Widely used isotope ratio mass spectrometers have limited capabilities to measure metabolites, drugs, or small polyatomic ions without the loss of structural isotopic information. A new approach has recently been introduced that uses electrospray ionization Orbitrap to measure multidimensional isotope signatures of intact polar compounds. Using nitrate as a model compound, this study aims to establish performance metrics for comparisons with conventional IRMS at the natural abundance level. We present a framework on how to convert isotopolog intensities to δ values that are commonly used in the isotope geochemistry community. The quantification of seven nitrate isotopologs provides multiple pathways for obtaining the primary N and O δ values including non-mass-dependent O isotope variations, as well as opportunities to explore nonrandom isotopic distributions (i.e., clumping effects) within molecular nitrate. Using automation and the adaptation of measurement principles that are specific to isotope ratio analysis, nitrate δ15NAIR, δ18OVSMOW, and δ17OVSMOW were measured with a long-term precision of 0.4‰ or better for isotopic reference materials and purified nitrate from environmental samples. In addition, we demonstrate promising results for unpurified environmental samples in liquid form. With these new developments, this study connects the two largely disparate mass spectrometry fields of bioanalytical MS and isotope ratio MS, thus providing a route to measure new isotopic signatures in diverse organic and inorganic solutes.An androgen receptor (AR) is an intensively studied treatment target for castration-resistant prostate cancer that is irresponsive to conventional antiandrogen therapeutics. Binding function 3 (BF3) inhibitors with alternative modes of action have emerged as a promising approach to overcoming antiandrogen resistance. However, how these BF3 inhibitors modulate AR function remains elusive, hindering the development of BF3-targeting agents. Here, we performed an integrated computational study to interrogate the binding mechanism of several known BF3 inhibitors with ARs. Our results show that the inhibitory effect of the BF3 antagonists arises from their allosteric modulation of the activation function (AF2) site, which alters the dynamic coupling between the BF3 and AF2 sites as well as the AF2-coactivator (SRC2-3) interaction. Moreover, the per-residue binding energy analyses reveal the "anchor" role of the linker connecting the phenyl ring and benzimidazole/indole in these BF3 inhibitors. Furthermore, the allosteric driver-interacting residues are found to include both "positive", e.g., Phe673 and Asn833, and "negative" ones, e.g., Phe826, and the differential interactions with these residues provide an explanation why stronger binding does not necessarily result in higher inhibitory activities. Finally, our allosteric communication pathway analyses delineate how the allosteric signals triggered by BF3 binding are propagated to the AF2 pocket through multiple short- and/or long-ranged transmission pathways. this website Collectively, our combined computational study provides a comprehensive structural mechanism underlying how the selected set of BF3 inhibitors modulate AR function, which will help guide future development of BF3 antagonists.Although the use of pesticides has highlighted obvious advantages on agricultural yields, intensive and widespread pesticide use raises serious environmental and health concerns. In particular, organophosphate pesticides represent >40% of the totality used in the field of agriculture, and developing countries face the issue of agricultural poisoning, also due to scarce monitoring programs. In this work, a decentralized, miniaturized, sustainable, and portable paper-based electrochemical biosensor for the quantification of organophosphorus pesticides' level has been realized. The proposed approach highlights the use of a very common paper-based substrate, namely, office paper. Office paper offers several advantages due to its nature it allows one to print conductive strips for electrochemical connection, loading bio-hybrid nanosized probes (Prussian blue, carbon black, and butyrylcholinesterase), evaluating pesticides and reducing waste disposal compared to plastic-based strips. The portable system has been characterized by a low detection limit of 1.3 ng/mL, and accordingly to total discovered pesticide contents in EU agricultural soils, up to ca. 3 μg/mL, it can offer a valuable tool for fast monitoring. To demonstrate its effectiveness, soil and fruit vegetables have been used to perform in situ quantification. Good recovery percentages between 90 and 110% have been achieved in different matrices, highlighting to be suitable for field measurements, and a good correlation has been obtained in comparison with LC-MS analysis.The all consequences of tobacco smoking on the lungs and kidney function in kidney transplant recipients are unknown. We investigate the impact of tobacco smoking on lung and kidney functions in kidney transplantation recipients. Finally, 55 patients were evaluated after kidney transplantation (age 50.8±13.4). Pulmonary function was performed using spirometer Pneumo Screen; anthropometry with body composition using electronic scale, dynamometer, and multi-frequency bioimpedance analysis. Biochemical parameters were measured in serum, eGFR was calculated according to the CKD-EPI formula. Smoking history was reported by 23 kidney transplant recipients (42%); among them 12 (22%) were current smokers (mean pack-years=28.3±15.2). There were significant differences of spirometry parameters (FEV1, FEV1/FVC, MMEF% predictive value) between non-smokers vs active smokers (p<0.003; p<0.005; p<0.04; respectively). Current smokers presented significantly lower eGFR and higher IL-6 serum levels compare to both-tion. Effective smoking cessation programs are required in patients before and after kidney transplantation.Dorsoventral (DV) patterning is a key landmark of embryonic development that is primarily regulated by bone morphogenetic protein (BMP) signaling. Disruption of DV patterning can result in downstream effects on cell specification and organogenesis. Zebrafish embryos have been extensively used to understand signaling pathways that regulate DV patterning because zebrafish embryos develop ex utero and, in contrast to mammalian embryos, which develop in utero, can be observed in real time using brightfield and fluorescence microscopy. Embryos with disrupted DV patterning are either dorsalized or ventralized, with lack of development of head or trunk/tail structures, respectively. Although these phenotypes are typically accompanied by effects on BMP signaling, exceptions exist where some drugs or environmental chemicals can disrupt DV patterning in the absence of effects on BMP signaling. Therefore, assessments of DV patterning should be accompanied by BMP signaling-specific readouts to confirm the role of BMP disruption.

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