Summary Gossypium hirsutum L. represents the largest source of textile fibre, and China is one of the largest cotton‐producing and cotton‐consuming countries in the world. To investigate the genetic architecture of the agronomic traits of upland cotton in China, a diverse and nationwide population containing 503 G. hirsutum accessions was collected for a genome‐wide association study (GWAS) on 16 agronomic traits. The accessions were planted in four places from 2012 to 2013 for phenotyping. The CottonSNP63K array and a published high‐density map based on this array were used for genotyping. The 503 G. hirsutum accessions were divided into three subpopulations based on 11 975 quantified polymorphic single‐nucleotide polymorphisms (SNPs). By comparing the genetic structure and phenotypic variation among three genetic subpopulations, seven geographic distributions and four breeding periods, we found that geographic distribution and breeding period were not the determinants of genetic structure. In addition, no obvious phenotypic differentiations were found among the three subpopulations, even though they had different genetic backgrounds. A total of 324 SNPs and 160 candidate quantitative trait loci (QTL) regions were identified as significantly associated with the 16 agronomic traits. A network was established for multieffects in QTLs and interassociations among traits. Thirty‐eight associated regions had pleiotropic effects controlling more than one trait. One candidate gene, Gh_D08G2376, was speculated to control the lint percentage (LP). This GWAS is the first report using high‐resolution SNPs in upland cotton in China to comprehensively investigate agronomic traits, and it provides a fundamental resource for cotton genetic research and breeding.

BackgroundSince upland cotton was introduced into China during the 1920s–1950s, hundreds of inbreed cultivars have been developed. To explore the molecular diversity, population structure and elite alleles, 503 inbred cultivars developed in China and some foreign cultivars from the United States and the Soviet Union were collected and analyzed by 494 genome-wide SSRs (Simple Sequence Repeats).MethodsFour hundred and ninety-four pairs of SSRs with high polymorphism and uniform distribution on 26 chromosomes were used to scan polymorphisms in 503 nation-wide upland cottons. The programming language R was used to make boxplots for the phenotypic traits in different environments. Molecular marker data and 6 fiber quality traits were analyzed by the method of MLM (mixed linear model) (P + G + Q + K) in the TASSEL software package on the basis of the population structure and linkage disequilibrium analysis. The loci of elite allelic variation and typical materials carrying elite alleles were identified based on phenotypic effect values.ResultsA total of 179 markers were polymorphic and generated 426 allele loci; the population based on molecular diversity was classified into seven subpopulations corresponding to pedigree origin, ecological and geographical distribution. The attenuation distance of linkage disequilibrium dropped significantly up to 0–5 cM. Association mapping for fiber quality showed that 216 marker loci were associated with fiber quality traits (P < 0.05) explaining 0.58 % ~ 5.12 % of the phenotypic variation, with an average of 2.70 %. Thirteen marker loci were coincident with other studies, and three were detected for the same trait. Seven quantitative trait loci were related to known genes in fiber development. Based on phenotypic effects, 48 typical materials that contained the elite allele loci related to fiber quality traits were identified and are widely used in practical breeding.ConclusionsThe molecular diversity and population structure of 503 nation-wide upland cottons in China were evaluated by 494 genome-wide SSRs, and association mapping for fiber quality revealed known and novel elite alleles. The molecular diversity provides a guide for parental mating in cotton breeding, and the association mapping results will aid in the fine-mapping genes related to fiber quality traits and facilitate further studies on candidate genes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2662-x) contains supplementary material, which is available to authorized users.

Chronic hepatitis B virus (HBV) infection is characterized by sustained liver inflammation with an influx of lymphocytes, which contributes to the development of cirrhosis and hepatocellular carcinoma. The mechanisms underlying this immune-mediated hepatic pathogenesis remain ill defined. We report in this article that repetitive infusion of anti-CD137 agonist mAb in HBV-transgenic mice closely mimics this process by sequentially inducing hepatitis, fibrosis, cirrhosis, and, ultimately, liver cancer. CD137 mAb initially triggers hepatic inflammatory infiltration due to activation of nonspecific CD8+ T cells with memory phenotype. CD8+ T cell-derived IFN-γ plays a central role in the progression of chronic liver diseases by actively recruiting hepatic macrophages to produce fibrosis-promoting cytokines and chemokines, including TNF-α, IL-6, and MCP-1. Importantly, the natural ligand of CD137 was upregulated significantly in circulating CD14+ monocytes in patients with chronic hepatitis B infection and closely correlated with development of liver cirrhosis. Thus, sustained CD137 stimulation may be a contributing factor for liver immunopathology in chronic HBV infection. Our studies reveal a common molecular pathway that is used to defend against viral infection but also causes chronic hepatic diseases.

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A population of 178 recombinant inbred lines (RILs) was developed using a single seed descendant from a cross between G. hirsutum. acc DH962 and G. hirsutum. cv Jimian5, was used to construct a genetic map and to map QTL for fiber and yield traits. A total of 644 polymorphic loci were used to construct a final genetic map, containing 616 loci and spanning 2016.44 cM, with an average of 3.27 cM between adjacent markers. Statistical analysis revealed that segregation distortion in the intraspecific population was more serious than that in the interspecific population. The RIL population and the two parents were phenotyped under 8 environments (two locations, six years), revealing a total of 134 QTL, including 64 for fiber qualities and 70 for yield components, independently detected in seven environments, explaining 4.40–15.28% of phenotypic variation (PV). Among the 134 QTL, 9 common QTL were detected in more than one environment, and 22 QTL and 19 new QTL were detected in combined analysis (E9). A total of 26 QTL hotspot regions were observed on 13 chromosomes and 2 larger linkage groups, and some QTL clusters related to fiber qualities or yield components were also observed. The results obtained in the present study suggested that to map accurate QTL in crops with larger plant types, such as cotton, phenotyping under multiple environments is necessary to effectively apply the obtained results in molecular marker-assisted selection breeding and QTL cloning.

Phytophthora species were surveyed by collecting soil samples and placing bait leaves in selected streams during June-October in the years 2005, 2006 and 2010 at three sites in oak forests in Diqing Tibetan Autonomous Prefecture of NW Yunnan province, China. Seventy-three isolates of Phytophthora spp. were recovered from 135 baited leaf samples and 81 soil samples. Eight Phytophthora species were identified by observation of morphological features and ITS1-5.8S-ITS2 rDNA sequence analysis. The eight taxa included two well-known species P. gonapodyides and P. cryptogea, two recently described species P. gregata and P. plurivora, two named but as yet undescribed taxa, P. taxon PgChlamydo and P. taxon Salixsoil, and two previously unrecognized species, Phytophthora sp.1 and P. sp.2. The most numerous species, P. taxon PgChlamydo, and the second most abundant species, P. taxon Salixsoil, were recovered at all three sites. Phytophthora cryptogea was detected only once at site Nixi. Phytophthora gregata and P. sp.2 were isolated from a stream only at site Bitahai, while the other three species were each found at two sites. Phylogenetic analysis revealed that the isolates belonged to three ITS clades, one species including six isolates in clade 2, six species including 66 isolates in clade 6 and one species in clade 8. There was a relatively rich species and genetic diversity of Phytophthora detected in the investigated regions where the forest biotic and abiotic factors affecting the growth and evolution of Phytophthora populations were diverse.

Nanomedicines (NMs) have played an increasing role in cancer therapy as carriers to efficiently deliver therapeutics into tumor cells. For this application, the uptake of NMs by tumor cells is usually a prerequisite to deliver the cargo to intracellular locations, which mainly relies on endocytosis. NMs can enter cells through a variety of endocytosis pathways. Different endocytosis pathways exhibit different intracellular trafficking routes and diverse subcellular localizations. Therefore, a comprehensive understanding of endocytosis mechanisms is necessary for increasing cellular entry efficiency and to trace the fate of NMs after internalization. This review focuses on endocytosis pathways of NMs in tumor cells, mainly including clathrin-and caveolae-mediated endocytosis pathways, involving effector molecules, expression difference of those molecules between normal and tumor cells, as well as the intracellular trafficking route of corresponding endocytosis vesicles. Then, the latest strategies for NMs to actively employ endocytosis are described, including improving tumor cellular uptake of NMs by receptor-mediated endocytosis, transporter-mediated endocytosis and enabling drug activity by changing intracellular routes. Finally, active targeting strategies towards intracellular organelles are also mentioned. This review will be helpful not only in explicating endocytosis and the trafficking process of NMs and elucidating anti-tumor mechanisms inside the cell but also in rendering new ideas for the design of highly efficacious and cancer-targeted NMs.