"The Sulfur Dance" Around Arenes and Heteroarenes - the Reversible Nature of Nucleophilic Aromatic Substitutions.

We disclose the features of a category of reversible nucleophilic aromatic substitutions in view of their significance and generality in dynamic aromatic chemistry. Exchange of sulfur components surrounding arenes and heteroarenes may occur at 25 °C, in a process that one may call a "sulfur dance". These SN Ar systems present their own features, apart from common reversible reactions utilized in dynamic covalent chemistry (DCC). By varying conditions, covalent dynamics may operate to provide libraries of thiaarenes with some selectivity, or conversion of a hexa(thio)benzene asterisk into another one. The reversible nature of SN Ar is confirmed by three methods: a convergence of the products distribution in reversible SN Ar systems, a related product redistribution between two per(thio)benzenes by using a thiolate promoter, and from kinetic/thermodynamic data. A four-component dynamic covalent system further illustrates the thermodynamically-driven formation of a thiacalix[2]arene[2]pyrimidine by sulfur component exchanges. This work stimulates the implementation of reversible SN Ar in aromatic chemistry and in DCC.

The Effect of Acidic and Alkaline Seawater on the F-Actin-Dependent Ca2+ Signals Following Insemination of Immature Starfish Oocytes and Mature Eggs.

In starfish, the addition of the hormone 1-methyladenine (1-MA) to immature oocytes (germinal vesicle, GV-stage) arrested at the prophase of the first meiotic division induces meiosis resumption (maturation), which makes the mature eggs able to respond to the sperm with a normal fertilization response. The optimal fertilizability achieved during the maturation process results from the exquisite structural reorganization of the actin cytoskeleton in the cortex and cytoplasm induced by the maturing hormone. In this report, we have investigated the influence of acidic and alkaline seawater on the structure of the cortical F-actin network of immature oocytes of the starfish (Astropecten aranciacus) and its dynamic changes upon insemination. The results have shown that the altered seawater pH strongly affected the sperm-induced Ca2+ response and the polyspermy rate. When immature starfish oocytes were stimulated with 1-MA in acidic or alkaline seawater, the maturation process displayed a strong dependency on pH in terms of the dynamic structural changes of the cortical F-actin. The resulting alteration of the actin cytoskeleton, in turn, affected the pattern of Ca2+ signals at fertilization and sperm penetration.

A critical review on the role of leakages in the facemask protection against SARS-CoV-2 infection with consideration of vaccination and virus variants.

The protection provided by facemasks has been extensively investigated since the beginning of the SARS-CoV-2 outbreak, focusing mostly on the filtration efficiency of filter media for filtering face pieces (FFP), surgical masks, and cloth masks. However, faceseal leakage is a major contributor to the number of potentially infectious airborne droplets entering the respiratory system of a susceptible individual. The identification of leaking spots and the quantification of leaking flows are crucial to estimate the protection provided by facemasks. This study presents a critical review on the measurement and calculation of facemask leakages and a quantitative analysis of their role in the risk of SARS-CoV-2 infection. It shows that the pairing between the mask dimensions and the wearer's face is essential to improve protection efficiency, especially for FFP2 masks, and summarizes the most common leaking spots at the interface between the mask and the wearer's face. Leakage is a crucial factor in the calculation of the protection provided by facemasks and outweighs the filtration performances. The fit factors measured among mask users were summarized for different types of face protection. The reviewed data were integrated into a computational model to compare the mitigation impact of facemasks with vaccination with consideration of new variants of SARS-CoV-2. Combining a high adoption rate of facemasks and a high vaccination rate is crucial to efficiently control the spread of highly infectious variants.

Effects of Dithiothreitol on Fertilization and Early Development in Sea Urchin.

The vitelline layer (VL) of a sea urchin egg is an intricate meshwork of glycoproteins that intimately ensheathes the plasma membrane. During fertilization, the VL plays important roles. Firstly, the receptors for sperm reside on the VL. Secondly, following cortical granule exocytosis, the VL is elevated and transformed into the fertilization envelope (FE), owing to the assembly and crosslinking of the extruded materials. As these two crucial stages involve the VL, its alteration was expected to affect the fertilization process. In the present study, we addressed this question by mildly treating the eggs with a reducing agent, dithiothreitol (DTT). A brief pretreatment with DTT resulted in partial disruption of the VL, as judged by electron microscopy and by a novel fluorescent polyamine probe that selectively labelled the VL. The DTT-pretreated eggs did not elevate the FE but were mostly monospermic at fertilization. These eggs also manifested certain anomalies at fertilization: (i) compromised Ca2+ signaling, (ii) blocked translocation of cortical actin filaments, and (iii) impaired cleavage. Some of these phenotypic changes were reversed by restoring the DTT-exposed eggs in normal seawater prior to fertilization. Our findings suggest that the FE is not the decisive factor preventing polyspermy and that the integrity of the VL is nonetheless crucial to the egg's fertilization response.

Quantitative modeling of the impact of facemasks and associated leakage on the airborne transmission of SARS-CoV-2.

The ongoing worldwide outbreak of COVID-19 has set personal protective equipment in the spotlight. A significant number of countries impose the use of facemasks in public spaces and encourage it in the private sphere. Even in countries where relatively high vaccination rates are achieved at present, breakthrough infections have been frequently reported and usage of facemasks in certain settings has been recommended again. Alternative solutions, including community masks fabricated using various materials, such as cotton or jersey, have emerged alongside facemasks following long-established standards (e.g., EN 149, EN 14683). In the present work, we present a computational model to calculate the ability of different types of facemasks to reduce the exposure to virus-laden respiratory particles, with a focus on the relative importance of the filtration properties and the fitting on the wearer's face. The model considers the facemask and the associated leakage, the transport of respiratory particles and their accumulation around the emitter, as well as the fraction of the inhaled particles deposited in the respiratory system. Different levels of leakages are considered to represent the diversity of fittings likely to be found among a population of non-trained users. The leakage prevails over the filtration performance of a facemask in determining the exposure level, and the ability of a face protection to limit leakages needs to be taken into account to accurately estimate the provided protection. Filtering facepieces (FFP) provide a better protection efficiency than surgical and community masks due to their higher filtration efficiency and their ability to provide a better fit and thus reduce the leakages. However, an improperly-fitted FFP mask loses a critical fraction of its protection efficiency, which may drop below the protection level provided by properly-worn surgical and community masks.

Multi-parameter optimization of attenuation data for characterizing grain size distributions and application to bimodal microstructures.

In this paper, the effect on the ultrasonic attenuation of the grain size heterogeneity in polycrystals is analyzed. First, new analytical developments allowing the extension of the unified theory of Stanke and Kino to general grain size distributions are presented. It is then shown that one can additively decompose the attenuation coefficient provided that groups of grains are defined. Second, the study is specialized to a bimodal distribution of the grain size for which microstructures are numerically modeled by means of the software Neper. The additive partition of the attenuation coefficient into contributions coming from large and small grains motivates the derivation of an optimization procedure for characterizing the grain size distribution. The aforementioned approach, which is based on a least squares minimization, is at last presented and illustrated on both analytical and numerical attenuation data. It is thus shown that the method provides satisfying approximations of volume fractions of large grains and modal equivalent diameters from the frequency-dependent attenuation coefficient.

Surface Wettability of a Natural Rubber Composite under Stretching: A Model to Predict Cell Survival.

We report the stress-strain effect of a stretchable natural rubber (NR)-calcium phosphate composite on the surface wettability (SW) using an innovative approach coupling a uniaxial tensile micromachine, goniometer, and microscope. In situ contact angle measurements in real time were performed during mechanical tension. Our results show that SW is guided by the stress-strain relationship with two different characteristics, depending on the static or dynamic experiments. The results evidenced the limits of the classical theory of wetting. Furthermore, based on the mechanically tunable SW of the system associated with the cytocompatibility of the NR composite, we have modeled such a system for application as a cell support. From the experimental surface energy value, our proposed 3D modeling numerical simulation predicted a window of opportunities for cell-NR survival under mechanical stimuli. The presented data and the thermodynamics-based theoretical approach enable not only accurate correlation of SW with mechanical properties of the NR composite but also provide huge potential for future cell supportability in view of tissue engineering.

Acyl Transfer Catalytic Activity in De Novo Designed Protein with N-Terminus of α-Helix As Oxyanion-Binding Site.

The design of catalytic proteins with functional sites capable of specific chemistry is gaining momentum and a number of artificial enzymes have recently been reported, including hydrolases, oxidoreductases, retro-aldolases, and others. Our goal is to develop a peptide ligase for robust catalysis of amide bond formation that possesses no stringent restrictions to the amino acid composition at the ligation junction. We report here the successful completion of the first step in this long-term project by building a completely de novo protein with predefined acyl transfer catalytic activity. We applied a minimalist approach to rationally design an oxyanion hole within a small cavity that contains an adjacent thiol nucleophile. The N-terminus of the α-helix with unpaired hydrogen-bond donors was exploited as a structural motif to stabilize negatively charged tetrahedral intermediates in nucleophilic addition-elimination reactions at the acyl group. Cysteine acting as a principal catalytic residue was introduced at the second residue position of the α-helix N-terminus in a designed three-α-helix protein based on structural informatics prediction. We showed that this minimal set of functional elements is sufficient for the emergence of catalytic activity in a de novo protein. Using peptide-αthioesters as acyl-donors, we demonstrated their catalyzed amidation concomitant with hydrolysis and proved that the environment at the catalytic site critically influences the reaction outcome. These results represent a promising starting point for the development of efficient catalysts for protein labeling, conjugation, and peptide ligation.

Protection Level and Reusability of a Modified Full-Face Snorkel Mask as Alternative Personal Protective Equipment for Healthcare Workers during the COVID-19 Pandemic.

The worldwide outbreak of COVID-19 has drastically increased pressure on medical resources and highlighted the need for rapidly available, large-scale, and low-cost personal protective equipment (PPE). In this work, an alternative full-face mask is adapted from a modified snorkel mask to be used as PPE with two medical-grade filters and a 3D-printed adapter. Since the mask covers the eyes, mouth, and nose, it acts as a full-face shield, providing additional protection to healthcare workers. The SARS-CoV-2 has a size between 60 nm and 140 nm, and airborne viral particles can be carried by larger droplets with sizes up to several millimeters. The minimum filtration efficiency of mechanical and electrostatic filters is usually reached between 30 nm and 300 nm. The filtration efficiency of different medical filters is measured for particles below 300 nm to cover the size of the SARS-CoV-2 and small virus-laden droplets, and determine the minimum efficiency. The filtration performance of the adapted full-face mask is characterized using NaCl particles below 500 nm and different fitting scenarios to determine the minimum protection efficiency. The mask is compared to a commercial respirator and characterized according to the EN 149 standard, demonstrating that the protection fulfills the requirements for the FFP2 level (filtering face-piece 2, stopping at least 94% of airborne particles). The device shows a good resistance to several cycles of decontamination (autoclaving and ethanol immersion), is easy to be produced locally at low cost, and helps to address the shortage in FFP2 masks and face shields by providing adequate protection to healthcare workers against particles <500 nm in size.

Self-aligned 3D microlenses in a chip fabricated with two-photon stereolithography for highly sensitive absorbance measurement.

Absorbance measurement is a widely used method to quantify the concentration of an analyte. The integration of absorbance analysis in microfluidic chips could significantly reduce the sample consumption and contribute to the system miniaturization. However, the sensitivity and limit of detection (LoD) of analysis in microfluidic chips with conventional configuration need improvements due to the limited optical pathway and unregulated light propagation. In this work, a 3D-microlens-incorporating microfluidic chip (3D-MIMC) with a greatly extended detection channel was innovatively fabricated using two-photon stereolithography. The fabrication was optimized with a proposed hierarchical modular printing strategy. Due to the incorporation of 3D microlenses, the light coupling efficiency and the signal-to-noise ratio (SNR) were respectively improved approximately 9 and 4 times. An equivalent optical path length (EOL) of 62.9 mm was achieved in a 3.7 µl detection channel for testing tartrazine samples. As a result, the sensitivity and LoD of the 3D-MIMC assay were correspondingly improved by one order of magnitude, compared with those of the 96-well plate assay. Notably, the 3D-MIMC has the potential to be integrated into a general microanalysis platform for multiple applications.

Dual-Functional Plasmonic Photothermal Biosensors for Highly Accurate Severe Acute Respiratory Syndrome Coronavirus 2 Detection.

The ongoing outbreak of the novel coronavirus disease (COVID-19) has spread globally and poses a threat to public health in more than 200 countries. Reliable laboratory diagnosis of the disease has been one of the foremost priorities for promoting public health interventions. The routinely used reverse transcription polymerase chain reaction (RT-PCR) is currently the reference method for COVID-19 diagnosis. However, it also reported a number of false-positive or -negative cases, especially in the early stages of the novel virus outbreak. In this work, a dual-functional plasmonic biosensor combining the plasmonic photothermal (PPT) effect and localized surface plasmon resonance (LSPR) sensing transduction provides an alternative and promising solution for the clinical COVID-19 diagnosis. The two-dimensional gold nanoislands (AuNIs) functionalized with complementary DNA receptors can perform a sensitive detection of the selected sequences from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through nucleic acid hybridization. For better sensing performance, the thermoplasmonic heat is generated on the same AuNIs chip when illuminated at their plasmonic resonance frequency. The localized PPT heat is capable to elevate the in situ hybridization temperature and facilitate the accurate discrimination of two similar gene sequences. Our dual-functional LSPR biosensor exhibits a high sensitivity toward the selected SARS-CoV-2 sequences with a lower detection limit down to the concentration of 0.22 pM and allows precise detection of the specific target in a multigene mixture. This study gains insight into the thermoplasmonic enhancement and its applicability in the nucleic acid tests and viral disease diagnosis.

[The trajectories and choices of Jean-Claude Schmitt]. / Trajetos e escolhas de Jean-Claude Schmitt.

In this interview, one of today's best-known French medievalists, Jean-Claude Schmitt, responds to various questions about his theoretical and methodological choices as well as the themes of his recent work. Schmitt is known as one of the main heirs of the anthropological history of Jacques Le Goff, and sums up his trajectory which resulted in a variety of work ranging from editing documents to work on medieval images, without ever losing sight of his commitment to questioning the beliefs of men and sojourns into the imagery of the Middle Ages in western culture.

Nesta entrevista, um dos mais renomados medievalistas franceses da atualidade, Jean-Claude Schmitt, responde a diferentes questões concernentes não apenas às suas escolhas teórico-metodológicas, mas também aos temas de seus últimos trabalhos. Conhecido como um dos principais herdeiros da história antropológica de Jacques Le Goff, Schmitt faz um balanço de uma trajetória que resultou em trabalhos diversos, desde edições de documentos até obras sobre as imagens medievais, sem nunca perder de vista o compromisso de interrogar as crenças dos homens e as permanências do imaginário da Idade Média na cultura ocidental.

Trajetos e escolhas de Jean-Claude Schmitt / The trajectories and choices of Jean-Claude Schmitt

Resumo Nesta entrevista, um dos mais renomados medievalistas franceses da atualidade, Jean-Claude Schmitt, responde a diferentes questões concernentes não apenas às suas escolhas teórico-metodológicas, mas também aos temas de seus últimos trabalhos. Conhecido como um dos principais herdeiros da história antropológica de Jacques Le Goff, Schmitt faz um balanço de uma trajetória que resultou em trabalhos diversos, desde edições de documentos até obras sobre as imagens medievais, sem nunca perder de vista o compromisso de interrogar as crenças dos homens e as permanências do imaginário da Idade Média na cultura ocidental.

Abstract In this interview, one of today's best-known French medievalists, Jean-Claude Schmitt, responds to various questions about his theoretical and methodological choices as well as the themes of his recent work. Schmitt is known as one of the main heirs of the anthropological history of Jacques Le Goff, and sums up his trajectory which resulted in a variety of work ranging from editing documents to work on medieval images, without ever losing sight of his commitment to questioning the beliefs of men and sojourns into the imagery of the Middle Ages in western culture.

Suitability of a PLCL fibrous scaffold for soft tissue engineering applications: A combined biological and mechanical characterisation.

Poly(lactide-co-ε-caprolactone) (PLCL) has been reported to be a good candidate for tissue engineering because of its good biocompatibility. Particularly, a braided PLCL scaffold (PLL/PCL ratio = 85/15) has been recently designed and partially validated for ligament tissue engineering. In the present study, we assessed the in vivo biocompatibility of acellular and cellularised scaffolds in a rat model. We then determined its in vitro biocompatibility using stem cells issued from both bone marrow and Wharton Jelly. From a biological point of view, the scaffold was shown to be suitable for tissue engineering in all these cases. Secondly, while the initial mechanical properties of this scaffold have been previously reported to be adapted to load-bearing applications, we studied the evolution in time of the mechanical properties of PLCL fibres due to hydrolytic degradation. Results for isolated PLCL fibres were extrapolated to the fibrous scaffold using a previously developed numerical model. It was shown that no accumulation of plastic strain was to be expected for a load-bearing application such as anterior cruciate ligament tissue engineering. However, PLCL fibres exhibited a non-expected brittle behaviour after two months. This may involve a potential risk of premature failure of the scaffold, unless tissue growth compensates this change in mechanical properties. This combined study emphasises the need to characterise the properties of biomaterials in a pluridisciplinary approach, since biological and mechanical characterisations led in this case to different conclusions concerning the suitability of this scaffold for load-bearing applications.

Is there a cause-and-effect relationship between physicochemical properties and cell behavior of alginate-based hydrogel obtained after sterilization?

Alginate-based hydrogel scaffolds are widely used in the field of cartilage regeneration and repair. If the effect of autoclaving on the alginate powder is well known, it is not the same for the possible effects of the sterilization UV treatment on the properties of the hydrogel after polymerization. To select an effective sterilization treatment of alginate-based materials, one must find what are inter-relationship between the characteristics (chemical, physical and mechanical) of alginate-based hydrogel during sterilization, and what consequences have affected on cell behavior. In this study, we investigated the influence of UV sterilization treatments (UV-1 and UV-2: 25 and 50min, respectively) and autoclaving to obtain alginate (Alg)/hyaluronic acid (HA) hydrogel, as well as further evaluated the relationship between physicochemical properties and cell behavior of Alg/HA hydrogel after UVs and autoclaving. The physicochemical properties of this mixture at the powder or polymerized states were analyzed using ATR-FTIR, HPLC-SEC, rheological, indentation testing and sterility testing. The cell behaviors of hydrogels were evaluated by cell viability and proliferation, and chondrogenic differentiation. The effects of treatment parameters and their correlation with the others characteristics were determined statistically by Principal Component Analysis (PCA). In this study, we have shown that the cell behavior in alginate-based hydrogels was not only regulated by physicochemical properties (as molar mass or/and viscosity), but also associated with the controlling of sterilization time. It can provide a basis for choosing an effective method of sterilization, which can keep the mechanical or physical-chemical properties of Alg-based hydrogel scaffold and maintain its cytocompatibility and its ability to induce chondrogenesis from mesenchymal stem cells.

Increased Extravascular Lung Water and Plasma Biomarkers of Acute Lung Injury Precede Oxygenation Impairment in Primary Graft Dysfunction After Lung Transplantation.

BACKGROUND: After lung transplantation (LT), early prediction of grade 3 pulmonary graft dysfunction (PGD) remains a research gap for clinicians. We hypothesized that it could be improved using extravascular lung water (EVLWi) and plasma biomarkers of acute lung injury. METHODS: After institutional review board approval and informed consent, consecutive LT recipients were included. Transpulmonary thermodilution-based EVLWi, plasma concentrations of epithelial (soluble receptor for advanced glycation endproducts [sRAGE]) and endothelial biomarkers (soluble intercellular adhesion molecule-1 and endocan [full-length and cleaved p14 fragment]) were obtained before and after LT (0 [H0], 6, 12, 24, 48 and 72 hours after pulmonary artery unclamping). Grade 3 PGD was defined according to the International Society for Lung and Heart Transplantation definition, combining arterial oxygen partial pressure (PaO2)/inspired fraction of oxygen (FiO2) ratio and chest X-rays. Association of clinical risk factors, EVLWi and biomarkers with grade 3 PGD was analyzed under the Bayesian paradigm, using logistic model and areas under the receiver operating characteristic curves (AUCs). RESULTS: In 47 LT recipients, 10 developed grade 3 PGD, which was obvious at H6 in 8 cases. Clinical risk factors, soluble intercellular adhesion molecule-1 and endocan (both forms) were not associated with grade 3 PGD. Significant predictors of grade 3 PGD included (1) EVLWi (optimal cutoff, 13.7 mL/kg; AUC, 0.74; 95% confidence interval [CI], 0.48-0.99), (2) PaO2/FiO2 ratio (optimal cutoff, 236; AUC, 0.68; 95% CI, 0.52-0.84), and (3) sRAGE (optimal cutoff, 11 760 pg/mL; AUC, 0.66; 95% CI, 0.41-0.91) measured at H0. CONCLUSIONS: Immediate postreperfusion increases in EVLWi and sRAGE along with impaired PaO2/FiO2 ratios were early predictors of grade 3 PGD at or beyond 6 hours and may trigger early therapeutic interventions.

Evolution of a constitutional dynamic library driven by self-organisation of a helically folded molecular strand.

Conversion of macrocyclic imine entities into helical strands was achieved through three- and four-component exchange reactions within constitutionally dynamic libraries. The generation of sequences of the intrinsic helicity codon, based on the hydrazone-pyrimidine fragment obtained by condensation of pyrimidine dialdehyde A with pyrimidine bis-hydrazine B, shifted the equilibrium between all the possible macrocycles and strands towards the full expression (>98%) of helical product [A/B]. Furthermore, it was shown that chain folding accelerated the dynamic exchange reactions among the library members. Lastly, in four-component experiments (involving A, B, E and either C or D), even though the macrocyclic entities ([A/C], [B/E]; [A/D], [B/E]) were the kinetically preferred products, over time dialdehyde A relinquished its initial diamine partners C or D to opt for bis-hydrazine B, which allowed the preferential formation of the helically folded strand. The present results indicate that self-organisation pressure was able to drive the dynamic system towards the selective generation of the strand undergoing helical folding.

Driven evolution of a constitutional dynamic library of molecular helices toward the selective generation of [2 x 2] gridlike arrays under the pressure of metal ion coordination.

Constitutional dynamics, self-assembly, and helical-folding control are brought together in the efficient Sc(OTf)3/microwave-catalyzed transimination of helical oligohydrazone strands, yielding highly diverse dynamic libraries of interconverting constituents through assembly, dissociation, and exchange of components. The transimination-type mechanism of the ScIII-promoted exchange, as well as its regioselectivity, occurring only at the extremities of the helical strands, allow one to perform directional terminal polymerization/depolymerization processes when starting with dissymmetric strands. A particular library is subsequently brought to express quantitatively [2 x 2] gridlike metallosupramolecular arrays in the presence of ZnII ions by component recombination generating the correct ligand from the dynamic set of interconverting strands. This behavior represents a process of driven evolution of a constitutional dynamic chemical system under the pressure (coordination interaction) of an external effector (metal ions).

Scandium(III) catalysis of transimination reactions. Independent and constitutionally coupled reversible processes.

Sc(OTf)(3) efficiently catalyzes the self-sufficient transimination reaction between various types of C=N bonds in organic solvents, with turnover frequencies up to 3600 h(-)(1) and rate accelerations up to 6 x 10(5). The mechanism of the crossover reaction in mixtures of amines and imines is studied, comparing parallel individual reactions with coupled equilibria. The intrinsic kinetic parameters for isolated reactions cannot simply be added up when several components are mixed, and the behavior of the system agrees with the presence of a unique mediator that constitutes the core of a network of competing reactions. In mixed systems, every single amine or imine competes for the same central hub, in accordance with their binding affinity for the catalyst metal ion center. More generally, the study extends the basic principles of constitutional dynamic chemistry to interconnected chemical transformations and provides a step toward dynamic systems of increasing complexity.