Expanding the Use of Benzothioxanthene Imides to Photochemistry: Eco-Friendly Aerobic Oxidation of Sulfides to Sulfoxides.

The sulfoxide moiety is one of the most commonly utilized groups in pharmaceutical and industrial chemistry. The need for sustainability and easy accessibility to sulfoxide moieties is deemed necessary, due to its ubiquity in natural products and potentially pharmaceutically active compounds. In this context, we report herein a sustainable, aerobic and environmentally friendly photochemical protocol based on the use of a benzothioxathene imide as the photocatalyst to selectively oxidise sulfides under mild irradiation (456 nm), in very low catalyst loading (0.01 mol%) and on water. In addition, to demonstrate the compatibility of our protocol with wide scope of substrates, the latter was successfully applied to the synthesis of the biologically-active Sulforaphane and Modafinil.

Probing Particle-Carbon/Binder Degradation Behavior in Fatigued Layered Cathode Materials through Machine Learning Aided Diffraction Tomography.

Understanding how reaction heterogeneity impacts cathode materials during Li-ion battery (LIB) electrochemical cycling is pivotal for unraveling their electrochemical performance. Yet, experimentally verifying these reactions has proven to be a challenge. To address this, we employed scanning µ-XRD computed tomography to scrutinize Ni-rich layered LiNi0.6Co0.2Mn0.2O2 (NCM622) and Li-rich layered Li[Li0.2Ni0.2Mn0.6]O2 (LLNMO). By harnessing machine learning (ML) techniques, we scrutinized an extensive dataset of µ-XRD patterns, about 100,000 patterns per slice, to unveil the spatial distribution of crystalline structure and microstrain. Our experimental findings unequivocally reveal the distinct behavior of these materials. NCM622 exhibits structural degradation and lattice strain intricately linked to the size of secondary particles. Smaller particles and the surface of larger particles in contact with the carbon/binder matrix experience intensified structural fatigue after long-term cycling. Conversely, both the surface and bulk of LLNMO particles endure severe strain-induced structural degradation during high-voltage cycling, resulting in significant voltage decay and capacity fade. This work holds the potential to fine-tune the microstructure of advanced layered materials and manipulate composite electrode construction in order to enhance the performance of LIBs and beyond.

Driving Triplet State Population in Benzothioxanthene Imide Dyes: Let's twist!

Controlling the formation of photoexcited triplet states is critical for many (photo)chemical and physical applications. Here, we demonstrate that a permanent out-of-plane distortion of the benzothioxanthene imide (BTI) dye promotes intersystem crossing by increasing spin-orbit coupling. This manipulation was achieved through a subtle chemical modification, specifically the bay-area methylation. Consequently, this simple yet efficient approach expands the catalog of known molecular engineering strategies for synthesizing heavy atom-free, dual redox-active, yet still emissive and synthetically accessible photosensitizers.

Polysphaeroides filiformis, a proterozoic cyanobacterial microfossil and implications for cyanobacteria evolution.

Deciphering the fossil record of cyanobacteria is crucial to understand their role in the chemical and biological evolution of the early Earth. They profoundly modified the redox conditions of early ecosystems more than 2.4 Ga ago, the age of the Great Oxidation Event (GOE), and provided the ancestor of the chloroplast by endosymbiosis, leading the diversification of photosynthetic eukaryotes. Here, we analyze the morphology, ultrastructure, chemical composition, and metals distribution of Polysphaeroides filiformis from the 1040-1006 Ma Mbuji-Mayi Supergroup (DR Congo). We evidence trilaminar and bilayered ultrastructures for the sheath and the cell wall, respectively, and the preservation of Ni-tetrapyrrole moieties derived from chlorophyll in intracellular inclusions. This approach allows an unambiguous interpretation of P. filiformis as a branched and multiseriate photosynthetic cyanobacterium belonging to the family of Stigonemataceae. It also provides a possible minimum age for the emergence of multiseriate true branching nitrogen-fixing and probably heterocytous cyanobacteria.

Effects of Erucamide on Fiber "Softness": Linking Single-Fiber Crystal Structure and Mechanical Properties.

Erucamide is known to play a critical role in modifying polymer fiber surface chemistry and morphology. However, its effects on fiber crystallinity and mechanical properties remain to be understood. Here, synchrotron nanofocused X-ray Diffraction (nXRD) revealed a bimodal orientation of the constituent polymer chains aligned along the fiber axis and cross-section, respectively. Erucamide promoted crystallinity in the fiber, leading to larger and more numerous lamellae crystallites. The nXRD nanostructual characterization is complemented by single-fiber uniaxial tensile tests, which showed that erucamide significantly affected fiber mechanical properties, decreasing fiber tensile strength and stiffness but enhancing fiber toughness, fracture strain, and ductility. To correlate these single-fiber nXRD and mechanical test results, we propose that erucamide mediated slip at the interfaces between crystallites and amorphous domains during stress-induced single-fiber crystallization, also decreasing the stress arising from the shear displacement of microfibrils and deformation of the macromolecular network. Linking the single-fiber crystal structure with the single-fiber mechanical properties, these findings provide the direct evidence on a single-fiber level for the role of erucamide in enhancing fiber "softness".

LiOH Decomposition by NiO/ZrO2 in Li-Air Battery: Chemical Imaging with Operando Synchrotron Diffraction and Correlative Neutron/X-Ray Computed-Tomography Analysis.

Li-air batteries attract significant attention due to their highest theoretical energy density among all existing energy storage technologies. Currently, challenges related to extending lifetime and long-term stability limit their practical application. To overcome these issues and enhance the total capacity of Li-air batteries, this study introduces an innovative approach with NiO/ZrO2 catalysts. Operando advanced chemical imaging with micrometer spatial resolution unveils that NiO/ZrO2 catalysts substantially change the kinetics of crystalline lithium hydroxide (LiOH) formation and facilitate its rapid decomposition with heterogeneous distribution. Moreover, ex situ combined neutron and X-ray computed tomography (CT) analysis, provide evidence of distinct lithium phases homogeneously distributed in the presence of NiO/ZrO2 . These findings underscore the material's superior physico-chemical and electronic properties, with more efficient oxygen diffusion and indications of lower obstruction to its active sites, avoiding clogging in the active electrode, a common cause of capacity loss. Electrochemical tests conducted at high current density demonstrated a significant kinetic enhancement of the oxygen reduction and evolution reactions, resulting in improved charge and discharge processes with low overpotential. This pioneering approach using NiO/ZrO2 catalysts represents a step toward on developing the full potential of Li-air batteries as high-energy-density energy storage systems.

Additive manufacturing of alloys with programmable microstructure and properties.

In metallurgy, mechanical deformation is essential to engineer the microstructure of metals and to tailor their mechanical properties. However, this practice is inapplicable to near-net-shape metal parts produced by additive manufacturing (AM), since it would irremediably compromise their carefully designed geometries. In this work, we show how to circumvent this limitation by controlling the dislocation density and thermal stability of a steel alloy produced by laser powder bed fusion (LPBF) technology. We show that by manipulating the alloy's solidification structure, we can 'program' recrystallization upon heat treatment without using mechanical deformation. When employed site-specifically, our strategy enables designing and creating complex microstructure architectures that combine recrystallized and non-recrystallized regions with different microstructural features and properties. We show how this heterogeneity may be conducive to materials with superior performance compared to those with monolithic microstructure. Our work inspires the design of high-performance metal parts with artificially engineered microstructures by AM.

Multi-scale characterization of the spatio-temporal interplay between elemental composition, mineral deposition and remodelling in bone fracture healing.

Bone mineralization involves a complex orchestration of physico-chemical responses from the organism. Despite extensive studies, the detailed mechanisms of mineralization remain to be elucidated. This study aims to characterize bone mineralization using an in-vivo long bone fracture healing model in the rat. The spatio-temporal distribution of relevant elements was correlated to the deposition and maturation of hydroxyapatite and the presence of matrix remodeling compounds (MMP-13). Multi-scale measurements indicated that (i) zinc is required for both the initial mineral deposition and resorption processes during mature mineral remodeling; (ii) Zinc and MMP-13 show similar spatio-temporal trends during early mineralization; (iii) Iron acts locally and in coordination with zinc during mineralization, thus indicating novel evidence of the time-events and inter-play between the elements. These findings improve the understanding of bone mineralization by explaining the link between the different constituents of this process throughout the healing time. STATEMENT OF SIGNIFICANCE: Bone mineralization involves a complex orchestration of physico-chemical responses from the organism, the detailed mechanisms of which remain to be elucidated. This study presents a highly novel multi-scale multi-modal investigation of bone mineralization using bone fracture healing as a model system. We present original characterization of tissue mineralization, where we relate the spatio-temporal distribution of important trace elements to a key matrix remodeling compound (MMP-13), the initial deposition and maturation of hydroxyapatite and further remodeling processes. This is the first time that mineralization has been probed down to the nanometric level, and where key mineralization components have been investigated to achieve a comprehensive and mechanistic understanding of the underlying mineralization processes during bone healing.

A new G-quadruplex-specific photosensitizer inducing genome instability in cancer cells by triggering oxidative DNA damage and impeding replication fork progression.

Photodynamic therapy (PDT) ideally relies on the administration, selective accumulation and photoactivation of a photosensitizer (PS) into diseased tissues. In this context, we report a new heavy-atom-free fluorescent G-quadruplex (G4) DNA-binding PS, named DBI. We reveal by fluorescence microscopy that DBI preferentially localizes in intraluminal vesicles (ILVs), precursors of exosomes, which are key components of cancer cell proliferation. Moreover, purified exosomal DNA was recognized by a G4-specific antibody, thus highlighting the presence of such G4-forming sequences in the vesicles. Despite the absence of fluorescence signal from DBI in nuclei, light-irradiated DBI-treated cells generated reactive oxygen species (ROS), triggering a 3-fold increase of nuclear G4 foci, slowing fork progression and elevated levels of both DNA base damage, 8-oxoguanine, and double-stranded DNA breaks. Consequently, DBI was found to exert significant phototoxic effects (at nanomolar scale) toward cancer cell lines and tumor organoids. Furthermore, in vivo testing reveals that photoactivation of DBI induces not only G4 formation and DNA damage but also apoptosis in zebrafish, specifically in the area where DBI had accumulated. Collectively, this approach shows significant promise for image-guided PDT.

Synchrotron-Based X-ray Fluorescence Imaging Elucidates Uranium Toxicokinetics in Daphnia magna.

A combination of synchrotron-based elemental analysis and acute toxicity tests was used to investigate the biodistribution and adverse effects in Daphnia magna exposed to uranium nanoparticle (UNP, 3-5 nm) suspensions or to uranium reference (Uref) solutions. Speciation analysis revealed similar size distributions between exposures, and toxicity tests showed comparable acute effects (UNP LC50: 402 µg L-1 [336-484], Uref LC50: 268 µg L-1 [229-315]). However, the uranium body burden was 3- to 5-fold greater in UNP-exposed daphnids, and analysis of survival as a function of body burden revealed a ∼5-fold higher specific toxicity from the Uref exposure. High-resolution X-ray fluorescence elemental maps of intact, whole daphnids from sublethal, acute exposures of both treatments revealed high uranium accumulation onto the gills (epipodites) as well as within the hepatic ceca and the intestinal lumen. Uranium uptake into the hemolymph circulatory system was inferred from signals observed in organs such as the heart and the maxillary gland. The substantial uptake in the maxillary gland and the associated nephridium suggests that these organs play a role in uranium removal from the hemolymph and subsequent excretion. Uranium was also observed associated with the embryos and the remnants of the chorion, suggesting uptake in the offspring. The identification of target organs and tissues is of major importance to the understanding of uranium and UNP toxicity and exposure characterization that should ultimately contribute to reducing uncertainties in related environmental impact and risk assessments.

Synthesis and Characterization of Stable Cu-Pt Nanoparticles under Reductive and Oxidative Conditions.

We report a synthesis method for highly monodisperse Cu-Pt alloy nanoparticles. Small and large Cu-Pt particles with a Cu/Pt ratio of 1:1 can be obtained through colloidal synthesis at 300 °C. The fresh particles have a Pt-rich surface and a Cu-rich core and can be converted into an intermetallic phase after annealing at 800 °C under H2. First, we demonstrated the stability of fresh particles under redox conditions at 400 °C, as the Pt-rich surface prevents substantial oxidation of Cu. Then, a combination of in situ scanning transmission electron microscopy, in situ X-ray absorption spectroscopy, and CO oxidation measurements of the intermetallic CuPt phase before and after redox treatments at 800 °C showed promising activity and stability for CO oxidation. Full oxidation of Cu was prevented after exposure to O2 at 800 °C. The activity and structure of the particles were only slightly changed after exposure to O2 at 800 °C and were recovered after re-reduction at 800 °C. Additionally, the intermetallic CuPt phase showed enhanced catalytic properties compared to the fresh particles with a Pt-rich surface or pure Pt particles of the same size. Thus, the incorporation of Pt with Cu does not lead to a rapid deactivation and degradation of the material, as seen with other bimetallic systems. This work provides a synthesis route to control the design of Cu-Pt nanostructures and underlines the promising properties of these alloys (intermetallic and non-intermetallic) for heterogeneous catalysis.

Synchrotron XRF and Histological Analyses Identify Damage to Digestive Tract of Uranium NP-Exposed Daphnia magna.

Micro- and nanoscopic X-ray techniques were used to investigate the relationship between uranium (U) tissue distributions and adverse effects to the digestive tract of aquatic model organism Daphnia magna following uranium nanoparticle (UNP) exposure. X-ray absorption computed tomography measurements of intact daphnids exposed to sublethal concentrations of UNPs or a U reference solution (URef) showed adverse morphological changes to the midgut and the hepatic ceca. Histological analyses of exposed organisms revealed a high proportion of abnormal and irregularly shaped intestinal epithelial cells. Disruption of the hepatic ceca and midgut epithelial tissues implied digestive functions and intestinal barriers were compromised. Synchrotron-based micro X-ray fluorescence (XRF) elemental mapping identified U co-localized with morphological changes, with substantial accumulation of U in the lumen as well as in the epithelial tissues. Utilizing high-resolution nano-XRF, 400-1000 nm sized U particulates could be identified throughout the midgut and within hepatic ceca cells, coinciding with tissue damages. The results highlight disruption of intestinal function as an important mode of action of acute U toxicity in D. magna and that midgut epithelial cells as well as the hepatic ceca are key target organs.

Gaze-based attention refocusing training in virtual reality for adult attention-deficit/hyperactivity disorder.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is characterized by substantial interindividual heterogeneity that challenges the systematic assessment and treatment. Considering mixed evidence from previous neurofeedback research, we present a novel feedback system that relies on gaze behavior to detect signs of inattention while performing a neuropsychological attention task in a virtual seminar room. More specifically, an audiovisual feedback was given whenever participants averted their gaze from the given task. METHODS: Eighteen adults with ADHD and 18 healthy controls performed a continuous performance task (CPT) in virtual reality under three counterbalanced conditions in which either gaze-based feedback, sham feedback, or no feedback was provided. In all conditions, phases of high and low virtual distraction alternated. CPT errors and reaction times, proportions of gaze dwell times (e.g., task focus or distraction focus), saccade characteristics, EEG theta/beta ratios, head movements, and an experience sampling of ADHD symptoms were analyzed. RESULTS: While patients can be discriminated well from healthy controls in that they showed more omission errors, higher reaction times, higher distraction-related dwell times, and more head movements, the feedback did not immediately improve task performance. It was also indicated that sham feedback was rather associated with an aggravation of symptoms in patients. CONCLUSIONS: Our findings demonstrate sufficient suitability and specificity for this holistic ADHD symptom assessment. Regarding the feedback, a single-session training was insufficient to achieve learning effects based on the proposed metacognitive strategies. Future longitudinal, multi-session trials should conclusively examine the therapeutic efficacy of gaze-based virtual reality attention training in ADHD. TRIAL REGISTRATION: drks.de (identifier: DRKS00022370).

Vadose-zone alteration of metaschoepite and ceramic UO2 in Savannah River Site field lysimeters.

Uranium dioxide (UO2) and metaschoepite (UO3•nH2O) particles have been identified as contaminants at nuclear sites. Understanding their behavior and impact is crucial for safe management of radioactively contaminated land and to fully understand U biogeochemistry. The Savannah River Site (SRS) (South Carolina, USA), is one such contaminated site, following historical releases of U-containing wastes to the vadose zone. Here, we present an insight into the behavior of these two particle types under dynamic conditions representative of the SRS, using field lysimeters (15 cm D x 72 cm L). Discrete horizons containing the different particle types were placed at two depths in each lysimeter (25 cm and 50 cm) and exposed to ambient rainfall for 1 year, with an aim of understanding the impact of dynamic, shallow subsurface conditions on U particle behavior and U migration. The dissolution and migration of U from the particle sources and the speciation of U throughout the lysimeters was assessed after 1 year using a combination of sediment digests, sequential extractions, and bulk and µ-focus X-ray spectroscopy. In the UO2 lysimeter, oxidative dissolution of UO2 and subsequent migration of U was observed over 1-2 cm in the direction of waterflow and against it. Sequential extractions of the UO2 sources suggest they were significantly altered over 1 year. The metaschoepite particles also showed significant dissolution with marginally enhanced U migration (several cm) from the sources. However, in both particle systems the released U was quantitively retained in sediment as a range of different U(IV) and U(VI) phases, and no detectable U was measured in the lysimeter effluent. The study provides a useful insight into U particle behavior in representative, real-world conditions relevant to the SRS, and highlights limited U migration from particle sources due to secondary reactions with vadose zone sediments over 1 year.

Intracellular bound chlorophyll residues identify 1 Gyr-old fossils as eukaryotic algae.

The acquisition of photosynthesis is a fundamental step in the evolution of eukaryotes. However, few phototrophic organisms are unambiguously recognized in the Precambrian record. The in situ detection of metabolic byproducts in individual microfossils is the key for the direct identification of their metabolisms. Here, we report a new integrative methodology using synchrotron-based X-ray fluorescence and absorption. We evidence bound nickel-geoporphyrins moieties in low-grade metamorphic rocks, preserved in situ within cells of a ~1 Gyr-old multicellular eukaryote, Arctacellularia tetragonala. We identify these moieties as chlorophyll derivatives, indicating that A. tetragonala was a phototrophic eukaryote, one of the first unambiguous algae. This new approach, applicable to overmature rocks, creates a strong new proxy to understand the evolution of phototrophy and diversification of early ecosystems.

Arabidopsis thaliana Zn2+-efflux ATPases HMA2 and HMA4 are required for resistance to the necrotrophic fungus Plectosphaerella cucumerina BMM.

Zinc is an essential nutrient at low concentrations, but toxic at slightly higher ones. It has been proposed that hyperaccumulator plants may use the excess zinc to fend off pathogens and herbivores. However, there is little evidence of a similar response in other plants. Here we show that Arabidopsis thaliana leaves inoculated with the necrotrophic fungus Plectosphaerella cucumerina BMM (PcBMM) accumulate zinc and manganese at the infection site. Zinc accumulation did not occur in a double mutant in the zinc transporters HEAVY METAL ATPASE2 and HEAVY METAL ATPASE4 (HMA2 and HMA4), which has reduced zinc translocation from roots to shoots. Consistent with a role in plant immunity, expression of HMA2 and HMA4 was up-regulated upon PcBMM inoculation, and hma2hma4 mutants were more susceptible to PcBMM infection. This phenotype was rescued upon zinc supplementation. The increased susceptibility to PcBMM infection was not due to the diminished expression of genes involved in the salicylic acid, ethylene, or jasmonate pathways since they were constitutively up-regulated in hma2hma4 plants. Our data indicate a role of zinc in resistance to PcBMM in plants containing ordinary levels of zinc. This layer of immunity runs in parallel to the already characterized defence pathways, and its removal has a direct effect on resistance to pathogens.

The Celsr3-Kif2a axis directs neuronal migration in the postnatal brain.

The tangential migration of immature neurons in the postnatal brain involves consecutive migration cycles and depends on constant remodeling of the cell cytoskeleton, particularly in the leading process (LP). Despite the identification of several proteins with permissive and empowering functions, the mechanisms that specify the direction of migration remain largely unknown. Here, we report that planar cell polarity protein Celsr3 orients neuroblasts migration from the subventricular zone (SVZ) to olfactory bulb (OB). In Celsr3-forebrain conditional knockout mice, neuroblasts loose directionality and few can reach the OB. Celsr3-deficient neuroblasts exhibit aberrant branching of LP, de novo LP formation, and decreased growth rate of microtubules (MT). Mechanistically, we show that Celsr3 interacts physically with Kif2a, a MT depolymerizing protein and that conditional inactivation of Kif2a in the forebrain recapitulates the Celsr3 knockout phenotype. Our findings provide evidence that Celsr3 and Kif2a cooperatively specify the directionality of neuroblasts tangential migration in the postnatal brain.

Inhibitory synapse dysfunction and epileptic susceptibility associated with KIF2A deletion in cortical interneurons.

Malformation of cortical development (MCD) is a family of neurodevelopmental disorders, which usually manifest with intellectual disability and early-life epileptic seizures. Mutations in genes encoding microtubules (MT) and MT-associated proteins are one of the most frequent causes of MCD in humans. KIF2A is an atypical kinesin that depolymerizes MT in ATP-dependent manner and regulates MT dynamics. In humans, single de novo mutations in KIF2A are associated with MCD with epileptic seizures, posterior pachygyria, microcephaly, and partial agenesis of corpus callosum. In this study, we conditionally ablated KIF2A in forebrain inhibitory neurons and assessed its role in development and function of inhibitory cortical circuits. We report that adult mice with specific deletion of KIF2A in GABAergic interneurons display abnormal behavior and increased susceptibility to epilepsy. KIF2A is essential for tangential migration of cortical interneurons, their positioning in the cerebral cortex, and for formation of inhibitory synapses in vivo. Our results shed light on how KIF2A deregulation triggers functional alterations in neuronal circuitries and contributes to epilepsy.

Endophytic Bacteria Bacillus subtilis, Isolated from Zea mays, as Potential Biocontrol Agent against Botrytis cinerea.

Plant diseases are one of the main factors responsible for food loss in the world, and 20-40% of such loss is caused by pathogenic infections. Botrytis cinerea is the most widely studied necrotrophic phytopathogenic fungus. It is responsible for incalculable economic losses due to the large number of host plants affected. Today, B. cinerea is controlled mainly by synthetic fungicides whose frequent application increases risk of resistance, thus making them unsustainable in terms of the environment and human health. In the search for new alternatives for the biocontrol of this pathogen, the use of endophytic microorganisms and their metabolites has gained momentum in recent years. In this work, we isolated endophytic bacteria from Zea mays cultivated in Colombia. Several strains of Bacillus subtilis, isolated and characterized in this work, exhibited growth inhibition against B. cinerea of more than 40% in in vitro cultures. These strains were characterized by studying several of their biochemical properties, such as production of lipopeptides, potassium solubilization, proteolytic and amylolytic capacity, production of siderophores, biofilm assays, and so on. We also analyzed: (i) its capacity to promote maize growth (Zea mays) in vivo, and (ii) its capacity to biocontrol B. cinerea during in vivo infection in plants (Phaseolus vulgaris).

Devonian agglutinated polychaete tubes: all in all it's just another grain in the wall.

Biomineralized and organic metazoan tubular skeletons are by far the most common in the fossil record. However, several groups of organisms are also able to agglutinate particles to construct more rigid structures. Here we present a novel type of agglutinated tube from the austral and endemic palaeobiota of the Malvinokaffric realm (Devonian, Brazil). This fossil is characterized by an agglutinated tube made of silt-sized particles forming an unusual flanged morphology that is not known from the fossil record. Besides being able to select specific particles, these organisms probably lived partially buried and were detritus/suspension feeders. Comparisons across different modern groups show that these fossils are strongly similar to tubes made by polychaetes, specifically from the family Maldanidae. If this interpretation is correct, then an early divergence of the Sedentaria clade may have occurred before the Devonian.