The ferroelectric Mott-Hubbard phase of organic (TMTTF)2X conductors

We present experimental evidences for a ferro-electric transition in the family of quasi one- dimensional conductors (TMTTF)2X. We interpret this new transition in the frame of the combined Mott-Hubbard state taking into account the double action of the spontaneous charge disproportionation on the TMTTF molecular stacks and of the X anionic potentials

Multiscalar cellular automaton simulates in-vivo tumour-stroma patterns calibrated from in-vitro assay data

Background: The tumour stroma -or tumour microenvironment- is an important constituent of solid cancers and it is thought to be one of the main obstacles to quantitative translation of drug activity between the preclinical and clinical phases of drug development. The tumour-stroma relationship has been described as being both pro- and antitumour in multiple studies. However, the causality of this complex biological relationship between the tumour and stroma has not yet been explored in a quantitative manner in complex tumour morphologies.Methods: To understand how these stromal and microenvironmental factors contribute to tumour physiology and how oxygen distributes within them, we have developed a lattice-based multiscalar cellular automaton model. This model uses principles of cytokine and oxygen diffusion as well as cell motility and plasticity to describe tumour-stroma landscapes. Furthermore, to calibrate the model, we propose an innovative modelling platform to extract model parameters from multiple in-vitro assays. This platform provides a novel way to extract meta-data that can be used to complement in-vivo studies and can be further applied in other contexts.Results: Here we show the necessity of the tumour-stroma opposing relationship for the model simulations to successfully describe the in-vivo stromal patterns of the human lung cancer cell lines Calu3 and Calu6, as models of clinical and preclinical tumour-stromal topologies. This is especially relevant to drugs that target the tumour microenvironment, such as antiangiogenics, compounds targeting the hedgehog pathway or immune checkpoint inhibitors, and is potentially a key platform to understand the mechanistic drivers for these drugs.Conclusion: The tumour-stroma automaton model presented here enables the interpretation of complex in-vitro data and uses it to parametrise a model for in-vivo tumour-stromal relationships

Evaluation of bread quality and volatile compounds of breads made by sourdoughs fermented by sediments of pulque (xaxtle) as starter culture

Sourdough is an important modern fermentation method of cereal flour and water. The fermentation process is carried out by lactic acid bacteria (LAB) and yeasts which confer specific flavor characteristics to the bread. The main aim of this research was to investigate the bread quality and volatile compounds of breads made by sourdoughs inoculated with sediments of pulque (xaxtle) used it as starter culture. Fifty five volatile compounds were found in the bread made with sourdoughs inoculated with xaxtle from three different regions of Mexico. Using gas chromatography-mass spectrometry, compounds as 3-hydroxy-2-butanone; 3-methyl-1-butanol; 2-methyl, 1-butanol; dimethyl disulfide; furfural, nonanal, phenyl ethyl alcohol and butanoic acid were presented in the flavor profile of the breads and having a positive response to sensory analysis made by evaluators. The xaxtle of Nanacamilpa (XN) and the xaxtle of Villa Alta (XV) were the best breads getting 8.3±0.03, 8.8±0.02, 6.2±0.08 and 8.2±0.01 scores in a scale from 0 to 10 in color, smell, texture and flavor attributes respectively which are positive attributes in favor of the quality bread. As a result of fermentation sourdough with LAB and yeasts from the xaxtle during 24 hours (30° C), the bread made with the sourdough inoculated with xaxtle of Milpa Alta (XM) showed the major acid flavor therefore its sample was less acceptable getting 8.1±0.01, 7.8±0.02, 5.3±0.01 and 7.9±0.01 in the same attributes evaluated. The xaxtle of Nanacamilpa, Tlaxcala (XN) run better than the others as starter fermentation culture for sourdoughs

Small molecules containing chalcogen elements (S, Se, Te) as new warhead to fight neglected tropical diseases

Neglected tropical diseases (NTDs) encompass a group of infectious diseases with a protozoan etiology, high incidence, and prevalence in developing countries. As a result, economic factors constitute one of the main obstacles to their management. Endemic countries have high levels of poverty, deprivation and marginalization which affect patients and limit their access to proper medical care. As a matter of fact, statistics remain un- collected in some affected areas due to non-reporting cases. World Health Organization and other organizations proposed a plan for the eradication and control of the vector, although many of these plans were halted by the COVID-19 pandemic. Despite of the available drugs to treat these pathologies, it exists a lack of effectiveness against several parasite strains. Treatment protocols for diseases such as American trypanosomiasis (Chagas disease), leishmaniasis, and human African trypanosomiasis (HAT) have not achieved the desired results. Un- fortunately, these drugs present limitations such as side effects, toxicity, teratogenicity, renal, and hepatic impairment, as well as high costs that have hindered the control and eradication of these diseases. This review focuses on the analysis of a collection of scientific shreds of evidence with the aim of identifying novel chalcogen- derived molecules with biological activity against Chagas disease, leishmaniasis and HAT. Compounds illustrated in each figure share the distinction of containing at least one chalcogen element. Sulfur (S), selenium (Se), and tellurium (Te) have been grouped and analyzed in accordance with their design strategy, chemical synthesis process and biological activity. After an exhaustive revision of the related literature on S, Se, and Te compounds, 183 compounds presenting excellent biological performance were gathered against the different causative agents of CD, leishmaniasis and HAT

Effect of topical berberine in murine cutaneous leishmaniasis lesions

Objectives: More effective topical treatments remain an unmet need for the localized forms of cutaneous leishmaniasis (CL). The aim of this study was to evaluate the efficacy and safety of a topical berberine cream in BALB/c mice infected with Leishmania major parasites. Methods: A cream containing 0.5% berberine-β-glycerophosphate salt and 2.5% menthol was prepared. Its physicochemical and stability properties were determined. The cream was evaluated for its capacity to reduce lesion size and parasitic load as well as to promote wound healing after twice-a-day administration for 35 days. Clinical biochemical profile was used for estimating off-target effects. In vitro time-to-kill curves in L. major-infected macrophages and skin and plasma pharmacokinetics were determined, aiming to establish pharmacokinetic/pharmacodynamic relationships. Results: The cream was stable at 40°C for 3 months and at 4°C for at least 8 months. It was able to halt lesion progression in all treated mice. At the end of treatment, parasite load in the skin was reduced by 99.9% (4 log) and genes involved in the wound healing process were up-regulated compared with untreated mice. The observed effects were higher than expected from in vitro time-to-kill kinetic and plasma berberine concentrations, which ranged between 0.07 and 0.22 μM. Conclusions: The twice-a-day administration of a topical berberine cream was safe, able to stop parasite progression and improved the appearance of skin CL lesions. The relationship between drug plasma levels and in vivo effect was unclear

Energy Analysis of Bare Electrodynamic Tethers

The design of an electrodynamic tether is a complex task that involves the control of dynamic instabilities, optimization of the generated power (or the descent time in deorbiting missions), and minimization of the tether mass. The electrodynamic forces on an electrodynamic tether are responsible for variations in the mechanical energy of the tethered system and can also drive the system to dynamic instability. Energy sources and sinks in this system include the following: 1) ionospheric impedance, 2) the potential drop at the cathodic contactor, 3) ohmic losses in the tether, 4) the corotational plasma electric field, and 5) generated power and/or 6) input power. The analysis of each of these energy components, or bricks, establishes parameters that are useful tools for tether design. In this study, the nondimensional parameters that govern the orbital energy variation, dynamic instability, and power generation were characterized, and their mutual interdependence was established. A space-debris mitigation mission was taken as an example of this approach for the assessment of tether performance. Numerical simulations using a dumbbell model for tether dynamics, the International Geomagnetic Reference Field for the geomagnetic field, and the International Reference Ionosphere for the ionosphere were performed to test the analytical approach. The results obtained herein stress the close relationships that exist among the velocity of descent, dynamic stability, and generated power. An optimal tether design requires a detailed tradeoff among these performances in a real-world scenario

New symmetrical quinazoline derivatives selectively induce apoptosis in human cancer cells

In the search of new symmetrical derivatives with anticancer activity, we have looked for novel compounds able to induce a selective proapoptotic mechanism in cancer cells. The potential antitumoral activity of several quinazoline derivatives was evaluated in vitro examining their cytotoxic effects against human breast, colon and bladder cancer cell lines. The IC(50) value of the compounds that showed cytotoxic activity was calculated. These compounds were tested for their ability to induce caspase-3 activation and nuclear chromatin degradation. Non-tumoral human cell lines were used to test the selectivity of the cytotoxic compounds against cancer cells. Several compounds showed no cytotoxicity in these cell lines. Finally, JRF12 (2,4-dibenzylaminoquinazoline) was chosen as the best candidate and its mechanism of action was studied in more detail. A time dependent evaluation of apoptosis was performed in the three cancer cell lines, followed by an evaluation of the cell cycle regulation involvement that showed a decrease of cells in G(1) phase and increase of cells in G(2) phase before cell death. 2,4-dibenzylaminoquinazoline treatment produces few changes in the expression of genes as evaluated by using oligonucleotide microarrays and Q-RT-PCR assays. In conclusion, 2,4-dibenzylaminoquinazoline is a promising anticancer drug showing cytostatic and apoptotic effects mainly in a transcription independent manner

Antiviral, antimicrobial and antibiofilm activity of selenoesters and selenoanhydrides

Selenoesters and the selenium isostere of phthalic anhydride are bioactive selenium compounds with a reported promising activity in cancer, both due to their cytotoxicity and capacity to reverse multidrug resistance. Herein we evaluate the antiviral, the biofilm inhibitory, the antibacterial and the antifungal activities of these compounds. The selenoanhydride and 7 out of the 10 selenoesters were especially potent antiviral agents in Vero cells infected with herpes simplex virus-2 (HSV-2). In addition, the tested selenium derivatives showed interesting antibiofilm activity against Staphylococcus aureus and Salmonella enterica serovar Typhimurium, as well as a moderate antifungal activity in resistant strains of Candida spp. They were inactive against anaerobes, which may indicate that the mechanism of action of these derivatives depends on the presence of oxygen. The capacity to inhibit the bacterial biofilm can be of particular interest in the treatment of nosocomial infections and in the coating of surfaces of prostheses. Finally, the potent antiviral activity observed converts these selenium derivatives into promising antiviral agents with potential medical applications.

Selenocompounds as Novel Antibacterial Agents and Bacterial Efflux Pump Inhibitors

Bacterial multidrug resistance is becoming a growing problem for public health, due to the development and spreading of bacterial strains resistant to antimicrobials. In this study, the antibacterial and multidrug resistance reversing activity of a series of seleno-carbonyl compounds has been evaluated. The effects of eleven selenocompounds on bacterial growth were evaluated in Staphylococcus aureus, methicillin resistant S. aureus (MRSA), Enterococcus faecalis, Escherichia coli, and Chlamydia trachomatis D. The combination effect of compounds with antibiotics was examined by the minimum inhibitory concentration reduction assay. Their efflux pump (EP) inhibitory properties were assessed using real-time fluorimetry. Relative expressions of EP and quorum-sensing genes were studied by quantitative PCR. Results showed that a methylketone selenoester had remarkable antibacterial activity against Gram-positive bacteria and potentiated the activity of oxacillin in MRSA. Most of the selenocompounds showed significant anti-chlamydial effects. The selenoanhydride and the diselenodiester were active inhibitors of the AcrAB-TolC system. Based on these results it can be concluded that this group of selenocompounds can be attractive potential antibacterials and EP inhibitors. The discovery of new derivatives with a significant antibacterial activity as novel selenocompounds, is of high impact in the fight against resistant pathogen