Removal of Pb (II) and Zn (II) in the mineral beneficiation wastewater by using cross-linked carboxymethyl starch-g-methacrylic acid as an effective flocculant.

The cross-linked carboxymethyl starch-g-methacrylic acid (CCMS-g-MAA) was prepared by using grafting and micro-cross-linking in the one-pot preparation process. CCMS-g-MAA presented high removal capacity of Pb (II) of 57.13 mg/g at pH = 4 and high removal capacity of Zn (II) of 51.41 mg/g at pH = 5 by using a sample dosage of 0.68 g/L. Characterization results of FTIR, TG, and XRD illustrate that methacrylic acid and sodium tri-metaphosphate were successfully introduced into the structure of carboxymethyl starch. SEM characterization presented that the sample particles were amorphous aggregates with surface voids, which was favorable for the adsorption of heavy metal ions from wastewater. Adsorption isotherm results indicated that Freundlich equation could be better used to describe the adsorption process of metal ions on CCMS-g-MAA. The adsorption kinetic results indicated that the pseudo-second-order model is more suitable to describe this removal process. XPS results indicated that metal ions interacted with functional groups on the surface of flocculant, especially carboxyl groups. The removal process may be purposed that metal ions were adsorbed by porous material, and then combined with surface functional groups of the flocculant via electrostatic interaction, chelation or ion exchange. Subsequently, metal ions were separated from the wastewater with flocs precipitated in the bottom of solution via bridging and patching. The obtained results illustrated that CCMS-g-MAA was an effective material for the treatment of wastewater containing polymetallic ions besides mineral beneficiation wastewater supported by its excellent regeneration.

Effect of trace element mixtures on the outcome of patients with esophageal squamous cell carcinoma: a prospective cohort study in Fujian, China.

BACKGROUND: The evidence about the effects of trace elements on overall survival(OS) of patients with esophageal squamous cell carcinoma(ESCC) is limited. This study aims to evaluate mixed effects of plasma trace elements on OS of ESCC. METHODS: This prospective cohort analysis included 497 ESCC patients with a median follow-up of 52.3 months. The concentrations of 17 trace elements were measured. We fitted Cox's proportional hazards regression, factor analysis and Bayesian kernel machine regression (BKMR) models to estimate the association between trace elements and OS. RESULTS: Our analysis found that in the single-element model, Co, Ni, and Cd were associated with an increased risk of death, while Ga, Rb, and Ba were associated with a decreased risk. Cd had the strongest risk effect among all elements. As many elements were found to be mutually correlated, we conducted a factor analysis to identify common factors and investigate their associations with survival time. The factor analysis indicated that the factor with high factor loadings in Ga, Ba and B was linked to a decreased risk of death, while the factor with high factor loadings in Co, Ti, Cd and Pb was associated with a borderline significantly increased risk. Using BKMR analysis to disentangle the interaction between elements in significant factors, we discovered that Ga interacted with Ba and both elements had U-shaped effects with OS. Cd, on the other hand, had no interaction with other elements and independently increased the risk of death. CONCLUSIONS: Our analysis revealed that Ga, Ba and Cd were associated with ESCC outcome, with Ga and Ba demonstrating an interaction. These findings provide new insights into the impact of trace elements on the survival of patients with ESCC.

Association between the Preoperative Dietary Antioxidant Index and Postoperative Quality of Life in Patients with Esophageal Squamous Cell Carcinoma: A Prospective Study Based on the TTD Model.

OBJECTIVE: Dietary antioxidants are associated with risk of death in cancer patients, and they were used to evaluate the prognosis of cancer patients. Dietary antioxidant index (DAI) can be used to evaluate dietary antioxidant content comprehensively; this study aimed to investigate the effect of preoperative DAI on health-related quality of life in patients with esophageal cell squamous carcinoma (ESCC). METHODS: Data on dietary intakes were collected using a validated food-frequency questionnaire (FFQ). DAI was calculated for all study participants based on FFQ data of each participant. The study involved conducting several follow-up activities with patients diagnosed with ESCC to evaluate their quality of life. The approach employed in the study was to conduct a telephone interview. The EORTC Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30, version 3.0) and the Esophageal Cancer Module (EORTC QLQ-OES18) were used to collect data on the quality of life of the patients; all patients completed the full follow-up. RESULTS: This prospective study was performed on 376 participants who were recruited from Fujian Cancer Hospital and First Hospital of Fujian Medical University. They all were diagnosed with ESCC. The results indicated that the time to deterioration of global health status (p = 0.043), cognitive functioning (p = 0.031), dry mouth (p = 0.019), and speech problems (p = 0.031) significantly delay in the high DAI group. Univariate and multivariate Cox regression analysis showed that global health status (HR = 0.718, 95% CI: 0.532-0.969), cognitive functioning (HR = 0.641, 95% CI: 0.450-0.913), dry mouth (HR = 0.637, 95% CI: 0.445-0.911), and speech problems (HR = 0.651, 95% CI: 0.449-0.945) were improved in the high DAI group. CONCLUSIONS: Prognostic value of preoperative DAI was significant for patients with ESCC who undergo surgical intervention. Its level was positively correlated with the postoperative quality of life of patients, which can delay and improve the occurrence of postoperative physical function and symptom deterioration.

Adsorption of Pb (II) and Cu (II) by magnetic beads loaded with xanthan gum.

Green and environmentally friendly and efficient separation adsorbents have attracted much attention in the treatment of heavy metal ions wastewater. In this study, xanthan gum (XG) was supported by fly ash magnetic beads (FAMB) to prepare adsorbent XG@FAMB. The effects of XG@FAMB dosage, pH value of the solution, adsorption time, and initial Pb (II) and Cu (II) concentration on its adsorption performance for Pb (II) and Cu (II) were investigated. The results show that under the conditions of pH 6, dosage of XG@FAMB 4.0 g/L, adsorption time 120 min, and initial concentration 60 mg/L, the maximum adsorption capacity of XG@FAMB for Pb (II) and Cu (II) was 14.93 mg/g and 14.88 mg/g, respectively. The adsorption process of Pb (II) and Cu (II) by XG@FAMB could be better described by the quasi-second-order kinetic model and Langmuir isothermal adsorption model, that is, the adsorption process is monolayer adsorption controlled by chemical action. The adsorption mechanism is that Pb (II) and Cu (II) coordinate with oxygen-containing functional groups hydroxyl and carboxyl on XG@FAMB surface, accompanied by electrostatic adsorption. XG@FAMB has the advantages of environmental protection of XG and easy solid-liquid separation of FAMB, and has a good removal effect on Pb (II) and Cu (II).

Development and Validation of a Prognostic Model for Esophageal Adenocarcinoma Based on Necroptosis-Related Genes.

Necroptosis is a newly developed cell death pathway that differs from necrosis and apoptosis; however, the potential mechanism of necroptosis-related genes in EAC and whether they are associated with the prognosis of EAC patients remain unclear. We obtained 159 NRGs from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and performed differential expression analysis of the NRGs in 9 normal samples and 78 EAC tumor samples derived from The Cancer Genome Atlas (TCGA). Finally, we screened 38 differentially expressed NRGs (DE-NRGs). The results of the GO and KEGG analyses indicated that the DE-NRGs were mainly enriched in the functions and pathways associated with necroptosis. Protein interaction network (PPI) analysis revealed that TNF, CASP1, and IL-1B were the core genes of the network. A risk score model based on four DE-NRGs was constructed by Least Absolute Shrinkage and Selection Operator (LASSO) regression, and the results showed that the higher the risk score, the worse the survival. The model achieved more efficient diagnosis compared with the clinicopathological variables, with an area under the receiver operating characteristic (ROC) curve of 0.885. The prognostic value of this model was further validated using Gene Expression Omnibus (GEO) datasets. Gene set enrichment analyses (GSEA) demonstrated that several metabolism-related pathways were activated in the high-risk population. Single-sample GSEA (ssGSEA) provided further confirmation that this prognostic model was remarkably associated with the immune status of EAC patients. Finally, the nomogram map exhibited a certain prognostic prediction efficiency, with a C-index of 0.792 and good consistency. Thus, the prognostic model based on four NRGs could better predict the prognosis of EAC and help to elucidate the mechanism of necroptosis-related genes in EAC, which can provide guidance for the target prediction and clinical treatment of EAC patients.

Exploring and applying genes to enhance the resistance to Fusarium head blight in wheat.

Fusarium head blight (FHB) is a destructive disease in wheat worldwide. Fusarium graminearum species complex (FGSC) is the main causal pathogen causing severe damage to wheat with reduction in both grain yield and quality. Additionally, mycotoxins produced by the FHB pathogens are hazardous to the health of human and livestock. Large numbers of genes conferring FHB resistance to date have been characterized from wheat and its relatives, and some of them have been widely used in breeding and significantly improved the resistance to FHB in wheat. However, the disease spreads rapidly and has been severe due to the climate and cropping system changes in the last decade. It is an urgent necessity to explore and apply more genes related to FHB resistant for wheat breeding. In this review, we summarized the genes with FHB resistance and mycotoxin detoxication identified from common wheat and its relatives by using forward- and reverse-genetic approaches, and introduced the effects of such genes and the genes with FHB resistant from other plant species, and host-induced gene silencing (HIGS) in enhancing the resistance to FHB in wheat. We also outlined the molecular rationale of the resistance and the application of the cloned genes for FHB control. Finally, we discussed the future challenges and opportunities in this field.

Improvement of postoperative quality of life in patients with esophageal squamous cell carcinoma: does tea consumption have a role?

BACKGROUND: To investigate the effect of tea consumption on the improvement of postoperative quality of life in male patients with esophageal squamous cell carcinoma (ESCC). METHODS: The quality of life information of 290 male patients with ESCC was collected. The time to deterioration and the number of events in each area of quality of life was calculated by time-to-deterioration (TTD) model. The association between postoperative tea drinking and postoperative quality of life in male ESCC patients was investigated using the Cox proportional risk model. RESULTS: Postoperative tea-drinking patients experienced delayed TTD in multiple domains, including general health, physical, role, emotional, and cognitive function, fatigue, nausea and vomiting, dyspnea, loss of appetite, constipation, diarrhea, eating problems, difficulty swallowing, choking while swallowing saliva, dry mouth, taste difficulties, coughing, and speech problems. The multivariate Cox regression analysis showed that drinking tea after surgery improved quality of life, including physical function (HR = 0.722, 95% CI: 0.559-0.933), role function (HR = 0.740, 95% CI: 0.557-0.983), eating problems (HR = 0.718, 95% CI: 0.537-0.960), odynophagia (HR = 0.682, 95% CI: 0.492-0.945), trouble swallowing saliva (HR = 0.624, 95% CI: 0.444-0.877), coughing (HR = 0.627, 95% CI: 0.442-0.889) and speech problems (HR = 0.631, 95% CI: 0.441-0.903). Furthermore, the improvement was more significant in patients who drank tea before surgery and continued to drink tea after surgery. CONCLUSIONS: Postoperative tea drinking had a positive effect on delay in clinical deterioration and improvements in multiple functions and symptoms associated with ESCC in men.

lncRNA XIST knockdown suppresses cell proliferation and promotes apoptosis in diabetic cataracts through the miR­34a/SMAD2 axis.

According to emerging evidence, long non­coding RNAs (lncRNAs) play critical roles in diabetes. The aim of the present study was to investigate the role and mechanism of X­inactive specific transcript (XIST) in cell proliferation, migration and apoptosis in diabetic cataracts (DC). SRA01/04 lens epithelial cells were treated with high glucose (HG). The levels of XIST, microRNA (miR)­34a and SMAD family member 2 (SMAD2) were examined via reverse transcription­quantitative PCR. MTT, Transwell, wound healing and TUNEL assays were performed to examine cell proliferation, invasion, migration and apoptosis, respectively. The interaction between miR­34a and XIST or SMAD2 was verified by luciferase reporter assay. It was found that the expression of XIST was increased and that of miR­34a was decreased in DC tissues and HG­treated SRA01/04 cells. XIST knockdown or miR­34a overexpression attenuated cell proliferation and migration, and induced apoptosis in HG­treated SRA01/04 cells. XIST targeted miR­34a and regulated DC progression through miR­34a. SMAD2 was identified as a target gene of miR­34a and was positively modulated by XIST. XIST knockdown inhibited cell proliferation and migration, and accelerated apoptosis in HG­stimulated SRA01/04 cells, and these effects were abrogated by SMAD2 overexpression. In conclusion, XIST promoted cell proliferation, migration and invasion, and inhibited apoptosis, through the miR­34a/SMAD2 axis in DC.

TMEM116 is required for lung cancer cell motility and metastasis through PDK1 signaling pathway.

Transmembrane protein (TMEM) is a family of protein that spans cytoplasmic membranes and allows cell-cell and cell-environment communication. Dysregulation of TMEMs has been observed in multiple cancers. However, little is known about TMEM116 in cancer development. In this study, we demonstrate that TMEM116 is highly expressed in non-small-cell lung cancer (NSCLC) tissues and cell lines. Inactivation of TMEM116 reduced cell proliferation, migration and invasiveness of human cancer cells and suppressed A549 induced tumor metastasis in mouse lungs. In addition, TMEM116 deficiency inhibited PDK1-AKT-FOXO3A signaling pathway, resulting in accumulation of TAp63, while activation of PDK1 largely reversed the TMEM116 deficiency induced defects in cancer cell motility, migration and invasive. Together, these results demonstrate that TMEM116 is a critical integrator of oncogenic signaling in cancer metastasis.

The effects of intrinsic apoptosis on cystogenesis in PKD1-deficient ADPKD pig model.

BACKGROUND: Apoptosis is a form of cell death that plays a critical role in the maintenance of tissue homeostasis involving the development and elimination of unwanted cells. Dysregulation of apoptosis appears to be associated in the pathogenesis of many human diseases. Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenetic disease and is mainly caused by mutations in PKD1. Previous studies proved that increased cell death occurred in ADPKD patients and animal models. However, the role of apoptosis in kidney cystogenesis is not clear. METHODS: In current study, due to the high similarities between human and pig, PKD1-deficient (PKD1+/-) pigs and PKD1-knockdown (PKD1KD) pig kidney epithelial cells were used to investigate the mechanisms of apoptosis in driving cystogenesis. RESULTS: In PKD1+/- pigs, increased intrinsic and extrinsic apoptosis were found at ages of 1 month and 3 months, whereas the autophagy and pyroptosis were not altered. Meanwhile, the intrinsic apoptosis was activated along with untouched extrinsic apoptosis in PKD1KD pig kidney cells. Thus, the intrinsic apoptosis played important roles in cystogenesis. CONCLUSIONS: This work provides detail analysis of the roles of different cell death types during cystogenesis in ADPKD pig model. The results suggested a potential new strategy for the diagnosis and treatment of ADPKD by targeting intrinsic apoptosis.

LncRNA MALAT1 accelerates non-small cell lung cancer progression via regulating miR-185-5p/MDM4 axis.

Non-small cell lung cancer (NSCLC) is the commonest malignancy with high death rate around the world. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is greatly overexpressed in multifarious cancers, including NSCLC. However, the precise mechanism of MALAT1 in NSCLC tumorigenesis is blurry. This paper aims to investigate the theory of MALAT1 action in NSCLC progression. The levels of MALAT1, microRNA (miR)-185-5p, and mouse double minute 4 protein (MDM4) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Cell proliferation and apoptosis were, respectively, determined by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay, and flow cytometry. Cell migratory and invasive abilities were inspected by transwell assay. The binding relationship between miR-185-5p and MALAT1 or MDM4 was confirmed by dual-luciferase reporter assay. The impacts of MALAT1 on tumor growth in vivo were measured by a xenograft experiment. We found MALAT1 and MDM4 were upregulated and MALAT1 positively regulated the MDM4 expression. MALAT1 and MDM4 deletion significantly hindered the proliferation, metastasis, and expedited the apoptosis of NSCLC cells. MDM4 overexpression partly overturned the influence of MALAT1 downregulation on cell development. Moreover, miR-185-5p, as a target of MALAT1, could directly target MDM4, and miR-185-5p upregulation exerted inhibitory effects on NSCLC cells. Besides, knockdown of MALAT1 inhibited tumor growth in vivo through miR-185-5p/MDM4 axis in NSCLC. Collectively, MALAT1 contributed to proliferation, migration, invasion, and impeded apoptosis by regulating the MDM4 expression mediated by miR-185-5p in NSCLC cells.

Deoxyshikonin inhibits cisplatin resistance of non-small-cell lung cancer cells by repressing Akt-mediated ABCB1 expression and function.

Drug resistance is a large challenge for the treatment of non-small-cell lung cancer (NSCLC). Deoxyshikonin is the naphthoquinol compound with anticancer activity. However, the role and mechanism of deoxyshikonin in cisplatin resistance of NSCLC remain poorly understood. Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Cell apoptosis was evaluated by flow cytometry and caspase-3 activity. We found that cisplatin-resistant A549/cis and H1299/cis cells had higher cisplatin resistance than A549 and H1299 cells, respectively. Deoxyshikonin contributed to cisplatin-induced viability inhibition and apoptosis in A549/cis and H1299/cis cells. Moreover, deoxyshikonin inhibited phosphorylation of Akt and the expression and function of ATP-binding cassette subfamily B member 1 (ABCB1). Activation of protein kinase B (Akt) pathway attenuated the effect of deoxyshikonin on cisplatin resistance and ABCB1 expression and function in A549/cis and H1299/cis cells. In conclusion, deoxyshikonin suppressed cisplatin resistance in cisplatin-resistant NSCLC cells by repressing Akt signaling-mediated ABCB1 expression.

The role of pulmonary mesenchymal cells in airway epithelium regeneration during injury repair.

BACKGROUND: The airways of mammalian lung are lined with highly specialized cell types that are the target of airborne toxicants and injury. Several epithelial cell types and bone marrow-derived mesenchymal stem cells have been identified to serve as stem cells during injury repair. However, the contributions of endogenous mesenchymal cells to recruitment, expansion or differentiation of stem cells, and repair and reestablishment of the normal composition of airway epithelium following injury have not been addressed. METHODS: The role of mouse pulmonary mesenchymal cells was investigated by lineage tracing using Dermo1-Cre; ROSAmTmG mice. In experimental models of lung injury by lipopolysaccharide and naphthalene, GFP-labeled Dermo1+ mesenchymal cells were traced during injury repair. In vitro lung explant culture treated with or without lipopolysaccharide was also used to verify in vivo data. RESULTS: During injury repair, a subgroup of GFP-labeled Dermo1+ mesenchymal cells were found to contribute to normal repair of the airway epithelium and differentiated into Club cells, ciliated cells, and goblet cells. In Club cell-specific naphthalene injury model, the process of Dermo1+ stem cell regenerating epithelial cells was dissected. The Dermo1+ stem cells was migrated into the airway epithelium layer sooner after injury, and sequentially differentiated transitionally to epithelial stem cells, such as neuroendocrine cells, and finally to newly differentiated Club cells, ciliated cells, and goblet cells in injury repair. CONCLUSION: In this study, a population of Dermo1+ mesenchymal stem cell was identified to serve as stem cells in airway epithelial cell regeneration during injury repair. The Dermo1+ mesenchymal stem cell differentiated into epithelial stem cells before reestablishing various epithelial cells. These findings have implications for understanding the regulation of lung repair and the potential for usage of mesenchymal stem cells in therapeutic strategies for lung diseases.

Leptin mediates the effects of melatonin on female reproduction in mammals.

Melatonin is a natural molecule produced in the pineal gland and other tissues. It participates in numerous biological activities including the regulation of reproduction. However, the mechanism by which melatonin affects mammalian female reproductive performance is not fully investigated. In the present study, it was observed that melatonin positively regulated the level of leptin in female mouse and pig. To understand the potential association between melatonin and leptin on the female reproductive activities, the melatonin receptor 1 MT1 knockout (MT1-/- ) mouse and Leptin knockout (Leptin-/- ) pig were created. It was found that the deficiency of M T1 caused low leptin secretion and litter size in mouse. Meanwhile, the deletion of leptin in pig did not affect melatonin production, but significantly reduced follicle-stimulating hormone, estradiol-17ß (E2), and Luteinizing hormone and increased progesterone (P) at estrum stage, which also led to smaller litter size than that in control. Melatonin treatment increased the production of leptin in pigs, while the supplementary of leptin was also able to improve the ovulation number, polar body rates, and expression of StAR in MT1-/- females. Therefore, it is first time, we described that leptin is the downstream target of melatonin in regulating female reproduction. These findings provide the novel information on the physiology of melatonin in animal reproduction.

Oxidative damage of SP-D abolishes control of eosinophil extracellular DNA trap formation.

The asthmatic airways are highly susceptible to inflammatory injury by air pollutants such as ozone (O3 ), characterized by enhanced activation of eosinophilic granulocytes and a failure of immune protective mechanisms. Eosinophil activation during asthma exacerbation contributes to the proinflammatory oxidative stress by high levels of nitric oxide (NO) production and extracellular DNA release. Surfactant protein-D (SP-D), an epithelial cell product of the airways, is a critical immune regulatory molecule with a multimeric structure susceptible to oxidative modifications. Using recombinant proteins and confocal imaging, we demonstrate here that SP-D directly bound to the membrane and inhibited extracellular DNA trap formation by human and murine eosinophils in a concentration and carbohydrate-dependent manner. Combined allergic airway sensitization and O3 exposure heightened eosinophilia and nos2 mRNA (iNOS) activation in the lung tissue and S-nitrosylation related de-oligomerisation of SP-D in the airways. In vitro reproduction of the iNOS action led to similar effects on SP-D. Importantly, S-nitrosylation abolished the ability of SP-D to block extracellular DNA trap formation. Thus, the homeostatic negative regulatory feedback between SP-D and eosinophils is destroyed by the NO-rich oxidative lung tissue environment in asthma exacerbations.

The risk factors, etiology, and drug resistance of infection after plastic surgery, and corresponding measures.

BACKGROUND: Explore the risk factors, etiology, and drug resistance of infection after plastic surgery, and present corresponding measures. METHODS: We retrospectively analyzed 980 patients who underwent head and facial plastic surgery from January 2013 to December 2015. Postoperative infection occurred in 169 patients. We analyzed the distribution of pathogenic bacteria in patients undergoing plastic surgery, reviewed the drug resistance of Gram negative (G-) bacteria and Gram positive (G+) bacteria, and analyzed the effects of surgical duration, prophylactic use of antibacterial agents, length of stay (LOS), and preoperative hair removal on infection after plastic surgery. RESULTS: G+ bacteria (mainly Staphylococcus aureus) accounted for 45.6%, while G- bacteria (mainly Pseudomonas aeruginosa and Klebsiella pneumoniae) accounted for 54.4% of total pathogenic bacteria in patients undergoing plastic surgery. The most commonly resistant antibacterial agents of Pseudomonas aeruginosa were sulfamethoxazole, ciprofloxacin, and cefotaxime; the most commonly resistant antibacterial agents of Klebsiella pneumoniae were sulfamethoxazole and gentamicin. The most commonly resistant antibacterial agents of Staphylococcus aureus were penicillin G, ampicillin, and sulfamethoxazole; for coagulase-negative staphylococcus, the most commonly resistant antibacterial agents were also penicillin G, ampicillin, and sulfamethoxazole. Both Staphylococcus aureus and coagulase-negative staphylococcus were sensitive to vancomycin and teicoplanin. Multi-factor logistic regression analysis showed that surgical duration >3 hours, no prophylactic use of antibacterial agents, and LOS>7 days were independent risk factors for postoperative infection. CONCLUSIONS: G- bacteria were more prevalent in infections after plastic surgery, and most bacteria were sensitive to imipenem and meropenem. Strict control of surgical duration, short LOS, intraoperative prophylactic use of antibacterial agents, and no preoperative hair removal were important for reducing postoperative infection.

Pretreatment Red Blood Cell Total Folate Concentration Is Associated With Response to Pemetrexed in Stage IV Nonsquamous Non-Small-cell Lung Cancer.

INTRODUCTION: Pemetrexed inhibits folate-dependent enzymes involved in pyrimidine and purine synthesis. Previous studies of genetic variation in these enzymes as predictors of pemetrexed efficacy have yielded inconsistent results. We investigated whether red blood cell (RBC) total folate, a phenotypic rather than genotypic, marker of cellular folate status was associated with the response to pemetrexed-based chemotherapy in advanced nonsquamous non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: We conducted a prospective cohort study of patients with stage IV nonsquamous NSCLC receiving first-line chemotherapy containing pemetrexed. The pretreatment RBC total folate level was quantified using liquid chromatography mass spectrometry. We then compared the objective response rate (ORR) between patients with RBC total folate concentrations greater than and less than an optimal cutoff value determined from the receiver operating characteristic curve. A logistic regression model was used to adjust for age, sex, and the use of bevacizumab. RESULTS: The ORR was 62% (32 of 52 patients). Receiver operating characteristic analysis was used to establish that a RBC total folate cutoff value of 364.6 nM optimally discriminated between pemetrexed responders and nonresponders. Patients with RBC total folate < 364.5 nM had an ORR of 27% compared with 71% for patients with RBC total folate > 364.5 nM (P = .01). This difference persisted after adjusting for age, sex, and the use of bevacizumab (odds ratio, 0.07; 95% confidence interval, 0.01-0.57; P = .01). CONCLUSION: A low pretreatment RBC total folate was associated with an inferior response to pemetrexed-based chemotherapy in stage IV nonsquamous NSCLC. Larger, multicenter studies are needed to validate RBC total folate as a predictive marker of pemetrexed response.

Potential Metabolic Activation of a Representative C2-Alkylated Polycyclic Aromatic Hydrocarbon 6-Ethylchrysene Associated with the Deepwater Horizon Oil Spill in Human Hepatoma (HepG2) Cells.

Exposure to polycyclic aromatic hydrocarbons (PAHs) is the major human health hazard associated with the Deepwater Horizon oil spill. C2-Chrysenes are representative PAHs present in crude oil and could contaminate the food chain. We describe the metabolism of a C2-chrysene regioisomer, 6-ethylchrysene (6-EC), in human HepG2 cells. The structures of the metabolites were identified by HPLC-UV-fluorescence detection and LC-MS/MS. 6-EC-tetraol isomers were identified as signature metabolites of the diol-epoxide pathway. O-Monomethyl-O-monosulfonated-6-EC-catechol, its monohydroxy products, and N-acetyl-l-cysteine(NAC)-6-EC-ortho-quinone were discovered as signature metabolites of the ortho-quinone pathway. Potential dual metabolic activation of 6-EC involving the formation of bis-electrophiles, i.e., a mono-diol-epoxide and a mono-ortho-quinone within the same structure, bis-diol-epoxides, and bis-ortho-quinones was observed as well. The identification of 6-EC-tetraol, O-monomethyl-O-monosulfonated-6-EC-catechol, its monohydroxy products, and NAC-6-EC-ortho-quinone supports potential metabolic activation of 6-EC by P450 and AKR enzymes followed by metabolic detoxification of the ortho-quinone through interception of its redox cycling capability by catechol-O-methyltransferase and sulfotransferase enzymes. The tetraols and catechol conjugates could be used as biomarkers of human exposure to 6-EC resulting from oil spills.

Serum apolipoprotein A-1 quantification by LC-MS with a SILAC internal standard reveals reduced levels in smokers.

BACKGROUND: Absolute quantification of protein biomarkers such as serum apolipoprotein A1 by both immunoassays and LC-MS can provide misleading results. RESULTS: Recombinant ApoA-1 internal standard was prepared using stable isotope labeling by amino acids in cell culture with [(13)C6(15)N2]-lysine and [(13)C9(15)N1]-tyrosine in human cells. A stable isotope dilution LC-MS method for serum ApoA-1 was validated and levels analyzed for 50 nonsmokers and 50 smokers. CONCLUSION: The concentration of ApoA-1 in nonsmokers was 169.4 mg/dl with an 18.4% reduction to 138.2 mg/dl in smokers. The validated assay will have clinical utility for assessing effects of smoking cessation and therapeutic or dietary interventions in high-risk populations.

Polymorphism in glassy silicon: inherited from liquid-liquid phase transition in supercooled liquid.

Combining molecular dynamics (MD) simulation and Voronoi polyhedral analyses, we discussed the microstructure evolution in liquid and glassy silicon during cooling by focusing on the fraction of various clusters. Liquid-liquid phase transition (LLPT) is detected in supercooled liquid silicon However, freezing the high-density liquid (HDL) to the glassy state is not achieved as the quenching rate goes up to 10(14) K/s. The polyamorphism in glassy silicon is found to be mainly associated with low-density liquid (LDL).