Gut-liver translocation of pathogen Klebsiella pneumoniae promotes hepatocellular carcinoma in mice.

Hepatocellular carcinoma (HCC) is accompanied by an altered gut microbiota but whether the latter contributes to carcinogenesis is unclear. Here we show that faecal microbiota transplantation (FMT) using stool samples from patients with HCC spontaneously initiate liver inflammation, fibrosis and dysplasia in wild-type mice, and accelerate disease progression in a mouse model of HCC. We find that HCC-FMT results in gut barrier injury and translocation of live bacteria to the liver.

In Situ Transformable Fibrillar Clusters Disrupt Intracellular Copper Metabolic Homeostasis by Comprehensive Blockage of Cuprous Ions Efflux.

Dysregulation of copper metabolism is intricately associated with the occurrence and therapeutic management of colorectal cancer. Previous studies have attempted to induce cuproptosis by delivering lethal doses of copper ions into tumor cells, often with systemic safety risks. In vivo, transformable peptide is modular and designed for various tumor-related proteins, which can affect protein function and distribution.

Mechanism exploration of synergistic photo-immunotherapy strategy based on a novel exosome-like nanosystem for remodeling the immune microenvironment of HCC.

The immunosuppressive tumor microenvironment (TME) has become a major challenge in cancer immunotherapy, with abundant tumor-associated macrophages (TAMs) playing a key role in promoting tumor immune escape by displaying an immunosuppressive (M2) phenotype. Recently, it was reported that M1 macrophage-derived nanovesicles (M1NVs) can reprogram TAMs to an anti-tumor M1 phenotype, thereby significantly alleviating the immunosuppressive TME and enhancing the anti-tumor efficacy of immunotherapy. Herein, we developed M1NVs loaded with mesoporous dopamine (MPDA) and indocyanine green (ICG), which facilitated the recruitment of M2 TAMs through synergistic photothermal and photodynamic therapy.

CRB1-associated retinal degeneration is dependent on bacterial translocation from the gut.

The Crumbs homolog 1 (CRB1) gene is associated with retinal degeneration, most commonly Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Here, we demonstrate that murine retinas bearing the Rd8 mutation of Crb1 are characterized by the presence of intralesional bacteria. While normal CRB1 expression was enriched in the apical junctional complexes of retinal pigment epithelium and colonic enterocytes, Crb1 mutations dampened its expression at both sites.

Probing long-lived radioactive isotopes on the double-logarithmic Segrè chart.

Isotopes have been widely applied in a variety of scientific subjects; many aspects of isotopes, however, remain not well understood. In this study, I investigate the relation between the number of neutrons () and the number of protons () in stable isotopes of non-radioactive elements and long-lived isotopes of radioactive elements at the double-linear scale (conventional Segrè chart) and the double-logarithmic scale. Statistical analyses show that is a power-law function of for these isotopes: = 0.

Effects of flora deficiency on the structure and function of the large intestine.

The significant anatomical changes in large intestine of germ-free (GF) mice provide excellent material for understanding microbe-host crosstalk. We observed significant differences of GF mice in anatomical and physiological involving in enlarged cecum, thinned mucosal layer and enriched water in cecal content. Furthermore, integration analysis of multi-omics data revealed the associations between the structure of large intestinal mesenchymal cells and the thinning of the mucosal layer.

Sonosensitizer Nanoplatforms Augmented Sonodynamic Therapy-Sensitizing Shikonin-Induced Necroptosis Against Hepatocellular Carcinoma.

Background: Apoptosis resistance of hepatocellular carcinoma (HCC) often leads to treatment failure. Nonetheless, overcoming the resistance of HCC to apoptosis by inducing necroptosis of tumor cells to bypass the apoptotic pathway may be a promising treatment strategy. Sonodynamic therapy (SDT) has broad prospects in disease treatment because of its noninvasive characteristic and spatiotemporal control.

Sono-Immunotherapy Mediated Controllable Composite Nano Fluorescent Probes Reprogram the Immune Microenvironment of Hepatocellular Carcinoma.

Background: Despite the clinical efficacy of immunotherapy in treating malignant tumors, its effectiveness is often hampered by the immunosuppressive nature of the tumor microenvironment (TME). In this study, we propose the design of a nanoscale ultrasound contrast agent capable of triggering macrophage polarization and immunogenic cell death (ICD) for the treatment of hepatocellular carcinoma (HCC) through sonodynamic treatment (SDT) and immunotherapy.

Methods: The re-educator (designated as ICG@C3F8-R848 NBs) is composed of the Toll-like receptor agonist resiquimod (R848) and the sonosensitizer Indocyanine green (ICG), utilizing nanobubbles (NBs) as carriers.

Gut microbiota-derived tryptophan metabolites alleviate liver injury via AhR/Nrf2 activation in pyrrolizidine alkaloids-induced sinusoidal obstruction syndrome.

Background And Aims: Hepatic sinusoidal obstruction syndrome (HSOS) is caused by toxic injury, such as pyrrolizidine alkaloids, to the liver sinusoidal endothelial cells, and the gut microbiota may be involved. However, the specific role and underlying mechanism of gut microbiota in HSOS is unknown.

Methods: HSOS model was established by gavage of monocrotaline (MCT) in rats.

High-fat diet impairs gut barrier through intestinal microbiota-derived reactive oxygen species.

Gut barrier disruption is a key event in bridging gut microbiota dysbiosis and high-fat diet (HFD)-associated metabolic disorders. However, the underlying mechanism remains elusive. In the present study, by comparing HFD- and normal diet (ND)-treated mice, we found that the HFD instantly altered the composition of the gut microbiota and subsequently damaged the integrity of the gut barrier.

Indole-3-carboxaldehyde ameliorates ionizing radiation-induced hematopoietic injury by enhancing hematopoietic stem and progenitor cell quiescence.

Indole-3-carboxaldehyde (I3A), one of tryptophan metabolites derived from gut microbiota, extends the lifespan of mice after high-dose ionizing radiation exposure. Persistent myelosuppression is the most common and fatal complication for victims of nuclear accidents and patients undergoing radiotherapy, with few therapeutic options available. However, whether and how I3A protects ionizing radiation-induced hematopoietic toxicity remain unknown.

Underwater instant adhesion mechanism of self-assembled amphiphilic hemostatic granular hydrogel from skin secretion.

The widespread use of biological tissue adhesives for tissue repair is limited by their weak adhesion in a wet environment. Herein, we report the wet adhesion mechanism of a dry granular natural bioadhesive from skin secretion (ADS). Once contacting water, ADS granules self-assemble to form a hydrophobic hydrogel strongly bonding to wet substrates in seconds.

Construction of a Humanized PBMC-PDX Model to Study the Efficacy of a Bacterial Marker in Lung Cancer Immunotherapy.

Commensal microbiome is a key factor of lung cancer immunotherapy efficacy. Elucidating the role of specific strains as bacterial markers in immunotherapy has drawn great attention from the academia. At present, most preclinical studies about the relationship between bacterial markers and immunotherapy rely on the syngeneic mouse models.

Prediction model of axillary lymph node status using automated breast ultrasound (ABUS) and ki-67 status in early-stage breast cancer.

Background: Automated breast ultrasound (ABUS) is a useful choice in breast disease diagnosis. The axillary lymph node (ALN) status is crucial for predicting the clinical classification and deciding on the treatment of early-stage breast cancer (EBC) and could be the primary indicator of locoregional recurrence. We aimed to establish a prediction model using ABUS features of primary breast cancer to predict ALN status.

Oxidative metabolisms catalyzed Earth's oxygenation.

The burial of organic carbon, which prevents its remineralization via oxygen-consuming processes, is considered one of the causes of Earth's oxygenation. Yet, higher levels of oxygen are thought to inhibit burial. Here we propose a resolution of this conundrum, wherein Earth's initial oxygenation is favored by oxidative metabolisms generating partially oxidized organic matter (POOM), increasing burial via interaction with minerals in sediments.

Targeted Phototherapy by Niobium Carbide for Mammalian Tumor Models Similar to Humans.

Background: In the past few decades, nanomaterial-mediated phototherapy has gained significant attention as an alternative antitumor strategy. However, its antitumor success is majorly limited to the treatment of subcutaneous tumors in nude mice. In fact, no studies have been previously conducted in this area/field on clinically-relevant big animal models.

RNA-Seq Technology Reveals the Mechanism of SDT Combined With Novel Nanobubbles Against HCC.

Sonodynamic therapy is widely used in the treatment and research of hepatocellular carcinoma. A novel targeted nanobubble complex mediated with Hematoporphyrin monomethyl ether and Lonidamine was structured as a sensitizer, characterized the properties, and studied the therapeutic effect on hepatocellular carcinoma. The complexes can promote the apoptosis of hepatocellular carcinoma cells and work better in combination with sonodynamic therapy.

RNA-Seq Explores the Mechanism of Oxygen-Boosted Sonodynamic Therapy Based on All-in-One Nanobubbles to Enhance Ferroptosis for the Treatment of HCC.

Background: The combination of sonodynamic therapy and oxygenation strategy is widely used in cancer treatment. However, due to the complexity, heterogeneity and irreversible hypoxic environment produced by hepatocellular carcinoma (HCC) tissues, oxygen-enhancing sonodynamic therapy (SDT) has failed to achieve the desired results. With the emergence of ferroptosis with reactive oxygen species (ROS) cytotoxicity, this novel cell death method has attracted widespread attention.

Dependability of Automated Breast Ultrasound (ABUS) in Assessing Breast Imaging Reporting and Data System (BI-RADS) Category and Size of Malignant Breast Lesions Compared with Handheld Ultrasound (HHUS) and Mammography (MG).

Purpose: This study aimed to evaluate the dependability of automated breast ultrasound (ABUS) compared with handheld ultrasound (HHUS) and mammography (MG) on the Breast Imaging Reporting and Data System (BI-RADS) category and size assessment of malignant breast lesions.

Patients And Methods: A total of 344 confirmed malignant lesions were recruited. All participants underwent MG, HHUS, and ABUS examinations.

Association of stress and functional gastrointestinal disorders in high school graduates.

Background: Psychosocial factors are seemed as important causes of functional gastrointestinal disorders (FGIDs). However, the role of stress in FGIDs in high school students under the pressure of college entrance examination is largely unknown. The aim of this study is to investigate the association between the stress and FGIDs in high school graduates.