Untargeted Metabolomics in Forensic Toxicology: A New Approach for the Detection of Fentanyl Intake in Urine Samples

The misuse of fentanyl, and novel synthetic opioids (NSO) in general, has become a public health emergency, especially in the United States. The detection of NSO is often challenged by the limited diagnostic time frame allowed by urine sampling and the wide range of chemically modified analogues, continuously introduced to the recreational drug market. In this study, an untargeted metabolomics approach was developed to obtain a comprehensive “fingerprint” of any anomalous and specific metabolic pattern potentially related to fentanyl exposure. In recent years, in vitro models of drug metabolism have emerged as important tools to overcome the limited access to positive urine samples and uncertainties related to the substances actually taken, the possible combined drug intake, and the ingested dose. In this study, an in vivo experiment was designed by incubating HepG2 cell lines with either fentanyl or common drugs of abuse, creating a cohort of 96 samples. These samples, together with 81 urine samples including negative controls and positive samples obtained from recent users of either fentanyl or “traditional” drugs, were subjected to untargeted analysis using both UHPLC reverse phase and HILIC chromatography combined with QTOF mass spectrometry. Data independent acquisition was performed by SWATH in order to obtain a comprehensive profile of the urinary metabolome. After extensive processing, the resulting datasets were initially subjected to unsupervised exploration by principal component analysis (PCA), yielding clear separation of the fentanyl positive samples with respect to both controls and samples positive to other drugs. The urine datasets were then systematically investigated by supervised classification models based on soft independent modeling by class analogy (SIMCA) algorithms, with the end goal of identifying fentanyl users. A final single-class SIMCA model based on an RP dataset and five PCs yielded 96% sensitivity and 74% specificity. The distinguishable metabolic patterns produced by fentanyl in comparison to other opioids opens up new perspectives in the interpretation of the biological activity of fentanyl.     

Structural Investigation of Magnesium Complexes Supported by a Thiopyridyl Scorpionate Ligand

Herein, we report the synthesis of a series of heteroleptic magnesium complexes stabilized with the scorpionate ligand tris(2-pyridylthio)methanide (Tptm). The compounds of the general formula [Mg(Tptm)(X)] (1-X; X = Cl, Br, I) were obtained via protonolysis reaction between the proligand and selected Grignard reagents. Attempts to isolate the potassium derivative K(Tptm) lead to decomposition of Tptm and formation of the alkene (C₅H₄N-S)₂C=C(C₅H₄N-S)₂, and this degradation was also modelled using DFT methods. Compound 1-I was treated with K(CH₂Ph), affording the degradation product [Mg(Bptm)₂] (2; Bptm = {CH(S-C₅NH₃)₂}⁻). We analyzed and quantified the steric properties of the Tptm ligand using the structural information of the compounds obtained in this study paired with buried volume calculations, also adding the structural data of HTptm and its CF₃-substituted congener (HTptm^CF3). These studies highlight the highly flexible nature of this ligand scaffold and its ability to stabilize various coordination motifs and geometries, which is a highly desirable feature in the design of novel organometallic reagents and catalysts.     

不同催化剂热解法制备硼碳氮纳米管过程中的影响

对以钴、镍、钴/镍、钴/二茂铁、镍/二茂铁和二茂铁为催化剂高温热解法制备的硼碳氮（BCN）纳米管的结构、产率等的影响进行了分析.实验中发现催化剂在BCN纳米管的生长过程中有重要作用.高分辨率透射电子显微镜图像显示在860℃时，以镍/二茂铁、钴/二茂铁为催化剂生成的BCN纳米管具有“竹节状”结构，且管壁较薄，镍、钴或镍/钴作催化剂生成的BCN纳米管不具有明显的“竹节状”结构，管壁较厚，且粗细不均匀，而以二茂铁作催化剂没有BCN纳米管生成.在所有生成的BCN纳米管中含有催化剂颗粒.通过对生成的BCN纳米管的结 关键词： BCN纳米管 热解 催化剂 拉曼光谱     

Control and Design Principles in Biological Mineralization

The control of crystal formation has been developed to a remarkable degree by many organisms. Oriented nucleation, control over crystal morphology, formation of unique composites of proteins and single crystals, and the production of ordered multicrystal arrays, are all well within the realm of biological capability. Understanding the control and design principles in biomineralization is a fascinating subject that may well contribute to the improved fabrication of synthetic materials on the one hand, and to the solution of many serious pathological problems involving mineralization, on the other.     

Aragonite Formation in the Chiton (Mollusca) Girdle

In the chitons (Polyplacophora, Mollusca), the body is not entirely protected by the shell. Mineralized spicules or scales often, but not always, decorate the exposed part of the girdle. Here, we report a study on the composition and ultrastructural organization of these mineralized skeletal parts in four different chiton species. In all specimens, the mineral component (97–98 wt‐%) is aragonite, and the organic matrix (2–3 wt‐%) consists of highly glycosylated proteins. X‐Ray diffraction and scanning electron microscopy show that the organic matrix fibers are aligned, morphologically and crystallographically, with the prismatic aragonite crystals. Matrix and mineral are thus clearly related. The matrix–mineral composite bundles are, however, assembled in the various skeletal parts examined with widely different degrees of alignment and order. In the same organism, the crystals are aligned within a range of ±15° in one type of spicule, while they are randomly oriented in another type. The wide heterogeneity in shape, density, and ultrastructure suggests that the girdle mineralized tissues do not fulfill a fundamental role necessary for the survival of the organism. This, together with the lack of chitin in the organic matrix, supports the hypothesis that they evolved separately from the other chiton mineralized tissues, namely the shell plates and teeth.     

全保护RGD三肽的合成方法研究

以两条路线、多种偶联试剂(DCC，EDCI，CDI，EEDQ)合成了全保护三肽Arg- Gly-Asp(RGD)．Boc-Arg(Tos)-OH经上述偶联剂短时活化，于合适条件下与Ts0H- G1y-OBzl缩合，均获得良好收率(43％-97％)．经Pd(OH)2／H2还原得到的Boc-Arg (Tos)-G1y-0H于22-27℃与HCl·Asp(OcHex)-OBzl偶联得到全保护三肽Boc-Arg (Tos)-Gly-Asp(OcHex)-OBzl(TM)，反应收率分别为76．4％(DCC／HOSu)，64．7％ -78．3％(DCC／HOBt)，66．7％-77．9％(EDCI／HOBt)．Boc-Gly-OH和HCl·Asp- (OcHex)-OBzl经DCC／HOBt或CDI活化，可得到碳端二肽Boc-Gly-Asp(OcHex)-OBzl (收率分别为81．2％，89．5％)，该二肽脱Boc后与Boc-Asp(Tos)-OH反应，经DCC ／HOBt，EDCI／HOBt，CDI，DCC／HOSu活化，均可生成目标分子TM，其反应收率分 别为40．4％，73．8％，67．8％，84．4％．     

Preparation and characterization of alumina supported silicalite membranes by sol–gel hydrothermal method

Two types of unsupported zeolites (silicalite-1 and silicalite-2) and porous alumina discs supports were prepared by the hydrothermal sol–gel synthesis method. The influence of the raw materials used as SiO₂ source, the temperature of the thermal treatment and the presence of the ceramic support on the crystallization of zeolites were studied. The reaction products were characterized by X-ray diffraction (XRD), IR spectroscopy (IR) and scanning electron microscopy (SEM) studies. The SiO₂ source had a significant effect on the final zeolite obtained: the use of colloidal silica sol (ZCS) as SiO₂ source in the synthesis led to ZSM-11 (silicalite-2) crystals, while the sodium silicate solution (ZSS) produced the ZSM-5 (silicalite-1) type. The presence of the alumina support influences the crystallization process of ZSM-5, as it improves nucleation and the ordering of the crystals.     

Electronic integrated multisensor tongue applied to grape juice and wine analysis

An integrated multisensor composed by six ISFET devices selective to common ions and heavy metals combined with a flow injection analysis (FIA) system has been applied as an electronic tongue to grape juice and wine sample analysis. The data obtained for several grape and wine variety samples analysis have been treated using multiparametric tools like principal component analysis (PCA) and soft independent modelling class analogy technique (SIMCA) for the patterning recognition and classification of samples and partial least squares (PLS) regression for quantification of several parameters of interest in wine production. The results obtained have demonstrated the potential of using those multisensors as electronic tongues not only for distinguishing the samples according to the grape variety and the vintage year but also for quantitative prediction of several sample parameters.     

Planning and scheduling of selective harvest with management zones delineation

This paper considers an integrated approach to two common problems in a precision agriculture framework: management zone delineation and selective harvest scheduling. Our model minimizes the total costs of harvest operations, establishing planning and scheduling for selective harvest of each selected management zone. Therefore, this tool provides important information for decision making of farmers in the field. Our integrated model is contrasted with the hierarchical approach commonly used in the literature for these cases, where the result of zoning problem is an input to schedule the harvest problem. Both problems were solved through a complete enumeration of all the potential management zones and demonstrated the advantages of our proposed model over the hierarchical approach. Our model reached an average reduction of 10% in harvest operations costs for different instances in a case study.

     

A New System of Multiple Emulsions with Lamellar Gel Phases from Vegetable Oil

Emulsions are excellent pharmaceutical vehicles used in both the pharmacy and cosmetic industries. Vegetable oils have several effects/benefits on skin and can be used in emulsions to release principal active components for cosmetic purposes. Herein, multiple W/O/W emulsions were formulated in a one-step emulsification method, and the resulting anisotropic structures were characterized by x-ray diffraction measurements. The multiple emulsions obtained were stable and maintained their anisotropic structures over 2 years. WAXS (wide-angle x-ray scattering) measurements of these emulsions suggested that the carbon chains of the surfactant around the globules are disposed in a gel network phase. Furthermore, SAXS (small-angle x-ray scattering) measurements indicated that the surfactant is organized in lamellar layers around the globules. Thus, for the first time, we demonstrated that stable lamellar gel phase multiple emulsions can be made from vegetable oils. In addition to having the advantage of being prepared in one step, these emulsions have desirable characteristics that can be used in the cosmetic industry as natural active principles with low surfactant concentration and the unique features of multiple emulsions with gel phases.