A comprehensive analysis of viral mutations is essential for understanding viral evolution, disease epidemiology, diagnosis, drug resistance, and immune escape. However, challenges remain in capturing complex mutation patterns and supporting diverse viral families with varying genome architectures. To address these challenges, we present VARIANT, an openly accessible web server for mutational analysis of RNA viral genomes and associated viral products across both single- and multi-segment virus genomes. The server takes as input a viral reference genome, a reference protein sequence, and/or multiple sequence alignment, and automatically provides full annotation of mutation types, including standard categories such as point mutations (missense, silent, and nonsense), insertions, deletions, and frameshift events in both coding and non-coding regions. In addition, VARIANT detects two biologically significant mutation patterns that are often overlooked by conventional software/packages: "row mutations", "hot mutations", and separately annotates potential programmed ribosomal frameshifting regions. The server currently contains automatic analysis of major viral pathogens, including SARS-CoV-2, HIV-1, Influenza H3N2, Ebola virus, and Chikungunya virus. It also allows users to analyze additional viruses by uploading custom genome information. Users can track VARIANT analysis progress in real time, visualize mutation distributions, and download structured results in ZIP format. VARIANT also incorporates dual graph topology analysis to classify frameshifting element structures from dot-bracket notation input. This feature enables systematic comparison of RNA secondary structure motifs across viral families by mapping structures to a comprehensive library of dual graph topologies. The web server is freely available at https://variant.up.railway.app/.

Sphingolipid dysregulation is an emerging feature of amyotrophic lateral sclerosis (ALS), but no systematic method separates species that may worsen axon-myelin membrane integrity from matter that may counteract it. We present an in-silico framework classifying sphingolipids and designed derivatives as candidate membrane-disruptive or candidate protective species, scored against real biological referents using externally published tools rather than a bespoke composite. Its central finding concerns a single, chemically defined difference in lipid state. In coarse-grained (MARTINI 3) molecular dynamics with three independent replicates per system, intact palmitoyl-sphingomyelin is indistinguishable from a pure-POPC bilayer (leaflet-mean Δ thickness + 0.001 nm, 95% CI brackets zero), whereas the modeled N-deacylated form thins it in every replicate (Δ=-0.043 nm, [- 0.046, - 0.041]), tracking a lyso-phosphatidylcholine detergent control (-0.083 nm, [- 0.087, - 0.080]) on two concordant estimators. Because only one lyso-sphingolipid is parameterized in public MARTINI 3, N-deacylation is not established here as a class-wide effect. Across eleven ALS studies (2021-2026), six report elevated serine-palmitoyltransferase (SPT) pathway sphingolipids, all in monogenic SPTLC1/SPTLC2 cohorts, whereas sporadic cohorts show disturbance without a shared direction. Because the simulations do not address whether this species is produced, accumulates, or reaches pathological concentrations in ALS tissue, we present the ALS connection as hypothesis-generating rather than direct evidence. Separately, an explicitly exploratory arm reports two designed modulators with predicted target engagement (Boltz-2) and an ADMET triage of their liabilities. The primary contribution is the membrane result with a wet-lab panel that makes it falsifiable.

As climate change intensifies, managed aquifer recharge (MAR) can enhance water security and strengthen drought resilience by capturing surface water, such as drain flows. Assessments of MAR impact and risks to groundwater-dependent receptors require numerical modeling. Yet many studies do not account for contrasting climatic conditions, surface-water and groundwater integration, and dual ensembles of MAR operations and of hydrologic/landscape parameters when quantifying uncertainty using the iterative ensemble smoother (IES) as done here for a proposed MAR in the Myalup region of Western Australia. For each MAR scenario, decision metrics-groundwater mounding, inundation and waterlogging, travel times to environmental receptors-were evaluated across the parameter ensemble. Spatial analysis from a likely IES realization showed drain discharge constraining mound expansion, recovery mitigating small increases in drain flow, localized inundation risk, and MAR plumes reaching downgradient wetlands within two decades. Predictive uncertainty of MAR scenarios varied substantially, with climate conditions as dominant control. Wettest and driest cases bracket divertible flow conditions. Inundation risk was greater for wet than dry scenarios, suggesting drier climates may reduce MAR impacts, although wet extremes must be accommodated. Recovery reduced mounding but barely altered transport pathways. Relocating MAR away from a drain lowered uncertainty and environmental impacts. MAR designs can be selected by minimizing probabilities of exceeding stakeholder-defined thresholds or balancing trade-offs between impact metrics. This dual-ensemble methodology of MAR scenarios and IES parameters provides robust and transferable uncertainty quantification for evidence-based MAR planning under hydrologic uncertainty and climatic extremes.

Dental fluorosis alters the structure and acid resistance of dental hard tissues and impairs bonding performance. For fluorotic teeth requiring direct composite resin restorations, veneers/full-crown restorations for abnormal color and morphology, as well as orthodontic bracket bonding, reliable enamel-dentin bonding remains a key clinical concern. Based on the histopathological features of hard tissues in fluorotic teeth, this paper reviews advances in clinical-bonding research and summarizes appropriate clinical bonding strategies to inform clinical diagnosis, treatment and further related research.

Orthodontic tooth movement results from alveolar bone remodeling induced by mechanical loads applied to the teeth over extended periods during the unloading phase of arch wires. In clinical practice, orthodontic arch wires are inserted into bracket slots without precise knowledge of the forces transmitted to individual teeth. Excessive loads may lead to undesirable side effects, whereas insufficient forces may fail to initiate bone remodeling and tooth movement. This study aims to develop a 3D numerical approach based on finite element method to simulate orthodontic tooth movement during the alignment phase while quantifying the loads applied by the superelastic nickel titanium arch wire. A common clinical case of buccal infraposition of the maxillary canine was selected. Patient-specific geometries of the teeth and alveolar bone were reconstructed from cone-beam computed tomography scans. A coupling strategy between the arch wire unloading response and an external bone remodeling model was implemented to predict teeth movement over a one-month treatment period as orthodontic appointments are typically scheduled every 4 weeks. During recovery to its initial shape, the arch wire delivered light and constant forces, leading to extrusion of the canine and intrusion of the adjacent first premolar and lateral incisor. This numerical framework captured the mechanical behavior of the superelastic nickel titanium arch wire and predicted teeth movement consistent with clinical ranges reported in the literature. This approach provides an efficient tool for orthodontists to predict patient-specific orthodontic outcomes and optimize treatment design during the leveling phase.

Background/Objectives: Direct bonding of orthodontic brackets is standard in fixed-appliance therapy, but clinical success depends on achieving reliable bond strength without compromising enamel integrity during debonding. This in vitro study evaluated whether applying a metal primer to stainless-steel bracket bases affects shear bond strength (SBS) to enamel, and whether primer coverage and bracket-base design influence adhesive-remnant distribution and enamel integrity. Methods: A total of 132 extracted human maxillary premolars were randomly allocated to six groups (n = 22 each) defined by bracket base design (mesh or integral) and primer coverage (none, full, or partial central coverage). Brackets were bonded with Transbond XT, and Reliance Metal Primer was applied according to group allocation. After 2000 thermal cycles (5-55 °C), specimens were debonded in shear at 1 mm/min. SBS was calculated, adhesive remnants were quantified with ImageJ and scored using the adhesive remnant index (ARI), and enamel damage was assessed using an enamel damage index (EDI). Results: Mean SBS values were 15.68 MPa (MC), 18.38 MPa (MF), 20.89 MPa (MP), 13.04 MPa (IC), 17.11 MPa (IF), and 12.66 MPa (IP). Two-way ANOVA showed significant main effects of bracket base design (F(1, 126) = 16.06, p < 0.001, partial η[2] = 0.113) and primer coverage (F(2, 126) = 3.98, p = 0.021, partial η[2] = 0.059), together with a significant bracket-base-design × primer-coverage interaction (F(2, 126) = 4.46, p = 0.014, partial η[2] = 0.066). ARI distributions differed significantly across the six experimental groups (χ[2](15) = 75.24, p < 0.001, Cramér's V = 0.436), whereas EDI scores did not differ significantly among groups (p = 0.756). Conclusions: The effect of the metal primer on SBS depended on bracket base design and primer coverage. Partial coverage produced the highest SBS among mesh-base brackets and was significantly higher than the mesh control. Among integral-base brackets, full coverage yielded the highest numerical SBS, but within-design pairwise differences were not significant. ARI failure patterns also varied significantly across the six experimental groups, whereas no significant difference in stereomicroscopically detectable enamel damage was observed.

Background/Objectives: Patients with fixed orthodontic appliances are at increased risk of plaque accumulation, gingivitis, and caries because brackets and bands hinder mechanical hygiene. This study evaluated whether regular home use of dual-light antibacterial photodynamic therapy (aPDT) supports oral hygiene during fixed orthodontic treatment in adolescents. Methods: In a single-center, randomized, assessor-blinded trial, forty-one adolescents starting fixed orthodontic treatment were randomised to a Control group (standard hygiene) or a Test group (standard hygiene plus home-use dual-light aPDT). Visible Plaque Index (VPI%), Bleeding on Probing (BOP%), and Orthodontic Plaque Index (OPI) were assessed at baseline and 12 weeks by an assessor blinded to allocation. After two protocol-driven exclusions, 39 participants (20 Test group, 19 Control group) were analysed. Site-level proportions were compared using the chi-square test. Results: VPI decreased in both groups, with a larger mean within-group reduction in the Test group (-7.0%) than in the Control group (-3.7%); exploratory site-level analysis showed a greater reduction in plaque-positive sites in the Test group at 12 weeks (p < 0.001). BOP increased in both groups but to a smaller extent in the Test group (mean +2.4% versus +5.7%), and a higher proportion of Test-group participants maintained BOP ≤ 10% (85% versus 58%); bleeding-positive sites were lower in the Test group at 12 weeks (p < 0.001). The Test group also showed a flatter distribution of OPI scores around orthodontic brackets. No device- or protocol-related adverse events were reported. Conclusions: In adolescents undergoing fixed orthodontic treatment, regular home use of dual-light aPDT was safe and associated with better site-level plaque and bleeding control, with directional but non-significant trends at the participant level. The findings support further evaluation of dual-light aPDT as an adjunct to mechanical hygiene during this vulnerable treatment period.

Microbially induced carbonate precipitation (MICP) is a candidate technology for groundwater contaminant immobilisation, aquifer permeability reduction, and CO2 trapping. Field-scale per-cell CaCO3 yields sit approximately two orders of magnitude below the laboratory kinetic ceiling, and treatment-protocol optimisation has produced incremental gains. We ask: is the field-scale yield gap in ureolytic MICP a fundamental kinetic constraint, or a structured loss profile with mechanism identifiable in each layer? We propose a Layered Bioenergetic Partitioning (LBP) framework decomposing the gap into in-vivo enzymatic overhead, maintenance and Jahns-mechanism diversion, Ca[2+]/CaCO3-induced inactivation (mechanistically integrated over contact time), post-treatment encapsulation, and delivery. Log-uniform sampling over bracket-valued factors gives 0.042 [0.015, 0.116] ng cell[-1]d[-1] for short treatments, reproducing observed yields across four datasets without parameter fitting. The framework contains single-factor limiting-step models as special cases and yields a falsifiable intervention-layer map that reorders MICP design priorities toward layer-targeted mitigations.