Knockdown of ASF1B inhibits cell proliferation, migration, invasion and cisplatin resistance in gastric cancer through the Myc pathway.

Gastric cancer (GC) is a prevalent malignancy in the digestive system that poses a serious threat to human health. Anti-silencing function 1B (ASF1B) performs an important role in the progression of numerous tumors; however, its function in GC still requires further elucidation. Using data from The Cancer Genome Atlas, the expression levels of ASF1B in GC tissues were analyzed and a survival curve for high-ASF1B expression and low-ASF1B expression groups was plotted using the Kaplan-Meier method. Reverse transcription-quantitative PCR was performed to evaluate ASF1B expression in GC tissues and cells. Small interfering RNAs targeting ASF1B were transfected into HGC-27 and AGS cells to silence ASF1B expression. Cell viability, proliferation, migration, invasion, and apoptosis in HGC-27 and AGS cells was assessed using cell counting kit-8 assay, colony formation assay, wound healing assay, Transwell assay and flow cytometry, respectively. The protein changes were assessed using western blotting. Gene Set Enrichment Analysis (GSEA) was used to identify ASF1B related pathways. The results demonstrated that ASF1B expression was increased in GC tissues and cells compared with adjacent healthy tissues and normal cells (GES-1), and high expression of ASF1B was associated with poor survival outcomes in patients with GC. Silencing ASF1B inhibited cell viability, colony formation, migration, invasion and cisplatin resistance, while also attenuating the apoptotic capability of HGC-27 and AGS cells. GSEA showed that ASF1B could activate the Myc-targets-v1 and Myc-targets-v2 pathways. Moreover, silencing ASF1B inhibited the Myc pathway-related proteins Myc, minichromosome maintenance (MCM)4 and MCM5. Overexpression of Myc reversed the inhibitory effect of ASF1B silencing on AGS cell proliferation, invasion and cisplatin resistance. In conclusion, the results indicate that knockdown of ASF1B may suppress GC cell proliferation, migration and invasion, and promote cell apoptosis and cisplatin sensitivity by modulating the Myc pathway, thereby offering novel possibilities for reversing cisplatin resistance in GC.

Hyperthermic Intraperitoneal Chemotherapy plus Intravenous Chemotherapy of Paclitaxel with or without Sintilimab in Gastric Cancer: A Comparative Study.

OBJECTIVE: To compare the clinical efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) plus intravenous chemotherapy of paclitaxel with or without sintilimab in peritoneal metastasis of gastric cancer. METHODS: A total of 120 patients assessed for eligibility with peritoneal metastasis of gastric cancer treated in the oncology department of our hospital from January 2019 to June 2020 were recruited. They were concurrently randomly assigned in a 1 : 1 ratio to receive HIPEC plus sintilimab-paclitaxel intravenous chemotherapy (study group) or plus paclitaxel intravenous chemotherapy only (control group). RESULTS: The objective remission rate (ORR) of ascites in the study group was significantly higher than that in the control group. Subgroup analysis showed that an age ≤60 years or well-differentiated tumors were associated with better objective remission. After treatment, significantly higher Karnofsky Performance Status (KPS) scores were observed in the study group versus those of the control group. Adverse events reported were comparable between groups. The study group obtained longer 12-month progression-free survival (PFS) and overall survival (OS) than those of the control group. CONCLUSION: On top of HIPEC, intravenous chemotherapy with sintilimab and paclitaxel constitute an effective alternative for patients with peritoneal metastasis of gastric cancer to enhance ascites remission, ameliorate the quality of life, and prolong survival, versus with paclitaxel alone.

Analysis and Performance Assessment of the Whole Genome Bisulfite Sequencing Data Workflow: Currently Available Tools and a Practical Guide to Advance DNA Methylation Studies.

DNA methylation is associated with transcriptional repression, genomic imprinting, stem cell differentiation, embryonic development, and inflammation. Aberrant DNA methylation can indicate disease states, including cancer and neurological disorders. Therefore, the prevalence and location of 5-methylcytosine in the human genome is a topic of interest. Whole-genome bisulfite sequencing (WGBS) is a high-throughput method for analyzing DNA methylation. This technique involves library preparation, alignment, and quality control. Advancements in epigenetic technology have led to an increase in DNA methylation studies. This review compares the detailed experimental methodology of WGBS using accessible and up-to-date analysis tools. Practical codes for WGBS data processing are included as a general guide to assist progress in DNA methylation studies through a comprehensive case study.

LncRNA PITPNA-AS1 promotes gastric cancer by increasing SOX4 expression via inhibition of miR-92a-3p.

BACKGROUND: Gastric cancer (GC) is a malignant tumor of digestive tract with high mortality. Elucidating the molecular mechanisms of GC and obtaining new molecular targets are particularly important for the prevention and treatment of GC. The discovery of long non-coding RNAs (lncRNAs) provides the possibility for further elucidating the molecular mechanisms of GC and discovering new molecular markers. AIM: Here, we aimed to explore the function and the mechanism of lncRNA PITPNA-AS1 in GC. METHODS: High-throughput lncRNA microarray was used to compare the differences in expression profiles between tumor tissues and adjacent tissues, and to filtrate the differentially expressed lncRNAs in tumors. To analyze the relationship between lncRNA expression and clinicopathological parameters in GC. The apoptosis was detected by down-regulation of lncRNA. The effect of down-regulated lncRNA PITPNA-AS1 on the migration and invasion of GC cells was determined by wound healing and Transwell assays. The function of lncRNA PITPNA-AS1 on tumor growth was verified by tumor experiment in nude mice. Analysis of target interaction relationship was performed by luciferase assay. RESULTS: The results of high throughput chip analysis identified that PITPNA-AS1 was up-regulated in GC tissues. Our data revealed that knockdown of PITPNA-AS1 was able to inhibit tumor development of GC cells. Meanwhile, PITPNA-AS1 could regulate SOX4 expression via targeting miR-92a-3p. CONCLUSION: Thus, we concluded that PITPNA-AS1 induced the development of GC cells by inhibiting miR-92a-3p and inducing SOX4. Our finding presents novel insights of GC, which may provide an underlying therapeutic target for GC treatment.

POM-Based MOF-Derived Co3O4/CoMoO4 Nanohybrids as Anodes for High-Performance Lithium-Ion Batteries.

Polyoxometalate (POM)-based metal-organic framework (MOF)-derived Co3O4/CoMoO4 nanohybrids were successfully fabricated by a facile solvothermal method combined with a calcination process, in which a Co-based MOF, that is, ZIF-67 acts as a template while a Keggin-type POM (H3PMo12O40) serves as a compositional modulator. The materials were characterized through scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), energy-dispersive spectroscopy (EDS) mapping, and electrochemical measurements. When the Co3O4/CoMoO4 nanohybrids were applied as anode materials for lithium-ion batteries (LIBs), they display large lithium storage capacity (around 900 mAh g-1 at 0.1 A g-1) and high cycling stability, and they can also exhibit good rate performances. This work might shed some light on the POM-based MOF host-guest synthesis strategy for the preparation of polymetallic oxides for enhanced electrochemical energy storage and further applications.

Lycorine inhibited the cell growth of non-small cell lung cancer by modulating the miR-186/CDK1 axis.

AIMS: Lycorine is a kind of natural alkaloid with anti-cancer potential. It has been demonstrated that lycorine processes high activity and specificity against the progression of cancers. However, the underlying molecular mechanisms by which lycorine regulates the formation and development of non-small cell lung cancer (NSCLC) remain largely unknown. MAIN METHODS: The effects of lycorine on the growth of NSCLC cells were determined by the cell counting kit-8 (CCK-8) assay, colony formation and flow cytometry analysis. RT-qPCR was performed to detect the expression of microRNA with lycorine treatment. The binding of miRNA and target genes was confirmed by luciferase reporter assay. KEY FINDINGS: Lycorine significantly inhibited the proliferation and induced apoptosis of NSCLC cells. Mechanistically, lycorine up-regulated the expression of microRNA-186 in NSCLC cells. Depletion of miR-186 significantly reversed the suppressive effect of lycorine on the proliferation of NSCLC cells. Furthermore, the cyclin dependent kinase 1 (CDK1) was identified as one of the binding candidates of miR-186. Experimental analysis showed that miR-186 bound the 3'-untranslated region (3'-UTR) of CDK1 and suppressed the level of CDK1 in NSCLC cells. Consistently, exposure of lycorine significantly decreased the expression of CDK1. Restoration of CDK1 remarkably attenuated the inhibition of lycorine on the proliferation of NSCLC cells. SIGNIFICANCE: Our results uncovered the novel molecular mechanism of lycorine in suppressing the progression of NSCLC partially via regulating the miR-186/CDK1 axis.

Duodenal Schwannoma as a Rare Association With Membranous Nephropathy: A Case Report.

Membranous nephropathy (MN) associated with malignancies is a well-known entity. However, its association with benign neoplasm is not broadly recognized. A 69-year-old man with recurrent nephrotic syndrome presented with pedal edema and proteinuria of 5 months' duration. Laboratory results showed hypoalbuminemia and hyperlipidemia. Proteinuria was estimated to be protein excretion of 3.5g/d. Studies were negative for viral hepatitis, syphilis, human immunodeficiency virus, autoimmune diseases, and paraproteinemia. Kidney biopsy disclosed MN with negative phospholipase A2 receptor (PLA2R) staining, favoring a secondary form of MN. Computed tomography detected a 7.6-cm duodenal schwannoma. Elective surgical resection was performed. Pathologic study showed that THSD7A (thrombospondin type 1 domain-containing 7A) was positive in both glomeruli and schwannoma. Commonly, secondary MN is related to underlying conditions, including lupus, hepatitis, and neoplasm, and can be medication induced. The risk for developing a concomitant neoplasm among patients with PLA2R-negative MN is up to 12 times higher than in the general population. Most of these neoplasms are malignancies, and the presence of autoantibodies directed at similar tissue targets is hypothesized as the potential mechanism. In our case, THSD7A may be the autoantibody that has linked the schwannoma and the development of MN. Although benign tumors rarely produce renal manifestations, effective treatment may lead to resolution of nephrotic syndrome.

Insight into the short- and long-term effects of quinoline on anammox granules: Inhibition and acclimatization.

The short- and long-term influence of quinoline on the properties of anaerobic ammonium oxidation (anammox) biogranules was evaluated. During batch tests, the bioactivity of anammox granules in the presence of different quinoline concentrations was monitored, and the IC50 of quinoline was calculated to be 13.1 mg L-1 using a non-competitive inhibition model. The response of anammox granules to pre-exposure to quinoline was dependent on metabolic status, and the presence of both quinoline and NO2--N had a rapid detrimental effect, resulting in a 64.5% decrease within 12 h. During continuous-flow experiments, the nitrogen removal rate (NRR) of the reactor decreased sharply within 3 days in the presence of 10 mg L-1 quinoline and then was restored to 2.6 kg N m-3 d-1. In the presence of quinoline-induced stress, the specific anammox activity and levels of extracellular polymeric substance and heme c were decreased, while settling velocity persistently increased. After cultivation and acclimation obtained by adding a medium level of quinoline to the influent, the anammox granule sludge was able to tolerate 10 mg L-1 quinoline in 178 days.

Red blood cell distribution width as an easily measurable biomarker of persistent inflammation and T cell dysregulation in antiretrovirally treated HIV-infected adults.

BACKGROUND: Chronic inflammation and immune dysfunction occur in human immunodeficiency virus (HIV)-infection despite stable antiretroviral therapy (ART). Red blood cell distribution width (RDW) has been shown to correlate with markers of inflammation in non-HIV conditions. The study objective was to determine associations between RDW with cellular markers of immune activation and immune dysfunction including soluble inflammatory mediators in ART treated HIV infection. METHODS: We performed a cross-sectional analysis of the Hawaii Aging with HIV-Cardiovascular study. RDW was defined as one standard deviation of RBC size divided by mean corpuscular volume multiplied by 100%. Correlations were analyzed between RDW, soluble inflammatory biomarkers and T cell activation (CD38 + HLA-DR+), senescence (CD28-CD57+), and immune exhaustion (PD-1, TIGIT, TIM-3 expression). RESULTS: Of 158 participants analyzed, median age was 50 years, duration of ART 12.6 years, virally suppressed 84.4%, and CD4 count 503 cells/mm3. Significant positive correlations were identified between RDW and soluble biomarkers including sICAM, IL-8, IL-6, SAA, TNF-α, sE-selection, fibrinogen, D-dimer, CRP, CD4/CD8 ratio, and frequency of multiple CD8 T-cell populations such as CD38 + HLA-DR + T-cells, single TIGIT+, and dual expressing of TIGIT + PD1+, TIGIT + TIM3+, and TIM3 + PD1+ CD8+ T-cell subsets (p < .05). Frequencies of CD38 + HLA-DR + CD8+ T-cells and TIGIT + CD8+ T-cells remained significant adjusting for baseline variables (p < .01). CONCLUSION: Our study revealed correlations between RDW with systemic inflammatory biomarkers and CD8+ T-cell populations related to immune activation and exhaustion in HIV-infected individuals on ART. Further studies are warranted to determine the utility of RDW as a marker of immune dysregulation in HIV.

Transcriptome analysis of Artemia sinica in response to Micrococcus lysodeikticus infection.

To enhance genomic resources and understand the molecular immune mechanisms underlying the response topathogens, we first performed a comparative gene transcription analysis from Micrococcus lysodeikticus-immunized Artemia sinica and from a control group through RNA-Seq technology, meanwhile the differentially expressed genes (DEGs) were investigated. In total, 80, 113, 984 clean reads were obtained and then assembled into 71,536 unigenes with an average length of 1115 bp and an N50 of 1783 bp. Unigenes were annotated by comparing against nr, Swiss-Prot\KEGG\ COG\ KOG\ GO and Pfam databases, and 27,689 unigenes (38.7%) were annotated in at least one database. After bacterial challenge, 183 and 298 genes were identified as remarkably up-regulated or down-regulated, respectively, amongst 481 were associated with 168 pathways, including classical immune-related pathways, such as 'Toll-like receptor signaling', 'the complement cascades', 'MAPK signaling pathway' and 'Apoptosis'. Besides, eight genes which were differently expressed immune-related were confirmed by using quantitative real-time PCR. This study characterized a gene expression pattern for normal and M. lysodeikticus -immunized A. sinica for the first time and sheds new light on the molecular mechanisms thus enabling future efforts on disease control programs in this valuable aquaculture species.

Cloning, expression pattern and functional characterization of interleukin-1 receptor-associated kinase 4, an important mediator of the Toll-like receptor signaling pathway, from Artemia sinica.

As a crucial component of Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) signaling pathways, IL-1R--associated kinase 4 (IRAK-4) plays a central role in innate immunity and embryonic development. Herein, we have characterized the full length cDNA of IRAK4 from Artemia sinica. Molecular characterization revealed that the sequence includes a 2550 bp open reading frame, encoding a predicted protein of 849 amino acids. The predicted protein contains a death domain in the N-terminus and two serine/threonine/tyrosine protein kinasedomains. Bioinformatics analysis showed that it belonged to a new member of the IRAK-4 family. The expression of AsIRAK-4 was researched in various stages during embryonic development by several molecular biology methods including real time PCR, Western blotting and immunohistochemistry. The results showed that AsIRAK-4 was constitutively expressed at all developmental stages from embryo to adult, and it was mainly expressed in the head and thorax at the early stages and on the surface of the alimentary canal at later stages. The highest expression level was at the 0 h, 15 h and 5 d stages of A. sinica. While challenged by Gram-positive and Gram-negative bacteria, AsIRAK-4 was remarkably upregulated with the rising concentration of bacteria. Our research revealed that AsIRAK-4 plays a vital role in growth, development and innate immunity of A. sinica.

Identifying electrochemical effects in a thermal-electrochemical co-driven system for CO2 capture.

Currently, the most promising amine absorption system for CO2 capture still faces the challenges of heavy steam consumption and a high energy penalty. Thus, a new thermal-electrochemical co-driven system (TECS) for CO2 capture was developed to resolve these problems. In the TECS, unknown electrochemical behaviors are quite essential to assess the CO2 capture performance. Electrochemical experiments were designed using response surface methodology (RSM) to identify electrochemical effects. The results show that the cathode process is slow and difficult, which is the main limitation in improving the performance of the TECS. Forced convection is necessary to improve the diffusion-controlled process and accelerate desorption. Four factors (Cu(ii) molality, CO2 loading, temperature, KNO3 molality) play an auxo-action role in determining anode and cathode reaction rates. A regression model is developed based on the experimental data, and optimum operating conditions are obtained. Regeneration energy consumption reaches about 1.3 GJ per t CO2, a decline of up to 70% compared with the traditional process. In addition, preliminary CO2 desorption experiments suggest that the mass transfer ascribed to the electrochemical process accounts for over 50% of the overall mass transfer coefficient in the CO2 desorption process.

Inhibitory effects of sulfamethoxazole on denitrifying granule properties: Short- and long-term tests.

The broad-spectrum antibiotic sulfamethoxazole (SMX) was chosen to assess its short- and long-term effects on denitrifying granules. The SMX concentration and pre-exposure time in batch testing influenced the denitrifying granule activity. In the continuous-flow experiments, no inhibitory effects on the upflow anaerobic sludge blanket performance were observed at SMX concentrations up to 100mgL-1, probably because of functional redundancy and long-term acclimation. The specific denitrifying activity first decreased to a minimum of 49.3% and then recovered to a level comparable to the initial level as the SMX concentration increased. The changing trend of the extracellular polymer content was consistent with the specific denitrifying activity throughout the process, and relatively high EPS loss ratios (maximum loss of 61.8%) were observed. Additionally, the diameter of the denitrifying granules monophonically increased to a final value of 35.0%. This research provided the application of denitrifying granules to treat wastewater that contained antibiotic.

DNA-Binding, Photocleavage, and Photodynamic Anti-cancer Activities of Pyridyl Corroles.

The DNA-binding, photocleavage, and antitumor activity of three free base pyridyl corroles 1, 2, and 3 have been investigated. The binding affinity toward CT-DNA decreases with increasing number of pentafluorophenyl, whereas the photocleavage activity toward pBR322 DNA becomes more efficient. Singlet oxygen was demonstrated as active species responsible for DNA cleavage. These corroles exhibited high cytotoxicity against three tested cancer cells (Hela, HapG2, and A549) and the cytotoxicity could be further enhanced under irradiation. Intracellular reactive oxygen species level was also monitored using HeLa Cells upon the combined treatment of corroles and light. These corroles could be absorbed by HeLa cells at low concentration. They can induce the decrease of mitochondrial membrane potential and apoptosis of tumor cells under irradiation.

Single-phase titania nanocrystallites and nanofibers from titanium tetrachloride in acetone and other ketones.

Single-phase titania nanomaterials were prepared by autoclaving titanium tetrachloride in acetone at 80-140 degrees C. Depending on the molar ratio of TiCl4 to acetone (TiCl4/Ac), TiO2 materials with different phases and morphologies were obtained. When the TiCl4 concentration was no higher than TiCl4/Ac=1/15, single-phase anatase TiO2 nanocrystals in sizes ranging from 4 to 10 nm were prepared by tuning TiCl4/Ac ratios from 1/90 to 1/15. However, when the TiCl4 concentration was high enough (e.g., TiCl4/Ac>or=1/10), single-phase rutile TiO2 nanofibers were obtained selectively. The materials were characterized comprehensively using X-ray diffraction, transmission electron microscopy, Raman spectroscopy, thermogravimetric analysis, and nitrogen adsorption measurements. With the aid of GC/MS analysis of organic products in the liquid phase, it is shown that the controlled hydrolysis of TiCl4 with water, which was in situ generated from the TiCl4-catalyzed aldol condensation reactions of acetones, played an important role in the formation of the titania nanomaterials. Some of the organic condensates may function to stabilize the phase and morphology of the materials. This mechanism was also supported by our success in using other ketones as alternatives to acetone in the synthesis.

[The effect of Hongjingtian (Gadol) injection on cardiac hemodynamics and myocardial oxygen consumption of dogs].

OBJECTIVE: To study the effect of Hongjingtian (Gadol) injection on cardiac hemodynamics and myocardial oxygen consumption for analyzing its underlying mechanism in the treatment of coronary heart disease. METHOD: A total of 20 dogs anesthetized with pentobarbital sodium (30 mg x kg(-1), i.v.) were evenly randomized into control group, low-dose Gadol (LDG) group, high-dose Gadol (HDG) group and Herbesser Injection group. The blood flow volume (BFV) of the left coronary artery and cardiac output (CO), left ventricular pressure (LVP), maximum ascending rate (dp/dtmax) of LVP, mean arterial pressure (MAP) of the femoral artery, oxygen contents of the coronary artery and coronary vein (venous sinus), oxygen consumption index (OCI), cardiac index (CI), coronary artery resistance (CAR) and total peripheral resistance (TPR) as well as oxygen utilization rate (OUR) were detected respectively. RESULT: After venous injection of Gadol, CAR, MAP, TPR, OCI, myocardial oxygen consumption and heart rate lowered significantly (P < 0.05-0.01), while BFV and blood oxygen content of the venous sinus increased considerably (P < 0.05-0.01) in comparison with pre-injection. No significant differences were found in LVP and myocardial contractivity between control group and LDG, and between control and HDG groups respectively. CONCLUSION: It showed dilation of the coronary artery and reduction of the cardiac afterload after injection of Gadol. Besides, CO and stroke volume increased considerably and the cardiac effective work was raised without any significant simultaneous increase of both myocardial contractility and LVP. A decrease in the myocardial oxygen consumption and reduction of OCI indicates an improvement of the oxygen supply of the myocardium, and a favorable regulation of the compliance of the cardiac vessels. As a result, the cardiovascular performance was ameliorated. The abovementioned improvement of these indexes may contribute to the therapeutic effect of Gadol in the treatment of coronary heart disease in clinic.