Substitution-Induced Mechanistic Switching in SAr-Warheads for Cysteine Proteases.

The aim of this study was to investigate the transition from non-covalent reversible over covalent reversible to covalent irreversible inhibition of cysteine proteases by making delicate structural changes to the warhead scaffold. To this end, dipeptidic rhodesain inhibitors with different -terminal electrophilic arenes as warheads relying on the SAr mechanism were synthesized and investigated. Strong structure-activity relationships of the inhibition potency, the degree of covalency, and the reversibility of binding on the arene substitution pattern were found.

Closing the RCT Gap-A Large Meta-Analysis on the Role of Surgery in Stage I-III Small Cell Lung Cancer Patients.

Introduction: Despite clear guideline recommendations, surgery is not consistently carried out as part of multimodal therapy in stage I small cell lung cancer (SCLC) patients. The role of surgery in stages II and III is even more controversial. In the absence of current randomized control trials (RCT), we performed a meta-analysis comparing surgery versus non-surgical treatment in stage I to III SCLC patients.

Caries status in 12-year-old children, geographical location and socioeconomic conditions across European countries: A systematic review and meta-analysis.

Background: Understanding of socioeconomic context might enable more efficient evidence-based preventive strategies in oral health.

Aim: The study assessed the caries-related socioeconomic macro-factors in 12-year-olds across European countries.

Design: This systematic review involved epidemiological surveys on the caries status of 12-year-olds from 2011 to 2022.

Structural basis of p53 inactivation by cavity-creating cancer mutations and its implications for the development of mutant p53 reactivators.

The cavity-creating p53 cancer mutation Y220C is an ideal paradigm for developing small-molecule drugs based on protein stabilization. Here, we have systematically analyzed the structural and stability effects of all oncogenic Tyr-to-Cys mutations (Y126C, Y163C, Y205C, Y220C, Y234C, and Y236C) in the p53 DNA-binding domain (DBD). They were all highly destabilizing, drastically lowering the melting temperature of the protein by 8-17 °C.

Optical Monitoring of Supramolecular Interactions in Polymers.

Many stimuli-responsive materials harness the reversible association of supramolecular binding motifs to enable advanced functionalities such as self-healing, switchable adhesion, or mechanical adaptation. Despite extensive research into the structure-property relationships of these materials, direct correlations between molecular-level changes in supramolecular binding and macroscopic material behaviors have mostly remained elusive. Here, we show that this challenge can be overcome with supramolecular binding motifs featuring integrated binding indicators.

Xenogeneic matrix for basal cell carcinoma reconstruction: a case report.

This case report introduces an innovative approach for tissue regeneration post-total excision of basal cell carcinoma utilizing a xenogeneic collagen matrix coupled with injectable platelet-rich fibrin. The clinical outcome underscores the efficacy and predictability of this protocol in soft tissue regeneration. While further investigation on a larger patient cohort is warranted to fully elucidate its effects and advantages, this technique holds promise in streamlining surgical procedures following excision of extraoral neoplasms.

Love yourself as a therapist, doubt yourself as an institution? Therapist and institution effects on outcome, treatment length, and dropout.

Objective: Research suggests that some therapists achieve better outcomes than others. However, an overlooked area of study is how institution differences impact patient outcomes independent of therapist variance. This study aimed to examine the role of institution and therapist differences in adult outpatient psychotherapy.

How personality factors, coping with identity-stress, and parental rearing styles contribute to the expression of somatic complaints in emerging adults in seven countries.

Objective: Somatic complaints are frequently named by emerging adults in many countries, but psychological factors contributing to the high level of these often medically unexplained symptoms have received little attention. This study examines the influence of shared risk factors on somatic complaints in a culturally diverse sample.

Methods And Measures: In a cross-cultural survey study of 2,113 emerging adults (mean age = 22.

Controversy on health-based guidance values for bisphenol A-the need of criteria for studies that serve as a basis for risk assessment.

Since 2006, the responsible regulatory bodies have proposed five health-based guidance values (HBGV) for bisphenol A (BPA) that differ by a factor of 250,000. This range of HBGVs covers a considerable part of the range from highly toxic to relatively non-toxic substances. As such heterogeneity of regulatory opinions is a challenge not only for scientific risk assessment but also for all stakeholders, the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG) analyzed the reasons for the current discrepancy and used this example to suggest improvements for the process of HBGV recommendations.

First Observation of a Three-Resonance Structure in e^{+}e^{-}→Nonopen Charm Hadrons.

We report the measurement of the inclusive cross sections for e^{+}e^{-}→nOCH (where nOCH denotes non-open charm hadrons) with improved precision at center-of-mass (c.m.) energies from 3.

German language adaptation of the Cogniphobia Scale for Headache Disorders (CS-HD) and development of a new short form (CS-HD-6).

Objective: This study is part of the ODIN-migraine (Optimization of Diagnostic Instruments in migraine) project. It is a secondary, a priori analysis of previously collected data, and aimed to assess the psychometric properties and factor structure of the Cogniphobia Scale for Headache Disorders (CS-HD). We aimed to construct a German-language version and a short version.

The p21CIP1-CDK4-DREAM axis is a master regulator of genotoxic stress-induced cellular senescence.

Cellular senescence, a major driver of aging, can be stimulated by DNA damage, and is counteracted by the DNA repair machinery. Here we show that in p16INK4a-deficient cells, senescence induction by the environmental genotoxin B[a]P or ionizing radiation (IR) completely depends on p21CIP1. Immunoprecipitation-based mass spectrometry interactomics data revealed that during senescence induction and maintenance, p21CIP1 specifically inhibits CDK4 and thereby activates the DREAM complex.

Associations between tobacco smoking status and patch test results-A cross-sectional pilot study from the Information Network of Departments of Dermatology (IVDK).

Background: Earlier studies suggested a potential association between tobacco smoking and nickel sensitization, but little is known about other contact allergens.

Objectives: To investigate the association of smoking status and contact sensitizations as well as subtypes of dermatitis, and to analyse the sensitization profiles of tobacco smokers.

Patients And Methods: Within the Information Network of Departments of Dermatology (IVDK), we performed a cross-sectional multicentre pilot study comprising 1091 patch-tested patients from 9 departments, comparing 541 patients with a history of cigarette smoking (281 current and 260 former smokers) with 550 never-smokers.

A Mean Field to Capture Asynchronous Irregular Dynamics of Conductance-Based Networks of Adaptive Quadratic Integrate-and-Fire Neuron Models.

Mean-field models are a class of models used in computational neuroscience to study the behavior of large populations of neurons. These models are based on the idea of representing the activity of a large number of neurons as the average behavior of mean-field variables. This abstraction allows the study of large-scale neural dynamics in a computationally efficient and mathematically tractable manner.

The influence of connective tissue grafting on the reconstruction of a missing facial bone wall using immediate implant placement and simultaneous bone reconstruction: a retrospective long-term cohort study.

Purpose: This retrospective cohort study evaluates the influence of connective tissue grafts (CTG) on bone regeneration at implant sites with total loss of the buccal bone wall treated with flapless immediate implant placement (IIP) and reconstruction with autogenous bone chips (AB) within a follow-up of up to 13 years.

Methods: Sixty implants were inserted in 55 patients in sites with total loss of the buccal bone wall between 2008 and 2021. The implants were inserted and the buccal gaps were grafted by AB.

Determination of Spin-Parity Quantum Numbers of X(2370) as 0^{-+} from J/ψ→γK_{S}^{0}K_{S}^{0}η^{'}.

Based on (10087±44)×10^{6}  J/ψ events collected with the BESIII detector, a partial wave analysis of the decay J/ψ→γK_{S}^{0}K_{S}^{0}η^{'} is performed. The mass and width of the X(2370) are measured to be 2395±11(stat)_{-94}^{+26}(syst)  MeV/c^{2} and 188_{-17}^{+18}(stat)_{-33}^{+124}(syst)  MeV, respectively. The corresponding product branching fraction is B[J/ψ→γX(2370)]×B[X(2370)→f_{0}(980)η^{'}]×B[f_{0}(980)→K_{S}^{0}K_{S}^{0}]=(1.

Population genomics and epigenomics of Spirodela polyrhiza provide insights into the evolution of facultative asexuality.

Many plants are facultatively asexual, balancing short-term benefits with long-term costs of asexuality. During range expansion, natural selection likely influences the genetic controls of asexuality in these organisms. However, evidence of natural selection driving asexuality is limited, and the evolutionary consequences of asexuality on the genomic and epigenomic diversity remain controversial.

DNA-empowered synthetic cells as minimalistic life forms.

Cells, the fundamental units of life, orchestrate intricate functions - motility, adaptation, replication, communication, and self-organization within tissues. Originating from spatiotemporally organized structures and machinery, coupled with information processing in signalling networks, cells embody the 'sensor-processor-actuator' paradigm. Can we glean insights from these processes to construct primitive artificial systems with life-like properties? Using de novo design approaches, what can we uncover about the evolutionary path of life? This Review discusses the strides made in crafting synthetic cells, utilizing the powerful toolbox of structural and dynamic DNA nanoscience.

Identification of Dual Inhibitors Targeting Main Protease (M) and Cathepsin L as Potential Anti-SARS-CoV-2 Agents.

In this structure-activity relationship (SAR) study, we report the development of dual inhibitors with antiviral properties targeting the SARS-CoV-2 main protease (M) and human cathepsin L (hCatL). The novel molecules differ in the aliphatic amino acids at the P2 site and the fluorine position on the phenyl ring at the P3 site. The identified dual inhibitors showed values within 1.

Three-Dimensional-Evaluation of Aortic Changes after Frozen Elephant Trunk (FET) in Zone 0 vs. Zone 2 in Acute Type A Aortic Dissection.

The management of aortic dissection has evolved significantly over the decades, with the frozen elephant trunk (FET) procedure emerging as a key technique for treating complex aortic pathologies. Recent practices involve deploying the FET prosthesis more proximally in the aorta (Zone 0) to reduce complications, leading to questions about its impact on long-term aortic remodeling compared to traditional Zone 2 deployment. This retrospective analysis utilized 3D segmentation software to assess the volumetric changes in aortic remodeling after acute Type A aortic dissections, comparing FET stent graft deployment in Zone 0 and Zone 2.

Early life exposure to queen mandibular pheromone mediates persistent transcriptional changes in the brain of honey bee foragers.

Behavioural regulation in insect societies remains a fundamental question in sociobiology. In hymenopteran societies, the queen plays a crucial role in regulating group behaviour by affecting individual behaviour and physiology through modulation of worker gene expression. Honey bee (Apis mellifera) queens signal their presence via queen mandibular pheromone (QMP).