α-Pyrone Derivatives from a Streptomyces Strain Resensitize Tamoxifen Resistance in Breast Cancer Cells

Tamoxifen resistance(TamR)is the underlying cause of treatment failure in many breast cancer patients receiving tamoxifen.In order to look for noncytotoxic natural products with the ability to reverse TamR,an extract from strain Streptomyces sp.KIB-H0495 was detected to be active.Subsequent large scale fermentation and isolation led to the isolation of four a-pyrone derivatives including two new compounds,violapyrones J(2)and K(3),and two known analogues,violapyrones B(1)and I(4).Further bioactivity assays indicated that only 1 and 3 exerted potent resensitization effects on MCF-7/TamR cells at a concentration of 1 lM.Owing to the simple structures of 1 and 3,these two compounds might have potential for further investigation as novel tamoxifen resensitization agent in breast cancer chemotherapy.

Identification of important precursors and theoretical toxicity evaluation of byproducts driving cytotoxicity and genotoxicity in chlorination

Chlorination,the most widely used disinfection process for water treatment,is unfortunately always accompanied with the formation of hazardous disinfection byproducts(DBPs).Various organic matter species,like natural organic matter(NOM)and amino acids,can serve as precursors of DBPs during chlorination but it is not clear what types of organic matter have higher potential risks.Although regulation of DBPs such as trihalomethanes has received much attention,further investigation of the DBPs driving toxicity is required.This study aimed to identify the important precursors of chlorination by measuring DBP formation from NOM and amino acids,and to determine the main DBPs driving toxicity using a theoretical toxicity evaluation of contributions to the cytotoxicity index(CTI)and genotoxicity index(GTI).The results showed that NOM mainly formed carbonaceous DBPs(CDBPs),such as trichloromethane,while amino acids mainly formed nitrogenous DBPs(N-DBPs),such as dichloroacetonitrile(DCAN).Among the DBPs,DCAN had the largest contribution to the toxicity index and might be the main driver of toxicity.Among the precursors,aspartic acid and asparagine gave the highest DCAN concentration(200 g/L)and the highest CTI and GTI.Therefore,aspartic acid and asparagine are important precursors for toxicity and their concentrations should be reduced as much as possible before chlorination to minimize the formation of DBPs.During chlorination of NOM,tryptophan,and asparagine solutions with different chlorine doses and reaction times,changes in the CTI and GTI were consistent with changes in the DCAN concentration.

Coexistence of isospin I=0 and I=1 pairings in asymmetric nuclear matter

The coexistence of neutron-neutron(n-n),proton-proton(p-p),and neutron-proton(n-p)pairings is investigated by adopting an effective density-dependent contact pairing potential.These three types of pairings can coexist only if the n-p pairing is stronger than the n-n and p-p pairings for the isospin asymmetric nuclear matter.In addition,the existence of n-n and p-p pairs might enhance n-p pairings in asymmetric nuclear matter when the n-p pairing strength is significantly stronger than the n-n and p-p ones.Conversely,the n-p pairing is reduced by the n-n and p-p pairs when the n-p pairing interaction approaches n-n and p-p pairings.