Global profiling reveals common and distinct N6-methyladenosine (m6A) regulation of innate immune responses during bacterial and viral infections.

N-methyladenosine (mA) is a dynamic post-transcriptional RNA modification influencing all aspects of mRNA biology. While mA modifications during numerous viral infections have been described, the role of mA in innate immune response remains unclear. Here, we examined cellular mA epitranscriptomes during infections of Pseudomonas aeruginosa and herpes simplex virus type 1 (HSV-1), and lipopolysaccharide (LPS) stimulation to identify mA-regulated innate immune response genes.

Hepatic recruitment of eosinophils and their protective function during acute liver injury.

Background & Aims: Beyond the classical description of eosinophil functions in parasite infections and allergic diseases, emerging evidence supports a critical role of eosinophils in resolving inflammation and promoting tissue remodeling. However, the role of eosinophils in liver injury and the underlying mechanism of their recruitment into the liver remain unclear.

Methods: Hepatic eosinophils were detected and quantified using flow cytometry and immunohistochemical staining.

Peritoneal Dialysis Catheter Placement: Percutaneous and Peritoneoscopic Techniques.

Chronic peritoneal dialysis (PD) is an underutilized renal replacement therapy in treating end-stage renal disease that has several advantages over hemodialysis. The success of continuous ambulatory PD is largely dependent on a functional long-term access to the peritoneal cavity. Several methods have been developed to place the PD catheter using both surgical and percutaneous techniques.

Social networks, high-risk anal HPV and coinfection with HIV in young sexual minority men.

Objectives: Young sexual minority men (SMM) exhibit a high prevalence and incidence of high-risk genotypes of human papillomavirus (hrHPV) anal infections and a confluence of a high prevalence of HIV and rectal STIs. Social determinants of health (SDOHs) are linked to social network contexts that generate and maintain racial disparities in HIV and STIs. A network perspective was provided to advance our knowledge of drivers of genotype-specific hrHPV infection and coinfection with HIV.

Popularity of Delta-8 THC on the Internet Across US States, 2021.

To assess the popularity of an emergent drug, delta-8 tetrahydrocannabinol (THC), and compare interest levels between US states with or without legalized recreational cannabis. We used Google Trends to assess the growth of interest among delta-8 THC-related search terms from May 17, 2020, to May 9, 2021. We examined differences between states with or without legalized cannabis using state-level Google Trends data from February 13 to May 13, 2021, and policy data from the National Conference of State Legislatures.

An estrogen-sensitive hypothalamus-midbrain neural circuit controls thermogenesis and physical activity.

Estrogen receptor–α (ERα) expressed by neurons in the ventrolateral subdivision of the ventromedial hypothalamic nucleus (ERα) regulates body weight in females, but the downstream neural circuits mediating this biology remain largely unknown. Here we identified a neural circuit mediating the metabolic effects of ERα neurons. We found that selective activation of ERα neurons stimulated brown adipose tissue (BAT) thermogenesis, physical activity, and core temperature and that ERα neurons provide monosynaptic glutamatergic inputs to 5-hydroxytryptamine (5-HT) neurons in the dorsal raphe nucleus (DRN).

2-Hydroxyglutarate destabilizes chromatin regulatory landscape and lineage fidelity to promote cellular heterogeneity.

The epigenome delineates lineage-specific transcriptional programs and restricts cell plasticity to prevent non-physiological cell fate transitions. Although cell diversification fosters tumor evolution and therapy resistance, upstream mechanisms that regulate the stability and plasticity of the cancer epigenome remain elusive. Here we show that 2-hydroxyglutarate (2HG) not only suppresses DNA repair but also mediates the high-plasticity chromatin landscape.

Polygenic risk prediction based on singular value decomposition with applications to alcohol use disorder.

Background/aim: The polygenic risk score (PRS) shows promise as a potentially effective approach to summarize genetic risk for complex diseases such as alcohol use disorder that is influenced by a combination of multiple variants, each of which has a very small effect. Yet, conventional PRS methods tend to over-adjust confounding factors in the discovery sample and thus have low power to predict the phenotype in the target sample. This study aims to address this important methodological issue.

Biomarkers for sepsis: more than just fever and leukocytosis-a narrative review.

A biomarker describes a measurable indicator of a patient's clinical condition that can be measured accurately and reproducibly. Biomarkers offer utility for diagnosis, prognosis, early disease recognition, risk stratification, appropriate treatment (theranostics), and trial enrichment for patients with sepsis or suspected sepsis. In this narrative review, we aim to answer the question, "Do biomarkers in patients with sepsis or septic shock predict mortality, multiple organ dysfunction syndrome (MODS), or organ dysfunction?" We also discuss the role of pro- and anti-inflammatory biomarkers and biomarkers associated with intestinal permeability, endothelial injury, organ dysfunction, blood-brain barrier (BBB) breakdown, brain injury, and short and long-term mortality.

Noradrenergic terminal short-term potentiation enables modality-selective integration of sensory input and vigilance state.

Recent years have seen compelling demonstrations of the importance of behavioral state on sensory processing and attention. Arousal plays a dominant role in controlling brain-wide neural activity patterns, particularly through modulation by norepinephrine. Noradrenergic brainstem nuclei, including locus coeruleus, can be activated by stimuli of multiple sensory modalities and broadcast modulatory signals via axonal projections throughout the brain.

Glycogen Storage Disease Type Ia: Current Management Options, Burden and Unmet Needs.

Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. Affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and kidney, putting them at risk of severe hypoglycaemia and secondary metabolic perturbations. Good glycaemic/metabolic control through strict dietary treatment and regular doses of uncooked cornstarch (UCCS) is essential for preventing hypoglycaemia and long-term complications.

Diet Inflammatory Index and Dementia Incidence: A Population-Based Study.

Background And Objectives: Aging is characterized by a functional shift of the immune system toward a proinflammatory phenotype. This derangement has been associated with cognitive decline and has been implicated in the pathogenesis of dementia. Diet can modulate systemic inflammation; thus, it may be a valuable tool to counteract the associated risk for cognitive impairment and dementia.

Myeloid-Specific Deficiency of Reduces Inflammation by Remodeling Phospholipids and Reducing Production of Arachidonic Acid-Derived Proinflammatory Lipid Mediators.

In response to infection or tissue damage, resident peritoneal macrophages (rpMACs) produce inflammatory lipid mediators from the polyunsaturated fatty acid (PUFA), arachidonic acid (AA). Long-chain acyl-CoA synthetase 4 (ACSL4) catalyzes the covalent addition of a CoA moiety to fatty acids, with a strong preference for AA and other PUFAs containing three or more double bonds. PUFA-CoA can be incorporated into phospholipids, which is the source of PUFA for lipid mediator synthesis.

Association between the CLOCK gene polymorphism and depressive symptom mediated by sleep quality among non-clinical Chinese Han population.

Background: Depression is a common mental disorder associated with sleep problems and the circadian clock genes may underlie the relationship between the two in clinical samples. However, little is known about whether poor sleep quality is associated with depressive symptom in healthy individuals and whether is mediated by specific single-nucleotide polymorphisms (SNPs).

Methods: Using a cross-sectional design, 444 university staff members were randomly recruited in Beijing.

Marine Brominated Tyrosine Alkaloids as Promising Inhibitors of SARS-CoV-2.

There have been more than 150 million confirmed cases of SARS-CoV-2 since the beginning of the pandemic in 2019. By June 2021, the mortality from such infections approached 3.9 million people.

Overcoming Gemcitabine Resistance in Pancreatic Cancer Using the BCL-X-Specific Degrader DT2216.

Pancreatic cancer is the third most common cause of cancer-related deaths in the United States. Although gemcitabine is the standard of care for most patients with pancreatic cancer, its efficacy is limited by the development of resistance. This resistance may be attributable to the evasion of apoptosis caused by the overexpression of BCL-2 family antiapoptotic proteins.

Statistical reanalysis of vascular event outcomes in primary and secondary vascular prevention trials.

Background: Vascular prevention trials typically use dichotomous event outcomes although this may be inefficient statistically and gives no indication of event severity. We assessed whether ordinal outcomes would be more efficient and how to best analyse them.

Methods: Chief investigators of vascular prevention randomised controlled trials that showed evidence of either benefit or harm, or were included in a systematic review that overall showed benefit or harm, shared individual participant data from their trials.

NRF1 association with AUTS2-Polycomb mediates specific gene activation in the brain.

The heterogeneous family of complexes comprising Polycomb repressive complex 1 (PRC1) is instrumental for establishing facultative heterochromatin that is repressive to transcription. However, two PRC1 species, ncPRC1.3 and ncPRC1.

The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin.

The epidemiology of invasive fungal infections is changing, with new populations at risk and the emergence of resistance caused by the selective pressure from increased usage of antifungal agents in prophylaxis, empiric therapy, and agriculture. Limited antifungal therapeutic options are further challenged by drug-drug interactions, toxicity, and constraints in administration routes. Despite the need for more antifungal drug options, no new classes of antifungal drugs have become available over the last 2 decades, and only one single new agent from a known antifungal class has been approved in the last decade.

Non-myeloablative umbilical cord blood transplantation for atypical dyskeratosis congenita.

Background: Short telomere syndrome (STS) in children may result in phenotypically heterogenous clinical spectrum ranging from completely asymptomatic to typical dyskeratosis congenita (DC). Patients with this cancer predisposition syndrome may have multiple organ dysfunctions including pulmonary fibrosis, liver cirrhosis, and bone marrow failure. Not all mutations in telomerase or telomere genes have been identified, and STS may pose a diagnostic and management challenge.

Efficacy and safety of gemcitabine plus doxorubicin in patients with renal medullary carcinoma.

Introduction: Renal medullary carcinoma (RMC) is a rare and lethal renal cell carcinoma characterized by the loss of tumor suppressor SMARCB1. Molecular profiling studies have suggested that RMC cells may be vulnerable to therapies that generate DNA damage, such as the combination of the nucleoside analog gemcitabine, and topoisomerase inhibitor doxorubicin.

Patients And Methods: We retrospectively analyzed the records of patients with RMC treated with gemcitabine plus doxorubicin at our institution between January 2005 and September 2020.

A selective antibiotic for Lyme disease.

Lyme disease is on the rise. Caused by a spirochete Borreliella burgdorferi, it affects an estimated 500,000 people in the United States alone. The antibiotics currently used to treat Lyme disease are broad spectrum, damage the microbiome, and select for resistance in non-target bacteria.

Inhibition of SARS-CoV-2 polymerase by nucleotide analogs from a single-molecule perspective.

The absence of 'shovel-ready' anti-coronavirus drugs during vaccine development has exceedingly worsened the SARS-CoV-2 pandemic. Furthermore, new vaccine-resistant variants and coronavirus outbreaks may occur in the near future, and we must be ready to face this possibility. However, efficient antiviral drugs are still lacking to this day, due to our poor understanding of the mode of incorporation and mechanism of action of nucleotides analogs that target the coronavirus polymerase to impair its essential activity.