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Rare vascular diseases such as hereditary haemorrhagic telangiectasia (HHT) represent a big challenge in biomedicine: complex pathomechanisms, limited patient material, and fragmented research communities slow down therapeutic progress. We argue that two elements are pivotal to bypass this problem. First, genuine partnership with patients—ranging from biospecimen donation to agenda setting—can unlock critical resources and align research with real-world needs. Second, molecular intersections between HHT and related pathologies call for coordinated, cross-disease programmes rather than isolated efforts. Recent multi-stakeholder gatherings hosted by patient organisations in Germany and elsewhere, such as the Second Scientific Symposium by the German HHT self-help group (Morbus Osler Selbsthilfe e.V.) in May 2025, have shown that when clinicians, basic scientists from different disciplines, and affected families co-design research questions, novel in vitro models can be generated more accurately, and pragmatic clinical trials emerge. Here, we outline actual opportunities for patient-integrated cellular model systems, shared biobanking, and comparative approaches across vascular malformation syndromes. In our opinion, letting informed and well-organised patient communities assemble such meetings opens unique opportunities twofold: on the one hand, the field can finally break out of its disease-specific silos; on the other hand, the development of novel HHT therapies could be accelerated by learning from progress in related pathologies.
In vertebrates and plants, dsRNA plays crucial roles as PAMP and as a mediator of RNAi. How higher fungi respond to dsRNA is not known. We demonstrate that Magnaporthe oryzae (Mo), a globally significant crop pathogen, internalizes dsRNA across a broad size range of 21 to about 3000 bp. Incubation of fungal conidia with 10 ng/μL dsRNA, regardless of size or sequence, induced aberrant germ tube elongation, revealing a strong sequence-unspecific effect of dsRNA in this fungus. Accordingly, the synthetic dsRNA analogue poly(I:C) and dsRNA of various sizes and sequences elicited canonical fungal stress pathways, including nuclear accumulation of the stress marker mitogen-activated protein kinase Hog1p and production of ROS. Leaf application of dsRNA to the cereal model species Brachypodium distachyon suppressed the progression of leaf blast disease. Notably, the sequence-unspecific effect of dsRNA depends on higher doses, while pure sequence-specific effects were observed at low concentrations of dsRNA ( < 0.03 ng/μL). The protective effects of dsRNA were further enhanced by maintaining a gap of at least seven days between dsRNA application and inoculation, and by stabilising the dsRNA in alginate-chitosan nanoparticles. Overall, our study opens up additional possibilities for the development and use of dsRNA pesticides in agriculture.
In this study, a novel approach was developed to increase the intracellular trehalose concentration in M. brunneum blastospores by uptake from the medium, improving their desiccation tolerance. Briefly, placing the blastospores in a hypotonic environment induced solute excretion, allowing significantly increased trehalose uptake during subsequent trehalose treatment. Conductivity changes and GC–MS analysis revealed that glycerol and lactate excretion is triggered in a hypotonic NaCl solution. After hypotonic + trehalose treatment, intracellular glycerol, lactate, and glucose levels increased, while other desiccation‑protective solutes remained unaffected. A fluorescence‑based single‑cell analysis of membrane stress and death during osmotic desiccation and rehydration showed that membrane stress and cell death were strongly amplified upon rehydration. Trehalose treatment reduced this amplification, while hypotonic + trehalose treatment minimised cell death and prevented a stress response during rehydration, though it increased membrane stress during desiccation. Newly formed germ tubes were identified as critical points of membrane failure during desiccation. Ultimately, the drying survival of blastospores was significantly improved by the hypotonic + trehalose treatment compared to untreated or trehalose‑only‑treated blastospores. In summary, this technique successfully enhanced blastospore desiccation tolerance and could be adapted to load cells with other solutes.
We developed a formulation of long double-stranded RNA (dsRNA) using interpolyelectrolyte complexes (IPECs) composed of the biopolymers chitosan and alginate, in order to protect the dsRNA from biotic and abiotic factors. Our primary objectives were to enhance stability of dsRNA against environmental nucleases and, secondarily, to mitigate the negative charge of the dsRNA, which may promote foliar uptake. Our approach relies on submicron particles with adjustable surface charge being either positive or negative. Following this approach, we obtained a high encapsulation efficiency of 94 %. Subsequently, we investigated the influence of the charge ratio and total polymer content on the size, size distribution and ζ-potential of the IPECs. We discovered that formulating at low polymer concentrations ≤0.05 g/L with charge ratios of ≤0.9 (+/ ) and ≥ 1.25 (+/ ), respectively, produced <100 nm particles. Furthermore, the IPEC formulation protected dsRNA from enzymatic degradation by RNase III and micrococcal nuclease. In addition, we observed outstanding protection of formulated dsRNA from heat degradation. Experiments on Nicotiana benthamiana plants showed that formulated dsRNA offered protection against tobacco mosaic virus. In essence, this formulation demonstrates versatility for the production of IPECs with customizable size, surface charge, and nucleic acid content.
From 2035 onwards, the European Union will no longer register any new vehicles that are not powered in a climate-neutral way. In alignment with this policy, Germany aims to perceived carbon neutrality by 2045, with the electrification of transport playing a central role. Corporate fleets are particularly well-suited for electrification due to their relatively short ownership cycles and frequent vehicle renewals. However, the pace of adoption in organizations remains slow. The success of such technological transitions depends largely on acceptance at the decision-making level. This study investigates the determinants of organizational decision-makers’ behavioral intention to electrify their corporate fleets prior to implementation. To this end, the newly developed Acceptance Model for Electrification (eAM) integrates the two-stage innovation decision-making process within companies. The model accounts for 60% of the variance in behavioral intention. Drawing on the findings, this paper proposes practical recommendations for policy development.
Rivers face constant anthropogenic stress, resulting in significant changes in microbial community composition. What remains unclear is whether stream microbiomes exhibit distinct resilience patterns in composition and/or activity upon exposure to different stressors. By subjecting 64 river-connected mesocosms to multiple stressors, we show that sediment microbiomes of small lowland rivers are highly sensitive to low flow velocity. This stress results in altered community compositions incapable of mitigating the applied stressor within a two-week timeframe despite functional stability (inferred via metagenomics). Transcriptomics revealed a systematic heat shock response in the community and a highly active, metabolically versatile, uncharacterized anaerobic keystone species. Increases in temperature (+ 3.5°C) or salinity (+ 0.5 mS/cm) elicited minor responses at community and transcriptomic levels (e.g., upregulation of photosystems). Following a two-week recovery, transcriptomic-inferred stress responses vanished completely, underscoring the river microbiome resilience. Given the complex community responses observed at the activity and compositional levels, we conclude that maintaining natural river flow is vital to preventing energy loss and reduced microbiome activity in river sediments.
The discharge of treated wastewater (TWW) into freshwater ecosystems poses a significant impact on microbial communities, particularly protists, which play a crucial role in nutrient cycling and ecosystem stability. While the ecological effects of TWW on microbial diversity have been studied, understanding the functional responses of protist communities remains limited. This study employs metatranscriptomics to unravel the temporal dynamics of protist community functions in response to TWW exposure. Using mesocosm experiment, water samples were analyzed over a ten-day period to monitor shifts in metabolic pathways and community interactions. Our results indicate that processed metatranscriptomic data, focusing on treatment-significant pathways, is more sensitive than traditional methods, such as meta-barcoding, and non-target screening, in detecting wastewater-induced perturbations. Early exposure to TWW significantly altered expression of pathways associated with signal transduction and environmental interaction, while general metabolic pathways showed resilience. Over time, the protist community showed signs of adaptation with expression levels stabilizing towards the end of the experiment. This study underscores the importance of focussing on functional shifts rather than just taxonomic changes for assessing wastewater impacts on freshwater ecosystems. Our findings advocate for the use of metatranscriptomics as a robust indicator for TWW detection, aiding in development of targeted environmental management strategies.
Significant progress in high-throughput analytical techniques has paved the way for novel approaches to integrating data sets from different compartments. This study leverages nontarget screening (NTS) via liquid chromatography-high-resolution mass spectrometry (LC-HRMS), a crucial technique for analyzing organic micropollutants and their transformation products, in combination with biological indicators. We propose a combined multivariate data processing framework that integrates LC-HRMS-based NTS data with other high-throughput data sets, exemplified here by 18S V9 rRNA and full-length 16S rRNA gene metabarcoding data sets. The power of data fusion is demonstrated by systematically evaluating the impact of treated wastewater (TWW) over time on an aquatic ecosystem through a controlled mesocosm experiment. Highly compressed NTS data were compiled through the implementation of the region of interest-multivariate curve resolution-alternating least-squares (MCR-ALS) method, known as ROIMCR. By integrating ANOVA-simultaneous component analysis with structural learning and integrative decomposition (SLIDE), the innovative SLIDE-ASCA approach enables the decomposition of global and partial common, as well as distinct variation sources arising from experimental factors and their possible interactions. SLIDE-ASCA results indicate that temporal variability explains a much larger portion of the variance (74.6%) than the treatment effect, with both contributing to global shared space variation (41%). Design structure benefits include enhanced interpretability, improved detection of key features, and a more accurate representation of complex interactions between chemical and biological data. This approach offers a greater understanding of the natural and wastewater-influenced temporal patterns for each data source, as well as reveals associations between chemical and biological markers in an exemplified perturbed aquatic ecosystem.
The decomposition of organic matter is essential for sustaining the health of freshwater ecosystems by enabling nutrient recycling, sustaining food webs, and shaping habitat conditions, which collectively enhance ecosystem resilience and productivity. Bacteria and fungi play a crucial role in this process by breaking down coarse particulate organic matter (CPOM), such as leaf litter, into nutrients available for other organisms. However, the specific contribution of bacteria and their functional interactions with fungi in freshwater sediments have yet to be thoroughly explored. In the following study, we enriched organic matter through the addition of alder (Alnus glutinosa) leaves into artificial stream channels (AquaFlow mesocosms). We then investigated enzyme expression, metabolic pathways, and community composition of fungi and bacteria involved in the degradation of CPOM through metatranscriptomics and amplicon sequencing. Enzymes involved in the degradation of lignin, cellulose, and hemicellulose were selectively upregulated with increased organic matter. Analysis of ITS and 16S rRNA gene sequences revealed that during decomposition, fungal communities were predominantly composed of Basidiomycota and Ascomycota, while bacterial communities were largely dominated by Pseudomonadota and Bacteroidota. The similar gene expression patterns of CPOM degradation related enzymes observed between bacteria and fungi indicate potential functional interaction between these microbial groups. This correlation in enzyme expression may indicate that bacteria and fungi are jointly involved in the breakdown of coarse particulate organic matter, potentially through mutualistic interaction. This study uncovers the specific enzymatic activities of bacteria and fungi and the importance of microbial interactions in organic matter decomposition, revealing their central role in facilitating nutrient cycling and maintaining the ecological health and stability of freshwater ecosystems.
The synergistic combination of various sorbitol-based organogelators with polyolefins allows the preparation of porous support structures for immobilized phase change materials (PCMs). Using a PCM as a solvent for the preparation leads to dimensionally stable composite materials with extremely high loading rates and low leakage of PCMs. Detailed investigations were performed on the kind of polyolefin support and its mass fraction concentration in the PCM, the temperature-dependent softening and failure under superimposed load, the efficiency of heat transport and the retention capacity over several melting/solidification cycles in various measurement setups. In particular, paraffin wax in combination with 1,2,3-trideoxy-4,6:5,7-bis-O-[(4-propylphenyl)methylene]-nonitol (TBPMN) and ultrahigh molecular weight polyethylene (UHMWPE) showed the best results in terms of high dimensional stability, low leakage, excellent processability and competitive heat capacity. The herein-established one-step preparation method saves time and energy compared to the loading of pre-formed porous supports and improves application-related properties at the same time.

