Interferon Regulatory Factor 4: An Alternative Marker for Plasma Cells in Daratumumab-Treated Patients With Multiple Myeloma.

Introduction: Anti-CD38 therapeutic modalities (e.g., daratumumab) can impede classical CD38 and CD138 gating use for plasma cell (PC) detection in multiple myeloma (MM) patients with minimal residual disease (MRD).

A large-scale surveillance revealed that KPC variants mediated ceftazidime-avibactam resistance in clinically isolated .

To monitor the resistance rate and gain a deeper understanding of the resistance mechanisms, we conducted over a 2-year surveillance focusing on the associated with the clinical usage of ceftazidime-avibactam (CZA) in a teaching hospital. A total of 4,641 . isolates were screened to identify the CZA resistance through antimicrobial susceptibility testing.

A label-free strategy for immobilization of GPCRs using site-specific encoded non-natural amino acids to develop a selectively chromatographic approach for pursuing potential ligands binding to 5-hydroxytryptamine 1A receptor.

G protein-coupled receptors (GPCRs) are one of the most prominent targets for drug discovery. Immobilizing GPCRs has proven to be an effective strategy for expanding the utility of GPCRs into nonbiological contexts. However, traditional strategies of immobilizing GPCRs have been severely challenged due to the loss of receptor function.

Enhancement of Macrophage Immunity against Chlamydial Infection by Natural Killer T Cells.

Lung macrophage (LM) is vital in host defence against bacterial infections. However, the influence of other innate immune cells on its function, including the polarisation of different subpopulations, remains poorly understood. This study examined the polarisation of LM subpopulations (monocytes/undifferentiated macrophages (Mo/Mφ), interstitial macrophages (IM), and alveolar macrophages (AM)).

Screening and evaluation of the hit compound from a DNA-encoded library derived from natural products based on immobilized endothelin receptor A.

The enormous growing demand for drug candidates binding to endothelin receptor A (ET) has made it necessary to continuously pursue new strategies for ligand screening and early evaluation. This work achieved the one-step immobilization of ET based on the bioorthogonal chemistry between the epidermal growth factor receptor tag (EGFR-tag) and ibrutinib. Comprehensive characterizations including Western blot analysis are performed to realize the morphology, antibody/ligand recognition activity, and specificity of the immobilized ET.

IFNγ-Producing B Cells Play a Regulating Role in Infection-Mediated Inhibition of Allergy.

The hygiene hypothesis suggests that some infections may inhibit the development of allergic diseases, but the mechanism remains unclear. Our previous study has shown that Chlamydia (Cm) lung infection can inhibit local eosinophilic inflammation induced by ovalbumin (OVA) through the modulation of dendritic cell (DC) and T cell responses in mice. In this study, we explored the role of B cells in the chlamydial-infection-mediated modulation of allergic responses.

Affinity Chromatographic Method for Determining Drug-Protein Interaction with Enhanced Speed Than Typical Frontal Analysis.

Revealing drug-protein interaction is highly important to select a drug candidate with improved drug-like properties in the early stages of drug discovery. This highlights the urgent need to develop assays that enable the analysis of drug-protein interaction with high speed. Herein, this purpose was realized by the development of an affinity chromatographic method with a two-fold higher speed than typical assays like frontal analysis and zonal elution.

IL-27 Signaling Promotes Th1 Response by Downregulating IL-10 Production in DCs during Chlamydial Respiratory Infection.

usually causes mucosal infections, bringing considerable morbidity and socioeconomic burden worldwide. We previously revealed that IL-27/IL-27R mediates protection against chlamydial invasion by promoting a protective Th1 response and suppressing neutrophilic inflammation. Here, we used the mouse model of () respiratory infections to further investigate the impact of IL-27 signaling in the DCs-regulated immune response, since an elevated IL-27/IL-27R expression in DCs was identified following chlamydial infection.

Dysbiosis and primary B-cell immunodeficiencies: current knowledge and future perspective.

According to Elie Metchnikoff, an originator of modern immunology, several pivotal functions for disease and health are provided by indigenous microbiota. Nonetheless, important mechanistic insights have been elucidated more recently, owing to the growing availability of DNA sequencing technology. There are 10 to 100 trillion symbiotic microbes (such as viruses, bacteria, and yeast) in each human gut microbiota.

Th17/Treg Imbalance: Implications in Lung Inflammatory Diseases.

Regulatory T cells (Tregs) and T helper 17 cells (Th17) are two CD4 T cell subsets with antagonist effects. Th17 cells promote inflammation, whereas Tregs are crucial in maintaining immune homeostasis. Recent studies suggest that Th17 cells and Treg cells are the foremost players in several inflammatory diseases.

SIFT-GVF-based lung edge correction method for correcting the lung region in CT images.

Juxtapleural nodules were excluded from the segmented lung region in the Hounsfield unit threshold-based segmentation method. To re-include those regions in the lung region, a new approach was presented using scale-invariant feature transform and gradient vector flow models in this study. First, the scale-invariant feature transform method was utilized to detect all scale-invariant points in the binary lung region.

The Application of Morphogo in the Detection of Megakaryocytes from Bone Marrow Digital Images with Convolutional Neural Networks.

The evaluation of megakaryocytes is an important part of the work up on bone marrow smear examination. It has significance in the differential diagnosis, therapeutic efficacy assessment, and predication of prognosis of many hematologic diseases. The process of manual identification of megakaryocytes are tedious and lack of reproducibility; therefore, a reliable method of automated megakaryocytic identification is urgently needed.

Nanotechnology-based diagnostic methods for coronavirus: From nucleic acid extraction to amplification.

The recent emergence of human coronaviruses (CoVs) causing severe acute respiratory syndrome (SARS) is posing a great threat to global public health. Therefore, the rapid and accurate identification of pathogenic viruses plays a vital role in selecting appropriate treatments, saving people's lives and preventing epidemics. Nucleic acids, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are natural biopolymers composed of nucleotides that store, transmit, and express genetic information.

Mathematical and experimental validation of an approach for simultaneously determining the binding parameters of two drugs to a receptor.

Quantifying drug-protein interactions has a pivotal role in both early phase drug development and clinical processes. Diverse affinity chromatographic methods like nonlinear chromatography can realize such quantification, however, their throughputs are challenged due to the loading of a single ligand during each run. This work derivatized a new equation for simultaneously determining the bindings of two ligands to a protein relying on assumption that the retention factors of the ligands are dependent on their injection amounts.

Nano-Codelivery of Temozolomide and siPD-L1 to Reprogram the Drug-Resistant and Immunosuppressive Microenvironment in Orthotopic Glioblastoma.

Glioblastoma (GBM) is an invasive cancer with high mortality in central nervous system. Resistance to temozolomide (TMZ) and immunosuppressive microenvironment lead to low outcome of the standardized treatment for GBM. In this study, a 2-deoxy-d-glucose modified lipid polymer nanoparticle loaded with TMZ and siPD-L1 (TMZ/siPD-L1@GLPN/dsb) was prepared to reprogram the TMZ-resistant and immunosuppressive microenvironment in orthotopic GBM.

Chemoattractants driven and microglia based biomimetic nanoparticle treating TMZ-resistant glioblastoma multiforme.

Currently, clinical treatment for temozolomide (TMZ)-resistant glioblastoma multiforme (GBM) is still a difficult problem. The aim of this paper is to set up a new GBM-targeted drug delivery system to treat TMZ-resistant GBM. Zoledronate (ZOL) not only induces apoptosis of TMZ-resistant GBM cells by down-regulation of farnesyl pyrophosphate synthetase (FPPS) but also increases the proportion of M1-type GBM associated macrophages (GAM).

IL-27/IL-27R Mediates Protective Immunity against Chlamydial Infection by Suppressing Excessive Th17 Responses and Reducing Neutrophil Inflammation.

IL-27, a heterodimeric cytokine of the IL-12 family, has diverse influences on the development of multiple inflammatory diseases. In this study, we identified the protective role of IL-27/IL-27R in host defense against respiratory infection and further investigated the immunological mechanism. Our results showed that IL-27 was involved in infection and that IL-27R knockout mice (WSX-1 mice) suffered more severe disease, with greater body weight loss, higher chlamydial loads, and more severe inflammatory reactions in the lungs than C57BL/6 wild-type mice.

IL-21/IL-21R Signaling Aggravated Respiratory Inflammation Induced by Intracellular Bacteria through Regulation of CD4 T Cell Subset Responses.

The IL-21/IL-21R interaction plays an important role in a variety of immune diseases; however, the roles and mechanisms in intracellular bacterial infection are not fully understood. In this study, we explored the effect of IL-21/IL-21R on chlamydial respiratory tract infection using a chlamydial respiratory infection model. The results showed that the mRNA expression of IL-21 and IL-21R was increased in -infected mice, which suggested that IL-21 and IL-21R were involved in host defense against lung infection.

Semaphorin 3E Protects against Chlamydial Infection by Modulating Dendritic Cell Functions.

Recent studies have identified semaphorin 3E (Sema3E) as a novel mediator of immune responses. However, its function in immunity to infection has yet to be investigated. Using a mouse model of chlamydial lung infection, we show that Sema3E plays a significant role in the host immune response to the infection.

Endogenous IL-17A mediated neutrophil infiltration by promoting chemokines expression during chlamydial lung infection.

Chlamydia is an obligate intracellular bacteria, which can infect cervix, urethra, conjunctiva, joints, lungs and so on. Neutrophils are important in host protection against microbial invasion during the early phase of infection. Here, to investigate the mechanism of IL-17A in recruiting neutrophils during Chlamydia muridarum (Cm) lung infection, we introduced IL-17A antibodies and IL-17 mice to confirm the effect of IL-17A on influencing neutrophil attractants expressions.