Oxidative MnO2 Template Assisted Electrochemical Fabrication of Graphene/Polypyrrole Supercapacitor Electrodes.

Improving the morphological structure of active materials is a reliable strategy for the fabrication of high-performance supercapacitor electrodes. In this study, we introduce a feasible approach to constructing the graphene/polypyrrole (PPy) composite film implanted onto the current collector through a two-step electrochemical deposition method utilizing MnO2 as an intermediary template. The reduced graphene oxide (rGO) hydrogel film is first hydrothermally grown on a carbon cloth (CC) substrate to obtain a porous rGO@CC electrode on which MnO2 is electrodeposited. Then the as-prepared rGO/MnO2@CC electrode is subjected to the electrochemical polymerization of pyrrole, with MnO2 acting as an oxidizing template to facilitate the oxidative polymerization of pyrrole, ultimately yielding an rGO/PPy composite film on CC. The PPy synthesized via this methodology exhibits a distinctive interconnected structure, resulting in superior electrochemical performance compared with the electrode with PPy directly electrodeposited on rGO@CC. The optimized electrode achieves an impressive specific capacitance of 583.6 F g-1 at 1 A g-1 and retains 83% of its capacitance at 20 A g-1, with a capacitance loss of only 9.5% after 5000 charge-discharge cycles. The corresponding all-solid-state supercapacitor could provide a high energy density of 22.5 Wh kg-1 and a power density of 4.6 kW kg-1, with a capacitance retention of 82.7% after 5000 charge-discharge cycles. Furthermore, the device also demonstrates good flexibility performance upon bending at 90 and 180°. This work presents an innovative method for the preparation of carbon material/conducting polymer electrodes with specific structural characteristics and superior performance.

One-Step Fabrication of Integrated Graphene/Polypyrrole/Carbon Cloth Films for Supercapacitor Electrodes.

The facile and cost-effective preparation of supercapacitor electrodes is significant for the application of this kind of electrochemical energy-storing module. In this work, we designed a feasible strategy to fabricate a binary active material onto a current collector in one step. A colloidal mixture of graphene oxide and pyrrole layered on a carbon cloth could undergo a redox reaction through a mild hydrothermal process to yield a reduced graphene oxide/polypyrrole hydrogel film anchored onto the carbon cloth. The integrated electrode with the porous graphene/polypyrrole active material could be directly utilized as a freestanding working electrode for electrochemical measurements and the assembly of supercapacitor devices. The as-prepared electrode could achieve a high capacitance of 1221 mF cm-2 at 1 mA cm-2 (531 F g-1) with satisfactory cycling stability. The constructed symmetric supercapacitor with two optimal electrodes could provide an energy density of 70.4 µWh cm-2 (15.3 Wh kg-1). This work offers a feasible pathway toward the integration of graphene/conducting polymer composites as electrochemical electrodes.

Enhancing QoE for Mobile Users by Environment-Aware HTTP Adaptive Streaming.

HTTP adaptive streaming (HAS) has become a dominated media streaming paradigm in today's Internet, which enriches the user's experience by matching the video quality with the dynamic network conditions. A range of HAS mechanisms have been proposed to enhance the Quality of Experience (QoE). However, existing mechanisms ignore the environmental impact in the QoE evaluation of mobile users, while the popularity of mobile video allows users to watch videos in diversified scenarios. In this paper, we propose an environment-aware HAS scheme that fully concentrates on the different criteria for evaluating video QoE under different environments. Using the advantage of the sensors in mobile phones, the scheme constructs and validates a video QoE model based on environment perception and then designs a model-driven, environment-aware HAS rate adaptation algorithm. We also evaluate the scheme with an environment-aware DASH (Dynamic Adaptive Streaming over HTTP) player in real mobile environments. Compared to the benchmark HAS mechanism, the experimental results demonstrate that our scheme can provide appropriate differentiated rate adaptation for different environments, resulting in a higher QoE.

Methotrexate and electrostimulation cooperate to alleviate the relapse of psoriasiform skin inflammation by suppressing memory T cells.

Methotrexate (MTX) is an immunosuppressant used to treat autoimmune diseases, including psoriasis. However, like other immunosuppressants, MTX alone does not prevent their recurrence. Electrostimulation (ES) has been utilized to treat some inflammatory disorders without any major side-effect. But it remains unknown if ES alone, or together with MTX, ameliorates autoimmune disease relapse: a sticky medical problem. In particular, the mechanisms underlying ES action remain unclear. The objective of this study was to determine an impact of ES and/or MTX on psoriasis relapse and their potential cooperation. We found that regional ES, but not MTX, ameliorated psoriasiform skin inflammation recurrence. Interestingly, treatment with both MTX and ES further prevented psoriasis recurrence compared to ES alone. Moreover, ES downregulated potassium channel Kv1.3 on T-cells and reduced CD4+/CD8+ effector memory (TEM) and CD8+ skin-resident memory T (TRM) cells, while ES plus MTX further decreased CD8+ TEM/TRM cells compared to ES alone. However, ES failed to further attenuate psoriasis recurrence or suppress T cell memory in Kv1.3-deficient mice, whereas lack of Kv1.3 itself ameliorated psoriasis relapse by shrinking T cell memory pool. Importantly, ES moderately inhibited T-cell proliferation in vitro. ES also reduced human CD8+ TRM cells and attenuated human skin lesions in humanized mice grafted with lesional skin from patients with recurrent psoriasis, with an enhanced efficacy in mice treated with both ES and MTX. Thus, ES and MTX cooperated to prevent psoriasis relapse by reducing T-cell memory via targeting potassium channel Kv1.3. Our studies may be implicated for treating human psoriasis.

The Benefit of the Optimized Formula of Yinxieling in Psoriasis Vulgaris via Regulation on Autophagy Based on microRNA Expression Profile and Network Pharmacology Analysis.

Background: Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients, causing enormous suffering and exerting considerable economic burdens on the health care system as a whole. In more than a decade of clinical use, the optimized formula of Yinxieling (PSORI-CM01) has consistently demonstrated its effectiveness for treating psoriasis. However, its underlying mechanism remains largely unexplored. Methods: The network pharmacology analysis was conducted to predict the mechanism and protective effect of PSORI-CM01 in treating psoriasis. Subsequently, we collected blood samples from 21 patients with psoriasis as part of a randomized, double-blind, and double-dummy clinical trial for microRNA expression profiling. Finally, it was experimentally confirmed that PSORI-CM01 improved psoriasis by regulating miR-20a-3p and miR-3184-3p expression. Results: As a result of the network pharmacology analysis, PSORI-CM01 improved psoriasis through the regulation of autophagy, cellular apoptosis, cellular proliferation, and anti-inflammatory processes. In the target-miRNA regulatory network, these key targets were mainly associated with the regulation of hsa-miR-20a-3p, hsa-miR-155-5p, has-miR-3184-3p, hsa-miR-328-3p and hsa-miR-124-3p. Based on the microRNA expression profiling results, the PSORI-CM01 treatment group exhibited five up-regulated genes and 16 down-regulated genes compared with the healthy control group. In particular, miR-20a-3p and miR-3184-3p were the primary differentially expressed microRNAs, and they were significantly enriched in the signaling pathways involving autophagy, apoptosis, proliferation, and anti-inflammation. Further experiments confirmed that PSORI-CM01 effectively regulates miR-20a-3p and miR-3184-3p, resulting in increased autophagy. Conclusion: We demonstrated by combining network pharmacology and clinical studies of miRNA expression profiles in PBMCs that PSORI-CM01 effectively modulated miR-20a-3p and miR-3184-3p, leading to an increase in autophagy and a decrease in keratinocyte proliferation.

Potential biomarkers for psoriasis topical treatment by in-depth serum proteomics.

BACKGROUND: Psoriasis is a chronic skin disease, and topical sequential therapy with a combination of calcipotriol and calcipotriol betamethasone is currently approved topical treatment. However, the exact mechanism by which this treatment regimen relieves psoriasis is unknown. METHOD: We assembled a cohort of 65 psoriasis patients and divided post-treatment cohort into responder group and non-responder group according to the Psoriasis Area Severity Index (PASI) score after 12-week treatment. We measured the expression levels of proteins in collected 130 serum samples using our in-depth proteomics platform with a data-independent acquisition mass spectrometer and antibody microarray. We performed bioinformatics analyses of the biologic processes and signaling pathways that were changed in the responder group and constructed a proteomics landscape of psoriasis pathogenesis response to treatment. We then validated the biomarkers of disease severity in an independent cohort of 88 samples using an enzyme-linked immunosorbent assay. RESULTS: We first identified 174 differentially expressed proteins (DEPs) for comparative analysis of proteins between responders and non-responders at baseline (p < 0.05). Then pathway analysis showed that the responders focused more on signaling molecules and interaction, complement and coagulation cascades, whereas the non-responders more on signal transduction and IL-17 signaling pathways. We further identified four candidate biomarkers (COLEC11, C1QA, BNC2, ITIH4) response to treatment. We also found 125 DEPs (p < 0.05) after treatment compared with before treatment in responder group. Pathway analysis showed an enrichment in pathways related to complement and coagulation cascades, phagosome, ECM-receptor interaction, cholesterol metabolism, vitamin digestion and absorption. CD14 was validated as potential biomarkers for the disease severity of psoriasis and treatment targets. CONCLUSION: In this work, we analyzed the response to topical sequential therapy and finally identified four biomarkers. Additionally, we found that topical sequential therapy may alleviate psoriasis by regulating lipid metabolism and modulating the immune response by affecting the complement activation process.

Multi-omics approach identifies PI3 as a biomarker for disease severity and hyper-keratinization in psoriasis.

BACKGROUND: Psoriasis is an immune-mediated inflammatory skin disease. Psoriasis severity evaluation is important for clinicians in the assessment of disease severity and subsequent clinical decision making. However, no objective biomarker is available for accurately evaluating disease severity in psoriasis. OBJECTIVE: To define and compare biomarkers of disease severity and progression in psoriatic skin. METHODS: We performed proteome profiling to study the proteins circulating in the serum from patients with psoriasis, psoriatic arthritis and ankylosing spondylitis, and transcriptome sequencing to investigate the gene expression in skin from the same cohort. We then used machine learning approaches to evaluate different biomarker candidates across several independent cohorts. In order to reveal the cell-type specificity of different biomarkers, we also analyzed a single-cell dataset of skin samples. In-situ staining was applied for the validation of biomarker expression. RESULTS: We identified that the peptidase inhibitor 3 (PI3) was significantly correlated with the corresponding local skin gene expression, and was associated with disease severity. We applied machine learning methods to confirm that PI3 was an effective psoriasis classifier, Finally, we validated PI3 as psoriasis biomarker using in-situ staining and public datasets. Single-cell data and in-situ staining indicated that PI3 was specifically highly expressed in keratinocytes from psoriatic lesions. CONCLUSION: Our results suggest that PI3 may be a psoriasis-specific biomarker for disease severity and hyper-keratinization.

Association of the characteristics of the blood metabolome and gut microbiome with the outcome of methotrexate therapy in psoriasis.

Metabolic status and gut microecology are implicated in psoriasis. Methotrexate (MTX) is usually the first-line treatment for this disease. However, the relationship between MTX and host metabolic status and the gut microbiota is unclear. This study aimed to characterize the features of blood metabolome and gut microbiome in patients with psoriasis after treatment with MTX. Serum and stool samples were collected from 15 patients with psoriasis. Untargeted liquid chromatography-mass spectrometry and metagenomics sequencing were applied to profile the blood metabolome and gut microbiome, respectively. We found that the response to MTX varied according to metabolomic and metagenomic features at baseline; for example, patients who had high levels of serum nutrient molecular and more enriched gut microbiota had a poor response. After 16 weeks of MTX, we observed a reduction in microbial activity pathways, and patients with a good response showed more microbial activity and less biosynthesis of serum fatty acid. We also found an association between the serum metabolome and the gut microbiome before intervention with MTX. Carbohydrate metabolism, transporter systems, and protein synthesis within microbes were associated with host metabolic clusters of lipids, benzenoids, and organic acids. These findings suggest that the metabolic status of the blood and the gut microbiome is involved in the effectiveness of MTX in psoriasis, and that inhibition of symbiotic intestinal microbiota may be one of the mechanisms of action of MTX. Prospective studies in larger sample sizes are needed to confirm these findings.

Punicalagin Alleviates Psoriasis by Inhibiting NF-κB-Mediated IL-1ß Transcription and Caspase-1-Regulated IL-1ß Secretion.

Psoriasis is a chronic and inflammatory skin disorder characterized by inflammation and epidermal hyperplasia. Punicalagin (PUN) is a main active ingredient of pomegranate (Punica granatum L.) peel with multiple biological activities, such as antibacterial, antioxidant and anti-tumor effects. However, the potential effect of PUN on psoriasis remains unknown. In this study, we want to investigate the pharmacological effect of PUN on psoriasis by using imiquimod (IMQ)-induced psoriatic mice model in vivo and tumor necrosis factor a (TNF-α) and interleukin-17A (IL-17A)-stimulated HaCaT cells in vitro. Our results showed that PUN can effectively alleviate the severity of psoriasis-like symptoms. Mechanistically, PUN potently suppresses the aberrant upregulation of interleukin-1ß (IL-1ß) and subsequent IL-1ß-mediated inflammatory cascade in keratinocytes by inhibiting the nuclear factor kappa B (NF-κB) activation and cleaved caspase-1 expression in vitro and in vivo. Taken together, our findings indicate that PUN can relieve psoriasis by repressing NF-κB-mediated IL-1ß transcription and caspase-1-regulated IL-1ß secretion, which provide evidence that PUN might represent a novel and promising candidate for the treatment of psoriasis.

Adipose-derived mesenchymal stem cells (AD-MSCs) in the treatment for psoriasis: results of a single-arm pilot trial.

BACKGROUND: Psoriasis is an immune-mediated inflammatory skin disease that causes significant physical and psychological burden to the patient. While there is currently no curative treatment, recent breakthroughs involving stem cell therapy, in particular, adipose tissue-derived from mesenchymal stem cells (AD-MSCs), have been promising. This single-arm study evaluated the feasibility, safety, and efficacy of AD-MSC infusions for the treatment of moderate to severe psoriasis. METHODS: A single-center, open-label pilot study was conducted involving seven subjects with moderate to severe psoriasis. Patients received intravenous injections of AD-MSCs (0.5×106 cells/kg) monthly for 12 weeks. The primary outcome was patient safety evaluated by the incidence of adverse events (AEs). Secondary parameters included changes in the Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), Body Surface Area (BSA), and Pruritus Scores on the Visual Analogue Scale (VAS). RESULTS: A total of 7 patients, including 6 males and 1 female, with an average age of 50.71 years (range, 35-65 years) were enrolled in this study. Four patients completed the trial and two participants completed the one-year follow-up. There were 16 AEs (including 1 grade 2 event and 15 grade 1 events) recorded during the treatment period and 1 serious adverse event (SAE) documented during the follow-up period. The most common AEs were transient fevers (5/16) which were likely to be related to the infusions, followed by pharyngitis (3/16), and headaches (2/16). Both of them were unlikely to be related to the infusions. The procedure was determined to be safe, and no SAEs relating to AD-MSCs were observed. Two patients reached and maintained a PASI-50, indicating a 50% improvement in the PASI score, after one year without any treatment. CONCLUSIONS: These results suggested that intravenous injection of AD-MSCs is safe and may be a therapeutic option for the treatment of patients with psoriasis. Future studies involving larger test cohorts and a control group are warranted.

The Gene Expression Analysis of Peripheral Blood Monocytes From Psoriasis Vulgaris Patients With Different Traditional Chinese Medicine Syndromes.

Psoriasis is chronic skin disease and an important health concern. Traditional Chinese Medicine (TCM) has shown great promise in the treatment of psoriasis. However, the correlation between TCM Syndromes and genomics of psoriasis has not been evaluated. Here, we analyzed gene expression profiling of monocytes from psoriasis vulgaris patients with different TCM syndrome types to reveal the molecular basis of different psoriasis syndromes. Of the 62 cases of psoriasis vulgaris recruited, 16, 23, and 23 cases were of blood-heat syndrome, blood stasis syndrome, and blood-dryness syndrome, respectively; 10 healthy controls were recruited as controls. Affymertix's Gene Chip ®clariom D gene chip was used to detect the gene expression profile of peripheral blood monocytes collected from recruited individuals. Compared with the healthy control group, 1570 genes were up-regulated and 977 genes were down-regulated in the psoriasis vulgaris patients group; 798 genes and 108 genes were up- and down-regulated in the blood-heat syndrome group respectively; 319 and 433 genes were up- and down-regulated in the blood-dryness syndrome group, respectively; and 502 and 179 genes were up-and down-regulated in the blood-stasis syndrome group. Our analyses indicated not only common differential genes and pathways between psoriasis syndrome groups and healthy controls, but also syndrome-specific genes and pathways. The results of this study link the three syndromes at the gene level and will be useful for clarifying the molecular basis of TCM syndromes of psoriasis. Clinical Trial Registration: (http://www.chictr.org.cn/showproj.aspx?proj=4390), identifier (ChiCTR-TRC-14005185).

Analysis of microRNA expression in peripheral blood monocytes of three Traditional Chinese Medicine (TCM) syndrome types in psoriasis patients.

BACKGROUND: To analyze the expression of miRNA (microRNA) in peripheral blood mononuclear cells in patients with Psoriasis vulgaris with different TCM syndromes by miRNA chip. It further revealed the micromaterial basis of different syndrome types of psoriasis at the miRNA level. METHODS: Peripheral blood monocytes were collected and prepared from 30 patients with Psoriasis vulgaris (including 9 patients of blood heat syndrome, 8 patients of blood stasis syndrome, and 13 patients of blood dry syndrome) and 9 healthy controls. The miRNA expression profile of peripheral blood monocytes was detected by Agilent Hum miRNA chip. RESULTS: Compared to the healthy control group, 156 upregulated and 242 downregulated miRNAs were detected in all psoriasis patients. Compared to the healthy control group, 40 miRNAs were upregulated and 44 were downregulated in the blood heat syndrome group. Furthermore, there were 49 upregulated miRNAs and 44 downregulated miRNAs in the dry syndrome group as compared to the healthy control group. Also, 67 miRNAs were upregulated and 154 miRNAs were downregulated in the blood stasis syndrome group as compared to the healthy control group. CONCLUSIONS: There are common different miRNAs and pathways, as well as specific miRNAs between the psoriasis and the healthy control groups.Trial registration ChiCTR-TRC-14005185 registered on August 8, 2014.