Methylation Mesa define functional regulatory elements for targeted gene activation.

DNA methylation and mRNA expression correlations are often presented with inconsistent evidence supporting causal regulation. We hypothesized that causal regulatory methylation elements would exhibit heightened demethylation sensitivity. To investigate, we analyzed 20 whole-genomic bisulfite sequenced samples before and after demethylation and identified narrow-width (45-294 bp) elements within a short plateau, termed Methylation Mesa (MM).

The interconnectedness of energy consumption with economic growth: A granger causality analysis.

In considering today's energy challenges, the link between the usage of renewable and non-renewable energy sources and economic growth has gained substantial policy attention. This research examines the complex relationship between these three variables to understand how non-renewable energy consumption and renewable energy consumption interact and what that means for economic growth. This study uses the Granger causality approach to explore the relationships between non-renewable energy consumption, renewable energy consumption, and economic development.

Druglike Molecules Binding to Large Membrane Proteins: Absolute Binding Free Energy Computation.

In this research, we employed the alchemical double-decoupling method alongside restraining potentials, coupled with the FEPMD method, to ascertain the standard binding free energy of a drug-like molecule termed BHQ and three analogous compounds engineered with progressive addition of bulky para-alkyl groups binding to SERCA (Ca-ATPase of skeletal muscle sarcoplasmic reticulum). Integral transmembrane proteins represent crucial drug targets in numerous therapeutic interventions, presenting computational challenges due to their considerable system sizes. Our approach integrated the generalized born potential method and the spherical solvent boundary potential method, allowing us to explicitly focus on the active binding site while treating the remainder of the system implicitly.

Extracellular vesicle surface display enhances the therapeutic efficacy and safety profile of cancer immunotherapy.

Immunotherapy has emerged as a mainstay in cancer therapy, yet its efficacy is constrained by the risk of immune-related adverse events. In this study, we present a nanoparticle-based delivery system that enhances the therapeutic efficacy of immunomodulatory ligands while concurrently limiting systemic toxicity. We demonstrate that extracellular vesicles (EVs), lipid bilayer enclosed particles released by cells, can be efficiently engineered via inverse electron demand Diels-Alder (iEDDA)-mediated conjugation to display multiple immunomodulatory ligands on their surface.

Thg1 family 3'-5' RNA polymerases as tools for targeted RNA synthesis.

Members of the 3'-5' RNA polymerase family, comprised of tRNA guanylyltransferase (Thg1) and Thg1-like proteins (TLPs), catalyze templated synthesis of RNA in the reverse direction to all other known 5'-3' RNA and DNA polymerases. The discovery of enzymes capable of this reaction raised the possibility of exploiting 3'-5' polymerases for posttranscriptional incorporation of nucleotides to the 5'-end of nucleic acids without ligation, and instead by templated polymerase addition. To date, studies of these enzymes have focused on nucleotide addition to highly structured RNAs, such as tRNA and other noncoding RNAs.

Correction: The Omega-3 Fatty Acid Eicosapentaenoic Acid Accelerates Disease Progression in a Model of Amyotrophic Lateral Sclerosis.

[This corrects the article DOI: 10.1371/journal.pone.

Differences in F pocket impact on HLA I genetic associations with autoimmune diabetes.

Introduction: Human leukocyte antigen (HLA) I molecules present antigenic peptides to activate CD8 T cells. Type 1 Diabetes (T1D) is an auto-immune disease caused by aberrant activation of the CD8 T cells that destroy insulin-producing pancreatic β cells. Some alleles were shown to increase the risk of T1D (T1D-predisposing alleles), while some reduce this risk (T1D-protective alleles).

Dendritic cell-targeted delivery of antigens using extracellular vesicles for anti-cancer immunotherapy.

Neoantigen delivery using extracellular vesicles (EVs) has gained extensive interest in recent years. EVs derived from tumour cells or immune cells have been used to deliver tumour antigens or antitumor stimulation signals. However, potential DNA contamination from the host cell and the cost of large-scale EV production hinder their therapeutic applications in clinical settings.

The Role of Diet in the Management of Irritable Bowel Syndrome: A Comprehensive Review.

Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder that has a significant impact on the general population. The suboptimal medical treatments available for IBS contribute to its large economic burden. The pathophysiology of IBS is complex, and treatments often focus on managing specific symptoms.

Red Blood Cell-Derived Extracellular Vesicles Display Endogenous Antiviral Effects and Enhance the Efficacy of Antiviral Oligonucleotide Therapy.

The COVID-19 pandemic has resulted in a large number of fatalities and, at present, lacks a readily available curative treatment for patients. Here, we demonstrate that unmodified red blood cell-derived extracellular vesicles (RBCEVs) can inhibit SARS-CoV-2 infection in a phosphatidylserine (PS) dependent manner. Using T cell immunoglobulin mucin domain-1 (TIM-1) as an example, we demonstrate that PS receptors on cells can significantly increase the adsorption and infection of authentic and pseudotyped SARS-CoV-2 viruses.

Irritable Bowel Syndrome: Treating the Gut and Brain/Mind at the Same Time.

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal (GI) disorders in the world. Although IBS does not affect a person's life span, it can significantly influence their quality of life. The treatment of IBS should be tailored to each patient's specific symptomatology because it can often be difficult to manage.

Identification of Confusing Medicine Proprietary Names: Toward Safe Medicine Use-A Cross-Sectional Study in Sri Lanka.

Background: Look-alike sound-alike (LASA) medications have similar pronunciation (phonetic) and/or manifestation (orthographic), which could create confusion among users and challenge the safe use of medicines. The availability of foreign products in local markets aggravates the situation. This study was designed to examine the registered medicine proprietary names in Sri Lanka to discern the presence of similar medicine names in the industry.

Endocytosis of red blood cell extracellular vesicles by macrophages leads to cytoplasmic heme release and prevents foam cell formation in atherosclerosis.

Extracellular vesicles (EVs) can be produced from red blood cells (RBCs) on a large scale and used to deliver therapeutic payloads efficiently. However, not much is known about the native biological properties of RBCEVs. Here, we demonstrate that RBCEVs are primarily taken up by macrophages and monocytes.

Nexus between carbon emissions, energy consumption, and economic growth: Evidence from global economies.

Renewable energy holds a remarkable role in clean energy adaptation due to the much lower carbon footprint it releases compared to other fossil fuels. It also has a positive impact by slowing down the rate of climate change. The study has examined the links between renewable and non-renewable energy use, CO2 emissions and economic growth in developed, developing, and LDCs and Economies in Transition between 1990 and 2019 in 152 countries.

Colon Cancer Screening Methods: 2023 Update.

Colorectal cancer (CRC) is a significant cause of morbidity and mortality worldwide. National screening guidelines have been implemented to identify and remove precancerous polyps before they become cancer. Routine CRC screening is advised for people with average risk starting at age 45 because it is a common and preventable malignancy.

Red blood cell extracellular vesicles deliver therapeutic siRNAs to skeletal muscles for treatment of cancer cachexia.

Cancer cachexia is a multifactorial syndrome characterized by a significant loss of skeletal muscle, which negatively affects the quality of life. Inhibition of myostatin (Mstn), a negative regulator of skeletal muscle growth and differentiation, has been proven to preserve muscle mass in muscle atrophy diseases, including cachexia. However, myostatin inhibitors have repeatedly failed clinical trials because of modest therapeutic effects and side effects due to the poor efficiency and toxicity of existing delivery methods.

Relative deprivation, inequality and the Covid-19 pandemic.

There is a growing concern that inequalities are hindering health outcomes. This paper's primary objective is to investigate the role of relative deprivation and inequality in explaining the daily spread of the Covid-19 pandemic. For this purpose, we use secondary cross-sectional data across 119 (developed and developing) countries from January 2020 - to April 2021.

Advances in Drug Delivery Systems Based on Red Blood Cells and Their Membrane-Derived Nanoparticles.

Red blood cells (RBCs) and RBC membrane-derived nanoparticles have been historically developed as bioinspired drug delivery systems to combat the issues of premature clearance, toxicity, and immunogenicity of synthetic nanocarriers. RBC-based delivery systems possess characteristics including biocompatibility, biodegradability, and long circulation time, which make them suited for systemic administration. Therefore, they have been employed in designing optimal drug formulations in various preclinical models and clinical trials to treat a wide range of diseases.

Endosomal escape of nucleic acids from extracellular vesicles mediates functional therapeutic delivery.

Extracellular vesicles hold great promise as a drug delivery platform for RNA-based therapeutics. However, there is a lack of experimental evidence for the intracellular trafficking of nucleic acid cargos, specifically, whether they are capable of escaping from the endolysosomal confinement in the recipient cells to be released into the cytosol and hence, interact with their cytoplasmic targets. Here, we demonstrated how red blood cell-derived extracellular vesicles (RBCEVs) release their therapeutic RNA/DNA cargos at specific intracellular compartments characteristic of late endosomes and lysosomes.

FAM3C in circulating tumor-derived extracellular vesicles promotes non-small cell lung cancer growth in secondary sites.

: Metastasis is a complex process with a molecular underpinning that remains unclear. We hypothesize that cargo proteins conducted by extracellular vesicles (EVs) released from tumors may confer growth and metastasis potential on recipient cells. Here, we report that a cytokine-like secreted protein, FAM3C, contributes to late-stage lung tumor progression.

A Comprehensive Review of Bradykinin-Induced Angioedema Versus Histamine-Induced Angioedema in the Emergency Department.

Angioedema (AE) is a condition that is frequently encountered in the emergency department (ED). It is a rare condition with localized, asymmetrical swelling of the skin and/or mucosa that is frequently nonpruritic and primarily affects locations with loose connective tissue. Physicians must have a thorough understanding of this condition since it can cause fatal airway compromise, which might be the presenting symptom.

Waking Up to Monkeypox in the Midst of COVID-19.

The first incidence of the monkeypox virus (MPXV) was reported in a Danish research facility. Even though first discovered in monkeys, rodents account for the largest reservoir of the disease. It is an encapsulated, brick-shaped double-stranded DNA virus strongly related to the smallpox virus.

, and to Prevent Type 2 Diabetes: An Integrative Review.

Diabetes mellitus has become a global pandemic progressively rising and affecting almost every household in all world regions. Diet is a significant root cause of type II diabetes; thus, the significance of dietary interventions in preventing and managing the disease cannot be neglected. Lowering the glycemic impact of diet is an alternative way of managing type II diabetes while improving insulin sensitivity.

Cucumis melo seed oil: agro-food by-product with natural anti-hyperlipidemic potential.

Background: Sweet melon (Cucumis melo) seed is generally considered as agro-waste, however, the current study aimed to use this waste as a valuable oil source. The seed oil extracted by two different extraction techniques (cold press and solvent extraction) was investigated for its anti-hyperlipidemic potential. Hyperlipidemic rabbits were fed on the diet supplemented with sweet melon seed oil for 6 weeks (42 days) and thoroughly examined for the change in their lipid profile.