RESUMEN
Due to their high energy density and cost-effectiveness, lithium-sulfur batteries (LSBs) are considered highly promising for the next generation of energy storage technologies. However, the soluble lithium-polysulfides (LiPSs) notorious for causing the shuttle effect and the sluggish redox kinetics have hindered their practical commercialization. To tackle these challenges, a heterostructural catalyst featuring NiS-NiCo2O4 interfaces is developed, which serves as an interlayer for LSBs. These interfacial sites leverage the advantages of polar NiCo2O4 and conductive NiS, enabling smooth Li+ diffusion, rapid electron transport, and effective immobilization of LiPSs. This synergistic approach promotes the conversion of sulfur species, resulting in a high discharge capacity of 526 mAh g-1 at 3 C for cells with the NiS-NiCo2O4 interlayer. Additionally, remarkable cycling stability is achievable with an areal sulfur loading of ≈5.0 mg cm-2. It is believed that this research paves the way for practical applications of LSBs.
RESUMEN
The incidence of autoimmune liver diseases (ALDs) and research on their pathogenesis are increasing annually. However, except for autoimmune hepatitis, which responds well to immunosuppression, primary biliary cholangitis and primary sclerosing cholangitis are insensitive to immunosuppressive therapy. Besides the known effects of the environment, genetics, and immunity on ALDs, the heterogeneity of target cells provides new insights into their pathogenesis. This review started by exploring the heterogeneity in the development, structures, and functions of hepatocytes and epithelial cells of the small and large bile ducts. For example, cytokeratin (CK) 8 and CK18 are primarily expressed in hepatocytes, while CK7 and CK19 are primarily expressed in intrahepatic cholangiocytes. Additionally, emerging technologies of single-cell RNA sequencing and spatial transcriptomic are being applied to study ALDs. This review offered a new perspective on understanding the pathogenic mechanisms and potential treatment strategies for ALDs.
RESUMEN
PARP inhibitors and HDAC inhibitors have been approved for the clinical treatment of malignancies, but acquired resistance of or limited effects on solid tumors with a single agent remain as challenges. Bioinformatics analyses and a combination of experiments had demonstrated the synergistic effects of PARP and HDAC inhibitors in triple-negative breast cancer. A series of novel dual PARP and HDAC inhibitors were rationally designed and synthesized, and these molecules exhibited high enzyme inhibition activity with excellent antitumor effects in vitro and in vivo. Mechanistically, dual PARP and HDAC inhibitors induced BRCAness to restore synthetic lethality and promoted cytosolic DNA accumulation, which further activates the cGAS-STING pathway and produces proinflammatory chemokines through type I IFN-mediated JAK-STAT pathway. Moreover, these inhibitors promoted neoantigen generation, upregulated antigen presentation genes and PD-L1, and enhanced antitumor immunity when combined with immune checkpoint blockade therapy. These results indicated that novel dual PARP and HDAC inhibitors have antitumor immunomodulatory functions in triple-negative breast cancer. Novel dual PARP and HDAC inhibitors induce BRCAness to restore synthetic lethality, activating tumoral IFN signaling via the cGAS-STING pathway and inducing cytokine production, promoting neoantigen generation and presentation to enhance the immune response.