Enrichment of Circulating Tumor Cells of Lung Cancer and Correlation With Serum Leukomonocyte and Tumor Biomarkers: A Retrospective Study.

STUDY DESIGN: Circulating tumor cells is important in the clinical diagnosis of cancer and there are a number of circulating tumor cell detection systems associated with different isolation strategies being validated. There is a novel platform, the CytoBot 2000, which utilizes a combination of physical and immunological technologies to isolate and capture circulating tumor cells. METHODS: In this retrospective study, 39 lung cancer patients and 11 normal healthy individuals were enrolled and performed circulating tumor cell tests and immunofluorescence staining with CytoBot 2000. The performance of this device was assessed by receiver operating characteristic curve. The clinical relevance of circulating tumor cells was assessed by Chi-square. The correlations between circulating tumor cell number and blood lymphocytes and tumor biomarkers were analyzed by Pearson correlation coefficient. RESULTS: The number of circulating tumor cell is significantly increased in lung cancer patients (3.74 > 0.45, P < .0001). The CytoBot 2000 presented a 100% (39/39) circulating tumor cell detection rate in lung cancer patients and 36% (4/11) in healthy individual blood samples, the sensitivity and specificity were 89.7% and 90.9%, respectively, and with the area under curve of 0.966. Further, there was a positive correlation between circulating tumor cell count and carcinoembryonic antigen 211 (R2 = 0.125, P = .027), but not blood lymphocytes (P = .089). CONCLUSIONS: This automatic platform showed excellent performance of circulating tumor cell detection by clinical sample. The tumor biomarkers increased with the number of circulating tumor cell in the lung cancer patients.

Effect of muscle activation on dynamic responses of neck of pilot during emergency ejection: a finite element study.

To determine the effect of muscle activation on the dynamic responses of the neck of a pilot during simulated emergency ejections. A complete finite element model of the pilot's head and neck was developed and dynamically validated. Three muscle activation curves were designed to simulate different activation times and levels of muscles during pilot ejection: A is the unconscious activation curve of the neck muscles, B is the pre-activation curve, and C is the continuous activation curve. The acceleration-time curves obtained during ejection were applied to the model, and the influence of the muscles on the dynamic responses of the neck was investigated by analyzing both angles of rotation of the neck segments and disc stresses. Muscle pre-activation reduced fluctuations in the angle of rotation in each phase of the neck. Continuous muscle activation caused a 20% increase in the angle of rotation compared to pre-activation. Moreover, it resulted in a 35% increase in the load on the intervertebral disc. The maximum stress on the disc occurred in the C4-C5 phase. Continuous muscle activation increased both the axial load on the neck and the posterior extension angle of rotation of the neck. Muscle pre-activation during emergency ejection has a protective effect on the neck. However, continuous muscle activation increases the axial load and rotation angle of the neck. A complete finite element model of the pilot's head and neck was established and three neck muscle activation curves were designed to investigate the effects of muscle activation time and level on the dynamic response of the pilot's neck during ejection. This increased insights into the protection mechanism of neck muscles on the axial impact injury of the pilot's head and neck.

Predicted health and environmental hazards of liquid crystal materials via quantitative structure-property relationship modeling.

Liquid crystal materials (LCMs) are considered as emerging contaminants with high persistent and bioaccumulative potentials, but their toxicological effects are not well understood. To address this issue, a list of 1431 LCMs commercially available in the market was established through literature reviews and surveys of LCM suppliers. Toxicological properties of 221 target LCMs were derived from the Classification and Labeling Inventory by the European Chemicals Agency. More than 80 % of target LCMs likely pose adverse effects on human health or aquatic ecosystems. Two quantitative structure-property relationship (QSPR) models developed from the toxicological properties of LCMs achieved approximately 90 % accuracy in external data sets. The probability-based approach was more efficient in defining the applicability domain for the QSPR models than a range- or distance-based approach. The highest accuracy was achieved for chemicals within the probability-based applicability domain. The QSPR models were applied to predict health and environmental hazards of 1210 LCMs that had not been notified to the Classification and Labeling Inventory, and 301 and 94 LCMs were recognized as posing potential hazards to human health and the environment, respectively. The present study highlights the potential detrimental effects of LCMs and offers a specific in silico technique for screening hazardous LCMs.

Emissions of Liquid Crystal Monomers from Obsolete Smartphone Screens in Indoor Settings: Characteristics and Human Exposure Risk.

Liquid crystal monomers (LCMs) have been found to accumulate in indoor environments, but the emission kinetics of LCMs from electronic devices are not well understood. Leakage from damaged liquid crystal displays may be an important mechanism for LCMs to enter the environment and become potential health hazards to humans. To address this issue, we conducted chamber experiments to characterize the emissions of LCMs from obsolete smartphone screens and estimated the doses of residential and occupational exposures to LCMs. The emission rates of the detected LCMs were in the ranges of 0.1-7 µg m-2 h-1 at 80 °C, 0.05-7 µg m-2 h-1 at 60 °C, and 0.002-0.2 µg m-2 h-1 at 25 °C. Liquid crystal monomers with large molecular weights and low volatilities tended to accumulate at screen surfaces and were re-emitted at elevated temperatures, leading to high emission rates of heavy LCMs upon thermal treatment. The estimated doses of residential and occupational exposures to individual LCMs were 0.0001-0.009 and 0.007-2 ng kg-1 d-1, respectively. As LCMs are potentially carcinogenic based on in silico assessments, LCMs emitted from obsolete smartphones in indoor settings may become human health hazards.

Astragaloside IV improved antioxidative stress capacity and related gene expression of the Keap1-Nrf2 pathway in grass carp (Ctenopharyngodon idella) hepatocytes under heat stress.

This study aims to investigate the protective effects of astragaloside IV (AS-IV) on the hepatocytes of grass carp (Ctenopharyngodon idella) on heat stress. Cultured cells were treated with AS-IV (0, 50, 100 and 200 µg/ml) at 28°C for 24 h and then exposed to heat stress by increasing the culturing temperature (32 ± 0.5°C) for 6 h. The increased temperatures significantly reduced cell viability and superoxide dismutase (SOD) activity, and increased malondialdehyde (MDA) levels in the 0 µg/ml AS-IV treatment group at 32°C, but the grass carp hepatocytes treated with 100 and 200 µg/ml AS-IV had significantly increased cell viability and SOD activity and decreased MDA levels. The mRNA levels of keap1a, keap1b, nrf2, gsh-px, cat, cu-zn sod, mgst1 and il-6 were significantly lower in the 0 µg/ml AS-IV treatment group at 32°C, while those of keap1a, nrf2, gsh-px, cat, cu-zn sod, gstp1, ho-1 and il-6 were significantly higher in cells treated with 100 or 200 µg/ml AS-IV. Our findings indicate that AS-IV could enhance the antioxidative stress capacity of grass carp hepatocytes under heat stress, and its mechanism may be associated with the activation of the Keap1-Nrf2 pathway. Thus, these results provide new insights into how to alleviate heat stress in grass carp.

Measurement of octanol-air partition coefficients for liquid crystals based on gas chromatography-retention time and its implication in predicting long-range transport potential.

Liquid crystals (LCs) are widely used in the modern society, but their environmental fate and related human health effects remain inadequately recognized. To assist in better understanding the environmental fate of LCs, the octanol-air partition coefficients (KOA) of 21 target LCs were determined with a gas chromatography-retention time (GC-RT) approach. Four classes of traditional organic pollutants, including polycyclic aromatic hydrocarbons, organochlorides, polybrominated diphenyl ethers, and polychlorinated biphenyls were employed as reference or calibration compounds. Cluster analysis indicated that the reference and calibration compounds somewhat influenced the relative and absolute magnitudes of GC-RT results. A quantitative structure-property relationship (QSPR) model was constructed from the experimental results and outperformed a widely-used model, KOAWIN, in estimating log KOA of LCs. This model was used to predict log KOAs for 116 LCs with the same element compositions and similar structures as the target LCs. Overall persistence and long-range transport potential were predicted based on the measured and estimated log KOA values, yielding consistent results. Several LCs were shown to have comparable characteristic travel distances and transport efficiencies as the traditional organic pollutants, suggesting they are potential environmental pollutants and the QSPR model is applicable in predicting the environmental fate of LCs.

Cosinor-rhythmometry for 24-h urinary sodium, potassium, creatinine excretion in the Chinese adult population.

BACKGROUND: The low accuracy of equations predicting 24-h urinary sodium excretion using a single spot urine sample contributed to the misclassification of individual sodium intake levels. The application of single spot urine sample is limited by a lack of representativity of urinary sodium excretion, possibly due to the circadian rhythm in urinary excretion. This study aimed to explore the circadian rhythm, characteristics, and parameters in a healthy young adult Chinese population as a theoretical foundation for developing new approaches. METHODS: Eighty-five participants (mean age 32.4 years) completed the 24-h urine collection by successively collecting each of the single-voided specimens within 24 h. The concentrations of the urinary sodium, potassium, and creatinine for each voided specimen were measured. Cosinor analysis was applied to explore the circadian rhythm of the urinary sodium, potassium, and creatinine excretion. The excretion per hour was computed for analyzing the change over time with repeated-measures analysis of variance and a cubic spline model. RESULTS: The metabolism of urinary sodium, potassium, and creatinine showed different patterns of circadian rhythm, although the urinary sodium excretion showed non-significant parameters in the cosinor model. A significant circadian rhythm of urinary creatinine excretion was observed, while the circadian rhythm of sodium was less significant than that of potassium. The circadian rhythm of urinary sodium and creatinine excretion showed synchronization to some extent, which had a nocturnal peak and fell to the lowest around noon to afternoon. In contrast, the peak of potassium was observed in the morning and dropped to the lowest point in the evening. The hourly urinary excretion followed a similar circadian rhythm. CONCLUSION: It is necessary to consider the circadian rhythm of urinary sodium, potassium, and creatinine excretion in adults while exploring the estimation model for 24-h urinary sodium excretion using spot urine.

Identification of six important amino acid residues of MenA from Bacillus subtilis natto for enzyme activity and formation of menaquinone.

The enzyme 1, 4-dihydroxy-2-naphthoic acid (DHNA) prenyltransferase (MenA) is a critical player in determining the efficiency of the menaquinone (MK) synthesis pathway and is an attractive target for the development of novel chemotherapeutics against pathogenic Gram-positive bacteria. However, there has been no report on structural properties or active region of MenA. To solve this challenge, we predicted the three-dimensiona structure and critical amino acid sites of MenA by bioinformatics analysis. Six amino acid sites were chosen by alligning the amino acid sequence of MenA from Bacillus subtilis natto with 4-hydroxybenzoate octaprenyl transferase (UbiA) from Escherichia coli, Aeropyrum pernix and Archaeoglobus fulgidus. Among them, four Asp sites located in two Asp-rich motifs (D78XXXXXD84 and D208XXXD212) were found to be indispensable amino acid residues in maintaining MenA activity. Site-directed mutagenesis of two other sites (Q67th, N74th) positively affected the catalytic activity of MenA and the MK titer. Q67R resulted in more than a 5-fold increase in specific 2-demethylmenaquinone (DMK) content (YP1/x) compared to wild-type, and the hydrophobic interaction between Cys63 and Arg67 could be the main reason according to the three-dimensional structure analysis. Moreover, a dramatic increase in specific MK content (YP2/x) was realized by co-expressing menG in EcMenA (Q67R). The results obtained could be useful not only in developing novel chemotherapeutics to combat potentially pathogenic Gram-positive bacteria, but also in regulating and optimizating E. coli mutant cultures for the efficient production of MK metabolites.

Endoscopic submucosal dissection for localised gastric amyloidosis mimicking malignancy / Disección submucosa endoscópica para la amiloidosis localizada gástrica que simula una malignidad

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Turning bulk materials into 0D, 1D and 2D metallic nanomaterials by selective aqueous corrosion.

The realization of the facile and green synthesis of low-dimensional nanomaterials is critical not only for energy storage but also for catalysis. A selective aqueous corrosion strategy is presented here for obtaining low-dimensional metals, including nanoparticles, nanofibers and nanosheets, based on the dealloying of aqueous-favoring metal from its bulk alloy.

Prazosin inhibits the growth and mobility of osteosarcoma cells.

BACKGROUND: Osteosarcoma is a primary malignant bone tumor that frequently occurs in adolescents and children, its high aggressiveness and rapid metastasis often resulting in poor prognoses. In previous studies, Prazosin has been shown to possess anti-proliferative properties against prostate cancer and glioblastoma cells. In our study, we investigated Prazosin's underlying mechanisms and its effects on the biological behaviors of osteosarcoma cells. METHODS: Osteosarcoma cell lines MG63 and 143B were treated with different concentrations of Prazosin, and a CCK8 assay assessed its effect on cell viability. Colony formation, Transwell and flow cytometry assays were used to examine its effects on cell proliferation, cell migration, and cell invasion and apoptosis, respectively. The expression of relevant proteins was then examined using western blotting. RESULTS: Our data showed that Prazosin dose-dependently reduced the viability of MG63 and 143B cells and significantly inhibited their clonogenic ability. Moreover, Prazosin attenuated the cell migration and invasion abilities of MG63 and 143B cells when compared with the NC group. It also accelerated cell apoptosis in mitochondrial pathways by regulating Bcl-2/Bax axis and caspase 3. Furthermore, Prazosin treatment inactivated the Akt/mTOR pathway by down-regulating Akt and mTOR phosphorylation (p-Akt, p-mTOR) and the expression of P70 and cyclin D1. CONCLUSIONS: Our data highlights the fact that Prazosin inhibits cell growth, inhibits the motility of osteosarcoma cells, and promotes apoptosis, suggesting that Prazosin is a potential anti-cancer agent in osteosarcoma therapy.

Early-life gut microbiome and cow's milk allergy- a prospective case - control 6-month follow-up study.

Increasing evidence suggests that perturbations in the intestinal microbiota in early infancy are implicated in the pathogenesis of food allergy (FA); existing evidence on the structure and composition of the intestinal microbiota in human beings with FA is limited and conflicting. The main object of the study was to compare the faecal microbiota between healthy and cow's milk allergy (CMA) infants at the baseline immediately after the diagnosis, and to evaluate the changes in the faecal microbiota after 6 months of treatment of CMA infants with hypoallergenic formula (HF), compared with healthy children fed on standard milk formulae. Sixty infants younger than 4 months of age with challenge-proven CMA and 60 healthy age-matched children were investigated in this prospective case - control follow-up study. Faecal samples were collected at baseline and at 6 months of follow-up, microbial diversity and composition were characterized by high-throughput 16S rRNA sequencing. The average age (±SD) of the infants at inclusion was 2.9 ±â€¯1.0 months. Children with CMA have lower gut microbiota diversity and an elevated Enterobacteriaceae to Bacteroidaceae (E/B ratio) in early infancy compared with healthy children (115.8 vs. 0.8, P = 0.0002). After 6 months of treatment with HF, CMA infants had a higher Lactobacillaceae (6.3% vs. 0.5%, P = 0.04) and lower Bifidobacteriaceae (0.3% vs. 8.2%, P = 0.03) and Ruminococcaceae (1.5% vs. 10.5%, P = 0.03) abundance compared with control children. Conclusion: Low gut microbiota diversity and an elevated E/B ratio in early infancy may contribute to the development of FA, including CMA. A strict elimination diet may weaken FA by reducing E/B ratio and promoting a gut microbiota that would benefit the acquisition of oral tolerance.

Children with cow's milk allergy following an elimination diet had normal growth but relatively low plasma leptin at age two.

AIM: To assess nutrient intake, growth and nutritional status of infants with cow's milk allergy (CMA) who follow a therapeutic elimination diet since the first few months of life. METHODS: Sixty infants younger than four months of age with challenge-proven CMA and 60 healthy age-matched children were investigated. Anthropometric and body composition (BC) were assessed up to 24 months. Dietary intake was recorded by the parents for three consecutive days before visits at 6, 12, 18 and 24 months. Blood albumin, prealbumin, retinol binding protein and metabolic-related hormones were examined at 24 months. RESULTS: The average age at enrolment was 2.9 ± 1.0 months. At the end of the follow-up, there were no differences in daily milk consumption, nutrient intake, weight and height z scores or BC measures between the groups; however, the plasma leptin level was lower in infants with CMA (1.67 ± 1.03 vs 2.05 ± 1.48) (ng/mL) (p < 0.05) compared to healthy children. CONCLUSIONS: Children with CMA who followed an elimination diet could achieve a normal nutritional status, except for relatively lower plasma leptin levels, at the age of 2. Further studies with larger cohorts and research on the long-term consequences of these early differences are needed.

Effect on Chest Deformation of Simultaneous Correction of Pectus Excavatum with Scoliosis.

Objective: This paper is to understand the effect of simultaneous correction of pectus excavatum with scoliosis and to provide some useful information for clinical orthopedic surgery design. Methods: The method of a three-dimensional reconstruction has been used to the reconstruction of the chest model of pectus excavatum with scoliosis, and the numerical stimulation has been conducted to the process of minimally invasive correction. Three kinds of correction methods have been considered in the numerical simulation, stretch spine, stretch spine and minimally invasive correction at the same time, and release stretch spine after stretch spine and minimally invasive correction of pectus excavatum at the same time. Results: It is found that stretch spine may help to correction of scoliosis but aggravate the sternum collapse, and release stretch spine after stretch spine and minimally invasive correction at the same time could not only be good at scoliosis but also improve the collapse of the sternum, which could help to improve the heartbeat and breath of the patients. Conclusion: Among the three kinds of correction methods, release stretch spine after stretch spine and minimally invasive correction at the same time could help to improve both the scoliosis and the collapse of the sternum.

Label-Free Fluorescent Detection of Trypsin Activity Based on DNA-Stabilized Silver Nanocluster-Peptide Conjugates.

Trypsin is important during the regulation of pancreatic exocrine function. The detection of trypsin activity is currently limited because of the need for the substrate to be labeled with a fluorescent tag. A label-free fluorescent method has been developed to monitor trypsin activity. The designed peptide probe consists of six arginine molecules and a cysteine terminus and can be conjugated to DNA-stabilized silver nanoclusters (DNA-AgNCs) by Ag-S bonding to enhance fluorescence. The peptide probe can also be adsorbed to the surface of graphene oxide (GO), thus resulting in the fluorescence quenching of DNA-AgNCs-peptide conjugate because of Förster resonance energy transfer. Once trypsin had degraded the peptide probe into amino acid residues, the DNA-AgNCs were released from the surface of GO, and the enhanced fluorescence of DNA-AgNCs was restored. Trypsin can be determined with a linear range of 0.0-50.0 ng/mL with a concentration as low as 1 ng/mL. This label-free method is simple and sensitive and has been successfully used for the determination of trypsin in serum. The method can also be modified to detect other proteases.

Lateral habenula as a link between thyroid and serotoninergic system modiates depressive symptoms in hypothyroidism rats.

Depression-like behavior is observed in both rats and people with hypothyroidism, which suggests that altered thyroid hormone levels are closely associated with mental illness. Furthermore, decreased serotonin (5-hydroxytryptamine, 5-HT) levels are found in some brain regions of hypothyroid rats with depression-like behavior. However, the mechanism underlying the effects of hypothyroidism on the central serotonin system is unclear. The lateral habenula (LHb) is related to both the serotonin and thyroid systems and also plays an important role in the pathogenesis of depression. Our study aimed to disclose the role of the LHb in the onset of depression-like behavior in thyroidectomy (TD) rats. Forced swimming (FST) and open-field tests (OFT) were performed to measure behavioral changes in TD rats. The expression of ß calmodulin-dependent protein kinase type II (ß CaMKII) in the LHb, cytochrome C oxidase (COX) activity in the LHb and dorsal raphe nucleus (DRN), and 5-HT levels in the DRN were assayed. We found that TD rats exhibited depression-like behavior in the FST and OFT. Compared with the sham group, neural activity and the expression of ß CaMKII in TD rats were higher in the LHb, and neural activity and 5-HT levels were lower in the DRN. Depressive behavior and decreased 5-HT levels in the DRN in TD rats were reversed by LHb lesioning. Our study indicates that depression-like behavior in TD rats can be attributed to decreased 5-HT levels in the DRN resulting from inhibition by an overactive LHb. The LHb mediates the effect of the thyroid system on 5-HT function in the DRN.

Abnormal Pupil Finding After an Orbital Floor Fracture in a Child.

PURPOSE: Trauma to the pupillary fibers can occur during repair of orbital floor fracture resulting in a fixed and dilated pupil. The authors report, discuss, and propose an etiology of an abnormal pupil in a child with an orbital floor fracture before surgical repair. METHODS: A case report is described. RESULTS: Although the orbital fracture was repaired, anisocoria persisted 18 months after the initial trauma. CONCLUSIONS: Pupillary function must be assessed before surgical repair of an orbital floor fracture as damage of the pupillary fibers can occur secondary to the orbital floor fracture.

Damage to dopaminergic neurons is mediated by proliferating cell nuclear antigen through the p53 pathway under conditions of oxidative stress in a cell model of Parkinson's disease.

Oxidative stress is widely considered as a central event in the pathogenesis of Parkinson's disease (PD). The mechanisms underlying the oxidative damage-mediated loss of dopaminergic neurons in PD are not yet fully understood. Accumulating evidence has indicated that oxidative DNA damage plays a crucial role in programmed neuronal cell death, and is considered to be at least partly responsible for the degeneration of dopaminergic neurons in PD. This process involves a number of signaling cascades and molecular proteins. Proliferating cell nuclear antigen (PCNA) is a pleiotropic protein affecting a wide range of vital cellular processes, including chromatin remodelling, DNA repair and cell cycle control, by interacting with a number of enzymes and regulatory proteins. In the present study, the exposure of PC12 cells to 1-methyl-4-phenylpyridinium (MPP+) led to the loss of cell viability and decreased the expression levels of PCNA in a dose- and time-dependent manner, indicating that this protein may be involved in the neurotoxic actions of MPP+ in dopaminergic neuronal cells. In addition, a significant upregulation in p53 expression was also observed in this cellular model of PD. p53 is an upstream inducer of PCNA and it has been recognized as a key contributor responsible for dopaminergic neuronal cell death in mouse models of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD. This indicates that MPP+-induced oxidative damage is mediated by the downregulation of PCNA through the p53 pathway in a cellular model of PD. Thus, our results may provide some novel insight into the molecular mechanisms responsible for the development of PD and provide new possible therapeutic targets for the treatment of PD.