Insect-transmitted plant virus balances its vertical transmission through regulating Rab1-mediated receptor localization.

Rice stripe virus (RSV) establishes infection in the ovaries of its vector insect, Laodelphax striatellus. We demonstrate that RSV infection delays ovarian maturation by inhibiting membrane localization of the vitellogenin receptor (VgR), thereby reducing the vitellogenin (Vg) accumulation essential for egg development. We identify the host protein L. striatellus Rab1 protein (LsRab1), which directly interacts with RSV nucleocapsid protein (NP) within nurse cells. LsRab1 is required for VgR surface localization and ovarian Vg accumulation. RSV inhibits LsRab1 function through two mechanisms: NP binding LsRab1 prevents GTP binding, and NP binding LsRab1-GTP complexes stimulates GTP hydrolysis, forming an inactive LsRab1 form. Through this dual inhibition, RSV infection prevents LsRab1 from facilitating VgR trafficking to the cell membrane, leading to inefficient Vg uptake. The Vg-VgR pathway is present in most oviparous animals, and the mechanisms detailed here provide insights into the vertical transmission of other insect-transmitted viruses of medical and agricultural importance.

Super-resolution reconstruction for early cervical cancer magnetic resonance imaging based on deep learning.

This study aims to develop a super-resolution (SR) algorithm tailored specifically for enhancing the image quality and resolution of early cervical cancer (CC) magnetic resonance imaging (MRI) images. The proposed method is subjected to both qualitative and quantitative analyses, thoroughly investigating its performance across various upscaling factors and assessing its impact on medical image segmentation tasks. The innovative SR algorithm employed for reconstructing early CC MRI images integrates complex architectures and deep convolutional kernels. Training is conducted on matched pairs of input images through a multi-input model. The research findings highlight the significant advantages of the proposed SR method on two distinct datasets at different upscaling factors. Specifically, at a 2× upscaling factor, the sagittal test set outperforms the state-of-the-art methods in the PSNR index evaluation, second only to the hybrid attention transformer, while the axial test set outperforms the state-of-the-art methods in both PSNR and SSIM index evaluation. At a 4× upscaling factor, both the sagittal test set and the axial test set achieve the best results in the evaluation of PNSR and SSIM indicators. This method not only effectively enhances image quality, but also exhibits superior performance in medical segmentation tasks, thereby providing a more reliable foundation for clinical diagnosis and image analysis.

Benzimidazole-based structure optimization to discover novel anti-gastric cancer agents targeting ROS/MAPK pathway.

Given the malignancy of gastric cancer, developing highly effective and low-toxic targeted drugs is essential to prolong patient survival and improve patient outcomes. In this study, we conducted structural optimizations based on the benzimidazole scaffold. Notably, compound 8 f presented the most potent antiproliferative activity in MGC803 cells and induced cell cycle arrest at the G0/G1 phase. Further mechanistic studies demonstrated that compound 8 f caused the apoptosis of MGC803 cells by elevating intracellular reactive oxygen species (ROS) levels and activating the mitogen-activated protein kinase (MAPK) signaling pathway, accompanied by corresponding markers change. In vivo investigations additionally validated the inhibitory effect of compound 8 f on tumor growth in xenograft models bearing MGC803 cells without obvious toxicity. Our studies suggest that compound 8 f holds promise as a potential and safe lead compound for developing anti-gastric cancer agents.

Experiment and analysis of physical, mechanical, and viscoelastic properties of the roots and stalks of green leafy vegetables.

Green leafy vegetables are an essential component of Chinese leafy vegetables. Due to their crisp stems and tender leaves, orderly harvester generally causes significant mechanical clamping damage. The physical and mechanical properties of green leafy vegetables are one of the important basis to design the orderly harvester. At the same time, they provide important parameters for the simulation and optimization of harvester. So, this paper measured the physical characteristic parameters of roots and stems of green leafy vegetables. Then, based on the TMS-Pro texture analyzer, the elasticity modulus of the roots and stems of green leafy vegetables were measured. The static friction coefficient, dynamic friction coefficient, and restitution coefficient of green leafy vegetables root-root, stem-stem, root-steel, and stem-steel were measured separately using a combination method of inclined plane and high-speed photography. Uniaxial compression creep experiments were carried out on whole and single leaf of green leafy vegetables using the TA.XT plus C universal testing machine. The constitutive equation of the four-element Burgers model was used to fit the deformation curve of the sample with time during the constant-pressure loading stage. The fitting determination coefficients R2 were all higher than 0.996, which verified the reasonable validity of the selected model. The above experimental results provide a parameter basis and theoretical support for the design and discrete element simulation optimization of orderly harvester critical components of green leafy vegetables.

Antitumor activity of dictamnine against colorectal cancer through induction of ferroptosis and inhibition of M2 macrophage polarization via the MAPK signaling.

Colorectal cancer (CRC) is an aggressive cancer type globally. Surgery and chemotherapy are often ineffective at curing CRC. Dictamnine is a natural product derived from Dictamnus dasycarpus Turcz. root bark and possesses multi-pharmacological properties, including anticancer effects. Nevertheless, the biological roles and the possible mechanism of dictamnine in CRC are still unclear. Here, we demonstrated that dictamnine blocked cell viability and proliferation in DLD-1 human colorectal adenocarcinoma cells and LoVo human colon cancer cells. Dictamnine triggered CRC cell ferroptosis, as evidenced by enhanced levels of reactive oxygen species, malondialdehyde, and Fe2+ levels, alongside downregulation of glutathione peroxidase 4 protein expression. In addition, CD163 (HPA ID: HPA046404) was highly expressed and CD68 (HPA ID: CAB000051) was lowly expressed in CRC tissues and CRC cell culture medium-cultured THP-1 monocytes-derived macrophages. The patients with CD163 low-expression lived much longer than those with CD163 high-expression, indicating that M2 polarization of macrophages was related to poor prognosis of CRC. Dictamnine markedly inhibited CD163 protein expression, transforming growth factor-ß and arginase 1 mRNA expressions and IL-10 production in macrophages with CRC cell co-culture, suggesting that dictamnine impeded M2 polarization of macrophages. Mechanistically, dictamnine repressed ERK phosphorylation in CRC cells. The treatment with the ERK activator tBHQ counteracted the effects of dictamnine on CRC cell proliferation and ferroptosis, as well as its inhibitory effect on M2 polarization of macrophages. Results of a xenograft model showed that dictamnine effectively hindered CRC tumor growth in vivo. Collectively, these data provide evidence for the clinical trials of dictamnine as a novel drug for CRC therapy.

Super-resolution algorithm for the characterization of sweat glands in fingerprint OCT images.

Optical coherence tomography (OCT) is a noninvasive optical imaging technique that can be used to produce three-dimensional images of fingerprints. However, the low quality and poor resolution of the regions of interest (ROIs) in OCT images make it challenging to segment small tissues accurately. To address this issue, a super-resolution (SR) network called ESRNet has been developed to enhance the quality of OCT images, facilitating their applications in research. Firstly, the performance of the SR images produced by ESRNet is evaluated by comparing it to those generated by five other SR methods. Specifically, the SR performance is evaluated using three upscale factors (2×, 3×, and 4×) to assess the quality of the enhanced images. Based on the results obtained from the three datasets, it is evident that ESRNet outperforms current advanced networks in terms of SR performance. Furthermore, the segmentation accuracy of sweat glands has been significantly improved by the SR images. The number of sweat glands in the top view increased from 102 to 117, further substantiating the performance of the ESRNet network. The spiral structure of sweat glands is clear to human eyes and has been verified by showing similar left-right-handed spiral numbers. Finally, a sweat gland recognition method for the SR 3D images is proposed.

A computer-aided determining method for the myometrial infiltration depth of early endometrial cancer on MRI images.

To classify early endometrial cancer (EC) on sagittal T2-weighted images (T2WI) by determining the depth of myometrial infiltration (MI) using a computer-aided diagnosis (CAD) method based on a multi-stage deep learning (DL) model. This study retrospectively investigated 154 patients with pathologically proven early EC at the institution between January 1, 2018, and December 31, 2020. Of these patients, 75 were in the International Federation of Gynecology and Obstetrics (FIGO) stage IA and 79 were in FIGO stage IB. An SSD-based detection model and an Attention U-net-based segmentation model were trained to select, crop, and segment magnetic resonance imaging (MRl) images. Then, an ellipse fitting algorithm was used to generate a uterine cavity line (UCL) to obtain MI depth for classification. In the independent test datasets, the uterus and tumor detection model achieves an average precision rate of 98.70% and 87.93%, respectively. Selecting the optimal MRI slices method yields an accuracy of 97.83%. The uterus and tumor segmentation model with mean IOU of 0.738 and 0.655, mean PA of 0.867 and 0.749, and mean DSC of 0.845 and 0.779, respectively. Finally, the CAD method based on the calculated MI depth reaches an accuracy of 86.9%, a sensitivity of 81.8%, and a specificity of 91.7% for early EC classification. In this study, the CAD method implements an end-to-end early EC classification and is found to be on par with radiologists in terms of performance. It is more intuitive and interpretable than previous DL-based CAD methods.

Design and experiments with a single spiral fixed depth ditching and fertilizing machine.

Aiming at the problems of low fertilization efficiency, mainly the process operation and inconsistent fertilization depth of domestic tea garden fertilizer machines, a single-spiral fixed depth ditching and fertilizing machine is appropriately designed. This machine is capable of performing the integrated operation of ditching, fertilization, and covering soil at the same time through the operation mode of single-spiral ditching and fertilization. The theoretical analysis and design of the structure of the main components are properly carried out. The fertilization depth can be adjusted through the established depth control system. The performance test reveals that the single-spiral ditching and fertilizing machine exhibits a maximum stability coefficient of 96.17% and a minimum of 94.29% in terms of trenching depth and a maximum of 94.23% and a minimum of 93.58% in terms of fertilization uniformity, meeting the production requirements of tea plantations.

Study on the relationship between hydrodynamic conditions and arsenic content in Quaternary sediments.

Groundwater is susceptible to arsenic contamination by sediment with high arsenic content, which is the primary culprit of regional arsenic pollution and poisoning. To explore the influence of the change in hydrodynamic conditions caused by changes in the sedimentary environment over time on arsenic content in sediments during the Quaternary, the hydrodynamic characteristics and arsenic content enrichment of borehole sediments were studied in typical high-arsenic groundwater areas of the Jianghan-Dongting Basin, China. The regional hydrodynamic conditions represented by each borehole location were analyzed, the correlation between the variation in groundwater dynamics characteristics and arsenic content in different hydrodynamic periods was analyzed, and the relationship between arsenic content and grain size distribution was quantitatively investigated using grain size parameter calculation, elemental analysis, and statistical estimates of arsenic content in borehole sediments. We observed that the relationship between arsenic content and hydrodynamic conditions differed between sedimentary periods. Furthermore, arsenic content in the sediments from the borehole at Xinfei Village was significantly and positively correlated with a grain size of 127.0-240.0 µm. For the borehole at Wuai Village, arsenic content was significantly and positively correlated with a grain size of 1.38-9.82 µm size (at 0.05 level of significance). However, arsenic content was inversely correlated with grain sizes of 110.99-716.87 and 133.75-282.07 µm at p values of 0.05 and 0.01, respectively. For the borehole at Fuxing Water Works, arsenic content was significantly and positively correlated with a grain size of 409.6-655.0 µm size (at 0.05 level of significance). Arsenic tended to be enriched in transitional and turbidity facies sediments with normal corresponding hydrodynamic strength but poor sorting. Furthermore, continuous and stable sedimentary sequences were conducive to arsenic enrichment. Fine-grain sediments provided abundant potential adsorption sites for high-arsenic sediments, but finer particle size was not correlated with higher arsenic levels.

Carbenoxolone disodium suppresses the migration of gastric cancer by targeting HDAC6.

Aim: Because of the severe morbidity and mortality of gastric cancer, discovering new candidate drugs has been an urgent issue. The close association between histone deacetylase 6 (HDAC6) and gastric cancer makes the development of HDAC6-targeted anti-gastric cancer drugs a viable idea. Methods & results: Carbenoxolone disodium was identified as a novel HDAC6 inhibitor. Cellular thermal shift assay, surface plasmon resonance assay and molecular docking confirmed its binding ability to HDAC6. Cell viability, wound healing and transwell assays as well as animal studies have demonstrated that carbenoxolone disodium could block the proliferation and migration of gastric cancer cells MGC-803 in vitro and in vivo. Conclusion: This is the first report to indicate that carbenoxolone disodium could be an HDAC6 inhibitor with potential for treatment of gastric cancer.

Design and experiments of an automatic depth-adjusting double screw trencher and fertiliserning.

In response to the problems of low fertilizer application efficiency, poor operation quality, and uneven application of fertilizer by domestic tea garden trenching and fertilizing machines, an automatic depth-adjusting double screw trenching and fertilizing machine was designed. The machine uses a double spiral furrowing and fertilizer application method, which can complete the integrated operation of furrowing, fertilizer application, and mulching at one time. The key components of the machine such as the screw-type fertilizer discharger, trenching, and fertilizer application mechanism are designed using theoretical analysis, and the trenching depth is automatically adjusted through the hydraulic control system to maintain a consistent depth. A single-factor test and a quadratic regression rotary orthogonal test were conducted to select the diameter of the spiral fertilizer discharger, the rotational speed of the spiral fertilizer discharger, and the rotational speed of the trenching and fertilizer application mechanisms. Based on these tests, the fertilizer application performance of the fertilizer machine was evaluated, and a mathematical model of the fertilizer application volume and coefficient of variation was established. The influence of the test factors on the coefficient of variation was also analyzed. In the study, 58.36 and 480.35 r/min were found to be the optimal rotational speeds for spiral fertilizer discharge and trenching and fertilizer application, respectively, while 88.90 mm was found to be the optimal diameter for spiral fertilizer discharge. The coefficient of variation for the spiral fertilizer discharge was 3.95%, which meets the tea plantation's fertilizer application requirements.

Silicon enhances plant resistance to Fusarium wilt by promoting antioxidant potential and photosynthetic capacity in cucumber (Cucumis sativus L.).

Fusarium wilt, caused by Fusarium oxysporum f. sp. cucumerinum (Fo), is a severe soil-borne disease affecting cucumber production worldwide, particularly under monocropping in greenhouses. Silicon (Si) plays an important role in improving the resistance of crops to Fusarium wilt, but the underlying mechanism is largely unclear. Here, an in vitro study showed that 3 mmol·l-1 Si had the best inhibitory effect on the mycelial growth of F. oxysporum in potato dextrose agar (PDA) culture for 7 days. Subsequently, the occurrence of cucumber wilt disease and its mechanisms were investigated upon treatments with exogenous silicon under soil culture. The plant height, stem diameter, root length, and root activity under Si+Fo treatment increased significantly by 39.53%, 94.87%, 74.32%, and 95.11% compared with Fo only. Importantly, the control efficiency of Si+Fo was 69.31% compared with that of Fo treatment. Compared with Fo, the activities of peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) significantly increased by 148.92%, 26.47%, and 58.54%, while the contents of H2O2, O 2 · - , and malondialdehyde (MDA) notably decreased by 21.67%, 59.67%, and 38.701%, respectively, in roots of cucumber plants treated with Si + Fo. Compared with Fo treatment, the net photosynthesis rate (Pn), stomatal conductance (Gs), transpiration rate (Tr), maximum RuBisCO carboxylation rates (Vcmax), maximum RuBP regeneration rates (Jmax), and activities of ribulose-1,5-bisphosphate carboxylase (RuBisCO), fructose-1,6-bisphosphatase (FBPase), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the expression of FBPA, TPI, SBPase, and FBPase in Si+Fo treatment increased significantly. Furthermore, Si alleviated stomatal closure and enhanced endogenous silicon content compared with only Fo inoculation. The study results suggest that exogenous silicon application improves cucumber resistance to Fusarium wilt by stimulating the antioxidant system, photosynthetic capacity, and stomatal movement in cucumber leaves. This study brings new insights into the potential of Si application in boosting cucumber resistance against Fusarium wilt with a bright prospect for Si use in cucumber production under greenhouse conditions.

CXCL12/CXCR7/ß-arrestin1 biased signal promotes epithelial-to-mesenchymal transition of colorectal cancer by repressing miRNAs through YAP1 nuclear translocation.

BACKGROUND: Chemokine CXC motif receptor 7 (CXCR7) is an atypical G protein-coupled receptor (GPCR) that signals in a biased fashion. CXCL12/CXCR7 biased signal has been reported to play crucial roles in multiple stages of colorectal cancer (CRC). However, the mechanism of CXCL12/CXCR7 biased signal in promoting CRC progression and metastasis remains obscure. RESULTS: We demonstrate that CXCR7 activation promotes EMT and upregulates the expression of Vimentin and doublecortin-like kinase 1 (DCLK1) in CRC cells with concurrent repression of miR-124-3p and miR-188-5p through YAP1 nuclear translocation. Cell transfection and luciferase assay prove that these miRNAs regulate EMT by targeting Vimentin and DCLK1. More importantly, CXCL12/CXCR7/ß-arrestin1-mediated biased signal induces YAP1 nuclear translocation, which functions as a transcriptional repressor by interacting with Yin Yang 1 (YY1) and recruiting YY1 to the promoters of miR-124-3p and miR-188-5p. Pharmacological inhibitor of YAP1 suppresses EMT and tumor metastasis upon CXCR7 activation in vivo in tumor xenografts of nude mice and inflammatory colonic adenocarcinoma models. Clinically, the expression of CXCR7 is positively correlated with nuclear YAP1 levels and EMT markers. CONCLUSIONS: Our studies reveal a novel mechanism and clinical significance of CXCL12/CXCR7 biased signal in promoting EMT and invasion in CRC progression. These findings highlight the potential of targeting YAP1 nuclear translocation in hampering CXCL12/CXCR7 biased signal-induced metastasis of colorectal cancer.

Consideration of high-quality development strategies for soil and water conservation on the loess plateau.

The construction of check dams is an important measure to prevent soil erosion on the Loess Plateau and reduce the amount of sediment entering the Yellow River. Based on an analysis of the current situation of soil and water conservation on the Loess Plateau and the three major problems faced by the traditional homogeneous soil check dam construction, the study of anti-scouring materials, hydrological calculation methods, dam design and construction technology and soil and water conservation monitoring are carried out in this paper. The results showed that the current soil and water conservation measures on the Loess Plateau have achieved remarkable outcomes. The new design and application concept of check dams with anti-burst and multi-sand interceptions is innovatively proposed in this paper. The new materials of solidified loess have good durability and anti-scouring characteristics and could meet the overflow and anti-scouring requirements of the new check dam. The small watershed high sand content of hydrological calculation can establish the upper limit of the flood sediment boundary for the anti-scouring protection layer of the check dam. The new technology of dam design and construction can achieve no collapse or slow collapse when encountering floods exceeding the standard. Intelligent monitoring systems can realize real-time dynamic monitoring for soil and water conservation on the Loess Plateau. The results will eventually contribute to the national strategy of the Ecological Protection and High Quality Development in the Yellow River basin.

GrpE is involved in mitochondrial function and is an effective target for RNAi-mediated pest and arbovirus control.

Laodelphax striatellus is a sap-feeding pest and the main insect vector of rice stripe virus (RSV). There is an urgent need to identify molecular targets to control this insect pest and plant arboviruses. In this study, we identified a L. striatellus gene (named LsGrpE) encoding a GroP-E-like protein. We found that the LsGrpE protein localized to mitochondria. Using gene-specific dsRNA to interfere with the expression of LsGrpE led to a significant increase in insect mortality, and most of the surviving insects could not develop into adults. Further analyses revealed that LsGrpE deficiency caused mitochondrial dysfunction and inhibited the insulin pathway, resulting in diabetes-like symptoms such as elevated blood sugar, inactive behaviour, developmental delay, and death. In addition, LsGrpE deficiency significantly reduced the RSV titre in surviving L. striatellus, and indirectly prevented viral vertical transmission by reducing the number of adults. We generated transgenic rice plants expressing LsGrpE-specific dsRNA, and the dsRNA was acquired by L. striatellus during feeding, resulting in increased insect mortality and the prevention of arboviral transmission. This study clarifies the function of LsGrpE and demonstrates that LsGrpE can be used as a molecular target of plant-generated dsRNA to resist this sap-feeding pest, a17nd therefore, its transmitted arboviruses.

Identification and comparative expression analysis of odorant-binding proteins in the reproductive system and antennae of Athetis dissimilis.

Odorant-binding proteins (OBPs) are prevalent in the antennal transcriptomes of different orders of insects. Studies on OBPs have focused on their role in the insect chemosensory system, but knowledge of their functions in the insect testis is limited. We sequenced the transcriptomes of the Athetis dissimilis reproductive organs and analyzed the expression of AdisOBP genes in different tissues. We identified 23 OBPs in the testis and ovaries and 31 OBPs in antennal transcriptomes. The results of real-time quantitative PCR revealed that 23 of the 54 OBP genes were highly expressed in both female and male antennae, including three that exhibited male-biased expression and 15 that exhibited female-biased expression. A total of 24 OBPs were highly expressed in the testis of A. dissimilis, while expression of OBPs in the ovaries was very low. These findings highlight the functional diversity of OBPs in insects and can facilitate further studies on the OBPs in A. dissimilis and lepidopteran species.

Monobenzone, a Novel and Potent KDM1A Inhibitor, Suppresses Migration of Gastric Cancer Cells.

Lysine-specific demethylase1 (KDM1A) is generally highly expressed in various cancer tissues, and promotes the initiation and development of cancers via diverse cellular signaling pathways. Therefore, KDM1A is a promising drug target in many cancers, and it is crucial to find effective KDM1A inhibitors, while none of them has entered into market. With the help of compound library, monobenzone, a local depigmentor using as a treating over-pigmentation in clinic, was characterized as an effective KDM1A inhibitor (IC50 = 0.4507 µM), which may competitively inhibit KDM1A reversibly. Further cellular study confirmed that monobenzone could inhibit the proliferation of gastric cancer cell lines MGC-803 and BGC-823 with IC50 as 7.82 ± 0.55 µM and 6.99 ± 0.51 µM, respectively, and erase the substrate of KDM1A, H3K4me1/2 and H3K9 me2, and inhibit the migration of gastric cancer cell by reversing epithelial-mesenchymal transition (EMT). As the structure of monobenzone is very simple and small, this study provides a novel backbone for the further optimization of KDM1A inhibitor and gives monobenzone potential new application.

Exosomal miR-4443 promotes cisplatin resistance in non-small cell lung carcinoma by regulating FSP1 m6A modification-mediated ferroptosis.

AIMS: Exosomal transfer of miRNAs affects recipient cell proliferation and chemoresistance. Here, we aimed to investigate the role of exosomal miRNAs in controlling cisplatin resistance in non-small cell lung carcinoma (NSCLC). MAIN METHODS: Paired tumor and normal tissue-derived exosomes were collected from NSCLC patients with low or high responsiveness to cisplatin treatment. The results showed that the microRNA-4443 (miR-4443) level was upregulated in cisplatin-resistant NSCLC tumor tissue-derived exosomes compared with cisplatin-sensitive tissue-derived exosomes. Cisplatin-resistant cells (A549-R) were generated from the parental cells (A549-S). Resistant exosomes conferred cisplatin resistance by transferring miR-4443 to sensitive cells. Moreover, overexpression of miR-4443 inhibited FSP1-mediated ferroptosis induced by cisplatin treatment in vitro and enhanced tumor growth in vivo. KEY FINDINGS: Through bioinformatics analysis and luciferase assays, METTL3 was confirmed as a direct target gene of miR-4443. Further mechanistic analysis showed that miR-4443 regulated the expression of FSP1 in an m6A manner via METLL3. SIGNIFICANCE: Our findings provide more in-depth insight into the chemoresistance of NSCLC and support the therapeutic potential of targeting ferroptosis.

Capsaicin: A "hot" KDM1A/LSD1 inhibitor from peppers.

Capsaicinoids are plant secondary metabolites, and capsaicin is the main principal that responsible to the pungency of chili peppers, with widely application as food additive. In our study, capsaicin was characterized as lysine specific demethylase 1A (KDM1A/LSD1) inhibitor with IC50 of 0.6 ± 0.0421 µM in biochemical level, and can bind KDM1A recombinant directly and reversibly. Further cellular study confirmed that capsaicin can bind and inhibit KDM1A in gastric cancer cell line BGC-823 and further inhibit cell invasion and migration by reversing epithelial-mesenchymal transition (EMT). In sum, our findings identified KDM1A as a target of capsaicin and reveals capsaicin as a modifier of histone methylation for the first time, which may provide a new skeleton for further optimization of KDM1A inhibitor.

Correction: CXCR7/CXCR4 heterodimer-induced histone demethylation: a new mechanism of colorectal tumorigenesis.

A correction to this paper has been published and can be accessed via a link at the top of the paper.