Host tissue factors predict immune surveillance and therapeutic outcomes in gastric cancer.

The immune composition of solid tumors is typically inferred from biomarkers, such as histologic and molecular classifications, somatic mutational burden, and PD-L1 expression. However, the extent to which these biomarkers predict the immune landscape in gastric adenocarcinoma-an aggressive cancer often linked to chronic inflammation-remains poorly understood. We leveraged high-dimensional spectral cytometry to generate a comprehensive single-cell immune landscape of tumors, normal tissue, and lymph nodes from patients in the Western Hemisphere with gastric adenocarcinoma.

RuvBL1/2 reduce toxic dipeptide repeat protein burden in multiple models of C9orf72-ALS/FTD.

A G4C2 hexanucleotide repeat expansion in is the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). Bidirectional transcription and subsequent repeat-associated non-AUG (RAN) translation of sense and antisense transcripts leads to the formation of five dipeptide repeat (DPR) proteins. These DPRs are toxic in a wide range of cell and animal models.

Best-Corrected Visual Acuity Quantitative Prediction for Cataract Patients: AI-Assisted Clinical Diagnostics Facilitation via the Inverse Problem Algorithm.

This study provided a quantitative prediction of best-corrected visual acuity (BCVA) for cataract patients using the inverse problem algorithm (IPA) technique earlier proposed by the authors. : To this end, seven risk factors (age, BMI, MAP, IOP, HbA1c, LDL-C, and gender) were linked by a semi-empirical formula by normalizing each factor into a dimensionless range of -1.0 to +1.

A Self-Cascade Penetrating Brain Tumor Immunotherapy Mediated by Near-Infrared II Cell Membrane-Disrupting Nanoflakes via Detained Dendritic Cells.

Immunotherapy can potentially suppress the highly aggressive glioblastoma (GBM) by promoting T lymphocyte infiltration. Nevertheless, the immune privilege phenomenon, coupled with the generally low immunogenicity of vaccines, frequently hampers the presence of lymphocytes within brain tumors, particularly in brain tumors. In this study, the membrane-disrupted polymer-wrapped CuS nanoflakes that can penetrate delivery to deep brain tumors via releasing the cell-cell interactions, facilitating the near-infrared II (NIR II) photothermal therapy, and detaining dendritic cells for a self-cascading immunotherapy are developed.

Revealing intact neuronal circuitry in centimeter-sized formalin-fixed paraffin-embedded brain.

Tissue-clearing and labeling techniques have revolutionized brain-wide imaging and analysis, yet their application to clinical formalin-fixed paraffin-embedded (FFPE) blocks remains challenging. We introduce HIF-Clear, a novel method for efficiently clearing and labeling centimeter-thick FFPE specimens using elevated temperature and concentrated detergents. HIF-Clear with multi-round immunolabeling reveals neuron circuitry regulating multiple neurotransmitter systems in a whole FFPE mouse brain and is able to be used as the evaluation of disease treatment efficiency.

Predictive value of NT-proBNP and hs-TnT for outcomes after pediatric congenital cardiac surgery.

Background: The available evidence regarding the predictive value of troponins and natriuretic peptides for early postoperative outcomes in pediatrics is limited, controversial, and based on small sample sizes. The authors aimed to investigate the association of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) with the in-hospital adverse outcomes after congenital cardiac surgeries.

Methods: A secondary analysis based on a prospective study of pediatric congenital heart disease (CHD) patients was conducted to investigate the association of NT-proBNP and hs-TnT tested within 6 h postoperatively with in-hospital adverse events.

Isotropic multi-scale neuronal reconstruction from high-ratio expansion microscopy with contrastive unsupervised deep generative models.

Background And Objective: Current methods for imaging reconstruction from high-ratio expansion microscopy (ExM) data are limited by anisotropic optical resolution and the requirement for extensive manual annotation, creating a significant bottleneck in the analysis of complex neuronal structures.

Methods: We devised an innovative approach called the IsoGAN model, which utilizes a contrastive unsupervised generative adversarial network to sidestep these constraints. This model leverages multi-scale and isotropic neuron/protein/blood vessel morphology data to generate high-fidelity 3D representations of these structures, eliminating the need for rigorous manual annotation and supervision.

Inverse Problem Algorithm-Based Time-Resolved Imaging of Head and Neck Computed Tomography Angiography Contrast Kinetics with Clinical Testification.

This study mitigated the challenge of head and neck CT angiography by IPA-based time-resolved imaging of contrast kinetics. To this end, 627 cerebral hemorrhage patients with dizziness, brain aneurysm, stroke, or hemorrhagic stroke diagnosis were randomly categorized into three groups, namely, the original dataset (450), verification group (112), and in vivo testified group (65), in the Affiliated BenQ Hospital of Nanjing Medical University. In the first stage, seven risk factors were assigned: age, CTA tube voltage, body surface area, heart rate per minute, cardiac output blood per minute, the actual injected amount of contrast media, and CTA delayed trigger timing.

In Situ Forming of Nitric Oxide and Electric Stimulus for Nerve Therapy by Wireless Chargeable Gold Yarn-Dynamos.

Endogenous signals, namely nitric oxide (NO) and electrons, play a crucial role in regulating cell fate as well as the vascular and neuronal systems. Unfortunately, utilizing NO and electrical stimulation in clinical settings can be challenging due to NO's short half-life and the invasive electrodes required for electrical stimulation. Additionally, there is a lack of tools to spatiotemporally control gas release and electrical stimulation.

The master energy homeostasis regulator PGC-1α exhibits an mRNA nuclear export function.

PGC-1α plays a central role in maintaining mitochondrial and energy metabolism homeostasis, linking external stimuli to transcriptional co-activation of genes involved in adaptive and age-related pathways. The carboxyl-terminus encodes a serine/arginine-rich (RS) region and an RNA recognition motif, however the RNA-processing function(s) were poorly investigated over the past 20 years. Here, we show that the RS domain of human PGC-1α directly interacts with RNA and the nuclear RNA export receptor NXF1.

A Y374X TDP43 truncation leads to an altered metabolic profile in amyotrophic lateral sclerosis fibroblasts driven by pyruvate and TCA cycle intermediate alterations.

A p.Y374X truncation in TARDBP was recently shown to reduce expression of TDP43 in fibroblasts isolated from ALS cases. In this follow up study focused on assessing the downstream phenotypic consequences of loss of TDP43 in the context of the truncation, we have shown a striking effect on the fibroblast metabolic profile.

High-throughput interrogation of immune responses using the Human Immune Profiling Pipeline.

The current abundance of immunotherapy clinical trials presents an opportunity to learn about the underlying mechanisms and pharmacodynamic effects of novel drugs on the human immune system. Here, we present a protocol to study how these immune responses impact clinical outcomes using large-scale high-throughput immune profiling of clinical cohorts. We describe the Human Immune Profiling Pipeline, which comprises an end-to-end solution from flow cytometry results to computational approaches and unsupervised patient clustering based on lymphocyte landscape.

Split dCas12a activator for lncRNA H19 activation to enhance BMSC differentiation and promote calvarial bone healing.

Healing of large calvarial bone defects in adults is challenging. We previously showed that inducing chondrogenic differentiation of mesenchymal stem cells from bone marrow (BMSC) or adipose tissue (ASC) before implantation can switch the repair pathway and improve calvarial bone healing. Split dCas12a activator is a new CRISPR activation system comprising the amino (N) and carboxyl (C) fragments of dCas12a protein, each being fused with synthetic transcription activators at both termini.

A cell-penetrant peptide blocking -repeat RNA nuclear export reduces the neurotoxic effects of dipeptide repeat proteins.

Hexanucleotide repeat expansions in are the most common genetic cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Studies have shown that the hexanucleotide expansions cause the noncanonical translation of transcripts into neurotoxic dipeptide repeat proteins (DPRs) that contribute to neurodegeneration. We show that a cell-penetrant peptide blocked the nuclear export of -repeat transcripts in HEK293T cells by competing with the interaction between SR-rich splicing factor 1 (SRSF1) and nuclear export factor 1 (NXF1).

Loss of TMEM106B exacerbates C9ALS/FTD DPR pathology by disrupting autophagosome maturation.

Disruption to protein homeostasis caused by lysosomal dysfunction and associated impairment of autophagy is a prominent pathology in amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD). The most common genetic cause of ALS/FTD is a G4C2 hexanucleotide repeat expansion in (C9ALS/FTD). Repeat-associated non-AUG (RAN) translation of G4C2 repeat transcripts gives rise to dipeptide repeat (DPR) proteins that have been shown to be toxic and may contribute to disease etiology.

Fabrication of Low-Molecular-Weight Hyaluronic Acid-Carboxymethyl Cellulose Hybrid to Promote Bone Growth in Guided Bone Regeneration Surgery: An Animal Study.

Guided bone regeneration surgery is an important dental operation used to regenerate enough bone to successfully heal dental implants. When this technique is performed on maxilla sinuses, hyaluronic acid (HLA) can be used as an auxiliary material to improve the graft material handling properties. Recent studies have indicated that low-molecular hyaluronic acid (L-HLA) provides a better regeneration ability than high-molecular-weight (H-HLA) analogues.

Controllable graphene oxide-based biocompatible hybrid interface as an anti-fibrotic coating for metallic implants.

In tissue engineering, foreign body reactions (FBRs) that may occur after the insertion of medical implants are a considerable challenge. Materials currently used in implants are mainly metals that are non-organic, and the lack of biocompatibility and absence of immune regulations may lead to fibrosis after long periods of implantation. Here, we introduce a highly biocompatible hybrid interface of graphene oxide (GO) and collagen type I (COL-I), where the topological nanostructure can effectively inhibit the differentiation of fibroblasts into myofibroblasts.