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1.
Biochim Biophys Acta Mol Basis Dis ; 1866(1): 165575, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31666206

RESUMO

Intervertebral disc degeneration (IVDD) is a well-known cause of lower back pain. Icariin has been shown to exert a protective effect on human nucleus pulposus (NP) cells and accordingly has implications for the prevention and treatment of IVDD; however, the molecular mechanisms underlying its action are not fully established. In this study, the mechanisms underlying its protection against hydrogen peroxide (H2O2)-induced oxidative stress injury were investigated. In vitro, we demonstrated that icariin inhibits H2O2-induced mitochondria-mediated apoptosis. It upregulates oxidative stress mediators, i.e., reactive oxygen species, and downregulates mitochondrial membrane potential. Nuclear factor erythroid 2-related factor 2 (Nrf-2) is a key factor involved in the regulation of the endogenous defense system. It was proved that icariin could activate the Nrf-2 signaling pathway, upregulate the protein expression of nuclear respiratory factor-1 and the mitochondrial transcription factor, promoting mitochondrial biogenesis in human NP cells. An Nrf-2 agonist and inhibitor promoted or partly abolished the protective effects of icariin on mitochondrial homeostasis. Moreover, it was demonstrated that the Nrf-2 signaling pathway could be inhibited by the phosphatidylinositol 3-Kinase/AKT pathway. In vivo, icariin ameliorated IVDD in a rat model by promoting Nrf-2 activity, and preserving extracellular matrix in NP cells. These data suggest that icariin could ameliorate IVDD in rat models in vivo. In summary, the protective effects of icariin on human NP cells may suppress the pathogenesis of IVDD via the Nrf-2 signaling pathway. Our findings suggest that the Nrf-2 signaling pathway is a novel therapeutic target for the treatment of IVDD.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31788929

RESUMO

The rational design of hierarchical hollow nanomaterials is of great importance to the high-rate and long-cycle anode materials in lithium-ion batteries. In this paper, multi-wall Sn/SnO2@carbon hollow nanofibers evolve from SnO2 nanofibers are designed and pro-gramable synthesized by electrospinning, polypyrrole coating and annealing reduction method. The synthesized hollow nanofibers have a special wire-in-double-wall-tube structure with larger specific surface area and abundant inner spaces, which can provide effective contacting area of electrolyte with electrode materials and more active sites for redox reaction. Furthermore, it shows excellent cycling stability by virtue of effectively alleviate the volume expansion caused pulverization of tin-based electrode materials. Even after 2000 cycles, the wire-in-double-wall-tube Sn/SnO2@carbon nanofibers exhibit a high specific capacity of 986.3 mAh g-1 (1 A·g-1) and still maintains 508.2 mAh g-1 at high current density of 5 A·g-1. This outstanding electrochemical performance suggests the multi-wall Sn/SnO2@ carbon hollow nanofibers are great promising for high performance energy storage systems.

3.
Cancer Imaging ; 19(1): 83, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801587

RESUMO

BACKGROUND: To investigate and compare the diagnostic performance in T staging for patients with esophagogastric junction cancer using high-resolution magnetic resonance imaging (HR MRI), as compared with conventional MRI at 3 Tesla. METHODS: A total of 118 patients with pathologically confirmed esophagogastric junction cancer were included and underwent multiparameter HR MRI (Cohort 1, 62 patients) or conventional MRI (Cohort 2, 56 patients). T2-weighted, T1-weighted, diffusion-weighted and contrast-enhanced T1-weighted images of each patient were evaluated by two radiologists who determined the preoperative T staging by consensus. Using pathologic staging as the gold standard, the consistency between HR MRI and pathology and between conventional MRI and pathology in T staging was calculated and compared. The overall accuracy, overstatement and understatement of HR MRI and conventional MRI in T staging of patients with esophagogastric junction cancer were computed and compared. Moreover, the diagnostic performance of HR MRI and conventional MRI in T staging (≤ T1 and ≥ T4) of patients with esophagogastric junction cancer were evaluated. RESULTS: There were no significant differences in age (p = 0.465) and sex (p = 0.175) between Cohorts 1 and 2. Excellent agreement was observed in the T staging of patients with esophagogastric junction cancer between pathology and HR MRI (kappa = 0.813), while moderate agreement was observed between pathology and conventional MRI (kappa = 0.486). Significant differences were observed in overall accuracy (88.7% vs 64.3%, p = 0.002) and understatement (1.6% vs 26.8%, p < 0.001) but not for overstatement (9.7% vs 8.9%, p = 0.889) in T staging between HR MRI and conventional MRI techniques. For differentiating the T stages of ≤ T1 from ≥ T2 and the T stages of ≤ T3 from ≥ T4, no significant differences were observed between the imaging techniques. CONCLUSIONS: HR MRI has good diagnostic performance and may serve as an alternative technique in the T staging of patients with esophagogastric junction cancer in clinical practice.

4.
BMC Plant Biol ; 19(1): 484, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31706291

RESUMO

BACKGROUND: Phosphatidyl ethanolamine-binding proteins (PEBPs) are involved in the regulation of plant architecture and flowering time. The functions of PEBP genes have been studied in many plant species. However, little is known about the characteristics and expression profiles of PEBP genes in wild peanut species, Arachis duranensis and Arachis ipaensis, the diploid ancestors of cultivated peanuts. RESULTS: In this study, genome-wide identification methods were used to identify and characterize a total of 32 peanut PEBP genes, 16 from each of the two wild peanut species, A. duranensis and A. ipaensis. These PEBP genes were classified into 3 groups (TERMINAL FLOWER1-like, FLOWERING LOCUS T-like, and MOTHER OF FT AND TFL1-like) based on their phylogenetic relationships. The gene structures, motifs, and chromosomal locations for each of these PEBPs were analyzed. In addition, 4 interchromosomal duplications and 1 tandem duplication were identified in A. duranensis, and 2 interchromosomal paralogs and 1 tandem paralog were identified in A. ipaensis. Ninety-five different cis-acting elements were identified in the PEBP gene promoter regions and most genes had different numbers and types of cis-elements. As a result, the transcription patterns of these PEBP genes varied in different tissues and under long day and short day conditions during different growth phases, indicating the functional diversities of PEBPs in different tissues and their potential functions in plant photoperiod dependent developmental pathways. Moreover, our analysis revealed that AraduF950M/AraduWY2NX in A. duranensis, and Araip344D4/Araip4V81G in A. ipaensis are good candidates for regulating plant architecture, and that Aradu80YRY, AraduYY72S, and AraduEHZ9Y in A. duranensis and AraipVEP8T in A. ipaensis may be key factors regulating flowering time. CONCLUSION: Sixteen PEBP genes were identified and characterized from each of the two diploid wild peanut genomes, A. duranensis and A. ipaensis. Genetic characterization and spatio-temporal expression analysis support their importance in plant growth and development. These findings further our understanding of PEBP gene functions in plant species.

5.
Sci Total Environ ; 688: 1405-1412, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31726568

RESUMO

Qinghai-Tibetan Plateau (QTP), >4000 m known as the "third pole of the earth" and is highly sensitive to nitrogen (N) deposition, understanding the effects of N deposition on multifaceted plant diversity (taxonomy diversity, functional diversity and phylogenetic diversity) in the alpine grasslands of Qinghai-Tibet Plateau are vital for the conservation of alpine plant diversity and the sustainability of alpine grasslands ecosystem services. We added N of different gradients to test the effects of soil acidification, soil eutrophication, and phosphorus limitation independently, and interactively on the multifaceted plant richness and evenness in both an alpine meadow and an alpine steppe of the QTP. We found that all the p-value of taxonomy diversity, functional diversity and phylogenetic diversity were >0.05 and values of R2 of fixed factors by nitrogen addition gradients was low (<0.10). In contrast to the alpine steppe, diversity of alpine meadow is more sensitive to soil factors than alpine steppe. Soil acidification caused by nitrogen deposition changed taxonomic evenness (p < 0.05), while eutrophication associated with nitrogen deposition altered taxonomic richness and phylogenetic evenness (p < 0.05) in the alpine meadow and functional richness (p < 0.05) in the alpine steppe. These findings suggest that the effects of N deposition on the multifaceted plant diversity (taxonomic, functional and phylogenetic diversity) varied with N deposition gradients and ecosystem types. Rational adaptation and mitigation techniques should be considered for different types of alpine grasslands on the QTP according to their different responses to the nitrogen deposition gradients in the future.

6.
Korean J Parasitol ; 57(5): 517-520, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31715693

RESUMO

Echinococcosis is a disease caused by the Echinococcus species that parasitizes in humans. Alveolar echinococcosis (AE) which is caused by Echinococcus multilocularis is harmful to humans. AE mainly occurs in the liver and can be transferred to retroperitoneal lymph nodes, lung, brain, bone, spleen and other organs through lymphatic and blood vessels. Cholangiocarcinoma can occur in the intrahepatic and extrahepatic bile ducts and is more common in the hilar. We reported a case of hilar bile duct alveolar echinococcosis which was originally misdiagnosed an cholangiocarcinoma.

7.
Bioorg Chem ; : 103385, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31669094

RESUMO

A series of homoerythrina alkaloid derivatives containing a 1,2,3-triazole moiety as PARP-1 inhibitors were designed and synthesized. And their anti-proliferative activity was further evaluated. Compound 10n had excellent activity to inhibit proliferation of A549 cells (IC50 = 1.89 µM), which was higher than harringtonine (IC50 = 10.55 µM), pemetrexed (IC50 = 3.39 µM), and rucaparib (IC50 = 4.91 µM). Furthermore, the selectivity index of compound 10n was higher than rucaparib and pemetrexed for lung cancer cells. Flow cytometry analysis showed that compound 10n significantly arrested the cell cycle in the S phase, then induced apoptosis of A549 cells (apoptosis rate is 46%), which effectively inhibited cell proliferation. Simultaneously, western blot analysis revealed that compound 10n could prevent the biosynthesis of PAR. Further analysis results revealed that compound 10n could inhibit the expression of cyclin A, down-regulate the expression of bcl-2/bax, activate caspase-3, and ultimately induce apoptosis of A549 cells. All the results indicated that compound 10n had potential research value as a novel PARP-1 inhibitor in antitumor, and it provided a new reference for further development of PARP-1 inhibitors.

8.
Anal Chim Acta ; 1092: 57-65, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31708033

RESUMO

A nanocomposite nanozyme has been fabricated through mineralizing gold-silver bimetals into Hemin (Hem)-coupled melamine (MA) polymer matrix for visual colorimetric analysis of H2O2 and glucose. Catalytic Hem was cross-linked onto MA scaffold for the mineralization of Au-Ag bimetals yielding the rod-like nanocomposite of MA-Hem/Au-Ag. It was discovered that the resulting nanocomposite could present high aqueous stability and especially improved catalysis, which was more than four-fold higher than that of native Hem. Catalytic kinetics studies indicate that the prepared nanocomposite nanozyme could present much higher affinities to the substrates than those of native Hem or even horseradish peroxidase. Herein, the so mineralized Au-Ag bimetals with the "silver effect" would act as "nanowires" for promoting the electron transferring of nanocomposite nanozyme. Moreover, the Hem-coupled MA polymer matrix with high specific surface area could ensure the high adsorption capacity for the reactant substrates and targeting analytes. The application feasibility of the developed nanocomposite nanozyme was demonstrated subsequently by the colorimetric assays for H2O2 and glucose separately in milk and blood samples, with the linear ranges of 0.010-2.50 mM and 0.0050-2.0 mM, respectively. Such a bimetal mineralization-based fabrication route may open a new door toward the design of diverse nanocomposites nanozymes with improved catalysis and adsorption performances.

9.
J Phys Chem Lett ; : 7537-7546, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31747279

RESUMO

Layered LiCoO2 has drawn tremendous attention as a modeling cathode for Li-ion batteries, while its structural instability, especially in the high delithiation region, remains unsolved. With the aim of revealing the structural fundamentals, LiCoO2 electrodes are investigated at a long delithiation range using both in situ and ex situ techniques. In the highly delithiated LiCoO2 electrode, the unique charge compensation process leads to a spatial charge gradient of Co2+/Co3+/Co4+ ions from surface to bulk, which can be further manipulated by structural distortion, Li extraction, and surface side reactions. The coordinated surface oxygen is shown to be electrochemically active and fully reversible in participating in the charge compensation during cycling. Moreover, the active lattice O can be significantly stabilized by introducing the undesired surface Li-Co antisites, which also play an effective role in accommodating the internal stress induced by volume changes. These findings effectively bridge the structural changes with the Li+/e- migration kinetics to elucidate the degradation of LiCoO2 cathode upon delithiation, demonstrating a rewarding avenue for improving the electrochemical performance of LiCoO2 itself and developing high energy density cathodes for the battery community as well.

10.
Twin Res Hum Genet ; : 1-8, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31767048

RESUMO

Twins Research Australia (TRA) is a community of twins and researchers working on health research to benefit everyone, including twins. TRA leads multidisciplinary research through the application of twin and family study designs, with the aim of sustaining long-term twin research that, both now and in the future, gives back to the community. This article summarizes TRA's recent achievements and future directions, including new methodologies addressing causation, linkage to health, economic and educational administrative datasets and to geospatial data to provide insight into health and disease. We also explain how TRA's knowledge translation and exchange activities are key to communicating the impact of twin studies to twins and the wider community. Building researcher capability, providing registry resources and partnering with all key stakeholders, particularly the participants, are important for how TRA is advancing twin research to improve health outcomes for society. TRA provides researchers with open access to its vibrant volunteer membership of twins, higher order multiples (multiples) and families who are willing to consider participation in research. Established four decades ago, this resource facilitates and supports research across multiple stages and a breadth of health domains.

11.
J Agric Food Chem ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31730344

RESUMO

Light-emitting diode (LED) based light sources, which can selectively and quantitatively provide different spectra, have been frequently applied to manipulate plant growth and development. In this study, the effects of different LED light spectra on the growth, phenolic compounds profile, antioxidant capacity, and transcriptional changes in genes regulating phenolic biosynthesis in soybean microgreens were investigated. The results showed that light illumination decreased the seedling length and yield but increased phenolic compound content. Blue light and ultraviolet-A (UV-A) induced significant increases in total phenolic and total flavonoid content, as compared with the white light control. Sixty-six phenolic compounds were identified in the soybean samples, of which isoflavone, phenolic acid, and flavonol were the main components. Ten phenolic compounds obtained from the orthogonal partial least-squares discriminant analysis (OPLS-DA) were reflecting the effect of light spectra. The antioxidant capacity was consistent with the phenolic metabolite levels, which showed higher levels under blue light and UV-A compared with the control. The highest transcript levels of phenolic biosynthesis-related genes were observed under blue light and UV-A. The transcript levels of GmCHI, GmFLS, and GmIOMT were also upregulated under far-red and red light. Taken together, our findings suggested that the application of LED light could pave a green and effective way to produce phenolic compound-enriched soybean microgreens with high nutritional quality, which could stimulate further investigations for improving plant nutritional value and should have a wide impact on maintaining human health.

12.
Chin Med J (Engl) ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31764182

RESUMO

BACKGROUND: Artificial intelligence-assisted image recognition technology is currently able to detect the target area of an image and fetch information to make classifications according to target features. This study aimed to use deep neural networks for computed tomography (CT) diagnosis of perigastric metastatic lymph nodes (PGMLNs) to simulate the recognition of lymph nodes by radiologists, and to acquire more accurate identification results. METHODS: A total of 1371 images of suspected lymph node metastasis from enhanced abdominal CT scans were identified and labeled by radiologists and were used with 18,780 original images for faster region-based convolutional neural networks (FR-CNN) deep learning. The identification results of 6000 random CT images from 100 gastric cancer patients by the FR-CNN were compared with results obtained from radiologists in terms of their identification accuracy. Similarly, 1004 CT images with metastatic lymph nodes that had been post-operatively confirmed by pathological examination and 11,340 original images were used in the identification and learning processes described above. The same 6000 gastric cancer CT images were used for the verification, according to which the diagnosis results were analyzed. RESULTS: In the initial group, precision-recall curves were generated based on the precision rates, the recall rates of nodule classes of the training set and the validation set; the mean average precision (mAP) value was 0.5019. To verify the results of the initial learning group, the receiver operating characteristic curves was generated, and the corresponding area under the curve (AUC) value was calculated as 0.8995. After the second phase of precise learning, all the indicators were improved, and the mAP and AUC values were 0.7801 and 0.9541, respectively. CONCLUSION: Through deep learning, FR-CNN achieved high judgment effectiveness and recognition accuracy for CT diagnosis of PGMLNs. TRIAL REGISTRATION: Chinese Clinical Trial Registry, No. ChiCTR1800016787; http://www.chictr.org.cn/showproj.aspx?proj=28515.

13.
Chin Med J (Engl) ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31764186

RESUMO

BACKGROUND: Early diagnosis and accurate staging are important to improve the cure rate and prognosis for pancreatic cancer. This study was performed to develop an automatic and accurate imaging processing technique system, allowing this system to read computed tomography (CT) images correctly and make diagnosis of pancreatic cancer faster. METHODS: The establishment of the artificial intelligence (AI) system for pancreatic cancer diagnosis based on sequential contrast-enhanced CT images were composed of two processes: training and verification. During training process, our study used all 4385 CT images from 238 pancreatic cancer patients in the database as the training data set. Additionally, we used VGG16, which was pre-trained in ImageNet and contained 13 convolutional layers and three fully connected layers, to initialize the feature extraction network. In the verification experiment, we used sequential clinical CT images from 238 pancreatic cancer patients as our experimental data and input these data into the faster region-based convolution network (Faster R-CNN) model that had completed training. Totally, 1699 images from 100 pancreatic cancer patients were included for clinical verification. RESULTS: A total of 338 patients with pancreatic cancer were included in the study. The clinical characteristics (sex, age, tumor location, differentiation grade, and tumor-node-metastasis stage) between the two training and verification groups were insignificant. The mean average precision was 0.7664, indicating a good training effect of the Faster R-CNN. Sequential contrast-enhanced CT images of 100 pancreatic cancer patients were used for clinical verification. The area under the receiver operating characteristic curve calculated according to the trapezoidal rule was 0.9632. It took approximately 0.2 s for the Faster R-CNN AI to automatically process one CT image, which is much faster than the time required for diagnosis by an imaging specialist. CONCLUSIONS: Faster R-CNN AI is an effective and objective method with high accuracy for the diagnosis of pancreatic cancer. TRIAL REGISTRATION: ChiCTR1800017542; http://www.chictr.org.cn.

14.
Biomark Med ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729251

RESUMO

Aim: This study profiled differentially expressed long noncoding RNAs (lncRNAs) in lung squamous cell carcinoma (LSCC) to predict LSCC overall survival (OS) using The Cancer Genome Atlas data. Materials & methods: The RNA-seq and clinical dataset of 475 LSCC patients was retrieved from The Cancer Genome Atlas database and statistically analyzed. Results: There were 67 upregulated and 32 downregulated lncRNAs in LSCCs and 12 lncRNAs associated with OS. The seven-lncRNA signature was associated with poor OS and RP11-150O12.6 and CTA-384D8.35 were associated with better OS (p < 0.001). The seven lncRNAs-mRNA interaction network analysis showed their association with 187 protein-coding genes for cancer development, cell migration, adhesion, proliferation, apoptosis, angiogenesis and the MAPK signaling pathways. Conclusion: This seven-lncRNA signature is useful to predict LSCC OS.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31751241

RESUMO

Despite growing progresses in recent years, cross-scenario person re-identification remains challenging, mainly due to the pedestrians commonly surrounded by highly-complex environment contexts. In reality, the human perception mechanism could adaptively find proper contextualized spatial-temporal clues towards pedestrian recognition. However, conventional methods fall short in adaptively leveraging the long-term spatial-temporal information due to ever-increasing computational cost. Moreover, CNN-based deep learning methods are hard to conduct optimization due to the non-differentiable property of the built-in context search operation. To ameliorate, this paper proposes a novel Context-Interactive CNN (CI-CNN) to dynamically find both spatial and temporal contexts by embedding multi-task Reinforcement Learning (MTRL). The CI-CNN streamlines the multi-task reinforcement learning by using an actor-critic agent to capture the temporal-spatial context simultaneously, which comprises a context-policy network and a context-critic network. The former network learns policies to determine the optimal spatial context region and temporal sequence range. Based on the inferred temporal-spatial cues, the latter one focuses on the identification task and provides feedback for the policy network. Thus, CI-CNN can simultaneously zoom in/out the perception field in spatial and temporal domain for the context interaction with the environment. By fostering the collaborative interaction between the person and context, our method could achieve outstanding performance on various public benchmarks, which confirms the rationality of our hypothesis, and verifies the effectiveness of our CI-CNN framework.

16.
Int J Cancer ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31609476

RESUMO

Interval breast cancers (those diagnosed between recommended mammography screens) generally have poorer outcomes and are more common among women with dense breasts. We aimed to develop a risk model for interval breast cancer. We conducted a nested case-control study within the Melbourne Collaborative Cohort Study involving 168 interval breast cancer patients and 498 matched control subjects. We measured breast density using the CUMULUS software. We recorded first-degree family history by questionnaire, measured body mass index (BMI) and calculated age-adjusted breast tissue aging, a novel measure of exposure to estrogen and progesterone based on the Pike model. We fitted conditional logistic regression to estimate odds ratio (OR) or odds ratio per adjusted standard deviation (OPERA) and calculated the area under the receiver operating characteristic curve (AUC). The stronger risk associations were for unadjusted percent breast density (OPERA = 1.99; AUC = 0.66), more so after adjusting for age and BMI (OPERA = 2.26; AUC = 0.70), and for family history (OR = 2.70; AUC = 0.56). When the latter two factors and their multiplicative interactions with age-adjusted breast tissue aging (p = 0.01 and 0.02, respectively) were fitted, the AUC was 0.73 (95% CI 0.69-0.77), equivalent to a ninefold interquartile risk ratio. In summary, compared with using dense breasts alone, risk discrimination for interval breast cancers could be doubled by instead using breast density, BMI, family history and hormonal exposure. This would also give women with dense breasts, and their physicians, more information about the major consequence of having dense breasts-an increased risk of developing an interval breast cancer.

17.
FEBS Lett ; 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31626714

RESUMO

The voltage-gated sodium channels (VGSCs) are aberrantly expressed in a variety of tumors and play an important role in tumor growth and metastasis. Here, we show that VGSCs auxiliary ß3 subunit, encoded by the SCN3B gene, promotes proliferation and suppresses apoptosis in HepG2 cells by promoting p53 degradation. ß3 significantly increases HepG2 cell proliferation, promotes tumor growth in mouse xenograft models, and suppresses senescence and apoptosis. We found that ß3 knockdown stabilizes p53 protein, leading to potentiation of p53-induced cell cycle arrest, senescence, and apoptosis. Mechanistic studies revealed that ß3 could bind to p53, promoting p53 ubiquitination and degradation by stabilizing the p53/MDM2 complex. Our results suggest that ß3 is a novel negative regulator of p53 and a potential oncogenic factor.

18.
Genes (Basel) ; 10(10)2019 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-31590287

RESUMO

For cancer diagnosis, many DNA methylation markers have been identified. However, few studies have tried to identify DNA methylation markers to diagnose diverse cancer types simultaneously, i.e., pan-cancers. In this study, we tried to identify DNA methylation markers to differentiate cancer samples from the respective normal samples in pan-cancers. We collected whole genome methylation data of 27 cancer types containing 10,140 cancer samples and 3386 normal samples, and divided all samples into five data sets, including one training data set, one validation data set and three test data sets. We applied machine learning to identify DNA methylation markers, and specifically, we constructed diagnostic prediction models by deep learning. We identified two categories of markers: 12 CpG markers and 13 promoter markers. Three of 12 CpG markers and four of 13 promoter markers locate at cancer-related genes. With the CpG markers, our model achieved an average sensitivity and specificity on test data sets as 92.8% and 90.1%, respectively. For promoter markers, the average sensitivity and specificity on test data sets were 89.8% and 81.1%, respectively. Furthermore, in cell-free DNA methylation data of 163 prostate cancer samples, the CpG markers achieved the sensitivity as 100%, and the promoter markers achieved 92%. For both marker types, the specificity of normal whole blood was 100%. To conclude, we identified methylation markers to diagnose pan-cancers, which might be applied to liquid biopsy of cancers.

19.
Anal Chem ; 91(22): 14737-14742, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31622079

RESUMO

In this work, a simple and highly selective colorimetric method has been developed for quantifying trace-level ATP using Fe3O4 nanoparticles (Fe3O4 NPs). It was discovered that Fe3O4 NPs could present the dramatically enhanced catalysis once anchored with ATP-specific aptamers (Apts), which is about 6-fold larger than that of bare Fe3O4 NPs. In the presence of ATP, however, the Apts would be desorbed from Fe3O4 NPs due to the Apts-target binding event, leading to the decrease of catalysis rationally depending on ATP concentrations. A colorimetric strategy was thereby developed to facilitate the highly selective detection of ATP, showing the linear concentrations ranging from 0.50 to 100 µM. Subsequently, the developed ATP sensor was employed for the evaluation of ATP in blood with the analysis performances comparably better than those of the documented detection methods, showing the potential applications in the clinical laboratory for the detective diagnosis of some ATP-indicative diseases. Importantly, such a catalysis-based detection strategy should be extended to other kinds of nanozymes with intrinsic catalysis properties (i.e., peroxidase and oxidase-like activities), promising as a universal candidate for monitoring various biological species simply by using target-specific recognition elements like Apts and antibodies.

20.
JAMA Oncol ; 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31580391

RESUMO

Importance: Moving to multigene testing for all women with breast cancer (BC) could identify many more mutation carriers who can benefit from precision prevention. However, the cost-effectiveness of this approach remains unaddressed. Objective: To estimate incremental lifetime effects, costs, and cost-effectiveness of multigene testing of all patients with BC compared with the current practice of genetic testing (BRCA) based on family history (FH) or clinical criteria. Design, Setting, and Participants: This cost-effectiveness microsimulation modeling study compared lifetime costs and effects of high-risk BRCA1/BRCA2/PALB2 (multigene) testing of all unselected patients with BC (strategy A) with BRCA1/BRCA2 testing based on FH or clinical criteria (strategy B) in United Kingdom (UK) and US populations. Data were obtained from 11 836 patients in population-based BC cohorts (regardless of FH) recruited to 4 large research studies. Data were collected and analyzed from January 1, 2018, through June 8, 2019. The time horizon is lifetime. Payer and societal perspectives are presented. Probabilistic and 1-way sensitivity analyses evaluate model uncertainty. Interventions: In strategy A, all women with BC underwent BRCA1/BRCA2/PALB2 testing. In strategy B, only women with BC fulfilling FH or clinical criteria underwent BRCA testing. Affected BRCA/PALB2 carriers could undertake contralateral preventive mastectomy; BRCA carriers could choose risk-reducing salpingo-oophorectomy (RRSO). Relatives of mutation carriers underwent cascade testing. Unaffected relative carriers could undergo magnetic resonance imaging or mammography screening, chemoprevention, or risk-reducing mastectomy for BC risk and RRSO for ovarian cancer (OC) risk. Main Outcomes and Measures: Incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained and compared with standard £30 000/QALY and $100 000/QALY UK and US thresholds, respectively. Incidence of OC, BC, excess deaths due to heart disease, and the overall population effects were estimated. Results: BRCA1/BRCA2/PALB2 multigene testing for all patients detected with BC annually would cost £10 464/QALY (payer perspective) or £7216/QALY (societal perspective) in the United Kingdom or $65 661/QALY (payer perspective) or $61 618/QALY (societal perspective) in the United States compared with current BRCA testing based on clinical criteria or FH. This is well below UK and US cost-effectiveness thresholds. In probabilistic sensitivity analysis, unselected multigene testing remained cost-effective for 98% to 99% of UK and 64% to 68% of US health system simulations. One year's unselected multigene testing could prevent 2101 cases of BC and OC and 633 deaths in the United Kingdom and 9733 cases of BC and OC and 2406 deaths in the United States. Correspondingly, 8 excess deaths due to heart disease occurred in the United Kingdom and 35 in the United States annually. Conclusions and Relevance: This study found unselected, high-risk multigene testing for all patients with BC to be extremely cost-effective compared with testing based on FH or clinical criteria for UK and US health systems. These findings support changing current policy to expand genetic testing to all women with BC.

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