No abstract

BackgroundAedes albopictus is distributed widely in China, as a primary vector of Dengue fever and Chikungunya fever in south of China. Chemical insecticide control is one of the integrated programmes to prevent mosquito-borne diseases. Long-term applications of pyrethroids have resulted in the development of resistance in Ae. albopictus populations in China. However, the susceptibility of Ae. albopictus to pyrethroids in Hainan Island was unclear. Knockdown resistance (kdr), caused by point mutations in the VGSC gene, is one of the mechanisms that confer resistance to DDT and pyrethroids. This study was to investigate the resistance level of Ae. albopictus populations in Haikou City to three pyrethroid insecticides, and elucidate the relationship between the resistant phenotype and kdr mutations.MethodsThe Aedes albopictus samples were collected in Xinbu Island (XI), Longtang Town (LT), Shishan Town (ST), Baishamen Park (BP), and Flower Market (FM) from Haikou City, Hainan Island, China. The larval susceptibility to deltamethrin, permethrin and beta-cypermethrin was tested by larval bioassays, and adult susceptibility to deltamethrin and DDT was determined by adult bioassays. The degree of resistance was determined by resistance ratio value (RR50 > 3) for larvae and by mortality for adult. The kdr alleles at codon 1534 of the VGSC gene were genotyped. The relationship between kdr genotypes and resistant phenotypes was analyzed by Chi-square test.ResultsOut of five populations, assessed by larval bioassays, XI was susceptible to deltamethrin and permethrin; LT was susceptible to permethrin and beta-cypermethrin; and ST was susceptible to permithrin. FM and BP both were resistant to all of the three pyrethroids, and FM showed the highest degree of resistance, with RR50 values from 65.17 to 436.36. A total of 493 individuals from the larval bioassays were genotyped for kdr alleles. Five alleles were detected, including two wildtype alleles, TTC(F) (67.04 %) and TTT(F) (0.41 %), and three mutant alleles, TGC(C) (0.30 %), TCC(S) (31.54 %) and TTG(L) (0.71 %). There was a clear correlation between mutant alleles (or F1534S) and resistant phenotypes (P < 0.01).ConclusionTwo novel kdr mutant alleles F1534S and F1534L were detected in the pyrethroid resistant populations of Ae. albopictus in Haikou Hainan, China. For the first time, the mutant F1534S was associated with pyrethroid resistance in Ae. albopictus.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-016-0125-x) contains supplementary material, which is available to authorized users.

Herein, we propose a drug-free approach to cancer therapy that involves cancer cell targeting calcification (CCTC). Several types of cancer cells, such as HeLa cells, characterized by folate receptor (FR) overexpression, can selectively adsorb folate (FA) molecules and then concentrate Ca(2+) locally to induce specific cell calcification. The resultant calcium mineral encapsulates the cancer cells, inducing their death, and in vivo assessments confirm that CCTC treatment can efficiently inhibit tumor growth and metastasis without damaging normal cells compared with conventional chemotherapy. Accordingly, CCTC remarkably improve the survival rate of tumor mice. Notably, both FA and calcium ions are essential ingredients in human metabolism, which means that CCTC is a successful drug-free method for tumor therapy. This achievement may further represent an alternative cancer therapy characterized by selective calcification-based substitution of sclerosis for tumor disease.

Chemotherapy-induced cytotoxicity in normal cells and organs triggers undesired lesions. Although targeted delivery is used extensively, more than half of the chemotherapy dose still concentrates in normal tissues, especially in the liver. Enabling normal cells or organs to defend against cytotoxicity represents an alternative method for improving chemotherapy. Herein, rationally designed nanomaterials are used as artificial organelles to remove unexpected cytotoxicity in normal cells. Nanocomposites of gold-oligonucleotides (Au-ODN) can capture intracytoplasmic doxorubicin (DOX), a standard chemotherapy drug, blocking the drug's access into the cell nucleus. Cells with implanted Au-ODN are more robust since their viability is maintained during DOX treatment. In vivo experiments confirm that the Au-ODN nanomaterials selectively concentrate in hepatocytes and eliminate DOX-induced hepatotoxicity, increasing the cell's capacity to resist the threatening chemotherapeutic milieu. The finding suggests that introducing functional materials as biological devices into living systems may be a new strategy for improving the regulation of cell fate in more complex conditions and for manufacturing super cells.

Mammalian male germ cell development is a stepwise cell-fate transition process; however, the full-term developmental profile of male germ cells remains undefined. Here, by interrogating the high-precision transcriptome atlas of 11,598 cells covering 28 critical time-points, we demonstrate that cell-fate transition from mitotic to post-mitotic primordial germ cells is accompanied by transcriptome-scale reconfiguration and a transitional cell state. Notch signaling pathway is essential for initiating mitotic arrest and the maintenance of male germ cells’ identities. Ablation of HELQ induces developmental arrest and abnormal transcriptome reprogramming of male germ cells, indicating the importance of cell cycle regulation for proper cell-fate transition. Finally, systematic human-mouse comparison reveals potential regulators whose deficiency contributed to human male infertility via mitotic arrest regulation. Collectively, our study provides an accurate and comprehensive transcriptome atlas of the male germline cycle and allows for an in-depth understanding of the cell-fate transition and determination underlying male germ cell development.