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Abstract Background SARS-CoV-2, a highly contagious coronavirus, is responsible for the global pandemic of COVID-19 in 2019. Currently, it remains uncertain whether SARS-CoV-2 possesses oncogenic or oncolytic potential in influencing tumor progression. Therefore, it is important to evaluate the clinical and functional role of SARS-CoV-2 on tumor progression. Methods Here, we integrated bioinformatic analysis of COVID-19 RNA-seq data from the GEO database and performed functional studies to explore the regulatory role of SARS-CoV-2 in solid tumor progression, including lung, colon, kidney and liver cancer. Results Our results demonstrate that infection with SARS-CoV-2 is associated with a decreased expression of genes associated with cancer proliferation and metastasis in lung tissues from patients diagnosed with COVID-19. Several cancer proliferation or metastasis related genes were frequently downregulated in SARS-CoV-2 infected intestinal organoids and human colon carcinoma cells. In vivo and in vitro studies revealed that SARS-CoV-2 nucleocapsid (N) protein inhibits colon and kidney tumor growth and metastasis through the N-terminal (NTD) and the C-terminal domain (CTD). The molecular mechanism indicates that the N protein of SARS-CoV-2 interacts with YBX1, resulting in the recruitment of PKM mRNA into stress granules mediated by G3BP1. This process ultimately destabilizes PKM expression and suppresses glycolysis. Conclusion Our study reveals a new function of SARS-CoV-2 nucleocapsid protein on tumor progression.

Effective engineering asset management (EAM) is critical to economic development and improving livability in society, but its complexity often impedes optimal asset functionalities. Digital twins (DTs) could revolutionize the EAM paradigm by bidirectionally linking the physical and digital worlds in real time. There is great industrial and academic interest in DTs for EAM. However, previous review studies have predominately focused on technical aspects using limited life-cycle perspectives, failing to holistically synthesize DTs for EAM from the managerial point of view. Based on a systematic literature review, we introduce an analytical framework for describing DTs for EAM, which encompasses three levels: DT 1.0 for technical EAM, DT 2.0 for technical−human EAM, and DT 3.0 for technical−environmental EAM. Using this framework, we identify what is known, what is unknown, and future directions at each level. DT 1.0 addresses issues of asset quality, progress, and cost management, generating technical value. It lacks multi-objective self-adaptive EAM, however, and suffers from high application cost. It is imperative to enable closed-loop EAM in order to provide various functional services with affordable DT 1.0. DT 2.0 accommodates issues of human−machine symbiosis, safety, and flexibility management, generating managerial value beyond the technical performance improvement of engineering assets. However, DT 2.0 currently lacks the automation and security of human−machine interactions and the managerial value related to humans is not prominent enough. Future research needs to align technical and managerial value with highly automated and secure DT 2.0. DT 3.0 covers issues of participatory governance, organization management, sustainable development, and resilience enhancement, generating macro social value. Yet it suffers from organizational fragmentation and can only address limited social governance issues. Numerous research opportunities exist to coordinate different stakeholders. Similarly, future research opportunities exist to develop DT 3.0 in a more open and complex system.

Community engagement is essential for creating social value and fostering high-quality development in megaprojects. However, organizing such engagement within public-private partnerships is particularly complex in weak institutional contexts, such as those found in sub-Saharan Africa. Existing research often depoliticizes community engagement, overlooking the critical role of government. Additionally, empirical studies on this phenomenon in sub-Saharan Africa remain scarce. In this study, we adopt a governmentality lens and a design science research method to identify meta-organizing and responsibilization as governmental strategies for organizing community engagement in weak institutional contexts, such as those in sub-Saharan Africa. Through an embedded case study of a megaproject in Nigeria, we develop two sets of design principles that form a transformational community engagement framework. Our findings have implications for community engagement practices in megaprojects within weak institutional contexts and contribute to mainstream external stakeholder engagement research.

This paper investigates the influence of non-financial firms’ involvement in shadow banking on the caliber of corporate innovation. It focuses on Chinese non-financial listed companies between 2012 and 2022 and delves deeper into the mechanism of economic policy uncertainty (EPU) in relation to the interplay between shadow banking and innovation quality. The findings reveal that firms participating in shadow banking activities experience a decline in innovation quality, with a more pronounced effect observed among state-owned enterprises (SOEs) and small and medium-sized enterprises (SMEs). Furthermore, EPU amplifies the negative impact of non-financial firms’ shadow banking on innovation quality. The outcomes of this study hold significant academic value and practical implications for curbing enterprise shadow banking, optimizing resource allocation structures, maintaining economic policy stability, and fostering high-quality businesses development.

Background: 8-oxoguanine DNA glycosylase can maintain genomic stability and integrity. However, it can interfere with the regular DNA damage repair process, possibly leading to the development of cancer and various other human diseases when its activity becomes abnormal. Current methods for detecting 8-oxoguanine DNA glycosylase activity often suffer from low sensitivity, time-consuming procedures, labor-intensive requirements, and the need for specialized equipment and trained professionals for execution. Consequently, there is an urgent need for a portable, user-friendly 8-oxoguanine DNA glycosylase assay that offers swift results and supports real-time testing. Results: We've developed a PERFUME method that combines primer exchange reaction and functionalized G-quadruplex/hemin DNAzyme for sensitive detection of Fpg, a typical 8-oxoguanine DNA glycosylase. Utilizing a single probe and T4 Polynucleotide Kinase (PNK) simplifies the experiment to a one-step reaction at 37 °C in 3 h, reducing sample consumption and improving sensitivity. We chose functionalized hemin cofactors, significantly improving catalytic efficiency and enhancing detection capability. This biosensor detects Fpg activity with a sensitivity as low as 0.11 U mL−1, displaying exceptional sensitivity, selectivity, and interference resistance in human serum and bacterial cell extracts under isothermal conditions. The biosensor demonstrates remarkable selectivity and ability for Fpg inhibitors screening. In addition, this biosensor enables reading the sample's RGB values using a smartphone, facilitating accurate quantification of Fpg activity without the necessity for specialized equipment. Significance: PERFUME simplifies Fpg detection by using a single hairpin and PNK in a one-step process. We utilize FUME to enhance catalytic efficiency, it surpassing the performance of traditional G-quadruplex/hemin DNAzyme methods. This approach excels in analyzing Fpg in human serum and bacterial extracts. It allows quantitative Fpg detection using UV–Vis and smartphones under isothermal conditions, making it valuable for clinical diagnosis.

Infections of hepatotropic viruses cause a wide array of liver diseases including acute hepatitis, chronic hepatitis and the consequently developed cirrhosis and hepatocellular carcinoma (HCC). Among the five classical hepatotropic viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV) usually infect human persistently and cause chronic hepatitis, leading to major troubles to humanity. Previous studies have revealed that several types of inflammasomes are involved in the infections of HBV and HCV. Here, we summarize the current knowledge about their roles in hepatitis B and C. NLRP3 inflammasome can be activated and regulated by HBV and HCV. It is found to exert antiviral function or mediates inflammatory response in viral infections depending on different experimental models. Besides NLRP3 inflammasome, IFI16 and AIM2 inflammasomes participate in the pathological process of hepatitis B, and NALP3 inflammasome may sense HCV infection in hepatocytes. The inflammasomes affect the pathological process of viral hepatitis through its downstream secretion of inflammatory cytokines interleukin-1β (IL-1β) and IL-18 or induction of pyroptosis resulting from cleaved gasdermin D (GSDMD). However, the roles of inflammasomes in different stages of viral infection remains mainly unclear. More proper experimental models of viral hepatitis should be developed for specific studies in future, so that we can understand more about the complexity of inflammasome regulation and multifunction of inflammasomes and their downstream effectors during HBV and HCV infections.

As urbanization accelerates and population structures change, healthcare buildings are becoming increasingly crowded. Predicting functional area demand is crucial to adapting to this trend and providing high-quality services. This paper introduces an innovative multi-stage method to forecast unbuilt projects using operational data from hospital information systems and building design models to automatically calculate spatial demands. The study’s main findings demonstrate that our method successfully outputs regional demand data, supporting hospital design validation and operational decision-making. Through processing and analyzing log data, this research identified the dynamic characteristics of user activities in hospital buildings and converted them into a time series data format. This method has iterative self-validation and self-optimization features and can maintain flexibility in different scenarios and frequently changing design drawings. This method will provide technical support for a wide range of hospital building stakeholders and has the potential to be applied to more types of buildings. These findings will contribute to various fields, including medical facility planning, design, and public health.

Virus infection is one of the greatest threats to human life and health. In response to viral infection, the host’s innate immune system triggers an antiviral immune response mostly mediated by inflammatory processes. Among the many pathways involved, the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome has received wide attention in the context of viral infection. The NLRP3 inflammasome is an intracellular sensor composed of three components, including the innate immune receptor NLRP3, adaptor apoptosis-associated speck-like protein containing CARD (ASC), and the cysteine protease caspase-1. After being assembled, the NLRP3 inflammasome can trigger caspase-1 to induce gasdermin D (GSDMD)-dependent pyroptosis, promoting the maturation and secretion of proinflammatory cytokines such as interleukin-1 (IL-1β) and interleukin-18 (IL-18). Recent studies have revealed that a variety of viruses activate or inhibit the NLRP3 inflammasome via viral particles, proteins, and nucleic acids. In this review, we present a variety of regulatory mechanisms and functions of the NLRP3 inflammasome upon RNA viral infection and demonstrate multiple therapeutic strategies that target the NLRP3 inflammasome for anti-inflammatory effects in viral infection.

Abstract Viral infection in respiratory tract usually leads to cell death, impairing respiratory function to cause severe disease. However, the diversity of clinical manifestations of SARS-CoV-2 infection increases the complexity and difficulty of viral infection prevention, and especially the high-frequency asymptomatic infection increases the risk of virus transmission. Studying how SARS-CoV-2 affects apoptotic pathway may help to understand the pathological process of its infection. Here, we uncovered SARS-CoV-2 imployed a distinct anti-apoptotic mechanism via its N protein. We found SARS-CoV-2 virus-like particles (trVLP) suppressed cell apoptosis, but the trVLP lacking N protein didn’t. Further study verified that N protein repressed cell apoptosis in cultured cells, human lung organoids and mice. Mechanistically, N protein specifically interacted with anti-apoptotic protein MCL-1, and recruited a deubiquitinating enzyme USP15 to remove the K63-linked ubiquitination of MCL-1, which stabilized this protein and promoted it to hijack Bak in mitochondria. Importantly, N protein promoted the replications of IAV, DENV and ZIKV, and exacerbated death of IAV-infected mice, all of which could be blocked by a MCL-1 specific inhibitor, S63845. Altogether, we identifed a distinct anti-apoptotic function of the N protein, through which it promoted viral replication. These may explain how SARS-CoV-2 effectively replicates in asymptomatic individuals without cuasing respiratory dysfunction, and indicate a risk of enhanced coinfection with other viruses. We anticipate that abrogating the N/MCL-1-dominated apoptosis repression is conducive to the treatments of SARS-CoV-2 infection as well as coinfections with other viruses.

NLRP3 inflammasome mainly controls interleukin-1β (IL-1β) secretion, leading to cell death called pyroptosis constituting a major antiviral host defense and inflammatory diseases upon viral infection. The RAF-MEK1/2-ERK1/2 cascade and downstream c-Jun/Fos and Activator protein-1 (AP1) signaling pathway control the degree of inflammatory response. Influenza A virus (IAV) infection is known to stimulate NLRP3 inflammasome activation and inflammatory responses. Nevertheless, the detailed mechanism by which IAV induces NLRP3 inflammasome activation involved in transcription of pro-IL-1β mRNA remains elusive. In our study, we found that IAV infection promotes pro-IL-1β mRNA transcription and activates NLRP3 inflammasome. Detailed studies reveal that type I interferon (IFN-α/IFN-β) as well as U0126 (a selective inhibitor of MEK-1 and MEK-2) typically inhibit IAV-mediated NLRP3 inflammasome activation via downregulating pro-IL-1β mRNA. Moreover, knock-down of c-Jun decreases pro-IL-1β mRNA and inhibits NLRP3 inflammasome activation upon IAV infection. Overall, the findings uncover that AP-1 signaling pathway promotes NLRP3 inflammasome activation upon IAV infection, which provides a new idea for the therapy of NLRP3 inflammasome-associated inflammatory diseases.

Abstract Molecular oxygen (O2) is essential for most biological reactions in mammalian cells. When the intracellular oxygen content decreases, it is called hypoxia. The process of hypoxia is linked to several biological processes, including pathogenic microbe infection, metabolic adaptation, cancer, acute and chronic diseases, and other stress responses. The mechanism underlying cells respond to oxygen changes to mediate subsequent signal response is the central question during hypoxia. Hypoxia-inducible factors (HIFs) sense hypoxia to regulate the expressions of a series of downstream genes expression, which participate in multiple processes including cell metabolism, cell growth/death, cell proliferation, glycolysis, immune response, microbe infection, tumorigenesis, and metastasis. Importantly, hypoxia signaling also interacts with other cellular pathways, such as phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) signaling, nuclear factor kappa-B (NF-κB) pathway, extracellular signal-regulated kinases (ERK) signaling, and endoplasmic reticulum (ER) stress. This paper systematically reviews the mechanisms of hypoxia signaling activation, the control of HIF signaling, and the function of HIF signaling in human health and diseases. In addition, the therapeutic targets involved in HIF signaling to balance health and diseases are summarized and highlighted, which would provide novel strategies for the design and development of therapeutic drugs.

Since Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was identified in late 2019, the coronavirus disease 2019 (COVID-19) pandemic has challenged public health around the world. Currently, there is an urgent need to explore antiviral therapeutic targets and effective clinical drugs. In this study, we systematically summarized two main therapeutic strategies against COVID-19, namely drugs targeting the SARS-CoV-2 life cycle and SARS-CoV-2-induced inflammation in host cells. The development of above two strategies is implemented by repurposing drugs and exploring potential targets. A comprehensive summary of promising drugs, especially cytokine inhibitors, and traditional Chinese medicine (TCM), provides recommendations for clinicians as evidence-based medicine in the actual clinical COVID-19 treatment. Considering the emerging SARS-CoV-2 variants greatly impact the effectiveness of drugs and vaccines, we reviewed the appearance and details of SARS-CoV-2 variants for further perspectives in drug design, which brings updating clues to develop therapeutical agents against the variants. Based on this, the development of broadly antiviral drugs, combined with immunomodulatory, or holistic therapy in the host, is prior to being considered for therapeutic interventions on mutant strains of SARS-CoV-2. Therefore, it is highly acclaimed the requirements of the concerted efforts from multi-disciplinary basic studies and clinical trials, which improves the accurate treatment of COVID-19 and optimizes the contingency measures to emerging SARS-CoV-2 variants.

Toll-like receptors (TLRs) are essential for the protection of the host from pathogen infections by initiating the integration of contextual cues to regulate inflammation and immunity. However, without tightly controlled immune responses, the host will be subjected to detrimental outcomes. Therefore, it is important to balance the positive and negative regulations of TLRs to eliminate pathogen infection, yet avert harmful immunological consequences. This study revealed a distinct mechanism underlying the regulation of the TLR network. The expression of sex-determining region Y-box 4 (Sox4) is induced by virus infection in viral infected patients and cultured cells, which subsequently represses the TLR signaling network to facilitate viral replication at multiple levels by a distinct mechanism. Briefly, Sox4 inhibits the production of myeloid differentiation primary response gene 88 (MyD88) and most of the TLRs by binding to their promoters to attenuate gene transcription. In addition, Sox4 blocks the activities of the TLR/MyD88/IRAK4/TAK1 and TLR/TRIF/TRAF3/TBK1 pathways by repressing their key components. Moreover, Sox4 represses the activation of the nuclear factor kappa-B (NF-κB) through interacting with IKKα/α, and attenuates NF-kB and IFN regulatory factors 3/7 (IRF3/7) abundances by promoting protein degradation. All these contributed to the down-regulation of interferons (IFNs) and IFN-stimulated gene (ISG) expression, leading to facilitate the viral replications. Therefore, we reveal a distinct mechanism by which viral pathogens evade host innate immunity and discover a key regulator in host defense.

It is with deep sorrow that we mourn the passing of the virologist Professor Jianguo Wu [...]

Abstract Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major pathological feature of Coronavirus Disease 2019 (COVID-19) and a crucial determinant in COVID-19 prognosis. Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for COVID-19 control. Here, we identify that SARS-CoV-2 ORF3a and host hypoxia-inducible factor-1α (HIF-1α) play key roles in the virus infection and pro-inflammatory responses. RNA sequencing shows that HIF-1α signaling, immune response, and metabolism pathways are dysregulated in COVID-19 patients. Clinical analyses indicate that HIF-1α production, inflammatory responses, and high mortalities occurr in elderly patients. HIF-1α and pro-inflammatory cytokines are elicited in patients and infected cells. Interestingly, SARS-CoV-2 ORF3a induces mitochondrial damage and Mito-ROS production to promote HIF-1α expression, which subsequently facilitates SARS-CoV-2 infection and cytokines production. Notably, HIF-1α also broadly promotes the infection of other viruses. Collectively, during SARS-CoV-2 infection, ORF3a induces HIF-1α, which in turn aggravates viral infection and inflammatory responses. Therefore, HIF-1α plays an important role in promoting SARS-CoV-2 infection and inducing pro-inflammatory responses to COVID-19.

SARS-CoV-2 infection has been shown to drive NLRP3 inflammasome activation and thereby cytokine storm, but how it does so is unclear. Here the authors show that the viral N protein can bind to NLRP3, resulting in enhanced interaction with ASC and thereby with the NLRP3 inflammasome.

Based on the Foucauldian concept of governmentality, this paper overcomes the atomistic view of external stakeholder engagement research to examine the specific conditions under which community engagement in urban infrastructure public-private partnerships (PPPs) can be transformational and create social value with and for communities. In particular, it shows that a transformational approach to community engagement is, in practice, closer to a form of governance that emphasizes involved stakeholders’ responsibility. It traces this line of argument through the literature and practice of social enterprises and other hybrid collaborations in the private sector. Conceptually, it contributes to a political and transformational understanding of community engagement within the context of public-private partnerships. First, by proposing a “governmentality analytical framework” for understanding and uncovering the often purposefully concealed dynamic power relations in the engagement process between the state, communities, and private investors. Second, by proposing a set of guiding principles on how to: empower communities to be organized; reconfigure the institutional environment to offer incentives and reliability; and design public-private partnerships as hybrid organizations capable of including other actors, such as non-governmental organizations.

Healthcare buildings are characterized by complex energy systems and high energy usage, therefore serving as the key areas for achieving energy conservation goals in the building sector. An accurate load prediction of hospital energy consumption is of paramount importance to a successful healthcare building energy management. In this study, eight machine learning models of single learning and ensemble learning were developed for predicting healthcare facilities’ energy consumption. To validate the performance of the proposed model, an experiment was conducted on a general hospital in Shanghai, China. It was found that the two ensemble models, Extreme Gradient Boosting (XGBoost) model and Random Forest (RF) model, outperformed single models in daily electrical load prediction. A further comparison between models trained with daily and weekly temporal resolution electrical data shows that it is more likely to achieve higher accuracy with finer time granularity. Through feature importance analysis, the most influential features under the daily and weekly electrical load prediction were identified. Based on the prediction results, it is expected that hospital facility managers will be able to conveniently assess the expected energy usage of their hospitals with the machine learning models.

This paper explores the influence mechanism of the marketization process and financial technology on corporate investment preference using panel data from 2013 to 2019 for China’s A-share listed companies. The study finds that both the marketization process and FinTech can facilitate increased R&D innovation and foreign equity investment by companies but discourage investment in their fixed assets, and FinTech has a “U-shaped effect” on corporate R&D and innovation. At the same time, the marketization process and FinTech show different threshold effects on corporate investment preferences with government subsidies as the threshold variable. It is found that market-based processes in small-scale enterprises are better able to promote investment in innovative R&D by companies—the marketization process for large enterprises has a greater impact on outward equity investment in the heterogeneity analysis. From the perspective of the nature of property rights, it is found that the marketization process and FinTech have a greater impact on non-state enterprises. As a result, in an era of rapid FinTech development, this paper enriches the relevant research on the impact of the marketization process on corporate investment preferences, which has important practical significance for policy formulation and corporate future development.

ASB17, a member of the ankyrin repeat and SOCS box-containing protein (ASB) family, has been supposed to act as an E3 ubiquitin ligase. Actually, little is known about its biological function. In this study, we found that ASB17 knocking-out impaired the expression of the pro-inflammatory cytokines CCL2 and IL-6 in bone marrow-derived dendritic cells (BMDCs) stimulated by lipopolysaccharide (LPS), indicating an inflammation-promoting role of this gene. We reveal that ASB17 promotes LPS-induced nuclear factor kappa B (NF-κB) signal activation through interacting with TNF receptor-associated factor 6 (TRAF6) which is a crucial adaptor protein downstream of toll-like receptors (TLR). ASB17 via its aa177–250 segment interacts with the Zn finger domain of TRAF6. The interaction of ASB17 stabilizes TRAF6 protein through inhibiting K48-linked TRAF6 polyubiquitination. Therefore, we suggest that ASB17 facilitates LPS-induced NF-κB activation by maintaining TRAF6 protein stability. The inflammation enhancer role of ASB17 is recognized here, which provides new understanding of the activation process of inflammation and immune response.

Gene therapy is a promising approach for treating tumors. Conventional approaches of DNA delivery depending on non-viral or viral vectors are unsatisfactory due to the concerns of biosafety and cell-targeting efficiency. The question how to deliver DNA into tumor cells efficiently and selectively is a major technological problem in tumor gene therapy. Here, we develop a vector-free gene transfer strategy to deliver genes effectively and selectively by taking advantage of targeting nucleolin. Nucleolin, a shuttle protein moving between cell membrane, cytoplasm and nuclei, is overexpressed in tumor cells. It has a natural ligand G-quadruplex (Gq). Gq-linked DNA (Gq-DNA) is likely to be internalized by ligand dependent uptake mechanisms independently of vectors after neutralizing negative charges of cell membrane by targeting nucleolin. This strategy is referred to as Gq-DNA transfection. Benefiting from its high affinity to nucleolin, Gq-DNA can be effectively delivered into nucleolin-positive tumor cells even nuclei. Gq-DNA transfection is characterized by low cytotoxicity, high efficiency, ease of synthesis, high stability in serum, direct access into nuclei, and specific nucleolin-positive tumor cell targeting.

Hepatitis B virus (HBV) infection is still one of the most dangerous viral illnesses. HBV infects around 257 million individuals worldwide. Hepatitis B in many individuals ultimately develops hepatocellular carcinoma (HCC), which is the sixth most common cancer and the third leading cause of cancer-related deaths worldwide. The innate immunity acts as the first line of defense against HBV infection through activating antiviral genes. Along with the immune responses, pro-inflammatory cytokines are triggered to enhance the antiviral responses, but this may result in acute or chronic liver inflammation, especially when the clearance of virus is unsuccessful. To a degree, the host innate immune and inflammatory responses dominate the HBV infection and liver pathogenesis. Thus, it is crucial to figure out the signaling pathways involved in the activation of antiviral factors and inflammatory cytokines. Here, we review the interplay between HBV and the signal pathways that mediates innate immune responses and inflammation. In addition, we summarize current therapeutic strategies for HBV infection via modulating innate immunity or inflammation. Characterizing the mechanisms that underlie these HBV-host interplays might provide new approaches for the cure of chronic HBV infection.

In the original publication of this manuscript [1], there are three errors in Fig. 1. The identified errors do not affect the conclusions of the work.

ABSTRACT Enteroviruses infect gastrointestinal epithelium cells, cause multiple human diseases, and present public health risks worldwide. However, the mechanisms underlying host immune responses in intestinal mucosa against the early enterovirus infections remain elusive. Here, we showed that human enteroviruses including enterovirus 71 (EV71), coxsackievirus B3 (CVB3), and poliovirus 1 (PV1) predominantly induce type III interferons (IFN-λ1 and IFN-λ2/3), rather than type I interferons (IFN-α and IFN-β), in cultured human normal and cancerous intestine epithelial cells (IECs), mouse intestine tissues, and human clinical intestine specimens. Mechanistic studies demonstrated that IFN-λ production is induced upon enterovirus infection through the Toll-like receptor 3/interferon regulatory factor 1 (TLR3/IRF1) signaling pathway in IECs. In turn, the supplementation of IFN-λ subsequently induces intrinsically antiviral responses against enterovirus replication. Notably, intraperitoneal injection in neonatal C57BL/6J mice with mouse recombinant IFN-λ2 protein represses EV71 replication and protects mice from viral lethal effects. Altogether, these results revealed a distinct mechanism by which the host elicited immune responses against enterovirus infections in intestine through activating the TLR3/IRF1/type III IFN axis. The new findings would provide an antiviral strategy for the prevention and treatment of enterovirus infections and associated diseases. IMPORTANCE Enterovirus infections are significant sources of human diseases and public health risks worldwide, but little is known about the mechanism of innate immune response in host intestine epithelial surface during the viral replication. We reported the epithelial immune response in cultured human normal and cancerous cells (IECs), mouse tissues, and human clinical intestine specimens following infection with enterovirus 71. The results mechanistically revealed type III interferons (IFN-λ1 and IFN-λ2/3), rather than type I interferons (IFN-α and IFN-β), as the dominant production through TLR3/IRF1 signaling upon multiple human enterovirus infection, including enterovirus 71 (EV71), coxsackievirus B3 (CVB3), and poliovirus 1 (PV1). IFN-λ subsequently induced antiviral activity against enterovirus replication in vitro and in vivo. These studies uncovered the role of the novel process of type III IFN production involved in the TLR3/IRF1 pathway in host intestine upon enterovirus infection, which highlighted a regulatory manner of antiviral defense in intestine during enterovirus infection.

The development of tuber-root models based on the physical properties of the root system of a plant is a prominent but complicated task. In this paper, a method for the construction of a 3D model of a potato tuber-root system is proposed, based on determining the characterization parameters of the potato tuber-root model. Three early maturing potato varieties, widely planted in Northeast China, were selected as the research objects. Their topological and geometric structures were analyzed to determine the model parameters. By actually digging potatoes in the field, field data measurement and statistical analysis of the parameters were performed, and a model parameter database was established. Based on the measured data, the root trajectory points were obtained by simulating the growth of the root tips. Then MATLAB was used to develop a system that would complete the construction of the potato tuber-root 3D visualization model. Finally, the accuracy of the model was verified experimentally. Case studies for the three different types indicated an acceptable performance of the proposed model, with a relative root mean square error of 6.81% and 15.32%, for the minimum and maximum values, respectively. The research results can be used to explore the interaction between the soil-tuber-root aggregates and the digging components, and provide a reference for the construction of root models of other tuber crops.

Megaprojects are implemented by different organisations, such as owners, consultants, and contractors. Gradually, these organisations and their connections can form business networks that influence both the market position of individual organisations and project performance. Previous research on large-scale projects mainly focused on static and homogeneous networks that were constructed by one individual project and/or carried out over one-off collaboration. However, this neglected the consideration of project network diversity, as well as repetitive, dynamic, cross-project coopetition relationship (i.e., collaboration and competition) and long-term business networks formed by key actors. Here, we chose Chinese skyscrapers over 300 meters that were built from 1996 to 2015 as typical megaproject cases and analysed the formation and evolution of megaproject business networks from the perspective of interorganisational coopetition. We identified the key actors involved and empirically studied their dynamic network positions over time. The main contributions of this study are threefold. First, we found that past collaboration experience has direct and dynamic impacts on the formation of megaproject business networks. Second, we identified key actors in the interorganisational business network and unveiled their dynamic positions with clear patterns. Third, we highlighted the temporal-spatial effect on the formation and development of business networks, alongside developments in the megaproject market. The findings of this study also provide practical applications for owners to choose collaboration partners and to build high-performance teams and for suppliers to enter and sustain the business in the megaprojects networks.

Abstract Background Interleukin-33 (IL-33) participates in various types of diseases including cancers. Previous studies of this cytokine in cancers mainly focused on its regulation on immune responses by which IL-33 modulated cancer progression. The IL-33 triggered signals in cancer cells remain unclear. Methods We analyzed IL-33 gene expression in human colorectal cancer (CRC) tissues and carried out gene enrichment analysis with TCGA Data Portal. We studied CRC proliferation in vivo by inoculating MC38 tumors in IL-33 transgenic mice. We investigated the cell proliferation in vitro with primary CRC cells isolated from fresh human CRC tissues, human CRC cell line HT-29 and mouse CRC cell line MC38. To evaluate the proliferation modulating effects of recombinant IL-33 incubation and other administrated factors, we measured tumor growth, colony formation, cell viability, and the expression of Ki67 and proliferating cell nuclear antigen (PCNA). We used several inhibitors, prostaglandin E2 (PGE2) neutralizing antibody, ST2 blocking antibody and specific shRNA expressing plasmid to study the pathway mediating IL-33-induced CRC proliferation. The IL-33 receptor ST2 in human CRC tissues was detected by immunohistochemistry staining and western blotting. The ST2-positive or negative subsets of primary CRC cells were acquired by flow cytometry sorting. Results We found that IL-33 expression was correlated with the gene signature of cell proliferation in 394 human CRC samples. The MC38 tumors grew more rapidly and the tumor Ki67 and PCNA were expressed at higher levels in IL-33 transgenic mice than in wild-type mice. IL-33 promoted cell growth, colony formation and expression of Ki67 and PCNA in primary CRC cells as well as CRC cell lines. IL-33 activated cycloxygenase-2 (COX2) expression and increased PGE2 production, whereas the COX2 selective inhibitor and PGE2 neutralizing antibody abolished the proliferation promoting effect of IL-33. ST2 blockade, ST2-negative sorting, NF-κB specific inhibitor and NF-κB specific shRNA (shP65) abrogated the COX2 induction caused by IL-33. Conclusion IL-33 facilitates proliferation of colorectal cancer dependent on COX2/PGE2. IL-33 functions via its receptor ST2 and upregulates COX2 expression through NF-κB signaling. Understanding the IL-33 signal transduction in CRC cells provides potential therapeutic targets for clinical treatment.

Top-pinning, spin-valve multilayer films with the structure Ta (5 nm)/Co75Fe25 (5 nm)/Cu (2.5 nm)/Co75Fe25 (5 nm)/Ir20Mn80 (12 nm)/Ta (8 nm) were prepared by high-vacuum DC magnetron sputtering. The effects of temperature on the film microstructure and magnetic properties were investigated by X-ray diffraction, atomic force microscopy, transmission electron microscopy, and vibrating sample magnetometry. The effects of temperature on the thermomagnetic stability of the spin-valve multilayers were studied based on the residence time of the sample in a reverse saturation field. The following effects were observed with increasing temperature: the IrMn(111) texture weakened; surface/interface roughness increased; interfacial diffusion was enhanced; the coercivities of the exchange bias field and pinned layer decreased; the coercivity of the free layer increased; relaxation became more obvious; and thermomagnetic stability decreased.

Facility management (FM) has received extensive attention from practitioners and researchers. While FM is continuously maturing as a scientific discipline and relevant studies are constantly growing, there are no holistic reviews of current research. The information in previous studies is generally scattered, and existing literature reviews mostly focused on specific aspects of FM. It is necessary for researchers and practitioners to obtain a thorough view of the current status in the FM field and future development trends that have been summarized and discussed in depth. Using a bibliometricqualitative analysis, a total of 724 academic journal papers on FM, between 1995 and 2018, were reviewed. A number of the latest advancements and emergent trends were identified based on knowledge maps in FM, including changing circumstances, enhancing information technology, all-around facility manager, strategic performance management, sustainable FM and innovative FM practice. It is hoped that this review can help researchers understand the current body of FM knowledge. The future directions were also highlighted in this study to help researchers identify areas where research is most needed. This study could also help practitioners to address upcoming challenges in the FM field.

To protect crops from diseases and increase yields, chemical agents are applied by boom sprayers. To achieve the optimal effect, the boom and the crop canopy should be kept at an appropriate distance. So, it is crucial to be able to distinguish the crop canopy from other plant leaves. Based on ultrasonic ranging, this paper adopts the fuzzy iterative self-organizing data analysis technique algorithm to identify the canopy location. According to the structural characteristics of the crop canopy, based on fuzzy clustering, the algorithm can dynamically adjust the number and center of clusters so as to get the optimal results. Therefore, the distances from the sensor to the canopy or the ground can be accurately acquired, and the influence of lower leaves on the measurement results can be alleviated. Potted corn plants from the 3-leaf stage to the 6-leaf stage were tested on an experiment bench. The results showed that the calculated distances from the sensor to the canopy using this method had good correlation with the manually measured distances. The maximum error of calculated values appeared at the 3-leaf stage. With the growth of plants, the error of calculated values decreased. The increased sensor moving speeds led to increased error due to the reduced data points. From the 3-leaf stage to the 5-leaf stage, the distances from the sensor to the ground can also be obtained at the same time. The method proposed in this paper provides a practical resolution to localize the canopy for adjusting the height of sprayer boom.

The organization is the key factor for megaprojects in which thousands of connections and relations intertwine and influence the project performance. However, organizational evolution in megaprojects has not been fully studied. This study investigates the evolution of the organizational network of a megaproject in China using social network analysis (SNA), and then proposes corresponding governance strategies. The result shows that megaproject organizations evolve towards more connected networks but are differentiated for various investors. For government invested projects, the organizational network is well connected, cooperative, yet unstable and require strategic long-term governance policies; for private invested projects, the network is stable, but collaboration among participants is low, which indicates a need to establish collaborative governance structures. The result complements the organizational evolution theory for megaprojects and offers effective strategies for governing megaproject organizations. This study also helps practitioners better understand the nature and characteristics of megaproject organizations.

As global crises such as COVID-19 become more frequent, many projects, which can be called blitz projects, will need to be completed extremely quickly in response. However, there remains a lack of theoretical support for their implementation as well as systematic strategies for managing their schedules. This article examines the responses to COVID-19 by three specialty field hospitals in China. Through reviews and cross-analysis of the influential factors and practices, and their effects on extreme schedule management, this article proposes a systematic strategic framework including the elements of mission, solution and innovation, organization and culture, communication, resources, dynamics, and adaptability. [ABSTRACT FROM AUTHOR]