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Considerable attention has been by far paid to stabilizing metallic Zn anodes, where side reactions and dendrite formation still remain detrimental to their practical advancement. Electrolyte modification or protected layer design is widely reported; nonetheless, an effective maneuver to synergize both tactics has been rarely explored. Herein, we propose a localized electrolyte optimization via the introduction of a dual-functional biomass modificator over the Zn anode. Instrumental characterization in conjunction with molecular dynamics simulation indicates local solvation structure transformation owing to the limitation of bound water with intermolecular hydrogen bonds, effectively suppressing hydrogen evolutions. Meanwhile, the optimized nucleation throughout the protein membrane allows uniform Zn deposition. Accordingly, the symmetric cell exhibits an elongated lifespan of 3280 h at 1.0 mA cm-2/1.0 mAh cm-2, while the capacity retention of the full cell sustains 91.1% after 2000 cycles at 5.0 A g-1. The localized electrolyte tailoring via protein membrane introduction might offer insights into operational metal anode protection.
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Background: Gap junction proteins (GJPs) are a class of channel proteins that are closely related to cell communication and tumor development. The objective of this study was to screen out GJPs related prognostic signatures (GRPS) associated with clear cell renal cell carcinoma (ccRCC). Materials and Methods: GJPs microarray data for ccRCC patients were obtained from The Gene Expression Omnibus (GEO) database, along with RNA sequencing data for tumor and paired normal tissues from The Cancer Genome Atlas (TCGA) database. In the TCGA database, least absolute shrinkage and selection Operator (LASSO) and Cox regression models were used to identify GJPs with independent prognostic effects as GRPS in ccRCC patients. According to the GRPS expression and regression coefficient from the multivariate Cox regression model, the risk score (RS) of each ccRCC patient was calculated, to construct the RS prognostic model to predict survival. Overall survival (OS) and progression-free survival (PFS) analyses; gene pan-cancer analysis; single gene survival analysis; gene joint effect analysis; functional enrichment analysis; tumor microenvironment (TME) analysis; tumor mutational burden (TMB) analysis; and drug sensitivity analysis were used to explore the biological function, mechanism of action and clinical significance of GRPS in ccRCC. Further verification of the genetic signature was performed with data from the GEO database. Finally, the cytofunctional experiments were used to verify the biological significance of GRPS associated GJPs in ccRCC cell lines. Results: GJA5 and GJB1, which are GRPS markers of ccRCC patients, were identified through LASSO and Cox regression models. Low expression of GJA5 and GJB1 is associated with poor patient prognosis. Patients with high-RS had significantly shorter OS and PFS than patients with low-RS (p< 0.001). The risk of death for individuals with high-RS was 1.695 times greater than that for those with low-RS (HR = 1.695, 95%CI= 1.439-1.996, p< 0.001). Receiver Operating Characteristic (ROC) curve showed the great predictive power of the RS prognostic model for the survival rate of patients. The area under curve (AUC) values for predicting 1-year, 3-year and 5-year survival rates were 0.740, 0.781 and 0.771, respectively. The clinical column chart was also reliable for predicting the survival rate of patients, with AUC values of 0.859, 0.846 and 0.796 for predicting 1-year, 3-year and 5-year survival, respectively. The GRPS was associated with immune cell infiltration, the TME, the TMB, and sensitivity to chemotherapy drugs. Further in vitro experiments showed that knockdown of GJA5 or GJB1 could promote the proliferation, migration and epithelial-mesenchymal transition (EMT) and inhibit apoptosis of ccRCC cells. Conclusion: GJA5 and GJB1 could be potential biological markers for predicting survival in patients with ccRCC.
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The cause of Posner-Schlossman syndrome (PSS) remains unknown and its frequent recurrence may eventually lead to irreversible damage of the optic nerve. The influence of immune factors in the pathophysiology of PSS is gaining more and more interest. Increasing evidence suggests that gut dysbiosis plays vital roles in a variety of neurodegenerative and immune-related diseases. However, alterations of the gut microbiota in PSS patients have not been well defined yet. In this study, 16S rRNA sequencing was used to explore the difference of gut microbiota between PSS patients and healthy controls, and the correlation between the microbiota profile and clinical features was also analyzed. Our data demonstrated a significant increase of Prevotella and Prevotellaceae, and a significant reduction of Bacteroides and Bacteroidaceae in PSS patients, and KEGG analysis showed dysfunction of gut microbiota between PSS patients and healthy controls. Interestingly, further analysis showed that the alteration of gut microbiota was correlated with the PSS attack frequency of PSS. This study demonstrated the gut microbiota compositional profile of PSS patients and speculated the risk microbiota of PSS, which is expected to provide new insights for the diagnosis and treatment of PSS.
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Microbioma Gastrointestinal , Microbiota , Humanos , ARN Ribosómico 16S/genéticaRESUMEN
The uneven texture evolution of Zn during electrodeposition would adversely impact upon the lifespan of aqueous Zn metal batteries. To address this issue, tremendous endeavors are made to induce Zn(002) orientational deposition employing graphene and its derivatives. Nevertheless, the effect of prototype graphene film over Zn deposition behavior has garnered less attention. Here, it is attempted to solve such a puzzle via utilizing transferred high-quality graphene film with controllable layer numbers in a scalable manner on a Zn foil. The multilayer graphene fails to facilitate a Zn epitaxial deposition, whereas the monolayer film with slight breakages steers a unique pinhole deposition mode. In-depth electrochemical measurements and theoretical simulations discover that the transferred graphene film not only acts as an armor to inhibit side reactions but also serves as a buffer layer to homogenize initial Zn nucleation and decrease Zn migration barrier, accordingly enabling a smooth deposition layer with closely stacked polycrystalline domains. As a result, both assembled symmetric and full cells manage to deliver satisfactory electrochemical performances. This study proposes a concept of "pinhole deposition" to dictate Zn electrodeposition and broadens the horizons of graphene-modified Zn anodes.
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Background: Cuproptosis is a novel form of cellular demise that occurs through a unique pathway involving lipoylated proteins in the tricarboxylic acid (TCA) cycle and is closely linked to mitochondrial metabolism. Nevertheless, the comprehensive elucidation of the impact of carcinogenesis-associated genes (CRGs) on prognosis, tumor microenvironment (TME), and therapeutic response in patients with gastric cancer (GC) remains unclear. Methods: In total, 1374 GC samples were gathered from three Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas database. The samples were then stratified into different subtypes through unsupervised clustering of the 13 CRG profiles. The CRG_score was developed to quantify CRG patterns of individual tumors. Subsequently, we investigated the associations among the various groups and clinicopathological features, immune infiltration features, TME mutation status, and response to immunotherapy. Results: The GC samples were divided into two clusters based on their distinct clinicopathological features, prognosis, and immune characteristics. Using LASSO and Cox regression analyses, 9 genes were identified for constructing a prognostic signature related to cuproptosis. The novel signature displayed outstanding durability and prognostic capability for the overall lifespan of individuals. Additionally, the expression levels of signature genes in GC tissues and adjacent normal tissues were tested by qRT-PCR. Moreover, we developed a remarkably dependable nomogram to enhance the practicality of the CRG_score in clinical settings. High tumor mutation burden, increased microsatellite instability-high, immune activation, along with good survival probability and increased immunoreactivity to immune checkpoint inhibitors, were distinguishing features of low CRG_scores. Conclusions: The findings of this study revealed the possible impacts of CRGs on the TME, clinical and pathological characteristics, and outlook of patients with GC. This signature was strongly linked to the immune response against GC and has the potential to serve as a valuable tool for predicting patient prognosis.
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Orientation guidance has shown its cutting edges in electrodeposition modulation to promote Zn anode stability toward commercialized standards. Nevertheless, large-scale orientational deposition is handicapped by the competition between Zn-ion reduction and mass transfer. Herein, a holistic electrolyte additive protocol is put forward via incorporating bio-derived dextrin molecules into a zinc sulfate electrolyte bath. Electrochemical tests in combination with molecular dynamics simulations demonstrate the alleviation of concentration polarization throughout accelerating Zn2+ diffusion and retarding their reduction. The predominant (101) texture on inert current collectors (i.e., Cu, Ti, and stainless steel) and (101)/(002) textures on Zn foils afford homogeneous electrical field distribution, which is contributed by the work difference to form the 2D nucleus and the adsorption of dextrin molecules, respectively. Consequently, the symmetric cell harvests a longevous cycling lifespan of over 4000 h at 0.5 mA cm-2 /0.5 mAh cm-2 while the Zn@Cu electrode sustains for 240 h at a high depth of discharge of 40%.
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Episcleral vasculature malformation is a significant feature of Sturge-Weber syndrome (SWS) secondary glaucoma, the density and diameter of which are correlated with increased intraocular pressure. We previously reported that the GNAQ R183Q somatic mutation was located in the SWS episclera. However, the mechanism by which GNAQ R183Q leads to episcleral vascular malformation remains poorly understood. In this study, we investigated the correlation between GNAQ R183Q and episcleral vascular malformation via surgical specimens, human umbilical vein endothelial cells (HUVECs), and the HUVEC cell line EA.hy926. Our findings demonstrated a positive correlation between episcleral vessel diameter and the frequency of the GNAQ R183Q variant. Furthermore, the upregulation of genes from the Notch signaling pathway and abnormal coexpression of the arterial marker EphrinB2 and venous marker EphB4 were demonstrated in the scleral vasculature of SWS. Analysis of HUVECs overexpressing GNAQ R183Q in vitro confirmed the upregulation of Notch signaling and arterial markers. In addition, knocking down of Notch1 diminished the upregulation of arterial markers induced by GNAQ R183Q. Our findings strongly suggest that GNAQ R183Q leads to malformed episcleral vasculatures through Notch-induced aberrant arteriovenous specification. These insights into the molecular basis of episcleral vascular malformation will provide new pathways for the development of effective treatments for SWS secondary glaucoma.
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Glaucoma , Síndrome de Sturge-Weber , Humanos , Síndrome de Sturge-Weber/genética , Transducción de Señal , Células Endoteliales de la Vena Umbilical Humana , Mutación , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genéticaRESUMEN
INTRODUCTION: The aim of the study was to evaluate the efficacy and safety of combined trabeculotomy-non-penetrating deep sclerectomy (CTNS) in the treatment of Sturge-Weber syndrome (SWS) secondary glaucoma. METHODS: This retrospective study reviewed cases that underwent CTNS as initial surgery for SWS secondary glaucoma at our Ophthalmology Department center from April 2019 to August 2020. Surgical success was defined as an intraocular pressure (IOP) ≤ 21 mm Hg with (qualified success) or without (complete success) the use of anti-glaucoma medications. IOP >21 mm Hg or <5 mm Hg despite 3 or more applications of anti-glaucoma medications on 2 consecutive follow-up visits or at the last follow-up, performance of additional glaucoma (IOP-lowering) surgery, or with vision-threatening complications were classified as failure. RESULTS: A total of 22 eyes of 21 patients were included. Twenty-one eyes were of early-onset type and 1 eye was of adulthood onset. For Kaplan-Meier survival analysis, the overall success rates at 1st and 2nd years were 95.2% and 84.9%, while the complete success rates at 1st and 2nd years were 42.9% and 36.7%. At the last follow-up (22.3 ± 4.0 months, range: 11.2â¼31.2), overall success was achieved in 19 (85.7%) eyes and complete success in 12 (52.4%) eyes. Postoperative complications included transient hyphema (11/22, 50.0%) and transient â degree shallow anterior chamber (1/22, 4.5%), and retinal detachment (1/22, 4.5%). No other severe com plications were detected during the follow-up. CONCLUSION: CTNS significantly reduces IOP in SWS secondary glaucoma patients who have serious episcleral vascular malformation. CTNS in SWS secondary glaucoma patients is safe and effective for short and medium periods. A randomized controlled study comparing the long-term prognosis of SWS early-onset and late-onset glaucoma underwent CTNS is worth conducting.
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Glaucoma , Síndrome de Sturge-Weber , Trabeculectomía , Humanos , Adulto , Trabeculectomía/efectos adversos , Síndrome de Sturge-Weber/complicaciones , Síndrome de Sturge-Weber/diagnóstico , Síndrome de Sturge-Weber/cirugía , Estudios Retrospectivos , Agentes Antiglaucoma , Resultado del Tratamiento , Glaucoma/cirugía , Glaucoma/etiología , Presión Intraocular , Esclerótica/cirugía , Estudios de SeguimientoRESUMEN
PURPOSE: To perform an in vivo evaluation of the changes in Schlemm's canal (SC) among patients with primary angle-closure disease (PACD) using swept-source optical coherence tomography (SS-OCT). METHODS: Patients diagnosed with PACD who had not undergone surgery were recruited. The SS-OCT quadrants scanned herein included the nasal and temporal sections at 3 and 9 o'clock, respectively. The diameter and cross-sectional area of the SC were measured. A linear mixed-effects model was performed to analyze the effects of parameters on the SC changes. The hypothesis of interest was related to the angle status (iridotrabecular contact, ITC/open angle, OPN), which was further explored with pairwise comparisons of the estimated marginal means (EMMs) of the SC diameter and SC area. In the ITC regions, the relationship between the trabecular-iris contact length (TICL) percentage and SC parameters was also studied by a mixed model. RESULTS: A total of 49 eyes of 35 patients were included for measurements and analysis. The percentage of observable SCs in the ITC regions was only 58.5% (24/41), whereas it was 86.0% (49/57) in the OPN regions (χ2 = 9.44, p = 0.002). ITC was significantly associated with a decreasing SC size. The EMMs for the diameter and cross-sectional area of SC at the ITC and OPN regions were 203.34 µm versus 261.41 µm (p = 0.006) and 3174.43 µm2 versus 5347.63 µm2 (p = 0.022), respectively. Sex, age, spherical equivalent refraction, intraocular pressure, axial length, extent of angle closure, history of acute attack and treatment with LPI were not significantly associated with SC parameters. In the ITC regions, a larger TICL percentage was significantly associated with a decrease in SC diameter and area (p = 0.003 and 0.019, respectively). CONCLUSIONS: The morphologies of SC could be affected by the angle status (ITC/OPN) in patients with PACD, and ITC was significantly associated with a decreasing SC size. These changes in SC as described by OCT scans might help to elucidate the progression mechanisms of PACD.
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Glaucoma de Ángulo Cerrado , Malla Trabecular , Humanos , Tomografía de Coherencia Óptica/métodos , Canal de Schlemm , Esclerótica , Tonometría Ocular , Presión Intraocular , Glaucoma de Ángulo Cerrado/diagnóstico , Glaucoma de Ángulo Cerrado/cirugíaRESUMEN
Background: The fibrinogen-to-prealbumin ratio (FPR), a novel immune-nutritional biomarker, has been reported to be associated with prognosis in several types of cancer, but the role of FPR in the prognosis of resectable pancreatic cancer has not been elucidated. Methods: A total of 263 patients with resectable pancreatic cancer were enrolled in this study and were randomly divided into a training cohort (n = 146) and a validation cohort (n = 117). Receiver operating characteristic curve (ROC) was used to calculate the cut-off values of immune-nutritional markers. The least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression were performed in the training cohort to identify the independent risk factors, based on which the nomogram was established. The performance of the nomogram was evaluated and validation by the training and validation cohort, respectively. Results: The optimal cutoff value for FPR was 0.29. Multivariate analysis revealed that FPR, controlling nutritional status (CONUT), carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and tumor node metastasis (TNM) stage were independent predictors of overall survival (OS). The nomogram was established by involving the five factors above. The C-index of the training cohort and validation cohort were 0.703 (95% CI: 0.0.646-0.761) and 0.728 (95% CI: 0.671-0.784). Decision curve analysis and time-dependent AUC showed that the nomogram had better predictive and discriminative ability than the conventional TNM stage. Conclusion: FPR is a feasible biomarker for predicting prognosis in patients with resectable pancreatic cancer. The nomogram based on FPR is a useful tool for clinicians in making individualized treatment strategies and survival predictions.
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INTRODUCTION: Primary angle-closure glaucoma (PACG) is a leading cause of irreversible blindness globally, and the number of patients with PACG rises every year. Yet, there is a lack of knowledge about the clinical characteristics, therapeutic options and profile of patients with PACG in China. Hence, we design the China Glaucoma Treatment Pattern Study â -Primary Angle-Closure Glaucoma (Ch-GTPâ ). The objective of this paper is to describe the design and methodology of Ch-GTP. The aim of this study is to characterise the profile and trend associated with initial PACG treatment for the last 10 years in China. METHODS: Ch-GTPâ is a national multicentre retrospective observational study that will randomly sample from 50 hospitals throughout China. Over 7000 patient records hospitalised for initial PACG treatment from 2011 to 2020 will be selected randomly. The data from electronic medical records will be uploaded to an encrypted online platform that will receive and collate data from all collaborating hospitals. Data abstraction and monitoring will be performed in a standardised manner by trained statisticians to ensure consistency. Systematic data cleaning will also be conducted by statisticians to ensure data integrity before final data storage. The outcomes will include four broad categories: (1) demographics, (2) clinical characteristics, (3) therapeutic strategies and procedures and (4) early outcomes at discharge. The demographic characteristics and early outcomes will be summarised using descriptive statistics. Comparative analyses of characteristics and treatment pattern changing trends for different regions and years will be used to test for significant differences (t-test or Mann-Whitney U test). ETHICS AND DISSEMINATION: The collaborating hospitals obtained local approval based on a standard ethics application from internal ethics committees or acknowledged an existent ethics approval of the leading institution with approval from internal ethics committees. Due to the retrospective nature, written informed consent from patients was waived by the ethics committee. The results will be published in academic journals and presented at national and international academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR2100054643.
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Glaucoma de Ángulo Cerrado , Glaucoma , Humanos , Ceguera , China , Glaucoma de Ángulo Cerrado/terapia , Presión Intraocular , Estudios RetrospectivosRESUMEN
Electroepitaxy is recognized as an effective approach to prepare metal electrodes with nearly complete reversibility. Nevertheless, large-scale manipulation is still not attainable owing to complicated interfacial chemistry. Here, the feasibility of extending Zn electroepitaxy toward the bulk phase over a mass-produced mono-oriented Cu(111) foil is demonstrated. Interfacial Cu-Zn alloy and turbulent electroosmosis are circumvented by adopting a potentiostatic electrodeposition protocol. The as-prepared Zn single-crystalline anode enables stable cycling of symmetric cells at a stringent current density of 50.0 mA cm-2 . The assembled full cell further sustaines a capacity retention of 95.7% at 5.0 A g-1 for 1500 cycles, accompanied by a controllably low N/P ratio of 7.5. In addition to Zn, Ni electroepitaxy can be realized by using the same approach. This study may inspire rational exploration of the design of high-end metal electrodes.
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Aleaciones , Galvanoplastia , Electrodos , ZincRESUMEN
Glaucoma is the major cause of irreversible blindness in the world characterized by progressive retinal neurodegeneration, in which local inflammation in retina is involved in persistent loss of retinal ganglion cells (RGCs). In order to explore whether aryl hydrocarbon receptor (AhR) and its agonists tryptophan metabolites are involved in the development of glaucoma, we collected serum and retinas from non-glaucoma controls and patients with glaucoma. Results showed altered serum tryptophan metabolism and reduced retinal AhR expression in glaucoma patients. We also showed intraperitoneally injection of tryptophan metabolite 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) down-regulated retinal local inflammation and protected RGC apoptosis from retinal ischemia/reperfusion (IR) injury via AhR activation. We further revealed that ITE could inhibit inflammation in BV2 microglia and alleviate the neurotoxicity of microglial conditioned medium to RGCs under IR. Finally, we illustrated the possible mechanism that ITE limited ERK and NFκB dependent microglial inflammation. In summary, these findings suggest the critical role of tryptophan metabolism and retinal AhR signaling in modulating local inflammation mediated by microglia in glaucoma, and provide a novel avenue to targeting the intrinsically altered AhR signaling resulted from disturbed tryptophan metabolism for glaucoma treatment.
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Glaucoma , Fármacos Neuroprotectores , Receptores de Hidrocarburo de Aril , Humanos , Antiinflamatorios , Isquemia , Fármacos Neuroprotectores/farmacología , Receptores de Hidrocarburo de Aril/metabolismo , Retina/metabolismo , Triptófano/farmacologíaRESUMEN
BACKGROUND: Sturge Weber syndrome (SWS), can cause extensive capillary malformations on the face, head, trunk, and other parts of the body, and the eyes can also suffer optic nerve injury. Secondary glaucoma can cause blindness, which has the characteristics of a relatively hidden onset and unclear pathogenesis. The treatment of SWS secondary glaucoma has always been difficult, and due to the characteristics of the disease, there is uncertainty about the long-term efficacy and safety of various treatment methods for such patients. METHODS: A total of 105 parents of children with SWS completed a self-designed general information questionnaire, a generalized anxiety questionnaire (GAD-7), a patient health questionnaire (PHQ-2), a stress perception scale (PSS-4), a simple coping scale (SCSQ) and a disease-uncertainty scale (PPUS). RESULTS: The total uncertainty score of parents of children with SWS was 79.07 ± 13.24, and the average item score was 2.82 ± 0.47. Multiple linear regression analysis revealed that anxiety and simple coping were the main influencing factors of disease uncertainty among parents of children with SWS (P < 0.05). CONCLUSIONS: Parents of children with SWS exhibit a high level of disease uncertainty. Medical staff should pay attention to the source of parents' disease uncertainty and provide targeted interventions, which are of great importance in reducing parents' disease uncertainty.
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Glaucoma , Síndrome de Sturge-Weber , Humanos , Niño , Síndrome de Sturge-Weber/complicaciones , Estudios Retrospectivos , Incertidumbre , Glaucoma/complicaciones , PadresRESUMEN
The development of infrared-radar compatible materials/devices is challenging because the requirements of material properties between infrared and radar stealth are contradictory. Herein, a composite of poly(3, 4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS) coated melamine foam is designed to integrate the advantages of the dual materials and the created heterogeneous interface between them. The as-designed PEDOT:PSS@melamine composite shows excellent mechanical properties, outstanding thermal insulation, and improved thermal infrared stealth performance. The relevant superb radar stealth performance including the minimum reflection loss value of -57.57 dB, the optimum ultra-wide bandwidth of 10.52 GHz, and the simulation of radar cross section reduction value of 17.68 dB m2 , can be achieved. The optimal specific electromagnetic wave absorption performance can reach up as high as 3263.02 dB·cm3 g-1 . The average electromagnetic interference shielding effectiveness value can be 30.80 dB. This study provides an approach for the design of high-performance stealth materials with infrared-radar compatibility.
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BACKGROUND: Glaucoma is the leading cause of irreversible blindness in the world. Elevated intraocular pressure (IOP) is recognized as one of the most critical factors, but the loss of retinal ganglia cells (RGCs) often persists when IOP is controlled. Recently, a large number of studies focus on the inflammatory and immune responses in the occurrence and development of glaucoma. Magnolol (MAG), the principal ingredient of magnoliae officinalis cortex, has anti-inflammatory effects, but its role and mechanism in retinal protection need to be further studied. METHODS: The neurodegeneration of retina in mice model following ischemia/reperfusion (IR) injury was evaluated by immunohistochemistry, hematoxylin and eosin (H&E) staining and electroretinography (ERG). The inflammation-regulatory effect of MAG was detected by quantitative RT-PCR, western blot, and immunohistochemistry. Peroxisome proliferator-activated receptor-γ (PPARγ) inhibitor assays by H&E staining and western blot were used to test the target and mechanism pathway of MAG. RESULTS: We found MAG relieved IR-induced retinal damages and inflammation. Further studies revealed MAG alleviated nuclear factor kappa B (NFκB)-dependent inflammatory process by preserving the expression of NFκB inhibitor alpha (IκBα), and it modulated microglia polarization after IR injury. PPARγ was a primary target of MAG, and treatment with PPARγ inhibitor GW9662 attenuated the neuroprotective and anti-inflammatory effects of MAG. CONCLUSIONS: Our findings revealed that MAG inhibits NFκB-dependent inflammatory processes by elevating PPARγ in mice retinas to achieve its neuroprotective role following IR, which suggesting that MAG could be developed to a novel anti-inflammatory therapeutic agent for relieving the progression of glaucoma.