Wide field-of-view laser-based white light transmitter for visible light communications.

The advancement demands of high-speed wireless data link ask for higher requirements on visible light communication (VLC), where wide coverage stands as a critical criterion. Here, we present the design and implementation of a transmitter structure capable of emitting a high-power wide-coverage white light laser. This laser source exhibits excellent stability, with an irradiation range extending to a half-angle of 20°. Its high brightness satisfies the needs of indoor illumination while maintaining excellent communication performance. Utilizing bit-loading discrete multi-tone modulation, a peak data transmission rate of 3.24 Gbps has been achieved, spanning 1 to 5 m. Remarkably, the data rates exceed 2.5 Gbps within a 40° range at a distance of 5 m, enabling a long-distance, wide coverage, high-speed VLC link for future mobile network applications.

Laser-Based Mobile Visible Light Communication System.

Mobile visible light communication (VLC) is key for integrating lighting and communication applications in the 6G era, yet there exists a notable gap in experimental research on mobile VLC. In this study, we introduce a mobile VLC system and investigate the impact of mobility speed on communication performance. Leveraging a laser-based light transmitter with a wide coverage, we enable a light fidelity (LiFi) system with a mobile receiving end. The system is capable of supporting distances from 1 m to 4 m without a lens and could maintain a transmission rate of 500 Mbps. The transmission is stable at distances of 1 m and 2 m, but an increase in distance and speed introduces interference to the system, leading to a rise in the Bit Error Rate (BER). The mobile VLC experimental system provides a viable solution to the issue of mobile access in the integration of lighting and communication applications, establishing a solid practical foundation for future research.

Titanium Dioxide and N-Doped Carbon Hybrid Nanofiber Modulated Ru Nanoclusters for High-Efficient Hydrogen Evolution Reaction Electrocatalyst.

The designing and fabricating highly active hydrogen evolution reaction (HER) electrocatalysts that can superior to Pt/C is extremely desirable but challenging. Herein, the fabrication of Ru/TiO2/N-doped carbon (Ru/TiO2/NC) nanofiber is reported as a novel and highly active HER electrocatalyst through electrospinning and subsequent pyrolysis treatment, in which Ru nanoclusters are dispersed into TiO2/NC hybrid nanofiber. As a novel support, experimental and theoretical calculation results reveal that TiO2/NC can more effectively accelerate water dissociation as well as optimize the adsorption strength of *H than TiO2 and NC, thus leading to a significantly enhanced HER activity, which merely requires an overpotential of 18 mV to reach 10 mA cm-2, outperforming Pt/C in an alkaline solution. The electrolytic cell composed of Ru/TiO2/NC nanofiber and NiFe LDH/NF can generate 500 and 1000 mA cm-2 at voltages of 1.631 and 1.753 V, respectively. Furthermore, the electrolytic cell also exhibits remarkable durability for at least 100 h at 200 mA cm-2 with negligible degradation in activity. The present work affords a deep insight into the influence of support on the activity of electrocatalyst and the strategy proposed in this research can also be extended to fabricate various other types of electrocatalysts for diverse electrocatalytic applications.

Severity-stratification of interstitial lung disease by deep learning enabled assessment and quantification of lesion indicators from HRCT images.

BACKGROUND: Interstitial lung disease (ILD) represents a group of chronic heterogeneous diseases, and current clinical practice in assessment of ILD severity and progression mainly rely on the radiologist-based visual screening, which greatly restricts the accuracy of disease assessment due to the high inter- and intra-subjective observer variability. OBJECTIVE: To solve these problems, in this work, we propose a deep learning driven framework that can assess and quantify lesion indicators and outcome the prediction of severity of ILD. METHODS: In detail, we first present a convolutional neural network that can segment and quantify five types of lesions including HC, RO, GGO, CONS, and EMPH from HRCT of ILD patients, and then we conduct quantitative analysis to select the features related to ILD based on the segmented lesions and clinical data. Finally, a multivariate prediction model based on nomogram to predict the severity of ILD is established by combining multiple typical lesions. RESULTS: Experimental results showed that three lesions of HC, RO, and GGO could accurately predict ILD staging independently or combined with other HRCT features. Based on the HRCT, the used multivariate model can achieve the highest AUC value of 0.755 for HC, and the lowest AUC value of 0.701 for RO in stage I, and obtain the highest AUC value of 0.803 for HC, and the lowest AUC value of 0.733 for RO in stage II. Additionally, our ILD scoring model could achieve an average accuracy of 0.812 (0.736 - 0.888) in predicting the severity of ILD via cross-validation. CONCLUSIONS: In summary, our proposed method provides effective segmentation of ILD lesions by a comprehensive deep-learning approach and confirms its potential effectiveness in improving diagnostic accuracy for clinicians.

Trigeminal nerve-derived substance P regulates limbal stem cells by the PI3K-AKT pathway.

Trigeminal nerve-derived substance P (SP), a widespread neuropeptide, is known to maintain the corneal epithelial homeostasis and promote the closure of wound healing. Using comprehensive in vivo and in vitro assays and RNA-sequencing analysis, we aimed to unveil the positive effects of SP on the biological characteristics of limbal stem cells (LSCs) and the underlying mechanism. SP enhanced the proliferation and stemness of LSCs in vitro. Correspondingly, it rescued corneal defects, corneal sensitivity, and the expression of LSC-positive markers in a neurotrophic keratopathy (NK) mouse model in vivo. Topical injection of a neurokinin-1 receptor (NK1R) antagonist caused similar pathological changes as in corneal denervated mice and attenuated LSC-positive markers levels. Mechanistically, we revealed that SP regulated LSCs functions by modulating the PI3K-AKT pathway. Our findings showed that the trigeminal nerve regulates LSCs by releasing SP, which may provide new insights into the regulation of LSCs' fate and stem cell therapy.

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.

Development of multifunctional unmanned aerial vehicles versus ground seeding and outplanting: What is more effective for improving the growth and quality of rice culture?

The agronomic processes are complex in rice production. The mechanization efficiency is low in seeding, fertilization, and pesticide application, which is labor-intensive and time-consuming. Currently, many kinds of research focus on the single operation of UAVs on rice, but there is a paucity of comprehensive applications for the whole process of seeding, fertilization, and pesticide application. Based on the previous research synthetically, a multifunctional unmanned aerial vehicle (mUAV) was designed for rice planting management based on the intelligent operation platform, which realized three functions of seeding, fertilizer spreading, and pesticide application on the same flight platform. Computational fluid dynamics (CFD) simulations were used for machine design. Field trials were used to measure operating parameters. Finally, a comparative experimental analysis of the whole process was conducted by comparing the cultivation patterns of mUAV seeding (T1) with mechanical rice direct seeder (T2), and mechanical rice transplanter (T3). The comprehensive benefit of different rice management processes was evaluated. The results showed that the downwash wind field of the mUAV fluctuated widely from 0 to 1.5 m, with the spreading height of 2.5 m, and the pesticide application height of 3 m, which meet the operational requirements. There was no significant difference in yield between T1, T2, and T3 test areas, while the differences in operational efficiency and input labor costs were large. In the sowing stage, T1 had obvious advantages since the working efficiency was 2.2 times higher than T2, and the labor cost was reduced by 68.5%. The advantages were more obvious compared to T3, the working efficiency was 4 times higher than in T3, and the labor cost was reduced by 82.5%. During the pesticide application, T1 still had an advantage, but it was not a significant increase in advantage relative to the seeding stage, in which operating efficiency increased by 1.3 times and labor costs were reduced by 25%. However, the fertilization of T1 was not advantageous due to load and other limitations. Compared to T2 and T3, operational efficiency was reduced by 80% and labor costs increased by 14.3%. It is hoped that this research will provide new equipment for rice cultivation patterns in different environments, while improving rice mechanization, reducing labor inputs, and lowering costs.

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.

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.

Bacterial agents and changes in drug susceptibilities in cases of chronic dacryocystitis, Southern China.

PURPOSE: This study aimed to determine the susceptibility and the changes of bacterial agents of chronic dacryocystitis and determine the risk factors for bacterial prevalence and drug sensitivity to provide a reference for clinical selection of antibiotics. METHODS: A case-control study was conducted using 112 patients with chronic dacryocystitis and 112 patients with non-infectious ophthalmopathy between August 2017 and April 2018. Lacrimal and conjunctival sac secretions were cultured for aerobic and anaerobic bacteria. Forty-five patients with chronic dacryocystitis between November 2014 and November 2015 were also included. RESULTS: Positive bacterial cultures were obtained from 61.9% and 50.9% of chronic dacryocystitis and non-infectious ophthalmopathy patients, but the detection rates for pathogenic bacteria were 18.3% and 2.7%, respectively (P > 0.001). Gram-negative and anaerobic bacteria were significantly more prevalent in the patient group compared with the control group (P = 0.001 and 0.005, respectively). Bacteria were detected at a significantly higher rate in patients with irritant symptoms (itch or foreign-body sensation) than in those without (OR = 9.333, P = 0.002), particularly Staphylococcus (OR = 9.783, P = 0.002). 11.6% (10/86) and 55.8% (48/86) showed resistance to levofloxacin and tobramycin, respectively. Compared with three years ago, the detection rate for Gram-positive cocci decreased from 51.1% to 27.8% (χ2 = 8.054, P = 0.005) CONCLUSIONS: Gram-positive cocci, Gram-negative bacilli, and anaerobic bacteria were the predominant pathogens. The prevalence of Gram-positive bacteria in cases of chronic dacryocystitis is decreasing.

Vaginal Exposure to Candida albicans During Early Gestation Results in Adverse Pregnancy Outcomes via Inhibiting Placental Development.

Vulvovaginal candidiasis (VVC) is considered the second most common cause of vaginitis after bacterial vaginosis and the most common lower genital tract infection during pregnancy. Candida albicans (C. albicans), an opportunistic pathogen, is the major species causing VVC. Recently, increasing researches have shown that lower reproductive tract infection during pregnancy can lead to various adverse pregnancy outcomes. However, the underlying mechanisms are not fully understood. Hence, we successfully established a mouse model of vaginal C. albicans infection and characterized the adverse pregnancy outcomes. C. albicans infection strikingly increased abortion rate and decreased litter size. Further analysis of placental development demonstrated that placental structure was abnormal, including that the area of spongiotrophoblast (Spo) and labyrinth (Lab) was reduced, and the formation of placental vessel was decreased in Lab zone. Accordingly, the expression of marker genes during placental development was downregulated. Collectively, the above findings revealed that vaginal C. albicans infection during pregnancy can inhibit placental development and ultimately lead to adverse pregnancy outcomes. This study enhances our comprehension of the effect of VVC on pregnancy, and placental dysplasia as a feasible orientation to explore VVC during pregnancy.

The embryonic stem cell microenvironment inhibits mouse glioma cell proliferation by regulating the PI3K/AKT pathway.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common malignant tumor of the central nervous system, accounting for 48.6% of malignant tumors. The current standard treatment plan includes the widest range of safe surgical resection, supplemented by local brain radiotherapy and temozolomide concurrent chemotherapy; this can cause serious side effects. Even so, the median survival time of GBM patients is only 8 months, and the 5-year survival rate is only 5.5%. It is imminent to find new treatments. Early studies have shown that chicken and zebrafish embryos can reprogram cancer cells into a non-tumorigenic phenotype through the embryonic microenvironment. However, the effect of embryonic stem cell microenvironment on GBM and its possible mechanism are not clear. METHODS: In this study, the glioblastoma cell line, U118, in the brain was investigated. There were four experimental groups: GB, GE, GA and GT. U118 cells were harvested after culturing for 72 hours. Cell proliferation, apoptosis, reactive oxygen species (ROS) were examined using vasculogenic mimicry assays, quantitative real-time polymerase chain reaction (QRT-PCR), western blotting (WB) and flow cytometry. The differences in the biological function of U118 cells and the PI3K/protein kinase B (AKT) signaling pathway were compared between the groups. RESULTS: Compared with the GB control group, the GE co-culture group and GT chemotherapy group showed reduced cell proliferation, increased apoptosis, increased ROS, as well as decreased or inhibited vasculogenic mimicry. Expressions of cyclin B1 and cyclin D1 were also notably reduced, while that of Bax, Bcl-2, p53, Caspase-3, GSK-3ß, p21, and p27 were significantly increased. Moreover, the expression of PI3K, AKT, and mTOR were markedly decreased, whereas expression of PTEN increased considerably. Also, the expression of positive regulatory factors significantly increased, however negative regulatory factors decreased in the GA group compared to the GE group. CONCLUSIONS: The ESC microenvironment reverses glioma malignancy, partially via inhibition of the PI3K signaling pathway. Our study may have a significant impact and important clinical implications for cell therapy in the treatment of glioma.

Discovery and Validation of a Metastasis-Related Prognostic and Diagnostic Biomarker for Melanoma Based on Single Cell and Gene Expression Datasets.

BACKGROUND: Single cell sequencing can provide comprehensive information about gene expression in individual tumor cells, which can allow exploration of heterogeneity of malignant melanoma cells and identification of new anticancer therapeutic targets. METHODS: Single cell sequencing of 31 melanoma patients in GSE115978 was downloaded from the Gene Expression Omniniub (GEO) database. First, the limma package in R software was used to identify the differentially expressed metastasis related genes (MRGs). Next, we developed a prognostic MRGs biomarker in the cancer genome atlas (TCGA) by combining univariate cox analysis and the least absolute shrinkage and selection operator (LASSO) method and was further validated in another two independent datasets. The efficiency of MRGs biomarker in diagnosis of melanoma was also evaluated in multiple datasets. The pattern of somatic tumor mutation, immune infiltration, and underlying pathways were further explored. Furthermore, nomograms were constructed and decision curve analyses were also performed to evaluate the clinical usefulness of the nomograms. RESULTS: In total, 41 MRGs were screened out from 1958 malignant melanoma cell samples in GSE115978. Next, a 5-MRGs prognostic marker was constructed and validated, which show more effective performance for the diagnosis and prognosis of melanoma patients. The nomogram showed good accuracies in predicting 3 and 5 years survival, and the decision curve of nomogram model manifested a higher net benefit than tumor stage and clark level. In addition, melanoma patients can be divided into high and low risk subgroups, which owned differential mutation, immune infiltration, and clinical features. The low risk subgroup suffered from a higher tumor mutation burden (TMB), and higher levels of T cells infiltrating have a significantly longer survival time than the high risk subgroup. Gene Set Enrichment Analysis (GSEA) revealed that the extracellular matrix (ECM) receptor interaction and epithelial mesenchymal transition (EMT) were the most significant upregulated pathways in the high risk group. CONCLUSIONS: We identified a robust MRGs marker based on single cell sequencing and validated in multiple independent cohort studies. Our finding provides a new clinical application for prognostic and diagnostic prediction and finds some potential targets against metastasis of melanoma.

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.

Comprehensive analysis of cancer hallmarks in cutaneous melanoma and identification of a novel unfolded protein response as a prognostic signature.

Molecular pathways regulating the initiation and development of melanoma are potential therapeutic targets for this aggressive skin cancer. Therefore, transcriptome profiles of cutaneous melanoma were obtained from a public database and used to systematically evaluate cancer hallmark pathways enriched in melanoma. Finally, the unfolded protein response pathway was screened out, and the unfolded protein response-related genes were used to develop a robust biomarker that can predict the prognosis of melanoma, especially for younger, metastatic and high Clark level patients. This biomarker was further validated in two other independent datasets. In addition, melanoma patients were divided into high- and low-risk subgroups by applying a risk score system. The high-risk group exhibited higher immune infiltration and higher expression of N6-methyladenosine RNA methylation regulators, and had significantly shorter survival times than the low-risk subgroup. Gene Set Enrichment Analysis revealed that, among the enriched genes, gene sets involved in immune response and the extracellular matrix receptor interaction were significantly activated in the high-risk group. Our findings thus provide a new clinical application for prognostic prediction as well as potential targets for treatment of melanoma.

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.

Corneal Recovery Following Rabbit Peripheral Blood Mononuclear Cell-Amniotic Membrane Transplantation with Antivascular Endothelial Growth Factor in Limbal Stem Cell Deficiency Rabbits.

Background: Limbal stem cell deficiency (LSCD) is a refractory ocular surface disorder characterized by progressive corneal epithelial degeneration, conjunctivalization, and neovascularization, potentially leading to blindness. There are currently no effective therapeutic options for patients experiencing routine symptomatic treatment failure. Transplantation of amniotic membrane (AM) with adherent stem cells (but not bare AM transplantation alone) has shown promise in preclinical studies for ocular surface restoration. A major limitation, however, is finding a reliable stem cell source. Stem cells can be isolated from the peripheral blood mononuclear cell (PBMC) population, and these PBMC-derived stem cells have numerous advantages over allogeneic and other autologous stem cell types for therapeutic application, including relative ease of acquisition, nonimmunogenicity, and the absence of ethical issues associated with embryonic stem cells. Experiment: We examined the efficacy of autologous PBMC-AM sheet cultures combined with postoperative antiangiogenesis treatment for corneal restoration in LSCD model rabbits. Rabbit PBMCs (rPBMCs) were isolated, labeled with EdU for in vivo tracing, and then cultured on AMs in conditioned medium before transplantation. Rabbits were transplanted with bare AMs (group 1), rPBMC-AM sheets (group 2), or rPBMC-AM sheets plus postoperative treatment with the vascular endothelial growth factor antagonist bevacizumab (group 3). Corneal opacity and neovascularization were monitored by slit-lamp imaging for 8 weeks and corneas were examined histologically at 1 and 2 months. Results: Corneal opacity decreased in all three groups over 8 weeks, but was significantly lower in group 2 and even lower in group 3. Corneal neovascularization was significantly higher in group 1 throughout the observation period, and significantly lower in group 3 than group 1 and 2 by 8 weeks post-transplant. At 4 weeks, the corneal surface completed epithelialization (although thinner than normal) in group 3 but still patchy in groups 1 and 2. By 8 weeks, the epithelium in group 3 was complete and smooth, resembling a normal epithelium. Integrin ß1 as a progenitor marker was also generally higher in groups 2 and 3. Conclusions: Autologous rPBMC-AM sheets with post-transplant topical bevacizumab can effectively facilitate corneal epithelium recovery in a LSCD model, suggesting clinical utility for LSCD-related ocular surface diseases. Impact statement Limbal stem cell deficiency (LSCD) increases corneal opacity and vascularization, resulting in severe visual impairment or even blindness. Traditional surgical limbal transplant is currently the main treatment option for LSCD, but carries the risks of rejection and immunosuppressant side effects. Autologous stem cell-based therapy is a promising alternative approach, but a reliable stem cell source is a major limitation. We report that transplantation of autologous rabbit peripheral blood mononuclear cell-amniotic membrane sheets plus antivascular endothelial growth factor restored avascular transparent cornea in a rabbit LSCD model. These results demonstrate a potentially effective approach for ocular surface reconstruction in bilateral LSCD.