TRACERx analysis identifies a role for FAT1 in regulating chromosomal instability and whole-genome doubling via Hippo signalling.

Chromosomal instability (CIN) is common in solid tumours and fuels evolutionary adaptation and poor prognosis by increasing intratumour heterogeneity. Systematic characterization of driver events in the TRACERx non-small-cell lung cancer (NSCLC) cohort identified that genetic alterations in six genes, including FAT1, result in homologous recombination (HR) repair deficiencies and CIN. Using orthogonal genetic and experimental approaches, we demonstrate that FAT1 alterations are positively selected before genome doubling and associated with HR deficiency.

Origins and impact of extrachromosomal DNA.

Extrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer. Here we examine the diversity of ecDNA elements across cancer, revealing the associated tissue, genetic and mutational contexts. By analysing data from 14,778 patients with 39 tumour types from the 100,000 Genomes Project, we demonstrate that 17.

The relationship between CXCR6+CD8+T cells and clinicopathological parameters in patients with primary biliary cholangitis.

Background: CXCR6+CD8+T cells have been implicated in the pathogenesis of various liver and autoimmune diseases. However, their involvement in primary biliary cholangitis (PBC) has not been elucidated.

Methods: We used immunohistochemistry and flow cytometry to quantify CXCR6+CD8+T cells in hepatic tissue and peripheral blood samples obtained from CXCR6+CD8+T cells obtained from PBC patients.

Replication timing alterations are associated with mutation acquisition during breast and lung cancer evolution.

During each cell cycle, the process of DNA replication timing is tightly regulated to ensure the accurate duplication of the genome. The extent and significance of alterations in this process during malignant transformation have not been extensively explored. Here, we assess the impact of altered replication timing (ART) on cancer evolution by analysing replication-timing sequencing of cancer and normal cell lines and 952 whole-genome sequenced lung and breast tumours.

Report on a case of liver-originating malignant melanoma of unknown primary.

Malignant melanoma (MM) frequently occurs in the skin or mucosa, whereas malignant melanoma of unknown primary (MUP) is diagnosed in patients with lymph nodes or visceral organs as the site of origin, where it is challenging to detect the primary lesion by comprehensive examination. MUP is possibly related to the spontaneous regression of the primary lesion. In addition, primary hepatic melanoma (PHM) usually refers to the primary MM occurring in the liver, with no typical primary lesions and no manifestations of tumor metastasis.

A female of progressive familial intrahepatic cholestasis type 3 caused by heterozygous mutations of ABCB4 gene and her cirrhosis improved after treatment of ursodeoxycholic acid: a case report.

Background: Progressive familial intrahepatic cholestasis (PFIC) is a group of rapidly progressive autosomal recessive disorders characterized by intrahepatic cholestasis. PFIC-3 is caused by mutations in the ATP-binding cassette subfamily B member 4 gene (ABCB4), which encodes multidrug resistance protein 3 (MDR3/ABCB4). Patients are usually in infancy or childhood, but cirrhosis and portal hypertension may be the first manifestation in older children or young adults.

DDX17 is required for efficient DSB repair at DNA:RNA hybrid deficient loci.

Proteins with RNA-binding activity are increasingly being implicated in DNA damage responses (DDR). Additionally, DNA:RNA-hybrids are rapidly generated around DNA double-strand breaks (DSBs), and are essential for effective repair. Here, using a meta-analysis of proteomic data, we identify novel DNA repair proteins and characterise a novel role for DDX17 in DNA repair.

Baicalin improved hepatic injury of NASH by regulating NRF2/HO-1/NRLP3 pathway.

Being at the important pathological stage and the critical treatment period of non-alcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) which is associated with fibrosis, hepatic and liver cancer has become a serious medical problem. As one of the major effective components in Scutellaria baicalensis, baicalin takes on anti-oxidant and anti-inflammatory activities. Nevertheless, its effects on NASH and its underlying molecular mechanism have not been thoroughly understood yet.

Plasma exchange treats severe intrahepatic cholestasis caused by dacomitinib: A case report.

Rationale: Dacomitinib-induced liver injury is often manifested by mild elevations of transaminases and bilirubin, and severe intrahepatic cholestasis caused by dacomitinib for simultaneous taking orally cytochrome P450 2D6 (CYP2D6) competitive substrates has been rarely reported.

Patient Concerns: The patient was a 69-year-old woman with non-small cell lung cancer (NSCLC) who was prescribed oral dacomitinib for a month; she was given oral loratadine due to "allergic rhinitis" and metoprolol extended action tablets due to "tachycardia" separately for a few days during the course of dacomitinib treatment. The patient developed liver damage, increased fatigue, yellow urine, and pruritus, with significantly elevated serum levels of bilirubin and glutamyltranspetidase.

Exploring therapeutic mechanisms of San-Huang-Tang in nonalcoholic fatty liver disease through network pharmacology and experimental validation.

Ethnopharmacological Relevance: San-Huang-Tang (SHT), a traditional Chinese medicine (TCM) formula, has been clinically used to treat obesity and type 2 diabetes mellitus. Recently it has proved that SHT have a good effect on non-alcoholic fatty liver disease (NAFLD).

Aim Of The Study: Our study was designed to investigate the therapeutic mechanisms of the SHT against NAFLD.

SARS-CoV-2 detection by a clinical diagnostic RT-LAMP assay.

The ongoing pandemic of SARS-CoV-2 calls for rapid and cost-effective methods to accurately identify infected individuals. The vast majority of patient samples is assessed for viral RNA presence by RT-qPCR. Our biomedical research institute, in collaboration between partner hospitals and an accredited clinical diagnostic laboratory, established a diagnostic testing pipeline that has reported on more than 252,000 RT-qPCR results since its commencement at the beginning of April 2020.

[Effect of Xiaoyao San on OVX combined with CUS anxiety and depression model rats based on hippocampal microglia M1 polarization].

To investigate the anti-anxiety and anti-depression effect and mechanism of Xiaoyao San on rats with ovariectomy(OVX) combined with chronic unpredictable stress(CUS) model. The model of perimenopausal depression was established by OVX and CUS; the level of anxiety and depression was evaluated by open field test; the levels of interleukin-1β(IL-1β) and interleukin-6(IL-6) mRNA in rat hippocampus were detected by Real-time qPCR; double staining immunofluorescence was used to detect the expression of ionized calcium binding adaptor molecule-1(Iba-1) and inducible nitric oxide synthase(iNOS) in microglia of rat dentate gyrus(DG); Western blot was used to detect the protein expression of Iba-1 and iNOS of microglia in DG region of rat hippocampus. The results showed that in the model group, the number of horizontal movement, the number of vertical movement and central residence time were significantly reduced, and the grooming time was significantly prolonged(P<0.

Author Correction: Scalable and robust SARS-CoV-2 testing in an academic center.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Xiao-Yao-San Formula Improves Cognitive Ability by Protecting the Hippocampal Neurons in Ovariectomized Rats.

Xiao-Yao-San (XYS) decoction is a traditional Chinese medicine formula. This study aimed to investigate the effect of XYS on cognitive abilities and its underlying mechanism in ovariectomized rats. Female Sprague-Dawley rats were ovariectomized and treated with XYS (3 g/kg or 9 g/kg) by gavage, with subcutaneous injection of 17- estradiol (E2, 2 g/kg) as a positive drug control and gavage of 1 ml saline (0.

Ovariectomy Induces Microglial Cell Activation and Inflammatory Response in Rat Prefrontal Cortices to Accelerate the Chronic Unpredictable Stress-Mediated Anxiety and Depression.

Perimenopausal women are associated with increased risks of depression and anxiety, which may be potentially related to the lack of ovarian hormone with antidepression activity in the body. However, the precise mechanism remains unclear so far. This study first adopted the Sprague-Dawley (SD) female rats to construct the ovariectomy (OVX) combined with a chronic unpredictable stress (CUS) model.

eIF4A2 drives repression of translation at initiation by Ccr4-Not through purine-rich motifs in the 5'UTR.

Background: Regulation of the mRNA life cycle is central to gene expression control and determination of cell fate. miRNAs represent a critical mRNA regulatory mechanism, but despite decades of research, their mode of action is still not fully understood.

Results: Here, we show that eIF4A2 is a major effector of the repressive miRNA pathway functioning via the Ccr4-Not complex.

Cryptotanshinone protects against pulmonary fibrosis through inhibiting Smad and STAT3 signaling pathways.

Cryptotanshinone (CTS), a lipophilic compound extracted from root of Salvia miltiorrhiza (Danshen), has demonstrated multiple pharmacological activities, including anti-inflammation, anti-proliferation and anti-infection. However, the effect of CTS on pulmonary fibrosis is unknown. This study aims to investigate the effects of CTS treatment on pulmonary fibrosis and its underlying mechanism.

Drosha drives the formation of DNA:RNA hybrids around DNA break sites to facilitate DNA repair.

The error-free and efficient repair of DNA double-stranded breaks (DSBs) is extremely important for cell survival. RNA has been implicated in the resolution of DNA damage but the mechanism remains poorly understood. Here, we show that miRNA biogenesis enzymes, Drosha and Dicer, control the recruitment of repair factors from multiple pathways to sites of damage.

The emerging role of RNAs in DNA damage repair.

This corrects the article DOI: 10.1038/cdd.2017.

The emerging role of RNAs in DNA damage repair.

Many surveillance and repair mechanisms exist to maintain the integrity of our genome. All of the pathways described to date are controlled exclusively by proteins, which through their enzymatic activities identify breaks, propagate the damage signal, recruit further protein factors and ultimately resolve the break with little to no loss of genetic information. RNA is known to have an integral role in many cellular pathways, but, until very recently, was not considered to take part in the DNA repair process.