Leipzig University

The search for novel anticancer drugs with reduced side effects and innovative therapeutic approaches remains a significant challenge. Non-steroidal anti-inflammatory drugs (NSAIDs), known to inhibit cyclooxygenase (COX) - an enzyme overexpressed in certain tumors - offer a promising avenue for cancer therapy. Additionally, icosahedral carboranes are emerging as a class of compounds with significant potential in drug design. Combining these two moieties into a single molecule presents a compelling strategy to develop drugs with dual mode of action and enhanced efficacy. Here, we report nido-carborane-NSAID conjugates, linking NSAIDs (ibuprofen, flurbiprofen or fenoprofen) to 7,8-dicarba-nido-undecaborate(-1) via methylene, ethylene or propylene spacers, which were prepared from their corresponding closo-carborane-NSAID conjugates. An efficient method for converting closo-carborane-NSAID conjugates to their corresponding nido derivatives is using CsF, without compromising the sensitive ester groups present in the system. The synthesized conjugates were thoroughly characterized using multinuclear (1H, 11B, and 13C) NMR spectroscopy. The nido-carborane conjugates demonstrated significantly enhanced COX inhibition potency compared to their closo-carborane counterparts, exhibiting a higher selectivity towards human COX-2. Furthermore, the nido-carborane conjugates with ibuprofen, flurbiprofen or fenoprofen incorporating propylene spacers 3b, 6b, and 9b, respectively, displayed the most potent activity against A549 lung cancer cells and in comparison to other tested molecules exhibited better selectivity towards malignant cells, as evidenced by selectivity index values. The main mechanism of action of these NSAID conjugates includes caspase dependent apoptosis synchronized by inhibited cell division and hyperproduction of superoxide anions, hydrogen peroxide and peroxynitrites.

The safety and efficacy of peripartum transfusion support depends on a comprehensive risk analysis, the provision of substantiated criteria for ordering blood products, and surveillance of outcomes over time. We aimed to determine bleeding frequencies and volumes of blood loss, associated patient risk factors, and the effectiveness of our transfusion support scheme. Birth records of 12,255 pregnant women who gave birth at our hospital were screened for haemorrhage volumes, mode of delivery, bleeding aetiology, accompanying risk factors as well as outcome. Transfusion related data was extracted from the electronic blood product database. A total of 204 (1.6 %) women who gave birth within the 5-year study period received at least one RBC transfusion within 48 h after delivery. Differences in haemorrhage volumes in all women compared to those receiving RBC transfusion confirmed an increased probability of RBC transfusion with larger haemorrhage volumes. Uterus atony bleeding (UAB) was the most common cause associated with transfusions. Six risk factors for RBC transfusion among transfused patients were identified that showed a probability of >10 %: Adherent placenta (31.4 %), preterm rupture of membranes (PROM) (25.5 %), age over 35 (25.0 %), a previous caesarean section (19.6 %), gestational diabetes mellitus (15.2 %), and a twin pregnancy (11.8 %). An overall crossmatch-to-transfusion (C/T) ratio of 2.75:1 was reached and no patient with major haemorrhage-related morbidity or mortality was recorded. Evaluation of peripartum haemorrhage and associated RBC transfusion using the described methodology revealed RBC transfusions in 1.6 % of all women who gave birth within the study period. The described blood ordering scheme demonstrates a safe and efficient utilisation of blood products.

Electrochemistry (EC) is an important and fascinating field in chemistry studying chemical reactions driven by electric current or, conversely, the generation of electric current from chemical reactions. Its hyphenation to mass spectrometry (MS), an ideal tool for the identification of reaction products in various systems, constitutes a valuable hybrid method for real time prediction and monitoring of electrochemical transformations. For the first time, we show how electrospray ionization - high-resolution mass spectrometry (ESI-HRMS) supports a systematic study on oxidation of benzenes of different hydroxylation grades, i.e. phenol and hydroxyphenols, in an electrochemical flow-through μ-prep cell. Besides giving valuable insights into the specifics of such systems in comparison to closed/static electrochemical cells, potentially non-favorable observations in coupling of EC and ESI are discussed. A correlation coefficient of ∼1 between the root square of the scan rate and the current suggested the kinetics to be controlled by diffusion. Pulse optimization further showed that the extent of oxidation product formation depends on the electrical potential, while MS analysis of oxidation of positional isomers of dihydroxybenzenes enabled a systematic assessment of oxidation susceptibility and associated reaction mechanisms. While the general product profile of a compound was rather robust, their intensity including the detected degree of polymerization depended on the type of supporting electrolyte, working electrode, and pH, with oligomers up to a degree of polymerization of ten (DP 10). Finally, we observed that the product profile of the electrochemical conversion resembled compound degradation in the environment, providing evidence that EC-MS hyphenation is a valuable tool for the elucidation and prediction of such processes.

Soil biodiversity and functioning are the foundation of ecosystem sustainability, but we do not know whether current nature conservation areas are efficiently protecting soils. Here, we investigated the contribution of terrestrial nature conservation areas to protect soil biodiversity and functioning across scales. We found no general positive effect on diversity of bacteria, fungi, protists, invertebrates, and nematodes, captured as richness, Shannon diversity and dissimilarity, and 5 soil functions (pathogen control, nutrient provision, soil carbon, soil organic matter decomposition, and soil aggregate stability). Our findings suggest that nature conservation areas show an inconsistent role in protecting soil biodiversity and functioning, as we found mostly non-significant and otherwise mixed effects across scales. Despite few positive and negative effects of protection status, our work highlights the urgent need to directly target soils in nature conservation.

This article presents household-level socioeconomic data on food-water-energy nexus consumption collected through a survey conducted during the first quarter of 2020 in the urban areas of the Pune Metropolitan Region, India. The dataset includes 1872 observations from households residing in both formal and informal settlements. Data were collected via door-to-door interviews in the local language using a comprehensive, structured questionnaire administered through a computer-assisted web interviewing mobile application developed by the World Bank. Quality control was ensured through digital data capture, daily monitoring during fieldwork, and post-collection data validation. The dataset comprises 606 variables, including consumption data for water, energy, and food, alongside socioeconomic factors such as household composition, income, housing conditions, migration history, and household-level strategies to cope with intermittent water supply. The dataset can be used for econometric modeling of household demand, parameterization of multi-agent models, comparative analyses across regions, and empirical studies examining household challenges related to water, energy, and food security.

IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder in which IgG4+ B cells and T cells interact to drive chronic organ inflammation. Patients with multiorgan involvement may become refractory to standard therapy, resulting in progressive organ damage and risk of organ failure. Here, we report a patient with treatment-refractory multiorgan IgG4-RD treated with CD19-directed chimeric antigen receptor (CAR) T cells and describe the clinical and immunologic effects over more than 12 months of follow-up. A 60-year-old man with IgG4-RD involving the pancreas, hepatobiliary tract, and lungs, who was refractory to long-term immunosuppression, received autologous CD19-directed CAR T cells. Disease course was monitored longitudinally and multimodal immune profiling was performed on peripheral blood. CAR T cell therapy was well tolerated, with only grade 1 cytokine release syndrome, no neurotoxicity, and transient cytopenias without infections. Treatment induced B-cell aplasia lasting 6 months, while serum IgG4 levels normalized by month 8 and remained within the reference range thereafter. FAPI (fibroblast activation protein inhibitor) PET/CT demonstrated regression of fibroinflammatory activity, accompanied by improved lung function and quality of life. Immunosuppressive therapy was completely discontinued without disease flares for more than 12 months. B cell reconstitution consisted predominantly of naïve and transitional subsets. This was paralleled by a decline in T follicular helper cells and CD4+ cytotoxic T cells and attenuation of fibro-inflammatory and B cell-mediated signaling networks on interactome analyses. In this treatment-refractory case of multiorgan IgG4-RD, CD19-directed CAR T cell therapy induced durable, treatment-free remission with normalization of serum IgG4 and improvement across multiple clinical endpoints. Multimodal immune profiling indicates that CAR T cells can reset the B cell compartment and dampen pathogenic T cell and stromal interactions, supporting prospective evaluation of CAR T cell therapy in IgG4-RD.

Positron emission tomography (PET) of the brain using [18F]fluorodeoxyglucose (FDG) is becoming increasingly important for the diagnosis and differential diagnosis of atypical parkinsonian syndrome such as multiple system atrophy (MSA), which is characterized by hypometabolism of the putamen, pons, and cerebellum. We report on a patient with clinically established MSA based on a rapidly progressive, poorly levodopa-responsive parkinsonian syndrome, multidomain autonomic failure, and imaging findings where hereditary spastic paraplegia was discussed as a differential diagnosis. PET images revealed a well-preserved glucose metabolism in the striatum, specifically in the putamen, while metabolism in the cerebellum was significantly reduced. This pattern of glucose metabolism might indicate a distinct subtype of synucleinopathy as proven by seed-amplification assay and should be taken into account when diagnosing patients with MSA.

The teaching of elementary skin lesions and the ABCDE rule are central components of undergraduate medical education in dermatology. This content is typically taught using photographs, moulages, or patient examples. Independent practice under supervision, however, is often difficult to implement in everyday clinical work. Standardized patients (SPs) equipped with moulages offer an opportunity to link technical content with communication skills. Using temporary, two-dimensional transfer tattoos or three-dimensional moulages, a wide range of common skin and nail changes can be realistically depicted on standardized patients and integrated into medical student teaching. Questionnaire-based evaluations and the results of a clinical, practical exam (Objective Structured Clinical Examination, OSCE) were used to assess the benefit and compare the required level of complexity. Eighty-six medical students in Leipzig participated in a voluntary small-group dermatology examination course to improve lesion description and skin cancer screening skills. Two-dimensional transfer tattoos specifically highlighted often-overlooked skin areas and supported training in conveying clinical findings. A total of 83.7 % of students reported a benefit from using two-dimensional tattoos. In the OSCE exam, no significant difference was observed between two- and three-dimensional depictions (p = 0.082; mean scores 22.54 vs. 23.28). Transfer tattoos provide a simple and effective means of creating realistic dermatology teaching and examination scenarios. Two-dimensional tattoos are not inferior to more complex three-dimensional moulages when used with standardized patients in an examination context.

This article focuses on the realization of incrementality in Polish verbal and nominal constructions. The object of investigation is clause-embedding reveal-type concepts like ‘prove’, ‘reveal’, or ‘show’. In Slavic languages, incremental relations have traditionally been examined in direct relation to (im)perfectivity, with imperfective verbs enforcing partial affectedness of events and objects, and perfective verbs enforcing their total affectedness. In the present paper, I take a closer look at the incremental output within the reveal-type concept. I investigate whether an incremental event comes with a fixed incremental path that remains intact independently of any morphological or syntactic modifications. My research question is: Is an incremental feature specified in the lexicon as is the aspectual value ‘(im)perfective’, or does it rather arise compositionally? To answer this question, I analyze the impact of the dative argument and the nominalization on the incremental output of clause-embedding reveal-type predicates. I demonstrate that incremental meanings are affected by the properties of an entire construction. Based on that, I propose to distinguish between two types of incrementality: the non-modifiable (im)perfectivity-dependent partial and total integration requirement, and the compositional incrementality that arises as an interplay between lexical semantics, argument structure, and the morphological shape of the respective lexeme.

Tree species differ in how they acquire nutrients through arbuscular mycorrhizal fungi (AMF) and ectomycorrhizal fungi (EMF) symbioses, yet how these contrasting mycorrhizal strategies regulate soil microbial nutrient mobilization and its coupling to tree nutrient status remains poorly resolved. Here, using a 10-year temperate tree diversity experiment, we quantified soil microbial community structure, phospholipid fatty acid (PLFA)-derived carbon (C) sources tracing, ecoenzymatic stoichiometry, and foliar nutrient pools to test how tree diversity and mycorrhizal type control the linkage between soil microbial nutrient acquisition and foliar nutrient pools. We found that the tree mycorrhizal type exerted a dominant control on microbial community structure. AMF-associated tree mixtures (plots dominated by AMF tree species) were characterized by saprotrophic Ascomycota, which exhibited a higher contribution of root-derived C to fungal biomass, whereas EMF-associated mixtures were dominated by symbiotrophic Basidiomycota that relied more strongly on detritus-derived C. Ecoenzymatic strategies diverged consistently with these contrasting C acquisition pathways. AMF-associated soils exhibited higher C-acquiring enzyme activity and a greater vector length (an index of microbial C acquisition investment), indicating stronger microbial investment in C acquisition from soil organic matter. In contrast, EMF-associated soils exhibited lower vector angles (indicating relative microbial investment in nitrogen versus phosphorus acquisition) and significantly higher nitrogen (N)-acquiring enzyme activity, reflecting enhanced microbial N acquisition. Across all tree mixtures, fungal community composition was tightly linked to ecoenzymatic stoichiometry, and both were significantly associated with foliar N pools. Partial least squares path modelling revealed that mycorrhizal type influenced foliar N pools primarily through indirect pathways contributed by fungal community structure and microbial N-acquisition strategy. Together, these results demonstrate that mycorrhizal type governs how soil microbes channel C from the tree into N mobilization pathways, thereby regulating the strength of belowground–aboveground N coupling. Our findings reveal a mechanism by which mycorrhizal associations, rather than tree diversity alone, shape soil microbe–tree interactions in temperate forest ecosystems.