The type-I, III nodal ring, type-I, III quadratic nodal point, and Dirac valley phonons in 2D kagome lattices M2C3(M = As, Bi, Cd, Hg, P, Sb, Zn).

Topological phases in kagome systems have garnered considerable interest since the introduction of the colloidal kagome lattice. Our study employs first-principle calculations and symmetry analysis to predict the existence of ideal type-I, III nodal rings (NRs), type-I, III quadratic nodal points (QNPs), and Dirac valley phonons (DVPs) in a collection of two-dimensional (2D) kagome lattices M2C3(M = As, Bi, Cd, Hg, P, Sb, Zn). Specifically, the Dirac valley points (DVPs) can be observed at two inequivalent valleys with Berry phases of +πand-π, connected by edge arcs along the zigzag and armchair directions. Additionally, the QNP is pinned at the Γ point, and two edge states emerge from its projections. Notably, these kagome lattices also exhibit ideal type-I and III nodal rings protected by time inversion and spatial inversion symmetries. Our work examines the various categories of nodal points and nodal ring phonons within the 2D kagome systems and presents a selection of ideal candidates for investigating topological phonons in bosonic systems.

Overview of anti-BCMA CAR-T immunotherapy for multiple myeloma and relapsed/refractory multiple myeloma.

Multiple myeloma (MM) is a haematological malignancy caused by malignant proliferation of plasma cells in bone marrow. In recent years, MM patients are commonly treated with chemotherapy, autologous stem cell transplantation, protease inhibitors, immunomodulatory drugs and monoclonal antibodies, however most patients eventually relapse. Therefore, more effective therapies are highly needed. Anti-BCMA CAR-T therapy, a novel and efficacious method for treating MM and relapsed/refractory multiple myeloma (RRMM), has been designed and applied in clinics. The CAR-T can specifically recognize the targeted molecule B cell maturation antigen (BCMA) and kill MM cells expressing BCMA and several clinical trials have revealed high response rates in the therapy. Herein, we summarize the developments, the current design and clinical trials, the side effects of anti-BCMA CAR-T therapy and comparison of it with other CAR-T therapies.

Study on the Mechanism of Selective Interaction of BR3 and BCMA with BAFF and APRIL.

BACKGROUND: B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) can activate signaling pathways by binding to specific receptors. BR3 (BAFF receptor) shows a unique selectivity for BAFF ligand, while B-cell maturation antigen (BCMA) exhibits a stronger interaction between APRIL-BCMA rather than BAFF-BCMA interaction. OBJECTIVE: The combined domains were fused with IgG1 Fc to better understand which domain affects the selective interaction of the receptor with BAFF and APRIL. METHODS: Since BR3 and BCMA both contain cysteine-rich repeat domains (CRD) with DxL motif, the binding domains of BR3 and BCMA were segmented into two parts in this study. BR3-1 (CFDLLVRHGVAC) and BCMA-1 (YFDSLLHACIPC) contained the conservative DxL motif, while BR3-2 (GLLRTPRPKPA) and BCMA-2 (QLRCSSNTPPLT) were adjacent to the CRDs yet still joined with BR3-1 and BCMA-1. Affinity between all possible combinations was then tested. RESULTS: The affinity of BR3-1-BCMA-2-Fc and BR3-1-BR3-2-Fc for BAFF was higher than BCMA-1-BR3-2-Fc and BCMA-1-BCMA-2-Fc. Moreover, BR3-1-BCMA-2-Fc and BCMA-1-BCMA- 2-Fc had affinity for APRIL, while BR3-1-BR3-2-Fc and BCMA-1-BR3-2-Fc hardly interacted with APRIL. CONCLUSION: BR3-1 region played a key role for interaction with BAFF, while BCMA-1 region exhibited weaker binding with BAFF. BCMA-2 region having an α-helix might contribute towards selectivity of APRIL-BCMA binding and BR3-2 rigid region had deleterious effects on the APRIL-BR3 interaction. These results provide comprehensive insights of the mechanism of selective interactions, and may promote specific antagonist design in the future.

Construction of small molecular CTLA4 analogs with CD80-binding affinity.

A variety of CTLA4-Fc fusion proteins and anti-CTLA4 monoclonal antibody have been approved. Given the shortcomings of macromolecular antibodies, recombinant proteins derived from the tenth unit of human type III fibronectin (FN3) termed monobody were studied as CTLA4 analogs in this study. A peptide EL161 derived from CD80-binding domain (MYPPPY motifs) in the complementarity determining region (CDR) 3 of CTLA4 was found to inhibit the interaction of CTLA4 with CD80 significantly. Afterward, the peptide EL16 as well as the CDR1 of CTLA4 which is also critical for its binding to CD80 were grafted onto FN3 and obtained a novel CD80 binding monobody protein CFN13.2 CFN13 showed 80% binding affinity compared to CTLA4. In addition, to increase the half-life, CFN13 was fused to human IgG1 Fc to generate CFN13-Fc fusion protein. As expected, CFN13-Fc bound to CD80 in a dosage-dependent manner as CFN13 did, and displayed 41.0% and 31.4% inhibition on the interaction of CTLA4-Fc with CD80 at 200 µg/ml and 100 µg/ml respectively. Moreover, peptide EL16 could inhibit CFN13-Fc binding to CD80 significantly, with the inhibition ratio of 64.3% and 52.8% at 100 and 50 µg/ml respectively, indicating that the peptide EL16 and CFN13-Fc shared the similar binding sites with CD80 and the CDR3 motif of CTLA4 contributed more than CDR1 in binding to CD80. In summary, our study provides insights into small molecular analogs of CTLA4.