Light on Alzheimer's disease: from basic insights to preclinical studies.

Alzheimer's disease (AD), referring to a gradual deterioration in cognitive function, including memory loss and impaired thinking skills, has emerged as a substantial worldwide challenge with profound social and economic implications. As the prevalence of AD continues to rise and the population ages, there is an imperative demand for innovative imaging techniques to help improve our understanding of these complex conditions. Photoacoustic (PA) imaging forms a hybrid imaging modality by integrating the high-contrast of optical imaging and deep-penetration of ultrasound imaging. PA imaging enables the visualization and characterization of tissue structures and multifunctional information at high resolution and, has demonstrated promising preliminary results in the study and diagnosis of AD. This review endeavors to offer a thorough overview of the current applications and potential of PA imaging on AD diagnosis and treatment. Firstly, the structural, functional, molecular parameter changes associated with AD-related brain imaging captured by PA imaging will be summarized, shaping the diagnostic standpoint of this review. Then, the therapeutic methods aimed at AD is discussed further. Lastly, the potential solutions and clinical applications to expand the extent of PA imaging into deeper AD scenarios is proposed. While certain aspects might not be fully covered, this mini-review provides valuable insights into AD diagnosis and treatment through the utilization of innovative tissue photothermal effects. We hope that it will spark further exploration in this field, fostering improved and earlier theranostics for AD.

Perioperative nutrition management in patients with spinal tuberculosis taking ERAS measures.

BACKGROUND AND OBJECTIVES: To explore the effect of nutrition management under ERAS concept in patients with spinal tuberculosis. METHODS AND STUDY DESIGN: The study was conducted in an orthopedic ward of a tertiary grade A special hospital in Beijing. The patients admitted from January 1, 2021 to June 27, 2023 were screened for inclusion. The qualified patients were randomized into experimental group or control group. The experimental group received perioperative nutrition management under the concept of ERAS while the control group received routine perioperative management in hospital. The data was collected on the next day of admission, the next day and the sixth day after operation, including laboratory indicators (lymphocyte count, hemoglobin level, etc), intraoperative bleeding volume, postoperative exhaust, defecation time, drainage volume, albumin infusion amount, nutritional risk score, length of stay, hospitalization costs, etc. Univariate analysis and multivariate analysis correcting for gender, age, and baseline values were performed using SPSS24.0. RESULTS: A total of 127 patients with spinal tuberculosis completed the study. Compared with the control group, the intraoperative blood loss (p=0.028) in the experimental group was significantly reduced, the postoperative exhaust time (p=0.012) and defecation time (p=0.012) were significantly shortened, and the nutritional status (p<0.001) was significantly improved. Besides, the results of multivariate analysis are robust after correcting potential confounding factors. CONCLUSIONS: Nutrition management under the concept of ERAS is helpful to reduce intraoperative bleeding, promote postoperative flatus and defecation, and improve nutritional status in patients with spinal tuberculosis, which may further improve their clinical outcome and prognosis.

Durable Janus membrane with on-demand mode switching fabricated by femtosecond laser.

Despite their notable unidirectional water transport capabilities, Janus membranes are commonly challenged by the fragility of their chemical coatings and the clogging of open microchannels. Here, an on-demand mode-switching strategy is presented to consider the Janus functionality and mechanical durability separately and implement them by simply stretching and releasing the membrane. The stretching Janus mode facilitates unidirectional liquid flow through the hydrophilic micropores-microgrooves channels (PG channels) fabricated by femtosecond laser. The releasing protection mode is designed for the in-situ closure of the PG channels upon encountering external abrasion and impact. The protection mode imparts the Janus membrane robustness to reserve water unidirectional penetration under harsh conditions, such as 2000 cycles mechanical abrasion, 10 days exposure in air and other rigorous tests (sandpaper abrasion, finger rubbing, sand impact and tape peeling). The underlying mechanism of gridded grooves in protecting and enhancing water flow is unveiled. The Janus membrane serves as a fog collector to demonstrate its unwavering mechanical durability in harsh real-world conditions. The presented design strategy could open up new possibilities of Janus membrane in a multitude of applications ranging from multiphase separation devices to fog harvesting and wearable health-monitoring patches.

Perturbed Progressive Learning for Semisupervised Defect Segmentation.

Recently, with the development of intelligent manufacturing, the demand for surface defect inspection has been increasing. Deep learning has achieved promising results in defect inspection. However, due to the rareness of defect data and the difficulties of pixelwise annotation, the existing supervised defect inspection methods are too inferior to be implemented in practice. To solve the problem of defect segmentation with few labeled data, we propose a simple and efficient method for semisupervised defect segmentation (SSDS), named perturbed progressive learning (PPL). On the one hand, PPL decouples the predictions of student and teacher networks as well as alleviates overfitting on noisy pseudo-labels. On the other hand, PPL encourages consistency across various perturbations in a broader stagewise scope, alleviating drift caused by the noisy pseudo-labels. Specifically, PPL contains two training stages. In the first stage, the teacher network gives the unlabeled data with pseudo-labels that are divided into the easy and hard groups. The labeled data and the unlabeled data in the easy group with their perturbation are both used to train for a better-performing student network. In the second stage, the unlabeled data in the hard group are predicted by the obtained student network, so the refined pseudo-labeled data are enlarged. All the pseudo-labeling data and labeled data with their perturbation are used to retrain the student network, progressively improving the defect feature representation. We build a mobile screen defect dataset (MSDD-3) with three classes of defects. PPL is implemented on MSDD-3 as well as other public datasets. Extensive experimental results demonstrate that PPL significantly surpasses the state-of-the-art methods across all evaluation partition protocols.

Surface-Induced Electronic and Vibrational Level Shifting of [Fe(py)2bpym(NCS)2] on Al(100).

It is essential that one understands how the surface degrees of freedom influence molecular spin switching to successfully integrate spin crossover (SCO) molecules into devices. This study uses density functional theory calculations to investigate how spin state energetics and molecular vibrations change in a Fe(II) SCO compound named [Fe(py)2bpym(NCS)2] when deposited on an Al(100) surface. The calculations consider an environment-dependent U to assess the local Coulomb correlation of 3d electrons. The results show that the adsorption configurations heavily affect the spin state splitting, which increases by 10-40 kJmol-1 on the surface, and this is detrimental to spin conversion. This effect is due to the surface binding energy variation across the spin transition. The preference for the low-spin state originates partly from the strong correlation effect. Furthermore, the surface environment constrains the vibrational entropy difference, which decreases by 8-17 Jmol-1K-1 (at 300 K) and leads to higher critical temperatures. These results suggest that the electronic energy splitting and vibrational level shifting are suitable features for characterizing the spin transition process on surfaces, and they can provide access to high-throughput screening of spin crossover devices.

Optimization of ultrasound-assisted cellulase degradation method on the extraction of mulberry leaf protein and its effect on the functional characteristics.

The mulberry leaf protein extracted by ultrasound-assisted cellulase degradation (UACD) method was optimized with the protein dissolution amount (PDA) as the index. The Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy of extracted mulberry leaf protein were measured. The functional characteristics of protein extracted by the UACD method were evaluated. Results showed that the extraction condition was optimized and adjusted to the following parameters: pH value of 7.20, ultrasound temperature of 35.00 °C, enzyme dosage of 4.20% and ultrasound time of 10.00 min. Under these optimized conditions, the experimental verification value of PDA was 13.87 mg/mL, which was approaching to the predicted value of 13.54 mg/mL. The analysis results of FTIR showed that after extraction by the UACD method, the mulberry leaf protein with the vibrational peak of ester carbonyl (C = O) absorption peak (1734.66 cm-1) disappeared. The α-helix content of protein extracted by the UACD decreased by 8.13%, and the ß-turn and random coil content of protein increased by 20.22% and 18.79%, respectively, compared to that of the blank. The microstructure of mulberry leaf protein showed that the UACD method could break the dense structure of protein raw materials, reduce the average size of proteins and increase the specific surface area and roughness of proteins. According to the results of functional characteristics, the mulberry leaf protein extracted by the UACD method presented the highest enzymolysis properties and solubility, which was beneficial for the application in the food industry. In conclusion, the UACD method was a very effective way to extract protein from mulberry leaf.

Super-Low-Dose Functional and Molecular Photoacoustic Microscopy.

Photoacoustic microscopy can image many biological molecules and nano-agents in vivo via low-scattering ultrasonic sensing. Insufficient sensitivity is a long-standing obstacle for imaging low-absorbing chromophores with less photobleaching or toxicity, reduced perturbation to delicate organs, and more choices of low-power lasers. Here, the photoacoustic probe design is collaboratively optimized and a spectral-spatial filter is implemented. A multi-spectral super-low-dose photoacoustic microscopy (SLD-PAM) is presented that improves the sensitivity by ≈33 times. SLD-PAM can visualize microvessels and quantify oxygen saturation in vivo with ≈1% of the maximum permissible exposure, dramatically reducing potential phototoxicity or perturbation to normal tissue function, especially in imaging of delicate tissues, such as the eye and the brain. Capitalizing on the high sensitivity, direct imaging of deoxyhemoglobin concentration is achieved without spectral unmixing, avoiding wavelength-dependent errors and computational noises. With reduced laser power, SLD-PAM can reduce photobleaching by ≈85%. It is also demonstrated that SLD-PAM achieves similar molecular imaging quality using 80% fewer contrast agents. Therefore, SLD-PAM enables the use of a broader range of low-absorbing nano-agents, small molecules, and genetically encoded biomarkers, as well as more types of low-power light sources in wide spectra. It is believed that SLD-PAM offers a powerful tool for anatomical, functional, and molecular imaging.

Geometry-Gradient Magnetocontrollable Lubricant-Infused Microwall Array for Passive/Active Hybrid Bidirectional Droplet Transport.

Manipulation of droplets has increasingly garnered global attention, owing to its multifarious potential applications, including microfluidics and medical diagnostic tests. To control the droplet motion, geometry-gradient-based passive transport has emerged as a well-established strategy, which induces a Laplace pressure difference based on the droplet radius differences in confined state and transport droplets with no consumption of external energy, whereas this transportation method has inevitably shown some critical limitations: unidirectionality, uncontrollability, short moving distance, and low velocity. Herein, a magnetocontrollable lubricant-infused microwall array (MLIMA) is designed as a key solution to this issue. In the absence of a magnetic field, droplets can spontaneously travel from the tip toward the root of the structure as a result of the geometry-gradient-induced Laplace pressure difference. When the subject of an external magnetic field, the microwalls bend and overlap sequentially, ultimately resulting in the formation of a continuous slippery meniscus surface. The formed meniscus surface can exert sufficient propulsive force to surmount the Laplace pressure difference of the droplet, thereby effectuating active transport. Through the continuous movement of the microwalls, droplets can be actively transported against the Laplace pressure difference from the root to the tip side of the MLIMA or continue to actively move to the root after finishing the passive self-transport. This work demonstrates passive/active hybrid bidirectional droplet transport capabilities, validates its feasibility in the accurate control of droplet manipulation, and exhibits great potential in chemical microreactions, bioassays, and the medical field.

Improved crystal quality and enhanced optical performance of GaN enabled by ion implantation induced high-quality nucleation.

Hetero-epitaxial growth of GaN often leads to high density of threading dislocations, which poses a significant challenge to the promotion of the performance of GaN-based devices. In this study, we address this issue by utilizing an Al-ion implantation pretreatment on sapphire substrates, which induces high-quality regularly arranged nucleation and promotes the crystal quality of GaN. Specifically, we demonstrate that an Al-ion dose of 1013 cm-2 leads to a reduction of full width at half maximum values of (002)/(102) plane X-ray rocking curves from 204.7/340.9 arcsec to 187.0/259.5 arcsec. Furthermore, a systematic investigation of GaN film grown on the sapphire substrate with various Al-ion doses is also performed, and the nucleation layer growth evolution on different sapphire substrates is analyzed. As confirmed by the atomic force microscope results of the nucleation layer, the ion implantation induced high-quality nucleation is demonstrated, which results in the improved crystal quality of the as-grown GaN films. Transmission electron microscope measurement also proves the dislocation suppression through this method. In addition, the GaN-based light-emitting diodes (LEDs) were also fabricated based on the as-grown GaN template and the electrical properties are analyzed. The wall-plug efficiency at 20 mA has risen from 30.7% to 37.4% of LEDs with Al-ion implantation sapphire substrate at a dose of 1013 cm-2. This innovative technique is effective in the promotion of GaN quality, which can be a promising high-quality template for LEDs and electronic devices.

An ultrasound-activatable platinum prodrug for sono-sensitized chemotherapy.

Despite the great success achieved by photoactivated chemotherapy, eradicating deep tumors using external sources with high tissue penetration depth remains a challenge. Here, we present cyaninplatin, a paradigm of Pt(IV) anticancer prodrug that can be activated by ultrasound in a precise and spatiotemporally controllable manner. Upon sono-activation, mitochondria-accumulated cyaninplatin exhibits strengthened mitochondrial DNA damage and cell killing efficiency, and the prodrug overcomes drug resistance as a consequence of combined effects from released Pt(II) chemotherapeutics, the depletion of intracellular reductants, and the burst of reactive oxygen species, which gives rise to a therapeutic approach, namely sono-sensitized chemotherapy (SSCT). Guided by high-resolution ultrasound, optical, and photoacoustic imaging modalities, cyaninplatin realizes the overall theranostics of tumors in vivo with superior efficacy and biosafety. This work highlights the practical utility of ultrasound to precisely activate Pt(IV) anticancer prodrugs for the eradication of deep tumor lesions and broadens the biomedical uses of Pt coordination complexes.

Simultaneous dual-modal photoacoustic and harmonic ultrasound microscopy with an optimized acoustic combiner.

Simultaneous photoacoustic (PA) and ultrasound (US) imaging provides rich optical and acoustic contrasts with high sensitivity, specificity, and resolution, making it a promising tool for diagnosing and assessing various diseases. However, the resolution and penetration depth tend to be contradictory due to the increased attenuation of high-frequency ultrasound. To address this issue, we present simultaneous dual-modal PA/US microscopy with an optimized acoustic combiner that can maintain high resolution while improving the penetration of ultrasound imaging. A low-frequency ultrasound transducer is used for acoustic transmission, and a high-frequency transducer is used for PA and US detection. An acoustic beam combiner is utilized to merge the transmitting and receiving acoustic beams with a predetermined ratio. By combining the two different transducers, harmonic US imaging and high-frequency photoacoustic microscopy are implemented. In vivo experiments on the mouse brain demonstrate the simultaneous PA and US imaging ability. The harmonic US imaging of the mouse eye reveals finer iris and lens boundary structures than conventional US imaging, providing a high-resolution anatomical reference for co-registered PA imaging.

Signal restoration algorithm for photoacoustic imaging systems.

In a photoacoustic (PA) imaging system, the detectors are bandwidth-limited. Therefore, they capture PA signals with some unwanted ripples. This limitation degrades the resolution/contrast and induces sidelobes and artifacts in the reconstructed images along the axial direction. To compensate for the limited bandwidth effect, we present a PA signal restoration algorithm, where a mask is designed to extract the signals at the absorber positions and remove the unwanted ripples. This restoration improves the axial resolution and contrast in the reconstructed image. The restored PA signals can be considered as the input of the conventional reconstruction algorithms (e.g., Delay-and-sum (DAS) and Delay-multiply-and-sum (DMAS)). To compare the performance of the proposed method, DAS and DMAS reconstruction algorithms were performed with both the initial and restored PA signals on numerical and experimental studies (numerical targets, tungsten wires, and human forearm). The results show that, compared with the initial PA signals, the restored PA signals can improve the axial resolution and contrast by 45% and 16.1 dB, respectively, and suppress background artifacts by 80%.

Array-based high-intensity focused ultrasound therapy system integrated with real-time ultrasound and photoacoustic imaging.

High-intensity focused ultrasound (HIFU) is a promising non-invasive therapeutic technique in clinical applications. Challenges in stimulation or ablation HIFU therapy are to accurately target the treatment spot, flexibly deliver or fast-move focus points in the treatment region, and monitor therapy progress in real-time. In this paper, we develop an array-based HIFU system integrated with real-time ultrasound (US) and photoacoustic (PA) imaging. The array-based HIFU transducer can be dynamically focused in a lateral range of ∼16 mm and an axial range of ∼40 mm via electronically adjusting the excitation phase map. To monitor the HIFU therapy progress in real-time, sequential HIFU transmission, PA imaging, PA thermometry, and US imaging are implemented to display the dual-modal images and record the local temperature changes. Co-registered dual-modal images show structural and functional information and thus can guide the HIFU therapy for precise positioning and dosage control. Besides therapy, the multi-element HIFU transducer can also be used to acquire US images to precisely align the imaging coordinates with the HIFU coordinates. Phantom experiments validate the precise and dynamic steering capability of HIFU ablation. We also show that dual-modal imaging can guide HIFU in the designated region and monitor the temperature in biological tissue in real-time.

Multivalent aptamer nanoscaffold cytosensor for glioma circulating tumor cells during Epithelial-Mesenchymal transition.

The key factor that causes glioma invasion and metastasis is circulating tumor cells (CTCs) undergoing epithelial-mesenchymal transition (EMT). Effective analysis of EMT-CTCs can provide an important foundation for early detection and prognosis monitoring of glioma, but the changes in the biomarkers of CTCs in different states of EMT make detection difficult. In this study, we developed a multivalent aptamer nanoscaffold-based electrochemical cytosensor (MAS-cytosensor) to efficiently detect EMT-CTCs. The two chains forming the MAS are composed of a specific aptamer detector, a binding region for DNA self-assembly, and a foothold for interface anchoring. When target CTCs exist, the bisaptamer detector on MAS can sensitively identify CTCs and pull them to the electrode surface, generating electrochemical signals. It has been demonstrated that the MAS-cytosensor can not only detect EMT-CTCs sensitively (detection limit of 6 cells/mL in buffer), but also allows for further downstream analysis after release with high viability. Overall, this cytosensor provides a reliable detection solution for CTCs regardless of their EMT status, and provides an efficient method for in-depth study role of the post-EMT CTCs in clinical application and metastasis mechanisms.

High-performance Marangoni hydrogel rotors with asymmetric porosity and drag reduction profile.

Miniaturized rotors based on Marangoni effect have attracted great attentions due to their promising applications in propulsion and power generation. Despite intensive studies, the development of Marangoni rotors with high rotation output and fuel economy remains challenging. To address this challenge, we introduce an asymmetric porosity strategy to fabricate Marangoni rotor composed of thermoresponsive hydrogel and low surface tension anesthetic metabolite. Combining enhanced Marangoni propulsion of asymmetric porosity with drag reduction of well-designed profile, our rotor precedes previous studies in rotation output (~15 times) and fuel economy (~34% higher). Utilizing thermoresponsive hydrogel, the rotor realizes rapid refueling within 33 s. Moreover, iron-powder dopant further imparts the rotors with individual-specific locomotion in group under magnetic stimuli. Significantly, diverse functionalities including kinetic energy transmission, mini-generator and environmental remediation are demonstrated, which open new perspectives for designing miniaturized rotating machineries and inspire researchers in robotics, energy, and environment.

Photocatalytic activity of MoS2 with water monolayers: Global optimization.

Atomically thin MoS2 has emerged to be promising for photocatalytic water splitting benefiting from its suitable geometrical and electronic structure for light harvesting. A better understanding of how water molecules affect the band edge levels of MoS2 is critical for promoting the interfacial reactivity. Here, we determine the structures of water monolayers on MoS2 using global optimizations achieved by molecular dynamics in combination with local minimization. It is shown that cyclic water clusters are formed on a surface through a hydrogen-bonding network. The absolute band edge positions are explored taking into account the derivative discontinuity of the exchange-correlation functional. Shifts in band edges are observed with the increase in H2O coverage, while bandgaps tend to be slightly decreased. In particular, the band alignment relative to water redox potentials has been investigated in detail. We find that the dimer configuration is likely to suppress the hydrogen evolution reaction (HER), while the polygon clusters lift the conduction band by 0.2-0.7 eV, and thus, they would enhance HER. This effect is explained in terms of the linear dependence of the band edge offset on an interface electric dipole arising from water assemblies.

Magnetically encoded 3D mesostructure with high-order shape morphing and high-frequency actuation.

Inspired by origami/kirigami, three-dimensional (3D) mesostructures assembled via a mechanics-guided approach, with reversible and maneuverable shape-morphing capabilities, have attracted great interest with regard to a broad range of applications. Despite intensive studies, the development of morphable 3D mesostructures with high-order (multi-degree-of-freedom) deformation and untethered high-frequency actuation remains challenging. This work introduces a scheme for a magnetically encoded transferable 3D mesostructure, with polyethylene terephthalate (PET) film as the skeleton and discrete magnetic domains as actuation units, to address this challenge. The high-order deformation, including hierarchical, multidirectional and blending shape morphing, is realized by encoding 3D discrete magnetization profiles on the architecture through ultraviolet curing. Reconfigurable 3D mesostructures with a modest structural modulus (∼3 GPa) enable both high-frequency (∼55 Hz) and large-deformation (∼66.8%) actuation under an alternating magnetic field. Additionally, combined with the shape-retention and adhesion property of PET, these 3D mesostructures can be readily transferred and attached to many solid substrates. On this basis, diverse functional devices, including a switchable colour letter display, liquid mixer, sequential flashlight and biomimetic sliding robot, are demonstrated to offer new perspectives for robotics and microelectronics.

On-Demand Maneuver of Millirobots with Reprogrammable Motility by a Hard-Magnetic Coating.

Millirobots that can be actuated and accurately steered by external magnetic fields, are highly desirable for bioengineering and wearable devices. However, existing designs of millirobots are limited by their specific material composition, hindering their wider application due to a lack of scalability. Here, we present a method for the generation of heterogeneous magnetic millirobots based on magnetic coatings. The coatings, composed of hard-magnetic CrO2 particles dispersed in an adhesive solution, impart magnetic actuation to diverse substrates with planar sheets or 3D structures. Millirobots constructed from the coatings can be readily reprogrammed with intricate magnetization profiles using laser localized heating, enabling reconfigurable shape changes under magnetic actuation. Using this approach, we demonstrate on-demand maneuvering capability of reconfiguring locomotion involving crawling, overturning and rolling with a single millirobot. Various functions, including the ability to catch a fast-moving ball, object transportation, and targeted assembly, have been achieved. This adhesive strategy facilitates the design of millirobots and may open avenues to the creation of complex millirobots for broad applications.

Freehand scanning photoacoustic microscopy with simultaneous localization and mapping.

Optical-resolution photoacoustic microscopy offers high-resolution, label-free hemodynamic and functional imaging to many biomedical applications. However, long-standing technical barriers, such as limited field of view, bulky scanning probes, and slow imaging speed, have limited the application of optical-resolution photoacoustic microscopy. Here, we present freehand scanning photoacoustic microscopy (FS-PAM) that can flexibly image various anatomical sites. We develop a compact handheld photoacoustic probe to acquire 3D images with high speed, and great flexibility. The high scanning speed not only enables video camera mode imaging but also allows for the first implementation of simultaneous localization and mapping (SLAM) in photoacoustic microscopy. We demonstrate fast in vivo imaging of some mouse organs, and human oral mucosa. The high imaging speed greatly reduces motion artifacts and distortions from tissue moving, breathing, and unintended handshaking. We demonstrate small-lesion localization in a large region of the brain. FS-PAM offers a flexible high-speed imaging tool with an extendable field of view, enabling more biomedical imaging applications.