Shape-controlled synthesis of hollow silica colloids.

In this work, hollow silica colloids with different shapes, such as pseudocubes, ellipsoids, capsules, and peanuts, have been synthesized through the following process: silica coating on the surface of hematite colloidal particles with different shapes (pseudocubes, ellipsoids, capsules, and peanuts) and the sequential acid dissolution of the hematite cores. The as-obtained hollow silica colloids with different shapes have uniform sizes, shapes, and shells.

The DEAD-box RNA helicase, DDX60, Suppresses immunotherapy and promotes malignant progression of pancreatic cancer.

Excessive proliferation, invasion, metastasis, and immune resistance in pancreatic cancer (PC) makes it one of the most lethal malignant tumors. Recently, DDX60 was found to be involved in the development of various tumors and in immunotherapy. Therefore, we aimed to investigate whether DDX60 is a new factor involved in PC immunotherapy. The DDX60 mRNA was screened using transcriptome sequencing (RNA-seq). The Cox and survival analysis of DDX60 was performed using the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. In addition, clinical and immune infiltration data in the databases were analyzed and plotted using the R language. Clinical samples and in vitro experiments were used to determine the molecular evolution of DDX60 during PC progression. We found that DDX60 was upregulated in PC tissues (P value = 0.0083) and was associated with poor prognosis and short survival time of patients with PC. Results of Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set variation analyses showed that viral defense, tumor, and immune-related pathways were significantly enriched in samples with high DDX60 expression. The Pearson correlation test demonstrated that DDX60 expression correlated strongly with immune checkpoint and immune system-related metagene clusters. Our results indicated that DDX60 promoted cell proliferation, migration, and invasion and was related to poor prognosis and immune resistance. Therefore, DDX60 may be a promising novel target for PC immunotherapy.

miR-33a-3p regulates METTL3-mediated AREG stability and alters EMT to inhibit pancreatic cancer invasion and metastasis.

Recent studies have shown that amphoteric regulatory protein (AREG), a member of the epidermal growth factor (EGF) family, is expressed in many cancers and is an independent prognostic indicator for patients with pancreatic cancer, but whether AREG is regulated at the epigenetic level to promote the development of pancreatic cancer (PC) has not been elucidated. Our results support the notion that AREG is overexpressed in pancreatic cancer tissues and cell lines. Functionally, the deletion of AREG impedes pancreatic cancer (PC) cell proliferation, migration, and invasion. In addition, we identified and validated that methyltransferase-like 3 (METTL3) induced the m6A modification on AREG and facilitated the stability of AREG mRNA after sequencing. Additionally, we obtained experimental evidence that miR-33a-3p targets and inhibits METTL3 from taking action, as predicted by using the miRDB and RNAinter. Remediation experiments showed that miR-33a-3p inhibits PC progression through METTL3. In summary, this research reveals that miR-33a-3p inhibits m6A-induced stabilization of AREG by targeting METTL3, which plays a key role in the aggressive progression of PC. AREG could be a potential target for PC treatment.

Insight into interface electronic structure of ZnIn2S4/TiO2 heterostructure for enhanced photoelectrochemical glycerol oxidation.

Developing a high-efficiency photoelectrochemical (PEC) electrode for the glycerol oxidation reaction (GOR) is important for producing valuable products. The PEC performance could be enhanced by rationally designing heterostructures with inhibited recombination of charge carriers. Nevertheless, the interface electronic structure of heterostructures has not been comprehensively analyzed. In this work, the PEC GOR performance of ZnIn2S4/TiO2 heterostructure photoanode showed 1.7 folds enhancement than that of pure TiO2 photoanode at 1.23 V vs. RHE. The ZnIn2S4/TiO2 heterostructure was simulated by constructing ZnIn2S4 on the TiO2 single crystal, which was beneficial for investigating the interface electronic structure of heterostructure. Single-particle spectroscopy demonstrated a significantly increased lifetime of charge carriers. Combined with the in-situ X-ray photoelectron spectroscopy, Kelvin probe force microscopy, work function, and electron paramagnetic resonance, the interface electronic structure of the ZnIn2S4/TiO2 heterostructure was proposed with a Z-scheme mechanism. This work provides a comprehensive strategy for analyzing the interface electronic structure of heterostructures.

Linc00662 m6A promotes the progression and metastasis of pancreatic cancer by activating focal adhesion through the GTF2B-ITGA1-FAK pathway.

Recurrence and metastasis are major factors associated with the poor prognosis of pancreatic cancer (PC). Previous studies have indicated that METTL3-mediated N6-methyladenosine (m6A) modification is closely associated with PC progression and prognosis. However, its underlying regulatory mechanisms remain unclear. In this study, we found that METTL3 was upregulated in PC tissues and cells and was associated with malignant tumor progression and poor progression-free survival in PC. Linc00662 was screened as a m6A-enriched RNA that promoted tumor growth and metastasis in PC cells and mouse models and was associated with poor clinical prognosis. Four m6A motifs were identified in Linc00662, which maintained the stability of Linc00662 in an IGF2BP3-coupled manner and were closely associated with the pro-tumor properties of Linc00662 in vitro and in vivo. ITGA1 was identified as a downstream gene regulated by Linc00662. Linc00662 recruites GTF2B to activate the transcription of ITGA1 in a m6A-dependent manner and initiates the formation of focal adhesions through the ITGA1-FAK-Erk pathway, thereby promoting malignant behavior in PC cells. The FAK inhibitor-Y15 obviously repressed tumor progression in Linc00662-overexpressing PC cells in vitro and in vivo. This study proposes a novel regulatory mechanism of Linc00662 in oncogene activation in PC and indicates that Linc00662 and its downstream genes are potential targets for PC therapy.

High-Performance Symmetric Supercapacitor Constructed Using Carbon Cloth Boosted by Engineering Oxygen-Containing Functional Groups.

Carbon materials display appealing physical, chemical, and mechanical properties and have been extensively studied as supercapacitor electrodes. The surface engineering further allows us to tune their capability of adsorption/desorption and catalysis. Therefore, a facile and inexpensive chemical-acid-etching approach has been developed to activate the carbon cloth as an electrode for supercapacitor. The capacitance of the acid-etched carbon cloth electrode can approach 5310 mF cm-2 at a current density of 5 mA cm-2 with remarkable recycling stability. The all-solid-state symmetric supercapacitor delivered a high energy density of 4.27 mWh cm-3 at a power density of 1.32 W cm-3. Furthermore, this symmetric supercapacitor exhibited outstanding mechanical flexibility, and the capacity remained nearly unchanged after 1000 bending cycles.

A novel anti Candida albicans drug screening system based on high-throughput microfluidic chips.

Due to the antibacterial resistance crisis, developing new antibacterials is of particular interest. In this study, we combined the antifungal drug amphotericin B with 50,520 different small molecule compounds obtained from the Chinese National Compound Library in an attempt to improve its efficacy against Candida albicans persister cells. To systematically study the antifungal effect of each compound, we utilized custom-designed high-throughput microfluidic chips. Our microfluidic chips contained microchannels ranging from 3 µm to 5 µm in width to allow Candida albicans cells to line up one-by-one to facilitate fluorescence-microscope viewing. After screening, we were left with 10 small molecule compounds that improved the antifungal effects of amphotericin B more than 30% against Candida albicans persister cells.

Association between angiotensinogen, angiotensin II receptor genes, and blood pressure response to an angiotensin-converting enzyme inhibitor.

BACKGROUND: To identify the genetic contribution to the variation in blood pressure (BP) response to angiotensin-converting enzyme inhibitors (ACEIs), single-nucleotide polymorphisms (SNPs) in the angiotensinogen (AGT), angiotensin receptor 1 (AGTR1), and angiotensin receptor 2 (AGTR2) genes were evaluated for their association with BP response to ACEI in Chinese patients with hypertension in a 2-stage design. METHODS AND RESULTS: We selected 1447 hypertensive patients from a 3-year benazepril postmarket surveillance trial and genotyped them for 14 SNPs in the AGT, AGTR1, and AGTR2 genes. The AGT rs7079 (C/T) SNP (3'-untranslated region) was significantly associated with the response of diastolic BP to benazepril (diastolic BP response: -7.4 mm Hg for subjects with the CC genotype, -8.9 mm Hg for CA, and -10.1 mm Hg for AA; P=0.001). Although there was no association of individual SNPs in the AGTR1 gene, there was a graded response between common haplotypes and systolic BP reduction in the order of haplotype 2 (H2)/lack of haplotype 3 (non-H3) (-13.6 mm Hg) > non-H2/non-H3 (-10.9 mm Hg) > H3/non-H2 (-6.6 mm Hg) (P=0.004). The total variations in response to ACEI therapy that were explained by the AGT SNP and AGTR1 haplotype groups were 13% for systolic and 9% to 9.6% for diastolic BP, respectively. CONCLUSIONS: AGT SNP rs7079 and AGTR1 haplotypes were associated with BP reduction in response to ACEI therapy in hypertensive Chinese patients. This will be useful in future studies, providing genetic markers to predict the hypertensive response to ACEI therapy.

Three VSX1 gene mutations, L159M, R166W, and H244R, are not associated with keratoconus.

PURPOSE: Three mutations, L159M, R166W, and H244R, in the VSX1 gene have been recently reported to be associated with keratoconus by direct sequencing in familial panels. In an attempt to confirm this observation, we surveyed the same mutations of the VSX1 gene for a white sporadic keratoconus case-control panel and a larger familial panel to test its association with keratoconus. METHODS: A case-control panel, with 77 keratoconus patients and 71 healthy controls, and a keratoconus familial panel, with 444 individuals from 75 families, were surveyed. DNA from each individual was tested for the previously reported mutations by ABI allelic discrimination technology (L159M and R166W) and restriction fragment length polymorphism assay (H244R). RESULTS: We observed no mutations of R166W and H244R and 1 heterozygous mutation of L159M in a healthy individual in the case-control panel. For the familial panel, we observed no polymorphism of R166W; 3 heterozygous for H244R, with 2 affected and 1 unaffected; and 5 heterozygous for L159M, with 3 affected and 2 unaffected. CONCLUSIONS: We cannot confirm the previously reported association of the polymorphism in the VSX1 gene with keratoconus. In our case-control sample panel and the larger familial sample panel, we did not observe the reported polymorphism of the VSX1 gene, and the distribution of these 3 polymorphisms was not significant enough to support a pathogenetic role in keratoconus.

Metallic Intermediate Phase Inducing Morphological Transformation in Thermal Nitridation: Ni3FeN-Based Three-Dimensional Hierarchical Electrocatalyst for Water Splitting.

Transition-metal nitrides have attracted a great deal of interest as electrocatalysts for water splitting due to their super metallic performance, high efficiency, and good stability. Herein, we report a novel design of hierarchical electrocatalyst based on Ni3FeN, where the presence of carbon fiber cloth as a scaffold can effectively alleviate the aggregation of Ni3FeN nanostructure and form three-dimensional conducting networks to enlarge the surface area and simultaneously enhance the charge transfer. The composition and morphological variations of NiFe precursors during annealing in different atmospheres were investigated. Such Ni3FeN/CC hierarchical electrocatalyst shows much improved electrochemical properties for water splitting in terms of overpotentials (105 and 190 mV at 10 mA/cm2 for hydrogen evolution reaction and oxygen evolution reaction, respectively) and stability.

Wound-healing promoting effect of total tannins from Entada phaseoloides (L.) Merr. in rats.

The healing of wounds has always provided challenges for the medical community whether chronic or acute. Modern and traditional medicine has proved that herbal medicine shown superiority over chemical drugs. Herein, we report an Entada phaseoloides (L.) Merr. extract with a total tannin content of 76.18% showed wound-healing promoting effect in rat model. We found significantly accelerated wound closure already on day 7 in animals treated with total Entada phaseoloides (L.) Merr. tannins (TEPT) as compared to vaseline treated controls (p<0.05). At day 15, histologically, the wounds in animals treated with TEPT were completely closed as compared to controls. In vitro, TEPT promotes fibroblast proliferation and migration into wounds of NIH3T3 with concentration range of 9.38-37.50µg/ml. TEPT also had an inhibitory action against Staphylococcus aureus with MBC of 1.5mg/ml and the result was further proved by transmission electron microscope. Thus, TEPT could promote wound shrinkage, improve healing rate and promote healing of infectious wounds in rats. And this effect may due to antibacterial activities and NIH3T3 cell pro-proliferative effect of the tannins compounds, which indicating that TEPT can be used as efficient treatment in traumatic injury.

Characterization of fly ash from a circulating fluidized bed incinerator of municipal solid waste.

Treatment and disposal of fly ash in China are becoming increasingly difficult, since its production has steadily risen and its features are uncertain. The excess pollutant components of fly ash are the key factor affecting its treatment and resource utilization. In this study, fly ash samples collected from a power plant with circulating fluidized incinerators of municipal solid waste (MSW) located in Shandong Province (eastern China) were studied. The results showed that there were no obvious seasonal differences in properties of fly ash. The content of total salt, Zn, and pH exceeded the national standards and low-ring polycyclic aromatic hydrocarbons (PAHs) and polychlorinated dibenzo-p-dioxins (PCDD) and dibenzofurans (Fs) were the main organic components of fly ash for this power plant, which posed great threats to the surrounding environment. The amount of Zn of fly ash was higher than other heavy metals, which should be due to alkaline batteries of MSW. The leachate of fly ash had low concentrations of heavy metals and the main soluble components were sulfates and chlorides. The major mineral crystals of fly ash were SiO2, CaSO4, and Fe2O3. The main organic pollutants were low-ring PAHs, polychlorinated PCDDs, and low-chlorinated PCDFs, and concentrations were lower than the limiting values of the national regulations. Additionally, the distribution of PCDD/Fs had either a positive or a negative linear correlation with fly ash and flue gas, which was associated with the chlorinated degree of PCDD/Fs. The analysis was conducted to fully understand the properties of fly ash and to take appropriate methods for further comprehensive utilization.

Association of single nucleotide polymorphisms in interferon signaling pathway genes and interferon-stimulated genes with the response to interferon therapy for chronic hepatitis C.

BACKGROUND/AIMS: Interferon signaling pathway genes (IPGs) and interferon-stimulated genes (ISGs) are associated with the host response to hepatitis C virus (HCV) infection. We studied single nucleotide polymorphisms (SNPs) in IPGs and ISGs for their associations with response to pegylated interferon alpha-2a (Peg-IFN-alpha) plus ribavirin therapy in HCV genotype-1 infected patients. METHODS: A two-stage study design was used. First, out of 118 SNPs selected, 91 SNPs from 5 IPGs and 12 ISGs were genotyped in a cohort of 374 treatment-naïve HCV patients and assessed for association with sustained virologic response (SVR). Next, 14 potentially functional SNPs from the OASL gene were studied in this cohort. RESULTS: Three OASL SNPs (rs3213545 and rs1169279 from stage I, and rs2859398 from stage II), were significantly associated with SVR [rs3213545: p=0.03, RR=1.27 (1.03-1.58); rs1169279: p=0.02, RR=1.32 (1.05-1.65) p=0.02; rs2859398: p=0.02, RR=1.29 (1.04-1.61)] after adjusting for other covariates. Further analysis showed that these three SNPs independently associated with SVR. Additionally, a similar trend towards the associations of these three SNPs with SVR was observed in a smaller, independent HCV cohort consisting of subjects from a number of clinical practice settings. CONCLUSIONS: Our study suggests that OASL variants are involved in the host response to IFN-based therapy in HCV patients.

A functional SNP of interferon-gamma gene is important for interferon-alpha-induced and spontaneous recovery from hepatitis C virus infection.

Cytokine polymorphisms are associated with disease outcome and interferon (IFN) treatment response in hepatitis C virus (HCV) infection. We genotyped eight SNPs spanning the entire IFN-gamma gene in two cohorts and assessed the association between those polymorphisms and treatment response or spontaneous viral clearance. The first cohort was composed of 284 chronically HCV-infected patients who had received IFN-alpha-based therapy and the second was 251 i.v. drug users who had either spontaneously cleared HCV or become chronically infected. A SNP variant located in the proximal IFN-gamma promoter region next to the binding motif of heat shock transcription factor (HSF), -764G, was significantly associated with sustained virological response [P = 0.01, odds ratio (OR) = 2.66 [corrected] (confidence interval 1.3-5.6)[corrected]]. The association was independently significant in multiple logistic regression (P = 0.04) along with race, viral titer, and genotype. This variant was also significantly associated with spontaneous recovery [P = 0.04, OR = 3.51 (1.0-12.5)] in the second cohort. Functional analyses show that the G allele confers a two- to three-fold higher promoter activity and stronger binding affinity to HSF1 than the C allele. Our study suggests that the IFN-gamma promoter SNP -764G/C is functionally important in determining viral clearance and treatment response in HCV-infected patients and may be used as a genetic marker to predict sustained virological response in HCV-infected patients.

NOD2 variants and antibody response to microbial antigens in Crohn's disease patients and their unaffected relatives.

BACKGROUND & AIMS: The Cdcs1 locus of the C3Bir mouse confers severe colitis associated with a decrease in innate immune function and an increase in adaptive T-cell responses to commensal bacterial products. The aim of our study was to determine if defects in innate immunity are similarly associated with increased adaptive immune responses to microbial antigens in Crohn's disease patients. METHODS: Sera from 732 patients, 220 unaffected relatives, and 200 healthy controls were tested for antibodies to oligomannan, the Pseudomonas fluorescens-related protein, Escherichia coli outer membrane porin C, CBir1 flagellin, and DNA from the same subjects was tested for 3 Crohn's disease-associated variants of the NOD2 gene, and 5 toll-like receptor (TLR) 2, 2 TLR4, and 2 TLR9 variants. The magnitude of responses to microbial antigens was examined according to variant status. RESULTS: NOD2 variant carriage increased in frequency with increasing number of positive antibodies and increasing cumulative quantitative response as measured by quartile sum (P for trend, .0008 and .0003, respectively). Mean antibody and quartile sums were higher for patients carrying any NOD2 variant versus those carrying none (2.24 vs 1.92 and 10.60 vs 9.72; P = .0008 and P = 0.0003, respectively). The mean quartile sum was higher for unaffected relatives carrying any NOD2 variant versus those carrying none (10.67 vs 9.75, respectively; P = .02). No association was found between any TLR variant and the magnitude of response. CONCLUSIONS: Patients with Crohn's disease and unaffected relatives carrying variants of the NOD2 gene have increased adaptive immune responses to microbial antigens.

Myxovirus-1 and protein kinase haplotypes and fibrosis in chronic hepatitis C virus.

UNLABELLED: Candidate genes, including myxovirus resistance-1 (Mx1), protein kinase (PKR), transforming growth factor-beta1 (TGF-beta), interleukin-10 (IL-10), and interferon-gamma (IFN-gamma), were evaluated for associations with liver fibrosis in 374 treatment-naive patients with genotype-1 chronic HCV infection [194 Caucasian Americans (CAs) and 180 African Americans (AAs)], using a genetic haplotype approach. Among the 18 haplotypes that occurred with a frequency >or=5% in the cohort overall, the Mx1-(-123C)-(+6886A)-(+19820G(379V))-(+38645T) (abbreviated Mx1-CAGT), and PKR-(+110T)-(+7949G)-(+13846A)-(+22937T)-(+40342T) (abbreviated PKR-TGATT) haplotypes were independently associated with less severe hepatic fibrosis (Ishak >or= 3 versus <3). These associations persisted after adjustment for potential confounders such as alcohol use, sex, age (which is strongly correlated with the estimated duration of HCV infection [Spearman's correlation coefficient (r(s)) = 0.6)], and race (for Mx1-CAGT: OR = 0.33; 95% CI: 0.16-0.68; P = 0.0027; and for PKR-TGATT: OR = 0.56; 95% CI: 0.32-0.98; P = 0.0405). Population structure was evaluated using the structured association method using data from 161 ancestry-informative markers and did not affect our findings. We used an independent cohort of 34 AA and 160 CA in an attempt to validate our findings, although notable differences were found in the characteristics of the two patient groups. Although we observed a similar protective trend for the Mx1-CAGT haplotype in the validation set, the association was not statistically significant. CONCLUSION: In addition to other factors, polymorphisms in cytokine genes may play a role in the progression of HCV-related fibrosis; however, further studies are needed.