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The special band structure of bilayer MoS2 makes it show strong nonlinear optical characteristics in the visible band, which provides a new way to develop visible nonlinear devices. In this paper, we present a theoretical analysis of the optical bistability (OB) in a silver–Bragg reflector structure by embedding bilayer MoS2 at the visible band. The nonlinear OB phenomenon is achieved due to the nonlinear conductivity of the bilayer MoS2 and the excitation of the optical Tamm state at the interface between the silver and the Bragg reflector. It is found that the hysteresis behavior and the threshold width of the OB can be effectively tuned by varying the incident light wavelength. In addition, the optical bistable behavior of the structure can be adjusted by varying the position of the MoS2 inset in the defect layer, the incident angle, and the structural parameters of the spacer layer. We believe the above results can provide a new paradigm for the construction of controllable bistable devices.

Background: Microvascular invasion (MVI) is associated with an unfavorable prognosis and early recurrence of hepatocellular carcinoma (HCC), which is the crucial pathological hallmark of immunotherapy. While microvascular invasion (MVI) in hepatocellular carcinoma (HCC) currently lacks a detailed single-cell analysis of the tumor microenvironment (TME), it holds significant promise for immunotherapy using immune checkpoint inhibitors (ICI). Methods: We performed single-cell RNA sequencing (scRNA-seq) on 3 MVI positive (MVIP) and 14 MVI-negative (MVIN) tumor tissues, as well as their paired adjacent non-tumoral tissues. Results: We identified SPP1+ macrophages and CD4+ proliferative T cells as intertumoral populations critical for the formation of cold tumors and immunosuppressive environments in MVI-positive patients and verified their prognostic value in correlation with MVIP HCC patients. Additionally, we identified SPP1+ dominated interactions between SPP1+ macrophages and the immunosuppressive T population as contributors to MVI destruction and tumorigenesis. Conclusions: We provide a comprehensive single-cell atlas of HCC patients with MVI, shedding light on the immunosuppressive ecosystem and upregulated signaling associated with MVI. These findings demonstrate that intercellular mechanisms drive MVI and provide a potential immunotherapeutic target for HCC patients with HCC and underlying MVI.

Abstract The African swine fever (ASF) pandemics pose a significant threat to the global swine industry, and the development of safe and effective vaccines is a daunting but necessary challenge. The level and persistence of immunity are very important for the effectiveness of the vaccine. Targeting antigens to antigen presenting cells (APCs) can greatly enhance immunogenicity. In this study, we developed a self-assembled nano-ASFV vaccine candidate (NanoFVax) targeting DCs, by covalently coupling the self-assembled 24-mer ferritin with the dominant B and T cell epitopes of the highly immunogenic ASFV antigen (p72, CD2v, pB602L and p30) and fused with the chemokine receptor XCL1 (a DC targeting molecule) through the SpyTag/SpyCatcher protein ligase system. Compared to monomeric protein, the nanoparticle vaccines can induce a more robust T-cell response, and the high-level antibody response against ASFV can last for more than 231 days. Therefore, the NanoFVax is a novel and promising vaccine candidate for ASFV. Graphical Abstract

The outbreak of African Swine Fever (ASF) has caused huge economic losses to the pig industry. There are no safe and effective vaccines or diagnostics available. The p30 protein serves as a key target for the detection of ASFV antibodies and is an essential antigenic protein for early serological diagnosis. Here, the p30 protein was purified after being expressed in E. coli and its immunogenicity was verified in sera from pigs naturally infected with ASFV. Furthermore, a monoclonal antibody (McAb) designated as McAb 1B4G2–4 (subtype IgG1/kappa-type) was produced and it was verified to specifically recognize the ASFV Pig/HLJ/2018/strain and eukaryotic recombinant ASFV p30 protein. The epitope identified by McAb 1B4G2–4, defining the unique B-cell epitope 164HNFIQTI170, was located using peptide scanning. Comparing amino acid (aa) sequence revealed that this epitope is conserved in all reference ASFV strains from different regions of China, including the highly pathogenic strain Georgia 2007/1 (NC_044959.2) that is widely distributed. It is also exposed to the surface of the p30 protein, suggesting that it could be an important B-cell epitope. Our study may serve as a basis for the development of serological diagnostic methods and subunit vaccines.

Abstract Background Immunotherapy has transformed cancer treatment patterns for advanced hepatocellular carcinoma (aHCC) in recent years. Therefore, the identification of predictive biomarkers has important clinical implications. Methods We collected medical records from 117 aHCC patients treated with anti-PD-1 antibody. Kaplan-Meier analysis and Cox proportional hazard regression were used to evaluate the association between peripheral blood biomarkers and overall survival (OS) and progression-free survival (PFS). Finally, the prognostic nomogram was constructed. Results The mPFS and mOS were 7.0 months and 18.7 months, respectively. According to Kaplan-Meier analysis and Cox regression analysis, we regarded the treatment regimen (p = 0.020), hemoglobin (Hb) at 6-week (p = 0.042), neutrophil-to-lymphocyte ratio (NLR) at 6-week (p

This paper presents a new multiple-input soft-switching DC–DC Ćuk converter for clean and renewable energy sources. The proposed converter can buck and boost the different voltages of renewable energy sources to produce a constant DC output voltage in a DC microgrid. In the proposed converter, edge-resonant soft-switching modules are used to perform better than the conventional multiple-input Ćuk converter. All switches in the edge-resonant soft-switching modules can realize zero-current switching turn-on and zero-voltage switching turn-off. By using these modules, the proposed converter can achieve lower current stress of the switches, wider soft-switching range, and higher power efficiency than the conventional multiple-input Ćuk converter. These advantages are achieved in the edge-resonant modules, which optimize soft-switching states and costs. In addition, the soft-switching states can be easily achieved because the edge-resonant soft-switching modules have a wide soft-switching range. Furthermore, the proposed converter can independently transfer the generated power from renewable energy sources to the DC microgrid. In this article, the operation principles and performance of the proposed converter are discussed in detail. The theoretical analysis is validated by experimental results obtained from a laboratory-scale prototype and full-scale real-time hardware-in-the-loop experiments.

BackgroundImmune checkpoint inhibitors (ICIs) have changed the treatment landscape of several cancer types. However, data are lacking with regard to the clinical responsiveness of ICIs in patients with advanced non-small cell lung cancer (NSCLC) after standard first-line chemotherapy. Therefore, we aimed to evaluate the clinical efficacy of ICI alone or in combination with chemotherapy for patients with advanced NSCLC after first-line platinum-based chemotherapy.MethodsWe retrospectively collected patients with confirmed advanced NSCLC who underwent ICI monotherapy or ICI plus chemotherapy after first-line platinum-based chemotherapy between January 2018 and December 2020. A propensity score matching analysis was used to balance baseline characteristics between the two treatment groups. Kaplan-Meier methods and multivariable Cox regressions were used for survival analyses.ResultsAmong 832 eligible patients, 222 received ICI monotherapy and 610 received ICI plus chemotherapy. The median overall survival (OS) of patients who received ICI plus chemotherapy was 16.0 months compared with 13.1 months in patients who received ICI monotherapy (HR: 0.64, 95% CI: 0.49-0.85, P = 0.002). After 1:1 propensity score matching, all baseline characteristics were well-balanced between the two treatment groups. Patients who received ICI plus chemotherapy had significantly longer OS than those who received ICI monotherapy (NR vs. 13.1 months, HR: 0.50, 95% CI: 0.34-0.71, P < 0.001). Meanwhile, the median time to treatment discontinuation was 4.4 months in the ICI-chemo group and 3.5 months in the ICI-mono group (HR: 0.72, 95% CI: 0.58-0.89, P = 0.002). The multivariate analysis indicated that treatment regimen was an independent prognostic factor for OS (HR: 0.488, 95% CI: 0.337-0.707, P < 0.001). Moreover, a nomogram that integrated both treatment regimens and clinicopathological factors was created for survival prediction.ConclusionOur study indicated that patients with advanced NSCLC who received ICI plus chemotherapy after first-line platinum-based chemotherapy tended to have longer OS than those who received ICI monotherapy. The multivariate analysis showed that treatment regimen was an independent prognostic factor for OS. Future prospective studies are needed to confirm these findings.

African swine fever (ASF) is an acute, virulent, and highly fatal infectious disease caused by the African swine fever virus (ASFV). There is no effective vaccine or diagnostic method to prevent and control this disease currently, which highlights the significance of ASF early detection. In this study, we chose an early antigen and a late-expressed antigen to co-detect the target antibody, which not only helps in early detection but also improves accuracy and sensitivity. CP204L and B602L were successfully expressed as soluble proteins in an Escherichia coli vector system. By optimizing various conditions, a dual-antigen indirect ELISA for ASFV antibodies was established. The assay was non-cross-reactive with antibodies against the porcine reproductive and respiratory syndrome virus, classical swine fever virus, porcine circovirus type 2, and pseudorabies virus. The maximum serum dilution for detection of ASFV-positive sera was 1:1600. The intra-batch reproducibility coefficient of variation was