HBV PreC interacts with SUV39H1 to induce viral replication by blocking the proteasomal degradation of viral polymerase.

Hepatitis B e antigen (HBeAg) seropositivity during the natural history of chronic hepatitis B (CHB) is known to coincide with significant increases in serum and intrahepatic HBV DNA levels. However, the precise underlying mechanism remains unclear. In this study, we found that PreC (HBeAg precursor) genetic ablation leads to reduced viral replication both in vitro and in vivo. Furthermore, PreC impedes the proteasomal degradation of HBV polymerase, promoting viral replication. We discovered that PreC interacts with SUV39H1, a histone methyltransferase, resulting in a reduction in the expression of Cdt2, an adaptor protein of CRL4 E3 ligase targeting HBV polymerase. SUV39H1 induces H3K9 trimethylation of the Cdt2 promoter in a PreC-induced manner. CRISPR-mediated knockout of endogenous SUV39H1 or pharmaceutical inhibition of SUV39H1 decreases HBV loads in the mouse liver. Additionally, genetic depletion of Cdt2 in the mouse liver abrogates PreC-related HBV replication. Interestingly, a negative correlation of intrahepatic Cdt2 with serum HBeAg and HBV DNA load was observed in CHB patient samples. Our study thus sheds light on the mechanistic role of PreC in inducing HBV replication and identifies potential therapeutic targets for HBV treatment.

Potential of lncRNAs to regulate cuproptosis in hepatocellular carcinoma: Establishment and validation of a novel risk model.

Cuproptosis, a distinct form of programmed cell death, is an emerging field in oncology with promising implications. This novel mode of cell death has the potential to become a regulatory target for tumor therapy, thus expanding the currently limited treatment options available for patients with cancer. Our research team focused on investigating the role of functional long non-coding RNA (lncRNAs) in hepatocellular carcinoma (HCC). We were particularly intrigued by the potential implications of HCC-lncRNAs on cuproptosis. Through a comprehensive analysis, we identified three cuproptosis-related lncRNAs (CRLs): AC018690.1, AL050341.2, and LINC02038. These lncRNAs were found to influence the sensitivity of HCC to cuproptosis. Based on our results, we constructed a risk model represented by the equation: risk score = 0.82 * AC018690.1 + 0.65 * AL050341.2 + 0.61 * LINC02038. Notably, significant disparities were observed in clinical features, such as the response rate to immunotherapy and targeted therapy, as well as in cellular characteristics, including the composition of the tumor immune microenvironment (TIME), when comparing the high- and low-risk groups. Most importantly, knockdown of these CRLs was confirmed to significantly weaken the resistance to cuproptosis in HCC. This effect resulted from the accelerated accumulation of lipoacylated-DLAT and lipoacylated-DLST. In summary, we identified three CRLs in HCC and established a novel risk model with potential clinical applications. Additionally, we proposed a potential therapeutic method consisting of sorafenib-copper ionophores-immunotherapy.

A Mammalian Conserved Circular RNA CircLARP1B Regulates Hepatocellular Carcinoma Metastasis and Lipid Metabolism.

Circular RNAs (circRNAs) have emerged as crucial regulators in physiology and human diseases. However, evolutionarily conserved circRNAs with potent functions in cancers are rarely reported. In this study, a mammalian conserved circRNA circLARP1B is identified to play critical roles in hepatocellular carcinoma (HCC). Patients with high circLARP1B levels have advanced prognostic stage and poor overall survival. CircLARP1B facilitates cellular metastatic properties and lipid accumulation through promoting fatty acid synthesis in HCC. CircLARP1B deficient mice exhibit reduced metastasis and less lipid accumulation in an induced HCC model. Multiple lines of evidence demonstrate that circLARP1B binds to heterogeneous nuclear ribonucleoprotein D (HNRNPD) in the cytoplasm, and thus affects the binding of HNRNPD to sensitive transcripts including liver kinase B1 (LKB1) mRNA. This regulation causes decreased LKB1 mRNA stability and lower LKB1 protein levels. Antisense oligodeoxynucleotide complementary to theHNRNPD binding sites in circLARP1B increases the HNRNPD binding to LKB1 mRNA. Through the HNRNPD-LKB1-AMPK pathway, circLARP1B promotes HCC metastasis and lipid accumulation. Results from AAV8-mediated hepatocyte-directed knockdown of circLARP1B or Lkb1 in mouse models also demonstrate critical roles of hepatocytic circLARP1B regulatory pathway in HCC metastasis and lipid accumulation, and indicate that circLARP1B may be potential target of HCC treatment.

Development and Application of Poly (Lactic Acid)/Poly (Butylene Adipate-Co-Terephthalate)/Thermoplastic Starch Film Containing Salicylic Acid for Banana Preservation.

Bananas are susceptible to the effects of endogenous enzymatic, leading to their rapid decay and deterioration. In order to mitigate economic losses and prolong the shelf life of bananas, the objective of this study was to develop a new and green gas-regulating packaging film. In this study, an active gas-regulating packaging film was prepared by extrusion, with mobil composition of matter (MCM)-41 loaded with salicylic acid (SA) as the active agent and poly (lactic acid) (PLA), poly (butylene adipate-co-terephthalate) (PBAT), and thermoplastic starch (TPS) as the base materials. The obtained films included PLA/PBAT/TPS, PLA/PBAT/TPS-SA, and PLA/PBAT/TPS-MCSA. These films were subsequently applied to banana preservation. The study focused on the variations in soluble solid content (SSC), rate of weight loss (RWL), malondialdehyde (MDA) content, and polyphenol oxidase (PPO) activity of bananas during the preservation process. The results showed that, compared with the PLA/PBAT/TPS film, the oxygen transmission rate of the PLA/PBAT/TPS-MCSA film increased from 384.36 ± 22.06 cm3·m-2·24 h-1·0.1 MPa-1 to 543.10 ± 3.47 cm3·m-2·24 h-1·0.1 MPa-1. Throughout the preservation period, the PLA/PBAT/TPS-MCSA film exhibited superior performance, effectively retarding the increase in banana SSC, RWL, and MDA while inhibiting the elevation of PPO activity and prolonging the shelf life of bananas by 4-5 days. However, this study needs to further investigate the mechanism of function of MCM-41 loaded with SA in banana preservation.

Cytoskeleton remodeling mediated by circRNA-YBX1 phase separation suppresses the metastasis of liver cancer.

Metastasis, especially intrahepatic, is a major challenge for hepatocellular carcinoma (HCC) treatment. Cytoskeleton remodeling has been identified as a vital process mediating intrahepatic spreading. Previously, we reported that HCC tumor adhesion and invasion were modulated by circular RNA (circRNA), which has emerged as an important regulator of various cellular processes and has been implicated in cancer progression. Here, we uncovered a nuclear circRNA, circASH2, which is preferentially lost in HCC tissues and inhibits HCC metastasis by altering tumor cytoskeleton structure. Tropomyosin 4 (TPM4), a critical binding protein of actin, turned out to be the major target of circASH2 and was posttranscriptionally suppressed. Such regulation is based on messenger RNA (mRNA)/precursormRNA splicing and degradation process. Furthermore, liquid-liquid phase separation of nuclear Y-box binding protein 1 (YBX1) enhanced by circASH2 augments TPM4 transcripts decay. Together, our data have revealed a tumor-suppressive circRNA and, more importantly, uncovered a fine regulation mechanism for HCC progression.

Resynchronized rhythmic oscillations of gut microbiota drive time-restricted feeding induced nonalcoholic steatohepatitis alleviation.

With the drive of the endogenous circadian clock and external cues such as feeding behavior, the microbial community generates rhythmic oscillations in composition and function. Microbial oscillations are crucial in orchestrating host metabolic homeostasis during the predictable 24-hour diurnal cycle. A time-restricted feeding (TRF) regimen is a promising dietary strategy to optimize energy utilization, alleviate metabolic syndrome and reinforce microbial cyclical fluctuations. However, the causative relationship between reinforced microbial rhythmicity and TRF-induced metabolic improvement remains elusive. In this study, we corroborated that the TRF regimen notably alleviated obesity and nonalcoholic steatohepatitis (NASH) with reinstated rhythmicity of genera such as Lactobacillus, Mucispirillum, Acetatifactor, and Lachnoclostridium. The reshaped microbial oscillations correlate with cyclical fluctuations in intestinal amino acids. Furthermore, fecal microbiota transplantation (FMT) indicated that only the TRF feeding phase-derived microbiota, but not the TRF fasting phase-derived microbiota, could protect mice from NASH and reinstate microbial rhythmicity, confirming that the microbiota improved NASH in a time-of-day-specific manner. The unique role of the TRF-feeding phase-derived microbiota was accompanied by regulation of the serotonergic synapse pathway and rejuvenation of the microbial production of indole derivatives. Our results revealed the discrepant characteristics between the feeding and fasting phases and the time-of-day-specific configuration of microbiota functionality in the TRF regimen.

Antioxidant mechanism of a continuous microenvironment regulation system for prolonging the shelf-life of red grapes.

Red grapes (Vitis vinifera L.) have a high sugar content, thin skins, and relatively short shelf-life after harvesting. We developed polylactic acid/polybutylene succinate film, prepared by extrusion of polylactic acid and polybutylene succinate, that significantly prolonged the shelf-life of red grapes from 8 to 12 days by delaying the loss of weight, loss of hardness, and reduction in soluble solid content after harvesting. Further mechanistic study showed that this modified atmosphere film delayed the senescence of harvested red grape, the phenomenon that was highly related to the lower active oxygen species production and higher antioxidant enzyme activity compared to the non-packaged grape. The proposed continuous and dynamic microenvironment regulation system is a promising method to study the mechanisms of respiratory metabolism in fruit and extends food shelf-life while reducing food waste. PRACTICAL APPLICATION: In this study, we designed a means to microenvironmental regulatory packaging that directly creates a continuous, dynamic, and monitorable microenvironment. To ensure that the fruit inside the package underwent coordinated aerobic and anaerobic respiration, we melt-extruded polylactic acid (PLA) and polybutylene succinate (PBS) to form a homogeneous biodegradable film. We demonstrated that the best preservation results were achieved with a film comprising an 80/20 PLA-to-PBS ratio. This film can prolong the shelf-life of fruits by regulating respiratory metabolism.

A circular RNA, circPTPN14, increases MYC transcription by interacting with FUBP1 and exacerbates renal fibrosis.

Fibrosis is a relentlessly progressive and irreversible cause of organ damage, as in chronic kidney disease (CKD), but its underlying mechanisms remain elusive. We found that a circular RNA, circPTPN14, is highly expressed in human kidneys with biopsy-proved chronic interstitial fibrosis, mouse kidneys subjected to ischemia/reperfusion (IR) or unilateral ureteral obstruction (UUO), and TGFß1-stimulated renal tubule epithelial cells (TECs). The intrarenal injection of circPTPN14 shRNA alleviated the progression of fibrosis in kidneys subjected to IR or UUO. Knockdown of circPTPN14 in TECs inhibited TGFß1-induced expression of profibrotic genes, whereas overexpressing circPTPN14 increased the profibrotic effect of TGFß1. The profibrotic action of circPTPN14 was ascribed to an increase in MYC transcription. The binding of circPTPN14 to the KH3 and KH4 domains of far upstream element (FUSE) binding protein 1 (FUBP1) enhanced the interaction between FUBP1 and FUSE domain, which was required for the initiation of MYC transcription. In human kidneys (n = 30) with biopsy-proved chronic interstitial fibrosis, the expression of circPTPN14 positively correlated with MYC expression. Taken together these studies show a novel mechanism in the pathogenesis of renal fibrosis, mediated by circPTPN14, which can be a target in the diagnosis and treatment of CKD.

The potential of mecciRNA in hepatic stellate cell to regulate progression of nonalcoholic hepatitis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) occupies a substantial proportion of chronic liver disease worldwide, of which pathogenesis needs further research. Recent studies have demonstrated the significant roles of circular RNAs (circRNAs) in NASH, while the function of a novel type of circRNAs, namely mitochondria-encoded circRNAs (mecciRNAs), remains elusive. Therefore, we aimed to investigate their potential to regulate the progression of NASH in this study. METHODS: GSE134146 was used to screen for differentially expressed mecciRNAs in NASH, while GSE46300 was used to identify NASH-related genes. To establish the mecciRNA-miRNA-mRNA networks, circMINE and miRNet databases were used for predicting downstream targets. Then, consensus clustering analysis was used to determine immune subtypes of NASH. Finally, we successfully validated our findings in vitro (LPS-treated hepatic stellate cells [HSCs]) and in vivo (MCD-diet mice) NASH models. RESULTS: We confirmed that circRNomics balance is disrupted in HSCs of NASH, while two mecciRNAs (hsa_circ_0089761 and hsa_circ_0089763) could function as competing for endogenous RNAs (ceRNAs) to regulate fibrosis-related signals. Furthermore, we constructed two ceRNA networks based on mecciRNAs for the first time. Cell and animal NASH models validated our findings that c-MYC and SMAD2/3 were upregulated in HSCs, while THBS1 and p-STAT3 were upregulated in hepatocytes. Moreover, we identified 21 core genes by overlapping the differentially expressed genes (NASH vs. Normal) with mecciRNA-targeted genes. According to their expression profiles, NASH patients could be divided in 2 different clusters, in which proinflammatory signals (TNF and IL-17 pathways) are significantly activated in Cluster 1. CONCLUSION: We successfully established two novel mecciRNA-miRNA-mRNA networks in HSCs and hepatocytes, which were further confirmed by in vitro and in vivo models. Meanwhile, the novel immunotyping model revealed the heterogeneity of NASH, thereby might guiding treatment options. Altogether, our study brought a distinct perspective on the relationship between mecciRNAs and NASH.

Akkermansia muciniphila Ameliorates Acetaminophen-Induced Liver Injury by Regulating Gut Microbial Composition and Metabolism.

The gut microbiota drives individual sensitivity to excess acetaminophen (APAP)-mediated hepatotoxicity. It has been reported that the bacterium Akkermansia muciniphila protects hosts against liver disease via the liver-gut axis, but its therapeutic potential for drug-induced liver injury remains unclear. In this study, we aimed to investigate the effect of A. muciniphila on APAP-induced liver injury and the underlying mechanism. Administration of A. muciniphila efficiently alleviated APAP-induced hepatotoxicity and reduced the levels of serum alanine aminotransferase (ALT) and aspartate transaminase (AST). A. muciniphila significantly attenuated APAP-induced oxidative stress and the inflammatory response, as evidenced by restoration of the reduced glutathione/oxidized glutathione (GSH/GSSG) balance, enhanced superoxide dismutase (SOD) activity, reduced proinflammatory cytokine production, and alleviation of macrophage and neutrophil infiltration. Moreover, A. muciniphila maintained gut barrier function, reshaped the perturbed microbial community and promoted short-chain fatty acid (SCFA) secretion. The beneficial effects of A. muciniphila were accompanied by alterations in hepatic gene expression at the transcriptional level and activation of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Our results suggested that A. muciniphila could be a potential pretreatment for APAP-induced liver injury. IMPORTANCE Our work revealed that A. muciniphila attenuated APAP-induced liver injury by alleviating oxidative stress and inflammation in the liver, and its hepatoprotective effect was accompanied by activation of the PI3K/Akt pathway and mediated by regulation of the composition and metabolic function of the intestinal microbiota. This finding suggested that the microbial community is a non-negligible impact on drug metabolism and probiotic administration could be a potential therapy for drug-induced liver injury.

Circular RNAs: characteristics, biogenesis, mechanisms and functions in liver cancer.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common malignancies globally. Despite aggressive and multimodal treatment regimens, the overall survival of HCC patients remains poor. MAIN: Circular RNAs (circRNAs) are noncoding RNAs (ncRNAs) with covalently closed structures and tissue- or organ-specific expression patterns in eukaryotes. They are highly stable and have important biological functions, including acting as microRNA sponges, protein scaffolds, transcription regulators, translation templates and interacting with RNA-binding protein. Recent advances have indicated that circRNAs present abnormal expression in HCC tissues and that their dysregulation contributes to HCC initiation and progression. Furthermore, researchers have revealed that some circRNAs might serve as diagnostic biomarkers or drug targets in clinical settings. In this review, we systematically evaluate the characteristics, biogenesis, mechanisms and functions of circRNAs in HCC and further discuss the current shortcomings and potential directions of prospective studies on liver cancer-related circRNAs. CONCLUSION: CircRNAs are a novel class of ncRNAs that play a significant role in HCC initiation and progression, but their internal mechanisms and clinical applications need further investigation.

CircUBAP2 Promotes MMP9-Mediated Oncogenic Effect via Sponging miR-194-3p in Hepatocellular Carcinoma.

BACKGROUND: The physiological regulatory functions of circRNAs have become a topic of intensive research in recent years. Increasing evidence supports a significant role of circRNAs during cancer initiation and progression, including hepatocellular carcinoma (HCC). MATERIALS AND METHODS: A bioinformatics analysis from three independent Gene Expression Omnibus (GEO) databases was performed to profile and screen the dysregulated circRNAs in HCC. RT-qPCR was used to examine the expression level of circUBAP2 in HCC and adjacent non-tumor tissues. Then, proliferation assays (CCK8 and colony formation) and migration assays (transwell and wound healing) were performed to examine effect of circUBAP2 in vitro. Immunoprecipitation, RNA pulldown, FISH, and dual-luciferase reporter assay was conducted to explore the circUBAP2-related mechanism for regulating HCC progression. Moreover, a mouse xenograft model and a mouse lung metastasis model confirmed the effect of circUBAP2 in vivo. RESULTS: In this study, we found a novel circRNA: circUBAP2, which was identified by bioinformatics analysis. Among 91 HCC patients, circUBAP2 was significantly upregulated in HCC tissues, and negatively correlated with aggressive clinical characteristics and prognosis. Functional assays demonstrated that circUBAP2 promoted cell proliferation, colony formation, migration, and invasion in vitro. Moreover, circUBAP2 enhanced tumor growth and pulmonary metastasis in vivo. Mechanistically, circUBAP2 acts as a competing endogenous RNA (ceRNA) for miR-194-3p, a tumor suppressor in HCC. We confirmed that MMP9 was direct target for miR-194-3p, which was regulated by circUBAP2. CONCLUSION: CircUBAP2 plays a significant role in promoting HCC via the miR-194-3p/MMP9 pathway and could serve as a promising prognostic biomarker and novel therapeutic target for HCC patients.

An integrated electrochemical POCT platform for ultrasensitive circRNA detection towards hepatocellular carcinoma diagnosis.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death. Circ-CDYL, one of the circular RNAs (circRNAs), is recognized as an independent marker for HCC early diagnosis. Point-of-care testing (POCT) of circRNA is essential and in great demand for clinical applications. Herein, we report a fully integrated electrochemical POCT platform for circRNA detection based on Au nanoflowers (AuNFs)/peptide nucleic acid (PNA) modified carbon-fiber microelectrode (CFME). PNA is applied as the recognition element, highly specified for a back-splice junction of circRNA. AuNFs increased active site for PNA probes, improving target-capturing efficiency at an ultralow level. The platform provides a linear range of 10 fM to 1 µM, with a detection limit as low as 3.29 fM. This biosensor demonstrates high specificity towards one-base mismatch and is stable for up to 24 days. The analytical performance has also been verified in human serum samples, demonstrating the potential utility in clinical POCT applications for HCC.

Whole-exon sequencing insights into pancreatic synovial sarcoma: a case report.

More than 30 cases of synovial sarcoma are sequenced on all organs of cBioPortal database, but it has not yet been reported before. Here, we reported a case of a 66-year-old male patient with an upper abdominal pain for half a month and a previous history of oral cancer. During this hospitalization, the patient underwent laparoscopic exploration followed by open pancreaticoduodenectomy. The histopathological diagnosis was pancreatic synovial sarcoma (PSS), and we further performed whole exome sequencing for this patient. We found that there are many copy number variations (CNV) of exon gene in all the 24 chromosomes, of which chr1, chr2, chr4 have the most exon gene amplification and chr21, chr22, chrY have the most exon gene deletion. Besides, GO (Gene Ontology) analysis showed that many driver-genes are related to chromosome or chromatin organization while KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis demonstrated that many driver-genes are enriched in the cancer-related pathways. Furthermore, we found mutations or CNV of the five vital driver-genes in the results of sequencing, including arid1a, arid1b, tp53, cdkn2a and asxl1. Of them, arid1a and arid1b in exon 1 are both in-frame mutations. By exploring the pathogenic genes of PSS, we have found some vital gene mutations and better understood the pathogenesis to promote the targeted treatment of primary PSS.

A tumor-suppressive circular RNA mediates uncanonical integrin degradation by the proteasome in liver cancer.

Circular RNAs (circRNAs) have emerged as important regulators of various cellular processes and have been implicated in cancer. Previously, we reported the discovery of several dysregulated circRNAs including circPABPC1 (polyadenylate-binding protein 1) in human hepatocellular carcinoma (HCC), although their roles in HCC development remained unclear. Here, we show that circPABPC1 is preferentially lost in tumor cells from clinical samples and inhibits both intrahepatic and distant metastases in a mouse xenograft model. This tumor-suppressive function of circPABPC1 can be attributed to its inhibition of cell adhesion and migration through down-regulating a key member of the integrin family, ITGB1 (ß1 integrin). Mass spectrometry and biochemical evidence demonstrate that circPABPC1 directly links ITGB1 to the 26S proteasome for degradation in a ubiquitination-independent manner. Our data have revealed an uncanonical route for integrin turnover and a previously unidentified mode of action for circRNAs in HCC that can be harnessed for anticancer treatment.

Androgen receptor affects the response to immune checkpoint therapy by suppressing PD-L1 in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with gender-related differences in onset and course. Androgen receptor (AR), a male hormone receptor, is critical in the initiation and progression of HCC. The role of AR in HCC has been mechanistically characterized and anti-AR therapies have been developed, showing limited efficacy. Immunotherapy targeting immune checkpoint proteins may substantially improve the clinical management of HCC. The mechanism by which AR influences HCC immune state remains unclear. In this study, we demonstrated that AR negatively regulated PD-L1, by acting as a transcriptional repressor of PD-L1. Notably, AR over-expression in HCC cells enhanced CD8+T function in vitro. We then verified the AR/PD-L1 correlation in patients. In animal experiment we found that lower AR expressed tumor achieved better response to PD-L1 inhibitor. Thus, AR suppressed PD-L1 expression, possibly contributing to gender disparity in HCC. Better understanding of the roles of AR during HCC initiation and progression will provide a novel angle to develop potential HCC immunotherapies.

AUNet: attention-guided dense-upsampling networks for breast mass segmentation in whole mammograms.

Mammography is one of the most commonly applied tools for early breast cancer screening. Automatic segmentation of breast masses in mammograms is essential but challenging due to the low signal-to-noise ratio and the wide variety of mass shapes and sizes. Existing methods deal with these challenges mainly by extracting mass-centered image patches manually or automatically. However, manual patch extraction is time-consuming and automatic patch extraction brings errors that could not be compensated in the following segmentation step. In this study, we propose a novel attention-guided dense-upsampling network (AUNet) for accurate breast mass segmentation in whole mammograms directly. In AUNet, we employ an asymmetrical encoder-decoder structure and propose an effective upsampling block, attention-guided dense-upsampling block (AU block). Especially, the AU block is designed to have three merits. Firstly, it compensates the information loss of bilinear upsampling by dense upsampling. Secondly, it designs a more effective method to fuse high- and low-level features. Thirdly, it includes a channel-attention function to highlight rich-information channels. We evaluated the proposed method on two publicly available datasets, CBIS-DDSM and INbreast. Compared to three state-of-the-art fully convolutional networks, AUNet achieved the best performances with an average Dice similarity coefficient of 81.8% for CBIS-DDSM and 79.1% for INbreast.

DRRNet: Dense Residual Refine Networks for Automatic Brain Tumor Segmentation.

Glioma is one of the most common and aggressive brain tumors. Segmentation and subsequent quantitative analysis of brain tumor MRI are routine and crucial for treatment. Due to the time-consuming and tedious manual segmentation, automatic segmentation methods are required for accurate and timely treatment. Recently, segmentation methods based on deep learning are popular because of their self-learning and generalization ability. Therefore, we propose a novel automatic 3D CNN-based method for brain tumor segmentation. In order to better capture the contextual information, we design the network architecture based on u-net and replace the simple skip connection with encoder adaptation blocks. To further improve the performance and reduce computational burden at the same time, we also use dense connected fusion blocks in decoder. We train our model with generalised dice loss function to alleviate the problem of class imbalance. The proposed model is evaluated on the BRATS 2015 testing dataset and obtains dice scores of 0.84, 0.72 and 0.62 for whole tumor, tumor core and enhancing tumor, respectively. Our model is accurate and efficient, achieving results that comparable to the reported state-of-the-art results.

Computer-Aided Grading of Gliomas Combining Automatic Segmentation and Radiomics.

Gliomas are the most common primary brain tumors, and the objective grading is of great importance for treatment. This paper presents an automatic computer-aided diagnosis of gliomas that combines automatic segmentation and radiomics, which can improve the diagnostic ability. The MRI data containing 220 high-grade gliomas and 54 low-grade gliomas are used to evaluate our system. A multiscale 3D convolutional neural network is trained to segment whole tumor regions. A wide range of radiomic features including first-order features, shape features, and texture features is extracted. By using support vector machines with recursive feature elimination for feature selection, a CAD system that has an extreme gradient boosting classifier with a 5-fold cross-validation is constructed for the grading of gliomas. Our CAD system is highly effective for the grading of gliomas with an accuracy of 91.27%, a weighted macroprecision of 91.27%, a weighted macrorecall of 91.27%, and a weighted macro-F1 score of 90.64%. This demonstrates that the proposed CAD system can assist radiologists for high accurate grading of gliomas and has the potential for clinical applications.

Leptin induces secretion of pro-inflammatory cytokines by human keratinocytes in vitro--a possible reason for increased severity of psoriasis in patients with a high body mass index.

Investigations about prevalence of obesity in psoriasis patients are increased nowadays. Higher serum levels of leptin in patients with psoriasis who are overweight or obese suggest that leptin may serve as a molecular link between psoriasis and metabolic comorbidities. However, the pathological functions of leptin in psoriasis are not clearly understood. We investigated the influence of being overweight or obese on the risk of psoriasis, and the relationship between serum leptin levels and the severity of psoriasis in Chinese Han patients. We also investigated biological effects of leptin on the proliferation and secretion of pro-inflammatory cytokines by human keratinocytes in vitro. Obesity was a significant risk factor for psoriasis in the Chinese Han population; however, we did not observe a significant correlation between Psoriasis Area and Severity Index (PASI) and body mass index (BMI). We observed a positive correlation between the serum leptin level and PASI in overweight and obese male patients with psoriasis. Strong leptin immunoreactivity was detected in the epidermis of psoriatic lesions, particularly in keratinocytes. Leptin significantly increased the proliferation and secretion of pro-inflammatory cytokines by keratinocytes in vitro. In conclusion, this study suggests leptin as a novel molecular link between psoriasis and obesity, which may help to explain the more server conditions of psoriasis in patients with obesity.