RNase T2 restricts TLR13-mediated autoinflammation in vivo.

RNA-sensing TLRs are strategically positioned in the endolysosome to detect incoming nonself RNA. RNase T2 plays a critical role in processing long, structured RNA into short oligoribonucleotides that engage TLR7 or TLR8. In addition to its positive regulatory role, RNase T2 also restricts RNA recognition through unknown mechanisms, as patients deficient in RNase T2 suffer from neuroinflammation.

Quantitative interpretation and modelling of continuous nonprotein respiratory quotients.

The Respiratory Exchange Ratio (RER), which is the ratio of total carbon dioxide produced over total oxygen consumed, serves as a qualitative measure to determine the substrate usage of a particular organism on the whole-body level. Quantification of RER by its direct conversion into %Glucose (%G) and %Lipid oxidation (%L) at a given timepoint can be done by utilizing nonprotein respiratory quotient tables. These tables, however, are limited to specific increments, and intermediate RER values are not covered by these tables.

Different PD-L1 Assays Reveal Distinct Immunobiology and Clinical Outcomes in Urothelial Cancer.

Testing for PD-L1 expression by immunohistochemistry (IHC) is used to predict immune checkpoint blockade (ICB) benefit but has performed inconsistently in urothelial cancer (UC) clinical trials. Different approaches are used for PD-L1 IHC. We analyzed paired PD-L1 IHC data on UC samples using the SP142 and 22C3 assays from the phase 3 IMvigor130 trial and found discordant findings summarized by four phenotypes: PD-L1 positive by both assays (PD-L1 double positive; PD-L1DP), PD-L1 positive by the SP142 assay only (SP142 single positive; SP142SP), PD-L1 positive by the 22C3 assay only (22C3 single positive; 22C3SP), and PD-L1 negative by both assays double negative (PD-L1 double negative; PD-L1DN).

ACQUIRED MUTATIONS IN PATIENTS WITH RELAPSED/REFRACTORY CLL WHO PROGRESSED IN THE ALPINE STUDY.

Some CLL patients who develop progressive disease (PD) during treatment with covalent Bruton tyrosine kinase inhibitors (cBTKi) acquire pathway resistance mutations in BTK or PLCG2. Here, we report gene mutation data from paired baseline and PD peripheral blood samples from 52 patients (zanubrutinib, n=24; ibrutinib, n=28) who, at an early median follow-up time of 25.7 months, progressed on zanubrutinib or ibrutinib treatment in the ALPINE trial (NCT03734016).

Addition by Subtraction: Reversing Epikeratophakia and Stromal Scarring in a Patient With Myopia Magna.

Purpose: To describe a three-phase surgical approach for managing progressive visual decline in a patient with myopia magna and a history of epikeratophakia.

Methods: A 55-year-old woman with previous epikeratophakia surgery in both eyes experienced progressive visual deterioration. The three-phase approach included: (1) removal of the epikeratophakia lenticule, (2) cataract extraction with intraocular lens implantation, and (3) transepithelial topography-guided photorefractive keratectomy (trans-PRK).

Impact of Local Air Pressure on Ion Mobilities and Data Consistency in diaPASEF-Based High Throughput Proteomics.

Data-independent acquisition (DIA) on ion mobility mass spectrometers enables deep proteome coverage and high data completeness in large-scale proteomics studies. For advanced acquisition schemes such as parallel accumulation serial fragmentation-based DIA (diaPASEF) stability of ion mobility (1/K) over time is crucial for consistent data quality. We found that minor changes in environmental air pressure systematically affect the vacuum pressure in the TIMS analyzer, causing ion mobility shifts.

Vitrimeric electrolytes - overview and perspectives.

Lithium batteries, essential for consumer electronics, transportation and the energy sector, still require further improvement in performance, safety, and sustainability. Traditonal organic solvent-based electrolytes, widely used in current systems, pose significant safety risks and restrict the development of next generation devices. Vitrimers are materials with unique physical and chemical properties, which offer a promising alternative to overcome these limitations, finally reaching processability and recyclability of solid electrolytes.

Grain-Boundary Corrosion in UO from a Defect Chemical Perspective: A Case Study of the Σ5(310)[001] Grain Boundary.

We combine atomistic and continuum simulation methods to study the defect chemistry of a model grain boundary in UO. Using atomistic methods, we calculate the formation energies of oxygen interstitials, uranium vacancies, and hole polarons (U ions) across the Σ5(310)[001] symmetric tilt grain boundary. This information is then used as input in a continuum model of point-defect concentrations at the grain boundary and in its vicinity, taking into account electrostatic (space-charge) effects.

Structural investigations of the benzoyl fluoride and the benzoacyl cation of low-melting compounds and reactive intermediates.

Acyl fluorides and acyl cations represent typical reactive intermediates in organic reactions, such as Friedel-Crafts acylation. However, the comparatively stable phenyl-substituted compounds have not been fully characterized yet, offering a promising backbone. Attempts to isolate the benzoacylium cation have only been carried out starting from the acyl chloride with weaker chloride-based Lewis acids.

Resolving spatiotemporal dynamics in bacterial multicellular populations: approaches and challenges.

SUMMARYThe development of multicellularity represents a key evolutionary transition that is crucial for the emergence of complex life forms. Although multicellularity has traditionally been studied in eukaryotes, it originates in prokaryotes. Coordinated aggregation of individual cells within the confines of a colony results in emerging, higher-level functions that benefit the population as a whole.

Pressure-driven phase transformations on MgCa(CO) huntite carbonate.

Magnesium and calcium carbonate minerals are significant reservoirs of Earth's carbon and understanding their behavior under different conditions is crucial for elucidating the mechanisms of deep carbon storage. Huntite, MgCa(CO), is one of the two stable calcium magnesium carbonate phases, together with dolomite. The distinctive cation coordination environment of Ca atoms compared to calcite-type and dolomite structures makes huntite a comparatively less dense phase.

The stress-protectant molecule trehalose mediates fluconazole tolerance in .

The incidence of non- infections has witnessed a substantial rise in recent decades. ), an opportunistic human fungal pathogen, is accountable for both superficial mucosal and life-threatening bloodstream infections, particularly in immunocompromised individuals. Distinguished by its remarkable resilience to environmental stressors, exhibits intrinsic tolerance to azoles and a high propensity to swiftly develop azole resistance during treatment.

Limited impact of hepatitis A virus 3C protease-mediated cleavage on the functions of NEMO in human hepatocytes.

NF-κB essential modulator (NEMO) is critically involved in the induction of interferons (IFNs) and pro-inflammatory cytokines. Hepatitis A virus (HAV) 3C protease was recently identified to cleave NEMO in non-hepatic cells. This study aimed at understanding efficiency and function of HAV 3C-mediated NEMO cleavage in hepatocytes.

A Proof-of-Concept for Safety Evaluation of Inhalation Exposure to Known Respiratory Irritants Using In Vitro and In Silico Methods.

There is increased interest in developing non-animal test systems for inhalation exposure safety assessments. However, defined methodologies are absent for predicting local respiratory effects from inhalation exposure to irritants. The current study introduces a concept for applying in vitro and in silico methods for inhalation exposure safety assessment.

Considerations and Challenges for Acute Inhalation Toxicity Testing and Classification of Zinc Sulphide Under REACH.

Zinc sulphide is a widely used inorganic powder, and its production has reached quantities greater than 1000 t/year. Therefore, in accordance with OECD guideline 436, an acute inhalation test was implemented to provide more accurate data. This study is crucial for ensuring the safety of workers exposed to zinc sulphide dust and complying with regulatory requirements for REACH.

Toxicity of the Herbicide Roundup Original DI in Tadpoles of and (Anura: Leptodactylidae).

Brazil is one of the largest consumers of herbicides in the world, and glyphosate-based herbicides (e.g., Roundup) are commonly applied in cropland.

Active Moss Biomonitoring of Mercury in the Mine-Polluted Area of Abbadia San Salvatore (Mt. Amiata, Central Italy).

Active biomonitoring of mercury (Hg) using non-indigenous moss bags was performed for the first time within and around the former Hg mining area of Abbadia San Salvatore (Mt. Amiata, central Italy). The purpose was to discern the Hg spatial distribution, identify the most polluted areas, and evaluate the impacts of dry and wet deposition on mosses.

Characterisation of Strains and Their Prophages That Carry Horse-Specific Leukocidin Genes .

Leukocidins of (.) are bicomponent toxins that form polymeric pores in host leukocyte membranes, leading to cell death and/or triggering apoptosis. Some of these toxin genes are located on prophages and are associated with specific hosts.

Streamlining the Journey of Research Into Clinical Practice: Making Your Patients and Practice Flourish Evaluation and Treatment of Pyogenic Spondylodiscitis of the Spine: AO Spine Knowledge Forum Trauma and Infection.

Study Design: Literature Review with clinical recommendations.

Objective: To highlight impactful studies on pyogenic spondylodiscitis (PS), identified by the AO Spine Knowledge Forum Trauma and Infection, with recommendations for their integration into clinical practice.

Methods: Five influential studies on PS that have the potential to shape current practice in spinal infections were selected and reviewed.

Assessment of the Knowledge, Attitude, and Perception (KAP) of Sheep Farmers Regarding Ticks and Tick-Borne Pathogens in Tunisia, North Africa.

Ticks and tick-borne pathogens (TBPs) are a threat to human and animal health worldwide. A structured questionnaire was used to assess the knowledge, attitudes/practices, and perceptions (KAP) of 86 farmers of extensive sheep farming systems across different agro-ecological areas in Tunisia. The response rate was about 91.

Safety, Tolerability, and Immunogenicity of the Invaplex Vaccine Co-Administered with the dmLT Adjuvant in Dutch and Zambian Adults: Study Protocol for a Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Phase Ia/b Clinical Trial.

Background: Shigella infections remain endemic in places with poor sanitation and are a leading cause of diarrheal mortality globally, as well as a major contributor to gut enteropathy and stunting. There are currently no licensed vaccines for shigellosis but it has been estimated that an effective vaccine could avert 590,000 deaths over a 20-year period. A challenge to effective Shigella vaccine development has been the low immunogenicity and protective efficacy of candidate Shigella vaccines in infants and young children.

Influenza Immunization in Very-Low-Birth-Weight Infants: Epidemiology and Long-Term Outcomes.

Background: Very-low-birth-weight infants (VLBWIs; birth weight < 1500 g) are at an increased risk of complicated influenza infection, which frequently includes pneumonia, encephalitis or even death. Data on influenza immunization and its outcome in VLBWIs are scarce. This study aimed to provide epidemiological data on influenza immunization for German VLBWIs and hypothesized that immunization would protect VLBWIs from infection-mediated neurodevelopmental impairment and preserves lung function at early school age.

Recombinant Anti-PF4 Antibodies Derived from Patients with Vaccine-Induced Immune Thrombocytopenia and Thrombosis (VITT) Facilitate Research and Laboratory Diagnosis of VITT.

Background/objectives: Adenoviral vector-based vaccines against COVID-19 rarely cause vaccine-induced immune thrombocytopenia and thrombosis (VITT), a severe adverse reaction caused by IgG antibodies against platelet factor 4 (PF4). To study VITT, patient samples are crucial but have become a scarce resource. Recombinant antibodies (rAbs) derived from VITT patient characteristic amino acid sequences of anti-PF4 IgG are an alternative to study VITT pathophysiology.

Clinical Outcome After Surgical Treatment of Traumatic Peroneal Nerve Injury: An Analysis of Risk Factors After Different Surgical Approaches.

Background: This study aims to analyze potential risk factors that may influence the clinical outcomes following surgical treatment of traumatic peroneal nerve lesions.

Methods: We conducted a retrospective analysis of patients with traumatic peroneal nerve injuries treated with decompression, split repair, or nerve grafting between 2010 and 2020. Motor function and potential risk factors were evaluated.