Optical control of electron spin states is important for quantum sensing and computing applications, as developed with the diamond nitrogen vacancy centre. This requires electronic excitations, excitons, with net spin. Here we report a molecular diradical where two trityl radical groups are coupled via a meta-linked fluorene bridge. The singlet exciton is at lower energy than the triplet because electron transfer from one of the radical non-bonding orbitals to the other is spin allowed, set by the charging energy for the double occupancy of the non-bonding level, the Hubbard U. Both excitons give efficient photoluminescence at 640 and 700 nm with near unity efficiency. The ground state exchange energy is low, 60 µeV, allowing control of ground state spin populations. We demonstrate spin-selective intersystem crossing and show coherent microwave control. We report up to 8% photoluminescence contrast at microwave resonance. This tuning of the singlet Mott–Hubbard exciton against the ‘bandgap’ exciton provides a new design platform for spin–optical materials.

The Eastern African region is an amalgamation of complex climate systems nestled in contrasting topographic barriers. Although rift basins are prime targets for studying the climate of the past, high-altitude climate archives in the context of paleoclimate research also offer invaluable insight and have yet to be fully explored. Here, we present a 17 kyr hydroclimate history of the Afro-alpine (4121 m a.s.l) Central Lake using a δ18O record established by analyzing hemicellulose-derived sugar biomarkers. The sugar biomarker patterns with a dominance of fucose indicate the predominance of autochthonous sedimentary organic matter. Therefore, the oxygen isotopic variability of the sugar biomarkers in general and of fucose in particular (δ18Ofucose) reflects δ18Olake water being controlled by climatic conditions, particularly lake water 18O enrichment by evaporation. Our δ18Ofucose record from Central Lake indicates strong enrichment during the Late Glacial. Around 15 cal kyr BP, the onset of more humid climate marks the beginning of the African Humid Period (AHP) in the Bale Mountains. The AHP was interrupted by an arid period during the Late Glacial – Holocene transition roughly coinciding with the Younger Dryas (YD). After the YD, humid climatic conditions prevailed again until the Late Holocene when a gradual shift towards drier climate started. Our δ18Ofucose record and interpretation agree well with the findings from adjacent low-altitude archives of Eastern Africa, the Indian Ocean paleoclimate records and the Asian Monsoon Domain, which suggests region-wide hydro-climatic teleconnections.

Mesopelagic fish are integral to ocean food webs and play an important role in carbon transport through their vertical migration behavior. Ocean deoxygenation caused by anthropogenic warming is expected to pose severe threats to mesopelagic fauna by enhancing physical stress and changing predator-prey relationships. In agreement with this expectation, our fish otolith record in a Mediterranean sediment core shows near absence of mesopelagic species during Sapropel deposition between ~7 and ~10 thousand years ago, concurrent with high surface productivity and low oxygenation of mid-depth waters. Instead, the otolith record is dominated by fish species adapted to epipelagic habitats, including European anchovy (Engraulis encrasicolus) and silvery lightfish (Maurolicus muelleri). Subsequent reoxygenation starting ~7 thousand years ago is accompanied by a three-fold increase in total otolith abundance. The large majority of these are mesopelagic lanternfish (Myctophidae) that dominate the otolith assemblage from the middle-Holocene to the present. Our findings corroborate expectations that future expansion of midwater deoxygenation could severely deplete mesopelagic fish communities over the coming centuries, with major impacts on marine fisheries, marine conservation, ocean food web structure, carbon storage and other marine ecosystem services.

Efficient delivery of the CRISPR/Cas9 system and its larger derivatives, base editors, and prime editors remain a major challenge, particularly in tissue-specific stem cells and induced pluripotent stem cells (iPSCs). This study optimized a novel family of cell-penetrating peptides, hPep, to deliver gene-editing ribonucleoproteins. The hPep-based nanoparticles enable highly efficient and biocompatible delivery of Cre recombinase, Cas9, base-, and prime editors. Using base editors, robust and nearly complete genome editing was achieved in the human cells: HEK293T (96%), iPSCs (74%), and muscle stem cells (80%). This strategy opens promising avenues for ex vivo and, potentially, in vivo applications. Incorporating silica particles enhanced the system's versatility, facilitating cargo-agnostic delivery. Notably, the nanoparticles can be synthesized quickly on a benchtop and stored as lyophilized powder without compromising functionality. This represents an important advancement in the feasibility and scalability of gene-editing delivery technologies.

Water under 2D confinement exhibits unique structural and dynamic behaviors distinct from bulk water, including phase transitions and altered hydrogen-bonding networks, making it of great scientific interest. While confinement in 2D materials like graphene, mica, or hexagonal boron nitride has been reported, their lack of intrinsic hydrophilicity or metallic conductivity limits their suitability for probing the interplay between confined water and electronic transport. MXenes, a family of 2D transition metal carbides and nitrides, overcome these limitations by combining high metallic conductivity (~104 S cm−1) with hydrophilicity, offering a unique platform to investigate confined water dynamics and their influence on electronic properties. Here, we show that temperature and confinement drive structural transitions of water within MXene interlayers, including the formation of localized ice clusters, amorphous ice, and dynamic hydrogen-bonded networks. These transformations disrupt stacking order, inducing a reversible metal-to-semiconductor transition and conductivity hysteresis in MXene films. Upon heating to 340 K, the dissociation of ice clusters restores interlayer spacing and metallic behavior. Our findings experimentally establish MXenes as an exceptional platform for studying the phase change of confined water, offering new insights into how nanoscale water dynamics modulate electronic properties and enabling the design of advanced devices with tunable interlayer interactions.

The olm (Proteus anguinus), with a predicted maximum lifespan of more than 100 years, is the longest-lived amphibian, which in addition possesses a range of unique adaptations to its dark, subterranean cave habitat. To assess the underlying molecular signatures, we present the first comprehensive transcriptome of the olm. Our study provides gene expression data across six organs and comparative genomics analyses, accessible via an interactive web server: http://comp-pheno.de/olm. The data uncover significant organ-specific gene expression, with the brain showing the highest number of organ-specific expressed genes. Our findings reveal significantly more genes under strong negative selection than positive selection, particularly in brain-specific expressed genes. Processes under positive selection in the olm resemble those in other long-lived species.

The human brain extracts complex information from visual inputs, including objects, their spatial and semantic interrelations, and their interactions with the environment. However, a quantitative approach for studying this information remains elusive. Here we test whether the contextual information encoded in large language models (LLMs) is beneficial for modelling the complex visual information extracted by the brain from natural scenes. We show that LLM embeddings of scene captions successfully characterize brain activity evoked by viewing the natural scenes. This mapping captures selectivities of different brain areas and is sufficiently robust that accurate scene captions can be reconstructed from brain activity. Using carefully controlled model comparisons, we then proceed to show that the accuracy with which LLM representations match brain representations derives from the ability of LLMs to integrate complex information contained in scene captions beyond that conveyed by individual words. Finally, we train deep neural network models to transform image inputs into LLM representations. Remarkably, these networks learn representations that are better aligned with brain representations than a large number of state-of-the-art alternative models, despite being trained on orders-of-magnitude less data. Overall, our results suggest that LLM embeddings of scene captions provide a representational format that accounts for complex information extracted by the brain from visual inputs.

Snow algal blooms lead to glacier and snow surface albedo reduction and subsequent melting. To explore snow algal distribution patterns and potential to cause blooms, we investigated snow algae in the Tibetan, Antarctic, Arctic, and Alps. Our results demonstrated that Tibetan and Alps had higher algal richness than Antarctic snow. Only 19 ASVs were shared among regions, with their relative abundance being lower in the Tibetan compared to the Arctic and Alps but similar in Antarctica. Furthermore, the algal community varied substantially across sampling sites, with 34% of the identified taxa endemic to Tibetan glacier snow. Cosmopolitan bloom-causing algae were scarce in most Tibetan Plateau snow, which was potentially limited by a low snow depth that prevented their growth. Alternatively, Hydrurus sp., which may cause golden-brown snow, was abundant (up to 54.4%) on Tibetan. Therefore, cosmopolitan and endemic species jointly enhance the potential of producing algal blooms in Tibetan glaciers.

Protein tagging with CRISPR-Cas9 enables the investigation of protein function in its native environment but is limited by low homology-directed repair (HDR) efficiency. Here, we present a protocol for fast antibiotic resistance-based gene editing with CRISPR-Cas9 (FAB-CRISPR), which streamlines N/C-terminal tagging using an antibiotic resistance cassette for rapid selection and enrichment of gene-edited cells. We describe in detail guide RNA and HDR donor plasmid cloning, transfection of editing reagents into HeLa cells, and subsequent enrichment and verification of gene-edited cells. For complete details on the use and execution of this protocol, please refer to Wong-Dilworth et al.,1 Stockhammer et al.,2 Stockhammer et al.,3 Heyza et al.,4 and Broadbent et al.5

The 28 March 2025 Mw 7.7 Myanmar earthquake on the Sagaing fault caused widespread building collapses and over 3800 fatalities, as well as strong shaking in Bangkok. Highfrequency backprojection very early on revealed an 500 km rupture. Following a bilateral subshear propagation, the rupture accelerated southward to at least 5.3 km/s, reaching the stable supershear regime, as also confirmed by Mach-cone analysis with Love waves. Pixel tracking analysis from optical and radar imagery confirms the rupture length and indicates a peak surface offset of 5 m and average offsets of 3-4 m along the rupture zone. Pseudodynamic rupture inversion constrained by seismic waveforms and the radarinterferometric deformation field indicates 4 m slip over 15 km depth range. The earthquake yielded unusually few aftershocks; its supershear rupture likely released most of the accumulated stress. It appears that the rupture almost certainly broke the Sagaing gap and very likely overlapped completely with the 1956 M 7.0 event. It may also have partially overlapped with the 1946 M 7.8 rupture zone in the north and the 1930 M 7.5 event in the south. Acceleration to supershear only started in the gap area, and the rupture decelerated and arrested after moving into the previously broken segment.

In this study, we present a novel approach for time-resolved, in situ analysis of isotope scrambling reactions over platinum nanoparticle catalysts using high-sensitivity gas-phase Raman spectroscopy. A recently developed spectrometer setup enables detection limits in the hundreds of ppm, a dynamic range spanning four orders of magnitude in mole fraction, and a temporal resolution of one second. Experiments were performed by introducing D2 gas to an H2-activated Pt nanoparticle catalyst in a closed sample, resulting in the formation of gaseous HD and H2. The time-resolved gas-phase mole fraction profiles show HD as the dominant product and only minor formation of H2. This observation is consistent with a predominantly associative exchange mechanism, in which D2 reacts directly with surface-bound hydrogen to produce HD. A superimposed exchange involving trace water vapor was also observed, with stepwise conversion of H2O to HDO and D2O via surface-mediated reactions. Mole fractions were quantified using a spectral fitting routine based on simulated Raman spectra derived from literature polarizabilities and energy levels. The reaction quotient of the hydrogen isotopologues converged over time toward literature values of the equilibrium constant, and measurements at defined H2/D2 ratios confirmed relative accuracies better than 2%. This Raman-based quantification method enables simultaneous, in situ detection of all relevant species with high accuracy and is ideally suited for studying transient, catalytic processes.

This paper makes the first comprehensive attempt to study within-country heterogeneity of housing returns. We introduce a new city-level data set covering 15 OECD countries over 150 years and show that national housing markets are characterized by systematic spatial variation in housing returns. Total returns in large agglomerations are close to 100 basis points lower per year than in other parts of the same country. Excess returns outside the large cities can be rationalized as compensation for higher risk, especially higher covariance with income growth and lower liquidity. Real estate in diversified large agglomerations is comparatively safe.

We consider the estimation of an unknown parameter 𝜃 via a many-body probe. The probe is initially prepared in a product state and many-body time-independent interactions enhance its 𝜃 sensitivity during the dynamics and/or in the steady state. We present bounds on the quantum Fisher information, and corresponding optimal interacting Hamiltonians, for two paradigmatic scenarios for encoding 𝜃 : (i) via unitary Hamiltonian dynamics (dynamical metrology), and (ii) in the Gibbs and diagonal ensembles (time-averaged dephased state), two ubiquitous steady states of many-body open dynamics. We then move to the specific problem of estimating the strength of a magnetic field via interacting spins and derive two-body interacting Hamiltonians that can approach the fundamental precision bounds. In this case, we additionally analyze the transient regime leading to the steady states and characterize trade-offs between equilibration times and measurement precision. Overall, our results provide a comprehensive picture of the potential of many-body control in quantum sensing.

Background

The brain endothelial cells (BECs) are essential for protecting the central nervous system (CNS) from xenobiotics and pathogens, including Neisseria meningitidis, while maintaining CNS homeostasis through tight junction (TJ) proteins and specialized transporters. Among these, multidrug resistance (MDR) transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are pivotal in restricting the entry of neurotoxic substances. Although the impact of N. meningitidis infection on BBB TJ is well-documented, its effect on MDR transporters remains largely unexplored.

Methods

We employed induced pluripotent stem cell-derived brain-like endothelial cells (iBECs) as an in vitro BECs model due to their human-like morphology and expression of junctional proteins and MDR transporters. iBECs were exposed to various N. meningitidis strains, isogenic mutants, heat-inactivated bacteria, conditioned media, or purified capsule polysaccharide (CPS). P-gp and BCRP activities were assessed using intracellular accumulation assays with Rhodamine 123 and Chlorin e6, respectively, in the presence of P-gp inhibitors cyclosporin A and PSC833 and BCRP inhibitor Ko143. Gene expression and protein levels were determined by qPCR and western blotting, and sphingolipid quantification was performed via liquid chromatography tandem-mass spectrometry (LC-MS/MS).

Results

Infection of iBECs with N. meningitidis inhibited P-gp activity, whereas BCRP activity remained unaffected. P-gp inhibition occurred without changes in gene expression or protein abundance. Cells infected with N. meningitidis showed reduced efficacy of P-gp inhibitors, an effect not seen with the BCRP inhibitor Ko143. N. meningitidis CPS was identified as a key factor in modulating P-gp activity. Notably, the inhibitory effect of N. meningitidis on P-gp activity was blocked by a specific sphingosine 1-phosphate receptor 1 (S1PR1) antagonist as well as by sphingosine kinase inhibitors, revealing a mechanistic link between S1PR1 signaling and P-gp modulation during infection. Furthermore, S1PR1 was upregulated in infected iBECs. Although LC-MS/MS measurement showed no increase in S1P levels in infected cells compared to uninfected controls, these findings suggest a crucial role for S1PR1 signaling in mediating the observed effects.

Conclusions

These findings demonstrate that N. meningitidis infection impairs P-gp function through S1PR1-dependent pathways, suggesting that targeting this signaling cascade may offer a novel therapeutic strategy to preserve BBB integrity during bacterial infections.

The human brain orchestrates object vision through an interplay of feedforward processing in concert with recurrent processing. However, where, when, and how recurrent processing contributes to visual processing is incompletely understood due to the difficulties in teasing apart feedforward and recurrent processing. We combined a backward masking paradigm with multivariate analysis on EEG and fMRI data to isolate and characterize the nature of recurrent processing. We find that recurrent processing substantially shapes visual representations across the ventral visual stream, starting early on at around 100 ms in early visual cortex (EVC) and two later phases of around 175 and 300 ms in lateral occipital cortex (LOC), adding persistent rather than transient neural dynamics to visual processing. Using convolutional neural network models for comparison with the brain, we show that recurrence changes the feature format in LOC from predominantly mid-level to more high-level features. Finally, we show that recurrence is mediated by four distinct spectro-temporal neural components, which span the theta to beta frequency range. Together, our results reveal the nature and mechanisms of the effects of recurrent processing on the visual representations in the human brain.

Thin film solar cell technologies are mainly based on polycrystalline absorber layers, which is also the case for kesterite-based photovoltaic devices. An alternative technology, which is promising and low cost, is based on kesterite-type C⁢u2⁢ZnSn⁢(S,Se)4 (CZTSSe) monograins as absorbers, which are fixed in a polymer matrix to form a flexible solar cell. The large band tailing observed in Cu-based kesterite-type semiconductors is believed to cause voltage losses, limiting the efficiency of kesterite-based devices. Cu/Zn disorder, which is always present in these compounds, is discussed in literature as a possible reason for band tailing. The experimental determination and quantification of Cu/Zn disorder is possible by in-depth analysis of neutron diffraction data. This work reveals that the purity of copper used in the synthesis of CZTSSe monograins has an influence on the degree of Cu/Zn disorder in the semiconductor and thus on optical and PV parameters. Comparing CZTSSe monograins, less Cu/Zn disorder was observed for the monograins synthesized using copper with higher purity; the respective monograin-based solar cell shows a higher power conversion efficiency. On the other hand, the band gap energy as well as the photoluminescence maximum (P⁢Lmax ) of both monograins are the same. Applying a low-temperature annealing procedure allowed us to increase the quality of monograins synthesized using 5N copper, very close to the one grown using 6N copper. The P⁢Lmax slightly shifts into higher energy, which is most likely an indication of the decreased Cu/Zn disorder, either moving the defect states toward the valence band or that it reduces the formation of the tail states near the conduction band minimum.

Background Injectable opioid agonist treatment (iOAT) is an effective option to support people living with opioid use disorder (OUD) who have not sufficiently benefitted from oral OAT. However, iOAT has been criticised based on theoretical and practical grounds for its dosing policies: Current regulations demand supervised, on-site application and require patients to frequently visit their treatment facility. The current study aims to investigate how patients experience on-site application and derive strategies to enhance the acceptability and effectiveness of iOAT-delivery.MethodsThis article is based on semi-structured interviews with 27 individuals currently or previously in iOAT in two German outpatient iOAT-clinics. We undertook an inductive qualitative content analysis, which included blinded, independent coding and the analysis of individual cases.ResultsComments regarding on-site application and daily visits to the clinic were grouped into positive and negative aspects, iOAT as the best alternative option, facilitators of daily visits, and suggestions for improvement. Positive aspects took the factors stability and social support in regard. Negative aspects ranged from general inconveniences to major impediments to individuals' daily lives and towards achieving psychosocial goals. Participants reported rigorous adherence to iOAT's treatment regime, often due to a perceived lack of alternative options. Meeting iOAT's demands was eased by the patients' coping-strategies and through facilitating measures implemented by iOAT-clinics. Despite acknowledgement of the potential detriments from easing regulations, take-home arrangements were frequently suggested by participants to improve iOAT.ConclusionsBeing required to attend the clinic for supervised iOAT-application is not experienced uniformly. While clinics can support their patients to cope with strict regulations, alternative approaches to iOAT-application should be considered to accommodate patients' individual needs. Examples from other treatment modalities (e.g., remote supervision and delivery services) might aid to reconcile individualisation while providing adequate safety measures and improve iOAT in the long term.

Background: Lu-177-radiopharmaceuticals can contain the metastable impurity [Lu-177m]lutetium with a physical half-life of 160.4 days, in varying concentrations depending on the route of production of the radionuclidic precursor [Lu-177]lutetium. Due to the long half-life of [Lu-177m]lutetium, difficulties with waste disposal or sterility testing could arise. Here, we analyzed several Lu-177-samples of different origins and suppliers regarding their Lu-177m-concentration.Results: All samples tested showed a Lu-177m-concentration in the range that was stated on the certificate of analysis from the supplier which is in accordance with the European Pharmacopoeia.Conclusions: Although all Lu-177m-concentrations were in accordance with the European Pharmacopoeia, we need to take into account the respective national legislation regarding radioactivity release limits. With regard to the German legislation, several probes for sterility testing in external laboratories could not be released for transport due to the concentration of [Lu-177m]lutetium. Moreover, waste water tanks should specifically be monitored for Lu-177m-concentration, when e.g. Lutathera (R) is administered in the clinic.

Objectives: The aim of the study was to investigate computed tomography-based thermography (CTT) for ablation zone prediction in microwave ablation (MWA).Methods: CTT was investigated during MWA in an in vivo porcine liver. For CTT, serial volume scans were acquired every 30 s during ablations and every 60 s immediately after MWA. After the procedure, contrast-enhanced computed tomography (CECT) was performed. After euthanasia, the liver was removed for sampling and further examination. Color-coded CTT maps were created for visualization of ablation zones, which were compared with both CECT and macroscopy. Average CT attenuation values in Hounsfield units (HU) were statistically correlated with temperatures using Spearman's correlation coefficient. CTT was retrospectively evaluated in one patient who underwent radiofrequency ablation (RFA) treatment of renal cell carcinoma.Results: A significant correlation between HU and temperature was found with r = - 0.77 (95% confidence interval (CI), - 0.89 to - 0.57) and p < 0.001. Linear regression yielded a slope of - 1.96 HU/degree celsius (95% CI, - 2.66 to - 1.26). Color-coded CTT maps provided superior visualization of ablation zones.Conclusion: Our results show that CTT allows visualization of the ablation area and measurement of its size and is feasible in patients, encouraging further exploration in a clinical setting.Critical relevance statement: CT-based thermography research software allows visualization of the ablation zone and is feasible in patients, encouraging further exploration in a clinical setting to assess risk reduction of local recurrence.