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Fluorinated biphenyls and their analogues (FBAs) are considered new persistent organic pollutants, but their endocrine-disrupting effects are still unknown. To fill this gap, the binding probability of 44 FBAs to different nuclear hormone receptors (NHRs) was predicted using Endocrine Disruptome. And molecular similarity and network toxicology analysis were used to strengthen the docking screening. The docking results showed that FBAs could have high binding potential for various NHRs, such as estrogen receptors β antagonism (ERβ an), liver X receptors α (LXRα), estrogen receptors α (ERα), and liver X receptors β (LXRβ). The similarity analysis found that the degree of overlap of the NHR repertoire was related to the Tanimoto coefficient of FBAs. Network toxicology verified a part of docking screening results and identified endocrine-disrupting pathways worthy of attention. This study found out potential endocrine-disrupting FBAs and their vulnerable, and developed a workflow that would leverage in silico approaches including molecular docking, similarity, and network toxicology for risk prioritization of potential endocrine-disrupting compounds.

Background: ATAD2 is closely related to the occurrence and proliferation of many tumors. Thus, exploring ATAD2 inhibitors is greatly significant for the prevention and treatment of tumors. In this study, the quantitative structure–activity relationship (QSAR) analyses of 57 naphthyridone derivatives were conducted using hologram quantitative structure–activity relationship (HQSAR) and topomer comparative molecular field analysis (topomer CoMFA). Method: The 57 naphthyridone derivatives were divided into the training (44 derivatives) and testing (13 derivatives) sets. HQSAR and topomer CoMFA models were obtained by applying the SYBYL-X software and validated using various validation parameters. Contribution maps from the best HQSAR model and the contour maps from the best topomer CoMFA model were analyzed. Results: The most effective HQSAR model exhibited significant cross-validated (q2 = 0.872) and non cross-validated (r2 = 0.972) correlation coefficients, and the most effective topomer CoMFA model had q2 = 0.861 and r2 = 0.962. Several external validation parameters, such as , , , , and , were used to calculate the correlation coefficients of the test set samples and validate both models. The result exhibited a powerful predictive capability. Graphical results from HQSAR and topomer CoMFA were validated by the binding mode in the crystal structure. Conclusion: The models may be beneficial to enhance the understanding of the structure–activity relationships for this class of compounds and also provide useful clues for the design of potential ATAD2 bromodomain inhibitors.

Molybdenum disulfide (MoS2) is an emerging class of new materials with a wide range of potential practical applications. However, the uncontrollability of monolayer MoS2 synthesized by traditional chemical vapor deposition method and the low responsivity of MoS2 photodetectors limit its further development in the field of photoelectric detection. To achieve controlled growth of monolayer MoS2 and construct MoS2 photodetectors with a high responsivity, we propose a novel single crystal growth strategy of high-quality MoS2 by controlling the Mo to S vapor ratio near the substrate, and deposit a layer of hafnium oxide (HfO2) on the surface of MoS2 to enhance the performance of the pristine metal-semiconductor-metal structure photodetector. At a reverse bias of 8 V, the HfO2 passivated MoS2 photodetector features an extremely high responsivity of 1201 AW − 1 , a response time of around 0.5 s, and a detectivity of 7.7 × 10 11 Jones . Meanwhile, we deeply investigate the effect of the HfO2 layer on the performance of the fabricated MoS2 photodetector and propose a physical mechanism to interpret the obtained experiment results. These results might facilitate a better understanding on the performance modulation of the MoS2 photodetectors and accelerate the development of MoS2-based optoelectronic devices.

MoSe2 from monolayer to bulk phase can realize the transition from a direct bandgap semiconductor to an indirect bandgap semiconductor. Its bandgap varies between 1.1 and 1.55 eV, which matches the solar spectral range, so Si-based heterojunction solar cells with MoSe2 as an active layer have great significance in the development of low-cost, high-efficiency and high-flexibility photovoltaic devices. In this work, MoSe2 thin films were synthesized by chemical vapor deposition using MoO3 and Se powders as precursor sources. The effects of different process parameters (Se source temperature, Mo source temperature, growth time, carrier gas flow rate and hydrogen ratio) on the synthesis of MoSe2 thin films were systematically investigated. The optimized experimental parameters were determined as follows: the molybdenum source temperature of 800[Formula: see text], the selenium source 20 cm away from molybdenum source, the growth time of 10 min, the carrier gas flow rate of 60 sccm, the hydrogen ratio of 10%. Then MoSe2/Si heterojunction solar cells were constructed via wet chemical transfer. The open-circuit voltage, short-circuit current density, filling factor and photovoltaic conversion efficiency of the fabricated solar cells were 0.19 V, 5.71 mA/cm2, 30.47% and 0.33%, respectively. Main factors affecting the photovoltaic performance of the MoSe2/Si solar cells have also been discussed. This work is very helpful for the development of MoSe2 material and relevant application in the field of solar cells.

In this work, MoS2 thin films were successfully synthesized by chemical vapor deposition (CVD) using MoO3 and sulfur powders as precursor sources. The effect of the MoO3 dosage and heating temperature on the quality of the synthesized MoS2 films are investigated and a detailed reaction mechanism is proposed to interpret the obtained experimental result. Furthermore, we have studied the influence of different metal back electrodes (including Ag and Au) on the photovoltaic performance of the fabricated MoS2/Si heterojunction solar cell. It is shown that, in comparison with the solar cell using Au as a metal back electrode, the solar cell using Ag as a metal back electrode has poor photovoltaic performance with the appearance of the S-type shape in the measured current density-voltage curve. Finally, numerical simulation based on AFORS-HET software has been carried out to investigate the photovoltaic performance of the [Formula: see text]-MoS2/[Formula: see text]-Si heterojunction solar cell under different work functions of the metal back electrode. The result of numerical simulation is consistent with our experiential result in the trend. This work is highly relevant to the development of transition metal dichalcogenides in the application of solar cells.

In order to reduce the toxicity and side effects of anti-tumor drugs and improve their therapeutic effect against cancer, photodynamic and chemical combination therapy has been exploited. However, the complicated preparation and metabolic toxicity of photosensitizer-loaded materials remain major obstacles for bioapplications. In this study, we designed and prepared a specific photosensitizer self-transporting drug-delivery system. First, 5,10,15,20-tetrakis(4-aminophenyl)-21H,23H-porphine (TAPP) was modified using specific molecules of d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) with a certain antitumor effect, to prepare a specific fluorescent amphiphilic system (TAPP-TPGS). Then, the drug-loaded fluorescence nanomicelle (TAPP-TPGS/PTX) was formed via self-assembly using the amphiphilic system and the anticancer drug paclitaxel (PTX). The carrier material could be used as a drug tracer and cancer therapy reagent to synergistically trace the chemotherapy drug and treat cancers. The biocompatibility and the enhanced antitumor effect of TAPP-TPGS/PTX were confirmed by in vitro and in vivo experiments. To detect the synergistic anticancer effect enhanced by TPGS, TAPP-mPEG synthesized with a similar method as TAPP-TPGS was used for a comparative analysis. The results showed that the excellent synergistic anticancer effect of the TAPP-TPGS/PTX was enhanced due to the introduction of TPGS. Thus, the specific porphyrin self-transporting nanomicelle is a very promising carrier material for applications in biomedicine.

Exosomes released from human umbilical cord mesenchymal stem cell (hucMSC-Ex) have been revealed to hold great potential for the development of new treatment approaches for various diseases, including inflammatory bowel disease (IBD). Lymphatic vessels are vital for IBD development and progression to colorectal cancer (CRC), as an occluded conduit for lymphatic fluid to return to the blood.The mechanism involved remains largely unexplored. Here, we investigate the therapeutic effect of hucMSC-Ex in a mouse model of IBD during the modulation of lymphangiogenesis.We established a dextran sulfate sodium (DSS)-induced IBD model in BALB/c mice and observed the influence of hucMSC-Ex on tissue repair, intestinal lymphatic function, changes in lymphangiogenesis, and infiltration of macrophages. We also evaluated the functional changes of human lymphatic endothelial cells (hLECs) in vitro to determine the mechanism by which hucMSC-Ex regulate lymphangiogenesis. Finally, we identified key molecules in hucMSC-Ex by sequencing, database comparison, and cell validation.Results showed that hucMSC-Ex alleviates IBD in mice by improving intestinal lymphatic drainage, inhibiting lymphangiogenesis, and infiltration of macrophages. Mechanistically, the miRNA sequencing results showed that miR-302d-3p was highly expressed in hucMSC-Ex and played an important role in inhibiting lymphangiogenesis by targeting Fms-related receptor tyrosine kinase 4 (FLT4). At the same time, the phosphorylation of AKT was inhibited and vascular endothelial growth factor receptor 3 (VEGFR3) was reduced.Collectively, our study suggests that hucMSC-Ex can regulate lymphangiogenesis via the miR-302d-3p/VEGFR3/AKT axis to ameliorate IBD. Our findings identify VEGFR3 as a potential therapeutic target in IBD, where tightly regulated lymphangiogenesis is crucial in its pathogenesis and progression.

Inflammatory bowel disease (IBD) can be caused by a variety of factors, including hereditary and environmental influences, that lead to dysfunction of the intestinal immune system. Mesenchymal stem cells (MSCs) exhibit important regulatory roles in relieving inflammation and repairing damaged tissues. Although neutrophils are important participants in the development of inflammatory reactions, they are also essential for maintaining intestinal balance during the process of mitigation of IBD by MSCs. Here, we constructed a dextran sulfate sodium (DSS)-induced mouse IBD model and evaluated the effects of treatment with human umbilical cord MSCs. Mouse body weight, faecal traits, colon/spleen gross morphology, tissue histology and immunohistochemical staining, and inflammatory factors were analysed. Magnetic beads were used to sort infiltrating neutrophils from intestinal tissues, and their phenotypes were identified. The neutrophil inflammatory environment was also simulated in vitro, and signalling pathways involved in MSC regulation of neutrophil phenotype were analysed. Human umbilical cord MSCs effectively alleviated DSS-induced weight loss, colon shortening, and intestinal mucosal injury, and reduced clinical disease activity index. The number of neutrophils that infiltrated the intestines of mice treated with human umbilical cord MSCs were decreased and polarised toward the N2 phenotype; at the same time, ERK phosphorylation was inhibited. In vitro experiments showed that addition of the ERK phosphorylation inhibitor, PD98059, down-regulated the expression of N1 neutrophils, while up-regulating that of N2 neutrophils. The colon tissues from patients with IBD were infiltrated with neutrophils. Further, relative to healthy controls, the markers of N1 neutrophils (ICAM-1, FAS, and CCL3) were highly expressed in colon tissues from patients with IBD, whereas the markers of N2 neutrophils (VEGF, CCL2, and CXCR4) were almost undetectable. In conclusion, during alleviation of IBD, human umbilical cord MSCs polarise neutrophils toward the "N2" phenotype by inhibiting activation of ERK signalling.

Background Human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes are recognized as novel cell-free therapeutic agents for inflammatory bowel disease (IBD), a condition caused by dysregulated intestinal mucosal immunity. In this event, macrophage pyroptosis, a process of cell death following the activation of NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammasomes, is believed to partially account for inflammatory reactions. However, the role of macrophage pyroptosis in the process of hucMSC-derived exosomes alleviating colitis remains unknown. This study aimed at exploring the therapeutic effect and mechanism of hucMSC-derived exosomes on colitis repair. Methods In vivo, we used BALB/c mice to establish a dextran sulfate sodium (DSS)-induced colitis model and administrated hucMSC-derived exosomes intravenously to estimate its curative effect. Human myeloid leukemia mononuclear (THP-1) cells and mouse peritoneal macrophages (MPMs) were stimulated with lipopolysaccharides (LPS) and Nigericin to activate NLRP3 inflammasomes, which simulated an inflammation environment in vitro. A microRNA mimic was used to verify the role of miR-378a-5p/NLRP3 axis in the colitis repair. Results hucMSC-derived exosomes inhibited the activation of NLRP3 inflammasomes in the mouse colon. The secretion of interleukin (IL)-18, IL-1β, and Caspase-1 cleavage was suppressed, resulting in reduced cell pyroptosis. The same outcome was observed in the in vitro cell experiments, where the co-culture of THP-1 cells and MPMs with hucMSC-derived exosomes caused decreased expression of NLRP3 inflammasomes and increased cell survival. Furthermore, miR-378a-5p was highly expressed in hucMSC-derived exosomes and played a vital function in colitis repair. Conclusion hucMSC-derived exosomes carrying miR-378a-5p inhibited NLRP3 inflammasomes and abrogated cell pyroptosis to protect against DSS-induced colitis.

Colorectal cancer (CRC) is a common malignant tumor of the gastrointestinal tract with nonobvious early symptoms and late symptoms of anemia, weight loss, and other systemic symptoms. Its morbidity and fatality rate are next only to gastric cancer, esophageal cancer, and primary liver cancer among digestive malignancies. In addition to the conventional surgical intervention, other therapies such as radiotherapy and chemotherapy and new treatment methods such as biologics and microbiological products have been introduced. As a promising cell therapy, mesenchymal stem cell (MSC) has attracted extensive research attention. MSCs are early undifferentiated pluripotent stem cells, which have the common features of stem cells, including self-replication, self-division, self-renewal, and multidirectional differentiation. MSCs come from a wide range of sources and can be extracted from a variety of tissues such as the bone marrow, umbilical cord, and fat. Current studies have shown that MSCs have a variety of biological functions such as immune regulation, tissue damage repair, and therapeutic effects on tumors such as CRC. This review outlines the overview of MSCs and CRC and summarizes the role of MSC application in CRC.

A small, nano-sized, water-soluble polyrotaxane (PR) was synthesized using a highly efficient one-pot synthesis strategy in a homogeneous water system, formed from β-cyclodextrin-(COOH)2, poly(propylene glycol)bis(2-aminopropyl ether) (PPG, 2 kDa) and a mono-(6-azido-6-desoxy)-β-cyclodextrin stopper via room temperature click chemistry. β-cyclodextrin-(COOH)2 and PR were characterized by one- and two-dimensional NMR as well as by high resolution transmission electron microscopy (HR-TEM). The number of carboxyl groups in one PR was determined by 1H NMR. Two-dimensional diffusion-ordered NMR spectroscopy (2D DOSY) and nuclear Overhauser enhancement spectroscopy (2D NOESY) show that β-cyclodextrin-(COOH)2 and PPG successfully formed an inclusion complex. HR-TEM revealed the morphology of water-soluble PR as a spherical nanoparticle with a size of approximately 3.5 nm ± 1.5 nm. PR was labeled with rhodamine to assess its biocompatibility and cell membrane penetrability in vitro. The in vivo real-time fluorescent imaging biodistribution experiments indicated that water-soluble PR can actively target tumor sites using an enhanced permeability and retention (EPR) effect, with a significantly prolonged blood circulation time in tumor-bearing mice.

Drug delivery carriers hold tremendous promise for improving cancer treatment, and polyrotaxane (PR) has shown excellent drug-carrying properties. However, there have been some reports that, when used as a drug carrier, water-soluble PR is not easily labeled with organic fluorescent dyes. Herein, we synthesized a drug-loaded fluorescent porphyrin-terminated PR (PR-COOH) which can be used as a tracer material in drug and gene delivery. The structure, morphology and zeta potential of PR-COOH were characterized by nuclear magnetic resonance, high-resolution transmission electron microscopy and zeta potentiometry. In this research, cisplatin (CDDP) is used as a model drug. The zeta potential, drug encapsulation efficiency and drug release of CDDP-loaded PR (PR-COOH-Pt) were studied. Confocal laser scanning microscopy showed that PR-COOH could be internalized by HeLa and CT26 cells. The antitumor efficacy of PR-COOH-Pt was investigated in vitro by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and in vivo by a xenograft tumor model. The results showed that PR-COOH-Pt could significantly inhibit tumor growth; thus PR-COOH-Pt has a promising role in cancer therapy.

The toxic effects of per- and polyfluoroalkyl substances (PFASs) on humans are mediated by nuclear hormone receptors (NHRs). However, data on the interaction of PFASs and NHRs is limited. Endocrine Disruptome, an inverse docking tool, was used in this study to simulate the docking of 49 common PFASs with 14 different types of human NHRs. According to the findings, 25 PFASs have a high or moderately high probability of binding to more than five NHRs, with androgen receptor (AR) and mineralocorticoid receptor (MR) being the most likely target NHRs. Molecular docking analyses revealed that the binding modes of PFASs with the two NHRs were similar to those of their corresponding co-crystallized ligands. PFASs, in particular, may disrupt the endocrine system by binding to MR. This finding is consistent with epidemiological research that has linked PFASs to MR-related diseases. Our findings may contribute to a better understanding of the health risks posed by PFASs.

A hologram quantitative structure–activity relationship (HQSAR) and topomer comparative molecular-field analysis (CoMFA) were performed on 51 molecules that belong to the azo dyes to determine their affinities to cellulose fiber. The best HQSAR model was obtained by using atoms. Hydrogen atoms as a fragment distinction and a fragment size of 3–6 showed a leave-one-out cross-validated correlation coefficient (q2LOO) of 0.849 and a non-cross-validated correlation coefficient (r2) of 0.927. The best topomer CoMFA model with steric and electrostatic field parameters based on three fragments gave satisfactory results (q2LOO = 0.821; r2 = 0.934). External predictions were made on a test set and compared with previously reported models. Topomer CoMFA steric, electrostatic, and HQSAR atomic contribution maps were generated to analyze the structural features of this data set that govern their affinity potency.

Aims: miR-181a and miR-181b have been investigated as prognostic biomarkers of colorectal cancer (CRC). However, there is controversy about the role of miR-181a and miR-181b in predicting CRC prognosis. Therefore, we performed this meta-analysis to evaluate prognostic values of miR-181a and miR-181b in CRC patients. Materials & methods: Studies were systemically searched from publications and analyzed, and 999 CRC cases in nine studies were examined in this meta-analysis. Results: Hazard ratio for overall survival of high miR-181a and miR-181b expression in CRC was 1.65. More prominent predictive effects were observed in black people, miR-181b group and small-sample-size group. Conclusion: High levels of miR-181a and miR-181b predict poor overall survival in CRC patients. miR-181a and miR-181b are promising biomarkers for CRC prognosis.

A kind of specific cyclodextrin polyrotaxanes (PRs) drug delivery system was developed for an effective drug delivery and enhancing antitumor effect. In this work, we prepared the PR by using α-CD derivatives and dicarboxyl-PEG (Mn = 4200) self-assembling and end-capping with β-CD derivatives. Then, we chose d-a-Tocopheryl polyethylene glycol 1000 succinate (TPGS) with an antitumor effect to modify the PR. The modified PRs have a certain anticancer effect and can assist the anticancer drug to treat cancer. The 10-hydroxycamptothecin (HCPT) was combined to the specific PRs by covalent bonds to prepare drug-loaded specificity PRs (PR-TPGS-HCPT). The enhanced antitumor activities of PR-TPGS-HCPT were studied by in vitro and in vivo experiments, and the experiment results proved that the TPGS could effectively assist the drug to treat cancer and prolong the lifetime of the tumor-bearing mice. Therefore, this research provides a promising drug-loaded material for the cancer treatment and the specific water-soluble PRs will have potential applications in the biomedical field.

This work is devoted to the applications of the multiple linear regression (MLR), multilayer perceptron neural network (MLP NN) and projection pursuit regression (PPR) to quantitative structure-property relationship analysis of bioconcentration factors (BCFs) of pesticides tested on Bluegill (Lepomis macrochirus). Molecular descriptors of a total of 107 pesticides were calculated with the DRAGON Software and selected by inverse enhanced replacement method. Based on the selected DRAGON descriptors, a linear model was built by MLR, nonlinear models were developed using MLP NN and PPR. The robustness of the obtained models was assessed by cross-validation and external validation using test set. Outliers were also examined and deleted to improve predictive power. Comparative results revealed that PPR achieved the most accurate predictions. This study offers useful models and information for BCF prediction, risk assessment, and pesticide formulation.

Quantitative structure–activity relationship (QSAR) studies were performed in this work to predict the pIC50 of non-glycoside sodium-dependent glucose cotransporter-2 (SGLT2) inhibitors (46 triazole derivatives). Four descriptors were selected from the pool of DRAGON descriptors using the enhanced replacement method. Three nonlinear regression methods—multilayer perceptron neural network (MLP NN), support vector machine (SVM), and projection pursuit regression (PPR)—were then used to build the QSAR models. The performance of the obtained models was assessed through the cross-validation and external validation of the test set. PPR produced a better model than MLP NN and SVM with coefficients of determination of 0.962 and 0.871 and root mean square errors of 0.162 and 0.471 for the training and test sets, respectively. This study developed simple and efficient approaches to predict the pIC50 of triazole derivatives and provided some insights into their structural features for the development of more potential SGLT2 inhibitors.

Aim: Sodium–glucose cotransporter 2 (SGLT2) is a promising target for diabetes therapy. We aimed to develop computational approaches to identify structural features for more potential SGLT2 inhibitors. Materials & methods: In this work, 46 triazole derivatives as SGLT2 inhibitors were studied using a combination of several approaches, including hologram quantitative structure–activity relationships (HQSAR), topomer comparative molecular field analysis (CoMFA), homology modeling, and molecular docking. HQSAR and topomer CoMFA were used to construct models. Molecular docking was conducted to investigate the interaction of triazole derivatives and homology modeling of SGLT2, as well as to validate the results of the HQSAR and topomer CoMFA models. Results: The most effective HQSAR and topomer CoMFA models exhibited noncross-validated correlation coefficients of 0.928 and 0.891 for the training set, respectively. External predictions were made successfully on a test set and then compared with previously reported models. The graphical results of HQSAR and topomer CoMFA were proven to be consistent with the binding mode of the inhibitors and SGLT2 from molecular docking. Conclusion: The models and docking provided important insights into the design of potent inhibitors for SGLT2.

Polychlorinated Dibenzodioxins (PCDDs), Dibenzofurans (PCDFs) and Biphenyls (PCBs) are industrial compounds or byproducts that can cause toxic effects after binding to aryl hydrocarbon receptor (AhR). But the mechanism about PCDDs, PCDFs and PCBs binding to AhR is unclear. To study the interaction and significant amino acid residues in binding of PCDDs, PCDFs and PCBs to AhR, a docking-based Comparative Molecular Similarity Indices Analysis (CoMSIA) was performed on a set of structurally diverse PCDDs, PCDFs and PCBs with known binding affinities. The docking-based CoMSIA model (non-cross-validated regression coefficient of 0.942 and cross-validated regression coefficient of 0.768) was developed and compared with previous report, the presented docking-based CoMSIA model showed good robustness and predictive performance. The obtained docking conformations and predictive CoMSIA model could provide clues to understand key residues and interactions between receptor and compounds of interest.

Sufentanil is a new kind of opioid analgesic and acts on μ opioid receptor. In this study, we aim to investigate the effects of sufentanil on gastric cancer cell line SGC-7901, after being exposed to different concentrations of sufentanil. Gastric cancer cells were exposed to sufentanil for a predetermined time at concentrations of 0, 0.5, 5, 50 and 500 nmol/l, respectively. Cell viability at different time points after exposure to sufentanil was tested by CCK-8 assay. FDA-PI staining was used to observe membrane integrity of gastric cancer SGC7901 cells. The apoptosis of gastric cancer cells was analyzed by Annexin V-FITC/PI Flow Cytometry and the changes of the cell cycle was determined by a detection kit. As a result, cell viability decreased in a dose- and time-dependent manner. Furthermore, with the concentration of sufentanil increased, the proportion of dead and apoptotic SGC-7901 cells increased, and more cells were arrested in G2/M phase. In a word, sufentanil can inhibit the cell viability and induce the apoptosis of gastric cancer SGC-7901 cells in vitro.

This study aimed to determine the most significant molecular features associated with the liver specificity of the carcinogenicity of N-nitroso compounds (NOCs). Accordingly, quantitative structure-activity relationship (QSAR) analysis was performed to extract molecular information from NOCs using a topological substructural molecular descriptor (TOPS-MODE) approach. A linear discriminant analysis (LDA) model of a series of NOCs for rat liver was developed using TOPS-MODE descriptors to predict nonliver- and liver-carcinogenic NOCs. Two descriptors exclusively calculated from the molecular structures of the compounds were selected by a genetic algorithm. The descriptors were then weighted with bond distances as well as the Abraham solute descriptor partition between water and aqueous solvent systems to indicate the importance of their roles in liver specificity. The performances of the LDA model were rigorously validated by leave-one-out cross-validation and external validation, with the prediction accuracy reaching 88.3% and 80.0%, respectively. The contributions of the different molecular fragments to rat-liver specificity were computed. The results served as important information related to liver specificity and were analyzed from the chemical-molecular perspective. The resulting model can provide an efficient method to discriminate between as well as extrapolate nonliver- and liver-carcinogenic NOCs. The contribution of the entire nitrosamine molecule was determined as being responsible for the liver specificity of nitrosamine carcinogenicity. Although the QSAR showed limitations in complex hepatocarcinogenicity, the proposed method may considerably help elucidate the role of nitrosamines in liver specificity from the chemical-molecular perspective. The nature of these enzyme-substrate interactions is characterized. Insight into the chemical-structural and biological factors related to the liver-specific biological activity of NOCs is also provided.

The quantitative structure–activity relationship (QSAR) of N-nitroso compounds (NOCs) for rat liver was developed by a topological sub-structural molecular-descriptors (TOPS-MODE) approach to predict non-liver-carcinogenic and liver-carcinogenic N-nitroso compounds based on a data set of 108 NOCs. Three descriptors calculated solely from the molecular structures of the compounds were selected by enhanced replacement method (ERM) and were weighted, respectively, with atomic weight, bond dipole moments and Abraham solute descriptor partition between water and aqueous solvent systems to indicate the importance of their roles in liver specificity. A detailed discussion on these three descriptors was carried out, and the contributions of different fragments to rat-liver specificity and the interactions among fragments were analyzed. Such results can offer some useful theoretical references for understanding the chemical structural and biological factors related to the liver-specific biological activity of NOCs.

Microcystin-leucine arginine (MC-LR), a cyclic heptapeptide produced by several bloom-forming cyanobacteria, has strong reproductive toxicity. We examined whether MC-LR could enter spermatogonia and investigated the toxic effects of MC-LR on spermatogonia in vitro. Multispecific organic anion-transporting polypeptides (Oatps), which transported MCs, were screened as well. Spermatogonia were exposed to 0, 0.5, 5, 50, and 500 nmol/L (nM) MC-LR for 6 h. Cell viability and total antioxidant capacity significantly decreased, meanwhile, the ratio of apoptotic cells, reactive oxidative species (ROS) production, mitochondrial membrane potential (MMP), and intracellular free Ca2+ increased after exposure to 5 nM and higher concentrations of MC-LR. MC-LR can immigrate into spermatogonia. At least 5 Oatps (Oatp1a5, -3a1, -6b1, -6c1, and -6d1) were detected at the mRNA level in spermatogonia, and the expression of these Oatps was affected by MC-LR, especially Oatp3a1. This study demonstrated that MC-LR can be transported into spermatogonia and leads to cytotoxicity.

A linear discriminant analysis (LDA) coupled with an enhanced replacement method (ERM) was used as an alternative method to predict the carcinogenicity of N-nitroso compounds (NOCs) in rats. This presented LDA based on the topological substructural molecular descriptors (TOPS-MODE) approach was developed to predict the carcinogenic and noncarcinogenic activity on a data set of 111 NOCs with a good classification value of 90.1%. The predictive power of the LDA model was validated through an external validation set (37 compounds) with a prediction accuracy of 94.6% and a leave-one-out cross-validation procedure (LOOCV) with a good prediction of 86.5%. This methodology showed that the TOPS-MODE descriptors weighted, respectively, by bond dipole moment and Abraham solute descriptor dipolarity/polarizability affected the NOC carcinogenicity. The contributions of certain bonds and fragments to carcinogenicity were used to assess biotransformation and carcinogenic mechanisms. The positive contribution of the carbon-nitrogen single bond (between the N-nitroso group and α-carbon to the N-nitroso group) indicated that the α-hydroxylation reaction could occur at the α-carbon or otherwise not occur. Similarly, the contributions from the molecular fragment could be applied to indicate whether the fragments generated an alkylating agent. These results suggested that this approach could discriminate between carcinogenic and noncarcinogenic NOCs, thereby providing insight into the structural features and chemical factors related to NOC carcinogenicity.

A new method for the simultaneous analysis of malachite green (MG) and crystal violet (CV) in fish samples has been developed. In the presence of thiocyanate, the second order data of MG or CV obtained from the spectra of MG or CV in a series of water–ethanol mixed solvents with various ethanol volume fractions could be expressed as the combination of two bilinear data matrices. With the bilinear model, the second order spectra data of mixtures containing MG and CV those coexist with interferents could be analysed using the second order calibration algorithms, and the simultaneous determination of MG and CV in fish samples could be achieved. The algorithms were based on residual bilinearisation (RBL) and unfolded partial least-squares/residual bilinearisation (U-PLS/RBL) respectively. The method has been successfully used to determine simultaneously MG and CV in some fish samples with satisfactory results.

A new spectrophotometric titration method coupled with chemometrics for the simultaneous determination of mixtures of weak acids has been developed. In this method, the titrant is a mixture of sodium hydroxide and an acid-base indicator, and the indicator is used to monitor the titration process. In a process of titration, both the added volume of titrant and the solution acidity at each titration point can be obtained simultaneously from an absorption spectrum by least square algorithm, and then the concentration of each component in the mixture can be obtained from the titration curves by principal component regression. The method only needs the information of absorbance spectra to obtain the analytical results, and is free of volumetric measurements. The analyses are independent of titration end point and do not need the accurate values of dissociation constants of the indicator and the acids. The method has been applied to the simultaneous determination of the mixtures of benzoic acid and salicylic acid, and the mixtures of phenol, o-chlorophenol and p-chlorophenol with satisfactory results.

Octanol/water (K(OW)) and octanol/air (K(OA)) partition coefficients are two important physicochemical properties of organic substances. In current practice, K(OW) and K(OA) values of some polychlorinated biphenyls (PCBs) are measured using generator column method. Quantitative structure-property relationship (QSPR) models can serve as a valuable alternative method of replacing or reducing experimental steps in the determination of K(OW) and K(OA). In this paper, two different methods, i.e., multiple linear regression based on dragon descriptors and hologram quantitative structure-activity relationship, were used to predict generator-column-derived log K(OW) and log K(OA) values of PCBs. The predictive ability of the developed models was validated using a test set, and the performances of all generated models were compared with those of three previously reported models. All results indicated that the proposed models were robust and satisfactory and can thus be used as alternative models for the rapid assessment of the K(OW) and K(OA) of PCBs.

Ple iotropic proinflammatory cytokines, interleukin- 1 (IL-1) and tumor necrosis factor-α (TNF-α), involved in the regulations of various immune responses, inflammatory processes and hematopoiesis. In the present study, the expression levels of IL-1 and TNF-α were detected by enzyme-linked immunosorbent assay (ELISA). Following the cytokine blockade as a successful clinical therapy for autoimm une diseases such as rheumatoid arthritis, the patients are more susceptible to a variety of opportunistic infections. IL-1 and TNF-α may be useful predictive biomarkers of diseases and offer potential targets for therapeutic intervention of inflammatory diseases. However, our results showed that the plasma IL-1 level was significantly higher in women compared to men (69.5 ± 19.8 pg/ ml in men and 80.1 ± 19.5 pg/ml in women, respectively); the plasma levels of TNF-α were higher in men than women (20.8 ± 4.9 pg/ml and 18.7 ± 7.1 pg/ml, respectively). The significant gender difference of plasma interleukin-1 (IL-1) and TNF-α levels present in healthy adults in Jiangsu Province, China (P=0.002 and P=0.015, respectively), and may be as a hint for sex differences of susceptibility to many diseases and elementary immune response.

Background. Many recent studies revealed that the single nucleotide polymorphisms have considerable effects on the susceptibility of cancer, such as prostate cancer, lung cancer and gastric cancer. The E-cadherin, a calcium-dependent transmembrane glycoprotein encoded by CDH1 gene, is critical for epithelial construction, intercellular adhesion and cell migration. Some associations have been reported between single nucleotide polymorphisms and gastric cancer in the Chinese population. Objective. To investigate whether the single nucleotide polymorphism in CDH1 gene is associated with the susceptibility of gastric cancer in the Chinese population. Material and methods. The genotypes of 5 known single nucleotide polymorphisms (rs33935154, rs121964871, rs121964874, rs121964875, rs121964876) were determined in 359 gastric cancer patients and 368 healthy controls. High resolution melting curve detection and sequencing analysis were used in the present study. Results. There is a statistical significance in the rs121964871 C>G polymorphism between gastric cancer patients and healthy controls (OR=1.769, 95%CI: 1.051-2.976). Elderly male individuals (>50 years of age) carrying this risk factor may be more susceptible to gastric cancer. Conclusions. The results indicated that the rs121964871 C>G polymorphism is associated with the susceptibility of gastric cancer in the Chinese population, with some age and sex-dependent tendencies observed.

An attractive method of generating second-order data was developed by a dropping technique to generate pH gradient simultaneously coupled with diode-array spectrophotometer scanning. A homemade apparatus designed for the pH gradient. The method and the homemade apparatus were used to simultaneously determine malachite green (MG) and crystal violet (CV) in water samples. The absorbance–pH second-order data of MG or CV were obtained from the spectra of MG or CV in a series of pH values of HCl–KCl solution. The second-order data of mixtures containing MG and CV that coexisted with interferents were analyzed using multidimensional partial least-squares with residual bilinearization. The method and homemade apparatus were used to simultaneously determine MG and CV in fish farming water samples and in river ones with satisfactory results. The presented method and the homemade apparatus could serve as an alternative tool to handle some analysis problems.

Sufentanil is a new kind of opioid analgesic and acts on μ opioid receptor. In this study, we aim to investigate the effects of sufentanil on gastric cancer cell line SGC-7901, after being exposed to different concentrations of sufentanil. Gastric cancer cells were exposed to sufentanil for a predetermined time at concentrations of 0, 0.5, 5, 50 and 500 nmol/l, respectively. Cell viability at different time points after exposure to sufentanil was tested by CCK-8 assay. FDA-PI staining was used to observe membrane integrity of gastric cancer SGC7901 cells. The apoptosis of gastric cancer cells was analyzed by Annexin V-FITC/PI Flow Cytometry and the changes of the cell cycle was determined by a detection kit. As a result, cell viability decreased in a dose- and time-dependent manner. Furthermore, with the concentration of sufentanil increased, the proportion of dead and apoptotic SGC-7901 cells increased, and more cells were arrested in G2/M phase. In a word, sufentanil can inhibit the cell viability and induce the apoptosis of gastric cancer SGC-7901 cells in vitro.

Polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) cause toxic effects after binding to an intracellular cytosolic receptor called the aryl hydrocarbon receptor (AhR). Thymic atrophy, weight loss, immunotoxicity, acute lethality, and induction of cytochrome P4501A1 have all been correlated with the binding affinity to AhR. To study the key molecular features for determining binding affinity to AhR, a homology model of AhR ligand-binding domains was developed, a molecular docking approach was employed to obtain docking-based conformations of all molecules in the whole set, and 3-dimensional quantitative structure-activity relationship (3D-QSAR) methodology, namely, comparative molecular field analysis (CoMFA), was applied. A partial least square analysis was performed, and QSAR models were generated for a training set of 59 compounds. The generated QSAR model showed good internal and external statistical reliability, and in a comparison with other reported CoMFA models using different alignment methods, the docking-based CoMFA model showed some advantages.

Polychlorinated dibenzodioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs) cause toxic effects after binding to an intracellular cytosolic receptor called the aryl hydrocarbon receptor (AhR). Thymic atrophy, weight loss, immunotoxicity, acute lethality, and induction of cytochrome P4501A1 have all been correlated with the binding affinity to AhR. To study the key molecular features for determining binding affinity to AhR, a homology model of AhR ligand-binding domains was developed, a molecular docking approach was employed to obtain docking-based conformations of all molecules in the whole set, and 3-dimensional quantitative structure-activity relationship (3D-QSAR) methodology, namely, comparative molecular field analysis (CoMFA), was applied. A partial least square analysis was performed, and QSAR models were generated for a training set of 59 compounds. The generated QSAR model showed good internal and external statistical reliability, and in a comparison with other reported CoMFA models using different alignment methods, the docking-based CoMFA model showed some advantages.

It was discovered that a second order spectra data matrix of Sudan I produced from the solvent components gradual change-visible absorption spectra can be expressed as the combination of two bilinear data matrices. Based on this discovery, a new method for the determination of Sudan I in gray systems using second order calibration algorithms has been developed. The second order calibration algorithms were based on the popular parallel factor analysis (PARAFAC) and rank annihilation factor analysis (RAFA), respectively. In the method described here, the components of the solvent were changed gradually by adding ethanol into cyclohexane, the absorption spectra of Sudan I and chilli samples in a series of cyclohexane-ethanol mixed solvents with various ethanol volume fractions were recorded, and then the second order data were obtained from the solvent components gradual change-visible absorption spectra. Thus, the concentration of Sudan I in a gray system could be determined from the spectra matrices using second order calibration algorithms. This method is simple, convenient and dependable. The method has been used to determine Sudan I in chilli powder with satisfactory results.