Electron harvesting bacteria are key targets to develop microbial electrosynthesis technologies, which are valid alternatives for the production of value-added compounds without utilization of fossil fuels. Geobacter sulfurreducens, that is capable of donating and accepting electrons from electrodes, is one of the most promising electroactive bacteria. Its electron transfer mechanisms to electrodes have been progressively elucidated, however the electron harvesting pathways are still poorly understood. Previous studies showed that the periplasmic cytochromes PccH and GSU2515 are overexpressed in current-consuming G. sulfurreducens biofilms. PccH was characterized, though no putative partners have been identified. In this work, GSU2515 was characterized by complementary biophysical techniques and in silico simulations using the AlphaFold neural network. GSU2515 is a low-spin monoheme cytochrome with a disordered N-terminal region and an α-helical C-terminal domain harboring the heme group. The cytochrome undergoes a redox-linked heme axial ligand switch, with Met91 and His94 as distal axial ligand in the reduced and oxidized state, respectively. The reduction potential of the cytochrome is negative and is modulated by the pH in the physiological range: -78 mV at pH 6 and -113 mV at pH 7. Such pH-dependence coupled to the redox-linked switch of the axial ligand allows the cytochrome to drive a proton-coupled electron transfer step that is crucial to confer directionality to the respiratory chain. Biomolecular interactions and electron transfer experiments indicated that GSU2515 and PccH form a redox complex. Overall, the data obtained highlights for the first time how periplasmic proteins bridge the electron transfer between the outer and inner membrane in the electron harvesting pathways of G. sulfurreducens.

Cancer treatment has yet to find a “silver bullet” capable of selectively and effectively kill tumor cells without damaging healthy cells. Nanomedicine is a promising field that can combine several moieties in one system to produce a multifaceted nanoplatform. The tumor microenvironment (TME) is considered responsible for the ineffectiveness of cancer therapeutics and the difficulty in the translation from the bench to bed side of novel nanomedicines. A promising approach is the use of combinatorial therapies targeting the TME with the use of stimuli-responsive nanomaterials which would increase tumor targeting. Contemporary combined strategies for TME-targeting nanoformulations are based on the application of external stimuli therapies, such as photothermy, hyperthermia or ultrasounds, in combination with stimuli-responsive nanoparticles containing a core, usually composed by metal oxides or graphene, and a biocompatible stimuli-responsive coating layer that could also contain tumor targeting moieties and a chemotherapeutic agent to enhance the therapeutic efficacy. The obstacles that nanotherapeutics must overcome in the TME to accomplish an effective therapeutic cargo delivery and the proposed strategies for improved nanotherapeutics will be reviewed. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.

To investigate the effect of different halogen substituents and leaving groups and the flexibility of ligands on the anticancer activity of copper complexes, sixteen copper(ii) complexes with eight different tridentate Schiff-base ligands containing pyridine and 3,5-halogen-substituted phenol moieties were synthesized and characterized by spectroscopic methods. Four of these complexes were also characterized by X-ray crystallography. The cytotoxicity of the complexes was determined in three different tumor cell lines (i.e.the A2780 ovarian, HCT116 colorectal and MCF7 breast cancer cell line) and in a normal primary fibroblast cell line. Complexes were demonstrated to induce a higher loss of cell viability in the ovarian carcinoma cell line (A2780) with respect to the other two tumor cell lines, and therefore the biological mechanisms underlying this loss of viability were further investigated. Complexes with ligandL1(containing a 2-pycolylamine-type motif) were more cytotoxic than complexes withL2(containing a 2-(2-pyridyl)ethylamine-type motif). The loss of cell viability in A2780 tumor cells was observed in the orderCu(Cl2-L1)NO3>Cu(Cl2-L1)Cl>Cu(Br2-L1)Cl>Cu(BrCl-L1)Cl. All complexes were able to induce reactive oxygen species (ROS) that could be related to the loss of cell viability. ComplexesCu(BrCl-L1)ClandCu(Cl2-L1)NO3were able to promote A2780 cell apoptosis and autophagy and for complexCu(BrCl-L1)Clthe increase in apoptosis was due to the intrinsic pathway.Cu(Cl2-L1)ClandCu(Br2-L1)Clcomplexes lead to cellular detachment allowing to correlate with the results of loss of cell viability. Despite the ability of theCu(BrCl-L1)Clcomplex to induce programmed cell death in A2780 cells, its therapeutic window turned out to be low making theCu(Cl2-L1)NO3complex the most promising candidate for additional biological applications.

Cancer is one of the worst health issues worldwide, representing the second leading cause of death. Current chemotherapeutic drugs face some challenges like the acquired resistance of the tumoral cells and low specificity leading to unwanted side effects. There is an urgent need to develop new compounds that may target resistant cells. The synthesis and characterization of two Cu(i) complexes of general formula [Cu(PP)(LL)][BF4], where PP is a phosphane ligand (triphenylphosphine or 1,2-bis(diphenylphosphano) ethane) and LL = is a heteroaromatic bidentate ligand (4,4′-dimethyl-2,2′-bipyridine and 6,3-(2-pyridyl)-5,6-diphenyl-1,2,4-triazine). The new compounds were fully characterized by spectroscopic techniques (NMR, FTIR and UV-vis.), elemental analysis (C, H, N and S) and two structures were determined by single X-ray diffraction studies. The antiproliferative potential of the new Cu(i) complexes were studied in tumor (breast adenocarcinoma, ovarian carcinoma and in colorectal carcinoma sensitive and resistant to doxorubicin) and normal (fibroblasts) cell lines. Complexes1-4did not show any antiproliferative potential. Amongst the complexes5-8, complex8shows high cytotoxic potential against colorectal cancer sensitive and resistant to doxorubicin and low cytotoxicity towards healthy cells. We show that complexes5-8can cleave pDNA and, in particular, thein vitropDNA cleavage is due to an oxidative mechanism. This oxidative mechanism corroborates the induction of reactive oxygen species (ROS), that triggers HCT116 cell deathviaapoptosis, as proved by the increased expression of BAX protein relative to BCL-2 protein and the depolarization of mitochondrial membrane potential, andviaautophagy. Additionally, complex8can block the cell cycle in the G1 phase, also exhibiting a cytostatic potential. Proteomic analysis confirmed the apoptotic, autophagic and cytostatic potential of complex8, as well as its ability to produce ROS and cause DNA damage. The interference of the complex in folding and protein synthesis and its ability to cause post-translational modifications was also verified. Finally, it was observed that the complex causes a reduction in cellular metabolism. The results herein demonstrated the potential of Cu(i) complexes in targeting doxorubicin sensitive and resistant cells which is positive and must be further explored usingin vivoanimal models.

Novel pharmacological strategies for the treatment of diabetic patients are now focusing on inhibiting glycogenolysis steps. In this regard, glycogen phosphorylase (GP) is a validated target for the discovery of innovative antihyperglycemic molecules. Natural products, and in particular flavonoids, have been reported as potent inhibitors of GP at the cellular level. Herein, free-energy calculations and microscale thermophoresis approaches were performed to get an in-depth assessment of the binding affinities and elucidate intermolecular interactions of several flavonoids at the inhibitor site of GP. To our knowledge, this is the first study indicating genistein, 8-prenylgenistein, apigenin, 8-prenylapigenin, 8-prenylnaringenin, galangin and valoneic acid dilactone as natural molecules with high inhibitory potency toward GP. We identified: i) the residues Phe285, Tyr613, Glu382 and/or Arg770 as the most relevant for the binding of the best flavonoids to the inhibitor site of GP, and ii) the 5-OH, 7-OH, 8-prenyl substitutions in ring A and the 4′-OH insertion in ring B to favor flavonoid binding at this site. Our results are invaluable to plan further structural modifications through organic synthesis approaches and develop more effective pharmaceuticals for Type 2 Diabetes treatment, and serve as the starting point for the exploration of food products for therapeutic usage, as well as for the development of novel bio-functional food and dietary supplements/herbal medicines.

Multifunctional polymeric coatings containing drug delivery vehicles can play a key role in preventing/reducing biofilm formation on implant surfaces. Their requirements are biocompatibility, good adhesion, and controllable drug release. Although cellulose acetate (CA) films and membranes are widely studied for scaffolding, their applications as a protective coating and drug delivery vehicle for metal implants are scarce. The reason is that adhesion to stainless steel (SS) substrates is non-trivial. Grinding SS substrates enhances the adhesion of dip-coated CA films while the adhesion of electrospun CA membranes is improved by an electrosprayed chitosan intermediate layer. PMMA microcapsules containing daptomycin have been successfully incorporated into CA films and fibres. The released drug concentration of 3 x10-3 mg/mL after 120 minutes was confirmed from the peak luminescence intensity under UV radiation of simulated body fluid (SBF) after immersion of the fibres.

Continuous wave terahertz (CW THz) imaging, is a variant of terahertz imaging that has been gaining scientific
and technological relevance in multiple areas. In this paper the fundamental phenomena of CW THz were
studied and a mathematical model was developed that successfully describes the Fabry–Perot interference for
such a system, opening the possibility for measurement of thicknesses and surface curvatures. The capabilities
of the system were tested using different types of defects, such as voids, water infiltrations and thin metallic
wires. The interactions between different materials, features and the radiation beam were numerically studied
using finite element method and the results agreed with the experiments. By comparing the results with other
Non-Destructive Testing methods, it was found that CW THz imaging is particularly interesting to image water
infiltrations and composite materials that incorporate conductive wires.

This study describes for the first time the iron- and copper-mediated gelation of FucoPol, fucose-rich bacterial polysaccharide. The ability of FucoPol to gel in the presence of metal cations, including iron(III) and copper(II), was used for the preparation of hydrogel beads. Iron mediated the formation of stable and not cytotoxic gel beads, while copper resulted in fragile and cytotoxic ones. Copper-mediated beads coated with an iron-mediated gel layer were more stable and had reduced cytotoxicity. The resulting polymeric structures had differing morphology, physical properties and cytotoxicity, which support their use in several applications, including biomedicine, agriculture and bioremediation.

{Fungal stains affect documents and artworks on paper all over the world, diminishing their chemical stability and compromising their readability. The present paper studies the suitability of agarose and gellan gum hydrogels to remove fungal stains from paper, using paper impregnated with alizarin as a model system to simulate the most common colorant molecules produced by fungi - polyketide quinones. The effect of pH variation on the efficacy of the gels was evaluated by UV spectrometry. The results show that the cleaning efficacy of the gels greatly depends on the gel matrix, the colorant molecules, and the pH balance of the process.}