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In this study, the effect of Al on the high temperature oxidation of Al-containing refractory high entropy alloys (RHEAs) Ta-Mo-Cr-Ti-xAl (x = 5; 10; 15; 20 at%) was examined. Oxidation experiments were performed in air for 24 h at 1200 °C. The oxidation kinetics of the alloy with 5 at% Al is notably affected by the formation of gaseous MoO3 and CrO3, while continuous mass gain was detected for alloys with the higher Al concentrations. The alloys with 15 and 20 at% Al form relatively thin oxide scales and a zone of internal corrosion due to the formation of dense CrTaO4 scales at the interface oxide/substrate. The alloys with 5 and 10 at% Al exhibit, on the contrary, thick and porous oxide scales because of fast growing Ta2O5. The positive influence of Al on the formation of Cr2O3 followed by the growth of CrTaO4 to yield a compact scale is explained by getter and nucleation effects.

The design and synthesis of a novel rotaxane/foldaxane hybrid architecture is reported. The winding of an aromatic oligoamide helix host around a dumbbell-shaped thread-like guest, or axle, already surrounded by a macrocycle was evidenced by NMR spectroscopy and X-ray crystallography. The process proved to depend on the position of the macrocycle along the axle and the associated steric hindrance. The macrocycle thus behaves as a switchable shield that modulates the affinity of the helix for the axle. Reciprocally, the foldamer helix acts as a supramolecular auxiliary that compartmentalizes the axle. In some cases, the macrocycle is forced to move along the axle to allow the foldamer to reach its best recognition site.

The NLRP3 inflammasome is a critical component of the innate immune response to sterile inflammation. Its regulation involves a priming step, required for up-regulation of inflammasome protagonists and an activation step leading to NLRP3 inflammasome complex assembly, which triggers caspase-1 activity. The IκKβ kinase regulates canonical NF-κB, a key pathway involved in transcriptional priming. We found that IκKβ also regulates the activation and function of the NLRP3 inflammasome beyond the priming step. Two unrelated IκKβ inhibitors, AFN700 and TPCA-1, when applied after priming, fully blocked IL-1β secretion triggered by nigericin in THP-1 cells. Both inhibitors prevented neither inflammasome assembly, as monitored by measuring the formation of ASC specks, nor the generation of caspase-1 p20, a hallmark of caspase-1 activity, but they impaired the initial cleavage and activation of procaspase-1. These data thus indicate that IκKβ activity is required for efficient activation of NLRP3, suggesting that IκKβ may fulfill a dual role in coupling priming and activation of the NLRP3 inflammasome.

The interfacial properties of multiphase systems are often difficult to quantify. We describe the observation and quantification of immiscible solvent entrapment on a carbonaceous electrode surface using microscopy-coupled electrogenerated chemiluminescence (ECL). As aqueous microdroplets suspended in 1,2-dichloroethane collide with a glassy carbon electrode surface, small volumes of the solvent become entrapped between the electrode and aqueous phase, resulting in an overestimation of the true microdroplet/electrode contact area. To quantify the contribution of solvent entrapment decreasing the microdroplet contact area, we drive an ECL reaction within the microdroplet phase using tris(bipyridine)ruthenium(II) chloride ([Ru(bpy)3]Cl2) as the ECL luminophore and sodium oxalate (Na2C2O4) as the co-reactant. Importantly, the hydrophilicity of sodium oxalate ensures that the reaction proceeds in the aqueous phase, permitting a clear contrast between the aqueous and 1,2-dichloroethane present at the electrode interface. With the contrast provided by ECL imaging, we quantify the microdroplet radius, apparent microdroplet contact area (aqueous + entrapped 1,2-dichloroethane), entrapped solvent contact area, and the number of entrapped solvent pockets per droplet. These data permit the extraction of the true microdroplet/electrode contact area for a given droplet, as well as a statistical assessment regarding the probability of solvent entrapment based on microdroplet size.

Destruction of the alveolar bone in the jaws can occur due to periodontitis, trauma or following tumor resection. Common reconstructive therapy can include the use of bone grafts with limited predictability and efficacy. Romosozumab, approved by the FDA in 2019, is a humanized sclerostin-neutralizing antibody (Scl-Ab) indicated in postmenopausal women with osteoporosis at high risk for fracture. Preclinical models show that Scl-Ab administration preserves bone volume during periodontal disease, repairs bone defects surrounding dental implants, and reverses alveolar bone loss following extraction socket remodeling. To date, there are no studies evaluating Scl-Ab to repair osseous defects around teeth or to identify the efficacy of locally-delivered Scl-Ab for targeted drug delivery. In this investigation, the use of systemically-delivered versus low dose locally-delivered Scl-Ab via poly(lactic-co-glycolic) acid (PLGA) microspheres (MSs) was compared at experimentally-created alveolar bone defects in rats. Systemic Scl-Ab administration improved bone regeneration and tended to increase cementogenesis measured by histology and microcomputed tomography, while Scl-Ab delivered by MSs did not result in enhancements in bone or cemental repair compared to MSs alone or control. In conclusion, systemic administration of Scl-Ab promotes bone and cemental regeneration while local, low dose delivery did not heal periodontal osseous defects in this study.

Aromatic oligoamides adopting helical conformations are synthesized by coupling carboxyl-terminated basic units having two, four, and eight residues to amine-terminated oligomer precursors. Coupling yields show no noticeable reduction with the size of the basic units or the final product. One- and two-dimensional NMR spectroscopy and computational studies demonstrate the reliable helical folding of these oligomers. The X-ray structure of 16mer

Purpose: Over 60% of patients with melanoma respond to immune checkpoint inhibitor (ICI) therapy, but many subsequently progress on these therapies. Second-line targeted therapy is based on BRAF mutation status, but no available agents are available for NRAS, NF1, CDKN2A, PTEN, and TP53 mutations. Over 70% of melanoma tumors have activation of the MAPK pathway due to BRAF or NRAS mutations, while loss or mutation of CDKN2A occurs in approximately 40% of melanomas, resulting in unregulated MDM2-mediated ubiquitination and degradation of p53. Here, we investigated the therapeutic efficacy of over-riding MDM2-mediated degradation of p53 in melanoma with an MDM2 inhibitor that interrupts MDM2 ubiquitination of p53, treating tumor-bearing mice with the MDM2 inhibitor alone or combined with MAPK-targeted therapy. Experimental Design: To characterize the ability of the MDM2 antagonist, KRT-232, to inhibit tumor growth, we established patient-derived xenografts (PDX) from 15 patients with melanoma. Mice were treated with KRT-232 or a combination with BRAF and/or MEK inhibitors. Tumor growth, gene mutation status, as well as protein and protein–phosphoprotein changes, were analyzed. Results: One-hundred percent of the 15 PDX tumors exhibited significant growth inhibition either in response to KRT-232 alone or in combination with BRAF and/or MEK inhibitors. Only BRAFV600WT tumors responded to KRT-232 treatment alone while BRAFV600E/M PDXs exhibited a synergistic response to the combination of KRT-232 and BRAF/MEK inhibitors. Conclusions: KRT-232 is an effective therapy for the treatment of either BRAFWT or PANWT (BRAFWT, NRASWT) TP53WT melanomas. In combination with BRAF and/or MEK inhibitors, KRT-232 may be an effective treatment strategy for BRAFV600-mutant tumors.

Foldamers combining aliphatic and aromatic main‐chain units often produce atypical structures that cannot easily be accessed from purely aromatic or aliphatic sequences. We report solid‐state evidence that sequences comprising α‐amino acids and quinoline‐based monomers adopt conformations that combine the folding propensities of both components. Foldamers 2 and 3 having an XQQ repeat motif (X=α‐amino acid, Q=quinoline) were synthesized. Crystals of 2 (X=Phe, Q with an anionic side chain) obtained from water revealed an aromatic helix where amide groups belonging to the α‐amino acids created a hydrogen‐bond array typical of peptidic helices. Crystals of 3 (X=Ser, Q with a lipophilic side chain) obtained from organic solvents revealed a helix‐turn‐helix structure in which α‐amino acid side chains interfere with main‐chain hydrogen bonding. High sequence‐dependency of the conformation is typical of peptides but is shown here to include aromatic folding features., Neatly stacked: Crystallographic studies of hybrid XQQ‐type foldamers (X=α‐amino acid, Q=quinoline) were performed to explore their folding behavior. A water‐soluble sequence folded into a P‐helix in which aromatic residues stack, whereas α‐amino acid residues form an array of hydrogen bonds as in an M α‐helix. An organic soluble sequence was shown to adopt an unusual helix‐turn‐helix‐like conformation in which side chains interfere with main‐chain behavior.

The recognition of either homomeric or heteromeric pairs of pentoses in an aromatic oligoamide double helical foldamer capsule was evidenced by circular dichroism (CD), NMR spectroscopy, and X‐ray crystallography. The cavity of the host was predicted to be large enough to accommodate simultaneously two xylose molecules and to form a 1:2 complex (one container, two saccharides). Solution and solid‐state data revealed the selective recognition of the α‐4C1‐d‐xylopyranose tautomer, which is bound at two identical sites in the foldamer cavity. A step further was achieved by sequestering a heteromeric pair of pentoses, that is, one molecule of α‐4C1‐d‐xylopyranose and one molecule of β‐1C4‐d‐arabinopyranose despite the symmetrical nature of the host and despite the similarity of the guests. Subtle induced‐fit and allosteric effects are responsible for the outstanding selectivities observed., Two monosacharides fit in an aromatic double helical foldamer container. Binding is shown to be selective in terms of the sugar anomer, pyranose/furanose tautomer, and helix handedness, and leads to well defined homomeric or heteromeric complexes. One heteromeric complex selectively forms out of 42 different possibilities.

Aromatic oligoamide double helices bearing a chiral oxazolylaniline moiety at the C-terminus were synthesized and their helix handedness was completely controlled (de > 99%). The absolute helix sense and the de values were evaluated by using 1H NMR, X-ray crystallography, and circular dichroism (CD). Using crystal structure analysis, the high efficiency of helix handedness induction was attributed to the close location of the asymmetric carbon center to the helix orbits via intramolecular hydrogen bonding. The CD experiments also showed that there is no loss of chiral induction either in the interconversion of single and double helices or by elongation of the sequences.

The TAR DNA-binding protein (TDP-43) self-assembles into prion-like aggregates considered to be the structural hallmark of amyotrophic lateral sclerosis and frontotemporal dementia. Here, we use a combination of electron microscopy, X-ray fiber diffraction, Fourier-transform infrared spectroscopy analysis, and solid-state NMR spectroscopy to investigate the molecular organization of different TDP constructs, namely the full-length TDP-43 (1-414), two C-terminal fragments [TDP-35 (90-414) and TDP-16 (267-414)], and a C-terminal truncated fragment (TDP-43 increment GaroS2), in their fibrillar state. Although the different protein constructs exhibit similar fibril morphology and a typical cross-beta signature by X-ray diffraction, solid-state NMR indicates that TDP-43 and TDP-35 share the same polymorphic molecular structure, while TDP-16 encompasses a well-ordered amyloid core. We identified several residues in the so-called C-terminal GaroS2 (368-414) domain that participates in the rigid core of TDP-16 fibrils, underlining its importance during the aggregation process. Our findings demonstrate that C-terminal fragments can adopt a different molecular conformation in isolation or in the context of the full-length assembly, suggesting that the N-terminal domain and RRM domains play an important role in the TDP-43 amyloid transition.

Bimetallic nanostructures can be attractive contrast-enhancing materials for dual modal imaging, allowing improved diagnosis ability using two different physical phenomena, following administration...

Campomanesia aurea O. Berg is a native plant of the biome Pampa, which belongs to the family Myrtaceae. The present study aimed to evaluate the antimicrobial and antibiofilme activity of the essential oil of Campomanesia aurea (EOCA) against Listeria monocytogenes ATCC 19114, Staphylococcus aureus ATCC 25923, Salmonella enteritidis ATCC 13076 and Pseudomonas aeruginosa ATCC 27853. An analysis of the chemical composition of the EOCA was realized through gas chromatography coupled to mass spectrometry (GC-MS). The analysis for in vitro evaluation of the antimicrobial and antibiofilm activity was realized by determination of the minimal inhibitory concentration (MIC) and that of the antibiofilm through utilization of 96-well plates with crystal violet, respectively. The action of standard (E)–nerolidol (major compound of the EOCA) was also tested. GC-MS analysis revealed the presence of the sesquiterpene (E)-nerolidol (56.04%) as the main compound in the EOCA. Antimicrobial activity of the EOCA against L. monocytogenes (MIC 5.0 mg mL−1) and S. aureus (MIC 0.7 mg mL−1) was observed. Inhibition of biofilm formation against L. monocytogenes, S. aureus and S. enteritidis could be observed for EOCA and (E)-nerolidol. The results demonstrate that the EOCA was efficient against inhibition of biofilm formation for most of the tested pathogens.

The work reported herein is an important continuation of our recent experimental and computational studies on Li[NixCoyMnz]O2 (x + y + z = 1) cathode materials for Li-ion batteries, containing mino...

Ototoxicity is a collateral effect of prolonged treatment with chloroquine which is a widely utilized as an anti-lupus and anti-malarial drug. Glial cells of inner ear are responsible for maintenance of neuronal cells homeostasis in auditory system. In the current study we have evaluated chloroquine-induced toxicity and protective effect of ascorbic acid treatment on Schwann glial cell cultures of inner ear. Glial cells were cultured from organ of Corti of mice cochlear structure. Purity of Schwann glial cell was confirmed by S100 protein staining. Cell viability was evaluated in control and cultures treated with different concentrations of chloroquine. Glutamate uptake and ROS production were measured by HPLC and DCFH-DA probe fluorescence, respectively. Results have shown that chloroquine treatment evoked concentration and time -dependent toxicity (LC50 = 70 μM) as well as significant decrease on glutamate uptake and high production of ROS in glial cell cultures. Co-treatment with ascorbic acid has prevented both chloroquine-induced ROS production and chloroquine toxicity on glial cell cultures. This pre-clinical study is the first one to demonstrate chloroquine-induced ROS production by glial cells of inner ear as well as the protective effect exerted by ascorbic acid on these cells.

International audience; Fungi are considered to cause grapevine trunk diseases such as esca that result in wood degradation. For instance, the basidiomycete Fomitiporia mediterranea (Fmed) is overabundant in white rot, a key type of wood-necrosis associated with esca. However, many bacteria colonize the grapevine wood too, including the white rot. In this study, we hypothesized that bacteria colonizing grapevine wood interact, possibly synergistically, with Fmed and enhance the fungal ability to degrade wood. We isolated 237 bacterial strains from esca-affected grapevine wood. Most of them belonged to the families Xanthomonadaceae and Pseudomonadaceae. Some bacterial strains that degrade grapevine-wood components such as cellulose and hemicellulose did not inhibit Fmed growth in vitro. We proved that the fungal ability to degrade wood can be strongly influenced by bacteria inhabiting the wood. This was shown with a cellulolytic and xylanolytic strain of the Paenibacillus genus, which displays synergistic interaction with Fmed by enhancing the degradation of wood structures. Genome analysis of this Paenibacillus strain revealed several gene clusters such as those involved in the expression of carbohydrate-active enzymes, xylose utilization and vitamin metabolism. In addition, certain other genetic characteristics of the strain allow it to thrive as an endophyte in grapevine and influence the wood degradation by Fmed. This suggests that there might exist a synergistic interaction between the fungus Fmed and the bacterial strain mentioned above, enhancing grapevine wood degradation. Further step would be to point out its occurrence in mature grapevines to promote esca disease development.

The anti-oxidative potential of Rhamnidium elaeocarpum extract was assessed using a green chemical bottom-up approach to produce ~ 80 nm cubic Fe3O4 nanoparticles. The protocol makes use of FeCl3 as the only precursor of magnetite, and it allows the obtaining of the material using water as solvent, and urea as a pH regulator. Besides, since the bark extract functions as both the capping and reducing agents, no unfriendly extra chemicals are required to promote the Fe3+ reduction to Fe2+. For comparison purposes, we also obtained iron oxide materials in the absence of the biomass, and it was observed that urea alone could not reduce Fe3+ to promote the formation of magnetite nanoparticles. In that case, other forms of iron oxide materials, with very low magnetic response, such as hematite (α-Fe2O3) and maghemite (γ-Fe2O3) were obtained. The bio-inspired catalyst (Fe3O4) was applied in the degradation of Rhodamine-B using H2O2. Under the studied conditions, a single portion of the catalyst could promote the dye degradation for at least 5 cycles (degradation > 94%), and the material could be rapidly isolated in between batches using a small neodymium magnet. We also found out that the iron oxides obtained in the absence of extract and urea exhibited a lower degradation efficiency, and could not be recycled in successive runs. An investigation on the toxicity of this new catalyst was also carried out on three model organisms and no toxicity enhancement could be induced by the presence of the as-synthesized magnetite nanoparticles.

As metalloproteins exemplify, the chemical and physical properties of metal centers depend not only on their first but also on their second coordination sphere. Installing arrays of functional groups around the first coordination sphere of synthetic metal complexes is thus highly desirable, but it remains a challenging objective. Here we introduce a novel approach to produce tailored second coordination spheres. We used bioinspired artificial architectures based on aromatic oligoamide foldamers to construct a rigid, modular and well-defined environment around a metal complex. Specifically, aza-aromatic monomers having a tethered [2Fe–2S] cluster have been synthesized and incorporated in conical helical foldamer sequences. Exploiting the modularity and predictability of aromatic oligoamide structures allowed for the straightforward design of a conical architecture able to sequester the metal complex in a confined environment. Even though no direct metal complex–foldamer interactions were purposely designed in this first generation model, crystallography, NMR and IR spectroscopy concurred to show that the aromatic oligoamide backbone alters the structure and fluxional processes of the metal cluster., Wrapping a [2Fe–2S] metal complex in an aromatic foldamer helix is introduced as a new approach to tailor a second coordination sphere.

Aim To test the hypothesis that the use of rhBMP2 in established defects requires additional growth factors such as rhVEGF to accomplish effective bone repair. Materials and methods Horizontal/vertical defects of 2 cm length and 1 cm height were created bilaterally in the alveolar crest of the maxillae of 18 minipigs together with the extraction of all premolar teeth and one molar tooth on both sides. After 3 months of healing, defects were augmented with 0.5 g particulate PDLLA/CaCO3 composite loaded with 400 µg rhBMP2/50 µg rhVEGF165 on one side and 800 µg rhBMP2 on the other in 12 test animals, whereas defects in six control animals were sham operated and left unfilled on one side and augmented with blank carriers on the other. After 4 and 13 weeks, the animals were evaluated each for area of new bone formation (mm²) and bone density (area %). Results Augmentations with carriers loaded with 800 g µrhBMP2 failed to induce significantly more bone than in the augmentations with unloaded carrier after 4 and 13 weeks (p = .1000, p = .381). Augmentations with carriers loaded with 400 µg rhBMP2 and 50 µg erhVEGF165 resulted in significantly increased bone formation after 13 weeks (p = .024) compared to blank carriers. Soft tissue in augmentations with combined rhBMP2/rhVEGF165 loading exhibited numerous microvessels compared to soft tissue in augmentations with rhBMP2. Conclusions It is concluded that effective bone regeneration in augmentations of established alveolar ridge defects may require the application of rhVEGF additionally to rhBMP2.

The effect of Ta on the oxidation resistance of the alloys Tax-(Mo-Cr-Ti-Al)1−x (x=0; 5; 10; 15; 20 at%) in air at 1200 °C was examined. The oxidation behavior improves continuously with the increasing Ta concentration. Alloys with Ta concentrations Ta≤10 at% exhibit poor oxidation. Severe evaporation of MoO3 occurred which was quantitatively estimated. The evaporation of MoO3 is drastically reduced in alloys with the higher Ta concentrations. At 15 and 20 at% Ta, protective CrTaO4 scales are found. The CrTaO4 scale formed on Ta20-(Mo-Cr-Ti-Al)80 grows according to the parabolic rate law as a result of oxygen inward diffusion.

The sequence of a near-complete genome (two RNA segments) of cowpea severe mosaic virus (CpSMV) in the Comovirus genus is revealed in South America. High-throughput sequencing (HTS) was performed using total RNA extracted from partially purified virus preparations obtained from infected yardlong bean leaves (Vigna unguiculata subsp. sesquipedalis), collected in Santa Izabel, state of Para, Brazil. The YLB (yardlong bean) isolate has an RNA-1 with 5896 nucleotides (nt) and an RNA-2 with 3515 nt, showing 74.2% and 67.9% identity, respectively, with the CpSMV-DG isolate sequences from the USA, the only complete genome available so far. Despite the low percentage in nt identity, the amino acid (aa) sequence of the viral protease together with the RNA-dependent RNA polymerase (Pro/RdRp) and the large and small coat proteins (CP-L/CP-S), used as species demarcation criteria of the Secoviridae family, showed 92.2% (Pro-RdRp) and 85.6% (CP-L/CL-S) identities between DG and YLB isolates sequences. The nucleotide identity of partial RNA-1 sequences of 2199 nt (part of the helicase, VPg, Pro, and 2/3 of the RdRP) varied from 95.1 to 95.3% among YLB and eleven isolates from Brazil available on GenBank. Phylogenetic analysis based on this 2199 nt sequence revealed that the YLB isolate was positioned in a different clade compared to other CpSMV isolates. An estimate of damage caused by CpSMV under experimental conditions revealed a reduction of 39.4% in the total number of pods and 54.3% in the total number of grains, regardless of the yardlong bean cultivar evaluated. The reduction of total weight of the grains by CpSMV infection was dependent on the cultivar and was higher in cv. De metro (66.2%) than in cv. Slin (38.9%).

International audience; Infectious proteins or prions are a remarkable class of pathogens, where pathogenicity and infectious state correspond to conformational transition of a protein fold. The conformational change translates into the formation by the protein of insoluble amyloid aggregates, associated in humans with various neurodegenerative disorders and systemic protein-deposition diseases. The prion principle, however, is not limited to pathogenicity. While pathological amyloids (and prions) emerge from protein misfolding, a class of functional amyloids has been defined, consisting of amyloid-forming domains under natural selection and with diverse biological roles. Although of great importance, prion amyloid structures remain challenging for conventional structural biology techniques. Solid-state nuclear magnetic resonance (SSNMR) has been preferentially used to investigate these insoluble, morphologically heterogeneous aggregates with poor crystallinity. SSNMR methods have yielded a wealth of knowledge regarding the fundamentals of prion biology and have helped to solve the structures of several prion and prion-like fibrils. Here, we will review pathological and functional amyloid structures and will discuss some of the obtained structural models. We will finish the review with a perspective on integrative approaches combining solid-state NMR, electron paramagnetic resonance and cryo-electron microscopy, which can complement and extend our toolkit to structurally explore various facets of prion biology.

The selective binding properties of a 13-mer oligoamide foldamer capsule composed of 4 different aromatic subunits are reported. The capsule was designed to recognize dicarboxylic acids through multiple-point interactions owing to a combination of protonation/deprotonation events, H-bonding, and geometrical constraints imparted by the rigidity of the foldamer backbone. Compared to tartaric acid, binding of 2,2-difluorosuccinic acid or 2,2,3,3-tetrafluorosuccinic acid resulted in symmetry breaking due to deprotonation of only one of the two carboxylic acid groups of the encapsulated species as shown by NMR studies in solution and by single-crystal X-ray diffraction in the solid state. An analogous 14-mer foldamer capsule terminated with a thiol anchoring group was used to probe the complexation event in self-assembled monolayers on Au substrates. Ellipsometry and polarization-modulation infrared absorption-reflection spectroscopy studies were consistent with the formation of a single molecule layer of the foldamer capsule oriented vertically with respect to the surface. The latter underwent smooth complexation of 2,2-difluorosuccinic acid with deprotonation of one of the two carboxylic acid groups. A significant (80-fold) difference in the charge transport properties of the monolayer upon encapsulation of the dicarboxylic acid was evidenced from conducting-AFM measurements (S = 1.1 × 10−9vs. 1.4 × 10−11 ohm−1 for the empty and complexed capsule, respectively). The modulation in conductivity was assigned to protonation of the aromatic foldamer backbone., Conductance through a monolayer of a helical foldamer host was found to vary by 80-fold depending on the presence or the absence of a guest in the host's cavity.

Malaria is a life-threatening disease caused by Plasmodium and represents one of the main public health problems in the world. Among alterations associated with the disease, we highlight the hepatic impairment resulting from the generation of oxidative stress. Studies demonstrate that liver injuries caused by Plasmodium infection are associated with unbalance of the antioxidant system in hepatocytes, although little is known about the role of antioxidant molecules such as glutathione and vitamin C in the evolution of the disease and in the liver injury. To evaluate disease complications, murine models emerge as a valuable tool due to their similarities between the infectious species for human and mice. Herein, the aim of this study is to evaluate the effect of antioxidants glutathione and vitamin C on the evolution of murine malaria and in the liver damage caused by Plasmodium berghei ANKA infection. Mice were inoculated with parasitized erythrocytes and treated with glutathione and vitamin C, separately, both at 8 mg/kg during 7 consecutive days. Our data showed that during Plasmodium infection, treatment with glutathione promoted significant decrease in the survival of infected mice, accelerating the disease severity. However, treatment with vitamin C promoted an improvement in the clinical outcomes and prolonged the survival curve of infected animals. We also showed that glutathione promoted increase in the parasitemia rate of Plasmodium-infected animals, although treatment with vitamin C has induced significant decrease in parasitemia rates. Furthermore, histological analysis and enzyme biochemical measurement showed that treatment with glutathione exacerbates liver damage while treatment with vitamin C mitigates the hepatic injury induced by the infection. In summary, the current study provided evidences that antioxidant molecules could differently modulate the outcome of malaria disease; while glutathione aggravated the disease outcome and liver injury, the treatment with vitamin C protects the liver from damage and the evolution of the condition.

Diversification of the structures and the applications possible for foldamers rely on expansion of the building block library available for their synthesis. In this work, we describe the synthesis of a range of three dimensional heteroaromatic monomers, based on iptycene scaffolds, that are suitable for the synthesis of aromatic oligoamide foldamers. These units can be obtained in gram quantities in up to 80 % yield through [4+2] cycloaddition between diester, diamine, and amino acid derivatives of 1,8-diazaanthracenes and a variety of dienophiles. X-ray structural studies of the monomers and an oligomer show that the new motif orients the two heterocyclic rings and attached groups at an angle of approximately 120° to each other, opening new geometric considerations for the design of this class of foldamer.

International audience; A photoresponsive diarylethene was incorporated in an achiral helical foldamer container. A carbohydrate guest was found to induce opposite handedness upon binding to the open and closed forms of the diarylethene-containing foldamer, thus enabling chiroptical switching of an achiral host mediated by a chiral guest.

International audience; Very slow kinetic evolution (days) of chiral nanoribbons based on amphiphilic molecular assemblies is investigated for various enantiomeric excess. In the early stage of ribbon formation, those formed for low enantiomeric excess (0

International audience; After extensive studies of 1D and 2D skeletal carbo‐mers based on C8π‐conjugatingdialkynylbutatriene units(DABs: ~C≡C–(R)C=C=C=C(R)–C≡C~) bridging spor sp2centers in carbo‐butene, ‐xylylene or ‐benzene derivatives, 3D versions are envisaged through carbo‐barrelenes and partially reduced derivatives thereofwhere two or three DAB blades span a bridge between sp3carbinol vertices or ether thereof. For R = Ph, stable representatives were synthesized through a pivotal [6]pericyclynedione, and extensively characterized by spectroscopic, electrochemical and crystallographic methods. Density functional theory calculations allow detailed analysis of structural and electronic features of the 7 Å high barrel‐shaped molecules, and show that they can behave as cages for ionic species. Beyond aesthetical concerns, the results could open prospects of applications in host‐guest supramolecular chemistry and single molecule charge transport.

The orchestration of ever larger conformational changes is made possible by the development of increasingly complex foldamers. Aromatic sheets, a rare motif in synthetic foldamer structures, have been designed so as to form discrete stacks of intercalated aromatic strands through the self‐assembly of two identical subunits. Ion‐mobility ESI‐MS confirms the formation of compact dimers. X‐ray crystallography reveals the existence of two distinct conformational dimeric states that require large changes to interconvert. Molecular dynamics simulation validates the stability of the two conformations and the possibility of their interconversion., Unexpected conformational changes involving a global concerted rearrangement of the structure have been evidenced in large multistranded aromatic sheets. Increasing foldamer size thus gives access to new and defined conformational trajectories.

Quality control of CBD oils on the Belgium market showed that the CBD content not always corresponds to the label claim. There is a pressing need to develop new analytical methods specifically developed to the assay of such oily samples. Analytical issues are, however, encountered for routine analyses due to the matrix complexity, high cost of cannabinoid standards and low Δ9-THC concentrations. An oily matrix could cause technical damages to analytical instruments and reduce the lifetime of the chromatographic columns. This paper proposes a procedure combining a sample cleanup by QuEChERS, removing the oily matrix, followed by a validated MRM GC-MS/MS method for the routine analysis of CBD oil samples. Eighteen CBD samples were selected on the Belgium market for analysis. This method allows the quantification of CBD, the legality check for the Δ9-THC content by a CBN standard and the screening of seven other cannabinoids namely CBN, CBDV, CBT, CBC, Δ8-THC, THCV and CBG. The method was validated at three concentration levels (0.5–1–2% (w/v)) for CBD and (0.05–0.1–0.2% (w/v)) for CBN. The detection limits for CBT, CBD, CBC, Δ8-THC, CBN and for the other cannabinoids of interest, were 10 and 14 ng/mL respectively. The accuracy profile values for CBD and CBN showed that the β-expectation tolerance intervals did not exceed the acceptance limits of ± 20%, meaning that 90% of future measurements will be included within this error range.

International audience; A multicomponent self-assembly reaction involving a bis-biphenolato ligand (LH 4), a 2,2′-bipyrimidine chelate substituted by two (anthryl)vinyl moieties (bAnt) and Ti(OiPr) 4 was investigated. An assembly {[Ti 3 (L) 3 (bAnt) 3 ]}, composed of three homochiral TiO 4 N 2 nodes, was characterized as being the ther-modynamically-end product. The crystal structure of this circular helicate highlighted an absence of symmetry for this compact compound. DOSY 1 H NMR indicated that the nuclearity Self-assembly processes driven by transition metals are highly powerful methods to access complex architectures. [1] These self-assembled architectures, which are impossible to obtain through conventional step-by-step synthetic strategies, result from the mutual programmed recognition between metal ions and organic ligands. An impressive number of rationally designed helicates, [2] cages, [3] squares, [4] spheres, [5] grids, [6] top-ological non-trivial molecules [7] and other architectures [8] have been reported so far. Whereas the main interest in self-assembly is focused on the thermodynamically-end products, the characterization and the isolation of intermediate architectures generated during the self-assembly is rather scarce. [9] This is mainly linked to the low energy barriers existing between transient compounds. However, it is an important issue since the full identification of intermediates could provide fundamental information to apprehend some mechanistic aspects of a self-assem-[a] Dr. 3527 observed in the solid state for [Ti 3 (L) 3 (bAnt) 3 ] was maintained in solution. An intermediate formulated as [Ti 4 (L) 4 (bAnt) 4 ] was isolated. The structural analysis revealed that [Ti 4 (L) 4 (bAnt) 4 ] was a symmetrical circular hollow helicate composed of four homochiral metallovertices. This study, supported by DFT calculation , brought some evidences on the sequences and the reasons leading to the symmetry decrease for this self-assembly process. bly reaction. Therefore, the isolation and characterization of one or several intermediates produced in the course of a self-assembly process is a challenging and major task. [10] Over the latest decade, our group has developed a tita-nium(IV)-based coordination chemistry involving a bis-biphe-nolato ligand named as LH 4 as shown in Figure 1, leading to neutral self-assembled helical structures. [11,12] By following a multicomponent self-assembly approach with the 2,2′-bipyrimi-dine (bpym) chelate, a circular trinuclear bowl-shaped helicate constructed around octahedral TiO 4 N 2 motifs, [Ti 3 (L) 3 (bpym) 3 ], was generated. [13] This study also highlighted the formation of a tetranuclear intermediate {[Ti 4 (L) 4 (bpym) 4 ]} detected only by mass-spectrometry and 1 H NMR. Figure 1. Structure of LH 4 and bAnt.

Although ammonia is a widely used interstellar thermometer, the estimation of its rotational and kinetic temperatures can be affected by the blended hyperfine components (HFCs). We have developed a new recipe, referred to as the hyperfine group ratio (HFGR), which utilizes only direct observables, namely the intensity ratios between the grouped HFCs. As tested on the model spectra, the empirical formulae in the HFGR can derive the rotational temperature (Trot) from the HFC group ratios in an unambiguous manner. We compared the HFGR with two other classical methods, intensity ratio and hyperfine fitting, based on both simulated spectra and real data. The HFGR has three major improvements. First, it does not require modelling the HFC or fitting the line profiles, so it is more robust against the effect of HFC blending. Second, the simulation-enabled empirical formulae are much faster than fitting the spectra over the parameter space, so both computer time and human time can be saved. Third, the statistical uncertainty of the temperature ΔTrot as a function of the signal-to-noise ratio (S/N) is a natural product of the HFGR recipe. The internal error of the HFGR is ΔTrot ≤ 0.5 K over a broad parameter space of rotational temperature (10–60 K), linewidth (0.3–4 km s−1) and optical depth (0–5). When there is spectral noise, the HFGR can also maintain a reasonable uncertainty level at ΔTrot ≤ 1.0 K when S/N > 4.

The templated clipping of a ferrocene-grafted isophthalic acid derivative to encircle a hydrogen-bonding axle through the reaction with 1,4-bis(aminomethyl)benzene is described. The constituent electroactive macrocycle of the resultant [2]rotaxane is a homologue of the versatile benchmark tetraamide variant developed by Leigh and co-workers. The relative templating effect of different hydrogen-bonding motifs in rotaxane and pseudorotaxane generation is compared, with yields varying from 0 to 41%. The electrochemical properties and single crystal X-ray structure of a doubly ferrocene-decorated [2]rotaxane are further reported.

In this work, we present a computational investigation on the structure and energetics of eleocarpanthraquinone, a newly isolated polyphenolic anthrone-antraquinone. Properties such as bond lengths, angles, atomic charges, bond dissociation enthalpies (BDEs), and ionization potential (IP) were determined through the use of density functional theory (DFT). The B3LYP and M06-2X exchange-correlation functionals were employed along with the 6-31+G(d,p), 6-31+ +G(d,p), and 6-311+G(d,p) basis sets for performing computations in the gas-phase, water, methanol, and ethanol. The conformation presenting all the hydroxyl groups undergoing hydrogen-bond interactions with neighboring oxygen atoms (conformation 5) was assigned as the most stable structure while its counterpart presenting no hydrogen-bond interaction was found to be 36.45 kcal/mol less stable than conformation 5 in the potential energy surface probed at the B3LYP/6-311+G(d,p) level of theory in the gas-phase, for instance. More importantly, the lowest O–H bond dissociation enthalpy was determined to be 93.80 kcal/mol at the B3LYP/6-311+G(d,p) level of theory in water against the 146.58 kcal/mol regarding the IP computed at the same approach, suggesting the hydrogen atom transfer mechanism as being preferred over the single electron transfer mechanism in regards to the antioxidant potential for the case of eleocarpanthraquinone; the same conclusion was drawn from the outcomes of all the other approaches used.

Liquid chromatography (LC) coupled to an electrochemical (EC) detector is a complementary analytical tool compared to LC coupled with optical or mass spectrometry detectors (LC-MS). LC-EC can be applied to the determination of molecules difficult to be analyzed by other commercially available detectors. New EC detector design and new working electrode material have extended the scope of application in the field of pharmaceutical compounds analysis. Combining EC with LC-MS offers additional advantages compared to optical detectors in terms of drug stability and drug metabolism mimicry studies. Selected literature devoted to pharmacologically active compounds in their dosage forms, herbal drugs in natural products, drug residues in feed and/or in biological samples are reported in this review.

Xylobiose sequestration in a helical aromatic oligoamide capsule was evidenced by circular dichroism, NMR spectroscopy, and crystallography. The preparation of the 5 kDa oligoamide sequence was made possible by the transient use of acid-labile dimethoxybenzyl tertiary amide substituents that disrupt helical folding and prevent double helix formation. Binding of other disaccharides was not detected. Crystallographic data revealed a complex composed of a d-xylobiose alpha anomer and two water molecules accommodated in the right-handed helix. The disaccharide was found to adopt an unusual all-axial compact conformation. A dense network of 18 hydrogen bonds forms between the guest, the cavity wall, and the two water molecules.

Equilibrated interfaces between Ni and yttrium stabilized zirconia (YSZ) were formed by solid-state dewetting of thin Ni films on the (111) surface of YSZ single crystals at 1350 °C and an oxygen partial pressure of P(O2) = 10−20 atm. The atomistic structure of the equilibrated solid-solid Ni [ 1 ¯ 10 ] 111 ∥ YSZ [ 1 1 ¯ 0 ] 111 interface was determined by monochromated and aberration-corrected scanning transmission electron microscopy, using different techniques. It was found that due to the large lattice mismatch between Ni and YSZ the interface reconstructs, and adopts a unique structure which consists of a high density of misfit dislocations. However, despite the large lattice mismatch, this interface is not incoherent. The interface was confirmed to be cation terminated, which is probably due to the low oxygen partial pressure used to reach equilibrium.

Silicon (Si) integration is a critical step toward future applications of multifunctional oxides as nanoscale electronics and spintronic devices, because of the low cost and scalability of silicon substrates. As a demonstration, self-assembled (La0.7Sr0.3MnO3)x: NiO1–x (LSMO:NiO) vertically aligned nanocomposite (VAN) thin films with exchange bias (EB) properties have been successfully deposited on buffered Si substrates. To enable the epitaxial growth of LSMO:NiO VAN, SrRuO3/TiN was first grown as the buffer layers on Si substrates. The composition of the two-phases has been varied with x = 0.25, 0.5, 0.75, and 1 to explore the electrical transport and magnetic properties of the VAN system on Si. The irreversible temperature Tirr was found to increase with increasing NiO composition, with the highest for (LSMO)0.25(NiO)0.75 of ∼275 K, when the field was applied in the out-of-plane direction. In addition, the EB effect has been observed for all the nanocomposite films, with the highest HEB value of 300 Oe...

Attention to semiconductor nanostructures with a narrow band gap energy and low production cost has increased in recent years, due to practical demands for use in various optoelectronics and communication devices. Colloidal nanostructures from the IV–VI semiconductors, such as lead and tin chalcogenides, seem to be the most suitable materials platform; however, their poor chemical and spectral stability has impeded practical applications. The present work explored the mechanism for formation of new nanostructures, SnTe/PbTe/SnO2, with a core/shell/shell heterostructure architecture. The preparation involved a single-step post-treatment for the preprepared SnTe cores, which simultaneously generated two different consecutive shells. The process followed a remarkable Kirkendall effect, where Sn ions diffused to the exterior surface from a region below the surface and left a ringlike vacancy area. Then Pb ions diffused inward and created a PbTe shell, filling the Sn-deficient region. Finally, the ejected Sn i...

We performed a multiscale study to understand the impact of pure exogenous compounds at low concentration on the crystallization of triacylglycerols (TAGs) in anhydrous milk fat (AMF). We selected butyric acid, an inhibitor of crystallization, and palmitic acid, a promotor, to investigate the influence of the chain length. Tripalmitin was also used as a promotor to assess the impact of fatty acid esterification. Melted blends containing the additives (1 wt%) were quenched at 25 °C. X-ray scattering data showed that AMF TAGs crystallized directly in the β’-2L form. The presence of additives did not modify the nanostructure of TAG crystals. However, they significantly altered the microstructure of AMF, as revealed by polarized light microscopy and rheology. This study emphasizes the interest of a multiscale approach to gain knowledge about the behavior of complex fat blends and of the use of modulators at low concentration to monitor their textural properties.

International audience; Synthetic hydrogen-bonding receptors are described, which incorporate a central electroactive ferrocene moiety grafted with two adjacent bis(amido)pyridine motifs and an aliphatic tether (14 and 18 methylene units for 1 and 2, respectively) completing the macrocycle. The crystallographic structure, barbiturate guest-binding studies and electrochemical data are provided for the more strongly-binding macrocycle 2.

Background: Despite initial response to chemotherapy, the prognosis of small cell lung cancer (SCLC) patients is limited. Following first-line therapy, the strongest predictor of durable progression-free survival (PFS) is remission quality. Febrile neutropenia (FN) is a frequent complication after chemotherapy, and its prevention could improve treatment density and degree of remission. Patients and Methods: We retrospectively analyzed 39 SCLC patients treated at a German tertiary care lung cancer center between 2013 and 2016. We extracted data sets from electronic records and analyzed anthropometric data, pretherapeutic blood values, and prognostic scores. Discriminant analysis was performed to predict FN. Results: PFS after first-line chemotherapy was significantly shorter in patients with FN (p = 0.003). Pretherapeutic albumin (p = 0.019), C-reactive protein (CRP; p < 0.001), lactate dehydrogenase (p = 0.041), neutrophil-to-lymphocyte ratio (p = 0.009), prognostic nutritional index (p = 0.018), and Glasgow prognostic score (p < 0.001) were significantly associated with FN. CRP in combination with absolute neutrophil count is a strong predictor of FN (positive predictive value 79.8%). Conclusion: SCLC patients with FN after chemotherapy showed significantly reduced PFS. Prevention of FN may improve treatment results. We identified pretherapeutic markers which can predict FN risk. This simple and cost-effective method could serve to identify the need for preventive measures against FN (e.g., prophylactic antibiotic treatment or granulocyte colony stimulating factor administration).

Constrained γ-amino acid gababutin (Gbn) based peptides that form different conformations have been synthesized. Striving to rationalize the impact of side chain orientations framing tetrapeptide-based supramolecular organic frameworks and morphological entities, Gbn incorporated hybrid peptides Boc-Gbn-Aib-Aaa-Aib-OMe (where Aaa = Phe(F) for peptide 1, Leu(L) for peptide 2 and Tyr(Y) for peptide 3) were synthesized by changing the amino acid at the third position. The solution state dual folded conformation (C12/C10 H-bonded) is probed by 2D NMR spectroscopy in support of a DMSO-d6 titration and VT NMR experiments. Peptides 1–3 adopt a C12/C10 type H-bonded dual folded conformation in the crystal state. In addition, distinct supramolecular frameworks result from the modification and orientation of the third residue side chain of peptides 1–3. A solvent induced morphological diversity of peptides 1–3 is attained by modifying the side chain backbone of the tetrapeptides, which are investigated by various microscopic (SEM and AFM) studies. Gbn-based peptides 1–3 show significant morphological and supramolecular packing properties, which are fairly different from those of their gabapentin (Gpn) based analogue peptides.

Ethoxyquin (EQ) is widely used as a synthetic antioxidant in animal feed, an antiscalding agent in apples and pears and as a color preservative in some spices. Since the presence of EQ in food products could cause negative health effects it is necessary to develop reliable analytical methods to evaluate the risk of human exposure. In this work, a sensitive, selective and accurate method based on solid-liquid extraction followed by clean-up with solid sorbent and liquid chromatography–electrochemical detection analysis with boron doped diamond electrode (LC–EC) for the determination of ethoxyquin and its dimer (EQDM) in pear skin and salmon samples, was developed. The method was validated according to the European Commission guidelines. The main variables of extraction were accurately optimized. The amounts of solid sorbents for clean-up procedure were optimized by using experimental design. A Box-Behnken design to obtain the optimum conditions was applied. For validation, a matrix-matched calibration was established and a recovery assay with spiked samples was carried out. The limits of detection (LODs) found were 0.05 and 0.1 mg kg −1 for EQ and its dimer, respectively. The precision (as relative standard deviation, RSD) was lower than 15% with recoveries of compounds close to 100% in spiked samples.