The most consistent accuracy data were found for transient elastography by FibroScan®, ELF test and ultrasound elastography, with an area under the receiver operating characteristics curve varying between 0.92 and 1.00 for detecting significant fibrosis. Due to the lack of validation, the accuracy and clinical utility of non-invasive fibrosis tests in children with NAFLD remains uncertain. As studies have solely been performed in tertiary care settings, accuracy data cannot directly be translated to screening populations.Due to the lack of validation, the accuracy and clinical utility of non-invasive fibrosis tests in children with NAFLD remains uncertain. As studies have solely been performed in tertiary care settings, accuracy data cannot directly be translated to screening populations.The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health concern and pose a serious threat to humanity. There is an urgent need for developing therapeutic drugs and (or) biologics to prevent the spread of the virus. The life cycle of SARS-CoV-2 shows that the virus enters host cells by first binding to angiotensin-converting enzyme 2 (ACE2) through its spike protein receptor-binding domain (RBD). Therefore, blocking the binding between of ACE2 and SARS-CoV-2 RBD can inhibit the virus infection in the host cells. In this study, by grafting the complementarity-determining regions (CDRs) of developed SARS-CoV, MERS-CoVs specific neutralizing antibodies (nAbs) include monoclonal antibodies (mAbs) as well as SARS-CoV-2 mAbs onto a known stable nanobody (Nb) scaffold, and a total of 16 Nbs sequences were designed. Five Nbs, namely CS01, CS02, CS03, CS10, and CS16, were selected based on the free energy landscape of protein docking verified by the recently reported Nb-RBD cocrystal structures. CS01, CS02, and CS03 occupied the ACE2 binding site of RBD, while CS10 and CS16 were proposed to inhibit the interaction between RBD and ACE2 through an allosteric mechanism. Based on the structures of the five Nbs in complex with RBD, seven brand-new Nbs with enhanced binding affinities (CS02_RD01, CS03_RD01, CS03_RD02, CS03_RD03, CS03_RD04, CS16_RD01, and CS16_RD02) were generated by redesign of residues on the interface of the five Nbs contact with SARS-CoV-2 RBD. In addition, the identified "hot spots" on the interface of each complex provide useful information to understand the binding mechanism of designed Nbs to SARS-CoV-2 RBD. In sum, the predicted stabilities and high binding affinities of the 11 (re)designed Nbs indicating the potential of the developed computational framework in this work to design effective agents to block the infection of SARS-CoV-2.In sharp contrast to hypervalent iodine(III) compounds, the isoelectronic bromine(III) counterparts have been little studied to date. This knowledge gap is mainly attributed to the difficult-to-control reactivity of λ3 -bromanes as well as to their challenging preparation from the highly toxic and corrosive BrF3 precursor. In this context, we present a straightforward and scalable approach to chelation-stabilized λ3 -bromanes by anodic oxidation of parent aryl bromides possessing two coordinating hexafluoro-2-hydroxypropanyl substituents. A series of para-substituted λ3 -bromanes with remarkably high redox potentials spanning a range from 1.86 V to 2.60 V vs. Ag/AgNO3 was synthesized by the electrochemical method. We demonstrate that the intrinsic reactivity of the bench-stable bromine(III) species can be unlocked by addition of a Lewis or a Brønsted acid. The synthetic utility of the λ3 -bromane activation is exemplified by oxidative C-C, C-N, and C-O bond forming reactions. Tropifexor (TXR) is a novel nonbile acid that acts as an agonist of farnesoid X receptor (FXR). TXR is currently in Phase 2 trials for the treatment of non-alcoholic steatohepatitis (NASH). Herein, we report the impact of TXR on in a piglet model in which cholestatic liver damage and fibrosis where induced by bile duct ligation (BDL). The piglets received BDL and TXR for 2wk. Hepatic, portal and colonic bile acid and amino acid profiles and gut microbiome were analysed. Portal fibroblast growth factor (FGF) 19 levels were measured using an enzyme-linked immunosorbent assay (ELISA). We first showed that bile acid metabolism and signalling are dysfunctional in patients with biliary atresia. Next, we observed that TXR potently suppresses BDL-induced liver injury, fibrosis and ductular reaction in piglets. Within the ileum, TXR enhances FGF19 expression and subsequently increases portal FGF19 levels. In the liver, TXR promotes the expression of small heterodimer partner (SHP) and inhibits cholesterol 7α-hydroxylase (CYP7A1). 1-Thioglycerol clinical trial Additionally, TXR increases the abundance of bile acid-biotransforming bacteria in the distal ileum and alters the composition of amino acids in the colon. Lastly, TXR ameliorates intestinal barrier injury in piglets subjected to BDL. TXR potently ameliorated cholestatic liver injury and fibrosis by modulating the gut-liver axis in piglets. It supports the clinical evaluation of TXR as a therapeutic strategy for cholestatic liver diseases, such as biliary atresia.TXR potently ameliorated cholestatic liver injury and fibrosis by modulating the gut-liver axis in piglets. It supports the clinical evaluation of TXR as a therapeutic strategy for cholestatic liver diseases, such as biliary atresia. Busulfan is a chemotherapy agent used in hematopoietic stem cell transplant (HSCT) conditioning regimens. Busulfan is associated with tonic-clonic seizures in ~10% of patients if administered without seizure prophylaxis. Historically, phenytoin was the most commonly utilized seizure prophylaxis agent; however, phenytoin is associated with CYP450 drug interactions and potentially increases the clearance of busulfan. Levetiracetam is being used more recently for busulfan seizure prophylaxis and is not associated with drug-drug interactions; however, data supporting use in pediatric patients are limited. The primary objective is to determine whether there is any difference in seizure rates or safety profile between phenytoin and levetiracetam when used for seizure prophylaxis. We conducted a retrospective chart review including patients who received busulfan between 2010 and 2019 were identified. The data were evaluated to compare the incidence of busulfan-induced seizures in HSCT patients receiving either phenytoin or levetiracetam and to determine the impact of drug-drug interactions on treatment outcomes/adverse events.