Decreasing Greenhouse Gas Emissions from the Municipal Solid Waste Sector in Chinese Cites.

Municipal solid waste (MSW) management systems play a crucial role in greenhouse gas (GHG) emissions in China. Although the government has implemented many policies to improve the MSW management system, the impact of these improvements on city-level GHG emission reduction remains largely unexplored. This study conducted a comprehensive analysis of both direct and downstream GHG emissions from the MSW sector, encompassing sanitary landfill, dump, incineration, and biological treatment, across 352 Chinese cities from 2001 to 2021 by adopting inventory methods recommended by the Intergovernmental Panel on Climate Change (IPCC). The results reveal that (1) GHG emissions from the MSW sector in China peaked at 70.6 Tg of CO2 equiv in 2018, followed by a significant decline to 47.6 Tg of CO2 equiv in 2021, (2) cities with the highest GHG emission reduction benefits in the MSW sector were historical emission hotspots over the past 2 decades, and (3) with the potential achievement of zero-landfilling policy by 2030, an additional reduction of 203.7 Tg of CO2 equiv is projected, with the emission reduction focus toward cities in South China (21.9%), Northeast China (17.8%), and Southwest China (17.3%). This study highlights that, even without explicit emission reduction targets for the MSW sector, the improvements of this sector have significantly reduced GHG emissions in China.

Global iron and steel plant CO2 emissions and carbon-neutrality pathways.

The highly energy-intensive iron and steel industry contributed about 25% (ref. 1) of global industrial CO2 emissions in 2019 and is therefore critical for climate-change mitigation. Despite discussions of decarbonization potentials at national and global levels2-6, plant-specific mitigation potentials and technologically driven pathways remain unclear, which cumulatively determines the progress of net-zero transition of the global iron and steel sector. Here we develop a CO2 emissions inventory of 4,883 individual iron and steel plants along with their technical characteristics, including processing routes and operating details (status, age, operation-years etc.). We identify and match appropriate emission-removal or zero-emission technologies to specific possessing routes, or what we define thereafter as a techno-specific decarbonization road map for every plant. We find that 57% of global plants have 8-24 operational years, which is the retrofitting window for low-carbon technologies. Low-carbon retrofitting following the operational characteristics of plants is key for limiting warming to 2 °C, whereas advanced retrofitting may help limit warming to 1.5 °C. If each plant were retrofitted 5 years earlier than the planned retrofitting schedule, this could lead to cumulative global emissions reductions of 69.6 (±52%) gigatonnes (Gt) CO2 from 2020 to 2050, almost double that of global CO2 emissions in 2021. Our results provide a detailed picture of CO2 emission patterns associated with production processing of iron and steel plants, illustrating the decarbonization pathway to the net-zero-emissions target with the efforts from each plant.

Assessing the city-level material stocks in landfills and the landfill mining potential of China.

Landfill mining has become an emerging issue in urban metabolism research and environmental remediation practices. Comprehensive understanding of the quantity and distribution of material stocks in landfills, as well as identifying hotspots of landfill mining potential, is of crucial importance. However, high-resolution datasets and systematic analytical tools remain insufficient. This study established a time-series landfill material stock inventory at prefecture level in China. An evaluation system for mining potential of landfills at prefecture level was then constructed using an integrated expert scoring and entropy weight method, based on ten indicators across five dimensions, including environmental impact, energy recovery, resource cycling, economic cost, and social aspect. The results show that over the past twenty years, the material stock in landfills was 2321.07 Tg (106 tons) in China, among which, soil-like materials, ash & stone and plastic & rubber were the three largest fractions, accounting for 61.06 wt%, 18.96 wt%, and 12.69 wt% of the total stock. Regional differences in landfill mining potential were found to be significant, with South China presenting the largest mining potential, while Southwest China showed the lowest. Cities with better economic development in China show the possibility to have greater landfill mining potential. This study established a methodology for the assessment of landfill mining potential for China or other countries, and provided scientific evidences for formulating regional-specific policies on landfill mining in China.

The maize ZmVPS23-like protein relocates the nucleotide-binding leucine-rich repeat protein Rp1-D21 to endosomes and suppresses the defense response.

Plants often utilize nucleotide-binding leucine-rich repeat (NLR) proteins to perceive pathogen infections and trigger a hypersensitive response (HR). The endosomal sorting complex required for transport (ESCRT) machinery is a conserved multisubunit complex that is essential for the biogenesis of multivesicular bodies and cargo protein sorting. VPS23 is a key component of ESCRT-I and plays important roles in plant development and abiotic stresses. ZmVPS23L, a homolog of VPS23-like in maize (Zea mays), was previously identified as a candidate gene in modulating HR mediated by the autoactive NLR protein Rp1-D21 in different maize populations. Here, we demonstrate that ZmVPS23L suppresses Rp1-D21-mediated HR in maize and Nicotiana benthamiana. Variation in the suppressive effect of HR by different ZmVPS23L alleles was correlated with variation in their expression levels. ZmVPS23 also suppressed Rp1-D21-mediated HR. ZmVPS23L and ZmVPS23 predominantly localized to endosomes, and they physically interacted with the coiled-coil domain of Rp1-D21 and mediated the relocation of Rp1-D21 from the nucleo-cytoplasm to endosomes. In summary, we demonstrate that ZmVPS23L and ZmVPS23 are negative regulators of Rp1-D21-mediated HR, likely by sequestrating Rp1-D21 in endosomes via physical interaction. Our findings reveal the role of ESCRT components in controlling plant NLR-mediated defense responses.

Contributions of key countries, enterprises, and refineries to greenhouse gas emissions in global oil refining, 2000-2021.

The refining industry is the third-largest source of global greenhouse gas (GHG) emissions from stationary sources, so it is at the forefront of the energy transition and net zero pathways. The dynamics of contributors in this sector such as crucial countries, leading enterprises, and key emission processes are vital to identifying key GHG emitters and supporting targeted emission reduction, yet they are still poorly understood. Here, we established a global sub-refinery GHG emission dataset in a long time series based on life cycle method. Globally, cumulative GHG emissions from refineries reached approximately 34.1 gigatons (Gt) in the period 2000-2021 with an average annual increasing rate of 0.7%, dominated by the United States, EU27&UK, and China. In 2021, the top 20 countries with the largest GHG emissions of oil refining accounted for 83.9% of global emissions from refineries, compared with 79.5% in 2000. Moreover, over the past two decades, 53.9-57.0% of total GHG emissions came from the top 20 oil refining enterprises with the largest GHG emissions in 12 of these 20 countries. Retiring or installing mitigation technologies in the top 20% of refineries with the largest GHG emissions and refineries with GHG emissions of more than 0.1 Gt will reduce the level of GHG emissions by 38.0%-100.0% in these enterprises. Specifically, low-carbon technologies installed on furnaces and boilers as well as steam methane reforming will enable substantial GHG mitigation of more than 54.0% at the refining unit level. Therefore, our results suggest that policies targeting a relatively small number of super-emission contributors could significantly reduce GHG emissions from global oil refining.

IFI16-dependent STING signaling is a crucial regulator of anti-HER2 immune response in HER2+ breast cancer.

Relapse to anti-HER2 monoclonal antibody (mAb) therapies, such as trastuzumab in HER2+ breast cancer (BC), is associated with residual disease progression due to resistance to therapy. Here, we identify interferon-γ inducible protein 16 (IFI16)-dependent STING signaling as a significant determinant of trastuzumab responses in HER2+ BC. We show that down-regulation of immune-regulated genes (IRG) is specifically associated with poor survival of HER2+, but not other BC subtypes. Among IRG, IFI16 is identified as a direct target of EZH2, the underexpression of which leads to deficient STING activation and downstream CXCL10/11 expression in response to trastuzumab treatment. Dual inhibition of EZH2 and histone deacetylase (HDAC) significantly activates IFI16-dependent immune responses to trastuzumab. Notably, a combination of a novel histone methylation inhibitor with an HDAC inhibitor induces complete tumor eradication and long-term T cell memory in a HER2+ BC mouse model. Our findings demonstrate an epigenetic regulatory mechanism suppressing the expression of the IFI16-CXCL10/11 signaling pathway that provides a survival advantage to HER2+ BC to confer resistance to trastuzumab treatment.

Hypoxia induces HIF1α-dependent epigenetic vulnerability in triple negative breast cancer to confer immune effector dysfunction and resistance to anti-PD-1 immunotherapy.

The hypoxic tumor microenvironment has been implicated in immune escape, but the underlying mechanism remains elusive. Using an in vitro culture system modeling human T cell dysfunction and exhaustion in triple-negative breast cancer (TNBC), we find that hypoxia suppresses immune effector gene expression, including in T and NK cells, resulting in immune effector cell dysfunction and resistance to immunotherapy. We demonstrate that hypoxia-induced factor 1α (HIF1α) interaction with HDAC1 and concurrent PRC2 dependency causes chromatin remolding resulting in epigenetic suppression of effector genes and subsequent immune dysfunction. Targeting HIF1α and the associated epigenetic machinery can reverse the immune effector dysfunction and overcome resistance to PD-1 blockade, as demonstrated both in vitro and in vivo using syngeneic and humanized mice models. These findings identify a HIF1α-mediated epigenetic mechanism in immune dysfunction and provide a potential strategy to overcome immune resistance in TNBC.

Ascorbate peroxidase 1 confers resistance to southern corn leaf blight in maize.

Southern corn leaf blight (SCLB), caused by Bipolaris maydis, is one of the most devastating diseases affecting maize production. However, only one SLCB resistance gene, conferring partial resistance, is currently known, underscoring the importance of isolating new SCLB resistance-related genes. Here, we performed a comparative proteomic analysis and identified 258 proteins showing differential abundance during the maize response to B. maydis. These proteins included an ascorbate peroxidase (Zea mays ascorbate peroxidase 1 (ZmAPX1)) encoded by a gene located within the mapping interval of a previously identified quantitative trait locus associated with SCLB resistance. ZmAPX1 overexpression resulted in lower H2 O2 accumulation and enhanced resistance against B. maydis. Jasmonic acid (JA) contents and transcript levels for JA biosynthesis and responsive genes increased in ZmAPX1-overexpressing plants infected with B. maydis, whereas Zmapx1 mutants showed the opposite effects. We further determined that low levels of H2 O2 are accompanied by an accumulation of JA that enhances SCLB resistance. These results demonstrate that ZmAPX1 positively regulates SCLB resistance by decreasing H2 O2 accumulation and activating the JA-mediated defense signaling pathway. This study identified ZmAPX1 as a potentially useful gene for increasing SCLB resistance. Furthermore, the generated data may be relevant for clarifying the functions of plant APXs.

Life cycle assessment and society willingness to pay indexes of food waste-to-energy strategies.

Food waste (FW) has received increasing attention because of its immense production quantities and significance to resource and environmental impacts related to disposal approaches. We combined life cycle assessment (LCA) with society's willingness to pay (WTP) index to evaluate energy, water, and environmental impacts on three food waste-to-energy (FWTE) options in China. For anaerobic digestion (AD) mode, the results showed that 1140 MJ of energy consumption could be saved by power generation from methane, power transmission, and biodiesel production from per ton of FW; the cost of climate change for treating FW was 137.8 kg CO2e t-1 FW, failing to be climate-sound due to the end life of digestate in practice. The total impact to AD mode in the form of monetized value for WTP was 13.3 CNY t-1 FW, of which the collection and transportation, pretreatment, AD reaction, wastewater treatment, biodiesel production, and residue landfilling stages contributed by 10.5%, 6.5%, 19.3%, 27.6%, 4.7%, and 75.7%, respectively, while biogas utilization offset it by 43.9%. Notably, a considerable amount of water used in AD prevented it from showing an advantage compared to incineration (-5.1 CNY t-1 FW), which performed best overall attributing to the generated electricity compensated for primary energy demand, water, and terrestrial acidification to a great extent. Landfilling turned out to be an unappealing FW disposal method due to the low landfill gas capture ratio. Given that AD is touted for its environmental benefits, potential approaches-such as developing a reliable and supportive technology to facilitate digestate recycling into agriculture-were discussed to improve its competitiveness and attractiveness. Our study employed a way to accumulate and compare impact indicators to better interpret FW management impacts and advantages, considering energy recovery, resource recycling, and the environment.

The potential roles of different metacaspases in maize defense response.

Metacaspases (MCs), a class of cysteine-dependent proteases, act as important regulators in plant defense response. In maize genome, there are 11 ZmMCs which have been categorized into two types (type I and II) based on their structural differences. In this study, we investigated the different transcript patterns of 11 ZmMCs in maize defense response mediated by the nucleotide-binding, leucine-rich-repeat protein Rp1-D21. We further predicted that many cis-elements responsive to salicylic acid (SA), methyl jasmonate (MeJA), abscisic acid (ABA) and auxin were identified in the promoter regions of ZmMCs, and several different transcription factors were predicted to bind to their promoters. We analyzed the localization of ZmMCs with previously identified quantitative trait loci (QTLs) in maize disease resistance, and found that all other ZmMCs, except for ZmMC6-8, are co-located with at least one QTL associated with disease resistance to southern leaf blight, northern leaf blight, gray leaf spot or Fusarium ear rot. Based on previous RNA-seq analysis, different ZmMCs display different transcript levels in response to Cochliobolous heterostrophus and Fusarium verticillioides. All the results imply that the members of ZmMCs might have differential functions to different maize diseases. This study lays the basis for further investigating the roles of ZmMCs in maize disease resistance.

Clinical therapeutic effects of high-flow nasal oxygen therapy in patients with acute exacerbation of chronic obstructive pulmonary disease: A protocol for systematic review and meta-analysis.

BACKGROUND: For patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated by respiratory acidosis, noninvasive ventilation therapy is thought to be the first-line treatment. In patients with AECOPD, the effect of high-flow nasal oxygen therapy is not well studied. In this study, the existing data will be synthesized to obtain an effective rate of movement of nasal oxygen therapy in patients with AECOPD. METHODS: Using PubMed, EMBASE, Cochrane Library, Web of Science, Scopus, a systematic search will be undertaken to identify randomized controlled trails (RCTs) on the clinical therapeutic effects of rate of movement of nasal oxygen therapy in patients with AECOPD without language constraints from their onset to November 2020. To classify potentially qualifying tests, we will also review Google Scholar, ClinicalTrials.gov, and the reference lists of included studies. Two independent reviewers will review inclusion trials and execute data extraction. Research bias and quality will be measured using the Cochrane Collaboration Bias Method 2.0. The findings of the analysis will be pooled using a formula of fixed-effects or random-effects. We will address any dispute by dialogue, and cases of disagreement will be mediated by a third author. RESULTS: The current research will examine the clinical therapeutic results of patients with AECOPD with rate of movement of nasal oxygen therapy. CONCLUSION: To assess the efficacy of rate of movement of nasal oxygen therapy in patients with AECOPD, the present analysis would provide consistent facts. OSF REGISTRATION NUMBER: November 18, 2020.osf.io/umd48. (https://osf.io/umd48/).

The impact of the COVID-19 pandemic on waste-to-energy and waste-to-material industry in China.

The COVID-19 pandemic created enormous uncertainty for achieving the sustainable development goals in waste management. China implemented a number of new policies recently to encourage waste-to-energy (WTE) and waste-to-material (WTM) industry, which was also impacted by the spread of COVID-19, while the impact on the solid waste industry was merely discussed. In this work, the quarter-level financial statement data of thirty listed companies in Chinese Stock Market were analyzed by applying ARIMA intervention analysis, moreover, a system dynamic model was established for examining the impacting pathway of the pandemic. Main results are: (1) the total annual turnover of total solid waste industry increased by 28.2 times in recent 14 years, however, the estimated turnover of solid waste industry in 2020 dropped around 55.8 billion CNY; (2) the WTE industry kept growing (+21%), the WTM industry dropped significantly (-28%), while the waste disposal industry and other solid waste industry varied slightly (-10% and +9%), comparing their turnovers in 2019 and 2020; (3) the average trade-prices of the secondary materials during the COVID-19 pandemic were only 43.4%-85.8% of the maximum price from 2017 to 2019, resulting in the decline of the WTM industry. Considering a possible sluggish growth of the solid waste industry, the waste separation and zero waste programs in China may meet non-trivial challenges in the future. Policy implications are put forward, such as quantitative simulating the long-term impact, increasing investment and incentive on waste recycling, and building an internal circulation system for waste management.

Maize metacaspases modulate the defense response mediated by the NLR protein Rp1-D21 likely by affecting its subcellular localization.

Plants usually employ resistance (R) genes to defend against the infection of pathogens, and most R genes encode intracellular nucleotide-binding, leucine-rich repeat (NLR) proteins. The recognition between R proteins and their cognate pathogens often triggers a rapid localized cell death at the pathogen infection sites, termed the hypersensitive response (HR). Metacaspases (MCs) belong to a cysteine protease family, structurally related to metazoan caspases. MCs play crucial roles in plant immunity. However, the underlying molecular mechanism and the link between MCs and NLR-mediated HR are not clear. In this study, we systematically investigated the MC gene family in maize and identified 11 ZmMCs belonging to two types. Further functional analysis showed that the type I ZmMC1 and ZmMC2, but not the type II ZmMC9, suppress the HR-inducing activity of the autoactive NLR protein Rp1-D21 and of its N-terminal coiled-coil (CCD21 ) signaling domain when transiently expressed in Nicotiana benthamiana. ZmMC1 and ZmMC2 physically associate with CCD21 in vivo. We further showed that ZmMC1 and ZmMC2, but not ZmMC9, are predominantly localized in a punctate distribution in both N. benthamiana and maize (Zea mays) protoplasts. Furthermore, the co-expression of ZmMC1 and ZmMC2 with Rp1-D21 and CCD21 causes their re-distribution from being uniformly distributed in the nucleocytoplasm to a punctate distribution co-localizing with ZmMC1 and ZmMC2. We reveal a novel role of plant MCs in modulating the NLR-mediated defense response and derive a model to explain it.

Estimating Physical Composition of Municipal Solid Waste in China by Applying Artificial Neural Network Method.

Physical composition of municipal solid waste (PCMSW) is the fundamental parameter in domestic waste management; however, high fidelity, wide coverage, upscaling, and year continuous data sets of PCMSW in China are insufficient. A traceable and predictable methodology for estimating PCMSW in China is established for the first time by analyzing 503 PCMSW data sets of 135 prefecture-level cities in China. A hyperspherical transformation method was used to eliminate the constant sum constraint in statistically analyzing PCMSW data. Moreover, a back-propagation (BP) neural network methodology was applied to establish quantitative models between city-level PCMSW and its socio-economic factors, including city size, per capita gross regional product, geographical location, gas coverage rate, and year. Results show that (1) national-level PCMSW in 2017 was estimated as organic fraction (53.7%), ash and stone (8.3%), paper (16.9%), plastic and rubber (13.6%), textile (2.3%), wood (2.2%), metal (0.6%), glass (1.5%), and others (1.0%); (2) organic fraction, paper, and plastics showed an increasing trend from 1990 to 2017, while ash and stone decreased significantly; (3) organic fractions in East, North, and Central-South China were higher than those in other regions. This enables us to fill the data gap in the practice of municipal solid waste management in China.

Maize ZmFNSI Homologs Interact with an NLR Protein to Modulate Hypersensitive Response.

Nucleotide binding, leucine-rich-repeat (NLR) proteins are the major class of resistance (R) proteins used by plants to defend against pathogen infection. The recognition between NLRs and their cognate pathogen effectors usually triggers a rapid localized cell death, termed the hypersensitive response (HR). Flavone synthase I (FNSI) is one of the key enzymes in the flavone biosynthesis pathway. It also displays salicylic acid (SA) 5-hydroxylase (S5H) activity. A close homolog of FNSI/S5H displays SA 3-hydroxylase (S3H) activity. Both FNSI/S5H and S3H play important roles in plant innate immunity. However, the underlying molecular mechanisms and the relationship between S5H and S3H with the NLR-mediated HR are not known in any plant species. In this study, we identified three genes encoding ZmFNSI-1, ZmFNSI-2 and ZmS3H that are significantly upregulated in a maize line carrying an autoactive NLR Rp1-D21 mutant. Functional analysis showed that ZmFNSI-1 and ZmFNSI-2, but not ZmS3H, suppressed HR conferred by Rp1-D21 and its signaling domain CCD21 when transiently expressed in N. benthamiana. ZmFNSI-1 and ZmFNSI-2 physically interacted with CCD21. Furthermore, ZmFNSI-1 and ZmFNSI-2 interacted with HCT, a key enzyme in lignin biosynthesis pathway, which can also suppress Rp1-D21-mediated HR. These results lay the foundation for the further functional analysis of the roles of FNSI in plant innate immunity.

Recycling sustainability of waste paper industry in Beijing City: An analysis based on value chain and GIS model.

China established a self-organized and market-driven recycling system, which was dominated by the informal sectors. In recent years, the amount of domestically-recycled waste paper grew slower than expectation in China, which may be resulted from a decline in economic sustainability of current recycling system. For understanding the waste paper recycling system in most cities in China, the economic mechanism remains unclear and the city-level data is extremely insufficient. In this work, an index of recycling sustainability (IRS, benefit divided by cost) is analyzed with a resolution of 1 km2 grid in Beijing City, by adopting value chain and GIS methodology. Five degrees of IRS are defined, from high-degree (IRS > 1.10) to low-degree (IRS < 0.95). Different stakeholders in the informal waste paper recycling system were interviewed to fill the data gap. Results show that: (1) from 2015 to 2018, the informal recycling of waste paper accounted for approximate 80% in Beijing; (2) the number of informal recyclables distribution sites decreased from 27 to 11, and their average distance to the city-center rose from 27.5 km to 40.9 km; (3) in 2015 and 2018, the grids with high-degree IRS accounted for 99.5% and 89.2%, respectively, indicating a sustainable waste paper recycling industry in Beijing; and (4) according to the scenario analysis, if the operating cost rises by 30%, the grids with low-degree IRS accounts for 98.5%, indicating a nontrivial challenges when the recycling cost keeps increasing in the future. Policy recommendations are put forward for a more sustainable paper waste recycling system in China.

[Characteristics and Environmental Impacts of Materials Stored in Municipal Solid Waste Landfills: A Case Study of the Guangdong-Hong Kong-Macao Greater Bay Area].

The composition of municipal solid waste (MSW) in landfills is complex; additionally, the waste stored in landfills continues to generate greenhouse gases, odors, and ground water pollutants even during the post-closure stage. Therefore, landfills are considered key fields of urban eco-environmental remediation. In this context, it is crucial to understand the storage, composition, physical, and chemical characteristics of waste, as well as its potential environmental impacts. However, very few studies have discussed these topics in detail. In this work, we focused on the Guangdong-Hong Kong-Macao Greater Bay Area (GBA), which has the highest urbanization rate and population density of all China. The generation, stock, physical components, and key elements of MSW in eleven cities of the GBA were analyzed based on both the scientific literature and statistical data. The main results are as follows:① the total amount of MSW produced by the cities was of 26.4 Tg in 2017, with an average annual increment of 0.8 Tg; moreover, the most used disposal method was the sanitary landfill (58.9% of the total); ② the total amount of MSW disposed in the landfills was equal to 230.1 Tg[including mainly food waste (109.6 Tg), plastic (38.9 Tg), and paper (29.6 Tg)]; ③ between 2001-2017, a total of 50.0 Tg of carbon were input in the landfills in the form MSW, of which 7.1 Tg of carbon were emitted as gas and 1.5 Tg were discharged as leachate; moreover, the total landfill carbon stock was equal to 41.4 Tg. Overall, this study provides fundamental data that can be used to determine the environmental impacts of MSW landfills and implement the eco-environmental remediation of urban landfill sites in the GBA.

MnSOD mediates shear stress-promoted tumor cell migration and adhesion.

Circulation of cancer cells in the bloodstream is a vital step for distant metastasis, during which cancer cells are exposed to hemodynamic shear stress (SS). The actions of SS on tumor cells are complicated and not fully understood. We previously reported that fluidic SS was able to promote migration of breast cancer cells by elevating the cellular ROS level. In this study, we further investigated the mechanisms regulating SS-promoted cell migration and identified the role of MnSOD in the related pathway. We found that SS could enhance tumor cell adhesion to extracellular matrix and endothelial monolayer, and MnSOD also regulated this process. Briefly, SS stimulates the generation of mitochondrial superoxide in tumor cells. MnSOD then converts superoxide into hydrogen peroxide, which activates ERK1/2 to promote tumor cell migration and activates FAK to promote tumor cell adhesion. Combining our previous and present studies, we present experimental evidence on the pro-metastatic effects of hemodynamic SS and reveal the underlying mechanism. Our findings provide new insights into the nature of cancer metastasis and the understanding of tumor cell responses to external stresses and have valuable implications for cancer therapy development.

Hemodynamic shear stress stimulates migration and extravasation of tumor cells by elevating cellular oxidative level.

Cancer cells are shed into the blood stream and are exposed to hemodynamic shear stress during metastasis. It has been shown that shear stress can destroy circulating tumor cells (CTCs) both in vitro and in vivo. However, it remains unclear whether shear stress can modulate the properties and functions of tumor cells in a manner that might help CTCs to exit circulation. In this study, we established a microfluidic circulatory system to apply physiological fluid shear stress on breast cancer cells and demonstrated that an arterial level of shear stress significantly enhanced tumor cell migration in transwell and wound healing assays, and enhanced extravasation in a transendothelial assay. Circulatory treatment elevated the intracellular levels of reactive oxygen species (ROS), which is an early and indispensable event for activating the extracellular signal-regulated kinases (ERK1/2). Subsequently, ERK1/2 activation promoted the migration of tumor cells and enhanced their extravasation. Finally, reducing cellular ROS production suppressed tumor cell extravasation in both a transendothelial assay and a zebrafish model. This new understanding of how fluid shear stress promotes tumor cell migration has important implications in cancer treatment and can help us to identify potential therapeutic targets for inhibiting tumor progression.