scATAC-seq generates more accurate and complete regulatory maps than bulk ATAC-seq.

Bulk ATAC-seq assays have been used to map and profile the chromatin accessibility of regulatory elements such as enhancers, promoters, and insulators. This has provided great insight into the regulation of gene expression in many cell types in a variety of organisms. To date, ATAC-seq has most often been used to provide an average evaluation of chromatin accessibility in populations of cells.

Comprehensive computational analysis of differentially expressed miRNAs and their influence on transcriptomic signatures in prostate cancer.

Prostate cancer presents a major health issue, with its progression influenced by intricate molecular factors. Notably, the interplay between miRNAs and changes in transcriptomic patterns is not fully understood. Our study seeks to bridge this knowledge gap, employing computational techniques to explore how miRNAs and transcriptomic alterations jointly regulate the development of prostate cancer.

The question of strains in AA amyloidosis.

The existence of transmissible amyloid fibril strains has long intrigued the scientific community. The strain theory originates from prion disorders, but here, we provide evidence of strains in systemic amyloidosis. Human AA amyloidosis manifests as two distinct clinical phenotypes called common AA and vascular AA.

Targeting fucosyltransferase FUT8 as a prospective therapeutic approach for DLBCL.

Diffuse large B-cell lymphoma (DLBCL) is characterized by its aggressive nature and resistance to standard chemotherapy, necessitating the development of new therapeutic approaches. The emergence of natural products and their derivatives has notably influenced cancer treatment, making morusinol, a medicine-derived monomer, a promising candidate. Here, we showed that morusinol exerted antitumor effects on DLBCL in vitro by inducing apoptosis and cell cycle arrest.

Bibliometric analysis of published works in ocular trauma: a growing focus on open globe injury.

Purpose: The purpose of this study is to analyze the trends and characteristics of ocular trauma research published from 2000 to 2022 to delineate the trajectory of the field's research, provide information about the network of key contributors, and help determine future research strategies and direction.

Methods: Web of Science was queried for published works using a series of keywords relating to ocular trauma: "globe rupture", "ruptured globe", "globe injury", "ocular trauma", "intraocular foreign body", "eye trauma", "eye injury", and "traumatic endophthalmitis". All article information was compiled using the VOSviewer software.

A neural network for long-term super-resolution imaging of live cells with reliable confidence quantification.

Super-resolution (SR) neural networks transform low-resolution optical microscopy images into SR images. Application of single-image SR (SISR) methods to long-term imaging has not exploited the temporal dependencies between neighboring frames and has been subject to inference uncertainty that is difficult to quantify. Here, by building a large-scale fluorescence microscopy dataset and evaluating the propagation and alignment components of neural network models, we devise a deformable phase-space alignment (DPA) time-lapse image SR (TISR) neural network.

Immunological characterization and prognostic of colon cancer evaluated by angiogenesis-related features: a computational analysis and in vitro experiments.

Background: Diseases are often caused by multiple factors, angiogenesis-related genes (ARGs) have been shown to be associated with cancer, however, their role in colon cancer had not been fully explored. This study investigated potential biomarkers based on ARGs to improve prognosis and treatment effect in colon cancer.

Methods: ARGs associated with colon cancer prognosis were identified using Cox regression analysis and LASSO analysis.

Cross-priming in cancer immunology and immunotherapy.

Cytotoxic T cell immune responses against cancer crucially depend on the ability of a subtype of professional antigen-presenting cells termed conventional type 1 dendritic cells (cDC1s) to cross-present antigens. Cross-presentation comprises redirection of exogenous antigens taken from other cells to the major histocompatibility complex class I antigen-presenting machinery. In addition, once activated and having sensed viral moieties or T helper cell cooperation via CD40-CD40L interactions, cDC1s provide key co-stimulatory ligands and cytokines to mount and sustain CD8 T cell immune responses.

Hallmark discoveries in the biology of non-Wilms tumour childhood kidney cancers.

Approximately 20% of paediatric and adolescent/young adult patients with renal tumours are diagnosed with non-Wilms tumour, a broad heterogeneous group of tumours that includes clear-cell sarcoma of the kidney, congenital mesoblastic nephroma, malignant rhabdoid tumour of the kidney, renal-cell carcinoma, renal medullary carcinoma and other rare histologies. The differential diagnosis of these tumours dates back many decades, when these pathologies were identified initially through clinicopathological observation of entities with outcomes that diverged from Wilms tumour, corroborated with immunohistochemistry and molecular cytogenetics and, subsequently, through next-generation sequencing. These advances enabled near-definitive recognition of different tumours and risk stratification of patients.

Integrating single-cell RNA and T cell/B cell receptor sequencing with mass cytometry reveals dynamic trajectories of human peripheral immune cells from birth to old age.

A comprehensive understanding of the evolution of the immune landscape in humans across the entire lifespan at single-cell transcriptional and protein levels, during development, maturation and senescence is currently lacking. We recruited a total of 220 healthy volunteers from the Shanghai Pudong Cohort (NCT05206643), spanning 13 age groups from 0 to over 90 years, and profiled their peripheral immune cells through single-cell RNA-sequencing coupled with single T cell and B cell receptor sequencing, high-throughput mass cytometry, bulk RNA-sequencing and flow cytometry validation experiments. We revealed that T cells were the most strongly affected by age and experienced the most intensive rewiring in cell-cell interactions during specific age.

CARD domains mediate anti-phage defence in bacterial gasdermin systems.

Caspase recruitment domains (CARDs) and pyrin domains are important facilitators of inflammasome activity and pyroptosis. Following pathogen recognition by nucleotide binding-domain, leucine-rich, repeat-containing (NLR) proteins, CARDs recruit and activate caspases, which, in turn, activate gasdermin pore-forming proteins to induce pyroptotic cell death. Here we show that CARD domains are present in defence systems that protect bacteria against phage.

Structure and mechanism of vitamin-K-dependent γ-glutamyl carboxylase.

γ-Glutamyl carboxylase (GGCX) is the sole identified enzyme that uses vitamin K (VK) as a cofactor in humans. This protein catalyses the oxidation of VK hydroquinone to convert specific glutamate residues to γ-carboxyglutamate residues in VK-dependent proteins (VDPs), which are involved in various essential biological processes and diseases. However, the working mechanism of GGCX remains unclear.

Bat genomes illuminate adaptations to viral tolerance and disease resistance.

Zoonoses are infectious diseases transmitted from animals to humans. Bats have been suggested to harbour more zoonotic viruses than any other mammalian order. Infections in bats are largely asymptomatic, indicating limited tissue-damaging inflammation and immunopathology.

Dynamic flow control through active matter programming language.

Cells use 'active' energy-consuming motor and filament protein networks to control micrometre-scale transport and fluid flows. Biological active materials could be used in dynamically programmable devices that achieve spatial and temporal resolution that exceeds current microfluidic technologies. However, reconstituted motor-microtubule systems generate chaotic flows and cannot be directly harnessed for engineering applications.

Molecular and pharmacological heterogeneity of ETV6::RUNX1 acute lymphoblastic leukemia.

ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukemia (ALL) associated with favorable prognosis, but the optimal therapy for this subtype remains unclear. Profiling the genomic and pharmacological landscape of 194 pediatric ETV6::RUNX1 ALL cases, we uncover two transcriptomic clusters, C1 (61%) and C2 (39%). Compared to C1, the C2 subtype features higher white blood cell counts and younger age at diagnosis, as well as better early treatment responses.

Categorization of 34 computational methods to detect spatially variable genes from spatially resolved transcriptomics data.

In the analysis of spatially resolved transcriptomics data, detecting spatially variable genes (SVGs) is crucial. Numerous computational methods exist, but varying SVG definitions and methodologies lead to incomparable results. We review 34 state-of-the-art methods, classifying SVGs into three categories: overall, cell-type-specific, and spatial-domain-marker SVGs.

Subcellular mitochondrial heterogeneity enables opposing metabolic demands.

Mitochondria perform essential metabolic processes that sustain cellular bioenergetics and biosynthesis. In a recent article, Ryu et al. explored how mitochondria coordinate biochemical reactions with opposing redox demands within the same cell.

Molecular regulation of mitophagy signaling in tumor microenvironment and its targeting for cancer therapy.

Aberrations emerging in mitochondrial homeostasis are restrained by mitophagy to control mitochondrial integrity, bioenergetics signaling, metabolism, oxidative stress, and apoptosis. The mitophagy-accompanied mitochondrial processes that occur in a dysregulated condition act as drivers for cancer occurrence. In addition, the enigmatic nature of mitophagy in cancer cells modulates the cellular proteome, creating challenges for therapeutic interventions.

Identification of the molecular characterization and tumor microenvironment of thoracic inflammatory myofibroblastic tumors.

Background: Inflammatory myofibroblastic tumors (IMTs), rare soft tissue neoplasms, are characterized by a blend of myofibroblastic proliferation and inflammatory features. While generally characterized by slow growth, IMTs can exhibit locally aggressive behavior, and in rare instances, metastasize to distant sites. This study elucidated the clinical characteristics, molecular profile, and tumor microenvironment of thoracic IMTs.

Posterior fossa ring-enhancing lesions in the adult immunocompetent host: illustrative cases, systematic review, and proposed diagnostic algorithm.

Purpose: Posterior fossa ring-enhancing lesions (PFREL) in the adult immunocompetent hosts pose a diagnostic challenge. We aimed to evaluate the spectrum of PFREL etiologies and propose a diagnostic algorithm.

Methods: This study involved a retrospective analysis of PFREL cases from our institution (January 2023 to April 2024) and a systematic literature review conducted using Embase and PubMed databases following the PRISMA 2020 guidelines.

MuSK regulates neuromuscular junction Nav1.4 localization and excitability.

The neuromuscular junction (NMJ) is the linchpin of nerve-evoked muscle contraction. Broadly, the function of the NMJ is to transduce nerve action potentials into muscle fiber action potentials (MFAPs). Efficient neuromuscular transmission requires both cholinergic signaling, responsible for generation of endplate potentials (EPPs), and excitation, the amplification of the EPP by postsynaptic voltage-gated sodium channels (Nav1.

PMP2+ Schwann cells maintain the survival of large-caliber motor axons.

Neurodegenerative diseases of both the central and peripheral nervous system are characterized by selective neuronal vulnerability, i.e., pathology that affects particular types of neurons.

Neuropathic corneal pain following refractive surgery: risk factors, clinical manifestations, imaging and proteomic characteristics.

Background/aims: To identify the risk factors for neuropathic corneal pain (NCP) following corneal refractive surgery and to report its clinical manifestations, imaging and proteomic characteristics.

Methods: This 1 year prospective cohort study included 100 eyes that underwent small incision lenticule extraction (SMILE) or laser-assisted in situ keratomileusis (LASIK). Ocular surface assessments, in-vivo confocal microscopy scans, tear neuromediators and proteomics analyses were performed.

The Rbfox1/LASR complex controls alternative pre-mRNA splicing by recognition of multipart RNA regulatory modules.

The Rbfox proteins regulate alternative pre-mRNA splicing by binding to the RNA element GCAUG. In the nucleus, most of Rbfox is bound to the large assembly of splicing regulators (LASR), a complex of RNA-binding proteins that recognize additional RNA motifs. However, it remains unclear how the different subunits of the Rbfox/LASR complex act together to bind RNA and regulate splicing.