Paeoniflorin modulates AGEs/RAGE/P38MAPK/ERK/mTOR autophagy pathway to improve cognitive dysfunction in MRL/lpr mice.

Objective: The objective of this study was to investigate the therapeutic effects of paeoniflorin (PA) on cognitive impairment and to elucidate its potential mechanisms in MRL/lpr mice, a model of systemic lupus erythematosus-associated cognitive dysfunction.

Method: Cognitive performance and behavioral responses were assessed using a comprehensive battery of tests, including the Morris water maze, the Novel object recognition test, and the Y maze. Neuropathological changes in the hippocampal regions were visualized through Nissl, HE and Immunohistochemistry staining.

Characterization and anti-tuberculosis effects of γδ T cells expanded and activated by heat-resistant antigen.

Tuberculosis (TB) is a chronic infectious disease caused by (Mtb) that poses a severe threat to human health. A variety of highly immunogenic tuberculosis proteins have been used as targets in vaccine development to mitigate the spread of TB. Although Th1-type immunity has long been considered a crucial part of resistance to Mtb, γδ T cells, the predominant source of IL-17, are not negligible in controlling the early stages of TB infection.

High-throughput single-cell analysis reveals Omp38-specific monoclonal antibodies that protect against infection.

Infections caused by () have emerged as a global public health concern because of high pathogenicity of this bacterium. Monoclonal antibodies (mAbs) have a lower likelihood of promoting drug resistance and offer targeted treatment, thereby reducing potential adverse effects; however, the therapeutic potential of mAbs targeting i has not been fully characterized. In this study, mAbs against the outer membrane proteins (OMPs) of were isolated in a high-throughput manner.

NAT10-mediated mRNA N-acetylcytidine reprograms serine metabolism to drive leukaemogenesis and stemness in acute myeloid leukaemia.

RNA modification has emerged as an important epigenetic mechanism that controls abnormal metabolism and growth in acute myeloid leukaemia (AML). However, the roles of RNA N-acetylcytidine (ac4C) modification in AML remain elusive. Here, we report that ac4C and its catalytic enzyme NAT10 drive leukaemogenesis and sustain self-renewal of leukaemic stem cells/leukaemia-initiating cells through reprogramming serine metabolism.

Analysis of the components of Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) and its regulation of γδ T-cell function.

Background: Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) is a peptide antigen released from the mycobacterial cytoplasm into the supernatant of Mycobacterium tuberculosis (Mtb) attenuated H37Ra strain after autoclaving at 121 °C for 20 min. Mtb-HAg can specifically induce γδ T-cell proliferation in vitro. However, the exact composition of Mtb-HAg and the protein antigens that are responsible for its function are currently unknown.

Immune responses induced by Mycobacterium tuberculosis heat-resistant antigen (Mtb-HAg) upon co-administration with Bacillus Calmette-Guérin in mice.

Objectives: To preliminarily assess the immunogenicity of Mtb-HAg in mice and the synergistic effect provided by HAg when co-immunised with BCG.

Methods: Mice were randomly grouped for different immunisations and then spleens were aseptically removed and lymphocytes were extracted for immediate detection of cytokines transcript levels and stimulation index(SI), cytokine secretion and multifunctional antigen-specific T cells were detected after incubation for different times.

Results: HAg extracted from active Mtb is a group of mixed polypeptides with molecular weights of (10-14) kDa.

Discovery of benzoheterocyclic-substituted amide derivatives as apoptosis signal-regulating kinase 1 (ASK1) inhibitors.

Three series of benzoheterocyclic-substituted amide derivatives were designed and synthesized as potent ASK1 inhibitors in this work. After undergoing continuous structural optimization, compound 17a was discovered to be a novel inhibitor of ASK1 with good potency (kinase, IC = 26 nM), noteworthy liver microsomal stability (human, = 340.4 min), good pharmacokinetic parameters (rat, p.

[Research progress on the effect of Mycobacterium tuberculosis heat-resistant antigen (MTB-HAg) on γδ T cells].

Mycobacterium tuberculosis heat resistant antigen (MTB-HAg) is a polypeptide antigen released from Mycobacterium tuberculosis (MTB) H37Ra to the supernatant after being autoclaved at 121 DegreesCelsius for 20 minutes. γδ T cells are unconventional T cells widely distributed in non-lymphoid tissues. They secrete cytokines such as TNF-α and IFN-γ, and play an important role in the immune response against MTB infection.

[The proportion of CD19CD25 Bregs in peripheral blood and the expression of PD-1 and PD-L1 on cell surface in patients with systemic lupus erythematosus and their correlation with clinical indicators].

Objective To investigate the expression and clinical significance of PD-1 and its ligand PD-L1 in peripheral blood CD19CD25 regulatory B cells (Bregs) in patients with systemic lupus erythematosus (SLE). Methods Peripheral blood samples were collected from 50 patients and 41 healthy controls (HCs). The proportion of CD19CD25Bregs in peripheral blood as well as the expression of PD-1B and PD-L1B cells on CD19CD25B cells, were detected by flow cytometry.

Dual regulation effect and mechanism of human myeloid-derived suppressor cells on anticolorectal cancer cells activity of Vγ9Vδ2 T cells.

Myeloid-derived suppressor cells (MDSC) are a group of immature inhibitory cells of bone marrow origin. Human γδ T cells (mainly Vγ9Vδ2 T cells) have emerged as dominant candidates for cancer immunotherapy because of their unique recognition pattern and broad killing activity against tumor cells. Intestinal mucosal intraepithelial lymphocytes are almost exclusively γδ T cells, so it plays an important role in inhibiting the development of colorectal cancer.

The effect of PD-1/PD-L1 signaling axis on the interaction between CD19B cells and CD4T cells in peripheral blood of patients with systemic lupus erythematosus.

Background: The defect of B cell self-tolerance and the continuous antigen presentation by T cells (TCs) mediated by autoreactive B cells (BCs) play a key role in the occurrence and development of systemic lupus erythematosus (SLE). PD-1/PD-L1 signaling axis negatively regulates the immune response of TCs after activation and maintains immune tolerance. However, the effect of PD-1/PD-L1 signaling axis on the interaction between CD19B/CD4TCs in the peripheral blood of patients with SLE has not been studied in detail.

Immunological effects of the PE/PPE family proteins of and related vaccines.

Tuberculosis (TB) is a chronic infectious disease caused by (), and its incidence and mortality are increasing. The BCG vaccine was developed in the early 20th century. As the most widely administered vaccine in the world, approximately 100 million newborns are vaccinated with BCG every year, which has saved tens of millions of lives.

Transcriptional analysis of human peripheral blood mononuclear cells stimulated by antigen.

Background: antigen (Mtb-Ag) is a polypeptide component with a molecular weight of 10-14 kDa that is obtained from the supernatant of the H37Ra strain after heat treatment. It stimulates the activation and proliferation of γδT cells in the blood to produce an immune response against tuberculosis. Mtb-Ag is therefore crucial for classifying and detecting the central genes and key pathways involved in TB initiation and progression.

Single-cell and bulk sequencing analyses reveal the immune suppressive role of PTPN6 in glioblastoma.

Glioblastoma (GBM) is a highly malignant brain cancer with a poor prognosis despite standard treatments. This investigation aimed to explore the feasibility of PTPN6 to combat GBM with immunotherapy. Our study employed a comprehensive analysis of publicly available datasets and functional experiments to assess PTPN6 gene expression, prognostic value, and related immune characteristics in glioma.

3D based generative PROTAC linker design with reinforcement learning.

Proteolysis targeting chimera (PROTAC), has emerged as an effective modality to selectively degrade disease-related proteins by harnessing the ubiquitin-proteasome system. Due to PROTACs' hetero-bifunctional characteristics, in which a linker joins a warhead binding to a protein of interest (POI), conferring specificity and a E3-ligand binding to an E3 ubiquitin ligase, this could trigger the ubiquitination and transportation of POI to the proteasome, followed by degradation. The rational PROTAC linker design is challenging due to its relatively large molecular weight and the complexity of maintaining the binding mode of warhead and E3-ligand in the binding pockets of counterpart.

A deep learning framework for accurate reaction prediction and its application on high-throughput experimentation data.

In recent years, it has been seen that artificial intelligence (AI) starts to bring revolutionary changes to chemical synthesis. However, the lack of suitable ways of representing chemical reactions and the scarceness of reaction data has limited the wider application of AI to reaction prediction. Here, we introduce a novel reaction representation, GraphRXN, for reaction prediction.

Application of message passing neural networks for molecular property prediction.

Accurate molecular property prediction, as one of the classical cheminformatics topics, plays a prominent role in the fields of computer-aided drug design. For instance, property prediction models can be used to quickly screen large molecular libraries to find lead compounds. Message-passing neural networks (MPNNs), a sub-class of Graph neural networks (GNNs), have recently been demonstrated to outperform other deep learning methods on a variety of tasks, including the prediction of molecular characteristics.

PE8 (Rv1040c) Promotes the Intracellular Survival of Recombinant Mycobacterium by Regulating Host Inflammatory Cytokines and Inhibiting Cell Late Apoptosis.

Tuberculosis is an important chronic and often fatal infectious disease mainly caused by the bacterium (Mtb). Mtb is one of the most successful pathogens that harbors several potential virulence factors not found in nonpathogenic mycobacteria. As the Mtb cell envelope is closely associated with its virulence and resistance, it is very important to understand the cell envelope for better treatment of causative pathogen.

Study on the effect of γδ T cells expanded to kill hepatocellular carcinoma cells.

Background: γδ T cells for tumor cell immunotherapy has recently become a hot topic.

Objective: To investigate the stimulation of expanded γδ T cells in vitro to kill liver cancer cells and its mechanism, and in vivo validation.

Methods: Peripheral blood mononuclear cells (PBMCs) were isolated and amplified.

[CXCL1 induces the contraction of endothelial cytoskeleton and increases permeability in mouse cerebral endothelium bEND.3 cells by promoting protein kinase B phosphorylation].

Objective To investigate the effects of C-X-C motif chemokine ligand 1 (CXCL1) and its receptor CXCR2 on the cerebral endothelial cytoskeleton rearrangement and permeability in the inflammation of septic encephalopathy. Methods The murine model of septic encephalopathy was established by intraperitoneal injection of LPS (10 mg/kg). The levels of TNF-α and CXCL1 in the whole brain tissue were detected by ELISA.

HTE- and AI-assisted development of DHP-catalyzed decarboxylative selenation.

1,4-Dihydropyridine (DHP) derivatives play key roles in biology, but are rarely used as catalysts in synthesis. Here, we developed a DHP derivative-catalyzed decarboxylative selenation reaction that showed a broad substrate scope, with the assistance of high-throughput experimentation (HTE) and artificial intelligence (AI). The AI-based model could identify the key structural features and give accurate prediction of unseen reactions ( = 0.

Corrigendum: Immunogenomic landscape in breast cancer reveals immunotherapeutically relevant gene signatures.

[This corrects the article DOI: 10.3389/fimmu.2022.

[Protein tyrosine phosphatase receptor type O (PTPRO) promotes phagocytic activity of alveolar epithelial cells via activating AKT signal pathway in LPS induced acute lung injury].

Objective To investigate the effect of protein tyrosine phosphatase receptor type O (PTPRO) on the phagocytic activity of alveolar epithelial cells in LPS-induced acute lung injury. Methods Mice were randomly divided into the normal control group and LPS stimulation group. The infiltration of inflammatory cells was detected by HE staining.

[Establishment of a THP-1 macrophage model infected by recombinant Mycobacterium smegmatis expressing green fluorescent protein].

Objective To establish a THP-1 macrophage model infected by Mycobacterium smegmatis expressing green fluorescent protein (GFP), to quickly locate and visually detect Mycobacterium smegmatis, and to provide a tracer tool to identify the pathogenesis of tuberculosis and develop new tuberculosis vaccines. Methods The enhanced green fluorescent protein (EGFP) gene sequence was amplified by PCR using pEGFP-N1 plasmid as a template to obtain the coding gene of EGFP, and the amplified product was cloned into the vector pALACE to establish the recombinant plasmid pALACE-EGFP. Electroporation transformed the pALACE-EGFP into Mycobacterium smegmatis, and recombinant Mycobacterium smegmatis clones were screened by hygromycin resistance.

Identification of key interferon-stimulated genes for indicating the condition of patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with highly heterogeneous clinical symptoms and severity. There is complex pathogenesis of SLE, one of which is IFNs overproduction and downstream IFN-stimulated genes (ISGs) upregulation. Identifying the key ISGs differentially expressed in peripheral blood mononuclear cells (PBMCs) of patients with SLE and healthy people could help to further understand the role of the IFN pathway in SLE and discover potential diagnostic biomarkers.