Accumulation of typical persistent organic pollutants and heavy metals in bioretention facilities: Distribution, risk assessment, and microbial community impact.

Bioretention facilities have proven highly effective in removing pollutants from runoff. However, there is a concerning paucity of research on the contamination characteristics and associated risks posed by refractory pollutants in these facilities following long-term operation. This research focuses on the distribution, sources, microbial community impact, and human health risks of pollutants in eight bioretention facilities that have been operational for 5-11 years. The results showed that the distribution of Cu, Zn, and Cd was closely related to anti-seepage measures. PAHs, PCBs, and OCPs primarily accumulated in the surface, with concentrations ranging from 7.42 to 20.34 mg/kg, 31.8-77.3 µg/kg, and 60.5-163.6 µg/kg, respectively. Their concentrations inversely correlate with the depth of the media. Although the majority of contaminants remained below their respective risk thresholds, their concentrations typically exceeded those of background soil values, indicating an enrichment phenomenon. Source analysis revealed that PAHs primarily originate from oil combustion, PCBs were linked to their related industrial products, DDTs had their main sources in technical DDx and residues from the use of dicofol, while HCHs were traced back to historical residues from agricultural activities. Microbial α-diversity (Chao 1 and Shannon) decreased by 8.3-23.4% and 0.8-4.4%, respectively, in different facilities after long-term operation. The most dominant microbial phylum in the facilities was Proteobacteria (all relative abundances >48%). The total relative abundance of dominant genera was 6.7-34.3% higher than the control site, and Pseudomonas, a typical POPs-heavy metal degrading bacterium, had the highest relative abundance (>1.2%). Cu, Zn, and Cd present no non-carcinogenic risks and have low potential ecological risks. However, the lifetime cancer risk for PAHs is 10-6 ∼10-4 in most facilities and is of concern. The cancer risk for PCBs is acceptable, while OCPs pose a low cancer risk only for children.

Pharmacological Mechanism of Sancao Yuyang Decoction in the Treatment of Oral Mucositis Based on Network Pharmacology and Experimental Validation.

Purpose: The network pharmacology analysis, molecular docking and experimental verification were performed to explore the pharmacological mechanisms of Sancao Yuyang Decoction (SCYYD) in the treatment of oral mucositis (OM). Methods: Active ingredients in SCYYD and their potential targets, as well as OM-related targets were screened from public databases. The core targets and signaling pathways of SCYYD against OM were determined by protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The ingredient-target-disease network and target-pathway network were constructed. Subsequently, molecular docking was carried out to predict the binding activity between active ingredients and key targets. Moreover, in vivo experiment was conducted to further verify the core targets predicted by network pharmacology analysis. Results: A total of 119 bioactive ingredients were screened from the corresponding databases. One hundred and eighty-six putative targets were retrieved and bioinformatics analysis was performed to reveal the top 5 potential candidate agents and 10 core targets. GO and KEGG enrichment analysis showed that SCYYD exerted excellent therapeutic effects on OM through several pathways, such as HIF-1 and Ras signaling pathway. Subsequently, molecular docking showed that main ingredients in SCYYD had optimal binding activities to the key protein targets. Moreover, the result of in vivo experiment indicated that SCYYD not only inhibited inflammation response and promoted wound healing of oral mucosa in OM rats, but also reversed high expressions of SRC, HSP90AA1, STAT3, HIF1α, mTOR, TLR4, MMP9, and low expression of ESR1. Conclusion: This study preliminarily uncovered the multiple compounds and multiple targets of SCYYD against OM using network pharmacology, molecular docking and in vivo verification, which provided a new insight of the pharmacological mechanisms of SCYYD in treatment of OM.

Circular RNA hsa_circ_0051246 acts as a microRNA-375 sponge to promote the progression of gastric cancer stem cells via YAP1.

Background: Gastric cancer (GC) stem cells play an important role in GC progression. Circular RNAs (circRNAs) act as microRNA (miRNA) sponges and inhibit the biological function of miRNAs in GC cytoplasm. MiRNAs also participate in GC progress. circ_0051246 was shown to be associated with miR-375 after analyzing GC microarray data GSE78091 and GSE83521. The oncoprotein Yes-associated protein 1 (YAP1) is targeted by miR-375 and can be inactivated via the Hippo tumor suppressor pathway. Due to insufficient research on circ_0051246, this study aimed to investigate its relationship with miR-375 and YAP1 in cancer stem cells (CSCs). Methods: SGC-7901 CSCs were used to establish knockdown/overexpression models of circ_0051246, miR-375, and YAP1. Malignant phenotypes of CSCs were assessed using Cell Counting Kit 8, colony/sphere formation, 5-Ethynyl-2'-deoxyuridine assay, flow cytometry, Transwell, and wound healing assays. To detect the interactions between circ_0051246, miR-375, and YAP1 in CSCs, a dual-luciferase reporter assay and fluorescence in situ hybridization were performed. In addition, 24 BALB/c nude mice were used to establish orthotopic xenograft tumor models. Four groups of mice were injected with CSCs (1 × 106 cells/100 µL) with circ_0051246 knockdown, miR-375 overexpression, or their respective control cells, and tumor progression and gene expression were observed by hematoxylin-eosin staining, immunohistochemistry. Western blot and quantitative real-time PCR were utilized to examine protein and gene expression, respectively. Results: Circ_0051246 silencing reduced viability, promoted apoptosis, and inhibited proliferation, migration and invasion of CSCs. The functional effects of miR-375 mimics were comparable to those of circ_0051246 knockdown; however, the opposite was observed after miR-375 inhibitors treatment of CSCs. Furthermore, circ_0051246-overexpression antagonized the miR-375 mimics' effects on CSCs. Additionally, YAP1 overexpression promoted CSC features, such as self-renewal, migration, and invasion, inhibited apoptosis and E-cadherin levels, and upregulated the expression of N-cadherin, vimentin, YAP1, neurogenic locus notch homolog protein 1, and jagged canonical notch ligand 1. Conversely, YAP1-silenced produced the opposite effect. Moreover, miR-375 treatment antagonized the malignant effects of YAP1 overexpression in CSCs. Importantly, circ_0051246 knockdown and miR-375 activation suppressed CSC tumorigenicity in vivo. Conclusion: This study highlights the promotion of circ_0051246-miR-375-YAP1 axis activation in GC progression and provides a scientific basis for research on the molecular mechanism of CSCs.

Research of the Active Components and Potential Mechanisms of Qingfei Gujin Decoction in the Treatment of Osteosarcoma Based on Network Pharmacology and Molecular Docking Technology.

Aim: Qingfei Gujin Decoction (QGD) has been shown to be effective against osteosarcoma. This research was aimed at investigating the main active ingredients and potential mechanisms of QGD acting on osteosarcoma through network pharmacology and molecular docking techniques. Methods: The active ingredients and targets of QGD were screened from the TCMSP database, and the predicted targets were obtained from the PharmMapper database. Meanwhile, the targets of osteosarcoma were collected using OMIM, PharmGKB, and DisGeNET databases. Then, GO and KEGG enrichment analyses were performed by RStudio. PPI and drug-ingredient-target networks were constructed using Cytoscape 3.2.1 to screen the major active ingredients, key networks, and targets. Finally, molecular docking of key genes and their regulatory active ingredients was performed using AutoDockTools 1.5.6 software. Results: 38 active ingredients were collected, generating 89 cross-targets; quercetin, luteolin, ß-sitosterol, and kaempferol were the main active ingredients of QGD acting on osteosarcoma, and major signaling pathways such as PI3K-Akt signaling pathway, MAPK signaling pathway, and IL-17 signaling pathway were observed. TP53, SRC, and ESR1 were identified as key proteins that docked well with their regulated compounds. Conclusion: QGD is effective against osteosarcoma through multicomponent, multitarget, and multipathway. This study was helpful for finding effective targets and compounds for osteosarcoma treatment.

Soothing liver-qi stagnation method for cancer-related depression: A protocol for systematic review and meta-analysis.

BACKGROUND: Cancer-related depression (CRD) is the most common mood disorder in patients with malignant tumors, negatively influencing the patient's daily life. Traditional Chinese medicine, as an alternative CRD therapy, has shown good treatment performance in recently years. Soothing liver-qi stagnation, as a classic therapy for depression, is based on traditional Chinese medicine theory. However, there is no evidence-based medical confirmation for the soothing liver-qi stagnation method for CRD treatment. METHODS: We will systematically search relevant articles from their inception to July 1, 2019 in the following electronic databases: the Cochrane Library, PubMed, EMBASE, Chinese National Knowledge Infrastructure Database, Chinese Biomedical Literature Database, Chinese Science and Technique Journals Database, and the Wan-fang Database. The primary outcome is the total scores of the Hamilton rating scale for depression and, the efficacy rate of reducing Hamilton rating scale for depression scores. The secondary outcomes are adverse reactions and quality of life as assessed by standard instruments. Two researchers will independently perform study selection, data extraction, and quality assessment. If there is any disagreement, it will be settled through third-party negotiations. We will assess the risk of bias and data synthesis using Review Manager (the Cochrane Collaboration) software, Version 5.3.0. RESULTS: This work will evaluate the clinical effectiveness and safety of the soothing liver-qi stagnation method for CRD. CONCLUSION: This study may provide evidence-based medical corroboration for clinical application of the soothing liver-qi stagnation method for CRD treatment. PROSPERO REGISTRATION NUMBER: CRD42019145678.

Comprehensive Analysis of a circRNA-miRNA-mRNA Network to Reveal Potential Inflammation-Related Targets for Gastric Adenocarcinoma.

Gastric cancer (GC) is the most common malignancy of the stomach. This study was aimed at elucidating the regulatory network of circRNA-miRNA-mRNA and identifying the precise inflammation-related targets in GC. The expression profiles of GSE83521, GSE78091, and GSE33651 were obtained from the GEO database. Interactions between miRNAs and circRNAs were investigated by the Circular RNA Interactome, and targets of miRNAs were predicted with miRTarBase. Then, a circRNA/miRNA/mRNA regulatory network was constructed. Also, functional enrichment analysis of selected differentially expressed genes (DEGs) was performed. The inflammation-/GC-related targets were collected in the GeneCards and GenLiP3 database, respectively. And a protein-protein interaction (PPI) network of DE mRNAs was constructed with STRING and Cytoscape to identify hub genes. The genetic alterations, neighboring gene networks, expression levels, and the poor prognosis of hub genes were investigated in cBioPortal, Oncomine, and Human Protein Atlas databases and Kaplan-Meier plotter, respectively. A total of 10 DE miRNAs and 33 DEGs were identified. The regulatory network contained 26 circRNAs, 10 miRNAs, and 1459 mRNAs. Functional enrichment analysis revealed that the selected 33 DEGs were involved in negative regulation of fat cell differentiation, response to wounding, extracellular matrix- (ECM-) receptor interaction, and regulation of cell growth pathways. THBS1, FN1, CALM1, COL4A1, CTGF, and IGFBP5 were selected as inflammation-related hub genes of GC in the PPI network. The genetic alterations in these hub genes were related to amplification and missense mutations. Furthermore, the genes RYR2, ERBB2, PI3KCA, and HELZ2 were connected to hub genes in this study. The hub gene levels in clinical specimens were markedly upregulated in GC tissues and correlated with poor overall survival (OS). Our results suggest that THBS1, FN1, CALM1, COL4A1, CTGF, and IGFBP5 were associated with the pathogenesis of gastric carcinogenesis and may serve as biomarkers and inflammation-related targets for GC.

Associations between interleukin gene polymorphisms and the risk of gastric cancer: A meta-analysis.

Recently, the roles of interleukin-2 (IL-2), IL-4, IL-6 and IL-8 gene polymorphisms in gastric cancer (GC) have been studied extensively, with conflicting results. Therefore, we conducted the present meta-analyses to better elucidate the roles of interleukin gene polymorphisms in GC. Eligible articles were searched in PubMed, MEDLINE, Embase, Web of Science and CNKI. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to detect any potential association between interleukin gene polymorphisms and the risk of GC. A total of 63 case-control studies was finally included in our analyses. Significant associations with the risk of GC were detected for the IL-6 rs1800796 and IL-8 rs4073 polymorphisms in overall analyses. Further subgroup analyses based on ethnicities of participants revealed that the IL-4 rs2243250, IL-6 rs1800796 and IL-8 rs4073 polymorphisms were significantly associated with the risk of GC in Asians. Moreover, IL-8 rs4073 polymorphism was also significantly associated with the risk of GC in Africans. In conclusion, our findings suggested that IL-4 rs2243250, IL-6 rs1800796 and IL-8 rs4073 polymorphisms may serve as genetic biomarkers of GC.

pMOSFETs Featuring ALD W Filling Metal Using SiH4 and B2H6 Precursors in 22 nm Node CMOS Technology.

In this paper, pMOSFETs featuring atomic layer deposition (ALD) tungsten (W) using SiH4 and B2H6 precursors in 22 nm node CMOS technology were investigated. It is found that, in terms of threshold voltage, driving capability, carrier mobility, and the control of short-channel effects, the performance of devices featuring ALD W using SiH4 is superior to that of devices featuring ALD W using B2H6. This disparity in device performance results from different metal gate-induced strain from ALD W using SiH4 and B2H6 precursors, i.e. tensile stresses for SiH4 (~2.4 GPa) and for B2H6 (~0.9 GPa).

Integration of Highly Strained SiGe in Source and Drain with HK and MG for 22 nm Bulk PMOS Transistors.

In this study, the integration of SiGe selective epitaxy on source/drain regions and high-k and metal gate for 22 nm node bulk pMOS transistors has been presented. Selective Si1-x Ge x growth (0.35 ≤ × ≤ 0.40) with boron concentration of 1-3 × 1020 cm-3 was used to elevate the source/drain. The main focus was optimization of the growth parameters to improve the epitaxial quality where the high-resolution x-ray diffraction (HRXRD) and energy dispersive spectrometer (EDS) measurement data provided the key information about Ge profile in the transistor structure. The induced strain by SiGe layers was directly measured by x-ray on the array of transistors. In these measurements, the boron concentration was determined from the strain compensation of intrinsic and boron-doped SiGe layers. Finally, the characteristic of transistors were measured and discussed showing good device performance.

[Analysis on metabolites with small molecule of serum in bone marrow suppression model mice with metabolomics method].

Bone marrow suppression is a common symptom in patients with malignant tumor after chemotherapy. Studying the changes of metabolites caused by bone marrow depression can provide insights for the diagnosis of bone marrow suppression disease and for the development of drug therapy. Male BalB/C mice were injected with cyclophosphamide to establish a bone marrow suppression model. Gas chromatography-mass spectrometry (GC-MS) with fingerprinting was used to analyze the normal and model mice blood metabolites. Principal component analysis and orthogonal to partial least squares discriminant analysis (OPLS-DA) on metabolomics for data multidimensional statistical analysis was also used. Compared to the normal group in terms of the metabolic profile of bone marrow suppression mice, there were 15 endogenous metabolites in mouse plasma, nine of which were statistically significantly different, including glucose-1-phosphate, 4-nitrophenol, acetanilide, cortisone, nicotinamide, loganin, caffeic acid, linoleic acid and oleic acid (P<0.05). These results indicate that metabolite can be used as an important marker in bone marrow suppression, which can help to reveal the pathogenesis of bone marrow suppression induced by chemotherapy and determine the disease development stage and the effectiveness of follow-up treatment.

High-dose methotrexate (HD-MTX) used as an adjunct with other chemotherapeutics for the treatment of osteosarcoma.

The objective of this study is to evaluate retrospectively the effectiveness of multiple-drug chemotherapeutics regimen that included high-dose methotrexate (HD-MTX) for treating primary osteosarcoma. 148 newly diagnosed patients with Stage I and II osteosarcoma who received HD-MTX/HD-MTX/DDP(cisplatin)/ADM(doxorubicin) and/or HD-MTX/IFO(Ifosfamide)/DDP/ADM before and after the surgery were retrospectively analyzed to measure the efficacy of this regimen. The significance of various variables as predictive prognostic factors of the patient survival rate was also evaluated. The overall 3-year survival rate of the patients was 79.73 %. The survival rate was improved to 85.71 % in the patients who received surgery and a complete 4-cycle chemotherapy. In addition, the rates of disease-free survival (DFS), local recurrence, and distant metastasis were 68.13, 3.30, and 10.81 %, respectively. Our analysis showed that completing 4-cycle chemotherapy produced a significant impact on the overall 3-year survival and DFS rates (P < 0.05). The overall 3-year survival was correlated with pathological fracture, chemotherapy completion, histological response, local recurrence, and distance metastasis (single-factor P < 0.05). Multivariate analysis further evidenced that these predictive factors were independently correlated to the survival rate (multi-factor P < 0.05). The complete 4-cycle multiple-drug chemotherapy consisting of HD-MTX, doxorubicin, cisplatin, and ifosfamide combined with surgical resection was found to be effective in improving the survival rate of osteosarcoma patients. Furthermore, the presence of pathological fracture, poor histological response, local recurrence, and distant metastasis was negatively correlated with the survival rate. Patient age, gender, location of primary tumor, and serum alkaline phosphatase level were not found to show the prognostic significance.