Mendelian randomization study and mediation analysis about the relation of inflammatory bowel disease and diabetic retinopathy: the further exploration of gut-retina axis.

Background: The concept of the gut-retinal axis proposed by previous scholars primarily focused on the relationship between intestinal microbiota and retinal diseases, and few further expanded the relationship between intestinal diseases and retinal diseases. To further substantiate the concept of the gut-retinal axis, we analyzed inflammatory bowel disease (IBD) and diabetic retinopathy (DR) using Mendelian randomization (MR), and use mediation analysis to further explore the potential substances that influence this causal relationship. Methods: The genome-wide association study's (GWAS) summary statistics for genetic variations were utilized in a Mendelian randomization (MR) investigation. GWAS data on IBD (including ulcerative colitis (UC), Crohn's disease (CD), and IBD) for non-Finnish Europeans (NFE) were sourced from published articles. In contrast, data on DR (including DR and diabetic maculopathy (DMP)) were obtained from FinnGen R9. The causal relationship has been investigated using inverse variance weighted (IVW), MR-Egger, and weighted median and sensitivity analysis was applied to verify the stability of the results. In addition, we applied mediation analysis to investigate whether circulating inflammatory proteins and plasma lipids played a mediating role, and calculated its effect ratio. Results: The causal relationship between IBD and DR was discovered by employing the inverse variance weighted (IVW) method and weighted median method. In forward MR, UC was significantly associated with lower risk of DR (IVW: OR=0.874; 95%CI= 0.835-0.916; P value= 1.28E-08) (Weighted median: OR=0.893; 95%CI= 0.837-0.954; P value= 7.40E-04). In reverse MR, it was shown that DR (IVW: OR=0.870; 95%CI= 0.828-0.914; P value= 2.79E-08)(Weighted median: OR=0.857; 95%CI= 0.801-0.916; P value= 6.40E-06) and DMP (IVW: OR=0.900; 95%CI= 0.865-0.937; P value= 3.34E-07)(Weighted median: OR=0.882; 95%CI= 0.841-0.924; P value= 1.82E-07) could reduce the risk of CD. What's more, DR is associated with a lower risk of IBD according to genetic prediction (IVW: OR=0.922; 95%CI= 0.873-0.972; P value= 0.002) (Weighted median: OR=0.924; 95%CI= 0.861-0.992; P value= 0.029). Fibroblast growth factor 21 (FGF21), phosphatidylcholine (PC), and triacylglycerol (TG) serve as mediators in these relationships. Conclusions: Our research offers novel insights and sources for investigating the gut-retina axis in the genetic relationship between IBD and DR. We discover four mediators and more about the association between the intestine and retinal disorders and provide more evidence for the gut-retinal axis theory.

How liquids charge the superhydrophobic surfaces.

Liquid-solid contact electrification (CE) is essential to diverse applications. Exploiting its full implementation requires an in-depth understanding and fine-grained control of charge carriers (electrons and/or ions) during CE. Here, we decouple the electrons and ions during liquid-solid CE by designing binary superhydrophobic surfaces that eliminate liquid and ion residues on the surfaces and simultaneously enable us to regulate surface properties, namely work function, to control electron transfers. We find the existence of a linear relationship between the work function of superhydrophobic surfaces and the as-generated charges in liquids, implying that liquid-solid CE arises from electron transfer due to the work function difference between two contacting surfaces. We also rule out the possibility of ion transfer during CE occurring on superhydrophobic surfaces by proving the absence of ions on superhydrophobic surfaces after contact with ion-enriched acidic, alkaline, and salt liquids. Our findings stand in contrast to existing liquid-solid CE studies, and the new insights learned offer the potential to explore more applications.

A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation.

BACKGROUND: This article reports an extremely rare case of lipoprotein glomerulopathy (LPG) with apolipoprotein E gene (APOE) Chicago mutation in a young Chinese male. Only five cases or families with APOE Chicago mutations have been reported in the literature. CASE PRESENTATION: The young male patient is manifested with nephrotic syndrome, accompanied by hyperlipidemia with a preferable increase in triglycerides and elevated ApoE level. Renal biopsy of the patient showed highly dilated glomerular capillaries filled with vacuolar lipids, segmentally fused podocyte foot processes, vacuolar degeneration of renal tubular epithelial cells and absence of electron-dense material, which indicates the diagnosis of LPG. Whole-exome gene sequencing identified the heterozygous mutation of NM_000041.4:c.494G > C (p.Arg165Pro), which is in the exon 4 of the APOE gene and also known as APOE Chicago mutation, a rare mutation of LPG. Further family pedigree gene analysis clarified that the mutation was inherited from the patient's mother, who does not have high ApoE levels or renal manifestations. This is also consistent with the incomplete penetrance of APOE gene mutations in LPG. Under lipid-lowering treatments, including a low-fat diet and fenofibrate, the patient's urinary protein was partially controlled, and the albumin level was recovered. CONCLUSION: Patients with nephrotic syndrome and elevated ApoE levels should be prompted into renal biopsy to avoid delay of appropriate treatment and unnecessary use of glucocorticoids. This case of LPG was diagnosed by renal biopsy and further verified with genetic sequencing. The timely diagnosis and treatment improved the patient's symptoms. This case is one of only six reported LPG cases or families with APOE Chicago mutation in the world.

The effects of Tripterygium wilfordii Hook F on renal outcomes in type 2 diabetic kidney disease patients with severe proteinuria: a single-center cohort study.

AIM: Tripterygium wilfordii Hook F (TwHF) has been shown to substantially reduce proteinuria in patients with diabetic kidney disease (DKD); however, the effect of TwHF on renal outcomes in DKD remains unknown. Accordingly, we aimed to establish the effects of TwHF on renal outcomes in patients with DKD. METHODS: Overall, 124 patients with DKD, induced by type 2 diabetes mellitus, with 24-h proteinuria > 2 g, and an estimated glomerular filtration rate > 30 mL/min/1.73 m2 were retrospectively investigated. The renal outcomes were defined as doubling serum creatinine levels or end-stage kidney disease. Kaplan-Meier curves and Cox regression analyses were performed to analyze prognostic factors for renal outcomes. RESULTS: By the end of the follow-up, renal outcomes were observed in 23 and 11 patients in the non-TwHF and TwHF groups, respectively (p = 0.006). TwHF significantly reduced the risk of renal outcomes (adjusted hazard ratio [HR] 0.271, 95% confidence interval [CI] 0.111-0.660, p = 0.004) in patients with chronic kidney disease (CKD) G3 (adjusted HR 0.274, 95%CI 0.081-0.932, p = 0.039). Based on the Kaplan-Meier analysis, 1- and 3-year proportions of patients without renal outcomes were significantly lower in the non-TwHF group than those in the TwHF group (92.8% vs. 95.5% and 47.2% vs. 76.8%, respectively; p = 0.0018). CONCLUSION: In DKD patients with severe proteinuria, TwHF could prevent DKD progression, especially in patients with CKD G3. A randomized clinical trial is needed to elucidate the benefits of TwHF on renal outcomes in patients with DKD.

MSCohi-O lenses for long-term retention of mesenchymal stem cells on ocular surface as a therapeutic approach for chronic ocular graft-versus-host disease.

Chronic ocular graft-versus-host disease (oGVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) and can lead to vision loss if not diagnosed and treated promptly. Currently, no approved drugs exist for oGVHD treatment. However, umbilical cord-derived mesenchymal stem cells (UCMSCs) have known immunoregulatory properties and have been employed in clinical trials for immune-mediated diseases. To address oGVHD, the application of UCMSCs to the ocular surface is a logical approach. Intravenous administration of UCMSCs poses risks, necessitating topical and local delivery. Retaining UCMSCs on the ocular surface remains a challenge. To overcome this, we invented mesenchymal stem cell-coating high oxygen-permeable hydrogel lenses combining UCMSCs and machinery to enable the long-term retention of UCMSCs on the ocular surface. Animal model experiments demonstrated that these lenses effectively retained UCMSCs, providing therapeutic benefits by decreasing corneal inflammation and damage, and inhibiting immune rejection and response, all crucial aspects in oGVHD treatment.

Long-Term Stability Challenges and Opportunities in Acidic Oxygen Evolution Electrocatalysis.

Polymer electrolyte membrane water electrolysis (PEMWE) has been regarded as a promising technology for renewable hydrogen production. However, acidic oxygen evolution reaction (OER) catalysts with long-term stability impose a grand challenge in its large-scale industrialization. In this review, critical factors that may lead to catalyst's instability in couple with potential solutions are comprehensively discussed, including mechanical peeling, substrate corrosion, active-site over-oxidation/dissolution, reconstruction, oxide crystal structure collapse through the lattice oxygen-participated reaction pathway, etc. Last but not least, personal prospects are provided in terms of rigorous stability evaluation criteria, in situ/operando characterizations, economic feasibility and practical electrolyzer consideration, highlighting the ternary relationship of structure evolution, industrial-relevant activity and stability to serve as a roadmap towards the ultimate application of PEMWE.

Embryonic stem cell extracellular vesicles reverse the senescence of retinal pigment epithelial cells by the p38MAPK pathway.

Retinal pigment epithelial (RPE) cellular senescence is regarded as an initiator for age-related macular degeneration (AMD). We previously demonstrated that by the coculture way, embryonic stem cells (ESCs) can reverse the senescence of RPE cells, but xenograft cells can cause a plethora of adverse effects. Extracellular vesicles (EVs) derived from ESCs can act as messengers to mediate nearby cell activities and have the same potential as ESCs to reverse RPE senescence. Furthermore, ESC-EVs have achieved preliminary efficacy while treating many age-related diseases. The present study aimed to test the effect of ESC-EVs on the replicative senescence model of RPE cells as well as its mechanism. The results showed that ESC-EVs enhanced the proliferative ability and cell cycle transition of senescent RPE cells, whereas reduced the senescence-associated galactosidase (SA-ß-gal) staining rate, as well as the levels of mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). Moreover, classical markers of cellular senescence p21WAF1/CIP1 (p21) and p16INK4a (p16) were downregulated. The bioinformatic analysis and further study showed that the inhibition of the p38MAPK pathway by ESC-EVs played a pivotal role in RPE cellular senescence-reversing effect, which was ameliorated or even abolished when dehydrocorydaline were administrated simultaneously, demonstrating that ESC-EVs can effectively reverse RPE cellular senesence by inhibiting the p38MAPK pathway, thus highlights the potential of ESC-derived EVs as biomaterials for preventative and protective therapy in AMD.

Tear film cytokines as prognostic indicators for predicting early recurrent pterygium.

Cytokine profiles in tears have become a noninvasive biomarker for various ocular surface diseases. Therefore, the preoperative profile of cytokines in tear samples of 89 primary pterygium patients were obtained from Zhongshan Ophthalmic Center during 2015-2017. Compared to the tear cytokines in primary groups, the concentrations of IL-8, MMP-1, MMP-9, bFGF and VEGF were generally higher in recurrent pterygium group. The five cytokines were used to build diagnostic models by multiple machine learning algorithms, which can accurately distinguish non-recurrent and recurrent samples of primary pterygium patients. Besides, these cytokines were significantly associated with Recurrent-free survival (RFS) time in pterygium patients and further applied to develop a prognostic model which can estimate the prognosis of pterygium after resection. Afterward, a novel nomogram combined risk score of cytokines related biomarker and clinical characteristics was constructed, which manifested ideal accuracies to predict the 1 and 2 years' probability of pterygium recurrent events. Thus, our finding provides a more simple and accurate prediction for early pterygium recurrence after resection. It also affords a useful tool for ophthalmologists to choose the optimal treatment strategies for pterygium patients.

Efficient synthesis 1,4-cyclohexanedicarboxaldehyde by an engineered alcohol oxidase.

In this study, we selected and engineered a flavin adenine dinucleotide (FAD)-dependent alcohol oxidase (AOX) to produce 1,4-cyclohexanedicarboxaldehyde (CHDA), an initial raw material for spiral compounds, from 1,4-cyclohexanedimethanol (CHDM). First, the structure of alcohol oxidase from Arthrobacter cholorphenolicus (AcCO) was analyzed, and the mechanism of AcCO-catalyzed primary alcohol oxidation was elucidated, demonstrating that the energy barrier of the hydride (H-) transfer (13.4 kcal·mol-1 and 20.4 kcal·mol-1) decreases the catalytic efficiency of the primary alcohol oxidation reaction. Therefore, we designed a protein engineering strategy to adjust the catalytically active conformation to shorten the distance of hydride (H-) transfer and further decreased the core energy barrier. Following this strategy, variant W4 (S101A/H351V/N378S/Q329N) was obtained with 112.5-fold increased catalytic efficiency to produce CHDA compared to that of the wild-type strain. The 3 L scale preparation of CHDA reached a titer up to 29.6 g·L-1 with a 42.2% yield by an Escherichia coli whole-cell catalyst, which demonstrates the potential of this system for industrial application.

Rapid and Persistent Suction Condensation on Hydrophilic Surfaces for High-Efficiency Water Collection.

Water collection by dew condensation emerges as a sustainable solution to water scarcity. However, the transient condensation process that involves droplet nucleation, growth, and transport imposes conflicting requirements on surface properties. It is challenging to satisfy all benefits for different condensation stages simultaneously. By mimicking the structures and functions of moss Rhacocarpus, here, we report the attainment of dropwise condensation for efficient water collection even on a hydrophilic surface gated by a liquid suction mechanism. The Rhacocarpus-inspired porous surface (RIPS), which possesses a three-level wettability gradient, facilitates a rapid, directional, and persistent droplet suction. Such suction condensation enables a low nucleation barrier, frequent surface refreshing, and well-defined maximum droplet shedding radius simultaneously. Thus, a maximum ∼160% enhancement in water collection performance compared to the hydrophobic surface is achieved. Our work provides new insights and a design route for developing engineered materials for a wide range of water-harvesting and phase-change heat-transfer applications.

Explosive Pancake Bouncing on Hot Superhydrophilic Surfaces.

The rapid detachment of liquid droplets from engineered surfaces in the form of complete rebound, pancake bouncing, or trampolining has been extensively studied over the past decade and is of practical importance in many industrial processes such as self-cleaning, anti-icing, energy conversion, and so on. The spontaneous trampolining of droplets needs an additional low-pressure environment and the manifestation of pancake bouncing on superhydrophobic surfaces requires meticulous control of macrotextures and impacting velocity. In this work, we report that the rapid pancake-like levitation of impinging droplets can be achieved on superhydrophilic surfaces through the application of heating. In particular, we discovered explosive pancake bouncing on hot superhydrophilic surfaces made of hierarchically non-interconnected honeycombs, which is in striking contrast to the partial levitation of droplets on the surface consisting of interconnected microposts. This enhanced droplet bouncing phenomenon, characterized by a significant reduction in contact time and increase in the bouncing height, is ascribed to the production and spatial confinement of pressurized vapor in non-interconnected structures. The manifestation of pancake bouncing on the superhydrophilic surface rendered by a bottom-to-up boiling process may find promising applications such as the removal of trapped solid particles.

Tumor Microenvironmental Competitive Endogenous RNA Network and Immune Cells Act as Robust Prognostic Predictor of Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is malignant hematologic tumors with frequent recurrence and cause high mortality. Its fate is determined by abnormal intracellular competitive endogenous RNA (ceRNA) network and extracellular tumor microenvironment (TME). This study aims to build a ceRNA network related to AML TME to explore new prognostic and therapeutic targets. The RNA expression data of AML were obtained from The Cancer Genome Atlas (TCGA) database. First, we used the ESTIMATE algorithm to calculate the immune cells and stromal cells infiltration scores in the TME and found that all scores were highly correlated with AML's prognostic characteristics. Subsequently, differentially expressed mRNAs and lncRNAs between high and low score groups were identified to construct a TME-related ceRNA network. Further, the Cox-lasso survival model was employed to screen out the hub prognostic ceRNA network composed of two mRNAs (EPB41L3, COL2A1), three miRNAs (hsa-mir-26a-5p, hsa-mir-148b-3p, hsa-mir-148a-3p), and two lncRNAs (CYP1B1-AS1, C9orf106), and construct nomograms. Finally, we used CIBERSORT algorithm and Kaplan-Meier survival analysis to identify the prognostic TME immune cells and found that naive B cells, M2-type macrophages, and helper follicular T cells were related to prognosis, and the hub ceRNAs were highly correlated with immune cell infiltration. This study provided a new perspective to elucidate how TME regulates AML process and put forward the new therapy strategies combining targeting tumor cells with disintegrating TME.

Common Genes Involved in Autophagy, Cellular Senescence and the Inflammatory Response in AMD and Drug Discovery Identified via Biomedical Databases.

Purpose: Retinal pigment epithelial cell autophagy dysfunction, cellular senescence, and the retinal inflammatory response are key pathogenic factors in age-related macular degeneration (AMD), which has been reviewed in our previously work in 2019. This study aims to identify genes collectively involved in these three biological processes and target drugs in AMD. Methods: The pubmed2ensembl database was used to perform text mining. The GeneCodis database was applied to analyze gene ontology biological process and the KEGG pathway. The STRING database was used to analyze protein-protein interaction analysis and hub genes were identified by the Cytoscape software. The Drug Gene Interaction Database was used to perform drug-gene interactions. Results: We identified 62 genes collectively involved in AMD, autophagy, cellular senescence, and inflammatory response, 19 biological processes including 42 genes, 11 enriched KEGG pathways including 37 genes, and 12 hub genes step by step via the above biomedical databases. Finally, five hub genes (IL-6, VEGF-A, TP53, IL-1ß, and transforming growth factor [TGF]-ß1) and their specific interaction modes were identified, corresponding with 24 target drugs with therapeutic potential for AMD. Conclusions: IL-6, VEGF-A, TP53, IL-1ß, and TGF-ß1 are pivotal in autophagy, cellular senescence, and the inflammatory response in AMD, corresponding with 24 drugs with therapeutic potential for AMD, providing definite molecular mechanisms for further research and new possibilities for AMD treatment in the future. Translational Relevance: IL-6, VEGF-A, TP53, IL-1ß, and TGF-ß1 may be new targets for AMD gene therapy and drug development.

Therapeutic effects and perspective of stem cell extracellular vesicles in aging and cancer.

Senescent cells can secrete a plethora of cytokines which induce senescent phenotype of neighboring cells and was called senescence-associated secretory phenotype. Previously, it was believed that cancer was caused by the infinite division and uncontrolled proliferation of cells. Based on this, anticancer treatments were all aimed at killing cancer cells. Cancer is now considered an age-related disease. Cancer cells are not exogenous, but one of the worst results of injuries which initially induce cell senescence. Therefore, reversing cell senescence can fundamentally prevent and treat cancer. Though current anticancer treatments induce the cancer cells apoptosis, they induce senescence of normal cells at the same time, thus promoting the occurrence and development of cancer and forming a vicious circle. Extracellular vesicles (EVs) are nano-sized vesicles which partially mirror their parent cells. In the tumor microenvironment, EVs of senescent cells can change the expression profile of cancer cells, contributing to their resistance to chemotherapy. There is growing evidence indicates that stem cell EVs exert effective antiaging and anticancer actions by transferring functional microRNAs and proteins. This review will summarize the therapeutic role of stem cell EVs in reversing aging and cancer, which suggests the broad clinical application perspective.

Preferential Vapor Nucleation on Hierarchical Tapered Nanowire Bunches.

Controlling vapor nucleation on micro-/nanostructured surfaces is critical to achieving exciting droplet dynamics and condensation enhancement. However, the underlying mechanism of nucleation phenomena remains unclear because of its nature of nanoscale and transience, especially for the complex-structured surfaces. Manipulating vapor nucleation via the rational surface design of micro-/nanostructures is extremely challenging. Here, we fabricate hierarchical surfaces comprising tapered nanowire bunches and crisscross microgrooves. Nanosteps are formed around the top of the nanowire bunches, where the nanowires all around agglomerate densely because of surface tension. The theoretical analysis and molecular dynamics simulation show that nanostep morphologies that are around the top of the nanowire bunches can enable a lower energy barrier and a higher nucleation capability than those of the sparsely packed nanowires at the center and bottom of the nanowire bunches. Vapor condensation experiments demonstrate that the nucleation preferentially occurs around the top of the nanowire bunches. The results provide guidelines to design micro-/nanostructures for promoting vapor nucleation and droplet removal in condensation.

Few-layer graphene on nickel enabled sustainable dropwise condensation.

Condensation is critical for a wide range of applications such as electrical power generation, distillation, natural gas processing, dehumidification and water harvest, and thermal management. Compared with "filmwise" mode of condensation (FWC) prevailing in industrial-scale systems, dropwise condensation (DWC) can provide an order of magnitude higher heat transfer rate owing to drastically reduced thermal resistance from the formation of discrete and mobile droplets. In the past, promoting DWC by controlling surface wetting has attracted wide attention, but DWC highly relies on non-wetting surfaces and only lasts days under practical conditions due to the poor reliability of coatings. Here, we developed nanostructured graphene coatings on nickel (Ni) substrates that we can control and enhance the nucleation of water droplets on graphene grain boundaries. Surprisingly, this enables DWC even under normal "wetting" conditions. This is contradictory to the widely accepted DWC mechanism. Moreover, the Ni-graphene surface enables exceptional long-term condensation from days to more than 3 years under practical or even more aggressive testing environments.

Reversed Senescence of Retinal Pigment Epithelial Cell by Coculture With Embryonic Stem Cell via the TGFß and PI3K Pathways.

Retinal pigment epithelium (RPE) cellular senescence is an important etiology of age-related macular degeneration (AMD). Aging interventions based on the application of stem cells to delay cellular senescence have shown good prospects in the treatment of age-related diseases. This study aimed to investigate the potential of the embryonic stem cells (ESCs) to reverse the senescence of RPE cells and to elucidate its regulatory mechanism. The hydrogen peroxide (H2O2)-mediated premature and natural passage-mediated replicative senescent RPE cells were directly cocultured with ESCs. The results showed that the proliferative capacity of premature and replicative senescent RPE cells was increased, while the positive rate of senescence-associated galactosidase (SA-ß-GAL) staining and levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were decreased. The positive regulatory factors of cellular senescence (p53, p21WAF1/CIP1, p16INK4a) were downregulated, while the negative regulatory factors of cellular senescence (Cyclin A2, Cyclin B1, Cyclin D1) were upregulated. Furthermore, replicative senescent RPE cells entered the S and G2/M phases from the G0/G1 phase. TGFß (TGFB1, SMAD3, ID1, ID3) and PI3K (PIK3CG, PDK1, PLK1) pathway-related genes were upregulated in premature and replicative senescent RPE cells after ESCs application, respectively. We further treated ESCs-cocultured premature and replicative senescent RPE cells with SB531542 and LY294002 to inhibit the TGFß and PI3K pathways, respectively, and found that p53, p21WAF1/CIP1 and p16INK4a were upregulated, while Cyclin A2, Cyclin B1, Cyclin D1, TGFß, and PI3K pathway-related genes were downregulated, accompanied by decreased proliferation and cell cycle transition and increased positive rates of SA-ß-GAL staining and levels of ROS and MMP. In conclusion, we demonstrated that ESCs can effectively reverse the senescence of premature and replicative senescent RPE cells by a direct coculture way, which may be achieved by upregulating the TGFß and PI3K pathways, respectively, providing a basis for establishing a new therapeutic option for AMD.

Immune Microenvironment Related Competitive Endogenous RNA Network as Powerful Predictors for Melanoma Prognosis Based on WGCNA Analysis.

Cutaneous melanoma is the most life-threatening skin malignant tumor due to its increasing metastasis and mortality rate. The abnormal competitive endogenous RNA network promotes the development of tumors and becomes biomarkers for the prognosis of various tumors. At the same time, the tumor immune microenvironment (TIME) is of great significance for tumor outcome and prognosis. From the perspective of TIME and ceRNA network, this study aims to explain the prognostic factors of cutaneous melanoma systematically and find novel and powerful biomarkers for target therapies. We obtained the transcriptome data of cutaneous melanoma from The Cancer Genome Atlas (TCGA) database, 3 survival-related mRNAs co-expression modules and 2 survival-related lncRNAs co-expression modules were identified through weighted gene co-expression network analysis (WCGNA), and 144 prognostic miRNAs were screened out by univariate Cox proportional hazard regression. Cox regression model and Kaplan-Meier survival analysis were employed to identify 4 hub prognostic mRNAs, and the prognostic ceRNA network consisting of 7 lncRNAs, 1 miRNA and 4 mRNAs was established. After analyzing the composition and proportion of total immune cells in cutaneous melanoma microenvironment through CIBERSORT algorithm, it is found through correlation analysis that lncRNA-TUG1 in the ceRNA network was closely related to the TIME. In this study, we first established cutaneous melanoma's TIME-related ceRNA network by WGCNA. Cutaneous melanoma prognostic markers have been identified from multiple levels, which has important guiding significance for clinical diagnosis, treatment, and further scientific research on cutaneous melanoma.

A novel lncRNA-miRNA-mRNA competitive endogenous RNA network for uveal melanoma prognosis constructed by weighted gene co-expression network analysis.

AIMS: Uveal melanoma (UM) is the most common and aggressive intraocular tumor in adults, and long-term survival of UM patients remains poor. Abnormal competitive endogenous RNA (ceRNA) networks promote the initiation and progression of many tumors and may thus serve as useful prognostic indicators. Here, we do a comprehensive analysis of long non-coding RNA (lncRNA)-microRNA (miRNA)-mRNA ceRNA networks as prognostic markers for UM. MATERIALS AND METHODS: The Cancer Genome Atlas UM dataset was used to identify survival-related mRNA and lncRNA modules through weighted gene co-expression network analysis (WGCNA). Prognostic miRNAs were identified using univariate Cox proportional hazard regression. We then used Cox and least absolute shrinkage and selection operator regression to screen for prognostic hub mRNAs and establish a hub ceRNA network. A nomogram of five hub mRNAs was constructed and Kaplan-Meier survival analysis performed. KEY FINDINGS: Six mRNA modules were constructed, two of which involved 1490 mRNAs that significantly correlated with survival. Among the three lncRNA modules constructed, one involved 199 survival-related lncRNAs. Five hub prognostic mRNAs were identified and a hub ceRNA network constructed, consisting of six lncRNAs, four miRNAs, and five mRNAs, with high prognostic value. SIGNIFICANCE: We describe a hub ceRNA network of survival-associated lncRNAs, miRNAs, and mRNA that may underlie a critical post-translational regulatory mechanism determining UM aggression. These hub RNAs may be valuable prognostic markers and therapeutic targets in UM.