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"Tang, M M"
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Sinking of microbial-associated microplastics in natural waters
Degraded plastic debris has been found in nearly all waters within and nearby urban developments as well as in the open oceans. Natural removal of suspended microplastics (MPs) by deposition is often limited by their excess buoyancy relative to water, but this can change with the attachment of biological matter. The extent to which the attached biological ballast affects MP dynamics is still not well characterised. Here, we experimentally demonstrate using a novel OMCEC (Optical Measurement of CEll colonisation) system that the biological fraction of MP aggregates has substantial control over their size, shape and, most importantly, their settling velocity. Polyurethane MP aggregates made of 80% biological ballast had an average size almost twice of those containing 5% biological ballast, and sank about two times slower. Based on our experiments, we introduce a settling velocity equation that accounts for different biological content as well as the irregular fractal structure of MP aggregates. This equation can capture the settling velocity of both virgin MPs and microbial-associated MP aggregates in our experiment with 7% error and can be used as a preliminary tool to estimate the vertical transport of MP aggregates made of different polymers and types of microbial ballast.
Journal Article
Global net climate effects of anthropogenic reactive nitrogen
Anthropogenic activities have substantially enhanced the loadings of reactive nitrogen (Nr) in the Earth system since pre-industrial times
1
,
2
, contributing to widespread eutrophication and air pollution
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,
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,
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–
6
. Increased Nr can also influence global climate through a variety of effects on atmospheric and land processes but the cumulative net climate effect is yet to be unravelled. Here we show that anthropogenic Nr causes a net negative direct radiative forcing of −0.34 [−0.20, −0.50] W m
−2
in the year 2019 relative to the year 1850. This net cooling effect is the result of increased aerosol loading, reduced methane lifetime and increased terrestrial carbon sequestration associated with increases in anthropogenic Nr, which are not offset by the warming effects of enhanced atmospheric nitrous oxide and ozone. Future predictions using three representative scenarios show that this cooling effect may be weakened primarily as a result of reduced aerosol loading and increased lifetime of methane, whereas in particular N
2
O-induced warming will probably continue to increase under all scenarios. Our results indicate that future reductions in anthropogenic Nr to achieve environmental protection goals need to be accompanied by enhanced efforts to reduce anthropogenic greenhouse gas emissions to achieve climate change mitigation in line with the Paris Agreement.
A comprehensive model framework is used to estimate the global net direct radiative forcing of anthropogenic reactive nitrogen as being about −0.34 W m
−2
, which has a cooling effect on the climate.
Journal Article
The p38-MK2-HuR pathway potentiates EGFRvIII–IL-1β-driven IL-6 secretion in glioblastoma cells
The microenvironment of glioblastoma (GBM) contains high levels of inflammatory cytokine interleukin 6 (IL-6), which contributes to promote tumour progression and invasion. The common epidermal growth factor receptor variant III (EGFRvIII) mutation in GBM is associated with significantly higher levels of IL-6. Furthermore, elevated IL-1β levels in GBM tumours are also believed to activate GBM cells and enhance IL-6 production. However, the crosstalk between these intrinsic and extrinsic factors within the oncogene-microenvironment of GBM causing overproduction of IL-6 is poorly understood. Here, we show that EGFRvIII potentiates IL-1β-induced IL-6 secretion from GBM cells. Importantly, exacerbation of IL-6 production is most effectively attenuated in EGFRvIII-expressing GBM cells with inhibitors of p38 mitogen-activated protein kinase (p38 MAPK) and MAPK-activated protein kinase 2 (MK2). Enhanced IL-6 production and increased sensitivity toward pharmacological p38 MAPK and MK2 inhibitors in EGFRvIII-expressing GBM cells is associated with increased MK2-dependent nuclear–cytoplasmic shuttling and accumulation of human antigen R (HuR), an IL-6 mRNA-stabilising protein, in the cytosol. IL-1β-stimulated activation of the p38 MAPK–MK2-HuR pathway significantly enhances IL-6 mRNA stability in GBM cells carrying EGFRvIII. Further supporting a role for the p38 MAPK–MK2-HuR pathway in the development of inflammatory environment in GBM, activated MK2 is found in more than 50% of investigated GBM tissues and correlates with lower grade and secondary GBMs. Taken together, p38 MAPK–MK2-HuR signalling may enhance the potential of intrinsic (EGFRvIII) and extrinsic (IL-1β) factors to develop an inflammatory GBM environment. Hence, further improvement of brain-permeable and anti-inflammatory inhibitors targeting p38 MAPK, MK2 and HuR may combat progression of lower grade gliomas into aggressive GBMs.
Journal Article
Pesticide mixtures in soil: a global outlook
In modern agriculture, pesticides are used in combinations to protect crops. The co-existence of multiple pesticides in soil can threaten the soil biodiversity that maintains ecosystem services, hence further posing a long-term risk on food security. Here, we introduce an assessment of global soil contamination by the residue of pesticide mixtures in nine cropping systems using a fully mechanistic, spatially explicit, and time-resolved model at 0.5° × 0.5° spatial resolution (approximately 55 × 55 km at the equator) fed with georeferenced agricultural quantities, soil properties, and hydroclimatic variables. We found that 8.3 million km2 of treated land have more than one detectable pesticide, with pendimethalin, glyphosate, paraquat, chlorpyrifos, and chlorothalonil being the five most frequently detected. The highest pesticide mixture content was found in the ‘orchards and grapes’ cropping system (95th percentile at 7.3 mg kg soil−1). Globally, the pesticide mixture in the topsoil of approximately 1.88 million km2 exceeded 1 mg kg soil−1 for more than 180 d in a year. We estimate that 0.2 million tonnes of pesticides leach below the root zone each year globally, with glyphosate contributing the greatest fraction. The major hotspots of soil pesticide contamination are located in South America and Asia, mainly in Brazil, Argentina, Chile, China, Malaysia, and Japan. Our study shows that the accumulation of pesticide mixtures in soil is a global environmental issue that has to be explicitly accounted for in the sustainability assessment of agricultural production. We propose the use of mechanistic modelling as a tool to aid in designing pesticide management strategies and minimise residue contamination.
Journal Article
Tumor-secreted exosomal miR-141 activates tumor-stroma interactions and controls premetastatic niche formation in ovarian cancer metastasis
Background
Metastatic colonization is one of the critical steps in tumor metastasis. A pre-metastatic niche is required for metastatic colonization and is determined by tumor-stroma interactions, yet the mechanistic underpinnings remain incompletely understood.
Methods
PCR-based miRNome profiling, qPCR, immunofluorescent analyses evaluated the expression of exosomal miR-141 and cell-to-cell communication. LC-MS/MS proteomic profiling and Dual-Luciferase analyses identified YAP1 as the direct target of miR-141. Human cytokine profiling, ChIP, luciferase reporter assays, and subcellular fractionation analyses confirmed YAP1 in modulating GROα production. A series of in vitro tumorigenic assays, an ex vivo model and Yap1 stromal conditional knockout (cKO) mouse model demonstrated the roles of miR-141/YAP1/GROα/CXCR1/2 signaling cascade. RNAi, CRISPR/Cas9 and CRISPRi systems were used for gene silencing. Blood sera, OvCa tumor tissue samples, and tissue array were included for clinical correlations.
Results
Hsa-miR-141-3p (miR-141), an exosomal miRNA, is highly secreted by ovarian cancer cells and reprograms stromal fibroblasts into proinflammatory cancer-associated fibroblasts (CAFs), facilitating metastatic colonization. A mechanistic study showed that miR-141 targeted YAP1, a critical effector of the Hippo pathway, reducing the nuclear YAP1/TAZ ratio and enhancing GROα production from stromal fibroblasts. Stromal-specific knockout (cKO) of Yap1 in murine models shaped the GROα-enriched microenvironment, facilitating in vivo tumor colonization, but this effect was reversed after Cxcr1/2 depletion in OvCa cells. The YAP1/GROα correlation was demonstrated in clinical samples, highlighting the clinical relevance of this research and providing a potential therapeutic intervention for impeding premetastatic niche formation and metastatic progression of ovarian cancers.
Conclusions
This study uncovers miR-141 as an OvCa-derived exosomal microRNA mediating the tumor-stroma interactions and the formation of tumor-promoting stromal niche through activating YAP1/GROα/CXCRs signaling cascade, providing new insight into therapy for OvCa patients with peritoneal metastases.
Journal Article
Genetic plasticity of the Shigella virulence plasmid is mediated by intra- and inter-molecular events between insertion sequences
Acquisition of a single copy, large virulence plasmid, pINV, led to the emergence of Shigella spp. from Escherichia coli. The plasmid encodes a Type III secretion system (T3SS) on a 30 kb pathogenicity island (PAI), and is maintained in a bacterial population through a series of toxin:antitoxin (TA) systems which mediate post-segregational killing (PSK). The T3SS imposes a significant cost on the bacterium, and strains which have lost the plasmid and/or genes encoding the T3SS grow faster than wild-type strains in the laboratory, and fail to bind the indicator dye Congo Red (CR). Our aim was to define the molecular events in Shigella flexneri that cause loss of Type III secretion (T3S), and to examine whether TA systems exert positional effects on pINV. During growth at 37°C, we found that deletions of regions of the plasmid including the PAI lead to the emergence of CR-negative colonies; deletions occur through intra-molecular recombination events between insertion sequences (ISs) flanking the PAI. Furthermore, by repositioning MvpAT (which belongs to the VapBC family of TA systems) near the PAI, we demonstrate that the location of this TA system alters the rearrangements that lead to loss of T3S, indicating that MvpAT acts both globally (by reducing loss of pINV through PSK) as well as locally (by preventing loss of adjacent sequences). During growth at environmental temperatures, we show for the first time that pINV spontaneously integrates into different sites in the chromosome, and this is mediated by inter-molecular events involving IS1294. Integration leads to reduced PAI gene expression and impaired secretion through the T3SS, while excision of pINV from the chromosome restores T3SS function. Therefore, pINV integration provides a reversible mechanism for Shigella to circumvent the metabolic burden imposed by pINV. Intra- and inter-molecular events between ISs, which are abundant in Shigella spp., mediate plasticity of S. flexneri pINV.
Journal Article
Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis
Procalcitonin is widely reported as a useful biochemical marker to differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome. In this systematic review, we estimated the diagnostic accuracy of procalcitonin in sepsis diagnosis in critically ill patients. 18 studies were included in the review. Overall, the diagnostic performance of procalcitonin was low, with mean values of both sensitivity and specificity being 71% (95% CI 67–76) and an area under the summary receiver operator characteristic curve of 0·78 (95% CI 0·73–0·83). Studies were grouped into phase 2 studies (n=14) and phase 3 studies (n=4) by use of Sackett and Haynes' classification. Phase 2 studies had a low pooled diagnostic odds ratio of 7·79 (95% CI 5·86–10·35). Phase 3 studies showed significant heterogeneity because of variability in sample size (meta-regression coefficient −0·592, p=0·017), with diagnostic performance upwardly biased in smaller studies, but moving towards a null effect in larger studies. Procalcitonin cannot reliably differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome in critically ill adult patients. The findings from this study do not lend support to the widespread use of the procalcitonin test in critical care settings.
Journal Article
Compilation and evaluation of gas phase diffusion coefficients of reactive trace gases in the atmosphere: volume 1. Inorganic compounds
Diffusion of gas molecules to the surface is the first step for all gas–surface reactions. Gas phase diffusion can influence and sometimes even limit the overall rates of these reactions; however, there is no database of the gas phase diffusion coefficients of atmospheric reactive trace gases. Here we compile and evaluate, for the first time, the diffusivities (pressure-independent diffusion coefficients) of atmospheric inorganic reactive trace gases reported in the literature. The measured diffusivities are then compared with estimated values using a semi-empirical method developed by Fuller et al. (1966). The diffusivities estimated using Fuller's method are typically found to be in good agreement with the measured values within ±30%, and therefore Fuller's method can be used to estimate the diffusivities of trace gases for which experimental data are not available. The two experimental methods used in the atmospheric chemistry community to measure the gas phase diffusion coefficients are also discussed. A different version of this compilation/evaluation, which will be updated when new data become available, is uploaded online (https://sites.google.com/site/mingjintang/home/diffusion).
Journal Article