Alternative splicing of IRF3 plays an important role in the development of hepatocarcinoma.

Alternative splicing is a process causing mRNA translation to produce different proteins, and it is crucial for the development of tumours. In this study, we constructed a prognostic model related to alternative splicing events in hepatocarcinoma using bioinformatics analysis, including the alternative splicing of CSAD, AFMID, ZDHHC16, and IRF3. The model is an independent prognostic factor and can accurately predict a patient's prognosis. IRF3 is a transcription factor related to the immune response. Its alternative splicing can affect the expression of various genes related to prognosis and plays an essential role in the tumour microenvironment. We also verified the expression of IRF3 exon skipping isoform in hepatocarcinoma at the mRNA level. In conclusion, we discovered that the alternative splicing of IRF3 is essential for the development of hepatocarcinoma. This study provides new insight into the development of treatments for hepatocarcinoma.

Human peritoneal tight junction, transporter and channel expression in health and kidney failure, and associated solute transport.

Next to the skin, the peritoneum is the largest human organ, essentially involved in abdominal health and disease states, but information on peritoneal paracellular tight junctions and transcellular channels and transporters relative to peritoneal transmembrane transport is scant. We studied their peritoneal localization and quantity by immunohistochemistry and confocal microscopy in health, in chronic kidney disease (CKD) and on peritoneal dialysis (PD), with the latter allowing for functional characterizations, in a total of 93 individuals (0-75 years). Claudin-1 to -5, and -15, zonula occludens-1, occludin and tricellulin, SGLT1, PiT1/SLC20A1 and ENaC were consistently detected in mesothelial and arteriolar endothelial cells, with age dependent differences for mesothelial claudin-1 and arteriolar claudin-2/3. In CKD mesothelial claudin-1 and arteriolar claudin-2 and -3 were more abundant. Peritonea from PD patients exhibited increased mesothelial and arteriolar claudin-1 and mesothelial claudin-2 abundance and reduced mesothelial and arteriolar claudin-3 and arteriolar ENaC. Transperitoneal creatinine and glucose transport correlated with pore forming arteriolar claudin-2 and mesothelial claudin-4/-15, and creatinine transport with mesothelial sodium/phosphate cotransporter PiT1/SLC20A1. In multivariable analysis, claudin-2 independently predicted the peritoneal transport rates. In conclusion, tight junction, transcellular transporter and channel proteins are consistently expressed in peritoneal mesothelial and endothelial cells with minor variations across age groups, specific modifications by CKD and PD and distinct associations with transperitoneal creatinine and glucose transport rates. The latter deserve experimental studies to demonstrate mechanistic links.Clinical Trial registration: The study was performed according to the Declaration of Helsinki and is registered at www.clinicaltrials.gov (NCT01893710).

Genetic instability-related lncRNAs predict prognosis and influence the immune microenvironment in breast cancer.

Genome instability is a hallmark of cancer, and the function of lncRNAs in regulating genomic stability has been gradually characterized. However, the prognostic value of lncRNAs related to genetic instability has not been found in breast cancer. Here we constructed a genetic instability-related lncRNA model including U62317.4, SEMA3B-AS1, MAPT-AS1, AC115837.2, LINC01269, AL645608.7, and GACAT2. This model can evaluate the risk and predict the survival outcomes of patients. Further analysis showed that the differentially expressed genes between the high- and low-risk groups were enriched in immunity and cornified envelope formation pathways. In addition, M2 macrophages infiltrated more obviously in the high-risk group. In summary, lncRNAs related to genetic instability may influence the development of breast cancer through immune infiltration and keratinization. This study provides a wider insight into breast cancer development and treatment.

Peripheral Dopamine Controlled by Gut Microbes Inhibits Invariant Natural Killer T Cell-Mediated Hepatitis.

Neurotransmitters have been shown to regulate immune responses, and thereby are critically related to autoimmune diseases. Here we showed that depletion of dopaminergic neurons significantly promoted activation of hepatic iNKT cells and augmented concanavalin A (Con A)-induced liver injury. The suppressive effect of dopamine on iNKT cells was mediated by D1-like receptor-PKA pathway. Clearance of gut microbiota by antibiotic cocktail reduced synthesis of dopamine in intestines and exacerbated liver damage, and that could be restored by recovery of gut microbiota or replenishment of D1-like receptor agonist. Our results demonstrate that peripheral dopamine controlled by gut microbes inhibits IL4 and IFNγ production in iNKT cells and suppresses iNKT cell-mediated hepatitis. Together, we propose a gut microbe-nervous system-immune system regulatory axis in modulating autoimmune hepatitis.

The mutual restraint effect between the expansion of Alternanthera philoxeroides (Mart.) Griseb and cadmium mobility in aquatic environment.

Alternanthera philoxeroides (Mart.) Griseb is one of the most malignant weeds in its invision habitats. While in the cadmium-contaminated aquatic environment, does A. philoxeroides possess good tolerance and adaptability? To demonstrate the effects of cadmium on A. philoxeroides in the polluted water bodies, a hydroponic stress experiment was conducted over a gradient of Cd concentrations (0, 2.5 and 5mg/l) in triplicate. The seedlings were cultured in a greenhouse and harvested on days 0, 10, 20, 30 and 40, respectively. The results showed the effects of mutual restraint between Cd and A. philoxeroides. The A. philoxeroides seedlings were enriched with large amounts of Cd, and the toxicity of Cd inhibited the rapid growth of A. philoxeroides and induced the rapid degradation of chlorophylls in its tissues. Furthermore, the use of iron plaque effectively immobilized Cd of 1123-2883mg/kg·DW on the root surface, thus it decreased the transferability of Cd in the aquatic environment. Due to its extensive adaptability, good Cd tolerance and the immobilization of Cd predominantly in the roots (the highest Cd concentration enriched was 7588.65±628.90mg/kg·DW in roots). A. philoxeroides effectively restrained the translocation of Cd and partitioned Cd in the roots within water bodies. CAPSULE: The antagonistic effect exists between the invasion of A. philoxeroides and cadmium mobility in aquatic environments.