Thrombospondin 1 enhances systemic inflammation and disease severity in acute-on-chronic liver failure.

BACKGROUND: The key role of thrombospondin 1 (THBS1) in the pathogenesis of acute-on-chronic liver failure (ACLF) is unclear. Here, we present a transcriptome approach to evaluate THBS1 as a potential biomarker in ACLF disease pathogenesis. METHODS: Biobanked peripheral blood mononuclear cells (PBMCs) from 330 subjects with hepatitis B virus (HBV)-related etiologies, including HBV-ACLF, liver cirrhosis (LC), and chronic hepatitis B (CHB), and normal controls (NC) randomly selected from the Chinese Group on the Study of Severe Hepatitis B (COSSH) prospective multicenter cohort underwent transcriptome analyses (ACLF = 20; LC = 10; CHB = 10; NC = 15); the findings were externally validated in participants from COSSH cohort, an ACLF rat model and hepatocyte-specific THBS1 knockout mice. RESULTS: THBS1 was the top significantly differentially expressed gene in the PBMC transcriptome, with the most significant upregulation in ACLF, and quantitative polymerase chain reaction (ACLF = 110; LC = 60; CHB = 60; NC = 45) was used to verify that THBS1 expression corresponded to ACLF disease severity outcome, including inflammation and hepatocellular apoptosis. THBS1 showed good predictive ability for ACLF short-term mortality, with an area under the receiver operating characteristic curve (AUROC) of 0.8438 and 0.7778 at 28 and 90 days, respectively. Enzyme-linked immunosorbent assay validation of the plasma THBS1 using an expanded COSSH cohort subjects (ACLF = 198; LC = 50; CHB = 50; NC = 50) showed significant correlation between THBS1 with ALT and γ-GT (P = 0.01), and offered a similarly good prognostication predictive ability (AUROC = 0.7445 and 0.7175) at 28 and 90 days, respectively. ACLF patients with high-risk short-term mortality were identified based on plasma THBS1 optimal cut-off value (< 28 µg/ml). External validation in ACLF rat serum and livers confirmed the functional association between THBS1, the immune response and hepatocellular apoptosis. Hepatocyte-specific THBS1 knockout improved mouse survival, significantly repressed major inflammatory cytokines, enhanced the expression of several anti-inflammatory mediators and impeded hepatocellular apoptosis. CONCLUSIONS: THBS1 might be an ACLF disease development-related biomarker, promoting inflammatory responses and hepatocellular apoptosis, that could provide clinicians with a new molecular target for improving diagnostic and therapeutic strategies.

Effects of Protection Time on Infection of Rice Panicle Blast.

Panicle blast, caused by Magnaporthe oryzae, is a destructive disease of rice worldwide. Clarifying the susceptibility of rice panicles at different stages is of great significance for effective disease management. Field experiments were conducted in two paddy fields at Wuyuan County in 2016 and 2017 to determine the effects of head covering and its timing on the infection of rice panicle blast. Results revealed that panicle blast was reduced significantly by covering rice heads with sulfuric acid paper bags, regardless of the covering time, ranging from initial heading to 15 days afterward, suggesting that rice panicles could be infected by blast pathogen even 15 days after initial heading. Panicle blast incidence was also found to be significantly influenced by plant dates, with higher panicle blast incidence observed in plots planted on early dates, suggesting adjusting plant dates could help rice panicles escape the infection by blast pathogen. The results from this study also highlighted the importance of cultivars and environmental conditions to panicle blast. In conclusion, besides planting blast-resistant cultivars, it is important to protect rice heads from the initial heading to the early dough stages, and fungicides should be applied according to infection warnings based on host, inoculum, and weather conditions.

Terrace-Like 2D Hierarchically Porous Iron/Cobalt Metal-Organic Framework: Ambient Fast Synthesis and Efficient Oxygen Evolution Reaction Application.

It is urgent to design a low-cost electrocatalyst with high activity to enhance the efficiency of oxygen evolution reaction (OER), which is limited by the slow four-electron transfer kinetics process. Nevertheless, traditional synthetic methods, including calcination and solvothermal, of the electrocatalysts are high-cost, low-yield, and energy-hogging, which limits their industrial application. Herein, an ambient fast synthetic method is developed to prepare terrace-like Fe/Co bimetal-organic framework (TFC-MOF) electrocatalyst materials in gram scale in 1 h. The method in this paper is designable based on coordination chemistry. Fe and Co ions can coordinate with the carboxyl groups on benzene-1,3,5-tricarboxylic acid (H3 BTC) to form a 2D-MOF structure. Structural characterizations, including SEM, TEM, and XRD are conducted to verify that the TFC-MOF is a terrace-like layered structure with uniform-sized mesoporous, which reduces the adsorption steric hindrance and facilitates the mass and electron transfer efficiency of OER. The TFC-MOF shows low overpotential, 255 mV at a current density of 10 mA cm-2 , and a low Tafel slope of 49.9 mV dec-1 , in an alkaline solution. This work provides a planar coordination strategy to synthesize 2D-MOF OER electrocatalyst on a large scale with low cost and low energy consumption, which will promote its practical OER applications.

ETS2 alleviates acute-on-chronic liver failure by suppressing excessive inflammation.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a syndrome with high short-term mortality. The mechanism of the transcription factor ETS2 in ACLF remains unclear. This study aimed to clarify the molecular basis of ETS2 in ACLF pathogenesis. Peripheral blood mononuclear cells from patients with HBV-ACLF (n = 50) were subjected to RNA sequencing. Transcriptome analysis showed that ETS2 expression was significantly higher in ACLF patients than in patients with chronic liver diseases and healthy subjects (all p < 0.001). Area-under-ROC analysis of ETS2 demonstrated high values for the prediction of 28-/90-day mortality in ACLF patients (0.908/0.773). Significantly upregulated signatures of the innate immune response (monocytes/neutrophils/inflammation-related pathways) were observed in ACLF patients with high ETS2 expression. Myeloid-specific ETS2 deficiency in liver failure mice resulted in deterioration of biofunctions and increased expression of pro-inflammatory cytokines (IL-6/IL-1ß/TNF-α). Knockout of ETS2 in macrophages confirmed the downregulation of IL-6 and IL-1ß caused by both HMGB1 and lipopolysaccharide, and an NF-κB inhibitor reversed the suppressive effect of ETS2. ETS2 is a potential prognostic biomarker of ACLF patients that alleviates liver failure by downregulating the HMGB1-/lipopolysaccharide-triggered inflammatory response and may serve as a therapeutic target for ACLF.

Base-Controlled Synthesis of Fluorescent Acridone Derivatives via Formal (4 + 2) Cycloaddition.

A transition-metal-free formal (4 + 2) cycloaddition for the direct assembly of acridone derivatives has been developed from simple and easily accessible o-aminobenzamides and 2-(trimethylsilyl)aryl triflates. The base played an important role in the selective controlled synthesis of N-H and N-aryl acridones. A preliminary study on the fluorescence properties of N-aryl acridones demonstrated that they could be used as fluorescent materials with a broad emission range.

PBMC transcriptomics identifies immune-metabolism disorder during the development of HBV-ACLF.

OBJECTIVE: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) pathophysiology remains unclear. This study aims to characterise the molecular basis of HBV-ACLF using transcriptomics. METHODS: Four hundred subjects with HBV-ACLF, acute-on-chronic hepatic dysfunction (ACHD), liver cirrhosis (LC) or chronic hepatitis B (CHB) and normal controls (NC) from a prospective multicentre cohort were studied, and 65 subjects (ACLF, 20; ACHD, 10; LC, 10; CHB, 10; NC, 15) among them underwent mRNA sequencing using peripheral blood mononuclear cells (PBMCs). RESULTS: The functional synergy analysis focusing on seven bioprocesses related to the PBMC response and the top 500 differentially expressed genes (DEGs) showed that viral processes were associated with all disease stages. Immune dysregulation, as the most prominent change and disorder triggered by HBV exacerbation, drove CHB or LC to ACHD and ACLF. Metabolic disruption was significant in ACHD and severe in ACLF. The analysis of 62 overlapping DEGs further linked the HBV-based immune-metabolism disorder to ACLF progression. The signatures of interferon-related, neutrophil-related and monocyte-related pathways related to the innate immune response were significantly upregulated. Signatures linked to the adaptive immune response were downregulated. Disruptions of lipid and fatty acid metabolism were observed during ACLF development. External validation of four DEGs underlying the aforementioned molecular mechanism in patients and experimental rats confirmed their specificity and potential as biomarkers for HBV-ACLF pathogenesis. CONCLUSIONS: This study highlights immune-metabolism disorder triggered by HBV exacerbation as a potential mechanism of HBV-ACLF and may indicate a novel diagnostic and treatment target to reduce HBV-ACLF-related mortality.

Light-Activated Reactive Oxygen Species-Responsive Nanocarriers for Enhanced Photodynamic Immunotherapy of Cancer.

Exploring polymeric nanoplatforms combined with reactive oxygen species (ROS) responsiveness with mitochondria targeting has emerged as an effective strategy for enhanced photodynamic therapy (PDT). Amphiphilic copolymers were synthesized by reacting acrylamide thioketal (TK) linkers with amino-terminated triphenylphosphonium-polyethylene glycol and dodecylamine for encapsulating chlorin e6 (Ce6) via self-assembly. Then, anionic cladding with tumor targeting deshelled in tumor acidic microenvironments was surface-anchored by electrostatic forces (BioPEGDMA@RM). After sequential targeting to the mitochondria of cancerous cells, BioPEGDMA@RM could be light-activated with Ce6 released upon ROS cleavage of TK linkages. It was found that Ce6-loaded BioPEGDMA@RM exhibited higher cytotoxicity on CT26 cells and performed stronger ability on the production of ROS than that without TK linkers. Moreover, a minimum illumination of 3 and 5 min could be required for achieving the maximum release of Ce6 and high in vitro cytotoxicity for Ce6-loaded BioPEGDMA@RM, respectively. Furthermore, Ce6-loaded BioPEGDMA@RM showed 1.29-fold and 1.21-fold higher tumor inhibition on BALB/c nude mice and Kunming mice and stimulated immunologic reactions with more generation of IFN-γ and TNF-α and activation of CD3+, CD4+, and CD8+ T-lymphocytes and DCs than that of Ce6-loaded nanoparticles without TK bonds. This work provided an academic reference for the development of ROS-responsive drug delivery systems for advanced PDT efficiency.

Evaluation of the Gastric Microbiome in Patients with Chronic Superficial Gastritis and Intestinal Metaplasia.

Objective To evaluate the gastric microbiome in patients with chronic superficial gastritis (CSG) and intestinal metaplasia (IM) and investigate the influence of Helicobacter pylori (H. pylori) on the gastric microbiome. Methods Gastric mucosa tissue samples were collected from 54 patients with CSG and IM, and the patients were classified into the following four groups based on the state of H. pylori infection and histology: H. pylori-negative CSG (n=24), H. pylori-positive CSG (n=14), H. pylori-negative IM (n=11), and H. pylori-positive IM (n=5). The gastric microbiome was analyzed by 16S rRNA gene sequencing. Results H. pylori strongly influenced the bacterial abundance and diversity regardless of CSG and IM. In H. pylori-positive subjects, the bacterial abundance and diversity were significantly lower than in H. pylori-negative subjects. The H. pylori-negative groups had similar bacterial composition and bacterial abundance. The H. pylori-positive groups also had similar bacterial composition but different bacterial relative abundance. The relative abundance of Neisseria, Streptococcus, Rothia, and Veillonella were richer in the I-HP group than in G-HP group, especially Neisseria (t=175.1, P<0.001). Conclusions The gastric microbial abundance and diversity are lower in H. pylori- infected patients regardless of CSG and IM. Compared to H. pylori-positive CSG group and H. pylori-positive IM, the relative abundance of Neisseria, Streptococcus, Rothia, and Veillonella is higher in H. pylori-positive patients with IM than in H. pylori-positive patients with CSG, especially Neisseria.

An Outbreak of Coxsackievirus A6 Infection in Adults of a Collective Unit, China, 2019.

Outbreaks/epidemics caused by coxsackievirus A6 (CVA6) have been reported continuously since 2008. However, outbreaks of ocular conjunctival hemorrhage caused by CVA6 in adults in a collective unit have not been reported. Methods. The epidemiological investigations were carried out according to the monitoring program, and the clinical data were collected from the treated hospitals. The nasopharyngeal swab specimens were collected to extract the total nucleic acid (DNA/RNA). The pathogen was determined using nucleic acid detection kits for 22 respiratory pathogens. The VP1 gene of this pathogen was amplified and sequenced. Sequence alignment and analysis were performed using BioEdit 7.0. The gene phylogenetic tree was constructed with MEGA4.0. Results. The factory emerged patients in succession from February 14 and reached the peak on the 18th. A total of 19 workers had symptoms in this factory up to March 31, 2019, giving an attack rate of 8.26%. The main symptoms were rash, ocular conjunctival hemorrhage, fever, and sore throat. The laboratory results showed that coxsackievirus A6 was the main pathogen causing this outbreak. The risk of taking a bath in the bathroom was 7.37 times higher than that of not taking a bath (95% confidence interval (CI): 1.67-32.79). Conclusion. This manuscript further enriched the infection-related information of CVA6, which was helpful to better identify and deal with the epidemic in the future.

Development and validation of a new prognostic score for hepatitis B virus-related acute-on-chronic liver failure.

BACKGROUND & AIMS: Early determination of the prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is important to guide clinical management and decrease mortality. The aim of this study was to develop a new simplified prognostic score to accurately predict outcomes in patients with HBV-ACLF. METHODS: Prospective clinical data from 2,409 hospitalized patients with acute deterioration of HBV-related chronic liver disease were used to develop a new prognostic score that was validated in an external group. RESULTS: A total of 954 enrolled patients with HBV-ACLF were diagnosed based on the Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF) criteria. Six predictive factors were significantly related to 28-day mortality and constituted a new prognostic score (=1.649×ln(international normalized ratio)+0.457×hepatic encephalopathy score+0.425×ln(neutrophil)+0.396×ln(total bilirubin)+0.576×ln(serum urea)+0.033×age). The C-indices of the new score for 28-/90-day mortality (0.826/0.809) were significantly higher than those of 4 other scores (COSSH-ACLF, 0.793/0.784; CLIF-C ACLF, 0.792/0.770; MELD, 0.731/0.727; MELD-Na, 0.730/0.726; all p <0.05). The prediction error rates of the new score for 28-day mortality were significantly lower than those of the 4 other scores: COSSH-ACLF (15.9%), CLIF-C ACLF (16.3%), MELD (35.3%) and MELD-Na (35.6%). The probability density function evaluation and risk stratification of the new score also showed the highest predictive values for mortality. These results were then validated in an external cohort. CONCLUSION: A new prognostic score based on 6 predictors, without an assessment of organ failure, can accurately predict short-term mortality in patients with HBV-ACLF and might be used to guide clinical management. LAY SUMMARY: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a complex syndrome that is associated with a high short-term mortality rate. We developed a simplified prognostic score for patients suffering from this condition based on a prospective multicentre cohort. This new score had better predictive ability than 4 other commonly used scores.

AAIT: A novel prognostic model for HIV-negative patients with cryptococcal meningoencephalitis New Scoring Model for Non-HIV Patients with CM.

Cryptococcal meningitis (CM) is a common opportunistic infection in HIV-negative patients, with mortality rates as high as those in the HIV-negative population. This requires accurate initial clinical decision-making, warranting the development of a prognostic score. Two groups of patients were investigated separately to develop a novel prognostic model (AAIT) for HIV-negative patients with CM. A retrospective analysis of 201 HIV-negative patients with CM was conducted to develop the CM prognostic score. In addition, the CM cohort (n = 21) was recruited longitudinally to verify the new prognostic score. Meanwhile, the association between the prognostic score and 1-year mortality of CM was expounded. AAIT (age, albumin, combined bacterial infection, and total triiodothyronine) is a novel prognostic score based on age, albumin level, combined bacterial infection, and total triiodothyronine (TT3) level, which were significantly higher in nonsurvivors than in survivors (0.68 [-0.70 to 1.55] vs - 1.72 [-3.75 to -0.73], P < .00). Regarding the AAIT-predicted 1-year mortality, the area under the receiver operating characteristic curve (AUROC) value was 0.857, whereas it was 0.965 for the validation cohort. In the induction period, different treatment options did not seem to significantly improve the 1-year survival rate. AAIT is a straightforward and clear prognostic score that can add value to predict the outcomes in HIV-negative patients with CM. In addition, controlling infection and increasing the albumin and TT3 levels may help improve clinical outcomes in HIV-negative patients with CM. LAY ABSTRACT: AAIT (age, albumin, combined bacterial infection, and total triiodothyronine) is a straightforward and clear prognostic score that can add value to predict the outcomes HIV-negative patients with CM.

Microbial Infections as a Trigger for Acute-on-Chronic Liver Failure: A Review.

ABSTRACT Microbial infection is an important cause of acute-on-chronic liver failure (ACLF), which is a syndrome that results in multiple organ dysfunction or failure and is accompanied by an increased short-term risk of mortality. Early detection and treatment of microbial infection can effectively reduce the mortality of patients with ACLF. However, antimicrobial resistance has recently increased due to the increased use of antimicrobial agents. Therefore, it is important to choose appropriate antibiotics and antifungal agents for early prevention or treatment of patients with microbial infection and ACLF to reduce the occurrence of drug resistance and to reduce patient mortality. This review summarizes the current status in the understanding of the epidemiology, pathogenesis, early diagnosis, treatment, and strategies for prevention of microbial infection in patients with ACLF.

Acid-Promoted Multicomponent Tandem Cyclization to Synthesize Fully Substituted Oxazoles via Robinson-Gabriel-Type Reaction.

An acid-promoted multicomponent reaction for the synthesis of diverse fully substituted oxazole derivatives from simple and readily available arylglyoxal monohydrates, nitriles, and various C-nucleophiles has been developed. This protocol features wide functional group diversity which is capable of installing 4-hydroxycoumarin, 2-naphthol, and 1,3-cyclohexanedione motifs to oxazoles. Mechanistic analysis indicates that a classical Robinson-Gabriel reaction served as the key step for this tandem transformation.

Different Mechanisms May Exist for HBsAg Synthesis and Secretion During Various Phases of Chronic Hepatitis B Virus Infection.

BACKGROUND The aim of this study was to characterize the expression and secretion of hepatitis B surface-antigen (HBsAg) in the hepatocytes of hepatitis B virus (HBV)-infected patients at different phases of infection; as such, the association of intrahepatic HBsAg expression with virological markers and the histological characteristics were analyzed. MATERIAL AND METHODS 302 chronic HBV infection patients who had not received antiviral therapy were stratified by HBeAg status. The proportion of HBsAg-positive cells was used as an indicator for HBsAg expression level. RESULTS In HBeAg-positive patients, there was a significant correlation between serum HBsAg and serum HBV DNA levels (r=0.569, p<0.001). Intrahepatic HBsAg expression and serum HBsAg level in HBeAg-positive patients were higher than those in HBeAg-negative patients (p=0.002 and p<0.001, respectively). A significant correlation between serum HBsAg level and intrahepatic HBsAg expression was found in HBeAg-negative patients (r=0.377, p<0.001), but not in HBeAg-positive patients (r=0.051, p=0.557). Very interestingly, the correlation between serum HBsAg level and HBsAg expression in hepatocytes gradually increased along with disease progression through the immune-tolerant, immune-clearance, inactive, and recovery phases of HBV infection (r=-0.184, 0.068, 0.492, and 0.575; and p=0,238, 0,722, 0.012, and 0.002, respectively). CONCLUSIONS Different mechanisms may be involved in HBsAg synthesis and secretion in different phases of chronic HBV infection.

[Two novel TSC2 frameshift mutations in tuberous sclerosis complex].

High-throughput sequencing was performed for the peripheral blood DNA from two probands in the family with tuberous sclerosis complex (TSC) to determine the sequences of TSC-related genes TSC1 and TSC2 and their splicing regions and identify mutation sites. Amplification primers were designed for the mutation sites and polymerase chain reaction and Sanger sequencing were used to verify the sequences of peripheral blood DNA from the probands and their parents. The two probands had c.3981-3982 insA (p.Asp1327AspfsX87) and c.4013-4014 delCA (p.Ser1338Cysfs) heterozygous mutations, respectively, in the TSC2 gene. The parents of proband 1 had no abnormalities at these two loci; the mother of proband 2 had c.4013-4014 delCA heterozygous mutation in the TSC2 gene, while the father and the grandparents of proband 2 had no abnormalities. c.3981-3982 insA mutation may cause early coding termination of amino acid sequence at the 1413th site, and c.4013-4014 delCA mutation may cause early coding termination of amino acid sequence at the 1412th site. These two mutations are the pathogenic mutations for families 1 and 2, respectively, and both of them are novel frameshift mutations, but their association with the disease needs to be further verified by mutant protein function cell model and animal model.

Acid-Catalyzed Multicomponent Tandem Double Cyclization: A One-pot, Metal-free Route to Synthesize Polyfunctional 4,9-Dihydropyrrolo[2,1-b]quinazolines.

An acid-catalyzed multicomponent tandem double cyclization protocol has been developed for the synthesis of polyfunctional 4,9-dihydropyrrolo[2,1-b]quinazolines from simple and readily available arylglyoxal monohydrates, 2-aminobenzylamine, and trans-ß-nitrostyrenes. This practical and metal-free reaction proceeds through an imine formation/cyclization/Michael addition/Henry cyclization protocol, resulting in the construction of four new bonds and two ring moieties directly in one pot.

Hepatitis B virus genotype A: design of reference sequences for sub-genotypes.

Genotype A of hepatitis B virus (HBV/A) is widespread and is currently divided into six sub-genotypes. Suitable reference sequences for different sub-genotypes can facilitate research on HBV/A. However, the current reference sequences for this virus are insufficient. In the present work, we retrieved 442 full-length HBV/A genomic sequences from the GenBank database and classified them into sub-genotypes by phylogenetic analysis. By the maximum likelihood method using the MEGA6.0 software, we established the reference sequences for different HBV/A sub-genotypes. Our analyses demonstrated that these reference sequences clustered phylogenetically with known strains, indicating that the reference sequences we established indeed belonged to the right sub-genotypes. HBV/A subtype sequences were selected by geographic origins and grouped as sub-genotypes including A1-South Africa, A2-Europe, A3-Cameroon, and A5-Haiti. Reference sequences of sub-genotypes A1, A2, A3, and A5 were constructed and deposited into GenBank (KP234050-KP234053). By applying phylogenetic analyses, we further determined the time to most recent common ancestor of HBV/A lineages. In conclusion, these newly established reference sequences can provide suitable reference standards for studies on the molecular biology and virology of HBV genotype A.

Development of algorithms based on serum markers and transient elastography for detecting significant fibrosis and cirrhosis in chronic hepatitis B patients: Significant reduction in liver biopsy.

AIM: To develop algorithms for detecting significant fibrosis and cirrhosis in chronic hepatitis B (CHB) patients with the aim of reducing unwarranted liver biopsy. METHODS: For 307 CHB patients, the aspartate aminotransferase-to-platelet ratio index (APRI), the fibrosis index based on four factors (FIB-4), and the result of transient elastography with FibroScan (FS) were obtained when a liver biopsy was carried out. All patients were classified based on APRI or FIB-4 score and further assessed by FS results. Patients who remained unclassified after two steps of evaluation were considered to need liver biopsy. RESULTS: Algorithm implementation found that APRI + FS significantly lowered the requirement for liver biopsy for the detection of significant fibrosis compared to either individual APRI or FS screening (65.1% vs 75.9% or 78.5%, P = 0.003 or <0.001, respectively). The combination of FIB-4 + FS significantly reduced the need for liver biopsy compared to single FIB-4 or FS (58.3% vs 67.4% or 78.5%, P = 0.019 or <0.001, respectively). The FIB-4 + FS algorithm also reduced the need for liver biopsy for detection of significant fibrosis in patients ≥50 years old compared to APRI + FS (22.6% vs 56.5%, P < 0.001), with a relatively lower accuracy (83.9% vs 98.4%, P = 0.004). Only 3.6% or 1.3% of patients needed liver biopsy for diagnosis of cirrhosis after screening with APRI + FS or FIB-4 + FS, respectively. CONCLUSION: The APRI + FS and FIB-4 + FS algorithms could significantly reduce the need for liver biopsy with high accuracy, sensitivity, and positive predictive value for diagnosis of significant fibrosis and cirrhosis in CHB patients.

Polymer Adsorption on Graphite and CVD Graphene Surfaces Studied by Surface-Specific Vibrational Spectroscopy.

Sum-frequency vibrational spectroscopy was employed to probe polymer contaminants on chemical vapor deposition (CVD) graphene and to study alkane and polyethylene (PE) adsorption on graphite. In comparing the spectra from the two surfaces, it was found that the contaminants on CVD graphene must be long-chain alkane or PE-like molecules. PE adsorption from solution on the honeycomb surface results in a self-assembled ordered monolayer with the C-C skeleton plane perpendicular to the surface and an adsorption free energy of ∼42 kJ/mol for PE(H(CH2CH2)nH) with n ≈ 60. Such large adsorption energy is responsible for the easy contamination of CVD graphene by impurity in the polymer during standard transfer processes. Contamination can be minimized with the use of purified polymers free of PE-like impurities.

Development of a novel lncRNA-derived immune gene score using machine learning-based ensembles for predicting the survival of HCC.

BACKGROUND: Long noncoding RNAs (lncRNAs) are implicated in the tumor immunology of hepatocellular carcinoma (HCC). METHODS: HCC mRNA and lncRNA expression profiles were used to extract immune-related genes with the ImmPort database, and immune-related lncRNAs with the ImmLnc algorithm. The MOVICS package was used to cluster immune-related mRNA, immune-related lncRNA, gene mutation and methylation data on HCC from the TCGA. GEO and ICGC datasets were used to validate the model. Data from single-cell sequencing was used to determine the expression of genes from the model in various immune cell types. RESULTS: With this model, the area under the curve (AUC) for 1-, 3- and 5-year survival of HCC patients was 0.862, 0.869 and 0.912, respectively. Single-cell sequencing showed EREG was significantly expressed in a variety of immune cell types. Knockdown of the EREG target gene resulted in significant anti-apoptosis, pro-proliferation and pro-migration effects in HepG2 and HUH7 cells. Moreover, serum and liver tissue EREG levels in HCC patients were significantly higher than those of healthy control patients. CONCLUSION: We built a prognostic model with good accuracy for predicting HCC patient survival. EREG is a potential immunotherapeutic target and a promising prognostic biomarker.