Activation of sphingosine-1-phosphate receptor 2 (S1PR2) upregulates dihydropyrimidine dehydrogenase (DPD) expression in colon cancer cells.

Introduction: Dihydropyrimidine dehydrogenase (DPD) is a major determinant of cancer 5-fluorouracyl (5-FU) resistance via its direct degradation. However, the mechanisms of tumoral DPD upregulation have not been fully understood.

Objectives: This study aimed to explore the role of S1PR2 in the regulation of tumoral DPD expression, identifying S1PR2 as the potential target for reversing 5-FU resistance.

The structural organisation of pentraxin-3 and its interactions with heavy chains of inter-α-inhibitor regulate crosslinking of the hyaluronan matrix.

Pentraxin-3 (PTX3) is an octameric protein, comprised of eight identical protomers, that has diverse functions in reproductive biology, innate immunity and cancer. PTX3 interacts with the large polysaccharide hyaluronan (HA) to which heavy chains (HCs) of the inter-α-inhibitor (IαI) family of proteoglycans are covalently attached, playing a key role in the (non-covalent) crosslinking of HC•HA complexes. These interactions stabilise the cumulus matrix, essential for ovulation and fertilisation in mammals, and are also implicated in the formation of pathogenic matrices in the context of viral lung infections.

Ni-induced selective precipitation of His-tagged recombinant proteins shortens purification time while maintaining high yield.

Nickel-NTA affinity chromatography is the current standard method for purifying Histagged recombinant proteins. However, this process involves repetitive tasks, can be time-consuming, and reduces protein yield. Here, we present a simple, fast, and handy method for purifying His-tagged proteins using free Ni²⁺.

Labelling of a live obligate anaerobe using fluorescent D-amino acids.

The probing of live bacteria via the incorporation of fluorescent D-amino acids (FDAAs) during peptidoglycan synthesis has been shown to be practical for visualizing both gram-positive and gram-negative bacterial species. This study demonstrates the reliability and applications of FDAA labelling for the fluorescent imaging of an obligate anaerobe.

Pulling Forces Dampen Torsional Fluctuations of Actin Filaments and Reduce Cooperative Cofilin Binding.

A variety of potential biological roles of mechanical forces have been proposed in the field of cell biology. In particular, mechanical forces alter the mechanical conditions within cells and their environment, exerting a strong effect on the reorganization of the actin cytoskeleton. Single-molecule imaging studies have provided evidence that an actin filament may act as a mechanosensor.

Revised Title - Quercetin Combined with Ciprofloxacin and Gentamicin Inhibits Biofilm Formation and Virulence in Staphylococcus aureus.

Biofilm formation, extracellular substance synthesis, and virulence factor production all have a major impact on drug tolerance and infection propagation caused by Staphylococcus aureus. Flavonoid compounds have been explored as potential solutions to enhance antibiotic efficacy against the biofilm formation of pathogenic microbes. Quercetin (QER) has previously demonstrated antibacterial and antibiofilm properties.

CTLA4-Ig reduces muscle fiber damage in a model of Duchenne muscular dystrophy by attenuating pro-inflammatory gene expression in myeloid lineage cells.

Duchenne muscular dystrophy (DMD) is a lethal, muscle-wasting, genetic disease that is greatly amplified by an immune response to the diseased muscles. The mdx mouse model of DMD was used to test whether the pathology can be reduced by treatments with a CTLA4-Ig fusion protein that blocks costimulatory signals required for activation of T-cells. CTLA4-Ig treatments reduced mdx sarcolemma lesions and reduced the numbers of activated T-cells, macrophages and antigen presenting cells in mdx muscle and reduced macrophage invasion into muscle fibers.

Nicotinic Acetylcholine Receptor Expression in Merkel Cell Carcinoma Is Associated With Clinical and Histopathologic Parameters.

Background: Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous malignancy with neuroendocrine differentiation. Several molecular pathways have been implicated in MCC development and multiple cell-of-origin candidates have been proposed, including neural crest cells, which express acetylcholine receptors (AChRs). The role of nicotinic acetylcholine receptors (nAChRs) in MCC has not been explored.

Multimodal hierarchical classification of CITE-seq data delineates immune cell states across lineages and tissues.

Single-cell RNA sequencing (scRNA-seq) is invaluable for profiling cellular heterogeneity and transcriptional states, but transcriptomic profiles do not always delineate subsets defined by surface proteins. Cellular indexing of transcriptomes and epitopes (CITE-seq) enables simultaneous profiling of single-cell transcriptomes and surface proteomes; however, accurate cell-type annotation requires a classifier that integrates multimodal data. Here, we describe multimodal classifier hierarchy (MMoCHi), a marker-based approach for accurate cell-type classification across multiple single-cell modalities that does not rely on reference atlases.

Ongoing chromothripsis underpins osteosarcoma genome complexity and clonal evolution.

Osteosarcoma is the most common primary cancer of the bone, with a peak incidence in children and young adults. Using multi-region whole-genome sequencing, we find that chromothripsis is an ongoing mutational process, occurring subclonally in 74% of osteosarcomas. Chromothripsis generates highly unstable derivative chromosomes, the ongoing evolution of which drives the acquisition of oncogenic mutations, clonal diversification, and intra-tumor heterogeneity across diverse sarcomas and carcinomas.

Intracellular protein-lipid interactions drive presynaptic assembly prior to neurexin recruitment.

Neurexin cell-adhesion molecules regulate synapse development and function by recruiting synaptic components. Here, we uncover a mechanism for presynaptic assembly that precedes neurexin recruitment, mediated by interactions between cytosolic proteins and membrane phospholipids. Developmental imaging in C.

Dopamine D1 receptor activation in the striatum is sufficient to drive reinforcement of anteceding cortical patterns.

Timed dopamine signals underlie reinforcement learning, favoring neural activity patterns that drive behaviors with positive outcomes. In the striatum, dopamine activates five dopamine receptors (D1R-D5R), which are differentially expressed in striatal neurons. However, the role of specific dopamine receptors in reinforcement is poorly understood.

Tissue remodeling during high-altitude pulmonary edema in rats: Biochemical and histomorphological analysis.

High altitude characterized by the low partial pressure of the oxygen is a life-threatening condition that contributes to the development of acute pulmonary edema and hypoxic lung injury. In this study, we aimed to investigate the contribution of some inflammatory and oxidative stress markers along with antioxidant system enzymes in the pathogenesis of HAPE (high-altitude pulmonary edema) formation. We incorporated the study on 42 male rats to unravel the role of mast cells (MCs) and TNF-α in the lung after the effect of acute hypobaric hypoxia.

Exploring Denosumab in the Treatment of Giant Cell Tumors: Clinical Evidence and Controversies.

Giant cell tumors (GCTs) are benign but locally aggressive bone neoplasms that primarily affect skeletally mature individuals. They are characterized by a tendency for recurrence and being associated with significant morbidity. Traditional treatment has focused on surgical resection; however, the role of medical therapies, such as Denosumab, a bone anti-resorptive drug, which has been Food and Drug Administration (FDA)-approved for unresectable GCTs since 2013, recently has gained prominence.

Siderophore synthetase-receptor gene coevolution reveals habitat- and pathogen-specific bacterial iron interaction networks.

Bacterial social interactions play crucial roles in various ecological, medical, and biotechnological contexts. However, predicting these interactions from genome sequences is notoriously difficult. Here, we developed bioinformatic tools to predict whether secreted iron-scavenging siderophores stimulate or inhibit the growth of community members.

Engineered extracellular vesicles with DR5 agonistic scFvs simultaneously target tumor and immunosuppressive stromal cells.

Small extracellular vesicles (sEVs) are nanosized vesicles. Death receptor 5 (DR5) mediates extrinsic apoptosis. We engineer DR5 agonistic single-chain variable fragment (scFv) expression on the surface of sEVs derived from natural killer cells.

3D genomic features across >50 diverse cell types reveal insights into the genomic architecture of childhood obesity.

The prevalence of childhood obesity is increasing worldwide, along with the associated common comorbidities of type 2 diabetes and cardiovascular disease in later life. Motivated by evidence for a strong genetic component, our prior genome-wide association study (GWAS) efforts for childhood obesity revealed 19 independent signals for the trait; however, the mechanism of action of these loci remains to be elucidated. To molecularly characterize these childhood obesity loci, we sought to determine the underlying causal variants and the corresponding effector genes within diverse cellular contexts.

CFTR dictates monocyte adhesion by facilitating integrin clustering but not activation.

Monocytes are critical in controlling tissue infections and inflammation. Monocyte dysfunction contributes to the inflammatory pathogenesis of cystic fibrosis (CF) caused by CF transmembrane conductance regulator (CFTR) mutations, making CF a clinically relevant disease model for studying the contribution of monocytes to inflammation. Although CF monocytes exhibited adhesion defects, the precise mechanism is unclear.

A histochemical approach to activity-based copper sensing reveals cuproplasia-dependent vulnerabilities in cancer.

Copper is an essential nutrient for sustaining vital cellular processes spanning respiration, metabolism, and proliferation. However, loss of copper homeostasis, particularly misregulation of loosely bound copper ions which are defined as the labile copper pool, occurs in major diseases such as cancer, where tumor growth and metastasis have a heightened requirement for this metal. To help decipher the role of copper in the etiology of cancer, we report a histochemical activity-based sensing approach that enables systematic, high-throughput profiling of labile copper status across many cell lines in parallel.

Pristimerin Promotes Ubiquitination of HSPA8 and Activates the VAV1/ERK Pathway to Suppress TNBC Proliferation.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis. The natural compound pristimerin has shown promising anti-tumor effect. Here, it is found that pristimerin significantly triggered the activation of autophagy initiation and induced apoptosis in TNBC.

Protocol for isolation of human bone marrow stromal cells and characterization of cellular metabolism.

Bone marrow stromal cells (BMSCs) serve as a valuable reservoir of multipotent stem cells important in the regulation of bone homeostasis and energy metabolism. Here, we present a protocol for isolating human BMSCs (hBMSCs) and characterizing their cellular metabolism related to hBMSC functional properties. We describe steps for bioenergetics, cell senescence, and production of reactive oxygen species (ROS), together with description of the data analysis.

Chitinase-3-like Protein 1 Reduces the Stability of Atherosclerotic Plaque via Impairing Macrophagic Efferocytosis.

CHI3L1 is strongly associated with atherosclerosis, but its role in macrophages remains unknown. In this study, we observed a significant up-regulation of CHI3L1 in both carotid plaques and serum of symptomatic patients, and demonstrated that CHI3L1 impairs the efferocytosis of macrophages by down-regulating crucial efferocytic mediator MFGE8 through inhibiting ATF2, which binds directly to the enhancer of MFGE8. In human plaques, we observed a negative correlation between CHI3L1 expression and both ATF2 and MFGE8 levels, further proved their involvement in plaque destabilization.

In Silico Structural Insights into a Glucanase from Clostridium perfringens and Prediction of Structural Stability Improvement Through Hydrophobic Interaction Network and Aromatic Interaction.

Glucanases are widely applied in industrial applications such as brewing, biomass conversion, food, and animal feed. Glucanases catalyze the hydrolysis of glucan to produce the sugar hemiacetal through hydrolytic cleavage of glycosidic bonds. Current study aimed to investigate structural insights of a glucanase from Clostridium perfringens through blind molecular docking, site-specific molecular docking, molecular dynamics (MD) simulation, and binding energy calculation.