Histone lysine methyltransferases MLL3 and MLL4 direct gene expression to produce platelets efficiently.

Circulating blood platelets are responsible for maintaining hemostasis. They are released into blood vessels from mature megakaryocytes. Although several transcription factors have been reported to orchestrate the transcriptional programs required for platelet production, how chromatin regulators control these processes is still poorly understood.

Changes in soil stoichiometry, soil organic carbon mineralization and bacterial community assembly processes across soil profiles.

Soil organic carbon (SOC) mineralization is essential to biogeochemical recycling in terrestrial ecosystem. However, the microbial mechanisms underlying the nutrient-induced SOC mineralization remain uncertain. Here, we investigated how SOC mineralization was linked to microbial assembly processes as well as soil nutrient availability and stoichiometric ratio in a paddy rice ecosystem at four soil profile levels.

The NFIB/CARM1 partnership is a driver in preclinical models of small cell lung cancer.

The coactivator associated arginine methyltransferase (CARM1) promotes transcription, as its name implies. It does so by modifying histones and chromatin bound proteins. We identified nuclear factor I B (NFIB) as a CARM1 substrate and show that this transcription factor utilizes CARM1 as a coactivator.

Regional Inequalities and Influencing Factors of Residents' Health in China: Analysis from the Perspective of Opening-Up.

While opening-up promotes regional economic development, its impact on the residents' health level cannot be ignored. Based on provincial data of China from 2009 to 2020, the Gini Coefficient and Theil Index are used to analyze the regional inequalities in residents' health in China. The Difference-in-Difference model is constructed to study the impact of China's opening-up policies and other factors on residents' health.

Using Potential Molecular Transformation To Understand the Molecular Trade-Offs in Soil Dissolved Organic Matter.

Understanding the chemical composition and molecular transformation in soil dissolved organic matter (DOM) is important to the global carbon cycle. To address this issue, ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) was applied to investigate DOM molecules in 36 paddy soils collected from subtropical China. All the detected 7576 unique molecules were divided into seven compound groups, and nine trade-off relationships between different compound groups were revealed based on principal component analysis and Pearson's correlation.

SPINDOC binds PARP1 to facilitate PARylation.

SPINDOC is tightly associated with the histone H3K4me3 effector protein SPIN1. To gain a better understanding of the biological roles of SPINDOC, we identified its interacting proteins. Unexpectedly, SPINDOC forms two mutually exclusive protein complexes, one with SPIN1 and the other with PARP1.

Genetic evidence for partial redundancy between the arginine methyltransferases CARM1 and PRMT6.

CARM1 is a protein arginine methyltransferase (PRMT) that acts as a coactivator in a number of transcriptional programs. CARM1 orchestrates this coactivator activity in part by depositing the H3R17me2a histone mark in the vicinity of gene promoters that it regulates. However, the gross levels of H3R17me2a in CARM1 KO mice did not significantly decrease, indicating that other PRMT(s) may compensate for this loss.

Discovery of First-in-Class Protein Arginine Methyltransferase 5 (PRMT5) Degraders.

The aberrant expression of protein arginine methyltransferase 5 (PRMT5) has been associated with multiple cancers. Using the proteolysis targeting chimera technology, we discovered a first-in-class PRMT5 degrader (MS4322). Here, we report the design, synthesis, and characterization of compound and two structurally similar controls (MS4370) and (MS4369), with impaired binding to the von Hippel-Lindau E3 ligase and PRMT5, respectively.

CARM1 inhibition reduces histone acetyltransferase activity causing synthetic lethality in CREBBP/EP300-mutated lymphomas.

Somatic mutations affecting CREBBP and EP300 are a hallmark of diffuse large B-cell lymphoma (DLBCL). These mutations are frequently monoallelic, within the histone acetyltransferase (HAT) domain and usually mutually exclusive, suggesting that they might affect a common pathway, and their residual WT expression is required for cell survival. Using in vitro and in vivo models, we found that inhibition of CARM1 activity (CARM1i) slows DLBCL growth, and that the levels of sensitivity are positively correlated with the CREBBP/EP300 mutation load.

Detecting Coal Pulverizing System Anomaly Using a Gated Recurrent Unit and Clustering.

The coal pulverizing system is an important auxiliary system in thermal power generation systems. The working condition of a coal pulverizing system may directly affect the safety and economy of power generation. Prognostics and health management is an effective approach to ensure the reliability of coal pulverizing systems.

A randomized controlled trial of a nurse-led education pathway for asthmatic children from outpatient to home.

Background: Education for asthmatic children in the outpatient department is insufficient.

Aim: To evaluate the efficacy of a nurse-led education pathway, a standard education programme, on children with asthma.

Methods: One hundred and eighty participants enrolled and were randomly assigned to either the control group or the intervention group.

The effect of goal setting in asthma self-management education: A systematic review.

Background: Asthma self-management education combining with behavior therapy is considered to be more effective. Goal setting is a common behavior change technique used to help patients self-manage their symptoms. However, empirical evidence around its effectiveness on asthma management lacks clarity.

Predictive accuracy of the Braden Q Scale in risk assessment for paediatric pressure ulcer: A meta-analysis.

Aims: Paediatric pressure ulcers are a serious problem to healthcare service. Thus, effective and early identification of the risk of developing pressure ulcer is essential. The Braden Q scale is a widely used tool in the risk assessment of paediatric pressure ulcer, but its predictive power is controversial.

PRMT1 loss sensitizes cells to PRMT5 inhibition.

PRMT5 is an arginine methyltransferase that accounts for the vast majority of the symmetric methylation in cells. PRMT5 exerts its function when complexed with MEP50/WDR77. This activity is often elevated in cancer cells and correlates with poor prognosis, making PRMT5 a therapeutic target.

The positive feedback loop between ILF3 and lncRNA ILF3-AS1 promotes melanoma proliferation, migration, and invasion.

Purpose: In our previous study, we identified that lncRNA ILF3 antisense RNA 1 (ILF3-AS1) is increased and has oncogenic roles in melanoma. However, the cause of the upregulation of ILF3-AS1 and the modulation between ILF3-AS1 and ILF3 in melanoma are still unknown. This study aimed to investigate the significances of the interaction between ILF3-AS1 and ILF3 in melanoma.

Long noncoding RNA ILF3-AS1 promotes cell proliferation, migration, and invasion via negatively regulating miR-200b/a/429 in melanoma.

Melanoma is the most malignant skin cancer, which account for most of skin-cancer-related deaths. Long noncoding RNA (lncRNA) is a class of noncoding RNAs with crucial roles in many cancers. However, the roles of lncRNAs in melanoma have not been well studied.

Comparing the Curative Efficacy of Different Skin Grafting Methods for Third-Degree Burn Wounds.

BACKGROUND Our research purpose was to compare the curative efficacy of different skin grafting methods for treating third-degree burn wounds. MATERIAL AND METHODS A total of 105 patients with third-degree burns were involved in this study. The burn wounds of these patients were treated using three different methods: Meek skin grafting, Stamp skin grafting, and Microskin grafting.

Regulation of the Alternative Splicing and Function of Cyclin T1 by the Serine-Arginine-Rich Protein ASF/SF2.

Positive transcription elongation factor-b (P-TEFb) is required for the release of RNA polymerase II (RNAPII) from its pause near the gene promoters and thus for efficient proceeding to the transcription elongation. It consists of two core subunits-CDK9 and one of T-typed or K-typed cyclin, of which, cyclin T1/CDK9 is the major and most studied combination. We have previously identified a novel splice variant of cyclin T1, cyclin T1b, which negatively regulates the transcription elongation of HIV-1 genes as well as several host genes.

Effects of miR-145-5p through NRAS on the cell proliferation, apoptosis, migration, and invasion in melanoma by inhibiting MAPK and PI3K/AKT pathways.

We aimed to detect the effects of miR-145-5p on the cell proliferation, apoptosis, migration, and invasion in NRAS-mutant, BRAF-mutant, and wild-type melanoma cells, in order to figure out the potential mechanisms and provide a novel therapeutic target of melanoma. RT-qPCR and western blot were used to detect the expression of miR-145-5p and NRAS in melanoma tumor tissues and cells, respectively. Luciferase assay was performed to determine whether miR-145-5p directly targeted NRAS.

Long Noncoding RNA PVT1 as a Novel Diagnostic Biomarker and Therapeutic Target for Melanoma.

Accumulating evidences indicated that plasmacytoma variant translocation 1 (PVT1) plays vital roles in several cancers. However, the expression, functions, and clinical values of PVT1 in melanoma are still unknown. In this study we measured the expression of PVT1 in clinical tissues and serum samples and explored the diagnostic value of PVT1 for melanoma and the effects of PVT1 on melanoma cell proliferation, cell cycle, and migration.

Long noncoding RNA MHENCR promotes melanoma progression via regulating miR-425/489-mediated PI3K-Akt pathway.

Increasing evidences demonstrated that long noncoding RNAs (lncRNAs) are frequently dysregulated and have critical roles in many tumors. However, the roles and functional mechanisms of lncRNAs in melanoma remain largely unknown. In this study, we identified a novel lncRNA MHENCR which was upregulated in melanoma tissues and further upregulated in metastatic melanoma.

PRMT5 regulates IRES-dependent translation via methylation of hnRNP A1.

The type II arginine methyltransferase PRMT5 is responsible for the symmetric dimethylation of histone to generate the H3R8me2s and H4R3me2s marks, which correlate with the repression of transcription. However, the protein level of a number of genes (MEP50, CCND1, MYC, HIF1a, MTIF and CDKN1B) are reported to be downregulated by the loss of PRMT5, while their mRNA levels remain unchanged, which is counterintuitive for PRMT5's proposed role as a transcription repressor. We noticed that the majority of the genes regulated by PRMT5, at the posttranscriptional level, express mRNA containing an internal ribosome entry site (IRES).

PRMT5 C-terminal Phosphorylation Modulates a 14-3-3/PDZ Interaction Switch.

PRMT5 is the primary enzyme responsible for the deposition of the symmetric dimethylarginine in mammalian cells. In an effort to understand how PRMT5 is regulated, we identified a threonine phosphorylation site within a C-terminal tail motif, which is targeted by the Akt/serum- and glucocorticoid-inducible kinases. While investigating the function of this posttranslational modification, we serendipitously discovered that its free C-terminal tail binds PDZ domains (when unphosphorylated) and 14-3-3 proteins (when phosphorylated).

Pharmacological interventions for melanoma: Comparative analysis using bayesian meta-analysis.

We conducted a network meta-analysis in order to compare different strategies for managing melanoma patients. Electronic databases were searched for eligible randomized trials that compared different strategies in efficacy and tolerability. Five interventions were associated with a significant improvement in PFS over chemotherapy (all HR < 1): Ipilimumab, Tremelimumab, Nivolumab, Pembrolizumab 2 mg/kg and Ipilimumab + Nivolumab.