Multiscale embedded printing of engineered human tissue and organ equivalents.

Creating tissue and organ equivalents with intricate architectures and multiscale functional feature sizes is the first step toward the reconstruction of transplantable human tissues and organs. Existing embedded ink writing approaches are limited by achievable feature sizes ranging from hundreds of microns to tens of millimeters, which hinders their ability to accurately duplicate structures found in various human tissues and organs. In this study, a multiscale embedded printing (MSEP) strategy is developed, in which a stimuli-responsive yield-stress fluid is applied to facilitate the printing process. A dynamic layer height control method is developed to print the cornea with a smooth surface on the order of microns, which can effectively overcome the layered morphology in conventional extrusion-based three-dimensional bioprinting methods. Since the support bath is sensitive to temperature change, it can be easily removed after printing by tuning the ambient temperature, which facilitates the fabrication of human eyeballs with optic nerves and aortic heart valves with overhanging leaflets on the order of a few millimeters. The thermosensitivity of the support bath also enables the reconstruction of the full-scale human heart on the order of tens of centimeters by on-demand adding support bath materials during printing. The proposed MSEP demonstrates broader printable functional feature sizes ranging from microns to centimeters, providing a viable and reliable technical solution for tissue and organ printing in the future.

MIB2 Functions in Oocyte Meiosis by Modulating Chromatin Configuration.

Chromatin configuration serves as a principal indicator of GV (germinal vesicle)-stage oocyte quality. However, the underlying mechanisms governing the chromatin configuration transition from NSN (non-surrounded nucleolus) to SN (surrounded nucleolus) remain unclear. In this study, by conducting a quantitative proteomic analysis, we identified an increased expression of the MIB2 (MIB E3 ubiquitin protein ligase 2) protein in SN oocytes. Specific depletion of MIB2 in SN oocytes not only leads to severe disruption of the meiotic apparatus and a higher incidence of aneuploidy but also adversely affects meiotic maturation and early embryo development. Notably, overexpression of MIB2 in NSN oocytes facilitates the chromatin configuration transition. Meantime, we observed that forced expression of MIB2 in NSN oocytes significantly mitigates spindle/chromosome disorganization and aneuploidy. In summary, our results suggest that chromatin configuration transition regulated by MIB2 is crucial for oocytes to acquire developmental competence.

Emerging Omicron subvariants evade neutralizing immunity elicited by vaccine or BA.1/BA.2 infection.

The newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2.75 and BA.2.76 subvariants contained 35 and 29 additional mutations in its spike (S) protein compared with the reference SARS-CoV-2 genome, respectively. Here, we measured the evasion degree of the BA.1, BA.2, BA.4, BA.5, BA.2.75, and BA.2.76 subvariants from neutralizing immunity in people previously infected with the Omicron BA.1 and BA.2, determined the effect of vaccination on immune evasion, and compared the titers of neutralizing antibodies in serums between acute infection and convalescence. Results showed that the neutralization effect of serums from patients with different vaccination statuses and BA.1/BA.2 breakthrough infection decreased with the Omicron evolution from BA.1 to BA.2, BA.4, BA.5, BA.2.75, and BA.2.76. This study also indicated that the existing vaccines could no longer provide effective protection, especially for the emerging BA.2.75 and BA.2.76 subvariants. Therefore, vaccines against emerging epidemic strains should be designed specifically. In the future, we can not only focus on the current strains, but also predict and design new vaccines against potential mutant strains. At the same time, we can combine the virus strains' infection characteristics to develop protective measures for virus colonization areas, such as nasal protection spray. Besides, further studies on the Y248N mutation of BA.2.76 subvariant were also necessary to explore its contribution to the enhanced immune evasion ability.

Evidence for human infection with avian influenza A(H9N2) virus via environmental transmission inside live poultry market in Xiamen, China.

H9N2 avian influenza virus (AIV) has become prevalent in the live poultry market (LPM) worldwide, and environmental transmission mode is an important way for AIVs to infect human beings in the LPM. To find evidence of human infection with the influenza A(H9N2) virus via environmental contamination, we evaluated one human isolate and three environmental isolates inside LPMs in Xiamen, China. The phylogeny, transmissibility, and pathogenicity of the four isolates were sorted out systematically. As for the H9N2 virus, which evolved alongside the "Avian-Environment-Human" spreading chain in LPMs from the summer of 2019 to the summer of 2020, its overall efficiency of contact and aerosol transmissibility improved, which might contribute to the increasing probability of human infection. This study indicated that environmental exposure might act as an important source of human infection in LPMs.

Dual active sites over Cu-ZnO-ZrO2 catalysts for carbon dioxide hydrogenation to methanol.

CO2 hydrogenation to methanol is a significant approach to tackle the problem of global warming and simultaneously meet the demand for the portable fuel. Cu-ZnO catalysts with various kinds of promoters have received wide attention. However, the role of promoter and the form of active sites in CO2 hydrogenation are still in debate. Here, various molar ratios of ZrO2 were added into the Cu-ZnO catalysts to tune the distributions of Cu0 and Cu+ species. A volcano-like trend between the ratio of Cu+/ (Cu+ + Cu0) and the amount of ZrO2 is presented, among which the CuZn10Zr (the molar ratio of ZrO2 is 10%) catalyst reaches the highest value. Correspondingly, the maximum value of space-time yield to methanol with 0.65 gMeOH/(gcat·hr) is obtained on CuZn10Zr at reaction conditions of 220°C and 3 MPa. Detailed characterizations demonstrate that dual active sites are proposed during CO2 hydrogenation over CuZn10Zr catalyst. The exposed Cu0 takes participate in the activation of H2, while on the Cu+ species, the intermediate of formate from the co-adsorption of CO2 and H2 prefers to be further hydrogenated to CH3OH than decomposing into the by-product of CO, yielding a high selectivity of methanol.

miR-140-3p suppresses the proliferation and migration of macrophages.

Macrophages benefit myelin debris removal, blood vessel formation, and Schwann cell activation following peripheral nerve injury. Identifying factors that modulate macrophage phenotype may advantage the repair and regeneration of injured peripheral nerves. microRNAs (miRNAs) are important regulators of many physiological and pathological processes, including peripheral nerve regeneration. Herein, we investigated the regulatory roles of miR-140-3p, a miRNA that was differentially expressed in injured rat sciatic nerves, in macrophage RAW264.7 cells. Observations from EdU proliferation assay demonstrated that elevated miR-140-3p decreased the proliferation rates of RAW264.7 cells while suppressed miR-140-3p increased the proliferation rates of RAW264.7 cells. Transwell-based migration assay showed that up-regulated and down-regulated miR-140-3p led to elevated and reduced migration abilities, respectively. However, the abundances of numerous phenotypic markers of M1 and M2 macrophages were not significantly altered by miR-140-3p mimic or inhibitor transfection. Bioinformatic analysis and miR-140-3p-induced gene suppression examination suggested that Smad3 might be the target gene of miR-140-3p. These findings illuminate the inhibitory effects of miR-140-3p on the proliferation and migration of macrophages and contribute to the cognition of the essential roles of miRNAs during peripheral nerve regeneration.

Exploration of Coincidence Detection of Cascade Photons to Enhance Preclinical Multi-Radionuclide SPECT Imaging.

We proposed a technique of coincidence detection of cascade photons (CDCP) to enhance preclinical SPECT imaging of therapeutic radionuclides emitting cascade photons, such as Lu-177, Ac-225, Ra-223, and In-111. We have carried out experimental studies to evaluate the proposed CDCP-SPECT imaging of low-activity radionuclides using a prototype coincidence detection system constructed with large-volume cadmium zinc telluride (CZT) imaging spectrometers and a pinhole collimator. With In-111 in experimental studies, the CDCP technique allows us to improve the signal-to-contamination in the projection (Projection-SCR) by ~53 times and reduce ~98% of the normalized contamination. Compared to traditional scatter correction, which achieves a Projection-SCR of 1.00, our CDCP method boosts it to 15.91, showing enhanced efficacy in reducing down-scattered contamination, especially at lower activities. The reconstructed images of a line source demonstrated the dramatic enhancement of the image quality with CDCP-SPECT compared to conventional and triple-energy-window-corrected SPECT data acquisition. We also introduced artificial energy blurring and Monte Carlo simulation to quantify the impact of detector performance, especially its energy resolution and timing resolution, on the enhancement through the CDCP technique. We have further demonstrated the benefits of the CDCP technique with simulation studies, which shows the potential of improving the signal-to-contamination ratio by 300 times with Ac-225, which emits cascade photons with a decay constant of ~0.1 ns. These results have demonstrated the potential of CDCP-enhanced SPECT for imaging a super-low level of therapeutic radionuclides in small animals.

Convolutional neural network advances in demosaicing for fluorescent cancer imaging with color-near-infrared sensors.

Significance: Single-chip imaging devices featuring vertically stacked photodiodes and pixelated spectral filters are advancing multi-dye imaging methods for cancer surgeries, though this innovation comes with a compromise in spatial resolution. To mitigate this drawback, we developed a deep convolutional neural network (CNN) aimed at demosaicing the color and near-infrared (NIR) channels, with its performance validated on both pre-clinical and clinical datasets. Aim: We introduce an optimized deep CNN designed for demosaicing both color and NIR images obtained using a hexachromatic imaging sensor. Approach: A residual CNN was fine-tuned and trained on a dataset of color images and subsequently assessed on a series of dual-channel, color, and NIR images to demonstrate its enhanced performance compared with traditional bilinear interpolation. Results: Our optimized CNN for demosaicing color and NIR images achieves a reduction in the mean square error by 37% for color and 40% for NIR, respectively, and enhances the structural dissimilarity index by 37% across both imaging modalities in pre-clinical data. In clinical datasets, the network improves the mean square error by 35% in color images and 42% in NIR images while enhancing the structural dissimilarity index by 39% in both imaging modalities. Conclusions: We showcase enhancements in image resolution for both color and NIR modalities through the use of an optimized CNN tailored for a hexachromatic image sensor. With the ongoing advancements in graphics card computational power, our approach delivers significant improvements in resolution that are feasible for real-time execution in surgical environments.

Mechanical analysis of radial performance in biodegradable polymeric vascular stents manufactured using micro-injection molding.

Micro-injection molding (MiM) is a promising technique for manufacturing biodegradable polymeric vascular stents (BPVSs) at scale, in which a trapezoidal strut cross section is needed to ensure high-quality de-molding. However, there is a lack of research on the influence of the strut cross-sectional shape on its mechanical properties, posing a challenge in determining the key geometries of the strut when using MiM to produce BPVSs. Hence, this work has investigated the relationships between the geometry parameters, including the de-molding angle, and the radial support property of BPVSs using the finite element method. The results reveal that the radial stiffness of BPVSs is significantly affected by the de-molding angle, which can be counteracted by adjusting strut height, bending radius, and strut thickness. Stress distribution analysis underscores the crucial role of the curved portion of the support ring during compression, with the inner side of the curved region experiencing stress concentration. A mathematical model has been established to describe the relationships between the geometry parameters and the radial support property of the BPVSs. Notably, the radius of the neutral layer emerges as a key determinant of radial stiffness. This study is expected to serve as a guideline for the development of BPVSs that can be manufactured using MiM.

The chromatin accessibility landscape of mouse oocytes during configuration transition.

The transition of chromatin configuration in mammalian oocytes from a non-surrounded nucleolus (NSN) to a surrounded nucleolus (SN) is critical for acquiring the developmental competence. However, the genomic and epigenomic features underlying this process remain poorly understood. In the present study, we first establish the chromatin accessibility landscape of mouse oocytes from NSN to SN stage. Through the integrative analysis of multi-omics, we find that the establishment of DNA methylation in oocytes is independent of the dynamics of chromatin accessibility. In contrast, histone H3K4me3 status is closely associated with the dynamics of accessible regions during configuration transition. Furthermore, by focusing on the actively transcribed genes in NSN and SN oocytes, we discover that chromatin accessibility coupled with histone methylation (H3K4me3 and H3K27me3) participates in the transcriptional control during phase transition. In sum, our data provide a comprehensive resource for probing configuration transition in oocytes, and offer insights into the mechanisms determining chromatin dynamics and oocyte quality.

Digital Light Processing 4D Printing of Poloxamer Micelles for Facile Fabrication of Multifunctional Biocompatible Hydrogels as Tailored Wearable Sensors.

The lack of both digital light processing (DLP) compatible and biocompatible photopolymers, along with inappropriate material properties required for wearable sensor applications, substantially hinders the employment of DLP 3D printing in the fabrication of multifunctional hydrogels. Herein, we discovered and implemented a photoreactive poloxamer derivative, Pluronic F-127 diacrylate, which overcomes these limitations and is optimized to achieve DLP 3D printed micelle-based hydrogels with high structural complexity, resolution, and precision. In addition, the dehydrated hydrogels exhibit a shape-memory effect and are conformally attached to the geometry of the detection point after rehydration, which implies the 4D printing characteristic of the fabrication process and is beneficial for the storage and application of the device. The excellent cytocompatibility and in vivo biocompatibility further strengthen the potential application of the poloxamer micelle-based hydrogels as a platform for multifunctional wearable systems. After processing them with a lithium chloride (LiCl) solution, multifunctional conductive ionic hydrogels with antifreezing and antiswelling properties along with good transparency and water retention are easily prepared. As capacitive flexible sensors, the DLP 3D printed micelle-based hydrogel devices exhibit excellent sensitivity, cycling stability, and durability in detecting multimodal deformations. Moreover, the DLP 3D printed conductive hydrogels are successfully applied as real-time human motion and tactile sensors with satisfactory sensing performances even in a -20 °C low-temperature environment.

Vertebral bone quality score provides preoperative bone density assessment for patients undergoing lumbar spine surgery: a retrospective study.

OBJECTIVE: The novel MRI-based vertebral bone quality (VBQ) score has been described as an opportunistic screening tool for osteoporosis, but the stability and practical value of this score deserve further investigation. The purpose of this study was to assess whether preoperative VBQ scores could assist in identifying reduced bone mineral density (BMD) or osteoporosis and evaluating the consistency between MRI systems with different field strengths. METHODS: The VBQ scores of the patients who underwent surgery for lumbar disc herniation and the single-level VBQ scores of each L1-4 vertebral body were measured and calculated with preoperative lumbar MRI noncontrast T1-weighted phases. The VBQ scores were evaluated for correlation analysis using dual-energy x-ray absorptiometry (DEXA) T-scores. The receiver operating characteristic (ROC) curve was used to evaluate the ability of the VBQ scores to identify patients with reduced BMD and with osteoporosis. Differences in CSF measurements at different levels of L1-4 were compared. Twenty-four patients who had been examined using another MRI machine were used as controls to test the interdevice agreement of the VBQ scores. RESULTS: The study included 100 patients with mean VBQ scores of 2.81 ± 0.28 (normal BMD), 3.06 ± 0.36 (osteopenia), and 3.43 ± 0.37 (osteoporosis). VBQ scores differed significantly between BMD subgroups (p < 0.001). The Pearson correlation coefficient showed a moderate negative linear correlation between novel VBQ scores and the lowest DEXA T-scores (r = -0.524). ROC analysis showed good discrimination of VBQ scores in patients with reduced BMD (area under the curve [AUC] 0.793) and with osteoporosis (AUC 0.810). The diagnostic thresholds of reduced BMD and osteoporosis according to the maximum Youden index were 3.06 (sensitivity 0.636, specificity 0.870, positive predictive value [PPV] 0.942, negative predictive value [NPV] 0.417) and 3.05 (sensitivity 0.875, specificity 0.618, PPV 0.519, NPV 0.913), respectively. CSF measurements at the L2, L3, and L4 levels were essentially identical and did not significantly affect the final VBQ scores (p > 0.05), whereas CSF measurements at the L1 level were found to be heterogeneous (p < 0.001). No significant differences were found in VBQ scores between the same brand of MRI machines at different field strengths (1.5 and 3.0 T, p = 0.107). CONCLUSIONS: The new VBQ score provides an additional screening opportunity for preoperative BMD assessment. A VBQ score < 3.05 essentially excludes osteoporosis, whereas a VBQ score ≥ 3.05 (especially ≥ 3.06) suggests the need for further examination. The VBQ score is comparable between different MRI systems.

Simulating and Predicting the Part Warping in Fused Deposition Modeling by Thermal-Structural Coupling Analysis.

As the most commonly used additive manufacturing technology, fused deposition modeling (FDM) still faces some technical issues caused by temperature change-induced unsteady thermal stress and warping. These issues can further lead to the deformation of printed parts and even terminate the printing process. In response to these issues, this article established a numerical model of temperature field and thermal stress field for FDM by finite element modeling and "birth-death element" technique to predict the deformation of the part. What makes sense in this process is that the logic of elements sort based on ANSYS Parametric Design Language (APDL) was proposed to sort the meshed elements, which was aimed to perform FDM simulation quickly on the model. In this work, the effects of the sheets shape and infill line directions (ILDs) on the distortion during FDM were simulated and verified. From the analysis of stress field and deformation nephogram, the simulation results indicated that ILD had greater effects on the distortion. Moreover, the sheet warping became most serious when the ILD was aligned with the diagonal of the sheet. The simulation results matched well with the experimental results. Thus, the proposed method in this work can be used to optimize the printing parameters for FDM process.

Experimental Evaluation of a 3-D CZT Imaging Spectrometer for Potential Use in Compton-Enhanced PET Imaging.

We constructed a prototype positron emission tomography (PET) system and experimentally evaluated large-volume 3-D cadmium zinc telluride (CZT) detectors for potential use in Compton-enhanced PET imaging. The CZT spectrometer offers sub-0.5-mm spatial resolution, an ultrahigh energy resolution (~1% @ 511 keV), and the capability of detecting multiple gamma-ray interactions that simultaneously occurred. The system consists of four CZT detector panels with a detection area of around 4.4 cm × 4.4 cm. The distance between the front surfaces of the two opposite CZT detector panels is ~80 mm. This system allows us to detect coincident annihilation photons and Compton interactions inside the detectors and then, exploit Compton kinematics to predict the first Compton interaction site and reject chance coincidences. We have developed a numerical integration technique to model the near-field Compton response that incorporates Doppler broadening, detector's finite resolutions, and the distance between the first and second interactions. This method was used to effectively reject random and scattered coincidence events. In the preliminary imaging studies, we have used point sources, line sources, a custom-designed resolution phantom, and a commercial image quality (IQ) phantom to demonstrate an imaging resolution of approximately 0.75 mm in PET images, and Compton-based enhancement.

Sacrificial scaffold-assisted direct ink writing of engineered aortic valve prostheses.

Heart valve disease has become a serious global health problem, which calls for numerous implantable prosthetic valves to fulfill the broader needs of patients. Although current three-dimensional (3D) bioprinting approaches can be used to manufacture customized valve prostheses, they still have some complications, such as limited biocompatibility, constrained structural complexity, and difficulty to make heterogeneous constructs, to name a few. To overcome these challenges, a sacrificial scaffold-assisted direct ink writing approach has been explored and proposed in this work, in which a sacrificial scaffold is printed to temporarily support sinus wall and overhanging leaflets of an aortic valve prosthesis that can be removed easily and mildly without causing any potential damages to the valve prosthesis. The bioinks, composed of alginate, gelatin, and nanoclay, used to print heterogenous valve prostheses have been designed in terms of rheological/mechanical properties and filament formability. The sacrificial ink made from Pluronic F127 has been developed by evaluating rheological behavior and gel temperature. After investigating the effects of operating conditions, complex 3D structures and homogenous/heterogenous aortic valve prostheses have been successfully printed. Lastly, numerical simulation and cycling experiments have been performed to validate the function of the printed valve prostheses as one-way valves.

3D printing-based full-scale human brain for diverse applications.

Surgery is the most frequent treatment for patients with brain tumors. The construction of full-scale human brain models, which is still challenging to realize via current manufacturing techniques, can effectively train surgeons before brain tumor surgeries. This paper aims to develop a set of three-dimensional (3D) printing approaches to fabricate customized full-scale human brain models for surgery training as well as specialized brain patches for wound healing after surgery. First, a brain patch designed to fit a wound's shape and size can be easily printed in and collected from a stimuli-responsive yield-stress support bath. Then, an inverse 3D printing strategy, called "peeling-boiled-eggs," is proposed to fabricate full-scale human brain models. In this strategy, the contour layer of a brain model is printed using a sacrificial ink to envelop the target brain core within a photocurable yield-stress support bath. After crosslinking the contour layer, the as-printed model can be harvested from the bath to photo crosslink the brain core, which can be eventually released by liquefying the contour layer. Both the brain patch and full-scale human brain model are successfully printed to mimic the scenario of wound healing after removing a brain tumor, validating the effectiveness of the proposed 3D printing approaches.

Bioinspired, vertically stacked, and perovskite nanocrystal-enhanced CMOS imaging sensors for resolving UV spectral signatures.

Imaging and identifying target signatures and biomedical markers in the ultraviolet (UV) spectrum is broadly important to medical imaging, military target tracking, remote sensing, and industrial automation. However, current silicon-based imaging sensors are fundamentally limited because of the rapid absorption and attenuation of UV light, hindering their ability to resolve UV spectral signatures. Here, we present a bioinspired imaging sensor capable of wavelength-resolved imaging in the UV range. Inspired by the UV-sensitive visual system of the Papilio xuthus butterfly, the sensor monolithically combines vertically stacked photodiodes and perovskite nanocrystals. This imaging design combines two complementary UV detection mechanisms: The nanocrystal layer converts a portion of UV signals into visible fluorescence, detected by the photodiode array, while the remaining UV light is detected by the top photodiode. Our label-free UV fluorescence imaging data from aromatic amino acids and cancer/normal cells enables real-time differentiation of these biomedical materials with 99% confidence.

Realization of thousand-second improved confinement plasma with Super I-mode in Tokamak EAST.

Mastering nuclear fusion, which is an abundant, safe, and environmentally competitive energy, is a great challenge for humanity. Tokamak represents one of the most promising paths toward controlled fusion. Obtaining a high-performance, steady-state, and long-pulse plasma regime remains a critical issue. Recently, a big breakthrough in steady-state operation was made on the Experimental Advanced Superconducting Tokamak (EAST). A steady-state plasma with a world-record pulse length of 1056 s was obtained, where the density and the divertor peak heat flux were well controlled, with no core impurity accumulation, and a new high-confinement and self-organizing regime (Super I-mode = I-mode + e-ITB) was discovered and demonstrated. These achievements contribute to the integration of fusion plasma technology and physics, which is essential to operate next-step devices.

Experimental Study of Injection Molding Replicability for the Micro Embossment of the Ultrasonic Vibrator.

It is challenging to fabricate micro features on an injection-molded polymer product. Ultrasonic vibration induced into micro-injection molding is helpful for flow of polymer melt. In this paper, a micro-injection mold integrated with ultrasonic vibration was designed and fabricated, and micro embossment was machined on the surface of the ultrasonic vibrator. Poly(methacrylic acid methyl ester) (PMMA) was used for injection molding experiments, with four ultrasonic power levels (0, 300, 600, and 900 W), three injection speed levels (60, 80, and 100 cm3/s), two injection pressure levels (60 and 90 MPa) and a mold temperature of 60 °C. It was found that ultrasonic vibration perpendicular to the middle surface of the cavity is beneficial in forming transverse microstructure, but is not conducive to generating longitudinal microstructure. Increase in injection pressure can improve molding qualities for both the longitudinal micro groove and the transverse micro groove. Increase in injection speed is not conducive to forming the longitudinal micro groove but benefits formation of the transverse micro groove. When ultrasonic vibration is applied at the injection and packing stages, molding quality of the longitudinal micro groove becomes worse, while that of the transverse micro groove becomes better.