Airy-beam holographic sonogenetics for advancing neuromodulation precision and flexibility.

Advancing our understanding of brain function and developing treatments for neurological diseases hinge on the ability to modulate neuronal groups in specific brain areas without invasive techniques. Here, we introduce Airy-beam holographic sonogenetics (AhSonogenetics) as an implant-free, cell type-specific, spatially precise, and flexible neuromodulation approach in freely moving mice. AhSonogenetics utilizes wearable ultrasound devices manufactured using 3D-printed Airy-beam holographic metasurfaces. These devices are designed to manipulate neurons genetically engineered to express ultrasound-sensitive ion channels, enabling precise modulation of specific neuronal populations. By dynamically steering the focus of Airy beams through ultrasound frequency tuning, AhSonogenetics is capable of modulating neuronal populations within specific subregions of the striatum. One notable feature of AhSonogenetics is its ability to flexibly stimulate either the left or right striatum in a single mouse. This flexibility is achieved by simply switching the acoustic metasurface in the wearable ultrasound device, eliminating the need for multiple implants or interventions. AhSonogentocs also integrates seamlessly with in vivo calcium recording via fiber photometry, showcasing its compatibility with optical modalities without cross talk. Moreover, AhSonogenetics can generate double foci for bilateral stimulation and alleviate motor deficits in Parkinson's disease mice. This advancement is significant since many neurological disorders, including Parkinson's disease, involve dysfunction in multiple brain regions. By enabling precise and flexible cell type-specific neuromodulation without invasive procedures, AhSonogenetics provides a powerful tool for investigating intact neural circuits and offers promising interventions for neurological disorders.

Protective effects of berberine in chronic copper-induced liver and gill injury in freshwater grouper (Acrossocheilus fasciatus).

This experiment aimed to investigate the protective effects of berberine on copper-induced liver and gill toxicities in freshwater grouper (Acrossocheilus fasciatus). Fish (initial weight 1.56 ± 0.10 g) were randomly distributed into 12 tanks (80 L, 20 fish per tank) and divided into four experimental groups: The control group, exposed to 0.02 mg/L Cu2+ (Cu group), exposed to 0.02 mg/L Cu2+ and fed 100 mg/kg berberine (BBR100 group), and exposed to 0.02 mg/L Cu2+ and fed 400 mg/kg berberine (BBR400 group). After a 30-day experiment, the results showed that berberine significantly increased the activities of catalase and glutathione peroxidase in the liver, gills, and serum inhibited by Cu2+ exposure (P < 0.05). Berberine inclusion significantly decreased the activities of lysozyme and acid phosphatase, as well as the content of immunoglobulin M compared to the Cu group (P < 0.05). Berberine significantly suppressed the expression of the proinflammatory cytokines interleukin-1ß, interleukin-6 signaling transducer, and NLR family pyrin domain containing 3 in the liver and gills induced by Cu2+ exposure while downregulating the expression of the anti-inflammatory cytokine transforming growth factor ß1. Additionally, berberine significantly reduced the activities of the liver injury markers alanine transaminase and aspartate transaminase, the levels of total cholesterol and triglyceride in serum, as well as alleviated the histopathological damage in the liver and gills caused by Cu2+ exposure. In summary, berberine enhanced antioxidant capacity, mitigated inflammation, and exerted significant protective effects on liver and gill damage in freshwater grouper under Cu2+ exposure.

Characterization of the Targeting Accuracy of a Neuronavigation-Guided Transcranial FUS System In Vitro, In Vivo, and In Silico.

Focused ultrasound (FUS)-enabled liquid biopsy (sonobiopsy) is an emerging technique for the noninvasive and spatiotemporally controlled diagnosis of brain cancer by inducing blood-brain barrier (BBB) disruption to release brain tumor-specific biomarkers into the blood circulation. The feasibility, safety, and efficacy of sonobiopsy were demonstrated in both small and large animal models using magnetic resonance-guided FUS devices. However, the high cost and complex operation of magnetic resonance-guided FUS devices limit the future broad application of sonobiopsy in the clinic. In this study, a neuronavigation-guided sonobiopsy device is developed and its targeting accuracy is characterized in vitro, in vivo, and in silico. The sonobiopsy device integrated a commercially available neuronavigation system (BrainSight) with a nimble, lightweight FUS transducer. Its targeting accuracy was characterized in vitro in a water tank using a hydrophone. The performance of the device in BBB disruption was verified in vivo using a pig model, and the targeting accuracy was quantified by measuring the offset between the target and the actual locations of BBB opening. The feasibility of the FUS device in targeting glioblastoma (GBM) tumors was evaluated in silico using numerical simulation by the k-Wave toolbox in glioblastoma patients. It was found that the targeting accuracy of the neuronavigation-guided sonobiopsy device was 1.7 ± 0.8 mm as measured in the water tank. The neuronavigation-guided FUS device successfully induced BBB disruption in pigs with a targeting accuracy of 3.3 ± 1.4 mm. The targeting accuracy of the FUS transducer at the GBM tumor was 5.5 ± 4.9 mm. Age, sex, and incident locations were found to be not correlated with the targeting accuracy in GBM patients. This study demonstrated that the developed neuronavigation-guided FUS device could target the brain with a high spatial targeting accuracy, paving the foundation for its application in the clinic.