High plastic Zr–Cu–Fe–Al–Nb bulk metallic glasses for biomedical applications

Four Zr–Cu–Fe–Al-based bulk metallic glasses（BMGs） with Zr contents greater than 65at% and minor additions of Nb were designed and prepared. The glass forming abilities, thermal stabilities, mechanical properties, and corrosion resistance properties of the prepared BMGs were investigated. These BMGs exhibit moderate glass forming abilities along with superior fracture and yield strengths compared to previously reported Zr–Cu–Fe–Al BMGs. Specifically, the addition of Nb into this quaternary system remarkably increases the plastic strain to 27.5%, which is related to the high Poisson＇s ratio and low Young＇s and shear moduli. The Nb-bearing BMGs also exhibit a lower corrosion current density by about one order of magnitude and a wider passive region than 316 L steel in phosphate buffer solution（PBS, pH 7.4）. The combination of the optimized composition with high deformation ability, low Young＇s modulus, and excellent corrosion resistance properties indicates that this kind of BMG is promising for biomedical applications.

Two novel sodium channel mutations associated with resistance to indoxacarb and metaflumizone in the diamondback moth, Plutella xylostella

Indoxacarb and metaflumizone belong to a relatively new class of sodium channel blocker insecticides （SCBIs）. Due to intensive use of indoxacarb, field-evolved indoxacarb resistance has been reported in several lepidopteran pests, including the dia- mondback moth Plutella xylostella, a serious pest of cruciferous crops. In particular, the BY 12 population of P. xylostella, collected from Baiyun, Guangdong Province of China in 2012, was 750-fold more resistant to indoxacarb and 70-fold more resistant to metaflu- mizone compared with the susceptible Roth strain. Comparison of complementary DNA sequences encoding the sodium channel genes of Roth and BY12 revealed two point mu- tations （F1845Y and V1848I） in the sixth segment of domain IV of the PxNav protein in the BY population. Both mutations are located within a highly conserved sequence region that is predicted to be involved in the binding sites of local anesthetics and SCBIs based on mammalian sodium channels. A significant correlation was observed among 10 field-collected populations between the mutant allele （Y 1845 or I 1848） frequencies （1.7% to 52.5%） and resistance levels to both indoxacarb （34- to 870-fold） and metaflumizone （1- to 70-fold）. The two mutations were never found to co-exist in the same allele of PxNav, suggesting that they arose independently. This is the first time that sodium channel muta- tions have been associated with high levels of resistance to SCBIs. F 1845Y and V 1848I are molecular markers for resistance monitoring in the diamondback moth and possibly other insect pest species.

Knockout of three aminopeptidase N genes does not affect susceptibility of Helicoverpa armigera larvae to Bacillus thuringiensis Cry1A and Cry2A toxins

Bacillus thuringiensis(Bt)insecticidal toxins have been globally utilized for control of agricultural insects through spraying or transgenic crops.Binding of Bt toxins to special receptors on midgut epithelial cells of target insects is a key step in the mode of action.Previous studies suggested aminopeptidase N1(APN1)as a receptor or putative receptor in several lepidopteran insects including Helicoverpa armigera through evidence from RNA interefence‐based gene silencing approaches.In the current study we tested the role of APNs in the mode of action of Bt toxins using clustered regularly interspaced palindromic repeats(CRISPR)/CRISPR‐associated protein 9‐mediated gene knockout.Three APN genes(HaAPN1,HaAPN2 and HaAPN5)were individually knocked out in a susceptible strain(SCD)of H.armigera to establish three homozygous knockout strains.Qualitative in vitro binding studies indicated binding of Cry1Ac or Cry2Ab to midgut brush border membrane vesicles was not obviously affected by APN knockout.Bioassay results showed that none of the three knockouts had significant changes in susceptibility to Cry1A or Cry2A toxins when compared with the SCD strain.This suggests that the three HaAPN genes we tested may not be critical in the mode of action of Cry1A or Cry2A toxins in H.armigera.

Identification of the ryanodine receptor mutation I4743M and its contribution to diamide insecticide resistance in Spodoptera exigua (Lepidoptera: Noctuidae)

Insect ryanodine receptors(RyRs)are the targets of diamide insecticides.Two point mutations G4946E and I4790M(numbering according to Plutella xylostella,PxRyR)in the transmembrane domain of the insect RyRs associated with diamide resistance have so far been identified in three lepidopteran pests,P.xylostella,Tuta absoluta and Chilo suppressalis.In this study,we identified one of the known RyR target site resistance mutations(I4790M)in a field-collected population of Spodoptera exigua.The field-collected WF population of S.exigua exhibited 154 fold resistance to chlorantraniliprole when compared with the susceptible WH-S strain.Sequencing the transmembrane domains of S.exigua RyR(SeRyR)revealed that the resistant WF strain was homozygous for the 14743M mutation(corresponding to I4790M in PxRyR),whereas the G4900E allele(corresponding to G4946E of PxRyR)was not detected.The 4743M allele was introgressed into the susceptible WH-S strain by crossing WF with WH-S,followed by three rounds of backcrossing with WH-S.The introgressed strain 4743M was homozygous for the mutant 4743M allele and shared about 94%of its genetic background with that of the recipient WH-S strain.Compared with WH-S,the near-isogenic 4743M strain showed moderate levels of resistance to chlorantraniliprole(21 fold),cyantraniliprole(25 fold)and flubendiamide(22 fold),suggesting that the I4743M mutation confers medium levels of resistance to all three diamides.Genetic analysis showed diamide resistance in the 4743M strain was inherited as an autosomal and recessive trait.Results from this study have direct implications for the design of appropriate resistance monitoring and management practices to sustainably control S.exigua.

Knockin of the G275E mutation of the nicotinic acetylcholine receptor (nAChR) α6 confers high levels of resistance to spinosyns in Spodoptera exigua

Spinosyns,including spinosad and spinetoram,act on the insect central nervous system,gradually paralyzing or destroying the target insect.Spinosad resistance is associated with loss-of-function mutations in the nicotinic acetylcholine receptor(nAChR)α6 subunit in a number of agricultural pests.Using gene editing,nAChRα6 has been verified as a target for spinosyns in five insect species.Recently,a point mutation(G275E)in exon 9 of nAChRα6 was identified in spinosad-resistant strains of Thrips palmi and Tuta absoluta.To date,no in vivo functional evidence has been obtained to support that this mutation is involved in spinosyn resistance in lepidopteran pests.In this study,the G275E mutation was introduced into the nAChR of Spodoptera exigua using clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)gene-editing technology.Reverse transcriptase-polymerase chain reaction and sequencing confirmed that this mutation was present in exon 9 of the nAChR transcripts in the edited 275E strain.The results of bioassays showed that the 275E strain was highly resistant to spinosad(230-fold)and spinetoram(792-fold)compared to the unedited background strain,directly confirming that the G275E mutation of the nAChRα6 subunit confers high levels of spinosyn resistance in S.exigua.Inheritance analysis showed that the resistance trait is autosomal and incompletely recessive.This study employs a reverse genetics approach to validate the functional role played by the G275E mutation in nAChRα6 of S.exigua in spinosyns resistance and provides another example of the use of CRISPR/Cas9 gene-editing technology to confirm the role played by candidate target site mutations in insecticide resistance.

Optimal Dividend and Dynamic Reinsurance Strategies with Capital Injections and Proportional Costs

We consider an optimization problem of an insurance company in the diffusion setting, which controls the dividends payout as well as the capital injections. To maximize the cumulative expected discounted dividends minus the penalized discounted capital injections until the ruin time, there is a possibility of （cheap or non-cheap） proportional reinsurance. We solve the control problems by constructing two categories of suboptimal models, one without capital injections and one with no bankruptcy by capital injection. Then we derive the explicit solutions for the value function and totally characterize the optimal strategies. Particularly, for cheap reinsurance, they axe the same as those in the model of no bankruptcy.

Genetic analysis and molecular detection of resistance to chlorpyrifos mediated by the A216S substitution in acetylcholinesterase-1 in the plant bug Apolygus lucorum

The green plant bug Apolygus lucorum is a major pest of Bacillus thuringiensis cotton in China.Previously,we reported that chlorpyrifos resistance in a laboratory-selected strain of A.lucorum(BZ-R)is associated with the homozygosis of an allele in the ace-1 gene encoding an alanine to serine substitution at position 216 of acetylcholinesterase-1.Here we describe the results of crosses between the resistant BZ-R strain(41-fold to chlorpyrifos)and the unselected susceptible BZ-S strain homozygous for the wild type alanine allele at position 216.Resistance to chlorpyrifos was inherited as a semi-dominant trait mainly controlled by a single autosomal gene and co-segregates strongly but not completely with the serine substitution in ace-1.Synergism bioassays and enzyme assays showed that minor contributions to resistance are also made by enhanced cytochrome P450 and carboxylesterase activities.A survey of 25 field populations from five Chinese provinces showed strong positive correlations between 50%lethal concentration against chlorpyrifos and S216 allele and genotype frequencies,although the most tolerant populations still only show 40%-50%S216 allele frequencies.The results above provide important information for designing effective resistance monitoring and management strategies for A.lucorum in China.