Photo-Cross-Linked Polymeric Dispersants of Comb-Shaped Benzophenone-Containing Poly(ether amine).

Efficient dispersion of nanoparticles (NPs) is a crucial challenge in the preparation and application of composites that contain NPs, particularly in coatings, inks, and related materials. Physical adsorption and chemical modification are the two common methods used to disperse NPs. However, the former suffers from desorption, and the latter is more specific and has limited versatility. To address these issues, we developed a novel photo-cross-linked polymeric dispersant, comb-shaped benzophenone-containing poly(ether amine) (bPEA), using a one-pot nucleophilic/cyclic-opening addition reaction. The results demonstrated that the bPEA dispersant forms a dense and stable shell on the surface of pigment NPs through physical adsorption and subsequent chemical photo-cross-linking, which effectively overcome the drawbacks of the desorption occurred in physical adsorption and the specificity of the chemical modification. By means of the dispersing effect of bPEA, the obtained pigment dispersions show high solvent, thermal, and pH stability without flocculation during storage. Moreover, the NPs dispersants show good compatibility with screen printing, coating, and 3D printing, endowing the ornamental products with high uniformity, color fastness, and less color shading. These properties make bPEA dispersants ideal candidates in fabrication dispersions of other NPs.

The lncRNA ZNF667-AS1 Inhibits Propagation, Invasion, and Angiogenesis of Gastric Cancer by Silencing the Expression of N-Cadherin and VEGFA.

Purpose: Gastric cancer is one of the most common malignancies with high mortality worldwide. It is known that long noncoding RNAs (lncRNAs) play important roles in the pathogenesis of gastric cancer. This study investigates the role of lncRNA ZNF667-AS1 in gastric cancer cells. Methods: We have applied real-time quantitative PCR (qPCR) to study the levels of ZNF667-AS1 in gastric cancer biopsies and cell lines. The effects of ZNF667-AS1 on the propagation, clonogenicity, metastasis, and angiogenesis of gastric cancer cells were evaluated by calorimetry, colony formation, cell migration, and angiogenesis assays. Western blotting was used to identify the levels of proteins involved in cancer invasion and angiogenesis signaling pathways. Result: It was found that lncRNA ZNF667-AS1 was downregulated in gastric cancer biopsies. Overexpression of ZNF667-AS1 reduced the propagation, migration, and angiogenesis of gastric cancer cells. Molecular mechanism studies displayed that the high level of lncRNA ZNF667-AS1 promoted the expression of E-cadherin and inhibited the expression of N-cadherin and VEGFA, leading to the inhibition of the proliferation, migration, and angiogenesis of gastric cancer cells. Conclusion: As a tumor suppressor gene, lncRNA ZNF667-AS1 significantly hinders the propagation, metastasis, and angiogenesis of gastric cancer cells by promoting the expression of E-cadherin and inhibiting the expression of N-cadherin and VEGFA. Therefore, lncRNA ZNF667-AS1 could play a synergistic therapeutic role by targeting tumor cells and vascular endothelial cells, which represents a new therapeutic scheme for novel therapeutics of gastric cancer.

Long non-coding RNA LUADT1 promotes nasopharyngeal carcinoma cell proliferation and invasion by downregulating miR-1207-5p.

Nasopharyngeal carcinoma (NPC) is a typical type of malignant tumor. This research paper aims to study the function and mechanism of long non-coding RNA lung adenocarcinoma-related transcript 1 (lncRNA-LUADT1) in the progression of NPC. In this study, the expressions of lncRNA-LUADT1, miR-1207-5p, and TEAD1 in NPC tissues and cell lines were detected by RT-qPCR. Initially, the expression of lncRNA-LUADT1 and TEAD1 were significantly up-regulated in NPC tissues and cells, while miR-1207-5p was significantly down-regulated. Next, miR-1207-5p was confirmed to bind to lncRNA-LUADT1 or TEAD1 by bioinformatics and luciferase reporter assay. In addition, after interfering with lncRNA-LUADT1 expression, experiments of CCK8, EDU staining, and Transwell invasion were used to detect proliferation, invasion, and migration of NPC cells. The results showed that interfering with lncRNA-LUADT1 expression could inhibit the proliferation, invasion, and migration of NPC cells. Western blot showed that lncRNA-LUADT1 knockdown significantly decreased the expression of Hippo/YAP pathway protein (YAP1 and TAZ). However, interfering with the expression of miR-1207-5p reversed these results. In addition, the nude mouse tumor formation experiment suggested that low-expressed lncRNA-LUADT1 reduced the volume and weight of tumor tissues. In summary, lncRNA-LUADT1 down-regulation could inhibit NPC cell proliferation and invasion, which may be achieved through regulating miR-1207-5p expression and affecting TEAD1 expression, thus inhibiting the activation of Hippo/YAP signaling pathway.

LINC00261 Suppresses Cisplatin Resistance of Esophageal Squamous Cell Carcinoma Through miR-545-3p/MT1M Axis.

To improve the survival rate and cure rate of patients, it is necessary to find a new treatment scheme according to the molecular composition of (ESCC) in esophageal squamous cell carcinoma. Long non-coding RNAs (lncRNAs) regulate the progression of ESCC by various pathophysiological pathways. We explored the possible function of the lncRNA LINC00261 (LINC00261) on cisplatin (DDP) resistance of ESCC and its relative molecular mechanisms. In the study, we found that LINC00261 was downregulated in ESCC tissues, cell lines, and DDP-resistant ESCC patients. Besides, overexpression of LINC00261 not only inhibited cell proliferation, and DDP resistance but also promotes cell apoptosis. Further mechanistic research showed that LINC00261 sponged miR-545-3p which was negatively correlated with the expression of LINC00261. In addition, functional experiments revealed that upregulation of miR-766-5p promoted proliferation and enhanced DDP resistance. Subsequently, MT1M was testified to be the downstream target gene of miR-545-3p. Rescue experiments revealed that overexpression of MT1M largely restores miR-545-3p mimics-mediated function on ESCC progression. Our results demonstrate that the LINC00261 suppressed the DDP resistance of ESCC through miR-545-3p/MT1M axis.

LncRNA EPB41L4A-AS2 represses Nasopharyngeal Carcinoma Metastasis by binding to YBX1 in the Nucleus and Sponging MiR-107 in the Cytoplasm.

Nasopharyngeal carcinoma (NPC) is known for its potential to progress to the lymph nodes and distant metastases at an early stage. As an important regulator in tumorigenesis biological processes, the functions of lncRNA in NPC tumor development remain largely unclear. In this research, the expression of EPB41L4A-AS2 in NPC tissues and cells was analyzed via real-time quantitative polymerase chain reaction (qRT-PCR). CCK8, colony formation, and EDU experiments were used to determine the viability of NPC cells. Transwell and wound healing assays were performed to test NPC cell migration and invasion. RNA pull-down and mass spectrometry analysis were used to identify potential binding proteins. Then, a popliteal lymph node metastasis model was established to test NPC metastasis. EPB41L4A-AS2 is repressed by transforming growth factor-beta, which is downregulated in NPC cells and tissue. It is associated with the presence of distant metastasis and adverse outcomes. The univariate and multivariate survival assays confirmed that EPB41L4A-AS2 expression was an independent predictor of progression-free survival (PFS) in patients with NPC. Biological analyses showed that overexpression of EPB41L4A-AS2 reduced the metastasis and invasion of NPC in vitro and in vivo, but had no significant effect on cell proliferation. Mechanistically, in the nucleus we identified that EPB41L4A-AS2 relies on binding to YBX1 to reduce the stability of Snail mRNA to enhance the expression of E-cadherin and reverse the progression of epithelial-to-mesenchymal transition (EMT). In the cytoplasm, we found that EPB41L4A-AS2 blocked the invasion and migration of NPC cells by promoting LATS2 expression via sponging miR-107. In a whole, the findings of this study help to further understand the metastasis mechanism of NPC and could help in the prevention and treatment of NPC metastasis.

Light-Induced Programmable 2D Ordered Patterns Based on a Hyperbranched Poly(ether amine) (hPEA)-Functionalized Graphene Film.

Dynamic complex surface topography with ordered and tunable morphologies, which can provide on-demand control of surface properties to realize smart surfaces, is gaining much attention yet remains challenging in terms of fabrication. Here, a facile, robust, and controllable method is demonstrated to fabricate programmable two-dimensional (2D) ordered patterns with multiresponsive 2D ultrathin materials, comprised of anthracene-capped hyperbranched poly(ether amine) (hPEA-AN)-functionalized graphene (hPEA-AN@G). By combining the stimuli-responsiveness and UV sensitivity of hPEA-AN and excellent out-of-plane deformation and NIR-to-thermal conversion of graphene, the process of "writing/uploading" initial information is conducted through the initial exposure to 365 nm UV light to generate the 2D ordered pattern first; second, inducing swelling strain via moisture to create the hierarchical topographic pattern (orderly oriented pattern) is the process of "modification and erasable rewriting"; third, alternating NIR or 254 nm UV light blanket exposure are the two ways of erasing the information. Consequently, taking advantage of the multiresponsive dynamic wrinkling/ordered patterning, we can program globally 2D ordered surface patterns with diverse morphologies on demand and manipulate the resulted surface properties as desired.

Raltitrexed versus 5-fluorouracil with cisplatin and concurrent radiotherapy for locally advanced nasopharyngeal carcinoma: An open labeled, randomized, controlled, and multicenter clinical trial.

BACKGROUND: This study aimed to compare the efficacy and toxicity of raltitrexed (Saiweijian® ) plus cisplatin (SP regimen) and 5-fluorouracil plus cisplatin (FP regimen) as concurrent chemoradiotherapy (CCRT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: Eligible patients (N = 135) were allocated randomly in a ratio of 1:1 to receive CCRT with either SP or FP. At least 2 cycles of chemotherapy was administrated during radiotherapy. Progression free survival (PFS) was primary endpoint. Secondary endpoints included overall survival (OS), loco-regional relapse free survival (LRRFS), distant metastasis free survival (DMFS) and toxicity. RESULTS: In this study, 68 patients received SP as CCRT, and 67 received FP. Objective responses were noted in 97.1% of the patients in the SP group and in 97.0% of the patients in the FP group (P = 1.00). At the end of a median 36 months follow-up period, the estimated 3-year PFS rates were 70.1% for SP and 66.6% for FP, respectively. The 3-year LRRFS, DMFS and OS rates were 88.9%, 74.7% and 84.0%, respectively, for the SP group, and 92.3%, 71.0% and 73.7%, respectively, for the FP group. Overall, there was no difference between treatment groups with regard to response or survival. The most frequent acute toxicities monitored in both groups were bone marrow suppression, gastrointestinal side effects and oral mucositis (OM). The overall incidence of grade 3-4 OM in the FP group (47.8%) was higher than in the SP group (11.8%). However, the incidence of other adverse effects observed in both groups was similar (P > .05). CONCLUSIONS: These data indicate that SP and FP therapies have similar efficacy in treating LA-NPC. The SP regimen showed a tolerable safety profile along with a lower frequency of severe OM and therefore, an improved life quality. In conclusion, SP was a well tolerated, effective, regimen for LA-NPC treatment.

Nanofiber-hydrogel composite-mediated angiogenesis for soft tissue reconstruction.

Soft tissue losses from tumor removal, trauma, aging, and congenital malformation affect millions of people each year. Existing options for soft tissue restoration have several drawbacks: Surgical options such as the use of autologous tissue flaps lead to donor site defects, prosthetic implants are prone to foreign body response leading to fibrosis, and fat grafting and dermal fillers are limited to small-volume defects and only provide transient volume restoration. In addition, large-volume fat grafting and other tissue-engineering attempts are hampered by poor vascular ingrowth. Currently, there are no off-the-shelf materials that can fill the volume lost in soft tissue defects while promoting early angiogenesis. Here, we report a nanofiber-hydrogel composite that addresses these issues. By incorporating interfacial bonding between electrospun poly(ε-caprolactone) fibers and a hyaluronic acid hydrogel network, we generated a composite that mimics the microarchitecture and mechanical properties of soft tissue extracellular matrix. Upon subcutaneous injection in a rat model, this composite permitted infiltration of host macrophages and conditioned them into the pro-regenerative phenotype. By secreting pro-angiogenic cytokines and growth factors, these polarized macrophages enabled gradual remodeling and replacement of the composite with vascularized soft tissue. Such host cell infiltration and angiogenesis were also observed in a rabbit model for repairing a soft tissue defect filled with the composite. This injectable nanofiber-hydrogel composite augments native tissue regenerative responses, thus enabling durable soft tissue restoration outcomes.

In Vivo Bioluminescence Imaging in a Rabbit Model of Orthopaedic Implant-Associated Infection to Monitor Efficacy of an Antibiotic-Releasing Coating.

BACKGROUND: In vivo bioluminescence imaging (BLI) provides noninvasive monitoring of bacterial burden in animal models of orthopaedic implant-associated infection (OIAI). However, technical limitations have limited its use to mouse and rat models of OIAI. The goal of this study was to develop a larger, rabbit model of OIAI using in vivo BLI to evaluate the efficacy of an antibiotic-releasing implant coating. METHODS: A nanofiber coating loaded with or without linezolid-rifampin was electrospun onto a surgical-grade locking peg. To model OIAI in rabbits, a medial parapatellar arthrotomy was performed to ream the femoral canal, and a bright bioluminescent methicillin-resistant Staphylococcus aureus (MRSA) strain was inoculated into the canal, followed by retrograde insertion of the coated implant flush with the articular surface. In vivo BLI signals were confirmed by ex vivo colony-forming units (CFUs) from tissue, bone, and implant specimens. RESULTS: In this rabbit model of OIAI (n = 6 rabbits per group), implants coated without antibiotics were associated with significantly increased knee width and in vivo BLI signals compared with implants coated with linezolid-rifampin (p < 0.001 and p < 0.05, respectively). On day 7, the implants without antibiotics were associated with significantly increased CFUs from tissue (mean [and standard error of the mean], 1.4 × 10 ± 2.1 × 10 CFUs; p < 0.001), bone (6.9 × 10 ± 3.1 × 10 CFUs; p < 0.05), and implant (5.1 × 10 ± 2.2 × 10 CFUs; p < 0.05) specimens compared with implants with linezolid-rifampin, which demonstrated no detectable CFUs from any source. CONCLUSIONS: By combining a bright bioluminescent MRSA strain with modified techniques, in vivo BLI in a rabbit model of OIAI demonstrated the efficacy of an antibiotic-releasing coating. CLINICAL RELEVANCE: The new capability of in vivo BLI for noninvasive monitoring of bacterial burden in larger-animal models of OIAI may have important preclinical relevance.

miR-32 promotes esophageal squamous cell carcinoma metastasis by targeting CXXC5.

MicroRNA-32 (miR-32) functioned as a tumor oncogene in some cancer, which control genes involved in important biological and pathological functions and facilitate the tumor growth and metastasis. However, the role of miR-32 modulates esophageal squamous cell carcinoma (ESCC) malignant transformation has not been clarified. Here, we focused on the function and the underlying molecular mechanism of miR-32 in ESCC. Results discovered a significant increased expression of miR-32 in ESCC tissues and cells. Downregulation of miR-32 inhibited the migration, invasion, adhesion of ESCC cell lines (EC9706 and KYSE450), and the levels of EMT protein in vitro. In vivo, miR-32 inhibitors decrease tumor size, tumor weight, and the number of metastatic nodules. Hematoxylin and eosin (H&E) results revealed that inhibition of miR-32 attenuate lung metastasis. Immunohistochemistry and immunofluorescence assay showed increased level of E-cadherin and decreased level of N-cadherin and Vimentin with treatment of miR-32 inhibitors. Furthermore, miR-32 targeted the 3'-untranslated region (3'-UTR) of CXXC5, and inhibited the level of mRNA and protein of CXXC5. There is a negative correlation between the expressions of CXXC5 and miR-32. Then, after EC9706 and KYSE450 cells cotransfected with si-CXXC5 and miR-32 inhibitors, the ability of cell migration, invasion, and adhesion was significantly reduced. In addition, the protein expression of EMT and TGF-ß signaling was also depressed. Collectively, these data supply an insight into the positive role of miR-32 in ESCC progression and metastasis, and its biological effects may attribute the inhibition of TGF-ß signaling mediated by CXXC5.

Tumor-suppressive microRNA-10a inhibits cell proliferation and metastasis by targeting Tiam1 in esophageal squamous cell carcinoma.

Aberrant microRNAs (miRNAs) expressions could contribute to the progression of numerous cancers, including esophageal squamous cell carcinoma, while miR-10a participates in multiple biological processes on cancers. However, the molecular mechanism of miR-10a in esophageal squamous cell carcinoma (ESCC) has not been investigated. Herein, miR-10a was significantly reduced in ESCC clinical tissues and ESCC cell lines (EC109 and TE-3). In addition, immunohistochemistry indicated that the expressions of α-SMA, Ki-67, and PCNA in tumor tissues were higher than that of controls. In vitro, overexpression of miR-10a dramatically suppressed cell proliferation and enhanced cell apoptosis, while the decrease of miR-10a expressed the opposite outcome. Specially, overexpression of miR-10a caused a G0/G1 peak accumulation. Moreover, miR-10a also negatively regulated ESCC cell migration and invasion. Furthermore, targetscan bioinformatics predictions and the dual-luciferase assay confirmed that Tiam1 was a direct target gene of miR-10a. The statistical analysis showed Tiam1 was negatively in correlation with miR-10a in ESCC patient samples. And silencing Tiam1 could lead to a decline on cell growth, invasion, and migration in ESCC cell lines, while it could enhance cell apoptosis and cause a G0/G1 peak accumulation. In vivo, it revealed that miR-10a notably decreased the tumor growth and metastasis in xenograft model and pulmonary metastasis model. And it showed a lower expressions of Tiam1 in the miR-10a mimics group by immunohistochemistry. Taken together the results, they indicated that miR-10a might function as a novel tumor suppressor in vitro and in vivo via targeting Tiam1, suggesting miR-10a to be a candidate biomarker for the ESCC therapy.

Long noncoding RNA UCA1 promotes the proliferation, invasion, and migration of nasopharyngeal carcinoma cells via modulation of miR-145.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common malignant tumor characterized by highly malignant local invasion and distant metastasis. Recently, increasing attention has been paid to long noncoding RNAs (lncRNAs), which play significant roles in tumorigenesis and progression. However, little is known about the potential role of the lncRNA urothelial carcinoma-associated 1 (UCA1) in NPC cell invasion and migration. METHODS: Real-time quantitative PCR was used to analyze the expression of lncRNA UCA1 in NPC cell lines and NP69. lncRNA UCA1 knock-down nasopharyngeal carcinoma cell line models were established through siRNA. Cell viability was evaluated by Cell counting kit-8 and Colony forming assay. The migration and invasion capacities were evaluated by wound healing and transwell migration and invasion assays. Western blot analysis were used to examine protein changes followed by UCA1 knock-down. RESULTS: Our study confirmed that UCA1 was upregulated in NPC cell lines and involved in NPC tumorigenesis according to our established UCA1-associated competing endogenous RNA network. Moreover, functional analyses indicated that the downregulation of UCA1 exerted inhibitory effects on cell proliferation, invasion, and migration. Mechanistic analyses revealed that UCA1 was the target of miR-145 and functioned as a sponge to repress miR-145 expression. Rescue experiments suggested that lncRNA UCA1 reversed the miR-145-mediated inhibition on oncogene ADAM17 expression, thus promoting the proliferation, invasion, and migration of NPC cells. CONCLUSION: LncRNA UCA1 functions as a tumor promoter in NPC. UCA1 promotes the proliferation and invasion of NPC cells by sponging miR-145, functionally altering ADAM17 expression targeted by miR-145. Our exploration of the underlying mechanism of UCA1 in NPC may provide novel therapeutic targets for NPC.

miR-184 Inhibits Tumor Invasion, Migration and Metastasis in Nasopharyngeal Carcinoma by Targeting Notch2.

BACKGROUND/AIMS: A recent study found that dysregulated microRNA-184 (miR-184) is involved in the proliferation and survival of nasopharyngeal carcinoma (NPC). This study aimed to evaluate the detailed mechanisms of invasion, migration and metastasis of NPC cells. METHODS: Quantitative reverse-transcription PCR (qRT-PCR) and Western blot were used to confirm the expression levels of miR-184 and Notch2. NPC cell invasion and migration were subsequently examined using in vitro cell invasion and wound-healing assays, respectively. MicroRNA (miRNA) target gene prediction databases and dual-luciferase reporter assay were adopted to validate the target genes of miR-184. RESULTS: MiR-184 was downregulated in the NPC cell lines. The miR-184 inhibitor increased the number of invading NPC cells, whereas miR-184 mimics inhibited the invasive ability of such cells. The protein level of E-cadherin decreased, whereas those of N-cadherin and vimentin increased in the anti-miR-184 group. This result showed that miR-184 inhibited NPC cell invasion and metastasis by regulating EMT progression. MiRNA target gene prediction databases indicated the potential of Notch2 as a direct target gene of miR-184. Such a notion was then validated by results of dual-luciferase reporter assay. Notably, shRNANotch2 restrained the EMT and partially abrogated the inhibitory effects of miR-184 on EMT progression in NPC cells. CONCLUSION: MiR-184 functions as a tumour-suppressive miRNA targeting Notch2 and inhibits the invasion, migration and metastasis of NPC.

Effectiveness of Cetuximab in Combination with Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: A 1:2 Propensity Score-matched Analysis.

Background: This study aimed to compare concurrent chemoradiotherapy (CCRT) plus cetuximab (C) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma(NPC). Methods: A total of 682 locoregionally advanced NPC patients who had undergone chemoradiotherapy with or without cetuximab were included. Propensity score-matching method was used to match patients. Progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between the two treatment arms. Results: After matching, 225 patients were identified for the analysis. Compared to CCRT, CCRT plus C was associated with significantly improved 3-year PFS (83.7% vs 71.9%, P = 0.036), LRFS (98.6% vs 90.2%, P = 0.034) but not OS (91.4% vs 85.4%, P = 0.117). Among patients with T4 and/or N3 category, CCRT plus C significantly prolonged 3-year PFS (81.0% vs 61.4%, P = 0.022) and increased 3-year OS (88.0% vs 77.9%, P = 0.086). No significant differences were observed between CCRT plus C and CCRT alone groups with regard to 3-year PFS, OS, LRFS and DMFS rates in stage III patients. Acute oral and oropharyngeal mucositis during radiotherapy were more common in the CCRT plus C than that in CCRT, but late toxicities were comparable. Conclusions: This study reveals that patients with locoregionally advanced NPC could benefit from the addition of cetuximab to CCRT, and this therapeutic gain mainly originated from T4 and/or N3 subgroup although suffering more acute moderate to severe toxicities.

Synthetic Nanofiber-Reinforced Amniotic Membrane via Interfacial Bonding.

Severe damage to the ocular surface can result in limbal stem cell (LSC) deficiency, which contributes to loss of corneal clarity, potential vision loss, chronic pain, photophobia, and keratoplasty failure. Human amniotic membrane (AM) is the most effective substrate for LSC transplantation to treat patients with LSC deficiency. However, the widespread use of the AM in the clinic remains a challenge because of the high cost for preserving freshly prepared AM and the weak mechanical strength of lyophilized AM. Here, we developed a novel composite membrane consisting of an electrospun bioabsorbable polymer fiber mesh bonded to a decellularized AM (dAM) sheet through interfacial conjugation. This membrane engineering approach drastically improved the tensile property and toughness of dAM, preserved similar levels of bioactivities as the dAM itself in supporting LSC attachment, growth, and maintenance, and retained significant anti-inflammatory capacity. These results demonstrate that the lyophilized nanofiber-dAM composite membrane offers superior mechanical properties for easy handling and suturing to the dAM, while presenting biochemical cues and basement membrane structure to facilitate LSC transplantation. This composite membrane exhibits major advantages for clinical applications in treating soft tissue damage and LSC deficiency.

Hyperbranched Poly(ether amine)@Poly(vinylidene fluoride) Hybrid Membrane with Oriented Nanostructures for Fast Molecular Filtration.

Porous membranes with uniform nanostructures and selective adsorption can realize molecular filtration with high flux and have gained great attention because of their wide application in water treatment and industrial separation. Herein, a novel hyperbranched poly(ether amine)@poly(vinylidene fluoride) (hPEA@PVDF) porous membrane with oriented nanostructures and selective adsorption of guest molecules was fabricated by applying the combined crystallization and diffusion method for the functionalization of the PVDF membrane. The resulting hPEA@PVDF porous membranes were fully characterized by scanning electron microscopy and X-ray photoelectron spectra. The results indicated that the hPEA@PVDF membrane exhibited oriented open channel structure and high water flux up to 2116 L m-2 h-1, in which the PVDF skeleton was covered by the amphiphilic hPEA layer. The adsorption behavior of hPEA@PVDF porous membranes to 12 hydrophilic dyes including batch adsorption and molecular filtration was systematically investigated. The results revealed that the hPEA@PVDF membrane possessed high adsorption capacity toward erythrosin B (577 µmol g-1) and eosin B (511 µmol g-1), while low adsorption capacity toward calcein (76 µmol g-1) and methylene blue (hardly adsorbed), indicating the selective adsorption behavior toward dyes in aqueous solution. On the basis of this selective property, the hPEA@PVDF could be used to separate the dye mixtures very efficiently through molecular filtration. In addition, the separation efficiency remained 100% after five adsorption-desorption cycles, indicating that it had great potential in practical applications.

Integrin αvß6 Promotes Lung Cancer Proliferation and Metastasis through Upregulation of IL-8-Mediated MAPK/ERK Signaling.

Lung cancer is notorious for high morbidity and mortality around the world. Interleukin (IL)-8, a proinflammatory chemokine with tumorigenic and proangiogenic effects, promotes lung cancer cells growth and migration and contributes to cell aggressive phenotypes. Integrin αvß6 is a receptor of transmembrane heterodimeric cell surface adhesion, and its overexpression correlates with poor survival from non-small cell lung cancer. However, the cross talk between αvß6 and IL-8 in lung cancer has not been characterized so far. Herein, human lung cancer samples were analyzed, and it revealed that the immunohistochemical and mRNA expression of integrin αvß6 was significantly correlated with the expression of IL-8. Furthermore, in vitro, integrin αvß6 increased cell proliferation, migration, and invasion by impairing the expressions of MMP-2 and MMP-9 and inhibited cell apoptosis in human lung cancer cells A549 and H460. In addition, integrin αvß6 upregulated IL-8 expression through activating MAPK/ERK signaling. The in vivo experiment showed that integrin αvß6 promoted tumor growth in xenograft model mice by accelerating tumor volume and reducing apoptosis. Meanwhile, lung metastasis model experiment suggested that integrin αvß6 stimulated tumor metastasis with the increase of lung/total weight and tumor nodules. Simultaneously, integrin αvß6 upregulated IL-8 expression detected by both Western blots and immunohistochemistry, along with the activation of MAPK/ERK signaling. Overall, these data suggested that, in vitro and in vivo, integrin αvß6 promoted lung cancer proliferation and metastasis, at least in part, through upregulation of IL-8-mediated MAPK/ERK signaling. Thus, the inhibition of integrin αvß6 and IL-8 may be the key for the treatment of lung cancer.

Ultralarge Nanosheets Fabricated by the Hierarchical Self-Assembly of Porphyrin-Ended Hyperbranched Poly (ether amine) (TPP-hPEA).

An ultralarge sheet with remarkable lateral dimensions of 10 µm × 10 µm-20 µm × 20 µm is fabricated by the hierarchical self-assembly of porphyrin-ended hyperbranched poly(ether amine) (tetraphenylporphyrin (TPP)-hPEA) in solution. The obtained TPP-hPEA amphiphiles can self-assemble from ultrathin single-layered nanosheets with a thickness of 4 nm to ultralarge multilayered nanosheets with thicknesses from 30 to 70 nm. The lateral dimensions increase from 2 × 2 µm to 5 × 5 µm, and eventually to 10 × 10 µm. In-situ dynamic light scattering and UV-vis spectroscopy studies suggest a hierarchical growth self-assembly mechanism with a self-assembly process that relies on π-π stacking. This 2D self-assembly method provides a significant potential guide for the preparation of ultralarge nanosheets in solution.

miR-613 inhibits cell migration and invasion by downregulating Daam1 in triple-negative breast cancer.

Dishevelled-associated activator of morphogenesis 1 (Daam1) is a formin protein and participates in regulating cell migration of triple-negative breast cancer (TNBC) cells. The specific miRNA targeting Daam1 and mediating cell migration and invasion remains obscure. This experiment investigated the suppressive role of miR-613 in TNBC cells. The luciferase activity of Daam1 3'-untranslated region (3'-UTR) based reporters constructed in HEK-293T and MCF-7 cells suggested that Daam1 was the target gene of miR-613. Overexpressed miR-613 reduced the protein level of Daam1, weakened RhoA activity, and retarded the cell migration, cell invasion and colony formation of TNBC cells. Overexpression of Daam1 or RhoA rescued cell migration and invasion in miR-613-overexpressed TNBC cells, but failed to reverse colony formation. MiR-613 was significantly downregulated in breast cancer tissues compared with that in adjacent normal tissues. This downregulation in TNBC tissues and lymphnode metastatic breast cancer tissues was more obvious than that in non-TNBC tissues and non-metastatic cancer tissues, respectively. MiR-613 weakens the resistance of TNBC cells against paclitaxel rather than adriamycin, cyclophosphamide, docetaxel, and kaempferol. Taken together, miR-613 is involved in cell migration and invasion of TNBC cells via targeting Daam1/RhoA signaling pathway.

Comparing the efficacy of induction-concurrent with concurrent-adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma: a propensity score matching analysis.

PURPOSE: This study aimed to compare the efficacy of induction-concurrent (IC-CCRT) with concurrent-adjuvant (CCRT-AC) chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated by intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: Data on 834 patients with newly diagnosed, non-metastatic stage III-IVA (except T3N0) NPC receiving either IC-CCRT or CCRT-AC between July, 2004 and December, 2014 were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance prognostic factors and match patients. Survival outcomes of matched patients between IC-CCRT and CCRT-AC were compared. RESULTS: The median follow-up duration is 45.2 months (range, 1.07-145.4 months). Overall, 309 pairs were selected by PSM. Univariate analysis revealed the CCRT-AC group achieved significantly higher 3-year DFS (83.9% vs. 78.7 %; P = 0.014) and OS (87.6% vs. 87.0%; P = 0.031). Multivariate analysis also identified treatment group (IC-CCRT vs. CCRT-AC) as an independent prognostic factor for 3-year DFS (HR, 1.546; 95% CI, 1.113-2.149; P = 0.009) and OS (HR, 1.487; 95% CI, 1.035-2.136; P = 0.032). Subgroup analysis revealed IC-CCRT was a protective factor for DMFS (HR, 0.145; 95% CI, 0.043-0.488; P = 0.002) in stage III disease; however, it could adversely affected DFS (HR, 2.009; 95% CI, 1.316-3.065; P = 0.001), OS (HR, 1.671; 95% CI, 1.060-2.636; P = 0.027) and DMFS (HR, 1.986; 95% CI, 1.155-3.416; P = 0.013) in stage IVA disease. CONCLUSIONS: CCRT-AC may be a more effective treatment modality in patients with stage IVA NPC disease, while IC-CCRT was superior in stage III disease.