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This matches the previously reported higher EGFR expression commonly found in NSCLC EVs. Through its rapid isolation kinetics and adaptability in marker targeting, the EVOD device provides a highly versatile liquid biopsy platform for clinicians to use in the fight against cancer.Microbes reprogrammed using advanced genetic circuits are envisaged as emerging living diagnostics for a wide range of diseases and play key roles in regulating gut microbiota to treat disease-associated symptoms in a non-invasive manner. Here, we developed a designer probiotic Escherichia coli that senses and responds to nitrate, a biomarker of gut inflammation. To this end, we first employed the NarX-NarL two-component regulatory system in E. coli to construct a nitrate-responsive genetic circuit. Next, we optimized the nitrate biosensor for the best performance using measures of sensitivity and specificity. We then introduced this genetic circuit into a probiotic E. coli Nissle 1917. We demonstrated that the designed biosensor can sense elevated nitrate levels during gut inflammation in mice with native gut microbiota. Moreover, using Boolean AND gate, we generated a genetically encoded biosensor for simultaneous sensing of the thiosulfate and nitrate biomarkers, thus increasing the tool's specificity for diagnosing gut inflammation. The nitrate-responsive genetic circuit will enable new approaches for non-invasive diagnostics of inflammation-associated diseases.Exosomal miRNAs have been discovered as important and reliable biomarkers for early diagnosis of tumors. However, it is still challenging to achieve accurate determination of trace exosomal miRNAs in real samples. Herein, we report an electrochemical strategy based on the cascade primer exchange reaction (PER) with MOF@Pt@MOF nanozyme for ultrasensitive detection of exosomal miRNA. α-cyano-4-hydroxycinnamic mouse Target-triggered PER that only includes a gated hairpin, a primer, and DNA polymerase can produce a long single strand in an autonomous and isothermal manner. Then, the nascent strand releases the protector B used to blockade capture probes, resulting in the binding of the nanozyme to sensing interface. Under the catalysis of the nanozyme, hydrogen peroxide (H2O2) is decomposed into H2O and O2, thus producing an amplified electrochemical signal. Benefiting from the cascade PER and the noticeable catalytic activity of the multiple-layered nanozyme, the established biosensor shows high sensitivity with limit of detection down to 0.29 fM and high specificity that can distinguish homologous miRNAs with single base mismatch. The developed strategy allows discrimination of tumor cells and breast cancer patients by detecting exosomal miRNA-21, and the results of this biosensor are consistent with qRT-PCR. Therefore, the electrochemical strategy has wide potential in the early screening of tumors.

Sleep disturbances are common among adolescents and are associated with elevated anxiety, and difficulties managing affect. Familial conflict is associated with both anxiety sensitivity and adolescent sleep disturbances. No work to date has examined how adolescent sleep disturbances may interact with anxiety sensitivity in relation to adolescent affective responding to parent-adolescent conflict. The current study was designed to address this gap in the literature by examining how adolescent sleep disturbances, anxiety sensitivity, conflict elicited anger, and conflict avoidance are associated.

Seventy-two American adolescents (n=39 males) between the ages of 12 and 16 years (M

=13.84, SD=1.38) completed a baseline assessment as well as a well-validated mother-adolescent laboratory-based conflict task.

For youth low in anxiety sensitivity, greater sleep disturbance related positively to conflict-elicited anger, which in turn predicted higher conflict avoidance. In contrast, this indirect effect was not significant for adolescents relatively higher in anxiety sensitivity. Instead, for these adolescents, increased sleep disturbances were associated with lower levels of conflict elicited anger.

Results suggest that the effects of sleep disturbances on conflict elicited anger may vary as a function of adolescent anxiety vulnerability. These findings highlight the importance of considering the unique effects of sleep disturbances on adolescent affect as a function of adolescent anxiety vulnerability.

Results suggest that the effects of sleep disturbances on conflict elicited anger may vary as a function of adolescent anxiety vulnerability. These findings highlight the importance of considering the unique effects of sleep disturbances on adolescent affect as a function of adolescent anxiety vulnerability.Human bladder stones, surgically removed from a 4 years old boy, were studied by X-ray diffraction (XRD) and by electron microprobe analyses (EPMA). XRD data show that the bladder stones are mainly composed of struvite with minor apatite. Tiny particles, less then 10 μm in size, composed of mercury (Hg) and selenium (Se) were found using scanning electron microscopy (SEM) and quantitative analysis by wave-length dispersive system (WDS). On the basis of their composition, the particles consist of tiemannite, a rare mineral with the ideal formula HgSe. The young patient was not exposed to relevant mercury contamination and has no teeth fillings of amalgam. Although this observation is not conclusive, we suggest that Hg was introduced as methylmercury by food. The discovered tiemannite can be classified as endogenous mineral, i.e., directly precipitated from the same fluids that formed the host bladder stones. This assumption is supported by the fact that tiemannite and struvite can crystallize at the same temperature and pH values. As proposed for the formation of tiemannite previously reported in the liver of cetaceans, we suggest that the tiemannite in the human body represents a probable product of demethylation of Hg. In this contribution, we suggest that Hg and Se were initially collected by urine in the human body and finally precipitated to form tiemannite under appropriate chemical-physical conditions together with the formation of the host bladder stone. This observation suggests that the precipitation and accumulation of metals, including Hg and Se, in the human body can be considered a physiological response to eliminate part of these trace elements, thus enabling detoxification.

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