Maternal tamoxifen exposure leads to abnormal primordial follicle assembly.

Tamoxifen (TAM) is an accredited drug used for treatment and prevention of breast cancer. Due to the long-term taking and the trend for women to delay childbearing, inadvertent conception occasionally occurs during TAM treatment. To explore the effects of TAM on a fetus, pregnant mice at gestation day 16.5 were orally administrated with different concentrations of TAM. Molecular biology techniques were used to analyze the effects of TAM on primordial follicle assembly of female offspring and the mechanism. It was found that maternal TAM exposure affected primordial follicle assembly and damaged the ovarian reserve in 3 dpp offspring. Up to 21 dpp, the follicular development had not recovered, with significantly decreased antral follicles and decreased total follicle number after maternal TAM exposure. Cell proliferation was significantly inhibited; however, the cell apoptosis was induced by maternal TAM exposure. Epigenetic regulation was also involved in the process of TAM induced abnormal primordial follicle assembly. The changed levels of H3K4me3, H3K9me3, and H3K27me3 presented the function of histone methylation in the regulation of the effects of maternal TAM exposure on the reproduction of female offspring. Moreover, the changed level of RNA m6A modification and the changed expression of genes related to transmethylation and demethylation proved the role of m6A in the process. Maternal TAM exposure led to abnormal primordial follicle assembly and follicular development by affecting cell proliferation, cell apoptosis, and epigenetics.

Visual Measurement System for Wheel-Rail Lateral Position Evaluation.

Railway infrastructure must meet safety requirements concerning its construction and operation. Track geometry monitoring is one of the most important activities in maintaining the steady technical conditions of rail infrastructure. Commonly, it is performed using complex measurement equipment installed on track-recording coaches. Existing low-cost inertial sensor-based measurement systems provide reliable measurements of track geometry in vertical directions. However, solutions are needed for track geometry parameter measurement in the lateral direction. In this research, the authors developed a visual measurement system for track gauge evaluation. It involves the detection of measurement points and the visual measurement of the distance between them. The accuracy of the visual measurement system was evaluated in the laboratory and showed promising results. The initial field test was performed in the Vilnius railway station yard, driving at low velocity on the straight track section. The results show that the image point selection method developed for selecting the wheel and rail points to measure distance is stable enough for TG measurement. Recommendations for the further improvement of the developed system are presented.

Dual challenges of heat wave and protective facemask-induced thermal stress in Hong Kong.

During the COVID-19 pandemic, wearing protective facemasks (PFMs) can effectively reduce infection risk, but the use of PFMs can amplify heat-related health risks. We studied the amplified PFM-induced human thermal stress via both field measurements and model simulations over a typical subtropical mountainous city, Hong Kong. First, a hot and humid PFM microenvironment has been observed with high temperature (34-35 °C) and high humidity (80-95%), resulting in an aggravated facial thermal stress with a maximal PFM-covered facial heat flux of 500 W/m2 under high-intensity activities. Second, to predict the overall PFM-inclusive human thermal stress, we developed a new facial thermal load model, S PFM and a new human-environment adaptive thermal stress (HEATS) model by coupling S PFM with an enhanced thermal comfort model to resolve modified human-environment interactions with the intervention of PFM under realistic climatic and topographical conditions. The model was then applied to predict spatiotemporal variations of PFM-inclusive physiological subjective temperature (PST) and corresponding heat stress levels during a typical heat wave event. It was found wearing PFM can significantly aggravate human thermal stress over Hong Kong with a spatially averaged PST increment of 5.0 °C and an additional spatial area of 158.4% exposed to the severest heat risks. Besides, PFM-inclusive PST was found to increase nonlinearly with terrain slopes at a rate of 1.3-3.9 °C/10°(slope), owing to elevated metabolic heat production. Furthermore, urban residents were found to have higher PFM-aggravated heat risks than rural residents, especially at night due to synergistic urban heat and moisture island effects.

MYB52 Negatively Regulates Pectin Demethylesterification in Seed Coat Mucilage.

Pectin, which is a major component of the plant primary cell walls, is synthesized and methyl-esterified in the Golgi apparatus and then demethylesterified by pectin methylesterases (PMEs) located in the cell wall. The degree of methylesterification affects the functional properties of pectin, and thereby influences plant growth, development and defense. However, little is known about the mechanisms that regulate pectin demethylesterification. Here, we show that in Arabidopsis (Arabidopsis thaliana) seed coat mucilage, the absence of the MYB52 transcription factor is correlated with an increase in PME activity and a decrease in the degree of pectin methylesterification. Decreased methylesterification in the myb52 mutant is also correlated with an increase in the calcium content of the seed mucilage. Chromatin immunoprecipitation analysis and molecular genetic studies suggest that MYB52 transcriptionally activates PECTIN METHYLESTERASE INHIBITOR6 (PMEI6), PMEI14, and SUBTILISIN-LIKE SER PROTEASE1.7 (SBT1.7) by binding to their promoters. PMEI6 and SBT1.7 have previously been shown to be involved in seed coat mucilage demethylesterification. Our characterization of two PMEI14 mutants suggests that PMEI14 has a role in seed coat mucilage demethylesterification, although its activity may be confined to the seed coat in contrast to PMEI6, which functions in the whole seed. Our demonstration that MYB52 negatively regulates pectin demethylesterification in seed coat mucilage, and the identification of components of the molecular network involved, provides new insight into the regulatory mechanism controlling pectin demethylesterification and increases our understanding of the transcriptional regulation network involved in seed coat mucilage formation.

Boron-bridged RG-II and calcium are required to maintain the pectin network of the Arabidopsis seed mucilage ultrastructure.

The structure of a pectin network requires both calcium (Ca2+) and boron (B). Ca2+ is involved in crosslinking pectic polysaccharides and arbitrarily induces the formation of an "egg-box" structure among pectin molecules, while B crosslinks rhamnogalacturonan II (RG-II) side chain A apiosyl residues in primary cell walls to generate a borate-dimeric-rhamnogalacturonan II (dRG-II-B) complex through a boron-bridge bond, leading to the formation of a pectin network. Based on recent studies of dRG-II-B structures, a hypothesis has been proposed suggesting that Ca2+is a common component of the dRG-II-B complex. However, no in vivo evidence has addressed whether B affects the stability of Ca2+ crosslinks. Here, we investigated the L-fucose-deficient dwarf mutant mur1, which was previously shown to require exogenous B treatment for phenotypic reversion. Imbibed Arabidopsis thaliana seeds release hydrated polysaccharides to form a halo of seed mucilage covering the seed surface, which consists of a water-soluble outer layer and an adherent inner layer. Our study of mur1 seed mucilage has revealed that the pectin in the outer layer of mucilage was relocated to the inner layer. Nevertheless, the mur1 inner mucilage was more vulnerable to rough shaking or ethylene diamine tetraacetic acid (EDTA) extraction than that of the wild type. Immunolabeling analysis suggested that dRG-II-B was severely decreased in mur1 inner mucilage. Moreover, non-methylesterified homogalacturonan (HG) exhibited obvious reassembly in the mur1 inner layer compared with the wild type, which may imply a possible connection between dRG-II-B deficiency and pectin network transformation in the seed mucilage. As expected, the concentration of B in the mur1 inner mucilage was reduced, whereas the distribution and concentration of Ca2+in the inner mucilage increased significantly, which could be the reason why pectin relocates from the outer mucilage to the inner mucilage. Consequently, the disruption of B bridges appears to result in the extreme sensitivity of the mur1 mucilage pectin complex to EDTA extraction, despite the reinforcement of the pectin network by excessive Ca2+. Therefore, we propose a hypothesis that B, in the form of dRG-II-B, works together with Ca2+to maintain pectin network crosslinks and ultimately the mucilage ultrastructure in seed mucilage. This work may serve to complement our current understanding of mucilage configuration.

CELLULOSE SYNTHASE-LIKE A2, a glucomannan synthase, is involved in maintaining adherent mucilage structure in Arabidopsis seed.

Mannans are hemicellulosic polysaccharides that are considered to have both structural and storage functions in the plant cell wall. However, it is not yet known how mannans function in Arabidopsis (Arabidopsis thaliana) seed mucilage. In this study, CELLULOSE SYNTHASE-LIKE A2 (CSLA2; At5g22740) expression was observed in several seed tissues, including the epidermal cells of developing seed coats. Disruption of CSLA2 resulted in thinner adherent mucilage halos, although the total amount of the adherent mucilage did not change compared with the wild type. This suggested that the adherent mucilage in the mutant was more compact compared with that of the wild type. In accordance with the role of CSLA2 in glucomannan synthesis, csla2-1 mucilage contained 30% less mannosyl and glucosyl content than did the wild type. No appreciable changes in the composition, structure, or macromolecular properties were observed for nonmannan polysaccharides in mutant mucilage. Biochemical analysis revealed that cellulose crystallinity was substantially reduced in csla2-1 mucilage; this was supported by the removal of most mucilage cellulose through treatment of csla2-1 seeds with endo-ß-glucanase. Mutation in CSLA2 also resulted in altered spatial distribution of cellulose and an absence of birefringent cellulose microfibrils within the adherent mucilage. As with the observed changes in crystalline cellulose, the spatial distribution of pectin was also modified in csla2-1 mucilage. Taken together, our results demonstrate that glucomannans synthesized by CSLA2 are involved in modulating the structure of adherent mucilage, potentially through altering cellulose organization and crystallization.

Gender disparities in summer outdoor heat risk across China: Findings from a national county-level assessment during 1991-2020.

Increasing anthropogenic global warming has emerged as a significant challenge to human health in China, as extreme heat hazards increasingly threaten outdoor-exposed populations. Differences in thermal comfort, outdoor activity duration, and social vulnerability between females and males may exacerbate gender inequalities in heat-related health risks, which have been overlooked by previous studies. Here, we combine three heat hazards and outdoor activity duration to identify the spatiotemporal variation in gender-specific heat risk in China during 1991-2020. We found that females' heat risk tends to be higher than that of males. Gender disparities in heat risk decrease in southern regions, while those in northern regions remain severe. Males are prone to overheating in highly urbanized areas, while females in low urbanized areas. Males' overheating risk is mainly attributed to population clustering associated with prolonged outdoor activity time and skewed social resource allocation. In contrast, females' overheating risk is primarily affected by social inequalities. Our findings suggest that China needs to further diminish gender disparities and accelerate climate adaptation planning.

Impacts of climate change, population growth, and power sector decarbonization on urban building energy use.

Climate, technologies, and socio-economic changes will influence future building energy use in cities. However, current low-resolution regional and state-level analyses are insufficient to reliably assist city-level decision-making. Here we estimate mid-century hourly building energy consumption in 277 U.S. urban areas using a bottom-up approach. The projected future climate change results in heterogeneous changes in energy use intensity (EUI) among urban areas, particularly under higher warming scenarios, with on average 10.1-37.7% increases in the frequency of peak building electricity EUI but over 110% increases in some cities. For each 1 °C of warming, the mean city-scale space-conditioning EUI experiences an average increase/decrease of ~14%/ ~ 10% for space cooling/heating. Heterogeneous city-scale building source energy use changes are primarily driven by population and power sector changes, on average ranging from -9% to 40% with consistent south-north gradients under different scenarios. Across the scenarios considered here, the changes in city-scale building source energy use, when averaged over all urban areas, are as follows: -2.5% to -2.0% due to climate change, 7.3% to 52.2% due to population growth, and -17.1% to -8.9% due to power sector decarbonization. Our findings underscore the necessity of considering intercity heterogeneity when developing sustainable and resilient urban energy systems.

Identification of Quantitative Trait Nucleotides and Development of Diagnostic Markers for Nine Fatty Acids in the Peanut.

The cultivated peanut (Arachis hypogaea L.) is an important oilseed crop worldwide, and fatty acid composition is a major determinant of peanut oil quality. In the present study, we conducted a genome-wide association study (GWAS) for nine fatty acid traits using the whole genome sequences of 160 representative Chinese peanut landraces and identified 6-1195 significant SNPs for different fatty acid contents. Particularly for oleic acid and linoleic acid, two peak SNP clusters on Arahy.09 and Arahy.19 were found to contain the majority of the significant SNPs associated with these two fatty acids. Additionally, a significant proportion of the candidate genes identified on Arahy.09 overlap with those identified in early studies, among which three candidate genes are of special interest. One possesses a significant missense SNP and encodes a known candidate gene FAD2A. The second gene is the gene closest to the most significant SNP for linoleic acid. It codes for an MYB protein that has been demonstrated to impact fatty acid biosynthesis in Arabidopsis. The third gene harbors a missense SNP and encodes a JmjC domain-containing protein. The significant phenotypic difference in the oleic acid/linoleic acid between the genotypes at the first and third candidate genes was further confirmed with PARMS analysis. In addition, we have also identified different candidate genes (i.e., Arahy.ZV39IJ, Arahy.F9E3EA, Arahy.X9ZZC1, and Arahy.Z0ELT9) for the remaining fatty acids. Our findings can help us gain a better understanding of the genetic foundation of peanut fatty acid contents and may hold great potential for enhancing peanut quality in the future.

Maternal ochratoxin A exposure impairs meiosis progression and primordial follicle formation of F1 offspring.

Ochratoxin A (OTA), a mycotoxin produced by Aspergillus and Penicillium fungi, widely contaminates feed, food and their raw materials. OTA has been proved to have hepatotoxicity and nephrotoxicity. Its reproductive toxicity needs to be further explored. We found that OTA inhibited the progression of meiosis, keeping more germ cells at leptotene and zygotene. Furthermore, OTA impaired primordial follicle formation, keeping more germ cells in cysts. Increased γH2AX suggested that DNA damage occurred both at the stages of meiosis and primordial follicle formation. The expression of RAD51 increased with the concentration of OTA at the stage of meiosis, while decreased later, suggesting the activated DNA repair induced by DNA damage then inhibited by persistent and excessive stress of DNA damage, which further induced apoptosis. DEGs caused by OTA were also mainly enriched in DNA damage and repair through RNA-seq analysis. Higher level of reactive oxygen species (ROS) and increased degree of oxidative damage marker 8-OHdG were both found in the ovaries exposed to OTA. We concluded that maternal OTA exposure affected meiosis progression and primordial follicle formation via oxidative damage and DNA repair. Clarification of the mechanism of OTA will contribute to the development of more effective detoxification strategies.

Maternal Zearalenone Exposure Affects Gut Microbiota and Follicular Development in Suckled Offspring.

Zearalenone (ZEN) is a mycotoxin that is widely present in feed and agricultural products. Studies have demonstrated that ZEN, as a type of estrogen analogue, can significantly affect the female reproductive system. Breast milk is the best nutrient for infant growth and development, but it is still unknown whether ZEN influences the fertility of offspring through suckling. In this study, we collected fecal and ovarian tissue from neonatal female offspring, whose mothers were exposed to ZEN for 21 days, and explored the effects of maternal ZEN exposure on intestinal microecology and follicular development in the mouse using 16S rRNA amplicon sequencing technology. Our findings suggested that maternal ZEN exposure significantly diminished ovarian reserve, increased apoptosis of ovarian granulosa cell (GC), and impacted the developmental competence of oocytes in lactating offspring. In addition, the results of 16S rRNA sequencing showed that the abundance of gut microbiota in offspring was significantly changed, including Bacteroidetes, Proteobacteria, and Firmicutes. This leads to alterations of glutathione metabolism and the expression of antioxidant enzymes in ovaries. In summary, our findings supported a potential relationship between gut microbiota and abnormal ovarian development caused by ZEN, which offers novel insights for therapeutic strategies for reproductive disorders induced by ZEN exposure.

The Genetic Base for Peanut Height-Related Traits Revealed by a Meta-Analysis.

Peanut (Arachis hypogaea L.) is an important oilseed crop worldwide, and peanut height has been shown to be closely related to yield, therefore a better understanding of the genetic base of plant height-related traits may allow us to have better control of crop yield. Plant height-related traits are quantitative traits that are genetically controlled by many genes, and distinct quantitive trait loci (QTLs) may be identified for different peanut accessions/genotypes. In the present study, in order to gain a more complete picture of the genetic base for peanut height-related traits, we first make use of the high quality NGS sequence data for 159 peanut accessions that are available within our research groups, to carry out a GWAS study for searching plant height-related regions. We then perform a literature survey and collect QTLs for two plant height-related traits (Ph: peanut main stem height, and Fbl: the first branch length) from earlier related QTL/GWAS studies in peanut. In total, we find 74 and 21 genomic regions that are, associated with traits Ph and Fbl, respectively. Annotation of these regions found a total of 692 and 229 genes for, respectively, Ph and Fbl, and among those genes, 158 genes are shared. KEGG and GO enrichment analyses of those candidate genes reveal that Ph- and Fbl-associated genes are both enriched in the biosynthesis of secondary metabolites, some basic processes, pathways, or complexes that are supposed to be crucial for plant development and growth.

DGE-seq analysis of MUR3-related Arabidopsis mutants provides insight into how dysfunctional xyloglucan affects cell elongation.

Our previous study of the Arabidopsis mur3-3 mutant and mutant plants in which the mur3-3 phenotypes are suppressed (xxt2mur3-3, xxt5mur3-3, xxt1xxt2mur3-3 and 35Spro:XLT2:mur3-3) showed that hypocotyl cell elongation is decreased in plants that synthesize galactose-deficient xyloglucan. To obtain genome-wide insight into the transcriptome changes and regulatory networks that may be involved in this decreased elongation, we performed digital gene expression analyses of the etiolated hypocotyls of wild type (WT), mur3-3 and the four suppressor lines. Numerous differentially expressed genes (DEGs) were detected in comparisons between WT and mur3-3 (1423), xxt2mur3-3 and mur3-3 (675), xxt5mur3-3 and mur3-3 (1272), xxt1xxt2mur3-3 and mur3-3 (1197) and 35Spro:XLT2:mur3-3 vs mur3-3 (121). 550 overlapped DEGs were detected among WT vs mur3-3, xxt2mur3-3 vs mur3-3, xxt5mur3-3 vs mur3-3, and xxt1xxt2mur3-3 vs mur3-3 comparisons. These DEGs include 46 cell wall-related genes, 24 transcription factors, 6 hormone-related genes, 9 protein kinase genes and 9 aquaporin genes. The expression of all of the 550 overlapped genes is restored to near wild-type levels in the four mur3-3 suppressor lines. qRT-PCR of fifteen of these 550 genes showed that their expression levels are consistent with the digital gene expression data. Overexpression of some of these genes (XTH4, XTH30, PME3, EXPA11, MYB88, ROT3, AT5G37790, WAG2 and TIP2;3) that are down-regulated in mur3-3 partially rescued the short hypocotyl phenotype but not the aerial phenotype of mur3-3, indicating that different mechanisms exist between hypocotyl cell elongation and leaf cell elongation.

Evolutionary Migration of the Disjunct Salt Cress Eutrema salsugineum (= Thellungiella salsuginea, Brassicaceae) between Asia and North America.

Eutrema salsugineum (= Thellungiella salsuginea Brassicaceae), a species growing in highly saline habitats, is a good model for use in salt-stress research. However, its evolutionary migrations and genetic variations within and between disjunct regions from central Asia to northern China and North America remain largely unknown. We examined genetic variations and phylogeographic patterns of this species by sequencing ITS, 9 chloroplast (cp) DNA fragments (4379 bp) and 10 unlinked nuclear loci (6510 bp) of 24 populations across its distributional range. All markers suggested the high genetic poverty of this species and the limited number of genetic variations recovered was congruently partitioned between central Asia, northern China and North America. Further modelling of nuclear population-genetic data based on approximate bayesian computation (ABC) analyses indicated that the long-distance dispersals after the recent origin of E. salsugineum may have occurred from central Asia to the other two regions respectively within 20000 years. The fast demographic expansions should have occurred in northern China in a more recent past. Our study highlights the importance of using ABC analyses and nuclear population genetic data to trace evolutionary migrations of the disjunct distributions of the plants in the recent past.

Association between thiopurine S-methyltransferase polymorphisms and thiopurine-induced adverse drug reactions in patients with inflammatory bowel disease: a meta-analysis.

PURPOSE: Thiopurine drugs are well established treatments in the management of inflammatory bowel disease (IBD), but their use is limited by significant adverse drug reactions (ADRs). Thiopurine S-methyltransferase (TPMT) is an important enzyme involved in thiopurine metabolism. Several clinical guidelines recommend determining TPMT genotype or phenotype before initiating thiopurine therapy. Although several studies have investigated the association between TPMT polymorphisms and thiopurine-induced ADRs, the results are inconsistent. The purpose of this study is to evaluate whether there is an association between TPMT polymorphisms and thiopurine-induced ADRs using meta-analysis. METHODS: We explored PubMed, Web of Science and Embase for articles on TPMT polymorphisms and thiopurine-induced ADRs. Studies that compared TPMT polymorphisms with-ADRs and without-ADRs in IBD patients were included. Relevant outcome data from all the included articles were extracted and the pooled odds ratio (OR) with corresponding 95% confidence intervals were calculated using Revman 5.3 software. RESULTS: Fourteen published studies, with a total of 2,206 IBD patients, which investigated associations between TPMT polymorphisms and thiopurine-induced ADRs were included this meta-analysis. Our meta-analysis demonstrated that TPMT polymorphisms were significantly associated with thiopurine-induced overall ADRs and bone marrow toxicity; pooled ORs were 3.36 (95%CI: 1.82-6.19) and 6.67 (95%CI: 3.88-11.47), respectively. TPMT polymorphisms were not associated with the development of other ADRs including hepatotoxicity, pancreatitis, gastric intolerance, flu-like symptoms and skin reactions; the corresponding pooled ORs were 1.27 (95%CI: 0.60-2.71), 0.97 (95%CI: 0.38-2.48), 1.82 (95%CI: 0.93-3.53), 1.28 (95%CI: 0.47-3.46) and 2.32 (95%CI: 0.86-6.25), respectively. CONCLUSIONS: Our meta-analysis demonstrated an association of TPMT polymorphisms with overall thiopurine-induced ADRs and bone marrow toxicity, but not with hepatotoxicity, pancreatitis, flu-like symptoms, gastric intolerance and skin reactions. These findings suggest that pretesting the TPMT genotype could be helpful in clinical practice before initiating thiopurine therapy. However, white blood cell count analysis should be the mainstay for follow-up.

Isothermal and rapid detection of pathogenic microorganisms using a nano-rolling circle amplification-surface plasmon resonance biosensor.

Rolling circle amplification (RCA) of DNA is a sensitive and cost effective method for the rapid identification of pathogens without the need for sequencing. In this study, a surface plasmon resonance DNA biosensor based on RCA with a gold (Au) nanoparticle surface was established for isothermal identification of DNA. The probes included a specific padlock probe, a capture probe (CP), which is bound to biotin, and an Au nanoparticle-modified probe, which hybridizes with the RCA products. The CP was assembled on gold nanoparticles to increase its ability to bind and hybridize. The linear padlock probe, which was designed to circularize by ligation upon recognition of the bacterial pathogen-specific sequence in 16S rDNA, hybridizes to fully complementary sequences within the CP. Upon recognition, each target gene DNA is distinguished by localization onto the corresponding channel on the chip surface. Then, the immobilized CPs act as primers to begin the in situ solid-phase RCA reaction, which produces long single-stranded DNA. The RCA products fixed on the chip surface cause significant surface plasmon resonance angle changes. We demonstrated that six different bacterial pathogens can be identified simultaneously and that 0.5 pM of synthetic oligonucleotides and 0.5 pg µl(-1) of genomic DNA from clinical samples can be detected by this method with low background signals. Therefore, the multiplex diagnostic method provides a highly sensitive and specific approach for the rapid identification of positive samples.

BRAFV600E mutation and its association with clinicopathological features of colorectal cancer: a systematic review and meta-analysis.

BACKGROUND: Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. The B-type Raf proto-oncogene (BRAF) plays an important role in the mitogen-activated protein kinase (MAPK) signaling cascade during CRC. The presence of BRAFV600E mutation can determine the response of a tumor to chemotherapy. However, the association between the BRAFV600E mutation and the clinicopathological features of CRC remains controversial. We performed a systematic review and meta-analysis to estimate the effect of BRAFV600E mutation on the clinicopathological characteristics of CRC. METHODS: We identified studies that examined the effect of BRAFV600E mutation on CRC within the PubMed, ISI Science Citation Index, and Embase databases. The effect of BRAFV600E on outcome parameters was estimated by odds ratios (ORs) with 95% confidence intervals (CIs) for each study using a fixed effects or random effects model. RESULTS: 25 studies with a total of 11,955 CRC patients met inclusion criteria. The rate of BRAFV600 was 10.8% (1288/11955). The BRAFV600E mutation in CRC was associated with advanced TNM stage, poor differentiation, mucinous histology, microsatellite instability (MSI), CpG island methylator phenotype (CIMP). This mutation was also associated with female gender, older age, proximal colon, and mutL homolog 1 (MLH1) methylation. CONCLUSIONS: This meta-analysis demonstrated that BRAFV600E mutation was significantly correlated with adverse pathological features of CRC and distinct clinical characteristics. These data suggest that BRAFV600E mutation could be used to supplement standard clinical and pathological staging for the better management of individual CRC patients, and could be considered as a poor prognostic marker for CRC.

High-resolution melting analysis for accurate detection of BRAF mutations: a systematic review and meta-analysis.

The high-resolution melting curve analysis (HRMA) might be a good alternative method for rapid detection of BRAF mutations. However, the accuracy of HRMA in detection of BRAF mutations has not been systematically evaluated. We performed a systematic review and meta-analysis involving 1324 samples from 14 separate studies. The overall sensitivity of HRMA was 0.99 (95% confidence interval (CI) = 0.75-0.82), and the overall specificity was very high at 0.99 (95% CI = 0.94-0.98). The values for the pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 68.01 (95% CI = 25.33-182.64), 0.06 (95% CI = 0.03-0.11), and 1263.76 (95% CI = 393.91-4064.39), respectively. The summary receiver operating characteristic curve for the same data shows an area of 1.00 and a Q* value of 0.97. The high sensitivity and specificity, simplicity, low cost, less labor or time and rapid turnaround make HRMA a good alternative method for rapid detection of BRAF mutations in the clinical practice.

BRAF mutations in patients with non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: BRAF mutations have been well described in non-small cell lung cancer (NSCLC) for several years, but the clinical features of patients harboring BRAF mutations are still not well described. We performed a meta-analysis to identify common clinical features in NSCLC patients carrying BRAF mutations. METHODS: We identified clinical studies that examined the association between BRAF mutations and features of NSCLC within PubMed, Embase and ISI Science Citation Index database up to October 2013. The effect size of clinical features was estimated by odds ratios (ORs) with 95% confidence interval (CI) for each study, using a fixed-effects or random-effects model. RESULTS: Ten studies with a total of 5599 NSCLC patients were included. There was a 3% (170/5599) BRAF mutation rate. BRAF mutations in NSCLC were significantly associated with adenocarcinomas (ADCs) (compared with non-ADCs, OR = 4.96, 95%CI = 2.29-10.75). There were no significant differences in gender, smoking and stage in patients with and without BRAF mutations. The BRAFV600E mutation was more frequent in women than non-BRAFV600E mutations (OR = 0.27, 95%CI = 0.12-0.59), and was closely related to never smokers (OR = 0.14, 95%CI = 0.05-0.42). CONCLUSIONS: These findings have important implications for the prediction of the NSCLC sub-types more accurately combined with other genetic changes.

Single-walled carbon nanotubes do not pierce aqueous phospholipid bilayers at low salt concentration.

Because of their unique physical, chemical, and electrical properties, carbon nanotubes are an attractive material for many potential applications. Their interactions with biological entities are, however, not yet completely understood. To fill this knowledge gap, we present experimental results for aqueous systems containing single-walled carbon nanotubes and phospholipid membranes, prepared in the form of liposomes. Our results suggest that dispersed single-walled carbon nanotubes, instead of piercing the liposome membranes, adsorb on them at low ionic strength. Transmission electron microscopy and dye-leakage experiments show that the liposomes remain for the most part intact in the presence of the nanotubes. Further, the liposomes are found to stabilize carbon nanotube dispersions when the surfactant sodium dodecylbenezenesulfonate is present at low concentrations. Quantifying the interactions between carbon nanotubes and phospholipid membranes could not only shed light on potential nanotubes cytotoxicity but also open up new research venues for their use in controlled drug delivery and/or gene and cancer therapy.