Single-cell and bulk RNAseq unveils the immune infiltration landscape and targeted therapeutic biomarkers of psoriasis.

Background: Psoriasis represents a multifaceted and debilitating immune-mediated systemic ailment afflicting millions globally. Despite the continuous discovery of biomarkers associated with psoriasis, identifying lysosomal biomarkers, pivotal as cellular metabolic hubs, remains elusive. Methods: We employed a combination of differential expression analysis and weighted gene co-expression network analysis (WGCNA) to initially identify lysosomal genes. Subsequently, to mitigate overfitting and eliminate collinear genes, we applied 12 machine learning algorithms to screen robust lysosomal genes. These genes underwent further refinement through random forest (RF) and Lasso algorithms to ascertain the final hub lysosomal genes. To assess their predictive efficacy, we conducted receiver operating characteristic (ROC) analysis and verified the expression of diagnostic biomarkers at both bulk and single-cell levels. Furthermore, we utilized single-sample gene set enrichment analysis (ssGSEA), CIBERSORT, and Pearson's correlation analysis to elucidate the association between immune phenotypes and hub lysosomal genes in psoriatic samples. Finally, employing the Cellchat algorithm, we explored potential mechanisms underlying the participation of these hub lysosomal genes in cell-cell communication. Results: Functional enrichment analyses revealed a close association between psoriasis and lysosomal functions. Subsequent intersection analysis identified 19 key lysosomal genes, derived from DEGs, phenotypic genes of WGCNA, and lysosomal gene sets. Following the exclusion of collinear genes, we identified 11 robust genes, further refined through RF and Lasso, yielding 3 hub lysosomal genes (S100A7, SERPINB13, and PLBD1) closely linked to disease occurrence, with high predictive capability for disease diagnosis. Concurrently, we validated their relative expression in separate bulk datasets and single-cell datasets. A nomogram based on these hub genes may offer clinical advantages for patients. Notably, these three hub genes facilitated patient classification into two subtypes, namely metabolic-immune subtype 1 and signaling subtype 2. CMap analysis suggested butein and arachidonic fasudil as preferred treatment agents for subtype 1 and subtype 2, respectively. Finally, through Cellchat and correlation analysis, we identified PRSS3-F2R as potentially promoting the expression of hub genes in the psoriasis group, thereby enhancing keratinocyte-fibroblast interaction, ultimately driving psoriasis occurrence and progression. Conclusion: Our study identifies S100A7, SERPINB13, and PLBD1 as potential diagnostic biomarkers, offering promising prospects for more precisely tailored psoriatic immunotherapy designs.

A drug-selectable acoustic reporter gene system for human cell ultrasound imaging.

A promising new field of genetically encoded ultrasound contrast agents in the form of gas vesicles has recently emerged, which could extend the specificity of medical ultrasound imaging. However, given the delicate genetic nature of how these genes are integrated and expressed, current methods of producing gas vesicle-expressing mammalian cell lines requires significant cell processing time to establish a clonal/polyclonal line that robustly expresses the gas vesicles sufficiently enough for ultrasound contrast. Here, we describe an inducible and drug-selectable acoustic reporter gene system that can enable gas vesicle expression in mammalian cell lines, which we demonstrate using HEK293T cells. Our drug-selectable construct design increases the stability and proportion of cells that successfully integrate all plasmids into their genome, thus reducing the amount of cell processing time required. Additionally, we demonstrate that our drug-selectable strategy forgoes the need for single-cell cloning and fluorescence-activated cell sorting, and that a drug-selected mixed population is sufficient to generate robust ultrasound contrast. Successful gas vesicle expression was optically and ultrasonically verified, with cells expressing gas vesicles exhibiting an 80% greater signal-to-noise ratio compared to negative controls and a 500% greater signal-to-noise ratio compared to wild-type HEK293T cells. This technology presents a new reporter gene paradigm by which ultrasound can be harnessed to visualize specific cell types for applications including cellular reporting and cell therapies.

Vortex-ultrasound for microbubble-mediated thrombolysis of retracted clots.

Endovascular sonothrombolysis has gained significant attention due to its benefits, including direct targeting of the thrombus with sonication and reduced side effects. However, the small aperture of endovascular transducers restricts the improvement of their potential clinical efficiency due to inefficient acoustic radiation. Hence, in an earlier study, we used vortex ultrasound with an endovascular ultrasound transducer to induce shear stress and enhance the clot lysis. In this study, the vortex acoustic transduction mechanism was investigated using numerical simulations and hydrophone tests. Following this characterization, we demonstrated the performance of the vortex ultrasound transducer in thrombolysis of retracted clots in in vitro tests. The test results indicated that the maximum lysis rates were 79.0% and 32.2% with the vortex ultrasound for unretracted and retracted clots, respectively. The vortex ultrasound enhanced the efficiency of the thrombolysis by approximately 49%, both for retracted and unretracted clots, compared with the typical non-vortex ultrasound technique. Therefore, the use of endovascular vortex ultrasound holds promise as a potential clinical option for the thrombolysis of retracted clots.

Design and simulation of acoustic vortex wave arrays for long-range underwater communication.

The formation and propagation of acoustic vortex waves have been of increasing interest for multiple applications, namely, underwater acoustic communications. Several methods have been presented to form these vortices in underwater environments; however, their performance and propagation over long distances is largely unstudied. Understanding the long-distance propagation of these waves is vital to enhancing their usefulness as an added degree of freedom in underwater acoustic communications systems. In this work, the ray tracing algorithm of bellhop is used to investigate the design parameters of vortex wave transducer and receiver arrays consisting of multiple rings of independently controlled transducers and simulate their performance.

A Model of High-Speed Endovascular Sonothrombolysis with Vortex Ultrasound-Induced Shear Stress to Treat Cerebral Venous Sinus Thrombosis.

This research aims to demonstrate a novel vortex ultrasound enabled endovascular thrombolysis method designed for treating cerebral venous sinus thrombosis (CVST). This is a topic of substantial importance since current treatment modalities for CVST still fail in as many as 20% to 40% of the cases, and the incidence of CVST has increased since the outbreak of the coronavirus disease 2019 pandemic. Compared with conventional anticoagulant or thrombolytic drugs, sonothrombolysis has the potential to remarkably shorten the required treatment time owing to the direct clot targeting with acoustic waves. However, previously reported strategies for sonothrombolysis have not demonstrated clinically meaningful outcomes (e.g., recanalization within 30 min) in treating large, completely occluded veins or arteries. Here, we demonstrated a new vortex ultrasound technique for endovascular sonothrombolysis utilizing wave-matter interaction-induced shear stress to enhance the lytic rate substantially. Our in vitro experiment showed that the lytic rate was increased by at least 64.3% compared with the nonvortex endovascular ultrasound treatment. A 3.1-g, 7.5-cm-long, completely occluded in vitro 3-dimensional model of acute CVST was fully recanalized within 8 min with a record-high lytic rate of 237.5 mg/min for acute bovine clot in vitro. Furthermore, we confirmed that the vortex ultrasound causes no vessel wall damage over ex vivo canine veins. This vortex ultrasound thrombolysis technique potentially presents a new life-saving tool for severe CVST cases that cannot be efficaciously treated using existing therapies.

Perfluorocarbon nanodroplet size, acoustic vaporization, and inertial cavitation affected by lipid shell composition in vitro.

Perfluorocarbon nanodroplets (PFCnDs) are ultrasound contrast agents that phase-transition from liquid nanodroplets to gas microbubbles when activated by laser irradiation or insonated with an ultrasound pulse. The dynamics of PFCnDs can vary drastically depending on the nanodroplet composition, including the lipid shell properties. In this paper, we investigate the effect of varying the ratio of PEGylated to non-PEGylated phospholipids in the outer shell of PFCnDs on the acoustic nanodroplet vaporization (liquid to gas phase transition) and inertial cavitation (rapid collapse of the vaporized nanodroplets) dynamics in vitro when insonated with focused ultrasound. Nanodroplets with a high concentration of PEGylated lipids had larger diameters and exhibited greater variance in size distribution compared to nanodroplets with lower proportions of PEGylated lipids in the lipid shell. PFCnDs with a lipid shell composed of 50:50 PEGylated to non-PEGylated lipids yielded the highest B-mode image intensity and duration, as well as the greatest pressure difference between acoustic droplet vaporization onset and inertial cavitation onset. We demonstrate that slight changes in lipid shell composition of PFCnDs can significantly impact droplet phase transitioning and inertial cavitation dynamics. These findings can help guide researchers to fabricate PFCnDs with optimized compositions for their specific applications.

Extreme material parameters accessible by active acoustic metamaterials with Willis coupling.

Active acoustic metamaterials incorporate electric circuit elements that input energy into an otherwise passive medium to aptly modulate the effective material properties. Here, we propose an active acoustic metamaterial with Willis coupling to drastically extend the tunability of the effective density and bulk modulus with the accessible parameter range enlarged by at least two orders of magnitude compared to that of a non-Willis metamaterial. Traditional active metamaterial designs are based on local resonances without considering the Willis coupling that limit their accessible effective material parameter range. Our design adopts a unit cell structure with two sensor-transducer pairs coupling the acoustic response on both sides of the metamaterial by detecting incident waves and driving active signals asymmetrically superimposed onto the passive response of the material. The Willis coupling results from feedback control circuits with unequal gains. These asymmetric feedback control circuits use Willis coupling to expand the accessible range of the effective density and bulk modulus of the metamaterial. The extreme effective material parameters realizable by the metamaterials will remarkably broaden their applications in biomedical imaging, noise control, and transformation acoustics-based cloaking.

Direct observation of Klein tunneling in phononic crystals.

Tunneling plays an essential role in many branches of physics and has found important applications. It is theoretically proposed that Klein tunneling occurs when, under normal incidence, quasiparticles exhibit unimpeded penetration through potential barriers independent of their height and width. We created a phononic heterojunction by sandwiching two types of artificial phononic crystals with different Dirac point energies. The direct observation of Klein tunneling as shown by the key feature of unity transmission is demonstrated. Our experiment reveals that Klein tunneling occurs over a broad band of acoustic frequency. The direct observation of Klein tunneling in phononic crystals could find applications in signal processing, supercollimated beams, and communications.

Observation of acoustic spin.

Unlike optical waves, acoustic waves in fluids are described by scalar pressure fields, and therefore are considered spinless. Here, we demonstrate experimentally the existence of spin in acoustics. In the interference of two acoustic waves propagating perpendicularly to each other, we observed the spin angular momentum in free space as a result of the rotation of local particle velocity. We successfully measured the acoustic spin, and spin-induced torque acting on a designed lossy acoustic probe that results from absorption of the spin angular momentum. The acoustic spin is also observed in the evanescent field of a guided mode traveling along a metamaterial waveguide. We found spin-momentum locking in acoustic waves whose propagation direction is determined by the sign of spin. The observed acoustic spin could open a new door in acoustics and its applications for the control of wave propagation and particle rotation.

Free-electron-laser coherent diffraction images of individual drug-carrying liposome particles in solution.

Using the excellent performances of a SACLA (RIKEN/HARIMA, Japan) X-ray free electron laser (X-FEL), coherent diffraction imaging (CDI) was used to detect individual liposome particles in water, with or without inserted doxorubicin nanorods. This was possible because of the electron density differences between the carrier, the liposome, and the drug. The result is important since liposome nanocarriers at present dominate drug delivery systems. In spite of the low cross-section of the original ingredients, the diffracted intensity of drug-free liposomes was sufficient for spatial reconstruction yielding quantitative structural information. For particles containing doxorubicin, the structural parameters of the nanorods could be extracted from CDI. Furthermore, the measurement of the electron density of the solution enclosed in each liposome provides direct evidence of the incorporation of ammonium sulphate into the nanorods. Overall, ours is an important test for extending the X-FEL analysis of individual nanoparticles to low cross-sectional systems in solution, and also for its potential use to optimize the manufacturing of drug nanocarriers.

High-speed acoustic communication by multiplexing orbital angular momentum.

Long-range acoustic communication is crucial to underwater applications such as collection of scientific data from benthic stations, ocean geology, and remote control of off-shore industrial activities. However, the transmission rate of acoustic communication is always limited by the narrow-frequency bandwidth of the acoustic waves because of the large attenuation for high-frequency sound in water. Here, we demonstrate a high-throughput communication approach using the orbital angular momentum (OAM) of acoustic vortex beams with one order enhancement of the data transmission rate at a single frequency. The topological charges of OAM provide intrinsically orthogonal channels, offering a unique ability to multiplex data transmission within a single acoustic beam generated by a transducer array, drastically increasing the information channels and capacity of acoustic communication. A high spectral efficiency of 8.0 ± 0.4 (bit/s)/Hz in acoustic communication has been achieved using topological charges between -4 and +4 without applying other communication modulation techniques. Such OAM is a completely independent degree of freedom which can be readily integrated with other state-of-the-art communication modulation techniques like quadrature amplitude modulation (QAM) and phase-shift keying (PSK). Information multiplexing through OAM opens a dimension for acoustic communication, providing a data transmission rate that is critical for underwater applications.

Observation of acoustic Dirac-like cone and double zero refractive index.

Zero index materials where sound propagates without phase variation, holds a great potential for wavefront and dispersion engineering. Recently explored electromagnetic double zero index metamaterials consist of periodic scatterers whose refractive index is significantly larger than that of the surrounding medium. This requirement is fundamentally challenging for airborne acoustics because the sound speed (inversely proportional to the refractive index) in air is among the slowest. Here, we report the first experimental realization of an impedance matched acoustic double zero refractive index metamaterial induced by a Dirac-like cone at the Brillouin zone centre. This is achieved in a two-dimensional waveguide with periodically varying air channel that modulates the effective phase velocity of a high-order waveguide mode. Using such a zero-index medium, we demonstrated acoustic wave collimation emitted from a point source. For the first time, we experimentally confirm the existence of the Dirac-like cone at the Brillouin zone centre.

Accessing the exceptional points of parity-time symmetric acoustics.

Parity-time (PT) symmetric systems experience phase transition between PT exact and broken phases at exceptional point. These PT phase transitions contribute significantly to the design of single mode lasers, coherent perfect absorbers, isolators, and diodes. However, such exceptional points are extremely difficult to access in practice because of the dispersive behaviour of most loss and gain materials required in PT symmetric systems. Here we introduce a method to systematically tame these exceptional points and control PT phases. Our experimental demonstration hinges on an active acoustic element that realizes a complex-valued potential and simultaneously controls the multiple interference in the structure. The manipulation of exceptional points offers new routes to broaden applications for PT symmetric physics in acoustics, optics, microwaves and electronics, which are essential for sensing, communication and imaging.