Single-cell eQTL mapping reveals cell subtype-specific genetic control and mechanism in malignant transformation of colorectal cancer.

Colorectal cancer (CRC) is a heterogeneous disease that develops through a stepwise accumulation, yet the underlying mechanisms at single-cell resolution remain unclear. Here, we profiled 751,531 single-cell transcriptomes, spatial transcriptomics, and snMultiomes from 142 multistage samples, revealing the cellular and molecular alterations and dynamic intercellular crosstalk during CRC development. Additionally, we created a CRC sc-eQTL map identifying 16,833 significant pairs across 28 cell subtypes, with over 76% of sc-eQTLs being cell-type-specific and fewer than 15% detectable in bulk datasets.

Targeting the ceramidase ACER3 attenuates cholestasis in mice by mitigating bile acid overload via unsaturated ceramide-mediated LXRβ signaling transduction.

Bile acid overload critically drives the pathogenesis of cholestatic liver injury (CLI). While ceramide metabolism has garnered increasing interest in liver research, the role of ceramides in CLI remains unclear. This study investigates the function of alkaline ceramidase 3 (ACER3)-catalyzed hydrolysis of unsaturated ceramides in CLI.

Advances in the Study of Necroptosis in Vascular Dementia: Focus on Blood-Brain Barrier and Neuroinflammation.

Background: Vascular dementia (VaD) includes a group of brain disorders that are characterized by cerebrovascular pathology.Neuroinflammation, disruption of the blood-brain barrier (BBB) permeability, white matter lesions, and neuronal loss are all significant pathological manifestations of VaD and play a key role in disease progression. Necroptosis, also known asprogrammed necrosis, is a mode of programmed cell death distinct from apoptosis and is closely associated with ischemic injury and neurodegenerative diseases.

Alcohol-induced C/EBP β-driven VIRMA decreases oxidative stress and promotes pancreatic ductal adenocarcinoma growth and metastasis via the m6A/YTHDF2/SLC43A2 pathway.

N6-methyladenosine (m6A) plays a role in the development of tumors. However, the specific role of VIRMA, an RNA methyltransferase, in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study shows that VIRMA expression is elevated in PDAC.

CD163 impairs HBV clearance in mice by regulating intrahepatic T cell immune response via an IL-10-dependent mechanism.

Background & Aims: Chronic hepatitis B (CHB) arises from a persistent hepatitis B virus (HBV) infection, complicating efforts for a functional cure. Kupffer cells (KCs), liver-resident macrophages, are pivotal in mediating immune tolerance to HBV. Although CD163 marks M2-polarized KCs, its precise role in HBV infection remains unclear and warrants further investigation.

Predicting CRISPR-Cas9 off-target effects in human primary cells using bidirectional LSTM with BERT embedding.

Motivation: Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 system is a ground-breaking genome editing tool, which has revolutionized cell and gene therapies. One of the essential components involved in this system that ensures its success is the design of an optimal single-guide RNA (sgRNA) with high on-target cleavage efficiency and low off-target effects. This is challenging as many conditions need to be considered, and empirically testing every design is time-consuming and costly.

A Wonderful Journey: The Diverse Roles of Adenosine Deaminase Action on RNA 1 (ADAR1) in Central Nervous System Diseases.

Background: Adenosine deaminase action on RNA 1 (ADAR1) can convert the adenosine in double-stranded RNA (dsRNA) molecules into inosine in a process known as A-to-I RNA editing. ADAR1 regulates gene expression output by interacting with RNA and other proteins; plays important roles in development, including growth; and is linked to innate immunity, tumors, and central nervous system (CNS) diseases.

Results: In recent years, the role of ADAR1 in tumors has been widely discussed, but its role in CNS diseases has not been reviewed.

Fast-spiking parvalbumin-positive interneurons: new perspectives of treatment and future challenges in dementia.

Central nervous system parvalbumin-positive interneurons (PV-INs) are crucial and highly vulnerable to various stressors. They also play a significant role in the pathological processes of many neuropsychiatric diseases, especially those associated with cognitive impairment, such as Alzheimer's disease (AD), vascular dementia (VD), Lewy body dementia, and schizophrenia. Although accumulating evidence suggests that the loss of PV-INs is associated with memory impairment in dementia, the precise molecular mechanisms remain elusive.

Present and future use of exosomes containing proteins and RNAs in neurodegenerative diseases for synaptic function regulation: A comprehensive review.

Neurodegenerative diseases (NDDs) are increasingly prevalent with global aging, demanding effective treatments. Exosomes, which contain biological macromolecules such as RNA (including miRNAs) and proteins like α-synuclein, tau, and amyloid-beta, are gaining attention as innovative therapeutics. This comprehensive review systematically explores the potential roles of exosomes in NDDs, with a particular focus on their role in synaptic dysfunction.

An atlas of genetic effects on cellular composition of the tumor microenvironment.

Deciphering the composition of the tumor microenvironment (TME) is critical for understanding tumorigenesis and to design immunotherapies. In the present study, we mapped genetic effects on cell-type proportions using single-cell and bulk RNA sequencing data, identifying 3,494 immunity quantitative trait loci (immunQTLs) across 23 cancer types from The Cancer Genome Atlas. Functional annotation revealed regulatory potential and we further assigned 1,668 genes that regulate TME composition.

The neuroprotective effects of normobaric oxygen therapy after stroke.

Background: Stroke, including ischemic and hemorrhagic stroke, is a severe and prevalent acute cerebrovascular disease. The development of hypoxia following stroke can trigger a cascade of pathological events, including mitochondrial dysfunction, energy deficiency, oxidative stress, neuroinflammation, and excitotoxicity, all of which are often associated with unfavorable prognosis. Nonetheless, a noninvasive intervention, referred to as normobaric hyperoxia (NBO), is known to have neuroprotective effects against stroke.

Ac2-26 reduced the liver injury after cardiopulmonary bypass in rats via AKT1/GSK3β/eNOS pathway.

Objective: About 10% of patients after cardiopulmonary bypass (CPB) would undergo acute liver injury, which aggravated the mortality of patients. Ac2-26 has been demonstrated to ameliorate organic injury by inhibiting inflammation. The present study aims to evaluate the effect and mechanism of Ac2-26 on acute liver injury after CPB.

Ac2-26 activated the AKT1/GSK3β pathway to reduce cerebral neurons pyroptosis and improve cerebral function in rats after cardiopulmonary bypass.

Background: Cardiopulmonary bypass (CPB) results in brain injury, which is primarily caused by inflammation. Ac2-26 protects against ischemic or hemorrhage brain injury. The present study was to explore the effect and mechanism of Ac2-26 on brain injury in CPB rats.

Current evidence of synaptic dysfunction after stroke: Cellular and molecular mechanisms.

Background: Stroke is an acute cerebrovascular disease in which brain tissue is damaged due to sudden obstruction of blood flow to the brain or the rupture of blood vessels in the brain, which can prompt ischemic or hemorrhagic stroke. After stroke onset, ischemia, hypoxia, infiltration of blood components into the brain parenchyma, and lysed cell fragments, among other factors, invariably increase blood-brain barrier (BBB) permeability, the inflammatory response, and brain edema. These changes lead to neuronal cell death and synaptic dysfunction, the latter of which poses a significant challenge to stroke treatment.

Elevated expression of HIGD1A drives hepatocellular carcinoma progression by regulating polyamine metabolism through c-Myc-ODC1 nexus.

Background: Hypoxia contributes to cancer progression through various molecular mechanisms and hepatocellular carcinoma (HCC) is one of the most hypoxic malignancies. Hypoxia-inducible gene domain protein-1a (HIGD1A) is typically induced via epigenetic regulation and promotes tumor cell survival during hypoxia. However, the role of HIGD1A in HCC remains unknown.

Emerging role of mesenchymal stem cells-derived extracellular vesicles in vascular dementia.

Vascular dementia (VD) is a prevalent cognitive disorder among the elderly. Its pathological mechanism encompasses neuronal damage, synaptic dysfunction, vascular abnormalities, neuroinflammation, and oxidative stress, among others. In recent years, extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have garnered significant attention as an emerging therapeutic strategy.

Sting mediates infection by reducing accumulation of reactive oxygen species.

The Gram-negative bacterium is the causative agent of query fever in humans and coxiellosis in livestock. infects a variety of cell types, tissues, and animal species including mammals and arthropods, but there is much left to be understood about the molecular mechanisms at play during infection in distinct species. Human stimulator of interferon genes (STING) induces an innate immune response through the induction of type I interferons (IFNs), and IFN promotes or suppresses replication, depending on tissue type.

Genetic Evidence for the Causal Association of Circulating Cytokines and Growth Factors With Coronary Artery Disease.

Background: Observational studies have suggested the potential role of inflammatory factors in the risk of coronary artery disease (CAD). We aimed to perform 2-sample Mendelian randomization (MR) analyses to assess the causal association between circulating cytokines/growth factors and CAD.

Methods And Results: The instrumental variables for 28 circulating cytokines and growth factors were identified from a genome-wide association study of 8293 European participants.

FRS2 regulated by miR-429 and miR-206 promotes angiogenesis in osteosarcoma.

FRS2 has demonstrated oncogenic roles in various malignancies, including liposarcoma and giant cell tumor of bone. However, its role in osteosarcoma remains less understood, and the upstream regulatory molecules influencing FRS2 remain unclear. This study aims to explore the clinical implications and biological function of FRS2 in osteosarcoma, and the potential regulatory microRNAs (miRNAs) governing its expression.

Metabolic engineering of Yarrowia lipolytica for high-level production of squalene.

Squalene is an important triterpene with a wide range of applications. Given the growing market demand for squalene, the development of microbial cell factories capable of squalene production is considered a sustainable method. This study aimed to investigate the squalene production potential of Yarrowia lipolytica.

Starch of oat derived nanostructured Fe/Mn bimetallic carbon materials for sulfamethoxazole degradation via peroxymonosulfate activation.

Fe/Mn bimetallic carbon materials were synthesized by combining oat and urea, followed by and carbonization processes, the activity and mechanism of the obtained materials in activating peroxymonosulfate (PMS) for sulfamethoxazole (SMX) degradation were determined. Data suggested that the obtained material (CN@FeMn-10-800) showed the optimal performance for SMX degradation under the1:8:0.05:0.

Astroglial Hmgb1 regulates postnatal astrocyte morphogenesis and cerebrovascular maturation.

Astrocytes are intimately linked with brain blood vessels, an essential relationship for neuronal function. However, astroglial factors driving these physical and functional associations during postnatal brain development have yet to be identified. By characterizing structural and transcriptional changes in mouse cortical astrocytes during the first two postnatal weeks, we find that high-mobility group box 1 (Hmgb1), normally upregulated with injury and involved in adult cerebrovascular repair, is highly expressed in astrocytes at birth and then decreases rapidly.