Multimodal integration of blood RNA and ctDNA reflects response to immunotherapy in metastatic urothelial cancer.

Background: Previously, we demonstrated that changes in circulating tumor DNA (ctDNA) are promising biomarkers for early response prediction (ERP) to immune checkpoint inhibitors (ICI) in metastatic urothelial cancer (mUC). In this study, we investigated the value of whole blood immunotranscriptomics for ERP-ICI and integrated both biomarkers into a multimodal model to boost accuracy.

Methods: Blood samples of 93 patients were collected at baseline and after 2-6 weeks of ICI for ctDNA (N=88) and immunotranscriptome (N=79) analyses.

HoxBlinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98-rearranged leukemia.

Although nucleoporin 98 (NUP98) fusion oncogenes often drive aggressive pediatric leukemia by altering chromatin structure and expression of HOX genes, underlying mechanisms remain elusive. Here, we report that a Hoxb-associated lncRNA HoxBlinc was aberrantly activated in NUP98-PHF23 fusion-driven leukemias. HoxBlinc chromatin occupancies led to elevated MLL1 recruitment and aberrant homeotic topologically associated domains (TADs) that enhanced chromatin accessibilities and activated homeotic/hematopoietic oncogenes.

Aerobic exercise prevents renal osteodystrophy via irisin-activated osteoblasts.

Renal osteodystrophy is commonly seen in patients with chronic kidney disease (CKD) due to disrupted mineral homeostasis. Given the impaired renal function in these patients, common anti-resorptive agents, including bisphosphonates, must be used with caution or even contraindicated. Therefore, an alternative therapy without renal burden to combat renal osteodystrophy is urgently needed.

Elevated protein lactylation promotes immunosuppressive microenvironment and therapeutic resistance in pancreatic ductal adenocarcinoma.

Metabolic reprogramming shapes tumor microenvironment (TME) and may lead to immunotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Elucidating the impact of pancreatic cancer cell metabolism in the TME is essential to therapeutic interventions. "Immune cold" PDAC is characterized by elevated lactate levels resulting from tumor cell metabolism, abundance of pro-tumor macrophages, and reduced cytotoxic T cell in the TME.

Interplay between Skeletal Muscle Catabolism and Remodeling of Arteriovenous Fistula via YAP1 Signaling.

Background: Arteriovenous (AV) fistulas are the preferred access for dialysis but have a high incidence of failure. This study aims to understand the crosstalk between skeletal muscle catabolism and AV fistula maturation failure.

Methods: Skeletal muscle metabolism and AV fistula maturation were evaluated in mice with chronic kidney disease (CKD).

Graph contrastive learning of subcellular-resolution spatial transcriptomics improves cell type annotation and reveals critical molecular pathways.

Imaging-based spatial transcriptomics (iST), such as MERFISH, CosMx SMI, and Xenium, quantify gene expression level across cells in space, but more importantly, they directly reveal the subcellular distribution of RNA transcripts at the single-molecule resolution. The subcellular localization of RNA molecules plays a crucial role in the compartmentalization-dependent regulation of genes within individual cells. Understanding the intracellular spatial distribution of RNA for a particular cell type thus not only improves the characterization of cell identity but also is of paramount importance in elucidating unique subcellular regulatory mechanisms specific to the cell type.

A comprehensive benchmarking for evaluating TCR embeddings in modeling TCR-epitope interactions.

The complexity of T cell receptor (TCR) sequences, particularly within the complementarity-determining region 3 (CDR3), requires efficient embedding methods for applying machine learning to immunology. While various TCR CDR3 embedding strategies have been proposed, the absence of their systematic evaluations created perplexity in the community. Here, we extracted CDR3 embedding models from 19 existing methods and benchmarked these models with four curated datasets by accessing their impact on the performance of TCR downstream tasks, including TCR-epitope binding affinity prediction, epitope-specific TCR identification, TCR clustering, and visualization analysis.

recovered from hospital patients, livestock and dogs in Nigeria share near-identical genome sequences.

Genomic data on from the African continent are currently lacking, resulting in the region being under-represented in global analyses of infection (CDI) epidemiology. For the first time in Nigeria, we utilized whole-genome sequencing and phylogenetic tools to compare isolates from diarrhoeic human patients (=142), livestock (=38), poultry manure (=5) and dogs (=9) in the same geographic area (Makurdi, north-central Nigeria) and relate them to the global population. In addition, selected isolates were tested for antimicrobial susceptibility (=33) and characterized by PCR ribotyping (=53).

Chitosan-Functionalized Fluorescent Calcium Carbonate Nanoparticle Loaded with Methotrexate: Future Theranostics for Triple Negative Breast Cancer.

Herein, fluorescent calcium carbonate nanoclusters encapsulated with methotrexate (Mtx) and surface functionalized with chitosan (25 nm) (@Calmat) have been developed for the imaging and treatment of triple-negative breast cancer (TNBC). These biocompatible, pH-sensitive nanoparticles demonstrate significant potential for targeted therapy and diagnostic applications. The efficacy of nanoparticles (NPs) was evaluated in MDA-MB-231 TNBC cell lines.

The patient and caregiver experience of CAR T-cell therapy: A qualitative analysis.

Background/purpose: Immunotherapies, such as CAR-T, have revolutionized cancer treatment for some cancers. However, these treatments often require active participation of a family member or friend to act as a caregiver at home for several weeks after infusion. Given the novelty of CAR-T, there is a need to better understand the experience of patients receiving these treatments and their caregivers.

Relaxin in pregnancy: a narrative review of a pleiotropic molecule.

Introduction: Relaxin is a hormone primarily produced by the corpus luteum during pregnancy, and it plays a critical role in various physiological processes related to pregnancy and childbirth.

Evidence Acquisition: Studies have suggested a possible link between relaxin levels and preterm birth. Relaxin's effects on the cervix and pelvic ligaments suggest it could influence the mode of delivery.

Exploring melatonin's signalling pathways in the protection against age-related skin deterioration.

Melatonin, renowned for regulating sleep-wake cycles, also exhibits notable anti-aging properties for the skin. Synthesized in the pineal gland and various tissues including the skin, melatonin's efficacy arises from its capacity to combat oxidative stress and shield the skin from ultraviolet (UV)-induced damage. Moreover, it curbs melanin production, thereby potentially ameliorating hyperpigmentation.

Progress and prospects in antisense oligonucleotide-mediated exon skipping therapies for Duchenne muscular dystrophy.

Recent years have seen enormous progress in the field of advanced therapeutics for the progressive muscle wasting disease Duchenne muscular dystrophy (DMD). In particular, four antisense oligonucleotide (ASO) therapies targeting various DMD-causing mutations have achieved FDA approval, marking major milestones in the treatment of this disease. These compounds are designed to induce alternative splicing events that restore the translation reading frame of the dystrophin gene, leading to the generation of internally-deleted, but mostly functional, pseudodystrophin proteins with the potential to compensate for the genetic loss of dystrophin.

Thermal proteome profiling unveils protein targets of deoxycholic acid in living neuronal cells.

Bile acids, synthesized in the liver and modified by the gut microbiota, play vital roles in various physiological processes. The dysregulation of bile acids has been extensively documented in patients with neurodegenerative diseases. However, limited attention has been given to the protein targets associated with microbiota-derived bile acids in neurological diseases.

Mechanistic studies of chondroitin sulfate/dermatan sulfate isolated from freshwater fish discards on osteogenesis in MC3T3-E1 cells.

Glycosaminoglycans (GAGs) are essential bone extracellular matrix molecules that regulate osteoblast differentiation. Numerous studies have explored endogenous and exogenous GAG osteoanabolic activities using appropriate in vitro and in vivo models. However, GAGs' underlying the mechanism of action and structure-function relationships need to be elucidated in detail.

Spatial single-cell maps reveal ST6GAL1 promoting ovarian cancer metastasis.

In this study, spatial and single-cell transcriptome techniques were used to investigate the role of beta-galactoside alpha-2,6-sialyltransferase 1 (ST6GAL1) in promoting peritoneal metastasis in ovarian cancer epithelial cells. We collected single-cell transcriptomic (GSE130000) and spatial transcriptomic datasets (GSE211956) from the Gene Expression Omnibus and RNA-sequencing data from The Cancer Genome Atlas. The Robust Cell Type Decomposition (RCTD) approach was implemented to integrate spatial and single-cell transcriptomic data.

Saving coral reefs: significance and biotechnological approaches for coral conservation.

Coral reefs are highly productive ecosystems that provide valuable services to coastal communities worldwide. However, both local and global anthropogenic stressors, threaten the coral-algal symbiosis that enables reef formation. This breakdown of the symbiotic relationship, known as bleaching, is often triggered by cumulative cell damage.

Therapeutic gene correction of HBB frameshift CD41-42 (-TCTT) deletion in human hematopoietic stem cells.

Β-thalassemia is one of the global health burdens. The CD41-42 (-TCTT) mutation at HBB is the most prevalent pathogenic mutation of β-thalassemia in both China and Southeast Asia. Previous studies focused on repairing the HBB CD41-42 (-TCTT) mutation in β-thalassemia patient-specific induced pluripotent stem cells, which were subsequently differentiated into hematopoietic stem and progenitor cells (HSPCs) for transplantation.

Computational Elucidation of Hub Genes and Pathways Correlated with the Development of 5-Fluorouracil Resistance in HCT 116 Colorectal Carcinoma Cell Line.

Colorectal cancer (CRC) is the third most deadly cancer diagnosed in both men and women. 5-Fluorouracil (5-FU) treatment frequently causes the CRC cells to become chemoresistance, which has a negative impact on prognosis. Using bioinformatic techniques, this work describes important genes and biological pathways linked to 5-FU resistance in CRC cells.