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To addreess the challenge of overcrowding in the urban rail transit system, this paper proposes a novel joint optimization strategy that optimizes the timetable and the passing facility's working status (PFWS) simultaneously according to the passenger demands. To this end, a mixed-integer nonlinear programming (MINLP) model is formulated to jointly minimize overcrowding on trains and platforms, as well as the passenger travel time. The passing facility setting and the passenger flow activities depiction are particularly taken into account by the rigorous constraints. Subsequently, we design a simulation-based hybrid variable neighborhood search (SHVNS) algorithm to efficiently generate near-optimal solution. This algorithm incorporates a variable neighborhood search (VNS) algorithm, a randomly reset strategy, and a simulation-based algorithm. The VNS algorithm includes five neighborhood operators to enhance search efficiency. Finally, various experiments with the real-world data from Chongqing rail transit line 6 in China are tested to prove the applicability and the performance of our proposed model and algorithm. The computational results show that the joint optimization strategy outperforms a current operation strategy in terms of the overcrowded situation on trains and platforms, often by more than 60%, and some management implications and theoretical support can be obtained for the urban rail transit operator. [ABSTRACT FROM AUTHOR]

• Interactions between metal(loid)s and gut microbiota vary greatly. • Generalizations cannot be easily made between single metal(loid) and gut microbiota. • Microbiota-related strategies are effective in metal(loid) detoxification. • Human intervention trials for microbiota-related strategies are urgently warranted. Human exposure to metal(loid)s has dramatically increased over the past five decades, which has triggered public concern worldwide. Recently, gut microbiota has been considered a target for metal(loid)s, and some literature has reviewed the interactions between gut microbiota and heavy metal(loid)s (HMs) with high toxicity. However, whether there is an interaction between gut microbiota and metal(loid)s with essential roles or some normal functions are far from clear to date. Importantly, in addition to traditional probiotics that have been clarified to alleviate the adverse effect of HMs on the body, some novel probiotics, prebiotics, synbiotics, and postbiotics may also exhibit comparable or even better abilities of metal(loid) remediation. In this review, we mainly outline and discuss recent research findings on the metal(loid)-gut microbiota interactions and microbiota-related protective strategies. [ABSTRACT FROM AUTHOR]

N-glycosylation is an essential eukaryotic posttranslational modification that affects various glycoprotein properties, including folding, solubility, protein-protein interactions, and half-life. N-glycans are processed in the secretory pathway to form varied ensembles of structures, and diversity at a single site on a glycoprotein is termed 'microheterogeneity'. To understand the factors that influence glycan microheterogeneity, we hypothesized that local steric and electrostatic factors surrounding each site influence glycan availability for enzymatic modification. We tested this hypothesis via expression of reporter N-linked glycoproteins in N-acetylglucosaminyl-transferase MGATl-null HEK293 cells to produce immature Man5GlcNAc2 glycoforms (38 glycan sites total). These glycoproteins were then sequentially modified in vitro from high mannose to hybrid and on to biantennary, core-fucosylated, complex structures by a panel of N-glycosylation enzymes, and each reaction time course was quantified by LC-MS/MS. Substantial differences in rates of in vitro enzymatic modification were observed between glycan sites on the same protein, and differences in modification rates varied depending on the glycoenzyme being evaluated. In comparison, proteolytic digestion of the reporters prior to N-glycan processing eliminated differences in in vitro enzymatic modification. Furthermore, comparison of in vitro rates of enzymatic modification with the glycan structures found on the mature reporters expressed in WT cells correlated well with the enzymatic bottlenecks observed in vivo. These data suggest higher order local structures surrounding each glycosylation site contribute to the efficiency of modification both in vitro and in vivo to establish the spectrum of microheterogeneity in N-linked glycoproteins. [ABSTRACT FROM AUTHOR]

• Quetiapine remarkably induced necroptosis. • CB1R antagonists or CB2R agonists inhibited necroptosis. • CB1R antagonists or CB2R agonists protected against quetiapine cardiotoxicity. Quetiapine is a common atypical antipsychotic used to treat mental disorders such as schizophrenia, bipolar disorder, and major depressive disorder. There has been increasing number of reports describing its cardiotoxicity. However, the molecular mechanisms underlying quetiapine-induced myocardial injury remain largely unknown. Herein, we reported a novel cell death type, quetiapine-induced necroptosis, which accounted for quetiapine cardiotoxicity in mice and proposed novel therapeutic strategies. Quetiapine-treated hearts showed inflammatory infiltration and evident fibrosis after 21-day continuous injection. The specific increases of protein levels of RIP3, MLKL and the phosphorylation of MLKL showed that quetiapine induced necroptotic cell death both in vivo and in vitro. Pharmacologic blockade of necroptosis using its specific inhibitor Necrostatin-1 attenuated quetiapine-induced myocardial injury in mice. In addition, quetiapine imbalanced the endocannabinoid system and caused opposing effects on two cannabinoid receptors (CB1R and CB2R). Specific antagonists of CB1R (AM 281, Rimonabant), but not its agonist ACEA significantly ameliorated the heart histopathology induced by chronic quetiapine exposure. By contrast, specific agonists of CB2R (JWH-133, AM 1241), but not its antagonist AM 630 exerted beneficial roles against quetiapine cardiotoxicity. The protective agents (AM 281, Rimonabant, AM 1241, and JWH-133) consistently inactivated the quetiapine-induced necroptosis signaling. Quetiapine bidirectionally regulates cannabinoid receptors and induces myocardial necroptosis, leading to cardiac toxic effects. Therefore, pharmacologic inhibition of CB1R or activation of CB2R represents promising therapeutic strategies against quetiapine-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

The magnetic enrichment behavior of monodispersed MFe 2 O 4 (M = Mg, Ca, Ni, Co, and Cu) ferrite nanoparticles with different size (10–130 nm) on the surface of a 15 mm o.d. NdFeB-N40 magnetic rod has been investigated. The materials were synthesized by a modified sol-gel method. They were characterized by XRD, TEM, and VSM. The magnetic field of the rod was modelled numerically using a finite element analysis software to obtain the input data for the magnitude of magnetic force. Three adsorption models can be used to describe the enrichment mechanism of ferrite nanoparticle depending on the magnetic permeability: (i) Freundlich adsorption model at low magnetic permeability (<10 μemu/Oe) which leads to the enrichment percentage below 50%, (ii) mixed (multilayer) adsorption model at intermediate permeability (10–50 μemu/Oe), and (iii) a monolayer adsorption at high permeability (>100 μemu/Oe) leading to the enrichment percentage above 90%. [ABSTRACT FROM AUTHOR]

Abstract Deoxynivalenol (DON) contamination is indicated as a worldwide problem since it causes economic losses for the grain and is a potential threat to both animal and human health. This study concentrated on DON-induced oxidative damage and the accompanying nuclear factor erythroid 2-related factor 2 (Nrf2) translocation during DON-induced maternal hepatotoxicity. The 0, 1.0 and 2.5 mg/kg/day of DON were used as doses for the experiment during gestation days. DON slightly increased the levels of ALT and AST in GD12.5 d instead of GD18.5 d. Oxidative stress and anti-oxidization system were both found to be activated in the experiment which marked by ROS, MDA and GSH increasing, especially on GD12.5 d. The levels of HO-1 were significantly increased by DON exposure at different two time points. Moreover, Nrf2 translocation appeared both in GD 12.5 d and GD 18.5 d. In conclusion, DON-induced ROS accumulation may cause maternal liver damage in the initial stages, but the related stimulation of Nrf2/HO-1 pathway improves the removal of ROS and decreases the level of oxidative stress thereby protecting the liver damage. Therefore, upregulating the Nrf2-dependent response is one of the potential methods that protects maternal liver from DON-induced oxidative damage. Graphical abstract Image 1 Highlights • DON-induced ROS accumulation may cause liver damage of pregnant mice. • Nrf2/HO-1 pathway improves the removal of ROS and decreases oxidative stress. • Nrf2/HO-1 pathway protects liver from DON-induced oxidative damage. [ABSTRACT FROM AUTHOR]

Abstract The turning circle is one of the most basic and important parameters that represents the turning performance of a ship. Steady turning diameter is an important indicator of maneuverability of ships and has received widespread attention. Fin stabilizers are currently added to ship designs for the primary purpose of producing roll-canceling moments during ordinary operation. The present work aims to investigate the effect of fin stabilizers on ship turning circle control during turning motion. The nonlinear 4-DOF mathematical model of a navy vessel is established. The forces and moments caused by propeller, rudder, fin stabilizers and wave disturbance are also modeled. The simulations of ship turning motion with and without fin stabilizers are carried out to explore the effect of fin stabilizers on ship turning performance. Based on the analysis of simulation results, an improved PID controller based on Monte Carlo simulation (MCS) optimization is developed to realize the turning circle control. The simulation results show that fin stabilizers are promising and effective for turning circle control during ship turns with a properly designed PID controller, which provides a new idea for attitude control in ship turning. [ABSTRACT FROM AUTHOR]

[Display omitted] • Alginate promotes weight loss in overweight adults, compared to maltodextrin. • Alginate decreased body fat in overweight subjects and did not affect lean mass. • Bile acid and related gut microbiota were changed after alginate intervention. • Alterations in gut microbiota were linked to weight loss induced by alginate. Being overweight is a risk for various chronic diseases. Alginate, a soluble dietary fiber extracted from seaweed, has been linked to weight loss with unclear mechanisms. We conducted a double-blind, randomized trial in overweight or normal-weight adults to explore alginate's weight loss effect and mechanism. Normal-weight or overweight participants were randomized to receive either alginate (15 g/day) or maltodextrin (13.8 g/day) for 14 weeks. Compared to maltodextrin (−0.91 kg; 95% CI, −1.91 to 0.10), alginate helped overweight subjects lose weight (−2.67 kg; 95% CI, −3.89 to −1.46) (P = 0.0017) after 14 weeks. In overweight subjects, alginate increased fecal-conjugated bile acids (taurocholate acid and taurochenodeoxycholic acid) and reduced bile acid-related bacteria (Bacteroides , Oscillibacter and Eubacterium). Our results indicate that alginate decreases weight and increases bile acid excretion in overweight subjects, related to gut microbiota alterations and inhibited intestinal bile acid absorption. [ABSTRACT FROM AUTHOR]

We theoretically investigate hybrid transparency effect, which incorporates both dipole-induced transparency (DIT) and all-optical electromagnetically induced transparency (EIT)-like effects, in the drop-filter cavity–waveguide system. It is shown that the hybrid transparency effect originates from not only destructive interference of the cavity fields but also interference between DIT and all-optical EIT-like effects, thus the disappearance and revival phenomena of transparency windows occur. Especially, the transmission amplitude of hybrid transparency effect is even larger than that of all-optical EIT-like effect in the case of large intrinsic loss of microcavity. Benefiting from the hybrid transparency effect, photonic Stern–Gerlach-like and Faraday rotation effects can be realizable in multiple regimes, which may be useful for hybrid quantum information processing with photon and solid state qubit. [ABSTRACT FROM AUTHOR]

Abstract Background Aflatoxins are strong cancerogenic compounds predominantly produced by certain strains of the Aspergillus genus. Due to their extreme stability in different conditions, it is very difficult to remove them completely in human diet and animal feeds. In this way aflatoxins are triggering numerous healthy problems (such as liver cancer) and thus becoming a huge burden to the hygiene system and food industry worldwide. Scope and approach Therefore, seeking for an effective technique to degrade aflatoxins to a threshold level has been a “hot-topic” among researchers. Traditional methods to detoxify aflatoxins include physical and chemical treatments, such as an extrusion cooking process and ammoniation, respectively. Meanwhile a bio-degradation by microorganisms gains its popularity due to its friendliness to both environment and body health. Natural phytochemicals (plant extracts) which have great capability to remove aflatoxins without causing any damage on human and animals come out as an improvement. Key findings and conclusion However, a fully and systematically discussion of the methods of detoxification for aflatoxins is still not available. Therefore, in the present review we briefly enumerate several traditional strategies, update newly methods, particularly the potential use of natural phytochemicals, and discuss some mechanisms during the detoxification period, summarizing merits and demerits of these methods. We suggest that this important information and our humble opinions could help researchers to understand the degradation of methods for aflatoxins. Graphical abstract Image 1 Highlights • Aflatoxin B 1 is classified as a Group I carcinogen by IARC. • Aflatoxin contamination is a great threat to human and animal health. • Physical, chemical and biological degradations are three major ways. • Phytochemicals have also been regarded as a promising approach. [ABSTRACT FROM AUTHOR]

Ship turning motion is an important part of ship maneuverability and is directly related to the safety of the ship sailing at sea. Ships experience a certain amount of rolling and heeling during turning. The rolling and heeling caused by turning and waves can be large enough to affect the ability of ships to perform their missions. Fin stabilizers are currently added to ship designs for the primary purpose of producing roll-canceling moments during ordinary operation. The present work aims to investigate the effect of fin stabilizers on ship roll reduction control during turning motion. The 6-DOF mathematical model of a multipurpose navy vessel as well as the models of forces and moments caused by hydrodynamic, propeller, rudder, fins and waves are established in MATLAB. Based on the simulation analysis of ship turning motion with and without fin stabilizers, a MIGA-based improved PID controller is developed. The simulation results of ship roll control during turns using the MIGA-PID controller are compared with the results of ZN-PID and LQR controllers. Simulation results show that fin stabilizers are also effective for roll reduction control during ship turns with an appropriate controller, and the present developed MIGA-PID controller can be a practical choice. [ABSTRACT FROM AUTHOR]

Deficiency in subunits of the conserved oligomeric Golgi (COG) complex results in pleiotropic defects in glycosylation and causes congenital disorders in humans. Insight regarding the functional consequences of this defective glycosylation and the identity of specific glycoproteins affected is lacking.Achemical glycobiology strategy was adopted to identify the surface glycoproteins most sensitive to altered glycosylation in COGdeficient Chinese hamster ovary (CHO) cells. Following metabolic labeling, an unexpected increase in GalNAz incorporation into several glycoproteins, including α-dystroglycan (α-DG), was noted in cog1-deficient ldlB cells. Western blotting analysis showed a significantly lower molecular weight for α-DG in ldlB cells compared with WT CHO cells. The underglycosylated α-DG molecules on ldlB cells are highly vulnerable to bacterial proteases that co-purify with V. cholerae neuraminidase, leading to rapid removal of the protein from the cell surface. The purified bacterial mucinase StcE can cleave both WT and ldlB α-DG but did not cause rapid degradation of the fragments, implicating other V. cholerae proteases in the final proteolysis of the fragments. Extending terminal glycosylation on the existing mucin-type glycans of ldlB α-DG stabilized the resulting fragments, indicating that fragment stability, but not the initial fragmentation of the protein, is influenced by the glycosylation status of the cell. This discovery highlights a functional importance for mucin-type O-glycans found on α-DG and reinforces a growing role for these glycans as regulators of extracellular proteolysis and protein stability. [ABSTRACT FROM AUTHOR]

Abstract Purpose To investigate effects and heat distribution of radiofrequency ablation (RFA) on vertebral tumors in vitro and in vivo swine experiments and its clinical application. Materials and methods RFA was performed on the swine spine in vitro and in vivo for 20 min at 90 °C at the electrode tip, and the temperature at the electrode tip and surrounding tissues were recorded. Clinical application of ablation combined with vertebroplasty was subsequently performed in 4 patients with spinal tumors. Results In the in vitro study, the mean temperature at the front and ventral wall of the spinal canal was 50.8 °C and 43.6 °C, respectively, at 20 mm significantly greater than 37.7 °C and 33.7 ± 1.7 °C, respectively, at 10 mm ablation depth. The coagulative necrosis area was significantly (P < 0.0001) greater at 20 mm depth than at 10 mm depth (mean 17.0 × 20.7 mm2 vs. 14.2 × 16.6 mm2). In the in vivo experiment, the local temperature increased significantly (P < 0.05) from around 36 °C before ablation to over 41 °C at 20 min after ablation, with the temperature at the electrode tip (90.4 °C) and within the vertebral body (67.0 °C) significantly (P < 0.05) greater than at the posterior (41.9 °C) and lateral wall (41.8 °C). From 2 to 5 weeks, bone remodeling began. Clinically, all four patients had successful RFA and vertebroplasty, with no neurological deficits. The pain scores were significanlty (P < 0.05) improved before (4.5–10, mean 8.0) compared with at four weeks (0–1.8, mean 1.8). Conclusion The clustered electrode can be efficiently and safely applied in the treatment of spinal tumors without damaging the spinal cord and adjacent nerves by heat distribution. [ABSTRACT FROM AUTHOR]

Deoxynivalenol (DON, vomitoxin) is the most frequent mycotoxin in grains and grain products. DON contamination in fodder and food is a serious threat for health, since it impairs the immune and gastrointestinal systems of both human and animals. Gut microbiota seems to play a more and more important part in human and animals' health according to related researches. Previous studies implied some associations among gut microbiota, DON and immune system. For example, DON affects immune system as well as the composition and abundance of gut microbiota, and the latter influences immune system as well. In the present short review, we not only provide the available information about the toxic consequences of DON-induced immunotoxicity on different animals and cell lines and discuss its main possible molecule mechanisms, but also summarize research results concerning the role of gut microbiota in DON-induced immunotoxicity and gender differences, with the aim to find some potential therapeutic strategies to tackle DON-induced immunotoxicity. [ABSTRACT FROM AUTHOR]

Acid hydrolases utilize a carbohydrate-dependent mechanism for lysosomal targeting. These hydrolases acquire a mannose 6-phosphate tag by the action of the GlcNAc-1-phosphotransferase enzyme, allowing them to bind receptors and traffic to endosomes. Loss of GlcNAc-1-phosphotransferase results in hydrolase hypersecretion and profound lysosomal storage. Little, however, is known about how these cellular phenotypes affect the trafficking, activity, and localization of surface glycoproteins. To address this question, we profiled the abundance of surface glycoproteins in WT and CRISPR-mediated GNPTAB-/- HeLa cells and identified changes in numerous glycoproteins, including the uptake receptor LRP1 and multiple receptor tyrosine kinases. Decreased cell surface LRP1 in GNPTAB-/- cells corresponded with a reduction in its steady-state level and less amyloid-β-40 (Aβ40) peptide uptake. GNPTAB-/- cells displayed elevated activation of several kinases including Met receptor. We found increased Met phosphorylation within both the kinase and the docking domains and observed that lower concentrations of pervanadate were needed to cause an increase in phospho-Met in GNPTAB-/-cells. Together, these data suggested a decrease in the activity of the receptor and non-receptor protein-tyrosine phosphatases that down-regulate Met phosphorylation. GNPTAB-/- cells exhibited elevated levels of reactive oxygen species, known to inactivate cell surface and cytosolic phosphatases by oxidation of active site cysteine residues. Consistent with this mode of action, peroxide treatment of parental HeLa cells elevated phospho-Met levels whereas antioxidant treatment of GNPTAB-/-cells reduced phospho-Met levels. Collectively, these findings identify new mechanisms whereby impaired lysosomal targeting can impact the activity and recycling of receptors. [ABSTRACT FROM AUTHOR]