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BackgroudAlthough recent studies have reported the regulation of the immune response in hepatocellular carcinoma (HCC) through DNA methylation, the comprehensive impact methylation modifications on tumor microenvironment characteristics and immunotherapy efficacy has not been fully elucidated.MethodsIn this research, we conducted a comprehensive assessment of the patterns of DNA methylation regulators and the profiles of the tumor microenvironment (TME) in HCC, focusing on 21 specific DNA methylation regulators. We subsequently developed a unique scoring system, a DNA methylation score (DMscore), to assess the individual DNA methylation modifications among the three distinct methylation patterns for differentially expressed genes (DEGs).ResultsThree distinct methylation modification patterns were identified with distinct TME infiltration characteristics. We demonstrated that the DMscore could predict patient subtype, TME infiltration, and patient prognosis. A low DMscore, characterized by an elevated tumor mutation burden (TMB), hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, and immune activation, indicates an inflamed tumor microenvironment phenotype with a 5-year survival rate of 7.8%. Moreover, a low DMscore appeared to increase the efficacy of immunotherapy in the anti-CTLA-4/PD-1/PD-L1 cohort.ConclusionsIn brief, this research has enhanced our understanding of the correlation between modifications in DNA methylation patterns and the profile of the tumor microenvironment in individuals diagnosed with HCC. The DMscore may serve as an alternative biomarker for survival and efficacy of immunotherapy in patients with HCC.

Abstract The issue of poor sexual performance of some male giant pandas seriously impairs the growth and the genetic diversity of the captive population, yet there is still no clear understanding of the cause of the loss of this ability and its underlying mechanism. In this study, we analyzed the gut microbiota and its function in 72 fecal samples obtained from 20 captive male giant pandas, with an equal allocation between individuals capable and incapable of natural mating. Additionally, we investigated fecal hormone levels and behavioral differences between the two groups. A correlation analysis was then conducted among these factors to explore the influencing factors of their natural mating ability. The results showed significant differences in the composition of gut microbiota between the two groups of male pandas. The capable group had significantly higher abundance of Clostridium sensu stricto 1 (padjusted = .0021, GLMM), which was positively correlated with fatty acid degradation and two‐component system functions (Spearman, padjusted

Fungal substance derived from bio-fermentation technology of Lepista sordida with yam in order to develop a beverage with health benefits, the quality of the fungal substance was studied through fourier transform infrared spectroscopy (FTIR), which was used as raw material, the beverage formulation was optimized by Box-Benhnken response surface experimental design on the basis of single factor experiment, the content of functional ingredients and antioxidant activity for the beverage were detected. The results showed that the obtained fungal substance not only had the basic components of yam, but also produced new functional components; the optimal formula was: 4.00% fungal substance, 4.11% xylitol, 0.75% citric acid, 0.24% carboxymethyl cellulose sodium (CMC-Na), the beverage was bright brown, sweet and sour, clear and transparent, with the unique aroma of the fungal substance, the sensory score was 88.7±0.40 points. The total flavonoids and phenolics were 58.43±0.94 and 45.77±0.43 mg/L. The maximum scavenging rates of the beverage to DPPH and hydroxyl radicals were 73.46% and 79.26%, which indicated that the beverage had certain antioxidant activity.

IntroductionSubmassive hepatic necrosis (SMHN, defined as necrosis of 15–90% of the entire liver on explant) is a likely characteristic pathological feature of ACLF in patients with hepatitis B cirrhosis. We aimed to comprehensively explore microbiome and bile acids patterns across enterhepatic circulation and build well-performing machine learning models to predict SMHN status.MethodsBased on the presence or absence of SMHN, 17 patients with HBV-related end-stage liver disease who received liver transplantation were eligible for inclusion. Serum, portal venous blood, and stool samples were collected for comparing differences of BA spectra and gut microbiome and their interactions. We adopted the random forest algorithm with recursive feature elimination (RF-RFE) to predict SMHN status.ResultsBy comparing total BA spectrum between SMHN (−) and SMHN (+) patients, significant changes were detected only in fecal (P = 0.015). Compared with the SMHN (+) group, the SMHN (−) group showed that UDCA, 7-KLCA, 3-DHCA, 7-KDCA, ISOLCA and α-MCA in feces, r-MCA, 7-KLCA and 7-KDCA in serum, γ-MCA and 7-KLCA in portal vein were enriched, and TUDCA in feces was depleted. PCoA analysis showed significantly distinct overall microbial composition in two groups (P = 0.026). Co-abundance analysis showed that bacterial species formed strong and broad relationships with BAs. Among them, Parabacteroides distasonis had the highest node degree. We further identified a combinatorial marker panel with a high AUC of 0.92.DiscussionOur study demonstrated the changes and interactions of intestinal microbiome and BAs during enterohepatic circulation in ACLF patients with SMHN. In addition, we identified a combinatorial marker panel as non-invasive biomarkers to distinguish the SMHN status with high AUC.

This work focuses on the mechanical properties and strengthening mechanism of Ni/Al nanolaminates, where dislocation strengthening and constraint dominate in the soft Al nanolayers. Nanoindentation and micropillar compression experiments highlight a constrained plasticity of Al nanolayers, which endows Ni/Al nanolaminates with a strain hardened behavior. Plasticity of Ni/Al nanolaminate begins with yielding of Al, and the Al yield strength depends on the individual layer thickness. Based on an inverse methodology, the Al yield strength as a function of Al grain size is determined. The results evidence a significant strengthening in the Al nanolayers. Specially, when Al layer thickness decreases from ≈110 nm to ≈16 nm, its yield strength is increased for ≈68 %, from ≈0.69 GPa to ≈1.16 GPa. The strengthening rule follows a confined layer slip model that is developed based on confining of single dislocation loops in nanolayers. Both the dislocation strengthening and the constraint effects in the Al layers contribute to a more sensitivity of Ni/Al strength with the variation of Al layer thickness, instead of Ni layer thickness. The work may forward the fundamental understanding in the strengthening mechanism and mechanical behavior of metallic nanolaminates with large elastoplastic mismatch.

In this work, a novel high-throughput methodology based on combinations of nanoindentation, indentation creep and push-in methods, is proposed to measure in-situ the micro-mechanical properties of typical polymer matrix composites at a wide temperature range. The Young's modulus and strain rate sensitivity of a polyimide matrix and the interfacial shear strength in a quartz fiber reinforced polyimide matrix composite are measured at 25–350 °C for the first time. The results highlight a linear softening of the polyimide matrix at high temperatures, which is evidenced by the approximate linear decrease of Young's modulus from ≈5.0 GPa at 25 °C to ≈1.1 GPa at 350 °C. In comparison, the strain rate sensitivity of the polyimide matrix is increased, from ≈0.032 at 25 °C to ≈0.062 at 350 °C. This evidences a stronger visco-plasticity of polyimide at higher temperatures. The shear strength of the fiber/matrix interface is also temperature dependent. As the testing temperature increases from 25 to 300 °C, the shear strength is decreased from ≈147 MPa to ≈40 MPa. Specially, the interfacial strength is extremely low at 350 °C (≈4 MPa), evidencing a failure of the composite at this temperature.

Purpose: The mortality of invasive pulmonary aspergillosis (IPA) in patients with liver failure was high. However, the prophylactic treatment in those patients with a high-risk factor in IPA has not been researched.Patients and methods: A multicenter, retrospective study was conducted in patients with liver failure. The study cohort of liver failure was randomly split into a training set for model development and the other served as the testing set for model verification. Multivariate analysis was performed to identify the risk factors of IPA. A weighted risk score for IPA was established. Anti-fungal treatment was prophylactically used in patients with medium and high IPA risk to evaluate the effect.Results: In total, 1,722 patients with liver failure were enrolled. Fifty-seven patients who received prophylactic treatment were excluded from the risk factor system study. About 1,665 patients were randomly split at a ratio of 2:1 into two datasets. Diabetes, glucocorticoids, plasma exchange, and hepatorenal syndrome (HRS) were risk factors in IPA in patients with liver failure, with weighted risk scores of 4, 7, 2, and 3, respectively. In the validation set and test set, the patients with risk scores of ≤ 3 presented low incidences of IPA at 4 and 2.7%. Patients with risk scores of 4–5 had an IPA incidence of 7.6% and 10.1%, and could be considered as a medium-risk group (p < 0.01 vs. the group with scores of ≤ 3), whereas those with risk scores of >5 manifested a significantly higher IPA incidence of 21.2 and 12.7%, who were considered a high-risk group (p < 0.01 vs. the groups with scores of 4–5 and >5, respectively). The IPA risk scores in the training set and the testing set were also analyzed by the ROC with an area under the ROC of 0.7152 and 0.6912. In this study, 57 patients received antifungal prophylaxis; the incidence of IPA was 1.8%, which was significantly lower after prophylactic antifungal therapy (p < 0.001).Conclusions: A weighted risk score for patients with liver failure, complicated with IPA, was established and confirmed in the testing cohort. Voriconazole prophylactic treatment to patients with liver failure with medium and high IPA risk can effectively prevent Aspergillus infection.

The persistence of immunity after hepatitis B vaccination is still under investigation in adults. In Chaoyang District, Beijing, people who were aged ≥ 18 years and completely immunized with HBV vaccine according to the standard procedure (0–1–6 months) were enrolled. Three groups were set for 1 (Y1), 5 (Y5) and 10 (Y10) years after the hepatitis B vaccination. The following data was collected and analyzed: antibody against hepatitis B virus surface antigen(anti-HBs) positive rates and geometric mean concentration (GMC) between the different compared groups through questionnaires and laboratory detection, including hepatitis B virus surface antigen (HBsAg), anti-HBs and antibody against hepatitis B virus core antigen(anti-HBc). All 600 subjects completed the questionnaires and serological tests. Among all subjects, the positive rates of HBsAg, anti-HBs and anti-HBc were 0, 70.5% (423/600) and 2.5% (15/600), respectively. The anti-HBs positive rates in Y1, Y5 and Y10 groups were 86.5% (173/200), 71.0% (142/200) and 54.0% (108/200) (χ2 = 50.8, p < 0.001) and showed a linear decreasing trend year by year (trend χ2 = 50.7, p < 0.001). The GMC in Y1, Y5 and Y10 groups were 296.6 mIU/mL, 51.6 mIU/mL and 25.5 mIU/mL (H = 64.8, p < 0.001), respectively. The anti-HBs positive rates and GMC decreased rapidly after the vaccination of adults against hepatitis B. Screening after 5–10 years and booster vaccination for the unprotected population is recommended.