Development of COVID-19 Vaccine Candidates Using Attenuated Recombinant Vesicular Stomatitis Virus Vectors with M Protein Mutations.

Recombinant vesicular stomatitis virus (rVSV) is a promising viral vaccine vector for addressing the COVID-19 pandemic. Inducing mucosal immunity via the intranasal route is an ideal strategy for rVSV-based vaccines, but it requires extremely stringent safety standards. In this study, we constructed two rVSV variants with amino acid mutations in their M protein: rVSV-M2 with M33A/M51R mutations and rVSV-M4 with M33A/M51R/V221F/S226R mutations, and developed COVID-19 vaccines based on these attenuated vectors.

Immune atlas of pituitary neuroendocrine tumors highlights endocrine-driven immune signature and therapeutic implication.

Whether the tumor microenvironment is shaped by endocrine hormone secretion, as well as its cellular heterogeneity and therapeutic implications in pituitary neuroendocrine tumors (pitNETs), remains poorly understood. We demonstrate that pitNETs exhibit a sparse immune infiltration. Mass cytometry of 97,418 immune cells from 56 pitNETs establishes a high-resolution atlas, with macrophages and T cells comprising the predominant populations.

Single-Cell RNA Sequencing and Its Applications in Pituitary Research.

Background: Mounting evidence underscores the significance of cellular diversity within the endocrine system and the intricate interplay between different cell types and tissues, essential for preserving physiological balance and influencing disease trajectories. The pituitary gland, a central player in the endocrine orchestra, exemplifies this complexity with its assortment of hormone-secreting and nonsecreting cells.

Summary: The pituitary gland houses several types of cells responsible for hormone production, alongside nonsecretory cells like fibroblasts and endothelial cells, each playing a crucial role in the gland's function and regulatory mechanisms.

Immune landscape and progress in immunotherapy for pituitary neuroendocrine tumors.

Pituitary neuroendocrine tumors (pitNETs) are the second most common primary brain tumors. Despite their prevalence, the tumor immune microenvironment (TIME) and its clinical implications remain largely unexplored. This review provides a comprehensive overview of current knowledge on the immune landscape and advancements in targeted immunotherapy for pitNETs.

Validation of a new kit for preeclampsia screening: A comprehensive analysis.

Objectives: Preeclampsia is a common pregnancy complication that significantly contributes to maternal mortality, perinatal mortality, and preterm delivery. The sFlt-1/PlGF (fms-like tyrosine kinase-1/placental growth factor) ratio has demonstrated robust diagnostic value for preeclampsia. This study assessed the analytical performance and diagnostic accuracy of a novel quantitative determination kit for sFlt-1 and PlGF for the diagnosis of preeclampsia.

B7-H3 in Brain Malignancies: Immunology and Immunotherapy.

The immune checkpoint B7-H3 (CD276), a member of the B7 family with immunoregulatory properties, has been identified recently as a novel target for immunotherapy for refractory blood cancers and solid malignant tumors. While research on B7-H3 in brain malignancies is limited, there is growing interest in exploring its therapeutic potential in this context. B7-H3 plays a crucial role in regulating the functions of immune cells, cancer-associated fibroblasts, and endothelial cells within the tumor microenvironment, contributing to the creation of a pro-tumorigenic milieu.

Exosomal RNAs in the development and treatment of pituitary adenomas.

Exosomes are small extracellular vesicles that carry various bioactive molecules including various RNAs that modulate the activities of recipient cells. It has drawn considerable attention as means of cell communication and drug delivery. Exosome plays important role in various tumors, but it is rarely summarized in pituitary adenoma (PA).

Single-cell transcriptomic analyses provide insights into the cellular origins and drivers of brain metastasis from lung adenocarcinoma.

Background: Brain metastasis (BM) is the most common intracranial malignancy causing significant mortality, and lung cancer is the most common origin of BM. However, the cellular origins and drivers of BM from lung adenocarcinoma (LUAD) have yet to be defined.

Methods: The cellular constitutions were characterized by single-cell transcriptomic profiles of 11 LUAD primary tumor (PT) and 10 BM samples (GSE131907).

METTL3 regulates mA methylation of PTCH1 and GLI2 in Sonic hedgehog signaling to promote tumor progression in SHH-medulloblastoma.

SHH subgroup medulloblastoma (SHH-MB) is one of the most common malignant pediatric tumors that arises in the cerebellum. Previously, we showed that RNA mA methylation participates in regulation of cerebellar development. Here we investigate whether dysregulated mA methylation contributes to tumorigenesis of SHH-MB.

Multi-Omics Investigations Revealed Underlying Molecular Mechanisms Associated With Tumor Stiffness and Identified Sunitinib as a Potential Therapy for Reducing Stiffness in Pituitary Adenomas.

Pituitary adenomas (PAs) are the second most common intracranial neoplasms. Total surgical resection was extremely important for curing PAs, whereas tumor stiffness has gradually become the most critical factor affecting the resection rate in PAs. We aimed to investigate the molecular mechanisms of tumor stiffening and explore novel medications to reduce stiffness for improving surgical remission rates in PA patients.

METTL3-mediated RNA m6A Hypermethylation Promotes Tumorigenesis and GH Secretion of Pituitary Somatotroph Adenomas.

Introduction: Pituitary growth hormone-secreting (GH) pituitary adenomas (PAs) cause mass effects and dysregulated hypersecretion of GH. However, somatic mutation burden is low in PAs. While progress has been made in identifying the epigenetic changes involved in GH-PA initiation, the precise details of its tumorigenesis in GH-PA patients remains to be elucidated.

Genome-wide 5-Hydroxymethylcytosine Profiling Analysis Identifies MAP7D1 as A Novel Regulator of Lymph Node Metastasis in Breast Cancer.

Although DNA 5-hydroxymethylcytosine (5hmC) is recognized as an important epigenetic mark in cancer, its precise role in lymph node metastasis remains elusive. In this study, we investigated how 5hmC associates with lymph node metastasis in breast cancer. Accompanying with high expression of TET1 and TET2 proteins, large numbers of genes in the metastasis-positive primary tumors exhibit higher 5hmC levels than those in the metastasis-negative primary tumors.

Genetic and Epigenetic Causes of Pituitary Adenomas.

Pituitary adenomas (PAs) can be classified as non-secreting adenomas, somatotroph adenomas, corticotroph adenomas, lactotroph adenomas, and thyrotroph adenomas. Substantial advances have been made in our knowledge of the pathobiology of PAs. To obtain a comprehensive understanding of the molecular biological characteristics of different types of PAs, we reviewed the important advances that have been made involving genetic and epigenetic variation, comprising genetic mutations, chromosome number variations, DNA methylation, microRNA regulation, and transcription factor regulation.

RNA mA methylation participates in regulation of postnatal development of the mouse cerebellum.

Background: N-methyladenosine (mA) is an important epitranscriptomic mark with high abundance in the brain. Recently, it has been found to be involved in the regulation of memory formation and mammalian cortical neurogenesis. However, while it is now established that mA methylation occurs in a spatially restricted manner, its functions in specific brain regions still await elucidation.

Region-specific RNA mA methylation represents a new layer of control in the gene regulatory network in the mouse brain.

N-methyladenosine (mA) is the most abundant epitranscriptomic mark found on mRNA and has important roles in various physiological processes. Despite the relatively high mA levels in the brain, its potential functions in the brain remain largely unexplored. We performed a transcriptome-wide methylation analysis using the mouse brain to depict its region-specific methylation profile.

Single-nucleotide polymorphisms in PtoCesA7 and their association with growth and wood properties in Populus tomentosa.

Cellulose synthase (CesA) genes encode the enzymes that synthesize cellulose; therefore, CesAs play central roles in plant development and affect the yield and quality of wood, essential properties for industrial applications of plant biomass. To effectively manipulate wood biosynthesis in trees and improve wood quality, we thus require a better understanding of the natural variation in CesAs. Association studies have emerged as a powerful tool for identification of variation associated with quantitative traits.

Allelic variation in PtGA20Ox associates with growth and wood properties in Populus spp.

Populus tomentosa is an economically important tree crop that produces wood for lumber, pulp, paper, and biofuels. Wood quality traits are likely to be strongly affected by the plant hormone gibberellic acid (GA), which regulates growth. GA20Ox encodes one of the major regulatory enzymes of GA biosynthesis and may therefore play a large role in growth and wood quality.