State-of-the-Art Liver Cancer Organoids: Modeling Cancer Stem Cell Heterogeneity for Personalized Treatment.

Liver cancer poses a global health challenge with limited therapeutic options. Notably, the limited success of current therapies in patients with primary liver cancers (PLCs) may be attributed to the high heterogeneity of both hepatocellular carcinoma (HCCs) and intrahepatic cholangiocarcinoma (iCCAs). This heterogeneity evolves over time as tumor-initiating stem cells, or cancer stem cells (CSCs), undergo (epi)genetic alterations or encounter microenvironmental changes within the tumor microenvironment.

Diagnostic Accuracy of Furosemide Stress Test and Cystatin-C for Predicting Acute Kidney Injury Progression in Children: A Prospective Cohort Study.

Objectives: To evaluate the predictive ability of furosemide stress test (FST), serum and urine cystatin-C in identifying progressive acute kidney injury (AKI) and the need for kidney replacement therapy (KRT).

Methods: Children aged one month to 18 y admitted in the pediatric intensive care unit (PICU) with Kidney Diseases Improving Global Outcomes (KDIGO) stage-1/2 AKI were enrolled. FST and serum and urine cystatin-C levels were performed and analyzed.

Impact of hemoadsorption with CytoSorb® on meropenem and piperacillin exposure in critically ill patients in a post-CKRT setup: a single-center, retrospective data analysis.

Purpose: CytoSorb® (CS) adsorbent is a hemoadsorption filter for extracorporeal blood purification often integrated into continuous kidney replacement therapy (CKRT). It is primarily used in critically ill patients with sepsis and related conditions, including cytokine storms and systemic inflammatory responses. Up to now, there is no evidence nor recommendation for the use of CS filters in sepsis (22).

Alterations of amino acids in older adults with Alzheimer's Disease and Vascular Dementia.

Metabolomics provide a promising tool for understanding dementia pathogenesis and identifying novel biomarkers. This study aimed to identify amino acid biomarkers for Alzheimer's Disease (AD) and Vascular Dementia (VD). By amino acid metabolomics, the concentrations of amino acids were determined in the serum of AD and VD patients as well as age-matched healthy controls.

Exploring the effect of hsa-miR-19b-3p on IL-1R1 expression and serum levels in alopecia areata.

Alopecia areata (AA) is an autoimmune condition marked by hair loss, linked to inflammatory processes involving the interleukin-1 receptor type 1 (IL-1R1) pathway. This study aims to explore the relationship between IL-1R1 gene expression, serum IL-1R1 levels, and hsa-miR-19b-3p in relation to AA severity. Using a case-control design, we assessed 100 AA patients and 100 healthy controls, measuring serum IL-1R1 through enzyme-linked immunosorbent assay (ELISA) and analyzing IL-1R1 gene and hsa-miR-19b-3p expression levels via quantitative real-time PCR (qRT-PCR).

Comparison of the amyloid plaque proteome in Down syndrome, early-onset Alzheimer's disease, and late-onset Alzheimer's disease.

Down syndrome (DS) is strongly associated with Alzheimer's disease (AD) due to APP overexpression, exhibiting Amyloid-β (Aβ) and Tau pathology similar to early-onset (EOAD) and late-onset AD (LOAD). We evaluated the Aβ plaque proteome of DS, EOAD, and LOAD using unbiased localized proteomics on post-mortem paraffin-embedded tissues from four cohorts (n = 20/group): DS (59.8 ± 4.

Role of Divalent Ions in Membrane Models of Polymyxin-Sensitive and Resistant Gram-Negative Bacteria.

Polymyxins, critical last-resort antibiotics, impact the distribution of membrane-bound divalent cations in the outer membrane of Gram-negative bacteria. We employed atomistic molecular dynamics simulations to model the effect of displacing these ions. Two polymyxin-sensitive and two polymyxin-resistant models of the outer membrane of were investigated.

Lineage-dependence of the neuroblastoma surfaceome defines tumor cell state-dependent and independent immunotherapeutic targets.

Background: Neuroblastoma is a heterogeneous disease with adrenergic (ADRN)- and therapy resistant mesenchymal (MES)-like cells driven by distinct transcription factor networks. Here, we investigate the expression of immunotherapeutic targets in each neuroblastoma subtype and propose pan-neuroblastoma and cell state specific targetable cell-surface proteins.

Methods: We characterized cell lines, patient-derived xenografts, and patient samples as ADRN-dominant or MES-dominant to define subtype-specific and pan-neuroblastoma gene sets.

Unsaturated Fatty Acids Are Decreased in Aβ Plaques in Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-beta (Aβ) plaques in the brain, contributing to neurodegeneration. This study investigates lipid alterations within these plaques using a novel, label-free, multimodal approach. Combining infrared (IR) imaging, machine learning, laser microdissection (LMD), and flow injection analysis mass spectrometry (FIA-MS), we provide the first comprehensive lipidomic analysis of chemically unaltered Aβ plaques in post-mortem human AD brain tissue.

A Novel Screening System to Characterize and Engineer Quorum Quenching Lactonases.

N-acyl l-homoserine lactones are signaling molecules used by numerous bacteria in quorum sensing. Some bacteria encode lactonases, which can inactivate these signals. Lactonases were reported to inhibit quorum sensing-dependent phenotypes, including virulence and biofilm.

Arrhythmogenic calmodulin variants D131E and Q135P disrupt interaction with the L-type voltage-gated Ca channel (Ca1.2) and reduce Ca-dependent inactivation.

Aim: Long QT syndrome (LQTS) and catecholaminergic polymorphism ventricular tachycardia (CPVT) are inherited cardiac disorders often caused by mutations in ion channels. These arrhythmia syndromes have recently been associated with calmodulin (CaM) variants. Here, we investigate the impact of the arrhythmogenic variants D131E and Q135P on CaM's structure-function relationship.

Data-Driven Equation-Free Dynamics Applied to Many-Protein Complexes: The Microtubule Tip Relaxation.

Microtubules (MTs) constitute the largest components of the eukaryotic cytoskeleton and play crucial roles in various cellular processes, including mitosis and intracellular transport. The property allowing MTs to cater to such diverse roles is attributed to dynamic instability, which is coupled to the hydrolysis of GTP (guanosine-5'-triphosphate) to GDP (guanosine-5'-diphosphate) within the β-tubulin monomers. Understanding the equilibrium dynamics and the structural features of both GDP- and GTP-complexed MT tips, especially at an all-atom level, remains challenging for both experimental and computational methods because of their dynamic nature and the prohibitive computational demands of simulating large, many-protein systems.

Storage and controlled release of fragrances maintaining a constant ratio of volatile compounds.

Controlled fragrance release at the right time, in the right place, depending on the context remains a technological challenge in the areas of psychophysiology, biochemistry and the entertainment industry. In this study, we demonstrate how bulk poly(dimethylsiloxane) (PDMS) templates may effectively take up and retain volatile organic compounds of essential orange oil in the original form without significantly shifting the scent profile. This is done depending on the sampling approach that follows a controllable and slow fragrance release maintaining a constant ratio of volatile compounds in a template-thickness, temperature and time-dependent manner.

Intercellular TIMP-1-CD63 signaling directs the evolution of immune escape and metastasis in KRAS-mutated pancreatic cancer cells.

Background And Aims: Oncogenic KRAS mutations are present in approximately 90% of pancreatic ductal adenocarcinoma (PDAC). However, Kras mutation alone is insufficient to transform precancerous cells into metastatic PDAC. This study investigates how KRAS-mutated epithelial cells acquire the capacity to escape senescence or even immune clearance, thereby progressing to advanced PDAC.

The epitope of the antibody used in the REAADS VWF activity assay is quaternary.

The REAADS VWF activity assay is often assumed to be specific for the A1 domain, the portion of VWF that binds platelet GPIbα. We tested this assay on the A1A2A3 region of VWF with each domain expressed independently of one another and together in combination as a tri-domain. The monoclonal antibody used in this assay is found to be insensitive to the single A domains and does not recognize free A1 domains as it is often assumed.

An accessible workflow for high-sensitivity proteomics using parallel accumulation-serial fragmentation (PASEF).

Deep and accurate proteome analysis is crucial for understanding cellular processes and disease mechanisms; however, it is challenging to implement in routine settings. In this protocol, we combine a robust chromatographic platform with a high-performance mass spectrometric setup to enable routine yet in-depth proteome coverage for a broad community. This entails tip-based sample preparation and pre-formed gradients (Evosep One) combined with a trapped ion mobility time-of-flight mass spectrometer (timsTOF, Bruker).

Understanding pectin cross-linking in plant cell walls.

Pectin is a major component of plant cells walls. The extent to which pectin chains crosslink with one another determines crucial properties including cell wall strength, porosity, and the ability of small, biologically significant molecules to access the cell. Despite its importance, significant gaps remain in our comprehension, at the molecular level, of how pectin cross-links influence the mechanical and physical properties of cell walls.

Evolution of the umbilical cord blood proteome across gestational development.

Neonatal health is dependent on early risk stratification, diagnosis, and timely management of potentially devastating conditions, particularly in the setting of prematurity. Many of these conditions are poorly predicted in real-time by clinical data and current diagnostics. Umbilical cord blood may represent a novel source of molecular signatures that provides a window into the state of the fetus at birth.

ERK-USP9X-coupled regulation of thymidine kinase 1 promotes both its enzyme activity-dependent and its enzyme activity-independent functions for tumor growth.

Thymidine kinase 1 (TK1), a crucial enzyme in DNA synthesis, is highly expressed in various cancers. However, the mechanisms underlying its elevated expression and the implications for tumor metabolism remain unclear. Here we demonstrate that activation of growth factor receptors enhances TK1 expression.