On-site preparation of sandwich plasmonic coupled SERS tape toward pesticide residue determination on food surface.

A sandwich plasmonic coupled surface enhanced Raman spectroscopy (SERS) tape is proposed prepared by peeling the chemical printed silver nanocorals (AgNCs) from Cu sheet with adhesive tape, which can sample targets from food surface and sandwich them between substrates and Cu sheet for SERS detection. The solid-to-solid transformation method for fabricating SERS tapes can effectively avoid the weakening of tape stickiness during the preparation process. The sandwich plasmonic coupled structure of AgNC substrate, targets, and Cu sheet display excellent SERS activity (EF = 1.62 × 107) for sensitive determination of analytes. In addition, due to the high heat conductivity of Cu sheet, the thermal effect of laser irradiation during SERS detection cannot damage the AgNC tapes, which ensures the reproducibility of subsequent quantification. The sandwich plasmonic coupled SERS tape is demonstrated to quantify malachite green (MG) and methyl parathion (MP) with good linear coefficients (> 0.98) by two typical calibration plots under different concentration ranges. The limit of detection (LOD) of the method is 0.17 ng/cm2 and 0.48 µg/cm2 (S/N = 3) for MG and MP. This method can realize the quantitative determination of MP and MG on the surface of fruits and fish scale with recoveries of 93-113%. The satisfactory detection results demonstrate the proposed sandwich plasmonic coupled AgNC tape can be successfully applied to SERS-based point-of-care testing (POCT) for pesticide residue determination, which will provide a new path for designing and constructing SERS tapes.

One-Step, On-Site Chemical Printing of a 3D Plasmon-Coupled Silver Nanocoral Substrate toward SERS-Based POCT.

Surface-enhanced Raman scattering (SERS) with the advantages of high sensitivity, nondestructive analysis, and a unique fingerprint effect shows great potential in point-of-care testing (POCT). However, SERS faces challenges in rapidly constructing a substrate with high repeatability, homogeneity, and sensitivity, which are the key factors that restrict its practical applications. In this study, we propose a one-step chemical printing strategy for synthesizing a three-dimensional (3D) plasmon-coupled silver nanocoral (AgNC) substrate (only need about 5 min) without any pretreatments and complex instruments. The galvanic replacement between AgNO3 and Cu sheets will provide both Ag0 for the formation of silver nanostructures and Cu2+ for the polymerization of fish sperm DNA (FSDNA). The protection of AgNCs is facilitated by the crosslinked FSDNA, which can improve the stability of the substrate and promote the control of its coral-like morphology. The obtained substrate displays excellent capacity of signal enhancement due to the 3D plasmon coupling both between nanocoral tentacles and between nanocorals and Cu sheets as well. Therefore, the AgNC substrates display high activity (enhancement factor = 1.96 × 108) and uniformity (RSD < 6%). Food colorants have been widely used in various foods to improve their color, but the inevitable toxicity of colorants seriously threatens food safety. Therefore, the proposed AgNC substrates were used to directly quantify three kinds of weak-affinity food colorant molecules including Brilliant Blue, Allura Red, and Sunset Yellow assisted by the capture by cysteamine hydrochloride (CA), showing the detection limits (S/N = 3) of 0.053, 0.087, and 0.089 ppm, respectively. The SERS method has been further applied in the detection of the three kinds of food colorants in both complex food samples and urine with recoveries of 91-119%. The satisfactory detection results suggest that the facile preparation strategy of AgNC substrates will be widely used in SERS-based POCT to promote the development of food safety and on-site healthcare.

Deep-E Enhanced Photoacoustic Tomography Using Three-Dimensional Reconstruction for High-Quality Vascular Imaging.

Linear-array-based photoacoustic computed tomography (PACT) has been widely used in vascular imaging due to its low cost and high compatibility with current ultrasound systems. However, linear-array transducers have inherent limitations for three-dimensional imaging due to the poor elevation resolution. In this study, we introduced a deep learning-assisted data process algorithm to enhance the image quality in linear-array-based PACT. Compared to our earlier study where training was performed on 2D reconstructed data, here, we utilized 2D and 3D reconstructed data to train the two networks separately. We then fused the image data from both 2D and 3D training to get features from both algorithms. The numerical and in vivo validations indicate that our approach can improve elevation resolution, recover the true size of the object, and enhance deep vessels. Our deep learning-assisted approach can be applied to translational imaging applications that require detailed visualization of vascular features.

Type-I Core-Shell ZnSe/ZnS Quantum Dot-Based Resistive Switching for Implementing Algorithm.

Core-shell semiconductor quantum dots (QDs) are one of the biggest nanotechnology successes so far. In particular, type-I QDs with straddling band offset possess the ability to enhance the charge carriers capturing which is useful for memory application. Here, the type-I core-shell QD-based bipolar resistive switching (RS) memory with anomalous multiple SET and RESET processes was demonstrated. The synergy and competition between space charge limited current conduction (arising from charge trapping in potential well of type-I QDs) and electrochemical metallization (ECM, originating from redox reaction of Ag electrode) process were employed for modulating the RS behavior. Through utilizing stochastic RS mechanisms in QD-based devices, four situations of RS behaviors can be classified into three states in Markov chain for implementing the application of a true random number generator. Furthermore, a 6 × 6 cross-bar array was demonstrated to realize the generation of random letters with case distinction.

3D finger vein biometric authentication with photoacoustic tomography.

Biometric authentication is the recognition of human identity via unique anatomical features. The development of novel methods parallels widespread application by consumer devices, law enforcement, and access control. In particular, methods based on finger veins, as compared to face and fingerprints, obviate privacy concerns and degradation due to wear, age, and obscuration. However, they are two-dimensional (2D) and are fundamentally limited by conventional imaging and tissue-light scattering. In this work, for the first time, to the best of our knowledge, we demonstrate a method of three-dimensional (3D) finger vein biometric authentication based on photoacoustic tomography. Using a compact photoacoustic tomography setup and a novel recognition algorithm, the advantages of 3D are demonstrated via biometric authentication of index finger vessels with false acceptance, false rejection, and equal error rates <1.23%, <9.27%, and <0.13%, respectively, when comparing one finger, a false acceptance rateimprovement>10× when comparing multiple fingers, and <0.7% when rotating fingers ±30.

Microbial imidazole propionate affects glomerular filtration rate in patients with diabetic nephropathy through association with HSP90α.

Imidazole propionate (ImP) is a detrimental metabolite produced by the fermentation of histidine intermediates via the intestinal flora. Here, the untargeted metabolite analysis of plasma metabolites from patients with diabetic nephropathy (DN), in combination with the Human Metabolome Database, revealed significantly increased levels of ImP in patients with DN, with a positive correlation with patients' blood creatinine concentration and urinary albumin-to-creatinine ratio, and a negative correlation with the glomerular filtration rate. RNA-seq was applied to detect the effects of ImP on renal tissue transcriptome in mice with DN. It demonstrated that ImP exacerbated renal injury in mice with DN and promoted renal tubular epithelial-mesenchymal transition (EMT), leading to renal mesenchymal fibrosis and renal impairment. Furthermore, ImP was found to directly target HAP90α and activate the PI3K-Akt signalling pathway, which is involved in EMT, by the drug affinity response target stability method. The findings showed that ImP may provide a novel target for DN quality, as it can directly bind to and activate HSP90, thereby facilitating the development of DN while acting as a potential indicator for the clinical diagnosis of DN.

Joint-tissue integrative analysis identifies high-risk genes for Parkinson's disease.

The loss of dopaminergic neurons in the substantia nigra and the abnormal accumulation of synuclein proteins and neurotransmitters in Lewy bodies constitute the primary symptoms of Parkinson's disease (PD). Besides environmental factors, scholars are in the early stages of comprehending the genetic factors involved in the pathogenic mechanism of PD. Although genome-wide association studies (GWAS) have unveiled numerous genetic variants associated with PD, precisely pinpointing the causal variants remains challenging due to strong linkage disequilibrium (LD) among them. Addressing this issue, expression quantitative trait locus (eQTL) cohorts were employed in a transcriptome-wide association study (TWAS) to infer the genetic correlation between gene expression and a particular trait. Utilizing the TWAS theory alongside the enhanced Joint-Tissue Imputation (JTI) technique and Mendelian Randomization (MR) framework (MR-JTI), we identified a total of 159 PD-associated genes by amalgamating LD score, GTEx eQTL data, and GWAS summary statistic data from a substantial cohort. Subsequently, Fisher's exact test was conducted on these PD-associated genes using 5,152 differentially expressed genes sourced from 12 PD-related datasets. Ultimately, 29 highly credible PD-associated genes, including CTX1B, SCNA, and ARSA, were uncovered. Furthermore, GO and KEGG enrichment analyses indicated that these genes primarily function in tissue synthesis, regulation of neuron projection development, vesicle organization and transportation, and lysosomal impact. The potential PD-associated genes identified in this study not only offer fresh insights into the disease's pathophysiology but also suggest potential biomarkers for early disease detection.

Deep Learning Enhanced Volumetric Photoacoustic Imaging of Vasculature in Human.

The development of high-performance imaging processing algorithms is a core area of photoacoustic tomography. While various deep learning based image processing techniques have been developed in the area, their applications in 3D imaging are still limited due to challenges in computational cost and memory allocation. To address those limitations, this work implements a 3D fully-dense (3DFD) U-net to linear array based photoacoustic tomography and utilizes volumetric simulation and mixed precision training to increase efficiency and training size. Through numerical simulation, phantom imaging, and in vivo experiments, this work demonstrates that the trained network restores the true object size, reduces the noise level and artifacts, improves the contrast at deep regions, and reveals vessels subject to limited view distortion. With these enhancements, 3DFD U-net successfully produces clear 3D vascular images of the palm, arms, breasts, and feet of human subjects. These enhanced vascular images offer improved capabilities for biometric identification, foot ulcer evaluation, and breast cancer imaging. These results indicate that the new algorithm will have a significant impact on preclinical and clinical photoacoustic tomography.

Review of imaging test phantoms.

Significance: Photoacoustic tomography has emerged as a prominent medical imaging technique that leverages its hybrid nature to provide deep penetration, high resolution, and exceptional optical contrast with notable applications in early cancer detection, functional brain imaging, drug delivery monitoring, and guiding interventional procedures. Test phantoms are pivotal in accelerating technology development and commercialization, specifically in photoacoustic (PA) imaging, and can be optimized to achieve significant advancements in PA imaging capabilities. Aim: The analysis of material properties, structural characteristics, and manufacturing methodologies of test phantoms from existing imaging technologies provides valuable insights into their applicability to PA imaging. This investigation enables a deeper understanding of how phantoms can be effectively employed in the context of PA imaging. Approach: Three primary categories of test phantoms (simple, intermediate, and advanced) have been developed to differentiate complexity and manufacturing requirements. In addition, four sub-categories (tube/channel, block, test target, and naturally occurring phantoms) have been identified to encompass the structural variations within these categories, resulting in a comprehensive classification system for test phantoms. Results: Based on a thorough examination of literature and studies on phantoms in various imaging modalities, proposals have been put forth for the development of multiple PA-capable phantoms, encompassing considerations related to the material composition, structural design, and specific applications within each sub-category. Conclusions: The advancement of novel and sophisticated test phantoms within each sub-category is poised to foster substantial progress in both the commercialization and development of PA imaging. Moreover, the continued refinement of test phantoms will enable the exploration of new applications and use cases for PA imaging.

Survival on land: A dark-grown seedling searching for path.

To initiate its development into a plant, a small dark-grown seedling (prior to its emergence from the ground) must penetrate through the growth media. The path that the seedling takes during this journey has yet to be explained. As such, we conducted non-destructive tests using CT scans to observe the growth of dark-grown seedlings in soil over time; we also developed a model to simulate the dynamics of an emerging seedling, and to examine effects of various growth medium conditions, including Lunar soil. It was previously postulated that, with gravitropism in a terrestrial growth medium, a dark-grown seedling would grow directly upright. However, our CT scan results showed that dark-grown soybean seedlings departed from the vertical path in soil, as far as a lateral distance of approximately 10 mm. The phenomenon of the non-straight path was also demonstrated by the model results. Through simulations, we found that an emerging seedling naturally weaves through the particles of growth medium, in search for the path of least resistance. As a result, the seedling ends up travelling a longer distance. Compared with a seedling that was artificially forced to take a straight path in a growth media, the seedling taking the natural path encountered significantly lower resistances (20% lower) from the growth medium, while travelled 12% longer distance during the emergence process. A seedling encountered a much higher impedance in Lunar soil. Our results suggest that taking the path of least resistance, in addition to shaping and orientating itself for mechanical advantage, are strategies evolved by plant species that have contributed to its vast success. An understanding of plant behavior and survival strategies on Earth lay the foundation for future research in agriculture in novel environments, including on celestial bodies.

Dual-Scan Photoacoustic Tomography for the Imaging of Vascular Structure on Foot.

Chronic leg ulcers are affecting approximately 6.5 million Americans, and they are associated with significant mortality, reduced quality of life, and high treatment costs. Since many chronic ulcers have underlying vascular insufficiency, accurate assessment of tissue perfusion is critical to treatment planning and monitoring. This study introduces a dual-scan photoacoustic (PA) tomography (PAT) system that can simultaneously image the dorsal and plantar sides of the foot to reduce imaging time. To account for the unique shape of the foot, the system employs height-adjustable and articulating baseball stages that can scan along the foot's contour. In vivo results from healthy volunteers demonstrate the system's ability to acquire clear images of foot vasculature, and results from patients indicate that the system can image patients with various ulcer conditions. We also investigated various PA features and examined their correlation with the foot condition. Our preliminary results indicate that vessel sharpness, occupancy, intensity, and density could all be used to assess tissue perfusion. This research demonstrated the potential of PAT for routine clinical tissue perfusion assessment.

Slit-based photoacoustic tomography with co-planar light illumination and acoustic detection for high-resolution vascular imaging in human using a linear transducer array.

Slit-based photoacoustic tomography is a high-resolution three-dimensional imaging technique for linear transducer array. The system was based on acoustic diffraction through a thin slit to increase the elevation coverage and spatial resolution. In this study, we introduce the third-generation slit-based photoacoustic tomography system with co-planar light illumination and acoustic detection. The new system possesses several innovations. First, we utilized an optically transparent slit, which enables both light illumination and acoustic diffraction. Second, we used a combination of cold and hot mirrors to provide co-planar light illumination and acoustic detection. Third, we designed a waterproof transducer array with a long acoustic focus tailored for the co-planar setup. Compared to the previous generations, which used side-illumination and metal slit, the new system provides a larger field of view and deeper imaging depth in a more compact manner. We tested the system in both phantoms and in vivo imaging. Detailed vascular structures from different regions can be clearly revealed, making the system valuable for translational imaging applications.

High-Frequency 3D Photoacoustic Computed Tomography Using an Optical Microring Resonator.

3D photoacoustic computed tomography (3D-PACT) has made great advances in volumetric imaging of biological tissues, with high spatial-temporal resolutions and large penetration depth. The development of 3D-PACT requires high-performance acoustic sensors with a small size, large detection bandwidth, and high sensitivity. In this work, we present a new high-frequency 3D-PACT system that uses a micro-ring resonator (MRR) as the acoustic sensor. The MRR sensor has a size of 80 µm in diameter, and was fabricated using the nanoimprint lithography technology. Using the MRR sensor, we have developed a transmission-mode 3D-PACT system that has achieved a detection bandwidth of ~23 MHz, an imaging depth of ~8 mm, a lateral resolution of 114 µm, and an axial resolution of 57 µm. We have demonstrated the 3D PACT's performance on in vitro phantoms, ex vivo mouse brain, and in vivo mouse ear and tadpole. The MRR-based 3D-PACT system can be a promising tool for structural, functional, and molecular imaging of biological tissues at depths.

Photoacoustic tomography of fingerprint and underlying vasculature for improved biometric identification.

Capitalizing on the photoacoustic effect, we developed a new fingerprint sensing system that can reveal both fingerprints and underlying vascular structures at a high spatial resolution. Our system is built on a 15 MHz linear transducer array, a research ultrasound system, and a 532-nm pulsed laser. A 3D image was obtained by scanning the linear array over the fingertip. The acquired fingerprint images strongly agreed with the images acquired from ultrasound. Additional experiments were also conducted to investigate the effect of acoustic coupling. We discovered that high-quality fingerprint and vessel images can be acquired from both wet and dry fingers using our photoacoustic system. The reduced subdermal features in dry coupling can be enhanced through post-processing. Compared to existing fingerprint scanners, the photoacoustic approach provides a higher quality 3D image of the fingerprint, as well as unique subdermal vasculature structures, making the system almost impossible to counterfeit.

LINC01116 boosts the progression of pituitary adenoma via regulating miR-744-5p/HOXB8 pathway.

Pituitary adenoma (PA) is one of the common intracranial tumors. In order to optimize status quo, seeking out potential biomarkers for pituitary adenoma diagnosis and treatment is urgent and important. Long non-coding RNAs (lncRNAs) have been related with progression of various cancers. Based on this reason and unknown role of long intergenic non-protein coding RNA 1116 (LINC01116) in pituitary adenoma, we aimed to explore the function and molecular mechanism of LINC01116 in pituitary adenoma. The RT-qPCR analysis showed that LINC01116 was abnormally overexpressed in pituitary adenoma cells. Down-regulated LINC01116 effectively suppressed cell proliferation and migration as well as epithelial-mesenchymal transition (EMT) progression in pituitary adenoma. Additionally, LINC01116 could competitively sponge miR-744-5p as shown by RIP, RNA pull down and luciferase reporter assays. Similarly, we also proved that homeobox B8 (HOXB8) was the target gene of miR-744-5p in pituitary adenoma cells. In the end, the rescue assays unmasked that HOXB8 could effectually reverse inhibition effect of LINC016 knockdown on pituitary adenoma cells proliferation, migration and EMT, further suggesting that LINC01116 expedited the pituitary adenoma progression by up-regulating HOXB8. Taken together, LINC01116 boosted the progression of pituitary adenoma cells via regulating miR-744-5p/HOXB8 pathway.

Investigation of the effects of laminin present in the basal lamina of the peripheral nervous system on axon regeneration and remyelination using the nerve acellular scaffold.

This study aimed to investigate the effects of laminin (LN) located in the basal lamina, which are important components of the peripheral nervous system-extracellular matrix, on axon regeneration and remyelination. Nerve acellular scaffolds (NASs) (S-untreated) were prepared using the acellular technique. The active component LN in the NASs was blocked (S-LN- ) or upregulated (S-LN+ ); S-LN+ contained seven times more LN than did the S-untreated group. The adhesion capacity of Schwann cells (SCs) to the three types of NAS (S-untreated, S-LN- , and S-LN+ ) was assessed in vitro. Our results showed that the adhesion of SCs to the NASs was significantly reduced in the S-LN- group, whereas no difference was observed between the S-LN+ and S-untreated groups. The pretreated NASs were used to repair nerves in a nerve injury mouse model with the animals divided into four groups (S-LN- group, S-untreated group, S-LN+ group, and autograft group). Two weeks after surgery, although there was no difference in the S-LN- group, S-untreated group and S-LN+ group, the newly formed basal lamina in the S-LN- group were significantly lower than those in the other two groups. Four weeks after surgery, the S-LN+ group had higher numbers of newly generated axons and their calibers, more myelinated fibers, thicker myelin sheaths, increased myelin basic protein expression, and improved recovery of neural function compared to those of the S-LN- and S-untreated groups, but all of these parameters were significantly worse than those of the autograft group. Downregulation of the LN level in the NAS leads to a reduction in all of the above parameters.

3D Bioprinting a human iPSC-derived MSC-loaded scaffold for repair of the uterine endometrium.

Common events in the clinic, such as uterine curettage or inflammation, may lead to irreversible endometrial damage, often resulting in infertility in women of childbearing age. Currently, tissue engineering has the potential to achieve tissue manipulation, regeneration, and growth, but personalization and precision remain challenges. The application of "3D cell printing" is more in line with the clinical requirements of tissue repair. In this study, a porous grid-type human induced pluripotent stem cell-derived mesenchymal stem cell (hiMSC)-loaded hydrogel scaffold was constructed using a 3D bioprinting device. The 3D-printed hydrogel scaffold provided a permissive in vitro living environment for hiMSCs and significantly increased the survival duration of transplanted hiMSCs when compared with hiMSCs administered locally in vivo. Using an endometrial injury model, we found that hiMSC transplantation can cause early host immune responses (the serological immune response continued for more than 1 month, and the local immune response continued for approximately 1 week). Compared with the sham group, although the regenerative endometrium failed to show full restoration of the normal structure and function of the lining, implantation of the 3D-printed hiMSC-loaded scaffold not only promoted the recovery of the endometrial histomorphology (endometrial tissue and gland regeneration) and the regeneration of endometrial cells (stromal cells and epithelial cells) and endothelial cells but also improved endometrial receptivity functional indicators, namely, pinopode formation and leukemia inhibitory factor and αvß3 expression, which partly restored the embryo implantation and pregnancy maintenance functions of the injured endometrium. These indicators were significantly better in the 3D-printed hiMSC-loaded scaffold group than in the unrepaired (empty) group, the hiMSCs alone group and the 3D scaffold group, and the empty group showed the worst repair results. Our study confirm that the 3D-printed hiMSC-loaded hydrogel scaffold may be a promising material for endometrial repair.

Perfluoropolyether Nanoemulsion Encapsulating Chlorin e6 for Sonodynamic and Photodynamic Therapy of Hypoxic Tumor.

Sonodynamic therapy (SDT) has emerged as an important modality for cancer treatment. SDT utilizes ultrasound excitation, which overcomes the limitations of light penetration in deep tumors, as encountered by photodynamic therapy (PDT) which uses optical excitations. A comparative study of these modalities using the same sensitizer drug can provide an assessment of their effects. However, the efficiency of SDT and PDT is low in a hypoxic tumor environment, which limits their applications. In this study, we report a hierarchical nanoformulation which contains a Food and Drug Administration (FDA) approved sensitizer chlorin, e6, and a uniquely stable high loading capacity oxygen carrier, perfluoropolyether. This oxygen carrier possesses no measurable cytotoxicity. It delivers oxygen to overcome hypoxia, and at the same time, boosts the efficiency of both SDT and PDT. Moreover, we comparatively analyzed the efficiency of SDT and PDT for tumor treatment throughout the depth of the tissue. Our study demonstrates that the strengths of PDT and SDT could be combined into a single multifunctional nanoplatform, which works well in the hypoxia environment and overcomes the limitations of each modality. The combination of deep tissue penetration by ultrasound and high spatial activation by light for selective treatment of single cells will significantly enhance the scope for therapeutic applications.

Dual Scan Mammoscope (DSM)-A New Portable Photoacoustic Breast Imaging System With Scanning in Craniocaudal Plane.

OBJECTIVE: We present a new photoacoustic tomography system that provides visualization of angiographic features in a human breast with mammogram-like images. METHODS: The system images a mildly compressed breast, from both top and bottom, using two 128-element, 2.25 MHz linear transducer arrays and line optical fiber bundles. The mild compression is achieved using plastic films, which is a more comfortable experience for the patient compared to rigid metal plates used in a traditional mammogram. RESULTS: We could image a D cup-sized breast of 7 cm thickness within 1 minute and achieve a spatial resolution of around 1 mm in all directions. CONCLUSION: Our system possesses the benefits of portability, speedy scanning, and patient comfort. The craniocaudal-view images can be easily correlated with existing imaging modalities for data interpretation. SIGNIFICANCE: Early cancer detection plays a critical role in overall cancer survival rate. Our system may address the limitations of mammogram and offer a radiation-free screening technique for patients with dense breasts.