Case Report: Tissue Origin Identification for Cancer of Unknown Primary: Gene Expression Profiling Approach

The treatment of cancer of unknown primary (CUP) is a huge challenge for clinicians. Gene expression profiling can help identify the tissue origin of tumors by detecting the expression levels of specific genes in tumor tissues. Herein, we report four CUP cases. All of them have been successfully identified with the corresponding primary tumor sites through gene expression profiling analysis. Then all patients received accurate treatment, providing reference to guide therapeutic decisions to treat CUP tumors in the future.

Prevalence of tet(X4) in Escherichia coli From Duck Farms in Southeast China

ObjectivesCarbapenems, colistin, and tigecycline are critically important antibiotics in clinics. After the global appearance of blaNDM and mcr mediating the resistance to carbapenems and colistin, respectively, tigecycline becomes the last-resort drug against severe human infections caused by multidrug-resistant bacteria. Recently, a mobile tigecycline resistance gene tet(X4) has been identified in Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii that causes high resistance to tigecycline and other tetracyclines. In this study, the prevalence of tet(X4) in E. coli isolates from duck and goose farms in Southeast China was identified and characterized.MethodsFeces, soil, sewage, and dust samples were collected from duck and goose farms along with the southeast coast provinces of China. Antimicrobial susceptibility testing and polymerase chain reaction screening were performed to investigate the phenotype and genotype of tigecycline resistance. Conjugation, S1 pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing were used to determine the transferability, genetic location, and the genomic characteristics of tet(X4).ResultsIn total, 1,716 samples were collected, and 16 isolates (0.9%) recovered from Guangdong, Shandong, and Jiangsu were positive for tet(X4) gene with tigecycline minimum inhibitory concentrations ≥16 mg/L. Notably, among these tet(X4)-positive E. coil isolates, seven of them were from the environment samples (soil and sewage). PFGE and multilocus sequence typing demonstrated that ST3997 was the most prevalent sequence type (eight isolates, 50%) in Jiangsu province. By conjugation assays, 11 isolates were able to transfer tet(X4) plasmid to E. coli C600 recipient, and these plasmids belonged to IncHI1 and IncX1 detected by sequence analysis. tet(X4) was found adjacent to an insertion sequence ISCR2 downstream and a catD gene upstream for all isolates. In addition, multiple-drug resistance to tigecycline, chlortetracycline, ampicillin, florfenicol, ciprofloxacin, gentamicin, trimethoprim/sulfamethoxazole, and fosfomycin was profiled in most of the tet(X4)-positive isolates.ConclusionThe identification of tet(X4) harboring E. coli strains in duck farms and their surrounding environment enlarges our knowledge of the variety and prevalence of tigecycline resistance. The prevalence of tet(X4) raises concern for the use of tetracyclines in animal farming, and the tet(X4) gene should be listed as primary gene for resistance surveillance.

Transgenic expression of Nix converts genetic females into males and allows automated sex sorting in Aedes albopictus

Aedes albopictus is a major vector of arboviruses. Better understanding of its sex determination is crucial for developing mosquito control tools, especially genetic sexing strains. In Aedes aegypti, Nix is the primary gene responsible for masculinization and Nix-expressing genetic females develop into fertile, albeit flightless, males. In Ae. albopictus, Nix has also been implicated in masculinization but its role remains to be further characterized. In this work, we established Ae. albopictus transgenic lines ectopically expressing Nix. Several were composed exclusively of genetic females, with transgenic individuals being phenotypic and functional males due to the expression of the Nix transgene. Their reproductive fitness was marginally impaired, while their flight performance was similar to controls. Overall, our results show that Nix is sufficient for full masculinization in Ae. albopictus. Moreover, the transgene construct contains a fluorescence marker allowing efficient automated sex sorting. Consequently, such strains constitute valuable sexing strains for genetic control.

Eco-Geography of Feral Cotton: A Missing Piece in the Puzzle of Gene Flow Dynamics Among Members of Gossypium hirsutum Primary Gene Pool

Mexico is the center of origin and genetic diversity of upland cotton (Gossypium hirsutum L.), the most important source of natural fiber in the world. Currently, wild and domesticated populations (including genetically modified [GM] varieties) occur in this country and gene flow among them has shaped the species’ genetic diversity and structure, setting a complex and challenging scenario for its conservation. Moreover, recent gene flow from GM cultivars to wild Mexican cotton populations has been reported since 2011. In situ conservation of G. hirsutum requires knowledge about the extent of its geographic distribution, both wild and domesticated, as well as the possible routes and mechanisms that contribute to gene flow between the members of the species wild-to-domesticated continuum (i.e., the primary gene pool). However, little is known about the distribution of feral populations that could facilitate gene flow by acting as bridges. In this study, we analyzed the potential distribution of feral cotton based on an ecological niche modeling approach and discussed its implications in the light of the distribution of wild and domesticated cotton. Then, we examined the processes that could be leading to the escape of seeds from the cultivated fields. Our results indicate that the climatic suitability of feral plants in the environmental and geographic space is broad and overlaps with areas of wild cotton habitat and crop fields, suggesting a region that could bridge cultivated cotton and its wild relatives by allowing gene flow between them. This study provides information for management efforts focused on the conservation of wild populations, native landraces, and non-GM domesticated cotton at its center of origin and genetic diversity.

STAT1: A novel candidate biomarker and potential therapeutic target of the recurrent aphthous stomatitis

At present, the recurrent aphthous stomatitis (RAS) are not completely clear. Therefore, identifying the underlying diagnostic biomarkers of RAS can provide new ideas for the diagnosis and treatment of RAS. The gene chip data of RAS (GSE37265) were downloaded from the NCBI Gene Expression Omnibus (GEO) database. Weighted Gene Co-Expression Network Analysis (WGCNA) was used to construct a co-expression module. A total of 16 co-expression modules were identified, and 30 hub genes in the turquoise module were identified. In addition, functional analysis of hub genes in modules of interest was performed, which indicated that such hub genes were mainly involved in pathways related to immune response, virus infection, epithelial cell, signal transduction. module two clusters (highly interconnected regions) were determined in the network, with score=17.647 and 10, respectively, cluster 1 and cluster 2 are linked by STAT1 and ICAM1, it is speculated that STAT1 may be a primary gene of RAS. Finally, genistein, daidzein, kaempferol, resveratrol, rosmarinic acid, triptolide, quercetin and (-)-epigallocatechin-3-gallate were selected from the TCMSP database, and both of them is the STAT-1 inhibitor. The results of reverse molecular docking suggest that in addition to triptolide, (-)-Epigallocatechin-3-gallate and resveratrol, the other 5 compounds (flavonoids) with similar structures may bind to the same position of STAT1 protein with different docking score. In conclusion, our results screened potential biomarkers that might contribute to the diagnosis and treatment of RAS, STAT1 protein is one of the potential therapeutic targets of RAS, and this target can be used to screen potential compounds.

Research on Gastric Cancer’s Drug-resistant Gene Regulatory Network Model

Objective: Based on bioinformatics, differentially expressed gene data of drug-resistance in gastric cancer were analyzed, screened and mined through modeling and network modeling to find valuable data associated with multi-drug resistance of gastric cancer. Methods: First, data sets were preprocessed from three aspects: data processing, data annotation and classification, and functional clustering. Secondly, based on the preprocessed data, each classified primary gene regulatory network was constructed by mining interactions among the genes. This paper computed the values of each node in each classified primary gene regulatory network and ranked these nodes according to their scores. On the basis of this, the appropriate core node was selected and the corresponding core network was developed. Results and Conclusion:: Finally, core network modules were analyzed, which were mined. After the correlation analysis, the result showed that the constructed network module had 20 core genes. This module contained valuable data associated with multi-drug resistance in gastric cancer.

Development and characterization of tetraploid castor plants

Castor is a prime industrial crop belonging to a monotypic genus and its genetic improvement depends on creating desired variability in the primary gene pool. This study reports the development of tetraploid castor plants through colchicine treatment. Seeds of three castor genotypes were soaked in aqueous solutions of colchicine with variable concentrations, and the LD50 value was determined. Of 1010 treated field-raised plants, three were identified as potential polyploids based on increases in a guard cell size and reductions in the number of stomata. The putative polyploid plants were selfed and the progeny were subjected to meiotic analysis. All the progeny were found to be tetraploid. The pairing of chromosomes was abnormal with univalent to octavalent configurations during meiosis-I, but the later parts of meiosis were normal. Seasonal variations in pollen fertility indicated the possible role of temperature-sensitive male sterility in causing the sterility in tetraploid plants. The tetraploid plants were phenotypically comparable with their diploid counterparts, but produced substantially bigger seeds. Thus, these tetraploid plants are valuable resources for basic and applied research in castor.

Divergent Selection and Primary Gene Flow Shape Incipient Speciation of a Riparian Tree on Hawaii Island

A long-standing goal of evolutionary biology is to understand the mechanisms underlying the formation of species. Of particular interest is whether or not speciation can occur in the presence of gene flow and without a period of physical isolation. Here, we investigated this process within Hawaiian Metrosideros, a hypervariable and highly dispersible woody species complex that dominates the Hawaiian Islands in continuous stands. Specifically, we investigated the origin of Metrosideros polymorpha var. newellii (newellii), a riparian ecotype endemic to Hawaii Island that is purportedly derived from the archipelago-wide M. polymorpha var. glaberrima (glaberrima). Disruptive selection across a sharp forest-riparian ecotone contributes to the isolation of these varieties and is a likely driver of newellii’s origin. We examined genome-wide variation of 42 trees from Hawaii Island and older islands. Results revealed a split between glaberrima and newellii within the past 0.3–1.2 My. Admixture was extensive between lineages within Hawaii Island and between islands, but introgression from populations on older islands (i.e., secondary gene flow) did not appear to contribute to the emergence of newellii. In contrast, recurrent gene flow (i.e., primary gene flow) between glaberrima and newellii contributed to the formation of genomic islands of elevated absolute and relative divergence. These regions were enriched for genes with regulatory functions as well as for signals of positive selection, especially in newellii, consistent with divergent selection underlying their formation. In sum, our results support riparian newellii as a rare case of incipient ecological speciation with primary gene flow in trees.