nges in tumour size and the biomarker alpha-fetoprotein) and the deterioration of liver function is less in those who have the hepatitis C virus, than in those who do not. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase upregulated in many tumor types and a promising target for cancer therapy. Here, we elucidated the functional role of FAK in intrahepatic cholangiocarcinoma (iCCA) development and progression. Expression levels and activation status of FAK were determined in human iCCA samples. The functional contribution of FAK to Akt/YAP murine iCCA initiation and progression was investigated using conditional Fak KO mice and constitutive Cre or inducible Cre mice, respectively. The oncogenic potential of FAK was further examined via overexpression of FAK in mice. In vitro cell line studies and in vivo drug treatment were applied to address the therapeutic potential of targeting FAK for iCCA treatment. FAK was ubiquitously upregulated and activated in iCCA lesions. Ablation of FAK strongly delayed Akt/YAP driven mouse iCCA initiation. FAK overexpression synergized with activated AKT to promote iCCA development and accelerated Akt/Jag1-driven cholangiocarcinitor treatment is highly detrimental for the growth of in vitro and in vivo iCCA models. This combination therapy might represent a valuable and novel treatment against human iCCA. We found that Focal Adhesion Kinase (FAK) is upregulated and activated in human and mouse intrahepatic cholangiocarcinoma (iCCA) samples. FAK promotes iCCA development, whereas deletion of FAK strongly suppresses iCCA initiation and progression. Mechanistically, we discovered that FAK regulates the YAP pathway. Combined FAK and CDK4/6 inhibitor treatment is highly detrimental for the growth of in vitro and in vivo iCCA models. This combination therapy might represent a valuable and novel treatment against human iCCA. Porto-sinusoidal vascular disease (PSVD) is a rare vascular liver disease of unknown etiology that causes portal hypertension. It usually affects young individuals and shortens live expectancy. The deregulated pathways involved in PSVD development are unknown and therefore we lack curative treatments. The purpose of this study was to integrate transcriptomic and clinical data by comprehensive network-based modeling in order to uncover altered biological processes in patients with PSVD. We obtained liver tissue samples from 20 consecutive patients with PSVD and 21 sex- and age-matched patients with cirrhosis and 13 histologically normal livers (HNL) (initial cohort) and performed transcriptomic analysis. Microarray data were analyzed using weighted gene correlation network analysis to identify clusters of highly correlated genes differently expressed in patients with PSVD. We next evaluated the molecular pathways enriched in patients with PSVD and the core-related genes from the most significantly enrichedems biology approach, we identify that pathways regulating endothelial function and tone may act as drivers of porto-sinusoidal vascular disease. Porto-sinusoidal vascular disease is a rare but life-shortening disease that affects mainly young people. Knowledge of the disrupted pathways involved in its development will help to identify novel therapeutic targets and new treatments. Using a systems biology approach, we identify that pathways regulating endothelial function and tone may act as drivers of porto-sinusoidal vascular disease.We consider Bazykin's model to address harvesting induced stability exchanges through bifurcation analysis. We examine the existence of hydra effects and analyze the stock pattern under predator harvesting. Prey harvesting cannot produce hydra effects in our model, whereas predator harvesting may cause multiple hydra effects. Our study reveals that type II response function and mutual interference among predators jointly induce multiple hydra effects and bistability. Bifurcations such as single Hopf-bifurcation, multiple Hopf-bifurcations and multiple saddle-node bifurcations appear for increasing harvesting rate on the predators. However, over-exploitation of the predators cannot generate any such bifurcation in our study. In simulations, the maximum sustainable yield (MSY) exists at a globally stable state. When predator is culled under increasing effort, basin of attraction of the equilibrium corresponding to the higher predator stock gets expanded, which alternatively is in favor of stock benefit for predators. The ecological theory developed in this study might be useful to understand conservation policy and fishery management.Stenotrophomonas maltophilia is a common conditional pathogen, and it is naturally resistant to most commonly used clinical antibiotics. The bacteriophage is considered to be a potential antibiotic alternative for treating multi-drug-resistant bacteria. In this study, a bacteriophage BUCT555 was isolated from hospital sewage for lysing the clinical multi-drug resistant Stenotrophomonas maltophilia. Electron microscopy studies revealed this phage belongs to the Podoviridae family. The double-stranded DNA genome of bacteriophage BUCT555 is composed of 39,440 bp with a GC content of 61.43%. The genome contains 57 open reading frames, 14 of which had assigned functions, while no virulence related genes, antibiotic resistance genes or tRNA were identified. The burst size of BUCT555 was 204 pfu per infected cell. https://www.selleckchem.com/products/vvd-214.html Structure proteins of bacteriophage BUCT555 generated by SDS-PAGE and HPLC-MS revealed that it contains seven proteins with molecular weight ranging from 19 to 89 kDa. BLASTn analysis showed that phage BUCT555 has 2% homology with other phages in NCBI database, suggesting BUCT555 is a new phage genus of Podoviridae that infects Stenotrophomonas maltophilia. Characterization of the bacteriophage BUCT555 enriches our knowledge about the diversity of Stenotrophomonas maltophilia bacteriophages. This study examined post-exercise glycemic variability in individuals with type 1 diabetes after acute bouts of resistance (RE) and aerobic exercise (AE) compared to a no-exercise day (CON). We hypothesized that exercise days would have greater glucose variability (standard deviation - SD, coefficient of variation - CV), and less time in range (TIR), compared to CON. A secondary analysis was conducted on previously collected data. Twelve active participants with type 1 diabetes performed three testing sessions in random order with at least 48h in between AE (45-min treadmill run at 60%VO ), RE (three sets of eight repetitions, seven weight-lifting exercises), and CON (45-min no-exercise control). Interstitial glucose levels were monitored by blinded continuous glucose monitoring (CGM). Glycemic variability was evaluated for 0-6h, overnight (0000-0600) and 24h after exercise. Mean CGM glucose, TIR, and time above/below range were similar among conditions (P>0.05). Lower SD (0.8 [0.5-1.1], 1.4 [0.9-2.