Inhibition of fatty acid synthase suppresses U-2 OS cell invasion and migration via downregulating the activity of HER2/PI3K/AKT signaling pathway in vitro

FASN plays an important role in the malignant phenotype of various tumors. Our previous studies show that inhibition FASN could induce apoptosis and inhibit proliferation in human osteosarcoma (OS) cell in vivo and vitro. The aim in this study was to investigate the effect of inhibition FASN on the activity of HER2/PI3K/AKT axis and invasion and migration of OS cell. The expression of FASN, HER2 and p-HER2(Y1248) proteins was detected by immunohistochemistry in OS tissues from 24 patients with pulmonary metastatic disease, and the relationship between FASN and p-HER2 as well as HER2 was investigated. The results showed that there was a positive correlation between FASN and HER2 as well as p-HER2 protein expression. The U-2 OS cells were transfected with either the FASN specific RNAi plasmid or the negative control RNAi plasmid. FASN mRNA was measured by RT-PCR. Western blot assays was performed to examine the protein expression of FASN, HER2, p-HER2(Y1248), PI3K, Akt and p-Akt (Ser473). Migration and invasion of cells were investigated by wound healing and transwell invasion assays. The results showed that the activity of HER2/PI3K/AKT signaling pathway was suppressed by inhibiting FASN. Meanwhile, the U-2OS cells migration and invasion were also impaired by inhibiting the activity of FASN/HER2/PI3K/AKT. Our results indicated that inhibition of FASN suppresses OS cell invasion and migration via down-regulation of the “HER2/PI3K/AKT” axis in vitro. FASN blocker may be a new therapeutic strategy in OS management.     

Comparative study of four rice cultivars with different levels of cadmium tolerance

Cadmium (Cd) has been identified as a significant pollutant due to its high solubility in water and soil and high toxicity to plants and animals. Rice, as one of the most important food crops, is grown in soils with variable levels of Cd and therefore, is important to discriminate the Cd tolerance of different rice cultivars to determine their suitability for cultivation in Cd-contaminated soils. This study investigates the primary mechanisms employed by four rice cultivars in attaining Cd tolerance. HA63 cultivar reduces Cd uptake by increasing Fe absorption through activation of phytosiderophores. T3028 cultivar accumulates the highest level of Cd in leaves while also activating its reactive oxygen species (ROS) scavenging system, including antioxidant enzymes and phytochelatins. In some rice cultivars (such as HA63), a cyanide-resistant respiration mechanism, important in Cd detoxification, was also promoted under the Cd stress. In conclusion, different rice cultivars may adopt different biochemical strategies and respond with different efficiency to Cd stress.     

Breast cancer-derived K172N,D301V mutations abolish Na/H exchanger regulatory factor 1 inhibition of platelet-derived growth factor receptor signaling

Na⁺/H⁺ exchanger regulatory factor 1 (NHERF1) is a scaffold protein known to interact with a number of cancer-related proteins. nherf1 Mutations (K172N and D301V) were recently identified in breast cancer cells. To investigate the functional properties of NHERF1, wild-type and cancer-derived nherf1 mutations were stably expressed in SKMES-1 cells respectively. NHERF1-wt overexpression suppressed the cellular malignant phenotypes, including proliferation, migration, and invasion. nherf1 Mutations (K172N and D301V) caused complete or partial loss of NHERF1 functions by affecting the PTEN/NHERF1/PDGFRβ complex formation, inactivating NHERF1 inhibition of PDGF-induced AKT and ERK activation, and attenuating the tumor-suppressor effects of NHERF1-wt. These results further demonstrated the functional consequences of breast cancer-derived nherf1 mutations (K172N and D301V), and suggested the causal role of NHERF1 in tumor development and progression.     

Effects of macrophyte-associated nitrogen cycling bacteria on denitrification in the sediments of the eutrophic Gonghu Bay, Taihu Lake

Integrated Elodea nuttallii-immobilized nitrogen cycling bacteria (INCB) technology was used for ecological restoration in the eutrophic Gonghu Bay, Taihu Lake. Sediment denitrification was investigated through microcosm incubations with four different treatments: bare sediment core as control without restoration, sediment + E. nuttallii, sediment + E. nuttallii + INCB, and sediment + INCB. The sediments with E. nuttallii-INCB assemblage (E-INCB) had the highest denitrification rates among all the treatments, and the E-INCB increased the denitrification rate by 162% in the sediments. The presence of macrophytes yielded a penetration depth of O₂ to more than 20 mm below the sediment–water interface (SWI), while the depth was only 4 mm in the sediments without macrophytes. The quantity of denitrifier in E-INCB sediments (within ~2 cm below the SWI) showed a significant increasing trend during one-month incubation, which was one order of magnitudes higher than that in the sediments without INCB. Macrophytes caused deeper O₂ penetration and increased oxic-anoxic interface, which could stimulate the coupled nitrification–denitrification. The high denitrification rate of the E-INCB treatment may result from the increased inorganic nitrogen content in the vicinity of the SWI, causing more nitrate to reach the anoxic denitrification zone. The results showed that E-INCB assemblage could increase benthic N removal by stimulating denitrification via combined O₂ penetration and enhanced microbial N cycling processes. E-INCB might be used as a potential restoration method for controlling fresh water system eutrophication.     

Population genetic characterisation of dominant Cryptosporidium parvum subtype IIaA15G2R1

The subtype IIaA15G2R1 at the 60 kDa glycoprotein (gp60) gene locus is the most dominant Cryptosporidium parvum infecting dairy cattle and humans in industrialised nations. The reasons for its high transmissibility are not clear, and it remains to be determined whether this subtype represents a homogeneous parasite population. In this study, we sequence-characterised 26 IIaA15G2R subtype specimens and 26 non-IIaA15G2R subtype specimens from the United States, Canada, United Kingdom and Spain at seven other known polymorphic loci, including CP47, CP56, DZ-HRGP, MSC6-5, MSC6-7, RPGR and ZPT. Extensive heterogeneity within IIaA15G2R1 and discordance in typing results between gp60 and other genetic markers were observed. Results of inter-locus and intra-ZPT linkage disequilibrium and recombination analyses indicated that the heterogeneity within IIaA15G2R1 and discordance in typing results among genetic loci were largely due to the occurrence of genetic recombination, mostly within the gp60 subtype IIaA15G2R1. Although there was no clear population diversion between IIaA15G2R and non-IIaA15G2R subtypes, results of STRUCTURE and F_ST analyses suggested the presence of at least two subpopulations; subpopulation 1 had an epidemic population structure and was widely distributed, whereas subpopulation 2 had a clonal population structure and consisted of geographically segregated multilocus subtypes. Genetic recombination between epidemic and geographically segregated C. parvum populations appeared to be a driving force in the emergence of a hyper-transmissible IIaA15G2R1 subtype. Genetic recombination was observed even between the zoonotic IIa subtype family and anthroponotic subtype family IIc at CP56, MSC6-7 and ZPT. Thus, the IIaA15G2R1 subtype at gp60 is likely a fitness marker for C. parvum and the wide spread of IIaA15G2R1 subtype around the world is probably independent of the sequence characteristics at other genetic loci.     

ZmGA3ox2, a candidate gene for a major QTL,qPH3.1, for plant height in maize

Maize plant height is closely associated with biomass, lodging resistance and grain yield. Determining the genetic basis of plant height by characterizing and cloning plant height genes will guide the genetic improvement of crops. In this study, a quantitative trait locus (QTL) for plant height, qPH3.1, was identified on chromosome 3 using populations derived from a cross between Zong3 and its chromosome segment substitution line, SL15. The plant height of the two lines was obviously different, and application of exogenous gibberellin A₃ removed this difference. QTL mapping placed qPH3.1 within a 4.0 cM interval, explaining 32.3% of the phenotypic variance. Furthermore, eight homozygous segmental isolines (SILs) developed from two larger F₂ populations further narrowed down qPH3.1 to within a 12.6 kb interval. ZmGA3ox2, an ortholog of OsGA3ox2, which encodes a GA3 β‐hydroxylase, was positionally cloned. Association mapping identified two polymorphisms in ZmGA3ox2 that were significantly associated with plant height across two experiments. Quantitative RT‐PCR showed that SL15 had higher ZmGA3ox2 expression relative to Zong3. The resultant higher GA₁ accumulation led to longer internodes in SL15 because of increased cell lengths. Moreover, a large deletion in the coding region of ZmGA3ox2 is responsible for the dwarf mutant d1‐6016. The successfully isolated qPH3.1 enriches our knowledge on the genetic basis of plant height in maize, and provides an opportunity for improvement of plant architecture in maize breeding.     

New β-phospholactam as a carbapenem transition state analog: Synthesis of a broad-spectrum inhibitor of metallo-β-lactamases

In an effort to test whether a transition state analog is an inhibitor of the metallo-β-lactamases, a phospholactam analog of carbapenem has been synthesized and characterized. The phospholactam 1 proved to be a weak, time-dependent inhibitor of IMP-1 (70%), CcrA (70%), L1 (70%), NDM-1 (53%), and Bla2 (94%) at an inhibitor concentration of 100 μM. The phospholactam 1 activated ImiS and BcII at the same concentration. Docking studies were used to explain binding and to offer suggestions for modifications to the phospholactam scaffold to improve binding affinities.