Intestinal Akkermansia muciniphila complements the efficacy of PD1 therapy in MAFLD-related hepatocellular carcinoma.

Immune checkpoint inhibitors are not effective for metabolic dysfunction-associated fatty liver disease (MAFLD)-hepatocellular carcinoma (HCC) patients, and identifying the key gut microbiota that contributes to immune resistance in these patients is crucial. Analysis using 16S rRNA sequencing reveals a decrease in Akkermansia muciniphila (Akk) during MAFLD-promoted HCC development. Administration of Akk ameliorates liver steatosis and effectively attenuates the tumor growth in orthotopic MAFLD-HCC mouse models.

Pharmacological activation of STAT1-GSDME pyroptotic circuitry reinforces epigenetic immunotherapy for hepatocellular carcinoma.

Background: Genomic screening uncovered interferon-gamma (IFNγ) pathway defects in tumours refractory to immune checkpoint blockade (ICB). However, its non-mutational regulation and reversibility for therapeutic development remain less understood.

Objective: We aimed to identify ICB resistance-associated druggable histone deacetylases (HDACs) and develop a readily translatable combination approach for patients with hepatocellular carcinoma (HCC).

Directional long-distance electron transfer from reduced to oxidized zones in the subsurface.

Electron transfer (ET) is the fundamental redox process of life and element cycling. The ET distance is normally as short as nanometers or micrometers in the subsurface. However, the redox gradient in the subsurface is as long as centimeters or even meters.

Amyloid-β oligomer-induced neurotoxicity by exosomal interactions between neuron and microglia.

A hallmark of Alzheimer's disease (AD) is amyloid-β (Aβ) plaque deposition in the brain, causing deficits in cognitive function. Amyloid-beta oligomers (AβOs), the soluble precursor peptides producing Aβ plaques, also produce neurotoxicity and microgliosis together with glycolytic reprogramming. Recently, monocarboxylate transporter 1 (MCT1), a key glycolysis regulator, and its ancillary protein, CD147, are found to play an important role in the secretion of exosomes, 30-200 nm vesicles in size, which are considered as toxic molecule carriers in AD.

Dependence of Biotic and Abiotic HO and •OH Production on the Redox Conditions and Compositions of Sediment during Oxygenation.

Reactive oxygen species (ROS) production in O-perturbed subsurface environments has been increasingly documented in recent years. However, the constraining conditions under which abiotic and/or biotic mechanisms predominate for ROS production remain ambiguous. Here, we demonstrate that the ROS production mechanism, biotic and abiotic, is determined by sediment redox properties and sediment compositions.

Targeting AXL induces tumor-intrinsic immunogenic response in tyrosine kinase inhibitor-resistant liver cancer.

Hepatocellular carcinoma (HCC) is an aggressive malignancy without effective therapeutic approaches. Here, we evaluate the tumor-intrinsic mechanisms that attenuate the efficacy of immune checkpoint inhibitor (ICI) that is observed in patients with advanced HCC who progress on first-line tyrosine kinase inhibitor (TKI) therapy. Upregulation of AXL observed in sorafenib- and lenvatinib-resistant HCCs is correlated with poor response towards TKI and ICI treatments.

Protein Posttranslational Modification in Stemness Remodeling and Its Emerging Role as a Novel Therapeutic Target in Gastrointestinal Cancers.

The posttranslational modifications (PTMs) of proteins, as critical mechanisms for protein regulation, are well known to enhance the functional diversity of the proteome and dramatically participate in complicated biological processes. Recent efforts in the field of cancer biology have illustrated the extensive landscape of PTMs and their crosstalk with a wide range of pro-tumorigenic signaling pathways that decisively contribute to neoplastic transformation, tumor recurrence, and resistance to oncotherapy. Cancer stemness is an emerging concept that maintains the ability of tumor cells to self-renew and differentiate and has been recognized as the root of cancer development and therapy resistance.

Financial well-being as a mediator of the relationship between multimorbidity and health-related quality of life in people with cancer.

Background: It is unknown whether financial well-being mediates the impact of multimorbidity on the health-related quality of life (HRQoL) of cancer patients.

Methods: Participants were recruited from three outpatient oncology clinics of Hong Kong public hospitals. Multimorbidity was assessed using the Charlson Comorbidity Index.

ADAR1-mediated RNA editing of SCD1 drives drug resistance and self-renewal in gastric cancer.

Targetable drivers governing 5-fluorouracil and cisplatin (5FU + CDDP) resistance remain elusive due to the paucity of physiologically and therapeutically relevant models. Here, we establish 5FU + CDDP resistant intestinal subtype GC patient-derived organoid lines. JAK/STAT signaling and its downstream, adenosine deaminases acting on RNA 1 (ADAR1), are shown to be concomitantly upregulated in the resistant lines.

Mechanistic Insight into Electron Transfer from Fe(II)-Bearing Clay Minerals to Fe (Hydr)oxides.

Electron transfer (ET) is the essence of most biogeochemical processes related to element cycling and contaminant attenuation, whereas ET between different minerals and the controlling mechanism remain elusive. Here, we used surface-associated Fe(II) as a proxy to explore ET between reduced nontronite NAu-2 (rNAu-2) and Fe (hydr)oxides in their coexisting systems. Results showed that ET could occur from rNAu-2 to ferrihydrite but not to goethite, and the ET amount was determined by the number of reactive sites and the reduction potential difference between rNAu-2 and ferrihydrite.

Electrokinetic-Enhanced Bioremediation of Trichloroethylene-Contaminated Low-Permeability Soils: Mechanistic Insight from Spatio-Temporal Variations of Indigenous Microbial Community and Biodehalogenation Activity.

Electrokinetic-enhanced bioremediation (EK-Bio), particularly bioaugmentation with injection of biodehalogenation functional microbes such as , has been documented to be effective in treating a low-permeability subsurface matrix contaminated with chlorinated ethenes. However, the spatio-temporal variations of indigenous microbial community and biodehalogenation activity of the background matrix, a fundamental aspect for understanding EK-Bio, remain unclear. To fill this gap, we investigated the variation of trichloroethylene (TCE) biodehalogenation activity in response to indigenous microbial community succession in EK-Bio by both column and batch experiments.

SERPINA12 promotes the tumorigenic capacity of HCC stem cells through hyperactivation of AKT/β-catenin signaling.

Background And Aims: HCC is an aggressive disease with poor clinical outcome. Understanding the mechanisms that drive cancer stemness, which we now know is the root cause of therapy failure and tumor recurrence, is fundamental for designing improved therapeutic strategies. This study aims to identify molecular players specific to CD133 + HCC to better design drugs that can precisely interfere with cancer stem cells but not normal stem cell function.

Integrated anaerobic-aerobic biodegradation of mixed chlorinated solvents by electrolysis coupled with groundwater circulation in a simulated aquifer.

Chlorinated solvents are widespread subsurface contaminants that are often present as complex mixtures. Complete biodegradation of mixed chlorinated solvents remains challenging because the optimal redox conditions for biodegradation of different chlorinated solvents differ significantly. In this study, anaerobic and aerobic conditions were integrated by electrolysis coupled with groundwater circulation for biodegradation of a mixture of chloroform (CF, 8.

SCYL3, as a novel binding partner and regulator of ROCK2, promotes hepatocellular carcinoma progression.

Background & Aims: SCY1-like pseudokinase 3 (SCYL3) was identified as a binding partner of ezrin, implicating it in metastasis. However, the clinical relevance and functional role of SCYL3 in cancer remain uncharacterized. In this study, we aimed to elucidate the role of SCYL3 in the progression of hepatocellular carcinoma (HCC).

Metabolic Plasticity of Cancer Stem Cells in Response to Microenvironmental Cues.

An increasing body of evidence suggests that cancer stem cells (CSCs) utilize reprogrammed metabolic strategies to adapt to a hostile tumor microenvironment (TME) for survival and stemness maintenance. Such a metabolic alteration in CSCs is facilitated by microenvironmental cues including metabolites such as glucose, amino acids and lipids, and environmental properties such as hypoxic and acidic TME. Similarly, metabolites uptake from the diet exerts critical imprints to the metabolism profile of CSCs and directly influence the maintenance of the CSC population.

Development of a Community-Based Network to Promote Anti-Drug Messaging and Identify Hidden Drug Abusers in Hong Kong.

Developing a community-based network by training peers as anti-drug ambassadors (ADAs) is a feasible strategy to identify hidden drug abusers. The Ask, Warn, Advise, Refer and Do-it-again (AWARD) model of smoking cessation is useful for enhancing people's confidence in making referrals to anti-drug services. This study evaluated the effectiveness of such a network by examining the change in knowledge, attitudes and practices (KAP) of 198 ADAs aged 13-18 before and after six months of our training.

Protocols to culture and harvest hepatic tumor organoids for metabolic assays.

Three-dimensional organoids, which resemble the pathophysiology and structural architecture of the original tissues, are a preferable model system for assessing metabolic activities in response to various environmental or nutritional changes. Here, we describe step-by-step protocols to establish and culture mouse and human hepatic tumor organoids. We also describe two straightforward and efficient approaches to harvest tumor organoids for investigating the effects of metabolites/drugs on viability and metabolic functions of tumor organoids.

Significant Contribution of Solid Organic Matter for Hydroxyl Radical Production during Oxygenation.

Dark formation of hydroxyl radicals (•OH) from soil/sediment oxygenation has been increasingly reported, and solid Fe(II) is considered as the main electron donor for O activation. However, the role of solid organic matter (SOM) in •OH production is not clear, although it represents an important electron pool in the subsurface. In this study, •OH production from oxygenation of reduced solid humic acid (HA) was investigated at pH 7.

Caspase-3-Induced Activation of SREBP2 Drives Drug Resistance via Promotion of Cholesterol Biosynthesis in Hepatocellular Carcinoma.

Unlabelled: Accumulating evidence has demonstrated that drug resistance can be acquired in cancer through the repopulation of tumors by cancer stem cell (CSC) expansion. Here, we investigated mechanisms driving resistance and CSC repopulation in hepatocellular carcinoma (HCC) as a cancer model using two drug-resistant, patient-derived tumor xenografts that mimicked the development of acquired resistance to sorafenib or lenvatinib treatment observed in patients with HCC. RNA sequencing analysis revealed that cholesterol biosynthesis was most commonly enriched in the drug-resistant xenografts.

Fe(II) oxygenation inhibits bacterial Mn(II) oxidation by P. putida MnB1 in groundwater under O-perturbed conditions.

Bacterial Mn(II) oxidation plays a crucial role in Mn cycling and the associated biogeochemistry in natural waters and is of practical concern in the clean-up of excess Mn from drinking water. Fe(II) usually occurring together with Mn(II) in groundwater is oxidized prior to Mn(II) when perturbed by O, but the impact of Fe(II) oxygenation on the subsequent bacterial Mn(II) oxidation remains unknown. Here we demonstrated that Fe(II) oxygenation largely inhibited the Mn(II)-oxidizing ability of MnB1 belong to Pseudomonas putida which is ubiquitous in groundwater.

The establishment of CDK9/RNA PolII/H3K4me3/DNA methylation feedback promotes HOTAIR expression by RNA elongation enhancement in cancer.

Long non-coding RNA HOX Transcript Antisense RNA (HOTAIR) is overexpressed in multiple cancers with diverse genetic profiles. Importantly, since HOTAIR heavily contributes to cancer progression by promoting tumor growth and metastasis, HOTAIR becomes a potential target for cancer therapy. However, the underlying mechanism leading to HOTAIR deregulation is largely unexplored.

Influence of feeder cells on transcriptomic analysis of pluripotent stem cells.

Objectives: Human pluripotent stem cells (hPSCs) are of great importance in both scientific research and regenerative medicine. The most classic and widely used culture method for hPSCs is co-culture with feeder cells, usually mouse embryonic fibroblasts. However, whether these feeder cell residues can affect the transcriptomic data analysis of hPSCs, especially gene or miRNA expression quantification, is still largely unknown.