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Physics of Fluids

AIP Publishing

Preprints posted in the last 30 days, ranked by how well they match Physics of Fluids's content profile, based on 13 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

1
Constrained Laser-Induced Cavitation for Miniaturized Treatment of Deep Vein Thrombosis

Yang, J.; Li, D.; Wang, K.; Zhong, P.; Yao, J.

2026-08-20 bioengineering 10.64898/2026.08.14.744960 medRxiv
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Chronic, mechanically resilient thrombi remain difficult to remove rapidly and safely using existing therapies, which are limited by slow treatment speeds, reduced efficacy against aged clots and risks associated with embolic debris. Here we introduce Constrained Laser-Induced Cavitation (CLIC), a novel approach that confines laser-induced cavitation bubble generation and collapse within a miniaturized waveguide to enhance thrombolysis. Optimized CLIC removed retracted clots at a mass-loss rate of 393.5 mg/min, [~]40-fold higher than reported state-of-the-art sonothrombolysis under similar conditions. Systematic variation of channel length and laser parameters showed that CLIC efficacy depends strongly on treatment geometry and cavitation dynamics. Post-treatment analysis revealed cylindrical channels consistent with clot removal dominated by fluid jetting and suction-driven evacuation, with cavitation shockwaves likely contributing a secondary role. Debris fragment measurements remained predominantly below a 1 mm embolic-risk threshold, consistent with a promising embolic safety profile. These findings establish CLIC as a viable strategy for rapid thrombolysis of chronic, mechanically resistant thrombi.

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Cost Minimisation and Threshold Analysis of Anatomical Endoscopic Enucleation of the Prostate

Ong, J.; Lau, R.; Chow, K. M.; Huned, D.; Teo, R.; Lee, H. J.; Lim, E. J.; Aslim, E.; Lim, Y. W.; Chen, K.; Tan, Y. Q.; Park, J. J.; Tung, J.

2026-08-17 urology 10.64898/2026.08.15.26360519 medRxiv
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Introduction Anatomical endoscopic enucleation of the prostate (AEEP) techniques, including bipolar enucleation (B-TUEP), holmium laser enucleation (HoLEP), thulium laser enucleation (ThuLEP), and thulium fibre laser enucleation (ThuFLEP), demonstrate comparable clinical outcomes for benign prostatic hyperplasia. As clinical equivalence is increasingly established, cost becomes a key determinant of modality selection. We performed a cost minimisation analysis comparing index procedural costs across AEEP modalities from an institutional perspective. Methods A cost minimisation model was developed from the institutional perspective, incorporating amortised capital costs, maintenance, and consumables. In addition to the base-case scenario of 180 cases per year, we modelled two additional case volume scenarios: low (50 cases/year) and high (500 cases/year) volume. Thu:YAG laser fibres were modelled on two scenarios: disposable single-use, and reusable fibres (up to 10 cases per fibre). Breakeven analysis determined the threshold volume at which each laser modality achieves cost parity with B-TUEP, and one-way sensitivity analysis was performed on key cost parameters. Analysis was limited to index procedural costs calculated in Singapore dollars. Results At the base case of 180 cases per year, B-TUEP had the lowest index procedure cost (SGD 1,018), followed by ThuFLEP (SGD 1,584), ThuLEP (1,599), and HoLEP (SGD 1,655). Breakeven analysis demonstrated that HoLEP, ThuLEP, and ThuFLEP can never achieve cost parity with B-TUEP when laser fibres are single-use, as laser modalities carry higher costs on both capital and per-case dimensions. ThuLEP with reusable fibres (10 uses per fibre) was the only modality to cross below B-TUEP, at a breakeven volume of 198 cases per year. At 500 cases per year with reusable fibres, ThuLEP achieved the lowest cost (SGD 847), representing a 15.4% saving over B-TUEP. Sensitivity analysis identified annual case volume and B-TUEP loop cost as the most influential parameters. Conclusion Index procedural costs in AEEP are strongly influenced by case volume and consumable strategy. While B-TUEP remains cost-efficient at low volume, high-volume practice combined with reusable Thu:YAG fibre technology enables cost parity and potential cost advantage for laser enucleation. These findings highlight the importance of economies of scale and device utilisation in technology adoption.

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Controlled Substrate Crossover from Cathode to Anode for Long-Term Autonomous Operation of Microbial Fuel Cells: A Transport-Reaction Modeling Study

Gamboa Velasquez, M.; Meneses Sandoval, R. G.; Balderrama Perez, J. M.; Medina Villafuerte, M. E.; Solis Valdivia, J. L.

2026-08-19 bioengineering 10.64898/2026.08.14.744300 medRxiv
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Microbial fuel cells (MFCs) have been widely investigated as decentralized bioelectrochemical systems capable of converting organic substrates into electricity. However, their long-term autonomous operation is constrained by substrate depletion in the anode compartment, leading to metabolic starvation of electroactive biofilms and a decline in power output. Conventional MFC design treats substrate crossover through the membrane separator as a parasitic loss that reduces coulombic efficiency. In this work, we propose a conceptual inversion of this paradigm by considering controlled cathodic-to-anodic substrate crossover as a passive mechanism to sustain basal microbial metabolism during periods of substrate scarcity. A transport-reaction framework is developed to quantify the balance between membrane-mediated substrate flux and microbial maintenance demand within the anode biofilm. Based on this balance, a dimensionless maintenance crossover Damkohler number (Dam) is introduced to define three operational regimes: starvation-dominated (Dam >> 1), balanced autonomous (Dam {approx} 1), and crossover-dominated (Dam << 1). The framework integrates membrane transport theory with biofilm kinetics to evaluate the effects of separator properties, substrate gradients, and current-dependent electro-osmotic transport on system stability. Order-of-magnitude analysis indicates that achievable crossover fluxes span several orders of magnitude depending on separator characteristics, suggesting that membrane properties critically influence system behavior. This perspective reframes substrate crossover from a loss mechanism to a potential design variable, offering a conceptual tool for enhancing resilience and guiding separator selection in MFCs intended for long-duration, and low-maintenance operation. HighlightsO_LIControlled crossover can sustain microbial metabolism in MFCs C_LIO_LIIntroduces maintenance crossover Damkohler number (Dam) C_LIO_LIIdentifies regimes for autonomous and starvation operation C_LIO_LILinks membrane properties to long-term system stability C_LIO_LIReframes crossover as a design variable, not only a loss C_LI

4
Absolute measures of time-difference-of-arrival positioning error in underwater acoustic telemetry setups

Campbell, J. A.; Lundberg, P.; Hölker, F.

2026-08-25 ecology 10.64898/2026.08.24.746702 medRxiv
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This brief communication presents two solutions for calculating absolute measures of error from time-difference-of-arrival (TDOA) positioning in underwater acoustic telemetry arrays. First, a Monte Carlo estimation of TDOA positioning error is derived. Next, a computationally inexpensive, approximate solution to the Monte Carlo method is presented. This approximate solution is achieved by solving the Jacobian of a closed-form TDOA positioning model. The positioning error covariance matrix returned from either method can then be used to report the accuracy of TDOA positions or utilized in state-space positioning models. Finally, calculations of the expected radial error are shown which serves as a simple summary statistic for reporting positioning error in real units.

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Laboratory efficacy of a solar-powered spatial repellent device against Anopheles mosquitoes

Jones, R. T.; Dennehy, J.; Turner, M. A.; Dyall, W.; Spencer, F. I.; Owusu, I.; Jenkins, A.; Hiscox, A.; Dewhirst, S. Y.; Logan, J. G.

2026-08-18 ecology 10.64898/2026.08.13.744622 medRxiv
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Spatial repellents represent a promising approach to complement existing malaria vector control interventions by reducing contact between mosquitoes and humans. However, the efficacy of passive spatial repellent devices may be affected by environmental conditions, particularly temperature and airflow, which can influence the release of volatile active ingredients. Active-release devices may provide more consistent delivery of spatial repellent compounds. We investigated the efficacy of a commercially available battery-powered spatial repellent device and a low-power solar-powered device designed for potential use in Africa. Laboratory trials were conducted to evaluate the efficacy of the two spatial repellent devices against Anopheles mosquitoes. Protective efficacy was assessed by comparing mosquito probing on human participants during spatial-repellent and control tests. The effect of the devices on mosquito entry into the test chamber was also assessed. The protective efficacy was 86% with the commercial battery-powered device and 80% with the low-power solar-powered device. A Wilcoxon rank-sum test showed that there was no significant difference between the performance of the two devices in terms of protective efficacy (p = 0.856) or entry inhibition (p = 0.7989). The low-power device could be charged using a small, household-level photovoltaic panel, to provide a potentially practical means of delivering spatial repellents in off-grid settings.

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Physics-Informed Estimation of Electrostatic Attraction During Fingertip Sliding Under Varying Speed and Normal Force

Kenanoglu, C. U.; Vardar, Y.

2026-08-11 biophysics 10.64898/2026.08.05.743019 medRxiv
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Electrostatic actuation is an emerging technology for generating tactile sensations on capacitive touchscreens through voltage-induced attractive forces between a fingertip and the surface. However, accurate control of electrostatic attraction during natural touchscreen interactions remains challenging because the applied normal force and sliding speed continuously vary, and their effects on the fingertip-screen contact and resulting actuation strength are not fully characterized. Here, we show how normal force and sliding speed systematically alter fingertip- screen contact area and electrical impedance, and use these measured changes to estimate electrostatic attraction during sliding. Contact area, interaction forces, and electrical impedance were measured simultaneously as participants slid their fingertips across an electrostatic surface under systematically varied normal forces and sliding speeds. These measurements revealed condition-dependent changes in fingertip contact, electrical interaction impedance, effective capacitance, derived effective gap thickness, and electrostatic attraction. We then incorporated these measured contact quantities into a physics-informed, data-driven model based on parallel-plate capacitor theory, in which effective capacitance, apparent contact area, and effective voltage determine the estimated electrostatic attraction. The resulting model links force- and speed-dependent changes in these quantities to electrostatic attraction while accounting for inter-participant variability through a participant-specific scaling factor. These findings provide experimentally grounded guidance for designing electrostatic surface-haptic feedback and future adaptive control strategies under realistic touch conditions.

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Three-dimensional Imaging of Colonial Cyanobacteria with Optical Coherence Tomography

Sinzato, Y. Z.; Uittenbogaard, R.; Visser, P. M.; Huisman, J.; Jalaal, M.

2026-08-28 ecology 10.64898/2026.08.27.747059 medRxiv
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The morphology of cyanobacterial colonies plays a key role in harmful cyanobacterial blooms, with implications for their vertical migration, resistance against grazing, and light availability. In this study, we introduce the use of Optical Coherence Tomography (OCT) to investigate the three-dimensional morphology of cyanobacterial colonies. The technique enables non-invasive 3D imaging of colonies up to several millimeters in size, providing access to detailed mesoscale morphological features. Gas vesicles inside cells were shown to strongly improve image quality. We describe the sample preparation and image acquisition protocol, as well as an image processing pipeline that extracts mesoscale morphological features and provides a volumetric visualization of colonies. The method was tested for representative colonies of different cyanobacterial species while a dataset of volumetric images and measured mesoscale features was acquired for natural colonies of Microcystis. We demonstrate the utility of 3D imaging by quantifying the effects of irregular colony morphologies on their flotation velocity and the light availability within colonies. We anticipate OCT to become a key imaging technique to monitor populations of cyanobacterial colonies and investigate colony formation, with potential extensions to other colonial and aggregated organisms in freshwater and marine environments.

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Fingertip-Surface Interfacial Shear Stress Varies with Sliding Conditions and Electrostatic Actuation

Kenanoglu, C. U.; Vardar, Y.

2026-08-20 biophysics 10.64898/2026.08.13.744590 medRxiv
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Fingertip friction plays a central role in tactile exploration and object manipulation. During sliding, tangential force depends jointly on the real contact area and the interfacial shear stress, both of which can be influenced by sliding conditions. However, changes in fingertip friction are often interpreted primarily through changes in real contact area, whereas the accompanying changes in interfacial shear stress remain less well characterized. This gap is especially relevant for electrostatic surface haptic displays, which modulate fingertip friction by applying a voltage between the finger and the touch surface. Here, we experimentally quantify the mean interfacial shear stress of a sliding fingertip on an electrostatically actuated touchscreen using simultaneous measurements of tangential force and optically resolved real contact area. Ten participants performed sliding trials across three speeds and three normal forces with and without electrostatic actuation. Interfacial shear stress increased with speed and decreased with normal force; in both cases, these trends arose because real contact area varied more strongly than tangential force. Electrostatic actuation further reduced interfacial shear stress, as increasing voltage produced a larger increase in real contact area than in tangential force. These findings show that interfacial shear stress varies systematically with sliding conditions and electrostatic actuation, clarifying how changes in real contact area and interfacial shear stress combine to shape fingertip-surface friction.

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Fine-scale flight behaviour reveals eagles' response to different uplift sources and highlights observational gaps in high-resolution weather models.

Frisoni, F.; Carrard, T.; U. Gruebler, M.; S. Hatzl, J.; Safi, K.; A. Sprenger, M.; Sumasgutner, P.; Wikelski, M.; Scacco, M.

2026-08-19 ecology 10.64898/2026.08.18.745477 medRxiv
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Understanding how animals respond to their physical environment requires environmental observations at the scale at which behavioural decisions are made. For soaring birds, the coarse resolution of weather products has long hindered the analysis of their behavioural response to fine-scale atmospheric dynamics, forcing uplift sources to be inferred largely from behaviour itself. Here, we combined high-resolution movement data from 24 golden eagles with the kilometre-scale COSMO weather model. We first classified thermal, orographic, and gravity-wave uplifts using independent atmospheric predictors and then quantified the birds' use of each uplift type and their fine-scale behavioural responses. Eagles relied predominantly on thermals, but opportunistically adjusted their use of uplift sources seasonally. The birds' flight behaviour could not reliably indicate which uplift type was primarily used, and thus suggests that both atmospheric processes and behavioural responses are better described as continua than discrete categories. Finally, we compared vertical wind velocities derived from eagles soaring behaviour with those modelled by the COSMO weather model, showing that most of the thermals exploited by eagles remain unresolved at kilometre-scale model resolution. Our results demonstrate how high-resolution weather models provide new insights into bird movement decisions, while also highlighting the potential of soaring birds as biologically embedded atmospheric sensors that could help closing the resolution gap in atmospheric models.

10
The impact of London's Ultra Low Emission Zone on respiratory prescribing: a synthetic control study

Williams, G. H.; Allen, T.

2026-09-01 epidemiology 10.64898/2026.08.27.26361515 medRxiv
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Urban air pollution remains a significant public health concern, contributing to premature deaths and adverse health outcomes. However, there is little causal research evaluating the effectiveness of policies designed to improve air quality. This study assesses the impact of all three stages of London's Ultra Low Emission Zone (ULEZ) on air pollution, via PM2.5 levels, and respiratory health, via prescription records for bronchodilator and respiratory corticosteroid medications. Analyses are at general practice level, using a generalised synthetic control method to estimate causal impacts. Stage 1 was associated with a statistically significant but negligible 0.77% reduction in PM2.5 levels, with no corresponding change in prescribing. Stage 2 produced a paradoxical 2.69% increase in PM2.5, alongside a 4.44% decrease in inhaled corticosteroid quantity but a 12.51% increase in average daily quantity (ADQ) usage, suggesting a worsening of disease severity among existing patients. Stage 3 yielded a 2.69% PM2.5 reduction and a modest 2.18% decrease in bronchodilator ADQ usage. Spillover effects beyond the ULEZ boundary were statistically significant, but negligible. We find overall that the ULEZ had minimal effects on both air quality and respiratory prescribing across all three stages. These findings provide new insights into the effectiveness of ULEZ policies in reducing air pollution and its associated health impacts, suggesting the zone's effects are considerably smaller than previously reported, and that integration with broader policy measures may be necessary to achieve meaningful public health gains.

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The comparative strengths and limitations of Nile Red and 9-(dicyanovinyl)-julolidine (DCVJ) fluorescent dyes for detecting microplastics and nanoplastics

Wallner, M.; Diaz, J.; Labbe, A. B.; Jacob, J. J.; Williams, Q.; Paytan, A.; Bagshaw, C. R.

2026-08-07 biophysics 10.64898/2026.08.03.742549 medRxiv
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Nile Red is widely used for the detection of microplastics because its fluorescence emission is sensitive to local polarity and can distinguish hydrophobic plastics from hydrophilic ones. The fluorescence of the molecular rotor, 9-(dicyanovinyl)-julolidine (DCVJ) is less sensitive to polarity but more to viscosity. DCVJ is less widely used for microplastic analysis, although it has been used to detect polystyrene nanobeads. Here, we compared these dyes with standard samples from the Hawaii Pacific University Polymer Kit 1.0 and confirmed that Nile Red, in general, was better for the detection and identification of microplastics. Fluorescence emission was analyzed using photography, as well as spectroscopy. The color and peak emission wavelength of some stained environmental microplastics were affected by additives. Raman spectroscopy was used to confirm the chemical identity of such samples. Although DCVJ emits green fluorescence on binding to some microplastics, a peak at 620 nm has been reported with polystyrene nanobeads, attributed to dimer/excimer formation. We confirmed this property and directly observed diffraction-limited spots using fluorescence microscopy, attributed to single or just a few nanobeads. Nile Red also stains polystyrene nanobeads and gave stronger signals than with DCVJ, but Nile Red was prone to false positives due to dye aggregation in aqueous solutions.

12
Evidence of tornadic phenomena in cerebral aneurysms

Mazzi, V.; Gallo, D.; Natarajan, T.; Schollenberger, J.; Calo, K.; Saloner, D.; Steinman, D. A.; Morbiducci, U.

2026-08-07 bioengineering 10.64898/2026.08.07.743435 medRxiv
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Cerebral aneurysms are abnormal outpouchings of arteries within the brain and occur in [~]1 in 30 adults. Their initiation, growth, and rupture have been linked to focal blood flow abnormalities--often termed "disturbed" or "hostile" hemodynamics--but commonly-used hemodynamic metrics yield conflicting associations with pathology and lack a unifying mechanistic interpretation. Building on a theoretically-grounded link between wall shear stress and near-wall vorticity, we hypothesized that a topology-based description of near-wall flow can operationalize the concept of hostile hemodynamics in a reproducible way. Inspired by atmospheric tornadic phenomena, we sought a principled taxonomy of coherent near-wall fluid structures with potential mechanobiological and clinical implications. Using high-fidelity computational fluid dynamics simulations in anatomically realistic geometries, we identified coherent near-wall fluid structures whose organization mirrors well-studied atmospheric phenomena: tornado-like columnar rotating cores; downburst-like nonrotating wall-impinging jets with tangential outflow, roll-cloud-like tangential vortices; and mixed configurations. These tornadic events on the aneurysm luminal surface were identified from wall shear stress topology, consistent with its theoretical connection to near-wall vorticity kinematics. The presence of tornadic phenomena--and their imprints on the aneurysm wall--was independently observed in vivo using 4D flow magnetic resonance imaging. By translating concepts from atmospheric physics into vascular biomechanics, this topology-based framework yields a unified mechanistic language for describing near-wall hemodynamics, resolving blood flow complexity into interpretable and reproducible coherent fluid structures, enabling standardized hemodynamic phenotyping, and supporting hypothesis-driven studies of aneurysms and other cardiovascular diseases where greater fluid-mechanical specificity and interpretability may strengthen links between mechanobiology and clinical risk.

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Modeling steady state thermoregulation of near-term human fetus

Payne, A.; Joshi, A.; Viswanathan, S. H.; Shah, S. P.; Zhang, D.; Lindsey, S. E.; Rykaczewski, K.

2026-08-21 biophysics 10.64898/2026.08.13.744721 medRxiv
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Maternal thermal strain is associated with adverse pregnancy outcomes, yet fetal temperatures cannot currently be directly measured, limiting quantification of fetal thermal strain. Here, we develop two steady-state models for estimating internal temperatures in a near-term fetus. First, we improve the only previously published human fetal thermoregulation model, deriving a closed-form solution within its simplified uniform-cylinder representation. Second, we introduce a multilayer, anatomically segmented model that resolves tissue-specific temperatures. Both couple the fetal body to central blood pool and amniotic fluid compartments and incorporate a new placenta-umbilical cord heat-exchanger representation. Predictions agree with available intrauterine scalp measurements, with fetal core and head-center temperatures approximately 0.5{degrees}C and 0.8{degrees}C above maternal core, respectively. Physiologically plausible changes in umbilical cord heat-exchanger effectiveness or blood flow increased fetal temperatures by approximately 0.3{degrees}C. These models enable estimation of otherwise inaccessible temperatures, while the multilayer formulation lays a foundation for transient, coupled maternal-fetal thermoregulation modeling.

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Design and Application of a μSiM Outer Blood-Retinal Barrier (OBRB) Model as a Drug Development Tool

Ling, K. C.; Jones, J.; Hepner, G.; Gurcan, A.; Gamariel, R.; Muriel-Torres, A.; Hsu, M.-c.; Mansouri, M.; Farajollahi, S.; Abhyankar, V. V.; Singh, R.; Benoit, D.; McGrath, J. L.

2026-08-24 bioengineering 10.64898/2026.08.23.746552 medRxiv
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The outer blood-retinal barrier (OBRB) is the primary interface through which systemically circulating drugs reach the retina. A tool that measures delivery across this barrier would support the development of targeted therapies as alternatives to repeated intravitreal injection, and the screening of drugs that reach the retina as an off-target toxicity. Such a tool should deliver drugs fluidically through a vascular compartment, measure transport across the retinal pigment epithelium (RPE), and display disease phenotypes relevant to efficacy. Here we adapt the SiM platform, which places epithelium and endothelium in direct juxtaposition across a permeable, optically transparent silicon nitride nanomembrane. ARPE-19 and human umbilical vein endothelial cells (HUVECs) were used as development cell sources. ARPE-19 monocultures reached a transepithelial electrical resistance of 68 {+/-} 26 {Omega} cm2 by 28 days, and ARPE-19 + HUVEC co-cultures reached a small-molecule permeability of 6.34 {+/-} 1.3 x 10-4 cm min-1 within 14 days, a state reported elsewhere only after longer culture. The barriers developed an intervening basement membrane. Drugs perfused through the basal vascular channel crossed into an open apical well, where sampling and mass spectrometry showed transport correlating with lipophilicity, as reported in vivo. The device also displayed two clinically relevant phenotypes. Digoxin at a clinically toxic concentration reduced viability in the co-barrier by about half and doubled permeability. In a vascularized configuration, VEGF drove endothelial invasion of the RPE layer, as seen in neovascular AMD. The SiM-OBRB therefore satisfies basic design criteria for measurement of drug bioavailability, toxicity, and efficacy.

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A Reduced Mechanobiological Framework for Platelet Priming: From Hemodynamic Shear to Mechanosensitive Calcium Entry

Chen, Y.; Liu, X.; Vigolo, D.; Zhuang-Hall, M. S.; Yong, K.-T.

2026-08-09 biophysics 10.64898/2026.08.03.742655 medRxiv
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BackgroundPlatelet activation in flowing blood is a multiscale process in which vessel-scale hemodynamics, red blood cell (RBC) mechanics, adhesive receptor interactions, and intracellular signalling jointly determine thrombotic risk. Individual components are well studied, but a single reduced description that carries each explicitly from vessel-scale flow to mechanosensitive calcium entry, with dimensionally consistent couplings, remains uncommon. ObjectivesWe develop and analyse a reduced, six-module mechanobiological framework for platelet priming spanning the cascade from hemodynamic shear to mechanosensitive calcium entry, and we delineate which elements are supported by existing evidence and which are new, testable hypotheses. MethodsThe framework comprises six coupled modules: (I) hemodynamic forcing from the incompressible Navier-Stokes equations, with an objective principal-strain-rate measure for extensional flow; (II) RBC-mediated platelet margination and near-wall delivery, closed by a near-wall arrival flux; (III) von Willebrand factor (VWF) activation with a bounded kernel and glycoprotein Ib (GPIb) catch-slip capture, resolved through an explicit contact area and a bond-dependent mobility that progressively immobilises wall-interacting platelets; (IV) a single-load membrane-stimulus formulation; (V) mechanosensitive gating and a dimensionally consistent cytosol-store calcium model with extracellular influx; and (VI) a phenomenological mechanical-memory state. We formally derive that the single-platelet stochastic dynamics and the continuum population balance form a Fokker-Planck pair, with the spatially varying diffusivity handled by an explicit drift correction. ResultsThe framework yields a family of mechanochemical dimensionless groups delineating priming regimes. Its central prediction is reformulated as a falsifiable, history-sensitive signature: in a conditioning-test protocol, a low-tension conditioning block charges the memory state, and a fixed sub-threshold test pulse then reports a delay-dependent calcium facilitation that decays on the memory time{tau} m and is distinguishable from no-memory gating, channel adaptation, and residual-calcium priming. We show explicitly that the previously proposed pulsatile-versus-monotone contrast is a nonlinear convexity/thresholding effect of the gating nonlinearity--its difference-in-differences is approximately zero-- and is therefore not a valid test of memory; the conditioning-test signature is. A second prediction links RBC stiffening to reduced near-wall delivery and captured-platelet calcium response, upstream of intrinsic platelet signalling. ConclusionsThe framework provides a dimensionally consistent, mechanistically grounded and hypothesis-generating description linking hemodynamic forcing to mechanosensitive calcium entry. It demonstrates how history-dependent platelet priming may arise from a phenomenological sensitisation state and proposes a conditioning-test protocol for comparison against adhesive, channel and intracellular-store persistence. The framework is calibratable rather than validated, and the quantitative outputs shown use representative uncalibrated parameters.

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Dissolution-Controlled Nanocrystalline Rifapentine Formulation for Tuberculosis Treatment

Barge, N. S.; Kalapala, Y. C.; Rajurkar, P.; Dravid, A. A.; Bhukya, N. K.; Saha, R.; Sanjay, V.; Chakrapani, H.; Agarwal, R.

2026-08-20 bioengineering 10.64898/2026.08.16.745059 medRxiv
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Current tuberculosis (TB) treatment suffers from drawbacks such as long regimens, high pill burden and side effects leading to non-adherence and poor treatment outcomes. Dissolution-controlled drug depot formulation with high drug loading is a clinically successful drug delivery strategy. Such depots reduce the dosing frequency for treatments requiring daily administration, thereby improving treatment adherence and compliance. However, dissolution-controlled depots for first-line TB drugs have not been demonstrated due to their high solubility and high dose requirements. In this study, we overcame this challenge by developing injectable, extended-release, dissolution-controlled depots of nanocrystalline rifapentine (NCRPT), microcrystalline rifapentine (MCRPT) and amorphous rifapentine microparticles (ARPT) with more than 75% loading. Crystalline formulations resulted in much slower depot dissolution compared to amorphous formulations. A single intramuscular (IM) injection of NCRPT in mice resulted in therapeutic serum concentrations for over a week. We then demonstrated the efficacy of NCRPT in both pre-exposure prophylaxis and therapeutic models of mice TB. NCRPT administered at 60 mg/kg once every two weeks demonstrated excellent efficacy in a mouse model of TB infection. In each case, a [~] 4-log-fold reduction in lung bacterial load compared to untreated mice was observed. These results open new avenues for developing LAI formulations of TB drugs and could improve patient compliance and TB management.

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Comparative Transcriptional Responses of Human Blood to Neutron and Photon Irradiation

Salah, A.; Wollschlaeger, D.; Giesen, U.; Schmidberger, H.; Marini, F.; Zahnreich, S.

2026-09-01 biophysics 10.64898/2026.08.28.747800 medRxiv
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Despite the well-known health risks of neutron exposures, key gaps remain in understanding neutron-induced molecular responses and identifying reliable biodosimetric markers that distinguish neutrons from photon exposure. We provide the first genome-wide analysis of the human blood transcriptional response to an accelerator-derived fission-like spectrum of neutrons versus photons, evaluating transcriptomic relative biological effectiveness (RBE) and radiation quality-discriminating gene signatures. Whole blood from healthy donors was irradiated ex vivo with X-rays (140 kV, 0-4 Gy, n = 3) or neutrons (0.1-8 MeV, 0-1 Gy, n = 2), incubated for 6 h or 24 h, and processed for RNA sequencing from peripheral blood mononuclear cells (PBMCs). Neutrons were markedly more potent than X-rays at inducing differentially expressed genes (DEGs) at equal doses, showing a peak response 6 h post-irradiation followed by a decline. In contrast, X-rays caused a continuous increase in DEGs up to 24 h (neutrons vs. X-rays at 1 Gy: 1,449 vs. 121 DEGs at 6 h; 996 vs. 621 DEGs at 24 h). A universal p53-centered 34-gene signature, including FDXR, EDA2R, GADD45A, and ZMAT3, showed highly monotonic dose responses (Spearman correlation coefficient {approx} 1) across donors, radiation qualities, and timepoints. Additionally, difference-in-differences analysis identified radiation quality-discriminating genes only at 6 h, with transcriptional convergence observed by 24 h, suggesting a very narrow time window for biodosimetric differentiation. We identified a neutron-specific gene signature driven by cGAS-STING-NF-{kappa}B signaling (RELB, NFKB1, C3, MALAT1) and suppression of B-cell and myeloid identity genes (IGHD, TCL1A, CLEC7A, TLR2), defining a biologically coherent neutron quality index with distinct immunomodulatory effects. For the first time, we assessed neutron RBEs at the gene, pathway, and global transcriptomic levels in a human blood model, reporting a global transcriptomic neutron RBE of 1.30 (95% CI: 1.14-1.49) at 6 h and 1.21 (95% CI: 1.14-1.28) at 24 h, providing a valuable basis for biodosimetry in mixed-field exposure scenarios. Our findings advance the mechanistic understanding of neutron radiation responses and support the development of biodosimetric approaches for mixed-field exposure scenarios.

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Visual and Instrumental Assessment of Interaction of UVC Radiation with Liposomes in FeCl3 Solutions

Subbotin, V. M.; Turner, B. A.; Davies, B. A.; Wu, K.; Fiksel, G.

2026-08-22 evolutionary biology 10.64898/2026.08.21.746308 medRxiv
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Previously, we have demonstrated that certain ferric salts common in Archean waters, such as iron trichloride and ferric ammonium citrate, can protect liposomes from destruction by short-wavelength UVC light. In this study, we investigate the propagation of 254 nm UV radiation through aqueous FeCl3 solutions and its interactions with liposomes. We then consider these findings in the context of early Earth UV environment, discuss their implications for our hypothesis of the Darwinian evolution of liposomes, and integrate them with our previous experimental results.

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Ambient PM2.5 Concentration and the Cardiovascular Response to Exercise Training: A Systematic Review and Meta-Analysis Across Global Pollution Gradients

Donaldson, J. A.; Cai, S.; Hansell, A. L.; Vande Hey, J. D.; Panchal, R.; Edwards, J.; Abdelrazik, A. M.; Yates, T. E.; Ng, A.; O'Driscoll, J.

2026-08-23 public and global health 10.64898/2026.08.20.26360886 medRxiv
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Background: Exercise training is a cornerstone intervention for cardiovascular disease, yet large cohort studies have reported attenuation of physical activity benefits at elevated air pollution concentrations, creating uncertainty around exercise prescription in polluted settings where cardiovascular disease burden is greatest. Objectives: To determine whether ambient PM2.5 concentration modifies the cardiovascular benefits of structured exercise training, using a global sample of trials spanning a >100-fold pollution gradient. Methods: We conducted a systematic review and multilevel meta-analysis of exercise training interventions reporting pre-post changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), peak oxygen uptake (VO2Max), or resting heart rate (HR) in adults. Annual ambient PM2.5 concentrations (3.5-283 g/m3) were assigned to each study location from CAMS ERA5 reanalysis data. Three-level random-effects models with cluster-robust variance estimation accounted for arms nested within studies. PM2.5 meta-regression was conducted unadjusted and adjusted for world region, exercise mode, trial duration, and health condition, with subgroup analyses by exercise mode and hypertension status. Results: Across 465 studies (27,629 participants), exercise training produced clinically meaningful benefits for all outcomes (SBP - mmHg, DBP - mmHg, VO2Max +3.2 ml/kg/min, HR - bpm; all p < 0.001), with benefits consistently larger in higher-pollution settings. Hypertensive participants showed the greatest improvements, particularly from aerobic exercise (SBP standardised mean difference 0.396 in the Low vs 1.020 in the High PM2.5 stratum). Although aerobic and resistance training participants experience similar chronic ambient PM2.5 exposure, only aerobic exercise showed a stratum gradient (interaction p = 0.074). Discussion: Exercise training delivers clinically meaningful cardiovascular benefits at every pollution level tested. The larger benefits observed in higher-pollution settings reflect the greater cardiovascular risk burden of those populations, and hypertensive patients stand to gain the most, particularly from aerobic exercise.

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Microplastic exposure alters immune-related gene expression in Culex quinquefasciatus mosquitoes and larval microbiota diversity

Tchatakoura, A.; Buysse, M.; Setier Rio, M.-L.; Roux, O.; Loiseau, C.; Aviles, A.

2026-08-28 ecology 10.64898/2026.08.27.747521 medRxiv
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Background: Microplastics have been detected in many freshwater ecosystems, including stagnant waters where mosquito larvae develop. Larvae are therefore exposed to microplastic pollution, which may affect their life history traits or microbiota along with immune gene expression. However, these effects have never been tested in mosquitoes, despite their major public health importance as vectors of numerous pathogens. Method: We exposed mosquito larvae, from hatching to adult emergence, to four concentrations of polyethylene microplastics (MPs): 0, 60, 200, and 600 MPs/mL. Fourth-instar larvae and newly emerged adult females were collected for each treatment. To investigate the effects of MPs on gene expression and bacterial microbiota, RNA sequencing and 16S metabarcoding approaches were performed on three biological replicates for each developmental stage. Results: Microplastic exposure induced a non-monotonic dose-dependent transcriptomic response. In larvae, only a limited number of genes were differentially expressed (five to eight per concentration), with immune-related genes downregulated at both low and high concentrations. In adult females, the intermediate concentration (200 MPs/mL) elicited the strongest response with 14 differentially expressed genes (DEGs). Regarding the microbiota, microplastic exposure reduced bacterial diversity in larvae, with the lowest diversity observed at the highest concentration. However, no significant changes were detected in the microbiota of adult females. Conclusion: Overall, this study shows that adult females are affected by larval exposure to MPs (i.e. differential expression in immune-related genes) and warrants further studies in this field. This includes: 1) investigating further the effects of MPs on mosquitoes' populations (e.g. through multi-generational studies), 2) gaining more environmentally relevant knowledge on MP effects (i.e. using MPs with a biofilm and/or adsorbed pollutants) and 3) focusing on the effects of MPs on mosquitoes' vectorial capacities.