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Supplementary Figure 1-7 Figure S1. Effects of KLF4 overexpression on tumorsphere formation and liver metastasis of cancer stem-like cells; Figure S2. Effect of Klf4 gene disruption on cell morphology of mouse pancreatic cancer cells; Figure S3. IHC staining of Klf4 and CD44 expressions in intestinal tissues Figure S4. KLF4 and CD44 expressions in PANC-1 cells; Figure S5. KLF4 inhibits CD44v and ESRP-1 expressions in pancreatic and colon cancer cells; Figure S6. KLF4 expression correlates with metastatic potential in human cancer cells; Figure S7. KLF4/CD44 expressions in primary and metastatic tumor tissues

Purpose:IFITM3, an IFN-inducible gene, is overexpressed in human colorectal cancer. In this study, we sought to determine the clinical significance and underlying mechanisms of its dysregulated expression in human colon tumor specimens and murine models of this disease.Experimental Design: IFITM3 expression in a tissue microarray of tumor and matched normal colon tissue specimens and lymph node metastasis specimens obtained from 203 patients with colon cancer was measured immunohistochemically.Results: IFITM3 was expressed at higher levels in colon tumors and, particularly, nodal metastases than in normal colon tissue. A Cox proportional hazards model showed that IFITM3 expression was an independent prognostic factor for disease-free survival in patients with colon cancer. Knockdown of IFITM3 expression by a specific siRNA significantly suppressed the proliferation, colony formation, migration, and invasion of colon cancer cells in vitro and tumor growth and metastasis in a xenograft model. Restored expression of KLF4, a putative tumor suppressor, downregulated IFITM3 expression in colon cancer cells in vitro. Two KLF4-binding sites in the IFITM3 promoter bound specifically to KLF4 protein in a chromatin immunoprecipitation assay and promoter mutagenesis analyses. Specific deletion of KLF4 led to IFITM3 overexpression in colon mucosa in Villin-Cre+;Klf4fl/fl mice. An inverse correlation between loss of KLF4 expression and IFITM3 overexpression was evident in human colon tumors.Conclusion: These clinical and mechanistic findings indicate that IFITM3 is a direct transcriptional target of KLF4 and that dysregulated KLF4 expression leads to aberrant IFITM3 expression, thus contributing to colon cancer progression and metastasis. Clin Cancer Res; 17(11); 3558–68. ©2011 AACR.

Supplemental Figure Legends Figure S1. Effects of KLF4 overexpression on tumorsphere formation and liver metastasis of cancer stem-like cells; Figure S2. Effect of Klf4 gene disruption on cell morphology of mouse pancreatic cancer cells; Figure S3. IHC staining of Klf4 and CD44 expressions in intestinal tissues; Figure S4. KLF4 and CD44 expressions in PANC-1 cells; Figure S5. KLF4 inhibits CD44v and ESRP-1 expressions in pancreatic and colon cancer cells; Figure S6. KLF4 expression correlates with metastatic potential in human cancer cells; Figure S7. KLF4/CD44 expressions in primary and metastatic tumor tissues

One file contains 3 Supplementary Tables: Supplementary Table S1. Clinicopathologic characteristics of the PDAC patients from whom the TMA specimens were obtained; Supplementary Table S2. STK33 protein expression in PDAC TMA specimens and its relationship with patient clinicopathologic characteristics; Supplementary Table S3. The sequences of the gene-specific primers used in real-time PCR analysis, vector constructs, and ChIP analysis

One file contains 8 Supplementary Figures and legends Supplementary Figure S1. STK33 expression patterns in human PDAC and adjacent normal pancreatic tissue specimens; Supplementary Figure S2. STK33 expression patterns in human PDAC cells; Supplementary Figure S3. Subcellular expression of STK33 and impact on patient OS; Supplementary Figure S4. Impacts of altered STK33 expression on cell proliferation; Supplementary Figure S5. STK33-promoted PDAC cell metastasis in vivo; Supplementary Figure S6. STK33 promoted PDAC lung metastasis in vivo; Supplementary Figure S7. Co-expression of STK33 and HIF-1α in PDAC tissue; Supplementary Figure S8. Impact of STK33 and HIF-1α expression on PDAC patient survival

Supplementary Tables Table S1. CD44 expression and clinicopathologic characteristics; Table S2. KLF4 expression and clinicopathologic characteristics; Table S3. Specific primers for target and control genes; Table S4. Antibodies for target and control protein expression in Western blot analyses

SADS-CoV is the documented spillover of a bat coronavirus that causes severe disease in pigs. Pigs are in frequent contact with both humans and other animals and theoretically possess a greater chance, compared to many other species, of promoting cross-species viral transmission.

PDF file - 77K, Cell scratch-wound assay; Cell migration assay; Cell invasion assay.

PDF file - 1105K, Supplementary Fig. S1. FOXM1 overexpression and its direct association with clinicopathological parameters in pancreatic cancer cases. Supplementary Fig. S2. FoxM1 isoforms and PCR primers and verifications using cDNA and tumor mRNA as templates. Supplementary Fig. S3. FOXM1b, FOXM1b1, and FOXM1b2 expression in pancreatic cancer cells. Supplementary Fig. S4. Influence of altered expression of FOXM1 isoforms on pancreatic tumor growth and metastasis. Supplementary Fig. S5. Suppression of pancreatic cancer cell migration and invasion by knockdown of FOXM1 expression. Supplementary Fig. S6. FOXM1 promoter activity in pancreatic cancer cells. Supplementary Fig. S7. FOXM1c signaling in pancreatic cancer.

Supplementary Figures 1-6 from Combining Betulinic Acid and Mithramycin A Effectively Suppresses Pancreatic Cancer by Inhibiting Proliferation, Invasion, and Angiogenesis

Structural hemispheric asymmetry has long been assumed to guide functional asymmetry of the human brain, but empirical evidence for this compelling hypothesis remains scarce. Recently, it has been suggested that microstructural asymmetries may be more relevant to functional asymmetries than macrostructural asymmetries. To investigate the link between microstructure and function, we analyzed multimodal MRI data in 907 participants. We quantified structural and functional asymmetries of the planum temporale (PT), a cortical area crucial for auditory-language processing. We found associations of functional PT asymmetries and several microstructural asymmetries, such as intracortical myelin content, neurite density, and neurite orientation dispersion. The PT microstructure per se also showed hemispheric-specific coupling with PT functional activity. All these functional-structural associations are highly specific to within-PT functional activity during auditory-language processing. These results suggest that structural asymmetry guides functional lateralization of the same brain area and highlight a critical role of microstructural PT asymmetries in auditory-language processing.

In fault diagnosis, partial least squares (PLS) is a popular data-driven method to identify abnormal key performance indicators (KPI). However, there are two problems in fault diagnosis when using PLS, including inaccurate fault subspace extraction and unidentified false alarms. In the first problem, the improved PLS (IPLS) model is adopted to obtain a precise subspace through orthogonal decomposition. In addition, to eliminate the normal value in fault data, a quality-related fault subspace (QRFS) extraction method is proposed, which can extract a purer quality-related fault subspace. In the second problem, to provide feedback for false alarms, a modified IPLS (M-IPLS) model is proposed to extract the quality-unrelated fault subspace. Based on the proposed fault subspace extraction methods, the fault can be reconstructed by a lower dimensional fault subspace and false alarms with feedback can improve the efficiency of diagnosis. Finally, two examples, including a numerical simulation and the Tennessee Eastman process (TEP), are used to show the effectiveness of the proposed method.

Strokes to the left and right hemisphere lead to distinctive behavioral profiles. Are left and right hemisphere strokes (LHS and RHS) associated with distinct or common poststroke neuroplasticity patterns? Understanding this issue would reveal hemispheric neuroplasticity mechanisms in response to brain damage. To this end, we investigated poststroke structural changes (2 weeks to 3 months post-onset) using longitudinal MRI data from 69 LHS and 55 RHS patients and 31 demographic-matched healthy control participants. Both LHS and RHS groups showed statistically common plasticity independent of the lesioned hemisphere, including 1) gray matter (GM) expansion in the ipsilesional and contralesional precuneus, and contralesional superior frontal gyrus; 2) GM shrinkage in the ipsilesional medial orbital frontal gyrus and middle cingulate cortex. On the other hand, only RHS patients had significant GM expansion in the ipsilesional medial superior and orbital frontal cortex. Importantly, these common and unique GM changes post-stroke largely overlapped with highly-connected cortical hub regions in healthy individuals. Moreover, they correlated with behavioral recovery, indicating that post-stroke GM volumetric changes in cortical hubs reflect compensatory rather than maladaptive mechanisms. These results highlight the importance of structural neuroplasticity in hub regions of the cortex, along with the hemispheric specificity, for stroke recovery.

Background Pancreaticobiliary reflux (PBR) causes chronic inflammation of the gallbladder mucosa and changes in the bile components, which are known to promote gallstone formation. This study aimed to investigate the bile biochemistry changes in gallstone patients with PBR and provide new clues for research on the involvement of PBR in gallstone formation. Methods Patients undergoing surgery for gallstones between December 2020 and May 2021 were eligible for inclusion. The bile biochemistry (including amylase, lipase, triglyceride, cholesterol, free fatty acids [FFAs], alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP], and γ-glutamyl transferase [γ-GT]) of the included gallstone patients was analysed to determine correlations with PBR. Results In this study, 144 gallstone patients who underwent surgery were enrolled. Overall, 15.97 % of the patients had an increased bile amylase level, which was associated with older age and significantly higher bile levels of ALP, lipase, triglyceride, and FFAs. Positive correlations were observed between amylase and lipase, triglyceride, FFAs levels in the gallbladder bile. However, the bile levels of triglyceride, FFAs, and lipase were positively correlated with each other only in the PBR group and showed no significant correlation in the control (N) group. In addition, elevated bile FFAs levels were found to be an independent risk factor for gallbladder wall thickening. Conclusions In conclusion, PBR-induced increase in FFAs and triglyceride in the gallbladder bile is a cause of gallstone formation, and an increase in bile ALP suggests the presence of cholestasis in PBR.

Introduction: Occult pancreaticobiliary reflux (OPBR) causes chronic inflammation of the gallbladder and associated mucosal malignant changes, but its pathogenic mechanism remains unclear. Objective The aim of this study was to investigate the pathogenic mechanism in OPBR through untargeted metabolomic analysis of bile collected during surgery. Methods Patients undergoing surgery for gallstones between December 2020 and May 2021 were eligible for inclusion. There were 30 OPBR patients and 338 non-OPBR patients, and 30 non-OPBR patients were randomly selected as normal controls. Metabolomics analysis was performed based on bile samples from patients in the OPBR group. Results The principal component analysis by liquid chromatography-mass spectrometry revealed that 30 metabolites were significantly different between patients with OPBR compared to controls. Among these characteristic metabolites, palmitic acid and arachidonic acid are known to be involved in gallstone formation, methionine and lysophosphatidylcholine are known to be associated with carcinogenesis. Conclusions The present study suggested that an LC/MS-based metabolomic studies provide an efficient and promising method for identifying potential biomarkers of OPBR. The identified characteristic metabolites in the OPBR group were significantly different to the control group.

Bats are reservoirs for diverse coronaviruses, including swine acute diarrhea syndrome coronavirus (SADS-CoV). SADS-CoV was first identified in diarrheal piglets in 2017. As a novel alphacoronavirus, SADS-CoV shares ~95% identity with bat alphacoronavirus HKU2. SADS-CoV has been reported to have broad cell tropism and inherent potential to cross host species barriers for dissemination. Thus far, no effective antiviral drugs or vaccines are available to treat infections with SADS-CoV. Therefore, knowledge of the protein-coding gene set and a subcellular localization map of SADS-CoV proteins are fundamental first steps in this endeavor. Here, all SADS-CoV genes were cloned separately into Flag-tagged plasmids, and the subcellular localizations of viral proteins, with the exception of nsp11, were detected using confocal microscopy techniques. As a result, nsp1, nsp3-N, nsp4, nsp5, nsp7, nsp8, nsp9, nsp10, nsp14, and nsp15 were localized in the cytoplasm and nuclear spaces, and these viral proteins may perform specific functions in the nucleus. All structural and accessory proteins were mainly localized in the cytoplasm. NS7a and membrane protein M colocalized with the Golgi compartment, and they may regulate the assembly of SADS-CoV virions. Maturation of SADS-CoV may occur in the late endosomes, during which envelope protein E is involved in the assembly and release of the virus. In summary, the present study demonstrates for the first time the location of all the viral proteins of SADS-CoV. These fundamental studies of SADS-CoV will promote studies of basic virology of SADS-CoV and support preventive strategies for animals with infection of SADS-CoV. IMPORTANCE SADS-CoV is the first documented spillover of a bat coronavirus that causes severe diseases in domestic animals. Our study is an in-depth annotation of the newly discovered swine coronavirus SADS-CoV genome and viral protein expression. Systematic subcellular localization of SADS-CoV proteins can have dramatic significance in revealing viral protein biological functions in the subcellular locations. Furthermore, our study promote understanding the fundamental science behind the novel swine coronavirus to pave the way for treatments and cures.

The traditional line matching method has the problems of inaccurate endpoint location, small matching quantity and long time-consuming for images with large viewpoint variation, and the present point matching technology for the same type of image is facing the challenge of improving the matching quantity and accuracy. To solve these problems, a feature matching method based on the maximum number of consecutive matching edge segment pairs (MNCME) is proposed. Firstly, structural edges are extracted from the comparative images and segmented by edge corners. Then, the disambiguating geometric attributes are utilized to describe the edge segment, and the similarity of edge segments is represented by the sum of the differences between their geometric attributes. Finally, the edge correspondence is established based on the maximum number of consecutive matching edge segment pairs. The generated matches contain lines and points. Through combining MNCME with SIFT, the number of point matches improves greatly. To verify the performance of this method, it is compared with the state-of-the-art feature matching technology, and a series of large viewpoint changing image pairs with high-definition and abundant structural information are adopted. The results of line matching show that MNCME has better matching accuracy and time efficiency than relevant line matching technologies. The point matching results show that MNCME + SIFT is superior to other related algorithms in matching quantity, speed and correctness.

In this paper, we propose an effective neural network algorithm to perform singular value decomposition (SVD) of a cross-correlation matrix between two data streams. Different from traditional algorithms, the newly proposed algorithm can extract not only the principal singular vectors but also the corresponding principal singular values. First, a dynamical system is obtained from the gradient flow, which is obtained from optimization of a novel information criterion. Then, based on the dynamical system, a stable neural network algorithm, which can extract the left and right principal singular vectors, is obtained. Moreover, by satisfying orthogonality instead of orthonormality, we are able to extract the normalization scale factor as the corresponding singular value. In this case, the principal singular triplet (principal singular vectors and the corresponding singular value) of the cross-correlation matrix can be extracted by using the proposed algorithm. What’s more, the proposed algorithm can also be used for multiple PSTs extraction on the basis of sequential method. Then, convergence analysis shows that the proposed algorithm converges to the stable equilibrium point with probability 1. Last, experiment results show that the proposed algorithm is fast and stable in convergence, and can also extract multiple PSTs efficiently.

This paper is concerned with the existence of positive radial solutions of the following resonant elliptic system: $$ \textstyle\begin{cases} -\Delta u=uv+f( \vert x \vert ,u), & 0< R_{1}< \vert x \vert < R_{2}, x\in \mathbb{R}^{N}, \\ -\Delta v=cg(u)-dv, & 0< R_{1}< \vert x \vert < R_{2}, x\in \mathbb{R}^{N}, \\ \frac{\partial u}{\partial \textbf{n}}=0= \frac{\partial v}{\partial \textbf{n}},& \vert x \vert =R_{1}, \vert x \vert =R_{2}, \end{cases} $$ { − Δ u = u v + f ( | x | , u ) , 0 < R 1 < | x | < R 2 , x ∈ R N , − Δ v = c g ( u ) − d v , 0 < R 1 < | x | < R 2 , x ∈ R N , ∂ u ∂ n = 0 = ∂ v ∂ n , | x | = R 1 , | x | = R 2 , where $\mathbb{R}^{N}$ R N ($N\geq 1$ N ≥ 1 ) is the usual Euclidean space, n indicates the outward unit normal vector, $f\in C([R_{1},R_{2}]\times [0,\infty ),\mathbb{R})$ f ∈ C ( [ R 1 , R 2 ] × [ 0 , ∞ ) , R ) , $g\in C([0,\infty ),[0,\infty ))$ g ∈ C ( [ 0 , ∞ ) , [ 0 , ∞ ) ) , and c and d are positive constants. By employing the classical fixed point theory we establish several novel existence theorems. Our main findings enrich and complement those available in the literature.