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Paxilline (PAX) is a tremorgenic mycotoxin that is thought to be associated with various syndromes in animals. To facilitate the determination of this toxin, a hapten was chemically synthesized and then respectively conjugated to Bovine Thyroglobulin (BTG) and Bovine serum albumin (BSA) for antibody production. Monoclonal antibody (mAb) 4F8 was finally obtained and used to establish an accurate and sensitive indirect competitive ELISA (icELISA). Various parameters that could impact the performance of icELISA were optimized, including the ion concentration, pH value and organic solvent. Under optimal condition, this assay exhibits an IC50 value as low as 0.84 µg L−1. The limit of detection (LOD) of the established icELISA method for PAX was 0.03–0.3 µg L−1. In conclusion, this study provided a rapid, sensitive, and high-throughput immunoassay for the detection of PAX in grains. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the leading contributors to cancer‐related death because the immunosuppressive tumor microenvironment (TME) limits its therapeutic efficacy. Gasdermin (GSDM)‐mediated pyroptosis is a new programmed cell death that can boost antitumor immune responses. However, inducing efficient pyroptosis to reverse the immunosuppressive TME is challenging. Herein, layered double hydroxide‐coated magnesium (Zn‐LDH@Mg) implants are designed and constructed as alternating magnetic field (AMF)‐activated pyroptosis inducers to induce highly effective pyroptosis in cancer cells. The powerful eddy‐thermal effects of Zn‐LDH@Mg implants markedly amplify pyroptosis in malignant cells through the Caspase‐1/GSDMD‐dependent canonical pathway. Moreover, Mg2+ and pyroptosis synergistically activate T cells (especially CD8+ T cells) and enhance the infiltration of immune‐supportive cells. This innovative strategy not only significantly suppresses the proliferation of the primary tumor but also stimulates the immune response to further enhance the efficacy of immune checkpoint inhibitors and impede the progression of distant tumors. This work not only emphasizes the importance of surface engineering strategies for the preparation of novel pyroptosis inducers but also highlights the effectiveness of the strategy in reversing the immunosuppressive TME to enhance immunotherapy, providing a new approach for the rational design of bioactive materials to increase the efficacy of immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Nucleos(t)ide analogues (NAs) as the first-line treatment for chronic hepatitis B (CHB) have been shown to partially restore the antiviral immunity of the patients. However, hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) patients have a relatively longer duration of HBV infection and lower level of HBV DNA. Whether NAs treatments have a different effect on their immune repertoires between CHB and HCC patients remains to be determined. Patients and Methods: In this study, 126 CHB patients and 85 HBV-related HCC patients who received or did not receive NAs treatment, as well as 361 healthy individuals were enrolled to analyze the effect of NAs treatment on T cell receptor β chain (TCRβ) and B cell receptor heavy chain (BCRh) repertoires in peripheral blood of the patients. Results: We found that after NAs therapy, the richness and evenness of TCRβ and BCRh repertoires in CHB patients were significantly lower than those in untreated patients and healthy controls, while the diversity of TCRβ and BCRh repertoires was stable in HCC patients. The alanine aminotransferase and HBV DNA levels were not correlated with the TCR or BCR diversity in CHB and HCC patients. Conclusion: The results suggest that NAs therapy could influence the overall T cell and B cell repertoires diversity in CHB patients but has minimal impact on HCC patients, indicating a significant difference in the potential to restore antiviral immunity between CHB and HCC patients by NAs treatment. [ABSTRACT FROM AUTHOR]

The extraction of targets from biological samples for immunoassays using organic solvents, such as methanol, is often necessary. However, high concentrations of organic solvents in extracts invariably lead to instability of the employed antibody, resulting in poor performance of the immunoassay. Evaluating the tolerance ability and exploring the molecular mechanisms of antibody tolerance in organic solvents are essential for the development of robust immunoassays. In this work, 25 monoclonal antibodies and methanol are utilized as models to address these questions. A novel protocol is initially established to precisely and rapidly determine antibody tolerance in methanol, identifying two distinct methanol effect patterns. Through a detailed investigation of the structural basis, a novel hypothesis regarding methanol effect patterns is proposed, termed "folding‐aggregation," which is subsequently validated through molecular dynamics simulations. Furthermore, the investigation of sequence basis reveals significant differences in residue types within the complementarity‐determining regions and ligand‐binding residues, distinguishing the two antibody methanol effect patterns. Moreover, the methanol effect patterns of the antibodies are defined by germline antibodies. This work represents the first exploration of antibody methanol effect patterns and associated molecular mechanisms, with potential implications for the discovery and engineering of tolerant antibodies for the development of robust immunoassays. [ABSTRACT FROM AUTHOR]

A new integrating model has been developed to couple tokamak edge multiscale magnetohydrodynamic (MHD) events and transport simulations, such as edge‐localized mode (ELM) cycles. As a proof of principle, we first start from a set of three‐field two‐fluid model equations, which includes the pressure, current, and vorticity. The equations are separated into the slowly evolving part of the axisymmetric component by taking a time average of the axisymmetric component. The time‐averaged fluxes, which are quadratic in fluctuating quantities, act as driven terms for the time‐averaged axisymmetric quantities that determine the plasma transport, and therefore the large‐scale evolution of the plasma profiles. Then the HL‐2A's ELM cycles are simulated using the model. Good agreements of ELM size and pedestal recovery time have been achieved for the solutions obtained from the coupled simulation compared with experiment. For one ELM cycle simulation, the coupled code can achieve a speedup of a factor of up to 30 over standalone code. [ABSTRACT FROM AUTHOR]

BackgroundIn recent years, electron cyclotron wave (ECW) heating and current drive (ECCD) have been widely used in tokamak discharge experiments. The inevitable presence of impurity particles in the tokamak plasma affects the ECCD through radiation energy, inhibition of turbulent transport, and change the collision rate. Changes in plasma density, temperature and other transport quantities caused by the change of impurity concentration, induce the changes of Shafranov displacement at the center of magnetic surface of the plasma.PurposeThis study aims to investigate the influence of impurity concentration changes on the ECW deposition position and current drive efficiency theoretically with consideration of all above related variations.MethodsThe One Modeling Framework for Integrated Tasks (OMFIT) platform was used to conduct integrated simulation study of the effect of impurity effect on ECW heating and current drive. The HL-2M Tokamak device parameters were combined with self-consistent coupled plasma equilibrium, external auxiliary heating and current drive, transport and other physical processes for simulation computation with the carbon ions as the unique impurity ions.ResultsThe simulation results show that when the influence of impurities on the plasma is considered, with the increase of the impurity concentration, the radial position of the ECW deposition first moves to the plasma core and then moves to the edge, and the current drive efficiency first increases and then decreases. Due to the competition between the radiation effect and the dilution effect of the impurity-plasma interaction, the radiation loss power basically increases linearly with the increase of Zeff, while the dilution effect suppresses the turbulence and improve the confinement, but the stabilization effect slows down with the increase of Zeff.ConclusionsWhen the influence of impurities on the plasma is not considered, the deposition position of ECW is basically unchanged, and the current drive efficiency decreases. Results of this study have guiding significance for electron cyclotron current drive (ECCD) to control the plasma current profile and control the instability of magnetic fluid.