GBDT Method Integrating Feature-Enhancement and Active-Learning Strategies-Sea Ice Thickness Inversion in Beaufort Sea.

Sea ice, as an important component of the Earth's ecosystem, has a profound impact on global climate and human activities due to its thickness. Therefore, the inversion of sea ice thickness has important research significance. Due to environmental and equipment-related limitations, the number of samples available for remote sensing inversion is currently insufficient. At high spatial resolutions, remote sensing data contain limited information and noise interference, which seriously affect the accuracy of sea ice thickness inversion. In response to the above issues, we conducted experiments using ice draft data from the Beaufort Sea and designed an improved GBDT method that integrates feature-enhancement and active-learning strategies (IFEAL-GBDT). In this method, the incident angle and time series are used to perform spatiotemporal correction of the data, reducing both temporal and spatial impacts. Meanwhile, based on the original polarization information, effective multi-attribute features are generated to expand the information content and improve the separability of sea ice with different thicknesses. Taking into account the growth cycle and age of sea ice, attributes were added for month and seawater temperature. In addition, we studied an active learning strategy based on the maximum standard deviation to select more informative and representative samples and improve the model's generalization ability. The improved GBDT model was used for training and prediction, offering advantages in dealing with nonlinear, high-dimensional data, and data noise problems, further expanding the effectiveness of feature-enhancement and active-learning strategies. Compared with other methods, the method proposed in this paper achieves the best inversion accuracy, with an average absolute error of 8 cm and a root mean square error of 13.7 cm for IFEAL-GBDT and a correlation coefficient of 0.912. This research proves the effectiveness of our method, which is suitable for the high-precision inversion of sea ice thickness determined using Sentinel-1 data.

Red Tide Detection Method Based on Improved U-Net Model-Taking GOCI Data in East China Sea as an Example.

In the coastal areas of China, the eutrophication of seawater leads to the continuous occurrence of red tide, which has caused great damage to Marine fisheries and aquatic resources. Therefore, the detection and prediction of red tide have important research significance. The rapid development of optical remote sensing technology and deep-learning technology provides technical means for realizing large-scale and high-precision red tide detection. However, the difficulty of the accurate detection of red tide edges with complex boundaries limits the further improvement of red tide detection accuracy. In view of the above problems, this paper takes GOCI data in the East China Sea as an example and proposes an improved U-Net red tide detection method. In the improved U-Net method, NDVI was introduced to enhance the characteristic information of the red tide to improve the separability between the red tide and seawater. At the same time, the ECA channel attention mechanism was introduced to give different weights according to the influence of different bands on red tide detection, and the spectral characteristics of different channels were fully mined to further extract red tide characteristics. A shallow feature extraction module based on Atrous Spatial Pyramid Convolution (ASPC) was designed to improve the U-Net model. The red tide feature information in a multi-scale context was fused under multiple sampling rates to enhance the model's ability to extract features at different scales. The problem of limited accuracy improvement in red tide edge detection with complex boundaries is solved via the fusion of deep and shallow features and multi-scale spatial features. Compared with other methods, the method proposed in this paper achieves better results and can detect red tide edges with complex boundaries, and the accuracy, precision, recall, and F1-score are 95.90%, 97.15%, 91.53%, and 0.94, respectively. In addition, the red tide detection experiments in other regions with relatively concentrated distribution also prove that the method has good applicability.

The role of cell death in SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), showing high infectiousness, resulted in an ongoing pandemic termed coronavirus disease 2019 (COVID-19). COVID-19 cases often experience acute respiratory distress syndrome, which has caused millions of deaths. Apart from triggering inflammatory and immune responses, many viral infections can cause programmed cell death in infected cells. Cell death mechanisms have a vital role in maintaining a suitable environment to achieve normal cell functionality. Nonetheless, these processes are dysregulated, potentially contributing to disease pathogenesis. Over the past decades, multiple cell death pathways are becoming better understood. Growing evidence suggests that the induction of cell death by the coronavirus may significantly contributes to viral infection and pathogenicity. However, the interaction of SARS-CoV-2 with cell death, together with its associated mechanisms, is yet to be elucidated. In this review, we summarize the existing evidence concerning the molecular modulation of cell death in SARS-CoV-2 infection as well as viral-host interactions, which may shed new light on antiviral therapy against SARS-CoV-2.

CC Chemokine 2 Promotes Ovarian Cancer Progression through the MEK/ERK/MAP3K19 Signaling Pathway.

Ovarian cancer is a gynecological tumor with an incidence rate lower than those of other gynecological tumor types and the second-highest death rate. CC chemokine 2 (CCL2) is a multifunctional factor associated with the progression of numerous cancers. However, the effect of CCL2 on ovarian cancer progression is unclear. Here, we found that exogenous CCL2 and the overexpression of CCL2 promoted the proliferation and metastasis of ovarian cancer cells. On the other hand, CCL2 knockdown via CRISPR/Cas9 inhibited ovarian cancer cell proliferation, migration, and invasion. The present study demonstrated that mitogen-activated protein three kinase 19 (MAP3K19) was the key CCL2 target for regulating ovarian cancer progression through transcriptome sequencing. Additionally, MAP3K19 knockout inhibited ovarian cancer cell proliferation, migration, and invasion. Furthermore, CCL2 increased MAP3K19 expression by activating the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. The present study showed the correlation between CCL2 and ovarian cancer, suggesting that CCL2 may be a novel target for ovarian cancer therapy.

Matrix stiffening facilitates the collective invasion of breast cancer through the periostin-integrin mechanotransduction pathway.

Matrix rigidity is a critical contributor to tumor progression; however, whether and how matrix stiffness modulates the collective invasion of tumor cells remain unknown. Here we demonstrate that increased matrix stiffness activates YAP to promote the secretion of periostin (POSTN) in cancer-associated fibroblasts, which in turn augments the matrix rigidity of mammary glands and breast tumor tissues by facilitating collagen crosslinking. Moreover, decreased tissue stiffening resulted from the POSTN deficiency impairs peritoneal metastatic potential of orthotopic breast tumors. Increased matrix stiffness also promotes three-dimensional (3D) collective breast tumor cell invasion via multicellular cytoskeleton remodeling. POSTN triggers the integrin/FAK/ERK/Cdc42/Rac1 mechanotransduction pathway during 3D collective invasion of breast tumor. Clinically, high POSTN expression correlates with high collagen levels in breast tumors and cooperatively determines the metastatic recurrence potential in breast cancer patients. Collectively, these findings indicate that matrix rigidity promotes 3D collective invasion of breast tumor cells via the YAP-POSTN-integrin mechanotransduction signaling.

A Combined Physical and Mathematical Calibration Method for Low-Cost Cameras in the Air and Underwater Environment.

Low-cost camera calibration is vital in air and underwater photogrammetric applications. However, various lens distortions and the underwater environment influence are difficult to be covered by a universal distortion compensation model, and the residual distortions may still remain after conventional calibration. In this paper, we propose a combined physical and mathematical camera calibration method for low-cost cameras, which can adapt to both in-air and underwater environments. The commonly used physical distortion models are integrated to describe the image distortions. The combination is a high-order polynomial, which can be considered as basis functions to successively approximate the image deformation from the point of view of mathematical approximation. The calibration process is repeated until certain criteria are met and the distortions are reduced to a minimum. At the end, several sets of distortion parameters and stable camera interior orientation (IO) parameters act as the final camera calibration results. The Canon and GoPro in-air calibration experiments show that GoPro owns distortions seven times larger than Canon. Most Canon distortions have been described with the Australis model, while most decentering distortions for GoPro still exist. Using the proposed method, all the Canon and GoPro distortions are decreased to close to 0 after four calibrations. Meanwhile, the stable camera IO parameters are obtained. The GoPro Hero 5 Black underwater calibration indicates that four sets of distortion parameters and stable camera IO parameters are obtained after four calibrations. The camera calibration results show a difference between the underwater environment and air owing to the refractive and asymmetric environment effects. In summary, the proposed method improves the accuracy compared with the conventional method, which could be a flexible way to calibrate low-cost cameras for high accurate in-air and underwater measurement and 3D modeling applications.

Gapless Genome Assembly of Puccinia triticina Provides Insights into Chromosome Evolution in Pucciniales.

Chromosome evolution drives species evolution, speciation, and adaptive radiation. Accurate genome assembly is crucial to understanding chromosome evolution of species, such as dikaryotic fungi. Rust fungi (Pucciniales) in dikaryons represent the largest group of plant pathogens, but the evolutionary process of adaptive radiation in Pucciniales remains poorly understood. Here, we report a gapless genome for the wheat leaf rust fungus Puccinia triticina determined using PacBio high-fidelity (HiFi) sequencing. This gapless assembly contains two sets of chromosomes, showing that one contig represents one chromosome. Comparisons of homologous chromosomes between the phased haplotypes revealed that highly frequent small-scale sequence divergence shapes haplotypic variation. Genome analyses of Puccinia triticina along with other rusts revealed that recent transposable element bursts and extensive segmental gene duplications synergistically highlight the evolution of chromosome structures. Comparative analysis of chromosomes indicated that frequent chromosomal rearrangements may act as a major contributor to rapid radiation of Pucciniales. This study presents the first gapless, phased assembly for a dikaryotic rust fungus and provides insights into adaptive evolution and species radiation in Pucciniales. IMPORTANCE Rust fungi (Pucciniales) are the largest group of plant pathogens. Adaptive radiation is a predominant feature in Pucciniales evolution. Chromosome evolution plays an important role in adaptive evolution. Accurate chromosome-scale assembly is required to understand the role of chromosome evolution in Pucciniales. We took advantage of HiFi sequencing to construct a gapless, phased genome for Puccinia triticina. Further analyses revealed that the evolution of chromosome structures in rust lineage is shaped by the combination of transposable element bursts and segmental gene duplications. Chromosome comparisons of Puccinia triticina and other rusts suggested that frequent chromosomal arrangements may make remarkable contributions to high species diversity of rust fungi. Our results present the first gapless genome for Pucciniales and shed light on the feature of chromosome evolution in Pucciniales.

Progress of cGAS-STING signaling in response to SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) is an epidemic respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can cause infections in millions of individuals, who can develop lung injury, organ failure, and subsequent death. As the first line of host defense, the innate immune system is involved in initiating the immune response to SARS-CoV-2 infection and the hyperinflammatory phenotype of COVID-19. However, the interplay between SARS-CoV-2 and host innate immunity is not yet well understood. It had become known that the cGAS-STING pathway is involved in the detection of cytosolic DNA, which elicits an innate immune response involving a robust type I interferon response against viral and bacterial infections. Nevertheless, several lines of evidence indicate that SARS-CoV-2, a single-stranded positive-sense RNA virus, triggered the cGAS-STING signaling pathway. Therefore, understanding the molecular and cellular details of cGAS-STING signaling upon SARS-CoV-2 infection is of considerable biomedical importance. In this review, we discuss the role of cGAS-STING signaling in SARS-CoV-2 infection and summarize the potential therapeutics of STING agonists as virus vaccine adjuvants.

Role of CC-chemokine ligand 2 in gynecological cancer.

Gynecological cancer is one of the most severe diseases that threaten the lives and health of women worldwide. Its incidence rate increases with each passing year and becomes more prevalent among young people. The prognosis of gynecological cancer remains poor despite significant advances in surgical removal and systemic chemotherapy. Several chemokines play a role in the progression of gynecologic cancers. CCL2 (CC-chemokine ligand 2), also termed MCP-1 (monocyte chemotactic protein 1), plays a significant physiological role in monocyte cell migration and the inflammatory response. Recent studies have demonstrated that CCL2 plays a pro-tumorigenic function in the tumor microenvironment. According to previous studies, CCL2 plays a significant role in the occurrence and development of gynecological cancers. Furthermore, recent studies noted that CCL2 could be a potential diagnostic biomarker and prognostic predictor. The purpose of this paper is to review the role of CCL2 in the occurrence and development of gynecological cancers and to discuss the potential therapeutic strategy of CCL2 for gynecological cancers, with a primary focus on breast cancer, ovarian cancer, cervical cancer, and endometrial cancer.

Underwater Holothurian Target-Detection Algorithm Based on Improved CenterNet and Scene Feature Fusion.

Aiming at the common problems, such as noise pollution, low contrast, and color distortion in underwater images, and the characteristics of holothurian recognition, such as morphological ambiguity, high similarity with the background, and coexistence of special ecological scenes, this paper proposes an underwater holothurian target-detection algorithm (FA-CenterNet), based on improved CenterNet and scene feature fusion. First, to reduce the model's occupancy of embedded device resources, we use EfficientNet-B3 as the backbone network to reduce the model's Params and FLOPs. At the same time, EfficientNet-B3 increases the depth and width of the model, which improves the accuracy of the model. Then, we design an effective FPT (feature pyramid transformer) combination module to fully focus and mine the information on holothurian ecological scenarios of different scales and spaces (e.g., holothurian spines, reefs, and waterweeds are often present in the same scenario as holothurians). The co-existing scene information can be used as auxiliary features to detect holothurians, which can improve the detection ability of fuzzy and small-sized holothurians. Finally, we add the AFF module to realize the deep fusion of the shallow-detail and high-level semantic features of holothurians. The results show that the method presented in this paper yields better results on the 2020 CURPC underwater target-detection image dataset with an AP50 of 83.43%, Params of 15.90 M, and FLOPs of 25.12 G compared to other methods. In the underwater holothurian-detection task, this method improves the accuracy of detecting holothurians with fuzzy features, a small size, and dense scene. It also achieves a good balance between detection accuracy, Params, and FLOPs, and is suitable for underwater holothurian detection in most situations.

The role of cyclophilins in viral infection and the immune response.

Cyclophilins (Cyps) are a subgroup of peptidyl-prolyl cis-trans isomerases (PPIases) that contain a highly conserved domain of PPIases. Sixteen Cyps have been identified in humans, among which the functions of five classical Cyp subtypes (CypA, B, C, D, and 40) have been studied in more detail. Cyps are widely expressed in almost all human tissues and are involved in several intracellular signaling pathways such as oxidative stress, mitochondrial dysfunction, cell migration, and apoptosis. Several studies have also demonstrated that Cyps play an important role in the development of cardiovascular diseases, neurodegeneration, cancer, and other diseases. However, as regulators of intercellular communication, Cyps have increasingly attracted attention as a result of their implications in viral infection. The specific motifs of Cyps can be targeted by viral proteins and thus promote either a viral infection or an antiviral response. This review highlights the present understanding of Cyps in viral infection and immune response. These effects will facilitate revealing the molecular mechanisms of several diseases induced by viruses and may provide novel insight into the development of corresponding drug-based treatment methods.

MST4 negatively regulates type I interferons production via targeting MAVS-mediated pathway.

BACKGROUND: Cytosolic RNA sensing can elicit immune responses against viral pathogens. However, antiviral responses must be tightly regulated to avoid the uncontrolled production of type I interferons (IFN) that might have deleterious effects on the host. Upon bacterial infection, the germinal center kinase MST4 can directly phosphorylate the adaptor TRAF6 to limit the inflammatory responses, thereby avoiding the damage caused by excessive immune activation. However, the molecular mechanism of how MST4 regulates virus-mediated type I IFN production remains unknown. METHODS: The expression levels of IFN-ß, IFIT1, and IFIT2 mRNA were determined by RT-PCR. The expression levels of p-IRF3, IRF3, RIG-I, MAVS, and MST4 proteins were determined by Western blot. The effect of secreted level of IFN-ß was measured by ELISA. The relationship between MST4 and MAVS was investigated by immunofluorescence staining and coimmunoprecipitation. RESULTS: In this study, we reported that MST4 can act as a negative regulator of type I IFN production. Ectopic expression of MST4 suppressed the Poly (I:C) (polyino-sinic-polycytidylic acid)- and Sendai virus (SeV)-triggered production of type I IFN, while the knockdown of MST4 enhanced the production of type I IFN. Mechanistically, upon SeV infection, the MST4 competed with TRAF3 to bind to the 360-540 domain of MAVS, thereby inhibiting the TRAF3/MAVS association. Additionally, MST4 facilitated the interaction between the E3 ubiquitin ligase Smurf1 and MAVS. This promoted the K48-linked ubiquitination of MAVS, thereby accelerating the ubiquitin-mediated proteasome degradation of MAVS. CONCLUSIONS: Our findings showed that MST4 acted as a crucial negative regulator of RLR-mediated type I IFN production. Video Abstract.

Expression and purification of recombinant human CCL5 and its biological characterization.

C-C motif chemokine ligand 5 (CCL5) is crucial in the tumor microenvironment. It has been previously reported to act as a key role in tumor invasion and metastasis. However, the function of exogenous CCL5 in ovarian cancer has not been well-characterized. The present study attempted to express and purify recombinant CCL5 protein and investigate the exogenous CCL5 in ovarian cancer cell proliferation. The human CCL5 was amplified and inserted into the pET-30a vectors for prokaryotic expression in Escherichia coli BL21. Soluble His-CCL5 was successfully expressed with 0.1 mmol/L of isopropyl-ß-D-1-tiogalactopiranoside at 25 ℃ and purified by affinity chromatography. Additionally, methyl thiazolyl tetrazolium (MTT) assay demonstrated that CCL5 promotes ovarian cancer cell proliferation; increases the phosphorylation levels of extracellular-signal-regulated kinase and mitogen-activated protein kinase/ERK kinase, and increases the mRNA levels of Jun, NF-κB2, Nras, Relb, and Traf2. Furthermore, treatment with the MEK inhibitor reduced the Jun, NF-κB2, and Traf2 mRNA levels, indicating that exogenous CCL5 increased ovarian cancer cell proliferation, through MEK/ERK pathway activation, and Jun, NF-κB2, and Traf2 expression. The present study provided primary data for further studies to discover more CCL5 functions in ovarian cancer.

Exogenous interleukin-1 beta promotes the proliferation and migration of HeLa cells via the MEK/ERK signaling pathway.

OBJECTIVE: Interleukin-1 beta (IL-1ß) is a crucial cytokine that has been implicated in cancer and metastasis development. However, its possible mechanistic role in cervical cancer remains unclear. This study aimed to investigate the functions of exogenous IL-1ß in cervical cancer cell proliferation and migration. METHODS: HeLa cell proliferation and migration were measured using MTT and Transwell assays. A lentivirus-mediated packaging system was used to construct an IL-1ß overexpressing cell line. MEK/ERK signal transduction was inhibited by pretreatment with the MEK inhibitor PD98059. qRT-PCR and Western blotting were used to test the expression of relevant genes. RESULTS: Exogenous IL-1ß promoted the proliferation and migration of HeLa cells. In addition, overexpression of IL-1ß in HeLa cells promoted cell proliferation. Mechanistically, exogenous IL-1ß increased the phosphorylated MEK and ERK levels in HeLa cells and the expression of JUN, RELB, and NF-κB2. Alternatively, blockade of MEK inhibited the promoting proliferation effects of IL-1ß and the expression of JUN, RELB, and NF-κB2. CONCLUSIONS: Our data suggest that exogenous IL-1ß regulates HeLa cell functions by regulating the MEK/ERK signaling pathway and by targeting JUN, RELB, and NF-κB2. Our study uncovered a potential association across IL-1ß, cervical tumor development, and cancer progression.

Cyclophilin A regulates the apoptosis of A549 cells by stabilizing Twist1 protein.

Cyclophilin A (CypA, also known as PPIA) is an essential member of the immunophilin family. As an intracellular target of the immunosuppressive drug cyclosporin A (CsA) or a peptidyl-prolyl cis/trans isomerase (PPIase), it catalyzes the cis-trans isomerization of proline amidic peptide bonds, through which it regulates a variety of biological processes, such as intracellular signaling, transcription and apoptosis. In this study, we found that intracellular CypA enhanced Twist1 phosphorylation at Ser68 and inhibited apoptosis in A549 cells. Mechanistically, CypA could mediate the phosphorylation of Twist1 at Ser68 via p38 mitogen-activated protein kinase (also known as MAPK14), which inhibited its ubiquitylation-mediated degradation. In addition, CypA increased interaction between Twist1 and p65 (also known as RELA), as well as nuclear accumulation of the Twist1-p65 complex, which regulated Twist1-dependent expression of CDH1 and CDH2. Our findings collectively indicate the role of CypA in Twist1-mediated apoptosis of A549 cells through stabilizing Twist1 protein.

SARS-CoV-2 3C-like protease antagonizes interferon-beta production by facilitating the degradation of IRF3.

The prevalence of SARS-CoV-2 is a great threat to global public health. However, the relationship between the viral pathogen SARS-CoV-2 and host innate immunity has not yet been well studied. The genome of SARS-CoV-2 encodes a viral protease called 3C-like protease. This protease is responsible for cleaving viral polyproteins during replication. In this investigation, 293T cells were transfected with SARS-CoV-2 3CL and then infected with Sendai virus (SeV) to induce the RIG-I like receptor (RLR)-based immune pathway. q-PCR, luciferase reporter assays, and western blotting were used for experimental analyses. We found that SARS-CoV-2 3CL significantly downregulated IFN-ß mRNA levels. Upon SeV infection, SARS-CoV-2 3CL inhibited the nuclear translocation of IRF3 and p65 and promoted the degradation of IRF3. This effect of SARS-CoV-2 3CL on type I IFN in the RLR immune pathway opens up novel ideas for future research on SARS-CoV-2.

Cyclophilin A inhibits A549 cell oxidative stress and apoptosis by modulating the PI3K/Akt/mTOR signaling pathway.

The excessive and inappropriate production of reactive oxygen species (ROS) can cause oxidative stress and is implicated in the pathogenesis of lung cancer. Cyclophilin A (CypA), a member of the immunophilin family, is secreted in response to ROS. To determine the role of CypA in oxidative stress injury, we investigated the role that CypA plays in human lung carcinoma (A549) cells. Here, we showed the protective effect of human recombinant CypA (hCypA) on hydrogen peroxide (H2O2)-induced oxidative damage in A549 cells, which play crucial roles in lung cancer. Our results demonstrated that hCypA substantially promoted cell viability, superoxide dismutase (SOD), glutathione (GSH), and GSH peroxidase (GSH-Px) activities, and attenuated ROS and malondialdehyde (MDA) production in H2O2-induced A549 cells. Compared with H2O2-induced A549 cells, Caspase-3 activity in hCypA-treated cells was significantly reduced. Using Western blotting, we showed that hCypA facilitated Bcl-2 expression and inhibited Bax, Caspase-3, Caspase-7, and PARP-1 expression. Furthermore, hCypA activates the PI3K/Akt/mTOR pathway in A549 cells in response to H2O2 stimulation. Additionally, peptidyl-prolyl isomerase activity was required for PI3K/Akt activation by CypA. The present study showed that CypA protected A549 cells from H2O2-induced oxidative injury and apoptosis by activating the PI3K/Akt/mTOR pathway. Thus, CypA might be a potential target for lung cancer therapy.

Purification of recombinant human chemokine CCL2 in E. coli and its function in ovarian cancer.

Chemokine (CC-motif) ligand 2 (CCL2) is an inflammatory cytokine that regulates the infiltration and migration of monocytes. It is highly expressed by both tumor and stromal cells and has been associated with tumorigenesis. However, the effect of the exogenous administration of CCL2 on ovarian cancer remains largely unknown. In this report, we attempted to establish an expression system in Escherichia coli to produce recombinant hCCL2. The recombinant plasmid containing the hCCL2 cDNA was prepared using the prokaryotic-expression plasmid pGEX-5X-3 and transformed into E. coli BL21. GST-hCCL2 was successfully induced by 0.1 mmol/L IPTG at 20 °C for 6 h, and the recombinant protein was purified using affinity chromatography. The purified protein was identified by SDS-PAGE and Western Blot. In vitro experiments revealed that rhCCL2 promoted the proliferation of ovarian cancer cells and increased the levels of phosphorylation of MEK and ERK1/2, and the levels of JUN, RELB and NF-κB2 mRNA. Furthermore, inhibition of ERK signaling by treatment with PD98059 decreased ovarian cancer cell proliferation and levels of JUN, RELB, and NF-κB2 mRNA, indicating that exogenous rhCCL2 increased the proliferation of ovarian cancer cells, partially by activating the MAPK/ERK pathway, and by targeting JUN, RELB, and NF-κB2. Our study uncovered a promoting role of exogenous CCL2 on ovarian cancer cell proliferation through the MAPK/ERK signaling pathway, which may facilitate the discovery of more potential roles of CCL2 in ovarian cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-020-02571-0.

Forkhead box O1-mediated ubiquitination suppresses RIG-I-mediated antiviral immune responses.

RNA virus infection activates the RIG-I-like Receptor (RLR) signaling pathway to produce type I interferons (IFNs), the key components of the antiviral immune response. Forkhead box O1 (FoxO1) is a host transcription factor that participates in multiple biological processes. In this study, FoxO1 was identified as a critical negative regulator of RIG-I-triggered signaling. FoxO1 promoted Sendai virus (SeV) replication and downregulated type I IFN production. Upon SeV infection, FoxO1 suppressed K63-linked ubiquitination of TRAF3 and the interaction between TRAF3 and TBK1, after which the production of type I IFNs via the interferon regulatory transcription factor 3 (IRF3) pathways was reduced. In addition, FoxO1 destabilized IRF3 by facilitating E3 ligase TRIM22- or TRIM21-mediated K48-linked ubiquitination of IRF3. Moreover, the inhibitory effect of FoxO1 was found to depend on its DNA binding domain (DBD). Thus, our findings highlight novel important roles of FoxO1 in controlling RLR-mediated antiviral innate immunity.

MicroRNA-873 inhibits colorectal cancer metastasis by targeting ELK1 and STRN4.

MicroRNAs (miRNAs) are a group of small non-coding RNAs that directly bind to the 3'-untranslated-region (3'UTR) of mRNA, thereby blocking gene expression post-transcriptionally. Accumulating evidence prove that microRNA-873 (miR-873) functions as a promoter or suppressor in various cancers, while whether it affects the progression of colorectal cancer (CRC) is yet unknown. Here we found that miR-873 was downregulated in human CRC clinical samples, mouse CRC specimens and cell lines with high metastatic potential. We also demonstrated that low miR-873 expression was closely associated with poor prognosis of CRC. Overexpressing miR-873 suppressed proliferation and metastasis of CRC cells both in vitro and in vivo, while inhibiting miR-873 expression promoted the proliferation, migration and invasion in vitro. Moreover, miR-873 exerted its function by perturbing the ERK-CyclinD1 pathway and the epithelial-mesenchymal transition (EMT) process. Furthermore, we revealed that miR-873 acted as a tumor-suppressive microRNA by directly binding to the 3'UTRs of ELK1 and STRN4 and suppressed their expression. Our study uncovered an inhibitory role of miR-873 in CRC progression and might provide a promising marker for CRC diagnosis and prognosis.