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Reverse thermally induced separation (RTIPS) was used to obtain a separation membrane with a better internal structure for a higher water flux and a surface that could easily form a hydration layer. In comparison to the traditional modification method, this work focused on the aspect that the internal structure obtained by changing the membrane-making method provided easier adhesion conditions for the dopamine/TiO2 hybrid nanoparticles (DA/TiO2 HNPs) obtained by biomimetic mineralization. It provided a basis for exploring the variation in adhesion with the water bath temperature and the amount of titanium added through the study of turbidity point, SEM images, water contact angle, thermogravimetric test, EDX, AFM, XPS, FTIR and other test results. The SEM images proved that the membrane obtained through the RTIPS method had a porous surface and spongy internal structure, furthermore, additional polymers were adsorbed. Use of EDX demonstrated that biomimetic mineralization prevented the production of agglomerated titanium dioxide. XPS and FTIR spectra confirmed the introduction and immobilization of HNP aggregation. Moreover, a decrease in the surface roughness and water contact angle further suggested an improvement in the hydrophilicity of the modified membrane. The introduction of HNP at a higher water bath temperature helped increase the water flux up to ten times, moreover, the oil-water separation efficiency could still reach over 99.50%. Lastly, a cycle test of the modified membrane under the optimal conditions helped confirm that the membrane forming conditions at this time could provide a better environment for the formation of the hydrophilic layer, which was conducive to the recycling of the separation membrane. In summary, more fixed more hydrophilic particles could be obtained through the RTIPS method based on biomimetic mineralization to prevent the accumulation of titanium dioxide, thus helping improve permeability and anti-fouling of the membrane.

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In this study, to mitigate the permeability-selectivity trade-off effect, Pluronic F127 (F127) and HKUST-1 were employed to construct high-performance membranes based on the reverse thermally induced phase separation (RTIPS) method. F127, as a hydrophilic modifier, was applied to increase permeability and resist polyethersulfone (PES) membrane fouling, while the collapse of HKSUT-1 caused by its instability in pure water improved the permeability and selectivity of the membrane. Characterizations demonstrated the successful synthesis of HKUST-1, together with the successful introduction of HKSUT-1 and F127 in PES membranes. It was observed that the membrane prepared by the RTIPS process possessed a uniformly porous surface and sponge-like cross-section with excellent mechanical properties, higher permeability, and selectivity compared to the dense skin and finger-like cross-section of the membrane prepared by the nonsolvent induced phase separation (NIPS) method. Moreover, the permeation and bovine serum albumin (BSA) rejection rate of the optimal membrane reached 2378 L/m2 h and 89.3%, respectively, which were far higher than those of the pure membrane. Hydrophilic F127 and many microvoids formed by the collapse of HKUST-1, played an important role in excellent antifouling properties, high permeability, and selectivity by pure water flux (PWF), flux recovery rate (FRR), BSA flux, and COD removal rate tests. Overall, the membrane with F127 and HKSUT-1 prepared via the RTIPS method not only obtained excellent antifouling properties but also mitigated the permeability-selectivity trade-off.

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In recent years, microplastics have emerged as a new marine pollutant and have attracted wide research attention. As the main activity areas of human beings in the coastal environment, gulfs have always been the hotspots of marine pollution. However, the distribution of microplastics in most small and medium-sized coastal environments has been rarely reported in China. To understand the characteristics of microplastic pollution in small and medium-sized inshore bays in China, the main types, abundance, and spatial distribution characteristics of microplastics in the surface water and sediments in Haizhou Bay of Jiangsu province were studied by qualitative and quantitative methods. The results showed that the abundances of microplastics in the surface water and sediments of Haizhou Bay were (2.60±1.40) n·m-3 and (0.33±0.26) n·g-1, respectively. In the domestic offshore environment, the abundance of microplastics was at a low level in the surface water, but at a high level in the sediments in Haizhou Bay (0.33-545.00 n·m-3 and 0.07-2.58 n·g-1, respectively). The range of size distribution of microplastics in water and sediments was 0.08-13.48 mm and 0.04-14.74 mm, respectively. More than 60% of the microplastics in water and sediments were small particles of sizes less than 2.00 mm. The shape of microplastics in Haizhou Bay was mainly fibrous, accounting for 92%. The main colors were blue and black, accounting for 70%. The materials were mainly man-made fibers and PET, accounting for 79.4%. There was a significant correlation between the distribution of microplastics in surface water and suspended matter concentration (P<0.05). The distribution of microplastics in sediments was affected by many factors, and its distribution pattern between the distribution of microplastics in surface water and the distribution of particle size in sediments was quite different. Through analysis of the morphological characteristics and composition of microplastics, the results showed that the microplastics in Haizhou Bay mainly come from mariculture and coastal land sources.

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A new method was presented to prepare hydrophilic PES/SPSF flat-sheet membrane by a reverse thermally induced phase separation (RTIPS) method to enhance permeability and hydrophilicity. SPSF was self-made and was blended to improve the hydrophilicity of PES flat-sheet membrane. The performance of PES/SPSF flat-sheet membrane, which varied with SPSF content and coagulation water bath temperature, was investigated by SEM, FTIR, AFM, pure water flux, BSA rejection rate, water contact angle and long-term testing. FTIR results proved the successful blending of SPSF with PES membrane, SEM images showed that dense skin surface and finger-like structure emerged in the membrane fabricated by NIPS method, while a porous top surface and sponge-like structure emerged in the membrane fabricated by RTIPS. The pure water flux and BSA rejection rate of the membrane for RTIPS were both higher than those for NIPS. AFM images revealed that surface roughness increased with the addition of SPSF. The water contact angle decreased with the increase of SPSF, which illustrated better hydrophilicity with the addition of SPSF. The flat-sheet PES membrane prepared with 2 wt% SPSF by RTIPS method exhibited decent properties, reaching maximum pure water flux (966 L m-2 h-1) and at the same time the BSA rejection rate was 79.2%. The long-term test proved that the anti-fouling performance of PES/SPSF membrane was better than that of PES membrane.

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The effect of zirconium-modified zeolite (ZrMZ) addition on the release and immobilization of phosphorus in heavily polluted river sediment was investigated using microcosm incubation experiments. Results showed that addition of ZrMZ to sediment greatly reduced concentrations of P in pore water and overlying water, also reducing the release flux of P across the interface between overlying water and sediment. The addition of ZrMZ to sediment resulted in the transformation of NH4Cl extractable P (NH4Cl-P), Na2S2O4/NaHCO3 extractable P (BD-P), and HCl extractable P (HCl-P) into NaOH extractable P (NaOH-rP) and residual P (Res-P) in sediment, thereby leading to the reduction of mobile P (sum of NH4Cl-P and BD-P) in sediment. Content of bioavailable P (BAP) including water soluble P (WSP), readily desorbable P (RDP), iron oxide paper strip extractable P (FeO-P), and anion resin extractable P (Resin-P) in sediment also declined following addition of ZrMZ. Control of P release from sediment by ZrMZ could be due to reduction of P in pore water and immobilization of P in sediment. Results of this work indicate that ZrMZ is very promising for controlling P release from sediments in heavily polluted rivers.

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Parkinson's disease (PD) is a movement-associated disorder that specifically affects dopamine-producing neurons. The disease causes demyelation that adversely impacts upon the motor activity of the brain. Currently there are no promising biomarkers for PD; improved understanding of the molecular mechanisms underlying the different pathological stages of PD are required to enable identification of a novel biomarker. The present study successfully established a PD mouse model via nasal injection of 1­methyl-4­phenyl-1,2,3,6-tetrahydropyridine. The expression of c­Jun N­termal kinase 3 (JNK3) and caspase­3 in two different pathological stages of PD were analysed using immunohistochemistry and western blot analysis. The results inidcated that the initial PD pathogenesis recovers on response to rasagiline. Immunohistochemistry and western blot analysis revealed that treatment with rasagiline positively regulated early­stage PD pathogenesis by downregulating the expression of JNK3 and upregulating caspase­3; however, there was no positive effect on the advanced stages of PD. Overall, these results concluded that rasagiline has the ability to inhibit the expression of JNK3 and upregulate caspase­3 in early stages of PD; however, rasagline appears to have no impact on JNK3 and caspase­3 levels in the advanced stages of PD.

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Overexpression lentivirus platform was established of OATP1B1 (organic anion transporting polypeptides 1B1) wild­type and mutant type genetic polymorphism in vitro, and using this platform we investigated and compared the uptake of tamoxifen and its metabolites by mutating the 388 and the 521 bases. The overexpression lentivirus cell platforms were successfully constructed, including OATP1B1*1a-HEK293T and OATP1B1*1b-HEK293T and OATP1B1*5-HEK293T cell model, the infection efficiency is not less than 80%. It shows a high level of gene expression at the mRNA and protein level. The tamoxifen and endoxifen can be taken up into the cells through organic anion transporter polypeptide 1B1, and OATP1B1521T>C inhibits the function of the transport protein, resulting in the content of drug in cell lysis liquid in OATP1B1*5-HEK293T group is lower than in OATP1B1*1a-HEK293T group (tamoxifen or endoxifen), with statistical significance. The content of the drug in cell lysis liquid in OATP1B1*1b-HEK293T group and the OATP1B1*1a-HEK293T group, similar with no statistical significance. These results suggest that tamoxifen and endoxifen can be transported by OATP1B1. However, OATP1B1 521T>C can inhibit the effects of OATP1B1 on tamoxifen and endoxifen in the cells.

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AIM: Simultaneous inhibition of VEGFR2 and Src may enhance the efficacy of VEGFR2-targeted cancer therapeutics. Hence, development of dual inhibitors on VEGFR2 and Src can be a useful strategy for such treatments. MATERIALS & METHODS: A multistep virtual screening protocol, comprising ligand-based support vector machines method, drug-likeness rules filter and structure-based molecular docking, was developed and employed to identify dual inhibitors of VEGFR2 and Src from a large commercial chemical library. Kinase inhibitory assays and cell viability assays were then used for experimental validation. RESULTS: A set of compounds belonging to six different molecular scaffolds was identified and sent for biological evaluation. Compound 3c belonging to the 2-amino-3-cyanopyridine scaffold exhibited good antiproliferative effect and dual-target activities against VEGFR2 and Src. CONCLUSION: This study demonstrated the ability of the multistep virtual screening approach to identify novel multitarget agents.

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AIM: To investigate the mechanisms underlying anticancer action of the benzimidazole acridine derivative N-{(1H-benzo[d]imidazol-2-yl)methyl}-2-butylacridin-9-amine(8m) against human colon cancer cells in vitro. METHODS: Human colon cancer cell lines SW480 and HCT116 were incubated in the presence of 8m, and then the cell proliferation and apoptosis were measured. The expression of apoptotic/signaling genes and proteins was detected using RT-PCR and Western blotting. ROS generation and mitochondrial membrane depolarization were visualized with fluorescence microscopy. RESULTS: 8m dose-dependently suppressed the proliferation of SW480 and HCT116 cells with IC50 values of 6.77 and 3.33 µmol/L, respectively. 8m induced apoptosis of HCT116 cells, accompanied by down-regulation of Bcl-2, up-regulation of death receptor-5 (DR5), truncation of Bid, cleavage of PARP, and activation of caspases (including caspase-8 and caspase-9 as well as the downstream caspases-3 and caspase-7). Moreover, 8m selectively activated JNK and p38 without affecting ERK in HCT116 cells. Knockout of JNK1, but not p38, attenuated 8m-induced apoptosis. In addition, 8m induced ROS production and mitochondrial membrane depolarization in HCT116 cells. Pretreatment with the antioxidants N-acetyl cysteine or glutathione attenuated 8m-induced apoptosis and JNK activation in HCT116 cells. CONCLUSION: The new benzimidazole acridine derivative, 8m exerts anticancer activity against human colon cancer cells in vitro by inducing both intrinsic and extrinsic apoptosis pathways via the ROS-JNK1 pathway.

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OBJECTIVE: To analyze the significant clinicopathologic factors related to tumor recurrence in patients with sinonasal squamous cell carcinomas (SCC) and to evaluate the effectiveness and plausibility of surgical salvage in the recurrent cases. METHODS: The clinicopatholgic data of 107 patients with primary sinonasal SCC treated from 1996 to 2007 were analyzed retrospectively. Univariate and multivariate logistic regression analyses were used to define the risk factors related to tumor recurrence. Salvage surgery with was selectively carried out in the recurrent sinonasal SCC using different surgical approaches, including lateral rhinotomy midfacial degloving or combined craniofacial approach. Immediate reconstruction of major surgical defects were performed with latissimus dorsi flap, pectoralis major myocutanneous flap, temperalis fasciomuscular flap, free rectus abdominis flap and free radial forearm flap. All patients were routinely follwed up and 5-year survival were calculated using directly calculating method and Kaplan-Meier's method. RESULTS: The 5-year survival rate of 107 cases was 52.3% (56/107). Local recurrence was the most common pattern of tumor relapse. Forty-four of the 107 cases had recurrence. Logistic regression analysis showed the T stag was the most important impacting factor for tumor recurrence (OR = 0.258, P = 0.001). Of 44 cases with recurrence, 33 cases underwent salvage surgery and the 5-year survival rate after salvage surgery was 29.1%. CONCLUSIONS: T stag is the most important impacting factor for tumor recurrence. Salvage surgery with immediate reconstruction of major surgical defects should be carried out in the selective cases of recurrent sinonasal SCC.

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OBJECTIVE: To study the location, treatment, life status of multiple primary cancers (MPCs) in head and neck squamous cell carcinomas. METHODS: The clinical data of 71 head and neck squamous carcinoma patients with MPCs were retrospectively analyzed. RESULTS: MPCs were seen in head and neck regions in 27 cases and in remote organs in 42 cases, two of which were triplicate primary cancers. Four cases were synchronous MPCs, including one patient with synchronous triplicate primary cancer. Other 67 cases were heterochronous MPCs, including one patient with heterochronous triplicate primary cancer. Of 67 heterochronous MPCs, the time interval between index tumor presentation and diagnosis of MPCs was eight months to twelve years. MPCs occurred in seventy percent index oral cavity squamous cancers, which were located in head and neck regions, and in sixty-two percent index hypopharynx cancers and seventy-nine percent index laryngeal cancers, which were located in remote organs. The incidence of MPCs in esophagus and lung was higher than that in other remote organs. Among the various MPCs in this serials, the incidence of the disease appeared to be the highest in esophagus, accounting for twenty-four percent of all cases. The total three- and five-year survival rates were 32.4% and 22.5%, respectively. Of all MPCs patients, the three-year survival rate for patients who received different therapies for their MPCs was obviously higher than that of untreated patients (P < 0.01, Chi-square test). CONCLUSIONS: Esophageal carcinoma is the most common second primary cancer among the various MPCs of the head and neck squamous carcinomas. Oral cavity cancers tend to have more MPCs in the head and neck regions, and laryngeal and hypopharyngeal cancers are easily to be associated with MPCs in the remote organs. Regular follow-up and early diagnosis with effective treatment can help to improve the survival of MPC patients in head and neck squamous cell carcinomas.

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OBJECTIVE: To investigate the risk clinicopathological factors of primary tumor in the prediction of cervical lymph node metastases and the cervical lymph node prognostic factors in hypopharyngeal squamous cell carcinoma. METHODS: A retrospective study was carried out to review the histopathological data from 98 hypopharyngeal squamous cell carcinoma patients. The relationship between histopathological parameters and cervical lymph node metastases were evaluated by means of a univariate chi2 test and multivariate stepwise logistic regression model. And the Cox regression model was used to define possible pathological parameters of neck node affecting survival including N staging, presence of cervical lymph node metastases and extracapsular nodal spread, size and number of positive neck nodes, and levels of positive neck nodes. RESULTS: The overall 5-year survival rate of patients with hypopharyngeal carcinoma was 28.6%. In a univariate and multivariate analysis, it was confirmed that size and growth pattern of primary tumor correlated to cervical lymph node metastases. In a multivariate Cox regression analysis, the most significant prognostic factors of cervical lymph node were the size of positive neck nodes and level involved. CONCLUSIONS: Cervical lymph node metastases were one of the most significant prognostic factors of hypopharyngeal carcinoma. The identification of patients at risk for cervical lymph node metastases and the management of the neck by coping with pathological factors of cervical lymph node affecting survival are very important to improve the treatment and prognosis of hypopharyngeal carcinoma.

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