Roseburia intestinalis-derived butyrate alleviates neuropathic pain.

Approximately 20% of patients with shingles develop postherpetic neuralgia (PHN). We investigated the role of gut microbiota in shingle- and PHN-related pain. Patients with shingles or PHN exhibited significant alterations in their gut microbiota with microbial markers predicting PHN development among patients with shingles.

N-Linked Fucosylated Glycans Are Biomarkers for Prostate Cancer with a Neuroendocrine and Metastatic Phenotype.

Prostate cancer is a heterogeneous disease with a spectrum of pathology and outcomes ranging from indolent to lethal. Although there have been recent advancements in prognostic tissue biomarkers, limitations still exist. We leveraged matrix-assisted laser desorption/ionization imaging of formalin-fixed, paraffin embedded prostate cancer specimens to determine if N-linked glycans expressed in the extracellular matrix of lethal neuroendocrine prostate cancer were also expressed in conventional prostate adenocarcinomas that were associated with poor outcomes.

DEK regulates B-cell proliferative capacity and is associated with aggressive disease in low-grade B-cell lymphomas.

This study sheds light on the pivotal role of the oncoprotein DEK in B-cell lymphoma. We reveal DEK expression correlates with increased tumor proliferation and inferior overall survival in cases diagnosed with low-grade B-cell lymphoma (LGBCL). We also found significant correlation between DEK expression and copy number alterations in LGBCL tumors, highlighting a novel mechanism of LGBCL pathogenesis that warrants additional exploration.

Single vs. multi-slice assessments of in vivo placental T2∗ measurements.

Introduction: Placental health is vital for maternal and fetal well-being, and placental T2∗ has been suggested to identify in vivo placental dysfunction prior to delivery. However, ideal regions of interest to best inform functional assessments of the placenta remain unknown. The aim of this study is to compare global and slice-wise measures of in-vivo placental T2∗ assessments.

Difluoromethoxide Is a Strong Leaving Group in the Photoredox Deoxyradiofluorination of 2-Phenylpyridines.

A 2-phenyl-3-difluoromethoxy-pyridinyl moiety features in potent phosphodiesterase 4D inhibitors that are considered to be candidate radiotracers for positron emission tomography if they are labeled with fluorine-18. Fluorine-18 could be installed as desired at the 3'-phenyl position with acridinium-mediated photoredox radiodeoxyfluorination in homologues bearing variously substituted 3'-aryloxy groups. However, a distal 3-difluoromethoxide (-OCHF) group strongly competes as a leaving group, especially when an electron-deficient aryloxy group is present at position 3'.

LoMAE: Simple Streamlined Low-Level Masked Autoencoders for Robust, Generalized, and Interpretable Low-Dose CT Denoising.

Low-dose computed tomography (LDCT) offers reduced X-ray radiation exposure but at the cost of compromised image quality, characterized by increased noise and artifacts. Recently, transformer models emerged as a promising avenue to enhance LDCT image quality. However, the success of such models relies on a large amount of paired noisy and clean images, which are often scarce in clinical settings.

Deficient RPE mitochondrial energetics leads to subretinal fibrosis in age-related neovascular macular degeneration.

Subretinal fibrosis permanently impairs the vision of patients with neovascular age-related macular degeneration. Despite emerging evidence revealing the association between disturbed metabolism in retinal pigment epithelium (RPE) and subretinal fibrosis, the underlying mechanism remains unclear. In the present study, single-cell RNA sequencing revealed, prior to subretinal fibrosis, genes in mitochondrial fatty acid oxidation are downregulated in the RPE lacking very low-density lipoprotein receptor (VLDLR), especially the rate-limiting enzyme carnitine palmitoyltransferase 1A (CPT1A).

Disrupted brain functional connectivity as early signature in cognitively healthy individuals with pathological CSF amyloid/tau.

Alterations in functional connectivity (FC) have been observed in individuals with Alzheimer's disease (AD) with elevated amyloid (Aβ) and tau. However, it is not yet known whether directed FC is already influenced by Aβ and tau load in cognitively healthy (CH) individuals. A 21-channel electroencephalogram (EEG) was used from 46 CHs classified based on cerebrospinal fluid (CSF) Aβ tau ratio: pathological (CH-PAT) or normal (CH-NAT).

Tetrachloromaxamycins: Divergent Total Synthesis and Initial Assessments.

Divergent total syntheses of binding pocket and peripherally modified tetrachlorovancomycins, a non-native synthetic glycopeptide, and their evaluation are disclosed. Central to the approach is the synthesis of a single late-stage intermediate that bears a residue 4 thioamide ([Ψ[C(═S)NH]Tpg]tetrachlorovancomycin (), LLS 15 steps, 14% overall) as a precursor to either of two key pocket modifications and their pairing with any combination of two peripheral modifications conducted without protecting groups. A stereochemical simplification achieved by the addition of two aryl chlorides removes two synthetically challenging atropisomer centers in native glycopeptides and streamlines the synthesis.

Direct Visualization of Molecular Stacking in Quasi-2D Hexagonal Ice.

Understanding ice nucleation and growth is of great interest to researchers due to its importance in the biological, cryopreservation, and environmental fields. However, microstructural investigations of ice on the molecular scale are still lacking. In this paper, a simple method is proposed to prepare quasi-2-dimensional ice I films, which have been characterized via cryogenic transmission electron microscope.

Transglutaminase 2-mediated histone monoaminylation and its role in cancer.

Transglutaminase 2 (TGM2) has been known as a well-characterized factor regulating the progression of multiple types of cancer, due to its multifunctional activities and the ubiquitous signaling pathways it is involved in. As a member of the transglutaminase family, TGM2 catalyzes protein post-translational modifications (PTMs), including monoaminylation, amide hydrolysis, cross-linking, etc., through the transamidation of variant glutamine-containing protein substrates.

Characterizing Relationships between T-cell Inflammation and Outcomes in Patients with High-Risk Neuroblastoma According to Mesenchymal and Adrenergic Signatures.

Unlabelled: Recent insights have identified adrenergic (ADRN) and mesenchymal (MES) cell lineages as distinct biologic cell types and T-cell inflammation as a prognostic marker in neuroblastoma. We hypothesized that elucidating unique and overlapping aspects of these biologic features could serve as novel biomarkers for informing ongoing efforts to improve therapeutic approaches for children with high-risk neuroblastoma. We identified lineage-specific, single-stranded super-enhancers to define ADRN and MES specific genes.

Advances in Vaccines for Melanoma.

Personalized neoantigen vaccines have achieved major advancements in recent years, with studies in melanoma leading progress in the field. Early clinical trials have demonstrated their feasibility, safety, immunogenicity, and potential efficacy. Advances in sequencing technologies and neoantigen prediction algorithms have substantively improved the identification and prioritization of neoantigens.

Racial and Ethnic Differences in the Prevalence of Severe Aortic Stenosis by Echocardiography.

Background: Understanding the burden of aortic stenosis (AS) across diverse racial and ethnic populations is important to ensure equitable resource allocation. This study explored whether severe AS rate varies by race and ethnicity.

Methods: The rates of severe AS, stratified by race and ethnicity, were calculated among 615,038 adults with a transthoracic echocardiogram.

PostFocus: automated selective post-acquisition high-throughput focus restoration using diffusion model for label-free time-lapse microscopy.

Motivation: High-throughput time-lapse imaging is a fundamental tool for efficient living cell profiling at single-cell resolution. Label-free phase-contrast video microscopy enables noninvasive, nontoxic, and long-term imaging. The tradeoff between speed and throughput, however, implies that despite the state-of-the-art autofocusing algorithms, out-of-focus cells are unavoidable due to the migratory nature of immune cells (velocities >10 μm/min).

Clinicopathologic Dissociation: Robust Lafora Body Accumulation in Malin KO Mice Without Observable Changes in Home-Cage Behavior.

Lafora disease (LD) is a syndrome of progressive myoclonic epilepsy and cumulative neurocognitive deterioration caused by recessively inherited genetic lesions of EPM2A (laforin) or NHLRC1 (malin). Neuropsychiatric symptomatology in LD is thought to be directly downstream of neuronal and astrocytic polyglucosan aggregates, termed Lafora bodies (LBs), which faithfully accumulate in an age-dependent manner in all mouse models of LD. In this study, we applied home-cage monitoring to examine the extent of neurobehavioral deterioration in a model of malin-deficient LD as a means to identify robust preclinical endpoints that may guide the selection of novel genetic treatments.

Development of PainFace software to simplify, standardize, and scale up mouse grimace analyses.

Facial grimacing is used to quantify spontaneous pain in mice and other mammals, but scoring relies on humans with different levels of proficiency. Here, we developed a cloud-based software platform called PainFace ( http://painface.net ) that uses machine learning to detect 4 facial action units of the mouse grimace scale (orbitals, nose, ears, whiskers) and score facial grimaces of black-coated C57BL/6 male and female mice on a 0 to 8 scale.

Chemical genetic screens reveal defective lysosomal trafficking as synthetic lethal with NF1 loss.

Neurofibromatosis type 1, a genetic disorder caused by pathogenic germline variations in NF1, predisposes individuals to the development of tumors, including cutaneous and plexiform neurofibromas (CNs and PNs), optic gliomas, astrocytomas, juvenile myelomonocytic leukemia, high-grade gliomas and malignant peripheral nerve sheath tumors (MPNSTs), which are chemotherapy- and radiation-resistant sarcomas with poor survival. Loss of NF1 also occurs in sporadic tumors, such as glioblastoma (GBM), melanoma, breast, ovarian and lung cancers. We performed a high-throughput screen for compounds that were synthetic lethal with NF1 loss, which identified several leads, including the small molecule Y102.

Exosomal Thomsen-Friedenreich Glycoantigen: A New Liquid Biopsy Biomarker for Lung and Breast Cancer Diagnoses.

Unlabelled: Exosomes are nanosized extracellular vesicles released by cells to transport biomolecules such as proteins and RNAs for intercellular communication. Exosomes play important roles in cancer development and metastasis; therefore, they have emerged as potential liquid biopsy biomarkers for cancer screening, diagnosis, and management. Many exosome cargos, including proteins, RNAs, and lipids, have been extensively investigated as biomarkers for cancer liquid biopsy.

Consequences of ionizing radiation exposure to the cardiovascular system.

Ionizing radiation is widely used in various industrial and medical applications, resulting in increased exposure for certain populations. Lessons from radiation accidents and occupational exposure have highlighted the cardiovascular and cerebrovascular risks associated with radiation exposure. In addition, radiation therapy for cancer has been linked to numerous cardiovascular complications, depending on the distribution of the dose by volume in the heart and other relevant target tissues in the circulatory system.