Targeting initial tumour-osteoclast spatiotemporal interaction to prevent bone metastasis.

Bone is the most common site of metastasis, and although low proliferation and immunoediting at the early stage make existing treatment modalities less effective, the microenvironment-inducing behaviour could be a target for early intervention. Here we report on a spatiotemporal coupling interaction between tumour cells and osteoclasts, and named the tumour-associated osteoclast 'tumasteoclast'-a subtype of osteoclasts in bone metastases induced by tumour-migrasome-mediated cytoplasmic transfer. We subsequently propose an in situ decoupling-killing strategy in which tetracycline-modified nanoliposomes encapsulating sodium bicarbonate and sodium hydrogen phosphate are designed to specifically release high concentrations of hydrogen phosphate ions triggered by tumasteoclasts, which depletes calcium ions and forms calcium-phosphorus crystals.

B-Cell Receptor Features and Database Establishment in Recovered COVID-19 Patients by Combining 5'-RACE with PacBio Sequencing.

Background: Antibodies induced by viral infection can not only prevent subsequent virus infection, but can also mediate pathological injury following infection. Therefore, understanding the B-cell receptor (BCR) repertoire of either specific neutralizing or pathological antibodies from patients convalescing from Coronavirus disease 2019 (COVID-19) infection is of benefit for the preparation of therapeutic or preventive antibodies, and may provide insight into the mechanisms of COVID-19 pathological injury.

Methods: In this study, we used a molecular approach of combining 5' Rapid Amplification of cDNA Ends (5'-RACE) with PacBio sequencing to analyze the BCR repertoire of all 5 and 2 genes in B-cells harvested from 35 convalescent patients after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Gasdermin D maintains bone mass by rewiring the endo-lysosomal pathway of osteoclastic bone resorption.

Gasdermin D (GSDMD)-mediated pyroptosis induces immunogenic cell death and promotes inflammation. However, the functions of GSDMD in tissue homeostasis remain unclear. Here, we identify a physiological function of GSDMD in osteoclasts via a non-lytic p20-generated protein, which prevents bone loss to maintain bone homeostasis.

Suppression of osteoclast multinucleation via a posttranscriptional regulation-based spatiotemporally selective delivery system.

Redundancy of multinucleated mature osteoclasts, which results from the excessive fusion of mononucleated preosteoclasts (pOCs), leads to osteolytic diseases such as osteoporosis. Unfortunately, the currently available clinical drugs completely inhibit osteoclasts, thus interfering with normal physiological bone turnover. pOC-specific regulation may be more suitable for maintaining bone homeostasis.

A myogenic niche with a proper mechanical stress environment improves abdominal wall muscle repair by modulating immunity and preventing fibrosis.

Volumetric muscle loss (VML) healing is often complicated by fibrosis, which impairs muscle regeneration and function. Adjusting mechanical stress in the repair environment may modulate immunity and reduce fibrosis. In this study, we aimed to create a biomaterial with suitable tension conditions and bidirectional tissue-inducing abilities to prevent fibrosis thus promote muscle regeneration and induce aponeurosis-like structures to restore muscle force transmission.

Next-Generation Sequencing Revealed a Distinct Immunoglobulin Repertoire with Specific Mutation Hotspots in Acute Myeloid Leukemia.

Immunoglobulin (Ig) is known as a hallmark of B-lymphocytes exerting antibody functions. However, our previous studies demonstrated that myeloblasts from acute myeloid leukemia (AML) patients could also express Ig with distinct roles. Here, we quantified Ig (IGHG and IGK) transcripts by real-time PCR and performed a comprehensive analysis of Ig repertoire (both heavy chains and light chains) in AML blasts.

Efferocytosis in the Central Nervous System.

The effective clearance of apoptotic cells is essential for maintaining central nervous system (CNS) homeostasis and restoring homeostasis after injury. In most cases of physiological apoptotic cell death, efferocytosis prevents inflammation and other pathological conditions. When apoptotic cells are not effectively cleared, destruction of the integrity of the apoptotic cell membrane integrity, leakage of intracellular contents, and secondary necrosis may occur.

Macrophage-Derived Immunoglobulin M Inhibits Inflammatory Responses via Modulating Endoplasmic Reticulum Stress.

Immunoglobulin (Ig), a characteristic marker of B cells, is a multifunctional evolutionary conserved antibody critical for maintaining tissue homeostasis and developing fully protective humoral responses to pathogens. Increasing evidence revealed that Ig is widely expressed in non-immune cells; moreover, Ig produced by different lineages cells plays different biological roles. Recently, it has been reported that monocytes or macrophages also express Ig.

Single-Cell Sequencing Confirms Transcripts and VDJ Rearrangements of Immunoglobulin Genes in Human Podocytes.

Most glomerular diseases are associated with inflammation caused by deposited pathogenic immunoglobulins (Igs), which are believed to be produced by B cells. However, our previous study indicated that the human podocyte cell line can produce IgG. In this study, we aimed to confirm the transcripts and characterize the repertoires of Igs in primary podocytes at single cell level.

Expression of immunoglobulin G in human proximal tubular epithelial cells.

Proximal tubular epithelial cells (PTECs) have innate immune characteristics, and produce proinflammatory factors, chemokines and complement components that drive epithelial‑mesenchymal transition (EMT). Our previous studies revealed that human mesangial cells and podocytes were able to synthesize and secrete immunoglobulin (Ig)A and IgG, respectively. The aim of the present study was to evaluate the expression of Igs in PTECs.

Single-cell RNA sequencing confirms IgG transcription and limited diversity of VDJ rearrangements in proximal tubular epithelial cells.

Increasing evidence has confirmed that immunoglobulins (Igs) can be expressed in non-B cells. Our previous work demonstrated that mesangial cells and podocytes express IgA and IgG, respectively. The aim of this work was to reveal whether proximal tubular epithelial cells (PTECs) express Igs.

More than one antibody of individual B cells revealed by single-cell immune profiling.

Antibodies have a common structure consisting of two identical heavy (H) and two identical light (L) chains. It is widely accepted that a single mature B cell produces a single antibody through restricted synthesis of only one VDJ (encoding the H-chain variable region) and one VJ (encoding the L-chain variable region) via recombination. Naive B cells undergo class-switch recombination (CSR) from initially producing membrane-bound IgM and IgD to expressing more effective membrane-bound IgG, IgA, or IgE when encountering antigens.