Enrichment of AT-TA transversion at 5′-CAG-3′ motif is not a unique mutational signature of aristolochic acid

<正>Aristolochic acids, mutational signature, and hepatocellular carcinoma Aristolochic acids (AA) are the etiologic agents of aristolochic acid nephropathy (AAN) and contribute to the global prevalence of chronic kidney disease and urothelial cancer (Grollman et al., 2007). DNA adducts formed by AA generate a unique AT transversions mutation spectrum at     

Modification of donor lymphocyte infusion: how to improve the outcome?

<正>Even after allogeneic hematopoietic stem cell transplantation(HSCT), which has been acknowledged as a curative procedure, relapse of leukemia remains the leading cause of death following transplantation and is a disappointment to transplant physicians. Leukemic relapse occurs due to leukemia cell escape from immune-mediated killing (immune escape) by pre-transplantation conditioning and post-transplantation immune control. Immune exhaustion of donor T     

Understanding Performance Degradation in Cation‐Disordered Rock‐Salt Oxide Cathodes

The collective redox activities of transition‐metal (TM) cations and oxygen anions have been shown to increase charge storage capacity in both Li‐rich layered and cation‐disordered rock‐salt cathodes. Repeated cycling involving anionic redox is known to trigger TM migration and phase transformation in layered Li‐ and Mn‐rich (LMR) oxides, however, detailed mechanistic understanding on the recently discovered Li‐rich rock‐salt cathodes is largely missing. The present study systematically investigates the effect of oxygen redox on a Li_1.3Nb_0.3Mn_0.4O₂ cathode and demonstrates that performance deterioration is directly correlated to the extent of oxygen redox. It is shown that voltage fade and hysteresis begin only after initiating anionic redox at high voltages, which grows progressively with either deeper oxidation of oxygen at higher potential or extended cycling. In contrast to what is reported on layered LMR oxides, extensive TM reduction is observed but phase transition is not detected in the cycled oxide. A densification/degradation mechanism is proposed accordingly which elucidates how a unique combination of extensive chemical reduction of TM and reduced quality of the Li percolation network in cation‐disordered rock‐salts can lead to performance degradation in these newer cathodes with 3D Li migration pathways. Design strategies to achieve balanced capacity and stability are also discussed.     

KIF13B enhances the endocytosis of LRP1 by recruiting LRP1 to caveolae

Multifunctional low-density lipoprotein (LDL) receptor-related protein 1 (LRP1) recognizes and internalizes a large number of diverse ligands, including LDL and factor VIII. However, little is known about the regulation of LRP1 endocytosis. Here, we show that a microtubule-based motor protein, KIF13B, in an unexpected and unconventional function, enhances caveolin-dependent endocytosis of LRP1. KIF13B was highly expressed in the liver and was localized on the sinusoidal plasma membrane of hepatocytes. KIF13B knockout (KO) mice showed elevated levels of serum cholesterol and factor VIII, and KO MEFs showed decreased uptake of LDL. Exogenous KIF13B, initially localized on the plasma membrane with caveolae, was translocated to the vesicles in the cytoplasm with LRP1 and caveolin-1. KIF13B bound to hDLG1 and utrophin, which, in turn, bound to LRP1 and caveolae, respectively. These linkages were required for the KIF13B-enhanced endocytosis of LRP1. Thus, we propose that KIF13B, working as a scaffold, recruits LRP1 to caveolae via LRP1–hDLG1–KIF13B–utrophin–caveolae linkage and enhances the endocytosis of LRP1.     

Focal adhesion kinase maintains,but not increases the adhesion of dental pulp cells

Focal adhesion kinase (FAK) functions as a key enzyme in the integrin-mediated adhesion-signalling pathway. Here, we aimed to investigate the effects of FAK on adhesion of human dental pulp (HDP) cells. We transfected lentiviral vectors to silence or overexpress FAK in HDP cells ex vivo. Early cell adhesion, cell survival and focal contacts (FCs)-related proteins (FAK and paxillin) were examined. By using immunofluorescence, the formation of FCs and cytoskeleton was detected, respectively. We found that both adhesion and survival of HDP cells were suppressed by FAK inhibition. However, FAK overexpression slightly inhibited cell adhesion and exhibited no change in cell survival compared with the control. A thick rim of cytoskeleton accumulated and smaller dot-shaped FCs appeared in FAK knockdown cells. Phosphorylation of paxillin (p-paxillin) was inhibited in FAK knockdown cells, verifying that the adhesion was inhibited. Less cytoskeleton and elongated FCs were observed in FAK-overexpressed cells. However, p-paxillin had no significant difference compared with the control. In conclusion, the data suggest that FAK maintains cell adhesion, survival and cytoskeleton formation, but excessive FAK has no positive effects on these aspects.     

Depression among Migrant and Left-Behind Children in China in Relation to the Quality of Parent-Child and Teacher-Child Relationships

The objective of this study was to examine rates of depression among migrant children (MC) and left-behind children (LBC) as compared to non-left-behind children (NLBC) and also to examine the relationship between depression among these children and the quality of their parent-child and teacher-child relationships. This study collected data from a large sample of 3,759 children aged from 8 to 17 years, including 824 who had been left behind by one parent (LBCO), 423 who had been left behind by both parents (LBCB), 568 MC and 1944 NLBC. Children’s Depression Inventory–Short Form was used to measure child depression. Parent-Child Relationship Scale (PCRS) and Teacher-Child Relationship Scale (TCRS) were used to measure the quality of parent-child and teacher-child relationships, respectively. The results showed that the prevalence of depression was 10.5% among NLBC, 13.1% among LBCO, 16.1% among LBCB, and 20.1% among MC. Depression was related to parent-child relationship quality and teacher-child relationship quality. Negative parent-child relationship was more relevant to depression than negative teacher-child relationship among LBCB, while negative teacher-child relationship was the most correlated with depression among MC.