Direct optical measurement of intramolecular distances with angstrom precision.

Optical investigations of nanometer distances between proteins, their subunits, or other biomolecules have been the exclusive prerogative of Förster resonance energy transfer (FRET) microscopy for decades. In this work, we show that MINFLUX fluorescence nanoscopy measures intramolecular distances down to 1 nanometer-and in planar projections down to 1 angstrom-directly, linearly, and with angstrom precision. Our method was validated by quantifying well-characterized 1- to 10-nanometer distances in polypeptides and proteins.

Inflammation in a ferroptotic environment.

Ferroptosis is an iron-dependent form of cell death, which finally culminates in lipid peroxidation and membrane damage. During the past decade, the interest in ferroptosis increased substantially and various regulatory components were discovered. The role of ferroptosis during inflammation and its impact on different immune cell populations is still under debate.

Machine learning and biological validation identify sphingolipids as potential mediators of paclitaxel-induced neuropathy in cancer patients.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a serious therapy-limiting side effect of commonly used anticancer drugs. Previous studies suggest that lipids may play a role in CIPN. Therefore, the present study aimed to identify the particular types of lipids that are regulated as a consequence of paclitaxel administration and may be associated with the occurrence of post-therapeutic neuropathy.

The German research consortium for the study of bipolar disorder (BipoLife): a quality assurance protocol for MR neuroimaging data.

Background: The German multicenter research consortium BipoLife aims to investigate the mechanisms underlying bipolar disorders. It focuses in particular on people at high risk of developing the disorder and young patients in the early stages of the disease. Functional and structural magnetic resonance imaging (MRI) data was collected in all participating centers.

Spectrum of Pathogens in Surgical Site Infections after Sarcoma Resection in the Peri-Pelvic and Pelvic Region. Distinct Location, Distinct Infection?

Soft tissue sarcomas (STS) often occur in the peri-pelvic region (proximal thigh, groin, gluteal region). A common complication following resection of STS is surgical site infection (SSI). The peri-pelvic site appears to be particularly problematic.

Serine ubiquitination of SQSTM1 regulates NFE2L2-dependent redox homeostasis.

The KEAP1-NFE2L2 axis is essential for the cellular response against metabolic and oxidative stress. KEAP1 is an adaptor protein of CUL3 (cullin 3) ubiquitin ligase that controls the cellular levels of NFE2L2, a critical transcription factor of several cytoprotective genes. Oxidative stress, defective autophagy and pathogenic infections activate NFE2L2 signaling through phosphorylation of the autophagy receptor protein SQSTM1, which competes with NFE2L2 for binding to KEAP1.

SAR Study of 4,8-Disubstituted Pyrimido[5,4-]pyrimidines Exhibiting Antitrypanosomal and Antileishmanial Activity.

A set of new derivatives of 4,8-disubstituted pyrimido[5,4-]pyrimidines were efficiently synthesized and evaluated against and promastigotes and intramacrophage amastigotes. The cytotoxicity was determined using the THP-1 cell line, and early ADME-Tox was carried out using assays for cytotoxicity (A549 and HEK293 cell lines) and CYP3A4 and hERG cardiotoxicity liabilities. All the new compounds were active against (0.

HIV, malnutrition, and noncommunicable disease epidemics among tuberculosis-affected households in east and southern Africa: A cross-sectional analysis of the ERASE-TB cohort.

Background: As a result of shared social and structural risk factors, people in households affected by tuberculosis may have an increased risk of chronic conditions; at the same time, tuberculosis screening may be an opportunity for interventions. We sought to describe the prevalence of HIV, nutritional disorders, and noncommunicable diseases (NCDs) among members of tuberculosis-affected households in 3 African countries.

Methods And Findings: A part of a multicountry cohort study, we screened for tuberculosis, HIV, nutritional disorders (underweight, anaemia, overweight/obesity), and NCDs (diabetes, hypertension, and chronic lung disease) among members of tuberculosis-affected households aged ≥10 years in Mozambique, Tanzania, and Zimbabwe.

The Contribution of Mast Cells to the Regulation of Elastic Fiber Tensometry in the Skin Dermis of Children with Marfan Syndrome.

Marfan syndrome (MFS) is a hereditary condition accompanied by disorders in the structural and regulatory properties of connective tissue, including elastic fibers, due to a mutation in the gene encodes for fibrillin-1 protein (FBN1 gene) and the synthesis of abnormal fibrillin-1 glycoprotein. Despite the high potential of mast cells (MCs) to remodel the extracellular matrix (ECM), their pathogenetic significance in MFS has not been considered yet. The group of patients with Marfan syndrome included two mothers and five children (three girls aged 4, 11, and 11 and two boys aged 12 and 13).

MultiMatch: geometry-informed colocalization in multi-color super-resolution microscopy.

With recent advances in multi-color super-resolution light microscopy, it is possible to simultaneously visualize multiple subunits within biological structures at nanometer resolution. To optimally evaluate and interpret spatial proximity of stainings on such an image, colocalization analysis tools have to be able to integrate prior knowledge on the local geometry of the recorded biological complex. We present MultiMatch to analyze the abundance and location of chain-like particle arrangements in multi-color microscopy based on multi-marginal optimal unbalanced transport methodology.

Automated design of multi-target ligands by generative deep learning.

Generative deep learning models enable data-driven de novo design of molecules with tailored features. Chemical language models (CLM) trained on string representations of molecules such as SMILES have been successfully employed to design new chemical entities with experimentally confirmed activity on intended targets. Here, we probe the application of CLM to generate multi-target ligands for designed polypharmacology.

Impact of blood glucose on cognitive function in insulin resistance: novel insights from ambulatory assessment.

Background/objectives: Insulin resistance (IR)-related disorders and cognitive impairment lead to reduced quality of life and cause a significant strain on individuals and the public health system. Thus, we investigated the effects of insulin resistance (IR), and blood glucose fluctuations on cognitive function under laboratory and free-living conditions, using ecological momentary assessment (EMA).

Subjects/methods: Baseline assessments included neuropsychological tests and blood analysis.

Intranasal Versus Oral Treatments for Allergic Rhinitis: A Systematic Review With Meta-Analysis.

Background: Treatments for allergic rhinitis include intranasal or oral medications.

Objective: To perform a systematic review with meta-analysis comparing the effectiveness of intranasal corticosteroids or antihistamines versus oral antihistamines or leukotriene receptor antagonists in improving allergic rhinitis symptoms and quality of life.

Methods: We searched four bibliographic databases and three clinical trial datasets for randomized controlled trials (1) assessing patients aged 12 years and older with seasonal or perennial allergic rhinitis, and (2) comparing intranasal corticosteroids or antihistamines versus oral antihistamines or leukotriene receptor antagonists.