Bioinformatic Analysis of Roquin Family Reveals Their Potential Role in Immune System.

The Roquin family is a recognized RNA-binding protein family that plays vital roles in regulating the expression of pro-inflammatory target gene mRNA during the immune process in mammals. However, the evolutionary status of the Roquin family across metazoans remains elusive, and limited studies are found in fish species. In this study, we discovered that the RC3H genes underwent a single round of gene duplication from a primitive ancestor during evolution from invertebrates to vertebrates. Furthermore, there were instances of species-specific gene loss events or teleost lineage-specific gene duplications throughout evolution. Domain/motif organization and selective pressure analysis revealed that Roquins exhibit high homology both within members of the family within the same species and across species. The three rc3h genes in zebrafish displayed similar expression patterns in early embryos and adult tissues, with rc3h1b showing the most prominent expression among them. Additionally, the promoter regions of the zebrafish rc3h genes contained numerous transcription factor binding sites similar to those of mammalian homologs. Moreover, the interaction protein network of Roquin and the potential binding motif in the 3'-UTR of putative target genes analysis both indicated that Roquins have the potential to degrade target mRNA through mechanisms similar to those of mammalian homologs. These findings shed light on the evolutionary history of Roquin among metazoans and hypothesized their role in the immune systems of zebrafish.

Inhibition of SK2 and ER stress ameliorated inflammation and apoptosis in liver ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) remains a major cause of mortality and morbidity after liver surgery. Endoplasmic reticulum (ER) stress is a critical mechanism of inflammatory injury during hepatic IRI. In this study, we investigated the effect of sphingosine kinases 2 (SK2) on ER stress and hepatic IRI. We established hepatic IRI mice and hepatocellular hypoxia/reoxygenation in vitro model. We observed the SK2 and ER stress protein IRE1α expression. Then, we used an SK2 inhibitor and knocked down IRE1α/SK2, to observe the effect of SK2 during IRI. Our results showed that the expression of ER stress and SK2 was significantly elevated during hepatic IRI. Inhibition of SK2 ameliorated liver inflammation and reduced cell apoptosis in hepatic IRI mice. Consistently, we found that the inhibition of IRE1α also downregulated SK2 expression and reduced mitochondrial membrane permeability. Furthermore, the knockdown of SK2 could also reduce cell damage and reduce the expression of inflammatory factors but did not influence ER stress-related signaling pathway. Taken together, our results suggested that ER stress and SK2 played important and regulatory roles in hepatic IRI. Inhibition of ER stress and SK2 could significantly improve liver function after hepatic IRI.

Evolutionary and Expression Analysis of MOV10 and MOV10L1 Reveals Their Origin, Duplication and Divergence.

MOV10 and MOV10L1 both encode ATP-dependent RNA helicases. In mammals, MOV10 and MOV10L1 participate in various kinds of biological contexts, such as defense of RNA virus invasion, neuron system, germ cell and early development. However, mov10 and mov10l1 in zebrafish are obscure and the evolutionary relationships of mov10 among different species remain unclear. In this study, we found MOV10 and MOV10L1 had some variations despite they possessed the conserved feature of RNA helicase, however, they may originate from a single ancestor although they shared limited homology. A single MOV10L1 gene existed among all species, while MOV10 gene experienced lineage-specific intra-chromosomal gene duplication in several species. Interestingly, the mov10 gene expanded to three in zebrafish, which originating from a duplication by whole genome specific duplication of teleost lineage followed by a specific intra-chromosome tandem duplication. The mov10 and mov10l1 showed distinct expression profiles in early stages, however, in adult zebrafish, three mov10 genes exhibited similar diverse expression patterns in almost all tissues. We also demonstrated mov10 genes were upregulated upon virus challenge, highlighting they had redundant conserved roles in virus infection. These results provide valuable data for the evolution of MOV10 and MOV10L1 and they are important to the further functional exploration.

Overexpression of MdATG8i Enhances Drought Tolerance by Alleviating Oxidative Damage and Promoting Water Uptake in Transgenic Apple.

Water deficit adversely affects apple (Malus domestica) productivity on the Loess Plateau. Autophagy plays a key role in plant responses to unfavorable environmental conditions. Previously, we demonstrated that a core apple autophagy-related protein, MdATG8i, was responsive to various stresses at the transcript level. Here, we investigated the function of this gene in the response of apple to severe drought and found that its overexpression (OE) significantly enhanced drought tolerance. Under drought conditions, MdATG8iOE apple plants exhibited less drought-related damage and maintained higher photosynthetic capacities compared with the wild type (WT). The accumulation of ROS (reactive oxygen species) was lower in OE plants under drought stress and was accompanied by higher activities of antioxidant enzymes. Besides, OE plants accumulated lower amounts of insoluble or oxidized proteins but greater amounts of amino acids and flavonoid under severe drought stress, probably due to their enhanced autophagic activities. Particularly, MdATG8iOE plants showed higher root hydraulic conductivity than WT plants did under drought conditions, indicating the enhanced ability of water uptake. In summary, the overexpression of MdATG8i alleviated oxidative damage, modulated amino acid metabolism and flavonoid synthesis, and improved root water uptake, ultimately contributing to enhanced drought tolerance in apple.

A novel hepatic lectin of zebrafish Danio rerio is involved in innate immune defense.

ASGPR (asialoglycoprotein receptor, also known as hepatic lectin) was the first identified animal lectin, which participated in a variety of physiological processes. Yet its detailed immune functions are not well studied in lower vertebrates. After reporting a zebrafish hepatic lectin (Zhl), we identified a novel hepatic lectin (zebrafish hepatic lectin-like, Zhl-l) in zebrafish. The zhl-l was mainly expressed in liver in a tissue specific manner. And challenge with LPS/LTA induced a significant change of zhl-l expression. What's more, recombinant C-type lectin domain (rCTLD) of Zhl-l had the activity of agglutinating and binding to both Gram-negative and Gram-positive bacteria. It promoted the phagocytosis of bacteria by carp macrophages. Moreover, rCTLD could bind to insoluble lipopolysaccharide (LPS), lipoteichoic acid (LTA) and peptidoglycan (PGN) independent of Ca2+, which was inhibited by galactose. Interestingly, Zhl-l was located in the membrane, and its overexpression could upregulate the production of pre-inflammatory cytokines. Taken together, these results indicated that Zhl-l played a role in immune defense, and would provide further information to understand functions of C-type lectin family and the innate immunity in vertebrates.

Inhibition of HIF1A-AS1 promoted starvation-induced hepatocellular carcinoma cell apoptosis by reducing HIF-1α/mTOR-mediated autophagy.

BACKGROUND: Hepatocellular carcinoma (HCC) is still a major health burden in China considering its high incidence and mortality. Long non-coding RNAs (lncRNAs) were found playing vital roles in tumor progression, suggesting a new way of diagnosis and prognosis prediction, or treatment of HCC. This study was designed to investigate the role of HIF1A-AS1 during the progression of HCC and to explore its related mechanisms. METHODS: The expression of HIF1A-AS1 was detected in 50 paired carcinoma tissues and adjacent normal tissues by quantitative real-time PCR assay. HCC cell apoptosis was induced by nutrient-deficient culture medium and detected by Cell Counting Kit-8 and flow cytometer assays. HIF1A-AS1 inhibition in HCC cells was accomplished by small interfering RNA transfection. RESULTS: HIF1A-AS1 was overexpressed in HCC tissues and was associated with tumor size, TNM stage, and lymph node metastasis. Compared with the low HIF1A-AS1 group, the high HIF1A-AS1 group had a shorter overall survival and a worse disease-free survival. HIF1A-AS1 expression was significantly higher in HCC cell lines (7721 and Huh7) than that in normal hepatocyte cell line L02 under normal culture condition. However, under nutrient-deficient condition, HIF1A-AS1 expression was significantly increased in both HCC and normal hepatocyte cell lines and was increased with the prolongation of nutrient-free culture. Inhibition of HIF1A-AS1 promoted starvation-induced HCC cell apoptosis. Furthermore, inhibition of HIF1A-AS1 could also reduce starvation-induced HCC cell autophagy. The expression of HIF-1α and phosphorylated mTOR was significantly decreased in HCC cells after HIF1A-AS1 inhibition. CONCLUSIONS: HIF1A-AS1, overexpressed in HCC and associated with HCC prognosis, could regulate starvation-induced HCC cell apoptosis by reducing HIF-1α/mTOR-mediated autophagy, promoting HCC cell progression.

Transcutaneous Electrical Acustimulation Improves Gastrointestinal Disturbances Induced by Transcatheter Arterial Chemoembolization in Patients With Liver Cancers.

BACKGROUND: Gastrointestinal (GI) disturbances occur in patients who receive chemotherapy via transcatheter arterial chemoembolization (TACE) and could last for an extended period of time in some cases. Antiemetic drugs have a potential risk of developing hepatic failure and are ineffective for delayed nausea and emesis. Transcutaneous electrical acustimulation (TEA) has recently been reported to exert antiemetic and prokinetic effects, but it is unknown whether it has an ameliorating effect on TACE-induced GI disturbances. AIM: This study was designed to evaluate effects and mechanisms of noninvasive TEA on GI symptoms in patients treated with TACE. MATERIALS AND METHODS: Seventy-four patients with liver cancers (eighteen female; age 63.4 ± 1.1 years) scheduled for TACE were randomized to TEA (n = 37) or sham-TEA (n = 37). TEA was performed via acupoints, ST36 and PC6 using parameters previously optimized for GI motility (1 h, bid) from the postoperative day 0 (POD0) to POD2. Sham-TEA was performed using the same parameters via non-acupoints. Symptom questionnaires were completed daily. The electrogastrogram (EGG) and electrocardiogram (ECG) were recorded in the fasting state for 30 mins to assess gastric slow waves and autonomic functions, respectively, before and after the 3-day treatment. RESULTS: 1) In the acute phase (<24 h), TEA showed no effects on any of GI symptoms, compared with sham-TEA. 2) In the delayed phase (>24 h), TEA, compared with sham-TEA, decreased the percentage of patients who experienced nausea on POD3 (0% vs. 13.5%, p = 0.021), the nausea score on POD3 (p = 0.022), the anorexia score on POD2 (p = 0.040) and POD3 (p = 0.004), and the bloating score (POD1-3: p < 0.01). 3) In comparison with sham-TEA, TEA increased the number of spontaneous bowel movements (p = 0.001) and the Bristol score of the first stool (p = 0.014) and decreased the number of patients with the use of laxatives (p = 0.022). 4) Physiologically, the 3-day TEA but not sham-TEA increased the percentage of normal gastric slow waves (p < 0.001) and vagal activity (p = 0.006). The vagal activity was negatively correlated with the anorexia score (r = -0.267, p = 0.026). It was found that the sympathovagal ratio and tumor size>5 cm were independent risk factors predicting the occurrence of nausea in patients after TACE. CONCLUSION: TEA improves major TACE-induced GI disturbances in the delayed phase, including nausea, bloating, impaired gastric pace-making activity, and constipation in patients with liver cancers via the autonomic pathway.

Polarimetric learning: a Siamese approach to learning distance metrics of algal Mueller matrix images.

Polarimetric measurements are becoming increasingly accurate and fast to perform in modern applications. However, analysis on the polarimetric data usually suffers from its high-dimensional nature spatially, temporally, or spectrally. This paper associates polarimetric techniques with metric learning algorithms, namely, polarimetric learning, by introducing a distance metric learning method called Siamese network that aims to learn good distance metrics of algal Mueller matrix images in low-dimensional feature spaces. As an experimental example, 12,162 Mueller matrix images of eight algal species are measured via a forward Mueller matrix microscope. Eight classical metric learning algorithms, including principle component analysis, multidimensional scaling, isometric feature mapping, t-distributed stochastic neighbor embedding, Laplacian eigenmaps, locally linear embedding, linear discriminant analysis, and metric learning to rank, are considered, by which the algal Mueller matrix images are mapped to two-dimensional (2D) feature spaces with different distance metrics. Support-vector-machine-based holdout sample classification accuracies of the 2D feature vectors are provided in a supervised manner for quantitative comparisons of the low-dimensional distance metrics, including the results of the eight metric learning algorithms and 16 Siamese architectures with varying convolution, inception, and full connection modules. This study shows that the Siamese approach is an effective metric learning algorithm that can adaptively extract features exhibiting empirical correlations with the fast-axis-orientation-dependent and spatially variant algal retardance induced by the algal microstructures.

Classification of morphologically similar algae and cyanobacteria using Mueller matrix imaging and convolutional neural networks.

We present the Mueller matrix imaging system to classify morphologically similar algae based on convolutional neural networks (CNNs). The algae and cyanobacteria data set contains 10,463 Mueller matrices from eight species of algae and one species of cyanobacteria, belonging to four phyla, the shapes of which are mostly randomly oriented spheres, ovals, wheels, or rods. The CNN serves as an automatic machine with learning ability to help in extracting features from the Mueller matrix, and trains a classifier to achieve a 97% classification accuracy. We compare the performance in two ways. One way is to compare the performance of five CNNs that differ in the number of convolution layers as well as the classical principle component analysis (PCA) plus the support vector machine (SVM) method; the other way is to quantify the differences of scores between full Mueller matrix and the first matrix element m11, which does not contain polarization information under the same conditions. As the results show, deeper CNNs perform better, the best of which outperforms the conventional PCA plus SVM method by 19.66% in accuracy, and using the full Mueller matrix earns 6.56% increase of accuracy than using m11. It demonstrates that the coupling of Mueller matrix imaging and CNN may be a promising and efficient solution for the automatic classification of morphologically similar algae.

GPU acceleration of Monte Carlo simulations for polarized photon scattering in anisotropic turbid media.

In earlier studies, we developed scattering models and the corresponding CPU-based Monte Carlo simulation programs to study the behavior of polarized photons as they propagate through complex biological tissues. Studying the simulation results in high degrees of freedom that created a demand for massive simulation tasks. In this paper, we report a parallel implementation of the simulation program based on the compute unified device architecture running on a graphics processing unit (GPU). Different schemes for sphere-only simulations and sphere-cylinder mixture simulations were developed. Diverse optimizing methods were employed to achieve the best acceleration. The final-version GPU program is hundreds of times faster than the CPU version. Dependence of the performance on input parameters and precision were also studied. It is shown that using single precision in the GPU simulations results in very limited losses in accuracy. Consumer-level graphics cards, even those in laptop computers, are more cost-effective than scientific graphics cards for single-precision computation.

[Minimally invasive treatment of tibial plateau fracture under arthroscopy monitoring].

Twenty six patients with fracture of tibial plateau was under arthroscopy assisted reduction, the joint surface of bone graft, and USES the steel plate fixation treatment. Average surgery time was 65 min (70-120 min), average fracture healing time was 15 weeks (12-17 weeks), joint surface anatomical reattachment rate was 92.9%. Using break knee function criteria evaluation of curative effect: 18 cases great 6 cases wed, 2 cases ok, fine rate was 92.3%. No infection, deep venous thrombosis and small leg fascia chamber syndrome and other complications. Conclusion is that treatment of tibial plateau fractures under arthroscope has advantages of small trauma, check intuitively and reset accurately, functional recovery of patients are satisfied, the treatment has certain clinical application value.

Role and mechanism of esketamine in improving postoperative cognitive dysfunction in aged mice through the TLR4/MyD88/p38 MAPK pathway.

Postoperative cognitive dysfunction (POCD) is a significant concern for the elderly population worldwide. This study explored the effects of esketamine on aged mice with POCD and investigate its mechanism of action involving the TLR4/MyD88/MAPK pathway. We administrated esketamine, along with lipopolysaccharide or anisomycin, to the aged POCD mouse models. We assessed their cognitive function using the Morris water maze test. Additionally, we evaluated histopathological changes/neuronal apoptosis in the mouse hippocampal CA1 area through HE/TUNEL stainings. Furthermore, we measured IL-1ß/IL-6/TNF-α/TLR4/MyD88/MAPK (p-p38/p38) levels in mouse hippocampal tissues using ELISA/RT-qPCR/Western blotting. Lastly, we analyzed the interaction between TLR4 and MyD88 using a co-immunoprecipitation assay. Our findings showed that esketamine effectively mitigated POCD in aged mice. This was evident from the improved cognitive performance observed in the Morris water maze test, characterized by reduced escape latency/increased number of platform crossing/a higher percentage of time spent in the target quadrant. Furthermore, esketamine exhibited a protective effect against neuronal apoptosis and reduced the levels of inflammatory factors. These findings suggest that esketamine exerts an anti-inflammatory effect by downregulating TLR4/MyD88, thereby attenuating the inflammatory response associated with POCD. Additionally, esketamine suppressed the p38 MAPK pathway by inhibiting the TLR4/MyD88 signaling cascade. Esketamine demonstrated its efficacy in improving postoperative inflammation and cognitive impairment in aged mice by inhibiting the TLR4/MyD88 pathway. The activation of p38 MAPK signaling diminished the beneficial effects of esketamine in aged POCD mice. Collectively, the underlying mechanism of esketamine in mitigating POCD in aged mice involves the suppression of the TLR4/MyD88/p38 MAPK pathway.

The survival benefit from surgery on patients with large-cell neuroendocrine carcinoma in the lung: a propensity-score matching study.

PURPOSE: This study aimed to investigate the prognostic significance of surgery in large-cell neuroendocrine carcinoma (LCNC) patients. METHODS: A total of 453 patients from the Surveillance, Epidemiology, and End Results database diagnosed with stage T1-4N0-2M0 LCNC from 2010 to 2015 were analyzed. The propensity-score matching analysis with a ratio of 1:1 was used to minimize the bias effect of other clinical characteristics, and 77 pairs of patients' data were performed for subsequent statistical analysis. The Cox proportional hazards model, Kaplan-Meier analysis, and Log-rank test were used in the present study. The primary observational endpoint was cancer-specific survival (CSS). RESULTS: The 1-year, 3-year, and 5-year CSS rates were 60.0%, 45.0%, and 42.0% in those 453 LCNC patients. Compared with patients who underwent surgical resection, patients without surgery had a lower 5-year CSS rate (18.0% vs. 52.0%, P < 0.001). After analyses of multivariable Cox regression, chemotherapy, T stage, N stage, and surgery were identified as independent prognostic indicators (all P < 0.05). In the cohort of old patients, the median survival time was longer in cases after surgery than those without surgery (13.0 months vs. NA, P < 0.001). Besides, in patients with different clinical characteristics, the receiving surgery was a protective prognostic factor (all hazard ratio < 1, all P < 0.05). In addition, for the cohort with stage T1-2N0-2M0, patients after the operation had more improved outcomes than patients without surgery (P < 0.001). CONCLUSIONS: We proposed that the surgery could improve the survival outcomes of LCNC patients with stage T1-4N0-2M0. Moreover, old patients could benefit from surgery.

Experimental study on compression mechanical characteristics of filled rock joints after multiple pre-impacts.

The prefabricated artificial filled jointed rock specimens are impacted by a self-made drop hammer impact device for many times, and the specimens with different degrees of cumulative damage characteristics are obtained. Then, the static and dynamic compression mechanical properties are studied by using universal testing machine and SHPB device. Through the static compression test, the strength and deformation characteristics of jointed rock specimens after multiple impacts are obtained, and the influence of the damage degree of jointed rock specimens characterized by wave velocity on the compressive strength of filled joints is analysed. Based on the results of SHPB impact test, the dynamic strength and deformation evolution, wave propagation law and energy dissipation law of filled joints after multiple impacts are analysed. During the SHPB test, the impact failure process of rock specimens is recorded by a high-speed camera. The experimental results show that the damage degree of jointed rock samples increases nonlinearly after multiple impacts. The attenuation laws of static strength and dynamic strength of rock samples under the same damage evolution conditions are different. With the increase of impact times, the failure mode of jointed rock samples after damage is simpler and tends to compression failure.

Sarcomatoid intrahepatic cholangiocarcinoma with good patient prognosis after treatment with Huaier granules following hepatectomy: A case report.

BACKGROUND: Sarcomatoid intrahepatic cholangiocarcinoma (SICC) is an extremely rare and highly invasive malignant tumor of the liver. The precise pathologic mechanism of SICC has not been clearly identified, and the prognosis is very poor. The effectiveness of the treatment strategy of radical hepatectomy combined with Huaier granules has not yet been reported. CASE SUMMARY: The patient was a 69-year-old male who presented with intermittent right upper abdominal pain for one month and 4-pound weight loss before admission. Abdominal magnetic resonance imaging and magnetic resonance cholangiopancreatography showed multiple stones in the bile ducts accompanied by dilatation of the intrahepatic and extrahepatic bile ducts. The preoperative diagnoses were right intrahepatic bile duct stones and extrahepatic bile duct stones; thus, surgical resection was performed. Choledochoscopy showed that the bile duct wall of the right anterior lobe was thickened, and a mass was visible in the duct. Then, a biopsy was performed, and rapid frozen-section biopsy analysis indicated that the tumor was malignant. The final diagnosis was SICC (T1aN0M0). Huaier granules were taken by the patient as anticancer therapy after surgery. The patient attended follow-up for 72 mo with no tumor recurrence or metastasis. CONCLUSION: Sarcomatous intrahepatic cholangiocarcinoma is an extremely rare, aggressive malignancy, and the diagnostic gold standard is pathological diagnosis. We reported the first case of successful treatment with Huaier granules as anticancer therapy after surgery, which indicated that Huaier granules are safe and effective. Further studies are needed to study the anticancer molecular mechanisms of Huaier granules in sarcomatous intrahepatic cholangiocarcinoma.

Cd248a and Cd248b in zebrafish participate in innate immune responses.

CD248, also known as endosialin or tumor endothelial marker 1, is a type I single transmembrane glycoprotein. CD248 has been demonstrated to be upregulated in cancers, tumors and many fibrotic diseases in human and mice, such as liver damage, pulmonary fibrosis, renal fibrosis, arthritis and tumor neovascularization. However, no definite CD248 orthologs in fish have been documented so far. In this study, we report the identification of cd248a and cd248b in the zebrafish. Both the phylogenetic analysis and the conserved synteny strongly suggested that zebrafish cd248a and cd248b are orthologs of the human CD248. Both cd248a and cd248b exhibited similar and dynamic expression pattern in early development, both genes had weak maternal expression, the zygotic transcripts were first seen in anterior somites and head mesenchyme, then shifted to eyes and head mesenchyme, later expanded to branchial arches, and gradually declined with development. The expression profiles of cd248a and cd248b were upregulated upon LPS (Lipopolysaccharide) challenge. Both Cd248a protein and Cd248b protein were localized on the cell membrane and cytoplasm, and overexpression of cd248a and cd248b induced the expression of pro-inflammatory cytokines, in vitro and in vivo. Moreover, deficiency of cd248a or cd248b both downregulated the expression of pro-inflammatory cytokines and upregulated anti-inflammatory cytokine. Additionally, loss of cd248a or cd248b both downregulated the expression of pro-inflammatory cytokines after LPS treatment. Taken together, these results indicated that cd248a and cd248b in zebrafish were involved in immune response and would provide further information to understand functions of Cd248 protein in innate immunity of fish.

Differentially Expressed Long Noncoding RNAs Involved in FUBP1 Promoting Hepatocellular Carcinoma Cells Proliferation.

BACKGROUND: Far upstream element-binding protein 1 (FUBP1) is reported to be involved in cancer development by regulating the transcription of c-myc gene through binding to far upstream element. Highly expressed FUBP1 was negatively correlated with survival rate of patients with hepatocellular carcinoma (HCC) and could promote the proliferation of HCC cells. However, the downstream mechanism of FUBP1 has not yet been clearly explained. This study is aimed at identifying the expression profiles of long noncoding RNA (lncRNA) in HCC cells in response to FUBP1 overexpression and at investigating the possible lncRNAs that participated in cell proliferation process regulated by FUBP1. METHODS: The overexpression of FUBP1 was mediated by lentiviral infection on 3 different types of HCC cell lines (MHCC97-H, MHCC97-L, and Huh-7). The expression of target genes was detected by quantitative reverse transcription-PCR (RT-PCR) and western blotting assays. Microarray and quantitative RT-PCR were applied to screen the differentially expressed lncRNAs in HCC cells after FUBP1 overexpression. The Cell Counting Kit-8 assay was used to confirm the growth vitality of HCC cells. RESULTS: The growth vitality of HCC cells was significantly increased after lentivirus infection. A total of 12 lncRNAs had the same expression trend in the 3 HCC cell lines in response to FUBP1 overexpression, including 3 upregulated lncRNAs and 9 downregulated lncRNAs. Coexpression analysis of dysregulated lncRNAs-mRNAs network showed that lnc-LYZ-2 was the lncRNA most relevant to FUBP1. Inhibition of lnc-LYZ-2 could significantly relieve the proproliferation effect of FUBP1 on HCC cells, suggesting that lnc-LYZ-2 was partially involved in proproliferation regulation of FUBP1. CONCLUSIONS: Our results indicated that FUBP1 induced the abnormal expression of lncRNAs and the FUBP1-lncRNAs coexpression network in HCC cells, which could provide theoretical and experimental basis for FUBP1-lncRNAs network involved in HCC development.

Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of hepatocellular carcinoma (HCC).

ABSTRACT: Growing evidence supports that the tumor microenvironment plays a key role in the development and progression of tumors. But immune microenvironment of hepatocellular carcinoma (HCC) has not yet been fully explored. In the present investigation, the clinical value and prognostic significance of immune-related genes in HCC were investigated.The immune and stromal scores of HCC were calculated through the application of Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data Algorithm based on the Cancer Genome Atlas database. Differentially expressed genes were identified using the "edgeR" package of the R software. Functional annotation and pathway enrichment were performed using "ggplots2" and "clusterProfiler" packages in R software. Protein-protein interaction network was constructed using STRING, and the hub genes were identified through the Cytoscape. Survival analysis was performed using Kaplan-Meier methods. Tumor Immune Estimation Resource algorithm was used to view the immune landscape of the microenvironment in HCC.Firstly, the immune and stromal scores of HCC were calculated and we found that the immune and stromal scores of HCC were closely related to the patients' prognosis. Then the differentially expressed genes were identified respectively stratified by the median value of the immune and stromal scores, and the immune-related genes that related to the prognosis in HCC patients were further identified. Functional enrichment analysis and protein-protein interaction networks further showed that these genes mainly participated in immune-related biological process. In addition, dendritic cells were found to be the most abundant in the microenvironment of HCC through Tumor Immune Estimation Resource algorithm and were significantly associated with the patients' prognosis. To robust the results, the immune-related genes were validated in an independent dataset from the Gene Expression Omnibus database.We arrived at a more comprehensive understanding of the microenvironment of HCC and extracted 7 immune-related genes that were significantly associated with the recurrence survival of HCC.

Phosphorylation of PED/PEA-15 at Ser116 and phosphorylation of p27 at Thr187 indicates a poor prognosis in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) constitutes a deadly cancer with a high rate of recurrence and metastasis. Phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes-15 (PED/PEA-15) is a protein involved in the metabolism of glucose that regulates numerous cellular processes, including cell division, apoptosis and migration in numerous types of cancer. However, PED/PEA-15 may act as a tumor-promotor or a tumor-suppressor depending on its phosphorylation status. In the present study, the association between the phosphorylation of PED/PEA-15 at Ser116 [PED/PEA-15(S116)], the phosphorylation of P27 at Thr187 [P-p27(T187)] and the clinicopathological features and prognosis of patients with HCC was assessed. The levels of PED/PEA-15(S116) and P-p27(T187) were determined using immunohistochemistry and western blotting analysis in resected liver tumor tissues and adjacent non-cancerous tissues obtained from 60 patients with HCC as well as normal liver tissues from 12 patients with benign lesions. The association between the expression levels of these two markers and the clinicopathological features of patients with HCC was explored. Using the Kaplan-Meier method, the prognostic value of PED/PEA-15(S116) and P-p27(T187) expression levels was determined. The results demonstrated that the levels of PED/PEA-15(S116) and P-p27(T187) proteins were remarkably higher in the HCC group compared with those in the adjacent and normal tissue groups (both P<0.05). In addition, a moderate positive correlation was observed between the levels of PED/PEA-15(S116) and P-p27(T187) (r=0.434; P<0.05). The levels of these two proteins were associated with the Edmondson grade, Tumor-Node-Metastasis (TNM) stage, vascular invasion and tumor multiplicity (all P<0.05). Furthermore, the Kaplan-Meier analysis results demonstrated that patients with HCC that presented with positive expression of PED/PEA-15(S116) and P-p27(T187) exhibited a dismal prognosis compared with that in patients with negative expression regarding the overall survival (OS), as well as disease-free survival (both P<0.05). Multivariate Cox analysis revealed that the TNM stage (P<0.05), vascular invasion (P<0.05), PED/PEA-15(S116) levels (P<0.001) and P-p27(T187) levels (P<0.05) were independent prognostic factors for OS in patients with HCC. In conclusion the results of the present study demonstrated that PED/PEA-15(S116) and P-p27(T187) levels were upregulated in HCC tissues compared with those in the adjacent and normal tissues; PED/PEA-15(S116) and P-p27(T187) expression may serve as an indicator of a poor prognosis in patients with HCC, suggesting that these proteins may be prospective therapeutic targets for HCC.

COVID-19 or treatment associated immunosuppression may trigger hepatitis B virus reactivation: A case report.

BACKGROUND: Since the initial recognition of coronavirus disease 2019 (COVID-19) in Wuhan, this infectious disease has spread to most areas of the world. The pathogenesis of COVID-19 is yet unclear. Hepatitis B virus (HBV) reactivation occurring in COVID-19 patients has not yet been reported. CASE SUMMARY: A 45-year-old hepatitis B man with long-term use of adefovir dipivoxil and entecavir for antiviral therapy had HBV reactivation after being treated with methylprednisolone for COVID-19 for 6 d. CONCLUSION: COVID-19 or treatment associated immunosuppression may trigger HBV reactivation.