Covalent-Frameworked 2D Crown Ether with Chemical Multifunctionality.

Here, we present the synthesis and characterization of a novel 2D crystalline framework, named C2O, which mainly consists of carbon and oxygen in a 2:1 molar ratio and features crown ether holes in its skeletal structure. The covalent-frameworked 2D crown ether can be synthesized on a gram-scale and exhibits fine chemical stability in various environments, including acid, base, and different organic solvents. The C2O efficiently activates KI through the strong coordination of K+ with crown ether holes in a rigid framework, which enhances the nucleophilicity of I- and significantly improves its catalytic activity for CO2 fixation with epoxides. The presence of C2O with KI results in remarkable increases in CO2 conversion from 5.7% to 99.9% and from 2.9% to 74.2% for epichlorohydrin and allyl glycidyl ether, respectively. Moreover, C2O possesses both electrophilic and nucleophilic sites at the edge of its framework, allowing for the customization of physicochemical properties by a diverse range of chemical modifications. Specifically, incorporating allyl glycidyl ether (AGE) as an electrophile or ethoxyethylamine (EEA) as a nucleophile into C2O enables the synthesis of C2O-AGE or C2O-EEA, respectively. These modified frameworks exhibit improved conversions of 97.2% and 99.9% for CO2 fixation with allyl glycidyl ether, outperforming unmodified C2O showing a conversion of 74.2%. This newly developed scalable, durable, and customizable covalent framework holds tremendous potential for the design and preparation of outstanding materials with versatile functionalities, rendering them highly attractive for a wide range of applications.

Magnetic Silica-Coated Fluorescent Microspheres (MagSiGlow) for Simultaneous Detection of Tumor-Associated Proteins.

Multiplexed bead assays for solution-phase biosensing often encounter cross-over reactions during signal amplification steps, leading to unwanted false positive and high background signals. Current solutions involve complex custom-designed and costly equipment, limiting their application in simple laboratory setup. In this study, we introduce a straightforward protocol to adapt a multiplexed single-bead assay to standard fluorescence imaging plates, enabling the simultaneous analysis of thousands of reactions per plate. This approach focuses on the design and synthesis of bright fluorescent and magnetic microspheres (MagSiGlow) with multiple fluorescent wavelengths serving as unique detection markers. The imaging-based, single-bead assay, combined with a scripted algorithm, allows the detection, segmentation, and co-localization on average of 7500 microspheres per field of view across five imaging channels in less than one second. We demonstrate the effectiveness of this method with remarkable sensitivity at low protein detection limits (100 pg/mL). This technique showed over 85 % reduction in signal cross-over to the solution-based method after the concurrent detection of tumor-associated protein biomarkers. This approach holds the promise of substantially enhancing high throughput biosensing for multiple targets, seamlessly integrating with rapid image analysis algorithms.

Efficient online real-time video stabilization with a novel least squares formulation and parallel AC-RANSAC.

A novel online real-time video stabilization algorithm (LSstab) that suppresses unwanted motion jitters based on cinematography principles is presented. LSstab features a parallel realization of the a-contrario RANSAC (AC-RANSAC) algorithm to estimate the inter-frame camera motion parameters. A novel least squares based smoothing cost function is then proposed to mitigate undesirable camera jitters according to cinematography principles. A recursive least square solver is derived to minimize the smoothing cost function with a linear computation complexity. LSstab is evaluated using a suite of publicly available videos against state-of-the-art video stabilization methods. Results show that LSstab achieves comparable or better performance, which attains real-time processing speed when a GPU is used.

Graphene Quantum Dots Alleviate Impaired Functions in Niemann-Pick Disease Type C in Vivo.

While the neuropathological characteristics of Niemann-Pick disease type C (NPC) result in a fatal diagnosis, the development of clinically available therapeutic agent remains a challenge. Here we propose graphene quantum dots (GQDs) as a potential candidate for the impaired functions in NPC in vivo. In addition to the previous findings that GQDs exhibit negligible long-term toxicity and are capable of penetrating the blood-brain barrier, GQD treatment reduces the aggregation of cholesterol in the lysosome through expressed physical interactions. GQDs also promote autophagy and restore defective autophagic flux, which, in turn, decreases the atypical accumulation of autophagic vacuoles. More importantly, the injection of GQDs inhibits the loss of Purkinje cells in the cerebellum while also demonstrating reduced activation of microglia. The ability of GQDs to alleviate impaired functions in NPC proves the promise and potential of the use of GQDs toward resolving NPC and other related disorders.

cAMP/EPAC Signaling Enables ETV2 to Induce Endothelial Cells with High Angiogenesis Potential.

Although the generation of ETV2-induced endothelial cells (iECs) from human fibroblasts serves as a novel therapeutic strategy in regenerative medicine, the process is inefficient, resulting in incomplete iEC angiogenesis. Therefore, we employed chromatin immunoprecipitation (ChIP) sequencing and identified molecular mechanisms underlying ETV2-mediated endothelial transdifferentiation to efficiently produce iECs retaining appropriate functionality in long-term culture. We revealed that the majority of ETV2 targets in human fibroblasts are related to vasculature development and signaling transduction pathways, including Rap1 signaling. From a screening of signaling pathway modulators, we confirmed that forskolin facilitated efficient and rapid iEC reprogramming via activation of the cyclic AMP (cAMP)/exchange proteins directly activated by cAMP (EPAC)/RAP1 axis. The iECs obtained via cAMP signaling activation showed superior angiogenesis in vivo as well as in vitro. Moreover, these cells could form aligned endothelium along the vascular lumen ex vivo when seeded into decellularized liver scaffold. Overall, our study provided evidence that the cAMP/EPAC/RAP1 axis is required for the efficient generation of iECs with angiogenesis potential.

Iterative wavefront reconstruction for strong turbulence using Shack-Hartmann wavefront sensor measurements.

An iterative wavefront reconstruction method using Shack-Hartmann wavefront sensor (SHWFS) measurements is presented in this paper. A new cost function for the wavefront reconstruction problem is derived and the solution is obtained iteratively using the gradient descent method. The proposed method aims to effectively handle the scintillated SHWFS measurements and to provide simpler and accurate ways to achieve branch-point-tolerant wavefront reconstruction suitable for adaptive optics compensation of strong turbulence. Simulated iterative wavefront reconstruction results show the effectiveness of the proposed method. A laboratory optical testbed is also presented to show the experimental implementation of the proposed method.

Biologically inspired artificial eyes and photonics.

Natural visual systems have inspired scientists and engineers to mimic their intriguing features for the development of advanced photonic devices that can provide better solutions than conventional ones. Among various kinds of natural eyes, researchers have had intensive interest in mammal eyes and compound eyes due to their advantages in optical properties such as focal length tunability, high-resolution imaging, light intensity modulation, wide field of view, high light sensitivity, and efficient light management. A variety of different approaches in the broad field of science and technology have been tried and succeeded to duplicate the functions of natural eyes and develop bioinspired photonic devices for various applications. In this review, we present a comprehensive overview of bioinspired artificial eyes and photonic devices that mimic functions of natural eyes. After we briefly introduce visual systems in nature, we discuss optical components inspired by the mammal eyes, including tunable lenses actuated with different mechanisms, curved image sensors with low aberration, and light intensity modulators. Next, compound eye inspired photonic devices are presented, such as microlenses and micromirror arrays, imaging sensor arrays on curved surfaces, self-written waveguides with microlens arrays, and antireflective nanostructures (ARS). Subsequently, compound eyes with focal length tunability, photosensitivity enhancers, and polarization imaging sensors are described.

Optimal Camera Pose and Placement Configuration for Maximum Field-of-View Video Stitching.

An optimal camera placement problem is investigated. The objective is to maximize the area of the field of view (FoV) of a stitched video obtained by stitching video streams from an array of cameras. The positions and poses of these cameras are restricted to a given set of selections. The camera array is designed to be placed inside the abdomen to support minimally invasive laparoscopic surgery. Hence, a few non-traditional requirements/constraints are imposed: Adjacent views are required to overlap to support image registration for seamless video stitching. The resulting effective FoV should be a contiguous region without any holes and should be a convex polygon. With these requirements, traditional camera placement algorithms cannot be directly applied to solve this problem. In this work, we show the complexity of this problem grows exponentially as a function of the problem size, and then present a greedy polynomial time heuristic solution that approximates well to the globally optimal solution. We present a new approach to directly evaluate the combined coverage area (area of FoV) as the union of a set of quadrilaterals. We also propose a graph-based approach to ensure the stitching requirement (overlap between adjacent views) is satisfied. We present a method to find a convex polygon with maximum area from a given polygon. Several design examples show that the proposed algorithm can achieve larger FoV area while using much less computing time.

Biologically Inspired Organic Light-Emitting Diodes.

Many animal species employ highly conspicuous traits as courtship signals for successful mating. Fireflies utilize their bioluminescent light as visual courtship signals. In addition to efficient bioluminescent light emission, the structural components of the firefly lantern also contribute to the enhancement of conspicuous optical signaling. Recently, these firefly lantern ultrastructures have attracted much interest and inspired highly efficient light management approaches. Here we report on the unique optical function of the hierarchical ultrastructures found in a firefly (Pyrocoelia rufa) and their biological inspiration of highly efficient organic light-emitting diode (OLED) applications. The hierarchical structures are comprised of longitudinal nanostructures and asymmetric microstructures, which were successfully replicated using geometry-guided resist reflow, replica molding, and polydimethylsiloxane (PDMS) oxidation. The external quantum efficiency (EQE) of the bioinspired OLEDs was enhanced by up to 61%. The bioinspired OLEDs clearly showed side-enhanced super-Lambertian emission with a wide-viewing angle. The highly efficient light extraction and wide-angle illumination suggest how the hierarchical structures likely improve the recognition of firefly optical courtship signals over a wide-angle range. At the same time, the biologically inspired designs provide a new paradigm for designing functional optical surfaces for lighting or display applications.

Cathepsin S contributes to microglia-mediated olfactory dysfunction through the regulation of Cx3cl1-Cx3cr1 axis in a Niemann-Pick disease type C1 model.

Microglia can aggravate olfactory dysfunction by mediating neuronal death in the olfactory bulb (OB) of a murine model of Niemann-Pick disease type C1 (NPC1), a fatal neurodegenerative disorder accompanied by lipid trafficking defects. In this study, we focused on the crosstalk between neurons and microglia to elucidate the mechanisms underlying extensive microgliosis in the NPC1-affected brain. Microglia in the OB of NPC1 mice strongly expressed CX3C chemokine receptor 1 (Cx3cr1), a specific receptor for the neural chemokine C-X3-C motif ligand 1 (Cx3cl1). In addition, a high level of Cx3cl1 was detected in NPC1 mouse-derived CSF due to enhanced catalytic activity of Cathepsin S (Ctss), which is responsible for Cx3cl1 secretion. Notably, nasal delivery of Cx3cl1 neutralizing antibody or Ctss inhibitor could inhibit the Cx3cl1-Cx3cr1 interaction and support neuronal survival through the suppression of microglial activation, leading to an improvement in the olfactory function in NPC1 mice. Relevant in vitro experiments revealed that intracellular cholesterol accumulation could act as a strong inducer of abnormal Ctss activation and, in turn, stimulated the Cx3cl1-Cx3cr1 axis in microglia via p38 mitogen-activated protein kinase signaling. Our data address the significance of Cx3cl1-Cx3cr1 interaction in the development of microglial neurotoxicity and suggest that Ctss is a key upstream regulator. Therefore, this study contributes to a better understanding of the crosstalk between neurons and microglia in the development of the neurodegeneration and provides a new perspective for the management of olfactory deficits and other microglia-dependent neuropathies. GLIA 2016;64:2291-2305.

Compact stereo endoscopic camera using microprism arrays.

This work reports a microprism array (MPA) based compact stereo endoscopic camera with a single image sensor. The MPAs were monolithically fabricated by using two-step photolithography and geometry-guided resist reflow to form an appropriate prism angle for stereo image pair formation. The fabricated MPAs were transferred onto a glass substrate with a UV curable resin replica by using polydimethylsiloxane (PDMS) replica molding and then successfully integrated in front of a single camera module. The stereo endoscopic camera with MPA splits an image into two stereo images and successfully demonstrates the binocular disparities between the stereo image pairs for objects with different distances. This stereo endoscopic camera can serve as a compact and 3D imaging platform for medical, industrial, or military uses.

Biologically inspired LED lens from cuticular nanostructures of firefly lantern.

Cuticular nanostructures found in insects effectively manage light for light polarization, structural color, or optical index matching within an ultrathin natural scale. These nanostructures are mainly dedicated to manage incoming light and recently inspired many imaging and display applications. A bioluminescent organ, such as a firefly lantern, helps to out-couple light from the body in a highly efficient fashion for delivering strong optical signals in sexual communication. However, the cuticular nanostructures, except the light-producing reactions, have not been well investigated for physical principles and engineering biomimetics. Here we report a unique observation of high-transmission nanostructures on a firefly lantern and its biological inspiration for highly efficient LED illumination. Both numerical and experimental results clearly reveal high transmission through the nanostructures inspired from the lantern cuticle. The nanostructures on an LED lens surface were fabricated by using a large-area nanotemplating and reconfigurable nanomolding with heat-induced shear thinning. The biologically inspired LED lens, distinct from a smooth surface lens, substantially increases light transmission over visible ranges, comparable to conventional antireflection coating. This biological inspiration can offer new opportunities for increasing the light extraction efficiency of high-power LED packages.

Recurrent intractable hiccups treated by cervical phrenic nerve block under electromyography: report of a case.

Intractable or persistent hiccups require intensive or invasive treatments. The use of a phrenic nerve block or destructive treatment for intractable hiccups has been reported to be a useful and discrete method that might be valuable to patients with this distressing problem and for whom diverse management efforts have failed. We herein report a successful treatment using a removable and adjustable ligature for the phrenic nerve in a patient with recurrent and intractable hiccups, which was employed under the guidance of electromyography.

Asymmetric optical microstructures driven by geometry-guided resist reflow.

We report a new method, termed geometry-guided resist reflow, for the batch fabrication of asymmetric optical microstructures. Thermoplastic microstructures reflow along the geometric boundaries of the adjacent thermoset microstructures above the glass transition temperature of thermoplastic resin. The shape profiles can be freely formed as a concave, convex, or linear shape and the slope angle can also be tuned from 7 to 68 degrees, depending on the geometric parameters. This new method provides a new route for developing functional optical elements.

Impact of systemic hypertension on inner retinal layer thickness and macular microvasculature in patients with diabetic retinopathy.

AIM: To investigate the effects of hypertension (HTN) on inner retinal thickness and macular microvasculature in patients with diabetic retinopathy (DR). METHODS: Subjects were classified into three groups: patients with type 2 diabetes mellitus (T2DM) (T2DM group), patients with DR (DR-HTN group), and patients with DR and HTN (DR + HTN group). The ganglion cell complex (GCC) thicknesses and the macular vessel density (VD) were compared. Linear regression analyses were performed to identify factors associated with the VD in the DR + HTN group. RESULTS: The mean GCC thicknesses were 112.2 ± 12.3, 109.2 ± 13.7, and 106.2 ± 11.2 µm in the T2DM, DR-HTN, and DR + HTN groups, respectively (P = 0.045). The mean VDs were 25.4 ± 5.0, 24.3 ± 8.9, and 21.2 ± 7.1% (P = 0.014) for the superficial capillary plexus (SCP) and 25.9 ± 4.3, 22.9 ± 8.5, and 20.2 ± 6.6% (P < 0.001) for the deep capillary plexus (DCP) in the T2DM, DR-HTN, and DR + HTN groups, respectively. In multivariate analyses, the duration of HTN was a significant factor associated with the VD of both SCP (B = -0.24, P = 0.010) and DCP (B = -0.21, P = 0.016). CONCLUSIONS: Patients with both DR and HTN had a thinner GCC and lower VDs of SCP and DCP than those with DR alone. These outcomes could be associated with the synergistic ischemic effects in DR patients with HTN. Moreover, the duration of HTN in DR patients was significantly associated with macular VD in both SCP and DCP.

Retinal neurodegeneration in diabetic retinopathy with systemic hypertension.

PURPOSE: To identify the impact of hypertension (HTN) on inner retinal layer thickness in patients with diabetic retinopathy (DR). METHODS: In this retrospective cross-sectional study, participants were divided into three groups: type 2 diabetes patients without DR (DM group), patients with DR (DR group), and patients with both DR and HTN (DR+HTN group). The peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell-inner plexiform layer (GC-IPL) thicknesses, measured using optical coherence tomography, were compared among the groups. RESULTS: A total of 470 eyes were enrolled: 224 eyes in the DM group, 131 eyes in the DR group, and 115 eyes in the DR+HTN group. The mean RNFL thicknesses were 95.0 ± 7.7, 92.5 ± 10.1, and 89.2 ± 11.2 µm, and the mean GC-IPL thicknesses were 84.0 ± 5.7, 82.0 ± 7.6, and 79.2 ± 8.1 µm in each group, respectively (all P < 0.001). In the DR+HTN group, the DR stage showed a significant association with pRNFL (B = - 5.38, P = 0.014) and GC-IPL (B = - 5.18, P = 0.001) thicknesses in multivariate analyses. Subgroup analyses revealed that pRNFL (P = 0.007) and GC-IPL (P = 0.005) thicknesses decreased significantly as DR progressed only in the DR+HTN group. CONCLUSIONS: Patients with both DR and HTN exhibited much thinner pRNFL and GC-IPL, compared with patients with DR only. These results may have been related to the amplified diabetic retinal neurodegeneration and synergistic impact of ischemia in DR patients with concurrent HTN. Additionally, the progression of DR resulted in more severe inner retinal damage when combined with HTN.

CRISPR/Cas13a-assisted amplification-free miRNA biosensor via dark-field imaging and magnetic gold nanoparticles.

MicroRNAs (miRNAs) are short (about 18-24 nucleotides) non-coding RNAs and have emerged as potential biomarkers for various diseases, including cancers. Due to their short lengths, the specificity often becomes an issue in conventional amplification-based methods. Next-generation sequencing techniques could be an alternative, but the long analysis time and expensive costs make them less suitable for routine clinical diagnosis. Therefore, it is essential to develop a rapid, selective, and accurate miRNA detection assay using a simple, affordable system. In this work, we report a CRISPR/Cas13a-based miRNA biosensing using point-of-care dark-field (DF) imaging. We utilized magnetic-gold nanoparticle (MGNPs) complexes as signal probes, which consist of 200 nm-sized magnetic beads and 60 nm-sized gold nanoparticles (AuNPs) linked by DNA hybridization. Once the CRISPR/Cas13a system recognized the target miRNAs (miR-21-5p), the activated Cas13a cleaved the bridge linker containing RNA sequences, releasing 60 nm-AuNPs detected and quantified by a portable DF imaging system. The combination of CRISPR/Cas13a, MGNPs, and DF imaging demonstrated amplification-free detection of miR-21-5p within 30 min at a detection limit of 500 attomoles (25 pM) and with single-base specificity. The CRISPR/Cas13a-assisted MGNP-DF assay achieved rapid, selective, and accurate detection of miRNAs with simple equipment, thus providing a potential application for cancer diagnosis.

Prediction of postoperative final degree and recurrence of pectus excavatum using machine learning algorithms.

Background: Chest wall re-depression after bar removal (BR) in pectus excavatum (PE) is insufficiently investigated. However, it is not easy to investigate chest wall re-depression due to its multifactorial characteristics. Herein, we investigated chest wall re-depression after BR using machine learning algorithms. To the best of my knowledge, this is the first study of chest wall re-depression after BR using machine learning algorithms. Methods: We retrospectively reviewed 199 consecutive subjects who underwent both minimally invasive repair of pectus excavatum (MIRPE) and BR at a single hospital from March 2012 to June 2020. We investigated attributes of chest wall re-depression and risk factors for recurrence after BR, predicted final degree and recurrence of PE after BR, and suggested the optimal age at the time of MIRPE based on recurrence. Data for the chest wall re-depression were analyzed to discover differences according to age group [<10 years (early repair group; EG) vs. ≥10 years (late repair group; LG)]. Results: We observed no significant difference between the Haller index and radiographical pectus index (RPI) (P=0.431) and a significant correlation between Haller index and RPI (P<0.001). RPI significantly increased for the first 6 months after BR in both age groups (both P<0.001) and was maintained at 1 year after BR. RPI value of the LG were significantly higher than those of the EG for the entire period after MIRPE (P=0.041). Recurrence of PE in the LG was significantly more frequent than in the EG (P<0.001). RPI values before and after MIRPE and age group were identified as independent risk factors for recurrence after BR (P<0.001, P=0.007, and P=0.001, respectively). The linear regression model outperformed for final RPI with performance scores of mean squared error 0.198, root mean squared error 0.445, mean absolute error 0.336, and R2 0.415. In addition, the logistic regression model outperformed for predicting recurrence with performance scores of 0.865 the area under the curve, 0.884 accuracy, 0.859 F1, 0.865 precision, and 0.884 recall. Conclusions: The present study shows that machine learning algorithms can provide good estimates for postoperative results in PE. An approach integrating machine learning models and readily available clinical data can be used to create other models in the thoracic surgery field.

Comparative outcomes of video-assisted thoracoscopic surgery versus open surgery for bronchogenic cysts in adults: a retrospective cohort study.

Background: Open thoracotomy has been the traditional surgical approach for patients with bronchogenic cysts (BCs). This study aimed to evaluate the safety and efficacy of video-assisted thoracoscopic surgery (VATS) compared to open surgery for the treatment of BCs in adults. Methods: This single-institution, retrospective cohort study included 117 consecutive adult patients who underwent VATS (group A) or open surgery (group B) for BC resection between February 2019 and January 2023. Data regarding clinical history, operation duration, length of hospital stay, 30-day mortality, and recurrence during follow-up were collected and analyzed. Results: Of the total cohort, 103 (88.0%) patients underwent VATS, while 14 (12.0%) patients underwent open surgery. Patients' age in group B were much older than group A (P=0.014), and no significant differences in other demographic and baseline clinical characteristics were observed between the groups. The VATS group had shorter median operation duration (96 vs. 149.5 min, P<0.001) and shorter mean length of hospital stay (5.0±5.5 vs. 8.6±4.0 days, P<0.001). One death occurred in the open surgery group. During a median follow-up of 34 (interquartile range, 20.8-42.5) months, no instances of BC recurrence were observed in either group. Conclusions: Compared to open surgery, VATS is also a safe and efficacious approach for treating BCs in adults. What's more, VATS offered shorter operative times and hospital stays. Considering the minimally invasive, VATS may be a better choice in most patients with bronchial cysts.

A new surgical technique for spontaneous esophagopleural fistula after pneumonectomy: cervical esophagogastrostomy via presternal and subcutaneous route, using a thoracic esophageal mucosal stripping.

We report a new surgical technique for spontaneous esophagopleural fistula after pneumonectomy. A 67-year-old man underwent right pneumonectomy for tuberculosis-destroyed lung 30 years previously and a right Eloesser window for empyema without any evidence of fistula 4 years previously. He presented to our hospital for food material spillage out of the Eloesser window when he was eating. The esophagopleural fistula was observed from the upper thoracic esophagus to the right postpneumonectomy dead space. He underwent left cervical esophagogastrostomy via a presternal subcutaneous route, using thoracic esophageal mucosal stripping. He was discharged without complications on postoperative day 12.