32 research outputs found

    Gene Expression Profiling for Diagnosis of Triple-Negative Breast Cancer: A Multicenter, Retrospective Cohort Study

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    Background: Triple-negative breast cancer (TNBC) accounts for 12–20% of all breast cancers. Diagnosis of TNBC is sometimes quite difficult based on morphological assessment and immunohistochemistry alone, particularly in the metastatic setting with no prior history of breast cancer.Methods: Molecular profiling is a promising diagnostic approach that has the potential to provide an objective classification of metastatic tumors with unknown primary. In this study, performance of a novel 90-gene expression signature for determination of the site of tumor origin was evaluated in 115 TNBC samples. For each specimen, expression profiles of the 90 tumor-specific genes were analyzed, and similarity scores were obtained for each of the 21 tumor types on the test panel. Predicted tumor type was compared to the reference diagnosis to calculate accuracy. Furthermore, rank product analysis was performed to identify genes that were differentially expressed between TNBC and other tumor types.Results: Analysis of the 90-gene expression signature resulted in an overall 97.4% (112/115, 95% CI: 0.92–0.99) agreement with the reference diagnosis. Among all specimens, the signature correctly classified 97.6% of TNBC from the primary site (41/42) and lymph node metastasis (41/42) and 96.8% of distant metastatic tumors (30/31). Furthermore, a list of genes, including AZGP1, KRT19, and PIGR, was identified as differentially expressed between TNBC and other tumor types, suggesting their potential use as discriminatory markers.Conclusion: Our results demonstrate excellent performance of a 90-gene expression signature for identification of tumor origin in a cohort of both primary and metastatic TNBC samples. These findings show promise for use of this novel molecular assay to aid in differential diagnosis of TNBC, particularly in the metastatic setting

    Bioactive Metabolites and Potential Mycotoxins Produced by Cordyceps Fungi: A Review of Safety

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    Ascomycete Cordyceps fungi such as C. militaris, C. cicadae, and C. guangdongensis have been mass produced on artificial media either as food supplements or health additives while the byproducts of culture substrates are largely used as animal feed. The safety concerns associated with the daily consumption of Cordyceps fungi or related products are still being debated. On the one hand, the known compounds from these fungi such as adenosine analogs cordycepin and pentostatin have demonstrated different beneficial or pharmaceutical activities but also dose-dependent cytotoxicities, neurological toxicities and or toxicological effects in humans and animals. On the other hand, the possibility of mycotoxin production by Cordyceps fungi has not been completely ruled out. In contrast to a few metabolites identified, an array of biosynthetic gene clusters (BGCs) are encoded in each genome of these fungi with the potential to produce a plethora of as yet unknown secondary metabolites. Conservation analysis of BGCs suggests that mycotoxin analogs of PR-toxin and trichothecenes might be produced by Cordyceps fungi. Future elucidation of the compounds produced by these functionally unknown BGCs, and in-depth assessments of metabolite bioactivity and chemical safety, will not only facilitate the safe use of Cordyceps fungi as human food or alternative medicine, but will also benefit the use of mass production byproducts as animal feed. To corroborate the long record of use as a traditional medicine, future efforts will also benefit the exploration of Cordyceps fungi for pharmaceutical purposes

    Grafting Onto Artemisia annua Improves Drought Tolerance in Chrysanthemum by Enhancing Photosynthetic Capacity

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    Drought stress drastically influences the yield and quality of chrysanthemums, and thus grafting has been widely used to improve tolerance to biotic and abiotic stresses. To explore the mechanisms underlying improvements in drought resistance afforded by grafting, we investigated the changes in growth, gas exchange, ribulose-1, 5-bisphosphate carboxylase/oxygenase (Rubisco) expression and activity, sugar components, and the relative expression of photosynthesis-related genes of chrysanthemum (Chrysanthemum morifolium Ramat. ‘Hangbaiju’) plants grafted onto Artemisia annua rootstocks under drought stress by withholding water for 6 d. The results revealed that the growth declines in the grafted chrysanthemums were relatively lower than those of the non-grafted plants under drought stress, and net photosynthetic rate, stomatal conductance, water use efficiency, and transpiration rate in the non-grafted chrysanthemums were significantly decreased. Moreover, the intercellular CO2 concentrations were significantly increased compared with the grafted plants at 5 and 6 d following drought stress. The grafted plants exhibited higher relative expression of the CmrbcL, CmrbcS, CmpsaB, and Cmcab genes, as well as higher Rubisco activity and chlorophyll content under the drought treatment. Sugar accumulation also increased under drought stress, particularly in the non-grafted plants. This result suggested that non-grafted chrysanthemums were less able to resist dehydration, and repressed the genes encoding the expression of photosynthetic components. In conclusion, using A. annua rootstock could alleviate drought stress in chrysanthemums by improving gas exchange capacity and maintaining CmrbcL, CmrbcS, Cmcab, and CmpsaB gene expression, thereby increasing Rubisco activity and improving photosynthetic performance. Keywords: artemisia annua, chrysanthemum, grafting, drought stress, sugar components, photosynthetic capacit

    From phyllosphere to insect cuticles: silkworms gather antifungal bacteria from mulberry leaves to battle fungal parasite attacks

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    Abstract Background Bacterial transfers from plants to insect herbivore guts have been well investigated. However, bacterial exchanges between plant phyllospheres and insect cuticles remain unclear, as does their related biological function. Results Here, we report that the cuticular bacterial loads of silkworm larvae quickly increased after molting and feeding on the white mulberry (Morus alba) leaves. The isolation and examination of silkworm cuticular bacteria identified one bacterium Mammaliicoccus sciuri that could completely inhibit the spore germination of fungal entomopathogens Metarhizium robertsii and Beauveria bassiana. Interestingly, Ma. sciuri was evident originally from mulberry leaves, which could produce a secreted chitinolytic lysozyme (termed Msp1) to damage fungal cell walls. In consistency, the deletion of Msp1 substantially impaired bacterial antifungal activity. Pretreating silkworm larvae with Ma. sciuri cells followed by fungal topical infections revealed that this bacterium could help defend silkworms against fungal infections. Unsurprisingly, the protective efficacy of ΔMsp1 was considerably reduced when compared with that of wild-type bacterium. Administration of bacterium-treated diets had no negative effect on silkworm development; instead, bacterial supplementation could protect the artificial diet from Aspergillus contamination. Conclusions The results of this study evidence that the cross-kingdom transfer of bacteria from plant phyllospheres to insect herbivore cuticles can help protect insects against fungal parasite attacks. Video Abstrac

    NPP-VIIRS DNB Daily Data in Natural Disaster Assessment: Evidence from Selected Case Studies

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    Whereas monthly and annual nighttime light (NTL) composite datasets are being increasingly used to estimate socioeconomic status, use of the National Polar-orbiting Partnership Visible Infrared Imaging Radiometer Suite (NPP-VIIRS) Day/Night Band (DNB) daily data has been limited for detecting and assessing the impact of short-term disastrous events. This study explores the application of daily NPP-VIIRS DNB data in assessing the impact of three types of natural disasters: earthquakes, floods, and storms. Daily DNB images one month prior to and 10 days after a disastrous event were collected and a Percent of Normal Light (PNL) image was produced as the ratio of the mean DNB radiance of the pre- and post-disaster images. Areas with a PNL value lower than one were considered as being affected by the event. The results were compared with the damaged proxy map and the flood proxy map generated using synthetic aperture radar data as well as the reported power outage rates. Our analyses show that overall NPP-VIIRS DNB daily data are useful for detecting damages and power outages caused by earthquake, storm, and flood events. Cloud coverage was identified as a major limitation in using the DNB daily data; rescue activities, traffic, and socioeconomic status of the areas also affect the use of DNB daily data in assessing the impact of natural disasters. Our findings offer new insight into the use of the daily DNB data and provide a practical guide for researchers and practitioners who may consider using such data in different situations or regions

    Identification and validation of a 44-gene expression signature for the classification of renal cell carcinomas

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    Abstract Background Renal cancers account for more than 3% of all adult malignancies and cause more than 23,400 deaths per year in China alone. The four most common types of kidney tumours include clear cell, papillary, chromophobe and benign oncocytoma. These histological subtypes vary in their clinical course and prognosis, and different clinical strategies have been developed for their management. Some kidney tumours can be very difficult to distinguish based on the pathological assessment of morphology and immunohistochemistry. Methods Six renal cell carcinoma microarray data sets, including 106 clear cell, 66 papillary, 42 chromophobe, 46 oncocytoma and 35 adjacent normal tissue samples, were subjected to integrative analysis. These data were combined and used as a training set for candidate gene expression signature identification. In addition, two independent cohorts of 1020 RNA-Seq samples from The Cancer Genome Atlas database and 129 qRT-PCR samples from Fudan University Shanghai Cancer Center (FUSCC) were analysed to validate the selected gene expression signature. Results A 44-gene expression signature derived from microarray analysis was strongly associated with the histological differentiation of renal tumours and could be used for tumour subtype classification. The signature performance was further validated in 1020 RNA-Seq samples and 129 qRT-PCR samples with overall accuracies of 93.4 and 93.0%, respectively. Conclusions A 44-gene expression signature that could accurately discriminate renal tumour subtypes was identified in this study. Our results may prompt further development of this gene expression signature into a molecular assay amenable to routine clinical practice

    The Relationship Between Urban 2-D/3-D Landscape Pattern and Nighttime Light Intensity

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    As spatial and socioeconomic processes are the two key aspects of urban development, revealing the relationship between these two key aspects is critical. Previous studies attempted to explain their correlation at the city or region level using built-up area metrics and nighttime light (NTL) data. However, more comprehensive studies on urban interior spatial characteristics and their relationship to NTL intensity are lacking in a three-dimension space. Using Luojia 1-01 nighttime light data, LiDAR digital surface model data, and other auxiliary data, this study applies an extreme gradient boosting regression model and Sharpley Additive exPlanations method to model and interpret the relationship between two-dimensional (2-D)/3-D landscape patterns and NTL intensity. Two study areas were selected to investigate the landscape–NTL relationship at the parcel and subdistrict levels. The major findings of this study include the following: 1) 2-D and 3-D urban landscape patterns have a close relationship with NTL intensity at the parcel and subdistrict scales; 2) the combinational metric of 2-D and 3-D landscape patterns has a stronger relationship with NTL intensity than either the 2-D or 3-D landscape metrics alone; 3) the correlations between most landscape metrics and NTL intensity are not simply positive or negative but change as metrics grow; and 4) the urban socioeconomic level is not only related to a single landscape metric sometimes but tends to the result of metrics interaction. These findings may help urban planners and government officials make more reasonable urban landscape planning policies under the goal of sustainable development
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