Serum lipidomic signatures in patients with varying histological severity of metabolic-dysfunction associated steatotic liver disease.

Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a spectrum of pathologies ranging from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Patients with metabolic associated steatohepatitis (MASH) with fibrosis are at greatest risk of liver and cardiovascular complications. To identify such at-risk MASLD patients, physicians are still reliant on invasive liver biopsies.

Toxicity and speciation of inorganic arsenics and their adverse effects on in vivo endpoints and oxidative stress in the marine medaka Oryzias melastigma.

Here, we investigate the effects of acute and chronic exposure to arsenate (AsV) and arsenite (AsIII) in the marine medaka Oryzias melastigma. In vivo effects, biotransformation, and oxidative stress were studied in marine medaka exposed to the two inorganic arsenics for 4 or 28 days. An investigation of embryonic development revealed no effect on in vivo parameters, but the hatching rate increased in the group exposed to AsIII.

Tumor phylogeography reveals block-shaped spatial heterogeneity and the mode of evolution in Hepatocellular Carcinoma.

Solid tumors are complex ecosystems with heterogeneous 3D structures, but the spatial intra-tumor heterogeneity (sITH) at the macroscopic (i.e., whole tumor) level is under-explored.

Multimodal molecular landscape of response to Y90-resin microsphere radioembolization followed by nivolumab for advanced hepatocellular carcinoma.

Background: Combination therapy with radioembolization (yttrium-90)-resin microspheres) followed by nivolumab has shown a promising response rate of 30.6% in a Phase II trial (CA209-678) for advanced hepatocellular carcinoma (HCC); however, the response mechanisms and relevant biomarkers remain unknown.

Methods: By collecting both pretreatment and on-treatment samples, we performed multimodal profiling of tissue and blood samples and investigated molecular changes associated with favorable responses in 33 patients from the trial.

Synergistic adverse effects of microfibers and freshwater acidification on host-microbiota interactions in the water flea Daphnia magna.

Microfibers are the most common type of microplastics in freshwater environments. Anthropogenic climate stressors, such as freshwater acidification (FA), can interact with plastic pollution to disrupt freshwater ecosystems. However, the underlying mechanisms responsible for the interactive effects of microfibers and FA on aquatic organisms remain poorly understood.

An Integrative Analysis of Nasopharyngeal Carcinoma Genomes Unraveled Unique Processes Driving a Viral-Positive Cancer.

As one of few viral-positive cancers, nasopharyngeal carcinoma (NPC) is extremely rare across the world but very frequent in several regions of the world, including Southern China (known as the Cantonese cancer). Even though several genomic studies have been conducted for NPC, their sample sizes are relatively small and systematic comparison with other cancer types has not been explored. In this study, we collected four-hundred-thirty-one samples from six previous studies and provided the first integrative analysis of NPC genomes.

Genome instability is associated with ethnic differences between Asians and Europeans in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the deadliest cancer types with diverse etiological factors across the world. Although large scale genomic studies have been conducted in different countries, integrative analysis of HCC genomes and ethnic comparison across cohorts are lacking. We first integrated genomes of 1,349 HCC patients from five large cohorts across the world and applied multiple statistical methods in identifying driver genes.

New High-Throughput Screening Identifies Compounds That Reduce Viability Specifically in Liver Cancer Cells That Express High Levels of SALL4 by Inhibiting Oxidative Phosphorylation.

Background & Aims: Some oncogenes encode transcription factors, but few drugs have been successfully developed to block their activity specifically in cancer cells. The transcription factor SALL4 is aberrantly expressed in solid tumor and leukemia cells. We developed a screen to identify compounds that reduce the viability of liver cancer cells that express high levels of SALL4, and we investigated their mechanisms.

A Chemically Well-Defined, Self-Assembling 3D Substrate for Long-Term Culture of Human Pluripotent Stem Cells.

Clinical applications of human pluripotent stem cells (PSCs) are limited by the lack of chemically well-defined scaffolds for cell expansion, differentiation, and implantation. In this study, we systematically screened various self-assembling hexapeptides to identify the best matrix for long-term 3D PSC culture. Lysine-containing Ac-ILVAGK-NH hydrogels maintained best the pluripotency of human embryonic and induced PSCs even after 30 passages.

Transcriptional regulatory networks in embryonic stem cells.

Transcriptional regulation is one of the most fundamental processes in biology, governing the morphology, function, and behavior of cells and thus the survival of organisms. The embryonic stem cell (ESC) provides a good model for the understanding of transcriptional regulation in vertebrate systems. Recent efforts have led to the identification of molecular events, which confer upon these cells the unique properties of pluripotency and self renewal.