Vaccines and antivirals have been developed to combat virus infection, but they face the challenges of rapid and unpredictable virus mutations, which have been widely observed during COVID-19. An alternative approach is, therefore, highly needed as an additional tool to prevent virus infection. As the infection of a virus usually starts by binding to its receptor, preventing virus interaction with host cells has been considered as a promising method and has been explored by various multivalent polymeric structures. However, like small-molecule pharmaceuticals, these carefully engineered polymeric structures rarely sustain broad-spectrum efficacy, because viral proteins are morphologically diverse and evolve rapidly, enabling resistance to polymeric inhibitors through mutations in receptor-binding domains (RBDs). To address these challenges, our group developed and investigated a new class of virus inhibitors based on self-assembled supramolecules. These nanosystems are built by noncovalent conjugation of small molecules or oligomers through hydrophobic interactions, π-π stacking, hydrogen bonding, electrostatic interactions, and so on. By carefully balancing the molecular geometry and directional forces, nanostructures of different dimensions (nanofiber, nanodisk, nanosheet, nanomicelle, etc.) are obtained and functionalized with binding groups to virus spike proteins inspired by mucins, which are natural polymers forming the mucus hydrogel to prevent virus infection. By using different functional building blocks, it is possible to build heteromutlivalent nanostructures through noncovalent synthesis targeting multiple binding domains simultaneously. Distinct from covalent polymeric structures, the dynamic nature of self-assembled nanosystems allows functional groups to automatically locate complementary binding pockets on viral spike protein, thereby adapting to mutation-driven RBD changes through the adaptive presentation of binding moieties. Besides binding to virus spike protein, these nanosystems also provide steric shielding of virus particles to prevent virus interaction with host cells. These supramolecular nanosystems exhibit low toxicity and broad-spectrum antiviral activity against viruses that use distinct binding receptors, including herpes simplex virus (HSV; sulfate binding), SARS-CoV-2 (sulfate binding), and influenza A virus (IAV; sialic acid binding). To forward the application of these nanosystems, their stability should be carefully evaluated, as diverse factors in physiological conditions could affect the self-assembly of the supramolecules. Although they have been proven to be stable in cell culture conditions, a deep investigation into biological systems is still necessary. One approach to improved stability might be introducing additional reversible bonds. Besides, translating these systems will require comprehensive biosafety and bioactivity evaluation and continued chemical innovation. Collectively, these findings demonstrate the feasibility of broad-spectrum antiviral inhibitors based on supramolecular assemblies and may open new routes to design broad-spectrum virus inhibitors to assist the combat with pathogens.

The inaccessibility of magnetic dendrimers stems not only from the complexity of their synthesis but more critically from the challenge of crystallising dendritic structures. Magnetic architectures are difficult to decipher without X-ray data considering magneto-structural correlations for the rational design of molecular magnets and better understanding of the physical and magnetic properties. Here, we report the synthesis and characterisation of a tuneable magnetic hetero-trimetallic dendrimer family, MLn3Co6, with Ln3+ = La, Gd, Tb, Dy and M3+ = Cr or Co. We present, for the first time, a hetero-trimetallic dendrimer with a fully resolved X-ray structure and direct mass spectrometry evidence, providing unprecedented insight into the structural and magnetic properties of metallo-dendrimers. Furthermore, the chemical flexibility enables the synthesis of species with distinct magnetic behaviours depending on the incorporated metal ions. The choice of spin carriers determines whether the system exhibits a high-spin molecule behaviour or slow relaxation of magnetisation.

Background

Despite the proven efficacy of antipsychotics in relapse prevention in schizophrenia and schizoaffective disorder, every third patient experiences a relapse within less than one year. Relapses can worsen psychosocial and treatment related outcomes and lead to substantial economic costs, primarily due to frequent and prolonged hospitalizations. The aim of this project is to evaluate a smartphone- and web-based digital solution for detecting early warning signs of schizophrenia and schizoaffective disorder to reduce relapses and subsequent hospitalizations.

Methods

This randomized controlled trial compares the add-on use of a smartphone-based app for monitoring relapse warning signs in patients with schizophrenia and schizoaffective disorders (ICD-10 F20/F25) used within the routine psychiatric outpatient treatment against treatment as usual (TAU) without any further study-related intervention. Patients in the intervention group use the app for one year, fill in the weekly ten-item Early Warning Signs Questionnaire (EWSQ-10P) and obtain in-app feedback. Clinicians can access the symptom trajectory via a browser-accessible dashboard. If a threshold is exceeded in the inbuilt automatic algorithm, an alert is sent to both, the clinician and patient, enabling timely contact and, as part of a shared decision-making process, an optional adjustment of treatment decision. A total of 110 outpatients are recruited across eight study sites.

Discussion

Continuous monitoring of early warning signs is expected to lead to behavioral changes and to decrease the necessity and duration of psychiatric hospital stays, thereby lowering healthcare costs. Additionally, the intervention could reduce symptom severity, alleviate medication adherence, shared decision-making, patient activation or quality of life. Qualitative data is collected to better understand patient needs and preferences regarding app usage and relapses. Insights gained from this study can be integrated into routine psychiatric care, improving the long-term treatment of patients with schizophrenia or schizoaffective disorder.

Trial registration

German Clinical Trials Register (ID: DRKS00034991; registration date: 30.08.2024).

Background

West Nile virus (WNV) is spreading rapidly to numerous countries in Europe. WNV maintains an enzootic cycle with many bird species as key amplifying hosts and mosquitoes of the Culex pipiens complex as main vectors. Worldwide, nine WNV lineages have been described so far. The objective of this study was to elucidate the genetic diversity of WNV in Germany in 2023 and 2024 with a focus on birds as reservoir hosts.

Methods

A total of 86 samples (25 from 2023, 61 from 2024) from dead and live birds submitted by German state veterinary laboratories and as part of a nationwide wild bird surveillance network. Samples were selected for whole genome sequencing (WGS) based on bird species, Ct value, and location. Viral RNA was extracted from bird samples and submitted to two WNV specific reverse transcription quantitative real-time polymerase chain reaction protocols. Subsequently, viral RNAs were amplified, WGS was performed using MinION technology and WGS data were processed to determine lineages and clusters.

Results

The majority of WNV RNA positive birds selected for WGS in 2023 and 2024 were Eurasian Goshawks ( Astur gentilis , n  = 45). In 2023, WNV RNA positive birds were identified in only six federal states, as opposed to 13 federal states in 2024. All WNV RNA positive bird samples from 2023 to 2024 belonged to WNV Lineage 2 (WNV-2). Of the 86 sequenced samples, ~ 73% clustered within subcluster 2.5.3.4.3c. This subcluster, which also includes closely related sequences from Austria, Czech Republic and Slovakia, represents the dominant circulating variant. The remaining sequences (~ 27%) grouped within cluster 2.5.3.2, demonstrating the co-circulation of at least two genetically distinct WNV-2 variants in Germany.

Conclusions

These findings highlight the ongoing geographic expansion and local establishment of WNV-2 seven years after the initial detection of this virus in Germany, characterized by continuous virus evolution and the predominance of subcluster 2.5.3.4.3c, which suggests regional connectivity of transmission chains, underscoring the importance of transboundary surveillance and coordinated control measures.

The article examines the processes of musealization and re-musealization of the Coleção do Nosso Sagrado, a collection of sacred objects that narrates a history of religious oppression in Brazil within a colonial context. An analysis of three specific pieces and their custodial processes at the Museu da República, managed in shared custody with researchers and religious leaders, serves as a case study for a critical, decolonial, and reparative museology.

In 1982, Bartnik and Simon proved that area maximizing hypersurfaces are smooth, strictly spacelike and maximal (mean curvature zero) away from a singular set which consists of light rays connecting boundary points. Around the same time, Leon Simon conjectured that area maximizing hypersurfaces ought to be of class C^{1,1} across their singular set, and pointed out that, if correct, this regularity statement could not be improved to C^2 in view of a certain example. In this paper, we prove Leon Simon’s conjecture.

roadband optical pulses with attosecond to femtosecond durations provide unique opportunities for studies of time-resolved electron dynamics. However, focusing these pulses—typically ranging from the vacuum ultraviolet to the soft-X-ray region—remains challenging. Conventional refractive lenses are not suitable owing to large dispersion and strong absorption, whereas reflective optics do not suffer from these issues but have high losses. Here we demonstrate a tunable hydrogen plasma lens to focus broadband extreme-ultraviolet attosecond pulses with energies of around 20 eV and 80 eV. Simulation results suggest that the stretching of attosecond pulses is negligible, and temporal compression is possible when atto-chirp is included. A key advantage of the plasma lens is its compatibility with nonlinear frequency conversion processes like high-harmonic generation. The different focusing properties of the fundamental and harmonic frequencies allow for an efficient separation of these components. Consequently, the transmission of high-harmonic generation beamlines can be increased to more than 80% and this approach can be suitable for applications requiring high photon flux.

Opioids remain a cornerstone of pain management, but currently used therapeutics are associated with serious side effects. While κ-opioid receptor (KOR) agonists offer an alternative to classical μ-opioid receptor (MOR) agonists, their clinical potential is limited by severe adverse effects. G protein-biased KOR agonists are a promising strategy for developing safer analgesics. In this study, we used virtual screening to develop novel dual-charged naltrexamine amide derivatives as tool compounds for investigating biased agonism at the KOR. All of the predicted ligands demonstrate low-nanomolar activity and G protein bias at both the KOR and MOR. Molecular dynamics simulations revealed a key allosteric communication involving TM4, TM5, and ICL2. These compounds achieve their effects through interactions with residues E209ECL2, D2235.35, E2976.58, and K2275.39. These findings provide insight into the structural mechanisms of KOR signaling bias and inform the rational design of improved KOR therapeutics.

The current loss of freshwater biodiversity calls for immediate action, including the mobilisation of existing data and tools to support long-term conservation. Yet, establishing a global baseline for the spatial distribution of freshwater habitats and the biodiversity they host remains difficult. Such task would require standardized, high-resolution environmental information to characterise freshwater habitats anywhere in the world. To address this challenge, we present the Environment90m dataset, which aggregates a large number of environmental layers into each of the 726 million sub-catchments of the Hydrography90m dataset, corresponding to single stream segments. Specifically, Environment90m includes 45 variables related to topography and hydrography, 19 climate variables for the observation period of 1981–2010, as well as projections for 2041–2070 and 2071–2100 under the Shared Socioeconomic Pathways (SSPs) 1.26, 3.70 and 5.85, and three global circulation models (UKESM1-0-LL, MPI-ESM1-2-HR and IPSL-CM6A-LR). Moreover, Environment90m includes 22 land cover categories for the annual time-series data from 1992–2020. In addition, we provide 15 soil variables and information on aridity and modelled streamflow. Summary statistics (i.e., mean, min, max, range, sd) are provided for all continuous variables, while for categorical data, the proportion of each category is calculated within each of the sub-catchments. The data is available at https://hydrography.org/environment90m (last access: 4 February 2026). To facilitate data download and processing, we provide dedicated functions within the hydrographr R-package, and extend these also to new functions for processing upstream data of lakes. For all underlying calculations, we used the open-source tools GDAL/OGR, GRASS-GIS and AWK, so that custom data can be easily generated using the hydrographr R-package. Environment90m, along with the tools, provides an array of opportunities for research and application in spatial freshwater biodiversity science, specifically biogeographic analyses and conservation exercises in freshwater ecosystems. The metadata of the Environment90m dataset is stored at 10.18728/igb-fred-995.0 .

Auf Grundlage eines umfassenden empirischen und theoretischen Wissens haben sich didaktische Grundpositionen etabliert, die normativ modellieren, wie qualitätsvoller arithmetischer Anfangsunterricht gestaltet sein sollte. Zugleich verweisen Studien darauf, dass der arithmetische Anfangsunterricht den aus fachlicher Perspektive formulierten Qualitätsansprüchen nicht gerecht wird. Im Rahmen dieses Beitrags wird der Eindruck einer Entfachlichung des arithmetischen Anfangsunterrichts empirisch fundiert: Einerseits werden aus mathematikdidaktischen Lehrbüchern die Qualitätsnormen identifiziert, die stabile Bezugspunkte für eine Didaktik des arithmetischen Anfangsunterrichts bilden. Andererseits werden Praktiken rekonstruiert, die sich im Rahmen eines ethnographischen Forschungsprojekts als typisch für den arithmetischen Anfangsunterricht erwiesen haben. Die Gegenüberstellung von Qualitätsnormen und typischen Praktiken verweist darauf, dass letztere die von Seiten der Mathematikdidaktik formulierten Qualitätsansprüche verletzen. Aus praxistheoretischer Perspektive ist solch eine Verletzung fachlich orientierter Qualitätsnormen nicht überraschend. Die festgestellten Normbrüche werden im Rahmen dieses Beitrags deshalb einer funktionalen Analyse unterzogen. Es zeigt sich, dass sich die typischen Praktiken trotz ihrer fachlichen Normbrüchigkeit zugleich als funktional erweisen: Sie sind anschlussfähig an eine Eigenlogik des „Schule-Haltens“ und tragen so zur Lösung von Problemen bei, die sich gerade in der Anfangsphase eines schulisch organisierten Mathematikunterrichts in besonderem Maße stellen.

Covalent inhibitors and chemical probes targeting ligandable cysteine residues have emerged as powerful tools for drug discovery and proteomics. In this study, we introduce vinyl phosphonamidates (VPAs) as a novel class of latent cysteine electrophiles and assess their reactivity, selectivity, and potential for developing covalent inhibitors. Compared to well-established chloroacetamide and acrylamide electrophiles, VPAs exhibit a significantly lower intrinsic reactivity toward the model thiol glutathione. Moreover, VPA-derived covalent fragments displayed only very limited nonspecific reactivity in human cell lysate. Encouraged by these results, we developed VPA-functionalized derivatives of the FDA-approved covalent inhibitors Afatinib and Ibrutinib and evaluated their ability to engage the target protein by gel-based and mass spectrometry-based activity-based protein profiling (ABPP). Compared to commonly employed Michael acceptor-based electrophilic groups, VPA-functionalized drug ligands displayed significantly less off-targets while maintaining inhibitor efficiency. Furthermore, we leveraged the modular nature and accessibility of VPAs to develop a bifunctional proteolysis targeting chimera (PROTAC) for targeted protein degradation. The demonstrated selectivity and modularity, as exemplified by the incorporation of various ligands on the phosphorus O -substituent, of the vinyl phosphonamidate group as a cysteine-directed electrophile highlight its ability to expand the chemical space in the development of covalent inhibitors with a favorable proteome-wide reactivity profile.

Polyuronic acids are important biopolymers in marine organisms, where they contribute to extracellular matrix modulation, cell signaling, and carbon cycling. However, the intrinsic structural heterogeneity of polyuronic acids has hindered efforts to establish clear structure–function relationships. Here, we report an automated glycan assembly (AGA) approach that enables the precise synthesis of β-(1–4)-linked d -glucuronic acid (GlcA) oligomers with defined chain lengths and glycosidic linkage stereochemistry. Molecular dynamics simulations revealed a characteristic 2-fold helical conformation, with rigidity in short oligomers and enhanced flexibility emerging in longer sequences. The calcium binding behavior of these oligomers was explored by NMR titrations, revealing diffuse electrostatic binding rather than localized chelation. Polyglucuronic acid (PGA) oligomers are a well-defined molecular model for dissecting ion-mediated interactions and provide a framework for designing uronic acid-based glycomaterials with tunable properties.

Amphiphilic nanogels (ANGs) are promising colloidal carriers to improve bioavailability of poorly water-soluble drugs. In contrast to conventional hydrophilic nanogels, ANGs contain additional hydrophobic domains in their network to load hydrophobic cargos. However, optimizing drug loading remains labour-intensive due to the lack of quantitative tools that accurately capture the complex ANG–drug interactions. To address this limitation and assess drug compatibility, we developed a quantitative framework based on Flory–Huggins interaction parameters ( χ ). Key to our approach is the empirical adjustment of the correction factor α to account for unequal contributions of dispersion forces, polar interactions, and hydrogen bonds. Using a model ANG and a library of hydrophobic drugs and dyes, we established selection rules for α based on the dominant interaction type: α = 1 for dispersion-dominated, α = 0.7 for polar, and α = 0.3 for hydrogen bond-dominated systems. This enabled systematic grouping of cargos and revealed strong monotonic negative correlations between adjusted χ values and experimental loading capacities. The resulting universal calibration curve links χ to drug loading content across diverse ANG–drug systems. Consequently, our framework suggests predictive potential of solubility parameter-based models, reduces experimental burden, and supports the rational design of ANG carriers tailored to specific hydrophobic drugs.

Do people change climate-related opinions when they learn that thousands protested? Two survey field experiments tested how turnout at major climate demonstrations shaped politically interested individuals’ views in a German national election. Turnout significantly increased perceived movement efficacy, especially among more involved participants, and potentially increased internal political efficacy. Pro-environmental attitudes and vote intentions remained unchanged. Protest days appear to signal collective capacity rather than drive immediate attitude change.

Hyperketonemia (HYK), defined by blood beta-hydroxybutyrate (BHB) ≥ 1.2 mmol/L, is described as a significant risk factor for cows developing postpartum (pp) diseases and impaired reproductive performance. The goal of the present study was to observe metabolic challenges in transition cows and to identify systemic markers reflecting HYK associated with lessened reproductivity. Fifty-four Simmental cows were monitored, revealing approximately 30% prevalence of HYK at the early pp period on 7, 14, or 28 days in milk (DIM). We assessed the dry matter intake, rumination time (RT), serum liver activity index, non-esterified fatty acids (NEFAs), acute phase proteins, and uterine and oviductal health. Elevated NEFA and reduced RT 14 days antepartum were a good predictor for HYK at 7 DIM. Hyperketonemia at 14 DIM resulted in higher milk yield compared with controls. We could neither detect differences in uterine health nor in reproductive key performance parameters between hyperketonemic and control cows, whereby the proportion of polymorphonuclear neutrophils in oviductal epithelia was significantly lower in hyperketonemic cows 14 DIM. We conclude that elevated concentrations of BHB in HYK 7, 14, or 28 DIM indicated energy supply to support physiological metabolic adaptations and lactation and that, in the absence of excessive inflammation during the transition period, HYK was not a risk factor for impaired fertility.

Clinical rotations are an integral part of the veterinary curriculum. Their effect on knowledge, skills and self-perception, however, has been poorly investigated. The aim of this study was to evaluate the effect of a structured small animal clinical rotation on veterinary students in these three areas. Participating students were asked to complete an online questionnaire with questions assessing knowledge, skills and self-perception before and after their clinical rotation. A total of 61 students completed the questionnaire before and 43 after the clinical rotation, leading to 41 pre-post matches for self-assessment of skills and self-perception and 39 pairs for knowledge-based questions. The percentage of correctly answered knowledge-based questions increased statistically significantly but only by one correct answer on average. Participants rated their skills in performing specific tasks significantly higher after the clinical rotation compared to before. All participants assessed themselves as competent at history taking, performing a general examination and endotracheal intubation after the clinical rotation. However, 30–40% of participants disagreed at least partly with the sentence that they can perform neurological and ophthalmological examinations as well as interpret blood results on their own after the clinical rotation. Participants rated themselves significantly higher regarding their self-perception in the role of small animal practitioner after the clinical rotation than at the start of the rotation. The study indicated that the clinical rotation improved students’ self-assessment of their skills and attitude but did not lead to a significant improvement in knowledge.

It is known that rainfall leads to a reduction in driving speed. However, the results of various studies are inconsistent regarding the amount of speed reduction. In this study, we combine high-resolution radar-based rainfall estimates for three days with heavy rainfall with driving speeds derived from floating car data on 1.5 million road sections in Germany. Using linear regression models, we investigate the functional relationship between rainfall and driving speeds depending on road section characteristics like speed limit and number of lanes. We find that the speed reduction due to rainfall is higher at road section with higher speed limits and on multi-lane roads. On highway road section with speed limits of 130 km/h, for example, heavy rainfall of more than 8 L/m2 in five minutes leads to an average speed reduction of more than 30%, although estimates at very high rainfall intensities are subject to increased uncertainty due to data sparsity. Cross-validation shows that including rainfall as a predictor for driving speed reduces mean squared errors by up 14% in general and up to 50% in heavy rainfall conditions. Furthermore, rainfall as a continuous variable should be preferred over categorical variables for a parsimonious model. Our results demonstrate that parsimonious, interpretable models combining radar rainfall data with floating car data can capture systematic rainfall-related speed reductions across a wide range of road types. However, the analysis should be interpreted strictly as a descriptive, event-specific study. It does not support generalizable inference across time, seasons, or broader traffic conditions. To make this approach suitable for operational applications such as real-time speed prediction, route planning, and traffic management, larger multi-event datasets and the consideration of effects like weekday structure and diurnal demand patterns are required to better constrain effects under heavy rainfall conditions.

Continuous digital monitoring of sheep behaviour shows potential for early stress detection. In Part 1 of this study, a novel accelerometer-based behaviour-recognition system using a nRF52832 microcontroller with Bluetooth wireless data transfer was developed and validated. A dedicated algorithm was developed to focus on the automatic detection of rumination, which also enables the classification of resting/idling and eating. The system achieved accuracies of 0.87 (rumination), 0.90 (resting/idling), and 0.86 (eating). Specificities were 0.87, 0.95, and 0.94; sensitivities 0.89, 0.80, and 0.60; and precisions 0.79, 0.88, and 0.73, respectively. In Part 2, four sheep were continuously monitored for 24 h to establish baseline behavioural durations. Animals were then relocated in pairs to an unfamiliar enclosure for a further 24 h observation period. Relocation resulted in a significant reduction in rumination time (−45.6%, p < 0.05) and a significant increase in resting/idling (+47.9%, p < 0.05), while time spent eating decreased but did not reach statistical significance (−36.2%). These findings indicate that detecting deviations from baseline rumination and resting/idling durations may serve as suitable ethological parameters for automated, sensor-based stress alerts. With further technical refinement and validation, the developed system shows strong potential as a reliable, non-invasive tool for monitoring key sheep stress indicators.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) and Acinetobacter baumannii (CRAB) pose significant therapeutic challenges due to their high resistance and global spread. Combination therapy with colistin (COL) and meropenem (MEM) was used to enhance antimicrobial activity. This study evaluated the COL-MEM combination against CRKP and CRAB isolates with a high resistance profile. A total of 58 carbapenem-resistant clinical isolates (31 CRKP and 27 CRAB), including extensively resistant and pandrug-resistant strains, were collected over a period of 12 months. Synergy between COL and MEM was assessed by microdilution checkerboard (MCB) and time-kill (TKA) assays. Carbapenemase genes were detected using molecular methods. The results showed that the COL-MEM combination yielded synergy (35.5% and 40.7%, respectively) and additive effects (35.5% and 37.0%, respectively), while no antagonism was observed. TKA confirmed bactericidal activity, especially at doubled MCB-detected concentrations, indicating dose-dependent activity. The significant reduction in the minimum inhibitory concentration in the combination indicated its potential for dose optimization, minimizing COL-associated toxicities. Genotypic profiling showed that the expression of blaNDM and blaOxa-48 can reduce synergy. These findings, obtained with isolates of high resistance, support the efficacy of this combination therapy and could reduce the dose-related side effects of COL. However, they also highlight genotype-specific variations and COL resistance mechanisms as limiting variables.