Well-Paired-Seq2: High-Throughput and High-Sensitivity Strategy for Characterizing Low RNA-Content Cell/Nucleus Transcriptomes.

Single-cell RNA sequencing (scRNA-seq) is a transformative technology that unravels the intricate cellular state heterogeneity. However, the Poisson-dependent cell capture and low sensitivity in scRNA-seq methods pose challenges for throughput and samples with a low RNA-content. Herein, to address these challenges, we present Well-Paired-Seq2 (WPS2), harnessing size-exclusion and quasi-static hydrodynamics for efficient cell capture. WPS2 exploits molecular crowding effect, tailing activity enhancement in reverse transcription, and homogeneous enzymatic reaction in the initial bead-based amplification to achieve 3116 genes and 8447 transcripts with an average of ∼20000 reads per cell. WPS2 detected 1420 more genes and 4864 more transcripts than our previous Well-Paired-Seq. It sensitively characterizes transcriptomes of low RNA-content single cells and nuclei, overcoming the Poisson limit for cell and barcoded bead capture. WPS2 also profiles transcriptomes from frozen clinical samples, revealing heterogeneous tumor copy number variations and intercellular crosstalk in clear cell renal cell carcinomas. Additionally, we provide the first single-cell-level characterization of rare metanephric adenoma (MA) and uncover potential specific markers. With the advantages of high sensitivity and high throughput, WPS2 holds promise for diverse basic and clinical research.

Conductive Lanthanide Metal-Organic Frameworks with Exceptionally High Stability.

Electrically conductive metal-organic frameworks (MOFs) have been extensively studied for their potential uses in energy-related technologies and sensors. However, achieving that goal requires MOFs to be highly stable and maintain their conductivity under practical operating conditions with varying solution environments and temperatures. Herein, we have designed and synthesized a new series of {[Ln4(µ4-O)(µ3-OH)3(INA)3(GA)3](CF3SO3)(H2O)6}n (denoted as Ln4-MOFs, Ln = Gd, Tm, and Lu, INA = isonicotinic acid, GA = glycolic acid) single crystals, where electrons are found to transport along the π-π stacked aromatic carbon rings in the crystals. The Ln4-MOFs show remarkable stability, with minimal changes in conductivity under varying solution pH (1-12), temperature (373 K), and electric field as high as 800 000 V/m. This stability is achieved through the formation of strong coordination bonds between high-valent Ln(III) ions and rigid carboxylic linkers as well as hydrogen bonds that enhance the robustness of the electron transport path. The demonstrated lanthanide MOFs pave the way for the design of stable and conductive MOFs.

Development of Human Adrenocortical Adenoma (HAA1) Cell Line from Zona Reticularis.

The human adrenal cortex is composed of distinct zones that are the main source of steroid hormone production. The mechanism of adrenocortical cell differentiation into several functionally organized populations with distinctive identities remains poorly understood. Human adrenal disease has been difficult to study, in part due to the absence of cultured cell lines that faithfully represent adrenal cell precursors in the early stages of transformation. Here, Human Adrenocortical Adenoma (HAA1) cell line derived from a patient's macronodular adrenocortical hyperplasia and was treated with histone deacetylase inhibitors (HDACis) and gene expression was examined. We describe a patient-derived HAA1 cell line derived from the zona reticularis, the innermost zone of the adrenal cortex. The HAA1 cell line is unique in its ability to exit a latent state and respond with steroidogenic gene expression upon treatment with histone deacetylase inhibitors. The gene expression pattern of differentiated HAA1 cells partially recreates the roster of genes in the adrenal layer that they have been derived from. Gene ontology analysis of whole genome RNA-seq corroborated increased expression of steroidogenic genes upon HDAC inhibition. Surprisingly, HDACi treatment induced broad activation of the Tumor Necrosis Factor (TNF) alpha pathway. This novel cell line we developed will hopefully be instrumental in understanding the molecular and biochemical mechanisms controlling adrenocortical differentiation and steroidogenesis.

Silencing of lncRNA LINC00514 inhibits the malignant behaviors of papillary thyroid cancer through miR-204-3p/CDC23 axis.

Numerous studies have provided that long noncoding RNAs (lncRNAs) possess important roles in regulating tumorigenesis. However, up to data, the role of LINC00514 in cancer, including thyroid cancer, remains unknown. In the present study, we found that LINC00514 expression was significantly upregulated in papillary thyroid cancer (PTC) tissues by bioinformatics analysis. Loss-of-function studies revealed that LINC00514 silencing inhibited the proliferation, migration and invasion of PTC cells while promoting apoptosis in vitro. Moreover, LINC00514 knockdown suppressed PTC growth in vivo. RNA-FISH showed that LINC00514 mainly locates in the nucleus of PTC cells. Through bioinformatics prediction, we identified that LINC00514 served as the sponge for miR-204-3p, and miR-204-3p directly targeted CDC23. Thus, LINC00514 promoted CDC23 expression via restraining miR-204-3p activity, leading to PTC progression. In sum, our findings demonstrated that LINC00514 contributes to PTC progression and might be a potential target for PTC therapy.

Integrated metabolomic profiling of hepatocellular carcinoma in hepatitis C cirrhosis through GC/MS and UPLC/MS-MS.

BACKGROUND & AIMS: The metabolic pathway disturbances associated with hepatocellular carcinoma (HCC) remain unsatisfactorily characterized. Determination of the metabolic alterations associated with the presence of HCC can improve our understanding of the pathophysiology of this cancer and may provide opportunities for improved disease monitoring of patients at risk for HCC development. To characterize the global metabolic alterations associated with HCC arising from hepatitis C (HCV)-associated cirrhosis using an integrated non-targeted metabolomics methodology employing both gas chromatography/mass spectrometry (GC/MS) and ultrahigh-performance liquid chromatography/electrospray ionization tandem mass spectrometry (UPLC/MS-MS). METHODS: The global serum metabolomes of 30 HCC patients, 27 hepatitis C cirrhosis disease controls and 30 healthy volunteers were characterized using a metabolomics approach that combined two metabolomics platforms, GC/MS and UPLC/MS-MS. Random forest, multivariate statistics and receiver operator characteristic analysis were performed to identify the most significantly altered metabolites in HCC patients vs. HCV-cirrhosis controls and which therefore exhibited a close association with the presence of HCC. RESULTS: Elevated 12-hydroxyeicosatetraenoic acid (12-HETE), 15-HETE, sphingosine, γ-glutamyl oxidative stress-associated metabolites, xanthine, amino acids serine, glycine and aspartate, and acylcarnitines were strongly associated with the presence of HCC. Elevations in bile acids and dicarboxylic acids were highly correlated with cirrhosis. CONCLUSIONS: Integrated metabolomic profiling through GC/MS and UPLC/MS-MS identified global metabolic disturbances in HCC and HCV-cirrhosis. Aberrant amino acid biosynthesis, cell turnover regulation, reactive oxygen species neutralization and eicosanoid pathways may be hallmarks of HCC. Aberrant dicarboxylic acid metabolism, enhanced bile acid metabolism and elevations in fibrinogen cleavage peptides may be signatures of cirrhosis.

Expansion of human centromeric arrays in cells undergoing break-induced replication.

Human centromeres are located within α-satellite arrays and evolve rapidly, which can lead to individual variation in array length. Proposed mechanisms for such alterations in length are unequal crossover between sister chromatids, gene conversion, and break-induced replication. However, the underlying molecular mechanisms responsible for the massive, complex, and homogeneous organization of centromeric arrays have not been experimentally validated. Here, we use droplet digital PCR assays to demonstrate that centromeric arrays can expand and contract within ∼20 somatic cell divisions of an alternative lengthening of telomere (ALT)-positive cell line. We find that the frequency of array variation among single-cell-derived subclones ranges from a minimum of ∼7% to a maximum of ∼100%. Further clonal evolution revealed that centromere expansion is favored over contraction. We find that the homologous recombination protein RAD52 and the helicase PIF1 are required for extensive array change, suggesting that centromere sequence evolution can occur via break-induced replication.

[Identification and expression analysis of the YABBY gene family in strawberry].

YABBY proteins are important transcription factors that regulate morphogenesis and organ development in plants. In order to study the YABBY of strawberry, bioinformatic technique were used to identify the YABBY gene families in Fragaria vesca (diploid) and Fragaria×ananassa (octoploid), and then analyze the sequence characters, phylogeny and collinearity of the family members. The RNA-seq data and the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) technique were used to assay the expression patterns of the family members. A green fluorescent protein (GFP) was fused with FvYABBYs and transiently expressed in tobacco leaf cells for the subcellular localization. As the results, six FvYABBY genes and 26 FxaYABBY genes were identified from F. vesca and F.×ananassa, respectively. The FvYABBY genes were grouped into five clades, and five family members were orthologous with AtYABBY genes of Arabidopsis. In F. vesca, all of the FvYABBYs were basically not expressed not expressed in root and receptacle, while FvYABBY1, FvYABBY2, FvYABBY5 and FvYABBY6 were highly expressed in leaf, shoot, flower and achene. In F.×ananassa, FxaYABBY1, FxaYABBY2, FxaYABBY5 and FxaYABBY6 were expressed in achene, and all FxaYABBY were poorly or not expressed in receptacle. Additionally, under the abiotic stresses of low temperature, high salt and drought, the expression of FvYABBY1, FvYABBY3, FvYABBY4 and FvYABBY6 were down-regulated, FvYABBY5 was up-regulated, and FvYABBY2 was up-regulated and then down-regulated. In tobacco leaf cells, the subcellular localization of FvYABBY proteins were in the nucleus. These results provides a foundation for the functional researches of YABBY gene in strawberry.

Advances in polymeric nano-delivery systems targeting hair follicles for the treatment of acne.

Acne is a common chronic inflammatory disorder of the sebaceous gland in the hair follicle. Commonly used external medications cause skin irritation, and the transdermal capacity is weak, making it difficult to penetrate the cuticle skin barrier. Hair follicles can aid in the breakdown of this barrier. As nanomaterials progress, polymer-based nanocarriers are routinely used for hair follicle drug delivery to treat acne and other skin issues. Based on the physiological and anatomical characteristics of hair follicles, this paper discusses factors affecting hair follicle delivery by polymer nanocarriers, summarizes the common combination technology to improve the targeting of hair follicles by carriers, and finally reviews the most recent research progress of different polymer nanodrug-delivery systems for the treatment of acne by targeting hair follicles.

Immune modulation of effector CD4+ and regulatory T cell function by sorafenib in patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a difficult to treat cancer characterized by poor tumor immunity with only one approved systemic drug, sorafenib. If novel combination treatments are to be developed with immunological agents, the effects of sorafenib on tumor immunity are important to understand. In this study, we investigate the impact of sorafenib on the CD4+CD25- effector T cells (Teff) and CD4+CD25+ regulatory T cells (Tregs) from patients with HCC. We isolated Teff and Treg from peripheral mononuclear cells of HCC patients to determine immune reactivity by thymidine incorporation, ELISA and flow cytometry. Teff cultured alone or with Treg were supplemented with different concentrations of sorafenib. The effects of sorafenib on Teff responses were dose-dependent. Pharmacologic doses of sorafenib decreased Teff activation by down regulating CD25 surface expression. In contrast, sub-pharmacologic concentrations of sorafenib resulted in Teff activation. These low doses of sorafenib in the Teff cultures led to a significant increase in Teff proliferation, IL2 secretion and up-regulation of CD25 expression on the cell surface. In addition, low doses of sorafenib in the suppression Teff/Treg cocultures restored Teff responses by eliminating Treg suppression. The loss of Treg suppressive function correlated with an increase in IL2 and IL6 secretion. Our findings show that sub-pharmacologic doses of sorafenib impact subsets of T cells differently, selectively increasing Teff activation while blocking Treg function. In conclusion, this study describes novel immune activating properties of low doses of sorafenib by promoting immune responsiveness in patients with HCC.

[Genome-wide identification of SUN gene family in Fragaria vesca and stresses-response analysis].

SUN gene is a group of key genes regulating plant growth and development. Here, SUN gene families of strawberry were identified from the genome of the diploid Fragaria vesca, and their physicochemical properties, genes structure, evolution and genes expression were also analyzed. Our results showed that there were thirty-one FvSUN genes in F. vesca and the FvSUNs encoded proteins were classified into seven groups, and the members in the same group showed high similarity in gene structures and conservative motifs. The electronic subcellular localization of FvSUNs was mainly in the nucleus. Collinearity analysis showed that the members of FvSUN gene family were mainly expanded by segmental duplication in F. vesca, and Arabidopsis and F. vesca shared twenty-three pairs of orthologous SUN genes. According to the expression pattern in different tissues shown by the transcriptome data of F. vesca, the FvSUNs gene can be divided into three types: (1) expressed in nearly all tissues, (2) hardly expressed in any tissues, and (3) expressed in special tissues. The gene expression pattern of FvSUNs was further verified by quantitative real-time polymerase chain reaction (qRT-PCR). Additionally, the seedlings of F. vesca were treated by different abiotic stresses, and the expression level of 31 FvSUNs genes were assayed by qRT-PCR. The expression of most of the tested genes was induced by cold, high salt or drought stress. Our studies may facilitate revealing the biological function and molecular mechanism of SUN genes in strawberry.

MPED: Quantifying Point Cloud Distortion Based on Multiscale Potential Energy Discrepancy.

In this article, we propose a new distortion quantification method for point clouds, the multiscale potential energy discrepancy (MPED). Currently, there is a lack of effective distortion quantification for a variety of point cloud perception tasks. Specifically, in human vision tasks, a distortion quantification method is used to predict human subjective scores and optimize the selection of human perception task parameters, such as dense point cloud compression and enhancement. In machine vision tasks, a distortion quantification method usually serves as loss function to guide the training of deep neural networks for unsupervised learning tasks (e.g., sparse point cloud reconstruction, completion, and upsampling). Therefore, an effective distortion quantification should be differentiable, distortion discriminable, and have low computational complexity. However, current distortion quantification cannot satisfy all three conditions. To fill this gap, we propose a new point cloud feature description method, the point potential energy (PPE), inspired by classical physics. We regard the point clouds are systems that have potential energy and the distortion can change the total potential energy. By evaluating various neighborhood sizes, the proposed MPED achieves global-local tradeoffs, capturing distortion in a multiscale fashion. We further theoretically show that classical Chamfer distance is a special case of our MPED. Extensive experiments show that the proposed MPED is superior to current methods on both human and machine perception tasks. Our code is available at https://github.com/Qi-Yangsjtu/MPED.

Expansion of human centromeric arrays in cells undergoing break-induced replication.

Human centromeres are located within α-satellite arrays and evolve rapidly, which can lead to individual variation in array lengths. Proposed mechanisms for such alterations in lengths are unequal cross-over between sister chromatids, gene conversion, and break-induced replication. However, the underlying molecular mechanisms responsible for the massive, complex, and homogeneous organization of centromeric arrays have not been experimentally validated. Here, we use droplet digital PCR assays to demonstrate that centromeric arrays can expand and contract within ~20 somatic cell divisions of a cell line. We find that the frequency of array variation among single-cell-derived subclones ranges from a minimum of ~7% to a maximum of ~100%. Further clonal evolution revealed that centromere expansion is favored over contraction. We find that the homologous recombination protein RAD52 and the helicase PIF1 are required for extensive array change, suggesting that centromere sequence evolution can occur via break-induced replication.

TCDM: Transformational Complexity Based Distortion Metric for Perceptual Point Cloud Quality Assessment.

The goal of objective point cloud quality assessment (PCQA) research is to develop quantitative metrics that measure point cloud quality in a perceptually consistent manner. Merging the research of cognitive science and intuition of the human visual system (HVS), in this paper, we evaluate the point cloud quality by measuring the complexity of transforming the distorted point cloud back to its reference, which in practice can be approximated by the code length of one point cloud when the other is given. For this purpose, we first make space segmentation for the reference and distorted point clouds based on a 3D Voronoi diagram to obtain a series of local patch pairs. Next, inspired by the predictive coding theory, we utilize a space-aware vector autoregressive (SA-VAR) model to encode the geometry and color channels of each reference patch with and without the distorted patch, respectively. Assuming that the residual errors follow the multi-variate Gaussian distributions, the self-complexity of the reference and transformational complexity between the reference and distorted samples are computed using covariance matrices. Additionally, the prediction terms generated by SA-VAR are introduced as one auxiliary feature to promote the final quality prediction. The effectiveness of the proposed transformational complexity based distortion metric (TCDM) is evaluated through extensive experiments conducted on five public point cloud quality assessment databases. The results demonstrate that TCDM achieves state-of-the-art (SOTA) performance, and further analysis confirms its robustness in various scenarios. The code will be publicly available at https://github.com/zyj1318053/TCDM.

Recent advances in cancer cell bionic nanoparticles for tumour therapy.

Nanoparticle-based drug delivery systems have found extensive use in delivering oncology therapeutics; however, some delivery vehicles still exhibit rapid immune clearance, lack of biocompatibility and insufficient targeting. In recent years, bionanoparticles constructed from tumour cell membranes have gained momentum as tumour-targeting therapeutic agents. Cancer cell membrane-coated nanoparticles (CCMCNPs) typically consist of a drug-loaded nanoparticle core coated with cancer cell membrane. CCMCNPs retain homologous tumour cell surface antigens, receptors and proteins, and it has been shown that the modified nanoparticles exhibit better homologous targeting, immune escape and biocompatibility. CCMCNPs are now widely used in a variety of cancer treatments, including photothermal, photodynamic and sonodynamic therapies, chemotherapy, immunotherapy, chemodynamical therapy or other combination therapies. This article presents different therapeutic approaches using multimodal antitumour therapy-combination of two or more therapies that treat tumours synergistically-based on tumour cell membrane systems. The advantages of CCMCNPs in different cancer treatments in recent years are summarised, thus, providing new strategies for cancer treatment research.

GPA-Net:No-Reference Point Cloud Quality Assessment with Multi-task Graph Convolutional Network.

With the rapid development of 3D vision, point cloud has become an increasingly popular 3D visual media content. Due to the irregular structure, point cloud has posed novel challenges to the related research, such as compression, transmission, rendering and quality assessment. In these latest researches, point cloud quality assessment (PCQA) has attracted wide attention due to its significant role in guiding practical applications, especially in many cases where the reference point cloud is unavailable. However, current no-reference metrics which based on prevalent deep neural network have apparent disadvantages. For example, to adapt to the irregular structure of point cloud, they require preprocessing such as voxelization and projection that introduce extra distortions, and the applied grid-kernel networks, such as Convolutional Neural Networks, fail to extract effective distortion-related features. Besides, they rarely consider the various distortion patterns and the philosophy that PCQA should exhibit shift, scaling, and rotation invariance. In this paper, we propose a novel no-reference PCQA metric named the Graph convolutional PCQA network (GPA-Net). To extract effective features for PCQA, we propose a new graph convolution kernel, i.e., GPAConv, which attentively captures the perturbation of structure and texture. Then, we propose the multi-task framework consisting of one main task (quality regression) and two auxiliary tasks (distortion type and degree predictions). Finally, we propose a coordinate normalization module to stabilize the results of GPAConv under shift, scale and rotation transformations. Experimental results on two independent databases show that GPA-Net achieves the best performance compared to the state-of-the-art no-reference PCQA metrics, even better than some full-reference metrics in some cases. The code is available at: https://github.com/Slowhander/GPA-Net.git.

Metabolic Characterization and Glyceraldehyde-3-Phosphate Dehydrogenase-Dependent Regulation of Epithelial Sodium Channels in hPheo1 Wild-type and SDHB Knockdown Cells.

Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors with limited curative treatment options outside of surgical resection. Patients with mutations in succinate dehydrogenase subunit B (SDHB) are at an increased risk of malignant and aggressive disease. As cation channels are associated with tumorigenesis, we studied the expression and activity of cation channels from the Degenerin superfamily in a progenitor cell line derived from a human PCC. hPheo1 wild-type (WT) and SDHB knockdown (KD) cells were studied to investigate whether epithelial sodium channels (ENaC) and acid-sensing ion channels (ASIC) are regulated by the activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). First, we performed targeted metabolomic studies and quantified changes in glycolysis pathway intermediates and citric acid cycle intermediates using hPheo1 WT cells and SDHB KD cells. Next, we performed protein biochemistry and electrophysiology studies to characterize the protein expression and activity, respectively, of these ion channels. Our western blot experiments show both ENaC alpha and ASIC1/2 are expressed in both hPheo1 WT and SDHB KD cells, with lower levels of a cleaved 60 kDa form of ENaC in SDHB KD cells. Single-channel patch clamp studies corroborate these results and further indicate channel activity is decreased in SDHB KD cells. Additional experiments showed a more significant decreased membrane potential in SDHB KD cells, which were sensitive to amiloride compared to WT cells. We provide evidence for the differential expression and activity of ENaC and ASIC hybrid channels in hPheo1 WT and SDHB KD cells, providing an important area of investigation in understanding SDHB-related disease.

Inferring Point Cloud Quality via Graph Similarity.

Objective quality estimation of media content plays a vital role in a wide range of applications. Though numerous metrics exist for 2D images and videos, similar metrics are missing for 3D point clouds with unstructured and non-uniformly distributed points. In this paper, we propose [Formula: see text]-a metric to accurately and quantitatively predict the human perception of point cloud with superimposed geometry and color impairments. Human vision system is more sensitive to the high spatial-frequency components (e.g., contours and edges), and weighs local structural variations more than individual point intensities. Motivated by this fact, we use graph signal gradient as a quality index to evaluate point cloud distortions. Specifically, we first extract geometric keypoints by resampling the reference point cloud geometry information to form an object skeleton. Then, we construct local graphs centered at these keypoints for both reference and distorted point clouds. Next, we compute three moments of color gradients between centered keypoint and all other points in the same local graph for local significance similarity feature. Finally, we obtain similarity index by pooling the local graph significance across all color channels and averaging across all graphs. We evaluate [Formula: see text] on two large and independent point cloud assessment datasets that involve a wide range of impairments (e.g., re-sampling, compression, and additive noise). [Formula: see text] provides state-of-the-art performance for all distortions with noticeable gains in predicting the subjective mean opinion score (MOS) in comparison with point-wise distance-based metrics adopted in standardized reference software. Ablation studies further show that [Formula: see text] can be generalized to various scenarios with consistent performance by adjusting its key modules and parameters. Models and associated materials will be made available at https://njuvision.github.io/GraphSIM or http://smt.sjtu.edu.cn/papers/GraphSIM.

[Biological function and molecular mechanism of the transcription factor GLKs in plants: a review].

GLKs (GOLDEN 2-LIKEs) are a group of plant-specific transcription factors regulating the chloroplast biogenesis, differentiation and function maintains by triggering the expression of the photosynthesis-associated nuclear genes (PhANGs). The GLKs also play important roles in nutrient's accumulation in fruits, leaf senescence, immunity and abiotic stress response. The expression of GLK genes were affected by multiple hormones or environmental factors. Therefore, GLKs were considered as the key nodes of regulatory network in plant cells, and potential candidates to improve the photosynthetic capacity of crops. Since numerous researches of GLKs have been reported in plants, the biological function, molecular mechanism of GLKs genes and its applications in breeding were summarized and a GLK-mediated signaling network model was developed. This review may facilitate future research and application of GLKs.

Identifying a novel IRF3/circUHRF1/miR-1306-5p/ARL4C axis in pancreatic ductal adenocarcinoma progression.

Pancreatic ductal adenocarcinoma (PDAC) is considered one most aggressive and lethal cancer types worldwide. While its underlying mechanisms are still poorly understood. CircRNAs play essential roles in various biological progression, including PDAC. Here, our results found that circUHRF1 was highly expressed in PDAC tumor tissues compared with normal tissues. Next, Cell or animal models were constructed, CCK-8, cell colony, EdU, flow cytometry assay, transwell migration, and Western blot assays were applied. CircUHRF1 knockdown influenced PDAC cell proliferation, apoptosis, migration and EMT level in vitro, and tumor growth in vivo. Subsequently, bioinformatics analysis, AGO2-RIP, RNA pull-down, and dual-luciferase reporter assays were used to explore the downstream targets in PDAC progression. Our findings suggest that circUHRF1 regulated ARL4C expression to promote PDAC progression through sponging miR-1306-5p. The role of miR-1306-5p in PDAC cellular progression has been elucidated, and the expression association between miR-1306-5p and circUHRF1 or ARL4C in PDAC tissues was analyzed. Furthermore, circUHRF1 expression in PDAC cells could be transcriptionally regulated by IRF3. Collectively, our study demonstrated the role of IRF3/circUHRF1/miR-1306-5p/ARL4C axis in PDAC progression. Our results suggest that circUHRF1 is one promising diagnosis or therapeutic target for PDAC management.Abbreviations : CircRNA; Circular RNAPDAC; pancreatic ductal adenocarcinomaUHRF1; Ubiquitin-like with PHD and RING finger domain 1ARL4C; ADP Ribosylation Factor Like GTPase 4CRIP; RNA immunoprecipitationEDU; 5-Ethynyl-2'-deoxyuridineEMT; epithelial to mesenchymal transitionAGO2; Argonaute RISC Catalytic Component 2CCK8; Cell counting Kit-8IRF3; Interferon Regulatory Factor 3.

Kinase inhibitor Sorafenib modulates immunosuppressive cell populations in a murine liver cancer model.

Accumulating evidence suggests that regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSC) are elevated in cancer patients and tumor-bearing hosts, and that depletion of Tregs and MDSC may enhance the anti-tumor immunity of the host. Sorafenib, a novel multi-kinase inhibitor, is approved for the treatment of several human cancers, including advanced hepatocellular carcinoma (HCC). Sorafenib is believed to inhibit tumor growth via anti-angiogenesis, cell cycle arrest, and inducing apoptosis. However, the impact of Sorafenib on immune cell populations in tumor-bearing hosts is unclear. In this report, we show that Tregs and MDSC are increased in the spleens and bone marrows of the BALB/c mice with liver hepatoma. The increase in Tregs and MDSC was positively correlated with tumor burden. Treatment of Sorafenib not only inhibited HCC cell growth in mice but also significantly decreased the suppressive immune cell populations: Tregs and MDSC. In conclusion, our study strongly suggests that Sorafenib can enhance anti-tumor immunity via modulating immunosuppressive cell populations in the murine liver cancer model.