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Introduction: Stem cell-based regenerative medicine has provided an excellent opportunity to investigate therapeutic strategies and innovative treatments for Alzheimer’s disease (AD). However, there is an absence of visual overviews to assess the published literature systematically. Methods: In this review, the bibliometric approach was used to estimate the searched data on stem cell research in AD from 2004 to 2022, and we also utilized CiteSpace and VOSviewer software to evaluate the contributions and co-occurrence relationships of different countries/regions, institutes, journals, and authors as well as to discover research hot spots and encouraging future trends in this field. Results: From 2004 to 2022, a total of 3,428 publications were retrieved. The number of publications and citations on stem cell research in AD has increased dramatically in the last nearly 20 years, especially since 2016. North America and Asia were the top 2 highest output regions. The leading country in terms of publications and access to collaborative networks was the USA. Centrality analysis revealed that the UCL (0.05) was at the core of the network. The Journal of Alzheimer’s Disease (n = 102, 2.98%) was the most productive academic journal. The analyses of keyword burst detection indicated that exosomes, risk factors, and drug delivery only had burst recently. Citations and co-citation achievements clarified that cluster #0 induced pluripotent stem cells, #2 mesenchymal stem cells, #3 microglia, and #6 adult hippocampal neurogenesis persisted to recent time. Conclusion: This bibliometric analysis provides a comprehensive guide for clinicians and scholars working in this field. These analysis and results hope to provide useful information and references for future understanding of the challenges behind translating underlying stem cell biology into novel clinical therapeutic potential in AD.

[EN] Rabbit coccidiosis is a very serious disease caused by protozoan parasites of the genus Eimeria, which increases the production rate of free radicals, especially reactive oxygen species. When the generation of free radicals exceeds the scavenging capacity of the body s antioxidant system, the oxidant-antioxidant balance is broken, resulting in oxidative stress. This study was designed to investigate the effect on the oxidant-antioxidant status of rabbits infected with E. intestinalis and E. magna. To this end, eighteen 30-d-old weaned rabbits were randomly allocated into three groups as follows: the E. intestinalis infection group with 3×103 sporulated oocysts of E. intestinalis, the E. magna infection group with 20×103 sporulated oocysts of E. magna, and the uninfected control group. We measured the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC) and the contents of malondialdehyde (MDA) in rabbits small intestinal tissues (duodenum, jejunum and ileum) of the three groupson day 8. The results showed that CAT activity and MDA levels significantly increased, while the activities of SOD, GSH-Px and T-AOC decreased after E. intestinalis and E. magna infection. Besides, the jejunum and ileum were particularly damaged in the rabbits. It is concluded that the pathological oxidative stress occurs during the E. intestinalis and E. magna infection process and the body s oxidant-antioxidant balance is disrupted., This experiment was supported by the National Natural Science Foundation Project of China (nos. 31960688 and 31360592) and the Natural Science Foundation Project of Jiangxi Province (no. 20181BAB204016).

The development of paraffin-selective adsorbents is desirable but extremely challenging because adsorbents usually prefer olefin over paraffin. Herein, a new pore-window-partition strategy is proposed for the rational design of highly efficient paraffin-preferred metal-organic framework (MOF) adsorbents. The power of this strategy is demonstrated by stepwise installations of linear bidentate N-donor linkers into a prototype MOF (SNNU-201) to produce a series of partitional MOF adsorbents (SNNU-202-204). With continuous pore-window partitions from SNNU-201 to SNNU-204, the isosteric heat of adsorption can be tuned from -34.4 to -19.4 kJ mol

Supplementary data is available online at https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awad105/7091433#supplementary-data . Accepted manuscripts are PDF versions of the author’s final manuscript, as accepted for publication by the journal but prior to copyediting or typesetting. They can be cited using the author(s), article title, journal title, year of online publication, and DOI. They will be replaced by the final typeset articles, which may therefore contain changes. The DOI will remain the same throughout. Copyright © The Author(s) 2023. The advent of clinical trials of disease-modifying agents for neurodegenerative disease highlights the need for evidence-based end point selection. Here we report the longitudinal PROSPECT-M-UK study of progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), multiple system atrophy (MSA) and related disorders, to compare candidate clinical trial end points. In this multicentre UK study, participants were assessed with serial questionnaires, motor examination, neuropsychiatric and MRI assessments at baseline, 6 and 12 months. Participants were classified by diagnosis at baseline and study end, into Richardson syndrome, PSP-subcortical (PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (PSP-frontal, PSP-speech and language and PSP-CBS subtypes), MSA-parkinsonism, MSA-cerebellar, CBS with and without evidence of Alzheimer’s disease pathology and indeterminate syndromes. We calculated annual rate of change, with linear mixed modelling and sample sizes for clinical trials of disease-modifying agents, according to group and assessment type. Two hundred forty-three people were recruited [117 PSP, 68 CBS, 42 MSA and 16 indeterminate; 138 (56.8%) male; age at recruitment 68.7 ± 8.61 years]. One hundred and fifty-nine completed the 6-month assessment (82 PSP, 27 CBS, 40 MSA and 10 indeterminate) and 153 completed the 12-month assessment (80 PSP, 29 CBS, 35 MSA and nine indeterminate). Questionnaire, motor examination, neuropsychiatric and neuroimaging measures declined in all groups, with differences in longitudinal change between groups. Neuroimaging metrics would enable lower sample sizes to achieve equivalent power for clinical trials than cognitive and functional measures, often achieving N < 100 required for 1-year two-arm trials (with 80% power to detect 50% slowing). However, optimal outcome measures were disease-specific. In conclusion, phenotypic variance within PSP, CBS and MSA is a major challenge to clinical trial design. Our findings provide an evidence base for selection of clinical trial end points, from potential functional, cognitive, clinical or neuroimaging measures of disease progression. The Progressive Supranuclear Palsy–Corticobasal Syndrome–Multiple System Atrophy (PROSPECT-M-UK) study is supported by grants for PROSPECT, cerebrospinal fluid biomarker measurements, and PROSPECT magnetic resonance imaging and Sara Koe Fellowship grants from the PSP Association UK, CBD Solutions, the MSA Trust, the Wellcome Trust (103838; 220258); the NIHR Cambridge Biomedical Research Centre and Cambridge Brain Bank (BRC 1215-20014; NIHR203312: The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care); Cambridge Centre for Parkinson-Plus; Medical Research Council (SUAG/092 116768); and the NIHR UCLH Biomedical Research Centre. Queen Square Brain Bank is supported by the Reta Lila Weston Institute for Neurological Studies and the MRC. The fluid biomarker measurements were supported in part by the UK Dementia Research Institute at UCL and a multiuser equipment grant from Wellcome Trust. The Cambridge Brain Bank is part of the Cambridge Human research Tissue Bank funded by the Biomedical Research Council. The Oxford Brain Bank is supported by the MRC, Brains for Dementia Research (Alzheimer’s Society and Alzheimer’s Research UK), and the NIHR Oxford Biomedical Research Centre. In addition, this study was supported by the Medical Research Council (MRC 548211) (Dr Jabbari); the Association of British Neurologists Clinical Research Training Fellowships (Dr Holland, Dr Goh and Dr Chelban); the MSA Trust (Dr Chelban, Dr Goh); Guarantors of Brain (Dr Chelban); CBD Solutions (Dr Revesz, and Dr Morris); the NIHR Oxford Health Clinical Research Facility (Dr Klein); the NIHR Queen Square Biomedical Research Centre based at UCLH (Dr Revesz and Dr Jaunmuktane) a Wallenberg Academy fellowship (Dr Zetterberg); the Monument Trust Discovery Award from Parkinson’s UK (Dr Hu). Dr Bocchetta is supported by a Fellowship award from the Alzheimer’s Society, UK (AS-JF-19a-004-517). Dr Bocchetta’s work was also supported by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK. Professor Rohrer is supported by the Miriam Marks Brain Research UK Senior Fellowship and has received funding from an MRC Clinician Scientist Fellowship (MR/M008525/1) and the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH). Professor Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C and #ADSF-21-831377-C), the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228), the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), European Union Joint Program for Neurodegenerative Disorders (JPND2021-00694), and the UK Dementia Research Institute at UCL. Professor Roncaroli’s work is supported by The Manchester Brain Bank, which is part of BDR, jointly funded by Alzheimer’s Society and Alzheimer’s Research UK. For the purpose of open access, the authors have applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission, under a Creative Commons Attribution 4.0 International License.

6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) is a potent regulator of glycolysis in tumor cells, and high PFKFB3 expression is significantly associated with the invasion and metastasis of several tumors. However, there are no comprehensive reports on whether PFKFB3 promotes tumor invasion and its mechanism in different cancer types. In addition, there are no systematic reports on the effect of PFKFB3 on the stemness and immune infiltration ability of different tumors and on the survival rate of patients. Herein, we conducted a pan-cancer analysis of PFKFB3 with the aim of exploring the key cellular and molecular mechanisms regulating the pathogenesis and progression of human cancers, and propose potential strategies for the prevention and treatment of cancer by targeting PFKFB3. Using bioinformatics analysis and integrative exploration from the Gene Expression Omnibus (GEO) and Cancer Genome Atlas (TCGA) databases, the differential expression of PFKFB3 or phosphorylated PFKFB3 and its correlation with tumor staging and stemness, survival prognosis, and immune invasion were extensively analyzed. The analysis showed differential expression of PFKFB3 in normal tissues and in various cancers. Increased PFKFB3 expression is positively correlated with the invasive ability and immune infiltration of 31 cancers and significantly affects the staging, stemness, prognosis, and survival rate of several cancers. Alterations in phosphorylated PFKFB3 and RNA modifications are also involved in the development and progression of various cancers. PFKFB3 is involved in multiple protein interactions and has complex molecular functions, such as ATP/ADP metabolic and glycolytic processes. Furthermore, PFKFB3 has a high mutation frequency, especially amplification, in multiple tumors. These findings highlight the significance of PFKFB3 in cancer progression, which might serve as a surrogate pan-cancer biomarker to predict the progression and outcome of cancers, as well as the invasion and immune infiltration of different cancers. Ethical compliance: This study did not involve any patient or animal samples and was approved by the academic committee of Tongji University.

Supplemental material, sj-pdf-1-mrj-10.1177_00222437221147088 for Debunking Misinformation About Consumer Products: Effects on Beliefs and Purchase Behavior by Jessica Fong, Tong Guo, and Anita Rao in Journal of Marketing Research

Supplemental material, sj-pdf-1-mrj-10.1177_00222437221147088 for Debunking Misinformation About Consumer Products: Effects on Beliefs and Purchase Behavior by Jessica Fong, Tong Guo, and Anita Rao in Journal of Marketing Research

Additional file 1: Supplementary Figure 1. Identification and distribution of lipid components. (A) Numbers of lipid species in lipid classes/subclasses detected by lipidomics analysis. Circular diagram of lipid subclass composition in non-metastatic group (B) and metastatic group (C). Supplementary Figure 2. The overlapped total ion chromatogram (TIC) of the plasma mixtures in negative and positive modes. Supplementary Table 1. Information of the instrument used in lipidomics analyses. Supplementary Table 2. Information of the reagents and internal standards used in lipidomics analyses. Supplementary Table 3. 655 unique lipids were identified and quantified. Supplementary Table 4. Baseline characteristics of patients in the training set and validation set. Supplementary Table 5. Associations of lipid species with distant metastasis-free survival (DMFS) of Nasopharyngeal carcinoma (NPC) by univariate Cox regression analysis. Only the lipid species with P value

AIM: To develop and evaluate a new fundus image optimization software based on red, green, blue channels (RGB) for the evaluation of age-related macular degeneration (AMD) in the Chinese population. METHODS: Fundus images that were diagnosed as AMD from the Shanghai Changfeng Study database were analyzed to develop a standardized optimization procedure. Image brightness, contrast, and color balance were measured. Differences between central lesion area and normal retinal area under different image brightness, contrast, and color balance were observed. The optimal optimization parameters were determined based on the visual system to avoid image distortion. A paired-sample diagnostic test was used to evaluate the enhancement software. Fundus optical coherence tomography (OCT) was used as the gold standard. Diagnostic performances were compared between original images and optimized images using McNemar's test. RESULTS: A fundus image optimization procedure was developed using 86 fundus images of 74 subjects diagnosed with AMD. By observing gray-scale images, choroid can be best displayed in red channel and retina in green channel was found. There was limited information in blue channel. Totally 104 participants were included in the paired sample diagnostic test to assess the performance of the optimization software. After the image enhancement, sensitivity increased from 74% to 88% (P=0.008), specificity decreased slightly from 88% to 84% (P=0.500), and Youden index increased by 0.11. CONCLUSION: The standardized image optimization software increases diagnostic sensitivity and may help ophthalmologists in AMD diagnosis and screening.

The concept of diabetic retinopathy (DR) has been extended from microvascular disease to neurovascular disease in which microglia activation plays a remarkable role. Fractalkine (FKN)/CX3CR1 is reported to regulate microglia activation in central nervous system diseases. To characterize the effect of FKN on microglia activation in DR, we employed streptozotocin-induced diabetic rats, glyoxal-treated R28 cells and hypoxia-treated BV2 cells to mimic diabetic conditions and explored retinal neuronal apoptosis, reactive oxygen species (ROS), as well as the expressions of FKN, Iba-1, TSPO, NF-κB, Nrf2 and inflammation-related cytokines. The results showed that FKN expression declined with diabetes progression and in glyoxal-treated R28 cells. Compared with normal control, retinal microglia activation and inflammatory factors surged in both diabetic rat retinas and hypoxia-treated microglia, which was largely dampened by FKN. The NF-κB and Nrf2 expressions and intracellular ROS were up-regulated in hypoxia-treated microglia compared with that in normoxia control, and FKN significantly inhibited NF-κB activation, activated Nrf2 pathway and decreased intracellular ROS. In conclusion, the results demonstrated that FKN deactivated microglia via inhibiting NF-κB pathway and activating Nrf2 pathway, thus to reduce the production of inflammation-related cytokines and ROS, and protect the retina from diabetes insult.

BACKGROUND: Patients with Parkinson's disease (PD) have variable rates of progression. More accurate prediction of progression could improve selection for clinical trials. Although some variance in clinical progression can be predicted by age at onset and phenotype, we hypothesise that this can be further improved by blood biomarkers. OBJECTIVE: To determine if blood biomarkers (serum neurofilament light (NfL) and genetic status (glucocerebrosidase, GBA and apolipoprotein E (APOE))) are useful in addition to clinical measures for prognostic modelling in PD. METHODS: We evaluated the relationship between serum NfL and baseline and longitudinal clinical measures as well as patients' genetic (GBA and APOE) status. We classified patients as having a favourable or an unfavourable outcome based on a previously validated model, and explored how blood biomarkers compared with clinical variables in distinguishing prognostic phenotypes . RESULTS: 291 patients were assessed in this study. Baseline serum NfL was associated with baseline cognitive status. Nfl predicted a shorter time to dementia, postural instability and death (dementia-HR 2.64; postural instability-HR 1.32; mortality-HR 1.89) whereas APOEe4 status was associated with progression to dementia (dementia-HR 3.12, 95% CI 1.63 to 6.00). NfL levels and genetic variables predicted unfavourable progression to a similar extent as clinical predictors. The combination of clinical, NfL and genetic data produced a stronger prediction of unfavourable outcomes compared with age and gender (area under the curve: 0.74-age/gender vs 0.84-ALL p=0.0103). CONCLUSIONS: Clinical trials of disease-modifying therapies might usefully stratify patients using clinical, genetic and NfL status at the time of recruitment.

Microglial activation has been studied extensively in diabetic retinopathy. We have previously detected activation and migration of microglia in 8-week-old diabetic rat retinas. It is widely acknowledged that microglia-mediated inflammation contributes to the progression of diabetic retinopathy. However, existing cell models do not explore the role of activated microglia in vitro. In this study, microglia were subject to various conditions mimicking diabetic retinopathy, including high glucose, glyoxal, and hypoxia. Under high glucose or glyoxal treatment, microglia demonstrated only partially functional changes, while under hypoxia, microglia became fully activated showing enlarged cell bodies, enhanced migration and phagocytosis as well as increased production of pro-inflammatory factors such as cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), and inducible nitric oxide synthase (iNOS). The data indicate that hypoxia-treated microglia is an optimal in vitro model for exploration of microglia activation in diabetic retinopathy.

Diabetic retinopathy, characterized as a microangiopathy and neurodegenerative disease, is the leading cause of visual impairment in diabetic patients. Many clinical features observed in diabetic retinopathy, such as capillary occlusion, acellular capillaries and retinal non-perfusion, aggregate retinal ischemia and represent relatively late events in diabetic retinopathy. In fact, retinal microvascular injury is an early event in diabetic retinopathy involving multiple biochemical alterations, and is manifested by changes to the retinal neurovascular unit and its cellular components. Currently, intravitreal anti-vascular endothelial growth factor therapy is the first-line treatment for diabetic macular edema, and benefits the patient by decreasing the edema and improving visual acuity. However, a significant proportion of patients respond poorly to anti-vascular endothelial growth factor treatments, indicating that factors other than vascular endothelial growth factor are involved in the pathogenesis of diabetic macular edema. Accumulating evidence confirms that low-grade inflammation plays a critical role in the pathogenesis and development of diabetic retinopathy as multiple inflammatory factors, such as interleukin-1β, monocyte chemotactic protein-1 and tumor necrosis factor -α, are increased in the vitreous and retina of diabetic retinopathy patients. These inflammatory factors, together with growth factors such as vascular endothelial growth factor, contribute to blood-retinal barrier breakdown, vascular damage and neuroinflammation, as well as pathological angiogenesis in diabetic retinopathy, complicated by diabetic macular edema and proliferative diabetic retinopathy. In addition, retinal cell types including microglia, Müller glia, astrocytes, retinal pigment epithelial cells, and others are activated, to secrete inflammatory mediators, aggravating cell apoptosis and subsequent vascular leakage. New therapies, targeting these inflammatory molecules or related signaling pathways, have the potential to inhibit retinal inflammation and prevent diabetic retinopathy progression. Here, we review the relevant literature to date, summarize the inflammatory mechanisms underlying the pathogenesis of diabetic retinopathy, and propose inflammation-based treatments for diabetic retinopathy and diabetic macular edema.

Aims Deep mining of the molecular mechanisms underlying diabetic retinopathy (DR) is critical for the development of novel therapeutic targets. This study aimed to identify key molecular signatures involved in experimental DR on the basis of integrated bioinformatics analysis. Materials and methods Four datasets consisting of 37 retinal samples were downloaded from the National Center of Biotechnology Information Gene Expression Omnibus (GEO). After batch-effect adjustment, bioinformatics tools such as Networkanalyst, Enrichr, STRING, and Metascape were used to evaluate the differentially expressed genes (DEGs), perform enrichment analysis, and construct protein-protein interaction (PPI) networks. The hub genes were identified using Cytoscape software. The DEGs of interest from the meta-analysis were confirmed by quantitative reverse transcription-polymerase chain reaction (RT-PCR) in diabetic rats and a high glucose-treated retinal cell model, respectively. Results A total of 743 DEGs related to lens differentiation, insulin resistance, and HDL cholesterol metabolism were obtained using the meta-analysis. Alterations of dynamic gene expression in the chloride ion channel, retinol metabolism, and fatty acid metabolism were involved in the course of DR in rats. Importantly, H3K27m3 modifications regulated the expression of most DEGs at the early stage of DR. This article is protected by copyright. All rights reserved. Conclusions Using an integrated bioinformatics approach, novel molecular signatures were obtained for different stages of DR progression, and the findings may represent distinct therapeutic strategies for DR patients.

Diabetic retinopathy(DR)is the most common complication of diabetes mellitus and remains the leading cause of blindness in working-age population. DR affects almost all the retinal cells, leading to the disruption and dysfunction of neurovascular unit and the neural-glial network. Erythropoietin(EPO), a glycoprotein hormone, plays a pivotal role in neuroprotection, neurotrophy, anti-inflammation, anti-apoptosis and anti-oxidation etc., in various central nervous system diseases. This review discussed the protective effect of EPO in DR so as to provide new options for DR treatment.

Age-related macular degeneration (AMD) is a major vision-threatening disease. Although mesenchymal stem cells (MSCs) exhibit beneficial neural protective effects, their limited differentiation capacity in vivo attenuates their therapeutic function. Therefore, the differentiation of MSCs into retinal pigment epithelial (RPE) cells in vitro and their subsequent transplantation into the subretinal space is expected to improve the outcome of cell therapy. Here, we transdifferentiated human umbilical cord MSCs (hUCMSCs) into induced RPE (iRPE) cells using a cocktail of five transcription factors (TFs): CRX, NR2E1, C-MYC, LHX2, and SIX6. iRPE cells exhibited RPE specific properties, including phagocytic ability, epithelial polarity, and gene expression profile. In addition, high expression of PTPN13 in iRPE cells endows them with an epithelial-to-mesenchymal transition (EMT)-resistant capacity through dephosphorylating syntenin1, and subsequently promoting the internalization and degradation of transforming growth factor-β receptors. After grafting into the subretinal space of the sodium iodate-induced rat AMD model, iRPE cells demonstrated a better therapeutic function than hUCMSCs. These results suggest that hUCMSC-derived iRPE cells may be promising candidates to reverse AMD pathophysiology.

Cross-talk between competitive endogenous RNAs (ceRNAs) may play a critical role in revealing potential mechanism of bovine follicular cysts. Ovarian cyst has always been an intractable scientific problem and has led to considerable economic losses to bovine breeding industry. However, its pathogenesis and molecular mechanisms are still not well understood. Here, this study aimed to investigate the role of non-coding RNAs (ncRNAs) and the ceRNA networks in bovine follicular cyst. Whole transcriptome sequencing of bovine follicular granulosa cells (GCs) was conducted to obtain the expression profiles of mRNAs, lncRNAs and miRNAs. The results for the identified expressions of 8,003 mRNAs, 579 lncRNAs and 205 miRNAs were often altered between cystic and normal follicular GCs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed on these differentially expressed mRNAs. Furthermore, the ceRNA network combining mRNAs, miRNAs, and lncRNAs using several bioinformatics methods based on co-expression analysis between the differentially expressed RNAs was conducted. Finally, the lncRNA NONBTAT027373.1-miR-664b-HSD17B7 pathway was verified by dual-luciferase reporting assay and RNA binding protein immunoprecipitation (RIP) assay. LncRNA NONBTAT027373.1 sponged miR-664b in GCs and prevented miR-664b from binding to the HSD17B7 3′-UTR. These results indicated that genes and lncRNAs related to steroid hormone synthesis and energy metabolism could play important roles in the formation of bovine cystic follicles through the ceRNA mechanism and represent candidate targets for further research. This can be used as a practical guideline for promoting healthy and highly efficient development in the bovine industry.

No abstract available.

Retinal Müller glial dysfunction and intracellular edema are important mechanisms leading to diabetic macular edema (DME). Aquaporin 11 (AQP11) is primarily expressed in Müller glia with unclear functions. This study aims to explore the role of AQP11 in the pathogenesis of intracellular edema of Müller glia in diabetic retinopathy (DR). Here, we found that AQP11 expression, primarily located at the endfeet of Müller glia, was down-regulated with diabetes progression, accompanied by intracellular edema, which was alleviated by intravitreal injection of lentivirus-mediated AQP11 overexpression. Similarly, intracellular edema of hypoxia-treated rat Müller cell line (rMC-1) was aggravated by AQP11 inhibition, while attenuated by AQP11 overexpression, accompanied by enhanced function in glutamate metabolism and reduced cell death. The down-regulation of AQP11 was also verified in the Müller glia from the epiretinal membranes (ERMs) of proliferative DR (PDR) patients. Mechanistically, down-regulation of AQP11 in DR was mediated by the HIF-1α-dependent and independent miRNA-AQP11 axis. Overall, we deciphered the AQP11 down-regulation, mediated by miRNA-AQP11 axis, resulted in Müller drainage dysfunction and subsequent intracellular edema in DR, which was partially reversed by AQP11 overexpression. Our findings propose a novel mechanism for the pathogenesis of DME, thus targeting AQP11 regulation provides a new therapeutic strategy for DME.

Background:. Accurate prediction of ischemic stroke is required for deciding anticoagulation use in patients with atrial fibrillation (AF). Even though only 6% to 8% of AF patients die from stroke, about 90% are indicated for anticoagulants according to the current AF management guidelines. Therefore, we aimed to develop an accurate and easy-to-use new risk model for 1-year thromboembolic events (TEs) in Chinese AF patients. Methods:. From the prospective China Atrial Fibrillation Registry cohort study, we identified 6601 AF patients who were not treated with anticoagulation or ablation at baseline. We selected the most important variables by the extreme gradient boosting (XGBoost) algorithm and developed a simplified risk model for predicting 1-year TEs. The novel risk score was internally validated using bootstrapping with 1000 replicates and compared with the CHA2DS2-VA score (excluding female sex from the CHA2DS2-VASc score). Results:. Up to the follow-up of 1 year, 163 TEs (ischemic stroke or systemic embolism) occurred. Using the XGBoost algorithm, we selected the three most important variables (congestive heart failure or left ventricular dysfunction, age, and prior stroke, abbreviated as CAS model) to predict 1-year TE risk. We trained a multivariate Cox regression model and assigned point scores proportional to model coefficients. The CAS scheme classified 30.8% (2033/6601) of the patients as low risk for TE (CAS score = 0), with a corresponding 1-year TE risk of 0.81% (95% confidence interval [CI]: 0.41%–1.19%). In our cohort, the C-statistic of CAS model was 0.69 (95% CI: 0.65–0.73), higher than that of CHA2DS2-VA score (0.66, 95% CI: 0.62–0.70, Z = 2.01, P = 0.045). The overall net reclassification improvement from CHA2DS2-VA categories (low = 0/high ≥1) to CAS categories (low = 0/high ≥1) was 12.2% (95% CI: 8.7%–15.7%). Conclusion:. In Chinese AF patients, a novel and simple CAS risk model better predicted 1-year TEs than the widely-used CHA2DS2-VA risk score and identified a large proportion of patients with low risk of TEs, which could potentially improve anticoagulation decision-making. Trial Registration:. www.chictr.org.cn (Unique identifier No. ChiCTR-OCH-13003729).

Age-related macular degeneration (AMD) is one of the most common leading causes of irreversible blindness, and there is no effective treatment for it. It has been reported that aging is the greatest risk factor for AMD, and epithelial-mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells plays an important role in the pathogenesis of AMD. To clarify the relationship between senescence and EMT in RPE cells, we used the replicative senescence model, H

The hostile microenvironment of the retina in patients with age-related macular degeneration (AMD) may trigger epithelial-to-mesenchymal transition (EMT) of grafted retinal pigment epithelial (RPE) cells, thus attenuating the therapeutic outcome. Here, we transformed human dedifferentiated induced pluripotent stem cell-derived RPE (iPSC-RPE) cells into induced RPE (iRPE) cells using a cocktail of four transcription factors (TFs)-CRX, MITF-A, NR2E1, and C-MYC. These critical TFs maintained the epithelial property of iRPE cells by regulating the expression of

Purpose: Autophagy is a key regulator of stem cell quiescence and self-renewal, especially in mesenchymal stem cells but related research on neural retinal stem cells is still limited. We are aimed to explore the function and mechanism of autophagy in the neural retinal stem cell.Methods: The published single cell sequencing data was involved to analysis the expression time course of IFITM3 in the mouse neural retinal progenitor cells (mNRPCs). The RNA interference was used to knock down the expression of IFITM3 in the mNRPCs. And the normal mNRPCs and mNRPCs with knockdown of IFITM3 were analysis with the CCK8 for the cell viability, RNA-seq for the mRNA expression, real-time quantitative PCR, immunofluorescence assay for the location of relative proteins, western blot for the levels of relative proteins and autophagy flux assay.Results: This study showed the mNRPCs in vivo and in vitro high expressed IFITM3 which are expressed in the mNRPCs. The proliferation of mNRPCs was greatly inhibited, and cell viability was greatly reduced after IFITM3 knockdown. Moreover, RNA-seq analysis showed that lysosomes were significant changed after IFITM3 knockdown. When cells were treated with rapamycin (RAMP), lysosome activation and agglomeration were evident in all groups. However, there was no significant difference between IFITM3 knockdown groups. The expression of LAMP1 was significantly increased, accompanied by increased lysosome agglomeration, in RAMP-treated cells and especially in IFITM3-knockdown cells. Further detection showed that SQSTM1/p62, HSC70 and LAMP-2A were upregulated, while there was no significant difference in LC3A/B expression, which demonstrated that the MA pathway was not activated but the CMA pathway was activated when knockdown of IFITM3. Conclusion: Our findings indicate that IFITM3 participates in regulating mNRPC viability and proliferation mainly through the CMA pathway, indicating that IFITM3 plays a significant role in maintaining the homeostasis of progenitor cell self-renewal by sustaining low-level activation of the CMA pathway to eliminate factors that are deleterious to cells and acts as a very important protector of RPCs.

Proliferative vitreoretinopathy (PVR) is a disease that causes severe blindness and is characterized by the formation of contractile fibrotic subretinal or epiretinal membranes. The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is a hallmark of PVR. This work aims to examine the role of a long noncoding RNA (lncRNA) named EMT-related lncRNA in RPE (ERLR, LINC01705-201 (ENST00000438158.1)) in PVR and to explore the underlying mechanisms. In this study, we found that ERLR is upregulated in RPE cells stimulated with transforming growth factor (TGF)-β1 as detected by lncRNA microarray and RT-PCR. Further studies characterized full-length ERLR and confirmed that it is mainly expressed in the cytoplasm. In vitro, silencing ERLR in RPE cells attenuated TGF-β1-induced EMT, whereas overexpressing ERLR directly triggered EMT in RPE cells. In vivo, inhibiting ERLR in RPE cells reduced the ability of cells to induce experimental PVR. Mechanistically, chromatin immunoprecipitation (ChIP) assays indicated that the transcription factor TCF4 directly binds to the promoter region of ERLR and promotes its transcription. ERLR mediates EMT by directly binding to MYH9 protein and increasing its stability. TCF4 and MYH9 also mediate TGF-β1-induced EMT in RPE cells. Furthermore, ERLR is also significantly increased in RPE cells incubated with vitreous PVR samples. In clinical samples of PVR membranes, ERLR was detected through fluorescent in situ hybridization (FISH) and colocalized with the RPE marker pancytokeratin (pan-CK). These results indicated that lncRNA ERLR is involved in TGF-β1-induced EMT of human RPE cells and that it is involved in PVR. This finding provides new insights into the mechanism and treatment of PVR.

Age-related macular degeneration (AMD) is mainly characterized by the progressive accumulation of drusen deposits and loss of photoreceptors and retinal pigment epithelial (RPE) cells. Because amyloid β (Aβ) is the main component of drusen, Aβ-induced activated microglia most likely lead to neuroinflammation and play a critical role in the pathogenesis of AMD. However, the relationship between activated microglia-mediated neuroinflammatory cytokines and photoreceptor death has not been clarified. By subretinal injection of Aβ42 in mice, we mimicked an inflammatory milieu of AMD to better understand how activated microglia-induced neuroinflammatory cytokines lead to photoreceptor apoptosis in the AMD progression. We demonstrated that subretinal injection of Aβ42 induces microglial activation and increases inflammatory cytokine release, which gives rise to photoreceptor apoptosis in mice. Our results were verified in vitro by co-culture of Aβ42 activated primary microglia and the photoreceptor cell line 661W. We also demonstrated that the p38 mitogen-activated protein kinase (MAPK) signaling pathway was involved in Aβ42-induced microglial activation and inflammatory cytokine release. Overall, our findings indicate that activated microglia-derived neuroinflammatory cytokines could contribute to photoreceptor apoptosis under the stimulation of Aβ42. Moreover, this study may provide a potential therapeutic approach for AMD. KEY MESSAGES: Further explore the association between activated microglia-derived neuroinflammatory cytokine secretion and photoreceptor apoptosis under the stimulation of Aβ42. Subretinal injection of Aβ42 induces the activation of microglia and increases proinflammatory cytokines IL-1β and COX-2 expression in the retina, which could give rise to the deterioration of visual function and aggravate photoreceptor apoptosis in mice. Primary microglial are activated and the levels of proinflammatory cytokines are increased by Aβ42 stimulation, which could increase the apoptosis of photoreceptor cell line 661W in vitro. The p38 MAPK signaling pathway is involved in microglial activation and photoreceptor apoptosis under Aβ42 treatment.

The pathophysiology of diabetic retinopathy (DR) was complex. Under hyperglycemic conditions, the release of proinflammatory cytokines and the adhesion of leukocytes to retinal capillaries contribute to endothelial damage and the subsequent increase in vascular permeability resulting in macular edema. Melatonin, produced in the retina to regulate redox reactions and dopamine metabolism, plays protective roles against inflammation and oxidative stress. Considering its anti-inflammatory and antioxidative properties, melatonin was speculated to exert beneficial effects in DR. In this study, we characterized the protective effects of melatonin on the inner blood-retinal barrier (iBRB), as well as the possible mechanisms in experimental DR. Results showed that in diabetic rat retinas, the leakage of iBRB and the expression of inflammatory factors (VEGF, TNF-α, IL-1β, ICAM-1, and MMP9) increased dramatically, while the expression of tight junction proteins (ZO-1, occludin, JAM-A, and claudin-5) decreased significantly. The above changes were largely ameliorated by melatonin. The in vivo data were confirmed in vitro. In addition, the protein expressions of p38 MAPK, NF-κB, and TXNIP were upregulated significantly in diabetes and were downregulated following melatonin treatment. Melatonin could maintain the iBRB integrity by upregulating the expression of tight junction proteins via inhibiting p38/TXNIP/NF-κB pathway, thus decreasing the production of inflammatory factors. This study may shed light on the development of melatonin-based DR therapy.

Epigenetics focuses on DNA methylation, histone modification, chromatin remodeling, noncoding RNAs, and other gene regulation mechanisms beyond the DNA sequence. In the past decade, epigenetic modifications have drawn more attention as they participate in the development and progression of diabetic retinopathy despite tight control of glucose levels. The underlying mechanisms of epigenetic modifications in diabetic retinopathy still urgently need to be elucidated. The diabetic condition facilitates epigenetic changes and influences target gene expression. In this review, we summarize the involvement of epigenetic modifications and metabolic memory in the development and progression of diabetic retinopathy and propose novel insights into the treatment of diabetic retinopathy.

Microglial activation in diabetic retinopathy and the protective effect of erythropoietin (EPO) have been extensively studied. However, the regulation of microglia in the retina and its relationship to inner blood–retinal barrier (iBRB) maintenance have not been fully characterised. In this study, we investigated the role of microglia in iBRB breakdown in diabetic retinopathy and the protective effects of EPO in this context. Male Sprague Dawley rats were injected intraperitoneally with streptozotocin (STZ) to establish the experimental model of diabetes. At 2 h after STZ injection, the right and left eyes were injected intravitreally with EPO (16 mU/eye, 2 μl) and an equivalent volume of normal saline (NaCl 154 mmol/l), respectively. The rats were killed at 2 or 8 weeks after diabetes onset. Microglia activation was detected by ionised calcium binding adaptor molecule (IBA)-1 immunolabelling. Leakage of the iBRB was evaluated by albumin staining and FITC-dextran permeability assay. BV2 cells and primary rat microglia under hypoxic conditions were used to model microglial activation in diabetic retinopathy. Phagocytosis was examined by confocal microscopy in flat-mounted retina preparations and in microglia and endothelial cell cocultures. Protein levels of IBA-1, CD11b, complement component 1r (C1r), and Src/Akt/cofilin signalling pathway components were assessed by western blotting. In diabetic rat retinas, phagocytosis of endothelial cells by activated microglia was observed at 8 weeks, resulting in an increased number of acellular capillaries (increased by 426.5%) and albumin leakage. Under hypoxic conditions, activated microglia transmigrated to the opposite membrane of the transwell, where they disrupted the endothelial cell monolayer by engulfing endothelial cells. The activation and phagocytic activity of microglia was blocked by intravitreal injection of EPO. In vitro, IBA-1, CD11b and C1r protein levels were increased by 50.9%, 170.0% and 135.5%, respectively, by hypoxia, whereas the phosphorylated proteins of Src/Akt/cofilin signalling pathway components were decreased by 74.2%, 47.8% and 39.7%, respectively, compared with the control; EPO treatment abrogated these changes. In experimental diabetic retinopathy, activated microglia penetrate the basement membrane of the iBRB and engulf endothelial cells, leading to iBRB breakdown. EPO exerts a protective effect that preserves iBRB integrity via activation of Src/Akt/cofilin signalling in microglia, as demonstrated in vitro. These data support a causal role for activated microglia in iBRB breakdown and highlight the therapeutic potential of EPO for the treatment of diabetic retinopathy.

This paper presents a study of flow ripple reduction method of a spool valves distribution radial piston pump (SVDRPP). Relief chamfers are adopted to prolong and moderate the opening processes of the delivery spool valves, thus to relieve the pressure surges as well as the consequent flow ripples, vibrations and noises. The mathematical model of this method is established and multiple numerical simulations are conducted to analyze the mechanism as well as the effectiveness of this method. According to the simulation results, different relief chamfer angles have varying influences on flow ripple reduction. Remarkable reduction of flow fluctuation from 43.4% to 36% could be achieved, when the relief chamfer angle is set around 30°. Comparisons between the relief chamfer method and the time delay method indicate that the former has better compatibility to the load pressure lower than the rated value; while the latter has better compatibility to the higher load pressure.

To study the biological functions and applications of human amniotic epithelial cell-derived extracellular vesicles (hAEC-EVs), the cargos of hAEC-EVs were analyzed using miRNA sequencing and proteomics analysis. The hAECs and hAEC-EVs in this study had specific characteristics. Multi-omics analyses showed that extracellular matrix (ECM) reorganization, inhibition of excessive myofibroblasts, and promotion of target cell adhesion to the ECM were their primary functions. We evaluated the application of hAEC-EVs for corneal alkali burn healing in rabbits and elucidated the fundamental mechanisms. Slit-lamp images revealed that corneal alkali burns induced central epithelial loss, stromal haze, iris, and pupil obscurity in rabbits. Slit-lamp examination and histological findings indicated that hAEC-EVs facilitated re-epithelialization of the cornea after alkali burns, reduced scar formation and promoted the restoration of corneal tissue transparency. Significantly fewer α-SMA-positive myofibroblasts were observed in the hAEC-EV-treated group than the PBS group. HAEC-EVs effectively promoted the proliferation and migration of hCECs and hCSCs in vitro and activated the focal adhesion signaling pathway. We demonstrated that hAEC-EVs were excellent cell-free candidates for the treatment of ECM lesion-based diseases, including corneal alkali burns. HAEC-EVs promoted ECM reorganization and cell adhesion of target tissues or cells via orderly activation of the focal adhesion signaling pathway.

Introduction. To describe the hyperreflective foci (HRF) on optical coherence tomography angiography (OCTA) in diabetic macular edema (DME) with subretinal fluid (SRF) and explore the association of HRF in the outer retina with photoreceptor integrity and visual outcomes after anti-vascular endothelial growth factor (anti-VEGF) treatment. Methods. We retrospectively reviewed 46 eyes (36 patients) with DME treated with anti-VEGF drugs. The following parameters, including best-corrected visual acuity (BCVA), central macular thickness (CMT), the height of subretinal fluid (SRF), the number of HRF in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and the outer retina, as well as the integrity of external limiting membrane (ELM) and ellipsoid zone (EZ), were evaluated and compared between the baseline and after 2 monthly injections of anti-VEGF drugs. The relationship between the HRF in the outer retina and the integrity of ELM and EZ, as well as BCVA was analyzed. Results. BCVA was significantly improved in DME after anti-VEGF treatment, however, for the subgroup of DME patients with SRF, visual acuity remained unchanged after anti-VEGF treatment (p < 0.05 vs. p = 0.375). The number of HRF (p < 0.05), CMT (p ＜ 0.001), and SRF height (p ＜ 0.001) were significantly reduced, accompanied with partial restoration of ELM and EZ integrity after anti-VEGF injection. The HRF in the outer retina was correlated with the final ELM (p = 0.036) and EZ (p = 0.004) status. The final BCVA was significantly better in eyes with intact ELM (p = 0.002) and EZ at final visit (p< 0.001). Conclusion. The number of HRF in outer retina was negatively associated with the microstructural restoration of ELM and EZ, as well as the visual outcome in DME patients with SRF after anti-VEGF treatment.

Microglial activation and melatonin protection have been reported in diabetic retinopathy (DR). Whether melatonin could regulate microglia to protect the inner blood–retinal barrier (iBRB) remains unknown. In this study, the role of microglia in iBRB breakdown and the mechanisms of melatonin’s regulation on microglia were explored. In diabetic rat retinas, activated microglia proliferated and migrated from the inner retina to the outer retina, accompanied by the obvious morphological changes. Meanwhile, significant leakage of albumin was evidenced at the site of close interaction between activated microglia and the damaged pericytes and endothelial cells. In vitro, inflammation-related cytokines, such as tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, and arginase-1 (Arg-1), were increased significantly in CoCl2-treated BV2 cells. The supernatant derived from CoCl2-treated BV2 cells significantly decreased the cell viability and disrupted the junctional proteins in both pericytes and endothelial cells, resulting in severe leakage. Melatonin suppressed the microglial overactivation, i.e., decreasing the cell number and promoting its anti-inflammatory properties in diabetic rat retinas. Moreover, the leakage of iBRB was alleviated and the pericyte coverage was restored after melatonin treatment. In vitro, when treated with melatonin in CoCl2-treated BV2 cells, the inflammatory factors were decreased, while the anti-inflammatory factors were increased, further reducing the pericyte loss and increasing the tight junctions. Melatonin deactivated microglia via inhibition of PI3K/Akt/Stat3/NF-κB signaling pathways, thus maintaining the integrity of iBRB. The present data support a causal role for activated microglia in iBRB breakdown and highlight the therapeutic potential of melatonin in the treatment of DR by regulating microglia.

Background: To evaluate the drainage function of retinal pigment epithelium (RPE) in patients with macular edema secondary to retinal vein occlusion (RVO-ME) after anti-vascular endothelial growth factor (anti-VEGF) treatment by optical coherence tomography angiography (OCTA).Patients and Methods: Twenty-eight eyes with RVO-ME were imaged. Best-corrected visual acuity (BCVA), the area of the foveal avascular zone (FAZ), the nonperfusion areas (NPAs), the central macular thickness (CMT), the vascular density of the superficial/deep capillary plexus (SCP/DCP), the height of subretinal fluid (SRF), and the number of hyperreflective foci (HRF) were compared before and after treatments.Results: Compared with pre-treatment, the CMT, NPAs, number of HRF and the height of SRF were decreased significantly after anti-VEGF treatment. There was no difference for BCVA, vascular density and FAZ area.Conclusion: The absorption of SRF and the decrease of HRF indicated the restoration of RPE drainage function and anti-inflammation by anti-VEGF treatment.

Supplemental material, sj-docx-1-tej-10.1177_20417314221122123 for Human amniotic epithelial cell-derived extracellular vesicles provide an extracellular matrix-based microenvironment for corneal injury repair by Shuqin Hu, Zhe Wang, Caixia Jin, Qizhen Chen, Yuchen Fang, Jiahui Jin, Jie Chen, Lixia Lu, Haibin Tian, Jingying Xu, Furong Gao, Juan Wang, Jieping Zhang, Hong-Ping Cui, Guo-Tong Xu and Qingjian Ou in Journal of Tissue Engineering

The performance gap between predicted and actual energy consumption in the building domain remains an unsolved problem in practice. The gap exists differently in both current mainstream methods: the first-principles model and the machine learning (ML) model. Inspired by the concept of time-series decomposition to identify different uncertainties, we proposed a hybrid-model approach by combining both methods to minimize this gap: 1. Use the first-principles method as an encoding tool to convert the building static features and predictable patterns in time-series simulation results; 2. The ML method combines the results as extra inputs with historical records simultaneously, trains the model to capture the implicit performance difference, and aligns to calibrate the output. To extend this approach in practice, a new concept in the modeling process: Level-of-Information (LOI), is introduced to leverage the balance between the investment of simulation modeling detail and the accuracy boost. The approach is tested over a three-year period, with hourly measured energy load from an operating commercial building in Shanghai. The result presents a dominant accuracy enhancement: The hybrid-model shows higher accuracy in prediction with better interpretability; More important, it releases the practitioners from modeling workload and computational resources in refining simulation. In summary, the approach provides a nexus for integrating domain knowledge via building simulation with data-driven methods. This mindset applies to solving general engineering problems and leads to improved prediction accuracy. The result and source data are available at https://github.com/ResearchGroup-G/PerformanceGap-Hybrid-Approach., Comment: 18 pages, 11 figures; The result and source data are available at https://github.com/ResearchGroup-G/PerformanceGap-Hybrid-Approach

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Additional file 1: Supplemental methods, figures and tables referenced in the text. Figure S1. Annotation results of secondary metabolic pathways based on KEGG; Figure S2. Nitrogen content and mean N:C ratio of different samples; Figure S3. Qualitative and quantitative analyses of urea and uric acid by enzymatic colorimetry; Figure S4. Dilution coating plate method and qPCR for estimating antibiotic efficacy; Figure S5. Nitrogenous waste degradation and EAA biosynthesis pathways constructed based on the KEGG database; Figure S6. Pathways for EAAs biosynthesis; Table S1. Statistical table of metagenomic assembly (DNA-seq); Table S2. Alpha diversity metrics calculated at the 97 % identity level (DNA-seq-based analysis); Table S3. Distribution of dominant species (%) in different taxonomic categories based on DNA-seq; Table S4. Statistical table of metatranscriptomics assembly (RNA-seq); Table S5. Distribution of dominant species (%) in different taxonomic categories based on RNA-seq; Table S6. The distribution of some functional genes in B. dorsalis; Table S7. Nutrient composition of the defined diets used in feeding trial.

Supplemental material, sj-docx-2-tej-10.1177_20417314221122123 for Human amniotic epithelial cell-derived extracellular vesicles provide an extracellular matrix-based microenvironment for corneal injury repair by Shuqin Hu, Zhe Wang, Caixia Jin, Qizhen Chen, Yuchen Fang, Jiahui Jin, Jie Chen, Lixia Lu, Haibin Tian, Jingying Xu, Furong Gao, Juan Wang, Jieping Zhang, Hong-Ping Cui, Guo-Tong Xu and Qingjian Ou in Journal of Tissue Engineering

Supplemental material, sj-docx-2-tej-10.1177_20417314221122123 for Human amniotic epithelial cell-derived extracellular vesicles provide an extracellular matrix-based microenvironment for corneal injury repair by Shuqin Hu, Zhe Wang, Caixia Jin, Qizhen Chen, Yuchen Fang, Jiahui Jin, Jie Chen, Lixia Lu, Haibin Tian, Jingying Xu, Furong Gao, Juan Wang, Jieping Zhang, Hong-Ping Cui, Guo-Tong Xu and Qingjian Ou in Journal of Tissue Engineering

Supplemental material, sj-docx-4-tej-10.1177_20417314221122123 for Human amniotic epithelial cell-derived extracellular vesicles provide an extracellular matrix-based microenvironment for corneal injury repair by Shuqin Hu, Zhe Wang, Caixia Jin, Qizhen Chen, Yuchen Fang, Jiahui Jin, Jie Chen, Lixia Lu, Haibin Tian, Jingying Xu, Furong Gao, Juan Wang, Jieping Zhang, Hong-Ping Cui, Guo-Tong Xu and Qingjian Ou in Journal of Tissue Engineering

Supplemental material, sj-docx-1-tej-10.1177_20417314221122123 for Human amniotic epithelial cell-derived extracellular vesicles provide an extracellular matrix-based microenvironment for corneal injury repair by Shuqin Hu, Zhe Wang, Caixia Jin, Qizhen Chen, Yuchen Fang, Jiahui Jin, Jie Chen, Lixia Lu, Haibin Tian, Jingying Xu, Furong Gao, Juan Wang, Jieping Zhang, Hong-Ping Cui, Guo-Tong Xu and Qingjian Ou in Journal of Tissue Engineering

Additional file 6. Supplementary Material.

Supplemental material, sj-docx-4-tej-10.1177_20417314221122123 for Human amniotic epithelial cell-derived extracellular vesicles provide an extracellular matrix-based microenvironment for corneal injury repair by Shuqin Hu, Zhe Wang, Caixia Jin, Qizhen Chen, Yuchen Fang, Jiahui Jin, Jie Chen, Lixia Lu, Haibin Tian, Jingying Xu, Furong Gao, Juan Wang, Jieping Zhang, Hong-Ping Cui, Guo-Tong Xu and Qingjian Ou in Journal of Tissue Engineering

Supplemental material, sj-docx-3-tej-10.1177_20417314221122123 for Human amniotic epithelial cell-derived extracellular vesicles provide an extracellular matrix-based microenvironment for corneal injury repair by Shuqin Hu, Zhe Wang, Caixia Jin, Qizhen Chen, Yuchen Fang, Jiahui Jin, Jie Chen, Lixia Lu, Haibin Tian, Jingying Xu, Furong Gao, Juan Wang, Jieping Zhang, Hong-Ping Cui, Guo-Tong Xu and Qingjian Ou in Journal of Tissue Engineering

Supplemental material, sj-docx-3-tej-10.1177_20417314221122123 for Human amniotic epithelial cell-derived extracellular vesicles provide an extracellular matrix-based microenvironment for corneal injury repair by Shuqin Hu, Zhe Wang, Caixia Jin, Qizhen Chen, Yuchen Fang, Jiahui Jin, Jie Chen, Lixia Lu, Haibin Tian, Jingying Xu, Furong Gao, Juan Wang, Jieping Zhang, Hong-Ping Cui, Guo-Tong Xu and Qingjian Ou in Journal of Tissue Engineering