Optimization of Layer Selection with Unreliable RI in LTE Systems

This paper investigates the optimization of transmission spatial layer selection with unreliable rank indicator (RI) in downlink LTE systems. Taking the block error rate (BLER) into consideration, we propose an accurate throughput calculation (ATC) algorithm at user equipment (UE) side as well as at evolved NodeB (eNB) side. On the basis of ATC algorithm, we propose an accurate RI selection algorithm to periodically choose the preferred number of transmission spatial layers at UE side. Further based on acknowledgement (ACK)/ negative acknowledgement (NACK) history, channel quality indicator (CQI) is adjusted at eNB side to achieve the throughput optimal target BLER. By substituting the derived BLER into ATC algorithm, the optimal number of transmitted spatial layers in current downlink channel is derived at eNB side. Simulation results show that both the proposed CQI adjustment scheme for spatial layer selection and RI selection algorithm yield up significant throughput improvement for different evaluation scenarios in LTE systems

Optical biopsy identification and grading of gliomas using label-free visible resonance Raman spectroscopy.

Glioma is one of the most refractory types of brain tumor. Accurate tumor boundary identification and complete resection of the tumor are essential for glioma removal during brain surgery. We present a method based on visible resonance Raman (VRR) spectroscopy to identify glioma margins and grades. A set of diagnostic spectral biomarkers features are presented based on tissue composition changes revealed by VRR. The Raman spectra include molecular vibrational fingerprints of carotenoids, tryptophan, amide I/II/III, proteins, and lipids. These basic in situ spectral biomarkers are used to identify the tissue from the interface between brain cancer and normal tissue and to evaluate glioma grades. The VRR spectra are also analyzed using principal component analysis for dimension reduction and feature detection and support vector machine for classification. The cross-validated sensitivity, specificity, and accuracy are found to be 100%, 96.3%, and 99.6% to distinguish glioma tissues from normal brain tissues, respectively. The area under the receiver operating characteristic curve for the classification is about 1.0. The accuracies to distinguish normal, low grade (grades I and II), and high grade (grades III and IV) gliomas are found to be 96.3%, 53.7%, and 84.1% for the three groups, respectively, along with a total accuracy of 75.1%. A set of criteria for differentiating normal human brain tissues from normal control tissues is proposed and used to identify brain cancer margins, yielding a diagnostic sensitivity of 100% and specificity of 71%. Our study demonstrates the potential of VRR as a label-free optical molecular histopathology method used for in situ boundary line judgment for brain surgery in the margins

Synergistic enhancement of cancer therapy using a combination of docetaxel and photothermal ablation induced by single-walled carbon nanotubes

Lei Wang1, Mingyue Zhang1, Nan Zhang1, Jinjin Shi1, Hongling Zhang1, Min Li1, Chao Lu2, Zhenzhong Zhang1 1School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China; 2University of Maryland, College Park, MD, USA Background: Single-walled carbon nanotubes (SWNT) are poorly soluble in water, so their applications are limited. Therefore, aqueous solutions of SWNT, designed by noncovalent functionalization and without toxicity, are required for biomedical applications. Methods: In this study, we conjugated docetaxel with SWNT via p-p accumulation and used a surfactant to functionalize SWNT noncovalently. The SWNT were then conjugated with docetaxel (DTX-SWNT) and linked with NGR (Asn-Gly-Arg) peptide, which targets tumor angiogenesis, to obtain a water-soluble and tumor-targeting SWNT-NGR-DTX drug delivery system. Results: SWNT-NGR-DTX showed higher efficacy than docetaxel in suppressing tumor growth in a cultured PC3 cell line in vitro and in a murine S180 cancer model. Tumor volumes in the S180 mouse model decreased considerably under near-infrared radiation compared with the control group. Conclusion: The SWNT-NGR-DTX drug delivery system may be promising for high treatment efficacy with minimal side effects in future cancer therapy. Keywords: single-walled carbon nanotubes, docetaxel, NGR peptide, tumor-targeting, near-infrared radiatio

Analysis of single-cell RNAseq identifies transitional states of T cells associated with hepatocellular carcinoma

BACKGROUND: Exhausted T cells and regulatory T cells (Tregs) comprise diverse subsets of tumor immunosuppressive microenvironment that play key roles in tumor progress. Understanding subset diversity in T cells is a critical question for developing cancer immunotherapy. METHODS: A total of 235 specimens from surgical resections of hepatocellular carcinoma (HCC) patients were examined for infiltration of exhausted T cell (Tex) in tumor and adjacent tissue. We conducted deep single-cell targeted immune profiling on CD3 RESULTS: We observed transitional differentiation of exhausted CD8 CONCLUSIONS: T cell exhaustion is a progressive process, and the gene-expression profiling displayed T cell exhaustion and anergy are different. Accordingly, it is possible that functional exhaustion is caused by the combination effects of passive defects and overactivation in stress response. The results help to understand the dynamic framework of T cells function in cancer which is important for designing rational cancer immunotherapies

Ultrasonographic diagnosis of ovarian tumors through the deep convolutional neural network

Objectives: The objective of this study was to develop and validate an ovarian tumor ultrasonographic diagnostic model based on deep convolutional neural networks (DCNN) and compare its diagnostic performance with that of human experts. Material and methods: We collected 486 ultrasound images of 192 women with malignant ovarian tumors and 617 ultrasound images of 213 women with benign ovarian tumors, all confirmed by pathological examination. The image dataset was split into a training set and a validation set according to a 7:3 ratio. We selected 5 DCNNs to develop our model: MobileNet, Xception, Inception, ResNet and DenseNet. We compared the performance of the five models through the area under the curve (AUC), sensitivity, specificity, and accuracy. We then randomly selected 200 images from the validation set as the test set. We asked three expert radiologists to diagnose the images to compare the performance of radiologists and the DCNN model. Results: In the validation set, AUC of DenseNet was 0.997 while AUC was 0.988 of ResNet, 0.987 of Inception, 0.968 of Xception and 0.836 of MobileNet. In the test set, the accuracy was 0.975 with the DenseNet model versus 0.825 (p < 0.0001) with the radiologists, and sensitivity was 0.975 versus 0.700 (p < 0.0001), and specificity was 0.975 versus 0.908 (p < 0.001). Conclusions: DensNet performed better than other DCNNs and expert radiologists in identifying malignant ovarian tumors from benign ovarian tumors based on ultrasound images, a finding that needs to be further explored in clinical trials

Resveratrol reduces inflammatory response and detrimental effects in chronic cerebral hypoperfusion by down-regulating stimulator of interferon genes/TANK-binding kinase 1/interferon regulatory factor 3 signaling

Inflammatory responses induced by chronic cerebral hypoperfusion (CCH) play a critical role in the progression of vascular dementia. Stimulator of interferon genes (STING) signaling function as a key mediator of inflammation and immunological responses in the central nervous system (CNS), and resveratrol (RES) exerts potent anti-inflammatory effects. However, the role of STING signaling and the relationship between RES and STING signaling in persistent hypoperfusion-induced cerebral inflammation remain unclear. In this study, Sprague–Dawley rats were subjected to either Sham or bilateral common carotid artery occlusion (2VO) surgery and received RES or vehicle daily by intraperitoneal injection for 4 or 8 weeks. Morris’s water maze was used for the analysis of cognitive function. The neuroinflammatory responses in white matter and hippocampus of the rat brain were assessed by Western blot, Immunofluorescence staining, and qRT-PCR analyses. Myelin integrity, neutrophil infiltration, and microglia proliferation were assessed by Immunohistochemistry and histologic analysis. We demonstrated that after CCH, neurons, microglia, and astrocyte under endoplasmic reticulum (ER) stress upregulated the expression of STING, TANK-binding kinase 1 (TBK1), and the transcription factor interferon regulatory factor 3 (IRF3), as well as translocation of IRF3 into the nucleus. These were accompanied by infiltration of neutrophils, activation of microglia, and overproduction of proinflammatory mediators. Improvements in cognitive deficits were related to reduced hippocampal neuronal cell death and increased myelin integrity in RES-treated rats. The neuroprotective effects of RES were associated with suppression of the expression of tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecule 1 (ICAM-1), VCAM-1, interferon-β (IFN-β), and IL-1β, likely through mitigation of the STING/TBK1/IRF3 pathway. These inhibitory effects exerted by RES also inhibited the levels of myeloperoxidase, reduced excess expression of reactive astrocytes, and activated microglia. In conclusion, the STING/TBK1/IRF3 axis may be critical for proinflammatory responses in cerebral tissue with persistent hypoperfusion, and RES exerts its anti-inflammatory effects by suppressing STING/TBK1/IRF3 signaling

C5aR1 shapes a non-inflammatory tumor microenvironment and mediates immune evasion in gastric cancer

C5a receptor 1 (C5aR1) is associated with various inflammatory processes, the pathogenesis of immune diseases, and tumor growth. However, its role in the tumor microenvironment of gastric cancer (GC) remains unclear. In this study, the expression of C5aR1 in GC and normal gastric mucosa tissues was compared using data retrieved from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, and the results were validated by in vitro qRT-PCR and immunohistochemical analyses. The relationship between C5aR1 expression and the overall survival of patients with GC was analyzed using the Kaplan–Meier method. Subsequently, enrichment analysis was performed, and the signaling pathways were screened. C5aR1 expression was also correlated with genes related to the immune checkpoint and immune cell infiltration. The results revealed that C5aR1 expression was enhanced in GC tissues compared to normal gastric tissues, and that patients with high expression of C5aR1 had a worse 10-year overall survival compared to those showing low expression of C5aR1. Functional analysis revealed that C5aR1 is a gene related to theimmune system and may play a crucial role in inflammatory and tumor immune responses. Additionally, C5aR1 showed a positive correlation with most immune checkpoint-related genes and a negative correlation with natural killer cells, dendritic cells, and CD8+ T cells. Immune evasion risk was observed to be significantly greater in patients with higher expression of C5aR1 than in those with lower expression. The results of this study reveal that C5aR1 shapes a non-inflammatory tumor microenvironment in GC and mediates immune evasion

MEIS2C and MEIS2D promote tumor progression via Wnt/β-catenin and hippo/YAP signaling in hepatocellular carcinoma

Abstract Background MEIS2 has been identified as one of the key transcription factors in the gene regulatory network in the development and pathogenesis of human cancers. Our study aims to identify the regulatory mechanisms of MEIS2 in hepatocellular carcinoma (HCC), which could be targeted to develop new therapeutic strategies. Methods The variation of MEIS2 levels were assayed in a cohort of HCC patients. The proliferation, clone-formation, migration, and invasion abilities of HCC cells were measured to analyze the effects of MEIS2C and MEIS2D (MEIS2C/D) knockdown with small hairpin RNAs in vitro and in vivo. Chromatin immunoprecipitation (ChIP) was performed to identify MEIS2 binding site. Immunoprecipitation and immunofluorescence assays were employed to detect proteins regulated by MEIS2. Results The expression of MEIS2C/D was increased in the HCC specimens when compared with the adjacent noncancerous liver (ANL) tissues. Moreover, MEIS2C/D expression negatively correlated with the prognosis of HCC patients. On the other hand, knockdown of MEIS2C/D could inhibit proliferation and diminish migration and invasion of hepatoma cells in vitro and in vivo. Mechanistically, MESI2C activated Wnt/β-catenin pathway in cooperation with Parafibromin (CDC73), while MEIS2D suppressed Hippo pathway by promoting YAP nuclear translocation via miR-1307-3p/LATS1 axis. Notably, CDC73 could directly either interact with MEIS2C/β-catenin or MEIS2D/YAP complex, depending on its tyrosine-phosphorylation status. Conclusions Our studies indicate that MEISC/D promote HCC development via Wnt/β-catenin and Hippo/YAP signaling pathways, highlighting the complex molecular network of MEIS2C/D in HCC pathogenesis. These results suggest that MEISC/D may serve as a potential novel therapeutic target for HCC.https://deepblue.lib.umich.edu/bitstream/2027.42/152244/1/13046_2019_Article_1417.pd