High L-Carnitine Levels Impede Viral Control in Chronic Hepatitis B Virus Infection

Persistent antigen exposure during chronic hepatitis B infection leads to exhausted immune responses, thus impeding viral control. In recent years, immunometabolism opens new therapeutic possibilities for the modulation of immune responses. Herein, we investigated the immunomodulatory effect of L-carnitine (L-Cn) on immune cells in chronic HBV infection. In this study, 141 treatment-naïve patients with chronic HBV infection, 38 patients who achieved HBsAg loss following antiviral treatment, and 47 patients who suffered from HBV-related HCC from real-life clinical practice were recruited. The plasma L-Cn levels were measured by ELISA. RNA sequencing was conducted to define the transcriptional profiles of peripheral blood mononuclear cells after L-Cn stimulation. In vitro assays were performed to assess the effect of L-Cn on immune cells; the frequencies and function of immune cells were analyzed by flow cytometry. We found that compared with patients with HBsAg loss, patients with HBsAg positivity and patients who suffered from HBV-related HCC had higher levels of L-Cn, and the plasma levels of L-Cn in the HBeAg-positive chronic hepatitis patients who had elevated ALT were significantly higher than that of HBeAg-negative chronic infection and HBsAg loss groups. Moreover, a positive correlation between plasma levels of L-Cn and HBsAg levels was found. Additionally, RNA sequencing analysis demonstrated that L-Cn altered the transcriptional profiles related to immune response. In vitro assays revealed that L-Cn suppressed the proliferation of and IFN-γ production by CD4+ and CD8+ T cells. It also down-regulated the proliferation and IgG production of B cells. Notably, L-Cn enhanced IL-10 secretion from regulatory T cells and up-regulated the expression of inhibitory receptors on T cells. Moreover, a variant in CPT2 (rs1799821) was confirmed to be associated with L-Cn levels as well as complete response in CHB patients following Peg-IFNα antiviral therapy. Taken together, the immunosuppressive properties of L-Cn may hinder the control of HBV in chronic HBV infection, implicating that L-Cn manipulation might influence the prognosis of patients with HBV infection

Features of immune response during antiviral therapy in patients with chronic hepatitis B

Host immune response is a double-edged sword and participates in liver injury and viral control in patients with HBV infection. Antiviral therapy with nucleos(t)ide analogues and interferon may improve prognosis through regulating host immune response. This article describes the role of host immune response in chronic HBV infection and its features during antiviral therapy and emphasizes the importance of host immune reconstruction in sustained control of HBV infection

Non-Hermitian non-equipartition theory for trapped particles

Abstract The equipartition theorem is an elegant cornerstone theory of thermal and statistical physics. However, it fails to address some contemporary problems, such as those associated with optical and acoustic trapping, due to the non-Hermitian nature of the external wave-induced force. We use stochastic calculus to solve the Langevin equation and thereby analytically generalize the equipartition theorem to a theory that we denote the non-Hermitian non-equipartition theory. We use the non-Hermitian non-equipartition theory to calculate the relevant statistics, which reveal that the averaged kinetic and potential energies are no longer equal to k B T/2 and are not equipartitioned. As examples, we apply non-Hermitian non-equipartition theory to derive the connection between the non-Hermitian trapping force and particle statistics, whereby measurement of the latter can determine the former. Furthermore, we apply a non-Hermitian force to convert a saddle potential into a stable potential, leading to a different type of stable state

Code Availability for Nature Communications Non-Hermitian Non-Equipartition Theory for Trapped Particles

Code Availability for Nature Communications Non-Hermitian Non-Equipartition Theory for Trapped Particles</p

Data Availability for Nature Communications Non-Hermitian Non-Equipartition Theory for Trapped Particles

Data Availability for Nature Communications Non-Hermitian Non-Equipartition Theory for Trapped Particles</p

Potential Antioxidative Activity of Homocysteine in Erythrocytes under Oxidative Stress

Homocysteine is an amino acid containing a free sulfhydryl group, making it probably contribute to the antioxidative capacity in the body. We recently found that plasma total homocysteine (total-Hcy) concentration increased with time when whole blood samples were kept at room temperature. The present study was to elucidate how increased plasma total-Hcy is produced and explore the potential physiological role of homocysteine. Erythrocytes and leukocytes were separated and incubated in vitro; the amount of total-Hcy released by these two kinds of cells was then determined by HPLC-MS. The effects of homocysteine and methionine on reactive oxygen species (ROS) production, osmotic fragility, and methemoglobin formation in erythrocytes under oxidative stress were studied. The reducing activities of homocysteine and methionine were tested by ferryl hemoglobin (Hb) decay assay. As a result, it was discovered that erythrocytes metabolized methionine to homocysteine, which was then oxidized within the cells and released to the plasma. Homocysteine and its precursor methionine could significantly decrease Rosup-induced ROS production in erythrocytes and inhibit Rosup-induced erythrocyte’s osmotic fragility increase and methemoglobin formation. Homocysteine (but not methionine) was demonstrated to enhance ferryl Hb reduction. In conclusion, erythrocytes metabolize methionine to homocysteine, which contributes to the antioxidative capability under oxidative stress and might be a supplementary protective factor for erythrocytes against ROS damage

Causal associations between chronic hepatitis B and COVID-19 in East Asian populations

Abstract Background The relationship between chronic hepatitis B (CHB) and Coronavirus disease 2019 (COVID-19) has been inconsistent in traditional observational studies. Methods We explored the total causal and direct causal associations between CHB and the three COVID-19 outcomes using univariate and multivariate Mendelian randomization (MR) analyses, respectively. Genome-wide association study datasets for CHB and COVID-19 were obtained from the Japan Biobank and the COVID-19 Host Genetics Initiative, respectively. Results Univariate MR analysis showed that CHB increased the risk of SARS-CoV-2 infection (OR = 1.04, 95% CI 1.01–1.07, P = 3.39E−03), hospitalized COVID-19 (OR = 1.10, 95% CI 1.06–1.13, P = 7.31E−08), and severe COVID-19 (OR = 1.16, 95%CI 1.08–1.26, P = 1.43E−04). A series of subsequent sensitivity analyses ensured the stability and reliability of these results. In multivariable MR analyses adjusting for type 2 diabetes, body mass index, basophil count, and smoking, genetically related CHB is still positively associated with increased risk of SARS-CoV-2 infection (OR = 1.06, 95% CI 1.02–1.11, P = 1.44E−03) and hospitalized COVID-19 (OR = 1.12, 95% CI 1.07–1.16, P = 5.13E−07). However, the causal link between CHB and severe COVID-19 was attenuated after adjustment for the above variables. In addition, the MR analysis did not support the causal effect of COVID-19 on CHB. Conclusions This study provides evidence that CHB increases COVID-19 susceptibility and severity among individuals of East Asian ancestry