Analysis of clinical characteristics of thyroid disorders in patients with chronic hepatitis B treated with pegylated-interferon alpha.

BACKGROUND: Thyroid disorders (TD) is a common complication of pegylated-interferon alpha (Peg-IFNα) therapy. Few studies have investigated the relationship between TD and the efficacy of interferon therapy for chronic hepatitis B (CHB). Therefore, we analyzed the clinical characteristics of TD in patients with CHB treated with Peg-IFNα, and evaluated the correlation between TD and Peg-IFNα treatment efficacy. METHODS: In this retrospective study, the clinical data of 146 patients with CHB receiving Peg-IFNα therapy were collected and analyzed. RESULTS: During the course of Peg-IFNα therapy, positive conversion of thyroid autoantibodies and TD occurred in 7.3% (85/1158) and 8.8% (105/1187) patients, respectively, and was diagnosed more often in women. The most common thyroid disorder was hyperthyroidism (53.3%), followed by subclinical hypothyroidism (34.3%). We found that thyroid function returned to normal in 78.7% of patients with CHB, and thyroid antibody levels returned to the negative range in approximately 50% of patients after interferon treatment cessation. Only 25% of patients with clinical TD required treatment. Compared with patients with hypothyroidism/subclinical hypothyroidism, patients with hyperthyroidism/subclinical hyperthyroidism showed greater reduction and seroclearance of hepatitis B surface antigen (HBsAg) levels. CONCLUSIONS: TD are not an absolute contraindication for interferon therapy; however, patients should be monitored closely during interferon therapy. In pursuit of functional cure, a balance between efficacy and safety must be achieved.

Durability of hepatitis B surface antigen seroclearance and subsequent risk for hepatocellular carcinoma: A meta-analysis.

Hepatitis B surface antigen (HBsAg) seroclearance is regarded as the ideal endpoint for antiviral treatment. However, reports on the durability of and outcomes after HBsAg seroclearance are few, which has become a focus in clinical practice. This meta-analysis was performed to evaluate the durability and hepatocellular carcinoma (HCC) incidence after HBsAg seroclearance after treatment cessation. We searched PubMed, Embase, Medline and Web of Science for studies that reported the durability and HCC incidence after HBsAg seroclearance published between 1 January 2000 and 31 January 2020. Data were analysed by a random-effects model. Thirty-eight studies and 43,924 patients were finally included. The results showed that HBsAg seroclearance was durable, with a pooled recurrence rate of 6.19% (95% CI: 4.10%-8.68%). There was no significant difference in recurrence rates after different seroclearance methods or among recurrence types and different regions. Anti-HBs seroconversion resulted in a significantly reduced recurrence rate (RR = 0.25, p < .001). Patients who experienced HBsAg seroclearance had significantly lower HCC incidence than HBsAg-positive (RR = 0.41, p < .001). The pooled HCC incidence after HBsAg seroclearance was 1.88%; this rate was reduced to 0.76% among patients without baseline cirrhosis. In conclusion, the analysis during an average follow-up of 4.74 years suggested that in patients who experienced sustained HBsAg seroclearance and anti-HBs seroconversion, this was associated with low HCC incidence. Patients without baseline cirrhosis benefited even more. We emphasize the importance of gaining HBsAg seroclearance while highlighting the benefits of achieving this as early as possible.

Durability of Interferon-induced Hepatitis B Surface Antigen Seroclearance.

Hepatitis B surface antigen (HBsAg) seroclearance has been recommended as an optimal endpoint of antiviral treatment by the latest chronic hepatitis B management guideline.1 However, few reports investigated the durability of response after HBsAg seroclearance, because of a lower HBsAg seroclearance rate and the difficulty of obtaining a sufficient number of samples for analysis. Our center has made a long-term commitment to investigate the personalized antiviral therapy for chronic hepatitis B. More than 300 patients achieved HBsAg seroclearance by interferon (IFN)-based antiviral treatment. In this study, the durability and the effects of hepatitis B virus (HBV) surface antibody (Anti-HBs) level on relapse after HBsAg seroclearance were investigated.

GmRAV1 regulates regeneration of roots and adventitious buds by the cytokinin signaling pathway in Arabidopsis and soybean.

The division and differentiation of cells are the basis of growth and development. Cytokinin plays an active role in cell growth division and differentiation. The Related to ABI3/VP1 (RAV) family comprises transcription factors in plants and all contain both AP2- and B3-like domains. In this study, GmRAV1 (Glycine max), which belongs to the AP2/ERF transcription factor family, was isolated and functionally characterized. Subcellular localization showed that GmRAV1 was localized to the nucleus and quantitative real-time polymerase chain reaction (qRT-PCR) analysis indicated that GmRAV1 was induced by cytokinin. Furthermore, compared with wild-type plants, plants overexpressing GmRAV1 showed dwarfism and late maturity. In contrast, the mutant of TEMPRANILLO (tem1) and GmRAV-i plants had an opposite phenotype. More interestingly, a root and shoot regeneration experiment indicated that GmRAV1 is one of the most important positive regulators of the cytokinin signaling pathway, which is involved in promoting root and shoot regeneration. In addition, RNA-seq and qRT-PCR results indicated that GmRAV1 is related to the key factors involved in the cytokinin signaling pathway, namely, cytokinin oxidase (GmCKX6 and GmCKX7), purine permease (GmPUP1), cell cyclin-related genes (GmCycA2;4, GmCycD3 and GmCYC1), cyclin-dependent kinase (GmCDKB2), cell division cycle (GmCDC20), E2F transcription factors (GmE2FE) and authentic response regulator (GmARR9). In conclusion, GmRAV1, one of the most important positive regulators involved in promoting root and shoot regeneration, was induced by cytokinin and is related to the key factors of the cytokinin signaling pathways.

Elevated Presepsin Levels are Associated with Severity and Prognosis of Severe Acute Pancreatitis.

BACKGROUND: Current clinical scoring systems are insufficient in the early identification of severe acute pancreatitis (SAP) patients at risk of developing potentially lethal complications. This present study was designed to evaluate the relationship of presepsin with disease severity, local complications, organ failure, and mortality of SAP. METHODS: Eighty-five SAP patients and 85 gender- and age-matched healthy volunteers were enrolled. Presepsin concentrations were measured on admission from SAP patients and at study entry from healthy individuals. RESULTS: Presepsin levels were obviously higher in patients than in healthy individuals (1078.35 ± 385.16 pg/mL vs. 95.23 ± 21.64 pg/mL). Presepsin was identified as an independent predictor of local complications, organ failure, and in-hospital mortality and was positively associated with traditional predictors including the Bedside Index for Severity in Acute Pancreatitis (BISAP), Acute Physiology and Chronic Health Care Evaluation II (APACHE-II), Ransom score, and computed tomography severity index (CTSI).With the receiver operating characteristic (ROC) analysis, presepsin predicted local complications, organ failure, and in-hospital mortality of SAP patients with high areas under receiver operating characteristic curve and its predictive value was similar to the traditional predictors that are currently used in clinical practice. CONCLUSIONS: Increased presepsin level was found to be an accurate predictor of disease severity and identified as a novel prognostic marker of local complications, organ failure, and mortality of SAP.

Role of Presepsin for the Assessment of Acute Cholangitis Severity.

BACKGROUND: Presepsin is a new emerging inflammatory biomarker. The primary purpose of this study was to elucidate the predictive usability of presepsin for severity assessment in patients with acute cholangitis (AC). METHODS: A total of 119 treatment-naive patients with AC (64 males, 55 females) were enrolled in this study. Patients were classified with Grade I (mild), Grade II (moderate), or Grade III (severe) AC based on severity assessment guidelines. Presepsin concentrations were measured on admission. RESULTS: The median presepsin concentrations were 297 pg/mL (interquartile range (IQR) 234 - 386 pg/mL), 590 pg/mL (IQR 559 - 619 pg/mL), and 857 pg/mL (IQR 740 - 960 pg/mL) in patients with mild, moderate, and severe AC, respectively. Presepsin concentrations were significantly higher in patients with severe AC than in patients with moderate AC (p < 0.01), and in patients with moderate AC than in patients with mild AC (p < 0.01). With the receiver operating characteristic (ROC) analysis, the areas under the curves (AUCs) for presepsin to discriminate patients with moderate and severe AC were 0.935 (95% confidence interval (CI) 0.877 to 0.993, p < 0.001) and 0.942 (95% CI 0.885 to 0.998, p < 0.001), respectively. CONCLUSIONS: Compared with other conventional biochemical indicators such as WBC, CRP, and PCT, presepsin may be a useful parameter for the severity assessment of AC.

[Urinary metabolomics study of the effects of Scutellaria baicalensis Georgi ethanol extract on D-galactose-induced rats].

The purpose of this study is to evaluate the anti-aging effects and reveal the underlying mechanism of Scutellaria baicalensis Georgi ethanol extract (SBG) in D-galactose-induced rats. Fifty rats were randomly divided into five groups: vehicle control group, D-galactose group, and D-galactose combined with 50, 100, 200 mg x kg(-1) SBG. A rat aging model was induced by injecting subcutaneously D-galactose (100 mg x kg(-1)) for ten weeks. At the tenth week, the locomotor activity (in open-field test) and the learning and memory abilities (in Morris water maze test) were examined respectively. The urine was collected using metabolic cages and analyzed by high-resolution 1H NMR spectroscopy combined with multivariate statistical analyses. The SBG at doses of 50, 100 and 200 mg x kg(-1) treatments groups could significantly ameliorate aging process in rats' cognitive performance. The 50, 100, 200 mg x kg(-1) SBG regulated citrate, pyruvate, lactate, trimethylamine (TMA), pantothenate, ß-hydroxybutyrate in urine favorably toward the control group. These biochemical changes are related to the disturbance in energy metabolism, glycometabolism and microbiome metabolism, which is helpful to further understanding the D-galactose induced aging rats and the therapeutic mechanism of SBG.

Prediction Model for the Clearance of Hepatitis B Surface Antigen in Patients with Chronic Hepatitis B before Interferon Therapy: A Prospective Case-Control Study.

To evaluate the prediction model comprised of patients' laboratory results and single-nucleotide polymorphism (SNP) markers of host gene for the clearance of hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) who underwent interferon (IFN)-α therapy, this prospective case-control study enrolled 131 patients with CHB who underwent IFN-α-based regimens in our hospital between January 2015 and September 2019. Among them, 56 cases were without HBsAg clearance, while the other 75 cases had HBsAg clearance. Multivariable logistic regression analysis showed that CYP27B1 rs4646536 (odd ratio [OR] = 0.155, 95% CI: 0.030-0.807, p = 0.027), PAK4 rs9676717 (OR = 11.237, 95% CI: 1.768-71.409, p = 0.010), IL28B rs12979860 (OR = 0.059, 95% CI: 0.006-0.604, p = 0.017), baseline HBsAg (OR = 0.170, 95% CI: 0.040-0.716, p = 0.016), and HBeAg status (OR = 3.971, 95% CI: 1.138-13.859, p = 0.031) were independently associated with HBsAg clearance. The model that included rs3077, rs4646536, rs9676717, rs2850015, rs12979860, baseline HBsAg, HBeAg status, and HBV DNA had the best prediction performance for HBsAg clearance prediction, with AUC = 0.877, 80% sensitivity, and 81% specificity. In conclusion, laboratory results and gene polymorphisms before treatment might have a good predictive value for HbsAg clearance after IFN-α treatment in CHB.

Analysis of Binding Modes between Three Perfluorosulfonates and GPER Based on Computational Simulation and Multiple Spectral Methods.

Perfluorinated compounds (PFCs) belong to a significant category of global environmental pollutants. Investigating the toxicological effects of PFCs within biological systems is of critical significance in various disciplines such as life sciences, environmental science, chemistry, and ecotoxicology. In this study, under simulated human physiological conditions (pH = 7.4), a combination of multiple spectroscopic techniques and computational simulations was employed to investigate the impact of perfluorinated compounds (PFCs) on the G protein-coupled estrogen receptor (GPER). Additionally, the research focused on exploring the binding modes and toxicological mechanisms between PFCs and GPER at the molecular level. All three perfluorinated sulfonic acids (PFSAs) can induce quenching of GPER fluorescence through static quenching and non-radiative energy transfer. Steady-state fluorescence calculations at different temperatures revealed apparent binding constants in the order of 106, confirming a strong binding affinity between the three PFSAs and GPER. Molecular docking studies indicated that the binding sites of PFSAs are located within the largest hydrophobic cavity in the head region of GPER, where they can engage in hydrogen bonding and hydrophobic interactions with amino acid residues within the cavity. Fourier transform infrared spectroscopy, three-dimensional fluorescence, and molecular dynamics simulations collectively indicate that proteins become more stable upon binding with small molecules. There is an overall increase in hydrophobicity, and alterations in the secondary structure of the protein are observed. This study deepens the comprehension of the effects of PFCs on the endocrine system, aiding in evaluating their potential impact on human health. It provides a basis for policy-making and environmental management while also offering insights for developing new pollution monitoring methods and drug therapies.

Exploring the mechanism of interaction between TBG and halogenated thiophenols: Insights from fluorescence analysis and molecular simulation.

Thyroxine-binding globulin (TBG) plays a vital role in regulating metabolism, growth, organ differentiation, and energy homeostasis, exerting significant effects in various key metabolic pathways. Halogenated thiophenols (HTPs) exhibit high toxicity and harmfulness to organisms, and numerous studies have demonstrated their thyroid-disrupting effects. To understand the mechanism of action of HTPs on TBG, a combination of competitive binding experiments, multiple fluorescence spectroscopy techniques, molecular docking, and molecular simulations was employed to investigate the binding mechanism and identify the binding site. The competition binding assay between HTPs and ANS confirmed the competition of HTPs with thyroid hormone T4 for the active site of TBG, resulting in changes in the TBG microenvironment upon the binding of HTPs to the active site. Key amino acid residues involved in the binding process of HTPs and TBG were further investigated through residue energy decomposition. The distribution of high-energy contributing residues was determined. Analysis of root-mean-square deviation (RMSD) demonstrated the stability of the HTPs-TBG complex. These findings confirm the toxic mechanism of HTPs in thyroid disruption, providing a fundamental reference for accurately assessing the ecological risk of pollutants and human health. Providing mechanistic insights into how HTPS causes thyroid diseases.

Microbial Degradation of Tetracycline Antibiotics: Mechanisms and Environmental Implications.

The escalating global consumption of tetracyclines (TCs) as broad-spectrum antibiotics necessitates innovative approaches to mitigate their pervasive environmental persistence and associated risks. While initiatives such as China's antimicrobial reduction efforts highlight the urgency of responsible TC usage, the need for efficient degradation methods remains paramount. Microbial degradation emerges as a promising solution, offering novel insights into degradation pathways and mechanisms. Despite challenges, including the optimization of microbial activity conditions and the risk of antibiotic resistance development, microbial degradation showcases significant innovation in its cost-effectiveness, environmental friendliness, and simplicity of implementation compared to traditional degradation methods. While the published reviews have summarized some aspects of biodegradation of TCs, a systematic and comprehensive summary of all the TC biodegradation pathways, reactions, intermediates, and final products including ring-opening products involved with enzymes and mechanisms of each bacterium and fungus reported is necessary. This review aims to fill the current gap in the literature by offering a thorough and systematic overview of the structure, bioactivity mechanism, detection methods, microbial degradation pathways, and molecular mechanisms of all tetracycline antibiotics in various microorganisms. It comprehensively collects and analyzes data on the microbial degradation pathways, including bacteria and fungi, intermediate and final products, ring-opening products, product toxicity, and the degradation mechanisms for all tetracyclines. Additionally, it points out future directions for the discovery of degradation-related genes/enzymes and microbial resources that can effectively degrade tetracyclines. This review is expected to contribute to advancing knowledge in this field and promoting the development of sustainable remediation strategies for contaminated environments.

Identification of Two Isoforms of Canine Tetherin in Domestic Dogs and Characterization of Their Antiviral Activity against Canine Influenza Virus.

Canine influenza virus (CIV) significantly threatens the canine population and public health. Tetherin, an innate immune factor, plays an important role in the defense against pathogen invasion and has been discovered to restrict the release of various enveloped viruses. Two isoforms of canine tetherin (tetherin-X1 and tetherin-X2) were identified in peripheral blood leukocytes of mixed-breed dogs using reverse transcription polymerase chain reaction (RT-PCR). Amino acid alignment revealed that relative to full-length tetherin (tetherin-X1) and truncated canine tetherin (tetherin-X2) exhibited deletion of 34 amino acids. The deletion occurred at the C-terminus of the coiled-coiled ectodomain and the N-terminus of the glycosylphosphatidylinositol (GPI)-anchor domain. Tetherin-X2 was localized subcellularly at the cell membrane, which was consistent with the localization of tetherin-X1. In addition, canine tetherin-X1 and tetherin-X2 restricted the release of H3N2 CIV. However, canine tetherin-X1 had higher antiviral activity than canine tetherin-X2, indicating that the C-terminus of the coiled-coiled ectodomain and the N-terminus of the GPI-anchor domain of canine tetherin (containing the amino acids deleted in tetherin-X2) are critical for its ability to restrict H3N2 CIV release. This study provides insights for understanding the key functional domains of tetherin that restrict CIV release.

Changing microbiome community structure and functional potential during permafrost thawing on the Tibetan Plateau.

Large amounts of carbon sequestered in permafrost on the Tibetan Plateau (TP) are becoming vulnerable to microbial decomposition in a warming world. However, knowledge about how the responsible microbial community responds to warming-induced permafrost thaw on the TP is still limited. This study aimed to conduct a comprehensive comparison of the microbial communities and their functional potential in the active layer of thawing permafrost on the TP. We found that the microbial communities were diverse and varied across soil profiles. The microbial diversity declined and the relative abundance of Chloroflexi, Bacteroidetes, Euryarchaeota, and Bathyarchaeota significantly increased with permafrost thawing. Moreover, warming reduced the similarity and stability of active layer microbial communities. The high-throughput qPCR results showed that the abundance of functional genes involved in liable carbon degradation and methanogenesis increased with permafrost thawing. Notably, the significantly increased mcrA gene abundance and the higher methanogens to methanotrophs ratio implied enhanced methanogenic activities during permafrost thawing. Overall, the composition and functional potentials of the active layer microbial community in the Tibetan permafrost region are susceptible to warming. These changes in the responsible microbial community may accelerate carbon degradation, particularly in the methane releases from alpine permafrost ecosystems on the TP.

Potent hepatitis B surface antigen response to treatment of hepatitis-B-e-antigen-positive chronic hepatitis B with α-interferon plus a nucleos(t)ide analog.

BACKGROUND AND AIM: Hepatitis B surface antigen (HBsAg) clearance is the closest cure outcome in hepatitis B. The goal of this study was to investigate clinical features in chronic hepatitis B patients achieving seroconversion of HBsAg after treatment with α-interferon (IFN-α) and a nucleos(t)ide analog. METHODS: This retrospective study enrolled 38 chronic hepatitis B patients treated with IFN-α plus a nucleos(t)ide analog who achieved HBsAg seroconversion during the period from June 2001 to May 2009. Clinical and laboratory data of the patients were collected before and after treatment every 3 months. All patients with HBsAg seroconversion in this study were followed up for at least 12 months post-treatment. RESULTS: A total of 38 out of 142 patients achieved HBsAg seroconversion after treatment with IFN-α and a nucleos(t)tide analog for a prolonged period of time (medium 31 months). The median time to hepatitis B e antigen seroconversion and to HBsAg seroconversion was 19.5 months (range 3-60 months) and 25.5 months (range 9-63 months), respectively. Thirty-six patients (95%) sustained HBsAg seroconversion during the post-treatment follow up. Three different HBsAg response patterns were observed with classical model accounting for 57.9% (22/38 cases), simultaneous transition mode accounting for 23.7% (9/38 cases), and HBsAg prior transition model accounting for 18.4% (7/38 cases). CONCLUSIONS: Extended treatment with IFN-α in combination with a nucleos(t)ide analog in patients with hepatitis-B-e-antigen-positive appears to be a promising approach for achieving a high rate of HBsAg clearance-the closest outcome to cure.

[Analysis of thyroid dysfunction and influencing factors in chronic hepatitis C patients treated with peg-IFNa-2a and ribavirin].

OBJECTIVE: To analyze the frequency of thyroid dysfunction and determine its influencing factors in chronic hepatitis C (CHC) patients treated with pegylated-interferon alpha (peg-IFNa)-2a and ribavirin (RBV) combination therapy. METHODS: A total of 194 CHC patients were treated with peg-IFNa-2a and RBV for 48 weeks. Development of thyroid dysfunction was recorded. Clinical and biological factors from pre-treatment (baseline) to post-treatment were statistically analyzed to determine correlation with thyroid dysfunction in this patient population. RESULTS: Fifty-two (26.80%) of 194 peg-IFNa-2a/RBV-treated patients developed thyroid dysfunction. Dysfunction severity ranged from hyperthyroidism (n = 1, 0.52%) and hypothyroidism (n = 10, 5.15%) to subclinical hyperthyroidism (n = 4, 2.06%) and subclinical hypothyroidism (n = 37, 19.07%). The dysfunction rate was significantly higher after peg-IFNa-2a/RBV treatment (26.80% vs. 12.37% at baseline, x2 = 12.829, P less than 0.05, odds ratio (OR) = 0.386, 95% confidence interval (CI): 0.226-0.657), in females (33.00% vs. 20.21% in males, P less than 0.05, 95% CI: 1.016-3.040), and in thyroid auto-antibody positive patients (64.29% vs. 23.89% in negative patients, P less than 0.05, 95% CI: 1.681-36.183). Early virological response did not have any significant effect on dysfunction rate (23.00% vs. 30.85% no early virological response, x2 = 1.522, P more than 0.05) nor did end of treatment response (27.19% vs. 26.25% no response at end of treatment, x2 = 0.021, P more than 0.05). Patients who developed thyroid dysfunction had higher interleukin (IL)-6 at baseline (i.e. before peg-IFNa-2a/RBV treatment) (27.08+/-14.90 vs. 11.65+/-5.46 in patients who maintained normal thyroid function, t = 3.127, P less than 0.05, 95% CI: 5.28-25.58). IL-6 levels were not significantly different between the two groups at 24 weeks (6.30+/-2.47 vs. 6.81+/-2.80, t = 0.352, P more than 0.05). IL-6 levels before and after 48 weeks of treatment in normal thyroid function patients were 27.08+/-14.90 and 6.30+/-2.47, t = 3.632, P less than 0.05, and in thyroid dysfunction patients were 11.65+/-5.46 and 6.81+/-2.80, t = 1.997, P more than 0.05. CONCLUSION: Peg-IFNa-2a/RBV combination therapy may cause thyroid dysfunction, especially hypothyroidism, in CHC patients. Female sex and thyroid auto-antibody positivity may put CHC patients at higher risk of developing thyroid dysfunction during peg-IFNa-2a/RBV therapy. Elevated IL-6 may be a predictive marker of peg-IFNa-2a/RBV-induced thyroid dysfunction.

[Efficacy of low-dose interferon therapy for treating chronic hepatitis C patients who cannot tolerate standard treatment].

OBJECTIVE: To investigate the therapeutic efficacy of interferon (IFN) therapy and risk of long-term administration for chronic hepatitis C (CHC) patients who cannot tolerate the standard treatment. METHODS: Forty-six CHC patients who had proven intolerant to standard treatments were treated with low-dose IFN (non-pegylated IFN: 60 to 300MIU QOD, or pegylated IFN: 50 to 90 mug/w) plus ribavirin (RBV; 0.6g to 0.9 g/d) for 72 weeks. RESULTS: Forty-three (93.5%) of the patients were able to tolerate the long-term treatment with low-dose IFN plus RBV. Only three patients experienced severe side effects (low white blood cell and platelet counts) that required treatment withdrawal. The virology response rates over treatment time were: rapid virologic response (RVR): 10.9%; early virus response (EVR): 30.4%; 24 week virologic response: 45.7%; and, 48 week virologic response: 47.8%. B-sonographic imaging revealed that three patients experienced improved liver morphology through the treatment course. The patients who achieved RVR, EVR, or 24 weeks virologic response also attained higher 48 week virologic response. The 24 week virologic response had the strongest predictive value of good prognosis. CONCLUSIONS: Our study demonstrated that long-term treatment with low-dose interferon plus ribavirin is effective for patients who are otherwise intolerant to standard treatment. In these patients, low-dose IFN plus RBV can obtain a high virologic response rate at 48 week. Furthermore, the 24 week virologic response is sufficiently predictive of treatment success. As with any treatment regimen, it is important for healthcare workers to monitor the disease status and potential side effects throughout the course of therapy.

Aggregation and conformational change of mushroom (Agaricus bisporus) polyphenol oxidase subjected to atmospheric cold plasma treatment.

Atmospheric cold plasma (ACP) is a novel nonthermal technology with potential applications in maintaining and improving food quality. The effect of ACP on the activity and structure of mushroom (Agaricus bisporus) polyphenol oxidase (PPO) was evaluated. Results demonstrated that the dielectric barrier discharge (DBD) based plasma technology could inactivate PPO (up to 69%) at 50 kV with the increased concentrations of H2O2 and NOx. An obvious enhancement of surface hydrophobicity was observed, whereas a gradual reduction of total sulfhydryl content was recorded with the increasing exposure time. Data from circular dichroism, atomic force microscopy, particle size distribution and fluorescence spectra displayed the rearrangement of secondary structure and disruption of the tertiary structure. Red shifts of fluorescence spectra showed positive correlations with the inactivation rate of PPO. Therefore, ACP treatment could be served as an alternative approach to inactivate undesirable enzymes to minimize the loss of food nutrition and quality.

Effect of the change in antiviral therapy indication on identifying significant liver injury among chronic hepatitis B virus infections in the grey zone.

Objective: In clinical practice, a substantial proportion of chronic hepatitis B virus (HBV) infections that do not fit into any of the usual immune states are considered to be in the "grey zone (GZ)". This study aimed to investigate the effect of the change in antiviral therapy indication on identifying significant hepatic injury among GZ patients. Methods: Patients with chronic HBV infections and a persistent normal alanine aminotransferase (ALT) level (PNALT) who underwent ultrasonography-guided percutaneous liver biopsy were examined retrospectively. Evidenced hepatic injury (EHI) was defined as an inflammation grade ≥2 (≥G2) and/or fibrosis stage ≥2 (≥F2). Complete clinical data, liver inflammation, and fibrosis grades were collected, and the levels of cytokines were detected by the Luminex technique, all of which were analysed to investigate the immune and histopathology states of the liver. Results: A total of 347 patients with chronic HBV infections and PNALT were categorized into immune tolerant (IT, n = 108), inactive HBV surface antigen (HBsAg) carrier (IHC, n = 61), GZ-1 (HBeAg positive in GZ, n = 92), and GZ-2 (HBeAg negative in GZ, n = 68) phases. Among them, 51.3% were in the GZ phase, and 50.1% presented with EHI. The IL-6 levels were higher in the EHI group than in the non-EHI group (2.77 vs. 1.53 pg/ml, Z = -13.32, p = 0.028). The monocyte chemoattractant protein 1 (MCP-1) level was positively correlated with HBV DNA (R = 0.64, p < 0.001) and HBeAg (R = 0.5, p < 0.001) but negatively correlated with fibrosis grade (R = -0.26, p = 0.048). The ratio of EHI in the GZ phase was 60.55%, which was significantly higher than that in patients in the IT (39.8%) and IHC phases (37.7%) (χ2 = 10.4, p = 0.006). A total of 46.69% of all patients exceeded the new ALT antiviral treatment threshold (30 U/L for men and 19 U/L for women). The EHI values in the IT and IHC phases below the new ALT threshold were 32.6% and 37.8%, respectively, whereas higher EHI values of 67.4% and 68.4% were seen in GZ-1 and GZ-2 patients, respectively, exceeding the new ALT threshold, and the difference was statistically significant (χ2 = 11.13, p < 0.001; χ2 = 14.22, p = 0.002). The median age in our cohort was 38.91 years, and only 21.03% were less than 30 years old. The EHI values in the IT and IHC patients <30 years old were 32.4% and 35.8%, respectively, while the ratio of EHI increased to 43.2% once patients were older than 30 years but still in the IT and IHC stages. Conclusion: Setting 30 years old as a cut-off and lowering the ALT threshold could facilitate screening for the presence of significant liver injury, especially for GZ patients. IL-6 was a good indicator of EHI, and MCP-1 was significantly positively correlated with HBV DNA but negatively correlated with liver fibrosis.

The Effect of Dielectric Barrier Discharge Plasma Gas and Plasma-Activated Water on the Physicochemical Changes in Button Mushrooms (Agaricus bisporus).

Button mushrooms (Agaricus bisporus) are highly popular worldwide due to their rich nutritional value and health benefits. However, the rapid water loss rate and browning restrict their economic value. The atmospheric cold plasma (ACP) generated by the plasma equipment used by dielectric barrier discharge preservation technology is widely used for food preservation since it is cost-efficient and environmentally friendly, generating no chemical residues. This study established four treatment groups, namely the direct ACP treatment group (DBD), plasma-activated water immersion group (PAW), pure water immersion group (PW), and control group (control), to explore the effect that ACP preservation technology has on button mushrooms. The results indicated that ACP treatment decreased the pH of pure water from 5.90 ± 0.03 to 5.16 ± 0.03, while significantly increasing the temperature (p < 0.05). During the storage period, the browning index (BI) and E value were the lowest in the PAW group, which exhibited the best hardness and sensory properties. Neither the pH nor water activity changed significantly during the storage period in any of the groups. The polyphenol oxidase (PPO) activity in the button mushroom decreased significantly compared with the control after plasma-activated water treatment. In summary, plasma-activated water significantly reduced the BI and E value of button mushrooms, inhibited PPO activity, and yielded the most stable sensory properties for the optimal preservation of button mushrooms.

Study on the Retreatment, Outcome, and Potential Predictors of Recurrence in Patients With Recurrence of Hepatitis B After Functional Cure.

Background: Studies about the retreatment and predictors for patients with hepatitis B recurrence after functional cure are rare. This study aimed to evaluate the effect of retreatment, outcome, and potential predictors of recurrence in patients with recurrence after functional cure. Methods: A long-term follow-up was conducted with 32 cumulatively obtained patients who relapsed after cessation of pegylated interferon (Peg-IFN)-based antiviral treatment. The decision of whether to treatment or which therapeutic method to use [Peg-IFN or nucleos(t)ide analogs (NAs)] was based on the patient's preferences and wishes. The rate of achieving functional cure and the clinical outcomes of different therapeutic methods were analyzed. Hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody (anti-HBc) levels were detected in patients with blood samples during follow-up to evaluate the predictive ability of recurrence. Results: The follow-up time of 32 recurrence cases was 42-532 weeks after recurrence (median 226 weeks). In the 20 patients who received retreatment (15 received Peg-IFN and 5 received NAs only), the rate of functional cure was 65.0% (13/20); it was 86.7% (13/15) in the patients retreated with Peg-IFN. Three cases experienced recurrence again. Five patients received NA treatment, and no functional cure was achieved. No drug intervention was administered for 12 patients, 2 of them with hepatitis B virus (HBV) DNA spontaneous clearance, and one patient achieved spontaneous hepatitis B surface antigen (HBsAg) clearance during follow-up. Patients who relapsed after functional cure with Peg-IFN treatment did not have liver cirrhosis or hepatocellular carcinoma during the follow-up, regardless of whether they received retreatment. Anti-HBs and anti-HBc levels at the end of therapy were predictors of recurrence (p < 0.001, p = 0.023). The value of combining the above two indicators in predicting recurrence was further improved, the areas under the receiver operating characteristic curves were 0.833, at combining predictors >-0.386, the predictive sensitivity and specificity for recurrence were 86.67% and 90.62%. Conclusion: The functional cure rate was above 80% for patients with recurrence treated by Peg-IFN. During the follow-up, liver cirrhosis and hepatocellular carcinoma were not observed in all recurrence cases. High levels of anti-HBs and anti-HBc at the time of drug discontinuation are less likely to relapse.