Divergent WNT signaling and drug sensitivity profiles within hepatoblastoma tumors and organoids.

Hepatoblastoma, the most prevalent pediatric liver cancer, almost always carries a WNT-activating CTNNB1 mutation, yet exhibits notable molecular heterogeneity. To characterize this heterogeneity and identify novel targeted therapies, we perform comprehensive analysis of hepatoblastomas and tumor-derived organoids using single-cell RNA-seq/ATAC-seq, spatial transcriptomics, and high-throughput drug profiling. We identify two distinct tumor epithelial signatures: hepatic 'fetal' and WNT-high 'embryonal', displaying divergent WNT signaling patterns.

Complex structural variation is prevalent and highly pathogenic in pediatric solid tumors.

In pediatric cancer, structural variants (SVs) and copy-number alterations contribute to cancer initiation as well as progression, thereby aiding diagnosis and treatment stratification. Although suggested to be of importance, the prevalence and biological relevance of complex genomic rearrangements (CGRs) across pediatric solid tumors is largely unexplored. In a cohort of 120 primary tumors, we systematically characterized patterns of extrachromosomal DNA, chromoplexy, and chromothripsis across five pediatric solid cancer types.

Why are clams steamed with wine in Mediterranean cuisine?

Wine is renowned for its rich content of polyphenols, including resveratrol (Res), known for their health promoting properties. Steamed clam with wine, a popular Mediterranean delicacy that highlights the role of wine as a key ingredient. However, despite these benefits, resveratrol's low bioavailability poses challenges.

Nutritional load in post-prandial oxidative stress and the pathogeneses of diabetes mellitus.

Diabetes mellitus affected more than 500 million of people globally, with an annual mortality of 1.5 million directly attributable to diabetic complications. Oxidative stress, in particularly in post-prandial state, plays a vital role in the pathogenesis of the diabetic complications.

Machine learning-enabled high-throughput industry screening of edible oils.

Long-term consumption of mixed fraudulent edible oils increases the risk of developing of chronic diseases which has been a threat to the public health globally. The complicated global supply-chain is making the industry malpractices had often gone undetected. In order to restore the confidence of consumers, traceability (and accountability) of every level in the supply chain is vital.

Targeting pediatric cancers via T-cell recognition of the monomorphic MHC class I-related protein MR1.

Human leukocyte antigen (HLA) restriction of conventional T-cell targeting introduces complexity in generating T-cell therapy strategies for patients with cancer with diverse HLA-backgrounds. A subpopulation of atypical, major histocompatibility complex-I related protein 1 (MR1)-restricted T-cells, distinctive from mucosal-associated invariant T-cells (MAITs), was recently identified recognizing currently unidentified MR1-presented cancer-specific metabolites. It is hypothesized that the MC.

Extracellular vesicle-mediated delivery of CRISPR/Cas9 ribonucleoprotein complex targeting proprotein convertase subtilisin-kexin type 9 (Pcsk9) in primary mouse hepatocytes.

The loss-of-function of the proprotein convertase subtilisin-kexin type 9 (Pcsk9) gene has been associated with significant reductions in plasma serum low-density lipoprotein cholesterol (LDL-C) levels. Both CRISPR/Cas9 and CRISPR-based editor-mediated Pcsk9 inactivation have successfully lowered plasma LDL-C and PCSK9 levels in preclinical models. Despite the promising preclinical results, these studies did not report how vehicle-mediated CRISPR delivery inactivating Pcsk9 affected low-density lipoprotein receptor recycling in vitro or ex vivo.

Systematic discovery of gene fusions in pediatric cancer by integrating RNA-seq and WGS.

Background: Gene fusions are important cancer drivers in pediatric cancer and their accurate detection is essential for diagnosis and treatment. Clinical decision-making requires high confidence and precision of detection. Recent developments show RNA sequencing (RNA-seq) is promising for genome-wide detection of fusion products but hindered by many false positives that require extensive manual curation and impede discovery of pathogenic fusions.

A Brief Review on Medicinal Plants-At-Arms against COVID-19.

COVID-19 pandemic caused by the novel SARS-CoV-2 has impacted human livelihood globally. Strenuous efforts have been employed for its control and prevention; however, with recent reports on mutated strains with much higher infectivity, transmissibility, and ability to evade immunity developed from previous SARS-CoV-2 infections, prevention alternatives must be prepared beforehand in case. We have perused over 128 recent works (found on Google Scholar, PubMed, and ScienceDirect as of February 2023) on medicinal plants and their compounds for anti-SARS-CoV-2 activity and eventually reviewed 102 of them.

Novel time-domain NMR-based traits for rapid, label-free Olive oils profiling.

Olive oil is one of the oldest and essential edible oils in the market. The classification of olive oils (e.g.

Long-Term Expansion of Murine Primary Hepatocyte Organoids.

The in vitro maintenance and expansion of primary hepatocytes provide immense opportunities for disease modeling and other biological, viral, and toxicological studies, as well as for applications in regenerative medicine such as cell transplantation for the treatment of metabolic liver diseases. Here, we describe a protocol for the isolation and in vitro culture of primary hepatocytes in a three-dimensional extracellular matrix gel. The inflammatory cytokine tumor necrosis factor alpha (TNFα) is crucial for the long-term expansion of mouse hepatocyte organoids by mimicking the regenerative response in vitro.

Two-dimensional nanostructures based '-onics' and '-omics' in personalized medicine.

With the maturing techniques for advanced synthesis and engineering of two-dimensional (2D) materials, its nanocomposites, hybrid nanostructures, alloys, and heterostructures, researchers have been able to create materials with improved as well as novel functionalities. One of the major applications that have been taking advantage of these materials with unique properties is biomedical devices, which currently prefer to be decentralized and highly personalized with good precision. The unique properties of these materials, such as high surface to volume ratio, a large number of active sites, tunable bandgap, nonlinear optical properties, and high carrier mobility is a boon to 'onics' (photonics/electronics) and 'omics' (genomics/exposomics) technologies for developing personalized, low-cost, feasible, decentralized, and highly accurate medical devices.

Wnt signaling regulates hepatocyte cell division by a transcriptional repressor cascade.

Cell proliferation is tightly controlled by inhibitors that block cell cycle progression until growth signals relieve this inhibition, allowing cells to divide. In several tissues, including the liver, cell proliferation is inhibited at mitosis by the transcriptional repressors E2F7 and E2F8, leading to formation of polyploid cells. Whether growth factors promote mitosis and cell cycle progression by relieving the E2F7/E2F8-mediated inhibition is unknown.

Review of Microdevices for Hemozoin-Based Malaria Detection.

Despite being preventable and treatable, malaria still puts almost half of the world's population at risk. Thus, prompt, accurate and sensitive malaria diagnosis is crucial for disease control and elimination. Optical microscopy and immuno-rapid tests are the standard malaria diagnostic methods in the field.

Multi-Omics Advancements towards Malaria Diagnosis.

malaria is one of the most lethal infectious diseases, with 7 million infections annually. One of the roadblocks to global malaria elimination is the lack of highly sensitive, specific, and accurate diagnostic tools. The absence of diagnostic tools in particular has led to poor differentiation among parasite species, poor prognosis, and delayed treatment.

Hepatocyte organoids and cell transplantation: What the future holds.

Historically, primary hepatocytes have been difficult to expand or maintain in vitro. In this review, we will focus on recent advances in establishing hepatocyte organoids and their potential applications in regenerative medicine. First, we provide a background on the renewal of hepatocytes in the homeostatic as well as the injured liver.

Effect of Cisplatin and Gemcitabine With or Without Berzosertib in Patients With Advanced Urothelial Carcinoma: A Phase 2 Randomized Clinical Trial.

Importance: Preclinical studies suggest that inhibition of single-stranded DNA repair by ataxia telangiectasia and Rad3 (ATR) may enhance the cytotoxicity of cisplatin, gemcitabine, and other chemotherapeutic agents. Cisplatin with gemcitabine remains the standard up-front therapy for treatment in patients with metastatic urothelial cancer.

Objective: To determine whether the use of the selective ATR inhibitor, berzosertib, could augment the activity of cisplatin with gemcitabine.

Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids.

Hepatic, pancreatic, and biliary (HPB) organoids are powerful tools for studying development, disease, and regeneration. As organoid research expands, the need for clear definitions and nomenclature describing these systems also grows. To facilitate scientific communication and consistent interpretation, we revisit the concept of an organoid and introduce an intuitive classification system and nomenclature for describing these 3D structures through the consensus of experts in the field.

Molecular phenotyping of oxidative stress in diabetes mellitus with point-of-care NMR system.

Diabetes mellitus is one of the fastest-growing health burdens globally. Oxidative stress, which has been implicated in the pathogenesis of diabetes complication (e.g.

Machine learning assistive rapid, label-free molecular phenotyping of blood with two-dimensional NMR correlational spectroscopy.

Translation of the findings in basic science and clinical research into routine practice is hampered by large variations in human phenotype. Developments in genotyping and phenotyping, such as proteomics and lipidomics, are beginning to address these limitations. In this work, we developed a new methodology for rapid, label-free molecular phenotyping of biological fluids (e.

Next-Generation Surrogate Wnts Support Organoid Growth and Deconvolute Frizzled Pleiotropy In Vivo.

Modulation of Wnt signaling has untapped potential in regenerative medicine due to its essential functions in stem cell homeostasis. However, Wnt lipidation and Wnt-Frizzled (Fzd) cross-reactivity have hindered translational Wnt applications. Here, we designed and engineered water-soluble, Fzd subtype-specific "next-generation surrogate" (NGS) Wnts that hetero-dimerize Fzd and Lrp6.