilization decreased soil pH, and increased soil organic carbon (C) and available N contents. Bacterial taxonomic diversity was decreased by N fertilization alone, but was increased by NPK fertilization. The effect of N fertilization on bacterial diversity varied with soil texture and water management, but was independent of crop type or N application rate. Changes in bacterial diversity were positively related to both soil pH and organic C content under N fertilization alone, but only to soil organic C under NPK fertilization. Microbial biomass C decreased with decreasing bacterial diversity under long‐term N fertilization. Nitrogen fertilization increased the relative abundance of Proteobacteria and Actinobacteria, but reduced the abundance of Acidobacteria, consistent with the general life history strategy theory for bacteria. The positive correlation between N application rate and the relative abundance of Actinobacteria indicates that increased N availability favored the growth of Actinobacteria. This first global analysis of long‐term N and NPK fertilization that differentially affects bacterial diversity and community composition provides a reference for nutrient management strategies for maintaining belowground microbial diversity in agro‐ecosystems worldwide.
This study explored the effects of long‐term N and NPK fertilization on soil bacterial community in agro‐ecosystems using a meta‐analysis of datasets across the globe. The long‐term N fertilization significantly decreased soil bacterial diversity, changed bacterial community composition, and favored the growth of Actinobacteria and Proteobacteria over Acidobacteria. The negative effect of N fertilization on bacterial diversity disappeared when N is coapplied with P and K. This study represents an important step forward for understanding the connection between elevated nutrient inputs, shifts in soil microbial communities, and altered ecosystem functioning.
The contamination of arsenic (As) and cadmium (Cd) in paddy soils is widely reported and these two metals are difficult to be co-remediated due to the contrasting chemical behaviors. This poses a ...challenge to simultaneously decrease their availability in soil and accumulation in rice via immobilization by amendments, especially in in-situ fields. This study compared the effects of carbide slag, lodestone and biochar on the bioavailability of As and Cd in soil and their accumulation in rice tissues and root Fe–Mn plaque at tillering and mature stages in a paddy field. The addition of three amendments significantly limited the mobilization of As and Cd in soil and decreased their accumulations in brown rice by 30–52% and 9–21%, respectively. Carbide slag was most whereas lodestone least effective in As and Cd immobilization in the tested contaminated soils. Community Bureau of Reference (BCR) sequential extraction analysis showed that the amendments changed the forms of As and Cd to less-available. Activated functional groups of the amendments (e.g. –OH, C–O, OC–O, OH− and CO32−) sequestered metals by precipitation, adsorption, ion exchange or electrostatic attributes contributed greatly to the As and Cd immobilization in soil. Furthermore, the amendments promoted the formation of Fe–Mn plaque in rice roots, which further limited the mobility of As and Cd in soil and prevented their transport from soil to rice roots. The application of carbide slag and biochar but not lodestone increased rice yield compared to the unamended control, indicating their applicability in situ remediation. Our study gives a strong reference to select immobilizing amendments for food safe production in co-contaminated paddy soils.
Display omitted
•Amendments increased the soil pH from the tillering to mature stage.•Lodestone did not affect bioavailability and plant accumulation of Cd and As.•Carbide slag and biochar promoted the formation of Fe–Mn plaque.•Cadmium was more readily to be fixed in the Fe–Mn plaque than As.•Carbide slag and biochar worked well to decrease the accumulation of Cd and As in rice.
PDF
