Spectrum of retinal microvascular ischemia in patients with COVID-19 based on multimodal imaging.

Purpose: To describe and evaluate the multimodal imaging findings in retinal microvascular ischemia associated with COVID-19 infection. Methods: Patients with COVID-19 associated retinal microvascular ischemia and visiting the outpatient Department of Ophthalmology, Shanghai General Hospital from December 2022, to February 2023, were documented and their multimodal images were retrospectively reviewed. Retinal microvascular ischemia was defined as the presence of isolated or multiple focal retinal whitening(s) on color fundus images. Patients with retinal vessel occlusion or retinopathies secondary to systematic disorders diagnosed before infection were excluded. Results: A total of 32 eyes from 21 patients were included, 24 (75.00 %) eyes with multiple retinal whitenings, while 8 (25.00 %) eyes with isolated lesions. When divided by the types of ischemia, 9 (28.13 %) eyes had only inner retinal involvement (known as cotton wool spot, CWS), 4 (12.50 %) eyes had only middle retinal involvement (known as paracentral acute middle maculopathy, PAMM), and 19 (59.38 %) eyes had both. In addition, 4 (12.50 %) eyes had coincident angular sign of Henle fiber layer hyperreflectivity (ASHH). Patients with hypertension tended to have multiple lesions rather than isolated lesion of retinal microvascular ischemia (P = 0.008). Transient uncontrolled high blood pressure or acute kidney injury was simultaneously detected in some cases. Conclusions: Ocular manifestation of COVID-19 associated microvascular ischemia can be variable, including CWS, PAMM and ASHH. Multimodal fundus imaging technologies are useful tools to reveal involved retinal layers, extent, and severity. Moreover, ocular manifestations may serve as a window of COVID-19 related microcirculation in other systems throughout the body.

Dual modes of ZFC3H1 confer selectivity in nuclear RNA sorting.

The export and degradation pathways compete to sort nuclear RNAs, yet the default pathway remains unclear. Sorting of mature RNAs to degradation, facilitated by the exosome co-factor poly(A) exosome targeting (PAXT), is particularly challenging for their resemblance to mRNAs intended for translation. Here, we unveil that ZFC3H1, a core PAXT component, is co-transcriptionally loaded onto the first exon/intron of RNA precursors (pre-RNAs). Interestingly, this initial loading does not lead to pre-RNA degradation, as ZFC3H1 adopts a "closed" conformation, effectively blocking exosome recruitment. As processing progresses, RNA fate can be reshaped. Longer RNAs with more exons are allowed for nuclear export. By contrast, short RNAs with fewer exons preferentially recruit transient PAXT components ZC3H3 and RBM26/27 to the 3' end, triggering ZFC3H1 "opening" and subsequent exosomal degradation. Together, the decoupled loading and activation of ZFC3H1 pre-configures RNA fate for decay while still allowing a switch to nuclear export, depending on mature RNA features.

Research on the causal relationship between fine particulate matter and type 2 diabetes mellitus: A two-sample multivariable mendelian randomization study.

BACKGROUND AND AIMS: Previous research has suggested a correlation between fine particulate matter (PM2.5) and type 2 diabetes mellitus (T2DM). However, the causality was vulnerable to confounding variables. METHODS AND RESULTS: A two-sample multivariable mendelian randomization study was designed to examine the causal connection between PM2.5 and T2DM. PM2.5 trait was investigated as exposure while T2DM-related traits as outcomes. The summary data were obtained from the Finngen database and the open genome-wide association study database. The mendelian randomization estimates were obtained using the inverse-variance weighted approach, and multiple sensitivity analyses were conducted. There were potential causal relationships between PM2.5 and T2DM (OR = 2.418; P = 0.019), PM2.5 and glycated hemoglobin (HbA1c) (OR = 1.590; P = 0.041), and PM2.5 and insulin metabolism. PM2.5 was found to have no causal effect on fasting glucose and insulin, 2-h glucose, and insulin-like growth factor binding protein-1 (P > 0.05), while had a potential protective effect against some diabetes complications. CONCLUSIONS: Our findings indicated potential causal relationships among PM2.5 and T2DM, especially the causal relationship between PM2.5 and long-term glucose levels.

RNASE4 promotes malignant progression and chemoresistance in hypoxic glioblastoma via activation of AXL/AKT and NF-κB/cIAPs signaling pathways.

Glioblastoma (GBM) is the most malignant brain tumor frequently characterized by a hypoxic microenvironment. In this investigation, we unveiled unprecedented role of Ribonuclease 4 (RNASE4) in GBM pathogenesis through integrative methodologies. Leveraging The Cancer Genome Atlas (TCGA) dataset and clinical specimens from normal brain tissues, low- and high-grade gliomas, alongside rigorous in vitro and in vivo functional analyses, we identified a consistent upregulation of RNASE4 correlating with advanced GBM pathological stages and poor clinical survival outcomes. Functional assays corroborated the pivotal influences of RNASE4 on key tumorigenic processes such as cell proliferation, migration, invasion, stemness properties and temozolomide (TMZ) resistance. Further, Gene Set Enrichment Analysis (GSEA) illuminated the involvement of RNASE4 in modulating epithelial-mesenchymal transition (EMT) via activation of AXL, AKT and NF-κB signaling pathways. Furthermore, recombinant human RNASE4 (hRNASE4)-mediated NF-κB activation through IκBα phosphorylation and degradation could result in the upregulation of inhibitors of apoptosis proteins (IAPs), such as cIAP1, cIAP2, and SURVIVIN. Notably, treating RNASE4-induced TMZ-resistant cells with the SURVIVIN inhibitor YM-155 significantly restored cellular sensitivity to TMZ therapy. Herein, this study positions RNASE4 as a potent prognostic biomarker and therapeutic target, offering new insights into molecular pathogenesis of GBM and new avenues for future therapeutic interventions.

Aggravation of Cd availability in the plastisphere of paddy soil.

Soil plastisphere has attracted many concerns, however, its influence on cadmium (Cd) availability in paddy soil was still unclear. This study carried out batch microcosmic and bagging experiments to explore the influence of microplastic (MPs) on Cd availability in paddy soil under flooding conditions in the view of plastisphere. Results showed that the presence of MPs could act as plastisphere micro-environment. The bacterial community composition changed dramatically around the plastisphere compared with MPs-contaminated bulk soil and control soil. The relative abundance of Symbiobacteraceae, Rhodocyclaceae and Bryobacteraceae was improved in the plastisphere which contributed to the enhanced the reduction of Fe(III) and sulfate in flooding paddy soil. The higher content of Fe(II) and S content contributed to the enrichment of Cd in the plastisphere which aggravated Cd availability in paddy soil under flooding conditions. The partial least squares structure equation modeling results confirmed the presence of MPs in paddy soil could act as plastisphere which could change the bacterial community composition and improve the content Fe and S that was conductive to gather Cd in plastisphere. This study shed lights on the understanding of the role of plastisphere on Cd availability in paddy field ecosystem under flooding conditions.

Identifying patients who benefit more from perioperative immunotherapy combinations for resectable non-small cell lung cancer based on clinical and molecular characteristics: a meta-analysis of randomized clinical trials.

PURPOSE: This study aims to identify patient subgroups who benefit more from perioperative immunotherapy combined with chemotherapy (IO-CT) based on clinical and molecular characteristics in resectable non-small cell lung cancer (NSCLC). METHODS: Randomized controlled trials (RCTs) on perioperative IO-CT were searched. Beneficial differences of IO-CT regimens across different patient subgroups were assessed by pooling trial-specific ratios in event-free survival (EFS), overall survival (OS), pathological complete response (pCR), and major pathological response (MPR). RESULTS: Six studies (n = 3003) involving five IO-CT regimens were included. Compared to CT alone, all IO-CT regimens significantly improved EFS, OS, MPR, and pCR, but increased toxicity. Toripa-chemo showed the best EFS and nivo-chemo showed the best OS. Patients with PD-L1 ≥ 1% had more EFS benefits compared to those with PD-L1 < 1% (HR [hazard ratio]: 1.55, 95% CI 1.17-2.04). Squamous NSCLC patients had significantly more pCR and MPR benefits than non-squamous NSCLC patients (pCR: OR [odds ratio] 0.68, 95% CI 0.49-0.95; MPR: OR 0.61, 95% CI 0.45-0.82). Former smokers had significantly higher pCR benefits than non-smokers (OR: 2.18; 95% CI 1.21-3.92). Additionally, OS benefit was significantly higher in patients < 65 years compared to those ≥ 65 years (HR ratio: 0.59, 95% CI 0.36-0.95). For MPR, males benefited significantly more from IO-CT compared to females (OR: 1.69, 95% CI 1.18-2.42). CONCLUSION: Perioperative IO-CT is more effective but more toxic than CT alone in resectable NSCLC. Patients with PD-L1 ≥ 1%, squamous NSCLC, a history of smoking, age < 65 years and male gender may experience greater benefits from perioperative IO-CT.

Efficient and Accurate Semi-Automatic Neuron Tracing with Extended Reality.

Neuron tracing, alternately referred to as neuron reconstruction, is the procedure for extracting the digital representation of the three-dimensional neuronal morphology from stacks of microscopic images. Achieving accurate neuron tracing is critical for profiling the neuroanatomical structure at single-cell level and analyzing the neuronal circuits and projections at whole-brain scale. However, the process often demands substantial human involvement and represents a nontrivial task. Conventional solutions towards neuron tracing often contend with challenges such as non-intuitive user interactions, suboptimal data generation throughput, and ambiguous visualization. In this paper, we introduce a novel method that leverages the power of extended reality (XR) for intuitive and progressive semi-automatic neuron tracing in real time. In our method, we have defined a set of interactors for controllable and efficient interactions for neuron tracing in an immersive environment. We have also developed a GPU-accelerated automatic tracing algorithm that can generate updated neuron reconstruction in real time. In addition, we have built a visualizer for fast and improved visual experience, particularly when working with both volumetric images and 3D objects. Our method has been successfully implemented with one virtual reality (VR) headset and one augmented reality (AR) headset with satisfying results achieved. We also conducted two user studies and proved the effectiveness of the interactors and the efficiency of our method in comparison with other approaches for neuron tracing.

Collaborative augmented reconstruction of 3D neuron morphology in mouse and human brains.

Digital reconstruction of the intricate 3D morphology of individual neurons from microscopic images is a crucial challenge in both individual laboratories and large-scale projects focusing on cell types and brain anatomy. This task often fails in both conventional manual reconstruction and state-of-the-art artificial intelligence (AI)-based automatic reconstruction algorithms. It is also challenging to organize multiple neuroanatomists to generate and cross-validate biologically relevant and mutually agreed upon reconstructions in large-scale data production. Based on collaborative group intelligence augmented by AI, we developed a collaborative augmented reconstruction (CAR) platform for neuron reconstruction at scale. This platform allows for immersive interaction and efficient collaborative editing of neuron anatomy using a variety of devices, such as desktop workstations, virtual reality headsets and mobile phones, enabling users to contribute anytime and anywhere and to take advantage of several AI-based automation tools. We tested CAR's applicability for challenging mouse and human neurons toward scaled and faithful data production.

Repair of Mechanical Cartilage Damage Using Exosomes Derived from Deer Antler Stem Cells.

BACKGROUND: Articular cartilage has limited self-repair capacity, and current clinical treatment options for cartilage defects are inadequate. However, deer antler cartilage possesses unique regenerative properties, with the ability to rapidly repair itself. This rapid self-repair process is closely linked to the paracrine factors released by deer antler stem cells. These findings present potential for the development of cell-free therapies for cartilage defects in clinical settings. The aim of this study was to investigate a novel method for repairing cartilage. METHODS: A rat model with articular cartilage defects was established through surgery. Hydrogels loaded with exosomes (Exos) derived from antler stem cells (ASC-Exos) were implanted into the rat cartilage defects. The extent of cartilage damage repair was assessed using histological methods. The effects of ASC-Exos on chondrocytes and rat bone marrow mesenchymal stem cells (BMSCs) were evaluated using cell viability assays, proliferation assays, and scratch assays. Additionally, the maintenance of the chondrocyte phenotype by ASC-Exos was assessed using real-time fluorescence quantitative PCR (qPCR) and western blot analysis. The protein components contained of the Exos were identified using data-independent acquisition (DIA) mass spectrometry. RESULTS: ASC-Exos significantly promoted the repair of cartilage tissue damage. The level of cartilage repair in the experimental group (ASC-Exos) was higher than that in the positive control (human adipose-derived stem cells, hADSC-Exos) and negative control (dulbecco's modified eagle medium) groups (p < 0.05). In vitro experiments demonstrated that ASC-Exos significantly enhanced the proliferation abilities of chondrocytes and the proliferation abilities and the migration abilities of BMSCs (p < 0.05). ASC-Exos up-regulated the expression levels of Aggrecan, Collagen II (COLII), and Sox9 mRNA and proteins in chondrocytes. Analysis of ASC-Exos protein components revealed the presence of active components such as Serotransferrin (TF), S100A4, and Insulin-like growth factor-binding protein 1 (IGF1). CONCLUSIONS: ASC-Exos have a significant effect on cartilage damage repair, which may be attributed to their promotion of chondrocyte and BMSCs proliferation and migration, as well as the maintenance of chondrocyte phenotype. This effect may be mediated by the presence of TF, S100A4, and IGF1.

Nonlinear adaptive robust control of tank bidirectional stabilizers with dead zone compensation based on extended state observer.

In this paper, the problem of highly performance motion control of tank bidirectional stabilizer with dead zone nonlinearity and uncertain nonlinearity is addressed. First, the electromechanical coupling dynamics model of bidirectional stabilizer is developed finely. Second, the dead zone nonlinearity in bidirectional stabilizer is characterized as the combination of an uncertain time-varying gain and a bounded disturbance term. Meanwhile, an adaptive robust controller with dead zone compensation is proposed by organically combining adaptive technique and extended state observer (ESO) through backstepping method. The adaptive technique is employed to reduce the impact of unknown system parameter and dead zone parameter. Furthermore, the ESO is constructed to compensate the lumped uncertainties including unmodeled dynamics and dead zone residual, and integrated together via a feedforward cancellation technique. Moreover, the adaptive robust control law is derived to ensure final global stability. In stability analysis, the asymptotic tracking performance of the proposed controller can be guaranteed as the uncertainty nonlinearities in tank bidirectional stabilizer are constant. It is also guaranteed to achieve bounded tracking performance when time-varying uncertainties exist. Extensive co-simulation and experimental results verify the superiority of the proposed strategy.

Contribution of ferroptosis and SLC7A11 to light-induced photoreceptor degeneration.

Progressive photoreceptor cell death is one of the main pathological features of age-related macular degeneration and eventually leads to vision loss. Ferroptosis has been demonstrated to be associated with retinal degenerative diseases. However, the molecular mechanisms underlying ferroptosis and photoreceptor cell death in age-related macular degeneration remain largely unexplored. Bioinformatics and biochemical analyses in this study revealed xC-, solute carrier family 7 member 11-regulated ferroptosis as the predominant pathological process of photoreceptor cell degeneration in a light-induced dry age-related macular degeneration mouse model. This process involves the nuclear factor-erythroid factor 2-related factor 2-solute carrier family 7 member 11-glutathione peroxidase 4 signaling pathway, through which cystine depletion, iron ion accumulation, and enhanced lipid peroxidation ultimately lead to photoreceptor cell death and subsequent visual function impairment. We demonstrated that solute carrier family 7 member 11 overexpression blocked this process by inhibiting oxidative stress in vitro and in vivo. Conversely, solute carrier family 7 member 11 knockdown or the solute carrier family 7 member 11 inhibitor sulfasalazine and ferroptosis-inducing agent erastin aggravated H2O2-induced ferroptosis of 661W cells. These findings indicate solute carrier family 7 member 11 may be a potential therapeutic target for patients with retinal degenerative diseases including age-related macular degeneration.

Immunohistochemistry identifies E-cadherin, N-cadherin and focal adhesion kinase (FAK) as predictors of stage I non-small cell lung carcinoma spread through the air spaces (STAS), and the combinations as prognostic factors.

Background: Spread through air spaces (STAS) is one of the multiple modes of lung cancer dissemination, yet its molecular and clinicopathological characterization remains poorly studied. This study aimed to investigate the effect of adhesion molecule expression levels on the incidence of STAS and postoperative recurrence in stage I lung cancer patients undergoing radical resection. Methods: E-cadherin, P-cadherin, N-cadherin, focal adhesion kinase (FAK), epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule 1 (NCAM1), vascular cell adhesion molecule 1 (VCAM1), intercellular cell adhesion molecule-1 (ICAM-1) were analyzed retrospectively using immunohistochemistry in patients undergoing radical resection for stage I non-small cell lung cancer (NSCLC). Patients were categorized into four groups based on adhesion molecule expression levels: "low/low", "high/low", "low/high", and "high/high", and the group with the lowest recurrence-free probability (RFP) was defined as high risk. Associations between those adhesion molecules' expression levels and STAS were determined by using the Chi-squared test and logistic regression model. RFP was analyzed by using the log-rank test and Cox proportional risk model. Results: As of January 1, 2024, 12 of 60 patients undergoing radical resection for stage I lung carcinoma had a disease recurrence. All 60 patients' tissue specimens were retrospectively analyzed, and there were no significant differences between patients with STAS-positive (n=30) and STAS-negative (n=30) in baseline clinicopathologic features, except for histological growth patterns. We found that low expression of E-cadherin, high expression of N-cadherin and FAK, and males were independent predictors of higher incidence of STAS. Multivariate Cox analysis showed that tumors with low E-cadherin/high N-cadherin, low E-cadherin/high FAK, and high N-cadherin/high FAK expression were important predictors of recurrence in patients with stage I lung carcinoma. In addition, females and high N-cadherin/high FAK were associated with a high risk of recurrence in patients with STAS. Conclusions: E-cadherin, N-cadherin, and FAK are predictors of STAS occurrence in stage I NSCLC, and their combinations are prognostic factors. The discovery of these molecular markers provides clinicians with a reliable means that may help in the early identification of individuals with a higher risk of recurrence in lung cancer patients, targeting personalized treatment plans such as aggressive adjuvant therapy or closer follow-up.

A dynamic online nomogram for predicts delayed postoperative bleeding after colorectal polyp surgery.

This study aims to analyze the risk factors associated with delayed postoperative bleeding (DPPB) following colorectal polyp surgery, develop a dynamic nomogram and evaluate the model efficacy, provide a reference for clinicians to identify the patients at high risk of DPPB. Retrospective study was done on patients who underwent endoscopic colorectal polypectomy at the First Hospital of Lanzhou University from January 2020 to March 2023. Differences between the group with and without DPPB were compared, and independent risk factors for DPPB occurrence were identified through univariate analysis and combination LASSO and logistic regression. A dynamic nomogram was constructed based on multiple logistic regression to predict DPPB following colorectal polyp surgery. Model evaluation included receiver operating characteristic (ROC), Calibration curve, Decision curve analysis (DCA). DPPB occurred in 38 of the 1544 patients included. multivariate analysis showed that direct oral anticoagulants (DOACs), polyp location in the right hemi colon, polyp diameter, drink, and prophylactic hemoclips were the independent risk factors for DPPB and dynamic nomogram were established. Model validation indicated area under the ROC curve values of 0.936, 0.796, and 0.865 for the training set, validation set, and full set, respectively. The calibration curve demonstrated a strong alignment between the predictions of the column-line diagram model and actual observations. The decision curve analysis (DCA) displayed a significant net clinical benefit across the threshold probability range of 0-100%. The dynamic nomogram aids clinicians in identifying high-risk patients, enabling personalized diagnosis and treatment.

Publication trends of Leber congenital amaurosis researches: a bibliometric study during 2002-2022.

AIM: To analyze the changes in scientific output relating to Leber congenital amaurosis (LCA) and forecast the study trends in this field. METHODS: All of the publications in the field of LCA from 2002 to 2022 were collected from Web of Science (WOS) database. We analyzed the quantity (number of publications), quality (citation and H-index) and development trends (relative research interest, RRI) of published LCA research over the last two decades. Moreover, VOSviewer software was applied to define the co-occurrence network of keywords in this field. RESULTS: A total of 2158 publications were ultimately examined. We found that the focus on LCA kept rising and peaked in 2015 and 2018, which is consistent with the development trend of gene therapy. The USA has contributed most to this field with 1162 publications, 56 674 citations and the highest H-index value (116). The keywords analysis was divided into five clusters to show the hotspots in the field of LCA, namely mechanism-related, genotype-related, local phenotype-related, system phenotype-related, and therapy-related. We also identified gene therapy and anti-retinal degeneration therapy as a major focus in recent years. CONCLUSION: Our study illustrates historical research process and future development trends in LCA field. This may help to guide the orientation for further clinical diagnosis, treatment and scientific research.

Multi-objective double layer water optimal allocation and scheduling framework combing the integrated surface water - groundwater model.

Balancing the water consumption of agricultural and ecological is the key point of sustainable social and economic development in an inland river basin. The growth of desert riparian forests in inland river basins mainly depends on a certain phreatic water table depth (PWTD). The main object of this study was to allocate and schedule water resources to regulate the PWTD and satisfy agricultural water demand. Therefore, a multi-objective double layer optimal allocation and scheduling framework based on the computationally efficient integrated surface water-groundwater model (ISGWM), which can simulate the surface water processes, groundwater recharge and discharge processes, and PWTD changes, was constructed and applied to the mainstream of Tarim River Basin (TRB). The top layer model of the framework is an optimal ecological water allocation model, and its optimal allocation results are used as the initial solution of the bottom layer model. The results show that under 5 different inflow frequencies, the agricultural water shortage rate is 0, 17.38 %, 17.41 %, 14.06 %, and 19.94 %, respectively. The PWTD regulation has a great performance. After the optimal scheduling, the proportions of good growth of the control area behind the gate under different inflow frequencies were 98.18 %, 98.18 %, 98.18 %, 90.91 %, and 94.55 %. Agricultural water shortage is mainly due to the non-uniformity distribution of intra-annual inflow and the lack of controlling hydraulic engineering. The regulation of PWTD can guarantee the growth of desert riparian forests on both sides of the mainstream of TRB. Besides, we explored the feasibility of exploiting groundwater to supplement agricultural water consumption. The groundwater exploitation should be controlled within the scope of not causing excessive increase of PWTD (difference between PWTD and target depth <1 m), due to the groundwater exploitation to supplement agricultural water will lead to the increase of PWTD. Overall, this framework, which regulates the PWTD with the change of ecological water supply based on the ISGWM, provides a new idea for the allocation and scheduling of agricultural and ecological water resources in arid inland river basins. It also provides a new method for the coupled cooperative operation of surface water and groundwater.

Electrochemical Reduction of CO2 into Syngas by N-Modified NiSb Nanowires.

Carbon dioxide reduction reaction (CO2RR) provides a promising method for syngas synthesis. However, it is challenging to balance the CO2RR activity and hydrogen (H2)/carbon monoxide (CO) ratios due to the limited mass transport and inefficient catalytic interface. Herein, we adopt a nitrogen (N)-modification method to synthesize N-modified nickel antimony nanowires (N-NiSb NWs/C), which are efficient for producing syngas with controllable H2/CO ratios. Significantly, the optimized N-NiSb NWs/C, with boosted electrochemical CO2RR activity, have the flexibility to control H2/CO ratios in syngas from nearly 1 to 4 in a wide potential range. The mechanistic discussion shows that the electronic structure of NiSb NWs/C can be optimized by using the synergistic effect between Ni and Sb, as well as the reasonable surface modification, so that a controllable syngas can be obtained. Our design provides an ideal platform for generating syngas with widely controllable H2/CO ratios.

Investigating the Effect of Chain Extender on the Phase Separation and Mechanical Properties of Polybutadiene-Based Polyurethane.

The thermodynamic incompatibility between the soft and hard segments of thermoplastic polyurethane (TPU) results in a microphase-separated behavior and excellent mechanical properties. However, the effect of the chain extender on the degree of microphase separation (DMS) and the resultant mechanical properties of TPU have not been well studied because of the complex interactions between the soft and hard segments. Herein, hydroxyl-terminated polybutadiene-based TPUs(HTPB-TPUs) without hydrogen bonding between the soft and hard segments are synthesized using hydroxyl-terminated polybutadiene, toluene diisocyanate, and four different chain extenders, and the effect of the chain extender structure on DMS is analyzed experimentally using a combination of analytical techniques. Furthermore, the solubility parameters of the soft and hard segments, glass transition temperatures, and hydrogen-bond density of the HTPB-TPUs, are computed using all-atom molecular dynamics simulations. The results clearly reveal that the chain extender significantly affects the DMS and thus the mechanical properties of HTPB-TPUs. This study paves the way for studying the relationship between the structure and properties of TPU.

Enhanced rotation sensing with high-order exceptional points in a multi-mode coupled-ring gyroscope.

Exceptional points (EPs) of non-Hermitian systems are sensitive to perturbations and facilitate the development of highly sensitive gyroscopes. We propose a compact multi-mode optical gyroscope protocol that incorporates two coupled rings and exhibits a fourth-order EP, achieving higher sensitivity compared to gyroscopes based on second-order EPs. We show that the gyroscope sensitivity can be further improved by deviating from the fourth-order EP due to the gain dependence on the cavity intensity. Furthermore, our protocol exhibits resilience against backscattering from counter-propagating modes, which leads to a reduced angular random walk (ARW) factor and increased sensitivity. These features make our protocol highly promising for advancing high-performance optical gyroscopes and enhancing angular velocity sensing technologies.

Publication trends of vascular endothelial growth factor (VEGF) and anti-VEGF treatment in neovascular age-related macular degeneration during 2001-2020: a 20-year bibliometric study.

PURPOSE: This study sought to provide an overview of the current research and further analyze publication trends in the field of vascular endothelial growth factor (VEGF) and anti-VEGF treatment for neovascular age-related macular degeneration (NVAMD). METHODS: We downloaded all related publications from 2001 to 2020 from the Web of Science Core Collection and conducted a bibliometric analysis using the bibiometrix package in R programming software. RESULTS: A total of 3717 publications were included in the analysis. The USA contributed the largest number of publications (1443), and achieved the highest number of citations (74,946) and H-index value (28). Johns Hopkins University, USA, was the top institution with the most publications, and Peter A. Campochiaro was the most productive professor at The Wilmer Eye Institute, USA. 9.60% of the total publications were from the Journal of Retinal and Vitreous Diseases. Trend analysis demonstrated that anti-VEGF therapy was introduced in early 2000 after steroids, and the last 2 decades have witnessed the blossom of several anti-VEGF agents. "Treat-and-extend" and "resistance" were two popular trend topics in recent years. CONCLUSIONS: The USA occupies a dominant position in the research field of VEGF and anti-VEGF treatments in NVAMD. Steroid administration, photodynamic therapy, and anti-VEGF therapy have been pivotal advances in the treatment of NVAMD patients over the past 2 decades. Limited acting period and resistance are potential investigation directions in future studies.