Positive association between insulin resistance and fatty liver disease in psoriasis: evidence from a cross-sectional study.

Background: Fatty liver disease (FLD) is a common comorbidity of psoriasis and is often referred to as non-alcoholic fatty liver disease (NAFLD). However, the role of inflammation or insulin resistance (IR) in FLD is inconclusive. The study aims to explore whether FLD in psoriasis patients is more related to insulin resistance or systemic inflammation level. Methods: Data for this study were collected from the Shanghai Psoriasis Effectiveness Evaluation Cohort, a prospective cohort that examines psoriasis characteristics in the Chinese population. IR was assessed using the triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) indicators. Systemic non-specific inflammation was assessed using the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), and systemic immune inflammation index (SII). Results: The analysis included a total of 647 patients. Subsequent logistic regression analysis revealed that NLR, dNLR, and SII were not significantly associated with FLD in psoriasis patients, while TyG and TyG-BMI showed significant associations with FLD. Subgroup analysis indicated that in the majority of subgroups, TyG and TyG-BMI were significantly associated with FLD, particularly TyG-BMI. Excluding individuals with methotrexate and acitretin resulted in consistent findings with the main analysis. Further analysis revealed a significantly higher diagnosis rate of metabolic-associated fatty liver disease (MAFLD) compared to NAFLD. Conclusions: Metabolic factors play a crucial role in FLD in patients with psoriasis, and TyG and TyG-BMI are potential predictors of FLD. Therefore, MAFLD can be recommend as a term to describe FLD in psoriasis patients. Trial registration: https://www.chictr.org.cn/showproj.html?proj=58256, identifier ChiCTR2000036186. A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population. Registered 31 August 2020.

Insulin Resistance Impairs Biological Agents Response in Moderate-to-Severe Plaque Psoriasis: Insights from a Prospective Cohort Study in China.

BACKGROUND: Psoriasis and insulin resistance (IR) are closely related, but it remains unclear whether IR affects the treatment of patients with psoriasis. OBJECTIVE: The objective of this study was to investigate whether IR impairs the treatment response to biologic agents in patients with moderate-to-severe plaque psoriasis. METHODS: This project was based on a prospective cohort study design. Data for this study were collected from the Shanghai Psoriasis Effectiveness Evaluation CoHort (SPEECH), which is a prospective cohort exploring treatment strategies for psoriasis in China. IR was assessed using the triglyceride glucose-body mass index (TyG-BMI). Psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA). Multiple logistic regression was used to explore the differences between patients with high and low levels of IR. Subgroup and sensitivity analyses were performed to examine the robustness of the study results. RESULTS: A total of 290 patients were included in the analysis. Based on the median TyG-BMI, the patients were divided into two groups: High and Low. The High group exhibited a higher prevalence of diabetes, higher BMI, fasting blood glucose, and triglyceride compared with the Low group. Further analysis of the treatment efficacy revealed that the High group had lower response rates for PASI 75, PASI 90, and PGA 0/1 after 12 weeks of treatment. In the Low group, 81.94% of patients achieved PASI 75, 58.33% achieved PASI 90, and 75.69% achieved PGA 0/1. However, the proportion of responses at each endpoint was significantly lower in the High group. The impairment in response to PGA 0/1 was more significant in the High group, indicated by lower odd ratios. Subsequent subgroup analysis and sensitivity analysis produced consistent results. CONCLUSION: IR is associated with lower effectiveness of biologics in patients with psoriasis. CLINICAL TRIAL REGISTRATION: [www.chictr.org.cn], identifier [ChiCTR2000036186].

Better efficacy, lower recurrence rate and decreased CD8+TRM with guselkumab treatment for generalized pustular psoriasis: A prospective cohort study from China.

Generalized pustular psoriasis (GPP) is a severe and uncommon form of psoriasis, for which treatment options are limited. There is an urgent need to expand the treatment options for GPP. Currently, adalimumab, secukinumab, and guselkumab are considered effective for GPP, but there is a lack of prospective direct comparative studies on their efficacy for GPP. We conducted a prospective, single-center, observational study on 50 GPP patients to compare the efficacy, safety, and recurrence rates of these three biologics. Adalimumab, secukinumab, and guselkumab resulted in varying degrees of improvement in patients with GPP, but guselkumab exhibited superior efficacy and a lower recurrence rate than the other two drugs. This enhanced response may be attributed to the significant reduction in CD8+ tissue-resident memory T cells within GPP lesions caused by guselkumab.

A novel online calculator based on clinical features and hematological parameters to predict total skin clearance in patients with moderate to severe psoriasis.

BACKGROUND: Treatment responses to biologic agents vary between patients with moderate to severe psoriasis; while some patients achieve total skin clearance (TSC), a proportion of patients may only experience partial improvement. OBJECTIVE: This study was designed to identify potential predictors for achieving TSC in psoriasis patients treated with IL-17 inhibitors. It also aimed to develop an easy-to-use calculator incorporating these factors by the nomogram to predict TSC response. METHODS: A total of 381 patients with psoriasis receiving ixekizumab were included in the development cohort and 229 psoriasis patients who initiated secukinumab treatment were included in the validation cohort. The study endpoint was achieving TSC after 12 weeks of IL-17 inhibitors treatment, defined as the 100% improvement in Psoriasis Area and Severity Index (PASI 100). Multivariate Cox regression analyses and LASSO analysis were performed to identify clinical predictors and blood predictors respectively. RESULTS: The following parameters were identified as predictive factors associated with TSC: previous biologic treatment, joint involvement, genital area affected, early response (PASI 60 at week 4), neutrophil counts and uric acid levels. The nomogram model incorporating these factors achieved good discrimination in the development cohort (AUC, 0.721; 95% CI 0.670-0.773) and validation cohort (AUC, 0.715; 95% CI 0.665-0.760). The calibration curves exhibited a satisfactory fit, indicating the accuracy of the model. Furthermore, the decision curve analysis confirmed the clinical utility of the nomogram, highlighting its favorable value for practical application. Web-based online calculator has been developed to enhance the efficiency of clinical applications. CONCLUSIONS: This study developed a practical and clinically applicable nomogram model for the prediction of TSC in patients with moderate to severe psoriasis. The nomogram model demonstrated robust predictive performance and exhibited significant clinical utility. Trial registration A multi-center clinical study of systemic treatment strategies for psoriasis in Chinese population;ChiCTR2000036186; Registered 31 August 2020; https://www.chictr.org.cn/showproj.html?proj=58256 .

Decreased risk of COVID-19 and long COVID in patients with psoriasis receiving IL-23 inhibitor: A cross-sectional cohort study from China.

Background: Although clinical trials and real-world data suggest that the risk of COVID-19 and its complications is not exacerbated in patients with psoriasis treated by biological agents, the evidence for this is still limited. Objectives: We aimed to assess the outcomes of COVID-19 among Chinese patients with psoriasis treated by IL-23 inhibitor, and to compare these variables in patients receiving other therapies. Methods: A cross-sectional cohort study was conducted to compare psoriasis treatment with IL-23 inhibitor to other treatment methods. All the patients received a questionnaire that contained questions about their psoriasis treatment, COVID-19 symptoms, and related risk factors. The prevalence of COVID-19 was calculated, and logistic regression analyses were performed to determine the association between treatment method and COVID-19 risk. The symptoms of COVID-19 and long COVID were described for each treatment group. Results: Between December 2022 and February 2023, 732 patients with psoriasis were included in the final analysis. 549 patients had a SARS-CoV-2 infection during the study period. Our results showed that individuals who worked outdoors had a decreased risk of COVID-19, as did those who had other allergic disease. With regard to the effect of the treatment regimens, IL-23 inhibitor treatment was associated with a decreased risk of COVID-19 compared to almost all the other treatments except acitretin. Fever was the most common symptom, but the maximum temperature and duration of fever were comparable among the treatment groups. Patients treated with IL-23 inhibitor were more likely to be asymptomatic after recovery compared to patients treated with methotrexate, narrow-bound ultra violet B, or TNF-α inhibitor. Conclusions: IL-23 inhibitor treatment may lower the risk of COVID-19 and long COVID. Thus, IL-23 inhibitor treatment might be beneficial and positively considered for patients with psoriasis who require systemic treatment during periods when there is a surge in COVID-19 cases.

Long-term efficacy and safety of dupilumab for severe bullous pemphigoid: A prospective cohort study.

BACKGROUND: Bullous pemphigoid (BP) is a common subepidermal bullous disease. Dupilumab is a novel treatment for BP. However, its long-term efficacy and safety have not been demonstrated in prospective studies. OBJECTIVE: Evaluate the long-term efficacy and safety of dupilumab in treating severe BP. METHODS: Patients were divided into two groups: the methylprednisolone monotherapy group (M), and the methylprednisolone and dupilumab combination therapy group (D + M). This study consisted of two stages. The first stage focused on the initial treatment phase, where the early efficacy and safety was evaluated. The study then entered the 12-month maintenance treatment stage, where we assessed recurrence in both groups. Additionally, we evaluated the rate of healing of skin lesions, glucocorticoids burden and length of hospital stay and various laboratory test indicators. RESULTS: After four weeks of treatment, the Bullous Pemphigoid Disease Area Index (BPDAI) and pruritus Numerical Rating Scale scores of the D + M group decreased significantly more than those of the M group. The median BPDAI at week 4 was 0 (range: 0.0-3.0) in the D + M group and 10.0 (5.0-12.0) in the M group (P < 0.001). Patients treated with dupilumab experienced a faster cessation of new blisters, quicker glucocorticoid reduction, shorter healing times, and shorter hospital stays (P < 0.001). Additionally, after two weeks of treatment, the levels of eosinophils and immunoglobulin E also decreased (P < 0.001). Follow-up studies further demonstrated that dupilumab monotherapy was associated with a lower recurrence rate. Notably, no serious adverse effects were observed in the study. CONCLUSIONS: Our study provides evidence for the efficacy of dupilumab in the treatment of BP based on prospective studies. Additionally, our findings suggest that dupilumab can be considered a reliable single-agent maintenance treatment due to its good safety profile and lower relapse.

Quality of Life Benefit and Clinical Predictors of Complete Skin Clearance in Psoriasis: A Multicenter, Prospective, Real-World Study.

BACKGROUND: Newer biologics, such as interleukin (IL)-17 inhibitors, make it possible to achieve complete skin clearance (CSC) in patients with moderate-to-severe psoriasis. However, the clinical meaningfulness and predictive factors of CSC in daily practice have not yet been fully investigated. OBJECTIVE: The study was conducted to, first, assess the impact of CSC on quality of life (QoL) improvements compared with treatment responses without clearance and, second, identify clinical parameters as predictors of CSC response in psoriasis patients treated with ixekizumab. METHODS: Patients attending 26 dermatology centers across China were recruited into this real-world setting between August 2020 and May 2022. Prospective cohort study in which response to ixekizumab was assessed using the Psoriasis Area and Severity Index (PASI) and Dermatology Quality of Life Index (DLQI). The absolute DLQI score and DLQI (0) response at week 12 were compared between groups achieving various levels of skin clearance. A stepwise logistic regression analysis was applied to identify which baseline clinical characteristics were predictive factors for CSC. RESULTS: After 12 weeks of treatment, 226 of 511 (44.2%) patients achieved CSC, defined as 100% improvement in PASI score (PASI-100). A significantly higher proportion of patients with CSC versus almost clear skin (PASI 90-99) achieved DLQI score of 0, corresponding to the experience of no impairment on QoL (54.4% vs. 37.7%, p = 0.001). Females patients were more likely than males to achieve CSC response (odds ratio [OR] = 1.83; 95% confidence interval [CI]: 1.24-2.70), while previous biologic treatment (OR = 0.43; 95% CI: 0.24-0.81) and joint affected (OR = 0.61; 95% CI: 0.42-0.89) were significantly associated with less CSC response. CONCLUSIONS: This study highlights the fact that clinical parameters are important in determining CSC response in psoriasis. In daily practice, achieving CSC represents a clinically meaningful treatment goal, especially from the patient perspective.

TMED3 promotes the development of malignant melanoma by targeting CDCA8 and regulating PI3K/Akt pathway.

BACKGROUND: Transmembrane emp24 domain containing (TMED) proteins are known to play pivotal roles in normal development, but have been reported to be implicated in pancreatic disease, immune system disorders, and cancers. As far as TMED3 is concerned, its roles in cancers are controversial. However, evidence describing TMED3 in the context of malignant melanoma (MM) is scarce. RESULTS: In this study, we characterized the functional significance of TMED3 in MM and identified TMED3 as a tumor-promoting factor in MM development. Depletion of TMED3 arrested the development of MM in vitro and in vivo. Mechanistically, we found that TMED3 could interact with Cell division cycle associated 8 (CDCA8). Knocking down CDCA8 suppressed cell events associated with MM development. On the contrary, elevating CDCA8 augmented cell viability and motility and even reversed the inhibitory effects of TMED3 knockdown on MM development. On the other hand, we found that the levels of P-Akt and P-PI3K were decreased in response to TMED3 downregulation, which was partially abolished following SC79 treatment. Thus, our suspicion was that TMED3 exacerbates MM progression via PI3K/Akt pathway. More notably, previously decreased P-Akt and P-PI3K in TMED3-depleted cells were rescued after overexpressing CDCA8. Also, previously impaired cell events due to CDCA8 depletion were ameliorated after SC79 addition, implying that TMED3 regulates PI3K-AKT pathway via CDCA8, thereby promoting MM development. CONCLUSIONS: Collectively, this study established the link between TMED3 and MM, and provides a potential therapeutic intervention for patients with MM harboring abundant TMED3.

Biologic and Small-Molecule Therapies for Moderate-to-Severe Psoriasis: Focus on Psoriasis Comorbidities.

Psoriasis is a systemic immune-mediated disease associated with an increased risk of comorbidities, such as psoriatic arthritis, cardiovascular disease, metabolic syndrome, inflammatory bowel disease, psychiatric disorders, and malignancy. In recent years, with the advent of biological agents, the efficacy and safety of psoriasis treatments have dramatically improved. Presently, tumor necrosis factor-α inhibitors, interleukin-17 inhibitors, interleukin-12/23 inhibitors, and interleukin-23 inhibitors are approved to treat moderate-to-severe psoriasis. Small-molecule inhibitors, such as apremilast and deucravacitinib, are also approved for the treatment of psoriasis. Although it is still unclear, systemic agents used to treat psoriasis also have a significant impact on its comorbidities by altering the systemic inflammatory state. Data from clinical trials and studies on the safety and efficacy of biologics and small-molecule inhibitors provide important information for the personalized care and treatment for patients with psoriasis. Notably, treatment with interleukin-17 inhibitors is associated with new-onset or exacerbations of inflammatory bowel disease. In addition, great caution needs to be taken when using tumor necrosis factor-α inhibitors in patients with psoriasis with concomitant congestive heart failure, multiple sclerosis, and malignancy. Apremilast may induce weight loss as an adverse effect, presenting also with some beneficial metabolic actions. A better understanding of the characteristics of biologics and small-molecule inhibitors in the treatment of psoriasis comorbidities can provide more definitive guidance for patients with distinct comorbidities.

Positive association between different triglyceride glucose index-related indicators and psoriasis: evidence from NHANES.

Background: Psoriasis is a chronic inflammatory skin disease with effects that extend beyond the skin. Insulin resistance (IR) has been associated with psoriasis, but it remains unclear how indicators related to the triglyceride glucose (TyG) index, which were associate with IR, are associated with the condition. Objective: The purpose of this study was to investigate the association between psoriasis and three TyG-related indicators: triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist to height ratio (TyG-WHtR), and triglyceride glucose-waist circumference (TyG-WC). Methods: Data from adults aged 20 to 80 years in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2006 and 2009 to 2014 were utilized. Institutional Review Board approval and documented written consent was obtained from participants by NHANES (Protocol #2005-06). The patients were divided into three groups based on TyG-BMI, TyG-WC, and TyG-WHtR: Q1 (1st quintile), Q2 (2nd-3rd quintiles), and Q3 (4th-5th quintiles). Differences between the groups were further explored. Multivariate logistic regressions were used to investigate the correlation between these three indicators and psoriasis, with results expressed as odds ratios (OR) and 95% confidence intervals (CI). Subgroup analysis and supplementary analysis was further conducted to explore potential influencing factors. Results: The study included 9,291 participants, of which 260 had psoriasis. Compared Q2 and Q3 of TyG-BMI, TyG-WC, and TyG-WHtR to Q1, there were significantly associate with psoriasis. Among the three indicators, TyG-WC consistently had the highest OR values in Models 1 and 2 (Model 1: Q3 OR (95% CI) = 2.155 (1.442-3.220); Model 2: Q3 OR (95% CI) = 2.029 (1.341-3.069)). While in Model 3, the TyG-BMI shows more significant relationship with psoriasis (Model 3 of TyG-BMI: Q3 OR (95% CI) = 1.948 (1.300-3.000)). Similar results were observed in the majority of subgroups and in supplementary analysis. Conclusion: This study identified a stable and strong positive association between TyG-related indicators (TyG-BMI, TyG-WC, and TyG-WHtR) and psoriasis. This association persisted even after adjusting for multiple factors. It is suggested that high IR is significantly associated with psoriasis.

Collision Electrochemical Synthesis of Metal Nanoparticles Using Electrons as Green Reducing Agent.

Synthesis of high-quality metal nanoparticles (NPs) is the premise toward their downstream diverse applications. Although some electrochemical synthesis strategies have been developed, the necessary use of high-concentration electrolyte solution as current pathway and reaction medium severely limits the colloidal stability of the growing NPs in the solution and their tunability in size and shape. Herein, we report a collision electrochemical method for the synthesis of metal NPs without the use of electrolyte solution. To this end, we designed an asymmetrical electrochemical cell to control the potential (i.e., to supply electrons) in the reaction system via a separated electrochemical cell, thereby enabling the electrochemical reaction occurring in an electrolyte-free growth solution. Consequently, this collision electrochemical method, using seed-mediated growth of NPs as examples, allows the synthesis of monodisperse homogeneous Au NPs and heterogeneous Pd- and Pt-coated Au NPs at a yield comparable to that achieved in common chemical synthesis. Furthermore, this method allows readily tailoring the morphology of the resultant metal NPs just by changing the concentration of the growth solution. Therefore, our green synthesis method is important for a variety of nanomaterials beyond metal NPs.

Multi-Omics Analysis of the Prognosis and Biological Function for TRPV Channel Family in Clear Cell Renal Cell Carcinoma.

Background: The transient receptor potential vanilloid (TRPV) channels family, TRPV1-6, has been identified to profoundly affect a wide spectrum of pathological processes in various cancers. However, the biological function and prognostic value of TRPVs in clear cell renal cell carcinoma (ccRCC) are still largely unknown. Methods: We obtained the gene expression data and clinical information of 539 ccRCC patients from The Cancer Genome Atlas (TCGA) database. A series of databases were used for data processing and visualization, including GEPIA, GeneMANIA, MethSurv, GSCA, TIMER, and starBase databases. Results: The mRNA expression of TRPV2/3 was upregulated while the expression of TRPV5/6 was downregulated in ccRCC tumor tissues. TRPV family members in ccRCC were rarely mutated (nearly 7 frequencies). The ROC curve showed that TRPV2/5/6 had a high diagnostic ability in discriminating ccRCC from the control samples (AUC>0.9). Higher levels of TRPV3 expression were associated with poor prognosis of ccRCC patients, while higher expression of TRPV4 was associated with favorable prognosis. The expression of TRPV3 in normal and ccRCC tissues was validated by Immunohistochemistry, and its expression was remarkably related to high histologic grade and advanced stage. Besides, TRPV3 exhibit a reduction of DNA methylation level with tumor progression, and 12 CpGs of TRPV3 were associated with a significant prognosis. In addition, TRPV3 expression was significantly associated with the accumulation of several tumor-infiltrating immune cells, especially regulatory T cells. Furthermore, high levels of TRPV3 induced the expression of immune checkpoints such as LAG3, CTLA4, PDCD1, and TIGIT. Finally, we predicted a key SNHG3/AL513497.1-miR-10b-5p-TRPV3 axis linking to carcinogenesis and progression of ccRCC. Conclusion: Our study may uncover TRPV channels-associated molecular mechanisms involved in the tumorigenesis and progression of ccRCC. TRPV family members might be diagnosed and prognostic markers and potential therapeutic targets for ccRCC patients.

Scutellarein protects against cardiac hypertrophy via suppressing TRAF2/NF-κB signaling pathway.

BACKGROUND: Scutellarein, a widely studied ingredient of scutellaria herbs, has higher bioavailability and solubility than that of scutellarin. Although the scutellarein had been reported to modulate numerous biological functions, its ability in suppressing cardiac hypertrophy remains unclear. Hence, the present study attempted to investigate whether scutellarein played critical roles in preventing phenylephrine (PE)-induced cardiac hypertrophy. METHODS AND RESULTS: Immunocytochemistry (ICC) was employed for evaluating the morphology of the treated cardiomyocytes. Real-time PCR and western blot were respectively applied to assess the mRNA levels and protein expression of the relevant molecules. Bioinformatics analyses were carried out to investigate the potential mechanisms by which scutellarein modulated the PE-induced cardiac hypertrophy. The results showed that Scutellarein treatment significantly inhibited PE-induced increase in H9c2 and AC16 cardiomyocyte size. Besides, scutellarein treatment also dramatically suppressed the expression of the cardiac hypertrophic markers: ANP, BNP and ß-MHC. Furthermore, the effects of scutellarein on attenuating the cardiac hypertrophy might be mediated by suppressing the activity of TRAF2/NF-κB signaling pathway. CONCLUSIONS: Collectively, our data indicated that scutellarein could protect against PE-induced cardiac hypertrophy via regulating TRAF2/NF-κB signaling pathway using in vitro experiments.

Comprehensive analysis of the prognosis and biological significance for IFIT family in skin cutaneous melanoma.

Interferon-induced protein with tetratricopeptide repeats (IFITs) genes, consisting of four members named IFIT1, IFIT2, IFIT3 and IFIT5, are involved in the progression of multiple cancer types, but their roles in skin cutaneous melanoma (SKCM) are still largely unknown. The TCGA-SKCM dataset, GSE15605 dataset and GSE100508 dataset were obtained in our study, and multiple online databases were used for data analysis and visualization, including GEPIA, GSCALite, MethSurv, DAVID, starBase and TIMER database. The mRNA expressing levels of all the four members included in IFIT family were elevated in SKCM tissues. In addition, ROC curve showed that the combined IFITs had a higher tumor prediction performance. Kaplan-Meier survival analysis revealed that the low expression of IFIT1/2/3/5 was associated with poor overall survival (OS) and disease-specific survival (DSS) in SKCM patients. Moreover, univariate and multivariate Cox regression analysis suggested that the low expression of IFIT2/3/5 was an independent risk factor for the prognosis of SKCM patients. Besides, cancer pathway activity analysis certified that the IFITs were involved in the apoptosis pathways, epithelial-mesenchymal transition (EMT) and cell cycle. Furthermore, drug sensitivity analysis indicated that the high expression of IFIT1/2/3 was sensitive to dasatinib drug. Additionally, the expressing levels of IFITs were found to be positively correlated with the level of immune cell infiltrates, immune biomarkers and m6A regulators. Finally, using bioinformatics analysis, we predicted that PAX8-AS1/Z83843.1-miR-92a-3p-IFIT2 axis might play crucial roles in the development and progression of SKCM. This study explored the prognostic values and biological significance of the IFITs in SKCM microenvironment. IFITs may serve as novel biomarkers for the diagnosis and prognosis of melanoma and potential immunotherapeutic targets.

Comprehensive Analyses of the Expression, Genetic Alteration, Prognosis Significance, and Interaction Networks of m6A Regulators Across Human Cancers.

Accumulating lines of evidence indicate that the deregulation of m6A is involved in various cancer types. The m6A RNA methylation is modulated by m6A methyltransferases, demethylases, and reader proteins. Although the aberrant expression of m6A RNA methylation contributes to the development and progression of multiple cancer types, the roles of m6A regulators across numerous types of cancers remain largely unknown. Here, we comprehensively investigated the expression, genetic alteration, and prognosis significance of 20 commonly studied m6A regulators across diverse cancer types using TCGA datasets via bioinformatic analyses. The results revealed that the m6A regulators exhibited widespread dysregulation, genetic alteration, and the modulation of oncogenic pathways across TCGA cancer types. In addition, most of the m6A regulators were closely relevant with significant prognosis in many cancer types. Furthermore, we also constructed the protein-protein interacting network of the 20 m6A regulators, and a more complex interacting regulatory network including m6A regulators and their corresponding interacting factors. Besides, the networks between m6A regulators and their upstream regulators such as miRNAs or transcriptional factors were further constructed in this study. Finally, the possible chemicals targeting each m6A regulator were obtained by bioinformatics analysis and the m6A regulators-potential drugs network was further constructed. Taken together, the comprehensive analyses of m6A regulators might provide novel insights into the m6A regulators' roles across cancer types and shed light on their potential molecular mechanisms as well as help develop new therapy approaches for cancers.

ERO1L promotes NSCLC development by modulating cell cycle-related molecules.

Lung cancer is the leading cause of cancer-related death worldwide. Previous studies revealed that endoplasmic reticulum oxidoreductase 1 alpha (ERO1L) played critical roles in the malignant behaviors of several cancer types, but its role in non-small cell lung cancer (NSCLC) remained unclear. In this study, we identified 26 upregulated and 102 downregulated genes in NSCLC using bioinformatics analyses, and these genes were enriched in the biological processes of the cell cycle. ERO1L was remarkably upregulated in NSCLC and overexpression of ERO1L was associated with poor prognosis of NSCLC. ERO1L deficiency markedly suppressed NSCLC cell proliferation, colony formation, migration, and invasion. ERO1L depletion caused a dramatically decreased expression of cell cycle-related factors in NSCLC cells. Collectively, our data validated that ERO1L could function as a tumor promoter in NSCLC, indicating the potential of targeting ERO1L for the treatment of NSCLC.

Theoretical study of binding interactions and vibrational Raman spectra of water in hydrogen-bonded anionic complexes: (H2O)n- (n = 2 and 3), H2O...X- (X = F, Cl, Br, and I), and H2O...M- (M = Cu, Ag, and Au).

Binding interactions and Raman spectra of water in hydrogen-bonded anionic complexes have been studied by using the hybrid density functional theory method (B3LYP) and ab initio (MP2) method. In order to explore the influence of hydrogen bond interactions and the anionic effect on the Raman intensities of water, model complexes, such as the negatively charged water clusters ((H2O)n-, n = 2 and 3), the water...halide anions (H2O...X-, X = F, Cl, Br, and I), and the water-metal atom anionic complexes (H2O...M-, M = Cu, Ag, and Au), have been employed in the present calculations. These model complexes contained different types of hydrogen bonds, such as O-H...X-, O-H...M-, O-H...O, and O-H...e-. In particular, the last one is a dipole-bound electron involved in the anionic water clusters. Our results showed that there exists a large enhancement in the off-resonance Raman intensities of both the H-O-H bending mode and the hydrogen-bonded O-H stretching mode, and the enhancement factor is more significant for the former than for the latter. The reasons for these spectral properties can be attributed to the strong polarization effect of the proton acceptors (X-, M-, O, and e-) in these hydrogen-bonded complexes. We proposed that the strong Raman signal of the H-O-H bending mode may be used as a fingerprint to address the local microstructures of water molecules in the chemical and biological systems.

Characterization of surface water on Au core Pt-group metal shell nanoparticles coated electrodes by surface-enhanced Raman spectroscopy.

We utilized the strategy of 'borrowing SERS activity', by chemically coating several atomic layers of a Pt-group metal on highly SERS-active Au nanoparticles, to obtain the first SERS (also Raman) spectra of surface water on Pt and Pd metals, and propose conceptual models for water adsorbed on Pt and Pd metal surfaces.

Surface-enhanced Raman spectroscopy using gold-core platinum-shell nanoparticle film electrodes: toward a versatile vibrational strategy for electrochemical interfaces.

The aim of this work is to further improve the molecular generality and substrate generality of SERS (i.e., to fully optimize the SERS activity of transition-metal electrodes). We utilized a strategy of borrowing high SERS activity from the Au core based on Au-core Pt-shell (Au@Pt) nanoparticle film electrodes, which can be simply and routinely prepared. The shell thickness from about one to five monolayers of Pt atoms can be well controlled by adjusting the ratio of the number of Au seeds to Pt(IV) ions in the solution. The SERS experimental results of carbon monoxide adsorption indicate that the enhancement factor for the Au@Pt nanoparticle film electrodes is more than 2 orders of magnitude larger than that of electrochemically roughened Pt electrodes. The practical virtues of the present film electrodes for obtaining rich and high-quality vibrational information for diverse adsorbates on transition metals are pointed out and briefly illustrated with systems of CO, hydrogen, and benzene adsorbed on Pt. We believe that the electrochemical applications of SERS will be broadened with this strategy, in particular, for extracting detailed vibrational information for adsorbates at transition-metal electrode interfaces.

Synthesis and properties of tadpole-shaped gold nanoparticles.

In this communication, gold nanoparticles with a tadpole shape were synthesized by a simple aqueous-phase chemical method. The unusual three-dimensional and crystallized structures were demonstrated by TEM, AFM, and HRTEM methods. The SEM and UV-visible absorption measurements and electrophoresis experiments revealed that the tadpoles had novel optical and electrical properties. These attractive structures and properties are expected to find uses in many fields such as electrics, optics, electrochemistry, and biological sensing.