Characteristics of different lipid droplet-mitochondrial contacts patterns during lipid droplet metabolism in T2DM-induced MASLD.

Mitochondrial function is crucial for hepatic lipid metabolism. Current research identifies two types of mitochondria based on their contact with lipid droplets: peridroplet mitochondria (PDM) and cytoplasmic mitochondria (CM). This work aimed to investigate the alterations of CM and PDM in metabolic dysfunction-associated steatotic liver disease (MASLD) induced by spontaneous type-2 diabetes mellitus (T2DM) in db/db mice.

The usage of the paris classification system in urine cytology in the diagnosis of non-muscle-invasive bladder cancer: a retrospective single-center study.

Purpose: This retrospective single-center study aimed to determine the correlation between The Paris System (TPS) urine cytology classification, cystoscopy findings, and non-muscle-invasive bladder cancer diagnosis. In addition, we sought to identify factors that might explain the abnormal cytology classification in cases in which no malignancy was detected.

Methods: A Total of 855 patients evaluated with urine cytology between 2017 and 2020 at Kuopio University Hospital were included.

A detoxified TLR4 agonist inhibits tumour growth and lung metastasis of osteosarcoma by promoting CD8+ cytotoxic lymphocyte infiltration.

Background: Osteosarcoma is the most common malignant bone tumour with limited treatment options and poor outcomes in advanced metastatic cases. Current immunotherapies show limited efficacy, highlighting the need for novel therapeutic approaches. Systemic immune activation by Toll-like receptor 4 (TLR4) immunostimulants has shown great promise; however, current TLR4 agonists' toxicity hinders this systemic approach in patients with osteosarcoma.

Exposomics: a review of methodologies, applications, and future directions in molecular medicine.

The exposome is the measure of all the exposures of an individual in a lifetime and how those exposures relate to health. Exposomics is the emerging field of research to measure and study the totality of the exposome. Exposomics can assist with molecular medicine by furthering our understanding of how the exposome influences cellular and molecular processes such as gene expression, epigenetic modifications, metabolic pathways, and immune responses.

Multiplexed spatial mapping of chromatin features, transcriptome and proteins in tissues.

The phenotypic and functional states of cells are modulated by a complex interactive molecular hierarchy of multiple omics layers, involving the genome, epigenome, transcriptome, proteome and metabolome. Spatial omics approaches have enabled the study of these layers in tissue context but are often limited to one or two modalities, offering an incomplete view of cellular identity. Here we present spatial-Mux-seq, a multimodal spatial technology that allows simultaneous profiling of five different modalities: two histone modifications, chromatin accessibility, whole transcriptome and a panel of proteins at tissue scale and cellular level in a spatially resolved manner.

A genome-wide atlas of human cell morphology.

A key challenge of the modern genomics era is developing empirical data-driven representations of gene function. Here we present the first unbiased morphology-based genome-wide perturbation atlas in human cells, containing three genome-wide genotype-phenotype maps comprising CRISPR-Cas9-based knockouts of >20,000 genes in >30 million cells. Our optical pooled cell profiling platform (PERISCOPE) combines a destainable high-dimensional phenotyping panel (based on Cell Painting) with optical sequencing of molecular barcodes and a scalable open-source analysis pipeline to facilitate massively parallel screening of pooled perturbation libraries.

Identification of ubiquitination-related key biomarkers and immune infiltration in Crohn's disease by bioinformatics analysis and machine learning.

Crohn's disease (CD) is a chronic inflammatory bowel disease with an unknown etiology. Ubiquitination plays a significant role in the pathogenesis of CD. This study aimed to explore the functional roles of ubiquitination-related genes in CD.

Clinical characteristics and esophageal motility in patients with gastric cardia submucosal tumors and associated changes after endoscopic resection.

Background: This study aimed to investigate the clinical characteristics and esophageal motility of patients with gastric cardia submucosal tumors (SMTs) and the associated changes after endoscopic resection based on high-resolution impedance manometry (HRIM).

Methods: From our electronic database, we identified patients who underwent pre-operative evaluation of gastric cardia SMTs between 2015 and 2023. All patients completed standardized symptom questionnaires and underwent endoscopic ultrasonography and HRIM.

Short-term outcomes of mesh-suture repair in the treatment of ventral hernias: a single-center study.

Background: Defect closure with mesh suture is a novel technique for hernia repair. Originally described as the construction of lightweight macroporous polypropylene mesh strips as a suture material, it is now available as an FDA-approved product. Mesh suture better distributes tensile forces and reduces fascial tearing compared to traditional suture but requires less implanted material and tissue dissection compared to planar mesh.

ASIC1a mediated nucleus pulposus cells pyroptosis and glycolytic crosstalk as a molecular basis for intervertebral disc degeneration.

Background: One of the etiologic components of degenerative spinal illnesses is intervertebral disc degeneration (IVDD), and the accompanying lower back pain is progressively turning into a significant public health problem. Important pathologic characteristics of IVDD include inflammation and acidic microenvironment, albeit it is unclear how these factors contribute to the disease.

Purpose: To clarify the functions of inflammation and the acidic environment in IVDD, identify the critical connections facilitating glycolytic crosstalk and nucleus pulposus cells (NPCs) pyroptosis, and offer novel approaches to IVDD prevention and therapy.

Long-term liver outcomes after metabolic surgery in compensated cirrhosis due to metabolic dysfunction-associated steatohepatitis.

No therapy has been shown to reduce the risk of major adverse liver outcomes (MALO) in patients with cirrhosis due to metabolic dysfunction-associated steatohepatitis (MASH). The Surgical Procedures Eliminate Compensated Cirrhosis In Advancing Long-term (SPECCIAL) observational study compared the effects of metabolic surgery and nonsurgical treatment in patients with obesity and compensated histologically proven MASH-related cirrhosis. Using a doubly robust estimation methodology to balance key baseline characteristics between groups, the time-to-incident MALO was compared between 62 patients (68% female) who underwent metabolic surgery and 106 nonsurgical controls (71% female), with a mean follow-up of 10.

Age-related p53 SUMOylation accelerates senescence and tau pathology in Alzheimer's disease.

Aging is a major risk factor for Alzheimer's disease (AD). With the prevalence of AD increased, a mechanistic linkage between aging and the pathogenesis of AD needs to be further addressed. Here, we report that a small ubiquitin-related modifier (SUMO) modification of p53 is implicated in the process which remarkably increased in AD patient's brain.

Crosstalk between GLTSCR1-deficient endothelial cells and tumour cells promotes colorectal cancer development by activating the Notch pathway.

Cancer stem cells (CSCs) typically reside in perivascular niches, but whether endothelial cells of blood vessels influence the stemness of cancer cells remains poorly understood. This study revealed that endothelial cell-specific GLTSCR1 deletion promotes colorectal cancer (CRC) tumorigenesis and metastasis by increasing cancer cell stemness. Mechanistically, knocking down GLTSCR1 induces the transformation of endothelial cells into tip cells by regulating the expression of Neuropilin-1 (NRP1), thereby increasing the direct contact and interaction between endothelial cells and tumour cells.

The lean body mass to visceral fat mass ratio is negatively associated with cardiometabolic disorders: a cross-sectional study.

The literature has documented conflicting and inconsistent associations between muscle-to-fat ratios and metabolic diseases. Additionally, different adipose tissues can have contrasting effects, with visceral adipose tissue being identified as particularly harmful. This study aimed to explore the relationship between the ratio of the lean mass index (LMI) to the visceral fat mass index (VFMI) and cardiometabolic disorders, including dyslipidemia, hypertension, and diabetes, as previous research on this topic is lacking.

Comparison of aesthetic perception and acceptability of silver diamine fluoride staining between Spanish and Italian parents.

Assessing parental aesthetic acceptability of Silver Diamine Fluoride (SDF) staining is crucial for its potential implementation in paediatric dentistry in different regions. This study aimed to compare aesthetic perceptions and acceptance of SDF staining between Spanish and Italian parents, and assess weather acceptability is influenced by location, child's cooperation, or demographic background. A cross-sectional comparative study was conducted among Spanish and Italian parents at three university dental clinics, using a validated Italian version of the questionnaire "Parental perceptions of Silver Diamine Fluoride Dental Color Changes".

Stem cells prevent long-term deterioration of renal function after renal artery revascularization in a renovascular hypertension model in rats.

Partial stenosis of the renal artery causes renovascular hypertension (RVH) and is accompanied by chronic renal ischemia, resulting in irreversible kidney damage. Revascularization constitutes the most efficient therapy for normalizing blood pressure (BP) and has significant benefits for renal function; however, the tissue damage caused by chronic hypoxia is not fully reversed. Mesenchymal stem cells (MSCs) have produced discrete results in minimizing RVH and renal tissue and functional improvements since the obstruction persists.

Modeling future sediment retention service in the Bagh-e-Shadi Forest protected area using InVEST and the ACCESS-ESM1-5 climate model.

Assessing the impact of climate change on water-related ecosystem services (ES) in Protected Areas (PAs) is essential for developing soil and water conservation strategies that promote sustainability and restore ES. However, the application of ES research in Protected Area (PA) management remains ambiguous and has notable shortcomings. This study primarily aimed to assess the SDR-InVEST (Sediment Delivery Ratio-Integrated Valuation of Ecosystem Services and Tradeoffs) model for estimating ES, including soil loss, sediment export, and sediment retention, under various climate change scenarios from 1997 to 2100 in the data-scarce region of the Bagh-e-Shadi Forest PA.

Cross-sectional study of proteomic differences between moderate and severe psoriasis.

Although an ongoing understanding of psoriasis vulgaris (PV) pathogenesis, little is known about the proteomic differences between moderate and severe psoriasis. In this cross-sectional study, we evaluated the proteomic differences between moderate and severe psoriasis using data-independent acquisition mass spectrometry (DIA-MS). 173 differentially expressed proteins (DEPs) were significantly differentially expressed between the two groups.

Relationship between neutropenia caused by nanoliposomal irinotecan/fluorouracil/leucovorin and treatment outcomes in the NAPOLEON-2 study (NN-2301).

The relationship between nanoliposomal irinotecan/fluorouracil/leucovorin (NFF) treatment outcomes and neutropenia in patients with pancreatic cancer has not been thoroughly examined. Thus, we conducted a retrospective analysis of data from patients with pancreatic cancer who were treated with NFF to investigate this relationship. Neutropenia was assessed according to the Common Terminology Criteria for Adverse Events across three cutoffs: A (grade 0 versus grade 1-4), B (grades 0-1 versus 2-4), and C (grades 0-2 versus 3-4).

International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma.

T-cell redirecting therapy (TCRT), specifically chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs) represent a remarkable advance in the treatment of multiple myeloma (MM). There are several products available around the world and several more in development targeting primarily B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GRPC5D). The relatively rapid availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherapy so MM physicians and patients can aim at optimal sequential use of these therapies.

The interplay of uncertainty, relevance and learning influences auditory categorization.

Auditory perception requires categorizing sound sequences, such as speech or music, into classes, such as syllables or notes. Auditory categorization depends not only on the acoustic waveform, but also on variability and uncertainty in how the listener perceives the sound - including sensory and stimulus uncertainty, the listener's estimated relevance of the particular sound to the task, and their ability to learn the past statistics of the acoustic environment. Whereas these factors have been studied in isolation, whether and how these factors interact to shape categorization remains unknown.

A fractal-fractional order modeling approach to understanding stem cell-chemotherapy combinations for cancer.

The main objective of this work is to study the mathematical model that combines stem cell therapy and chemotherapy for cancer cells. We study the model using the fractal fractional derivative with the Mittag-Leffler kernel. In the analytical part, we study the existence of the solution and its uniqueness, which was studied based on the fixed point theory.

Squared diffusion-weighted imaging for improving the detection of clinically significant prostate cancer.

Aim of this study was to proof the concept of optimizing the contrast between prostate cancer (PC) and healthy tissue by DWI post-processing using a quadrature method. DWI post-processing was performed on 30 patients (median age 67 years, prostate specific antigen 8.0 ng/ml) with PC and clear MRI findings (PI-RADS 4 and 5).