General anesthesia is administered to millions of children annually, yet its long-term effects on neurodevelopment remain a concern. It was previously reported that even a single early exposure to general anesthesia for minor surgery impairs visual attention in children. This study investigates the effects of early repeated general anesthesia exposure on visual system maturation in mice and explores the role of tissue-type plasminogen activator in mediating these effects during development. Male SWISS and C57BL/6J mice (wild-type or deficient for tissue-type plasminogen activator) were exposed to general anesthesia with 1.3% isoflurane in 50% oxygen for 90 min per day from postnatal days 4 to 10. Control animals received 50% oxygen alone. Visual system integrity and inflammation were assessed at postnatal day 15 and at 6 weeks using behavioral tests, high-resolution imaging, and immunohistochemistry. In SWISS mice, circulating tissue-type plasminogen activator levels were measured using a biochemical approach, and neurovascular coupling was evaluated by functional ultrasound imaging. Early repeated general anesthesia exposure delayed eyelid opening (median postnatal day 13 [95% CI, 0.52 to 1.45] vs. postnatal day 15 [95% CI, 0.62 to 1.92]; P < 0.0001), caused lasting visual function deficits (depth perception and oculomotor reflex), and reduced retinal (0.2627 ± 0.04 mm vs. 0.1667 ± 0.03 mm; P < 0.0001) and primary visual cortex thickness (0.8000 ± 0.08 mm vs. 0.7282 ± 0.05 mm; P = 0.0235). Notably, lower circulating tissue-type plasminogen activator levels were observed in general anesthesia-exposed SWISS mice (11.580 ± 2.19 ng/ml vs. 7.654 ± 1.31 ng/ml; P = 0.0082). Tissue-type plasminogen activator-deficient mice exhibited attenuated or absent general anesthesia-induced visual alterations. These findings indicate that early repeated exposure to general anesthesia disrupts visual system maturation in mice and suggest that altered tissue-type plasminogen activator pathways may contribute to these effects, identifying tissue-type plasminogen activator as a potential marker of anesthesia-related neurodevelopmental vulnerability. Additional experimental work will be required to further support this association and clarify its underlying mechanisms.

Excessive sodium intake is a major contributor to cardiovascular disease and mortality. Reducing daily sodium consumption to below 2 g (~5 g of salt) effectively lowers cardiovascular mortality rates. The growing reach of social media and short-form video content offers new opportunities to disseminate health information through scalable, digital interventions such as short, animated storytelling (SAS) videos. We evaluated the effect of a sodium-focused SAS video on knowledge and behavioral expectation to reduce dietary sodium, as well as measuring voluntary post-trial engagement. In this four-arm, parallel, randomized controlled trial, 8616 U.S. adults were randomly assigned to one of four conditions: (1) SAS video + survey, (2) survey only, (3) attention-placebo video + survey, or (4) no exposure. Participants completed follow-up surveys 2 weeks later. Single exposure to the SAS video significantly improved knowledge, both immediately and 2 weeks later, while increasing behavioral expectation to reduce sodium intake at both timepoints. Post-trial voluntary engagement with the intervention was high. These findings highlight the potential of scalable, digital storytelling interventions to enhance dietary knowledge and motivation for behavior change. Identifying demographic groups most likely to engage with SAS content may inform the design of targeted strategies to reduce cardiovascular risk. ClinicalTrials.gov NCT05735457, 02/21/23.

Abstract In structured light three-dimensional (3D) measurement, the high dynamic range (HDR) imaging for varying reflectivity objects with snapshot and with high accuracy is still a great challenge. This paper proposes a snapshot HDR structured light method based on polarizer modulated polarization imaging technology. In our snapshot HDR 3D reconstruction method, a linear polarizer is placed in front of the four channels polarization camera, which allows the polarization camera to capture four images with different brightness levels in a single exposure for both metal and non-metallic objects in our developed structured light system. The optimal rotation angle is investigated and determined to maximize the accuracy of the polarization structured light 3D measurement system for complex varying reflectivity objects. Experimental results demonstrate that our proposed method can perform snapshot HDR imaging for fringe projection structured light 3D measurement and outperform four-exposure HDR fusion method, which requires less acquisition times, making it more suitable for dynamic measurements.

The prevalence of neurodegenerative diseases and mental health disorders has been increasing over the past few decades. While genetic and lifestyle factors are important to the etiology of these illnesses, the pathogenic role of environmental factors, especially toxicants such as pesticides encountered over the life span, is receiving increased attention. As an environmental factor, organophosphates pose a constant threat to human health due to their widespread use as pesticides, their deployment by rogue militaries, and their use in terrorist attacks. The standard organophosphate-antidotal regimen provides modest efficacy against lethality, although morbidity remains high, and there is little evidence that it attenuates long-term neurobehavioral sequelae. Here we show that a novel intranasally administered treatment strategy with specific gangliosides can prevent the organophosphate-related alterations in important neurotrophin pathways that are involved in cognition and depression. We found that a single exposure to the organophosphate diisopropylfluorophosphate (DFP) in mice leads to persistent decreases in the neurotrophins NGF and BDNF and their receptors, TrkA and TrkB. Moreover, 7 days of repeated intranasal administration of gangliosides GM1 or GD3 24 h after the DFP injection prevented the neurotrophin receptor alterations. As NGF and BDNF signaling are involved in cognitive function and depression symptoms, respectively, intranasal administration of GM1 or GD3 may offer a preventative strategy against organophosphate-related alterations in these brain functions. Our study thus supports the potential of a novel therapeutic strategy for neurological and psychiatric deficits associated with a class of poisons that endangers millions of people worldwide.

Photon FLASH spares radiation-induced changes in cardiac function, remodelling and arrythmia in a preclinical model.

Rationale: The efficacy of drug delivery to the brain is constrained by the impermeability of the blood-brain barrier (BBB) in healthy tissues and the heterogeneous permeability of the blood-tumor barrier (BTB) in gliomas. Focused ultrasound (FUS) has emerged as a promising technique to transiently modulate vascular permeability, however its effects vary across different brain tissues. This study systematically evaluates the effects of FUS-induced vascular permeability modulation in the gray matter (GM), white matter (WM), and brain tumors, considering their distinct tissue architectures, vascular densities, and permeability profile. Additionally, we compare the delivery of bevacizumab (antiangiogenic monoclonal antibody) and methotrexate (small-molecule chemotherapeutic) to determine how molecular size influences vascular-level permeability and extravasation distances.Methods: A total of n = 48 Fischer-344 rats, including both healthy and tumor-bearing cohorts, underwent magnetic resonance imaging (MRI)-guided FUS using a feedback-controlled algorithm to modulate microbubble pressure based on microbubble emissions. Tumors were either untreated or received a single FUS exposure, while healthy tissues, including GM and WM, were treated with either a single exposure, or a repeated exposure administered 30 minutes after the first one. MR images were used to assess contrast enhancement before and after sonication. Drug deposition was quantified via fluorescence microscopy in terms of local signal intensities and distances of extravasation. Tissue-specific vascular characteristics, including vessel diameters, densities, and inter-vessel distances, were also analysed.Results: The lack of MRI contrast enhancement in untreated tissues suggested a healthy permeability status of the BBB in GM and WM, while a compromised BTB was observed in tumors. Following FUS treatments, contrast enhancement significantly increased in all tissues, with tumors exhibiting the most pronounced effects. Repeated FUS further enhanced permeability in GM and WM, achieving drug deposition levels comparable to those observed in tumors after a single treatment. At the vascular level, FUS exposure led to significant increases in drug extravasation distances, particularly in tumors. Vascular densities were approximately threefold higher in GM, compared to WM and tumors (GM:WM:Tumor 3.2:1:1), yet both drug signal intensities and extravasation distance correlated more strongly with the number of treatments than with baseline vascularity. Fluorescence microscopy revealed that bevacizumab extravasation was primarily localized near vessel lumens, whereas methotrexate exhibited significantly greater extravascular diffusion, reaching distances spanning entire inter-vessel spaces, consistent with its lower molecular weight. At the individual vessel level, white matter showed significantly lower drug signal intensity than gray matter following a single treatment.Conclusion: This study provides vascular-level insights into how FUS-mediated drug delivery is influenced by tissue architecture, vascular properties, treatment regimen, and drug molecular weight. Notably, at the individual vessel level, drug extravasation varies between the different tissue types, and thus vascular density is not the sole driver of differences in drug deposition in these tissues. The study findings highlight the potential of repeated FUS exposures for enhancing the deposition of therapeutics across the physiologically intact BBB of both the gray and white matter, reaching levels comparable to those observed in the pathologically compromised BTB of gliomas. Thus, sonications prescribed over previously permeabilized tissues facilitate deeper drug penetration into interstitial compartments, allowing therapeutics to reach cells further from vessel lumens despite inherent tissue-specific differences.

Knowing the minimal detectable dose can facilitate the interpretation of a hair test result: II. Case example with ibutamoren (MK-677), a growth hormone secretagogue.

Co-exposure effects of polystyrene nanoplastics and silver nanoparticles in constructed wetlands: Microbial and macrophyte responses.

Impacts of sodium benzoate and lysozyme on nitrification performance and resistance genes: Acute effects of single and co-exposure at different concentrations.

Subchronic co-exposure to dibutyl phthalate and benzo(a)pyrene exacerbates renal inflammation and fibrosis in rat: Crosstalk between tubular epithelial cells and fibroblasts.

Deciphering the quantitative relationship between NRF2 and SRXN1 through semi-mechanistic computational modeling.

Characteristics of toxicokinetics and metabolic transformation of flonicamid in rats.

Exposome-wide association study of environmental toxicant exposure and insulin resistance: Findings from US National Health and Nutrition Examination Survey.

Polystyrene microplastics alter the toxicity of 6PPD to zebrafish (Danio rerio) larvae.

Systemic toxicity in mammals dermally exposed to field-collected weathered oil fragments from the largest South Atlantic spill: Experimental evidence from a realistic exposure scenario.

Exploring retinoic acid-induced skin irritation: Pathological and mechanistic insights from an ex vivo porcine skin model.

Exposure of a freshwater ecosystem to a mixture of two relevant engineered nanomaterials revealed distinct aggregation dynamics, behavior, and fate.

There is growing concern regarding potential neurotoxicity and long-term neuro-cognitive outcomes in young children receiving general anesthetics (GAs) and sedatives. Most currently used anesthetics and sedatives have shown to be potentially neurotoxic in animal studies. However, three landmark human studies have provided compelling evidence that a single brief exposure to GAs at an early age does not affect neurocognitive or behavioral outcomes. It is unclear if multiple exposures to GAs and sedatives in early childhood lead to worse neurocognitive or behavioral outcomes. This review article will summarize the evidence in both animal and human studies and discuss the limitations in both. Furthermore, we will suggest strategies to limit GA and sedative exposure in young children, as well as propose future directions of study.

Hepatic toxicity induced by exposure to glyphosate/aminomethylphosphonic acid and oxytetracycline alone or in combination in zebrafish: A novel mechanism of the gut-liver axis.

&lt;b&gt;Aims&lt;/b&gt; : High-resolution spectrographs are central to modern exoplanet research and are particularly effective for detecting Earth-like planets whose radial velocity (RV) signals can be only a few tens of centimeters per second. Achieving this level of precision requires highly accurate wavelength calibration. A key factor in this process is the modeling of the instrumental profile (IP), which describes the response of the spectrograph to incoming light. The true IP of a high-resolution instrument is often complex. It may show asymmetry or extended wings and change across the detector because of optical aberrations, variations in fiber illumination, and environmental effects. These features lead to systematic errors in the measured line centers when traditional parametric models such as Gaussian functions are used, and they limit the achievable RV precision.&lt;br&gt; &lt;b&gt;Methods:&lt;/b&gt; This work introduces a non-parametric IP modeling method based on Gaussian Process Regression (GPR). The IP is treated as a smooth function with a flexible covariance structure instead of being constrained by a predefined analytic form. GPR learns both the global structure and small-scale features of the line shape directly from the data. Since the IP varies slowly across the detector, the method divides each spectral order into several consecutive spatial segments. Each segment is fitted independently, capturing local variations. The model includes measurement uncertainties and provides a probabilistic description of the IP. Adjacent segments are linked with smooth interpolation to ensure a continuous IP across the entire order. Model performance is evaluated using reduced chi-squared and root mean square error (RMSE), allowing quantitative assessment and comparison with traditional approaches.&lt;br&gt; &lt;b&gt;Results:&lt;/b&gt; The method is tested with laser frequency comb (LFC) exposures from the fiber-fed High Resolution Spectrograph (HRS) on the 2.16 m telescope at Xinglong Observatory. The LFC produces a dense and highly stable set of emission lines and is well suited for validating IP reconstruction. Three experiments show clear and consistent improvements. Using odd-numbered lines to predict evennumbered ones within a single exposure reduces the RMSE by 35.6% compared with a Gaussian model, showing better determination of line centers. Applying an IP model trained on one exposure to a later exposure reduces the RMSE by 42.5%, demonstrating improved stability when the model is transferred between exposures. A comparison between two channels in the same exposure shows a 37.1% improvement in calibration consistency, indicating reduced channel-tochannel systematics.&lt;br&gt; &lt;b&gt;Conclusions:&lt;/b&gt; The results show that GPR provides a more accurate description of the instrumental profile and its spatial variation than traditional parametric models. The improved reconstruction of the IP leads to more accurate line center measurements and a more stable and precise wavelength solution. This capability is important for pushing the RV precision of high-resolution spectrographs toward the centimeter-per-second level. GPR offers a promising approach for modeling instrumental profiles and supports the precision required for detecting Earth-like exoplanets.