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.

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.

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.

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).

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.

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.

Spatio-Chemical Heterogeneity of Defect-Engineered Metal-Organic Framework Crystals Revealed by Full-Field Tomographic X-ray Absorption Spectroscopy.

The introduction of structural defects in metal-organic frameworks (MOFs), often achieved through the fractional use of defective linkers, is emerging as a means to refine the properties of existing MOFs. These linkers, missing coordination fragments, create unsaturated framework nodes that may alter the properties of the MOF. A property-targeted utilization of this approach demands an understanding of the structure of the defect-engineered MOF. We demonstrate that full-field X-ray absorption near-edge structure computed tomography can help to improve our understanding. This was demonstrated by visualizing the chemical heterogeneity found in defect-engineered HKUST-1 MOF crystals. A non-uniform incorporation and zonation of the defective linker was discovered, leading to the presence of clusters of a second coordination polymer within HKUST-1. The former is suggested to be responsible, in part, for altered MOF properties; thereby, advocating for a spatio-chemically resolved characterization of MOFs.

Nickel Poisoning of a Cracking Catalyst Unravelled by Single-Particle X-ray Fluorescence-Diffraction-Absorption Tomography.

Ni contamination from crude oil in the fluid catalytic cracking (FCC) process is one of the primary sources of catalyst deactivation, thereby promoting dehydrogenation-hydrogenation and speeding up coke growth. Herein, single-particle X-ray fluorescence, diffraction and absorption (µXRF-µXRD-µXAS) tomography is used in combination with confocal fluorescence microscopy (CFM) after thiophene staining to spatially resolve Ni interaction with catalyst components and study zeolite degradation, including the processes of dealumination and Brønsted acid sites distribution changes. The comparison between a Ni-lean particle, exposed to hydrotreated feedstock, and a Ni-rich one, exposed to non-hydrotreated feedstock, reveals a preferential interaction of Ni, found in co-localization with Fe, with the γ-Al2 O3 matrix, leading to the formation of spinel-type hotspots. Although both particles show similar surface zeolite degradation, the Ni-rich particle displays higher dealumination and a clear Brønsted acidity drop.

Metaschoepite Dissolution in Sediment Column Systems-Implications for Uranium Speciation and Transport.

Metaschoepite is commonly found in U-contaminated environments and metaschoepite-bearing wastes may be managed via shallow or deep disposal. Understanding metaschoepite dissolution and tracking the fate of any liberated U is thus important. Here, discrete horizons of metaschoepite (UO3·nH2O) particles were emplaced in flowing sediment/groundwater columns representative of the UK Sellafield Ltd. site. The column systems either remained oxic or became anoxic due to electron donor additions, and the columns were sacrificed after 6- and 12-months for analysis. Solution chemistry, extractions, and bulk and micro/nano-focus X-ray spectroscopies were used to track changes in U distribution and behavior. In the oxic columns, U migration was extensive, with UO22+ identified in effluents after 6-months of reaction using fluorescence spectroscopy. Unusually, in the electron-donor amended columns, during microbially mediated sulfate reduction, significant amounts of UO2-like colloids (>60% of the added U) were found in the effluents using TEM. XAS analysis of the U remaining associated with the reduced sediments confirmed the presence of trace U(VI), noncrystalline U(IV), and biogenic UO2, with UO2 becoming more dominant with time. This study highlights the potential for U(IV) colloid production from U(VI) solids under reducing conditions and the complexity of U biogeochemistry in dynamic systems.

High-intensity x-ray microbeam for macromolecular crystallography using silicon kinoform diffractive lenses.

Macromolecular crystallography often requires focused high-intensity x-ray beams for solving challenging protein structures from micrometer-sized crystals using current synchrotron radiation sources. The design of optical focusing schemes for hard x-rays showing high efficiency and flexibility in beam size is therefore continuously pursued. Here, we present an innovative solution based on a two-stage demagnification of the undulator source for photon energies from 6 keV to 19 keV, commissioned at the X10SA beamline of the Swiss Light Source, where a secondary source is imaged by two crossed silicon kinoform x-ray diffractive lenses with 75 nm outermost zone width. A source-size limited spot with a size of 4.8 µm×1.7 µm(h×v,FWHM) and flux of 7.5×1010 photons/s at 12.4 keV is demonstrated at the sample position.

Localization and Speciation of Iron Impurities within a Fluid Catalytic Cracking Catalyst.

Fluid catalytic cracking is a chemical conversion process of industrial scale. This process, utilizing porous catalysts composed of clay and zeolite, converts heavy crude-oil fractions into transportation fuel and petrochemical feedstocks. Among other factors iron-rich reactor and feedstream impurities cause these catalyst particles to permanently deactivate. Herein, we report tomographic X-ray absorption spectroscopy measurements that reveal the presence of dissimilar iron impurities of specific localization within a single deactivated particle. Whereas the iron natural to clay in the composite seems to be unaffected by operation, exterior-facing and feedstream-introduced iron was found in two forms. Those being minute quantities of ferrous oxide, located near regions of increased porosity, and impurities rich in Fe3+ , preferentially located in the outer dense part of the particle and suggested to contribute to the formation of an isolating amorphous silica alumina envelope.

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.

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 oxidize 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.

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".

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.

Heavy-atom-free π-twisted photosensitizers for fluorescence bioimaging and photodynamic therapy.

As the field of preclinical research on photosensitizers (PSs) for anticancer photodynamic therapy (PDT) continues to expand, a focused effort is underway to develop agents with innovative molecular structures that offer enhanced targeting, selectivity, activation, and imaging capabilities. In this context, we introduce two new heavy-atom-free PSs, DBXI and DBAI, characterized by a twisted π-conjugation framework. This innovative approach enhances the spin-orbit coupling (SOC) between the singlet excited state (S1) and the triplet state (T1), resulting in improved and efficient intersystem crossing (ISC). Both PSs are highly effective in producing reactive oxygen species (ROS), including singlet oxygen and/or superoxide species. Additionally, they also demonstrate remarkably strong fluorescence emission. Indeed, in addition to providing exceptional photocytotoxicity, this emissive feature, generally lacking in other reported structures, allows for the precise monitoring of the PSs' distribution within specific cellular organelles even at nanomolar concentrations. These findings underscore the dual functionality of these PSs, serving as both fluorescent imaging probes and light-activated therapeutic agents, emphasizing their potential as versatile and multifunctional tools in the field of PDT.

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.

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.