Vasoprotective effects of lysophosphatidic acid inhibit vascular injury caused by SARS-CoV-2 infection.

Vasculitis and vascular injury are induced in coronavirus disease 2019 (COVID-19) patients, suggesting an association between multi-organ failure and sequelae. Vascular endothelial dysfunction induced by severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) disrupts vascular barrier function, activates coagulation pathways, and induces extravasation of inflammatory cells. In addition to employing standard anti-inflammatory and antiviral agents, using treatments that stabilize and protect blood vessels following SARS-CoV-2 infection is a potentially effective strategy to relieve COVID-19 severity.

Trajectory analysis reveals an uncommitted neuroblastic state in MYCN-driven neuroblastoma development.

Background: Understanding the factors that determine the spontaneous regression of pre-cancerous lesions is critical to advancing cancer prevention. Neuroblastoma, a pediatric cancer, undergoes spontaneous regression more frequently than other types of cancer.

Methods: Here, we analyzed the transcriptomic features of spontaneous regression in pre-cancerous neuroblasts using Th-MYCN mice, an animal model that closely resembles human neuroblastoma.

Survivability and life support in sealed mini-ecosystems with simulated planetary soils.

Establishing a sustainable life-support system for space exploration is a formidable challenge due to the vast distances, high costs, and environmental differences from Earth. Building upon the lessons from the Biosphere 2 experiment, we introduce the novel "Ecosphere" and "Biosealed" systems, self-sustaining ecosystems within customizable, enclosed containers. These systems incorporate terrestrial ecosystems and groundwater layers, offering a potential model for transplanting Earth-like biomes to extraterrestrial environments.

DeepKINET: a deep generative model for estimating single-cell RNA splicing and degradation rates.

Messenger RNA splicing and degradation are critical for gene expression regulation, the abnormality of which leads to diseases. Previous methods for estimating kinetic rates have limitations, assuming uniform rates across cells. DeepKINET is a deep generative model that estimates splicing and degradation rates at single-cell resolution from scRNA-seq data.

LineageVAE: reconstructing historical cell states and transcriptomes toward unobserved progenitors.

Motivation: Single-cell RNA sequencing (scRNA-seq) enables comprehensive characterization of the cell state. However, its destructive nature prohibits measuring gene expression changes during dynamic processes such as embryogenesis or cell state divergence due to injury or disease. Although recent studies integrating scRNA-seq with lineage tracing have provided clonal insights between progenitor and mature cells, challenges remain.

Acidic extracellular pH drives accumulation of N1-acetylspermidine and recruitment of protumor neutrophils.

An acidic tumor microenvironment plays a critical role in tumor progression. However, understanding of metabolic reprogramming of tumors in response to acidic extracellular pH has remained elusive. Using comprehensive metabolomic analyses, we demonstrated that acidic extracellular pH (pH 6.

Hypoxia activates SREBP2 through Golgi disassembly in bone marrow-derived monocytes for enhanced tumor growth.

Bone marrow-derived cells (BMDCs) infiltrate hypoxic tumors at a pre-angiogenic state and differentiate into mature macrophages, thereby inducing pro-tumorigenic immunity. A critical factor regulating this differentiation is activation of SREBP2-a well-known transcription factor participating in tumorigenesis progression-through unknown cellular mechanisms. Here, we show that hypoxia-induced Golgi disassembly and Golgi-ER fusion in monocytic myeloid cells result in nuclear translocation and activation of SREBP2 in a SCAP-independent manner.

Topological data analysis of protein structure and inter/intra-molecular interaction changes attributable to amino acid mutations.

The presence of some amino acid mutations in the amino acid sequence that determines a protein's structure can significantly affect that 3D structure and its biological function. However, the effects upon structural and functional changes differ for each displaced amino acid, and it is very difficult to predict these changes in advance. Although computer simulations are very effective at predicting conformational changes, they struggle to determine whether the amino acid mutation of interest induces sufficient conformational changes, unless the researcher is a specialist in molecular structure calculations.

Convergent genomic diversity and novel BCAA metabolism in intrahepatic cholangiocarcinoma.

Background: Driver alterations may represent novel candidates for driver gene-guided therapy; however, intrahepatic cholangiocarcinoma (ICC) with multiple genomic aberrations makes them intractable. Therefore, the pathogenesis and metabolic changes of ICC need to be understood to develop new treatment strategies. We aimed to unravel the evolution of ICC and identify ICC-specific metabolic characteristics to investigate the metabolic pathway associated with ICC development using multiregional sampling to encompass the intra- and inter-tumoral heterogeneity.

Increased flexibility of the SARS-CoV-2 RNA-binding site causes resistance to remdesivir.

Mutations continue to accumulate within the SARS-CoV-2 genome, and the ongoing epidemic has shown no signs of ending. It is critical to predict problematic mutations that may arise in clinical environments and assess their properties in advance to quickly implement countermeasures against future variant infections. In this study, we identified mutations resistant to remdesivir, which is widely administered to SARS-CoV-2-infected patients, and discuss the cause of resistance.

Smoking enhances the expression of angiotensin-converting enzyme 2 involved in the efficiency of severe acute respiratory syndrome coronavirus 2 infection.

Smoking is one of the risk factors most closely related to the severity of coronavirus disease 2019 (COVID-19). However, the relationship between smoking history and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is unknown. In this study, we evaluated the ACE2 expression level in the lungs of current smokers, ex-smokers, and nonsmokers.

Detecting time-evolving phenotypic components of adverse reactions against BNT162b2 SARS-CoV-2 vaccine via non-negative tensor factorization.

Symptoms of adverse reactions to vaccines evolve over time, but traditional studies have focused only on the frequency and intensity of symptoms. Here, we attempt to extract the dynamic changes in vaccine adverse reaction symptoms as a small number of interpretable components by using non-negative tensor factorization. We recruited healthcare workers who received two doses of the BNT162b2 mRNA COVID-19 vaccine at Chiba University Hospital and collected information on adverse reactions using a smartphone/web-based platform.

Metabolic remodeling of pyrimidine synthesis pathway and serine synthesis pathway in human glioblastoma.

Glioblastoma is the most common brain tumor with dismal outcomes in adults. Metabolic remodeling is now widely acknowledged as a hallmark of cancer cells, but glioblastoma-specific metabolic pathways remain unclear. Here we show, using a large-scale targeted proteomics platform and integrated molecular pathway-level analysis tool, that the de novo pyrimidine synthesis pathway and serine synthesis pathway (SSP) are the major enriched pathways in vivo for patients with glioblastoma.

Metabolome and transcriptome analysis on muscle of sporadic inclusion body myositis.

Objective: Sporadic inclusion body myositis (sIBM) is the most common acquired myopathy in patients older than 50 years of age. sIBM is hardly responds to any immunosuppressing theraphies, and its pathophysiology remains elusive. This study aims to explore pathogenic pathways underlying sIBM and identify novel therapeutic targets using metabolomic and transcriptomic analyses.

An analysis modality for vascular structures combining tissue-clearing technology and topological data analysis.

The blood and lymphatic vasculature networks are not yet fully understood even in mouse because of the inherent limitations of imaging systems and quantification methods. This study aims to evaluate the usefulness of the tissue-clearing technology for visualizing blood and lymphatic vessels in adult mouse. Clear, unobstructed brain/body imaging cocktails and computational analysis (CUBIC) enables us to capture the high-resolution 3D images of organ- or area-specific vascular structures.

UVB-Induced Skin Autoinflammation Due to Mutation and Its Inhibition by Anti-IL-1β Antibody.

NLRP1 (NACHT and leucine-rich repeat-containing protein family, pyrin domain-containing protein 1) is an innate immune sensor that is involved in the formation of inflammasome complexes. NLRP1 hyperactivity has been reported to cause inherited autoinflammatory diseases including familial keratosis lichenoides chronica and NLRP1-associated autoinflammation with arthritis and dyskeratosis. We generated (the mouse homologue of human ) gain-of-function knock-in ( KI) mice with UVB irradiation-induced autoinflammatory skin lesions.