Molecular mechanism of drug inhibition of URAT1.

Hyperuricemia, characterized by elevated serum urate levels, is a key factor in the pathogenesis of gout. URAT1 is essential for renal urate reabsorption and has emerged as a critical therapeutic target for managing hyperuricemia. However, the precise transport mechanism and the inhibitory effects of uricosuric drugs on URAT1 remain unclear.

MLKL is involved in the regulation of skin wound healing and interplay between macrophages and myofibroblasts in mice.

Mixed lineage kinase domain-like protein (MLKL), a critical necroptosis effector, is strongly linked to inflammation, a key component of skin wound healing. However, its precise role in the wound healing process remains inadequately characterized. This study revealed sustained MLKL overexpression throughout the wound healing process, not limited to the early inflammation phase.

Molecular insights into the α6β4 nicotinic acetylcholine receptor function and ligand recognition.

The α6β4 nicotinic acetylcholine receptor (nAChR) is found in the sensory neurons of dorsal root ganglia. It is a promising therapeutic target for pain. However, the difficultly of heterologous functional expression of α6β4 receptor has hindered the discovery of drugs that target it.

Autoimmune disease and risk of lymphoma: analysis from real-world data and Mendelian randomization study.

Background: Autoimmune diseases (AIDs) appear to be the primary predisposing factors for lymphoma. This study aims to investigate the causal effects between AIDs and lymphomagenesis.

Methods: A two-sample Mendelian randomization (MR) framework was employed to estimate the causal effect through UK Biobank (UKB) and FinnGen cohorts.

Matrine alleviates Staphylococcus aureus-induced acute lung injury in mice by inhibiting MLKL and NLRP3-mediated inflammatory activity.

Acute lung injury (ALI) is a serious clinical condition with high incidence and mortality. The inflammatory response induced by gram-positive bacteria, especially Staphylococcus aureus (S. aureus), is a key factor contributing to ALI progression and other infectious diseases.

Taurochenodeoxycholic acid ameliorates the Staphylococcus aureus infection-induced acute lung injury through toll-like receptor 2 in mice.

Acute lung injury (ALI) is a significant clinical problem associated with high morbidity and mortality. Inflammation induced by gram-positive bacterial pathogens, specifically Staphylococcus aureus (S. aureus), plays a major role in ALI development and other infectious diseases.

Transport and inhibition mechanisms of the human noradrenaline transporter.

The noradrenaline transporter (also known as norepinephrine transporter) (NET) has a critical role in terminating noradrenergic transmission by utilizing sodium and chloride gradients to drive the reuptake of noradrenaline (also known as norepinephrine) into presynaptic neurons. It is a pharmacological target for various antidepressants and analgesic drugs. Despite decades of research, its structure and the molecular mechanisms underpinning noradrenaline transport, coupling to ion gradients and non-competitive inhibition remain unknown.

N-acetyltransferase 10 facilitates tumorigenesis of diffuse large B-cell lymphoma by regulating AMPK/mTOR signalling through N4-acetylcytidine modification of SLC30A9.

Background: Accumulating studies suggested that posttranscriptional modifications exert a vital role in the tumorigenesis of diffuse large B-cell lymphoma (DLBCL). N4-acetylcytidine (ac4C) modification, catalyzed by the N-acetyltransferase 10 (NAT10), was a novel type of chemical modification that improves translation efficiency and mRNA stability.

Methods: GEO databases and clinical samples were used to explore the expression and clinical value of NAT10 in DLBCL.

The roles of Braun Lipoprotein in inducing tolerance of bovine endometrium infected by Escherichia coli.

Escherichia coli (E. coli), a Gram-negative bacterium, is the primary pathogen responsible for endometritis in dairy cattle. The outer membrane components of E.

Structural bases of inhibitory mechanism of Ca1.2 channel inhibitors.

The voltage-gated calcium channel Ca1.2 is essential for cardiac and vessel smooth muscle contractility and brain function. Accumulating evidence demonstrates that malfunctions of Ca1.

NCAPD3 promotes diffuse large B-cell lymphoma progression through modulating SIRT1 expression in an H3K9 monomethylation-dependent manner.

Introduction: Condensin, a family of structural maintenance of chromosome complexes, has been shown to regulate chromosome compaction and segregation during mitosis. NCAPD3, a HEAT-repeat subunit of condensin II, plays a dominant role in condensin-mediated chromosome dynamics but remains unexplored in lymphoma.

Objectives: The study aims to unravel the molecular function and mechanism of NCAPD3 in diffuse large B-cell lymphoma (DLBCL).

Prostaglandin D is involved in the regulation of inflammatory response in Staphylococcus aureus-infected mice macrophages.

Staphylococcus aureus (S. aureus) is one of the most infamous and widespread bacterial pathogens, causing a hard-to-estimate number of uncomplicated skin infections and probably hundreds of thousands to millions of more severe, invasive infections globally per year. S.

Transport and inhibition mechanisms of human VMAT2.

Vesicular monoamine transporter 2 (VMAT2) accumulates monoamines in presynaptic vesicles for storage and exocytotic release, and has a vital role in monoaminergic neurotransmission. Dysfunction of monoaminergic systems causes many neurological and psychiatric disorders, including Parkinson's disease, hyperkinetic movement disorders and depression. Suppressing VMAT2 with reserpine and tetrabenazine alleviates symptoms of hypertension and Huntington's disease, respectively.

Maintenance and consolidation strategies for patients with untreated advanced follicular lymphoma: A systematic review and network meta-analysis of randomized trials.

Background: The emergence of novel and efficient antibody maintenance approaches has provided more options for post-induction treatment of advanced follicular lymphoma (FL), and further comparisons are required to determine the most clinically beneficial regimen. The authors conducted a systematic review and meta-analysis to evaluate the maintenance or consolidation strategy.

Methods: The authors performed two independent searches in PubMed, Web of Science, the Cochrane library databases, Scopus, and Embase for randomized controlled trials (RCTs) evaluating maintenance or consolidation therapy in untreated FL patients.

Targeting YTHDF2 inhibits tumorigenesis of diffuse large B-cell lymphoma through ACER2-mediated ceramide catabolism.

Introduction: Epigenetic alterations play crucial roles in diffuse large B-cell lymphoma (DLBCL). Disturbances in lipid metabolism contribute to tumor progression. However, studies in epigenetics, especially its critical regulator YTH N6-methyladenosine RNA binding protein 2 (YTHDF2), on lipid metabolism regulation in DLBCL are unidentified.

Histone regulator KAT2A acts as a potential biomarker related to tumor microenvironment and prognosis of diffuse large B cell lymphoma.

Background: Recent studies have indicated that epigenetic alterations contribute significantly to lymphoma pathogenesis. A type of epigenetic regulation known as histone acetylation plays a crucial role in transcriptional regulation in eukaryotic cells. Specifically, a significant effect of histone acetylation modifications on the abnormal progression and microenvironment of diffuse large B-cell lymphoma (DLBCL) has been observed.

Activation of STING by SAMHD1 Deficiency Promotes PANoptosis and Enhances Efficacy of PD-L1 Blockade in Diffuse Large B-cell Lymphoma.

Genomic instability is a significant driver of cancer. As the sensor of cytosolic DNA, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a critical role in regulating anti-tumor immunity and cell death. However, the role and regulatory mechanisms of STING in diffuse large B-cell lymphoma (DLBCL) are still undefined.

Prostaglandin D regulates Escherichia coli-induced inflammatory responses through TLR2, TLR4, and NLRP3 in macrophages.

Prostaglandin D (PGD) synthesis is closely associated with the innate immune response mediated by pattern recognition receptors (PPRs). We determined PGD synthesis whether mediated by Toll-like receptor 2 (TLR2), TLR4 and Nod-like receptor pyrin domain-containing protein 3 (NLRP3) in Escherichia coli (E. coli)-, lipopolysaccharide (LPS)- and Braun lipoprotein (BLP)-stimulated macrophages.

α-KG inhibits tumor growth of diffuse large B-cell lymphoma by inducing ROS and TP53-mediated ferroptosis.

Metabolic reprogramming is a hallmark of human malignancies. Dysregulation of glutamine metabolism is essential for tumorigenesis, microenvironment remodeling, and therapeutic resistance. Based on the untargeted metabolomics sequencing, we identified that the glutamine metabolic pathway was up-regulated in the serum of patients with primary DLBCL.

Two-state model explaining thermodynamic regulation of thermo-gating channels.

Temperature-sensitive ion channels, such as those from the TRP family (thermo-TRPs) present in all animal cells, serve to perceive heat and cold sensations. A considerable number of protein structures have been reported for these ion channels, providing a solid basis for revealing their structure-function relationship. Previous functional studies suggest that the thermosensing ability of TRP channels is primarily determined by the properties of their cytosolic domain.

Single-cell transcriptome analysis profiles the expression features of TMEM173 in BM cells of high-risk B-cell acute lymphoblastic leukemia.

Background: As an essential regulator of type I interferon (IFN) response, TMEM173 participates in immune regulation and cell death induction. In recent studies, activation of TMEM173 has been regarded as a promising strategy for cancer immunotherapy. However, transcriptomic features of TMEM173 in B-cell acute lymphoblastic leukemia (B-ALL) remain elusive.

Metabolic Reprogramming in Hematologic Malignancies: Advances and Clinical Perspectives.

Metabolic reprogramming is a hallmark of cancer progression. Metabolic activity supports tumorigenesis and tumor progression, allowing cells to uptake essential nutrients from the environment and use the nutrients to maintain viability and support proliferation. The metabolic pathways of malignant cells are altered to accommodate increased demand for energy, reducing equivalents, and biosynthetic precursors.