Modified Fluoroquinolones as Antimicrobial Compounds Targeting Chlamydia trachomatis

Chlamydia trachomatis causes the most common sexually transmitted bacterial infection and trachoma, an eye infection. Untreated infections can lead to sequelae, such as infertility and ectopic pregnancy in women and blindness. We previously enhanced the antichlamydial activity of the fluoroquinolone ciprofloxacin by grafting a metal chelating moiety onto it. In the present study, we pursued this pharmacomodulation and obtained nanomolar active molecules (EC₅₀) against this pathogen. This gain in activity prompted us to evaluate the antibacterial activity of this family of molecules against other pathogenic bacteria, such as Neisseria gonorrhoeae and bacteria from the ESKAPE group. The results show that the novel molecules have selectively improved activity against C. trachomatis and demonstrate how the antichlamydial effect of fluoroquinolones can be enhanced.     

Solid Tumors and Kinase Inhibition: Management and Therapy Efficacy Evolution

The increasing numbers of cancer cases worldwide and the exceedingly high mortality rates of some tumor subtypes raise the question about if the current protocols for cancer management are effective and what has been done to improve upon oncologic patients’ prognoses. The traditional chemo-immunotherapy options for cancer treatment focus on the use of cytotoxic agents that are able to overcome neoplastic clones’ survival mechanisms and induce apoptosis, as well as on the ability to capacitate the host’s immune system to hinder the continuous growth of malignant cells. The need to avert the highly toxic profiles of conventional chemo-immunotherapy and to overcome the emerging cases of tumor multidrug resistance has fueled a growing interest in the field of precision medicine and targeted molecular therapies in the last couple of decades, although relatively new alternatives in oncologic practices, the increased specificity, and the positive clinical outcomes achieved through targeted molecular therapies have already consolidated them as promising prospects for the future of cancer management. In recent years, the development and application of targeted drugs as tyrosine kinase inhibitors have enabled cancer treatment to enter the era of specificity. In addition, the combined use of targeted therapy, immunotherapy, and traditional chemotherapy has innovated the standard treatment for many malignancies, bringing new light to patients with recurrent tumors. This article comprises a series of clinical trials that, in the past 5 years, utilized kinase inhibitors (KIs) as a monotherapy or in combination with other cytotoxic agents to treat patients afflicted with solid tumors. The results, with varying degrees of efficacy, are reported.     

Biological hydrogen production by Anabaena sp. - Yield, energy and CO2 analysis including fermentative biomass recovery

This paper presents laboratory results of biological production of hydrogen by photoautrotophic cyanobacterium Anabaena sp. Additional hydrogen production from residual Cyanobacteria fermentation was achieved by Enterobacter aerogenes bacteria. The authors evaluated the yield of H₂ production, the energy consumption and CO₂ emissions and the technological bottlenecks and possible improvements of the whole energy and CO₂ emission chain.The authors did not attempt to extrapolate the results to an industrial scale, but to highlight the processes that need further optimization.The experiments showed that the production of hydrogen from cyanobacteria Anabaena sp. is technically viable. The hydrogen yield for this case was 0.0114 kgH₂/kg_biomass which had a rough energy consumption of 1538 MJ/MJH₂ and produced 114640 gCO₂/MJH₂. The use of phototrophic residual cyanobacteria as a substrate in a dark-fermentation process increased the hydrogen yield by 8.1% but consumed 12.0% more of energy and produced 12.1% more of CO₂ showing that although the process increased the overall efficiency of hydrogen production it was not a viable energy and CO₂ emission solution. To make cyanobacteria-based biofuel production energy and environmentally relevant, efforts should be made to improve the hydrogen yield to values which are more competitive with glucose yields (0.1 kgH₂/kg_biomass). This could be achieved through the use of electricity with at least 80% of renewables and eliminating the unessential processes (e.g. pre-concentration centrifugation).     

Novel carbon‐based material for perovskite solar cells back‐contact

Perovskite solar cells are one of the most promising photovoltaic technology, presenting the fastest power conversion efficiency (PCE) growth from 3.8 % to 24.2 % in just 10 years. However, there are still challenges hindering its commercialization such as the expensive back‐contact made of gold. Carbon‐based materials, mainly carbon pastes made of carbon black and graphite, have already proven to be good candidates as back‐contacts because of their features such as low cost, high conductivity, and high stability. In this work, the replacement of gold back‐contact by a carbon paper with a microporous layer coated with a PEDOT:PSS dispersion is reported. To the best of the author's knowledge, this material has never been reported for perovskite solar cells. A PCE of 9.22 % was obtained, representing 62 % of the PCE obtained for the same cell but with a gold back‐contact.     

Determination of sensory thresholds of Mentha piperita L. essential oil in selected tropical fruit juices and efficacy of sensory accepted concentrations combined with mild heat to inactivate foodborne pathogens

This study determined the compromised acceptance threshold (CAT) and rejection threshold (RT) of Mentha piperita L. essential oil (MPEO) in cajá, guava and mango juices. The MPEO concentrations below the RT values were evaluated alone or combined with mild heat treatment (MHT; 54 °C) to inactivate ≥5-log₁₀ of Escherichia coli O157:H7 and Salmonella Enteritidis PT 4 in the same juices. The CAT of MPEO varied from 0.30 to 0.32 μL mL⁻¹, while the RT was 1.34 or 1.36 μL mL⁻¹ in the tested juices. Only concentrations of MPEO close, or higher than the RT caused ≥5-log₁₀ reductions in the tested pathogens in cajá, guava and mango juices. Combined with MHT, concentrations of MPEO below the RT reduced ≥5-log₁₀ of both pathogens in juices. These findings indicate that MPEO concentrations below the RT in combination with MHT is a feasible preservation technology to ensure the safety of tropical fruit juices.     

Uncertainty analysis based on sensitivity applied to angle-ply composite structures

This article describes a finite element-based formulation for the statistical analysis of the response of stochastic structural composite systems whose material properties are described by random fields. A first-order technique is used to obtain the second-order statistics for the structural response considering means and variances of the displacement and stress fields of plate or shell composite structures. Propagation of uncertainties depends on sensitivities taken as measurement of variation effects. The adjoint variable method is used to obtain the sensitivity matrix. This method is appropriated for composite structures due to the large number of random input parameters. Dominant effects on the stochastic characteristics are studied analyzing the influence of different random parameters. In particular, a study of the anisotropy influence on uncertainties propagation of angle-ply composites is carried out based on the proposed approach.     

A mathematical model for the solute drag effect on recrystallization

The model for the solute drag effect in phase transformations has been applied to recrystallization, i.e., moving grain boundaries. In this model, the total driving force is dissipated by the interfacial energy, the finite interfacial mobility, the solute drag in boundaries, and diffusion in the matrix ahead of the interface, of which all are taken into account consistently. The effects of the Gibbs energy of segregation and the diffusivity of impurity atoms in boundaries were investigated. The results show that the Gibbs energy of segregation mainly affects the critical composition at which the drastic change in the boundary velocity appears, and the diffusivity of impurity atoms in boundaries mainly affects the velocity reduced by the solute drag effect. In other words, the Gibbs energy of segregation and the diffusivity of impurity atoms in boundaries can be evaluated from experimental data by means of the present model. This model was applied to the Al−Mg system, and the Gibbs energy of segregation and the diffusivity of Mg in boundaries were evaluated from experimental data. The evaluated Gibbs energy of segregation agrees with the estimate based on elastic energy considerations. The diffusivity estimated from this model is smaller than that measured along the grain boundary. ZI-KUI LIU, formerly with the Department of Materials Science and Engineering, Royal Institute of Technology     

Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer

Based on the rapid increase in incidence of inflammatory bowel disease (IBD), the identification of susceptibility genes and cell populations contributing to this condition is essential. Previous studies suggested multiple genes associated with the susceptibility of IBD; however, due to the analysis of whole-tissue samples, the contribution of individual cell populations remains widely unresolved. Single-cell RNA sequencing (scRNA-seq) provides the opportunity to identify underlying cellular populations. We determined the enrichment of Crohn’s disease (CD)-induced genes in a publicly available Crohn’s disease scRNA-seq dataset and detected the strongest induction of these genes in innate lymphoid cells (ILC1), highly activated T cells and dendritic cells, pericytes and activated fibroblasts, as well as epithelial cells. Notably, these genes were highly enriched in IBD-associated neoplasia, as well as sporadic colorectal cancer (CRC). Indeed, the same six cell populations displayed an upregulation of CD-induced genes in a CRC scRNA-seq dataset. Finally, after integrating and harmonizing the CD and CRC scRNA-seq data, we demonstrated that these six cell types display a gradual increase in gene expression levels from a healthy state to an inflammatory and tumorous state. Together, we identified cell populations that specifically upregulate CD-induced genes in CD and CRC patients and could, therefore, contribute to inflammation-associated tumor development.