Multiresolution Time-Domain Scheme for Terminal Response of Two-Conductor Transmission Lines

This paper derives a multiresolution time-domain (MRTD) scheme for the two-conductor lossless transmission line equations based on Daubechies’ scaling functions. And a method is proposed to generate the scheme at the terminal and near the terminal of the lines. The stability and numerical dispersion of this scheme are studied, and the proposed scheme shows a better dispersion property than the conventional FDTD method. Then the MRTD scheme is extended to the two-conductor lossy transmission line equations. The MRTD scheme is implemented with different basis functions for both lossless and lossy transmission lines. Numerical results show that the MRTD schemes which use the scaling functions with high vanishing moment obtain more accurate results

Multiresolution Time-Domain Analysis of Multiconductor Transmission Lines Terminated in Linear Loads

This paper derives a multiresolution time-domain (MRTD) scheme for the multiconductor transmission line (MTL) equations based on Daubechies’ scaling functions. The terminations are characterized by a state-variable formulation which allows a general description of the termination networks. For the linear load terminations, a method incorporating the terminal constraints is proposed to work out the scheme at and close to the terminations. The MRTD scheme is implemented with different basis functions for linear components including resistances, inductances, and capacitances. Numerical results show that the MRTD schemes obtain a more stable result than the conventional finite difference time-domain (FDTD) method with a coarse space step.This work was supported by the National Natural Science Foundation of China (no. 11271370

Immune-checkpoint protein VISTA in allergic, autoimmune disease and transplant rejection

Negative checkpoint regulators (NCRs) reduce the T cell immune response against self-antigens and limit autoimmune disease development. V-domain Ig suppressor of T cell activation (VISTA), a novel immune checkpoint in the B7 family, has recently been identified as one of the NCRs. VISTA maintains T cell quiescence and peripheral tolerance. VISTA targeting has shown promising results in treating immune-related diseases, including cancer and autoimmune disease. In this review, we summarize and discuss the immunomodulatory role of VISTA, its therapeutic potential in allergic, autoimmune disease, and transplant rejection, as well as the current therapeutic antibodies, to present a new method for regulating immune responses and achieving durable tolerance for the treatment of autoimmune disease and transplantation

Tumor-associated microglia and macrophages in glioblastoma: From basic insights to therapeutic opportunities

Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Currently, the standard treatment of glioblastoma includes surgery, radiotherapy, and chemotherapy. Despite aggressive treatment, the median survival is only 15 months. GBM progression and therapeutic resistance are the results of the complex interactions between tumor cells and tumor microenvironment (TME). TME consists of several different cell types, such as stromal cells, endothelial cells and immune cells. Although GBM has the immunologically “cold” characteristic with very little lymphocyte infiltration, the TME of GBM can contain more than 30% of tumor-associated microglia and macrophages (TAMs). TAMs can release cytokines and growth factors to promote tumor proliferation, survival and metastasis progression as well as inhibit the function of immune cells. Thus, TAMs are logical therapeutic targets for GBM. In this review, we discussed the characteristics and functions of the TAMs and evaluated the state of the art of TAMs-targeting strategies in GBM. This review helps to understand how TAMs promote GBM progression and summarizes the present therapeutic interventions to target TAMs. It will possibly pave the way for new immune therapeutic avenues for GBM patients

Influence of Sparger Type on Mass Transfer in a Pilot-Scale Internal Loop Airlift Reactor

In a pilot-scale internal loop airlift reactor with a height of 5.5 m and a main column diameter of 0.484 m, the influence of three gas sparger structures (ladder distributor, tri-nozzle sparger and perforated plate) on the volumetric mass transfer coefficient kLa was investigated. It was found that the perforated plate produces the highest gas holdup difference and circulating liquid velocity between the riser and the downcomer. The perforated plate provides the most efficient mass transfer due to the more uniform gas distribution and higher circulating liquid velocity, followed by the ladder distributor and tri-nozzle spargers. Compared with the tri-nozzle sparger, the perforated plate increases the value of kLa by up to 16% at a superficial velocity of 0.15 m/s. Interestingly, the analysis of the liquid-phase mass transfer coefficient kL and specific area a with respect to gas velocity shows that the mass transfer rate is primarily controlled by a. By comparing the predictions of different mass transfer models, the slip velocity model based on penetration theory yields a satisfactory agreement with the experimental results within ±15% error. Meanwhile, empirical correlations regarding gas holdup and kLa were developed and were found to have good consistency with experimental values

BCMA/CD47-directed universal CAR-T cells exhibit excellent antitumor activity in multiple myeloma

Abstract Background BCMA-directed autologous chimeric antigen receptor T (CAR-T) cells have shown excellent clinical efficacy in relapsed or refractory multiple myeloma (RRMM), however, the current preparation process for autologous CAR-T cells is complicated and costly. Moreover, the upregulation of CD47 expression has been observed in multiple myeloma, and anti-CD47 antibodies have shown remarkable results in clinical trials. Therefore, we focus on the development of BCMA/CD47-directed universal CAR-T (UCAR-T) cells to improve these limitations. Methods In this study, we employed phage display technology to screen nanobodies against BCMA and CD47 protein, and determined the characterization of nanobodies. Furthermore, we simultaneously disrupted the endogenous TRAC and B2M genes of T cells using CRISPR/Cas9 system to generate TCR and HLA double knock-out T cells, and developed BCMA/CD47-directed UCAR-T cells and detected the antitumor activity in vitro and in vivo. Results We obtained fourteen and one specific nanobodies against BCMA and CD47 protein from the immunized VHH library, respectively. BCMA/CD47-directed UCAR-T cells exhibited superior CAR expression (89.13-98.03%), and effectively killing primary human MM cells and MM cell lines. BCMA/CD47-directed UCAR-T cells demonstrated excellent antitumor activity against MM and prolonged the survival of tumor-engrafted NCG mice in vivo. Conclusions This work demonstrated that BCMA/CD47-directed UCAR-T cells exhibited potent antitumor activity against MM in vitro and in vivo, which provides a potential strategy for the development of a novel “off-the-shelf” cellular immunotherapies for the treatment of multiple myeloma. Graphic Abstrac

A novel SLC3A2-targeting antibody-drug conjugate exerts potent antitumor efficacy in head and neck squamous cell cancer

The development of innovative therapeutic strategies for head and neck squamous cell carcinoma (HNSCC) is a critical medical requirement. Antibody-drug conjugates (ADC) targeting tumor-specific surface antigens have demonstrated clinical effectiveness in treating hematologic and solid malignancies. Our investigation revealed high expression levels of SLC3A2 in HNSCC tissue and cell lines. This study aimed to develop a novel anti-SLC3A2 ADC and assess its antitumor effects on HNSCC both in vitro and in vivo. This study developed a potent anti-SLC3A2 ADC (19G4-MMAE) and systematically investigated its drug delivery potential and antitumor efficacy in preclinical models. This study revealed that 19G4-MMAE exhibited specific binding to SLC3A2 and effectively targeted lysosomes. Moreover, 19G4-MMAE induced a significant accumulation of reactive oxygen species (ROS) and apoptosis in SLC3A2-positive HNSCC cells. The compound demonstrated potent antitumor effects derived from MMAE against SLC3A2-expressing HNSCC in preclinical models, displaying a favorable safety profile. These findings suggest that targeting SLC3A2 with an anti-SLC3A2 ADC could be a promising therapeutic approach for treating HNSCC patients

AP-64, Encoded by C5orf46, Exhibits Antimicrobial Activity against Gram-Negative Bacteria

Antimicrobial peptides (AMPs), which are evolutionarily conserved components of the innate immune response, contribute to the first line of defense against microbes in the skin and at mucosal surfaces. Here, we report the identification of a human peptide, encoded by the chromosome 5 open reading frame 46 (C5orf46) gene, as a type of AMP, which we termed antimicrobial peptide with 64 amino acid residues (AP-64). AP-64 is an anionic amphiphilic peptide lacking cysteines (MW = 7.2, PI = 4.54). AP-64 exhibited significant antibacterial activity against Gram-negative bacteria, including Escherichia coli DH5α, Escherichia coli O157:H7, Vibrio cholerae, and Pseudomonas aeruginosa. Moreover, AP-64 was efficient in combating Escherichia coli O157:H7 infections in a mouse model and exhibited cytotoxic effects against human T-cell lymphoma Jurkat and B-cell lymphoma Raji cells. We also observed that Gm94, encoded by mouse C5orf46 homologous gene, closely resembles AP-64 in its antibacterial properties. Compared with other human AMPs, AP-64 has distinct characteristics, including a longer sequence length, absence of cysteine residues, a highly anionic character, and cell toxicity. Together, this study identified that AP-64 is an AMP worthy of further investigation