Determination of the absolute configuration of bioactive indole-containing pyrazino[2,1-b]quinazoline-3,6-diones and study of their in vitro metabolic profile

In recent decades, fungi-derived naturally occurring quinazolines have emerged as potential drug candidates. Nevertheless, most studies are conducted for bioactivity assays, and little is known about their absorption, distribution, metabolism, and elimination (ADME) properties. To perform metabolic studies, the synthesis of the naturally occurring quinazolinone, fiscalin B (1), and its chloro derivative, 4-((1H-indol-3-yl)methyl)-8,10-dichloro-1-isobutyl-1,2-dihydro-6H-pyra-zino[2,1-b]quinazoline-3,6(4H)-dione (2), disclosed as an antibacterial agent, was performed in a gram scale using a microwave-assisted polycondensation reaction with 22% and 17% yields, respec-tively. The structure of the non-natural (+)-fiscalin B was established, for the first time, by X-ray crystallography as (1R,4S)-1, and the absolute configuration of the naturally occurring fiscalin B (- )-1 was confirmed by comparison of its calculated and experimental electronic circular dichroism (ECD) spectra as (1S,4R)-1. In vitro metabolic studies were monitored for this class of natural products for the first time by ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry (HRMS). The metabolic characteristics of 1 and 2 in human liver microsomes indicated hydration and hydroxylation mass changes introduced to the parent drugs.This research was supported by national funds provided by FCT—Foundation for Science and Technology and European Regional Development Fund (ERDF) and COMPETE under the Strategic Funding of CIIMAR UIDB/04423/2020 (Group of Natural Products and Medicinal Chemistry-CIIMAR) and LAQV-REQUIMTE (UIDB/50006/2020) and the project PTDC/SAU-PUB/28736/2017 (Reference: POCI-01–0145-FEDER-028736), as well as CHIRALBIOACTIVE-PI-3RL-IINFACTS-2019. This work is also a result of the project ATLANTIDA (Reference: NORTE-01-0145-FEDER-000040), supported by the Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement and through the European Regional Development Fund (ERDF). Additionally, this research was supported by the Agency for the Improvement of Higher Education Personnel (CAPES) (Finance Code 001), National Council for Scientific and Technological Development (CNPq) (Grant Number 406064/2018-05), São Paulo Research Foundation (FAPESP) (Grant Number: 2020/05965-8 and Ph.D. scholarships 2018/03035-3 and 2019/15040-4)

Trends and challenges in the Portuguese penitentiary system: from law to practice

This article focuses on the trends and challenges faced by the Portuguese penitentiary system between 2000 and 2017, taking into account the Portuguese Penal Law, penal statistics, national and international reports, and studies regarding the Portuguese prison system. The description of the changes in the Penal Law helps us to understand, on one hand, the changes in penal statistics over time and, on the other hand, the inconsistencies between the law in books and law in practice

Living biointerfaces based on non-pathogenic bacteria to direct cell differentiation

Genetically modified Lactococcus lactis, non-pathogenic bacteria expressing the FNIII7-10 fibronectin fragment as a protein membrane have been used to create a living biointerface between synthetic materials and mammalian cells. This FNIII7-10 fragment comprises the RGD and PHSRN sequences of fibronectin to bind α5β1 integrins and triggers signalling for cell adhesion, spreading and differentiation. We used L. lactis strain to colonize material surfaces and produce stable biofilms presenting the FNIII7-10 fragment readily available to cells. Biofilm density is easily tunable and remains stable for several days. Murine C2C12 myoblasts seeded over mature biofilms undergo bipolar alignment and form differentiated myotubes, a process triggered by the FNIII7-10 fragment. This biointerface based on living bacteria can be further modified to express any desired biochemical signal, establishing a new paradigm in biomaterial surface functionalisation for biomedical applications

A survey of performance enhancement of transmission control protocol (TCP) in wireless ad hoc networks

This Article is provided by the Brunel Open Access Publishing Fund - Copyright @ 2011 Springer OpenTransmission control protocol (TCP), which provides reliable end-to-end data delivery, performs well in traditional wired network environments, while in wireless ad hoc networks, it does not perform well. Compared to wired networks, wireless ad hoc networks have some specific characteristics such as node mobility and a shared medium. Owing to these specific characteristics of wireless ad hoc networks, TCP faces particular problems with, for example, route failure, channel contention and high bit error rates. These factors are responsible for the performance degradation of TCP in wireless ad hoc networks. The research community has produced a wide range of proposals to improve the performance of TCP in wireless ad hoc networks. This article presents a survey of these proposals (approaches). A classification of TCP improvement proposals for wireless ad hoc networks is presented, which makes it easy to compare the proposals falling under the same category. Tables which summarize the approaches for quick overview are provided. Possible directions for further improvements in this area are suggested in the conclusions. The aim of the article is to enable the reader to quickly acquire an overview of the state of TCP in wireless ad hoc networks.This study is partly funded by Kohat University of Science & Technology (KUST), Pakistan, and the Higher Education Commission, Pakistan

Using the Pneumatic method to estimate embolism resistance in species with long vessels: A commentary on the article “A comparison of five methods to assess embolism resistance in trees”

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordComparisons among methods are essential to validate plant traits measured across studies. However, a rigorous analysis is a complex task that needs to take into account not only the principle of the method and its correct use, but also inherent intraspecific trait variability, something we feel is not fully considered by Sergent et al. (2020). They compared the Bench dehydration, MicroCT, and Pneumatic methods using three long-vesseled species and found divergence among these methods. As a key finding, Sergent and colleagues reported unreliable estimates of Ψ50 for Olea europaea when using the Pneumatic method in a such long-vesseled species. Here, we tested this finding by measuring independently vulnerability curves for O. europaea. Our results reinforce the viability of the Pneumatic method to estimate embolism vulnerability in long-vesseled species, as already found by others. Briefly, we also discuss important procedures when using the Pneumatic method and encourage further experiments, as the only way to know better the limitations of available methods and improve our understanding about plant water relations.São Paulo Research Foundation (FAPESP)Royal SocietyNational Council for Scientific and Technological Development (CNPq, Brazil

Towards a higher photostability of ZnO photo-electrocatalysts in the degradation of organics by using MMO substrates

In this work, it is proposed a novel strategy to increase the photostability of the ZnO photoelectrocatalyst under prolonged light irradiation, without the addition or deposition of metals and/or semiconductor oxides during their synthesis. This strategy is based on the use of a mixed metal oxide (MMO-Ru0.3Ti0.7O2) coating as the substrate for the electrodeposition of ZnO. To assess it, the electrodeposition of ZnO films on Ti and Ti/MMO substrates and the photoelectrocatalytic activity of these materials for the degradation of the herbicide clopyralid were studied. The results showed that the substrate directly influenced the photo-stability of the ZnO film. Under the incidence of UV light and polarization, the novel Ti/MMO/ZnO electrode showed greater photocurrent stability as compared to Ti/ZnO, which is a very important outcome because the behavior of these electrodes was similar when compared in terms of the degradation of clopyralid. Single electrolysis was not able to degrade efficiently clopyralid at the different potentials studied. However, the irradiation of UV light on the polarized surface of the Ti/ZnO and Ti/MMO/ZnO electrodes increased markedly the degradation rate of clopyralid. A synergistic effect was observed between light and electrode polarization, since the rate of degradation of clopyralid was twice as high in photoelectrocatalysis (PhEC) than in photocatalysis (PhC) and different intermediates were formed. From these results, mechanisms of degradation of clopyralid for the PhC and PhEC systems with the Ti/ZnO and Ti/MMO/ZnO electrodes were presented. Therefore, the Ti/MMO/ZnO electrode could be a cheap and simple alternative to be applied in the efficient photodegradation of organic pollutants, presenting the great advantage of having a facile synthesis and high capacity to work at relatively low potentials.En este trabajo se propone una estrategia novedosa para incrementar la fotoestabilidad del fotoelectrocatalizador de ZnO bajo irradiación de luz prolongada, sin la adición o deposición de metales y / o óxidos semiconductores durante su síntesis. Esta estrategia se basa en el uso de un óxido de metal mixto (MMO-Ru 0.3 Ti 0.7 O 2) revestimiento como sustrato para la electrodeposición de ZnO. Para evaluarlo se estudió la electrodeposición de películas de ZnO sobre sustratos de Ti y Ti / MMO y la actividad fotoelectrocatalítica de estos materiales para la degradación del herbicida clopyralid. Los resultados mostraron que el sustrato influyó directamente en la fotoestabilidad de la película de ZnO. Bajo la incidencia de la luz ultravioleta y la polarización, el nuevo electrodo de Ti / MMO / ZnO mostró una mayor estabilidad de fotocorriente en comparación con Ti / ZnO, lo cual es un resultado muy importante porque el comportamiento de estos electrodos fue similar en términos de degradación de clopyralid. La electrólisis simple no fue capaz de degradar eficazmente la clopiralida a los diferentes potenciales estudiados. Sin embargo, la irradiación de luz ultravioleta sobre la superficie polarizada de los electrodos de Ti / ZnO y Ti / MMO / ZnO aumentó notablemente la tasa de degradación del clopiralida. Se observó un efecto sinérgico entre la luz y la polarización del electrodo, ya que la tasa de degradación de clopiralida fue dos veces mayor en fotoelectrocatálisis (PhEC) que en fotocatálisis (PhC) y se formaron diferentes intermedios. A partir de estos resultados, se presentaron los mecanismos de degradación de clopiralida para los sistemas PhC y PhEC con los electrodos Ti / ZnO y Ti / MMO / ZnO. Por tanto, el electrodo Ti / MMO / ZnO podría ser una alternativa barata y sencilla para ser aplicada en la fotodegradación eficiente de contaminantes orgánicos, presentando la gran ventaja de tener una síntesis fácil y alta capacidad para trabajar a potenciales relativamente bajos. Se observó un efecto sinérgico entre la luz y la polarización del electrodo, ya que la tasa de degradación de clopiralida fue dos veces mayor en fotoelectrocatálisis (PhEC) que en fotocatálisis (PhC) y se formaron diferentes intermedios. A partir de estos resultados, se presentaron los mecanismos de degradación de clopiralida para los sistemas PhC y PhEC con los electrodos Ti / ZnO y Ti / MMO / ZnO. Por tanto, el electrodo Ti / MMO / ZnO podría ser una alternativa barata y sencilla para ser aplicada en la fotodegradación eficiente de contaminantes orgánicos, presentando la gran ventaja de tener una síntesis fácil y alta capacidad para trabajar a potenciales relativamente bajos. Se observó un efecto sinérgico entre la luz y la polarización del electrodo, ya que la tasa de degradación de clopiralida fue dos veces mayor en fotoelectrocatálisis (PhEC) que en fotocatálisis (PhC) y se formaron diferentes intermedios. A partir de estos resultados, se presentaron los mecanismos de degradación de clopiralida para los sistemas PhC y PhEC con los electrodos Ti / ZnO y Ti / MMO / ZnO. Por tanto, el electrodo Ti / MMO / ZnO podría ser una alternativa barata y sencilla para ser aplicada en la fotodegradación eficiente de contaminantes orgánicos, presentando la gran ventaja de tener una síntesis fácil y alta capacidad para trabajar a potenciales relativamente bajos. dado que la tasa de degradación de clopiralida fue dos veces más alta en fotoelectrocatálisis (PhEC) que en fotocatálisis (PhC) y se formaron diferentes intermedios. A partir de estos resultados, se presentaron los mecanismos de degradación de clopiralida para los sistemas PhC y PhEC con los electrodos Ti / ZnO y Ti / MMO / ZnO. Por tanto, el electrodo Ti / MMO / ZnO podría ser una alternativa barata y sencilla para ser aplicada en la fotodegradación eficiente de contaminantes orgánicos, presentando la gran ventaja de tener una síntesis fácil y alta capacidad para trabajar a potenciales relativamente bajos. dado que la tasa de degradación de clopiralida fue dos veces más alta en fotoelectrocatálisis (PhEC) que en fotocatálisis (PhC) y se formaron diferentes intermedios. A partir de estos resultados, se presentaron los mecanismos de degradación de clopiralida para los sistemas PhC y PhEC con los electrodos Ti / ZnO y Ti / MMO / ZnO. Por tanto, el electrodo Ti / MMO / ZnO podría ser una alternativa barata y sencilla para ser aplicada en la fotodegradación eficiente de contaminantes orgánicos, presentando la gran ventaja de tener una síntesis fácil y alta capacidad para trabajar a potenciales relativamente bajos

Enzyme-Linked Immunosorbent Assay-Format Tissue Culture Infectious Dose-50 Test for Titrating Dengue Virus

A dengue nonstructural protein 1 (NS1) antigen capture enzyme-linked immunosorbent assay (ELISA)-based tissue culture infectious dose-50 (TCID50) test (TCID50-ELISA) was developed as an alternative to the standard plaque assay for titrating dengue virus. Virus titers obtained by TCID50-ELISA were comparable to those obtained by the plaque assay and by the traditional TCID50-cytopathic effect (CPE) test (TCID50-CPE), with a better reproducibility and a lower coefficient of variation. Quantitative comparison of TCID50-ELISA and TCID50-CPE resulted in a correlation coefficient of 0.976. Moreover, this new method showed a wider application to C6/36, Vero E6, BHK-21, and Vero cells compared with other titration methods. In summary, the novel TCID50-ELISA method described here provides a more reliable and more accurate alternative compared to the plaque assay and TCID50-CPE for titration of dengue virus