Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA.

Biofilm formation is one of main causes of bacterial antimicrobial resistance infections. It is known that the soluble lectins LecA and LecB, produced by Pseudomonas aeruginosa, play a key role in biofilm formation and lung infection. Bacterial lectins are therefore attractive targets for the development of new antibiotic-sparing anti-infective drugs. Building synthetic glycoconjugates for the inhibition and modulation of bacterial lectins have shown promising results. Light-sensitive lectin ligands could allow the modulation of lectins activity with precise spatiotemporal control. Despite the potential of photoswitchable tools, few photochromic lectin ligands have been developed. We have designed and synthesized several O- and S-galactosyl azobenzenes as photoswitchable ligands of LecA and evaluated their binding affinity with isothermal titration calorimetry. We show that the synthesized monovalent glycoligands possess excellent photophysical properties and strong affinity for targeted LecA with K d values in the micromolar range. Analysis of the thermodynamic contribution indicates that the Z-azobenzene isomers have a systematically stronger favorable enthalpy contribution than the corresponding E-isomers, but due to stronger unfavorable entropy, they are in general of lower affinity. The validation of this proof-of-concept and the dissection of thermodynamics of binding will help for the further development of lectin ligands that can be controlled by light.

One-Pot Synthesis of Bioinspired Peptide-Decorated Apatite Nanoparticles for Nanomedicine.

Hybrid organic-inorganic bio-inspired apatite nanoparticles (NPs) are attractive for biomedical applications and especially in nanomedicine. Unfortunately, their applications in nanomedicine are limited by their broad particle size distributions and uncontrolled drug loading due to their multistep synthesis process.  Besides, very few attempts at exposing bioactive peptides on apatite NPs are made. In this work, an original one-pot synthesis of well-defined bioactive hybrid NPs composed of a mineral core of bioinspired apatite surrounded by an organic corona of bioactive peptides is reported. Dual stabilizing-bioactive agents, phosphonated polyethylene glycol-peptide conjugates, are prepared and directly used during apatite precipitation i) to form the organic corona during apatite precipitation, driving the size and shape of resulting hybrid NPs with colloidal stabilization and ii) to expose peptide moieties (RGD or YIGSR sequences) at the NPs periphery in view of conferring additional surface properties to enhance their interaction with cells. Here, the success of this approach is demonstrated, the functionalized NPs are fully characterized by Fourier-transform infrared, Raman, X-ray diffraction, solid and liquid state NMR, transmission electron microscopy, and dynamic light scattering, and their interaction with fibroblast cells is followed, unveiling a synergistic proliferative effect.

Strontium-driven physiological to pathological transition of bone-like architecture: A dose-dependent investigation.

Whilst strontium (Sr2+) is widely investigated for treating osteoporosis, it is also related to mineralization disorders such as rickets and osteomalacia. In order to clarify the physiological and pathological effects of Sr2+ on bone biomineralization , we performed a dose-dependent investigation in bone components using a 3D scaffold that displays the hallmark features of bone tissue in terms of composition (osteoblast, collagen, carbonated apatite) and architecture (mineralized collagen fibrils hierarchically assembled into a twisted plywood geometry). As the level of Sr2+ is increased from physiological-like to excess, both the mineral and the collagen fibrils assembly are destabilized, leading to a drop in the Young modulus, with strong implications on pre-osteoblastic cell proliferation. Furthermore, the microstructural and mechanical changes reported here correlate with that observed in bone-weakening disorders induced by Sr2+ accumulation, which may clarify the paradoxical effects of Sr2+ in bone mineralization. More generally, our results provide physicochemical insights into the possible effects of inorganic ions on the assembly of bone extracellular matrix and may contribute to the design of safer therapies for treating osteoporosis. STATEMENT OF SIGNIFICANCE: Physiological-like (10% Sr2+) and excess accumulation-like (50% Sr2+) doses of Sr2+ are investigated in 3D biomimetic assemblies possessing the high degree of organization found in the extracellular of bone. Above the physiological dose, the organic and inorganic components of the bone-like scaffold are destabilized, resulting in impaired cellular activity, which correlates with bone-weakening disorders induced by Sr2+.

Silica Supported Organometallic IrI Complexes Enable Efficient Catalytic Methane Borylation.

Catalytic C-H borylation is an attractive method for the conversion of the most abundant hydrocarbon, methane (CH4), to a mild nucleophilic building block. However, existing CH4 borylation catalysts often suffer from low turnover numbers and conversions, which is hypothesized to result from inactive metal hydride agglomerates. Herein we report that the heterogenization of a bisphosphine molecular precatalyst, [(dmpe)Ir(cod)CH3], onto amorphous silica dramatically enhances its performance, yielding a catalyst that is 12-times more efficient than the current standard for CH4 borylation. The catalyst affords over 2000 turnovers at 150 °C in 16 h with a selectivity of 91.5% for mono- vs diborylation. Higher catalyst loadings improve yield and selectivity for the monoborylated product (H3CBpin) with 82.8% yield and >99% selectivity being achieved with 1255 turnovers. X-ray absorption and dynamic nuclear polarization-enhanced solid-state NMR spectroscopic studies identify the supported precatalyst as an IrI species, and indicate that upon completion of catalysis, multinuclear Ir polyhydrides are not formed. This is consistent with the hypothesis that immobilization of the organometallic Ir species on a surface prevents bimolecular decomposition pathways. Immobilization of the homogeneous IrI fragment onto amorphous silica represents a unique and simple strategy to improve the TON and longevity of a CH4 borylation catalyst.

Exploring the emergence of a tipping point for conservation with increased recognition of social considerations.

Despite a common understanding of the harmful impacts of Western conservation models that separate people from nature, widespread progress toward incorporating socioeconomic, political, cultural, and spiritual considerations in conservation practice is lacking. For some, the concept of nature-based solutions (NbS) is seen as an interdisciplinary and holistic pathway to better integrate human well-being in conservation. We examined how conservation practitioners in the United States view NbS and how social considerations are or are not incorporated in conservation adaptation projects. We interviewed 28 individuals working on 15 different such projects associated with the Wildlife Conservation Society's Climate Adaptation Fund. We completed 2 rounds of iterative coding in NVivo 12.6.1 to identify in the full text of all interview responses an a priori set of themes related to our research questions and emergent themes. Many respondents saw this moment as a tipping point for the field (one in which the perceived values of social considerations are increasing in conservation practice) (76%) and that social justice concerns and the need to overcome racist and colonial roots of Western conservation have risen to the forefront. Respondents also tentatively agreed that NbS in conservation could support social and ecological outcomes for conservation, but that it was far from guaranteed. Despite individual intention and awareness among practitioners to incorporate social considerations in conservation practice, structural barriers, including limited funding and inflexible grant structures, continue to constrain systemic change. Ultimately, systemic changes that address power and justice in policy and practice are required to leverage this moment to more fully address social considerations in conservation.

Exploración del surgimiento de un punto de inflexión para la conservación con el incremento del reconocimiento de las consideraciones sociales Resumen A pesar de que se conoce el impacto dañino de los modelos occidentales de conservación que separan a las personas de la naturaleza, aun faltan avances para la incorporación de las consideraciones socioeconómicas, políticas, culturales y espirituales dentro de la práctica de la conservación. Hay quienes consideran el concepto de soluciones basadas en la naturaleza (SbN) como una vía interdisciplinaria y holística para integrar de mejor manera el bienestar humano en la conservación. Analizamos cómo los conservacionistas de los EE. UU. perciben a las SbN y cómo se incorporan o no las consideraciones sociales en los proyectos de conservación y adaptación. Entrevistamos a 28 individuos que trabajan en 15 de estos proyectos asociados con el Fondo de Adaptación al Clima de la Wildlife Conservation Society. Completamos dos rondas de codificación iterativa en NVivo 12.6.1 para identificar a priori un conjunto de temas relacionado con nuestras preguntas y temas nacientes dentro del texto completo de las respuestas a la entrevista. Muchos de los respondientes (76%) consideraron este momento como un punto de inflexión para el campo de investigación (uno en el que están incrementando los valores percibidos de las consideraciones sociales en la práctica de la conservación) y que las cuestiones de justicia social y la necesidad de sobreponerse a las raíces racistas y colonialistas de la conservación occidental han dado un paso al frente. En principio, los respondientes también acordaron que las SbN en la conservación podrían respaldar los resultados sociales y ecológicos para la conservación, pero que no era algo cercano a ser una garantía. A pesar de la intención y conciencia individual de los conservacionistas para incorporar a las consideraciones sociales dentro de la práctica de la conservación, las barreras estructurales, incluyendo el financiamiento limitado de las estructuras poco flexibles de los subsidios, todavía restringen el cambio sistémico. Finalmente, se necesitan cambios sistémicos que aborden el poder y la justicia en las políticas y las prácticas para potenciar este momento para tratar plenamente las consideraciones sociales en la conservación.

Fast autofocusing using tiny transformer networks for digital holographic microscopy.

The numerical wavefront backpropagation principle of digital holography confers unique extended focus capabilities, without mechanical displacements along z-axis. However, the determination of the correct focusing distance is a non-trivial and time consuming issue. A deep learning (DL) solution is proposed to cast the autofocusing as a regression problem and tested over both experimental and simulated holograms. Single wavelength digital holograms were recorded by a Digital Holographic Microscope (DHM) with a 10x microscope objective from a patterned target moving in 3D over an axial range of 92 µm. Tiny DL models are proposed and compared such as a tiny Vision Transformer (TViT), tiny VGG16 (TVGG) and a tiny Swin-Transfomer (TSwinT). The proposed tiny networks are compared with their original versions (ViT/B16, VGG16 and Swin-Transformer Tiny) and the main neural networks used in digital holography such as LeNet and AlexNet. The experiments show that the predicted focusing distance ZRPred is accurately inferred with an accuracy of 1.2 µm in average in comparison with the DHM depth of field of 15 µm. Numerical simulations show that all tiny models give the ZRPred with an error below 0.3 µm. Such a prospect would significantly improve the current capabilities of computer vision position sensing in applications such as 3D microscopy for life sciences or micro-robotics. Moreover, all models reach an inference time on CPU, inferior to 25 ms per inference. In terms of occlusions, TViT based on its Transformer architecture is the most robust.

Synthesis of Hybrid Polyphenol/Hydroxyapatite Nanomaterials with Anti-Radical Properties.

Plant-derived natural bioactive molecules are of great therapeutic potential but, so far, their application in nanomedicine has scarcely been studied. This work aimed at comparing two methodologies, i.e., adsorption and in situ incorporation, to prepare hybrid polyphenol/hydroxyapatite nanoparticles. Two flavonoids, baicalin and its aglycone derivative baicalein, and two phenolic acids derived from caffeic acid, rosmarinic and chlorogenic acids, were studied. Adsorption of these polyphenols on pre-formed hydroxyapatite nanoparticles did not modify particle size or shape and loading was less than 10% (w/w). In contrast, presence of polyphenols during the synthesis of nanoparticles significantly impacted and sometimes fully inhibited hydroxyapatite formation but recovered particles could exhibit higher loadings. For most hybrid particles, release profiles consisted of a 24 h burst effect followed by a slow release over 2 weeks. Antioxidant properties of the polyphenols were preserved after adsorption but not when incorporated in situ. These results provide fruitful clues for the valorization of natural bioactive molecules in nanomedicine.

MiGriBot: A miniature parallel robot with integrated gripping for high-throughput micromanipulation.

Although robotic micromanipulation using microtweezers has been widely explored, the current manipulation throughput hardly exceeds one operation per second. Increasing the manipulation throughput is thus a key factor for the emergence of robotized microassembly industries. This article presents MiGriBot (Millimeter Gripper Robot), a miniaturized parallel robot with a configurable platform and soft joints, designed to perform pick-and-place operations at the microscale. MiGriBot combines in a single robot the benefits of a parallel kinematic architecture with a configurable platform and the use of soft joints at the millimeter scale. The configurable platform of the robot provides an internal degree of freedom that can be used to actuate microtweezers using piezoelectric bending actuators located at the base of the robot, which notably reduces the robot's inertia. The soft joints make it possible to miniaturize the mechanism and to avoid friction. These benefits enable MiGriBot to reach a throughput of 10 pick-and-place cycles per second of micrometer-sized objects, with a precision of 1 micrometer.

A Heterogeneous Palladium Catalyst for the Polymerization of Olefins Prepared by Halide Abstraction Using Surface R3 Si+ Species.

The silylium-like surface species [i Pr3 Si][(RF O)3 Al-OSi≡)] activates (N^N)Pd(CH3 )Cl (N^N=Ar-N=CMeMeC=N-Ar, Ar=2,6-bis(diphenylmethyl)-4-methylbenzene) by chloride ion abstraction to form [(N^N)Pd-CH3 ][(RF O)3 Al-OSi≡)] (1). A combination of FTIR, solid-state NMR spectroscopy, and reactions with CO or vinyl chloride establish that 1 shows similar reactivity patterns as (N^N)Pd(CH3 )Cl activated with Na[B(ArF )4 ]. Multinuclear 13 C{27 Al} RESPDOR and 1 H{19 F} S-REDOR experiments are consistent with a weakly coordinated ion-pair between (N^N)Pd-CH3 + and [(RF O)3 Al-OSi≡)]. 1 catalyzes the polymerization of ethylene with similar activities as [(N^N)Pd-CH3 ]+ in solution and incorporates up to 0.4 % methyl acrylate in copolymerization reactions. 1 produces polymers with significantly higher molecular weight than the solution catalyst, and generates the highest molecular weight polymers currently reported in copolymerization reactions of ethylene and methylacrylate.

Inorganic phosphate in growing calcium carbonate abalone shell suggests a shared mineral ancestral precursor.

The presence of phosphate from different origins (inorganic, bioorganic) is found more and more in calcium carbonate-based biominerals. Phosphate is often described as being responsible for the stabilization of the transient amorphous calcium carbonate phase. In order to specify the composition of the mineral phase deposited at the onset of carbonated shell formation, the present study investigates, down to the nanoscale, the growing shell from the European abalone Haliotis tuberculata, using a combination of solid state nuclear magnetic resonance, scanning transmission electron microscope and spatially-resolved electron energy loss spectroscopy techniques. We show the co-occurrence of inorganic phosphate with calcium and carbonate throughout the early stages of abalone shell formation. One possible hypothesis is that this first-formed mixed mineral phase represents the vestige of a shared ancestral mineral precursor that appeared early during Evolution. In addition, our findings strengthen the idea that the final crystalline phase (calcium carbonate or phosphate) depends strongly on the nature of the mineral-associated proteins in vivo.

Micrometer Positioning Accuracy With a Planar Parallel Continuum Robot.

Parallel Continuum Robots (PCR) have several advantages over classical articulated robots, notably a large workspace, miniaturization capabilities and safe human-robot interactions. However, their low accuracy is still a serious drawback. Indeed, several conditions have to be met for PCR to reach a high accuracy, namely: a repeatable mechanical structure, a correct kinematic model, and a proper estimation of the model's parameters. In this article, we propose a methodology that allows reaching a micrometer accuracy with a PCR. This approach emphasizes the importance of using a repeatable continuum mechanism, identifying the most influential parameters of an accurate kinematic model of the robot and precisely measuring them. The experimental results show that the proposed approach allows to reach an accuracy of 3.3 µm in position and 0.5 mrad in orientation over a 10 mm long circular path. These results push the current limits of PCR accuracy and make them good potential candidates for high accuracy automatic positioning tasks.

Natural climate solutions for Canada.

Alongside the steep reductions needed in fossil fuel emissions, natural climate solutions (NCS) represent readily deployable options that can contribute to Canada's goals for emission reductions. We estimate the mitigation potential of 24 NCS related to the protection, management, and restoration of natural systems that can also deliver numerous co-benefits, such as enhanced soil productivity, clean air and water, and biodiversity conservation. NCS can provide up to 78.2 (41.0 to 115.1) Tg CO2e/year (95% CI) of mitigation annually in 2030 and 394.4 (173.2 to 612.4) Tg CO2e cumulatively between 2021 and 2030, with 34% available at ≤CAD 50/Mg CO2e. Avoided conversion of grassland, avoided peatland disturbance, cover crops, and improved forest management offer the largest mitigation opportunities. The mitigation identified here represents an important potential contribution to the Paris Agreement, such that NCS combined with existing mitigation plans could help Canada to meet or exceed its climate goals.

Social comfort zones for transformative conservation decisions in a changing climate.

Novel management interventions intended to mitigate the impacts of climate change on biodiversity are increasingly being considered by scientists and practitioners. However, resistance to more transformative interventions remains common across both specialist and lay communities and is generally assumed to be strongly entrenched. We used a decision-pathways survey of the public in Canada and the United States (n = 1490) to test two propositions relating to climate-motivated interventions for conservation: most public groups are uncomfortable with interventionist options for conserving biodiversity and given the strong values basis for preferences regarding biodiversity and natural systems more broadly, people are unlikely to change their minds. Our pathways design tested and retested levels of comfort with interventions for forest ecosystems at three different points in the survey. Comfort was reexamined given different nudges (including new information from trusted experts) and in reference to a particular species (bristlecone pine [Pinus longaeva]). In contrast with expectations of public unease, baseline levels of public comfort with climate interventions in forests was moderately high (46% comfortable) and increased further when respondents were given new information and the opportunity to change their choice after consideration of a particular species. People who were initially comfortable with interventions tended to remain so (79%), whereas 42% of those who were initially uncomfortable and 40% of those who were uncertain shifted to comfortable by the end of the survey. In short and across questions, comfort levels with interventions were high, and where discomfort or uncertainty existed, such positions did not appear to be strongly held. We argue that a new decision logic, one based on anthropogenic responsibility, is beginning to replace a default reluctance to intervene with nature.

Zonas de Comodidad Social ante las Decisiones de Conservación Transformadoras en un Clima Cambiante Resumen Los científicos y los practicantes de la conservación cada vez consideran más a las intervenciones novedosas de manejo con la intención de mitigar los impactos del cambio climático sobre la biodiversidad. Sin embargo, la resistencia a las intervenciones más transformadoras es común en especialistas y no profesionales y generalmente se asume que está fuertemente arraigada. Usamos una encuesta sobre toma de decisiones del público en Canadá y en los Estados Unidos (n = 1490) para evaluar dos propuestas relacionadas a intervenciones de conservación motivadas por el clima: la mayoría de los grupos de público están incómodos con las opciones intervencionistas para conservar la biodiversidad y dada la sólida base de valores para las preferencias con respecto a la biodiversidad y a los sistemas naturales en general, es poco probable que las personas cambien de opinión. Nuestro diseño de encuesta analizó y reanalizó los niveles de comodidad con respecto a las intervenciones para los ecosistemas boscosos en tres puntos distintos dentro del estudio. La comodidad fue reexaminada con diferentes impulsos (incluyendo información nueva proveniente de expertos confiables) y en referencia a una especie particular (Pinus longaeva). Contrario a las expectativas de malestar del público, los niveles de línea base de la comodidad del público frente a las intervenciones climáticas en los bosques fueron moderadamente altos (46% de comodidad) e incrementaron cuando a los respondientes se les proporcionó información nueva y la oportunidad de cambiar su elección después de considerar a una especie particular. Las personas que al inicio estaban cómodas con las intervenciones tendieron a permanecer así (79%), mientras que el 42% de aquellos que estuvieron incómodos inicialmente y el 40% de aquellos que estuvieron inseguros cambiaron a estar cómodos para el final del estudio. En resumen, los niveles de comodidad frente a las intervenciones fueron elevados, y cuando existieron malestar o incertidumbre, dichas posiciones no parecieron mantenerse con fuerza. Argumentamos que una lógica de decisión basada en la responsabilidad antropogénica está comenzando a reemplazar una renuencia predeterminada a intervenir en la naturaleza.

R-R-T (resistance-resilience-transformation) typology reveals differential conservation approaches across ecosystems and time.

Conservation practices during the first decade of the millennium predominantly focused on resisting changes and maintaining historical or current conditions, but ever-increasing impacts from climate change have highlighted the need for transformative action. However, little empirical evidence exists on what kinds of conservation actions aimed specifically at climate change adaptation are being implemented in practice, let alone how transformative these actions are. In response, we propose and trial a novel typology-the R-R-T scale, which improves on existing concepts of Resistance, Resilience, and Transformation-that enables the practical application of contested terms and the empirical assessment of whether and to what extent a shift toward transformative action is occurring. When applying the R-R-T scale to a case study of 104 adaptation projects funded since 2011, we find a trend towards transformation that varies across ecosystems. Our results reveal that perceptions about the acceptance of novel interventions in principle are beginning to be expressed in practice.

Baicalein-modified hydroxyapatite nanoparticles and coatings with antibacterial and antioxidant properties.

Aseptic loosening and bacterial infections are the two main causes of failure for metallic implants used for joint replacement. A coating that is both bioactive and possesses antimicrobial properties may address such shortcomings and improve the performance of the implant. We have sought to study the properties of combining hydroxyapatite-based nanoparticles or coatings with baicalein, a plant-extracted molecule with both antibacterial and antioxidant properties. (B-type) carbonated hydroxyapatite nanoparticles prepared by a chemical wet method could subsequently adsorbed by soaking in a baicalein solution. The amount of adsorbed baicalein was determined to be 63 mg.g-1 by thermogravimetric measurements. In a second approach, baicalein was adsorbed on a biomimetic calcium-deficient hydroxyapatite planar coating (12 µm thick) deposited on Ti6Al4V alloy from an aqueous solution of calcium, phosphate, sodium and magnesium salts. Soaking of the hydroxyapatite coated on titanium alloy in a baicalein solution induced partial dissolution/remodeling of the upper surface of the coating. However, the observed remodeling of the surface was much more pronounced in the presence of a baicalein solution, compared to pure water. The presence of adsorbed baicalein on the HAp layer, although it could not be precisely quantified, was assessed by XPS and fluorescence analysis. Planar coatings exhibited significant antibacterial properties against Staphylococcus epidermidis. Baicalein-modified nanoparticles exhibited significant antioxidant properties. These results illustrate the potential of hydroxyapatite used as a carrier for natural biologically-active molecules and also discuss the challenges associated with their applications as antibacterial agents.

Solid-State Phase Transformation and Self-Assembly of Amorphous Nanoparticles into Higher-Order Mineral Structures.

Materials science has been informed by nonclassical pathways to crystallization, based on biological processes, about the fabrication of damage-tolerant composite materials. Various biomineralizing taxa, such as stony corals, deposit metastable, magnesium-rich, amorphous calcium carbonate nanoparticles that further assemble and transform into higher-order mineral structures. Here, we examine a similar process in abiogenic conditions using synthetic, amorphous calcium magnesium carbonate nanoparticles. Applying a combination of high-resolution imaging and in situ solid-state nuclear magnetic resonance spectroscopy, we reveal the underlying mechanism of the solid-state phase transformation of these amorphous nanoparticles into crystals under aqueous conditions. These amorphous nanoparticles are covered by a hydration shell of bound water molecules. Fast chemical exchanges occur: the hydrogens present within the nanoparticles exchange with the hydrogens from the surface-bound H2O molecules which, in turn, exchange with the hydrogens of the free H2O molecule of the surrounding aqueous medium. This cascade of chemical exchanges is associated with an enhanced mobility of the ions/molecules that compose the nanoparticles which, in turn, allow for their rearrangement into crystalline domains via solid-state transformation. Concurrently, the starting amorphous nanoparticles aggregate and form ordered mineral structures through crystal growth by particle attachment. Sphere-like aggregates and spindle-shaped structures were, respectively, formed from relatively high or low weights per volume of the same starting amorphous nanoparticles. These results offer promising prospects for exerting control over such a nonclassical pathway to crystallization to design mineral structures that could not be achieved through classical ion-by-ion growth.

Unveiling the Interstitial Pressure between Growing Ice Crystals during Ice-Templating Using a Lipid Lamellar Probe.

What is the pressure generated by ice crystals during ice-templating? This work addresses this crucial question by estimating the pressure exerted by oriented ice columns on a supramolecular probe composed of a lipid lamellar hydrogel during directional freezing. This process, also known as freeze-casting, has emerged as a unique processing technique for a broad class of organic, inorganic, soft, and biological materials. Nonetheless, the pressure exerted during and after crystallization between two ice columns is not known, despite its importance with respect to the fragility of the frozen material, especially for biological samples. By using the lamellar period of a glycolipid lamellar hydrogel as a common probe, we couple data obtained from ice-templated-resolved in situ synchrotron small-angle X-ray scattering (SAXS) with data obtained from controlled adiabatic desiccation experiments. We estimate the pressure to vary between 1 ± 10% kbar at -15 °C and 3.5 ± 20% kbar at -60 °C.

Laser-Assisted Delivery of Molecules in Fungal Cells.

Fungal infections are becoming a global health problem. A major limiting factor for the development of antifungals is the high impermeability of the rigid and thick fungal cell wall. Compared to mammalian cells, fungal cells are more resilient to perforation due to the presence of this carbohydrate armor. While a few methods have been reported to penetrate the fungal cell wall, such as electroporation, biolistics, glass beads, and the use of monovalent cations, such methods are generally time-consuming, compromise cell viability, and often lead to low permeation rates. In addition, their use remains limited to in vitro applications due to the collateral damage that these techniques could cause to healthy living tissues. Presented in this study is a delivery approach based on the generation of transient breaks, or pores, in the cell wall. Breaks are generated by cavitation and shock waves resulting from the irradiation of gold nanoparticles with a femtosecond infrared laser. Such an approach enabled the delivery of membrane impermeable molecules (i.e., calcein and plasmid DNA) into Saccharomyces cerevisiae, a fungal model organism. This method is expected to exhibit high biocompatibility and holds potential for clinical applications for the treatment of fungal infections given that neither the laser irradiation nor the nanoparticles have been found to damage cells. Mechanistical aspects of photoporation, such as the proximity needed between the nanoparticle and the cell membrane for these processes to take place, are also discussed. Hence, the laser-assisted drug delivery approach described here is suitable for further preclinical evaluation in oral, vaginal, and skin mycoses where current treatments are insufficient due to host-related adverse reactions, poor fungal cell penetration, or risk of developing antifungal resistance.

A soft-chemistry approach to the synthesis of amorphous calcium ortho/pyrophosphate biomaterials of tunable composition.

The development of amorphous phosphate-based materials is of major interest in the field of biomaterials science, and especially for bone substitution applications. In this context, we herein report the synthesis of gel-derived hydrated amorphous calcium/sodium ortho/pyrophosphate materials at ambient temperature and in water. For the first time, such materials have been obtained in a large range of tunable orthophosphate/pyrophosphate molar ratios. Multi-scale characterization was carried out thanks to various techniques, including advanced multinuclear solid state NMR. It allowed the quantification of each ionic/molecular species leading to a general formula for these materials: [(Ca2+y Na+z H+3+x-2y-z)(PO43-)1-x(P2O74-)x](H2O)u. Beyond this formula, the analyses suggest that these amorphous solids are formed by the aggregation of colloids and that surface water and sodium could play a role in the cohesion of the whole material. Although the full comprehension of mechanisms of formation and structure is still to be investigated in detail, the straightforward synthesis of these new amorphous materials opens up many perspectives in the field of materials for bone substitution and regeneration. STATEMENT OF SIGNIFICANCE: The metastability of amorphous phosphate-based materials with various chain length often improves their (bio)chemical reactivity. However, the control of the ratio of the different phosphate entities has not been yet described especially for small ions (pyrophosphate/orthophosphate) and using soft chemistry, whereas it opens the way for the tuning of enzyme- and/or pH-driven degradation and biological properties. Our study focuses on elaboration of amorphous gel-derived hydrated calcium/sodium ortho/pyrophosphate solids at 70 °C with a large range of orthophosphate/pyrophosphate ratios. Multi-scale characterization was carried out using various techniques such as advanced multinuclear SSNMR (31P, 23Na, 1H, 43Ca). Analyses suggest that these solids are formed by colloids aggregation and that the location of mobile water and sodium could play a role in the material cohesion.

Design of an optically-locked interferometer for attosecond pump-probe setups.

We present the design and performance of an active stabilization system for attosecond pump-probe setups based on a Mach-Zehnder interferometer configuration. The system employs a CW laser propagating coaxially with the pump and probe beams in the interferometer. The stabilization is achieved with a standalone feedback controller that adjusts the length of one of its arms to maintain a constant relative phase between the CW beams. With this system, the time delay between the pump and probe beams is stabilized within 10 as rms over several hours. The system is easy to operate and only requires a few minutes to set up before any pump/probe measurements.