Fragment-based discovery of dual ligand pharmacophores for lipid-sensing transcription factors for designed polypharmacology.

Designed polypharmacology aims to exploit additive or synergistic effects of simultaneous multi-target modulation. Multifactorial diseases like metabolic dysfunction requiring multi-drug treatment may significantly benefit from this concept. To identify multi-target lead pharmacophores for the development of designed dual ligands, we performed a focused two-stage screening of fatty acid mimetic fragments for modulation of the nuclear receptors THR, PPAR, FXR and RXR which are involved in transcriptional regulation of metabolic balance.

Prognostic Stratification of pN1 Prostate Cancer After Radical Prostatectomy: A Competing Risk Analysis from a Multi-institutional Cohort.

Background And Objective: Lymph node-positive (pN1) prostate cancer (PCa) is a heterogeneous disease, and a clear definition of prognostic groups is urgently needed. We aimed to assess cancer-related mortality (CRM) in different prognostic groups of pN1 patients, created based on the pathological PCa characteristics and number of positive lymph nodes (LN+).

Methods: We conducted a retrospective, multicentre cohort study including 894 patients with pN1 disease treated at 15 European high-volume centres.

Photosystem II-Carbon Nitride Photoanodes for Scalable Biophotoelectrochemistry.

Photosystem II (PSII) is a vital photosynthetic enzyme with the potential for sustainable bioelectricity and fuel generation. However, interfacing PSII with intricate, small-scale electrodes for practical applications has been challenging. This study addresses this by creating protonated macroporous carbon nitride (MCN) as support and developing a scalable spray-freeze method to wire PSII with MCN.

CD4+T-cells create a stable mechanical environment for force-sensitive TCR:pMHC interactions.

Mechanical forces acting on ligand-engaged T-cell receptors (TCR) have previously been implicated in T-cell antigen recognition and ligand discrimination, yet their magnitude, frequency, and impact remain unclear. Here, we quantitatively assess forces across various TCR:pMHC pairs with different bond lifetimes at single-molecule resolution, both before and during T-cell activation, on platforms that either include or exclude tangential force registration. For this purpose, we use glass-supported lipid bilayers presenting pMHC conjugated to a molecular force sensor unit at its base, adhesion factors and costimulatory molecules to the approaching T-cells.

The scent of a crowd.

Maize plants recruit immunity-modulating soil microbes in response to high-density planting.

Association Between Maternal Dietary Fatty Acid Intake and Fatty Acid Composition of Placental Phospholipids.

Fatty acid status during the perinatal period is important for optimal offspring growth and development. : We aimed to test the association between maternal fatty acid (FA) intake during the third trimester of pregnancy and the FA composition of placental phospholipids, a marker of maternal fatty acid status. : This cohort study was performed on 54 mothers participating in the PREOBE study.

Treatment Strategies for First-Line PD-L1-Unselected Advanced NSCLC: A Comparative Review of Immunotherapy-Based Regimens by PD-L1 Expression and Clinical Indication.

Lung cancer remains the leading cause of cancer-related mortality worldwide. Advances in screening, diagnosis, and management have transformed clinical practice, particularly with the integration of immunotherapy and target therapies. A systematic literature search was carried out for the period between October 2016 to September 2024.

Inter-Organellar Ca Homeostasis in Plant and Animal Systems.

The regulation of calcium (Ca) homeostasis is a critical process in both plant and animal systems, involving complex interplay between various organelles and a diverse network of channels, pumps, and transporters. This review provides a concise overview of inter-organellar Ca homeostasis, highlighting key regulators and mechanisms in plant and animal cells. We discuss the roles of key Ca channels and transporters, including IPRs, RyRs, TPCs, MCUs, TRPMLs, and P2XRs in animals, as well as their plant counterparts.

The mRNA Translation Inhibitor Vioprolide A Prevents Inflammatory Pain-Like Behaviour With Limited Action on Already Established Pain-Like Behaviour in Mice.

Background: Accumulating evidence indicates that pharmacological inhibition of the translational machinery is a therapeutic strategy for various diseases. However, whether inhibitors of mRNA translation might be suitable for pain therapy remains poorly understood. Here, we tested the potential analgesic effects of the natural product vioprolide A, which targets nucleolar protein 14 (NOP14) that is essential for ribosome biogenesis, in mouse models of pain.

insights into irregular voice production as a complex nonlinear system-a case study.

The human voice exhibits diverse expressions, primarily generated by the regular oscillatory movement of both vocal folds. However, further vocal tract structures can also oscillate, as observed in different singing styles, supraglottic voice substitutes and functional voice disorders. To describe the spectrum of irregular phonation types from a nonlinear systems perspective, we conducted investigations with a professional metal singer using transnasal high-speed digital imaging combined with electroglottography and acoustic data.

[Severe degenerative changes of the temporomandibular joint associated with diffuse sclerosing osteomyelitis].

Background: Diffuse sclerosing osteomyelitis (DSO) is a rare chronic disease, which is associated with severe jaw pain, swelling of the mandible and trismus. Involvement of the temporomandibular joint is rare and reports on cases with severe destruction of the temporomandibular joint in DSO patients are so far uncommon.

Case Report: The following case report describes a 26 year-old female patient, who presented with a acute otitis media, followed by chronic mastoiditis and osteomyelitis of the skull base in her medical history, and who developed DSO in the left mandible with severe degenerative changes of the TMJ in the course of the disease.

mRNA prime-boost vaccination promotes clonal continuity in germinal center reactions and broadens SARS-CoV-2 variant coverage.

mRNA- and adenovirus-based (rAd) SARS-CoV-2 vaccines have been widely used in various homologous and heterologous prime-boost combinations. It remains unknown, however, which vaccination regimens effectively promote B cell clonal continuity (i.e.

Isolation of kinetically-stabilised diarylchalcogenide radical cations.

Chalcogenide radical cations [RE] (E = S, Se, Te) are commonly short-lived intermediates of fundamental interest. Sulfide radical cations in particular are associated in vivo with oxidative stress and neuropathological processes. Having succeeded in the preparation of meta-terphenyl-based dichalcogenide radical cations [RE] (E = S, Se, Te), and a telluride analogue [RTe] in the past, we aimed to complete the series regarding sulfur and selenium.

The potential of artificial intelligence in the early detection of systemic diseases during routine dental care.

Objective Artificial intelligence (AI) is transforming healthcare by significantly enhancing diagnostic capabilities across various disciplines. This review explores AI's potential to support dentists in identifying systemic diseases and conditions, such as skin cancer, autism spectrum disorder, hypertension, diabetes, halitosis, osteoporosis and carotid artery calcification, during routine dental care. It highlights the role of AI-based technologies in early detection and improved patient outcomes.

A multilab investigation into the N2pc as an indicator of attentional selectivity: Direct replication of Eimer (1996).

The N2pc is widely employed as an electrophysiological marker of an attention allocation. This interpretation was largely driven by the observation of an N2pc elicited by an isolated relevant target object, which was reported as Experiment 2 in Eimer (1996). All subsequent refined interpretations of the N2pc had to take this crucial finding into account.

Hypertensive Disorders in Pregnancy (HDP): Diagnostics and Therapy. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/018, June 2024).

This S2k guideline of the German Society of Gynecology and Obstetrics (DGGG) contains consensus-based recommendations for the care and treatment of women with hypertension in pregnancy. It aims to serve as a guide for all professions involved in the care of pregnant women and to improve interprofessional and interdisciplinary cooperation. A new focus was placed on patients' long-term health beyond the postpartum period.

Gender-based violence and child nutrition in fragile settings: exploring intersections and opportunities for evidence generation.

Gender-based violence (GBV) is disproportionately perpetrated against women and girls, due to harmful gender and social norms, structural gender-based power inequalities and pervasive discrimination against women and girls globally. In settings of fragility (eg, weak governance and humanitarian emergencies), risk factors for GBV are exacerbated while protective factors are eroded. Adequate nutrition is critical for mental and physical health and ensuring adequate nutrition for children in fragile settings is particularly critical.

Dose-Dependent Modulation of NMDA Receptors: Neuroprotective Mechanisms against Oxidative Stress in Hippocampal Neurons.

N-Methyl-D-Aspartate (NMDA) receptors are involved in synaptic plasticity and neuronal communication. They have various responses to oxidative stress based on the dosage of agonists or antagonists that may be applied. This study focuses on modulation of NMDA receptors in primary hippocampal neurons in oxidative stress condition to understand the effects of NMDA receptor activation and inhibition.

Effects of moderate-protein and high-protein diets, including mealworm meal or poultry by-product meal, on immunological variables in healthy adult dogs.

Background: Insect meals are increasingly being used as an ingredient in diets for dogs. However, little is known about their effects on the immune function of the animals. In the present investigation, mealworm meal was included in two complete diets with either a moderate or a high protein concentration (3.

Application of Solid Higher-Order Zincates Enables a Ni/Lassaletta-Ligand-Catalyzed, Atroposelective Negishi Cross-Coupling Reaction.

A novel atroposelective Negishi cross-coupling reaction employing recently discovered solid higher-order zincates as highly transmetalating-active reagents has been developed. Applying an earth-abundant Ni/Lassaletta-ligand-based catalyst, highly useful atropoisomeric biaryls were prepared in generally high yields and enantiomeric purities. The catalyst showed high activity toward a large variety of (pseudo)halide substrates and higher-order zincates of different synthetic origins, as well as significant catalyst control, even when employing a chiral sulfoxide substrate.

Reflection-Enhanced Raman Identification of Single Bacterial Cells Patterned Using Capillary Assembly.

Raman spectroscopy is an enticing tool for the rapid identification of pathogenic bacteria and has the potential to meet the demand for early diagnosis and timely treatment of patients. However, it remains a challenge to devise a reliable Raman detection platform to obtain reproducible signals from single bacterial cells. Herein, we utilize a reflective Ag/SiO film that enhances the intrinsically weak Raman signals by re-excitation of the bacteria and reflection of downward-scattered photons, with maximum Raman intensities recorded by exciting the central edge of each single cell.

Associations of breastfeeding with maternal and child health outcomes: umbrella review.

Background: Breastfeeding (BF) has been reported to be beneficial for both mothers and their offspring, but the evidence for these associations has not been systematically evaluated.

Objectives: This umbrella review aims to assess the credibility of existing evidence regarding the associations between BF and health outcomes in mothers and offspring.

Methods: For each health outcome, evidence levels were determined using reanalyzed random-effects estimates, between-study heterogeneity, 95% predictive intervals, publication bias, small-study effects, and excess significance bias.

Shrinking of C-S bonds of organosulfonic acids in superacidic media-investigation of the protonation of methanesulfonic acid and benzenesulfonic acid and their limits.

The reactions of methanesulfonic acid and benzenesulfonic acid in the binary superacidic systems HF/MF (M = As and Sb) were investigated to explore the strengthening effects of protonation on the C-S bond and the limits of the protonability of sulfonic acids. Herein, we report the monoprotonated species of methanesulfonic acid and benzenesulfonic acid, respectively. The salts were characterized by low-temperature vibrational spectroscopy, single-crystal X-ray diffraction, and NMR spectroscopic measurements.

An nf-core framework for the systematic comparison of alternative modeling tools: the multiple sequence alignment case study.

The computational complexity of many key bioinformatics problems has resulted in numerous alternative heuristic solutions, where no single approach consistently outperforms all others. This creates difficulties for users trying to identify the most suitable tool for their dataset and for developers managing and evaluating alternative methods. As data volumes grow, deploying these methods becomes increasingly difficult, highlighting the need for standardized frameworks for seamless tool deployment and comparison in high-performance computing (HPC) environments.