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Abstract Utilization of digital technologies for cataract screening in primary care is a potential solution for addressing the dilemma between the growing aging population and unequally distributed resources. Here, we propose a digital technology-driven hierarchical screening (DH screening) pattern implemented in China to promote the equity and accessibility of healthcare. It consists of home-based mobile artificial intelligence (AI) screening, community-based AI diagnosis, and referral to hospitals. We utilize decision-analytic Markov models to evaluate the cost-effectiveness and cost-utility of different cataract screening strategies (no screening, telescreening, AI screening and DH screening). A simulated cohort of 100,000 individuals from age 50 is built through a total of 30 1-year Markov cycles. The primary outcomes are incremental cost-effectiveness ratio and incremental cost-utility ratio. The results show that DH screening dominates no screening, telescreening and AI screening in urban and rural China. Annual DH screening emerges as the most economically effective strategy with 341 (338 to 344) and 1326 (1312 to 1340) years of blindness avoided compared with telescreening, and 37 (35 to 39) and 140 (131 to 148) years compared with AI screening in urban and rural settings, respectively. The findings remain robust across all sensitivity analyses conducted. Here, we report that DH screening is cost-effective in urban and rural China, and the annual screening proves to be the most cost-effective option, providing an economic rationale for policymakers promoting public eye health in low- and middle-income countries.

In today’s volatile, uncertain, complex, and ambiguous (VUCA) work environments, mitigating employee burnout and turnover has become a critical concern. The enhancement of employee engagement stands out as a pivotal focus in corporate human resource management. Coaching leadership focuses on the encouragement and inspiration of employees, which can effectively stimulate the internal potential of employees, enhance work ability and enhance engagement. However, previous research on the relationship between coaching leadership style and employee engagement are limited, thus obscures the essential function in enterprise development and core competitiveness. The research collected 402 valid responses from MBA and EMBA students at the School of Business, and examines the effect of coaching leadership on employee engagement. Results indicate that coaching leadership significantly enhances multiple facets of employee engagement, including vigor, devotion, and absorption. Crucially, organizational self-esteem emerges as a mediating factor, while learning goal orientation strengthens the positive effects of coaching leadership. This research sheds light on the nuanced dynamics of effective leadership in contemporary workplaces, also it underscores the need for more nuanced, industry-specific analyses and broader exploration of moderating variables. Ultimately, the insights garnered hold profound implications for leadership training, human resource strategies, and performance metrics, emphasizing a more integrative and holistic approach to leadership and employee development in vocational contexts.

Background In adult patients with high myopia (HM), progressive axial elongation poses a significant risk for the development of subsequent ocular complications that may lead to visual impairment. Effective strategies to reduce or prevent further axial elongation in highly myopic adult patients have not been available so far. Recent studies suggested that medically lowering intraocular pressure (IOP) may reduce axial elongation.Objective This clinical randomised controlled trial (RCT) aims to evaluate the efficacy of medical IOP reduction in adult patients with progressive HM (PHM).Trial design Single-centre, open-label, prospective RCT.Methods This RCT will recruit 152 participants with PHM at the Zhongshan Ophthalmic Center (ZOC). Randomised in a ratio of 1:1, participants will receive IOP-lowering eyedrops (intervention group) or will be followed without treatment (control group) for 12 months. Follow-up visits will be conducted at 1, 6 and 12 months after baseline. Only one eye per eligible participant will be included for analysis. The primary outcome is the change in axial length (AL) within the study period of 12 months. Secondary outcomes include the incidence and progression of visual field (VF) defects, changes in optic disc morphology and incidence and progression of myopic maculopathy. Difference in AL changes between the two groups will be analysed using linear regression analysis. For the secondary outcomes, a multifactor Poisson regression within a generalised linear model will be used to estimate the relative risk of progression in VF defects and myopic maculopathy, and the rate of thinning in retinal nerve fibre layer and ganglion cell-inner plexiform will be assessed through Kaplan-Meier curves and log-rank tests.Ethics and dissemination Full ethics approval for this trial has been obtained from the Ethics Committee of ZOC, Sun Yat-sen University, China (ID: 2023KYPJ110). Results of this trial will be disseminated through peer-reviewed journals and conference presentations.Trial registration number NCT05850936.

Abstract Background Traditional problem-based learning (PBL) relying on tutored learning in small groups is very resource-intensive. Little is known about the benefits of PBL in a large classroom setting. This paper introduced a PBL case into the traditional didactic biochemistry course and investigated the acceptability of total online or partial online PBL in a large classroom setting introduced during the coronavirus pandemic. Methods The students were allocated into either total online Group 1, partial online Group 2, or partial online and with poorer academic performance Group 3. A questionnaire comprising of 8 closed-ended questions and 2 open-ended questions and final exam performances were used to evaluate the acceptability of total online or partial online PBL in a large classroom setting. The 8 closed-ended questions were analysed by the Kruskal–Wallis test or chi-square tests. The word cloud analysis of the 2 open-ended questions were conducted by Wenjuanxing. Students’ performances in the final examination were analysed by One-way Anova. Results Both total online and partial online PBL were rated highly by the students. Overall, there were no significant differences in the effectiveness evaluation of PBL between Group 2 and Group 3. There were no significant differences in final exam performances between Group 1 and Group 2. However, Group 1 rated the effectiveness of PBL much higher than Group 2 and 3. Word cloud analysis of the 2 open-ended questions showed students’ positive perspectives of PBL. In biochemistry teaching, from the perspective of the students, the expected optimal number of useful PBL cases might be 2. Conclusions Both total online and partial online PBL in a large classroom setting were widely accepted as a beneficial supplement to traditional biochemistry classes.

Abstract Behect’s disease is a chronic vasculitis characterized by complex multi-organ immune aberrations. However, a comprehensive understanding of the gene-regulatory profile of peripheral autoimmunity and the diverse immune responses across distinct cell types in Behcet’s disease (BD) is still lacking. Here, we present a multi-omic single-cell study of 424,817 cells in BD patients and non-BD individuals. This study maps chromatin accessibility and gene expression in the same biological samples, unraveling vast cellular heterogeneity. We identify widespread cell-type-specific, disease-associated active and pro-inflammatory immunity in both transcript and epigenomic aspects. Notably, integrative multi-omic analysis reveals putative TF regulators that might contribute to chromatin accessibility and gene expression in BD. Moreover, we predicted gene-regulatory networks within nominated TF activators, including AP-1, NF-kB, and ETS transcript factor families, which may regulate cellular interaction and govern inflammation. Our study illustrates the epigenetic and transcriptional landscape in BD peripheral blood and expands understanding of potential epigenomic immunopathology in this disease.

Excessive alcohol consumption has led to the prevalence of gastrointestinal ailments. Alleviating gastric disorders attributed to alcohol-induced thinning of the mucus layer has centered on enhancing mucin secretion as a pivotal approach. In this study, foxtail millet bran polyphenol BPIS was divided into two components with MW < 200 D and MW > 200 D by molecular interception technology. Combined with MTT, cell morphology observation, and trypan blue staining, isoferulic acid (IFA) within the MW < 200 D fraction was determined as the effective constituent to mitigate ethanol-induced damage of gastric epithelial cells. Furthermore, a Wistar rat model with similar clinical features to alcohol-induced gastric mucosal injury was established. Then, gastric morphological observation, H&E staining, and assessments of changes in gastric hexosamine content and gastric wall binding mucus levels were carried out, and the results revealed that IFA (10 mg/Kg) significantly ameliorated alcohol-induced gastric mucosal damage. Finally, we applied techniques including Co-IP, molecular docking, and fluorescence spectroscopy and found that IFA inhibited the alcohol-induced downregulation of N-acetylgalactosamintransferase 2 (GALNT2) activity related to mucus synthesis through direct interaction with GALNT2 in gastric epithelial cells, thus promoting mucin synthesis. Our study lays a foundation for whole grain dietary intervention tailored to individuals suffering from alcoholic gastric mucosal injury.

Abstract Although VEGF-B was discovered as a VEGF-A homolog a long time ago, the angiogenic effect of VEGF-B remains poorly understood with limited and diverse findings from different groups. Notwithstanding, drugs that inhibit VEGF-B together with other VEGF family members are being used to treat patients with various neovascular diseases. It is therefore critical to have a better understanding of the angiogenic effect of VEGF-B and the underlying mechanisms. Using comprehensive in vitro and in vivo methods and models, we reveal here for the first time an unexpected and surprising function of VEGF-B as an endogenous inhibitor of angiogenesis by inhibiting the FGF2/FGFR1 pathway when the latter is abundantly expressed. Mechanistically, we unveil that VEGF-B binds to FGFR1, induces FGFR1/VEGFR1 complex formation, and suppresses FGF2-induced Erk activation, and inhibits FGF2-driven angiogenesis and tumor growth. Our work uncovers a previously unrecognized novel function of VEGF-B in tethering the FGF2/FGFR1 pathway. Given the anti-angiogenic nature of VEGF-B under conditions of high FGF2/FGFR1 levels, caution is warranted when modulating VEGF-B activity to treat neovascular diseases.

Glaucoma is the leading cause of irreversible blindness worldwide. In the pathogenesis of glaucoma, activated microglia can lead to retinal ganglion cells (RGCs) apoptosis and death, however, the molecular mechanisms remain largely unknown. We demonstrate that phospholipid scramblase 1 (PLSCR1) is a key regulator promoting RGCs apoptosis and their clearance by microglia. As evidenced in retinal progenitor cells and RGCs of the acute ocular hypertension (AOH) mouse model, overexpressed PLSCR1 induced its translocation from the nucleus to the cytoplasm and cytomembrane, as well as elevated phosphatidylserine exposure and reactive oxygen species generation with subsequent RGCs apoptosis and death. These damages were effectively attenuated by PLSCR1 inhibition. In the AOH model, PLSCR1 led to an increase in M1 type microglia activation and retinal neuroinflammation. Upregulation of PLSCR1 resulted in strongly elevated phagocytosis of apoptotic RGCs by activated microglia. Taken together, our study provides important insights linking activated microglia to RGCs death in the glaucoma pathogenesis and other RGC-related neurodegenerative diseases.

Abstract Background Age-related macular degeneration (AMD), characterized by the degeneration of retinal pigment epithelium (RPE) and photoreceptors, is the leading cause of irreversible vision impairment among the elderly. RPE senescence is an important contributor to AMD and has become a potential target for AMD therapy. HTRA1 is one of the most significant susceptibility genes in AMD, however, the correlation between HTRA1 and RPE senescence hasn’t been investigated in the pathogenesis of AMD. Methods Western blotting and immunohistochemistry were used to detect HTRA1 expression in WT and transgenic mice overexpressing human HTRA1 (hHTRA1-Tg mice). RT-qPCR was used to detect the SASP in hHTRA1-Tg mice and ARPE-19 cells infected with HTRA1. TEM, SA-β-gal was used to detect the mitochondria and senescence in RPE. Retinal degeneration of mice was investigated by fundus photography, FFA, SD-OCT and ERG. The RNA-Seq dataset of ARPE-19 cells treated with adv-HTRA1 versus adv-NC were analyzed. Mitochondrial respiration and glycolytic capacity in ARPE-19 cells were measured using OCR and ECAR. Hypoxia of ARPE-19 cells was detected using EF5 Hypoxia Detection Kit. KC7F2 was used to reduce the HIF1α expression both in vitro and in vivo. Results In our study, we found that RPE senescence was facilitated in hHTRA1-Tg mice. And hHTRA1-Tg mice became more susceptible to NaIO3 in the development of oxidative stress-induced retinal degeneration. Similarly, overexpression of HTRA1 in ARPE-19 cells accelerated cellular senescence. Our RNA-seq revealed an overlap between HTRA1-induced differentially expressed genes associated with aging and those involved in mitochondrial function and hypoxia response in ARPE-19 cells. HTRA1 overexpression in ARPE-19 cells impaired mitochondrial function and augmented glycolytic capacity. Importantly, upregulation of HTRA1 remarkably activated HIF-1 signaling, shown as promoting HIF1α expression which mainly located in the nucleus. HIF1α translation inhibitor KC7F2 significantly prevented HTRA1-induced cellular senescence in ARPE-19 cells, as well as improved the visual function in hHTRA1-Tg mice treated with NaIO3. Conclusions Our study showed elevated HTRA1 contributes to the pathogenesis of AMD by promoting cellular senescence in RPE through damaging mitochondrial function and activating HIF-1 signaling. It also pointed out that inhibition of HIF-1 signaling might serve as a potential therapeutic strategy for AMD. Video Abstract

Abstract Background Treatment of pediatric cataract remains challenging because of the extremely high incidence of postoperative adverse events (AEs), especially the AEs related to the locations of secondary implanted intraocular lens (IOL). There are two common locations for secondary IOL implantation in pediatric aphakic eyes: ciliary sulcus or in-the-bag implantation. However, there are currently no large, prospective studies comparing complication rates and visual prognosis of in-the-bag versus ciliarysulcus secondary IOL implantation in pediatric patients. Whether or how much secondary in-the-bag IOL implantation benefits the pediatric patients more than sulcus implantation and deserves to be performed routinely by surgeons remains to be elucidated. Here, we describe the protocol of a randomized controlled trial (RCT) designed to evaluate the safety and efficacy of two approaches of IOL implantation in pediatric aphakia. Methods The study is a multicenter, single-blinded RCT with 10 years of follow-up. Overall, a minimum of 286 eyes (approximately 228 participants assuming 75% have two study eyes) will be recruited. This study will be carried out in four eye clinics across China. Consecutive eligible patients are randomized to undergo either secondary in-the-bag IOL implantation or secondary sulcus IOL implantation. Participants with two eyes eligible will receive the same treatment. The primary outcomes are IOL decentration and the incidence of glaucoma-related AEs. The secondary outcomes include the incidence of other AEs, IOL tilt, visual acuity, and ocular refractive power. Analysis of the primary and secondary outcomes is to be based on the intention-to-treat and per-protocol analysis. Statistical analyses will include the χ 2 test or Fisher’s exact test for the primary outcome, mixed model and generalized estimated equation (GEE) model for the secondary outcome, Kaplan–Meier survival curves for the cumulative probability of glaucoma-related AEs over time in each group. Discussion To the best of our knowledge, this study is the first RCT to evaluate the safety and efficacy of secondary IOL implantation in pediatric aphakia. The results will provide high-quality evidence for the clinical guidelines for the treatment of pediatric aphakia. Trial registration ClinicalTrials.gov NCT05136950. Registered on 1 November 2021.

Abstract Background Chronic inflammation significantly contributes to photoreceptor death in blinding retinal diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Bromodomain and extraterminal domain (BET) proteins are epigenetic readers that act as key proinflammatory factors. We recently found the first-generation BET inhibitor JQ1 alleviated sodium iodate-induced retinal degeneration by suppressing cGAS-STING innate immunity. Here, we investigated the effects and mechanism of dBET6, a proteolysis‑targeting chimera (PROTAC) small molecule that selectively degrades BET by the ubiquitin‒proteasome system, in light-induced retinal degeneration. Methods Mice were exposed to bright light to induce retinal degeneration, and the activation of cGAS-STING was determined by RNA-sequencing and molecular biology. Retinal function, morphology, photoreceptor viability and retinal inflammation were examined in the presence and absence of dBET6 treatment. Results Intraperitoneal injection of dBET6 led to the rapid degradation of BET protein in the retina without detectable toxicity. dBET6 improved retinal responsiveness and visual acuity after light damage (LD). dBET6 also repressed LD-induced retinal macrophages/microglia activation, Müller cell gliosis, photoreceptor death and retinal degeneration. Analysis of single-cell RNA-sequencing results revealed cGAS-STING components were expressed in retinal microglia. LD led to dramatic activation of the cGAS-STING pathway, whereas dBET6 suppressed LD-induced STING expression in reactive macrophages/microglia and the related inflammatory response. Conclusions This study indicates targeted degradation of BET by dBET6 exerts neuroprotective effects by inhibiting cGAS-STING in reactive retinal macrophages/microglia, and is expected to become a new strategy for treatment of retinal degeneration.

Summary: RNA-binding protein with multiple splicing (RBPMS) plays a crucial role in cardiac mesoderm specification and cardiovascular development, as well as being a typical marker for whole retinal ganglion cells (RGCs). However, there is a lack of animal models to spatiotemporally trace the location and function of RBPMS-expressing cells in vivo. In this study, we develop a tamoxifen-inducible RBPMS-tdTomato reporter mouse line to track RBPMS-expressing cells during embryogenesis and adulthood. This mouse line allows us to identify and locate RBPMS-tdTomato-positive cells among various tissues, especially in RGCs and smooth muscle cells, which assist to simulate related retinal degenerative diseases, model and examine choroidal neovascularization non-invasively in vivo. Our results show that the RBPMSCreERT2-tdTomato mouse line is a valuable tool for lineage tracing, disease modeling, drug screening, as well as isolating specific target cells.

Plant-derived exosome-like nanovesicles (PELNs) are bilayer membrane-enclosed nanovesicles secreted by plant cells, serving as carriers of various substances such as proteins, RNA, and metabolites. The mounting evidence suggests that PELN plays a crucial role in transmembrane signaling, nutrient transportation, apoptosis, and regulation of gut microbiota composition. This makes it a promising “dark nutrient” for plants to modulate human physiology and pathogenesis. A comprehensive understanding of PELN formation, uptake, and functional mechanisms can offer novel insights into plant nutrition and functional properties, thereby facilitating the precise development of plant-based foods and drugs. This article provides a summary of PELN extraction and characterization, as well as absorption and delivery processes. Furthermore, it focuses on the latest discoveries and underlying physiological mechanisms of PELN’s functions while exploring future research directions.

In the current era, as modern cities increasingly face environmental disasters and inherent challenges, the creation and enhancement of resilient cities have become critical. China’s urban resilience exhibits significant imbalances and inadequacies at the provincial level. This study delves into the evolution of urban resilience in various Chinese provinces, offering valuable insights for building and nurturing resilient cities. Initially, a comprehensive evaluation system for China’s urban resilience was established, incorporating 24 indicators across three key resilience aspects: resistance, adaptability, and recovery. The entropy weight method was used to develop an urban resilience evaluation model, and the Moran index and spatial cold–hot-spot analysis were applied to examine the spatiotemporal dynamics of urban resilience across China’s 31 provinces from 2012 to 2021. Moreover, the geographically and temporally weighted regression model was employed to analyze the spatial distribution of factors affecting urban resilience. The results show a general upward trend in urban resilience across Chinese provinces, with notable regional differences and concentrations. A significant decrease in urban resilience is observed from southeastern coastal cities to inland regions. The regression model highlights spatial variations in the impact of different factors, with the same factor having varying effects in different provinces. This research provides a thorough understanding of the factors influencing urban resilience in China, contributing to both theoretical and practical discussions on the topic. It lays a strong scientific groundwork for the development and advancement of resilient cities in China.

Uveitis is a complex autoimmune inflammatory disease of the eye and defining molecules involved is a priority. Here the authors use scRNA sequencing in mouse experimental autoimmune uveitis (EAU) and show PIM1 promotes the imbalance of Th17 and Treg cells, and find elevated PIM-1 in human uveitis disease.

Single-cell RNA-sequencing and chromatin accessibility analysis reveal transcriptomic and epigenomic changes between healthy patients and those affected by the systemic autoimmune disorder Vogt-Koyanagi-Harada disease.

Genome topology provides a structural basis for epigenome-mediated transcriptional regulation in eukaryotes. Here the authors characterized the 3D genome of stratified squamous epithelia. They generated a Hi-C map of human limbal stem/progenitor cells (LSCs) and integrated these data with epigenomics, transcription factor binding maps, and transcriptome data.

Building type prediction is a critical task for urban planning and population estimation. The growing availability of multi-source data presents rich semantic information for building type prediction. However, existing residential building prediction methods have problems with feature extraction and fusion from multi-type data and multi-level interactions between features. To overcome these limitations, we propose a deep learning approach that takes both the internal and external characteristics of buildings into consideration for residential building prediction. The internal features are the shape characteristics of buildings, and the external features include location features and semantic features. The location features include the proximity of the buildings to the nearest road and areas of interest (AOI), and the semantic features are mainly threefold: spatial co-location patterns of points of interest (POI), nighttime light, and land use information of the buildings. A deep learning model, DeepFM, with multi-type features embedded, was deployed to train and predict building types. Comparative and ablation experiments using OpenStreetMap and the nighttime light dataset were carried out. The results showed that our model had significantly higher classification performance compared with other models, and the F1 score of our model was 0.9444. It testified that the external semantic features of the building significantly enhanced the predicted performance. Moreover, our model showed good performance in the transfer learning between different regions. This research not only significantly enhances the accuracy of residential building identification but also offers valuable insights and ideas for related studies.

Although many studies have characterized genetic variation in human populations, few have investigated structural variation and few have been in non-European populations. Here, the authors have performed long read sequencing on 405 Chinese individuals to identify structural variants and link them to phenotypes.

N 6-methyladenosine (m6A) is the most prevalent mRNA internal modification and has been shown to regulate the development, physiology, and pathology of various tissues. However, the functions of the m6A epitranscriptome in the visual system remain unclear. In this study, using a retina-specific conditional knockout mouse model, we show that retinas deficient in Mettl3, the core component of the m6A methyltransferase complex, exhibit structural and functional abnormalities beginning at the end of retinogenesis. Immunohistological and single-cell RNA sequencing (scRNA-seq) analyses of retinogenesis processes reveal that retinal progenitor cells (RPCs) and Müller glial cells are the two cell types primarily affected by Mettl3 deficiency. Integrative analyses of scRNA-seq and MeRIP-seq data suggest that m6A fine-tunes the transcriptomic transition from RPCs to Müller cells by promoting the degradation of RPC transcripts, the disruption of which leads to abnormalities in late retinogenesis and likely compromises the glial functions of Müller cells. Overexpression of m6A-regulated RPC transcripts in late RPCs partially recapitulates the Mettl3-deficient retinal phenotype. Collectively, our study reveals an epitranscriptomic mechanism governing progenitor-to-glial cell transition during late retinogenesis, which is essential for the homeostasis of the mature retina. The mechanism revealed in this study might also apply to other nervous systems.

Summary: Background: Targeting helper T cells, especially Th17 cells, has become a plausible therapy for many autoimmune diseases. Methods: Using an in vitro culture system, we screened an epigenetics compound library for inhibitors of IFN-γ and IL-17 expression in murine Th1 and Th17 cultures. Findings: This identified IOX1 as an effective suppressor of IL-17 expression in both murine and human CD4+ T cells. Furthermore, we found that IOX1 suppresses Il17a expression directly by targeting TET2 activity on its promoter in Th17 cells. Using established pre-clinical models of intraocular inflammation, treatment with IOX1 in vivo reduced the migration/infiltration of Th17 cells into the site of inflammation and tissue damage. Interpretation: These results provide evidence of the strong potential for IOX1 as a viable therapy for inflammatory diseases, in particular of the eye. Funding: This study was supported by the National Key Research and Development Program of China 2021YFA1101200 (2021YFA1101204) to LW and XW; the National Natural Science Foundation of China 81900844 to XH and 82171041 to LW; the China Postdoctoral Science Foundation 2021M700776 and the Scientific Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine 20221373 to YZ; and the National Institute for Health Research (NIHR) Biomedical Research Centre at Moorfields Eye Hospital NHS (National Health Service) Foundation Trust and University College London Institute of Ophthalmology, UK (DAC, LPS, PJPL, MS, ADD and RWJL). The views expressed are those of the authors and not necessarily those of the NIHR or the UK's Department of Health and Social Care.

The treatment of complex cerebrovascular diseases (CCVDs) at the skull base, such as complex intracranial aneurysms, carotid-cavernous sinus fistulas, and intracranial artery traumatic injuries, is a difficult clinical problem despite advances in endovascular and surgical therapies. Covered stents or stent graft insertion is a new concept for endovascular treatment that focuses on arterial wall defect reconstruction, differing from endovascular lesion embolization or flow diverter therapies. In recent years, covered stents specifically designed for cerebrovascular treatment have been applied in the clinical setting, allowing thousands of patients with CCVDs to undergo intraluminal reconstruction treatment and achieving positive results, even in the era of flow diverters. Since there is no unified reference standard for the application of covered stents for treating CCVDs, it is necessary to further standardize and guide the clinical application of this technique. Thus, we organized authoritative experts in the field of neurointervention in China to write an expert consensus, which aims to summarize the results of covered stent insertion in the treatment of CCVDs and propose suitable standards for its application in the clinical setting. Based on the contents of this consensus, clinicians can use individualized intraluminal reconstruction treatment techniques for patients with CCVDs.

BackgroundRecent years have witnessed a gradual increase in the number of female methamphetamine users. Meanwhile, female methamphetamine users are more likely to have psychological problems than male methamphetamine users. The association between diet and psychological problems have been found among non-methamphetamine user. The present study aims to investigate the relationship between dietary intake frequency and psychological problems in female methamphetamine users.Materials and MethodsA total of 109 female methamphetamine users, collected from a Compulsory Isolated Drug Rehabilitation Centre in northern China, participated in the study. All participants completed the Symptom Checklist 90 (SCL-90) questionnaire to assess psychological status. The relation of dietary intake frequency with the SCL-90 score was tested in partial correlation analysis. Multivariable regression models were used to calculate odds ratios to evaluate the association of dietary intake frequency with psychological problems.ResultsOf the current female methamphetamine population, 33 participants were diagnosed with psychological problems using SCL-90. In the terms of dietary intake frequency, the frequency of nut intake in the psychiatric symptom group was significantly lower than that in the asymptomatic group. However, there was no difference in the frequency of other food intakes between the two groups. The frequency of nut intake was negatively correlated with the total score of SCL-90 and 8 different symptom clusters of psychopathologies on SCL-90. Logistic regression analysis indicated that the increased frequency of nut intake was associated with a lower risk of psychological problems.ConclusionIn the female methamphetamine population, increasing the frequency of nut intake may reduce the risk of psychological problems for female methamphetamine users.

Mobile health (mHealth) services have been widely used in medical services and health management through mobile devices and multiple channels, such as smartphones, wearable equipment, healthcare applications (Apps), and medical platforms. However, the number of the users who are currently receiving the mHealth services is small. In China, more than 70% of internet users have never used mHealth services. Such imbalanced situation could be attributed to users’ traditional concept of medical treatment, psychological factors (such as low self-efficacy) and privacy concerns. The purpose of this study is to explore the direct and indirect effects of mHealth users’ self-efficacy and privacy concerns on their intention to adopt mHealth services, providing guidelines for mHealth service providers to enhance users’ intention of adoption. A questionnaire was designed by the research team and 386 valid responses were collected from domestic participants in China. Based on the unified theory of acceptance and use of technology (UTAUT) model, a research model integrated self-efficacy and privacy concerns was constructed to investigate their effects on users’ intention to adopt mobile mHealth services. The results show that self-efficacy could facilitate users’ intention to adopt mHealth services, and had a significantly positive effect on perceived ubiquity, effort expectancy, performance expectancy and subjective norm. This study verifies the direct and indirect effects of self-efficacy and privacy concerns on users’ intention to adopt mHealth services, providing a different perspective for studying mHealth adoption behavior. The findings could provide guidelines for mHealth service providers to improve their service quality and enhance users’ intention of adoption.

ObjectiveAcute ischemic stroke is common in elder patients. This study investigates whether using the balloon-guided catheter (BGC) would improve the effect of stent thrombectomy (Solitaire FR With Intracranial Support Catheter for Mechanical Thrombectomy, SWIM) for patients with acute ischemic stroke due to large vessel occlusion (AIS-LVO).MethodThe data of 209 patients with AIS-LVO underwent SWIM were collected retrospectively from January 2017 to June 2021. These patients were divided into two groups based on whether they used of BGC or not. The propensity score matching (PSM) analysis was used to compare the differences in the first pass effect (FPE), successful recanalization, embolus escape rate, symptomatic intracranial hemorrhage (sICH), 90-day clinical favorable outcome, 90-day all-cause mortality, and complications in the patients treated with SWIM combined with balloon-guided catheter or conventional catheter.ResultsAmong the 209 patients, 44 patients were treated with BGC and 165 patients were not. After matching, a total of 111 patients were included. The results showed that there was no statistical difference in FPE (35.1% in non-BGC group compared to 24.3% in BGC group, matched RR, 0.59; 95% CI, 0.24–1.44), successful recanalization (89.2 vs. 91.9%, matched RR, 1.37; 95%CI, 0.34–5.51), embolus escape (6.8 vs. 8.1%, matched RR, 1.22; 95%CI, 0.28–5.40), sICH (8.1 vs. 13.5%; matched RR, 1.77; 95%CI 0.50–6.24), 90-day clinical favorable outcome (48.7 vs. 54.1%, matched RR, 1.11; 95%CI 0.51–2.46), 90-day all-cause mortality (17.6 vs. 21.6%, matched RR, 1.29; 95%CI 0.48–3.47), and the incidence of complications (6.8 vs. 5.4%, matched RR, 0.79 95%CI 0.15–4.27). These results indicate that using SWIM as the first-line treatment for patients with AIS-LVO, there is no statistical significance in FPE, final successful recanalization, distal emboli, sICH, procedural time, 90-day favorable outcome, 90-day mortality, and complications with or without BGC.ConclusionBalloon-guided catheter does not affect the result of using SWIM as the first-line treatment for patients with AIS-LVO. Our results will guide daily practice, with the adoption of the use of a guided catheter without a balloon.

Abstract The methyltransferase EZH2 plays an important role in regulating chromatin conformation and gene transcription. Phosphorylation of EZH2 at S21 by AKT kinase suppresses its function. However, protein phosphatases responsible for the dephosphorylation of EZH2‐S21 remain elusive. Here, it is demonstrated that EZH2 is highly expressed in the ocular lens, and AKT‐EZH2 axis is important in TGFβ‐induced epithelial‐mesenchymal transition (EMT). More importantly, it is identified that MYPT1/PP1 dephosphorylates EZH2‐S21 and thus modulates its functions. MYPT1 knockout accelerates EMT, but expression of the EZH2‐S21A mutant suppresses EMT through control of multiple families of genes. Furthermore, the phosphorylation status and gene expression modulation of EZH2 are implicated in control of anterior subcapsular cataracts (ASC) in human and mouse eyes. Together, the results identify the specific phosphatase for EZH2‐S21 and reveal EZH2 dephosphorylation control of several families of genes implicated in lens EMT and ASC pathogenesis. These results provide important novel information in EZH2 function and regulation.

Abstract The current dogma in ophthalmology and vision research presumes the intraocular environment to be sterile. However, recent evidence of intestinal bacterial translocation into the bloodstream and many other internal organs including the eyes, found in healthy and diseased animal models, suggests that the intraocular cavity may also be inhabited by a microbial community. Here, we tested intraocular samples from over 1000 human eyes. Using quantitative PCR, negative staining transmission electron microscopy, direct culture, and high-throughput sequencing technologies, we demonstrated the presence of intraocular bacteria. The possibility that the microbiome from these low-biomass communities could be a contamination from other tissues and reagents was carefully evaluated and excluded. We also provide preliminary evidence that a disease-specific microbial signature characterized the intraocular environment of patients with age-related macular degeneration and glaucoma, suggesting that either spontaneous or pathogenic bacterial translocation may be associated with these common sight-threatening conditions. Furthermore, we revealed the presence of an intraocular microbiome in normal eyes from non-human mammals and demonstrated that this varied across species (rat, rabbit, pig, and macaque) and was established after birth. These findings represent the first-ever evidence of intraocular microbiota in humans.

Corneal epithelium shares similar molecular signatures to other stratified epithelia. Here, the authors map super-enhancers and accessible chromatin in corneal epithelium, identifying a transcription regulatory circuit, including RUNX1, PAX6, and SMAD3, required for corneal epithelial identity and homeostasis.

Urban planning and function layout have important implications for the journeys of a large percentage of commuters, which often make up the majority of daily traffic in many cities. Therefore, the analysis and forecast of traffic flow among urban functional areas are of great significance for detecting urban traffic flow directions and traffic congestion causes, as well as helping commuters plan routes in advance. Existing methods based on ride-hailing trajectories are relatively effective solution schemes, but they often lack in-depth analyses on time and space. In the paper, to explore the rules and trends of traffic flow among functional areas, a new spatiotemporal characteristics analysis and forecast method of traffic flow among functional areas based on urban ride-hailing trajectories is proposed. Firstly, a city is divided into areas based on the actual urban road topology, and all functional areas are generated by using areas of interest (AOI); then, according to the proximity and periodicity of inter-area traffic flow data, the periodic sequence and the adjacent sequence are established, and the topological structure is learned through graph convolutional neural (GCN) networks to extract the spatial correlation of traffic flow among functional areas. Furthermore, we propose an attention-based gated graph convolutional network (AG-GCN) forecast method, which is used to extract the temporal features of traffic flow among functional areas and make predictions. In the experiment, the proposed method is verified by using real urban traffic flow data. The results show that the method can not only mine the traffic flow characteristics among functional areas under different time periods, directions, and distances, but also forecast the spatiotemporal change trend of traffic flow among functional areas in a multi-step manner, and the accuracy of the forecasting results is higher than that of common benchmark methods, reaching 96.82%.

Most single-cell RNA sequencing methods have limited ability to profile the transcriptome at isoform resolution. Here the authors develop scRCAT-seq to characterize the 5′- and 3′-ends of transcripts in single cells, and identify cell-type specific alternative transcript isoforms.

Electron probe microanalysis (EPMA) is promising for accurately determining elemental components in micro-areas of individual phytolith particles, interpreting compositional features and formation mechanisms of phytoliths in plants, identifying archeological and sedimental phytolith. However, the EPMA method of analyzing mounted slide phytoliths has not well been defined. In this study, we attempted different EPMA methods to determine the elemental compositions of phytoliths in mounted slides. Direct analysis of carbon (DAC) with other elements in phytolith could obtain abnormally high total values and carbon values. The method of carbon excluded in measuring elements (non-carbon analysis (NCA)) was feasible to obtain elemental compositions in phytolith. The NCA method was conducive to obtain the factual elemental compositions of an individual phytolith (morphotype) when the carbon content of phytolith was relatively low. The EPMA results of phytoliths from 20 bamboo species (three genera) showed that phytolith was dominantly composed of SiO2 but also included low contents of diverse other elements. The EPMA of phytoliths can provide the elemental composition of micro-areas of an individual phytolith particle. The elemental compositions of phytolith varied with their morphotypes, the genera and ecotype of bamboos. The EPMA of elemental compositions in phytoliths is a potential tool to study the formation mechanism of phytoliths, plant taxonomical identification, archaeological and paleoenvironmental reconstruction.

Herpes simplex keratitis (HSK) is the most common cause of corneal blindness in developed nations, caused by primary or recurrent herpes simplex virus 1 (HSV-1) infection of the cornea. Latent infection of HSV-1, especially in the trigeminal ganglion (TG), causes recurrence of HSV-1 infection. As antiviral treatment is not effective on latent HSV-1, to test the possibility of inhibiting HSV-1 by SpCas9 (Streptococcus pyogenes Cas9) or SaCas9 (Staphylococcus aureus Cas9), ICP0 and ICP4, two important genes required for HSV-1 replication and reactivation, were chosen as targets. In Vero cells, SpCas9 and SaCas9 targeting ICP0 or ICP4 can effectively inhibit the proliferation of HSV-1 without affecting cell viability. No significant guide RNA (gRNA)-dependent off-targets were observed in the human genome by digenome sequencing and deep sequencing verification. Adeno-associated virus 1 (AAV1)-mediated delivery of SaCas9 inhibits HSV-1 replication by targeting ICP4 in mouse primary TG neuronal cells. SpCas9 and SaCas9 are able to inhibit HSV-1 infection in Vero cells and mouse TG neuronal cultures with high efficiency and good biosafety. AAV1-mediated delivery of SaCas9 shows great potential in treating HSK and inhibiting HSV-1 in TG neurons. Further investigations may be needed to test the inhibition of latent infections, which may result in the development of novel methods for treating viral diseases.

Abstract A challenge of chronic diseases that remains to be solved is how to liberate patients and medical resources from the burdens of long-term monitoring and periodic visits. Precise management based on artificial intelligence (AI) holds great promise; however, a clinical application that fully integrates prediction and telehealth computing has not been achieved, and further efforts are required to validate its real-world benefits. Taking congenital cataract as a representative, we used Bayesian and deep-learning algorithms to create CC-Guardian, an AI agent that incorporates individualized prediction and scheduling, and intelligent telehealth follow-up computing. Our agent exhibits high sensitivity and specificity in both internal and multi-resource validation. We integrate our agent with a web-based smartphone app and prototype a prediction-telehealth cloud platform to support our intelligent follow-up system. We then conduct a retrospective self-controlled test validating that our system not only accurately detects and addresses complications at earlier stages, but also reduces the socioeconomic burdens compared to conventional methods. This study represents a pioneering step in applying AI to achieve real medical benefits and demonstrates a novel strategy for the effective management of chronic diseases.

Anti-VEGF therapy has many limitations that might be resolved by using combination treatment approaches. Here, the authors demonstrate that the dual-targeting of VEGF and PDGF is required for targeting resistant FGF2+ tumors which depend on the recruitment of pericytes on tumor microvessels.

Class 1 type I CRISPR–Cas systems have not been as extensively developed for genome engineering as Class 2 systems. Here the authors modify the Type I–F CRISPR–Cas system for transcriptional activation of gene expression.

Abstract Background Acute glaucoma, characterized by a sudden elevation in intraocular pressure (IOP) and retinal ganglion cells (RGCs) death, is a major cause of irreversible blindness worldwide that lacks approved effective therapies, validated treatment targets and clear molecular mechanisms. We sought to explore the potential molecular mechanisms underlying the causal link between high IOP and glaucomatous RGCs death. Methods A murine retinal ischemia/ reperfusion (RIR) model and an in vitro oxygen and glucose deprivation/reoxygenation (OGDR) model were used to investigate the pathogenic mechanisms of acute glaucoma. Results Our findings reveal a novel mechanism of microglia-induced pyroptosis-mediated RGCs death associated with glaucomatous vision loss. Genetic deletion of gasdermin D (GSDMD), the effector of pyroptosis, markedly ameliorated the RGCs death and retinal tissue damage in acute glaucoma. Moreover, GSDMD cleavage of microglial cells was dependent on caspase-8 (CASP8)-hypoxia-inducible factor-1α (HIF-1α) signaling. Mechanistically, the newly identified nucleotide-binding leucine-rich repeat-containing receptor (NLR) family pyrin domain-containing 12 (NLRP12) collaborated with NLR family pyrin domain-containing 3 (NLRP3) and NLR family CARD domain-containing protein 4 (NLRC4) downstream of the CASP8-HIF-1α axis, to elicit pyroptotic processes and interleukin-1β (IL-1β) maturation through caspase-1 activation, facilitating pyroptosis and neuroinflammation in acute glaucoma. Interestingly, processing of IL-1β in turn magnified the CASP8-HIF-1α-NLRP12/NLRP3/NLRC4-pyroptosis circuit to accelerate inflammatory cascades. Conclusions These data not only indicate that the collaborative effects of NLRP12, NLRP3 and NLRC4 on pyroptosis are responsible for RGCs death, but also shed novel mechanistic insights into microglial pyroptosis, paving novel therapeutic avenues for the treatment of glaucoma-induced irreversible vision loss through simultaneously targeting of pyroptosis.

Congenital cataract is one of the leading causes of blindness in children worldwide. About one-third of congenital cataracts are caused by genetic defects. LSS, which encodes lanosterol synthase, is a causal gene for congenital cataracts. LSS is critical in preventing abnormal protein aggregation of various cataract-causing mutant crystallins; however, its roles in lens development remain largely unknown. In our study, we generated a mouse model harboring Lss G589S mutation, which is homologous to cataract-causing G588S mutation in human LSS. LssG589S/G589S mice exhibited neonatal lethality at postal day 0 (P0), whereas these mice showed severe opacity in eye lens. Also, we found that cataract was formed at E17.5 after we examined the opacity of embryonic lens from E13.5 to E18.5. Moreover, disrupted lens differentiation occurred at E14.5 prior to formation of the opacity of eye lens, shown as delayed differentiation of lens secondary fiber and disordered lens fiber organization. In addition, RNA-seq analysis indicated that cholesterol synthesis signaling pathways were significantly downregulated. Overall, our findings provide clear evidence that a mouse model harboring a homozygous Lss G589S mutation can recapitulate human congenital cataract. Our study points out that LSS functions as a critical determinant of lens development, which will contribute to better understanding LSS defects in cataractogenesis and developing therapies for cataracts.

Introduction Myopia is the common cause of reduced uncorrected visual acuity among school-age children. It is more prevalent in urban than in rural areas. Although many myopia studies have focused on the effect of urbanisation, it remains unclear how visual experience in urban regions could affect childhood myopia. This study aims to investigate the incidence and prevalence of myopia among school-age children in urban and rural settings, thereby identifying the environmental factors that affect the onset and progression of myopia.Methods and analysis A school-based cohort study will be conducted. We will enroll all first-grade students from an urban (10 primary schools) and a rural (10 primary schools) regions of Zhaoqing city, China. Over 3-year follow-up period, students will receive detailed eye examinations annually and complete questionnaires about living habits and environment. In a 5% random subsample of the cohort, physical activity, light intensity and eye-tracking data will be obtained using wearable devices, and high-resolution macular images will be obtained by optical coherence tomography (OCT). The primary outcome is incident myopia, defined as myopia (spherical equivalent refractive of at least −0.5D) detected during follow-up among those without myopia at baseline.Ethics and dissemination Ethics approval was obtained from the ethics committee of the Zhongshan Ophthalmic Center (number: 2019KYPJ171). Study findings will be published in a peer-reviewed journal.Trial registration number NCT04219228.

Breast cancer is the most frequently diagnosed malignant tumor in women. Foxtail millet is an important cereal food and exhibits a wide range of nutrition. We previously extracted total polyphenols composed of 12 compounds from foxtail millet bran (named BPIS). In this study, we find that BPIS inhibits the proliferation of breast cancer cells by restraining the cellular membrane synthesis via suppressing the conversion of saturated fatty acids (SFA) to monounsaturated fatty acids (MUFA). Mechanically, BPIS decreases the glucose regulated protein 78 (GRP78) level, which further inhibits the expression of SREBP-1 and downstream-target SCD1. Combining molecular docking, MTT screening and in vivo model, we ultimately identify that vitexin and syringic acid are the main active ingredients. Our data showed that the combination of vitexin and syringic acid suppress the proliferation of breast cancer cells, which support further study of BPIS as a new dietary assistant strategy to improve breast cancer.

Glaucoma and other optic neuropathies affect millions of people worldwide, ultimately causing progressive and irreversible degeneration of retinal ganglion cells (RGCs) and blindness. Previous research into cell replacement therapy of these neurodegenerative diseases has been stalled due to the incapability for grafted RGCs to integrate into the retina and project properly along the long visual pathway. In vivo RGC regeneration would be a promising alternative approach but mammalian retinas lack regenerative capacity. It therefore has long been a great challenge to regenerate functional and properly projecting RGCs for vision restoration in mammals. Here we show that the transcription factors (TFs) Math5 and Brn3b together are able to reprogram mature mouse Müller glia (MG) into RGCs. The reprogrammed RGCs extend long axons that make appropriate intra-retinal and extra-retinal projections through the entire visual pathway to innervate both image-forming and non-image-forming brain targets. They exhibit typical neuronal electrophysiological properties and improve visual responses in RGC loss mouse models. Together, our data provide evidence that mammalian MG can be reprogrammed by defined TFs to achieve in vivo regeneration of functional RGCs as well as a promising new therapeutic approach to restore vision to patients with glaucoma and other optic neuropathies.

Due to continuous urbanization and an increasing need to improve living quality, citizens’ pursuit of landscape quality in residential communities is constantly improving in developing countries, e.g., China. This is especially true in the period when citizens were locked down in their home cities or communities in the context of the COVID-19 pandemic. Studying whether the current landscape in residential communities still meets citizens’ needs is of significance as it is crucial for city planners, landscape architects, and city managers. In this study, we used the analytic hierarchy process method to evaluate the landscape quality of five residential communities, using the case city of Yangling, China. In total, 516 valid questionnaires were collected in May 2022. The results showed that good organization of residential roads and pedestrian systems, the rationality of rest facilities, and the hierarchical richness of plants were the most important aspects for residents. Based on these, optimization design strategies were summarized. We hope to provide a reference for future landscape optimization of existing residential communities, especially in developing countries.

Due to their status as non-professionals, the reputations of Volunteered Geographic Information (VGI) contributors have a very important impact on data quality. In the process of contributor reputation evaluation in OpenStreetMap (OSM), it is very difficult to calculate the semantic similarity between object versions contributed by volunteers. Aimed at this issue, this paper proposes a model of contributor’s reputation based on semantic similarity of ontology concepts. Firstly, contributors are classified into three categories based on an improved WPCA and classification method. Then, an initial reputation is set for every OSM user in each class according to these categories and related research. Secondly, the related concept ontology is constructed for OSM entities; then, the semantic similarity of the object version is calculated according to the similarity of concept attributes and the semantic distance of concept. The contributor’s evaluation reputation is computed by synthesizing the semantic similarity, geometric similarity, and topological similarity of object versions. Thirdly, the contributor’s evaluation reputation and the initial reputation is aggregated to obtain the contributor’s reputation; finally, the OSM data of Rutland, England, is used as an example to verify the validity of our model. The experimental results show that the proposed model can obtain a more comprehensive contributor’s evaluation by fusing with the semantic similarity of ontology concept. The evaluation bias caused only by the semantic change between versions can be eliminated. Moreover, the obtained user’s reputation is positively correlated with the data quality. The contributor’s reputation evaluation method proposed in this paper is an effective method for evaluating the contributor’s reputation in OSM-like systems.

Retinal degenerative diseases are frequently caused by the loss of retinal neural cells such as photoreceptors. Cell replacement is regarded as one of the most promising therapies. Multiple types of stem and somatic cells have been tested for photoreceptor conversion. However, current induction efficiencies are still low and the molecular mechanisms underlying reprogramming remain to be clarified. In this work, by combining treatment with small molecules, we directly reprogrammed human fetal retinal pigment epithelial (RPE) cells into chemically induced photoreceptor-like cells (CiPCs) in vitro. Bulk and single-cell RNA sequencing, as well as methylation sequencing, were performed to understand the transcriptional and epigenetic changes during CiPCs conversion. A multi-omics analysis showed that the direct reprogramming process partly resembled events of early retina development. We also found that the efficiency of CiPCs conversion from RPE is much better than that from human dermal fibroblasts (HDF). The small molecules effectively induced RPE cells into CiPCs via suppression of the epithelial-to-mesenchymal transition (EMT). Among the signaling pathways involved in CiPCs conversion, glutamate receptor activation is prominent. In summary, RPE cells can be efficiently reprogrammed into photoreceptor-like cells through defined pharmacological modulations, providing a useful cell source for photoreceptor generation in cell replacement therapy for retinal degenerative diseases.

Purpose: We performed single-cell RNA sequencing (scRNA-seq), an unbiased and high-throughput single cell technology, to determine phenotype and function of peripheral immune cells in patients with diabetic macular edema (DME).Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from DME patients and healthy controls (HC). The single-cell samples were loaded on the Chromium platform (10x Genomics) for sequencing. R package Seurat v3 was used for data normalizing, clustering, dimensionality reduction, differential expression analysis, and visualization.Results: We constructed a single-cell RNA atlas comprising 57,650 PBMCs (24,919 HC, 32,731 DME). We divided all immune cells into five major immune cell lineages, including monocytes (MC), T cells (TC), NK cells (NK), B cells (BC), and dendritic cells (DC). Our differential expression gene (DEG) analysis showed that MC was enriched of genes participating in the cytokine pathway and inflammation activation. We further subdivided MC into five subsets: resting CD14++ MC, proinflammatory CD14++ MC, intermediate MC, resting CD16++ MC and pro-inflammatory CD16++ MC. Remarkably, we revealed that the proinflammatory CD14++ monocytes predominated in promoting inflammation, mainly by increasingly production of inflammatory cytokines (TNF, IL1B, and NFKBIA) and chemokines (CCL3, CCL3L1, CCL4L2, CXCL2, and CXCL8). Gene Ontology (GO) and pathway analysis of the DEGs demonstrated that the proinflammatory CD14++ monocytes, especially in DME patients, upregulated inflammatory pathways including tumor necrosis factor-mediated signaling pathway, I-kappaB kinase/NF-kappaB signaling, and toll-like receptor signaling pathway.Conclusion: In this study, we construct the first immune landscape of DME patients with T2D and confirmed innate immune dysregulation in peripheral blood based on an unbiased scRNA-seq approach. And these results demonstrate potential target cell population for anti-inflammation treatments.

Methods for stem cell-derived, three-dimensional retinal organoids induction have been established and shown great potential for retinal development modeling and drug screening. Herein, we reported an exogenous-factors-free and robust method to generate retinal organoids based on “self-formed ectodermal autonomous multi-zone” (SEAM) system, a two-dimensional induction scheme that can synchronously generate multiple ocular cell lineages. Characterized by distinct morphological changes, the differentiation of the obtained retinal organoids could be staged into the early and late differentiation phases. During the early differentiation stage, retinal ganglion cells, cone photoreceptor cells (PRs), amacrine cells, and horizontal cells developed; whereas rod PRs, bipolar cells, and Müller glial cells were generated in the late differentiation phase, resembling early-phase and late-phase retinogenesis in vivo. Additionally, we modified the maintenance strategy for the retinal organoids and successfully promoted their long-term survival. Using 3D immunofluorescence image reconstruction and transmission electron microscopy, the substantial mature PRs with outer segment, inner segment and ribbon synapse were demonstrated. Besides, the retinal pigment epithelium (RPE) was induced with distinct boundary and the formation of ciliary margin was observed by co-suspending retina organoids with the zone containing RPE. The obtained RPE could be expanded and displayed similar marker expression, ultrastructural feature and functional phagocytosis to native RPE. Thus, this research described a simple and robust system which enabled generation of retina organoids with substantial mature PRs, RPE and the ciliary margin without the need of exogenous factors, providing a new platform for research of retinogenesis and retinal translational application.

Road intersections are essential to road networks. How to precisely recognize road intersections based on GPS data is still challenging in intelligent transportation systems. Road intersection recognition involves detecting intersections and recognizing its scope. There are few works on intersections’ scope recognition. The existing methods always focus on road intersection detection. It includes two parts: one is selecting turning points from GPS data and extracting their geometric features, another is clustering them into center coordinates of road intersections. However, the accuracy of road intersection detection still has improvement room due to two drawbacks: (1) Besides geometric features, spatial features explored from GPS data and the interactions among all features are also important to represent intersections’ semantics more accurately, and (2) How to capture the points around intersections for clustering has great impact on the accuracy of intersection detection. To solve the preceding problems, we propose a novel approach for road intersection recognition via combining a classification model and clustering algorithm based on GPS data, which involves detecting the center coordinate and computing the radius of the intersection. Firstly, we distil geometric features and spatial features from historical GPS points. These features are inputted into the Extreme Deep Factorization Machine (xDeepFM) model which is applied for capturing the GPS points nearby road intersections. Secondly, the preceding points are clustered into center coordinates of road intersections by the Density-Based Spatial Clustering of Applications with Noise algorithm (DBSCAN). Thirdly, we present a new method of radius computing by integrating Delaunay triangulation with circle shape structure. Experiments are carried out on the GPS data of Chengdu, China. Compared with some state-of-the-art methods, our approach achieves higher accuracy on road intersection recognition based on GPS data. The precision, recall, and f-measure of our proposed center coordinates detection method are respectively 99.0%, 92.7%, and 95.8% when the matching area’s radius is 30 m. Moreover, the error of the proposed radius calculation method is less than 26.5%.

The integrity of lens epithelial cells (LECs) lays the foundation for lens function and transparency. By contrast, epithelial-mesenchymal transition (EMT) of LECs leads to lens fibrosis, such as anterior subcapsular cataracts (ASC) and fibrotic forms of posterior capsule opacification (PCO). However, the underlying mechanisms remain unclear. Here, we aimed to explore the role of long non-coding RNA (lncRNA) H19 in regulating TGF-β2-induced EMT during lens fibrosis, revealing a novel lncRNA-based regulatory mechanism. In this work, we identified that lncRNA H19 was highly expressed in LECs, but downregulated by exposure to TGF-β2. In both human lens epithelial explants and SRA01/04 cells, knockdown of H19 aggravated TGF-β2-induced EMT, while overexpressing H19 partially reversed EMT and restored lens epithelial phenotypes. Semi-in vivo whole lens culture and H19 knockout mice demonstrated the indispensable role of H19 in sustaining lens clarity through maintaining LEC features. Bioinformatic analyses further implied a potential H19-centered regulatory mechanism via Smad-dependent pathways, confirmed by in vitro experiments. In conclusion, we uncovered a novel role of H19 in inhibiting TGF-β2-induced EMT of the lens by suppressing Smad-dependent signaling, providing potential therapeutic targets for treating lens fibrosis.

Visual neuroadaptation is believed to play an important role in determining the final visual outcomes following intraocular lens (IOL) implantation. To investigate visual neuroadaptation in patients with age-related cataracts (ARCs) after phacoemulsification with multifocal and monofocal IOL implantation, we conducted a prospective, controlled clinical trial in Zhongshan Ophthalmology Center. This study included 22 patients with bilateral ARCs: 11 patients underwent phacoemulsification and multifocal IOL (Mu-IOL) implantation, and 11 patients underwent phacoemulsification and monofocal IOL (Mo-IOL) implantation. Visual disturbances (glare and halos), visual function (including visual acuity, retinal straylight, contrast sensitivity, and visual evoked potentials) and visual cortical function (fractional amplitude of low-frequency fluctuations, fALFF) in Bowman’s areas 17–19 as the region of interest were assessed before and after surgeries. The results showed that the fALFF values of the visual cortex in the Mu-IOL group decreased at 1 week postoperatively and recovered to baseline at 3 months and then improved at 6 months, compared with preoperative levels (at a whole-brain threshold of P < 0.05, AlphaSim-corrected, voxels > 228, repeated measures analysis of variance). Significantly increased fALFF values in the visual cortex were detected 1 week after surgery in the Mo-IOL group and decreased to baseline at 3 and 6 months. The fALFF of the lingual gyrus was negatively correlated with visual disturbances (P < 0.05). To conclude, early postoperative visual neuroadaptation was detected in the Mu-IOL group by resting-state fMRI analysis. The different changing trends of postoperative fALFF values in the two groups indicated distinct neuroadaptations patterns after Mu-IOL and Mo-IOL implantation.

Protein sumoylation is one of the most important post-translational modifications regulating many biological processes (Flotho A & Melchior F. 2013. Ann Rev. Biochem. 82:357–85). Our previous studies have shown that sumoylation plays a fundamental role in regulating lens differentiation (Yan et al., 2010. PNAS, 107(49):21034-9.; Gong et al., 2014. PNAS. 111(15):5574–9). Whether sumoylation is implicated in lens pathogenesis remains elusive. Here, we present evidence to show that the protein inhibitor of activated STAT-1 (PIAS1), a E3 ligase for sumoylation, is implicated in regulating stress-induced lens pathogenesis. During oxidative stress-induced cataractogenesis, expression of PIAS1 is significantly altered at both mRNA and protein levels. Upregulation and overexpression of exogenous PIAS1 significantly enhances stress-induced apoptosis. In contrast, silence of PIAS1 with CRISPR/Cas9 technology attenuates stress-induced apoptosis. Mechanistically, different from other cells, PIAS1 has little effect to activate JNK but upregulates Bax, a major proapoptotic regulator. Moreover, Bax upregulation is derived from the enhanced transcription activity of the upstream transcription factor, p53. As revealed previously in other cells by different laboratories, our data also demonstrate that PIAS1 promotes SUMO1 conjugation of p53 at K386 residue in lens epithelial cells and thus enhances p53 transcription activity to promote Bax upregulation. Silence of Bax expression largely abrogates PIAS1-mediated enhancement of stress-induced apoptosis. Thus, our results demonstrated that PIAS1 promotes oxidative stress-induced apoptosis through positive control of p53, which specifically upregulates expression of the downstream proapoptotic regulator Bax. As a result, PIAS1-promoted apoptosis induced by oxidative stress is implicated in lens pathogenesis.