Redox status of thioredoxin-1 （TRX1） determines the sensitivity of human liver carcinoma cells （HepG2） to arsenic trioxide-induced cell death

lntracellular redox homeostasis plays a critical role in determining tumor cells＇ sensitivity to drug-induced apoptosis. Here we investigated the role of thioredoxin-1 （TRX1）, a key component of redox regulation, in arsenic trioxide （AS2O3）-induced apoptosis. Over-expression of wild-type TRX1 in HepG2 cells led to the inhibition of As2O3-induced cytochrome c （cyto c） release, caspase activation and apoptosis, and down-regulation of TRX1 expression by RNAi sensitized HepG2 cells to As2O3-induced apoptosis. Interestingly, mutation of the active site of TRX1 from Cys^32/35 to Ser^32/35 converted this molecule from an apoptotic protector to an apoptotic promoter. In an effort to understand the mechanisms of this conversion, we used isolated mitochondria from mouse liver and found that recombinant wild-type TRX1 could protect mitochondria from the apoptotic changes. In contrast, the mutant form of TRX1 alone elicited mitochondria-related apoptotic changes, including the mitochondrial permeability transition pore （mPTP） opening, loss of mitochondrial membrane potential, and cyto c release from mitochondria. These apoptotic effects were inhibited by cyclosporine A （CsA）, indicating that mutant TRX1 targeted to mPTP. Alteration of TRX1 from its reduced form to oxidized form in vivo by 2,4-dinitrochlorobenzene （DNCB）, a specific inhibitor ofTRX reductase, also sensitized HepG2 cells to As203-induced apoptosis. These data suggest that TRX1 plays a central role in regulating apoptosis by blocking cyto c release, and inactivation of TRX1 by either mutation or oxidization of the active site cysteines may sensitize tumor cells to As2O3-induced apoptosis.

Regulation of tumor cell migration by protein tyrosine phosphatase (PTP)-proline-, glutamate-, serine-,and threonine-rich sequence(PEST)

Protein tyrosine phosphatase (PTP)-proline-,glutamate-,serine-,and threonine-rich sequence (PEST) is ubiquitously expressed and is a critical regulator of cell adhesion and migration.PTP-PEST activity can be regulated transcriptionally via gene deletion or mutation in several types of human cancers or via post-translational modifications,including phosphorylation,oxidation,and caspase-dependent cleavage.PTP-PEST interacts with and dephosphorylates cytoskeletal and focal adhesion-associated proteins.Dephos-phorylation of PTP-PEST substrates regulates their enzymatic activities and/or their interaction with other proteins and plays an essential role in the tumor cell migration process.

Chinese version of NCCN Clinical Practice Guidelines in Oncology officially authorized by NCCN

The publishing conference of the Chinese version of National Comprehensive Cancer Network （NCCN） Clinical Practice Guidelines in Oncology （hereinafter referred to as NCCN Guidelines） and the inaugural peer reviewer meeting of NCCN Clinical Practice Guidelines in Oncology： Digestive System Cancers （hereinafter referred to as NCCN Guidelines on Digestive System Cancers） were held in People＇s Medical Publishing House in January 28^th, 2016 （Figure 1）.

Large-scale land-sea interactions extend ozone pollution duration in coastal cities along northern China

Land-sea atmosphere interaction(LSAI)is one of the important processes affecting ozone(O_(3))pollution in coastal areas.The effects of small-scale LSAIs like sea-land breezes have been widely studied.However,it is not fully clear how and to what extent the large-scale LSAIs affect O_(3) pollution.Here we explored an O_(3) episode to illuminate the role of large-scale LSAIs in O_(3) pollution over the BohaieYellow Seas and adjacent areas through observations and model simulations.The results show that the northern Bohai Sea's coastal region,influenced by the Mongolian High,initially experienced a typical unimodal diurnal O_(3) variation for three days,when O_(3) precursors from BeijingeTianjineHebei,Shandong,and Northeast China were transported to the BohaieYellow Seas.Photochemical reactions generated O_(3) within marine air masses,causing higher O_(3) levels over the seas than coastal regions.As the Mongolian High shifted eastward and expanded,southerly winds on its western edge transported O_(3)-rich marine air masses toward the coast,prolonging pollution for an additional three days and weakening diurnal variations.Subsequently,emissions from the Korean Peninsula and marine shipping significantly affected O_(3) levels in the northern Bohai Sea(10.7%and 13.7%,respectively).Notably,Shandong's emissions played a substantial role in both phases(27.5%and 26.1%,respectively).These findings underscore the substantial impact of large-scale LSAIs driven by the Mongolian High on O_(3) formation and pollution duration in coastal cities.This insight helps understand and manage O_(3) pollution in northern Bohai Sea cities and broadly applies to temperate coastal cities worldwide.

Brassinosteroids inhibit miRNA-mediated translational repression by decreasing AGO1 on the endoplasmic reticulum

Translational repression is a conserved mechanism in microRNA(miRNA)-guided gene silencing.In Arabidopsis,ARGONAUTE1(AGO1),the major miRNA effector,localizes in the cytoplasm for mRNA cleavage and at the endoplasmic reticulum(ER)for translational repression of target genes.However,the mechanism underlying miRNA-mediated translational repression is poorly understood.In particular,how the subcellular partitioning of AGO1 is regulated is largely unexplored.Here,we show that the plant hormone brassinosteroids(BRs)inhibit miRNA-mediated translational repression by negatively regulating the distribution of AGO1 at the ER in Arabidopsis thaliana.We show that the protein levels rather than the transcript levels of miRNA target genes were reduced in BR-deficient mutants but increased under BR treatments.The localization of AGO1 at the ER was significantly decreased under BR treatments while it was increased in the BR-deficient mutants.Moreover,ROTUNDIFOLIA3(ROT3),an enzyme involved in BR biosynthesis,co-localizes with AGO1 at the ER and interacts with AGO1 in a GW motif-dependent manner.Complementation analysis showed that the AGO1-ROT3 interaction is necessary for the function of ROT3.Our findings provide new clues to understand how miRNA-mediated gene silencing is regulated by plant endogenous hormones.