Private University in the Principality of Liechtenstein

The interface between biomaterials and biological systems is crucial for medical implants and tissue engineering. Surface modifications are a key strategy for controlling interactions. Synthetic glycopolymers offer a versatile toolbox, mimicking the structure and function of natural glycoconjugates like mucins. This review highlights the significance of glycopolymers for targeted surface modifications of established biomaterials, such as silicones and poly(meth)acrylates. Controlled polymerization techniques, like the reversible-addition-fragmentation chain-transfer (RAFT) polymerization, enable the synthesis of well-defined glycopolymer architectures. Glycopolymeric surface functionalization creates tailored interfaces for different biological responses, from preventing protein and cell adhesion to promoting specific cell-type binding. The focus lies on using single, well-characterized polymeric base materials and tuning their surface properties through glycopolymer coatings to achieve various and specific functions. This approach opens new dimensions in the development of advanced biomaterials for applications like contact lenses, drug delivery systems, and biosensors and also possesses potential regulatory advantages by leveraging the safety profiles of existing materials.

<title>Abstract</title> A unique multi-receptor complex comprising GPR97, CD177, CD16b, and PAR2 was recently identified as a positive modulator of human neutrophil activation. GPR97, an adhesion G protein-coupled receptor (adhesion GPCR), binds to membrane-bound CD177-associated proteinase 3 (mPR3) and enhances its enzymatic activity. The GPR97-stimulated mPR3 then cleaves and activates PAR2, another GPCR, leading to robust inflammatory responses. However, the underlying GPR97-mediated PAR2 transactivation mechanism and its downstream signaling pathways remain poorly understood. Herein, we demonstrate that PAR2 is a unique lipid raft-dependent substrate of GPR97-activated mPR3. We further identify specific mPR3 cleavage sites on PAR2 and uncover novel intramolecular agonist peptides responsible for PAR2 activation. Lastly, we delineate the downstream signaling networks elicited by these peptide agonists, highlighting the roles of distinct G proteins and signaling effectors in shaping inflammatory responses. Collectively, our findings unveil a novel GPR97-mediated PAR2 transactivation mechanism that contributes to neutrophil activation.

Abstract Introduction Remnant cholesterol (RC) represents the cholesterol content of ApoB48- and ApoB100-containing atherogenic triglyceride-rich lipoproteins, such as chylomicrons, very-low-density lipoproteins (VLDL), and intermediate-density lipoproteins (IDL) and is calculated as total cholesterol minus low-density lipoprotein cholesterol (LDL-C) minus high-density lipoprotein cholesterol (HDL-C). RC has gained attention as a marker for cardiovascular event risk and mortality. Purpose The purpose of the study was to investigate whether RC predicts all-cause mortality in patients with established coronary artery disease, independent of the total ApoB particle count. Methods We included 1,481 patients with angiographically confirmed coronary artery disease. The mean age was 65.1 ± 10.4 years, 415 (28%) of the patients were female. The mean follow-up period was 11.3 ± 5.1 years. Results During follow-up, 52.2% (n=773) of our patients died. At baseline, the mean RC level was 23 ± 23 mg/dL, and the mean ApoB level was 96 ± 29 mg/dL. A Cox regression model demonstrated that RC was a significant predictor of all-cause mortality after adjustment for age, smoking, LDL-C, HDL-C, hypertension, type 2 diabetes, BMI, and also ApoB, with a hazard ratio (HR) for all-cause mortality of 1.14 (95% CI: 1.01–1.27, p=0.028). In contrast, ApoB was not associated with all-cause mortality after adjustment for RC (HR 0.998, 95% CI: 0.793–1.13, p=0.524). Conclusion We conclude that RC is an independent predictor of all-cause mortality, irrespective of the ApoB particle count. This finding underscores the atherogenic significance of the cholesterol content, rather than the ApoB particle count, of triglyceride-rich lipoproteins.

The multiple peptide resistance factor (MprF) is a bifunctional membrane protein found in many bacteria, including Pseudomonas aeruginosa and Staphylococcus aureus. MprF modifies inner leaflet lipid headgroups through aminoacylation and translocates modified lipid to the outer leaflet. This activity provides increased resistance to antimicrobial agents. MprF presents a promising target in multiresistant pathogens, but structural information is limited and both substrate specificity and energization of MprF-mediated lipid transport are poorly understood. Here, we present the cryo-EM structure of MprF from P. aeruginosa (PaMprF) bound to a synthetic nanobody. PaMprF adopts an "open" conformation with a wide, lipid-exposed groove on the periplasmic side that induces a local membrane deformation in molecular dynamics simulations. Using an in vitro liposome transport assay, we demonstrate that PaMprF translocates a wide range of different lipids without an external energy source. This suggests that PaMprF is the first dedicated lipid scramblase to be characterized in bacteria.

MotivationAccurate blood group allele determination is essential for both research and clinical applications. While next-generation sequencing and third-generation sequencing technologies provide a wealth of genomic data, secondary analysis pipelines often struggle with detecting variations in paralogous regions and maintaining haplotype integrity. Existing tools for blood group allele determination are frequently proprietary and lack the flexibility needed to address these challenges. To bridge this gap, we developed bloodAGENT, a versatile and open-source tool designed for analyzing genomic variation and resolving blood group alleles.ResultsbloodAGENT achieves high concordance in blood group allele determination under typical conditions but reveals a strong dependence on data completeness. Simulations show that dropout rates are the primary determinant of concordance and ambiguities, with noticeable declines at dropout rates as low as 5%. While phasing breaks have a minor overall impact, their importance remains evident in specific scenarios. These results highlight bloodAGENT’s robustness and its potential for handling complex genomic analyses.Availability and implementationhttps://github.com/ikmb/bloodAGENT.git.

Health literacy reflects the ability to make appropriate health decisions and affects health outcomes. It therefore is an important parameter in patient care and for health care providers. Health literacy in patients undergoing coronary angiography, the standard procedure for the definite evaluation of coronary artery disease (CAD) is unclear and is addressed in the present study. We recruited 515 consecutive patients (383 men and 132 women) undergoing coronary angiography for the evaluation of established or suspected stable CAD in a tertiary care setting in central Europe. Health literacy was measured using the validated HLS-EU-Q16 questionnaire. A response rate of 80.4% was achieved. Overall, 177 patients (i.e. 34.3% of the cohort) had type 2 diabetes (T2DM); the prevalence of T2DM was 36.8% in men and in 27.3% in women (p=0.047). Comparing T2DM patients to those who did not have diabetes, overall median health literacy scores (HLS) were 13 [IQR=11-15] vs. 13 [IQR=10-15] among men (p=0.424) and 12 [IQR=10-15] vs. 13 [IQR=10.25-15] among women (p=0.517). Prevalence rates of adequate (HLS 13-16), problematic (HLS 9-12) and inadequate (HLS 0-8) health literacy did not differ significantly between patients with T2DM vs. subjects without T2DM (53.0% vs. 55.4%, 34.8% vs. 29.9% and 12.2% vs. 14.7% among men and 37.5% vs. 55.6%, 45.8% vs. 31.9% and 16.7% vs. 12.5% among women, respectively. We conclude that among patients undergoing coronary angiography for the evaluation of established or suspected stable CAD, health literacy regardless of sex is suboptimal both in patients with T2DM and in non-diabetic subjects.

The A Body Shape index (ABSI) is a validated measure of visceral adiposity that is calculated based on waist circumference, height and BMI. Its power to predict cardiovascular events in patients with coronary artery disease (CAD) is unclear and is addressed in the present study. We prospectively recorded cardiovascular events in a cohort of 938 patients with CAD over a mean follow-up time of 8.1±4.2 years. At baseline, the ABSI was higher in patients with type 2 diabetes (T2DM; n=308) than in those who did not have diabetes (8.4±0.6 vs. 8.3±0.5; p=0.032). Prospectively, the ABSI significantly predicted the incidence of cardiovascular events (n=389) after adjustment for age, gender, smoking, hypertension, LDL cholesterol, HDL cholesterol, and T2DM (standardized adjusted HRs 1.12 [1.03-1.22]; p=0.009, respectively). T2DM in turn also significantly predicted cardiovascular events in this model with a HR of 1.23 [1.02-1.49]; p=0.034 after adjustment for ABSI. We conclude that ABSI and T2DM are mutually independent risk factors for cardiovascular events in patients with established CAD.

The triglyceride-glucose index (TyG) is a validated biomarker of insulin resistance. Its power to predict major cardiovascular events (MACE) in patients with established cardiovascular disease is unclear and is addressed in the present study. We enrolled 1790 consecutive patients, 1481 with angiographically proven CAD and 309 with sonographically proven PAD. Prospectively, MACE were recorded over a mean follow-up period of 10.7±5.0 years. At baseline, the TyG index was significantly higher in patients with T2DM (n=586) than in non-diabetic subjects (9.2±0.7 vs. 8.7±0.5; p&lt;0.001). During follow-up, 916 of our patients suffered MACE. The event rate was significantly higher in patients with T2DM than in non-diabetic subjects (60.2 vs. 47.7%; p&lt;0.001). The TyG index in Cox regression models adjusting for age, sex, hypertension, smoking, body mass index, and LDL cholesterol independently predicted MACE in the total study population (standardized adjusted HR 1.21 [1.12-1.30], p&lt;0.001); HRs in patients without T2DM and in diabetic subjects were 1.08 [0.95-1.25], p=0.272 and 1.16 [1.03-1.31], p=0.013, respectively, with no evidence of an interaction between TyG and T2DM (p=0.093). With T2DM additionally entered into the regression model, TyG in the total study population predicted cardiovascular events independently from the presence of T2DM (HR 1.12 [1.03- 1.23], p=0.008), while T2DM remained independently predictive of MACE after adjustment for TyG (HR 1.42 [1.19-1.67]; p&lt;0.001). From our data we conclude that the TyG index and T2DM are mutually independent predictors of MACE in patients with CAD.

Background/Objectives: High breast density is a risk factor for breast cancer and can reduce the sensitivity of mammography. Given the influence of breast density on patient risk stratification and screening accuracy, it is crucial to monitor the prevalence of extremely dense breasts within local populations. Moreover, there is a lack of comprehensive understanding regarding breast density prevalence in Switzerland. Therefore, this study aimed to determine the prevalence of breast density in a selected Swiss population. Methods: To overcome the potential variability in breast density classifications by human readers, this study utilized commercially available deep convolutional neural network breast classification software. A retrospective analysis of mammographic images of women aged 40 years and older was performed. Results: A total of 4698 mammograms from women (58 ± 11 years) were included in this study. The highest prevalence of breast density was in category C (heterogeneously dense), which was observed in 41.5% of the cases. This was followed by category B (scattered areas of fibroglandular tissue), which accounted for 22.5%. Conclusions: Notably, extremely dense breasts (category D) were significantly more common in younger women, with a prevalence of 34%. However, this rate dropped sharply to less than 10% in women over 55 years of age.