Unveiling the Potential of Migrasomes: A Machine-Learning-Driven Signature for Diagnosing Acute Myocardial Infarction.

BACKGROUND: Recent studies have demonstrated that the migrasome, a newly functional extracellular vesicle, is potentially significant in the occurrence, progression, and diagnosis of cardiovascular diseases. Nonetheless, its diagnostic significance and biological mechanism in acute myocardial infarction (AMI) have yet to be fully explored. METHODS: To remedy this gap, we employed an integrative machine learning (ML) framework composed of 113 ML combinations within five independent AMI cohorts to establish a predictive migrasome-related signature (MS). To further elucidate the biological mechanism underlying MS, we implemented single-cell RNA sequencing (scRNA-seq) of cardiac Cd45+ cells from AMI-induced mice. Ultimately, we conducted mendelian randomization (MR) and molecular docking to unveil the therapeutic effectiveness of MS. RESULTS: MS demonstrated robust predictive performance and superior generalization, driven by the optimal combination of Stepglm and Lasso, on the expression of nine migrasome genes (BMP1, ITGB1, NDST1, TSPAN1, TSPAN18, TSPAN2, TSPAN4, TSPAN7, TSPAN9, and WNT8A). Notably, ITGB1 was found to be predominantly expressed in cardiac macrophages in AMI-induced mice, mechanically regulating macrophage transformation between anti-inflammatory and pro-inflammatory. Furthermore, we showed a positive causality between genetic predisposition towards ITGB1 expression and AMI risk, positioning it as a causative gene. Finally, we showed that ginsenoside Rh1, which interacts closely with ITGB1, could represent a novel therapeutic approach for repressing ITGB1. CONCLUSIONS: Our MS has implications in forecasting and curving AMI to inform future diagnostic and therapeutic strategies for AMI.

Leveraging a neutrophil-derived PCD signature to predict and stratify patients with acute myocardial infarction: from AI prediction to biological interpretation.

BACKGROUND: Programmed cell death (PCD) has recently been implicated in modulating the removal of neutrophils recruited in acute myocardial infarction (AMI). Nonetheless, the clinical significance and biological mechanism of neutrophil-related PCD remain unexplored. METHODS: We employed an integrative machine learning-based computational framework to generate a predictive neutrophil-derived PCD signature (NPCDS) within five independent microarray cohorts from the peripheral blood of AMI patients. Non-negative matrix factorization was leveraged to develop an NPCDS-based AMI subtype. To elucidate the biological mechanism underlying NPCDS, we implemented single-cell transcriptomics on Cd45+ cells isolated from the murine heart of experimental AMI. We finally conducted a Mendelian randomization (MR) study and molecular docking to investigate the therapeutic value of NPCDS on AMI. RESULTS: We reported the robust and superior performance of NPCDS in AMI prediction, which contributed to an optimal combination of random forest and stepwise regression fitted on nine neutrophil-related PCD genes (MDM2, PTK2B, MYH9, IVNS1ABP, MAPK14, GNS, MYD88, TLR2, CFLAR). Two divergent NPCDS-based subtypes of AMI were revealed, in which subtype 1 was characterized as inflammation-activated with more vibrant neutrophil activities, whereas subtype 2 demonstrated the opposite. Mechanically, we unveiled the expression dynamics of NPCDS to regulate neutrophil transformation from a pro-inflammatory phase to an anti-inflammatory phase in AMI. We uncovered a significant causal association between genetic predisposition towards MDM2 expression and the risk of AMI. We also found that lidoflazine, isotetrandrine, and cepharanthine could stably target MDM2. CONCLUSION: Altogether, NPCDS offers significant implications for prediction, stratification, and therapeutic management for AMI.

StripeRust-Pocket: A Mobile-Based Deep Learning Application for Efficient Disease Severity Assessment of Wheat Stripe Rust.

Wheat stripe rust poses a marked threat to global wheat production. Accurate and effective disease severity assessments are crucial for disease resistance breeding and timely management of field diseases. In this study, we propose a practical solution using mobile-based deep learning and model-assisted labeling. StripeRust-Pocket, a user-friendly mobile application developed based on deep learning models, accurately quantifies disease severity in wheat stripe rust leaf images, even under complex backgrounds. Additionally, StripeRust-Pocket facilitates image acquisition, result storage, organization, and sharing. The underlying model employed by StripeRust-Pocket, called StripeRustNet, is a balanced lightweight 2-stage model. The first stage utilizes MobileNetV2-DeepLabV3+ for leaf segmentation, followed by ResNet50-DeepLabV3+ in the second stage for lesion segmentation. Disease severity is estimated by calculating the ratio of the lesion pixel area to the leaf pixel area. StripeRustNet achieves 98.65% mean intersection over union (MIoU) for leaf segmentation and 86.08% MIoU for lesion segmentation. Validation using an additional 100 field images demonstrated a mean correlation of over 0.964 with 3 expert visual scores. To address the challenges in manual labeling, we introduce a 2-stage labeling pipeline that combines model-assisted labeling, manual correction, and spatial complementarity. We apply this pipeline to our self-collected dataset, reducing the annotation time from 20 min to 3 min per image. Our method provides an efficient and practical solution for wheat stripe rust severity assessments, empowering wheat breeders and pathologists to implement timely disease management. It also demonstrates how to address the "last mile" challenge of applying computer vision technology to plant phenomics.

Minocycline prevents photoreceptor degeneration in Retinitis pigmentosa through modulating mitochondrial homeostasis.

Minocycline, a broad-spectrum tetracycline antibiotic, has been shown to possess anti-inflammatory and antioxidative effects in various neurodegenerative diseases. However, its specific effects on retinitis pigmentosa (RP) have not been thoroughly investigated. Therefore, the objective of this study was to explore the potential role of minocycline in treating RP. In this investigation, we used rd1 to explore the antioxidant effect of minocycline in RP. Minocycline therapy effectively restored retinal function and structure in rd1 mice at 14 days postnatal. Additionally, minocycline inhibited the activation of microglia. Moreover, RNA sequencing analysis revealed a significant downregulation in the expression of mitochondrial genes within the retina of rd1 mice. Further KEGG and GO pathway analysis indicated impaired oxidative phosphorylation and electron transport chain processes. TEM confirmed the presence of damaged mitochondria in photoreceptors, while JC-1 staining demonstrated a decrease in mitochondrial membrane potential, accompanied by an increase in mitochondrial reactive oxygen species (ROS) levels. However, treatment with minocycline successfully reversed the abnormal expression of mitochondrial genes and reduced the levels of mitochondrial ROS, thereby providing protection against photoreceptor degeneration. Collectively, minocycline demonstrated the ability to rescue photoreceptor cells in RP by effectively modulating mitochondrial homeostasis and subsequently inflammation. These findings hold significant implications for the development of potential therapeutic strategies for RP.

Single-cell RNA sequencing reveals the heterogeneity and interactions of immune cells and Müller glia during zebrafish retina regeneration.

ABSTRACT: Inflammation plays a crucial role in the regeneration of fish and avian retinas. However, how inflammation regulates Müller glia (MG) reprogramming remains unclear. Here, we used single-cell RNA sequencing to investigate the cell heterogeneity and interactions of MG and immune cells in the regenerating zebrafish retina. We first showed that two types of quiescent MG (resting MG1 and MG2) reside in the uninjured retina. Following retinal injury, resting MG1 transitioned into an activated state expressing known reprogramming genes, while resting MG2 gave rise to rod progenitors. We further showed that retinal microglia can be categorized into three subtypes (microglia-1, microglia-2, and proliferative) and pseudotime analysis demonstrated dynamic changes in microglial status following retinal injury. Analysis of cell-cell interactions indicated extensive crosstalk between immune cells and MG, with many interactions shared among different immune cell types. Finally, we showed that inflammation activated Jak1-Stat3 signaling in MG, promoting their transition from a resting to an activated state. Our study reveals the cell heterogeneity and crosstalk of immune cells and MG in zebrafish retinal repair, and may provide valuable insights into future mammalian retina regeneration.

Home Anxiety Assessment and Influencing Factors among Adolescent Athletes in Yantai City.

OBJECTIVE: To understand the prevalence of home-related anxiety among adolescent athletes during the novel coronavirus pandemic and to ascertain the factors influencing this anxiety. METHODS: We employed cluster sampling to select 1150 adolescent athletes (aged 8-18 years) from six sports training schools in Yantai City, Shandong Province. Mental health status was assessed and recorded. Chi-square tests and multivariable logistic regression were used to analyze the factors contributing to athletes' anxiety. RESULTS: The survey revealed a COVID-19 infection rate of 38.23% (437 individuals) with an anxiety score of 40.98 ± 8.20 and an anxiety detection rate of 11.29% (129 individuals) during the COVID-19 epidemic. Female athletes exhibited a higher anxiety rate of 14.40% compared to 8.40% in male athletes. Multivariate analysis identified female gender as a risk factor for anxiety (OR = 1.64), while participation in aquatics emerged as a protective factor (OR = 0.24, 95% CI: 1.08-2.48). Professional training duration exceeding three years increased anxiety risk (OR = 3.05, 95% CI: 1.67-5.58), as did not seeking help during difficulties (OR = 2.59, 95% CI: 1.33-5.01). Interestingly, parental care was linked to increased anxiety risk (OR = 2.44, 95% CI 1.34-4.44), while care from friends was protective (OR = 0.60, 95% CI: 0.36-1.01), which was possibly due to the pressure associated with parental expectations. CONCLUSIONS: Adolescent athletes, particularly females and those with extended training durations, exhibit a heightened susceptibility to anxiety. This study also highlights that athletes who proactively seek assistance during challenging situations tend to experience lower anxiety levels. Additionally, a lack of COVID-19 infection and the involvement of concerned parents contribute to reduced anxiety among these young athletes.

Microneedle delivery system with rapid dissolution and sustained release of bleomycin for the treatment of hemangiomas.

Hemangioma of infancy is the most common vascular tumor during infancy and childhood. Despite the proven efficacy of propranolol treatment, certain patients still encounter resistance or face recurrence. The need for frequent daily medication also poses challenges to patient adherence. Bleomycin (BLM) has demonstrated effectiveness against vascular anomalies, yet its use is limited by dose-related complications. Addressing this, this study proposes a novel approach for treating hemangiomas using BLM-loaded hyaluronic acid (HA)-based microneedle (MN) patches. BLM is encapsulated during the synthesis of polylactic acid (PLA) microspheres (MPs). The successful preparation of PLA MPs and MN patches is confirmed through scanning electron microscopy (SEM) images. The HA microneedles dissolve rapidly upon skin insertion, releasing BLM@PLA MPs. These MPs gradually degrade within 28 days, providing a sustained release of BLM. Comprehensive safety assessments, including cell viability, hemolysis ratio, and intradermal reactions in rabbits, validate the safety of MN patches. The BLM@PLA-MNs exhibit an effective inhibitory efficiency against hemangioma formation in a murine hemangioma model. Of significant importance, RNA-seq analysis reveals that BLM@PLA-MNs exert their inhibitory effect on hemangiomas by regulating the P53 pathway. In summary, BLM@PLA-MNs emerge as a promising clinical candidate for the effective treatment of hemangiomas.

Unveiling blood pressure-associated genes in aortic cells through integrative analysis of GWAS and RNA modification-associated variants.

Background: Genome-wide association studies (GWAS) have identified more than a thousand loci for blood pressure (BP). Functional genes in these loci are cell-type specific. The aim of this study was to elucidate potentially functional genes associated with BP in the aorta through the utilization of RNA modification-associated single-nucleotide polymorphisms (RNAm-SNPs). Methods: Utilizing large-scale genetic data of 757,601 individuals from the UK Biobank and International Consortium of Blood Pressure consortium, we identified associations between RNAm-SNPs and BP. The association between RNAm-SNPs, gene expression, and BP were examined. Results: A total of 355 RNAm-SNPs related to m6A, m1A, m5C, m7G, and A-to-I modification were associated with BP. The related genes were enriched in the pancreatic secretion pathway and renin secretion pathway. The BP GWAS signals were significantly enriched with m6A-SNPs, highlighting the potential functional relevance of m6A in physiological processes influencing BP. Notably, m6A-SNPs in CYP11B1, PDE3B, HDAC7, ACE, SLC4A7, PDE1A, FRK, MTHFR, NPPA, CACNA1D, and HDAC9 were identified. Differential methylation and differential expression of the BP genes in FTO-overexpression and METTL14-knockdown vascular smooth muscle cells were detected. RNAm-SNPs were associated with ascending and descending aorta diameter and the genes showed differential methylation between aortic dissection (AD) cases and controls. In scRNA-seq study, we identified ARID5A, HLA-DPB1, HLA-DRA, IRF1, LINC01091, MCL1, MLF1, MLXIPL, NAA16, NADK, RERG, SRM, and USP53 as differential expression genes for AD in aortic cells. Conclusion: The present study identified RNAm-SNPs in BP loci and elucidated the associations between the RNAm-SNPs, gene expression, and BP. The identified BP-associated genes in aortic cells were associated with AD.

miR-125b-5p delivered by adipose-derived stem cell exosomes alleviates hypertrophic scarring by suppressing Smad2.

Background: Hypertrophic scarring is the most serious and unmet challenge following burn and trauma injury and often leads to pain, itching and even loss of function. However, the demand for ideal scar prevention and treatment is difficult to satisfy. We aimed to discover the effects and mechanisms of adipose-derived stem cell (ADSC) exosomes in hypertrophic scarring. Methods: ADSC exosomes were isolated from the culture supernatant of ADSCs and identified by nanoparticle tracking analysis, transmission electron microscopy and western blotting. The effect of ADSC exosomes on wound healing and scar formation was detected by the wound model of BALB/c mice. We isolated myofibroblasts from hypertrophic scar tissue and detected the cell viability, proliferation and migration of myofibroblasts. In addition, collagen formation and fibrosis-related molecules were also detected. To further disclose the mechanism of ADSC exosomes on fibrosis in myofibroblasts, we detected the expression of Smad2 in hypertrophic scar tissue and normal skin and the regulatory mechanism of ADSC exosomes on Smad2. Injection of bleomycin was performed in male BALB/c mice to establish an in vivo fibrosis model while ADSC exosomes were administered to observe their protective effect. The tissue injury of mice was observed via hematoxylin and eosin and Masson staining and related testing. Results: In this study, we found that ADSC exosomes could not only speed up wound healing and improve healing quality but also prevent scar formation. ADSC exosomes inhibited expression of fibrosis-related molecules such as α-smooth muscle actin, collagen I (COL1) and COL3 and inhibited the transdifferentiation of myofibroblasts. In addition, we verified that Smad2 is highly expressed in both hypertrophic scar tissue and hypertrophic fibroblasts, while ADSC exosomes downregulated the expression of Smad2 in hypertrophic fibroblasts. Further regulatory mechanism analysis revealed that microRNA-125b-5p (miR-125b-5p) is highly expressed in ADSC exosomes and binds to the 3' untranslated region of Smad2, thus inhibiting its expression. In vivo experiments also revealed that ADSC exosomes could alleviate bleomycin-induced skin fibrosis and downregulate the expression of Smad2. Conclusions: We found that ADSC exosomes could alleviate hypertrophic scars via the suppression of Smad2 by the specific delivery of miR-125b-5p.

A "turn-on" fluorescent sensor for herbicide quizalofop-p-ethyl based on cyanostilbene-pyridine macrocycle.

Quizalofop-p-ethyl is a widely used herbicide that also poses a risk to human health and environmental safety. However, there is still a lack of simple and in-situ detecting method for quizalofop-p-ethyl so far. In this work, the fluorescent sensor was firstly developed on detection of quizalofop-p-ethyl based on cyanostilbene-pyridine macrocycle (CPM). CPM was prepared by the "1 + 1" condensation of pyridine-substituted cyanostilbene derivative with 4,4'-Bis(chloromethyl)biphenyl in 68 % yield. The weak fluorescence of CPM in aqueous media transferred to strong orange fluorescence after sensing quizalofop-p-ethyl. This sensing behavior exhibited high selectivity among 28 kinds of herbicides and ions. The limitation of detection (LOD) was 2.98 × 10-8 M and the limitation of quantification (LOQ) was 9.94 × 10-8 M (λex = 390 nm, λem = the maximum emission between 512 nm and 535 nm) with a dynamic range of 0.01-0.9 eq. The binding constant (Ka) of quizalofop-p-ethyl to the sensor CPM was 3.2 × 106 M-1. The 1:1 sensing mechanism was confirmed as that quizalofop-p-ethyl was located in the cavity of CPM, which enhanced aggregating effect and reduced the intramolecular rotation of aromatic groups for better AIE effect. The sensing ability of CPM for quizalofop-p-ethyl had been efficiently applied in test paper experiments, agricultural product tests and real water samples, revealing that CPM has good application prospect for simple and in-situ detection of quizalofop-p-ethyl in real environment.

Mitochondria-mediated ferroptosis induced by CARD9 ablation prevents MDSCs-dependent antifungal immunity.

BACKGROUND: Caspase Recruitment Domain-containing protein 9 (CARD9) expressed in myeloid cells has been demonstrated to play an antifungal immunity role in protecting against disseminated candidiasis. Hereditary CARD9 ablation leads to fatal disseminated candidiasis. However, the myeloid cell types and molecular mechanisms implicated in CARD9 protecting against disseminated candidiasis remain wholly elusive. METHODS: The role of CARD9 ablation in exacerbating disseminated candidiasis was determined in vivo and in vitro. The molecular mechanism by which CARD9 ablation promotes acute kidney injury in disseminated candidiasis was identified by RNA-sequencing analysis. The expression of mitochondrial proteins and ferroptosis-associated proteins were measured by Quantitative real-time PCR and western blot. RESULTS: CARD9 ablation resulted in a reduced proportion of myeloid-derived suppressor cells (MDSCs) and a substantially lower expression of solute carrier family 7 member 11 (SLC7A11) in the kidneys, which increased susceptibility to acute kidney injury and renal ferroptosis during disseminated Candida tropicalis (C. tropicalis) infection. Moreover, CARD9-deficient MDSCs were susceptible to ferroptosis upon stimulation with C. tropicalis, which was attributed to augmented mitochondrial oxidative phosphorylation (OXPHOS) caused by reduced SLC7A11 expression. Mechanistically, C-type lectin receptors (CLRs)-mediated recognition of C. tropicalis promoted the expression of SLC7A11 which was transcriptionally manipulated by the Syk-PKCδ-CARD9-FosB signaling axis in MDSCs. FosB enhanced SLC7A11 transcription by binding to the promoter of SLC7A11 in MDSCs stimulated with C. tropicalis. Mitochondrial OXPHOS, which was negatively regulated by SLC7A11, was responsible for inducing ferroptosis of MDSCs upon C. tropicalis stimulation. Finally, pharmacological inhibition of mitochondrial OXPHOS or ferroptosis significantly increased the number of MDSCs in the kidneys to augment host antifungal immunity, thereby attenuating ferroptosis and acute kidney injury exacerbated by CARD9 ablation during disseminated candidiasis. CONCLUSIONS: Collectively, our findings show that CARD9 ablation enhances mitochondria-mediated ferroptosis in MDSCs, which negatively regulates antifungal immunity. We also identify mitochondria-mediated ferroptosis in MDSCs as a new molecular mechanism of CARD9 ablation-exacerbated acute kidney injury during disseminated candidiasis, thus targeting mitochondria-mediated ferroptosis is a novel therapeutic strategy for acute kidney injury in disseminated candidiasis.

Corrigendum: Characterization of pannexin1, connexin32, and connexin43 in spotted sea bass (Lateolabrax maculatus): they are important neuro-related immune response genes involved in inflammation-induced ATP release.

[This corrects the article DOI: 10.3389/fimmu.2022.870679.].

Disruption of a DNA G-quadruplex causes a gain-of-function SCL45A1 variant relevant to developmental disorders.

SLC45A1 encodes a glucose transporter protein highly expressed in the brain. Mutations in SLC45A1 may lead to neurological diseases and developmental disorders, but its exact role is poorly understood. DNA G-quadruplexes (DNA G4s) are stable structures formed by four guanine bases and play a role in gene regulation and genomic stability. Changes in DNA G4s may affect brain development and function. The mechanism linking alterations in DNA G-quadruplex structures to SLC45A1 pathogenicity remains unknown. In this study, we identify a functional DNA G-quadruplex and its key binding site on SLC45A1 (NM_001080397.3: exon 2: c.449 G>A: p.R150K). This variant results in the upregulation of mRNA and protein expression, which may lead to intellectual developmental disorder with neuropsychiatric features. Mechanistically, the mutation is found to disrupt DNA G-quadruplex structures on SLC45A1, leading to transcriptional enhancement and a gain-of-function mutation, which further causes increased expression and function of the SLC45A1 protein. The identification of the functional DNA G-quadruplex and its effects on DNA G4s may provide new insights into the genetic basis of SLC45A1 pathogenicity and highlight the importance of DNA G4s of SLC45A1 in regulating gene expression and brain development.

High-fat diet consumption promotes adolescent neurobehavioral abnormalities and hippocampal structural alterations via microglial overactivation accompanied by an elevated serum free fatty acid concentration.

Mounting evidence suggests that high-fat diet (HFD) consumption increases the risk for depression, but the neurophysiological mechanisms involved remain to be elucidated. Here, we demonstrated that HFD feeding of C57BL/6J mice during the adolescent period (from 4 to 8 weeks of age) resulted in increased depression- and anxiety-like behaviors concurrent with changes in neuronal and myelin structure in the hippocampus. Additionally, we showed that hippocampal microglia in HFD-fed mice assumed a hyperactive state concomitant with increased PSD95-positive and myelin basic protein (MBP)-positive inclusions, implicating microglia in hippocampal structural alterations induced by HFD consumption. Along with increased levels of serum free fatty acids (FFAs), abnormal deposition of lipid droplets and increased levels of HIF-1α protein (a transcription factor that has been reported to facilitate cellular lipid accumulation) within hippocampal microglia were observed in HFD-fed mice. The use of minocycline, a pharmacological suppressor of microglial overactivation, effectively attenuated neurobehavioral abnormalities and hippocampal structural alterations but barely altered lipid droplet accumulation in the hippocampal microglia of HFD-fed mice. Coadministration of triacsin C abolished the increases in lipid droplet formation, phagocytic activity, and ROS levels in primary microglia treated with serum from HFD-fed mice. In conclusion, our studies demonstrate that the adverse influence of early-life HFD consumption on behavior and hippocampal structure is attributed at least in part to microglial overactivation that is accompanied by an elevated serum FFA concentration and microglial aberrations represent a potential preventive and therapeutic target for HFD-related emotional disorders.

[Application of anterior region suture of popliteal hiatus in treatment of discoid lateral meniscus injury with instability in popliteal tendon region].

Objective: To discuss the application of anterior region suture of the popliteal hiatus (PH) under arthroscopy in the treatment of discoid lateral meniscus (DLM) injury with instability in the popliteal tendon region. Methods: The clinical data of 53 patients (56 knees) with DLM injury who met the selection criteria between March 2014 and November 2022 were retrospectively analyzed. There were 15 males and 38 females, aged 8-55 years with an average age of 36.5 years. Fourteen cases had a history of trauma, while the remaining 39 cases had no clear history of trauma. The disease duration ranged from 1 day to 6 years, with an average duration of 15.6 months. According to the Watanabe classification, there were 40 knees of complete type and 16 knees of incomplete type. The preoperative International Knee Documentation Committee (IKDC) knee joint score was 51.2±8.3, the Lysholm score was 59.6±11.2, and the visual analogue scale (VAS) score was 4.7±1.3. After the arthroscopic meniscal plasty, the instability of the popliteal tendon region meniscus was checked by probing traction. Subsequently, the Out-inside technique or a combination of Out-inside and All-inside techniques was used to suture the anterior region of the PH. The stability of the meniscus after suturing was assessed, and if necessary, further suturing using the All-inside technique at the posterior region of the PH, the posterior horn of the meniscus, and using the Out-inside technique at the anterior horn of the meniscus was performed. Postoperative complications were recorded. The effectiveness was evaluated using pre- and post-operative IKDC scores, Lysholm scores, and VAS scores. Results: After operation, knee joint pain, crepitus, and locking disappeared, with McMurray and grinding tests turning negative. All patients were followed up 12-93 months with an average of 57.5 months. There was no complication such as common peroneal nerve injury, deep vein thrombosis of the lower limbs, joint infection, or joint stiffness. At last follow-up, the IKDC knee joint score was 76.7±5.5, the Lysholm score was 94.0±4.1, and the VAS score was 1.1±0.8. The differences compared with preoperative scores were significant ( t=-22.090, P<0.001; t=-23.704, P<0.001; t=19.767, P<0.001). Conclusion: Suturing of the anterior region of the PH is crucial in the treatment of DLM injury with instability in the popliteal tendon region.

Designer graphene oxide ultrathin flat lens with versatile focusing property.

Graphene oxide (GO) flat lens has a thickness in nanoscale. They modulates the light field via both phase and amplitude modulation and hence possess excellent focusing property. In this paper, we develop a systematic design method to realize the ultrathin GO flat lens with various focusing properties. By using the Rayleigh-Sommerfield theory, the focusing property of ultrathin GO lenses is accurately calculated, then the genetic algorithm (GA) is employed to design the GO lenses. The lens works at visible frequency can have a large radius and long working distance. By setting different optimization objectives, extraordinary focusing property including sub-diffraction limit focusing with FWHM (∼1.96λ) and achromatic focusing with the wavelengths (450 nm, 550 nm, 650 nm) can be achieved. These innovative designs are fabricated and tested.

Association of socioeconomic status with the management outcome of unruptured intracranial arteriovenous malformation.

OBJECTIVE: The longitudinal management of unruptured brain arteriovenous malformation (bAVM) is crucial. To date, no study in the United States has evaluated the impact of socioeconomic status (SES) on bAVM outcome. Herein, the authors aimed to clarify the impact of SES, as indicated by the area deprivation index (ADI), on bAVM outcome. METHODS: A retrospective analysis of an institutional bAVM database was conducted. Non-hereditary hemorrhagic telangiectasia patients with a single unruptured bAVM in the period from 1990 to 2021 were included in the analysis. The ADI was categorized as low (ADI ≤ 15th percentile), mid (15th percentile < ADI < 85th percentile), and high (ADI ≥ 85th percentile), with a low ADI indicating the most advantaged group. Patient baseline and follow-up data were analyzed. The primary outcome of interest was nonindependence (modified Rankin Scale [mRS] score > 2) at the last follow-up. A multivariable logistic regression model was performed. RESULTS: A total of 589 patients with unruptured bAVMs were included in the study. The mean patient age at diagnosis was 37.2 years, and 283 patients (48.0%) were male. Of the bAVMs, 238 (40.4%) had a low Spetzler-Martin grade (SMG < III), 194 (32.9%) had a moderate grade (SMG III), and 157 (26.7%) had a high grade (SMG > III). Sixty-nine patients (11.7%) were in the low-ADI group, 476 (80.8%) in the mid-ADI group, and 44 (7.5%) in high-ADI group. Increasing age (OR 1.02, 95% CI 1.01-1.04, p < 0.001), poor baseline mRS score (OR 3.27, 95% CI 1.32-7.88, p = 0.008), treatment with surgery plus radiosurgery with or without embolization (OR 3.21, 95% CI 1.03-9.81, p = 0.041), mid SMG (OR 1.94, 95% CI 1.11-3.44, p = 0.021), high SMG (OR 2.08, 95% CI 1.13-3.88, p = 0.020), longer follow-up (OR 1.05, 95% CI 1.03-1.08, p < 0.001), and mid ADI (OR 3.08, 95% CI 1.34-8.39, p = 0.015) were significantly associated with a poor outcome. A high ADI tended toward a poor outcome (OR 2.93, 95% CI 0.92-9.88, p = 0.071). Eventual obliteration of a bAVM was the only protective predictor of poor outcome (OR 0.55, 95% CI 0.30-0.98, p = 0.046). CONCLUSIONS: This study revealed that relatively disadvantaged patients with unruptured bAVMs are more likely to experience nonindependent outcomes at the last follow-up, after adjusting for confounding variables. An emphasis on social support may be beneficial for patients with a lower SES.

Influence of Lens Thickness on Accuracy of Kane, Hill-RBF 3.0, Barrett Universal II, Emmetropia Verifying Optical, and Pearl-DGS Formulas in Eyes with Nonhigh Myopia and High Myopia.

PURPOSE: To investigate the influence of lens thickness (LT) on accuracy of Kane, Hill-RBF 3.0 Barrett Universal II (BUII), Emmetropia Verifying Optical (EVO), and Pearl-DGS formulas in eyes with different axial lengths (AL). METHODS: The prospective cohort study was conducted at Eye and ENT Hospital of Fudan University. Patients who had uneventful cataract surgery between March 2021 and July 2023 were recruited. Manifest refraction was conducted two-month post-surgery. Eyes were divided into 4 groups based on AL: short (<22mm), medium (22-24.5 mm), medium long (24.5-26mm) and very long (≥26mm). In each AL group, eyes were then divided into 3 subgroups based on the LT measured with IOLmaster700: thin (<4.5 mm), medium (4.5-5.0 mm), and thick (≥ 5 mm). The influence of LT on accuracy of Kane, Hill-RBF 3.0, BUII, EVO, and Pearl-DGS formulas were investigated in each AL group. RESULTS: A total of 327 eyes from 327 patients were analyzed, with 64, 102, 73 and 88 eyes in each AL group, respectively. In eyes with AL < 24.5 mm, myopic PE was significantly associated with greater LT using all the 5 formulas (all p < 0.05). Backward stepwise multivariate regression analyses revealed that LT was an important influencing factor for PE in all 5 formulas, particularly in eyes with AL <24.5 mm. In eyes with AL <24.5 mm and LT > 5.0 mm, PE of all 5 formulas calculated with the optional parameter LT were more myopic than those calculated without LT. CONCLUSIONS: Thicker LT was associated with more myopic PE among eyes with AL <24.5 mm when using all 5 formulas. Further optimization of current formulas is necessary, especially for eyes with short AL and thick LT.

Exosomes from adipose-derived stem cells restore fibroblast function and accelerate diabetic wound healing.

Background: Diabetes is common yet challenging chronic disease, that affects a wide range of people around the world. Complex cellular environments around diabetic wounds tend to damage the function of effector cells, including vascular endothelial cells (VECs), fibroblasts and epithelial cells. This study aims to analyze the differences between diabetic wounds and normal skin as well as whether adipose-derived stem cell (ADSC) exosome could promote healing of diabetic wound. Methods: Human diabetic wounds and normal skin were collected and stained with HE, Masson, CD31 and 8-hydroxy-2 deoxyguanosine immunohistochemical staining. RNA-seq data were collected for further bioinformatics analysis. ADSC exosomes were isolated and identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting. The effect of ADSC exosomes on diabetic wound healing was assessed on full thickness wounds in mice. To further verify the regulative impact of ADSCs exosomes in high glucose treated fibroblasts, we isolated fibroblasts from normal skin tissue and measured the cell viability, apoptosis rate, proliferation and migration of fibroblasts. In addition, collagen formation and fibrosis-related molecules were also detected. To further disclose the mechanism of ADSC exosomes on the function of high glucose treated fibroblasts, we detected the expression of apoptosis related molecules including BCL2, Bax, and cleaved caspase-3. Results: Histological observation indicated that perilesional skin tissues from diabetic patients showed structural disorder, less collagen disposition and increased injury compared with normal skin. Bioinformatics analysis showed that the levels of inflammatory and collagen synthesis related molecules, as well as oxidative stress and apoptosis related molecules, were significantly changed. Furthermore, we found that ADSC exosomes could not only speed up diabetic wound healing, but could also improve healing quality. ADSC exosomes restored high glucose induced damage to cell viability, migration and proliferation activity, as well as fibrosis-related molecules such as SMA, collagen 1 and collagen 3. In addition, we verified that ADSC exosomes downregulated high glucose induced increased apoptosis rate in fibroblast and the protein expression of Bax as well as cleaved caspases 3. Conclusions: This study indicated that ADSC exosomes alleviated high glucose induced damage to fibroblasts and accelerate diabetic wound healing by inhibiting Bax/caspase 3.