Tryptophan metabolism in digestive system tumors: unraveling the pathways and implications.

Tryptophan (Trp) metabolism plays a crucial role in influencing the development of digestive system tumors. Dysregulation of Trp and its metabolites has been identified in various digestive system cancers, including esophageal, gastric, liver, colorectal, and pancreatic cancers. Aberrantly expressed Trp metabolites are associated with diverse clinical features in digestive system tumors. Moreover, the levels of these metabolites can serve as prognostic indicators and predictors of recurrence risk in patients with digestive system tumors. Trp metabolites exert their influence on tumor growth and metastasis through multiple mechanisms, including immune evasion, angiogenesis promotion, and drug resistance enhancement. Suppressing the expression of key enzymes in Trp metabolism can reduce the accumulation of these metabolites, effectively impacting their role in the promotion of tumor progression and metastasis. Strategies targeting Trp metabolism through specific enzyme inhibitors or tailored drugs exhibit considerable promise in enhancing therapeutic outcomes for digestive system tumors. In addition, integrating these approaches with immunotherapy holds the potential to further enhance treatment efficacy.

Automatically transferring supervised targets method for segmenting lung lesion regions with CT imaging.

BACKGROUND: To present an approach that autonomously identifies and selects a self-selective optimal target for the purpose of enhancing learning efficiency to segment infected regions of the lung from chest computed tomography images. We designed a semi-supervised dual-branch framework for training, where the training set consisted of limited expert-annotated data and a large amount of coarsely annotated data that was automatically segmented based on Hu values, which were used to train both strong and weak branches. In addition, we employed the Lovasz scoring method to automatically switch the supervision target in the weak branch and select the optimal target as the supervision object for training. This method can use noisy labels for rapid localization during the early stages of training, and gradually use more accurate targets for supervised training as the training progresses. This approach can utilize a large number of samples that do not require manual annotation, and with the iterations of training, the supervised targets containing noise become closer and closer to the fine-annotated data, which significantly improves the accuracy of the final model. RESULTS: The proposed dual-branch deep learning network based on semi-supervision together with cost-effective samples achieved 83.56 ± 12.10 and 82.67 ± 8.04 on our internal and external test benchmarks measured by the mean Dice similarity coefficient (DSC). Through experimental comparison, the DSC value of the proposed algorithm was improved by 13.54% and 2.02% on the internal benchmark and 13.37% and 2.13% on the external benchmark compared with U-Net without extra sample assistance and the mean-teacher frontier algorithm, respectively. CONCLUSION: The cost-effective pseudolabeled samples assisted the training of DL models and achieved much better results compared with traditional DL models with manually labeled samples only. Furthermore, our method also achieved the best performance compared with other up-to-date dual branch structures.

Efficient generation of functional hepatocyte-like cells from mouse liver progenitor cells via indirect co-culture with immortalized human hepatic stellate cells.

BACKGROUND: Differentiation of liver progenitor cells (LPCs) to functional hepatocytes holds great potential to develop new strategies for hepatocyte transplantation and the screening of drug-induced cytotoxicity. However, reports on the efficient and convenient hepatic differentiation of LPCs to hepatocytes are few. The present study aims to investigate the possibility of generating functional hepatocytes from LPCs in an indirect co-culture system. METHODS: Mouse LPCs were co-cultured in Transwell plates with an immortalized human hepatic stellate cell line (HSC-Li) we previously established. The morphology, expression of hepatic markers, and functions of mouse LPC-derived cells were monitored and compared with those of conventionally cultured LPCs. RESULTS: Co-culturing with HSC-Li cells induced differentiation of mouse LPCs into functional hepatocyte-like cells. The differentiated cells were morphologically transformed into hepatocyte-like cells 3 days after co-culture initiation. In addition, the differentiated cells expressed liver-specific genes and possessed hepatic functions, including glycogen storage, low-density lipoprotein uptake, albumin secretion, urea synthesis, and cytochrome P450 1A2 enzymatic activity. CONCLUSIONS: Our method, which employs indirect co-culture with HSC-Li cells, can efficiently induce the differentiation of LPCs into functional hepatocytes. This finding suggests that this co-culture system can be a useful method for the efficient generation of functional hepatocytes from LPCs.

Efficacy of coupled low-volume plasma exchange with plasma filtration adsorption in treating pigs with acute liver failure: A randomised study.

BACKGROUND & AIMS: Extracorporeal blood purification systems for supportive therapy of liver failure are widely used. We developed a novel blood purification system, named Li's artificial liver system (Li-ALS), which couples low-volume plasma exchange (low-volume PE) with plasma filtration adsorption (PFA). This study aims to evaluate the efficacy of our novel system in pigs with acute liver failure (ALF). METHODS: Thirty-two pigs were infused with D-galactosamine (1.3g/kg) to induce ALF. All animals were equally and randomly divided into four groups: the ALF control group received intensive care, the PFA group underwent five hour plasma recycling filtration and adsorption purification, the low-volume PE group received one hour low-volume PE, and the Li-ALS group underwent one hour low-volume PE, followed by five hour PFA. Intervention was initiated 36hours after drug administration. The efficacy of each treatment was assessed by survival time and improvement in hematological, biochemical, and immunohistological parameters. RESULTS: Pigs in the Li-ALS group survived longer than those in the other groups (p<0.001, ALF control: 60±2h; PFA group: 74±2h; low-volume PE group: 75±2h; and Li-ALS group: 90±3h). Liver enzyme, bilirubin, bile acid and blood ammonia levels were decreased significantly after Li-ALS treatment, and increases in inflammatory cytokines were ameliorated. A higher hepatocyte regeneration index was also observed in the Li-ALS group. CONCLUSION: Our novel Li-ALS could expedite liver regeneration and improve survival time; hence, it could be promising for treating ALF.

Establishment and characterization of an immortalized human hepatic stellate cell line for applications in co-culturing with immortalized human hepatocytes.

BACKGROUND AND OBJECTIVE: The liver-specific functions of hepatocytes are improved by co-culturing hepatocytes with primary hepatic stellate cells (HSC). However, primary HSC have a short lifespan in vitro, which is considered a major limitation for their use in various applications. This study aimed to establish immortalized human HSC using the simian virus 40 large T antigen (SV40LT) for applications in co-culturing with hepatocytes and HSC in vitro. METHODS: Primary human HSC were transfected with a recombinant retrovirus containing SV40LT. The immortalized human HSC were characterized by analyzing their gene expression and functional characteristics. The liver-specific functions of hepatocytes were evaluated in a co-culture system incorporating immortalized human hepatocytes with HSC-Li cells. RESULTS: The immortalized HSC line, HSC-Li, was obtained after infection with a recombinant retrovirus containing SV40LT. The HSC-Li cells were longitudinally spindle-like and had numerous fat droplets in their cytoplasm as shown using electron microscopy. Hepatocyte growth factor (HGF), VEGF Receptor 1(Flt-1), collagen type Iα1 and Iα2 mRNA expression levels were observed in the HSC-Li cells by RT-PCR. Immunofluorescence staining showed that the HSC-Li cells were positive for α-smooth muscle actin (α-SMA), platelet-derived growth factor receptor-beta (PDGFR-ß), vimentin, and SV40LT protein expression. The HSC-Li cells produced both HGF and transforming growth factor-beta1 (TGF-ß1) in a time-dependent manner. Real-time PCR showed that albumin, CYP3A5, CYP2E1, and UGT2B7 mRNA expression generally increased in the co-culture system. The enzymatic activity of CYP1A2 under the co-culture conditions also generally increased as compared to the monoculture of immortalized human hepatocytes. CONCLUSIONS: We successfully established the immortalized human HSC cell line HSC-Li. It has the specific phenotypic and functional characteristics of primary human HSC, which would be a useful tool to develop anti-fibrotic therapies. Co-culturing with the HSC-Li cells improved the liver-specific functions of hepatocytes, which may be valuable and applicable for bioartificial liver systems.

Effects of plasma exchange combined with continuous renal replacement therapy on acute fatty liver of pregnancy.

BACKGROUND: Acute fatty liver of pregnancy (AFLP) in the third trimester or early postpartum period can lead to fatal liver damage. Its traditional therapy is not very effective in facilitating hepatic recovery. The safety and effect of plasma exchange (PE) in combination with continuous renal replacement therapy (CRRT) (PE+CRRT) for AFLP still needs evaluation. METHODS: Five AFLP patients with hepatic encephalopathy and renal failure were subjected to PE+CRRT in our department from 2007 to 2012. Their symptoms, physical signs and results were observed, and all relevant laboratory tests were compared before and after PE+CRRT. RESULTS: All the 5 patients were well tolerated to the therapy. Four of them responded to the treatment and showed improvement in clinical symptoms/signs and laboratory results, and they were cured and discharged home after the treatment. One patient succeeded in bridging to transplantation for slowing down hepatic failure and its complications process after 2 treatment sessions. Intensive care unit stay and hospital stay were 9.4 (range 5-18) and 25.0 days (range 11-42), respectively. CONCLUSION: PE+CRRT is safe and effective and should be used immediately at the onset of hepatic encephalopathy and/or renal failure in patients with AFLP.

Road surface crack detection based on improved YOLOv5s.

In response to the issues of low efficiency and high cost in traditional manual methods for road surface crack detection, an improved YOLOv5s (you only look once version 5 small) algorithm was proposed. Based on this improvement, a road surface crack object recognition model was established using YOLOv5s. First, based on the Res2Net (a new multi-scale backbone architecture) network, an improved multi-scale Res2-C3 (a new multi-scale backbone architecture of C3) module was suggested to enhance feature extraction performance. Second, the feature fusion network and backbone of YOLOv5 were merged with the GAM (global attention mechanism) attention mechanism, reducing information dispersion and enhancing the interaction of global dimensions features. We incorporated dynamic snake convolution into the feature fusion network section to enhance the model's ability to handle irregular shapes and deformation problems. Experimental results showed that the final revision of the model dramatically increased both the detection speed and the accuracy of road surface identification. The mean average precision (mAP) reached 93.9%, with an average precision improvement of 12.6% compared to the YOLOv5s model. The frames per second (FPS) value was 49.97. The difficulties of low accuracy and slow speed in road surface fracture identification were effectively addressed by the modified model, demonstrating that the enhanced model achieved relatively high accuracy while maintaining inference speed.

Effects of N6-methyladenosine modification on metabolic reprogramming in digestive tract tumors.

N6-methyladenosine (m6A), the most abundant RNA modification within cells, participates in various biological and pathological processes, including self-renewal, invasion and proliferation, drug resistance, and stem cell characteristics. The m6A methylation plays a crucial role in tumors by regulating multiple RNA processes such as transcription, processing, and translation. Three protein types are primarily involved in m6A methylation: methyltransferases (such as METTL3, METTL14, ZC3H13, and KIAA1429), demethylases (such as FTO, ALKBH5), and RNA-binding proteins (such as the family of YTHDF, YTHDC1, YTHDC2, and IGF2BPs). Various metabolic pathways are reprogrammed in digestive tumors to meet the heightened growth demands and sustain cellular functionality. Recent studies have highlighted the extensive impact of m6A on the regulation of digestive tract tumor metabolism, further modulating tumor initiation and progression. Our review aims to provide a comprehensive understanding of the expression patterns, functional roles, and regulatory mechanisms of m6A in digestive tract tumor metabolism-related molecules and pathways. The characterization of expression profiles of m6A regulatory factors and in-depth studies on m6A methylation in digestive system tumors may provide new directions for clinical prediction and innovative therapeutic interventions.

Phylogenetic Partitioning of Gansu Flora: Unveiling the Core Transitional Zone of Chinese Flora.

Floristic regions, conventionally established using species distribution patterns, have often overlooked the phylogenetic relationships among taxa. However, how phylogenetic relationships influence the historical interconnections within and among biogeographic regions remains inadequately understood. In this research, we compiled distribution data for seed plants in Gansu, a region of significant biogeographic diversity located in northwestern China.We proposed a novel framework for floristic regions within Gansu, integrating distribution data and phylogenetic relationships of genera-level native seed plants, aiming to explore the relationship between phylogenetic relatedness, taxonomic composition, and regional phylogenetic delineation. We found that (1) phylogenetic relatedness was strongly correlated with the taxonomic composition among floras in Gansu. (2) The southeastern Gansu region showed the lowest level of spatial turnover in both phylogenetic relationships and the taxonomic composition of floristic assemblages across the Gansu region. (3) Null model analyses indicated nonrandom phylogenetic structure across the region, where most areas showed higher phylogenetic turnover than expected given the underlying taxonomic composition between sites. (4) Our results demonstrated a consistent pattern across various regionalization schemes and highlighted the preference for employing the phylogenetic dissimilarity approach in biogeographical regionalization investigations. (5) Employing the phylogenetic dissimilarity approach, we identified nine distinct floristic regions in Gansu that are categorized into two broader geographical units, namely the northwest and southeast. (6) Based on the phylogenetic graphic regions of China across this area.

Establishment and characterization of immortalized human hepatocyte cell line for applications in bioartificial livers.

An immortalized human hepatocyte cell line, HepLi5, was established via transfection of Simian virus 40 large T antigen (SV40 LT) into primary human hepatocytes. The morphologic and functional characteristics of HepLi5 cells were evaluated. The expression of SV40 LT in HepLi5 cells was detected by reverse transcription-PCR (RT-PCR) and western blotting. mRNA expression of liver-enriched genes, including glutamine synthetase, albumin, and cytochrome P450 was detected via RT-PCR in HepLi5 cells. Activity of CYP1A2, one of the drug-metabolizing P450 enzymes, was detected. Subcutaneous injection of HepLi5 cells into nude mice did not induce tumors within 3 months. Short Tandem Repeat results confirmed the authenticity of the cell line. Clinical-grade quantities of HepLi5 cells could be harvested using large-scale culture in roller bottles after which their cellular function was significantly enhanced. Therefore, the immortalized HepLi5 cells are a suitable cell source for applications in bioartificial livers.

Current biogeographical roles of the Kunlun Mountains.

Large-scale patterns of biodiversity and formation have garnered increasing attention in biogeography and macroecology. The Qinghai-Tibet Plateau (QTP) is an ideal area for exploring these issues. However, the QTP consists of multiple geographic subunits, which are understudied. The Kunlun Mountains is a geographical subunit situated in the northern edge of the QTP, in northwest China. The diversity pattern, community phylogenetic structures, and biogeographical roles of the current flora of the Kunlun Mountains were analyzed by collecting and integrating plant distribution, regional geological evolution, and phylogeography. A total of 1911 species, 397 genera, and 75 families present on the Kunlun Mountains, of which 29.8% of the seed plants were endemic to China. The mean divergence time (MDT) of the Kunlun Mountains flora was in the early Miocene (19.40 Ma). Analysis of plant diversity and MDT indicated that the eastern regions of the Kunlun Mountains were the center of species richness, endemic taxa, and ancient taxa. Geographical origins analysis showed that the Kunlun Mountains flora was diverse and that numerous clades were from East Asia and Tethyan. Analysis of geographical origins and geological history together highlighted that the extant biodiversity on the Kunlun Mountains appeared through species recolonization after climatic fluctuations and glaciations during the Quaternary. The nearest taxon index speculated that habitat filtering was the most important driving force for biodiversity patterns. These results suggest that the biogeographical roles of the Kunlun Mountains are corridor and sink, and the corresponding key processes are species extinction and immigration. The Kunlun Mountains also form a barrier, representing a boundary among multiple floras, and convert the Qinghai-Tibet Plateau into a relatively closed geographical unit.

Current patterns of plant diversity and phylogenetic structure on the Kunlun Mountains.

Large-scale patterns of biodiversity and the underlying mechanisms that regulate these patterns are central topics in biogeography and macroecology. The Qinghai-Tibet Plateau serves as a natural laboratory for studying these issues. However, most previous studies have focused on the entire Qinghai-Tibet Plateau, leaving independent physical geographic subunits in the region less well understood. We studied the current plant diversity of the Kunlun Mountains, an independent physical geographic subunit located in northwestern China on the northern edge of the Qinghai-Tibet Plateau. We integrated measures of species distribution, geological history, and phylogeography, and analyzed the taxonomic richness, phylogenetic diversity, and community phylogenetic structure of the current plant diversity in the area. The distribution patterns of 1911 seed plants showed that species were distributed mainly in the eastern regions of the Kunlun Mountains. The taxonomic richness, phylogenetic diversity, and genera richness showed that the eastern regions of the Kunlun Mountains should be the priority area of biodiversity conservation, particularly the southeastern regions. The proportion of Chinese endemic species inhabiting the Kunlun Mountains and their floristic similarity may indicate that the current patterns of species diversity were favored via species colonization. The Hengduan Mountains, a biodiversity hotspot, is likely the largest source of species colonization of the Kunlun Mountains after the Quaternary. The net relatedness index indicated that 20 of the 28 communities examined were phylogenetically dispersed, while the remaining communities were phylogenetically clustered. The nearest taxon index indicated that 27 of the 28 communities were phylogenetically clustered. These results suggest that species colonization and habitat filtering may have contributed to the current plant diversity of the Kunlun Mountains via ecological and evolutionary processes, and habitat filtering may play an important role in this ecological process.

T-SPOT with CT image analysis based on deep learning for early differential diagnosis of nontuberculous mycobacteria pulmonary disease and pulmonary tuberculosis.

OBJECTIVES: This study aimed to establish a diagnostic algorithm combining T-SPOT with computed tomography image analysis based on deep learning (DL) for early differential diagnosis of nontuberculous mycobacteria pulmonary disease (NTM-PD) and pulmonary tuberculosis (PTB). METHODS: A total of 1049 cases were enrolled, including 467 NTM-PD and 582 PTB cases. A total of 320 cases (160 NTM-PD and 160 PTB) were randomized as the testing set and were analyzed using T-SPOT combined with the DL model. The testing cases were first divided into T-SPOT-positive and -negative groups, and the DL model was then used to separate the cases into four subgroups further. RESULTS: The precision was found to be 91.7% for the subgroup of T-SPOT-negative and DL classified as NTM-PD, and 89.8% for T-SPOT-positive and DL classified as PTB, which covered 66.9% of the total cases, compared with the accuracy rate of 80.3% of T-SPOT alone. In the other two remaining groups, where the T-SPOT prediction was inconsistent with the DL model, the accuracy was 73.0% and 52.2%, separately. CONCLUSION: Our study shows that the new diagnostic system combining T-SPOT with DL based computed tomography image analysis can greatly improve the classification precision of NTM-PD and PTB when the two methods of prediction are consistent.

Bioartificial liver system based on choanoid fluidized bed bioreactor improve the survival time of fulminant hepatic failure pigs.

Bioartificial liver (BAL) support system has been proposed as potential treatment method for end-stage liver diseases. We described an improved BAL system based on a choanoid fluidized bed bioreactor containing alginate-chitosan encapsulated primary porcine hepatocytes. The feasibility, safety, and efficiency of this device were estimated using an allogeneic fulminant hepatic failure (FHF) model. FHF was induced with intravenous administration of D-galactosamine. Thirty FHF pigs were divided into three groups: (1) an FHF group which was only given intensive care; (2) a sham BAL group which was treated with the BAL system with empty encapsulation, and (3) a BAL group which was treated with the BAL system containing encapsulated freshly isolated primary porcine hepatocytes. The survival times and biochemical parameters of these animals were measured, and properties of the encapsulations and hepatocytes before and after perfusion were also evaluated. Compared to the two control groups, the BAL-treated group had prolonged the survival time and decreased the blood lactate levels, blood glucose, and amino acids remained stable. No obvious ruptured beads or statistical decline in viability or function of encapsulated hepatocytes were observed. This new fluidized bed BAL system is safe and efficient. It may represent a feasible alternative in the treatment of liver failure.

Prevalence of hepatitis B and C in HIV-infected patients: a meta-analysis.

BACKGROUND: Hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share similar routes of transmission by sexual intercourse or drug use by parenteral injection, so coinfection is common. This study aimed to determine the prevalence of coinfection with either HCV or HBV in patients infected with HIV. DATA SOURCES: A meta-analysis was performed to quantify HBV coinfection with HCV in HIV patients. Published studies in the English and Chinese language medical literature involving cohorts of HIV patients concomitantly infected with HBV and/or HCV were collected from the PubMed database, ISI Web of Science, the Cochrane library clinical trials registry, CNKI (China National Knowledge Infrastructure) and Google Scholar, for relevant articles before November 2009. The search was conducted with the following key words: hepatitis C, HCV, hepatitis B, HBV, human immunodeficiency virus, HIV, and coinfection. Data were extracted from relevant studies by two investigators. RevMan 5.0 software was used to perform the meta-analysis. RESULTS: We identified 22 studies involving 17 664 patients. Substantial differences in the HCV rate compared to the HBV rate in HIV patients were found in the overall analysis [odds ratio (OR)=3.00; 95% confidence interval (CI) 1.90-4.73]. A subgroup analysis showed similar results in a European group, but not in Asian or African groups. However, a meta-analysis between HIV+HBV+HCV+ and HIV+HBV+HCV- patients showed no significant difference (OR=0.91; 95% CI 0.57-1.45). Although subgroup analysis still lacked essential differences, different regions seemed to have different patterns. CONCLUSIONS: HCV-HIV coinfection is more frequent than HBV-HIV coinfection overall. However, HCV infection does not affect the prevalence of HBV infection in HIV-positive patients.

Prognostic models for acute liver failure.

BACKGROUND: Acute liver failure (ALF) remains a dramatic and unpredictable disease with high morbidity and mortality. Early and accurate prognostic assessment of patients with ALF is critically important for optimum clinical pathway. DATA SOURCES: Five English-language medical databases, MEDLINE, ScienceDirect, OVID, Springer Link and Wiley Interscience were searched for articles on "acute liver failure", "prognosis", and related topics. RESULTS: Multi-variable prognostic models including the King's College Hospital criteria and the model for end-stage liver disease score have been widely used in determination of the prognosis of ALF, but the results are far from satisfactory. Other prognostic indicators including serum Gc-globulin, arterial blood lactate, serum phosphate, arterial blood ammonia, and serum alpha-fetoprotein are promising but await further assessement. CONCLUSIONS: A reliable prognostic model to be developed in the future should not only have predictive value for poor outcome but also help to predict the survival of patients without a liver transplantation. Further studies are necessary to assess the prognostic accuracy of any new models.

Effects of plasma from patients with acute on chronic liver failure on function of cytochrome P450 in immortalized human hepatocytes.

BACKGROUND: The bioartificial liver is anticipated to be a promising alternative choice for patients with liver failure. Toxic substances which accumulate in the patients' plasma exert deleterious effects on hepatocytes in the bioreactor, and potentially reduce the efficacy of bioartificial liver devices. This study was designed to investigate the effects of plasma from patients with acute on chronic liver failure (AoCLF) on immortalized human hepatocytes in terms of cytochrome P450 gene expression, drug metabolism activity and detoxification capability. METHODS: Immortalized human hepatocytes (HepLi-2 cells) were cultured in medium containing fetal calf serum or human plasma from three patients with AoCLF. The cytochrome P450 (CYP3A5, CYP2E1, CYP3A4) expression, drug metabolism activity and detoxification capability of HepLi-2 cells were assessed by RT-PCR, lidocaine clearance and ammonia elimination assay. RESULTS: After incubation in medium containing AoCLF plasma for 24 hours, the cytochrome P450 mRNA expression of HepLi-2 cells was not significantly decreased compared with control culture. Ammonia elimination and lidocaine clearance assay showed that the ability of ammonia removal and drug metabolism remained stable. CONCLUSIONS: Immortalized human hepatocytes can be exposed to AoCLF plasma for at least 24 hours with no significant reduction in the function of cytochrome P450. HepLi-2 cells appear to be effective in metabolism and detoxification and can be potentially used in the development of bioartificial liver.

Identification and Validation of Immune-Related Gene Prognostic Signature for Hepatocellular Carcinoma.

Immune-related genes (IRGs) have been identified as critical drivers of the initiation and progression of hepatocellular carcinoma (HCC). This study is aimed at constructing an IRG signature for HCC and validating its prognostic value in clinical application. The prognostic signature was developed by integrating multiple IRG expression data sets from TCGA and GEO databases. The IRGs were then combined with clinical features to validate the robustness of the prognostic signature through bioinformatics tools. A total of 1039 IRGs were identified in the 657 HCC samples. Subsequently, the IRGs were subjected to univariate Cox regression and LASSO Cox regression analyses in the training set to construct an IRG signature comprising nine immune-related gene pairs (IRGPs). Functional analyses revealed that the nine IRGPs were associated with tumor immune mechanisms, including cell proliferation, cell-mediated immunity, and tumorigenesis signal pathway. Concerning the overall survival rate, the IRGPs distinctly grouped the HCC samples into the high- and low-risk groups. Also, we found that the risk score based on nine IRGPs was related to clinical and pathologic factors and remained a valid independent prognostic signature after adjusting for tumor TNM, grade, and grade in multivariate Cox regression analyses. The prognostic value of the nine IRGPs was further validated by forest and nomogram plots, which revealed that it was superior to the tumor TNM, grade, and stage. Our findings suggest that the nine-IRGP signature can be effective in determining the disease outcomes of HCC patients.

Identification of prognostic biomarkers of hepatocellular carcinoma via long noncoding RNA expression and copy number alterations.

Aim: This study aimed to identify long noncoding RNAs (lncRNAs) with potential to be prognostic biomarkers of hepatocellular carcinoma (HCC) by analyzing copy number alterations (CNAs). Methods: RNA Sequencing data of 369 HCC patients was downloaded from The Cancer Genome Atlas database and analyzed with a series of systematic bioinformatics methods. Results: LncRNA-CNA association analysis revealed that many lncRNAs were located in sites frequently amplified or deleted. Three upregulated lncRNAs (LINC00689, SNHG20 and MAFG-AS1) with copy amplification and one downregulated lncRNA TMEM220-AS1 with copy deletion were associated with poor prognosis of HCC. Conclusion: This study reveals that differentially expressed lncRNAs correlate with CNAs in HCC. Moreover, the differentially expressed lncRNAs and their copy amplification/deletions could be promising prognostic biomarkers of HCC.

Transcriptomics Curation of SARS-CoV-2 Related Host Genes in Mice With COVID-19 Comorbidity: A Pilot Study.

The pandemic of coronavirus disease 2019 (COVID-19), a respiratory disease caused by a novel severe acute respiratory syndrome coronavirus-2, is causing substantial morbidity and mortality. Along with the respiratory symptoms, underlying diseases in senior patients, such as diabetes, hypertension, and coronary heart disease, are the most common comorbidities, which cause more severe outcomes and even death. During cellular attachment and entry of severe acute respiratory syndrome coronavirus-2, the key protein involved is the angiotensin I converting enzyme 2 (ACE2), which is located on the membrane of host cells. Here, we aim to curate an expression profile of Ace2 and other COVID-19 related genes across the available diabetes murine strains. Based on strictly manual curation and bioinformatics analysis of the publicly deposited expression datasets, Ace2 and other potentially involved genes such as Furin, Tmprss2, Ang, and Ang2 were examined. We found that Ace2 expression is rather ubiquitous in three selected diabetes prone strains (db/db, ob/ob and diet-induced obese). With the most abundant datasets present, the liver shows a medium Ace2 expression level compared with the lungs, pancreatic islets, brain and even T cells. Age is a more critical factor for Ace2 expression in db/db compared with the other two strains. Besides Ace2, the other four host genes showed varied levels of correlation to each other. To accelerate research on the interaction between COVID-19 and underlying diseases, the Murine4Covid transcriptomics database (www.geneureka.org/Murine4Covid) will facilitate the design of research on COVID-19 and comorbidities.