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Background: The goal of this study was to investigate the difference between the learning curves of different maneuvers in laparoscopic spleen-preserving splenic hilar lymphadenectomy for advanced upper gastric cancer. Methods: From January 2010 to April 2014, 53 consecutive patients who underwent laparoscopic spleen-preserving splenic hilar lymphadenectomy via the traditional-step maneuver (group A) and 53 consecutive patients via Huang's three-step maneuver (group B) were retrospectively analyzed. Results: No significant difference in patient characteristics were found between the two groups. The learning curves of groups A and B were divided into phase 1 (1-43 cases and 1-30 cases, respectively) and phase 2 (44-53 cases and 31-53 cases, respectively). Compared with group A, the dissection time, bleeding loss and vascular injury were significantly decreased in group B. No significant differences in short-term outcomes were found between the two maneuvers. The multivariate analysis indicated that the body mass index, short gastric vessels, splenic artery type and maneuver were significantly associated with the dissection time in group B. No significant difference in the survival curve was found between the maneuvers. Conclusions: The learning curve of Huang's three-step maneuver was shorter than that of the traditional-step maneuver, and the former represents an ideal maneuver for laparoscopic spleen-preserving splenic hilar lymphadenectomy. To shorten the learning curve at the beginning of laparoscopic spleen-preserving splenic hilar lymphadenectomy, beginners should beneficially use Huang's three-step maneuver and select patients with advanced upper gastric cancer with a body mass index of less than 25 kg/m² and the concentrated type of splenic artery. [ABSTRACT FROM AUTHOR]

Abstract: Studies of sand saltation are currently concentrating on wind tunnel experiments, theoretical analyses and numerical simulations under ideal as well as controllable conditions. These theoretical analyses and numerical simulations cannot accurately predict sand movements in field environments. In this paper, we simulate wind field patterns for two different surfaces of complex microtopography using the computational fluid dynamic model, FLUENT. To demonstrate that the model can successfully reproduce wind patterns in complex microtopography, we first simulate a well-studied mesquite bush and coppice dune field from the Chihuahuan Desert. This is then followed by an analysis of the wind field pattern around a large barchan dune that is complex in shape. For this case, the wind pattern was linked with a sediment transport equation to estimate sediment flux and transport. Finally, as shown by the simulation results, the sand flux, from the right horn to the left horn of the dune, first increased then decreased after reaching its maximum at the intersection of the brink and the longitudinal centreline of the dune. [Copyright &y& Elsevier]

Balb/cA mice were used to study the in vivo effect of N-acetyl cysteine, S-allyl cysteine, S-ethyl cysteine, S-methyl cysteine and S-propyl cysteine, all derived from garlic, on glutathione (GSH) concentration and catalase and glutathione peroxidase (GPX) activities in plasma, kidney and liver. Cysteine was used for comparison. The effects of these compounds on the levels of fibronectin, triglyceride (TG), cholesterol and α-tocopherol were also evaluated. Cysteine or cysteine-containing compounds were added to drinking water at 1 g/L. After 4 wk of treatment, GSH levels in kidney and liver were greater (P < 0.05) than in controls. Cysteine decreased catalase and GPX activities in liver, and enhanced both Fe[sup 2+]- and glucoseinduced lipid oxidation in plasma, kidney and liver compared with the control group (P < 0.05). However, the administration of the five cysteine-containing compounds enhanced catalase and GPX activities in kidney and liver, and reduced Fe[sup 2+]- and glucose-induced lipid oxidation in plasma, kidney and liver compared with the control and cysteine-treated groups (P < 0.05). Intake of the five cysteine-containing compounds reduced fibronectin, TG and cholesterol concentrations in plasma and liver, and increased the α-tocopherol concentration in plasma, kidney and liver compared with the control and cysteine-treated groups (P < 0.05). The five cysteine-containing compounds derived from garlic had marked effects on antioxidant enzymes and spared α-tocopherol in mice. Furthermore, these compounds reduced fibronectin, TG and cholesterol concentrations in plasma. These data indicate that these compounds have a range of protective effects for cardiovascular disease prevention or therapy. KEY WORDS: cysteine-containing compounds; catalase; glutathione peroxidase; triglyceride. [ABSTRACT FROM AUTHOR]

Oxidative stress-induced DNA damage, the senescence-associated secretory phenotype (SASP), and impaired autophagy all are general features of senescent cells. However, the cross-talk among these events and processes is not fully understood. Here, using NIH3T3 cells exposed to hydrogen peroxide stress, we show that stress-induced DNA damage provokes the SASP largely via cytosolic chromatin fragment (CCF) formation, which activates a cascade comprising cGMP-AMP synthase (cGAS), stimulator of interferon genes protein (STING), NF-κB, and SASP, and that autolysosomal function inhibits this cascade. We found that CCFs accumulate in senescent cells with activated cGAS-STING-NF-κB signaling, promoting SASP and cellular senescence. We also present evidence that the persistent accumulation of CCFs in prematurely senescent cells is partially associated with a defect in DNA-degrading activity in autolysosomes and reduced abundance of activated DNase 2α. Intriguingly, we found that metformin- or rapamycin-induced activation of autophagy significantly lessened the size and levels of CCFs and repressed the activation of the cGAS-STING-NF-κB-SASP cascade and cellular senescence. These effects of autophagy activators indicated that autolysosomal function contributes to CCF clearance and SASP suppression, further supported by the fact that the lysosome inhibitor bafilomycin A1 blocked the role of autophagy-mediated CCF clearance and senescence repression. [ABSTRACT FROM AUTHOR]

α44 integrin plays a crucial role in retention and release of neutrophils from bone marrow. Although α44 integrin is known to be a potential target of reactive oxygen species (ROS)--induced cysteine glutathionylation, the physiological significance and underlying regulatory mechanism of this event remain elusive. Here, using in vitro and in vivo biochemical and cell biology approaches, we show that physiological ROS-induced glutathionylation of α44 integrin in neutrophils increases the binding of neutrophil-associated α44 integrin to vascular cell adhesion molecule 1 (VCAM-1) on human endothelial cells. This enhanced binding was reversed by extracellular glutaredoxin 1 (Grx1), a thiol disulfide oxidoreductase promoting protein deglutathionylation. Furthermore, in a murine inflammation model, Grx1 disruption dramatically elevated α44 glutathionylation and subsequently enhanced neutrophil egress from the bone marrow. Corroborating this observation, intravenous injection of recombinant Grx1 into mice inhibited α44 glutathionylation and thereby suppressed inflammation-induced neutrophil mobilization from the bone marrow. Taken together, our results establish ROS-elicited glutathionylation and its modulation by Grx1 as pivotal regulatory mechanisms controlling α44 integrin affinity and neutrophil mobilization from the bone marrow under physiological conditions. [ABSTRACT FROM AUTHOR]

Objective To investigate the association between preoperative lymph node size (Ns) and prognosis of radical gastrectomy for gastric cancer. Methods The clinical and pathological data of 970 patients undergoing radical gastrectomy for gastric cancer were retrospectively analyzed. The correlation between Ns and the identified variables for the prediction of overall survival (OS) and disease-free survival (DFS) was examined. Results Three hundred and thirty-one (34.1%) of 970 patients developed recurrence, which was most commonly in local lymph nodes. The average Ns was 1.52 cm in patients with recurrence, which was significantly higher than the 1.14 cm observed in patients without recurrence (p < 0.001). Patients were categorized into three groups as follows (Ns category):Ns0:≤1.10 cm, Ns1:1.10-1.70 cm, and Ns2:>1.70 cm, determined using the X-tile program. In univariate and multivariate analyses, Ns category, age, tumor size, lymphadenectomy, adjuvant chemotherapy and TNM stage were independent prognostic factors for DFS. Stratified analysis only in stage III was there a significant difference in the Ns category based on TNM stage. Furthermore, in the stage III subgroup, univariate and multivariate analyses revealed that Ns category, lymphadenectomy, and TNM stage was independent prognostic factors for DFS. A nomogram were developed to predict the 3-year DFS rate. Conclusions Preoperative Ns is an independent prognostic factor for DFS of patients after radical surgery for gastric cancer. The proposed nomogram combined with Ns could be a simple and effective approach to predict the 3-year DFS of stage III patients. [ABSTRACT FROM AUTHOR]

On 13rd December 2012, the Chang’e-2 probe made a successful flyby of the asteroid 4179 Toutatis in deep space about 7 million kilometers away from the earth, and acquired a series of optical images with a high resolution better than 3 m. In this paper, we process the radiation calibration data of the imaging camera by the least squares fitting method, to obtain the relative calibration matrix and absolute calibration coefficients to correct the original asteroid images and calibration data, then to make inversion of the asteroid surface radiance at the imaging time. According to the Hapke's description about the application of the Nicodemus’ definition of reflectance in the planetary science, the hemispherical albedo of Toutatis is obtained. The surface hemispherical albedos at the R, G, and B bands are 0.2083, 0.1269, and 0.1346, respectively, and the asteroid's mean surface hemispherical albedo is 0.1566. The results indicate that Toutatis is somewhat a red object in the visible spectral band. [ABSTRACT FROM AUTHOR]

Cytokinesis is the final stage of cell division in which the cytoplasm of a cell is divided into two daughter cells after the segregation of genetic material, and the central spindle and midbody are considered to be the essential structures required for the initiation and completion of cytokinesis. Here, we determined that the centrosome protein Cep57, which is localized to the central spindle and midbody, acts as a spindle organizer and is required for cytokinesis. Depletion of Cep57 disrupted microtubule assembly of the central spindle and further led to abnormal midbody localization of MKLP1, Plk1, and Aurora B, which resulted in cytokinesis failure and the formation of binuclear cells. Furthermore, we found that Cep57 directly recruited Tektin 1 to the midbody matrix to regulate microtubule organization. Thus, our data reveal that Cep57 is essential for cytokinesis via regulation of central spindle assembly and formation of the midbody. [ABSTRACT FROM AUTHOR]

Abstract: Type 2 diabetes mellitus is a global health issue. Patients with poor glycemic control often suffer from cardiovascular, cerebrovascular, neuropathic, and nephropathic complications as well as other chronic conditions. Therapeutic guidelines recommend that diabetic patients should maintain their HbA1c level below a certain target in order to minimize the risk of developing complications. However, hypoglycemia is recognized as a major impediment to the adequate control of type 2 diabetes. Hypoglycemia can manifest symptoms of varying degrees of severity. Moreover, an association between hypoglycemia and cardiovascular morbidity and mortality has been reported. Here, we present a post hoc Taiwan subgroup analysis of these data collected in the RECAP-DM study to indicate probably more emphasis and concern on hypoglycemia in type 2 diabetic patients in Taiwan. In this analysis, we found no significant difference was observed in treatment-related satisfaction between Taiwanese patients with or without hypoglycemia. Another finding of our study further shows that varying order of hypoglycemic symptoms or severity has no effect on patients’ assessment of health-related quality of life scores. We need to pay more attention to this issue because of its enduring impact on compliance and concerns about hypoglycemia in type 2 diabetic patients. Nevertheless, socio-demographic characteristics are also important factors influencing glycemic control and patients’ health-related quality of life. Future interventions and therapeutic algorithms should emphasize the probable patients’ unawareness or neglect on hypoglycemia in diabetic patients. [Copyright &y& Elsevier]

Human pancreatitis-associated protein was identified in pathognomonic lesions of Alzheimer disease, a disease characterized by the presence of filamentous protein aggregates. Here, we showed that at physiological pH, human pancreatitis-associated protein forms non-Congo Red-binding, proteinase K-resistant fibrillar aggregates with diameters from 6 up to as large as 68 nm. Interestingly, circular dichroism and Fourier transform infrared spectra showed that, unlike typical amyloid fibrils, which have a cross-β-sheet structure, these aggregates have a very similar secondary structure to that of the native protein, which is composed of two α-helices and eight β-strands, as determined by NMR techniques. Surface structure analysis showed that the positively charged and negatively charged residues were clustered on opposite sides, and strong electrostatic interactions between molecules were therefore very likely, which was confirmed by cross-linking experiments. In addition, several hydrophobic residues were found to constitute a continuous hydrophobic surface. These results and protein aggregation prediction using the TANGO algorithm led us to synthesize peptide Thr84 to Ser116, which, very interestingly, was found to form amyloid-like fibrils with a cross-β structure. Thus, our data suggested that human pancreatitis-associated protein fibrillization is initiated by protein aggregation primarily because of electrostatic interactions, and the loop from residues 84 to 116 may play an important role in the formation of fibrillar aggregates with a native-like conformation. [ABSTRACT FROM AUTHOR]

Anionic citrate is a major component of venom, but the role of venom citrate in toxicity other than its inhibitory effect on the cation-dependent action of venom toxins is poorly understood. By immobilizing Chinese hamster ovary cells in microcapillary tubes and heparin on sensor chips, we demonstrated that heparan sulfate-mediated cell retention of the major cardiotoxin (CTX) from the Taiwan cobra, CTX A3, near membrane surfaces is citrate-dependent. X-ray determination of a CTX A3-heparin hexasaccharide complex structure at 2.4 Å resolution revealed a molecular mechanism for toxin retention in which heparin-induced conformational changes of CTX A3 lead to citrate-mediated dimerization. A citrate ion bound to Lys-23 and Lys-31 near the tip of loop II stabilizes hydrophobic contact of the CTX A3 homodimer at the functionally important loop I and II regions. Additionally, the heparin hexasaccharide interacts with five CTX A3 molecules in the crystal structure, providing another mechanism whereby the toxin establishes a complex network of interactions that result in a strong interaction with cell surfaces presenting heparan sulfate. Our results suggest a novel role for venom citrate in biological activity and reveal a structural model that explains cell retention of cobra CTX A3 through heparan sulfate-CTX interactions. [ABSTRACT FROM AUTHOR]