Exploring the protective effect and mechanism of icariside II on the bladder in a rat model of radiation cystitis based on transcriptome sequencing.

PURPOSE: Radiation cystitis (RC) is a complex and common complication after radiotherapy for pelvic cancer. Icariside II (ICAII) is a flavonoid compound extracted from Epimedium, a traditional Chinese medicine, with various pharmacological activities. The aim of the present study was to investigate the cysto-protective effects of ICAII in RC rats and its possible mechanisms. MATERIALS AND METHODS: A rat model of induced radiation cystitis using pelvic X-ray irradiation was used, and bladder function was assessed by bladder volume and bladder leakage point pressure (LPP) after ICAII treatment. HE and Masson stains were used to assess the histopathological changes in the bladder. IL-6, TNF-α, IL-10, IL-4 and IL-1ß were measured by ELISA to assess the level of inflammation. The gene-level changes in ICAII-treated RC were observed by transcriptome sequencing, and then the potential targets of action and biological mechanisms were explored by PPI, GO and KEGG enrichment analysis of the differentially expressed genes. Finally, the predicted targets of action were experimentally validated using immunohistochemistry, RT-qPCR, molecular docking and CETSA. RESULTS: ICAII significantly increased bladder volume and the LPP, ameliorated pathological damage to bladder tissues, decreased the levels of IL-6, TNF-α, and IL-1ß, and increased the levels of IL-10 and IL-4 in radiation-injured rats. A total of 90 differentially expressed genes were obtained by transcriptome sequencing, and PPI analysis identified H3F3C, ISG15, SPP1, and LCN2 as possible potential targets of action. GO and KEGG analyses revealed that these differentially expressed genes were mainly enriched in the pathways metabolism of xenobiotics by cytochrome P450, arachidonic acid metabolism, Staphylococcus aureus infection and chemical carcinogenesis - reactive oxygen species. Experimental validation showed that ICAII could significantly increase the expression of H3F3C and ISG15 and inhibit the expression of SPP1 and LCN2. ICAII binds well to H3F3C, ISG15, SPP1 and LCN2, with the best binding ability to H3F3C. Furthermore, ICAII inhibited the protein degradation of H3F3C in bladder epithelial cells. CONCLUSIONS: ICAII may alleviate the bladder inflammatory response and inhibit the fibrosis process of bladder tissues through the regulation of H3F3C, ISG15, SPP1, and LCN2 targets and has a protective effect on the bladder of radioinjured rats. In particular, H3F3C may be one of the most promising therapeutic targets.

Construction of the Glycolysis Metabolic Pathway Inside an Artificial Cell for the Synthesis of Amino Acid and Its Reversible Deformation.

The bottom-up construction of artificial cells is beneficial for understanding cell working mechanisms. The glycolysis metabolism mimicry inside artificial cells is challenging. Herein, the glycolytic pathway (Entner-Doudoroff pathway in archaea) is reconstituted inside artificial cells. The glycolytic pathway comprising glucose dehydrogenase (GDH), gluconate dehydratase (GAD), and 2-keto-3-deoxygluconate aldolase (KDGA) converts glucose molecules to pyruvate molecules. Inside artificial cells, pyruvate molecules are further converted into alanine with the help of alanine dehydrogenase (AlaDH) to build a metabolic pathway for synthesizing amino acid. On the other hand, the pyruvate molecules from glycolysis stimulate the living mitochondria to produce ATP inside artificial cells, which further trigger actin monomers to polymerize to form actin filaments. With the addition of methylcellulose inside the artificial cell, the actin filaments form adjacent to the inner lipid bilayer, deforming the artificial cell from a spherical shape to a spindle shape. The spindle-shaped artificial cell reverses to a spherical shape by depolymerizing the actin filament upon laser irradiation. The glycolytic pathway and its further extension to produce amino acids (or ATP) inside artificial cells pave the path to build functional artificial cells with more complicated metabolic pathways.

Knockdown of AMIGO2 suppresses proliferation and migration through regulating PPAR-γ in bladder cancer.

PURPOSE: This study aims to reveal the relationship between AMIGO2 and proliferation, migration and tumorigenicity of bladder cancer, and explore the potential molecular mechanisms. METHODS: The expression level of AMIGO2 is measured by qRT-PCR and immunohistochemistry (IHC). Stable AMIGO2 knockdown cell lines T24 and 5637 were established by lentivirus transfection. Cell Counting Kit (CCK-8 assay) was produced to determine cell proliferation, flow cytometry analysis was utilized to detect cell cycle, and wound healing assay was proceeded to test migration ability of bladder cancer cells. Xenograft mouse model was established for investigating the effect of AMIGO2 on tumor formation in vivo. The RNA Sequencing technology was applied to explore the underlying mechanisms. The expression level of PPAR-γ was measured by Western Blot. RESULTS: AMIGO2 was upregulated in bladder cancer cells and tissues. Inhibited expression of AMIGO2 suppresses cell proliferation and migration. Low AMIGO2 expression inhibited tumorigenicity of 5637 in nude mice. According to RNA-Seq and bioinformatics analysis, 917 DEGs were identified. The DEGs were mainly enriched in cell-cell adhesion, peroxisome proliferators-activated receptors (PPARs) signaling pathway and some other pathways. PPAR-γ is highly expressed in bladder cancer cell lines T24 and 5637, but when AMIGO2 is knocked down in T24 and 5637, the expression level of PPAR-γ is also decreased, and overexpression of PPAR-γ could reverse the suppression effect of cell proliferation and migration caused by the inhibition of AMIGO2. CONCLUSION: AMIGO2 is overexpressed in bladder cancer cells and tissues. Knockdown of AMIGO2 suppresses bladder cancer cell proliferation and migration. These processes might be regulated by PPAR-γ signaling pathway.

Ultrasmall Polyphenol-NAD+ Nanoparticle-Mediated Renal Delivery for Mitochondrial Repair and Anti-Inflammatory Treatment of AKI-to-CKD Progression.

As a central metabolic molecule, nicotinamide adenine dinucleotide (NAD+) can potentially treat acute kidney injury (AKI) and chronic kidney disease (CKD); however, its bioavailability is poor due to short half-life, instability, the deficiency of targeting, and difficulties in transmembrane transport. Here a physiologically adaptive gallic acid-NAD+ nanoparticle is designed, which has ultrasmall size and pH-responsiveness, passes through the glomerular filtration membrane to reach injured renal tubules, and efficiently delivers NAD+ into the kidneys. With an effective accumulation in the kidneys, it restores renal function, immune microenvironment homeostasis, and mitochondrial homeostasis of AKI mice via the NAD+-Sirtuin-1 axis, and exerts strong antifibrotic effects on the AKI-to-CKD transition by inhibiting TGF-ß signaling. It also exhibits excellent stability, biodegradable, and biocompatible properties, ensuring its long-term safety, practicality, and clinical translational feasibility. The present study shows a potential modality of mitochondrial repair and immunomodulation through nanoagents for the efficient and safe treatment of AKI and CKD.

Structural insights into the unique pH-responsive characteristics of the anti-TIGIT therapeutic antibody Ociperlimab.

TIGIT is mainly expressed on T cells and is an inhibitory checkpoint receptor that binds to its ligand PVR in the tumor microenvironment. Anti-TIGIT monoclonal antibodies (mAbs) such as Ociperlimab and Tiragolumab block the TIGIT-PVR interaction and are in clinical development. However, the molecular blockade mechanism of these mAbs remains elusive. Here, we report the crystal structures of TIGIT in complex with Ociperlimab_Fab and Tiragolumab_Fab revealing that both mAbs bind TIGIT with a large steric clash with PVR. Furthermore, several critical epitopic residues are identified. Interestingly, the binding affinity of Ociperlimab toward TIGIT increases approximately 17-fold when lowering the pH from 7.4 to 6.0. Our structure shows a strong electrostatic interaction between ASP103HCDR3 and HIS76TIGIT explaining the pH-responsive mechanism of Ociperlimab. In contrast, Tiragolumab does not show an acidic pH-dependent binding enhancement. Our results provide valuable information that could help to improve the efficacy of therapeutic antibodies for cancer treatment.

High-Fidelity, Low-Hysteresis Bionic Flexible Strain Sensors for Soft Machines.

Stretchable flexible strain sensors based on conductive elastomers are rapidly emerging as a highly promising candidate for popular wearable flexible electronic and soft-mechanical sensing devices. However, due to the intrinsic limitations of low fidelity and high hysteresis, existing flexible strain sensors are unable to exploit their full application potential. Herein, a design strategy for a successive three-dimensional crack conductive network is proposed to cope with the uncoordinated variation of the output resistance signal arising from the conductive elastomer. The electrical characteristics of the sensor are dominated by the successive crack conductive network through a greater resistance variation and a concise sensing mechanism. As a result, the developed elastomer bionic strain sensors exhibit excellent sensing performance in terms of a smaller overshoot response, a lower hysteresis (∼2.9%), and an ultralow detection limit (0.00179%). What's more, the proposed strategy is universal and applicable to many conductive elastomers with different conductive fillers (including 0-D, 1-D, and 2-D conductive fillers). This approach improves the sensing signal accuracy and reliability of conductive elastomer strain sensors and holds promising potential for various applications in the fields of e-skin and soft robotic systems.

Ligustilide-loaded liposome ameliorates mitochondrial impairments and improves cognitive function via the PKA/AKAP1 signaling pathway in a mouse model of Alzheimer's disease.

BACKGROUND: Oxidative stress is an early event in the development of Alzheimer's disease (AD) and maybe a pivotal point of interaction governing AD pathogenesis; oxidative stress contributes to metabolism imbalance, protein misfolding, neuroinflammation and apoptosis. Excess reactive oxygen species (ROS) are a major contributor to oxidative stress. As vital sources of ROS, mitochondria are also the primary targets of ROS attack. Seeking effective avenues to reduce oxidative stress has attracted increasing attention for AD intervention. METHODS: We developed liposome-packaged Ligustilide (LIG) and investigated its effects on mitochondrial function and AD-like pathology in the APPswe/PS1dE9 (APP/PS1) mouse model of AD, and analyzed possible mechanisms. RESULTS: We observed that LIG-loaded liposome (LIG-LPs) treatment reduced oxidative stress and ß-amyloid (Aß) deposition and mitigated cognitive impairment in APP/PS1 mice. LIG management alleviated the destruction of the inner structure in the hippocampal mitochondria and ameliorated the imbalance between mitochondrial fission and fusion in the APP/PS1 mouse brain. We showed that the decline in cAMP-dependent protein kinase A (PKA) and A-kinase anchor protein 1 for PKA (AKAP1) was associated with oxidative stress and AD-like pathology. We confirmed that LIG-mediated antioxidant properties and neuroprotection were involved in upregulating the PKA/AKAP1 signaling in APPswe cells in vitro. CONCLUSION: Liposome packaging for LIG is relatively biosafe and can overcome the instability of LIG. LIG alleviates mitochondrial dysfunctions and cognitive impairment via the PKA/AKAP1 signaling pathway. Our results provide experimental evidence that LIG-LPs may be a promising agent for AD therapy.

Regulation of species metabolism in synthetic community systems by environmental pH oscillations.

Constructing a synthetic community system helps scientist understand the complex interactions among species in a community and its environment. Herein, a two-species community is constructed with species A (artificial cells encapsulating pH-responsive molecules and sucrose) and species B (Saccharomyces cerevisiae), which causes the environment to exhibit pH oscillation behaviour due to the generation and dissipation of CO2. In addition, a three-species community is constructed with species A' (artificial cells containing sucrose and G6P), species B, and species C (artificial cells containing NAD+ and G6PDH). The solution pH oscillation regulates the periodical release of G6P from species A'; G6P then enters species C to promote the metabolic reaction that converts NAD+ to NADH. The location of species A' and B determines the metabolism behaviour in species C in the spatially coded three-species communities with CA'B, CBA', and A'CB patterns. The proposed synthetic community system provides a foundation to construct a more complicated microecosystem.

GMRE-iUnet: Isomorphic Unet fusion model for PET and CT lung tumor images.

Lung tumor PET and CT image fusion is a key technology in clinical diagnosis. However, the existing fusion methods are difficult to obtain fused images with high contrast, prominent morphological features, and accurate spatial localization. In this paper, an isomorphic Unet fusion model (GMRE-iUnet) for lung tumor PET and CT images is proposed to address the above problems. The main idea of this network is as following: Firstly, this paper constructs an isomorphic Unet fusion network, which contains two independent multiscale dual encoders Unet, it can capture the features of the lesion region, spatial localization, and enrich the morphological information. Secondly, a Hybrid CNN-Transformer feature extraction module (HCTrans) is constructed to effectively integrate local lesion features and global contextual information. In addition, the residual axial attention feature compensation module (RAAFC) is embedded into the Unet to capture fine-grained information as compensation features, which makes the model focus on local connections in neighboring pixels. Thirdly, a hybrid attentional feature fusion module (HAFF) is designed for multiscale feature information fusion, it aggregates edge information and detail representations using local entropy and Gaussian filtering. Finally, the experiment results on the multimodal lung tumor medical image dataset show that the model in this paper can achieve excellent fusion performance compared with other eight fusion models. In CT mediastinal window images and PET images comparison experiment, AG, EI, QAB/F, SF, SD, and IE indexes are improved by 16.19%, 26%, 3.81%, 1.65%, 3.91% and 8.01%, respectively. GMRE-iUnet can highlight the information and morphological features of the lesion areas and provide practical help for the aided diagnosis of lung tumors.

ZnS/SnS2 Heterostructures Encapsulated in N-Doped Carbon Nanofibers for High-Performance Alkali Metal-Ion Batteries.

Heterogeneous composite ZnS/SnS2 is designed to meet various requirements for alkali metal-ion batteries. The composite is prepared using an electrostatic spinning method and encapsulated in N-doped carbon fibers after high-temperature vulcanization. The special structure of the composite provides a dependable interconnection and fast conductive network for alkali metal ions. The conductive carbon network shortens the diffusion path and greatly improves the migration efficiency of the alkali metal ions in the electrode. As expected, when the current density is 0.1 A g-1, the ZnS/SnS2@NCNFs maintain a high discharge capacity of more than 1437.5, 1321.2, and 861.6 mA h g-1 for lithium-ion, sodium-ion, and potassium-ion batteries, respectively. What is more, a full cell using a prelithiated composite anode and a LiFePO4 cathode is tested and shows excellent electrochemical performance. This work provides new perspectives for the development of novel anodes that can efficiently store alkali metal ions, as well as for the fine-structure design of materials.

Rice stripe virus p2 protein interacts with ATG5 and is targeted for degradation by autophagy.

Autophagy can be induced by viral infection and plays antiviral roles in plants, but the underlying mechanism is not well understood. In our previous reports, we have demonstrated that the plant ATG5 plays an essential role in activating autophagy in rice stripe virus (RSV)-infected plants. We also showed that eIF4A, a negative factor of autophagy, interacts with and inhibits ATG5. We here found that RSV p2 protein interacts with ATG5 and can be targeted by autophagy for degradation. Expression of p2 protein induced autophagy and p2 protein was shown to interfere with the interaction between ATG5 and eIF4A, while eIF4A had no effect on the interaction between ATG5 and p2. These results indicate an additional information on the induction of autophagy in RSV-infected plants.

Xanthophyll esterases in association with fibrillins control the stable storage of carotenoids in yellow flowers of rapeseed (Brassica juncea).

Biosynthesis, stabilization, and storage of carotenoids are vital processes in plants that collectively contribute to the vibrant colors observed in flowers and fruits. Despite its importance, the carotenoid storage pathway remains poorly understood and lacks thorough characterization. We identified two homologous genes, BjA02.PC1 and BjB04.PC2, belonging to the esterase/lipase/thioesterase (ELT) family of acyltransferases. We showed that BjPCs in association with fibrillin gene BjFBN1b control the stable storage of carotenoids in yellow flowers of Brassica juncea. Through genetic, high-resolution mass spectrometry and transmission electron microscopy analyses, we demonstrated that both BjA02.PC1 and BjB04.PC2 can promote the accumulation of esterified xanthophylls, facilitating the formation of carotenoid-enriched plastoglobules (PGs) and ultimately producing yellow pigments in flowers. The elimination of BjPCs led to the redirection of metabolic flux from xanthophyll ester biosynthesis to lipid biosynthesis, resulting in white flowers for B. juncea. Moreover, we genetically verified the function of two fibrillin genes, BjA01.FBN1b and BjB05.FBN1b, in mediating PG formation and demonstrated that xanthophyll esters must be deposited in PGs for stable storage. These findings identified a previously unknown carotenoid storage pathway that is regulated by BjPCs and BjFBN1b, while offering unique opportunities for improving the stability, deposition, and bioavailability of carotenoids.

Application of machine learning algorithm in prediction of lymph node metastasis in patients with intermediate and high-risk prostate cancer.

PURPOSE: This study aims to establish the best prediction model of lymph node metastasis (LNM) in patients with intermediate- and high-risk prostate cancer (PCa) through machine learning (ML), and provide the guideline of accurate clinical diagnosis and precise treatment for clinicals. METHODS: A total of 24,470 patients with intermediate- and high-risk PCa were included in this study. Multivariate logistic regression model was used to screen the independent risk factors of LNM. At the same time, six algorithms, namely random forest (RF), naive Bayesian classifier (NBC), xgboost (XGB), gradient boosting machine (GBM), logistic regression (LR) and decision tree (DT) are used to establish risk prediction models. Based on the best prediction performance of ML algorithm, a prediction model is established, and the performance of the model is evaluated from three aspects: area under curve (AUC), sensitivity and specificity. RESULTS: In multivariate logistic regression analysis, T stage, PSA, Gleason score and bone metastasis were independent predictors of LNM in patients with intermediate- and high-risk PCa. By comprehensively comparing the prediction model performance of training set and test set, GBM model has the best prediction performance (F1 score = 0.838, AUROC = 0.804). Finally, we developed a preliminary calculator model that can quickly and accurately calculate the regional LNM in patients with intermediate- and high-risk PCa. CONCLUSION: T stage, PSA, Gleason and bone metastasis were independent risk factors for predicting LNM in patients with intermediate- and high-risk PCa. The prediction model established in this study performs well; however, the GBM model is the best one.

Deep learning methods for medical image fusion: A review.

The image fusion methods based on deep learning has become a research hotspot in the field of computer vision in recent years. This paper reviews these methods from five aspects: Firstly, the principle and advantages of image fusion methods based on deep learning are expounded; Secondly, the image fusion methods are summarized in two aspects: End-to-End and Non-End-to-End, according to the different tasks of deep learning in the feature processing stage, the non-end-to-end image fusion methods are divided into two categories: deep learning for decision mapping and deep learning for feature extraction. According to the different types of the networks, the end-to-end image fusion methods are divided into three categories: image fusion methods based on Convolutional Neural Network, Generative Adversarial Network, and Encoder-Decoder Network; Thirdly, the application of the image fusion methods based on deep learning in medical image field is summarized from two aspects: method and data set; Fourthly, evaluation metrics commonly used in the field of medical image fusion are sorted out from 14 aspects; Fifthly, the main challenges faced by the medical image fusion are discussed from two aspects: data sets and fusion methods. And the future development direction is prospected. This paper systematically summarizes the image fusion methods based on the deep learning, which has a positive guiding significance for the in-depth study of multi modal medical images.

Enhancing the stability of lutein emulsions with a water-soluble antioxidant and a oil-soluble antioxidant.

Lutein is critical for protecting the eye against light damage. The low solubility and high sensitivity of lutein to environmental stresses prevent its further application. The hypothesis is that the combination of one water-soluble antioxidant and one oil-soluble antioxidant will be beneficial to improve the stability of lutein emulsions. A low-energy method was performed to prepare lutein emulsions. The combination of a lipid-soluble antioxidant (propyl gallate or ethylenediaminetetraacetic acid) and a water-soluble antioxidant (tea polyphenol or ascobic acid) were investigated for improving the lutein retention rates. It was shown that the highest lutein retention rate was achieved by using propyl gallate and tea polyphenol, 92.57%, at Day 7. It was proven that the lutein retention rates of emulsions with propyl gallate and tea polyphenol were 89.8%, 73.5% and 55.2% at 4 °C, 25 °C and 37 °C, respectively, at Day 28. The current study is helpful to prepare for the further application of lutein emulsions for ocular delivery.

Peptide chain release factor DIG8 regulates plant growth by affecting ROS-mediated sugar transportation in Arabidopsis thaliana.

Chloroplasts have important roles in photosynthesis, stress sensing and retrograde signaling. However, the relationship between chloroplast peptide chain release factor and ROS-mediated plant growth is still unclear. In the present study, we obtained a loss-of-function mutant dig8 by EMS mutation. The dig8 mutant has few lateral roots and a pale green leaf phenotype. By map-based cloning, the DIG8 gene was located on AT3G62910, with a point mutation leading to amino acid substitution in functional release factor domain. Using yeast-two-hybrid and BiFC, we confirmed DIG8 protein was characterized locating in chloroplast by co-localization with plastid marker and interacting with ribosome-related proteins. Through observing by transmission electron microscopy, quantifying ROS content and measuring the transport efficiency of plasmodesmata in dig8 mutant, we found that abnormal thylakoid stack formation and chloroplast dysfunction in the dig8 mutant caused increased ROS activity leading to callose deposition and lower PD permeability. A local sugar supplement partially alleviated the growth retardation phenotype of the mutant. These findings shed light on chloroplast peptide chain release factor-affected plant growth by ROS stress.

Development and evaluation of an artificial intelligence system for children intussusception diagnosis using ultrasound images.

Accurate identification of intussusception in children is critical for timely non-surgical management. We propose an end-to-end artificial intelligence algorithm, the Children Intussusception Diagnosis Network (CIDNet) system, that utilizes ultrasound images to rapidly diagnose intussusception. 9999 ultrasound images of 4154 pediatric patients were divided into training, validation, test, and independent reader study datasets. The independent reader study cohort was used to compare the diagnostic performance of the CIDNet system to six radiologists. Performance was evaluated using, among others, balance accuracy (BACC) and area under the receiver operating characteristic curve (AUC). The CIDNet system performed the best in diagnosing intussusception with a BACC of 0.8464 and AUC of 0.9716 in the test dataset compared to other deep learning algorithms. The CIDNet system compared favorably with expert radiologists by outstanding identification performance and robustness (BACC:0.9297; AUC:0.9769). CIDNet is a stable and precise technological tool for identifying intussusception in ultrasound scans of children.

Role of mechanotransduction mediated by YAP/TAZ in the treatment of neurogenic erectile dysfunction with low-intensity pulsed ultrasound.

BACKGROUND: Erectile dysfunction (ED) and weakness of the penis are processes related to hemodynamic alteration. Low-intensity pulsed ultrasound (LIPUS), as a new mechanical modality for the treatment of ED, deserves to be explored in depth for the biomechanical mechanisms it exerts. OBJECTIVE: The aim of this study was to explore the role of YAP/TAZ-mediated mechanotransduction in mechanical therapy for the treatment of neurogenic erectile dysfunction (NED). MATERIALS AND METHODS: Forty-two male SD rats (12 w old) were randomly divided into sham-operated (n = 14), bilateral cavernous nerve injury (BCNI, n = 14), and LIPUS-treated (n = 14) groups. Intracavernosal pressure/mean arterial pressure (ICP/MAP) was measured 14 and 28 days after treatment. Penile tissue specimens were collected for pathological examination, and the changes in YAP, TAZ, connective tissue growth factor (CTGF), CYR61, LATS1, and p38 mitogen-activated protein kinase expression levels were assessed by Western blot, real-time quantitative polymerase chain reaction (RT-qPCR) and immunological staining. RESULTS: Compared with BCNI, LIPUS significantly improved ICP/MAP levels and enhanced histopathological changes. The penile expression levels of YAP, TAZ, CTGF, and CYR61 were significantly downregulated in the BCNI group (p < 0.01), and LIPUS upregulated the expression levels of these proteins (p < 0.05). The expression levels of p-LATS1 and LATS1 were not significantly different among the groups (p > 0.05). Interestingly, the expression level of p-p38/p38 significantly increased in BCNI rats (p < 0.05), which was reversed by LIPUS treatment (p < 0.05). However, the p38 inhibitor SB203580 did not change the expression of YAP/TAZ in rat primary smooth muscle cells or mouse MOVAS cells (p > 0.05). DISCUSSION AND CONCLUSION: LIPUS can effectively improve penile erectile function in NED rats. The underlying mechanism may be related to the regulation of YAP/TAZ-mediated mechanotransduction. However, the upstream regulatory signal may differ from the classical Hippo pathway.

Inhibition of Posterior Capsule Opacification by Adenovirus-Mediated Delivery of Short Hairpin RNAs Targeting TERT in a Rabbit Model.

PURPOSE: Posterior capsule opacification (PCO) is the most common postoperative complication after cataract surgery and cannot yet be eliminated. Here, we investigated the inhibitory effects of telomerase reverse transcriptase (TERT) gene silencing on PCO in a rabbit model. METHODS: After rabbit lens epithelial cells (LECs) were treated with adenovirus containing short hairpin RNAs (shRNA) targeting TERT (shTERT group), adenovirus containing scramble nonsense control shRNA (shNC group) or PBS (control group), quantitative real-time polymerase chain reaction and Western blotting were used to measure the expression levels of TERT, and a scratch assay was performed to assess the LEC migration. New Zealand white rabbits underwent sham cataract surgery followed by an injection of adenovirus carrying shTERT into their capsule bag. The intraocular pressure and anterior segment inflammation were evaluated on certain days, and EMT markers (α-SMA and E-cadherin) were evaluated by Western blotting and immunofluorescence. The telomerase activity of the capsule bag was detected by ELISA. At 28 d postoperatively, hematoxylin and eosin staining of the cornea and iris and electron microscopy of the posterior capsule were performed. RESULTS: Application of shTERT to LECs downregulated the expression levels of TERT mRNA and protein. The scratch assay results showed a decrease in the migration of LECs in the shTERT group. In vivo, shTERT decreased PCO formation after cataract surgery in rabbits and downregulated the expression of EMT markers, as determined by Western blotting and immunofluorescence. In addition, telomerase activity was suppressed in the capsule bag. Despite slight inflammation in the iris, histologic results revealed no toxic effects in the cornea and iris. CONCLUSION: TERT silencing effectively reduces the migration and proliferation of LECs and the formation of PCO. Our findings suggest that TERT silencing may be a potential preventive strategy for PCO.