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To address the issue of automated apple harvesting in orchards, we propose a YOLOv5-RACF algorithm for identifying apples and calculating apple diameters. This algorithm employs the robot operating dystem (ROS) to control the robot's locomotion system, Lidar mapping, and navigation, as well as the robotic arm's posture and grasping operations, achieving automated apple harvesting and placement. The tests were conducted in an actual orchard environment. The algorithm model achieved an average apple detection accuracy (mAP@0.5) of 98.748% and a (mAP@0.5:0.95) of 90.02%. The time to calculate the diameter of one apple was 0.13 s, with a measurement accuracy within an error range of 1-3 mm. The robot takes an average of 9 s to pick an apple and return to the initial pose. These results demonstrate the system's efficiency and reliability in real agricultural environments.

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The COVID-19 pandemic caused by SARS-CoV-2 resulted in a global public health crisis. In addition to vaccines, the development of effective therapy is highly desirable. Targeting a protein that plays a critical role in virus replication may allow pan-spectrum antiviral drugs to be developed. Among SARS-CoV-2 proteins, helicase (i.e., non-structural protein 13) is considered as a promising antiviral drug target due to its highly conserved sequence, unique structure and function. Herein, we demonstrate SARS-CoV-2 helicase as a target of bismuth-based antivirals in virus-infected mammalian cells by a metal-tagged antibody approach. To search for more potent bismuth-based antivirals, we further screened a panel of bismuth compounds towards inhibition of ATPase and DNA unwinding activity of nsp13 and identified a highly potent bismuth compound Bi(5-aminotropolonate)3, namely Bi(Tro-NH2)3 with an IC50 of 30 nM for ATPase. We show that bismuth-based compounds inhibited nsp13 unwinding activity via disrupting the binding of ATP and the DNA substrate to viral helicase. Binding of Bi(iii) to nsp13 also abolished the interaction between nsp12 and nsp13 as evidenced by immunofluorescence and co-immunoprecipitation assays. Finally, we validate our in vitro data in SARS-CoV-2 infected mammalian cells. Notably, Bi(6-TG)3 exhibited an EC50 of 1.18 ± 0.09 µM with a selective index of 847 in VeroE6-TMPRSS2 infected cells. This study highlights the important role of helicase for the development of more effective antiviral drugs to combat SARS-CoV-2 infection.

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Uveal melanoma (UVM), an uncommon yet potentially life-threatening ocular cancer, arises from melanocytes in the uveal tract of the eye. The exploration of novel oncotargets for UVM is of paramount importance. In this study, we show that PCK1 (phosphoenolpyruvate carboxykinase 1) expression is upregulated in various UVM tissues as well as in primary UVM cells and immortalized lines. Furthermore, bioinformatics studies reveal that PCK1 overexpression in UVM correlates with advanced disease stages and poor patient survival. Genetic silencing (utilizing viral shRNA) or knockout (via CRISPR/Cas9) of PCK1 significantly curtailed cell viability, proliferation, cell cycle progression, and motility, while provoking apoptosis in primary and immortalized UVM cells. Conversely, ectopic overexpression of PCK1, achieved through a viral construct, bolstered UVM cell proliferation and migration. Gαi3 expression and Akt phosphorylation were reduced following PCK1 silencing or knockout, but increased after PCK1 overexpression in UVM cells. Restoring Akt phosphorylation through a constitutively active mutant Akt1 (S473D) ameliorated the growth inhibition, migration suppression, and apoptosis induced by PCK1 silencing in UVM cells. Additionally, ectopic expression of Gαi3 restored Akt activation and counteracted the anti-UVM cell effects by PCK1 silencing. In vivo, the growth of subcutaneous xenografts of primary human UVM cells was significantly inhibited following intratumoral injection of adeno-associated virus (aav) expressing PCK1 shRNA. PCK1 depletion, Gαi3 downregulation, Akt inhibition, proliferation arrest, and apoptosis were detected in PCK1-silenced UVM xenografts. Collectively, our findings demonstrate that PCK1 promotes UVM cell growth possibly by modulating the Gαi3-Akt signaling pathway.

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2'-Deoxynucleosides and analogues play a vital role in drug development, but their preparation remains a significant challenge. Previous studies have focused on ß-2'-deoxynucleosides with the natural ß-configuration. In fact, their isomeric α-2'-deoxynucleosides also exhibit diverse bioactivities and even better metabolic stability. Herein, we report that both α- and ß-2'-deoxynucleosides can be prepared with high yields and stereoselectivity using a remote directing diphenylphosphinoyl (DPP) group. It is particularly efficient to prepare α-2'-deoxynucleosides with an easily accessible 3,5-di-ODPP donor. Instead of acting as a H-bond acceptor on a 2-(diphenylphosphinoyl)acetyl (DPPA) group in our previous studies for syn-facial O-glycosylation, the phosphine oxide moiety here acts as a remote participating group to enable highly antifacial N-glycosylation. This proposed remote participation mechanism is supported by our first characterization of an important 1,5-briged P-heterobicyclic intermediate via variable-temperature NMR spectroscopy. Interestingly, antiproliferative assays led to a α-2'-deoxynucleoside with IC50 values in the low micromole range against central nervous system tumor cell lines SH-SY5Y and LN229, whereas its ß-anomer exhibited no inhibition at 100 µM. Furthermore, the DPP group significantly enhanced the antitumor activities by 10 times.

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Butyrylcholinesterase (BChE) is a promising biomarker and effective therapeutic target for Alzheimer's disease (AD). Herein, we designed a BChE-activated near-infrared (NIR) probe, DTNP, which could be activated by BChE and inhibit its enzymatic activity. DTNP is composed of a cyclopropane moiety as the recognition unit, a NIR fluorophore hemicyanine as the NIR reporter, and a BChE inhibitor as the therapeutic unit. DTNP specifically binds BChE with high sensitivity and exhibits strong "turn-on" NIR fluorescence as well as nerve cell protection. In vivo imaging shows DTNP has favorable blood-brain barrier permeability and long-term tracking ability with preliminary competence in AD diagnosis. DTNP can significantly inhibit BChE activity, promote the release of ACh, and rescue learning deficits and cognitive impairment. Therefore, DTNP, the first reported and partially validated theranostic probe for the detection of BChE in AD, may provide a foundation and inspiration for imaging and therapy in AD.

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Macrophages/microglia are immune system defense and homeostatic cells that develop from bone marrow progenitor cells. According to the different phenotypes and immune responses of macrophages (Th1 and Th2), the two primary categories of polarized macrophages/microglia are those conventionally activated (M1) and alternatively activated (M2). Macrophage/microglial polarization is a key regulating factor in the development of inflammatory disorders, cancers, metabolic disturbances, and neural degeneration. Macrophage/microglial polarization is involved in inflammation, oxidative stress, pathological angiogenesis, and tissue healing processes in ocular diseases, particularly in diabetic retinopathy (DR). The functional phenotypes of macrophages/microglia affect disease progression and prognosis, and thus regulate the polarization or functional phenotype of microglia at different DR stages, which may offer new concepts for individualized therapy of DR. This review summarizes the involvement of macrophage/microglia polarization in physiological situations and in the pathological process of DR, and discusses the promising role of polarization in personalized treatment of DR.

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PURPOSE: The NCCN guidelines do not recommend surgery for T3-4N0M0/T1-4N1-2M0 small cell lung cancer (SCLC) due to a lack of evidence. METHODS: Data of patients with T3-4N0M0/T1-4N1-2M0 SCLC were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to determine the impact of surgery on this population. The Kaplan-Meier method, univariable and multivariable Cox proportional hazard regression, and propensity score matching (PSM) were used to compare the overall survival (OS) between the surgery and non-surgery groups. In addition, we explored whether sublobectomy, lobectomy, and pneumonectomy could provide survival benefits. RESULTS: In total, 8572 patients with SCLC treated without surgery and 342 patients treated with surgery were included in this study. The PSM-adjusted hazard ratio (HR, 95% CI) for surgery vs. no surgery, sublobectomy vs. no surgery, lobectomy vs. no surgery, pneumonectomy vs. no surgery, and lobectomy plus adjuvant chemoradiotherapy vs. chemoradiotherapy were 0.71 (0.61-0.82) (P < 0.001), 0.91 (0.70-1.19) (P = 0.488), 0.60 (0.50-0.73) (P < 0.001), 0.57 (0.28-1.16) (P = 0.124), and 0.73 (0.56-0.96) (P = 0.023), respectively. The subgroup analysis demonstrated consistent results. CONCLUSIONS: Lobectomy improved OS in patients with T3-4N0M0/T1-4N1-2M0 SCLC, while pneumonectomy also demonstrated a tendency to improve OS without statistical significance; however, sublobectomy showed no survival benefit.

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BACKGROUND: Pathological neovascularization plays a pivotal role in the onset and progression of tumors and neovascular eye diseases. Despite notable advancements in the development of anti-angiogenic medications that target vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), the occurrence of adverse reactions and drug resistance has somewhat impeded the widespread application of these drugs. Therefore, additional investigations are warranted to explore alternative therapeutic targets. In recent years, owing to the swift advancement of high-throughput sequencing technology, pan-cancer analysis and single-cell sequencing analysis have emerged as pivotal methodologies and focal areas within the domain of omics research, which is of great significance for us to find potential targets related to the regulation of pathological neovascularization. METHODS: Pan-cancer analysis and scRNA-seq data analysis were employed to forecast the association between Actin filament-associated protein 1 like 1 (AFAP1L1) and the development of tumors and endothelial cells. Tumor xenograft model and ocular pathological neovascularization model were constructed as well as Isolectin B4 (IsoB4) staining and immunofluorescence staining were used to assess the effects of AFAP1L1 on the progression of neoplasms and neovascular eye diseases in vivo. Transwell assay, wound scratch assay, tube forming assay, three-dimensional germination assay, and rhodamine-phalloidin staining were used to evaluate the impact of AFAP1L1 on human umbilical vein endothelial cells (HUVECs) function in vitro; Dual luciferase reporting, qRT-PCR and western blot were used to investigate the upstream and downstream mechanisms of pathological neovascularization mediated by AFAP1L1. RESULTS: Our investigation revealed that AFAP1L1 plays a crucial role in promoting the development of various tumors and demonstrates a strong correlation with endothelial cells. Targeted suppression of AFAP1L1 specifically in endothelial cells in vivo proves effective in inhibiting tumor formation and ocular pathological neovascularization. Mechanistically, AFAP1L1 functions as a hypoxia-related regulatory protein that can be activated by HIF-1α. In vitro experiments demonstrated that reducing AFAP1L1 levels can reverse hypoxia-induced excessive angiogenic capacity in HUVECs. The principal mechanism of angiogenesis inhibition entails the regulation of tip cell behavior through the YAP-DLL4-NOTCH axis. CONCLUSION: In conclusion, AFAP1L1, a newly identified hypoxia-related regulatory protein, can be activated by HIF-1α. Inhibiting AFAP1L1 results in the inhibition of angiogenesis by suppressing the germination of endothelial tip cells through the YAP-DLL4-NOTCH axis. This presents a promising therapeutic target to halt the progression of tumors and neovascular eye disease.

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Assessment and prognostic value of serum uric acid (SUA) and neuron-specific enolase (NSE) on the efficacy of intravenous thrombolytic therapy in cerebral infarction. A retrospective analysis was performed on clinical data of 159 patients with acute cerebral infarction who received rt-PA intravenous thrombolytic therapy from 2015 to 2020 and patients with an mRS>2 points were assigned to the poor prognosis group and with mRS≤2 to the good prognosis group. The receiver operating characteristic curve (ROC) was used to examine the prognostic value of SUA and NSE in intravenous thrombolytic therapy for acute cerebral infarction, and logistic regression analysis was utilized to elucidate the predictive features. SUA levels were adversely correlated with prognosis, whereas NSE was positively correlated with prognosis (r=0.465 and -0.501, P=0.000 and 0.000). The ROC curve showed that the predictive accuracy of SUA was 77.4% and of NSE was 71%. SUA≤337.5 mmol/l and NSE≥24.50 ng/ml are considered viable criteria to predict the curative effect and prognostic value of intravenous thrombolytic therapy for acute cerebral infarction. SUA and NSE demonstrate great potential to accurately predict the therapeutic effect and prognosis of intravenous thrombolytic therapy for acute cerebral infarction.

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Background: Most of previous studies on predictive models for patients with small cell lung cancer (SCLC) were single institutional studies or showed relatively low Harrell concordance index (C-index) values. To build an optimal nomogram, we collected clinicopathological characteristics of SCLC patients from Surveillance, Epidemiology, and End Results (SEER) database. Methods: 24,055 samples with SCLC from 2010 to 2016 in the SEER database were analyzed. The samples were grouped into derivation cohort (n=20,075) and external validation cohort (n=3,980) based on America's different geographic regions. Cox regression analyses were used to construct nomograms predicting cancer-specific survival (CSS) and overall survival (OS) using derivation cohort. The nomograms were internally validated by bootstrapping technique and externally validated by calibration plots. C-index was computed to compare the accuracy and discrimination power of our nomograms with the 8th of version AJCC TNM staging system and nomograms built in previous studies. Decision curve analysis (DCA) was applied to explore whether the nomograms had better clinical efficiency than the 8th version of AJCC TNM staging system. Results: Age, sex, race, marital status, primary site, differentiation, T classification, N classification, M classification, surgical type, lymph node ratio, radiotherapy, and chemotherapy were chosen as predictors of CSS and OS for SCLC by stepwise multivariable regression and were put into the nomograms. Internal and external validations confirmed the nomograms were accurate in prediction. C-indexes of the nomograms were relatively satisfactory in derivation cohort (CSS: 0.761, OS: 0.761) and external validation cohort (CSS: 0.764, OS: 0.764). The accuracy of the nomograms was superior to that of nomograms built in previous studies. DCA showed the nomograms conferred better clinical efficiency than 8th version of TNM staging system. Conclusions: We developed practical nomograms for CSS (https://guowei2020.shinyapps.io/DynNom-CSS-SCLC/) and OS (https://drboidedwater.shinyapps.io/DynNom-OS-SCLC/) prediction of SCLC patients which may facilitate clinicians in individualized therapeutics.

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The rapid development of computer science over the past few decades has led to unprecedented progress in the field of artificial intelligence (AI). Its wide application in ophthalmology, especially image processing and data analysis, is particularly extensive and its performance excellent. In recent years, AI has been increasingly applied in optometry with remarkable results. This review is a summary of the application progress of different AI models and algorithms used in optometry (for problems such as myopia, strabismus, amblyopia, keratoconus, and intraocular lens) and includes a discussion of the limitations and challenges associated with its application in this field.

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Wet age-related macular degeneration (wAMD) is the leading cause of blindness among the elderly in industrialized nations. Anti-vascular epidermal growth factor (VEGF) therapy via intravitreal injection is the most effective clinical treatment for wAMD due to high concentrations of VEGF that promote choroidal neovascularization. While PIWI proteins participate in various biological processes, their function in AMD remains unclear. In this study, we discovered that PIWIL4 expression is elevated in a laser-induced choroidal neovascularization (CNV) model and that it regulates angiogenesis in vitro and in vivo. Differentially expressed piwi-interacting RNAs (piRNAs) were identified in a CNV model and were shown to potentially regulate angiogenesis via bioinformatics analysis. PIWIL4 knockdown inhibits VEGF secretion and VEGFR2 phosphorylation. Overall, PIWIL4 may serve as a novel target to block pathological choroidal neovascularization, and the study of the PIWI-piRNAs pathway in wAMD highlights its broad function in somatic cells.

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Background: This research aimed to investigate the predictive performance of log odds of positive lymph nodes (LODDS) for the long-term prognosis of patients with node-positive lung neuroendocrine tumors (LNETs). Methods: We collected 506 eligible patients with resected N1/N2 classification LNETs from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The study cohort was split into derivation cohort (n=300) and external validation cohort (n=206) based on different geographic regions. Nomograms were constructed based on the derivation cohort and validated using the external validation cohort to predict the 1-, 3-, and 5-year cancer-specific survival (CSS) and overall survival (OS) of patients with LNETs. The accuracy and clinical practicability of nomograms were tested by Harrell's concordance index (C-index), integrated discrimination improvement (IDI), net reclassification improvement (NRI), calibration plots, and decision curve analyses. Results: The Cox proportional-hazards model showed the high LODDS group (-0.79≤LODDS) had significantly higher mortality compared to those in the low LODDS group (LODDS<-0.79) for both CSS and OS. In addition, age at diagnosis, sex, histotype, type of surgery, radiotherapy, and chemotherapy were also chosen as predictors in Cox regression analyses using stepwise Akaike information criterion method and included in the nomograms. The values of C-index, NRI, and IDI proved that the established nomograms were better than the conventional eighth edition of the TNM staging system. The calibration plots for predictions of the 1-, 3-, and 5-year CSS/OS were in excellent agreement. Decision curve analyses showed that the nomograms had value in terms of clinical application. Conclusions: We created visualized nomograms for CSS and OS of LNET patients, facilitating clinicians to bring individually tailored risk assessment and therapy.

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Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer. Fatty acid metabolism takes part in malignancy progression. However, the roles fatty acid metabolism plays in LUAD are still unclear. Methods: The transcriptomic and clinical data of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were extracted. ssGSEA, WGCNA, univariable Cox regression, and LASSO Cox regression analyses were performed to identify the fatty acid metabolism-related genes which influenced the overall survival (OS) and build a fatty acid-related risk score (FARS) model. A nomogram was established based on the FARS and other clinicopathological features, and ROC and calibration plots were used to validate the prediction accuracy. The tumor microenvironment (TME) of patients with high and low FARS was compared. Results: A total of 38 genes were identified to be independently related to the survival outcome and put into a FARS model. High FARS patients exhibited significantly worse OS. The nomogram included the FARS and pathological stage, and the AUC of the nomogram predicting 1-, 2-, 3-, 4-, and 5-year OS was 0.789, 0.807, 0.798, 0.809, and 0.753, respectively. Calibration plots also indicated good accuracy. Moreover, the samples of the high FARS had higher expression of PDL1. Conclusion: We constructed a FARS model which could accurately predict the survival outcome of the LUAD patients. The genes of the FARS are related to the tumor microenvironment and patients with high FARS can potentially benefit more from anti-PD1/PDL1 immunotherapy. In addition, the mechanisms of the genes in the FARS affecting prognosis are worthy of further research to develop new gene-targeted drugs.

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BACKGROUND: Log odds of positive lymph nodes (LODDS) is a novel lymph node (LN) descriptor that demonstrates promising prognostic value in many tumors. However, there is limited information regarding LODDS in patients with non-small cell lung cancer (NSCLC), especially those receiving neoadjuvant therapy followed by lung surgery. METHODS: A total of 2059 patients with NSCLC who received neoadjuvant therapy and surgery were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We used the X-tile software to calculate the LODDS cutoff value. Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curve analysis were performed to compare predictive values of the American Joint Committee on Cancer (AJCC) N staging descriptor and LODDS. Univariate and multivariate Cox regression and inverse probability of treatment weighting (IPTW) analyses were conducted to construct a model for predicting prognosis. RESULTS: According to the survival analysis, LODDS had better differentiating ability than the N staging descriptor (log-rank test, P < 0.0001 vs. P = 0.031). The ROC curve demonstrated that the AUC of LODDS was significantly higher than that of the N staging descriptor in the 1-, 3-, and 5-year survival analyses (all P < 0.05). Univariate and multivariate Cox regression analyses showed that LODDS was an independent risk factor for patients with NSCLC receiving neoadjuvant therapy followed by surgery both before and after IPTW (all P < 0.001). A clinicopathological model with LODDS, age, sex, T stage, and radiotherapy could better predict prognosis. CONCLUSIONS: Compared with the AJCC N staging descriptor, LODDS exhibited better predictive ability for patients with NSCLC receiving neoadjuvant therapy followed by surgery. A multivariate clinicopathological model with LODDS demonstrated a sound performance in predicting prognosis.

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Background: N2 stage disease constitutes approximately 20%-30% of all non-small cell lung cancer (NSCLC). Concurrently, surgery remains the first-choice treatment for patients with N2 NSCLC if feasible. However, the role of pneumonectomy in N2 NSCLC has rarely been investigated and remains controversial. Methods: We enrolled 26,798 patients with T1-4N2M0 NSCLC (stage IIIA/IIIB) from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. We compared the overall survival (OS) and cancer-specific survival (CSS) between patients who received pneumonectomy and those who did not receive surgery. The Kaplan-Meier method, Cox regression analyses, and propensity score matching (PSM) were applied to demonstrate the effect of pneumonectomy. Results: Patients receiving pneumonectomy had a significantly better OS and CSS than those without pneumonectomy both before [adjusted-HR (95% CI): 0.461 (0.425-0.501) for OS, 0.444 (0.406-0.485) for CSS] and after PSM [adjusted-HR (95% CI): 0.499 (0.445-0.560) for OS, 0.457 (0.405-0.517) for CSS] with all p-values <0.001. Subgroup analysis demonstrated concordant results stratified by demographic or clinicopathological variables. In sensitivity analysis, no significant difference was observed between patients receiving single pneumonectomy and chemoradiotherapy without surgery in OS and CSS both before [unadjusted-HR (95% CI): 1.016 (0.878-1.176) for OS, 0.934 (0.794-1.099) for CSS, p = 0.832] and after PSM [unadjusted-HR (95% CI): 0.988 (0.799-1.222) for OS, 0.938 (0.744-1.182) for CSS] with all p-values >0.4. Conclusion: For patients with T1-4N2M0 NSCLC (stage IIIA/IIIB), pneumonectomy is an independent protective factor of OS and should be considered when applicable.

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The emergence of SARS-CoV-2 variants of concern compromises vaccine efficacy and emphasizes the need for further development of anti-SARS-CoV-2 therapeutics, in particular orally administered take-home therapies. Cocktail therapy has shown great promise in the treatment of viral infection. Herein, we reported the potent preclinical anti-SARS-CoV-2 efficacy of a cocktail therapy consisting of clinically used drugs, e.g. colloidal bismuth subcitrate (CBS) or bismuth subsalicylate (BSS), and N-acetyl-l-cysteine (NAC). Oral administration of the cocktail reduced viral loads in the lung and ameliorated virus-induced pneumonia in a hamster infection model. The mechanistic studies showed that NAC prevented the hydrolysis of bismuth drugs at gastric pH via the formation of the stable component [Bi(NAC)3], and optimized the pharmacokinetics profile of CBS in vivo. Combination of bismuth drugs with NAC suppressed the replication of a panel of medically important coronaviruses including Middle East respiratory syndrome-related coronavirus (MERS-CoV), Human coronavirus 229E (HCoV-229E) and SARS-CoV-2 Alpha variant (B.1.1.7) with broad-spectrum inhibitory activities towards key viral cysteine enzymes/proteases including papain-like protease (PLpro), main protease (Mpro), helicase (Hel) and angiotensin-converting enzyme 2 (ACE2). Importantly, our study offered a potential at-home treatment for combating SARS-CoV-2 and future coronavirus infections.

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BACKGROUND: Diabetic nephropathy (DN), a diabetic complication, is the leading cause of end-stage renal disease. KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), a long non-coding RNA, has been unmasked to participate in the pathogenesis of DN. However, the specific mechanism by which KCNQ1OT1 regulates podocyte injury remains unclear. METHODS: Relative expression of KCNQ1OT1 was measured with quantitative real-time polymerase chain reaction (qRT-PCR). The levels of inflammatory cytokines were analyzed by enzyme linked immunosorbent assay (ELISA). The viability, proliferation, and apoptosis of high glucose (HG)-treated podocyte were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays. Protein levels were analyzed by western blotting. The regulatory mechanism of KCNQ1OT1 was surveyed by bioinformatics analysis, dual-luciferase reporter, and RNA immunoprecipitation (RIP) assays. RESULTS: We observed an apparent upregulation in KCNQ1OT1 expression in serums of DN patients and HG-treated podocytes. Furthermore, KCNQ1OT1 downregulation alleviated HG-induced inflammation, proliferation repression, and apoptosis in podocytes. Notably, KCNQ1OT1 was identified as a miR-23b-3p sponge, and miR-23b-3p directly targeted Semaphorin-3A (Sema3A). Moreover, miR-23b-3p silencing reversed KCNQ1OT1 knockdown-mediated effects on inflammation, proliferation, and apoptosis of HG-induced podocytes. Also, Sema3A overexpression reversed the effects of miR-23b-3p mimic on inflammation, proliferation, and apoptosis of HG-induced podocytes. Importantly, KCNQ1OT1 regulated Sema3A expression by sponging miR-23b-3p. CONCLUSIONS: HG-induced KCNQ1OT1 promoted inflammation, proliferation repression, and apoptosis of podocytes via increasing Sema3A expression through sponging miR-23b-3p. This study provided evidence to support the involvement of KCNQ1OT1 in the pathogenesis of DN.

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Background: Posner-Schlossman syndrome (PSS) is a relatively rare cause of chronic secondary open-angle glaucoma (OAG), but the exact cause is unknown. This study aimed to determine potential risk factors for OAG secondary to PSS and to provide a basis for early intervention in the development of PSS. Methods: This was a retrospective case-control study. Nine cases diagnosed with PSS and seven cases diagnosed with OAG secondary to PSS were selected and their aqueous humor assays at the first occurrence of PSS were collected. Clinical characteristics including age, sex, disease duration, eye laterality, baseline visual acuity, maximum IOP, corneal endothelial cell density, visual field, retinal nerve fiber layer thickness, cup-to-disk ratio, keratic precipitates, anterior chamber inflammation, and aqueous humor cytokine assay results were compared between the two groups. Results: The cytomegalovirus (CMV) positivity was 55.60% in patients with PSS and 100% in patients with OAG secondary to PSS. Corneal endothelial cell density was lower in patients with CMV-positive PSS (p = 0.0116). Concentrations of basic fibroblast growth factor (bFGF), interleukin (IL)-6, and vascular cell adhesion molecule (VCAM) in patients with PSS and IL-8, IL-6, and VCAM in patients with OAG secondary to PSS were higher than standard reference values; and IL-8 concentration was significantly higher in patients with OAG secondary to PSS (p = 0.0229). There were significant positive correlations between IL-8 and IL-6, IL-6 and VCAM (p = 0.0304, p = 0.0172) and a significant negative correlation between bFGF and vascular endothelial growth factor (VEGF) (p = 0.0497). Simultaneous increase of IL-8 and IL-6 concentration levels could be used as a cytokine indicator to predict secondary OAG in patients with PSS (p = 0.0095). Conclusion: Simultaneous increase of IL-8 and IL-6 concentrations may be an important cause of accelerated secondary OAG in patients with PSS, with IL-8 playing a more critical role. IL-8 and IL-6 may be more reliable cytokine markers for predicting secondary OAG in PSS, However, the high possibility of secondary OAG in patients with CMV-positive PSS should not be ignored. Regulation of IL-8 and IL-6 levels may be a new strategy of preventing OAG secondary to PSS.