Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Despite progress in diagnostics and treatment of HCC, its prognosis remains poor. Emerging studies ...showed that long noncoding RNAs (lncRNAs) have crucial regulatory roles in cancer biology. In the current study, differentially expressed lncRNAs between HCC and paired non-tumor tissues were identified using microarrays. The effects of a specific differentially expressed lncRNA (termed ZEB1-AS1) on tumor progression were investigated in vitro and in vivo. We found that ZEB1-AS1 is frequently upregulated in HCC samples, especially in metastatic tumor tissues. DNA methylation analysis shows a tumor-specific ZEB1-AS1 promoter hypomethylation. Aberrant methylation is tightly correlated with overexpression of ZEB1-AS1 in HCC. Patients with ZEB1-AS1 hypomethylation or with high ZEB1-AS1 expression have poor recurrence-free survival. Functionally, ZEB1-AS1 promotes tumor growth and metastasis, acts as an oncogene in HCC. The ZEB1-AS1 gene is located in physical contiguity with ZEB1 and positively regulates the ZEB1 expression. ZEB1 inhibition partially abrogates ZEB1-AS1-induced epithelial to mesenchymal transition (EMT) and cancer metastasis. Our results provide novel insights into the function of lncRNA-driven hepatocarcinogenesis, highlight the important role of ZEB1-AS1 and ZEB1 in HCC progression, and indicate that ZEB1-AS1 may be served as a valuable prognostic biomarker for HCC.
Domain walls may play an important role in future electronic devices, given their small size as well as the fact that their location can be controlled. Here, we report the observation of ...room-temperature electronic conductivity at ferroelectric domain walls in the insulating multiferroic BiFeO(3). The origin and nature of the observed conductivity are probed using a combination of conductive atomic force microscopy, high-resolution transmission electron microscopy and first-principles density functional computations. Our analyses indicate that the conductivity correlates with structurally driven changes in both the electrostatic potential and the local electronic structure, which shows a decrease in the bandgap at the domain wall. Additionally, we demonstrate the potential for device applications of such conducting nanoscale features.
Abstract Background Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor ...rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression. Methods Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects. Results The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control. Conclusions Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.
Cell invasion and migration significantly contribute to tumor metastasis. Microtubule-associated protein 4 (MAP4) protein is one member of microtubule-associate proteins family. It is responsible for ...stabilization of microtubules by modulation of microtubule dynamics. However, there is little information about the involvement of MAP4 in human cancer. Here we show that MAP4 serves as a regulator of invasion and migration in esophageal squamous cancer cells. By activating the ERK-c-Jun-vascular endothelial growth factor A signaling pathway, MAP4 promotes cell invasion and migration in vitro, tumor growth and metastasis in mouse models. Immunohistochemical staining of operative tissues indicated that MAP4 expression was associated with tumor stage, lymph node metastasis and shorter survival of the patients with esophageal squamous cell carcinoma (ESCC). Multivariate Cox regression analysis showed that MAP4 is an independent prognostic indicator. In the serial sections of ESCC tissues, there was a positive correlation between MAP4 and vascular endothelial growth factor A expression. Notably, an intratumoral injection of MAP4-small interfering RNA (siRNA) remarkably inhibited the growth of the tumors that formed by the MAP4-expressing ESCC cells in nude mice, and a combination of MAP4-siRNA and Bevacizumab significantly enhanced the inhibition effect. Our data suggest that MAP4 is probably a useful prognostic biomarker and a potential therapeutic target for the disease.
The analysis of concentration‐discharge (C‐Q) relationships from low‐frequency observations is commonly used to assess solute sources, mobilization, and reactive transport processes at the catchment ...scale. High‐frequency concentration measurements are increasingly available and offer additional insights into event‐scale export dynamics. However, only few studies have integrated inter‐annual and event‐scale C‐Q relationships. Here, we analyze high‐frequency measurements of specific conductance (EC), nitrate (NO3‐N) concentrations and spectral absorbance at 254 nm (SAC254, as a proxy for dissolved organic carbon) over a two year period for four neighboring catchments in Germany ranging from more pristine forested to agriculturally managed settings. We apply an integrated method that adds a hysteresis term to the established power law C‐Q model so that concentration intercept, C‐Q slope and hysteresis can be characterized simultaneously. We found that inter‐event variability in C‐Q hysteresis and slope were most pronounced for SAC254 in all catchments and for NO3‐N in forested catchments. SAC254 and NO3‐N event responses in the smallest forested catchment were closely coupled and explainable by antecedent conditions that hint to a common near‐stream source. In contrast, the event‐scale C‐Q patterns of EC in all catchments and of NO3‐N in the agricultural catchment without buffer zones around streams were less variable and similar to the inter‐annual C‐Q relationship indicating a homogeneity of mobilization processes over time. Event‐scale C‐Q analysis thus added key insights into catchment functioning whenever the inter‐annual C‐Q relationship contrasted with event‐scale responses. Analyzing long‐term and event‐scale behavior in one coherent framework helps to disentangle these scattered C‐Q patterns.
Key Points
We compare event‐scale and inter‐annual concentration‐discharge relationships in four adjoined catchments with contrasting land use
The variability of event‐scale C‐Q relationships was shaped by land use and antecedent conditions for biogeochemically reactive but not for geogenic solutes
For biogeochemically reactive solutes, event‐scale C‐Q patterns can contrast the inter‐annual pattern obtained from all observations
The precipitation behavior of copper-rich phase in an austenitic stainless steel and the interface structure between the precipitates and the matrix have been investigated combining transmission ...electron microscopy and coarsening analysis. The fine dispersed Cu precipitates were spherical and highly stable in the austenite matrix, with the size being only 32nm in diameter even after a long time 10,000h aging at 650°C. The average size of Cu precipitate was increasing with aging time, as predicted by the Lifshitz–Slyozov–Wagner theory. The coherent relationship between the precipitates and the matrix was preserved during the whole aging process, even at the later stage. The interfacial energy of Cu in the austenitic matrix has been independently derived from the data on coarsening experiment based on two kinds of approximations: γ-Fe and Fe–18Cr–9Ni–3Cu matrix were considered separately instead of complex austenite in this study. It was 0.086J/m2 for Cu/γ-Fe and 0.017J/m2 for Cu/Fe–18Cr–9Ni–3Cu. Both values are satisfied with the range of coherent interfacial energy. The coherent interfacial structure and highly stable microstructure play a key role on strengthening materials.
Efficient detection of metastases is important for patient' treatment. This prospective study was to explore the clinical value of contrast-enhanced T2 FLAIR in imaging brain metastases using ...half-dose gadobenate dimeglumine.
In vitro signal intensity of various gadolinium concentrations was explored by spin-echo T1-weighted imaging and T2 FLAIR. Then, 46 patients with lung cancer underwent nonenhanced T2 FLAIR before administration of half-dose gadobenate dimeglumine and 3 consecutive contrast-enhanced T2 FLAIR sequences followed by 1 spin-echo T1WI after administration of half-dose gadobenate dimeglumine. After an additional dose of 0.05 mmol/kg, 3D brain volume imaging was performed. All brain metastases were classified as follows: solid-enhancing, ≥ 5 mm (group A); ring-enhancing, ≥ 5 mm (group B); and lesion diameter of <5 mm (group C). The contrast ratio of the lesions on 3 consecutive phases of contrast-enhanced T2 FLAIR was measured, and the percentage increase of contrast-enhanced T2 FLAIR among the 3 groups was compared.
In vitro, the maximal signal intensity was achieved in T2 FLAIR at one-eighth to one-half of the contrast concentration needed for maximal signal intensity in T1WI. In vivo, the mean contrast ratio values of metastases on contrast-enhanced T2 FLAIR for the 3 consecutive phases ranged from 63.64% to 83.05%. The percentage increase (PI) values of contrast-enhanced T2 FLAIR were as follows: PI
< PI
(
= .001) and PI
< PI
(
< .001). The degree of enhancement of brain metastases on contrast-enhanced T2 FLAIR was lower than on 3D brain volume imaging (
< .001) in group A, and higher than on 3D brain volume imaging (
< .001) in group C.
Small or ring-enhancing metastases can be better visualized on delayed contrast-enhanced T2 FLAIR using a half-dose high-relaxivity contrast agent.
The pure skin perforator (PSP) flap is gaining popularity for its remarkable thinness. The subdermal dissection technique was recently introduced, allowing for a quicker elevation of a PSP flap. In ...this report, we present our two-year experience utilizing subdermal dissection for harvesting PSP flaps.
All patients who had undergone PSP flap reconstruction at our hospital from February 2021 to February 2023 were included. Demographic data, intraoperative variables, flap characteristics, and postoperative outcomes were collected. Surgical planning involved locating the perforator using ultrasound and harvesting the flap using the subdermal dissection technique.
A total of 26 PSP flap reconstructions were conducted on 24 patients aged between 15 and 86 years. The flaps were based on perforators issuing from the superficial circumflex iliac artery in 24 cases, and from the descending branch of the lateral circumflex femoral artery in 2 cases. Flap sizes ranged from 3 × 1.5 cm to 19 × 6 cm, with a mean thickness of 3.48 mm. The average time for flap harvest was 131.92 min. Postoperatively, we observed four cases of partial necrosis, 1 total flap loss, and 2 instances of vascular thrombosis at the anastomosis site. The flaps exhibited good pliability without contracture, and no debulking procedures were required during the follow-up period (minimum 6 months, range 6-24; mean 9.4615).
The subdermal dissection technique is a safe and efficient approach for elevating PSP flaps. Our initial experience with this technique has been encouraging, and it currently serves as our preferred reconstructive option for defects requiring thin reconstruction.
To investigate the utilization of an end-to-end multimodal convolutional model in the rapid and accurate diagnosis of pancreatic diseases using abdominal CT images.
In this study, a novel lightweight ...label-free end-to-end multimodal network (eeMulNet) model was proposed for the rapid and precise diagnosis of abnormal pancreas. The eeMulNet consists of two steps: pancreatic region localization and multimodal CT diagnosis integrating textual and image data. A research dataset comprising 715 CT scans with various types of pancreas diseases and 228 CT scans from a control group was collected. The training set and independent test set for the multimodal classification network were randomly divided in an 8:2 ratio (755 for training and 188 for testing).
The eeMulNet model demonstrated outstanding performance on an independent test set of 188 CT scans (Normal: 45, Abnormal: 143), with an area under the curve (AUC) of 1.0, accuracy of 100%, and sensitivity of 100%. The average testing duration per patient was 41.04 seconds, while the classification network took only 0.04 seconds.
The proposed eeMulNet model offers a promising approach for the diagnosis of pancreatic diseases. It can support the identification of suspicious cases during daily radiology work and enhance the accuracy of pancreatic disease diagnosis. The codes and models of eeMulNet are publicly available at Rudeguy1/eeMulNet (github.com).
•A label-free end-to-end multimodal network (eeMulNet) model were proposed.•On an independent test set of CT, the area under the curve was 1.0.•The classification network only took 0.04 seconds duration per patient.
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