SARS-CoV-2 Vaccine-Related Liver Failure: Active Hepatitis B and Comprehensive Literature Analysis

SARS-CoV-2 infection or vaccination is closely associated with liver injury, and autoimmune hepatitis episodes have been described, but liver failure has not been reported. Here, we report the case of a 41-year-old man, presenting with fatigue, anorexia after activity, greasy, decreased intake, yellow urine, and occasionally acid reflux in the stomach, occurring 2–3 weeks after receiving the first dose of inactivated SARS-CoV-2 vaccination, thought to be associated with his underlying chronic hepatitis B and fatty liver condition. The patient took the drug irregularly and did not achieve viral conversion to negative and appear rtA181T-resistant HBV mutation. Recently, the laboratory results showed abnormal liver function with high alanine aminotransferase (ALT), aspartate aminotransferase (AST), and γ-glutamyl transferase (GGT), and there was no improvement in liver function after hepatoprotective therapy, and the serum hepatitis B virus (HBV) concentration was greater than 2.0 × 106 IU/mL. Later, after being admitted to our hospital, it was found that he was in, malaise, jaundice, his eyes and sclera were yellow, his lungs were coarse breath sounds, his liver function was abnormally elevated, and his HBV virus developed a drug-resistant mutation. He has no history of autoimmune disease and tests negative for autoimmune antibodies. He became severely ill after intermittently stopping HBV treatment, worsened liver injury after inactivated SARS-CoV-2 vaccination, and was diagnosed with acute-on-chronic liver failure (ACLF). By summarizing the case report, it will provide important information on the vaccine safety assessment of vaccine components, immunization routes, and dosage for people with underlying liver disease

Twist Promotes Tumor Metastasis in Basal-Like Breast Cancer by Transcriptionally Upregulating ROR1

Rationale: Twist is a key transcription factor for induction of epithelial-mesenchymal transition (EMT), which promotes cell migration, invasion, and cancer metastasis, confers cancer cells with stem cell-like characteristics, and provides therapeutic resistance. However, the functional roles and targeted genes of Twist in EMT and cancer progression remain elusive. Methods: The potential targeted genes of Twist were identified from the global transcriptomes of T47D/Twist cells by microarray analysis. EMT phenotype was detected by western blotting and immunofluorescence of marker proteins. The dual-luciferase reporter and chromatin immunoprecipitation assays were employed to observe the direct transcriptional induction of ROR1 by Twist. A lung metastasis model was used to study the pro-metastatic role of Twist and ROR1 by injecting MDA-MB-231 cells into tail vein of nude mice. Bio-informatics analysis was utilized to measure the metastasis-free survival of breast cancer patients. Results: Twist protein was proved to directly activate the transcription of ROR1 gene, a receptor of Wnt5a in non-canonical WNT signaling pathway. Silencing of ROR1 inhibited EMT process, cell migration, invasion, and cancer metastasis of basal-like breast cancer (BLBC) cells. Knockdown of ROR1 also ameliorated the pro-metastatic effect of Twist. Furthermore, analyses of clinical specimens indicated that high expression of both ROR1 and Twist tightly correlates with poor metastasis-free survival of breast cancer patients. Conclusion: ROR1 is a targeted gene of Twist. Twist/ROR1 signaling is critical for invasion and metastasis of BLBC cells

JNK Pathway-Associated Phosphatase/DUSP22 Suppresses CD4+ T-Cell Activation and Th1/Th17-Cell Differentiation and Negatively Correlates with Clinical Activity in Inflammatory Bowel Disease

This study aimed to investigate the role of JNK pathway-associated phosphatase (JKAP) in inflammatory bowel disease (IBD). JKAP expression was analyzed in the intestinal mucosa of 81 IBD patients and 25 healthy controls (HCs) by qPCR and immunoblotting. The correlations of JKAP with clinical activity and inflammatory cytokines were performed. JKAP expression before and after infliximab treatment was also measured. CD4+ T cells were isolated from peripheral blood in active IBD patient and HCs and transduced with lentivirus-encoding JKAP (LV-JKAP), anti-JKAP (LV-anti-JKAP), or empty vector (LV-scramble), and JKAP functions on IBD CD4+ T cells were subsequently investigated. JKAP expression was decreased in inflamed mucosa of active IBD patients and was negatively correlated with disease activity [Crohn’s disease activity index (CDAI), Mayo index, C-reactive protein, and erythrocyte sedimentation rate], interleukin-17, and tumor necrosis factor (TNF)-α levels. Anti-TNF-α treatment up-regulated JKAP expression in CD patients, and baseline JKAP expression was elevated in response patients than in failure patients. Transduction of LV-JKAP into CD4+ T cells inhibited the percentages of CD25+ and CD69+ cells and proliferation. Moreover, inhibition of JKAP promotes Th1/Th17 cell differentiation. Our data indicated that the decreased expression of JKAP in intestinal mucosa contributed to the pathogenesis of IBD, through facilitating CD4+ T-cell activation, proliferation, and Th1/Th17-cell differentiation

Gender-Specific Differences in Clinical Profile and Biochemical Parameters in Patients with Cushing's Disease: A Single Center Experience

Cushing's disease (CD) is remarkably prevalent among females; however, more severe clinical presentation and adverse outcomes have been found in males. The purpose of this study was to investigate the overall clinical profile and biochemical parameters in patients with CD to identify the gender differences. Here we describe our series of CD patients referred to our medical center during 2012-2013. Among 73 cases, females presented a marked preponderance compared to males. Males had significantly higher ACTH, BMI, HbA1c, systolic blood pressure, and hemoglobin than females. For the first time, the incidence of fatty liver and hepatic function was also shown to be elevated in males. Multiple linear regression analysis was performed to further investigate the correlation of risk factors with hypokalemia, HbA1c, and systolic blood pressure. Gender and serum cortisol were associated with hypokalemia. Age, gender, and serum cortisol were significantly associated with HbA1c. Additionally, only gender was significantly associated with systolic blood pressure. Regarding clinical presentation, purple striae seemed to occur more frequently in males than in females. Thus, more severe clinical presentation, biochemical parameters, and complications were found in males than in females. Clinical professionals should pay more attention to the diagnosis and management of males with CD

Elevated Serum IL-21 Levels Are Associated With Stable Immune Status in Kidney Transplant Recipients and a Mouse Model of Kidney Transplantation

Allograft rejection after renal transplantation remains a challenge to overcome. Interleukin (IL)-21, a cytokine with pleiotropic effects, maintains immune homeostasis post-transplantation. Here, we report higher levels of IL-21 in kidney transplant recipients with non-rejection (NR) than in recipients with T cell-mediated rejection (TCMR, P \u3c 0.001) and antibody-mediated rejection (ABMR, P = 0.005). We observed a negative correlation between IL-21 and creatinine (Cr) levels (P = 0.016). The receiving operating characteristic (ROC) curve showed a promising diagnostic value of IL-21 to identify acute rejection with an area under the curve (AUC) of 0.822 (P \u3c 0.001). In contrast, exogenous administration of IL-21 accelerated acute rejection in a comparative translational kidney transplant (KT) mouse model. Reduced IL-21 levels in the peripheral blood were observed in KT mice after IL-21 injection. Further analysis revealed that increased IL-21 levels in the spleen induced proliferation of CD4+ T cells and CD19+ B cells after IL-21 treatment. Our findings suggest a critical function of IL-21 in kidney transplantation and the potential involvement of the IL-21/IL-21R pathway in acute rejection management

Critical review of nuclear power plant carbon emissions

Nuclear power plays a crucial role in achieving the target of carbon neutrality to build a sustainable society. However, it is not “carbon-free” when considering its entire life cycle. Therefore, accurate accounting and monitoring of its generated carbon emissions are required to avoid miscalculations of nuclear energy as a clean energy source. In this study, the life-cycle carbon emissions of nuclear power plants (NPPs) with different reactor types are reviewed. In addition to the characteristic differences among different reactors, disparities in the review results originate from the varying emissions at the respective stages of the nuclear fuel cycle, technology choices at each stage and accounting methods and boundaries. The carbon emissions resulting from NPP construction and operation are underestimated due to the limited data and methods, which creates uncertainty in the evaluation of NPP carbon emissions. An integrated framework for carbon emissions accounting considering the construction and operation of NPPs (CACO-NPP) is proposed. This integrated framework aims to improve the accounting accuracy for carbon emissions originating from NPPs. An emerging Generation III NPP with the latest technology, HPR1000 (an advanced pressurized water reactor), was adopted as a case study. The results show that the total emissions resulting from vegetation loss, equipment manufacturing and labor input during construction and operation are 1232.91 Gg CO2 with a carbon intensity of 1.31 g CO2/kWh, indicating the notable mitigation capability of Generation III NPPs. By combining the maturity of HPR1000 technology with successive design improvements, the carbon emissions of such reactor types could be further reduced. This development is very important for realizing China’s carbon neutrality target

Exercise ameliorates the FGF21–adiponectin axis impairment in diet-induced obese mice

Objective: The protective effects of exercise against glucose dysmetabolism have been generally reported. However, the mechanism by which exercise improves glucose homeostasis remains poorly understood. The FGF21–adiponectin axis participates in the regulation of glucose metabolism. Elevated levels of FGF21 and decreased levels of adiponectin in obesity indicate FGF21–adiponectin axis dysfunction. Hence, we investigated whether exercise could improve the FGF21–adiponectin axis impairment and ameliorate disturbed glucose metabolism in diet-induced obese mice. Methods: Eight-week-old C57BL/6J mice were randomly assigned to three groups: low-fat diet control group, high-fat diet group and high-fat diet plus exercise group. Glucose metabolic parameters, the ability of FGF21 to induce adiponectin, FGF21 receptors and co-receptor levels and adipose tissue inflammation were evaluated after 12 weeks of intervention. Results: Exercise training led to reduced levels of fasting blood glucose and insulin, improved glucose tolerance and better insulin sensitivity in high-fat diet-induced obese mice. Although serum FGF21 levels were not significantly changed, both total and high-molecular-weight adiponectin concentrations were markedly enhanced by exercise. Importantly, exercise protected against high-fat diet-induced impaired ability of FGF21 to stimulate adiponectin secretion. FGF21 co-receptor, β-klotho, as well as receptors, FGFR1 and FGFR2, were upregulated by exercise. We also found that exercise inhibited adipose tissue inflammation, which may contribute to the improvement in the FGF21–adiponectin axis impairment. Conclusions: Our data indicate exercise protects against high-fat diet-induced FGF21–adiponectin axis impairment, and may thereby exert beneficial effects on glucose metabolism