IPO7 promotes pancreatic cancer progression via regulating ERBB pathway

Background: Importin 7 (IPO7) belongs to the Importin β family and is implicated in the progression of diverse human malignancies. This work is performed to probe the role of IPO7 in pancreatic cancer development and its potential downstream mechanisms. Methods: IPO7 expression in PC and paracancerous tissues were measured using Immunohistochemistry (IHC) staining and qRT-PCR. Western blotting was utilized to detect the expression level of IPO7 in PC cells and immortalize the pancreatic ductal epithelial cell line. After constructing the IPO7 overexpression and knockdown models, the effect of IPO7 on the proliferation of PC cells was analyzed by the CCK-8 and EdU assay. The migration and invasion of PC cells were examined by wound healing assay and Transwell experiment. The apoptosis rate of PC cells was analyzed by flow cytometry and TUNEL assay. The Gene Set Enrichment Analysis (GSEA) was used to determine the enrichment pathways of IPO7. The effect of IPO7 on the ERBB2 expression was determined using Western blotting. A xenograft mouse model was applied to investigate the carcinogenic effect of IPO7 in vivo. Results: IPO7 expression was remarkably elevated in the cancer tissues of PC patients. IPO7 overexpression remarkably enhanced PC cell proliferation, migration and invasion and suppressed apoptosis, while knockdown of IPO7 exerted the opposite effect. Mechanistically, IPO7 facilitated the malignant phenotype of PC cells by up-regulating ERBB2 expression. In addition, knockdown of IPO7 inhibited tumor growth and lung metastasis in vivo. Conclusion: IPO7 can act as an oncogenic factor and accelerate PC progression by modulating the ERBB pathway

An Improved Histogram Based Boosting Detection Rate Video Watermarking Algorithm

The existing histogram based video watermarking algorithm with temporal modulated is robust to combined attacks, but the watermark detection rate is not high due to watermark cannot embedded to the smoothness and still areas effectively. To increase the watermark detection rate, in this paper, we proposed the improved algorithm of shot segmentation first and then propose an improved video watermarking algorithm which firstly construct the watermark template in each frame video in the same shot through computing block based histogram and selecting the position of the relative high variance. Then we embed the watermark template into the video frame by temporal modulation without changing the destination of the shot group of the consecutive frames. The watermark sequence is extracted by comparing the correlation distribution of video frame and corresponding watermark template in the time domain. Experimental results demonstrate that the proposed algorithm is robust to recording attacks and guarantee the watermarking video quality at the same time, besides the watermark sequences can embedded to the smoothness and still areas effectively, and the watermark detection rate can increase by about 10% than previous methods

Incremental learning-based visual tracking with weighted discriminative dictionaries

Existing sparse representation-based visual tracking methods detect the target positions by minimizing the reconstruction error. However, due to complex background, illumination change, and occlusion problems, these methods are difficult to locate the target properly. In this article, we propose a novel visual tracking method based on weighted discriminative dictionaries and a pyramidal feature selection strategy. First, we utilize color features and texture features of the training samples to obtain multiple discriminative dictionaries. Then, we use the position information of those samples to assign weights to the base vectors in dictionaries. For robust visual tracking, we propose a pyramidal sparse feature selection strategy where the weights of base vectors and reconstruction errors in different feature are integrated together to get the best target regions. At the same time, we measure feature reliability to dynamically adjust the weights of different features. In addition, we introduce a scenario-aware mechanism and an incremental dictionary update method based on noise energy analysis. Comparison experiments show that the proposed algorithm outperforms several state-of-the-art methods, and useful quantitative and qualitative analyses are also carried out

Unsupervised image saliency detection with Gestalt-laws guided optimization and visual attention based refinement.

Visual attention is a kind of fundamental cognitive capability that allows human beings to focus on the region of interests (ROIs) under complex natural environments. What kind of ROIs that we pay attention to mainly depends on two distinct types of attentional mechanisms. The bottom-up mechanism can guide our detection of the salient objects and regions by externally driven factors, i.e. color and location, whilst the top-down mechanism controls our biasing attention based on prior knowledge and cognitive strategies being provided by visual cortex. However, how to practically use and fuse both attentional mechanisms for salient object detection has not been sufficiently explored. To the end, we propose in this paper an integrated framework consisting of bottom-up and top-down attention mechanisms that enable attention to be computed at the level of salient objects and/or regions. Within our framework, the model of a bottom-up mechanism is guided by the gestalt-laws of perception. We interpreted gestalt-laws of homogeneity, similarity, proximity and figure and ground in link with color, spatial contrast at the level of regions and objects to produce feature contrast map. The model of top-down mechanism aims to use a formal computational model to describe the background connectivity of the attention and produce the priority map. Integrating both mechanisms and applying to salient object detection, our results have demonstrated that the proposed method consistently outperforms a number of existing unsupervised approaches on five challenging and complicated datasets in terms of higher precision and recall rates, AP (average precision) and AUC (area under curve) values

3D-Epigenomic Regulation of Gene Transcription in Hepatocellular Carcinoma.

The fundamental cause of transcription dysregulation in hepatocellular carcinoma (HCC) remains elusive. To investigate the underlying mechanisms, comprehensive 3D-epigenomic analyses are performed in cellular models of THLE2 (a normal hepatocytes cell line) and HepG2 (a hepatocellular carcinoma cell line) using integrative approaches for chromatin topology, genomic and epigenomic variation, and transcriptional output. Comparing the 3D-epigenomes in THLE2 and HepG2 reveal that most HCC-associated genes are organized in complex chromatin interactions mediated by RNA polymerase II (RNAPII). Incorporation of genome-wide association studies (GWAS) data enables the identification of non-coding genetic variants that are enriched in distal enhancers connecting to the promoters of HCC-associated genes via long-range chromatin interactions, highlighting their functional roles. Interestingly, CTCF binding and looping proximal to HCC-associated genes appear to form chromatin architectures that overarch RNAPII-mediated chromatin interactions. It is further demonstrated that epigenetic variants by DNA hypomethylation at a subset of CTCF motifs proximal to HCC-associated genes can modify chromatin topological configuration, which in turn alter RNAPII-mediated chromatin interactions and lead to dysregulation of transcription. Together, the 3D-epigenomic analyses provide novel insights of multifaceted interplays involving genetics, epigenetics, and chromatin topology in HCC cells

Involvement of 5-HT1A receptors of the thalamic descending pathway in the analgesic effect of intramuscular heating-needle stimulation in a rat model of lumbar disc herniation

BackgroundIntramuscular (IM) heating-needle therapy, a non-painful thermal therapy, has been found to exert an analgesic effect via the thalamic ventromedial (VM) nucleus, solely by reducing the triggering threshold for descending inhibition; this could be modulated by intracephalic 5-hydroxytryptamine-1A (5-HT1A) receptors, rather than via the regular analgesia pathway. In this study, the effect and the potential serotonergic mechanism of IM heating-needle stimulation at 43°C were explored in the case of the pathological state of lumbar disc herniation (LDH).MethodsA modified classic rat model of LDH, induced via autologous nucleus pulposus implantation, was utilized. IM inner heating-needles were applied at the attachment point of skeletal muscle on both sides of the L4 and L5 spinous processes. WAY-100635 and 8-OH-DAPT, 5-HT1A receptor antagonist and agonist, were separately injected into the bilateral thalamic mediodorsal (MD) and VM nucleus via an intrathalamic catheter. Nociception was assessed by bilateral paw withdrawal reflexes elicited by noxious mechanical and heat stimulation.ResultsIM heating-needle stimulation at a temperature of 43°C for 30 or 45 min significantly relieved both mechanical and heat hyperalgesia in the rat model of LDH (P < 0.05). Heat hyperalgesia was found to be significantly enhanced by administration of WAY-100635 into the thalamic VM nucleus, blocking the effect of heating-needle stimulation in a dose-dependent manner (P < 0.05), while no effects were detected after injection into the thalamic MD nucleus (P > 0.05). Injection of 8-OH-DAPT into the thalamic MD nucleus exerted no modulating effects on either mechanical or heat hyperalgesia (P > 0.05).ConclusionIM heating-needle stimulation at 43°C for 30 min may activate 5-HT1A mechanisms, via the thalamic VM nucleus, to attenuate hyperalgesia in a rat model of LDH. This innocuous form of thermal stimulation is speculated to selectively activate the descending inhibition mediated by the thalamic VM nucleus, exerting an analgesic effect, without the involvement of descending facilitation of the thalamic MD nucleus

Lineage tracing for multiple lung cancer by spatiotemporal heterogeneity using a multi-omics analysis method integrating genomic, transcriptomic, and immune-related features

IntroductionThe distinction between multiple primary lung cancer (MPLC) and intrapulmonary metastasis (IPM) holds clinical significance in staging, therapeutic intervention, and prognosis assessment for multiple lung cancer. Lineage tracing by clinicopathologic features alone remains a clinical challenge; thus, we aimed to develop a multi-omics analysis method delineating spatiotemporal heterogeneity based on tumor genomic profiling.MethodsBetween 2012 and 2022, 11 specimens were collected from two patients diagnosed with multiple lung cancer (LU1 and LU2) with synchronous/metachronous tumors. A novel multi-omics analysis method based on whole-exome sequencing, transcriptome sequencing (RNA-Seq), and tumor neoantigen prediction was developed to define the lineage. Traditional clinicopathologic reviews and an imaging-based algorithm were performed to verify the results.ResultsSeven tissue biopsies were collected from LU1. The multi-omics analysis method demonstrated that three synchronous tumors observed in 2018 (LU1B/C/D) had strong molecular heterogeneity, various RNA expression and immune microenvironment characteristics, and unique neoantigens. These results suggested that LU1B, LU1C, and LU1D were MPLC, consistent with traditional lineage tracing approaches. The high mutational landscape similarity score (75.1%), similar RNA expression features, and considerable shared neoantigens (n = 241) revealed the IPM relationship between LU1F and LU1G which were two samples detected simultaneously in 2021. Although the multi-omics analysis method aligned with the imaging-based algorithm, pathology and clinicopathologic approaches suggested MPLC owing to different histological types of LU1F/G. Moreover, controversial lineage or misclassification of LU2’s synchronous/metachronous samples (LU2B/D and LU2C/E) traced by traditional approaches might be corrected by the multi-omics analysis method. Spatiotemporal heterogeneity profiled by the multi-omics analysis method suggested that LU2D possibly had the same lineage as LU2B (similarity score, 12.9%; shared neoantigens, n = 71); gefitinib treatment and EGFR, TP53, and RB1 mutations suggested the possibility that LU2E might result from histology transformation of LU2C despite the lack of LU2C biopsy and its histology. By contrast, histological interpretation was indeterminate for LU2D, and LU2E was defined as a primary or progression lesion of LU2C by histological, clinicopathologic, or imaging-based approaches.ConclusionThis novel multi-omics analysis method improves the accuracy of lineage tracing by tracking the spatiotemporal heterogeneity of serial samples. Further validation is required for its clinical application in accurate diagnosis, disease management, and improving prognosis

Interaction between Dysfunctional Connectivity at Rest and Heroin Cues-Induced Brain Responses in Male Abstinent Heroin-Dependent Individuals

BACKGROUND: The majority of previous heroin cue-reactivity functional magnetic resonance imaging (fMRI) studies focused on local function impairments, such as inhibitory control, decision-making and stress regulation. Our previous studies have demonstrated that these brain circuits also presented dysfunctional connectivity during the resting state. Yet few studies considered the relevance of resting state dysfunctional connectivity to task-related neural activity in the same chronic heroin user (CHU). METHODOLOGY/PRINCIPAL FINDINGS: We employed the method of graph theory analysis, which detected the abnormality of brain regions and dysregulation of brain connections at rest between 16 male abstinent chronic heroin users (CHUs) and 16 non-drug users (NDUs). Using a cue-reactivity task, we assessed the relationship between drug-related cue-induced craving activity and the abnormal topological properties of the CHUs' resting networks. Comparing NDUs' brain activity to that of CHUs, the intensity of functional connectivity of the medial frontal gyrus (meFG) in patients' resting state networks was prominently greater and positively correlated with the same region's neural activity in the heroin-related task; decreased functional connectivity intensity of the anterior cingulate cortex (ACC) in CHUs at rest was associated with more drug-related cue-induced craving activities. CONCLUSIONS: These results may indicate that there exist two brain systems interacting simultaneously in the heroin-addicted brain with regards to a cue-reactivity task. The current study may shed further light on the neural architecture that supports craving responses in heroin dependence

Acute Gaseous Air Pollution Exposure and Hospitalizations for Acute Ischemic Stroke: A Time-Series Analysis in Tianjin, China

Background: Stroke has always been an important problem troubling human health. Short-term exposure to air pollutants is associated with increased hospital admissions. The rise of pollutants such as O3 has caused a huge social and economic burden. This study aims to explore the relationship between short-term exposure to ambient gaseous pollutants and daily hospitalizations for ischemic stroke, utilizing a four-year time-series study in Tianjin. Methods: Collecting the data of gaseous pollutants (NO2, SO2, CO, O3), meteorological data (including daily average temperature and relative humidity) and the number of hospitalizations due to ischemic stroke in Tianjin Medical University General Hospital from 2013 to 2016. Poisson regression generalized additive model with single-day and multi-day moving average lag structure was used to estimate adverse effects of gaseous pollutants on daily hospitalizations. Subgroup analysis was performed to detect modification effect by gender and age. Results: In total, there were 9081 ischemic stroke hospitalizations. After controlling for the meteorological factors in the same period, no significant findings were found with the increase of NO2, SO2, CO and O3 concentrations at most of the time in the single-pollutant model. Similarly, in the stratified analysis, no associations between gaseous pollutants and ischemic stroke were observed in this study. Conclusions: Short-term exposure to NO2, SO2, CO and O3 was not distinctly associated with daily hospitalizations for ischemic stroke in Tianjin. Multicenter studies in the future are warranted to explore the associations between gaseous pollution exposure and ischemic stroke