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Developing effective marine water quality criteria (WQC) is crucial for controlling marine contamination and protecting marine life. The WQC for copper is urgently needed due to the toxicity and widespread of copper contamination. In this work, both short-term water quality criteria (SWQC) and long-term water quality criteria (LWQC) under 10 % effect endpoints were derived by using the model averaging of species sensitivity distribution (SSD10) method for Bohai Bay. The WQC values were obtained directly from the hazardous concentration for 5 % of species (HC5) values, which removes the influence of arbitrary assessment factor (AF). Modifications to the acute-chronic ratio (ACR) strategies and the inclusion of the test toxicity data of local species also improved the accuracy and applicability of the WQC values. The derived SWQC and LWQC were 2.21 and 0.45 µg/L, respectively. Furthermore, the overall risk level of copper in Bohai Bay was evaluated by using the risk quotient (RQ) method, and the results showed it was at a moderate-low level. This study provides a new approach for the derivation of the WQC for Cu and the risk assessment of Bohai Bay, which is essential for the protection of local aquatic life and provides guidance to the establishment of the national WQC.

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Although the tetanus neurotoxin (TeNT) delivers its protease domain (LC) across the synaptic vesicle lumen into the cytosol via its receptor binding domain (HC) and translocation domain (HN), the molecular mechanism coordinating this membrane translocation remains unresolved. Here, we report the high-resolution crystal structures of full-length reduced TeNT (rTeNT, 2.3 Å), TeNT isolated HN (TeNT/iHN, 2.3 Å), TeNT isolated HC (TeNT/iHC, 1.5 Å), together with the solution structures of TeNT/iHN and beltless TeNT/iHN (TeNT/blHN). TeNT undergoes significant domains rotation of the HN and LC were demonstrated by structural comparison of rTeNT and non-reduced-TeNT (nrTeNT). A linker loop connects the HN and HC is essential for the self-domain rotation of TeNT. The TeNT-specific C869-C1093 disulfide bond is sensitive to the redox environment and its disruption provides linker loop flexibility, which enables domain arrangement of rTeNT distinct from that of nrTeNT. Furthermore, the mobility of C869 in the linker loop and the sensitivity to redox condition of C1093 were confirmed by crystal structure analysis of TeNT/iHC. On the other hand, the structural flexibility of HN was investigated by crystallographic and solution scattering analyses. It was found that the region (residues 698-769), which follows the translocation region had remarkable change in TeNT/iHN. Besides, the so-called belt region has a high propensity to swing around the upper half of TeNT/iHN at acidic pH. It provides the first overview of the dynamics of the Belt in solution. These newly obtained structural information that shed light on the transmembrane mechanism of TeNT.

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Pronation external rotation (PER) fractures are unstable ankle fractures that require anatomically stable fixation. However, due to the long distance between the fibula and the posterior malleolus in PER IV, existing approaches may make it difficult for the fixation of the associated posterior joint and the lateral malleolus. We describe an S-type posterolateral approach for the open reduction and internal fixation of posterior malleolar fractures with an associated lateral malleolar fracture in PER IV.

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Polyphosphate (polyP), which is found in various microorganisms and human cells, is an anionic biopolymer consisting of inorganic phosphates linked by high-energy phosphate bonds. Previous studies revealed that polyPs strongly promoted the amyloid formation of several amyloidogenic proteins; however, the mechanism of polyP-induced amyloid formation remains unclear. In the present study using ß2-microglobulin (ß2m), a protein responsible for dialysis-related amyloidosis, we investigated amyloid formation in the presence of various chain lengths of polyPs at different concentrations under both acidic (pH 2.0 to 2.5) and neutral pH (pH 7.0 to 7.5) conditions. We found that the amyloid formation of ß2m at acidic pH was significantly accelerated by the addition of polyPs at an optimal polyP concentration, which decreased with an increase in chain length. The results obtained indicated that electrostatic interactions between positively charged ß2m and negatively charged polyPs play a major role in amyloid formation. Under neutral pH conditions, long polyP with 60 to 70 phosphates induced the amyloid formation of ß2m at several micromoles per liter, a similar concentration range to that in vivo. Since ß2m with an isoelectric point of 6.4 has a slightly negative net charge at pH 7, polyPs were unlikely to interact with ß2m electrostatically. PolyPs appear to dehydrate water molecules around ß2m under the unfolded conformation, leading to the preferential stabilization of less water-exposed amyloid fibrils. These results not only revealed the pH-dependent mechanism of the amyloid formation of ß2m but also suggested that polyPs play an important role in the development of dialysis-related amyloidosis.

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Accurate information on eye position in the orbit is available from visual feedback, efference copy of the oculomotor commands and proprioceptive signals from the extraocular muscles (EOM). Whereas visual feedback and oculomotor commands have been extensively studied, central processing of EOM proprioceptive signals remains to be elucidated. A challenge to the field is to develop an approach to induce passive eye movements without physically contacting the eyes. A novel method was developed to generate passive eye movements in rats. A small rare-earth magnet disk (0.7 mm diameter, 0.5 mm thickness) was attached to the surface of a rat's eyeball. A metal rod (5 mm diameter) wrapped with an electromagnetic (EM) coil was placed near the magnet (8-15 mm). By passing currents to the EM coil, electromagnetic force (EMF) was generated and acted upon the magnet and induced passive eye movements. The EMF induced well-defined passive eye movements, whose directions were dependent on current polarity and amplitudes and peak velocities were dependent on current intensity and duration. Peak velocities of the EMF-induced eye movements were linearly related to amplitudes, exhibiting main sequence relationships similar to that of saccades in awake rats and eye movements induced by electrical microstimulation of the abducens nucleus in anesthetized rats. Histological examination showed that repetitive EMF stimulations did not appear to result in damages in the EOM fibers. These results validated the EMF approach as a novel tool to investigate EOM proprioceptive signals and their roles in visual localization and gaze control.

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OBJECTIVE: The purposes of this study were to determine whether autophagy was involved in cisplatin (CDDP) resistance and to investigate the role of the autophagy in the regulation of chemosensitivity to CDDP in laryngeal cancer Hep-2 cells. METHODS: A WST-1 assay was performed to determine cell viability and cell proliferation. Autophagy activation and proapoptotic effects were characterized using monodansylcadaverine labeling and Hoechest staining, respectively. Western blot analysis was used to detect the expression of apoptotic and autophagy-related genes. Flow cytometry was used to assess cell apoptosis ratio. RESULTS: Exposure to CDDP induced the aggregation of autophagosomes in the cytoplasms of Hep-2 cells and up-regulated the expression of Beclin 1 and LC3II. However, CDDP treatment could not lead to obvious inhibition of cell proliferation, which implies that the autophagy may protect CDDP-treated cells from undergoing cell death. Meanwhile, the WST-1 assay indicated that knockdown of the autophagic gene Beclin 1 sensitized Hep-2 cells to CDDP. Furthermore, CDDP-mediated apoptotic cell death was further potentiated by pretreatment with autophagy inhibitor 3-methyladenine or small interfering RNA against Beclin 1. For the definite mechanism of Beclin 1-enhancing chemosensitivity to CDDP, we found that Beclin1 augmented CDDP-induced apoptotic signaling via enhancing caspase-9 and caspase-3 activity but not caspase-8. CONCLUSION: Our results suggest that functional autophagy in response to CDDP may lead to cell survival in Hep-2 cells, whereas defective autophagy may contribute to CDDP-induced apoptosis in Hep-2 cells. Thus, modulators of autophagy may be used beneficially as adjunctive therapeutic agents during the treatment of laryngeal cancer with CDDP therapy.

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OBJECTIVE: To study the expressions of key assemblies of cytoskeleton, Fascin-1, Ezrin and Paxillin, in laryngeal squamous cell carcinoma (LSCC) and their correlation with clinicopathologic characteristics, cancer recurrence and survival of patients with LSCC. METHODS: The expressions of Fascin-1, Ezrin and Paxillin proteins were detected by immunohistochemistry in 199 cases of LSCC. Unconditional Logistic regression model or Cox proportional hazards model was used for the analyses of recurrent risks and prognostic factors. RESULTS: Significantly increased expression of Fascin-1, Ezrin or Paxillin expression was showed in the LSCC with poorly differentiated, positively cervical lymph nodal metastasis, and clinical stage III + IV respectively (P < 0.05). The expressions of three kinds of proteins in the recurrent cases were higher than those in non-recurrent cases respectively (χ(2) were 42.479, 43.673 and 22.261, P < 0.05). The highest recurrence rate (69.1%) was observed in group of cases with the highly co-expression of the three kinds of proteins (P < 0.05). The expression of Fascin-1 (OR = 7.89, 95%CI 2.26 - 27.53, P = 0.001), or Ezrin (OR = 2.51, 95%CI 1.18 - 5.32, P < 0.001) was independent risk for recurrence. Five-year disease-free survival rates of patients with high expression of Fascin-1, Ezrin or Paxillin were lower than those of patients with negative or low expressions for the proteins (P < 0.05). Patients with highly co-expression of three kinds of proteins showed the poorest survival prognosis, with a 5-year disease free survival (DFS) of only 26.4% (P < 0.05), and expressions of three proteins were independent prognostic factors for 5-year DFS (P < 0.05). CONCLUSION: Fascin-1, Ezrin, and Paxillin were correlative with LSCC progression and might be potential predictors for cancer recurrence and survival of patients with LSCC, as well as therapeutic targets for LSCC.

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BACKGROUND AND AIMS: Tumor-specific T regulatory cells (Treg) play a critical role in tumor cell survival. The development of tumor-specific Treg is not fully understood. This study aims to elucidate the role of matrix metalloproteinase (MMP)9 in tumor tolerance development. METHODS: We recruited 38 patients with laryngeal cancer (LC) in this study. MMP9 levels in the LC were measured by western blotting. Immune cells were isolated from LC tissue for indicated experiments. The cells' activities were characterized by flow cytometry. RESULTS: High levels of MMP9 were detected in LC that plays a critical role in the development of tolerogenic dendritic cells and LC-specific Tregs. The isolated LC Tregs have the ability to suppress tumor-specific CD8 T cells in a tumor antigen-specific manner. CONCLUSIONS: This study reveals a novel mechanism in tumor tolerance in which MMP9 plays a critical role in tumor survival. The data imply that MMP9 may be a potential target in the treatment of malignant tumors.

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OBJECTIVE: To determine the optimal surgical modality for T3 glottic carcinoma. METHODS: Clinical data of 57 cases of T3 glottic carcinoma were retrospectively reviewed. Their clinical characteristics, surgical procedures and prognosis were analyzed. At different ages and by surgical procedures performed, the 3-year disease-free survival rate of the patients were analyzed. RESULTS: All cases underwent surgical procedures including total laryngectomy, near total laryngectomy and partial laryngectomy, and the 3-year disease-free survival rate was 63.2% (36/57). The 3-year disease-free survival rate of patients who received total laryngectomy was 66.7% (16/24), near total laryngectomy 50.0% (4/8), and partial laryngectomy 64.0% (16/25, P = 0.694). The 3-year survival rate of the cases ≥ 70.0 years old was 70.0% (7/10), and that of < 70 years old was 61.7% (29/47, P = 0.621). Thirty-six cases had neck dissection, including 2 cases with radical neck dissection, 6 cases with modified neck dissection, and 28 cases with selective neck dissection. The lymph node metastasis rate of all cases was 17.5%. Ten cases were diagnosed as postoperative local recurrence, including 1 cases treated with total laryngectomy, 2 cases treated with near total laryngectomy and 7 cases treated with partial laryngectomy. CONCLUSIONS: Both total laryngectomy and partial laryngectomy are important surgical procedures for treating patients with T3 glottic carcinoma. The optimal individual surgical procedure for the patient with T3 glottic carcinoma should be determined on the basis of the local lesions and physical status. Total laryngectomy is prior to partial laryngectomy for the patients with T3 glottic carcinoma ≥ 70 years old.

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OBJECTIVE: The purpose of this study was to investigate the clinical value of radiolabeled tracer method, methylene blue method and combination of these two methods in detection of sentinel lymph node (SLN), and to evaluate the accuracy of SLN in predicting the cervical lymph nodes status in laryngeal carcinoma patients with clinically negative neck lymph nodes (cN0 ). METHODS: Forty-one patients with cN0 laryngeal neoplasms underwent SLN detection using both of radiolabeled tracer and methylene blue. SLN imaging was performed with laryngoscope-guided injection of radioactive isotope 99Tc(m)-sulfur colloid (SC) into the laryngeal carcinoma before surgery, then all these patients underwent intraoperative lymphatic mapping with a handheld gamma-detecting probe. After mapping of SLN, methylene blue was subsequently injected at the same spots around the tumor in order to identify SLN during surgery. The results of SLN detection by isotope tracer, dye and combination of both methods were compared. RESULTS: The SLN detection rates by radiolabeled tracer, methylene blue and combined method were 87.8%, 70.7% and 92.7%, respectively (P < 0.01). The number of detected SLN was significantly different between radiolabeled tracer method and combined method (P < 0.05), and also between blue dye method and combined method (P < 0.01). However, no statistically significant difference was found between methylene blue method and radiolabeled tracer method (P > 0.05). Nine patients were found to have lymph node metastasis by final pathological examination. The sensitivity, accuracy and negative predictive values of SLN detection by the combined method using radiolabeled tracer and methylene blue were 88.9%, 97.4% and 96.7%, respectively. CONCLUSION: The combined method using radiolabeled tracer and methylene blue can improve the accuracy of sentinel lymph node detection. Furthermore, sentinel lymph node detection can accurately predict the cervical lymph node status in cN0 laryngeal carcinoma.

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OBJECTIVE: To investigate the effect and mechanisms of Compound Astragalus Recipe (CAR) for regulating cellular immune in patients with myasthenia gravis (MG). METHODS: Sixty MG patients were equally assigned to two groups randomly, the test group administered with CAR and the control group with prednisone for 3 months. Changes of patients' symptoms and adverse reactions were observed. The peripheral lymphocyte subsets distribution was examined by flow cytometry, and the levels of immunoglobulins and complements in the peripheral blood were measured by immuno-turbidimetry before and after treatment. RESULTS: The total effective rate in the test group after 12-week treatment reached 80% (24/30), while that of the control group reached 83.3% (25/30), difference between them showed no statistical significance (P > 0.05). CD4+ and CD4+/CD8+ ratio were lowered significantly in both groups, but the decrement of CD4+/CD8+ ratio in the test group was more significant than that in the control group, showing significance between groups (P < 0.05). While CD8+ in the test group after treatment was significantly increased as compared with that before treatment (P < 0.05), but with no significant difference in comparing with that in the control group (P > 0.05). Serum levels of IgM and IgA in MG patients were significantly higher than normal range (P < 0.01). Levels of C3 and C4 were significantly increased in both groups after treatment (P < 0.05). Moderate high level of ALT and AST revealed transiently at the 2nd week in 5 patients of the control group, while no adverse reaction was found in the test group. CONCLUSION: One of the mechanisms for CAR in playing its immuno-modulate effect may be its regulation on lymphocyte subsets distribution and humoral immune function.

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The kinetics of absorption, desorption, and degradation of sulfur mustard (HD) in alkyd coating was experimentally studied, and a one-dimension mass transfer model for the transportation of HD molecule in alkyd coating was established on the experimental data. The obtained results indicated that the persistence of HD molecule could be greatly increased due to the absorption of HD droplets by alkyd coating, and there still occurred the desorption of HD as vapor from coating for more than 3 days even after decontamination of HD droplets onto coating. It was also experimentally shown that the majority of HD both absorbed and desorbed was accomplished at an early stage, less than 10 h, and HD molecule was able to be degraded within the alkyd coating probably through the reactions of hydrolysis and elimination. The diffusion coefficient and degradation rate constant of HD in alkyd coating were determined to be practically around 10(-9) cm2/s and 2.4 x 10(-5) min(-1), respectively.

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