Advances in Circular RNA in the Pathogenesis of Epilepsy.

Recent studies evidenced the involvement of circular RNA (circRNA) in neuroinflammation, apoptosis, and synaptic remodeling suggesting an important role for circRNA in the occurrence and development of epilepsy. This review provides an overview of circRNAs considered to be playing regulatory roles in the process of epilepsy and to be involved in multiple biological epilepsy-related processes, such as hippocampal sclerosis, inflammatory response, cell apoptosis, synaptic remodeling, and cell proliferation and differentiation. This review covers the current research status of differential expression of circRNA-mediated seizures, m6A methylation, demethylation-mediated seizures in post transcriptional circRNA modification, as well as the mechanisms of m5C- and m7G-modified circRNA. In summary, this article reviews the research progress on the relationship between circRNA in non-coding RNA and epilepsy.

Utilizing network pharmacology, molecular docking, and animal models to explore the therapeutic potential of the WenYang FuYuan recipe for cerebral ischemia-reperfusion injury through AGE-RAGE and NF-κB/p38MAPK signaling pathway modulation.

BACKGROUND: Stroke is a debilitating condition with high morbidity, disability, and mortality that significantly affects the quality of life of patients. In China, the WenYang FuYuan recipe is widely used to treat ischemic stroke. However, the underlying mechanism remains unknown, so exploring the potential mechanism of action of this formula is of great practical significance for stroke treatment. OBJECTIVE: This study employed network pharmacology, molecular docking, and in vivo experiments to clarify the active ingredients, potential targets, and molecular mechanisms of the WenYang FuYuan recipe in cerebral ischemia-reperfusion injury, with a view to providing a solid scientific foundation for the subsequent study of this recipe. MATERIALS AND METHODS: Active ingredients of the WenYang FuYuan recipe were screened using the traditional Chinese medicine systems pharmacology database and analysis platform. Network pharmacology approaches were used to explore the potential targets and mechanisms of action of the WenYang FuYuan recipe for the treatment of cerebral ischemia-reperfusion injury. The Middle Cerebral Artery Occlusion/Reperfusion 2 h Sprague Dawley rat model was prepared, and TTC staining and modified neurological severity score were applied to examine the neurological deficits in rats. HE staining and Nissl staining were applied to examine the pathological changes in rats. Immunofluorescence labeling and Elisa assay were applied to examine the expression levels of certain proteins and associated factors, while qRT-PCR and Western blotting were applied to examine the expression levels of linked proteins and mRNAs in disease-related signaling pathways. RESULTS: We identified 62 key active ingredients in the WenYang FuYuan recipe, with 222 highly significant I/R targets, forming 138 pairs of medication components and component-targets, with the top five being Quercetin, Kaempferol, Luteolin, ß-sitosterol, and Stigmasterol. The key targets included TP53, RELA, TNF, STAT1, and MAPK14 (p38MAPK). Targets related to cerebral ischemia-reperfusion injury were enriched in chemical responses, enzyme binding, endomembrane system, while enriched pathways included lipid and atherosclerosis, fluid shear stress and atherosclerosis, AGE-RAGE signaling in diabetic complications. In addition, the main five active ingredients and targets in the WenYang FuYuan recipe showed high binding affinity (e.g. Stigmasterol and MAPK14, total energy <-10.5 Kcal/mol). In animal experiments, the WenYang FuYuan recipe reduced brain tissue damage, increased the number of surviving neurons, and down-regulated S100ß and RAGE protein expression. Moreover, the relative expression levels of key targets such as TP53, RELA and p38MAPK mRNA were significantly down-regulated in the WenYang FuYuan recipe group, and serum IL-6 and TNF-a factor levels were reduced. After WenYang FuYuan recipe treatment, the AGE-RAGE signaling pathway and downstream NF-kB/p38MAPK signaling pathway-related proteins were significantly modulated. CONCLUSION: This study utilized network pharmacology, molecular docking, and animal experiments to identify the potential mechanism of the WenYang FuYuan recipe, which may be associated with the regulation of the AGE-RAGE signaling pathway and the inhibition of target proteins and mRNAs in the downstream NF-kB/p38MAPK pathway.

Optical vectorial-mode parity Hall effect: a case study with cylindrical vector beams.

The vectorial optical field (VOF) assumes a pivotal role in light-matter interactions. Beyond its inherent polarization topology, the VOF also encompasses an intrinsic degree of freedom associated with parity (even or odd), corresponding to a pair of degenerate orthogonal modes. However, previous research has not delved into the simultaneous manipulation of both even and odd parities. In this study, we introduce and validate the previously unexplored parity Hall effect for vectorial modes using a metasurface design. Our focus lies on a cylindrical vector beam (CVB) as a representative case. Through the tailored metasurface, we effectively separate two degenerate CVBs with distinct parities in divergent directions, akin to the observed spin states split in the spin Hall effect. Additionally, we provide experimental evidence showcasing the capabilities of this effect in multi-order CVB demultiplexing and parity-demultiplexed CVB-encoded holography. This effect unveils promising opportunities for various applications, including optical communication and imaging.

High-performance, large-area flexible SERS substrates prepared by reactive ion etching for molecular detection.

In the realm of molecular detection, the surface-enhanced Raman scattering (SERS) technique has garnered increasing attention due to its rapid detection, high sensitivity, and non-destructive characteristics. However, conventional rigid SERS substrates are either costly to fabricate and challenging to prepare over a large area, or they exhibit poor uniformity and repeatability, making them unsuitable for inspecting curved object surfaces. In this work, we present a flexible SERS substrate with high sensitivity as well as good uniformity and repeatability. First, the flexible polydimethylsiloxane (PDMS) substrate is manually formulated and cured. SiO2/Ag layer on the substrate can be obtained in a single process by using ion beam sputtering. Then, reactive ion etching is used to etch the upper SiO2layer of the film, which directly leads to the desired densely packed nanostructure. Finally, a layer of precious metal is deposited on the densely packed nanostructure by thermal evaporation. In our proposed system, the densely packed nanostructure obtained by etching the SiO2layer directly determines the SERS ability of the substrate. The bottom layer of silver mirror can reflect the penetrative incident light, the spacer layer of SiO2and the top layer of silver thin film can further localize the light in the system, which can realize the excellent absorption of Raman laser light, thus enhancing SERS ability. In the tests, the prepared substrates show excellent SERS performance in detecting crystalline violet with a detection limit of 10-11M. The development of this SERS substrate is anticipated to offer a highly effective and convenient method for molecular substance detection.

Bioinformatics identification of potential biomarkers and therapeutic targets for ischemic stroke and vascular dementia.

Ischemic stroke and vascular dementia, as common cerebrovascular diseases, with the former causing irreversible neurological damage and the latter causing cognitive and memory impairment, are closely related and have long received widespread attention. Currently, the potential causative genes of these two diseases have yet to be investigated, and effective early diagnostic tools for the diseases have not yet emerged. In this study, we screened new potential biomarkers and analyzed new therapeutic targets for both diseases from the perspective of immune infiltration. Two gene expression profiles on ischemic stroke and vascular dementia were obtained from the NCBI GEO database, and key genes were identified by LASSO regression and SVM-RFE algorithms, and key genes were analyzed by GO and KEGG enrichment. The CIBERSORT algorithm was applied to the gene expression profile species of the two diseases to quantify the 24 subpopulations of immune cells. Moreover, logistic regression modeling analysis was applied to illustrate the stability of the key genes in the diagnosis. Finally, the key genes were validated using RT-PCR assay. A total of 105 intersecting DEGs genes were obtained in the 2 sets of GEO datasets, and bioinformatics functional analysis of the intersecting DEGs genes showed that GO was mainly involved in the purine ribonucleoside triphosphate metabolic process，respiratory chain complex，DNA-binding transcription factor binding and active transmembrane transporter activity. KEGG is mainly involved in the Oxidative phosphorylation, cAMP signaling pathway. The LASSO regression algorithm and SVM-RFE algorithm finally obtained three genes, GAS2L1, ARHGEF40 and PFKFB3, and the logistic regression prediction model determined that the three genes, GAS2L1 (AUC: 0.882), ARHGEF40 (AUC: 0.867) and PFKFB3 (AUC: 0.869), had good diagnostic performance. Meanwhile, the two disease core genes and immune infiltration were closely related, GAS2L1 and PFKFB3 had the highest positive correlation with macrophage M1 (p < 0.001) and the highest negative correlation with mast cell activation (p = 0.0017); ARHGEF40 had the highest positive correlation with macrophage M1 and B cells naive (p < 0.001), the highest negative correlation with B cell memory highest correlation (p = 0.0047). RT-PCR results showed that the relative mRNA expression levels of GAS2L1, ARHGEF40, and PFKFB3 were significantly elevated in the populations of both disease groups (p < 0.05). Immune infiltration-based models can be used to predict the diagnosis of patients with ischemic stroke and vascular dementia and provide a new perspective on the early diagnosis and treatment of both diseases.

Asymptotic dispersion engineering for ultra-broadband meta-optics.

Dispersion decomposes compound light into its monochromatic components, which is detrimental to broadband imaging but advantageous for spectroscopic applications. Metasurfaces provide a unique path to modulate the dispersion by adjusting structural parameters on a two-dimensional plane. However, conventional linear phase compensation does not adequately match the meta-unit's dispersion characteristics with required complex dispersion, hindering at-will dispersion engineering over a very wide bandwidth particularly. Here, we propose an asymptotic phase compensation strategy for ultra-broadband dispersion-controlled metalenses. Metasurfaces with extraordinarily high aspect ratio nanostructures have been fabricated for arbitrary dispersion control in ultra-broad bandwidth, and we experimentally demonstrate the single-layer achromatic metalenses in the visible to infrared spectrum (400 nm~1000 nm, NA = 0.164). Our proposed scheme provides a comprehensive theoretical framework for single-layer meta-optics, allowing for arbitrary dispersion manipulation without bandwidth restrictions. This development is expected to have significant applications in ultra-broadband imaging and chromatography detection, among others.

Association of C-reactive protein gene polymorphisms with the risk of ischemic stroke: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: The heterogeneous, complex condition known as ischemic stroke (IS) is brought on by the interaction of a number of risk factors and genetic variables. The association between C-reactive protein (CRP) gene polymorphisms and IS has, however, been the subject of inconsistent findings. Therefore, we conducted a meta-analysis to comprehensively address possible associations of CRP genes with the risk of IS. METHODS: A comprehensive literature search for all the published articles was performed in electronic databases including PubMed, EMBASE, Cochrane Library, and Google Scholar from January 1, 1950 to June 30, 2022. Odds ratio (OR) with 95% Confidence interval (CIs) along with fixed/random effect models were used to calculate summary estimates. RESULTS: Twelve case-control studies totalling 3880 IS cases and 5233 controls were included for the association of CRP gene polymorphisms (rs1800947, rs1130864, rs3093059, rs2794521, and rs1205). Across all genotyping models, we discovered that rs1130864, rs3093059, rs2794521, and rs1205SNPs were not substantially related to IS risk. A trend for significant association for rs1800947 under dominant (OR = 1.19; 95% CI = 0.97 to 1.48), recessive (OR = 1.49; 95% CI = 0.71 to 3.14) and allelic model (OR = 1.21; 95% CI = 0.99 to 1.48) was observed. However, protective association for rs1130864 under dominant (OR = 0.80; 95% CI = 0.70 to 0.91) and rs3093059 under allelic model (OR = 0.18; 95% CI = 0.14 to 0.22) was found. CONCLUSION: Our thorough study revealed that the CRP gene variants rs1800947, rs1130864, rs3093059, rs2794521, and rs1205 could not be related to the risk of ischemic stroke. However, additional research must focus on the rs1800947 polymorphisms in a particular group.

Topologically optimized concentric-nanoring metalens with 1 mm diameter, 0.8†NA and 600†nm imaging resolution in the visible.

Metalenses can achieve diffraction-limited focusing via localized phase modification of the incoming light beam. However, the current metalenses face to the restrictions on simultaneously achieving large diameter, large numerical aperture, broad working bandwidth and the structure manufacturability. Herein, we present a kind of metalenses composed of concentric nanorings that can address these restrictions using topology optimization approach. Compared to existing inverse design approaches, the computational cost of our optimization method is greatly reduced for large-size metalenses. With its design flexibility, the achieved metalens can work in the whole visible range with millimeter size and a numerical aperture of 0.8 without involving high-aspect ratio structures and large refractive index materials. Electron-beam resist PMMA with a low refractive index is directly used as the material of the metalens, enabling a much more simplified manufacturing process. Experimental results show that the imaging performance of the fabricated metalens has a resolution better than 600 nm corresponding to the measured FWHM of 745 nm.

Analysis of antiplatelet therapy adherence in patients with ischemic cerebral stroke.

BACKGROUND: The related factors affecting the adherence of ischemic cerebral stroke (ICS) patients to antiplatelet therapy have attracted much attention. METHODS: Patients with ICS (confirmed by CT or MRI) were enrolled from January 2020 to July 2021. The demographic data were retrospectively investigated and analyzed. The adherence calculation was as follows: Adherence = number of tablets taken/number of tablets needed to be taken. Adherence < 100% was defined as nonadherence. Severe nonadherence is defined as adherence ≤ 75%. RESULTS: A total of 229 patients with ICS were enrolled. We found no significant difference in the proportion of patients with nonadherence, while the proportion of severe nonadherence in the aspirin group was significantly higher (p < .001). Multivariable analysis indicated that medical insurance (odds ratio [OR] = 0.071, p < .001) and regular exercise (OR = 0.438, p = .015) were independent factors associated with adherence. In addition, only medical insurance (OR = 5.475, p < .001) and aspirin treatment (OR = 0.228, p < .001) were independent risk factors associated with severe nonadherence. We therefore constructed a nomogram plot and a model as follows: Adherence risk score = 3 × medical insurance + regular exercise. Patients were divided into low-risk and high-risk groups for adherence based on the median model score. A total of 13.3% of patients in the low-risk group were nonadherent patients compared with 53.4% in the high-risk group (p < .001). Similarly, 8.4% of patients in the low-risk group had severe nonadherence compared with 19.9% in the high-risk group (p = .022). Moreover, in low-risk patients, no significant difference was observed. In patients with high risk, aspirin-treated patients showed significantly decreased adherence compared with the other two groups. CONCLUSION: Medical insurance and regular exercise were independent factors for antiplatelet therapy adherence. For patients with high model scores, timely intervention is necessary.

Angular momentum holography via a minimalist metasurface for optical nested encryption.

Metasurfaces can perform high-performance multi-functional integration by manipulating the abundant physical dimensions of light, demonstrating great potential in high-capacity information technologies. The orbital angular momentum (OAM) and spin angular momentum (SAM) dimensions have been respectively explored as the independent carrier for information multiplexing. However, fully managing these two intrinsic properties in information multiplexing remains elusive. Here, we propose the concept of angular momentum (AM) holography which can fully synergize these two fundamental dimensions to act as the information carrier, via a single-layer, non-interleaved metasurface. The underlying mechanism relies on independently controlling the two spin eigenstates and arbitrary overlaying them in each operation channel, thereby spatially modulating the resulting waveform at will. As a proof of concept, we demonstrate an AM meta-hologram allowing the reconstruction of two sets of holographic images, i.e., the spin-orbital locked and the spin-superimposed ones. Remarkably, leveraging the designed dual-functional AM meta-hologram, we demonstrate a novel optical nested encryption scheme, which is able to achieve parallel information transmission with ultra-high capacity and security. Our work opens a new avenue for optionally manipulating the AM, holding promising applications in the fields of optical communication, information security and quantum science.

The Effect of Fabrication Error on the Performance of Mid-Infrared Metalens with Large Field-of-View.

Mid-infrared large field-of-view (FOV) imaging optics play a vital role in infrared imaging and detection. The metalens, which is composed of subwavelength-arrayed structures, provides a new possibility for the miniaturization of large FOV imaging systems. However, the inaccuracy during fabrication is the main obstacle to developing practical uses for metalenses. Here, we introduce the principle and method of designing a large FOV doublet metalens at the mid-infrared band. Then, the quantitative relationship between the fabrication error and the performance of the doublet metalens with a large FOV from four different fabrication errors is explored by using the finite-difference time-domain method. The simulation results show that the inclined sidewall error has the greatest impact on the focusing performance, and the interlayer alignment error deforms the focusing beam and affects the focusing performance, while the spacer thickness error has almost no impact on the performance. The contents discussed in this paper can help manufacturers determine the allowable processing error range of the large FOV doublet metalens and the priority level for optimizing the process, which is of significance.

Tunable Polarization-Multiplexed Achromatic Dielectric Metalens.

Tunable metasurfaces provide a compact and efficient strategy for optical active wavefront shaping. Varifocal metalens is one of the most important applications. However, the existing tunable metalens rarely serves broadband wavelengths restricting their applications in broadband imaging and color display due to chromatic aberration. Herein, an electrically tunable polarization-multiplexed achromatic metalens integrated with twisted nematic liquid crystals (TNLCs) in the visible region is demonstrated. The phase profiles at different wavelengths under two orthogonal polarization channels are customized by the particle swarm optimization algorithm and matched with the dielectric metaunits database to achieve polarization-multiplexed achromatic performance. By combining the broadband linear polarization conversion ability of TNLC, the tunability of varifocal achromatic metalens is realized by applying different voltages. Further, the electrically tunable customized dispersion-manipulated metalens and switchable color metaholograms are demonstrated. The proposed devices will accelerate the application of metasurfaces in broadband zoom imaging, AR/VR displays and spectral detection.

Advances of circRNA-miRNA-mRNA regulatory network in cerebral ischemia/reperfusion injury.

Ischemic stroke (IS) is the most common type of stroke, and its pathophysiological process is more complex. In recent years, the key regulatory roles of non-coding RNA (miRNA, circRNA) and mRNA in the development of IS have attracted more attention. In the process of cerebral ischemia/reperfusion injury, circRNA can regulate nerves, blood vessels and immune system through miRNA/mRNA axis, so as to affect the neurovascular unit of IS. The combination of these noncoding RNAs and mRNAs can be used as non-invasive biomarkers and therapeutic tools for IS diagnosis, prognosis and brain injury. Therefore, it is very important to study the potential molecular mechanism, activation pathway and treatment methods of circRNA/miRNA/mRNA network in IS. This review will focus on the latest progress of circRNA/miRNA/mRNA regulatory network, we have also included some circRNAs, which does not mediate through a miRNA, so we also include circRNA -mRNA network. And explore the application prospect of these RNAs as potential therapeutic targets in the prevention and treatment of IS.

Phase-Field Model for Drug Release of Water-Swellable Filaments for Fused Filament Fabrication.

This paper treats the drug release process as a phase-field problem and a phase-field model capable of simulating the dynamics of multiple moving fronts, transient drug fluxes, and fractional drug release from swellable polymeric systems is proposed and validated experimentally. The model can not only capture accurately the positions and movements of the distinct fronts without tracking the locations of fronts explicitly but also predict well the release profile to the completion of the release process. The parametric study has shown that parameters including water diffusion coefficient, drug saturation solubility, drug diffusion coefficient, initial drug loading ratio, and initial porosity are critical in regulating the drug release kinetics. It has been also demonstrated that the model can be applied to the study of swellable filaments and has wide applicability for different materials. Due to explicit boundary position tracking being eliminated, the model paves the way for practical use and can be extended for dealing with geometrically complex drug delivery systems. It is a useful tool to guide the design of new controlled delivery systems fabricated by fused filament fabrication.

Dielectric metalens for miniaturized imaging systems: progress and challenges.

Lightweight, miniaturized optical imaging systems are vastly anticipated in these fields of aerospace exploration, industrial vision, consumer electronics, and medical imaging. However, conventional optical techniques are intricate to downscale as refractive lenses mostly rely on phase accumulation. Metalens, composed of subwavelength nanostructures that locally control light waves, offers a disruptive path for small-scale imaging systems. Recent advances in the design and nanofabrication of dielectric metalenses have led to some high-performance practical optical systems. This review outlines the exciting developments in the aforementioned area whilst highlighting the challenges of using dielectric metalenses to replace conventional optics in miniature optical systems. After a brief introduction to the fundamental physics of dielectric metalenses, the progress and challenges in terms of the typical performances are introduced. The supplementary discussion on the common challenges hindering further development is also presented, including the limitations of the conventional design methods, difficulties in scaling up, and device integration. Furthermore, the potential approaches to address the existing challenges are also deliberated.

Metasurface-enabled on-chip multiplexed diffractive neural networks in the visible.

Replacing electrons with photons is a compelling route toward high-speed, massively parallel, and low-power artificial intelligence computing. Recently, diffractive networks composed of phase surfaces were trained to perform machine learning tasks through linear optical transformations. However, the existing architectures often comprise bulky components and, most critically, they cannot mimic the human brain for multitasking. Here, we demonstrate a multi-skilled diffractive neural network based on a metasurface device, which can perform on-chip multi-channel sensing and multitasking in the visible. The polarization multiplexing scheme of the subwavelength nanostructures is applied to construct a multi-channel classifier framework for simultaneous recognition of digital and fashionable items. The areal density of the artificial neurons can reach up to 6.25 × 106 mm-2 multiplied by the number of channels. The metasurface is integrated with the mature complementary metal-oxide semiconductor imaging sensor, providing a chip-scale architecture to process information directly at physical layers for energy-efficient and ultra-fast image processing in machine vision, autonomous driving, and precision medicine.

FCP-Net: A Feature-Compression-Pyramid Network Guided by Game-Theoretic Interactions for Medical Image Segmentation.

Medical image segmentation is a crucial step in diagnosis and analysis of diseases for clinical applications. Deep convolutional neural network methods such as DeepLabv3+ have successfully been applied for medical image segmentation, but multi-level features are seldom integrated seamlessly into different attention mechanisms, and few studies have fully explored the interactions between medical image segmentation and classification tasks. Herein, we propose a feature-compression-pyramid network (FCP-Net) guided by game-theoretic interactions with a hybrid loss function (HLF) for the medical image segmentation. The proposed approach consists of segmentation branch, classification branch and interaction branch. In the encoding stage, a new strategy is developed for the segmentation branch by applying three modules, e.g., embedded feature ensemble, dilated spatial mapping and channel attention (DSMCA), and branch layer fusion. These modules allow effective extraction of spatial information, efficient identification of spatial correlation among various features, and fully integration of multi-receptive field features from different branches. In the decoding stage, a DSMCA module and a multi-scale feature fusion module are used to establish multiple skip connections for enhancing fusion features. Classification and interaction branches are introduced to explore the potential benefits of the classification information task to the segmentation task. We further explore the interactions of segmentation and classification branches from a game theoretic view, and design an HLF. Based on this HLF, the segmentation, classification and interaction branches can collaboratively learn and teach each other throughout the training process, thus applying the conjoint information between the segmentation and classification tasks and improving the generalization performance. The proposed model has been evaluated using several datasets, including ISIC2017, ISIC2018, REFUGE, Kvasir-SEG, BUSI, and PH2, and the results prove its competitiveness compared with other state-of-the-art techniques.

Bibliometric and visual analysis of cerebral revascularization from 1999 to 2022.

Background: Cerebral revascularization is a neurosurgical procedure used to restore the cerebral collateral circulation channel. This study examines the countries, institutions, authors, journals, keywords, and references related to the disease in the field of cerebral revascularization from 1999 to 2022 from a bibliometrics perspective, evaluates the changes of knowledge structure clustering and identifies the new hot spots and new research directions in this field. Methods: The Web of Science Core Collection (WOSCC) database and the PICOS retrieval method were used to conduct a comprehensive search for articles and reviews pertaining to cerebral revascularization. The final filtered data were bibliometrically and visually drawn using Microsoft office 365, CiteSpace (v.6.1.R2), and VOSviewer (v.1.6.18). Results: From 1999 to 2022, a total of 854 articles pertaining to cerebral revascularization, which originated from 46 nations, 482 institutions, and 686 researchers, were extracted from the WOSCC database, and the number of publications in this field of study was rising. The United States held the highest proportion in the ranking analysis of countries, institutions, authors, and journals. By analyzing co-citations, the scientific organization of this field and the development status of frontier fields were realized. Cerebral revascularization, moyamoya disease, extracranial intracranial bypass, and occlusion are the current research focal points in the field of cerebral revascularization. Hyperperfusion and vascular disorder may also become a new study focus in this discipline in the near future. Conclusion: Using the method of bibliometrics, this study analyzed and reviewed the articles in the field of cerebral revascularization, which enabled scholars to better comprehend the dynamic process in this field and provided a foundation for future in-depth research.