Cellulosomes are highly sophisticated molecular nanomachines that participate in the deconstruction of complex polysaccharides, notably cellulose and hemicellulose. Cellulosomal assembly is orchestrated by the interaction of enzyme-borne dockerin (Doc) modules to tandem cohesin (Coh) modules of a non-catalytic primary scaffoldin. In some cases, as exemplified by the cellulosome of the major cellulolytic ruminal bacterium Ruminococcus flavefaciens, primary scaffoldins bind to adaptor scaffoldins that further interact with the cell surface via anchoring scaffoldins, thereby increasing cellulosome complexity. Here we elucidate the structure of the unique Doc of R. flavefaciens FD-1 primary scaffoldin ScaA, bound to Coh 5 of the adaptor scaffoldin ScaB. The RfCohScaB5-DocScaA complex has an elliptical architecture similar to previously described complexes from a variety of ecological niches. ScaA Doc presents a single-binding mode, analogous to that described for the other two Coh-Doc specificities required for cellulosome assembly in R. flavefaciens. The exclusive reliance on a single-mode of Coh recognition contrasts with the majority of cellulosomes from other bacterial species described to date, where Docs contain two similar Coh-binding interfaces promoting a dual-binding mode. The discrete Coh-Doc interactions observed in ruminal cellulosomes suggest an adaptation to the exquisite properties of the rumen environment.

A series of 4-ethynylaniline gold(I) complexes containing monophosphane (1,3,5-triaza-7-phosphaadamantane (pta; 2), 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (3), and PR3 , with R=naphthyl (4), phenyl (5), and ethyl (6)) and diphosphane (bis(diphenylphosphino)acetylene (dppa; 7), trans-1,2-bis(diphenylphosphino)ethene (dppet; 8), 1,2-bis(diphenylphosphino)ethane (dppe; 9), and 1,3-bis(diphenylphosphino)propane (dppp; 10)) ligands have been synthesized and their efficiency against tumor cells evaluated. The cytotoxicity of complexes 2-10 was evaluated in human colorectal (HCT116) and ovarian (A2780) carcinoma as well as in normal human fibroblasts. All the complexes showed a higher antiproliferative effect in A2780 cells, with the cytotoxicity decreasing in the following order 5>6=9=10>8>2>4>7>3. Complex 4 stands out for its very high selectivity towards ovarian carcinoma cells (IC50 =2.3 mum) compared with colorectal carcinoma and normal human fibroblasts (IC50 >100 mum), which makes this complex very attractive for ovarian cancer therapy. Its cytotoxicity in these cells correlates with the induction of the apoptotic process and an increase of intracellular reactive oxygen species (ROS). The effects of the nuclearity, rigidity, and solubility of these complexes on their biological activity were also analyzed. X-ray crystal structure determination allowed the identification of short N-Hpi contacts as the main driving forces for the three-dimensional packing in these molecules.

Many diseases have their treatment options narrowed and end up being fatal if detected during later stages. As a consequence, point-of-care devices have an increasing importance for routine screening applications in the health sector due to their portability, fast analyses and decreased cost. For that purpose, a multifunctional chip was developed and tested using gold nanoprobes to perform RNA optical detection inside a microfluidic chip without the need of molecular amplification steps. As a proof-of-concept, this device was used for the rapid detection of chronic myeloid leukemia, a hemato-oncological disease that would benefit from early stage diagnostics and screening tests. The chip passively mixed target RNA from samples, gold nanoprobes and saline solution to infer a result from their final colorimetric properties. An optical fiber network was used to evaluate its transmitted spectra inside the chip. Trials provided accurate output results within 3 min, yielding signal-to-noise ratios up to 9 dB. When compared to actual state-of-art screening techniques of chronic myeloid leukemia, these results were, at microscale, at least 10 times faster than the reported detection methods for chronic myeloid leukemia. Concerning point-of-care applications, this work paves the way for other new and more complex versions of optical based genosensors.

Infectious diseases remain one of the leading causes of morbidity and mortality worldwide. The WHO and CDC have expressed serious concern regarding the continued increase in the development of multidrug resistance among bacteria. Therefore, the antibiotic resistance crisis is one of the most pressing issues in global public health. Associated with the rise in antibiotic resistance is the lack of new antimicrobials. This has triggered initiatives worldwide to develop novel and more effective antimicrobial compounds as well as to develop novel delivery and targeting strategies. Bacteria have developed many ways by which they become resistant to antimicrobials. Among those are enzyme inactivation, decreased cell permeability, target protection, target overproduction, altered target site/enzyme, increased efflux due to over-expression of efflux pumps, among others. Other more complex phenotypes, such as biofilm formation and quorum sensing do not appear as a result of the exposure of bacteria to antibiotics although, it is known that biofilm formation can be induced by antibiotics. These phenotypes are related to tolerance to antibiotics in bacteria. Different strategies, such as the use of nanostructured materials, are being developed to overcome these and other types of resistance. Nanostructured materials can be used to convey antimicrobials, to assist in the delivery of novel drugs or ultimately, possess antimicrobial activity by themselves. Additionally, nanoparticles (e.g., metallic, organic, carbon nanotubes, etc.) may circumvent drug resistance mechanisms in bacteria and, associated with their antimicrobial potential, inhibit biofilm formation or other important processes. Other strategies, including the combined use of plant-based antimicrobials and nanoparticles to overcome toxicity issues, are also being investigated. Coupling nanoparticles and natural-based antimicrobials (or other repurposed compounds) to inhibit the activity of bacterial efflux pumps; formation of biofilms; interference of quorum sensing; and possibly plasmid curing, are just some of the strategies to combat multidrug resistant bacteria. However, the use of nanoparticles still presents a challenge to therapy and much more research is needed in order to overcome this. In this review, we will summarize the current research on nanoparticles and other nanomaterials and how these are or can be applied in the future to fight multidrug resistant bacteria.

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) represents the most common genetic subtype of adult ALL (20%-30%) and accounts for approximately 50% of all cases in the elderly. It has been considered the subgroup of ALL with the worst outcome. The introduction of tyrosine kinase inhibitors (TKIs) allows complete hematologic remission virtually in all patients, with improved disease-free survival and overall survival. Nevertheless, the emergence of resistant mutations in BCR-ABL1 may require different TKI strategies to overcome the patient's resistance and disease relapse. Here, we report a Ph+B-ALL case with persistent minimal residual disease (MRD) after treatment with dasatinib. The patient expressed the P190(BCR-ABL1) isoform and a novel BCR-ABL1 mutation, p.Y440C. The latter is in the C-terminal lobe of the kinase domain, which likely induces deviations in the protein structure and activity and destabilizes its inactive conformation. The treatment was substituted by bosutinib, which binds to the active conformation of the protein, prior to allogeneic bone marrow transplant to overcome the lack of a complete response to dasatinib. These findings strengthen the importance of BCR-ABL1 mutational screening in Ph+ patients, particularly for those who do not achieve complete molecular remission.

Abstract POxylated polyurea dendrimer (PUREG4OOx48)-based nanoparticles were loaded with paclitaxel (PTX) and doxorubicin (DOX) and micronized with chitosan (CHT) by using supercritical CO2-assisted spray drying (SASD). Respirable, biocompatible, and biodegradable dry powder formulations (DPFs) were produced to effectively transport and deliver the chemotherapeutics with a controlled rate to the deep lung. In vitro studies performed with the use of the lung adenocarcinoma cell line showed that DOX@PUREG4OOx48 nanoparticles were much more cytotoxic than the free drug. Additionally, the DPFs did not show higher cytotoxicity than the respective nanoparticles, and DOX-DPFs showed a higher chemotherapeutic effect than PTX formulations in adenocarcinoma cells.

A simple oxidative ring rearrangement of diversely substituted 1-(2-amminoaryl)-tetrahydro-β-carbolines has been developed to generate architecturally interesting tetrahydro-1H-indolo[2,3-b]pyrrolo[3,2-c]quinolones. This unique transformation involves four reaction centers (aniline, C1-carboline and C2/C3 of indole) and utilizes tert-butylhypochlorite as the reagent. The generic nature of the reaction was demonstrated by the synthesis of a wide variety of analogs 9a–j. A putative reaction mechanism was proposed. Cytotoxicity screening of these compounds against three human cancer cells (A2780 ovarian and HCT116 colorectal carcinoma cell lines and A549 lung adenocarcinoma cell line) revealed selective inhibition of proliferation of the A2780 human ovarian carcinoma cell line by one of the molecules 9a with an IC50 of 14 μM. No cytotoxic activity was observed in human normal fibroblasts for concentrations up to 100 μM. Compound 9a induced hyperpolarization of the mitochondrial membrane potential of the A2780 cell line leading to an increase of reactive oxygen species (ROS) that trigger cell death via apoptosis. Interestingly, compound 9a was also able to induce cell death via autophagy. Compounds that induce apoptosis and autophagy, thus leading to cancer cells’ death, are good candidates for cancer therapy.

A new and never before reported hetero-arylidene-9(10H)-anthrone structure (4) was unexpectedly isolated on reaction of 1,2-dimethyl-3-ethylimidazolium iodide (2) and 9-anthracenecarboxaldehyde (3) under basic conditions. Its structure was unequivocally confirmed by X-ray crystallography. No cytotoxicity in human healthy fibroblasts and in two different cancer cell lines was observed, indicating its applicability in biological systems. Compound 4 interacts with CT-DNA by intercalation between the adjacent base pairs of DNA with a high binding affinity [Kb = 2.0 (±0.20) × 105 m–1], which is 10 × higher than that described for doxorubicin [Kb = 3.2 (±0.23) × 104 m–1]. Furthermore, compound 4 quenches the fluorescence emission of a GelRed–CT-DNA system with a quenching constant (KSV) of 3.3 (±0.3) × 103 m–1 calculated by the Stern–Volmer equation.

A simple process of commercial paper functionalisation via in situ polymerisation of conductive polymers onto cellulose fibres was investigated and applied as electrodes in paper-based batteries. The functionalisation involved polypyrrole (PPy) and Poly (3,4-ethylenedioxythiophene) (PEDOT) as conductive polymers with the process of functionalisation optimised for each polymer individually with respect to oxidant-to-monomer ratios and polymerisation times and temperature. Paper with conductivity values of 44 mS/cm was obtained by exposing the samples to pyrrole vapour for a period of 30 min at room temperature; however, polymerisation at temperatures of 40 °C lead to higher conductivity values to up 141 mS/cm. Consequently, functionalised PPy and PEDOT papers were applied as cathodes in batteries with Al foil anodes and commercial paper soaked in an electrolyte solution of NaCl.

A simple process of commercial paper functionalisation via in situ polymerisation of conductive polymers onto cellulose fibres was investigated and applied as electrodes in paper-based batteries. The functionalisation involved polypyrrole (PPy) and Poly (3,4-ethylenedioxythiophene) (PEDOT) as conductive polymers with the process of functionalisation optimised for each polymer individually with respect to oxidant-to-monomer ratios and polymerisation times and temperature. Paper with conductivity values of 44 mS/cm was obtained by exposing the samples to pyrrole vapour for a period of 30 min at room temperature; however, polymerisation at temperatures of 40 °C lead to higher conductivity values to up 141 mS/cm. Consequently, functionalised PPy and PEDOT papers were applied as cathodes in batteries with Al foil anodes and commercial paper soaked in an electrolyte solution of NaCl.

A novel cellulose-based bio-battery made of electrospun fibers activated by biological fluids has been developed. This work reports a new concept for a fully organic bio-battery that takes advantage of the high surface to volume ratio achieved by an electrospun matrix composed of sub-micrometric fibers that acts simultaneously as the separator and the support of the electrodes. Polymer composites of polypyrrole (PPy) and polyaniline (PANI) with cellulose acetate (CA) electrospun matrix were produced by in situ chemical oxidation of pyrrole and aniline on the CA fibers. The structure (CA/PPy|CA|CA/PANI) generated a power density of 1.7 mW g−1 in the presence of simulated biological fluids, which is a new and significant contribution to the domain of medical batteries and fully organic devices for biomedical applications.

A novel cellulose-based bio-battery made of electrospun fibers activated by biological fluids has been developed. This work reports a new concept for a fully organic bio-battery that takes advantage of the high surface to volume ratio achieved by an electrospun matrix composed of sub-micrometric fibers that acts simultaneously as the separator and the support of the electrodes. Polymer composites of polypyrrole (PPy) and polyaniline (PANI) with cellulose acetate (CA) electrospun matrix were produced by in situ chemical oxidation of pyrrole and aniline on the CA fibers. The structure (CA/PPy|CA|CA/PANI) generated a power density of 1.7 mW g−1 in the presence of simulated biological fluids, which is a new and significant contribution to the domain of medical batteries and fully organic devices for biomedical applications.

Developments in thermoelectric (TE) transparent p-type materials are scarce and do not follow the trend of the corresponding n-type materials – a limitation of the current transparent thermoelectric devices. P-type thermoelectric thin films of CuI have been developed by three different methods in order to maximise optical transparency (>70% in the visible range), electrical (σ = 1.1 × 104 Sm−1) and thermoelectric properties (ZT = 0.22 at 300 K). These have been applied in the first planar fully transparent p-n type TE modules where gallium-doped zinc oxide (GZO) thin films were used as the n-type element and indium thin oxide (ITO) thin films as electrodes. A thorough study of power output in single elements and p-n modules electrically connected in series and thermally connected in parallel is inclosed. This configuration allows for a whole range of highly transparent thermoelectric applications.

The heterogenization of the highly active monovacant polyoxotungstate ([PW11O39]7 −, abbreviated as PW11) was achieved by preparing the corresponding long chain quaternary ammonium salt (ODA7PW11, ODA = CH3(CH2)17(CH3)3N). The complete cation exchange confers total heterogeneity to the monovacant catalyst while keeping its oxidative catalytic activity. In fact, the heterogeneous catalyst allowed for the complete desulfurization of a multicomponent model diesel (2000 ppm S) after 40 min of reaction, conciliating extraction (using BMIMPF6 solvent) and oxidation (ECODS process using H2O2 oxidant). The heterogeneous catalyst has shown a superior desulfurization performance when compared with the homogeneous quaternary ammonium TBAPW11 catalyst (TBA = (C4H9)4 N). Both hybrid catalysts have been successfully reused in consecutive ECODS cycles. Additionally, the long carbon chain cations provide a protective environment around the polyoxometalate allowing for ODA7PW11 to retain its heterogeneity and structure after the ECODS process.

In the present work composite membranes were produced by combining magnetic nanoparticles (NPs) with cellulose acetate (CA) membranes for magnetic hyperthermia applications. The non-woven CA membranes were produced by electrospinning technique, and magnetic NPs were incorporated by adsorption at fibers surface or by addition to the electrospinning solution. Therefore, different designs of composite membranes were obtained. Superparamagnetic NPs synthesized by chemical precipitation were stabilized either with oleic acid (OA) or dimercaptosuccinic acid (DMSA) to obtain stable suspensions at physiological pH. The incorporation of magnetic NP into CA matrix was confirmed by scanning and transmission electron microscopy. The results showed that adsorption of magnetic NPs at fibers’ surface originates composite membranes with higher heating ability than those produced by incorporation of magnetic NPs inside the fibers. However, adsorption of magnetic NPs at fibers’ surface can cause cytotoxicity depending on the NPs concentration. Tensile tests demonstrated a reinforcement effect caused by the incorporation of magnetic NPs in the non-woven membrane.

One strategy that has gained much attention in the last decades is the understanding and further mimicking of structures and behaviours found in nature, as inspiration to develop materials with additional functionalities. This review presents recent advances in stimuli-responsive gels with emphasis on functional hydrogels and microgels. The first part of the review highlights the high impact of stimuli-responsive hydrogels in materials science. From macro to micro scale, the review also collects the most recent studies on the preparation of hybrid polymeric microgels composed of a nanoparticle (able to respond to external stimuli), encapsulated or grown into a stimuli-responsive matrix (microgel). This combination gave rise to interesting multi-responsive functional microgels and paved a new path for the preparation of multi-stimuli “smart” systems. Finally, special attention is focused on a new generation of functional stimuli-responsive polymer hydrogels able to self-shape (shape-memory) and/or self-repair. This last functionality could be considered as the closing loop for smart polymeric gels.

In this paper the rheological characterization of Pluronic/water systems filled with alginate microparticles is presented. The rheological characterization of the Pluronic/water systems allowed for the choice of the best Pluronic concentration taking into account its applications as injectable hydrogels for tissue repair. The effect on the rheological behavior of the addition of alginate microparticles, to be loaded with the drug, was analyzed and the maximum concentration of microparticles determined.

In this work 2H NMR spectroscopy and 1H NMR relaxometry and diffusometry were used to characterise water order and dynamics in cellulose acetate/silica asymmetric membranes. Two hydrated membranes were characterised allowing the identification of extra ordering of the water molecules and the presence in each membrane of up to two spectral components with different degrees of order and different T1 values. The mechanism behind this order increase was ascribed to the rapid exchange of the water molecules between the pore walls and its interior. T1 relaxometry dispersions allowed for the identification of the relevant mechanisms of pore-confined water motion, with rotations mediated by translational displacements (RMTD) as the dominant mechanism in the low frequency region. Using the RMTD low cut off frequency along with the in situ directly measured diffusion constant it was possible do determine characteristic lengths of correlated water motion in both membranes studied, which fall in ranges compatible with typical pore dimensions in similar membranes.