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IGFBP6, a member of the IGF binding protein (IGFBP) family, is a specific inhibitor of insulin-like growth factor II (IGF-II) and can inhibit the growth of malignant tumors overexpressing IGF-II. Type 2 diabetes (T2D) is a basic disorder of glucose metabolism that can be regulated by IGF-related pathways. We performed bioinformatics analysis of the TCGA database to explore the possible mechanism of IGFBP6 in breast cancer (BC) metabolism and prognosis and collected clinical samples from BC patients with and without T2D to compare and verify the prognostic effect of IGFBP6. In our study, the levels of IGFBP1–6 were positively correlated with overall survival (OS) in patients with breast cancer. IGFBP6 was upregulated in estrogen receptor (ER)-positive BC, and ER-positive and progesterone receptor (PR) positive patients had a higher expression level of IGFBP6 than ER-negative and PR-negative patients. IGFBP6 could be used as an independent prognostic factor in BC. The expression of IGFBP6 was decreased in BC tissue, and BC tissue from patients with T2D had lower IGFBP6 expression levels than BC tissue from patients without T2D. IGFBP6 is mainly involved in the PI3K–Akt and TGF-β signaling pathways and tumor microenvironment regulation. In terms of metabolism, the expression of IGFBP6 was negatively correlated with that of most glucose metabolism-related genes. IGFBP6 expression was mainly correlated with mutations in TP53, PIK3CA, CDH1, and MAP3K1. In addition, the upregulation of IGFBP6 in BC increased the drug sensitivity to docetaxel, paclitaxel and gemcitabine. Overall, these results indicated that high expression of IGFBP6 is associated with a good prognosis in BC patients, especially in those without T2D. It is not only involved in the maintenance of the tumor microenvironment in BC but also inhibits the energy metabolism of cancer cells through glucose metabolism-related pathways. These findings may provide a new perspective on IGFBP6 as a potential prognostic marker for BC. [ABSTRACT FROM AUTHOR]

Skin damage is one of the most prevalent human injuries, which affects the health of human beings. However, skin damage is often accompanied by bacterial infection and wound microenvironment changes, causing damage to normal cells and inhibiting wound healing. Herein, we designed a thermal-responsive antibacterial hydrogel (GAG hydrogel) loaded with catalase (CAT)-like Au@Pt@MgSiO3 nanoparticles (APM NPs) and gentamicin (GM) to promote wound healing. The GAG hydrogel was used in a photothermal therapy (PTT)/antibiotic combination to kill bacteria, reduce the use of antibiotics, improve the wound microenvironment, promote cell proliferation, and accelerate wound healing. Under near-infrared laser irradiation, APM NPs in the hydrogel generated local hyperthermia to kill bacteria. Meanwhile, the generated heat led to a change in the hydrogel's morphology, enabling it to release GM and APM NPs to prevent the overuse of antibiotics. Subsequently, the CAT-like ability of the APM NPs decreased the oxidative stress caused by hydrogen peroxide (H2O2), thus remodeling the wound microenvironment. Then, the weakly acidic microenvironment of the wound caused the decomposition of the APM NPs and the release of magnesium ions (Mg2+), promoting the growth and migration of cells for wound healing. Therefore, the studied thermal-responsive antibacterial (GAG) hydrogel has potential in the field of wound healing. [ABSTRACT FROM AUTHOR]

The Fermi level of graphene on different substrates usually changes significantly due to the interface difference between graphene and two-dimensional semiconductors. This feature opens many possibilities of manipulating optoelectronic devices by constructing graphene heterostructures through interface modification. Herein, we report the fabrication and optoelectronic response of an unconventional heterojunction device based on a graphene–MoSe2 hybrid interface. Different from the traditional three or more layered structure where the semiconductor is sandwiched between two electrodes, this device contains only two atomic layers: the MoSe2 layer serving as the photon absorber and the graphene layer functioning as the charge acceptor and both electrodes. This structure looks like short-circuited but shows an obvious photoelectric response, which is aided by electron transfers from MoSe2 to graphene. The photocurrent generation is explored quantitatively with electronic dynamics of graphene aided with ultrafast measurements. The two-layered architecture simplifies the fabrication of atomic-thick optoelectronic devices, allowing the as-grown semiconductors to be directly used and eliminating the damage-prone transfer process. [ABSTRACT FROM AUTHOR]

The development of colitis‐associated colorectal cancer is known to be associated with the inflammation‐dysplasia‐carcinoma pathway, and thus, chronic inflammation represents an inducer and promoter of cancer. To inhibit the evolution from colitis to colorectal cancer and provide an efficient anticancer therapy, a surface‐engineered vanadium carbide MXene nanoenzyme (MXenzyme) is developed with both amino functionalization and gallium doping (Ga/V2C‐NH2). Benefiting from multiple enzyme‐mimicking activities, MXenzymes have shown great potential to decrease excessive reactive oxygen species and inhibit the levels of proinflammatory cytokines, resulting in good anti‐inflammatory effects on dextran sulfate sodium‐induced acute colitis. Moreover, the gallium‐doped MXene with an amino‐functionalized surface can mediate improved MXene‐tumor interactions and inhibitory effects on cell proliferation, achieving precise and efficient chemo‐photothermal therapy. Elemental doping into MXene is also highlighted as a feasible strategy to achieve the loading and controlled release of gallium. As a result, complete tumor ablation without further recurrence is observed for the colon cancer‐bearing mice that receive Ga/V2C‐NH2 and near infrared irradiation, while the MXenzyme system displays excellent biocompatibility at both the cellular and animal levels. These findings not only enrich the research of MXene, but also illustrate its efficient therapeutic promise in anti‐inflammation and photoenhanced antitumor therapy of colon diseases. [ABSTRACT FROM AUTHOR]

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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Objectives: The precise pathogenesis of psoriasis remains incompletely explored. We aimed to better understand the underlying mechanisms of psoriasis, using a systems biology approach based on transcriptomics and microbiome profiling. Methods: We collected the skin tissue biopsies and swabs in both lesional and non‐lesional skin of 13 patients with psoriasis, 15 patients with psoriatic arthritis and healthy skin from 12 patients with ankylosing spondylitis. To study the similarities and differences in the molecular profiles between these three conditions, and the associations between the host defence and microbiota composition, we performed high‐throughput RNA‐sequencing to quantify the gene expression profile in tissues. The metagenomic composition of 16S on local skin sites was quantified by clustering amplicon sequences and counted into operational taxonomic units. We further analysed associations between the transcriptome and microbiome profiling. Results: We found that lesional and non‐lesional samples were remarkably different in terms of their transcriptome profiles. The functional annotation of differentially expressed genes showed a major enrichment in neutrophil activation. By using co‐expression gene networks, we identified a gene module that was associated with local psoriasis severity at the site of biopsy. From this module, we found a 'core' set of genes that was functionally involved in neutrophil activation, epidermal cell differentiation and response to bacteria. Skin microbiome analysis revealed that the abundances of Enhydrobacter, Micrococcus and Leptotrichia were significantly correlated with the genes in core network. Conclusions: We identified a core gene network that associated with local disease severity and microbiome composition, involved in the inflammation and hyperkeratinization in psoriatic skin. [ABSTRACT FROM AUTHOR]

In this study, hot stamping tests on continuous glass fiber (GF)-reinforced thermoplastic (PP) composites were conducted under different process parameters using a self-designed hemispherical hot stamping die with a heating system. The effects of parameters such as preheating temperature, stamping depth, and stamping speed on the formability of the fabricated parts were analyzed using optical microscopy and scanning electron microscopy (SEM). The test results show that the suitable stamping depth should be less than 15 mm, the stamping speed should be less than 150 mm/min, and the preheating temperature should be about 200 °C. From the edge of the formed parts to their pole area, a thin-thick-thin characteristic in thickness was observed. Under the same preheating temperature, the influence of stamping depth on the thickness variation of the formed parts was more significant than the stamping speed. The primary defects of the formed parts were cracking, wrinkling, delamination, and fiber exposure. Resin poverty often occurred in the defect area of the formed parts and increased with stamping depth and stamping speed. [ABSTRACT FROM AUTHOR]

Early diagnosis is an effective strategy for decreasing breast cancer mortality. Ultrasonography is one of the most predominant imaging modalities for breast cancer owing to its convenience and non-invasiveness. The present study aimed to develop a model that integrates age with Breast Imaging Reporting and Data System (BI-RADS) lexicon to improve diagnostic accuracy of ultrasonography in breast cancer. This retrospective study comprised two cohorts: A training cohort with 975 female patients from Renmin Hospital of Wuhan University (Wuhan, China) and a validation cohort with 500 female patients from Maternal and Child Health Hospital of Hubei Province (Wuhan, China). Logistic regression was used to construct a model combining BI-RADS score with age and to determine the age-based prevalence of breast cancer to predict a cut-off age. The model that integrated age with BI-RADS scores demonstrated the best performance compared with models based solely on age or BI-RADS scores, with an area under the curve (AUC) of 0.872 (95% CI: 0.850-0.894, P<0.001). Furthermore, among participants aged <30 years, the prevalence of breast cancer was lower than the lower limit of the reference range (2%) for BI-RADS subcategory 4A lesions but within the reference range for BI-RADS category 3 lesions, as indicated by linear regression analysis. Therefore, it is recommended that management for this subset of participants are categorized as BI-RADS category 3, meaning that biopsies typically indicated could be replaced with short-term follow-up. In conclusion, the integrated assessment model based on age and BI-RADS may enhance accuracy of ultrasonography in diagnosing breast lesions and young patients with BI-RADS subcategory 4A lesions may be exempted from biopsy. [ABSTRACT FROM AUTHOR]

Early evidence indicated that cancer patients are at increased risk of adverse outcomes and mortality after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To determine the putative mechanism by which SARS-CoV-2 affects patients with cancers, we conducted a preliminary exploration at the molecular level. We collected differentially expressed proteins (DEPs) in the lung, liver, kidney, and thyroid of postmortem coronavirus disease 2019 (COVID-19) and non-COVID-19 patients from iProX database. Furthermore, we collected differentially expressed genes (DEGs) related to overall survival (OS) in lung cancer, liver cancer, kidney cancer and thyroid cancer based on the Cancer Genome Atlas (TCGA) database. We obtained the intersection of DEPs and DEGs and identified the roles of shared and remaining DEPs in corresponding cancers based on published research. Finally, we found 192, 179, 154 and 147 DEPs in lung, liver, kidney and thyroid tissues and 486, 1140, 2245 and 31 DEGs related to OS in lung cancer, liver cancer, kidney cancer and thyroid cancer, respectively. 4, 8, 6 and 0 shared genes/proteins and 48, 42, 14 and 10 remaining proteins were verified to play a role in lung cancer, liver cancer, kidney cancer and thyroid cancer, respectively. Changes in 85% (44/52), 78% (39/50), 80% (16/20) and 90% (9/10) of the verified genes/proteins, including shared and remaining genes, showed poor effects on patients with the 4 cancer types with COVID-19. In conclusion, the changes in genes/proteins caused by SARS-CoV-2 might dictate the different degrees of adverse outcomes in patients with different tumors. [ABSTRACT FROM AUTHOR]

Objective: Osteoarthritis (OA) presents cartilage damage in addition to chronic inflammation. However, self-recovery of damaged cartilage in an inflammatory environment is not possible. Mesenchymal stem cells (MSCs) in the bone marrow are a source of regenerative repair of damaged cartilage. To date, whether intra-luminal administration of the bone marrow can delay the progression of OA is still unknown. This study, therefore, aimed to explore the role of intra-bone marrow injection of Magnesium isoglycyrrhizinate (MgIG) in delaying the OA progression and to investigate the underlying mechanism. Methods: Rabbit OA models were established using the anterior cruciate ligament transection method while a catheter was implanted into the bone marrow cavity. 1 week after surgery, MgIG treatment was started once a week for 4 weeks. The cartilage degradation was analyzed using hematoxylin–eosin staining, Masson's trichrome staining and Alcian blue staining. Additionally, the pro-inflammatory factors and cartilage regeneration genes involved in the cartilage degeneration and the underlying mechanisms in OA were detected using enzyme-linked immunosorbent assay, quantitative real-time PCR (qRT-PCR) and Western blotting. Results: The results of histological staining revealed that intra-bone marrow injection of MgIG reduced degeneration and erosion of articular cartilage, substantially reducing the Osteoarthritis Research Society International scores. Furthermore, the productions of inflammatory cytokines in the bone marrow cavity and articular cavity such as interleukin-1β(IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) were inhibited upon the treatment of MgIG. At the same time, the expression of alkaline phosphate, tartrate-resistant acid phosphatase-5b (TRAP-5b) and C-telopeptides of type II collagen (CTX-II) in the blood also decreased and was positively correlated. On the contrary, cartilage-related genes in the bone marrow cavity such as type II collagen (Col II), Aggrecan (AGN), and SRY-box 9 (SOX9) were up-regulated, while matrix metalloproteinase-3 (MMP-3) was down-regulated. Mechanistically, MgIG was found to exert an anti-inflammatory effect and impart protection to the cartilage by inhibiting the NF-κB pathway. Conclusion: Intra-bone marrow injection of MgIG might inhibit the activation of the NF-κB pathway in the progression of OA to exert an anti-inflammatory effect in the bone marrow cavity and articular cavity, thereby promoting cartilage regeneration of MSCs in the bone marrow, making it a potential new therapeutic intervention for the treatment of OA. [ABSTRACT FROM AUTHOR]

The evolution of writing system reflects the development of civilization. Using a single molecular layer of "ink" to record invisible messages on an atomic‐layered paper represents the ultimate thinness of classical writing system and steganography. A stable and convenient atomic‐thin information steganography under ambient conditions is realized using a monolayer of water as "ink," an atomic layer of MoS2 as paper, and a laser as the pen. Physically adsorbed monolayered water molecules produce p‐type doping to the monolayer MoS2, leading to its photoluminescence (PL) enhancement. Information is written using a laser to remove surface water with designed patterns and is read out by PL imaging. The information is transparent to visible light and can retain for at least one week until erased by a humidification treatment. The method reaches the thinnest limit of writing and achieves repeatable data storage, providing promising applications in steganography and high‐density storage at the atomic‐thin level. [ABSTRACT FROM AUTHOR]

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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). [ABSTRACT FROM AUTHOR]

Liver cancer accounts for 6% of all malignancies causing death worldwide, and hepatocellular carcinoma (HCC) is the most common histological type. HCC is a heterogeneous cancer, but how the tumour microenvironment (TME) of HCC contributes to the progression of HCC remains unclear. In this study, we investigated the immune microenvironment by multiomics analysis. The tumour immune infiltration characteristics of HCC were determined at the genomic, epigenetic, bulk transcriptome and single-cell levels by data from The Cancer Genome Atlas portal and the Gene Expression Omnibus (GEO). An epigenetic immune-related scoring system (EIRS) was developed to stratify patients with poor prognosis. SPP1, one gene in the EIRS system, was identified as an immune-related predictor of poor survival in HCC patients. Through receptor-ligand pair analysis in single-cell RNA-seq, SPP1 was indicated to mediate the crosstalk between HCC cells and macrophages via SPP1-CD44 and SPP1-PTGER4 association. In vitro experiments further validate SPP1 can trigger the polarization of macrophages to M2-phenotype tumour-associated macrophages (TAMs). [ABSTRACT FROM AUTHOR]

A self-designed mold was used to conduct hemispherical non-isothermal deep drawing tests for the double-layer glass-fiber-reinforced polypropylene composite unidirectional laminates. The effects of preheating temperature and drawing speed of composite unidirectional laminates on the thickness distribution and forming quality of the part were investigated through microscopic observation and other methods. The results indicated that an increase in preheating temperature resulted in the formation of the thinner laminates. The surface quality of the laminates was improved with an increase in drawing speed. The laminates presented cracks and delamination defects with a drawing speed of over 150 mm/min. [ABSTRACT FROM AUTHOR]

Background: Epigenetic alterations contribute greatly to metastasis and dissemination in hepatocellular carcinoma (HCC). SMARCC1, as a SWI/SNF chromatin remodeling factor, has been reported to play important roles in many cancers. For the first time, with the bioinformatics analysis and wet-bench experiments, we explored the biological significance of SMARCC1 and its potential as putative therapeutic target in HCC. Methods: The mRNA expression profiles and prognostic value of SMARCC1 were analyzed in the Oncomine, UALCAN and Kaplan–Meier Plotter databases. The expression of SMARCC1 and associated clinicopathological factors were further evaluated using a tissue microarray. Differentially expressed genes associated with SMARCC1 in HCC were obtained and analyzed via the LinkedOmics and GEPIA databases and Cytoscape software. To verify the important role of SMARCC1 in HCC, we knocked down and overexpressed SMARCC1 in different hepatic cell lines and conducted several functional experiments. Then, we evaluated the mutation profiles and transcriptional regulators of SMARCC1 using the cBioPortal, COSMIC, CistromeDB and TCGA databases. Finally, we addressed the relationship of SMARCC1 expression with immune cell infiltration via TIMER database analysis. Results: Through data mining and tissue microarray verification, we found that the protein and mRNA levels of SMARCC1 are high in tumor tissues, which has remarkable diagnostic value in HCC patients. SMARCC1 and its hub genes showed prognostic value in HCC. Furthermore, we confirmed that SMARCC1 influenced the proliferation, migration, and invasion of HCC cells. Moreover, correlation analyses revealed that SMARCC1 expression was positively correlated with ZBTB40 transcription factors and negatively correlated with the DNA methylation level. Overall, we found that SMARCC1 affects immune infiltration and plays a tumor-promoting role in HCC. Conclusions: SMARCC1 is overexpressed and is a putative prognostic predictor in HCC. Due to the tumor-promoting role of SMARCC1, treatments inhibiting DNA methyltransferases and transcription factors or weakening the role of SMARCC1 in immune infiltration might improve the survival of HCC patients. [ABSTRACT FROM AUTHOR]

The low photoluminescence (PL) quantum yields of transition metal dichalcogenide monolayers have been a limiting factor for their optoelectronic applications. Various and even inconsistent mechanisms have been proposed to modulate their PL efficiencies. Herein, we use PL/Raman microspectroscopy and the corresponding in situ mapping, atomic force microscopy, and field-effect transistor (FET) characterization to investigate the changes in the structural and optical properties of monolayer MoS2. Relatively low power density (<4.08 × 105 W cm−2) of laser irradiation in ambient air can cause a slight PL suppression effect on monolayer MoS2, whereas relatively high power density (∼1.02 × 106 W cm−2) of laser irradiation brings significant PL enhancement. Experiments under different atmospheres reveal that the laser-irradiation-induced enhancement only occurs in the atmosphere containing O2 and is more remarkable in pure O2. In addition, physically adsorbed water can also induce PL enhancement of monolayer MoS2. FET devices suggest that the adsorbed water produces a p-doping effect on MoS2, and the laser irradiation in ambient air generates an n-doping effect, and both types of doping can enhance the PL intensity. The island-shaped defects caused by laser irradiation can be stabilized by oxygen atoms and act as trapping centers for excited trions or electrons, thus reducing the non-radiative recombination ratio and enhancing the PL intensity. The physically adsorbed water works in a similar way. A low power density of laser irradiation can sweep away the originally adsorbed H2O on the surface, thus reducing the PL. [ABSTRACT FROM AUTHOR]

Objectives: Cyclin-dependent kinase 19 (CDK19) is a component of the mediator coactivator complex, which is required for transcriptional activation. In this study, we utilized public databases and wet-bench hepatic cell line experiments to elucidate the potential roles of CDK19 in hepatocellular cancer (HCC).Materials and Methods: We studied the relationships between CDK19 expression and several clinical features related to HCC via the Oncomine and UALCAN databases. The prognostic value of CDK19 was tested using the Kaplan-Meier Plotter database. We presented the mutations of CDK19 and addressed the relation of CDK19 expression with immune cell infiltration by means of the cBioPortal, Catalogue of Somatic Mutations in Cancer (COSMIC) and Tumor IMmune Estimation Resource (TIMER) databases. Hub genes were obtained and further analyzed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database. To test the in silico findings, we knocked down CDK19 with short hairpin RNA (shRNA) technology in two hepatic cell lines and conducted several functional characterization experiments.Results: Marked CDK19 upregulation was found in HCC tissues versus normal liver tissues, and CDK19 mRNA expression had high diagnostic value in HCC patients. Subgroup analysis showed that CDK19 overexpression was associated with sex, tumor stage and TP53 mutation status. The prognostic value of CDK19 upregulation for overall survival (OS) was significant in patients with stage 2-3, stage 3-4, and grade 2 disease. One percent of the patients had CDK19 mutations, but no relationship between CDK19 mutation and prognosis was observed. CDK19 was positively correlated with the abundances of CD4 + T cells, macrophages and dendritic cells. We identified 10 genes correlated with CDK19, 8 of which presented excellent prognostic value in HCC. These hub genes were directly involved in cell division and regulation of the G2/M cell cycle transition. Protein-protein interaction (PPI) and pathway predictions indicated that CDK19 is highly likely to be involved in several cellular functions, such as proliferation, migration, and invasion. These functions were strongly interfered from two independent hepatic cell lines after CDK19 knockdown.Conclusions: CDK19 could be a prognostic marker in HCC, and its therapeutic potential in HCC needs further study. [ABSTRACT FROM AUTHOR]

The amount of public proteomics data is rapidly increasing but there is no standardized format to describe the sample metadata and their relationship with the dataset files in a way that fully supports their understanding or reanalysis. Here we propose to develop the transcriptomics data format MAGE-TAB into a standard representation for proteomics sample metadata. We implement MAGE-TAB-Proteomics in a crowdsourcing project to manually curate over 200 public datasets. We also describe tools and libraries to validate and submit sample metadata-related information to the PRIDE repository. We expect that these developments will improve the reproducibility and facilitate the reanalysis and integration of public proteomics datasets. The number of publicly available proteomics datasets is growing rapidly, but a standardized approach for describing the associated metadata is lacking. Here, the authors propose a format and a software pipeline to present and validate metadata, and integrate them into ProteomeXchange repositories. [ABSTRACT FROM AUTHOR]

Over the past few decades, researchers have become aware of the importance of non-coding RNA, which makes up the vast majority of the transcriptome. Long non-coding RNAs (lncRNAs) in turn constitute the largest fraction of non-coding transcripts. Increasing evidence has been found for the crucial roles of lncRNAs in both tissue homeostasis and development, and for their functional contributions to and regulation of the development and progression of various human diseases such as cancers. However, so far, only few findings with regards to functional lncRNAs in cancers have been translated into clinical applications. Based on multiple factors such as binding affinity of miRNAs to their lncRNA sponges, we analyzed the competitive endogenous RNA (ceRNA) network for the colorectal cancer RNA-seq datasets from The Cancer Genome Atlas (TCGA). After performing the ceRNA network construction and survival analysis, the lncRNA KCNQ1OT1 was found to be significantly upregulated in colorectal cancer tissues and associated with the survival of patients. A KCNQ1OT1-related lncRNA-miRNA-mRNA ceRNA network was constructed. A gene set variation analysis (GSVA) indicated that the expression of the KCNQ1OT1 ceRNA network in colorectal cancer tissues and normal tissues were significantly different, not only in the TCGA-COAD dataset but also in three other GEO datasets used as validation. By predicting comprehensive immune cell subsets from gene expression data, in samples grouped by differential expression levels of the KCNQ1OT1 ceRNA network in a cohort of patients, we found that CD4+, CD8+, and cytotoxic T cells and 14 other immune cell subsets were at different levels in the high- and low-KCNQ1OT1 ceRNA network score groups. These results indicated that the KCNQ1OT1 ceRNA network could be involved in the regulation of the tumor microenvironment, which would provide the rationale to further exploit KCNQ1OT1 as a possible functional contributor to and therapeutic target for colorectal cancer. [ABSTRACT FROM AUTHOR]

In this paper, the compound (E)‐N‐(3,5‐dimethylphenyl)‐2‐(3‐chlorobenzylidene)thiosemicarb‐azone was synthesized and characterized by elemental analysis, Fourier transform infrared (FT‐IR), 1H nuclear magnetic resonance (NMR), 13C NMR. The crystal structure was determined by single‐crystal X‐ray diffraction tool, indicating that the compound belongs to the orthorhombic crystal system of the Fdd2 space group, where a = 14.0472(12) Å, b = 57.148(4) Å, c = 7.9633(6) Å, the chemical formula is C16H16ClN3S, Mr = 317.83, V = 6392.7(9) Å3, Z = 16, Dc = 1.321 Mg/m3, F(000) = 2656, R = 0.0339, wR = 0.0903. Analysis of crystal data shows that the molecular conformation has good planarity. Hirshfeld surface and two‐dimensional (2D) fingerprints were used to analyze the intermolecular hydrogen bonds. In addition, a more comprehensive theoretical calculation studies were carried out on synthetic compound, such as potential energy surface (PES) scan, reduced density gradient (RDG), and independent gradient model (IGM) analysis, atoms in molecules (AIM) analysis, highest occupied molecular orbital–lowest unoccupied molecular orbital (HOMO–LUMO) and UV‐visible spectra analysis. The combination of experimental and theoretical data proved that non‐covalent bonds play a vital role in maintaining the stability of molecule. Finally, molecular docking was used to research the interaction between the synthetic compound and the receptor protein (4C2L). Meanwhile, the results obtained by in vitro antifungal assay indicated that the synthetic compound possesses the most remarkable inhibitory effect for Fusarium graminearum. [ABSTRACT FROM AUTHOR]

Background. This study aimed to explore the mechanisms of action of the PSORI-CM01 and Yinxieling formulas in the treatment of patients with psoriasis vulgaris by analyzing gene expression in peripheral blood mononuclear cells (PBMCs). Methods. PBMC samples were collected from 21 patients before and after treatment. The study included nine patients in the PSORI-CM01 treatment group, 12 patients in the Yinxieling treatment group, and nine patients in the healthy control group. Gene expression levels in PBMCs were determined using the Affymetrix gene chip technology. Results. In the PSORI-CM01 group before and after treatment, a total of 668 differentially expressed genes were found, of which 445 were upregulated and 223 were downregulated. Before and after Yinxieling treatment, 657 differentially expressed genes were found, of which 168 were upregulated and 489 were downregulated. Venn analysis showed that 78 genes were not differentially expressed in the PSORI-CM01 group and 74 were not differentially expressed in the Yinxieling group compared with those in the controls. Among these genes, 72 genes were common to both groups, which were the genes on which the two drugs acted jointly. The results of KEGG analysis and Venn analysis on the signalling pathways of drug action in treatment groups showed that haemostasis and pathways involving Rho GTPases were common signalling pathways of drug action in the two groups. Conclusions. By a comparative analysis of the treatment groups, we found that both drugs have a positive effect on patients with psoriasis vulgaris, primarily by regulating the pathways related to platelet activation, aggregation, and blood coagulation. Trial registration: ChiCTR, ChiCTR-TRC-14005185, Registered 8 August 2014, http://www.chictr.org.cn/showproj.aspx?proj=4390 [ABSTRACT FROM AUTHOR]

Interferon-alpha (IFN-α) and nucleot(s)ide analogs (NAs) are first-line drugs for the treatment of chronic hepatitis B virus (HBV) infections. Generally, NAs target the reverse transcription of HBV pregenomic RNA, but they cannot eliminate covalently-closed-circular DNA (cccDNA). Although effective treatment with NAs can dramatically decrease HBV proteins and DNA loads, and even promote serological conversion, cccDNA persists in the nucleus of hepatocytes due to the lack of effective anti-cccDNA drugs. Of the medications currently available, only IFN-α can potentially target cccDNA. However, the clinical effects of eradicating cccDNA using IFN-α in the hepatocytes of patients with HBV are not proficient as well as expected and are not well understood. Herein, we review the anti-HBV mechanisms of IFN-α involving cccDNA modification as the most promising approaches to cure HBV infection. We expect to find indications of promising areas of research that require further study to eliminate cccDNA of HBV in patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The beneficial effect of quercetin in rheumatic diseases is unclear. Studies have already confirmed that human umbilical cord mesenchymal stem cells (hUCMSCs) alleviate some symptoms of rheumatoid arthritis (RA) by their immunosuppressive capacities. This study explored whether there are additive effects of quercetin and hUCMSCs on peripheral blood mononuclear cells (PBMCs) under simulated rheumatic conditions. hUCMSCs were pretreated with quercetin (10 μM) before coculture with TNF-α/IFN-γ-stimulated PBMCs at a ratio of 1:1 for 3 days. PBMC proliferation was inhibited, and the proportion of Th17 cells was shifted. These effects may be related to the effect of quercetin on functional molecules in hUCMSCs, including nitric oxide (NO), indoleamine 2,3-dioxygenase (IDO), interleukin 6 (IL-6) and Toll-like receptor-3 (TLR-3) and the Akt/IκB pathways. These results suggest that quercetin effectively promoted the immunoregulatory effect of hUCMSCs by inhibiting the Akt/IκB pathway, activating the Toll-like receptor-3 pathway, and regulating downstream cytokines. [ABSTRACT FROM AUTHOR]

The crosstalk between ferroptosis and cancer metastasis remains unclear. Here, we identify AMER1 as a key regulator of ferroptosis. AMER1 loss causes resistance to ferroptosis in colorectal cancer (CRC) cells. Interestingly, AMER1-deficient CRC cells preferentially form distant metastases, while AMER1-naive CRC cells mainly invade lymph nodes. Moreover, the ferroptosis inhibitor liproxstatin-1 effectively promotes hematogenous transfer of AMER1-naive cells. Mechanistically, AMER1 binds to SLC7A11 and ferritin light chain (FTL) and recruits β-TrCP1/2, which degrade SLC7A11 and FTL by ubiquitination. Therefore, AMER1 deficiency increases cellular cystine levels but decreases the pool of labile free iron, thereby enhancing resistance to ferroptosis in CRC cells. Thus, AMER1 deficiency increases the survival of CRC cells in the blood under conditions of high oxidative stress and then promotes hematogenous metastasis of CRC. In conclusion, AMER1 mediates the crosstalk between ferroptosis and cancer metastasis, which provides a window of opportunity for treating metastatic colorectal cancer patients with AMER1 mutations. [Display omitted] • AMER1 has a high rate of truncating mutation in CRC with synchronous liver metastases • AMER1 functions as a common upstream regulator of system x c − and the labile iron pool • AMER1 regulates ubiquitination and degradation of SLC7A11 and FTL • AMER1 deficiency inhibits ferroptosis and facilitates CRC cell hematogenous metastasis Lei et al. identify AMER1 as a key regulator of ferroptosis in colorectal cancer. AMER1 acts as a common upstream regulator of system x c − and the labile iron pool by promoting ubiquitination and degradation of SLC7A11 and FTL, and its deficiency suppresses ferroptosis and facilitates CRC cell hematogenous metastasis. [ABSTRACT FROM AUTHOR]

Background. Psoriasis is a chronic autoimmune-mediated skin disease that is characterized by persistent localized erythematous scaly plaque. Tripterygium wilfordii Hook F (TwHF), a well-known Chinese medicine that has been used for centuries in China to treat immune diseases, inflammation, and tumor, is accompanied by a degree of toxic effects. Its clinical efficacy and safety on psoriasis are incompletely understood. Aim. To summarize evidence concerning the efficacy and safety of TwHF in treating psoriasis. Methods. EMBASE, Ovid MEDLINE, PubMed, Web of Science, Springer, Cochrane Library, CNKI, CBM, Wanfang, and VIP database were searched up to October 2017. The included literature was assessed and extracted by two independent reviewers. To enhance the available evidence, a systematic review was performed to examine all relevant published literature relating to randomized controlled trials (RCTs) of TwHF. Relative ratios (RRs) and 95% confidence intervals (CIs) were calculated, and a meta-analysis was conducted with RevMan 5.3 software. Results. Twenty eligible RCTs with 1872 participants were included for systematic review and meta-analysis. Studies were assessed using the Cochrane risk of bias tool. The meta-analysis of add-on effect of TwHF conferred benefit for psoriasis: combination treatment with compound glycyrrhizin (four studies, OR = 0.34, 95% CI 0.22–0.52, P<0.00001, I2=0%), combination treatment with acitretin (three studies, OR = 0.25, 95% CI 0.10–0.63, P=0.003, I2=50%), and combination treatment with compound amino-polypeptide tablet (three studies, OR = 0.37, 95% CI 0.22–0.63, P=0.0002, I2=0%). Conclusions. Despite several mild side effects of TwHF, there is evidence that TwHF is an effective therapy for psoriasis. However, the conclusions are limited by the small number of included trials. More well-designed RCTs with extensive follow-up periods are warranted to clarify the effects and safety of TwHF in treating psoriasis. Trial Registration. This review was registered in the International Prospective Register of Systematic Reviews (CRD42016041363). [ABSTRACT FROM AUTHOR]

Clinical practice guidelines play an important role in reducing the variations in clinical practices and improving the quality of care. To assess the real effect, measuring its implementation situation is needed. The implementation situation can be reflected by testing the consistency between the actual clinical practice and the guideline. We constructed an instrument to measure the implementation situation of Traditional Chinese Medicine (TCM) guideline through consistency testing. The main objectives of our study were to validate the instrument and evaluate the implementation situation of menopause syndrome guideline of TCM, using the data from the consistency test of comparing the medical records with the guideline. A total of 621 cases were included for data analysis. Cronbach’s Alpha coefficient is 0.73. The model fit of 7 items in four dimensions was good (SRMR = 0.04; GFI = 0.97; NFI = 0.97; TLI = 0.96; CFI = 0.98; AGFI = 0.90). This instrument is of good reliability and validity. It can help the guideline developers to measure the implementation situation, find the reasons affecting the implementation, and revise the guideline. The method of using consistency test to measure the implementation situation may provide a sample for evaluating the guideline implementation in other fields. [ABSTRACT FROM AUTHOR]

Inspired by pinecone, here we develop a novel kind of direct chemical vapour deposition (CVD) derived graphene-encapsulated porous Si nanoparticles (NPs) on graphene foam (GF). The CVD derived graphene sheets on the surface of Si NPs are partly overlapped, act as the squamae of a pinecone, preventing the direct exposure to the electrolyte. When the Si NPs expand, a sliding between the graphene layers occurs, providing an effective way to accommodate the volume expansion and stabilize the solid electrolyte interphase. As a result, the pinecone-like graphene-encapsulated Si electrodes exhibit a high capacity of 1600 mA h g−1 at a current density of 2100 mA g−1 after 300 cycles and a capacity higher than 800 mA h g−1 at a current density of 8400 mA g−1. [ABSTRACT FROM AUTHOR]

The purpose of this review was to evaluate the efficacy and safety of acupuncture therapies in the treatment of psoriasis vulgaris. Embase, CENTRAL, PubMed, AMED, CINAHL, CNKI, CQVIP, CBM, and Wanfang databases were searched from inceptions to May 2013 for prospective randomized controlled trials evaluating acupuncture therapies for psoriasis vulgaris. No language limitations were applied. Studies were assessed using the Cochrane risk of bias tool. The primary outcome was Psoriasis Area Severity Index (PASI) score. Six studies (involving 522 participants) met the eligibility criteria for this review, and 5 were included in quantitative analysis. Due to the diversity of interventions, comparators and reported outcomes, meta-analysis was not possible. Results from single studies produced conflicting results for the outcomes PASI reduction, lesion reduction (non-PASI), PASI score, and relapse rate. There is some evidence of benefit of acupuncture therapies for the treatment of psoriasis vulgaris. However, the conclusions are limited by the small number of included trials and conflicting results from single studies. More research is needed to clarify the effect of acupuncture therapies for psoriasis vulgaris. © 2015 S. Karger GmbH, Freiburg [ABSTRACT FROM AUTHOR]

Micro RNAs (mi RNAs) play very important roles in the control of immune cell and keratinocyte development and function and are implicated in skin inflammatory diseases, including psoriasis. mi RNA miR-17-92 was reported to promote the differentiation of Th1 and Th1 cells and to regulate cell proliferation and apoptosis. Here we showed that imiquimod ( IMQ) differentially regulates the expression of miR-17-92 cluster in the mouse skin, upregulating miR-17 and miR-19 families and downregulating miR-92. To investigate whether miR-17-92 cluster is functionally involved in the psoriasis, we have generated three mutant mice with specific deletion or overexpression of miR-17-92 cluster in keratinocytes, or with deletion of miR-17-92 cluster in T cells. Interestingly, deletion or overexpression of miR-17-92 cluster in keratinocytes, or deletion of miR-17-92 in T cells did not significantly affect IMQ-induced psoriasis-like dermatitis development in the mutant mice compared with wild-type littermates. Thus, mi RNA miR-17-92 cluster may not be a key factor regulating imiqumod-induced psoriasis-like dermatitis. [ABSTRACT FROM AUTHOR]

Psoriasis is a chronic inflammatory skin disease that is associated with multiple coexisting conditions. Extensive literature suggests that psoriasis is a T-cell-mediated condition, and its pathogenesis is related to dysfunction of the immune system. Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous myeloid cells that have suppressive effects on T cells. MDSCs are present at very low levels in healthy individuals but can substantially expand in tumours or inflammatory conditions. PSORI-CM02, a Chinese medical formula designed based on the Chinese medicine theory (Blood Stasis), has been prescribed extensively for psoriasis therapy and shows a stable clinical effect and safety. This study discusses the mechanisms of MDSCs involved in disease development and therapeutic progress. Our data provides evidence that monocytic myeloid-derived suppressor cells (M-MDSCs) play a role in IMQ-induced psoriatic dermatitis. Functional characterization and correlation analysis indicated that MDSCs are positively correlated with Th17 cells. PSORI-CM02 alleviated IMQ-induced psoriatic dermatitis and suppressed the proliferation of Th17 cells via M-MDSC-induced Arg1 upregulation, suggesting M-MDSCs could be a novel therapeutic target for psoriasis, and PSORI-CM02 exerted its effects via the perturbation of M-MDSCs and Th17 cell crosstalk. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis vulgaris is a common skin disease characterized by persistent localized erythematous scaly plaques, typically on the elbows, knees, and scalp. It is an immune-abnormal disease that progresses slowly over a long period with frequent symptom recurrence. Current studies have shown that acupuncture is an effective therapy for psoriasis. However, the scientific evidence of the efficacy of auricular acupressure treatment for patients with psoriasis is still insufficient. Therefore, we designed a randomized controlled clinical trial to investigate the effect, safety, and cost-effectiveness of auricular acupressure in addition to medication in patients with psoriasis.Methods and Analysis: This on-going study is a two-arm parallel, assessor-blinded, randomized controlled trial in which 180 participants with psoriasis will be recruited and then randomly allocated into two groups in a 1:1 ratio. Equal randomization will be conducted using a computer-generated random allocation sequence. Participants in the intervention group will receive auricular acupressure treatment once per week for 4 weeks, and calcipotriol betamethasone ointment for topical use once daily for 4 weeks. Participants in the control group will receive only calcipotriol betamethasone ointment treatment once daily for 4 weeks. All patients will be followed up for 12 weeks. The primary outcome is relapse rate. The secondary outcomes include time to relapse, rebound rate, time to new onset, Psoriasis Area and Severity Index score improvement rate, body surface area affected, a visual analogue scale, and Dermatology Life Quality Index. Cost-effectiveness analysis will be carried out from a health and community care provider perspective.Discussion: This multicenter randomized controlled trial will provide important clinical evidence for the effect and safety of auricular acupressure as a complementary therapy in patients with psoriasis.Trial Registration: Chinese Clinical Trial Registry, ChiCTR-TRC-14004916 . Registered on 20 May 2014. This protocol is version 3.0 which was updated on 24 September 2016. [ABSTRACT FROM AUTHOR]

Background: This study aimed to develop the clinical practice guidelines applicability evaluation (CPGAE-V1.0) scale and to evaluate its validity and reliability.Methods: One hundred fifty assessors were invited to rate two rounds of importance scoring of the applicability indicators by using the 5-point Likert scale. Approved indicators formed the CPGAE-V1.0 scale, consisting of 19 items, arranged into 4 domains. We enrolled eligible clinicians from 8 institutions to evaluate 9 clinical practice guidelines using the CPGAE-V1.0 scale. Content validity, construct validity, internal reliability, intra-rater reliability, and responsiveness were analyzed.Results: A total of 220 clinicians participated, and the response rate was 98.6% (217/220). The CPGAE-V1.0 scale had favorable content validity. The four-factor model produced acceptable fit indices. The scale had an excellent internal consistency and item discrimination. It could identify the degree of applicability of the different dimensions between different guidelines. In all domains, 77.8% (7/9) of CPGs in the minimum-scoring domain were concentrated in the "coordination of support" domain.Conclusions: The CPGAE-V1.0 scale is a valid and reliable instrument for measuring the applicability of CPG. [ABSTRACT FROM AUTHOR]