Effects of LinTT1-peptide conjugation on the properties of poly(ethylene glycol)-block-(ε-caprolactone) nanoparticles prepared by the nanoprecipitation method.

Functionalization of polymer nanoparticles (NPs) with targeting peptides is of interest for drug delivery applications to enhance tumor accumulation and penetration. Herein, we evaluated the feasibility of two different methods for the attachment of a tumor-penetrating peptide LinTT1 (AKRGARSTA) to poly(ethylene glycol)-block-poly(ε-caprolactone) (PCL-PEG) NPs: (1) "post-conjugation" onto pre-formed nanoparticles, and (2) "pre-conjugation", the synthesis and purification of peptide-polymer conjugates and subsequent nanoprecipitation of the conjugates diluted with non-functionalized polymers. Conjugation of the labelled peptide via maleimide-thiol chemistry was verified by gel permeation chromatography (GPC) and fluorescence measurements.

Guruism and Cultic Social Dynamics in Psychedelic Practices and Organisations.

This chapter explores the risks of guruism and cultic social dynamics in organisations that work with psychedelic drugs, which include therapist offices, clinics, research departments, retreat centres, training programmes, NGOs, underground ceremonies and new religious movements. It has been hypothesised, and argued by experienced practitioners, that psychedelics can increase suggestibility, amplify transference and facilitate an intense form of projective mechanisms in the recipients. They may thereby lead to ego-inflation and feelings of grandiosity and omnipotence in those giving the drugs and intensify cultic social dynamics in psychedelic communities - all of which can create conditions that make cases of harm and misconduct more likely to occur and go unreported.

God Knows Best: Exploring the God Locus of Health Control, Race-Ethnicity, and Risk-Taking and Protective Behaviors Interrelationship in the USA.

The health implications of engaging in risk-taking or protective behaviors can have long-lasting effects on an individual's life. In recent years, there has been a growing interest in how religious attitudes and beliefs influence an individual's health behaviors. However, research on the role of the God Locus of Health Control (GLHC) in the religion-health literature is lacking.

Cardiac conduction system regeneration prevents arrhythmias after myocardial infarction.

Arrhythmias are a hallmark of myocardial infarction (MI) and increase patient mortality. How insult to the cardiac conduction system causes arrhythmias following MI is poorly understood. Here, we demonstrate conduction system restoration during neonatal mouse heart regeneration versus pathological remodeling at non-regenerative stages.

Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial.

New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.

Clinicogenomic landscape of pancreatic adenocarcinoma identifies KRAS mutant dosage as prognostic of overall survival.

Nearly all pancreatic adenocarcinomas (PDAC) are genomically characterized by KRAS exon 2 mutations. Most patients with PDAC present with advanced disease and are treated with cytotoxic therapy. Genomic biomarkers prognostic of disease outcomes have been challenging to identify.

Evaluating generalizability of oncology trial results to real-world patients using machine learning-based trial emulations.

Randomized controlled trials (RCTs) evaluating anti-cancer agents often lack generalizability to real-world oncology patients. Although restrictive eligibility criteria contribute to this issue, the role of selection bias related to prognostic risk remains unclear. In this study, we developed TrialTranslator, a framework designed to systematically evaluate the generalizability of RCTs for oncology therapies.

Sustained virologic suppression of multidrug-resistant HIV in an individual treated with anti-CD4 domain 1 antibody and lenacapavir.

The clinical management of people with multidrug-resistant (MDR) human immunodeficiency virus (HIV) remains challenging despite continued development of antiretroviral agents. A 58-year-old male individual with MDR HIV and Kaposi sarcoma (KS) was treated with a new antiretroviral regimen consisting of anti-CD4 domain 1 antibody UB-421 and capsid inhibitor lenacapavir. The individual experienced delayed but sustained suppression of plasma viremia and a substantial increase in the CD4 T cell count.

Large floods drive changes in cause-specific mortality in the United States.

Flooding greatly endangers public health and is an urgent concern as rapid population growth in flood-prone regions and more extreme weather events will increase the number of people at risk. However, an exhaustive analysis of mortality following floods has not been conducted. Here we used 35.

Proteomic changes upon treatment with semaglutide in individuals with obesity.

Obesity and type 2 diabetes are prevalent chronic diseases effectively managed by semaglutide. Here we studied the effects of semaglutide on the circulating proteome using baseline and end-of-treatment serum samples from two phase 3 trials in participants with overweight or obesity, with or without diabetes: STEP 1 (n = 1,311) and STEP 2 (n = 645). We identified evidence supporting broad effects of semaglutide, implicating processes related to body weight regulation, glycemic control, lipid metabolism and inflammatory pathways.

Deciphering the core shunt mechanism in Arabidopsis cuticular wax biosynthesis and its role in plant environmental adaptation.

Plant cuticular waxes serve as highly responsive adaptations to variable environments. Aliphatic waxes consist of very-long-chain (VLC) compounds produced from 1-alcohol- or alkane-forming pathways. The existing variation in 1-alcohols and alkanes across Arabidopsis accessions revealed that 1-alcohol amounts are negatively correlated with aridity factors, whereas alkanes display the opposite behaviour.

Pan-phylum genomes of hornworts reveal conserved autosomes but dynamic accessory and sex chromosomes.

Hornworts, one of the three bryophyte phyla, show some of the deepest divergences in extant land plants, with some families separated by more than 300 million years. Previous hornwort genomes represented only one genus, limiting the ability to infer evolution within hornworts and their early land plant ancestors. Here we report ten new chromosome-scale genomes representing all hornwort families and most of the genera.

Hornworts reveal a spatial model for pyrenoid-based CO-concentrating mechanisms in land plants.

Pyrenoid-based CO-concentrating mechanisms (pCCMs) turbocharge photosynthesis by saturating CO around Rubisco. Hornworts are the only land plants with a pCCM. Owing to their closer relationship to crops, hornworts could offer greater translational potential than the green alga Chlamydomonas, the traditional model for studying pCCMs.

MTCH2 controls energy demand and expenditure to fuel anabolism during adipogenesis.

Mitochondrial carrier homolog 2 (MTCH2) is a regulator of apoptosis, mitochondrial dynamics, and metabolism. Loss of MTCH2 results in mitochondrial fragmentation, an increase in whole-body energy utilization, and protection against diet-induced obesity. In this study, we used temporal metabolomics on HeLa cells to show that MTCH2 deletion results in a high ATP demand, an oxidized cellular environment, and elevated utilization of lipids, amino acids, and carbohydrates, accompanied by a decrease in several metabolites.

A bipartite bacterial virulence factor targets the complement system and neutrophil activation.

The complement system and neutrophils constitute the two main pillars of the host innate immune defense against infection by bacterial pathogens. Here, we identify T-Mac, a novel virulence factor of the periodontal pathogen Treponema denticola that allows bacteria to evade both defense systems. We show that T-Mac is expressed as a pre-protein that is cleaved into two functional units.

Partitioning of fatty acids between membrane and storage lipids controls ER membrane expansion.

Biogenesis of membrane-bound organelles involves the synthesis, remodeling, and degradation of their constituent phospholipids. How these pathways regulate organelle size remains poorly understood. Here we demonstrate that a lipid-degradation pathway inhibits expansion of the endoplasmic reticulum (ER) membrane.

Hypoxia promotes tumor immune evasion by suppressing MHC-I expression and antigen presentation.

Hypoxia is a common feature of solid tumors that has previously been linked to resistance to radiotherapy and chemotherapy, and more recently to immunotherapy. In particular, hypoxic tumors exclude T cells and inhibit their activity, suggesting that tumor cells acquire a mechanism to evade T-cell recognition and killing. Our analysis of hypoxic tumors indicates that hypoxia downregulates the expression of MHC class I and its bound peptides (i.

Chaperone-mediated insertion of mitochondrial import receptor TOM70 protects against diet-induced obesity.

Outer mitochondrial membrane (OMM) proteins communicate with the cytosol and other organelles, including the endoplasmic reticulum. This communication is important in thermogenic adipocytes to increase the energy expenditure that controls body temperature and weight. However, the regulatory mechanisms of OMM protein insertion are poorly understood.

Duration of cryostorage is not associated with rates of thaw survival, fertilization, blastulation and ploidy, or pregnancy outcomes of vitrified human oocytes.

Purpose: This study is to evaluate duration of oocyte cryostorage and association with thaw survival, fertilization, blastulation, ploidy rates, and pregnancy outcomes in patients seeking fertility preservation.

Methods: Retrospective cohort study to evaluate clinical outcomes in patients who underwent fertility preservation from 2011 to 2023 via oocyte vitrification for non-oncologic indications. Primary outcome was thaw survival rate.