Moringa oleifera L. Nanosuspension Extract Administration Affects Heat Shock Protein-10 and -70 under Orthodontics Mechanical Force In Vivo.

Objective:  The mechanical stimulation known as orthodontic mechanical force (OMF) causes biological reactions in orthodontic tooth movement (OTM). Heat shock protein-70 (HSP-70) needs pro-inflammatory cytokines to trigger bone resorption in OTM; nevertheless, heat shock protein-10 (HSP-10), a "Alarmin" cytokine, should control these pro-inflammatory cytokines to get the best alveolar bone remodeling (ABR). L.

Mechanisms of RNA alternative splicing dysregulation in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype with poor prognosis. RNA alternative splicing dysregulation plays a critical role in the initiation and progression of TNBC. This article systematically introduces the basic process of RNA splicing and then focuses on reviewing the aberrant alternative splicing events and their biological effects in TNBC: 1) Multiple splicing-related factors promote tumor cell proliferation and mediate chemotherapy resistance by regulating the alternative splicing of genes involved in cell survival and drug response; 2) dysregulation of splicing regulatory networks leads to altered splicing of multiple metastasis-related genes, promoting tumor invasion and metastasis; 3) aberrant alternative splicing events participate in tumor progression by affecting the expression of DNA damage repair genes; 4) dysregulation of alternative splicing is also involved in the regulation of tumor immune evasion and stem cell properties.

Geospatial mapping of drug-resistant tuberculosis prevalence in Africa at national and sub-national levels.

Objective: To map subnational and local prevalence of drug-resistant tuberculosis (DR-TB) across Africa.

Methods: We assembled a geolocated dataset from 173 sources across 31 African countries, comprising drug susceptibility test results and covariate data from publicly available databases. We used Bayesian model-based geostatistical framework with multivariate Bayesian logistic regression model to estimate DR-TB prevalence at lower administrative levels.

Evaluating student understanding of pharmacodynamics core concepts.

Pharmacodynamics is an essential subdiscipline of pharmacology that underpins safe and effective prescribing and therapeutic decision-making, as well as drug discovery and development. The exponential increase in the number of therapeutic drugs has prompted members of the pharmacology educator community to question existing pharmacology curricula focused on individual drugs and move toward a curriculum focused on conceptual understanding. A first step towards conceptual understanding is to establish what students currently know about pharmacodynamic core concepts.

Triple-action cancer therapy using laser-activated NO-releasing metallomicellar nanophotosensitizer for pyroptosis-driven immune reprogramming.

Cancer photoimmunotherapy represents an intelligent and highly efficient therapeutic approach that harnesses the photothermal effect to precisely target and ablate tumor tissues, while simultaneously modulating the immune system to achieve tumor elimination. The integration of multifunctional therapeutic modalities for combined photoimmunotherapy requires advanced drug delivery systems. However, the design of a single nanoagent capable of serving as a multifunctional nanophotosensitizer remains a significant challenge.

Longitudinal Twin Growth Discordance Patterns and Adverse Perinatal Outcomes.

Objective: The objective of this study was to conduct a longitudinal assessment of inter-twin growth and Doppler discordance, to identify possible distinct patterns, and to investigate the predictive value of longitudinal discordance patterns for adverse perinatal outcomes in twin pregnancies.

Methods: This retrospective cohort study included twin pregnancies followed and delivered at a tertiary University Hospital in London (UK), between 2010 and 2023. We included pregnancies with at least three ultrasound assessments after 18 weeks and delivery after 34 weeks' gestation.

Chronic GIPR agonism results in pancreatic islet GIPR functional desensitisation.

Objective: There is renewed interest in targeting the glucose-dependent insulinotropic polypeptide receptor (GIPR) for treatment of obesity and type 2 diabetes. G-protein coupled receptor desensitisation is suggested to reduce the long-term efficacy of glucagon-like-peptide 1 receptor (GLP-1R) agonists and may similarly affect the efficacy of GIPR agonists. We explored the extent of pancreatic GIPR functional desensitisation with sustained agonist exposure.

Endoscopic Ultrasound-Guided Drainage of Intra-Abdominal Abscess Using 15-mm vs. 10-mm Lumen-Apposing Metal Stents: An International Case-Matched Study.

Background And Aims: Efficacy and safety of EUS-guided placement of lumen-apposing metal stents (LAMS) has been reported yet advantage of using 15-mm LAMS over 10-mm LAMS yet to be explored.

Methods: International, retrospective, case-matched study of patients with intra-abdominal abscess who underwent EUS-guided drainage with 15-mm (case) and 10-mm (control) LAMS between 03/2019 and 09/2022.

Results: 51 patients underwent EUS-guided drainage using LAMS [15-mm 29 (57%), 10-mm 22 (43%)].

Detection of genetic variability in dairy cattle infectivity for bovine tuberculosis.

This study investigated the genetics of bovine tuberculosis (bTB) infectivity in Holstein-Friesian dairy cows using British national data. The analyses included cows with recorded sires from herds affected by bTB outbreaks between 2000 and 2022. Animals were considered bTB-positive if they reacted positively to the skin test and/or had positive post-mortem findings.

Neutrophil Extracellular Traps (NETs) as a Potential Target for Anti-Aging: Role of Therapeutic Apheresis.

Neutrophil extracellular traps (NETs) are large structures composed of chromatin, histones and granule-derived proteins released extracellularly by neutrophils. They are generally considered to be a part of the antimicrobial defense strategy, preventing the dissemination of pathogens. However, overproduction of NETs or their ineffective clearance can drive various pathologies, many of which are associated with advanced age and involve uncontrolled inflammation, oxidative, cardiovascular and neurodegenerative stress as underlying mechanisms.

Prevalence of Nicotine Pouch Use Among Youth and Adults in Great Britain-Analysis of Cross-Sectional, Nationally Representative Surveys.

Background: The public health impact of new nicotine products will depend on their use by different population groups. We assessed the prevalence of nicotine pouch use among youth and adults in Great Britain (GB).

Aims And Methods: Cross-sectional annual Action on Smoking and Health Smokefree GB Adult Surveys 2020-2024 (n: 12 247 to 13 266, 18+) and Action on Smoking and Health Smokefree GB Youth Survey 2024 (n = 2872 11-18-year-olds).

Microfluidic-SERS platform with in-situ nanoparticle synthesis for rapid E. coli detection in food.

A microfluidic-surface enhanced Raman spectroscopy (SERS) platform for rapid detection of Escherichia coli in food products is proposed. By implementing a Y-junction serpentine microfluidic channel, we achieved in-situ synthesis of silver nanoparticles (AgNPs), for enhancing SERS signal intensity. The synthesis of AgNPs was guided by specific aptamers bound to the bacterial cell, which facilitated formation of nanoparticles.

N-glycosylation-modifications-driven conformational dynamics attenuate substrate inhibition of d-lactonohydrolase.

Achieving enzyme catalysis at high substrate concentrations is a substantial challenge in industrial biocatalysis, and the role of glycosylation in post-translational modifications that modulate enzyme substrate inhibition remains poorly understood. This study provides insights into the role of N-glycosylation in substrate inhibition by comparing the catalytic properties of d-lactonohydrolase (d-Lac) derived from Fusarium moniliforme expressed in prokaryotic and eukaryotic hosts. Experimental evidence indicates that recombinant d-Lac expressed in Pichia pastoris (PpLac-WT) exhibits higher hydrolysis rates at a substrate concentration of 400 g/L, with reduced substrate inhibition and enhanced stability compared to the recombinant d-Lac expressed in Escherichia coli (EcLac-WT).

Linking childhood allostatic load, early adversity and the emergence of mental health symptoms in early adulthood: Analysis of the ALSPAC longitudinal birth cohort.

Background: It has been well-established that the allostatic load (AL) index, a cumulative score of multi-system dysregulation in response to chronic stress, is significantly increased at the time of a psychiatric diagnosis. However, no studies have investigated if there is an association between the AL index in childhood and the later development of mental health symptoms in young adults.

Methods: Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a population cohort from Bristol, United Kingdom, we investigated the AL index at age 9 years and the risks for mental health symptoms at age 24 years.

PFAS contamination in tap water: Target and suspect screening of zwitterionic, cationic, and anionic species across Canada and beyond.

This study investigated the occurrence of perfluoroalkyl and polyfluoroalkyl substances (PFAS), including anionic, cationic, and zwitterionic compounds, in drinking water. Between 2021-2023, an expanded list of 76 target PFAS was screened in tap water samples mainly from Canada, but also including tap water samples from the Eastern United States, Mexico, South America (Argentina), the Caribbean (Dominican Republic, Cuba), Africa (Algeria, Cameroon, Central African Republic, Morocco, Rwanda, Tunisia), Europe (France, Greece, Italy, Spain, and the United Kingdom) and Asia (Japan, Vietnam, Iran, and Türkiye). An additional ∼ 200 suspect-target PFAS were screened using high-resolution Orbitrap mass spectrometry.

Neural network surrogate and projected gradient descent for fast and reliable finite element model calibration: A case study on an intervertebral disc.

Accurate calibration of finite element (FE) models is essential across various biomechanical applications, including human intervertebral discs (IVDs), to ensure their reliability and use in diagnosing and planning treatments. However, traditional calibration methods are computationally intensive, requiring iterative, derivative-free optimization algorithms that often take days to converge. This study addresses these challenges by introducing a novel, efficient, and effective calibration method demonstrated on a human L4-L5 IVD FE model as a case study using a neural network (NN) surrogate.

Coupling tree-ring and geomorphic analyses to reconstruct the 1950s massive Glacier Lake Outburst Flood at Grosse Glacier, Chilean Patagonia.

Over recent decades, global warming has led to sustained glacier mass reduction and the formation of glacier lakes dammed by potentially unstable moraines. When such dams break, devastating Glacial Lake Outburst Floods (GLOFs) can occur in high mountain environments with catastrophic effects on populations and infrastructure. To understand the occurrence of GLOFs in space and time, build frequency-magnitude relationships for disaster risk reduction or identify regional links between GLOF frequency and climate warming, comprehensive databases are critically needed.

Right Ventricular Injury Definition and Management in Veno-Venous Extracorporeal Membrane Oxygenation.

Right ventricular injury (RVI) in respiratory failure receiving veno-venous extracorporeal membrane oxygenation (VV ECMO) is associated with significant mortality. A scoping review is necessary to map the current literature and guide future research regarding the definition and management of RVI in patients receiving VV ECMO. We searched for relevant publications on RVI in patients receiving VV ECMO in Medline, EMBASE, and Web of Science.

Status of Sepsis Care in European Hospitals: Results from an International Cross-Sectional Survey.

Rationale: Early detection, standardized therapy, adequate infrastructure and strategies for quality improvement should constitute essential components of every hospital's sepsis plan.

Objectives: To investigate the extent to which recommendations from the sepsis guidelines are implemented and the availability of infrastructure for the care of patients with sepsis in acute hospitals.

Methods: A multidisciplinary cross-sectional questionnaire was used to investigate sepsis care in hospitals.

In silico drug repurposing at the cytoplasmic surface of human aquaporin 1.

Aquaporin 1 (AQP1) is a key channel for water transport in peritoneal dialysis. Inhibition of AQP1 could therefore impair water transport during peritoneal dialysis. It is not known whether inhibition of AQP1 occurs unintentionally due to off-target interactions of administered medications.

Kinetic Oscillation Stimulation for the Preventive Treatment of Chronic Migraine: A Randomized, Double-Blind, Sham-Controlled Trial.

Background And Objectives: The Chordate System administers kinetic oscillation stimulation (K.O.S) into the nasal cavity thereby potentially modulating the activity of trigemino-autonomic reflex.

Polymorphisms, Homocysteine Elevation, and Ischemic Stroke Susceptibility in East Asian and European Populations.

Background And Objectives: Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme that regulates folate and homocysteine metabolism. Genetic variation in has been implicated in cerebrovascular disease risk, although research in diverse populations is lacking. We thus aimed to investigate the effect of genetically predicted MTHFR activity on risk of ischemic stroke (IS) and its main subtypes using a multiancestry Mendelian randomization (MR) approach.

Targeted Next-Generation Sequencing of Cell-Free DNA to Detect -Immunoglobulin Translocation and Epstein-Barr Virus DNA in Plasma of Burkitt Lymphoma Patients in East Africa.

Purpose: Epstein-Barr virus (EBV)-positive Burkitt lymphoma (BL) affects children in sub-Saharan Africa, but diagnosis via tissue biopsy is challenging. We explored a liquid biopsy approach using targeted next-generation sequencing to detect the -immunoglobulin (-Ig) translocation and EBV DNA, assessing its potential for minimally invasive BL diagnosis.

Materials And Methods: The panel included targets for the characteristic -Ig translocation, mutations in intron 1 of , mutations in exon 2 of , and three EBV genes: EBV-encoded RNA (EBER)1, EBER2, and EBV nuclear antigen 2.

Anti-Apartheid at the periphery: a case study of grassroots activism in Dundee, 1967-1990.

The histories of the global anti-apartheid struggle, and particularly the British Anti-Apartheid Movement (AAM), have predominantly been examined through a transnational and national prism, creating an inaccurate impression of a highly centralized and homogeneous movement. We argue, however, that refining the analysis to focus on the local setting reveals a more complex and diverse movement, which has not been fully captured in the existing scholarship. Using Dundee as a case study, this article charts the emergence, character, and evolution of anti-apartheid sentiment and activity in this small, peripheral industrial Scottish city.