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Abstract Background Cisplatin is integral to ovarian cancer treatment, yet resistance to this drug often results in adverse patient outcomes. The association of circular RNA (circRNA) with cisplatin resistance in ovarian cancer has been observed, but the mechanisms governing this relationship require further elucidation. Methods High-throughput sequencing was utilized to profile circRNA expression in cisplatin-resistant ovarian cancer cells. Gain-and-loss-of-function experiments assessed the impact on cisplatin sensitivity, both in vitro and in vivo. Fluorescence in situ hybridization was conducted to determine the cellular distribution of circRNAs, and RNA pulldown and immunoprecipitation experiments were performed to identify associated binding proteins. Results The study revealed that circ_ARHGEF28 is overexpressed in certain cisplatin-resistant ovarian cancer tissues and cell lines, and is associated with reduced progression-free survival in patients. It was observed that circ_ARHGEF28 contributes to cisplatin resistance in ovarian cancer models, both in vitro and in vivo. Importantly, circ_ARHGEF28 was found to interact directly with MST1/2, inhibiting the SARAH coiled-coil binding domains and consequently deactivating the Hippo pathway. Conclusion This investigation identifies circ_ARHGEF28 as a novel circRNA that contributes to cisplatin resistance in ovarian cancer by suppressing the Hippo pathway. Therapeutic strategies targeting circ_ARHGEF28 may offer a potential avenue to mitigate cisplatin resistance in ovarian cancer treatment.

Abstract Corneal neovascularization (CNV) is one of the common blinding factors worldwide, leading to reduced vision or even blindness. However, current treatments such as surgical intervention and anti-VEGF agent therapy still have some shortcomings or evoke some adverse effects. Recently, SU6668, an inhibitor targeting angiogenic tyrosine kinases, has demonstrated growth inhibition of neovascularization. But the hydrophobicity and low ocular bioavailability limit its application in cornea. Hereby, we proposed the preparation of SU6668 pure nanoparticles (NanoSU6668; size ~135 nm) using a super-stable pure-nanomedicine formulation technology (SPFT), which possessed uniform particle size and excellent aqueous dispersion at 1 mg/mL. Furthermore, mesenchymal stem cell membrane vesicle (MSCm) was coated on the surface of NanoSU6668, and then conjugated with TAT cell penetrating peptide, preparing multifunctional TAT-MSCm@NanoSU6668 (T-MNS). The T-MNS at a concentration of 200 µg/mL was treated for CNV via eye drops, and accumulated in blood vessels with a high targeting performance, resulting in elimination of blood vessels and recovery of cornea transparency after 4 days of treatment. Meanwhile, drug safety test confirmed that T-MNS did not cause any damage to cornea, retina and other eye tissues. In conclusion, the T-MNS eye drop had the potential to treat CNV effectively and safely in a low dosing frequency, which broke new ground for CNV theranostics.

To present a modified technique for the reconstruction of a large cyclodialysis cleft with capsular tension ring (CTR) and continuous and cerclage sutures without scleral flaps in 12 cases. The mean visual acuity was 0.75 ± 0.47 logarithm of the minimal angle of resolution (logMAR), and the average intraocular pressure (IOP) was 3.35 ± 0.41 mmHg before surgery. Ultrasound biomicroscopy (UBM) revealed a ciliary cleft of 4.3 ± 3.5 clock hours. We performed the modified technique for the reconstruction of a large cyclodialysis cleft. Postoperative visual acuity improved to 0.48 ± 0.26 logMAR, and the IOP improved to 15.88 ± 3.81 mmHg. Postoperative UBM showed that cyclodialysis disappeared in the whole circumference of 12 eyes. The postoperative complications included 42% (5 eyes) with a temporary elevation of IOP and 16% (2 eyes) with a posterior shift of the ciliary body. No other complications were detected during the follow-up. Based on the results, our modified technique might be useful for most cyclodialysis clefts.

Abstract Background To investigate the effects of vitamin C on central retinal thickness and choroidal thickness. Methods A total of 69 patients diagnosed with vitamin C deficiency and 1:1 age- and gender-matched 69 healthy individuals with normal serum vitamin C were included in this study. Demographic characteristics of the individuals were collected. All patients underwent a comprehensive ophthalmic examination. Subfoveal choroidal thickness and retinal thickness were measured using a swept-source optical coherence tomography (SS-OCT). Results The average retinal thickness was 269.07 ± 13.51 μm in the vitamin C deficiency group and 276.92 ± 13.51 μm in the control group. The average choroidal thickness was 195.62 ± 66.40 μm in the in the vitamin C deficiency group and 238.86 ± 55.08 μm in the control group. There was a significant decrease in both average choroidal thickness and retinal thickness in vitamin C deficiency group compared with normal individuals (p

Dry eye is a common ocular disease that results in discomfort and impaired vision, impacting an individual's quality of life. A great number of drugs administered in eye drops to treat dry eye are poorly soluble in water and are rapidly eliminated from the ocular surface, which limits their therapeutic effects. Therefore, it is imperative to design a novel drug delivery system that not only improves the water solubility of the drug but also prolongs its retention time on the ocular surface. Herein, we develop a copolymer from mono-functional POSS, PEG, and PPG (MPOSS-PEG-PPG, MPEP) that exhibits temperature-sensitive sol-gel transition behavior. This thermo-responsive hydrogel improves the water solubility of FK506 and simultaneously provides a mucoadhesive, long-acting ocular delivery system. In addition, the FK506-loaded POSS hydrogel possesses good biocompatibility and significantly improves adhesion to the ocular surface. In comparison with other FK506 formulations and the PEG-PPG-FK506 (F127-FK506) hydrogel, this novel MPOSS-PEG-PPG-FK506 (MPEP-FK506) hydrogel is a more effective treatment of dry eye in the murine dry eye model. Therefore, delivery of FK506 in this POSS hydrogel has the potential to prolong drug retention time on the ocular surface, which will improve its therapeutic efficacy in the management of dry eye.

ObjectiveThe aim of the study is to develop and validate a deep learning model to predict the platinum sensitivity of patients with epithelial ovarian cancer (EOC) based on contrast-enhanced magnetic resonance imaging (MRI).MethodsIn this retrospective study, 93 patients with EOC who received platinum-based chemotherapy (≥4 cycles) and debulking surgery at the Sun Yat-sen Memorial Hospital from January 2011 to January 2020 were enrolled and randomly assigned to the training and validation cohorts (2:1). Two different models were built based on either the primary tumor or whole volume of the abdomen as the volume of interest (VOI) within the same cohorts, and then a pre-trained convolutional neural network Med3D (Resnet 10 version) was transferred to automatically extract 1,024 features from two MRI sequences (CE-T1WI and T2WI) of each patient to predict platinum sensitivity. The performance of the two models was compared.ResultsA total of 93 women (mean age, 50.5 years ± 10.5 [standard deviation]) were evaluated (62 in the training cohort and 31 in the validation cohort). The AUCs of the whole abdomen model were 0.97 and 0.98 for the training and validation cohorts, respectively, which was better than the primary tumor model (AUCs of 0.88 and 0.81 in the training and validation cohorts, respectively). In k-fold cross-validation and stratified analysis, the whole abdomen model maintained a stable performance, and the decision function value generated by the model was a prognostic indicator that successfully discriminates high- and low-risk recurrence patients.ConclusionThe non-manually segmented whole-abdomen deep learning model based on MRI exhibited satisfactory predictive performance for platinum sensitivity and may assist gynecologists in making optimal treatment decisions.

Abstract Background Mycobacterium houstonense is rapidly growing mycobacteria (RGM) that belongs to M. fortuitum group. So far, there have been few associated reports of human diseases induced by M. houstonense worldwide. Case presentation We present a delayed-onset postoperative endophthalmitis caused by M. houstonense after glaucoma drainage implant (GDI) surgery. The ocular infection lasted for 2 months without appropriate treatment that developed into endophthalmitis and the patient underwent an emergency enucleation. Conclusion Implant erosion and a delay in diagnosis of ocular infection could lead to irreversible damage as observed in our case. Ophthalmologists should be alert for ocular RGM infection, and prompt laboratory diagnosis with initiation of effective multidrug therapy might prevent loss of vision.

Abstract Background Posterior scleritis is an uncommon vision-threatening disorder that is often recurrent and difficult to cure due to its complex etiology. In HIV patients, posterior scleritis may develop several months after significant rise in CD4+ T-lymphocyte, even after several years, which may be diagnosed as late-onset immune recovery scleritis. Case presentation Here we report a case of posterior scleritis in a HIV positive patient who presented with severe periocular pain and decreased vision in the left eye, with exudative retinal detachment and optic nerve involvement. Conclusions Early differential diagnosis of immune recovery posterior scleritis and intensive corticosteroids treatment, can prevent vision loss effectively in HIV patients.

Abstract Background Intravitreal methotrexate has been proven to be an effective treatment method for vitreoretinal lymphoma. However, keratopathy occurs as the major side effect during treatment in most cases. The purpose of this study is to describe the characteristics of primary central nervous system lymphoma (PCNSL) with intraocular involvement and to attempt to reduce the incidence of keratopathy caused by intravitreal methotrexate. Methods The medical records of 22 PCNSL patients with intraocular involvement (33 eyes) were reviewed. Patients were divided into two groups. Group A (22 eyes) received the induction-consolidation-maintenance regimen, which consisted of intravitreal methotrexate injection at a dosage of 400 μg/0.1 ml twice a week for the first four weeks, weekly for the following eight weeks, and then monthly for the last nine months. Patients with a poor systemic condition were assigned to Group B (8 eyes), who were started on the treatment protocol described above and switched directly to monthly injection (9 months) when ocular remission was achieved. Results Blurred vision (31%) and floaters (25%) were common presenting symptoms. Vitritis was the most common clinical sign and was present in 29 eyes (90%) on B-ultrasound examination. Diagnosis was made by 25G-pars plana vitrectomy, and most diagnoses were diffuse large B-cell lymphoma. Ocular remission was achieved after 8.2 (SD = 4.6) injections of methotrexate. The mean VA (visual acuity) was improved from LogMAR 0.65 to 0.3 (P = 0.002). Keratopathy was observed in 21 eyes (66%) after an average of 8.2 (SD = 2.3) injections. With a reduced injection frequency, the incidence of keratopathy was lowered from 86.4% (Group A) to 25.0% (Group B) without ocular recurrence during follow-up. Conclusions Intravitreal methotrexate is a safe, effective and flexible treatment for PCNSL patients with intraocular involvement. Keratopathy is the most common adverse effect and can be controlled by reducing the injection frequency.

Acquired resistance to chemotherapy can lead to multi-drug resistance and poor prognosis in cancer. Here, the authors show that Rac1 increases glycolysis and non-oxidative pentose phosphate pathway activity leading to neoadjuvant chemotherapy (NAC) resistance, thus its inhibition sensitizes resistant breast cancer PDXs to NAC.

In recent years, the application of impulsive semi-dynamic system in state-dependent feed-back control has attracted extensive attention, but most models only discuss their special cases without delving into their complex dynamics. Therefore, we establish the wild and sterile mosquito system with integrated mosquito control, and use the Poincaré map method to conduct a comprehensive analysis of the model dynamics. First, the main properties of Poincaré map such as monotonicity, continuous differentiability, extremum and fixed point are discussed. Second, we prove the existence and stability of boundary periodic solution and study the influence of its parameters on the system. Then the ex-istence and global stability of the order-1 periodic solution and the existence condition of the order-k (k > 1) periodic solution are analyzed. Finally, our conclusion is verified by numerical analysis. The results show that the population density of wild mosquitoes can be controlled below the threshold by integrated mosquito control.

Purpose. Researches have confirmed that the retinal and choroidal thickness in patients with autoimmune disease-associated uveitis displays significant changes. However, the relationships between rheumatoid factor (RF) and thickness of the retina and choroid in individuals without ocular manifestations remain unclear. The aim of this study is to assess the associations of RF with retinal and choroidal thickness. Methods. The individuals enrolled in the cross-sectional research received full ocular examinations. The participants were classified as the RF (+) group (RF≥15.0 IU/ml) and the RF (−) group (RF

Purpose. To evaluate the relationships between C-reactive protein (CRP) and retinal and choroidal thickness by swept-source optical coherence tomography (SS-OCT). Methods. The participants included in the prospective cross-sectional study underwent a comprehensive ophthalmic examination. Based on the CRP values, the subjects were divided into the CRP (+) group (CRP≥8.2 mg/L) and the CRP (−) group (CRP

Purpose. To assess whether bone mineral density, indicated by the lumbar X-ray scan, is related to changes in choroid thickness in normal subjects. Methods. This study included 355 patients with decreased bone mineral density and 355 age- and sex-matched healthy subjects. Lumbar BMD was measured by dual-energy X-ray absorptiometry (DXA). Choroidal thickness was measured using swept-source optical coherence tomography (SS-OCT). Blood pressure (BP), cholesterol, triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were recorded on the same day. Results. There was a significant difference in average choroidal thickness between low BMD subjects and normal subjects p=0.003. The BP, cholesterol, triglyceride, HDL, and LDL showed no significant difference between the two groups. The correlations showed that average choroidal thicknesses were associated with BMD in the entire population (r = 0.125, p=0.001). Conclusion. The choroidal thickness is thinner in low BMD populations compared with normal individuals. There is a strong positive correlation of choroidal thickness with BMD, regardless of age, sex, and other demographic and clinical factors.

Abstract Resistance to radiotherapy is frequently encountered in clinic, leading to poor prognosis of cancer patients. Long noncoding RNAs (lncRNAs) play important roles in the development of radioresistance due to their functions in regulating the expression of target genes at both transcriptional and posttranscriptional levels. Exploring key lncRNAs and elucidating the mechanisms contributing to radioresistance are crucial for the development of effective strategies to reverse radioresistance, which however remains challenging. Here, actin filament‐associated protein 1 antisense RNA1 (lncAFAP1‐AS1) is identified as a key factor in inducing radioresistance of triple‐negative breast cancer (TNBC) via activating the Wnt/β‐catenin signaling pathway. Considering the generation of a high concentration of reduction agent glutathione (GSH) under radiation, a reduction‐responsive nanoparticle (NP) platform is engineered for effective lncAFAP1‐AS1 siRNA (siAFAP1‐AS1) delivery. Systemic delivery of siAFAP1‐AS1 with the reduction‐responsive NPs can synergistically reverse radioresistance by silencing lncAFAP1‐AS1 expression and scavenging intracellular GSH, leading to a dramatically enhanced radiotherapy effect in both xenograft and metastatic TNBC tumor models. The findings indicate that lncAFAP1‐AS1 can be used to predict the outcome of TNBC radiotherapy and combination of systemic siAFAP1‐AS1 delivery with radiotherapy can be applied for the treatment of recurrent TNBC patients.

Triple negative breast cancer (TNBC) accounts for less than a quarter of breast cancer but has the poorest survival outcome and is prone to relapse as well as metastasis due to its aggressiveness and lack of therapeutic target. Herein, we analyzed the TCGA datasets of lncRNA expressional profiles of breast cancer vs. normal tissue and TNBC vs. Non-TNBC subtypes and screened a long non-coding RNA (lncRNA) MNX1-AS1 overexpressing in TNBC. We found that MNX1-AS1 were upregulated in TNBC tumor tissues and correlated with poor survival outcome in TNBC patients. Silencing MNX1-AS1 reduced the aggressiveness of TNBC in vitro and in vivo. By using RNA pulldown assay followed by western blotting and RNA immunoprecipitation (RIP), we identified Stat3 was the MNX1-AS1 binding protein and MNX1-AS1 upregulated the phosphorylation of Stat3 by enhancing the interaction between p-JAK and Stat3. The present study suggested that targeting MNX1-AS1 may represent a promising therapeutic strategy to TNBC.

Abstract In this paper, a predator–prey model with ratio-dependent and impulsive state feedback control is constructed, where the pest growth rate is related to an Allee effect. Firstly, the existence condition of the homoclinic cycle is obtained by analyzing the control parameter q. The existence, uniqueness and asymptotic stability of the periodic orbit are discussed by using the geometric theory of the differential equations, the method of successor functions and analog of the Poincaré criterion. Secondly, we formulate a control optimization with a minimal total cost in pest management, and we obtain an optimal economic threshold. Finally, we verify the main results by numerical simulation.

Lung cancer (LC) is a common lethal malignancy with rapid progression and metastasis, and Ring1 and YY1 binding protein (RYBP) has been shown to suppress cell growth in human cancers. This study aimed to investigate the role of RYBP in LC progression and metastasis. In this study, a total of 149 LC patients were recruited, and the clinical stage of their tumors, metastasis status, survival time, presence of epidermal growth factor receptor (EGFR) mutation, and RYBP expression levels were measured. RYBP silencing and overexpression were experimentally performed in LC cell lines and in nude mice, and the expressions of genes in EGFR-related signaling pathways and epithelial-mesenchymal transition (EMT) were detected. The results showed that RYBP was downregulated in LC compared with adjacent normal tissues, and low RYBP expression was associated with a more severe clinical stage, high mortality, high metastasis risk, and poor survival. Cell proliferation and xenograft growth were inhibited by RYBP overexpression, whereas proliferation and xenograft growth were accelerated by RYBP silencing. EGFR and phosphorylated-EGFR levels were upregulated when RYBP was silenced, whereas EGFR, p-EGFR, p-AKT, and p-ERK were downregulated when RYBP was overexpressed. Low RYBP expression was related to a high metastasis risk, and metastasized tumors showed low RYBP levels. Cell migration and invasion were promoted by silencing RYBP but were inhibited by overexpressed RYBP. In addition, the EMT marker vimentin showed diminished expression, and E-cadherin was promoted by the overexpression of RYBP. In conclusion, our data suggest that RYBP suppresses cell proliferation and LC progression by impeding the EGFR-ERK and EGFR-AKT signaling pathways and thereby inhibiting cell migration and invasion and LC metastasis through the suppression of EMT.

An integrated pest management prey-predator model with ratio-dependent and impulsive feedback control is investigated in this paper. Firstly, we determine the Poincaré map which is defined on the phase set and discuss its main properties including monotonicity, continuity, and discontinuity. Secondly, the existence and stability of the boundary order-one periodic solution are proved by the method of Poincaré map. According to the Poincaré map and related differential equation theory, the conditions of the existence and global stability of the order-one periodic solution are obtained when ΦyAyA. Furthermore, we prove the existence of the order-kk≥2 periodic solution under certain conditions. Finally, we verify the main results by numerical simulation.

In this paper, an impulsive semidynamic system of the relationship between plankton and herbivore is established, and the Poincaré map method is used to extend the new properties of the model. We define the Poincaré map of the impulsive point series in phase concentration and analyze the characteristics. A comprehensive and detailed analysis of the periodic solution is performed. In addition, the numerical simulations illustrate the correctness of our arguments. The results show that plankton and herbivore can survive stably under effective control.

Purpose. To assess whether to continue aspirin therapy while having uncomplicated phacoemulsification cataract surgery with different incisions. Methods. Consecutive patients having cataract surgery under topical anesthesia with different incisions between May 2016 and August 2017 were followed. 236 eyes of 166 patients on routine aspirin therapy were randomized into 2 groups: continuation group, 112 eyes; discontinuation group, 124 eyes. 121 eyes of 94 patients on no routine anticoagulant therapy were used as the control group. Patients were examined 1 day preoperatively and 1 day and 7 days postoperatively. Intraoperative and postoperative complications were recorded. Results. Statistically, there was no significant difference about postoperative BCVA among three groups. A higher incidence of subconjunctival hemorrhage was shown in the continuation group than in the discontinuation group and the control group (17.0% versus 8.1%, p=0.038; 17.0% versus 7.4%, p=0.025, resp.). Although corneal edema was greater in clear corneal incision cases than that of scleral tunnel incision cases (22.5% versus 12.0%, p=0.009), subconjunctival hemorrhage was greater in scleral tunnel incision cases (14.9% versus 6.6%, p=0.011). Subgroup analyses revealed that patients of scleral tunnel incision who continued taking aspirin had a higher incidence of subconjunctival hemorrhage compared with those who discontinued (25.5% versus 10.9%, p=0.038), but no same conclusion in clear corneal incision cases (8.8% versus 5.0%, p=0.483). Conclusions. The outcomes indicated that phacoemulsification cataract surgery under topical anesthesia could be safely performed without ceasing systemic aspirin therapy. Clear corneal incision could be a better choice in patients treated with aspirin.

Hyperspectral data is not linearly separable, and it has a high characteristic dimension. This paper proposes a new algorithm that combines a deep belief network based on the Boltzmann machine with a self-organizing neural network. The primary features of the hyperspectral image are extracted with a deep belief network. The weights of the network are fine-tuned using the labeled sample. Feature vectors extracted by the deep belief network are classified by a self-organizing neural network. The method reduces the spectral dimension of the data while preserving the large amount of original information in the data. The method overcomes the long training time required when using self-organizing neural networks for clustering, as well as the training difficulties of Deep Belief Networks (DBN) when the labeled sample size is small, thereby improving the accuracy and robustness of the semi-supervised classification. Simulation results show that the structure of the network can achieve higher classification accuracy when the labeled sample is deficient.

Food is a critical environmental factor that influences animal survival, especially for small passerines due to their high mass-specific metabolic rates. Basal metabolic rate (BMR) reflects the energy expended by endothermic animals for basic physiological processes and constitutes a major part of their daily energy budget. Some birds have been shown to employ compensatory mechanisms during food shortages, temporarily reducing these self-maintenance expenditures without using hypothermia. However, the mechanisms of BMR adjustment remain unexplored. In the present study, we assessed the phenotypic variation in basal thermogenesis of Eurasian Tree Sparrows (Passer montanus) by comparing a control group to groups fasted for 6, 12, 18, and 24 h. We focused on the correlation between a reduction in energy metabolism and the alterations of cellular metabolic activities, mitochondrial substrate supply, and changes in serum thyroid hormones during fasting. Our data indicated that fasting groups had significantly lower body mass, BMR, body temperature, and body fat content. Furthermore, fasting groups had significantly lower glycogen levels, mitochondrial state 4 respiration and cytochrome c oxidase (CCO) activity in the liver, and CCO activity in pectoral muscle. The levels of avian uncoupling protein (av-UCP) mRNA were significantly reduced, while the levels of myostatin protein in pectoral muscle were significantly increased in the fasting groups. Furthermore, the groups subjected to fasting exhibited significantly lower levels of serum glucose, triglyceride, thyroxine (T4), and triiodothyronine (T3). Positive correlations were observed between the following pairs of variables: log BMR and log body mass, log body mass and log body fat, log BMR and log state 4 respiration in the liver, log BMR and log CCO activity in the liver and muscle, log BMR and log av-UCP mRNA expression, whereas a negative correlation was observed between log BMR and log myostatin level. In addition, a positive correlation was also detected between log T3 and each of the following: log BMR, state 4 respiration, and log CCO activity in the liver. Our results suggested that decreased metabolic thermogenesis via down-regulation in cellular aerobic capacity of organs and serum thyroid hormones may be an important survival strategy for fasting Tree Sparrows to reduce energy expenditure.

The fitting efficiency of lines or arcs fitting methods for various structural designs cannot meet the design requirements, and the fitting accuracy also needs to be improved. Therefore, this paper proposes a novel algorithm that uses a smaller number of elliptical arc segments to accurately fit the curve, while point-to-point continuity and a tangent relationship between all connected line segments of the curve can be maintained (G1 continuity). This algorithm uses elliptical arcs for curve fitting, and the advantage of using this conventional quadratic curve is that it does not require a higher-order equation to achieve that all connected line segments are tangent to each other, and its feature data is easily obtainable. In this paper, the novel elliptic arc fitting algorithm is used for the sine function curve, butterfly curve, parabola function curve, spiral line function curve and NURBS curve. The results show that this proposed method could be used to fit the curves with a smaller number of elliptical arc segments while satisfying the accuracy requirements. This algorithm with a simple solution method requires a significant reduction in the number of fitting segments while achieving the same fitting accuracy as other algorithms. It provides new ideas for the field of geometric modeling, tool path generation for numerical control (NC) machining and robot path planning.