Search

Background Immunotherapy, especially immune checkpoint inhibition, has provided powerful tools against cancer. We aimed to detect the expression of common immune checkpoints and evaluate their prognostic values in nasopharyngeal carcinoma (NPC). Methods The expression of 9 immune checkpoints consistent with 13 features was detected in the training cohort (n = 208) by immunohistochemistry and quantified by computational pathology. Then, the LASSO cox regression model was used to construct an immune checkpoint-based signature (ICS), which was validated in a validation cohort containing 125 patients. Results High positive expression of PD-L1 and B7-H4 was observed in tumour cells (TCs), whereas PD-L1, B7-H3, B7-H4, IDO-1, VISTA, ICOS and OX40 were highly expressed in tumour-associated immune cells (TAICs). Eight of the 13 immune features were associated with patient overall survival, and an ICS classifier consisting of 5 features (B7-H3TAIC, IDO-1TAIC, VISTATAIC, ICOSTAIC, and LAG3TAIC) was established. Patients with high-risk scores in the training cohort had shorter overall (P

Solid evidence shows that tumor-initiating cells (T-ICs) are the root of tumor relapse and drug resistance, which lead to a poor prognosis in patients with hepatocellular carcinoma (HCC). Through an in vitro liver T-IC enrichment approach, we identified nuclear factor (erythroid-derived 2)-like 2 (NRF2) as a transcription regulator that is significantly activated in enriched liver T-IC populations. In human HCCs, NRF2 was found to be overexpressed, which was associated with poor patient survival. Through a lentiviral based knockdown approach, NRF2 was found to be critical for regulating liver T-IC properties, including self-renewal, tumorigenicity, drug resistance and expression of liver T-IC markers. Furthermore, we found that ROS-induced NRF2 activation regulates sorafenib resistance in HCC cells. Mechanistically, NRF2 was found to physically bind to the promoter of sonic hedgehog homolog (SHH), which triggers activation of the sonic hedgehog pathway. The effect of NRF2 knockdown was eliminated upon administration of recombinant SHH, demonstrating that NRF2 mediated T-IC function via upregulation of SHH expression. Our study suggests a novel regulatory mechanism for the canonical sonic hedgehog pathway that may function through the NRF2/SHH/GLI signaling axis, thus mediating T-IC phenotypes.

Circular RNAs (circRNAs) have been implicated in cancer progression through largely unknown mechanisms. Herein, we identify an N6-methyladenosine (m6A) modified circRNA, circNSUN2, frequently upregulated in tumor tissues and serum samples from colorectal carcinoma (CRC) patients with liver metastasis (LM) and predicts poorer patient survival. The upregulated expression of circNSUN2 promotes LM in PDX metastasis models in vivo and accelerates cancer cells invasion in vitro. Importantly, N6-methyladenosine modification of circNSUN2 increases export to the cytoplasm. By forming a circNSUN2/IGF2BP2/HMGA2 RNA-protein ternary complex in the cytoplasm, circNSUN2 enhances the stability of HMGA2 mRNA to promote CRC metastasis progression. Clinically, the upregulated expressions of circNSUN2 and HMGA2 are more prevalent in LM tissues than in primary CRC tissues. These findings elucidate that N6-methyladenosine modification of circNSUN2 modulates cytoplasmic export and stabilizes HMGA2 to promote CRC LM, and suggest that circNSUN2 could represent a critical prognostic marker and/or therapeutic target for the disease.

Objectives Although the genomic landscape of small‐cell carcinoma of the oesophagus (SCCE) has been dissected, its transcriptome‐level aberration and immune microenvironment status are unknown. Methods Using ultra‐deep whole transcriptome sequencing, we analysed the expression profile of nine paired SCCE samples and compared the transcriptome with public transcriptomic data set of normal oesophageal mucosa and other cancer types. Based on the transcriptome data, the immune signatures were investigated. The genomic data of 55 SCCE samples were also applied for immune checkpoint blockade therapy (ICBT) biomarker evaluation including microsatellite instability (MSI) status, tumor mutation burden (TMB) and neoantigen burden (TNB). Also, we evaluated the CD8, CD68 and programmed death‐ligand 1 (PD‐L1) in 62 retrospective SCCE samples with IHC assay. Results Differential expression analysis revealed that the cell cycle, p53, and Wnt pathways are significantly deregulated in SCCE. Immune microenvironment analysis showed that high leucocyte infiltration and adaptive immune resistance did occur in certain individuals, while the majority showed a relatively suppressive immune status. Immune checkpoints such as CD276 and LAG‐3 were upregulated, and higher M2 macrophage infiltration in tumor tissues. Furthermore, normal tissues adjacent to the tumors of SCCE presented a more activated inflammatory status than tumor‐free healthy controls. These observations showed that ICBT might benefit SCCE patients. As the critical biomarker of ICBT, TMB of SCCE was 3.64 with the predictive objective response rate 13.2%, while the PD‐L1‐positive rate was 43%. Conclusions Our study systematically characterized the immune microenvironment in small‐cell carcinoma of the esophagus and provided evidence that several patients with SCCE may benefit from immune checkpoint blockade therapy., In this study, transcriptomic aberrance and immune microenvironment of small‐cell carcinoma of the esophagus (SCCE) was comprehensively characterized with transcriptome and immunohistochemistry analysis. Assessment of immune checkpoint blockade (ICB) treatment biomarkers provides a rationale for use of ICB treatment in patients with SCCE.

Background: Cancer metastasis is the major reason for cancer-related deaths, but the mechanism of cancer metastasis still unclear. Adrenomedullin (ADM), a peptide hormone, functions as a local paracrine and autocrine mediator with multiple biological activities, such as angiogenesis, cell proliferation, and anti-inflammation. However, the expression and potential function of ADM in triple-negative breast cancer (TNBC) remain unclear. Methods: Real-time polymerase chain reaction and western blotting were performed to examine the expression of ADM in TNBC tissues and cell lines. A total of 458 TNBC tissue samples and adjacent nontumor tissue samples were detected by immunochemistry to determine the correlation between ADM expression and clinicopathological characteristics. We determined the role and mechanistic pathways of ADM in tumor metastasis in cell lines. Results: Our data showed that ADM expression was noticeably decreased in TNBC samples and cell lines. Low expression levels correlate with an increased risk of recurrence and metastasis. Furthermore, low ADM expression was associated with poor prognosis and was an independent marker for TNBC. In vitro, ADM may decrease cancer cell invasion, which is likely the result of its effect on the cancer cell epithelial-mesenchymal transition. Conclusions: Our findings suggest that ADM is a valuable biomarker for TNBC prognosis and an anti-metastasis candidate therapeutic target in triple-negative breast cancer.

Incidental detection of lymphoma in lymph node (LN) dissection for carcinoma is extremely rare. The occurrence and clinicopathological features of this rare condition have not been characterised. The medical records of 11,889 consecutive patients who underwent LN dissection for carcinoma in the abdominopelvic cavity were retrospectively reviewed. Among these patients, 11 had lymphomas detected in LN dissections and 7 had no previous history of lymphoma, representing an incidental detection rate of 0.06% (7/11889). The patients had a median age of 63 years (range, 48–69 years), and the male-to-female ratio was 1:2.5. The sites and histological types of the carcinoma were as follows: adenocarcinoma of the sigmoid colon (2 cases), endometrioid adenocarcinoma of the endometrium (2 cases), squamous carcinoma of the uterine cervix (1 case), adenocarcinoma of the stomach (1 case), and adenocarcinoma of the rectum (1 case). All incidental lymphoma cases (100%, 7/7) were low-grade B cell non-Hodgkin lymphoma (B-NHL), including 5 cases of follicular lymphoma (grades 1–2) and 2 cases of small lymphocytic lymphoma. The median follow-up interval was 39 months (5–65 months). All the patients were alive at the end of the follow-up period. Low-grade B-NHL can be incidentally detected during LN dissection for carcinoma in the abdominopelvic cavity. The subtype of incidental lymphoma is likely related to the epidemiology of lymphoma classes in the corresponding area. We should be aware of simultaneous occurrence of incidental lymphoma during lymphadenectomy for carcinoma.

Dominant coral-associated Endozoicomonas bacteria species are hypothesized to play a role in the coral sulfur cycle by metabolizing dimethylsulfoniopropionate (DMSP) into dimethylsulfide (DMS); however, no sequenced genome to date harbors genes for this process. In this study, we assembled high-quality (>95% complete) draft genomes of strains of the recently added species Endozoicomonas acroporae (Acr-14T, Acr-1, and Acr-5) isolated from the coral Acropora sp. and performed a comparative genomic analysis on the genus Endozoicomonas. We identified DMSP CoA-transferase/lyase—a dddD gene homolog in all sequenced genomes of E. acroporae strains—and functionally characterized bacteria capable of metabolizing DMSP into DMS via the DddD cleavage pathway using RT-qPCR and gas chromatography (GC). Furthermore, we demonstrated that E. acroporae strains can use DMSP as a carbon source and have genes arranged in an operon-like manner to link DMSP metabolism to the central carbon cycle. This study confirms the role of Endozoicomonas in the coral sulfur cycle.

Background: Sentinel lymph node biopsy (SLNB) is an efficient approach for detecting lymphatic metastasis in oncological surgeries. However, its benefits have long been confined by the lack of a precise intraoperative pathological examination. We therefore aimed to determine the diagnostic performance and optimal protocol of frozen section examination (FSE) in SLNB for cervical cancer. Methods: PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang Data and China National Knowledge Infrastructure were searched from inception to April 30, 2019, for studies concerning SLNB combined with FSE in cervical cancer. Sensitivity of FSE in detecting SLN metastasis was the primary diagnostic indicator to be evaluated. Definitive pathological examination was the reference standard. Findings: The pooled sensitivity of FSE among 31 eligible studies (1887 patients) was 0·77 (95% credible interval [CI] 0·66-0·85) with high heterogeneity (Q=99·09, I2=69·73%). Two representative FSE protocols were identified from 26 studies, described as equatorial (E-protocol, SLN was bisected and sections were taken from the maximum surface) and latitudinal (Lprotocol, SLN was cut at intervals and sections were taken from each cutting surface). Meta-regression analysis showed that FSE protocol was the only source of heterogeneity (p 2 mm) were missed in 4 and 20 patients; small-volume metastases (≤2 mm) were detected in 13 and 2 patients, respectively, under L- and E-protocol. The pooled sensitivity of FSE using L-protocol would reach 0·97 (95% CI 0·89-0·99) if only marcometastases were considered. These findings were robust to sensitivity analyses. Interpretation: The sectioning protocol determines the accuracy of FSE in detecting SLN metastases. With L-protocol, FSE can provide precise intraoperative pathology for SLNB, which enables immediate decision-making for individualized managements. Funding Statement: Health and Medical Cooperation Innovation Special Program of Guangzhou Municipal Science and Technology. (Number: 158100075). Declaration of Interests: HT and J-HL report being investigators of an ongoing multicenter trial regarding SLNB in cervical cancer (CSEM 010, NCT02642471) funded by a government project (Health and Medical Cooperation Innovation Special Program of Guangzhou Municipal Science and Technology, Number: 158100075). J-HL receives lecture fees from AstraZeneca and Roche, outside the submitted work. All other authors declare no competing interests. Ethics Approval Statement: This study was registered with PROSPERO (CRD42019130044).

The physical microenvironment is a critical mediator of tumor behavior. However, detailed biological and mechanistic insight is lacking. The present study reveals the role of chemotherapy‐enriched CD133+ liver cancer stem cells (CSCs) with THBS2 deficiency. This subpopulation of cells contributes to a more aggressive cancer and functional stemness phenotype in hepatocellular carcinoma (HCC) by remodeling the extracellular matrix (ECM) through the regulation of matrix metalloproteinase (MMP) activity, collagen degradation, and matrix stiffness. The local soft spots created by these liver CSCs can enhance stemness and drug resistance and provide a route of escape to facilitate HCC metastasis. Interestingly, a positive feed‐forward loop is identified where a local soft spot microenvironment in the HCC tumor is enriched with CD133 expressing cells that secrete markedly less ECM‐modifying THBS2 upon histone H3 modification at its promoter region, allowing the maintenance of a localized soft spot matrix. Clinically, THBS2 deficiency is also correlated with low HCC survival, where high levels of CSCs with low THBS2 expression in HCC are associated with decreased collagen fiber deposits and an invasive tumor front. The findings have implications for the treatment of cancer stemness and for the prevention of tumor outgrowth through disseminated tumor cells., Chemotherapy enrichment for CD133 expressing cells with deficient THBS2 expression, which facilitates the promotion of cancer stemness properties in hepatocellular carcinoma (HCC) cells through extracellular matrix remodeling, is described. The resultant local soft microenvironment induces mechanoepigenetic changes through histone H3 modifications, facilitating a positive feedback loop that supports the clonogenic expansion of a HCC cells with high CD133 and low THBS2 expression.

Cancer patients are more susceptible to severe coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Angiotensin-converting enzyme 2 (ACE2) is the functional host receptor for SARS-CoV-2 entering into human cells. Bioinformatics’ analyses have revealed that ACE2 is upregulated in some cancer cells. In the present study, we evaluated ACE2 protein expression levels in several common malignancies compared to non-cancerous normal tissues. ACE2 expression was elevated in colorectal adenocarcinoma, pancreatic adenocarcinoma, gastric adenocarcinoma, and papillary renal cell carcinoma cancer. Yet, it was suppressed in chromophobe renal cell carcinoma, testicular germ cell tumors, and papillary thyroid carcinoma. Two tumor tissue microarrays were used to evaluate the prognostic value of ACE2 expression in patients with gastric adenocarcinoma, and colorectal adenocarcinoma without COVID-19. No significant survival benefit was found for patients with overexpression of ACE2 in the tumor. In the tumor vasculature, ACE2 expression was observed in only 54% of the tumor micro-vessels. Using an in vitro co-culture of endothelial cells and tumor cells overexpressing fusion protein ACE2-red fluorescent protein, we did not observe any clear and convincing intercellular transfer of ACE2 from cancer cells into endothelial cells. In summary, alteration of ACE2 expression was found in common malignancies, but there is no evidence of intercellular transfer of ACE2 from cancer cells to endothelial cells.

As a novel hydrophobic monomer, polytetrahydrofuran diacrylate (PTMGDA) was synthesized by the esterification reaction between polyethylene tetrahydrofuran (PTMG) and acryloyl chloride (AC). In situ free radical polymerization reaction method was utilized to fabricate poly (vinylidene fluoride) (PVDF)-PTMGDApoly(ethylene oxide) dimethacrylate (PEGMA) ulrafiltration (UF) membranes. The performances of PVDFPTMGDA- PEGMA UF membranes in terms of morphologies, mechanical properties, separation properties and hydrophilicities were investigated. The introduction of the PTMGDA-PEGMA dopants not only increased the membranes' pure water flux, but also improved their mechanical properties and the dynamic contact angles. The addition of the PTMGDA/PEGMA dopants led to the formation of the finger-like structure in the membrane bulk. With the increase concentration of PTMGDA/PEGMA dopants, the porosity and the mean effective pore size increased. Those performances were coincide with the physicochemical properties of the casting solutions.

Purpose To investigate the profiles of cognitive impairment through Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) in patients with chronic traumatic brain injury (TBI) or stroke and to evaluate the sensitivity of the two scales in patients with TBI. Methods In this cohort study, a total of 230 patients were evaluated, including TBI group (n = 103) and stroke group (n = 127). The cognitive functions of two groups were evaluated by designated specialists using MoCA (Beijing version) and MMSE (Chinese version). Results Compared with the patients with stroke, the patients with TBI received significantly lower score in orientation subtest and recall subtest in both tests. MoCA abnormal rates in the TBI group and stroke group were 94.17% and 86.61% respectively, while MMSE abnormal rates were 69.90% and 57.48%, respectively. In the TBI group, 87.10% patients with normal MMSE score had abnormal MoCA score and in the stroke group, about 70.37% patients with normal MMSE score had abnormal MoCA score. The diagnostic consistency of two scales in the TBI group and the stroke group were 72% and 69%, respectively. Conclusion In our rehabilitation center, patients with TBI may have more extensive and severe cognitive impairments than patients with stroke, prominently in orientation and recall domain. In screening post-TBI cognitive impairment, MoCA tends to be more sensitive than MMSE.

Nearly 20% patients with stage II A colon cancer will develop recurrent disease post-operatively. The present study aims to develop a scoring system based on Artificial Neural Network (ANN) model for predicting 10-year survival outcome. The clinical and molecular data of 117 stage II A colon cancer patients from Sun Yat-sen University Cancer Center were used for training set and test set; poor pathological grading (score 49), reduced expression of TGFBR2 (score 33), over-expression of TGF-β (score 45), MAPK (score 32), pin1 (score 100), β-catenin in tumor tissue (score 50) and reduced expression of TGF-β in normal mucosa (score 22) were selected as the prognostic risk predictors. According to the developed scoring system, the patients were divided into 3 subgroups, which were supposed with higher, moderate and lower risk levels. As a result, for the 3 subgroups, the 10-year overall survival (OS) rates were 16.7%, 62.9% and 100% (P < 0.001); and the 10-year disease free survival (DFS) rates were 16.7%, 61.8% and 98.8% (P < 0.001) respectively. It showed that this scoring system for stage II A colon cancer could help to predict long-term survival and screen out high-risk individuals for more vigorous treatment.

Ultrafine alumina powders were synthesized through pyrocatechol and resorcinol mediated sol-gel process. Aluminum nitrate was applied as the Al source and PVP was the dispersant. X-ray diffraction (XRD) study displayed that γ-Al2O3 powders formed in the range of 800-900 °C, and then γ-Al2O3 transformed to α-Al2O3 at higher temperatures, pure α-Al2O3 powders could be obtained at 1000 °C by using resorcinol as organic monomer. The results of transmission electron microscopy (TEM) revealed that Al2O3 nanoparticles with γ crystalline phase had grain sizes in the range of 5-40 nm. Scanning electron microscopy (SEM) observation displayed that the morphology of the prepared α-Al2O3 powders had aggregated bodies formed by Al2O3 grains in the range of 0.2-0.5μm. These results provide a new way of preparation of alumina powders.

Photovoltaic (PV) cell cracks in wafer-based silicon PV modules are a well-known problem. In order to extract the fault characteristics of the cracked PV modules, we investigate and collect the cracked PV modules in several large PV power plants. The I-V characteristics of the cracked PV modules are tested. The test results show that the I-V curves of the cracked PV modules show a convex function step, and the reason for the I-V characteristics of the cracked PV module is analysed. A method for online diagnosis of PV module crack through I-V curve is proposed.

Circular RNAs (circRNAs) have been implicated in cancer progression through largely unknown mechanisms. Herein, we identify an N6-methyladenosine (m6A) modified circRNA, circNSUN2, frequently upregulated in tumor tissues and serum samples from colorectal carcinoma (CRC) patients with liver metastasis (LM) and predicts poorer patient survival. The upregulated expression of circNSUN2 promotes LM in PDX metastasis models in vivo and accelerates cancer cells invasion in vitro. Importantly, N6-methyladenosine modification of circNSUN2 increases export to the cytoplasm. By forming a circNSUN2/IGF2BP2/HMGA2 RNA-protein ternary complex in the cytoplasm, circNSUN2 enhances the stability of HMGA2 mRNA to promote CRC metastasis progression. Clinically, the upregulated expressions of circNSUN2 and HMGA2 are more prevalent in LM tissues than in primary CRC tissues. These findings elucidate that N6-methyladenosine modification of circNSUN2 modulates cytoplasmic export and stabilizes HMGA2 to promote CRC LM, and suggest that circNSUN2 could represent a critical prognostic marker and/or therapeutic target for the disease., Liver metastasis of colorectal cancer leads to poor prognosis. Here the authors report that an N6-methyladenosine modified circular RNA is upregulated in colorectal cancer and promotes liver metastasis by enhancing the stability of HMGA2 mRNA.

Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) may account for 8-9% of all gastric cancer (GC) patients. All previous reports on EBVaGC were retrospective. Prospective study is warranted to evaluate the exact role of EBV status in predicting the prognosis of GC. It is of special interest to figure out whether dynamic detection of plasma EBV-DNA load could be a feasible biomarker for the monitor of EBVaGC. From October 2014 to September 2017, we consecutively collected GC patients (n = 2,760) from Sun Yat-sen University Cancer Center for EBER examination. We detected EBV-DNA load in plasma and tissue samples of EBVaGC patients at baseline. Subsequently, plasma EBV-DNA load was dynamically monitored in EBVaGC patients. The overall prevalence of EBVaGC is 5.1% (140/2,760). The incidence rate of EBVaGC decreased with advanced AJCC 7th TNM stage (p < 0.001), with the corresponding percentages of 9.3, 9.9, 6.7 and 1.4% for Stage I, II, III and IV patients. EBVaGC patients were predominately young males with better histologic differentiation and earlier TNM stage than EBV-negative GC (EBVnGC) patients. EBVaGC patients were confirmed to had a favorable 3-year survival rate (EBVaGC vs. EBVnGC: 76.8% vs. 58.2%, p = 0.0001). Though only 52.1% (73/140) EBVaGC patients gained detectable EBV-DNA and 43.6% (61/140) reached a positive cutoff of 100 copies/ml, we found the plasma EBV-DNA load in EBVaGC decreased when patients got response, while it increased when disease progressed. Our results suggested that plasma EBV-DNA is a good marker in predicting recurrence and chemotherapy response for EBVaGC patients.

Chun-Hua Wang,1,2,* Li-Li Liu,1,2,* Ding-Zhun Liao,3,* Mei-Fang Zhang,1,2 Jia Fu,1,2 Shi-Xun Lu,1,2 Shi-Lu Chen,1,2 Hong Wang,1,2 Shao-Hang Cai,1,2 Chris Zhiyi Zhang,1,2 Hui-Zhong Zhang,2 Jing-Ping Yun1,2 1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; 2Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; 3Department of Pathology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China *These authors contributed equally to this work Introduction: Prenylated Rab acceptor 1 domain family member 2 (PRAF2), a novel oncogene, has been shown to be essential for the development of several human cancers; however, its role in hepatocellular carcinoma (HCC) remains unclear. Materials and methods: PRAF2 mRNA and protein expressions were examined in fresh tissues by quantitative reverse transcription-polymerase chain reaction and Western blot, respectively, and in 518 paraffin-embedded HCC samples by immunohistochemistry. The correlation of PRAF2 expression and clinical outcomes was determined by the Student’s t-test, Kaplan–Meier test, and multivariate Cox regression analysis. The role of PRAF2 in HCC was investigated by cell viability, colony formation, and migration assays in vitro and with a nude mouse model in vivo. Results: In our study, the PRAF2 expression was noticeably increased in HCC tissues at both the mRNA and protein levels compared with that of the nontumorous tissues. Kaplan–Meier analysis indicated that high PRAF2 expression was correlated with worse overall survival in a cohort of 518 patients with HCC. The prognostic implication of PRAF2 was verified by stratified survival analysis. The multivariate Cox regression model revealed PRAF2 as an independent poor prognostic factor for overall survival (hazard ratio = 1.244, 95% CI: 1.039–1.498, P

The first synthesis of polyflavanostilbene B (1), which has seven contiguous stereocenters including two quaternary carbon centers, from abundant polymeric (-)-epicatechin gallate on a gram scale in three steps without the use of protecting groups is reported. The key transformations of this strategy include a regioselective and stereoselective substitution of resveratrol to give the 4-derivative of (-)-epicatechin 3-gallate and an iron-catalyzed cyclization reaction. The possible radical cyclization mechanism in the formation of the hexahydrocyclopenta[c]furan core is also discussed.

Concomitant chronic kidney disease (CKD) and coronary artery disease (CAD) is known to have poor outcomes. With a thorough literature review, we discuss the pathophysiological basis behind accelerated atherosclerosis in CKD, and the role of percutaneous coronary intervention (PCI) in these patients, focusing on drug-eluting stents, coronary artery bypass grafting, and adverse outcomes. We discuss factors contributing to poor outcomes in these patients, and the need for more work in this subgroup.

Deregulation of alternative splicing contributes to the malignant progression of cancer. Little is known about the significant alternative splicing events in hepatocellular carcinoma (HCC). High-throughput sequencing revealed that coiled-coil domain containing 50 (CCDC50) pre-mRNA is aberrantly spliced in 50% of our HCC cases. A BaseScope assay was performed to examine the expression of CCDC50S (a truncated oncogenic splice variant) in HCC tissues. Compared with benign liver tumors and several other types of solid tumors, CCDC50S mRNA was up-regulated in HCC, with a diagnostic potential (sensitivity, 0.711; specificity, 0.793). High expression of CCDC50S mRNA in HCC was significantly correlated with poor tumor differentiation, advanced tumor node metastasis (TNM) stage, and unfavorable prognosis. Overexpression of CCDC50S exerted tumorigenic activities that promoted HCC growth and metastasis by activation of Ras/forkhead box protein O4 (Foxo4) signaling. Either suppression of mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) phosphorylation or overexpression of Foxo4 markedly attenuated CCDC50S-mediated phenotypes. Furthermore, serine- and arginine-rich splicing factor 3 (SRSF3) directly bound to CCDC50S mRNA to maintain its stability in the cytoplasm. The cytosolic retention of SRSF3 was mediated by the interaction of hepatitis B virus-encoded X protein (HBx) and 14-3-3β. Ectopic HBx expression induced expression of cytosolic SRSF3 and CCDC50S. Conclusion: Our study provided compelling evidence that up-regulation of CCDC50S was modulated by HBx/SRSF3/14-3-3β complex and enhanced oncogenic progression of HCC through the Ras/Foxo4 signaling pathway. These data suggest that CCDC50S may serve as a diagnostic and prognostic biomarker and probably a promising therapeutic target in HCC.

Leucine-rich-alpha-2-glycoprotein1 (LRG1) is a novel oncogene-associated protein which has been clarified vital to the progression of human cancers, but its role in hepatocellular carcinoma (HCC) remains unclear. Here, we showed that the expression of LRG1 was noticeably increased in HCC tissues, compared to the nontumorous tissues. High LRG1 expression was significantly associated with tumor size (P = 0.004), tumor differentiation (P = 0.010), TNM stage (P < 0.001) and vascular invasion (P = 0.019). Kaplan-Meier analysis showed that LRG1 expression was closely correlated to overall survival and disease-free survival in a training cohort of 474 patients with HCC. The correlation was further validated in an independent cohort of 303 HCC patients. The prognostic implication of LRG1 was confirmed by stratified survival analyses. Multivariate Cox regression model indicated LRG1 as an independent poor prognostic indicator for overall survival (Hazard ratio = 1.582, 95% confident interval: 1.345–1.862, P < 0.001) and disease-free survival (Hazard ratio = 1.280, 95% confident interval: 1.037–1.581, P = 0.022) in HCC. In vitro data showed that LRG1 markedly promoted cell migration but has no effect on cell proliferation. Collectively, our data show that LRG1 is markedly up-regulated and serves as an independent factor of poor outcomes in HCC. Our study therefore provides a promising biomarker for prognostic prediction in clinical management of HCC.

CAP2 has been suggested as a potential diagnostic biomarker for early hepatocellular carcinoma (HCC). However, its prognostic significance in HCC remains unclear. Here, we show that CAP2 expression is much higher in HCC tissues than that in paracarcinoma tissues, at both mRNA and protein levels. Data of immunohistochemistry (IHC) revealed that CAP2 was markedly up-regulated in 77.3% of HCC cases. High CAP2 expression, defined by the median score of IHC, was present in 53.3% of the patients. Kaplan-Meier analysis indicated that high CAP2 expression was associated with poor overall survival (P < .0001), disease-free survival (P = .013) and recurrence probability (P = .004) in a training cohort of 312 HCC patients. The prognostic implication of CAP2 in HCC was further confirmed in a validation cohort of 208 HCC patients and by stratified survival analysis. Multiple Cox regression analysis indicated CAP2 as an independent predictor for overall survival (hazard ratio (HR) = 1.615, 95% confidence interval: 1.345-1.938, P < .001). Collectively, we conclude that CAP2 is increased in HCC and is a novel unfavorable biomarker for prognostic prediction for patients with this deadly disease.

OBJECTIVE Tumor necrosis has been indicated as a factor for the poor clinical outcome in human cancers. We aim to disclose the association between tumor necrosis and overall survival and recurrence-free survival in node-negative upper urinary tract urothelial carcinoma patients treated with radical nephroureterectomy. METHODS A retrospective cohort of 100 patients with upper urinary tract urothelial carcinoma from January 1990 to June 2011 was enrolled in this study. Univariate analysis with Log-rank test and multivariate analysis with Cox proportional hazards regression models were conducted to determine the correlations of tumor necrosis with overall survival and recurrence-free survival. RESULTS Tumor necrosis was presented in 48 patients with upper urinary tract urothelial carcinoma and was significantly associated with the advanced pathological stage (P < 0.001), high tumor grade (P < 0.001), subsequent bladder tumor (P = 0.018), vascular invasion (P < 0.001) and lymph node metastasis (P = 0.026). Multivariate analysis revealed tumor necrosis as an independent unfavorable predictor of overall survival in node-negative upper urinary tract urothelial carcinoma patients by multivariate analysis (hazard ratio = 9.23, 95% confidence interval = 1.05-80.89, P = 0.045). CONCLUSIONS Tumor necrosis was an independent factor of adverse clinical outcomes in node-negative upper urinary tract urothelial carcinoma patients who received radical nephroureterectomy. Evaluation of tumor necrosis might be of clinical significance to determine whether patients with node-negative upper urinary tract urothelial carcinoma should be given further therapy after radical nephroureterectomy.

// Hong Yang 1, 2 , Xiao-dong Li 1, 2 , Ying Zhou 1 , Xiaojiao Ban 1 , Ting-ting Zeng 1 , Lei Li 1 , Bao-zhu Zhang 1 , Jingping Yun 1 , Dan Xie 1 , Xin-Yuan Guan 1, 3 , Yan Li 1 1 Sun Yat-sen University Cancer Center, State key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China 2 Guangdong Esophageal Cancer Institute, Guangzhou, China 3 Department of Clinical Oncology, The University of Hong Kong, Hong Kong, China Correspondence to: Yan Li, e-mail: liy6@mail.sysu.edu.cn Keywords: esophageal squamous cell carcinoma (ESCC), EIF5A2, stemness, chemoresistance Received: June 19, 2015 Accepted: July 08, 2015 Published: July 20, 2015 ABSTRACT Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies of the digestive tract in East Asian countries. Multimodal therapies, including adjuvant chemotherapy and neo-adjuvant chemotherapy, have become more often used for patients with advanced ESCC. However, the chemotherapy effect is often limited by patients’ drug resistance. This study demonstrated that EIF5A2 (eukaryotic translation initiation factor 5A2) overexpression induced stemness and chemoresistance in ESCC cells. We showed that EIF5A2 overexpression in ESCC cells resulted in increased chemoresistance to 5-fluorouracil (5-FU), docetaxel and taxol. In contrast, shRNAs suppressing eIF5A2 increased tumor sensitivity to these chemotherapeutic drugs. In addition, EIF5A2 overexpression was correlated with a poorer overall survival in patients with ESCC who underwent taxane-based chemotherapy after esophagectomy ( P < 0.05). Based on these results, we suggest that EIF5A2 could be a predictive biomarker for selecting appropriate chemo-treatment for ESCC patients and EIF5A2 inhibitors might be considered as combination therapy to enhance chemosensitivity in patients with ESCC.

We develop a novel polyvinylidene fluoride (PVDF) hollow fiber membrane utilizing the concept of in-situ self-assembly modulation, which is in terms of in-situ synthesis of amphiphilic copolymers and in-situ solubilization of polyvinylpyrrolidone (PVP). Utilizing the polytetrahydrofuran dimethacrylate ester (PTMGDA) and polyethylene glycol monomethyl ether methyl methacrylate (PEGMA) as reaction monomers, amphiphilic copolymers are in-situ synthesized, denoted as “P(PTMGDA-r-PEGMA)”. Results show that P(PTMGDA-r-PEGMA) and PVP have the synergistic effects on configuration and separation performance of PVDF membrane. P(PTMGDA-r-PEGMA) with high ratio in hydrocarbon chain (75.2%) and PVP not only effectively tunes micro-structure of the dope solutions but also results in the enhancement of the resultant membranes’ break strength and their stable permeability. Besides, the supramolecular aggregates of PVDF-P(PTMGDA-r-PEGMA)–PVP (size: 76–157 nm) work as “template” dependence of the macrovoids, which appear in the fibers׳ sponge-like cross-section structure, hence leading to the narrowing pore size distribution. Furthermore, the macrovoids’ size enlarges with the increase of content of P(PTMGDA-r-PEGMA) and PVP. It is also found that the permeation flux is controlled by the diffusion of PVP from the interior dope solution and pore-forming of P(PTMGDA-r-PEGMA) during demixing process, which is consistent with the in-situ self-assembly modulation concept. Finally, the newly developed PVDF hollow fiber membranes demonstrate remarkable long-term stable permeability.

Pyruvate kinase M2 (PKM2) contributes to the Warburg effect, a hallmark of cancer. We showed that PKM2 levels were correlated with overall survival (hazard ration = 1.675, 95% confidence interval: 1.389–2.019, P < 0.001) and disease-free survival (hazard ration = 1.573, 95% confidence interval: 1.214–2.038, P < 0.001) in a cohort of 490 patients with HCC. The correlations were further validated in an independent cohort of 148 HCC patients. Multivariate analyses revealed that PKM2 was an independent indicator of poor outcome in HCC. The knockdown of PKM2 in HCC cells inhibited cell proliferation and induced apoptosis in vitro and in vivo. Bim siRNA markedly abolished the PKM2-depletion-induced apoptosis. PKM2 depletion decreased the degradation of Bim. In clinical samples, PKM2 expression was reversely correlated with Bim expression. Combination of PKM2 and Bim levels had the best prognostic significance. We suggest that PKM2 serves as a promising biomarker for poor prognosis of patients with HCC and its knockdown induces HCC apoptosis by stabilizing Bim.

POTE ankyrin domain family, member G (poteg) belongs to POTE family. The POTE family is composed of many proteins which are very closely related and expressed in prostate, ovary, testis, and placenta. Some POTE paralogs are related with some cancers. Here we showed that down-regulation of POTEG was detected in about 60% primary esophageal squamous cell carcinoma (ESCC) tumor tissues. Clinical association studies determined that POTEG down-regulation was significantly correlated with tumor differentiation, lymph nodes metastasis and TNM staging. Kaplan-Meier analysis determined that POTEG down-regulation was associated with poorer clinical outcomes of ESCC patients (P = 0.026). Functional studies showed that POTEG overexpression could suppress tumor cell growth and metastasis capacity in vitro and in vivo. Molecular analyses revealed that POTEG downregulated CDKs, leading to subsequent inhibition of Rb phosphorylation, and consequently arrested Cell Cycle at G1/S Checkpoint. POTEG overexpression induced apoptosis by activating caspases and PARP, and regulating canonical mitochondrial apoptotic pathways. On the other side, POTEG inhibited epithelial-mesenchymal transition and suppressed tumor cell metastasis. In conclusion, our study reveals a functionally important control mechanism of POTEG in esophageal cancer pathogenesis, suggesting potential use in the ESCC intervention and therapeutic strategies.

Context.— According to the American Joint Committee on Cancer's Cancer Staging Manual, 7th edition, TNM classification, tumor deposit (TD)–positive colorectal cancers (CRCs) are classified as N1c. The effects of radiotherapy and the effects of the updated American Joint Committee on Cancer 7th edition TNM N1c classification for patients with TD-positive CRC are unclear. Objective.— To investigate outcomes of radiotherapy in patients with resected TD-positive CRC. Design.— Resected TD-positive CRCs diagnosed from 2010 to 2014 were identified in the Surveillance, Epidemiology, and End Results 18 database. Factors associated with overall survival (OS) and cancer-specific survival (CSS) were investigated using Kaplan-Meier and Cox proportional hazards models. Results.— We included 2712 qualified CRC patients, who either underwent adjuvant radiotherapy (n = 187; 6.9%) or received no radiotherapy (n = 2525; 93.1%). Univariate Cox proportional models showed improved CSS among all CRC patients who underwent adjuvant radiotherapy (CSS hazard ratio, 0.73; 95% CI, 0.57–0.95) and among rectal cancer patients when separated by location (hazard ratio, 0.57; 95% CI, 0.40–0.83), although these associations were attenuated in multivariable-adjusted models. There was improved OS among rectal cancer patients (hazard ratio, 0.77; 95% CI, 0.59–0.99). In subgroup analyses, radiotherapy was not associated with OS or CSS in either metastatic or nonmetastatic CRC patients. Instead, N1c category (versus N0) was associated with a worse OS (hazard ratio, 1.43; 95% CI, 1.31–1.57) but was not associated with CSS. Conclusions.— Radiotherapy did not independently improve OS among TD-positive CRC patients. In this study, classifying TD positivity as N1c was associated with worse OS than classifying TD positivity as N0. The findings seem to challenge the benefits of radiotherapy and the new N1c classification of TD for TD-positive CRC patients.

SATB2 (Special AT-rich sequence-binding protein 2) has recently been shown to be a specific biomarker of colorectal cancer (CRC). The aim of this study was to investigate the diagnostic potential of SATB2 as a means of detecting a CRC origin for liver metastases. SATB2 expression was examined in a resection cohort of 101 CRC and 273 non-CRC adenocarcinoma samples using immunohistochemistry (IHC). The diagnostic accuracy of CRC origins of liver metastases based on SATB2 and a three marker panel of SATB2, CK20 and CDX2 was evaluated using an independent cohort of 192 liver biopsies. IHC showed 97 of the 101 (96.0%) primary CRC samples were SATB2 positive, compared to only 6 of the 273 (2.1%) samples of other cancer types. The sensitivity, specificity and AUC values of SATB2 expression in resection samples were 97%, 97.1% and 0.977, respectively. Meanwhile, for the liver biopsy samples, the sensitivity, specificity and AUC values of a CRC liver metastases was 92.2%, 97.8% and 0.948 for SATB2, 95.1%, 91.0% and 0.959 for CK20, and 100%, 85.4% and 0.976 for CDX2, respectively. Further analysis demonstrated that all three-marker positivity was detected in 92/103 (89.3%) CRC and 2/89 (2.2%) non-CRC liver metastases sampled by biopsy. Our findings suggest that SATB2, as measured by IHC, could serve as a promising diagnostic biomarker of CRC metastases. Combining evaluation of SATB2 with CK20 and CDX2 to form a three marker panel further improved the detection of metastatic CRCs in liver biopsy tissues., Highlights • SATB2 protein could serve as a promising diagnostic biomarker of CRC. • SATB2 expression can distinguish liver metastases with CRC origins from other forms of adenocarcinoma. • A three marker panel of SATB2, CK20 and CDX2 used on liver biopsy samples is valuable when assessing g a CRC origin. Liver metastasis is the leading cause of cancer-related morbidity and mortality in colorectal cancer (CRC) patients. Since histological diagnosis from liver needle biopsy is based solely on tiny fragments of tissue, it can sometimes be quite difficult to distinguish CRC from non-CRCs. Thus, there is a current need for searching and identifying of specific biomarkers that can improve the accuracy of diagnosis. Our results indicate that SATB2 could serve as a promising diagnostic biomarker of CRC metastases; and that a three marker panel of SATB2, CK20 and CDX2 used on liver biopsy samples is valuable.

The American Joint Committee on Cancer (AJCC) staging system is inadequate for an accurate prognosis in nasopharyngeal carcinoma (NPC). Thus, new biomarkers are under intense investigation. Here, we investigated whether the density of TILs could predict prognosis in NPC. First, we used 1490 cases of nasopharyngeal carcinoma samples from two independent cohorts to evaluate the density and distribution of tumor-infiltrating lymphocytes (TILs). Second, in one cohort, we assessed associations between TILs and clinical outcomes in 593 randomly selected samples (defined as the training set) and validated findings in the remaining 593 samples (defined as the validation set). Furthermore, we confirmed the prognostic value of TILs in a second independent cohort of 304 cases (defined as the independent set). Based on multivariable Cox regression analysis, we also established an effective prognostic nomogram including TILs to improve accuracy in predicting disease-free survival (DFS) for patients with nondisseminated NPC. We found that high TILs in the training set were significantly associated with favorable DFS [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28-0.58, p 0.001], overall survival (OS, HR 0.42, 95% CI 0.27-0.64, p 0.001), distant metastasis-free survival (DMFS, HR 0.37, 95% CI 0.23-0.58, p 0.001) and local-regional recurrent free survival (LRRFS, HR 0.43, 95% CI 0.25-0.73, p = 0.002). Multivariate analysis showed that TILs are an independent prognostic indicator for DFS in all cohorts. In summary, this study indicated that TILs may reflect the immunological heterogeneity of NPC and could represent a new prognostic biomarker.

Gastric cancer (GC) is the second cause of cancer-related death. Cisplatin (CDDP) is widely used as the standard GC treatment, but relapse and metastasis are common because of intrinsic or acquired drug resistance. The mitogen-activated protein kinase phosphatases (MAPK)-extracellular signal regulated kinases (ERK) pathway contributes to GC progression and drug resistance, but targeting the MAPK-ERK pathway is challenging in GC therapy. Here, we demonstrated that dual-specificity phosphatases 6 (DUSP6) was overexpressed in GC and predicted poor overall survival and progression-free survival. Knockdown DUSP6 inhibited GC proliferation, migration, invasion and induced apoptosis. (E/Z)-BCI hydrochloride (BCI), a DUSP6 small molecule inhibitor, increased the activity of ERK but interestingly decreased the expression of ERK response genes in BGC823, SGC7901 and CDDP-resistant SGC7901/DDP cells. BCI also caused cell death through the DNA damage response (DDR) pathway. Moreover, BCI inhibited cell proliferation, migration and invasion in a receptor-independent manner and enhanced CDDP cytotoxicity at pharmacological concentrations in the GC cells. In vivo experiments further showed that BCI enhances the antitumor effects of CDDP in cell-based xenografts and PDX models. In summary, our findings indicated that disruption of DUSP6 by BCI enhanced CDDP-induced cell death and apoptosis in GC may partly through ERK and DDR pathways. Thus, this study suggests that DUSP6 is a potential prognostic biomarker and a promising target for GC therapy.

Iridoplasts (modified plastids in adaxial epidermal cells) reported from Begonia were originally hypothesized to cause iridescence, which was broadly accepted for decades. However, several species of Begonia with iridoplasts are not iridescent causing confusion. Here chloroplast ultrastructure was observed in 40 taxa of Begoniaceae to explore the phenomenon of iridescence. However, 22 Begonias and Hillebrandia were found to have iridoplasts, but only nine display visually iridescent blue to blue-green leaves. Unexpectedly, a new type of plastid, a 'minichloroplast,' was found in the abaxial epidermal cells of all taxa, but was present in adaxial epidermal cells only if iridoplasts were absent. Comparative ultrastructural study of iridoplasts and a shading experiment of selected taxa show that a taxon with iridoplasts does not inevitably have visual iridescence, but iridescence is greatly affected by the spacing between thylakoid lamellae (stoma spacing). Thus, we propose instead the name 'lamelloplast' for plastids filled entirely with regular lamellae to avoid prejudging their function. To evaluate photosynthetic performance, chlorophyll fluorescence (F v /F m ) was measured separately from the chloroplasts in the adaxial epidermis and lower leaf tissues by using leaf dermal peels. Lamelloplasts and minichloroplasts have much lower photosynthetic efficiency than mesophyll chloroplasts. Nevertheless, photosynthetic proteins (psbA protein of PSII, RuBisCo and ATPase) were detected in both plastids as well as mesophyll chloroplasts in an immunogold labeling. Spectrometry revealed additional blue to blue-green peaks in visually iridescent leaves. Micro-spectrometry detected a blue peak from single blue spots in adaxial epidermal cells confirming that the color is derived from lamelloplasts. Presence of lamelloplasts or minichloroplasts is species specific and exclusive. High prevalence of lamelloplasts in Begoniaceae, including the basal clade Hillebrandia, highlights a unique evolutionary development. These new findings clarify the association between iridescence and lamelloplasts, and with implications for new directions in the study of plastid morphogenesis.

To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, 9 more questions are presented as follows. Question 31: How does aging process inhibit the formation of sarcoma? Question 32: Is intratumoral morphological heterogeneity the consequence of tumor genomic instability or the cause of aggressive tumor behavior? Can we identify more aggressive tumors by computationally analyzing the morphological heterogeneity of the tumor tissues? Question 33: How to pre-surgically differentiate irradiation-induced ulceration from cancerous ulceration? Question 34: Why is epidermal growth factor receptor (EGFR) 19 Del-positive tumor more sensitive to targeted therapy than EGFR 21 L858R-positive tumor in patients with non-small cell lung cancer? Question 35: Can an Epstein–Barr virus vaccine be developed to reduce the incidence of EBV-related malignancies? Question 36: What is the unique feature in sarcoma vasculature that causes the intrinsic resistance of sarcoma against anti-angiogenic therapy? Question 37: How many ways can sarcoma cells protect themselves from the attacks of cytotoxic drugs? Question 38: How stable does the tumor heterogeneity remain along with cytotoxic chemotherapy? Question 39: How to generate a prognostic classifier for diffuse low-grade gliomas by integrating genetic and epigenetic signatures with histological features?

Cardiac rhabdomyoma (CR) is the most common cardiac tumor in newborns. Approximately 75% of cases are associated with tuberous sclerosis complex. Although these tumors usually spontaneously regress after 2 years of age, they can be life-threatening when they obstruct major cardiac inflow or outflow pathways. Everolimus is an inhibitor of the mammalian target of rapamycin, reducing its production of the proteins harmartin and tuberin. Everolimus has demonstrated a remarkable suppression effect in children with tuberous sclerosis complex at doses of 4.7–5.6 mg/M2/day and serum trough levels of 5–15 ng/mL. Since 2012, five case reports of neonates with CR have also reported the tumor-regressing effect of everolimus. However, the optimal dosage for neonates is still unknown. Over the past 2 years, we have deliberately used a low dose everolimus regimen (0.3–0.67 mg/M2/day) in three neonates with large CRs, in an effort to maintain serum trough levels at 3–7 ng/mL. In all three cases, the tumors regressed smoothly within 2 months. Regarding the drug’s side effect of predisposing patients to infection, we observed that adenovirus pneumonia occurred in one case at 3 months of age, and chicken pox occurred in another case at 9 months of age; both recovered smoothly. Our three cases of neonatal CR demonstrate that a low-dose everolimus regimen is an effective treatment for tumor regression.

The dysregulation of transcription factors contributes to the unlimited growth of cancer cells. Zic2 has been shown to be crucial to the progression of human cancers. However, its role in hepatocellular carcinoma (HCC) remains unclear. Our data showed that Zic2 expression gradually increased from normal to cancer to metastatic tissues. Zic2 overexpression promoted, whereas Zic2 knockdown inhibited, cell proliferation and migration in vitro as well as tumor growth and metastasis in vivo. Gene microarray results indicated that PAK4 was a potential target of Zic2. The knockdown of Zic2 decreased, whereas Zic2 re-expression increased, the expression of PAK4. ChIP and luciferase assays indicated that Zic2 directly bound to the PAK4 promoter and modulated its activity. PAK4 interference attenuated Zic2-mediated cell growth via modulating the Raf/MEK/ERK pathway. In a cohort of 615 patients, Zic2 was positively correlated with PAK4 and associated with worse overall and disease-free survival. Multivariate analyses revealed that Zic2 and PAK4 were independent indicators of a poor outcome in HCC. In addition, Zic2 expression was inversely correlated with miR-1271 expression. Re-introduction of miR-1271 attenuated Zic2-promoted cell proliferation and migration. Taken together, our findings suggest that the newly identified miR-1271/Zic2/PAK4 axis plays an important role in HCC progression and may serve as a potential therapeutic target for HCC.

The interforce between the magnetic composite forward osmosis (FO) membranes and the magnetic draw solution was proposed to reduce the internal concentration polarization (ICP) of FO process, and realized the synergetic permeability improvement of resultant FO membranes. The key factor was the successful fabrication of the Fe3O4 magnetic nanoparticles (MNPs) with small-size and narrow distribution via co-precipitation method. The cellulose triacetate (CTA) magnetic composite FO membranes were fabricated using Fe3O4 as additive via in situ interfacial polymerization, and named CTA-Fe3O4. Dynamic light scattering (DLS) and zeta results showed that the coated sodium oleate on the MNPs explained their reducing aggregation and the stability of various pHs. The MNPs' surface segregation during demixing process resulted in the improvement of hydrophilicity, Fe content and roughness of resultant CTA-Fe3O4 composite FO membranes. Furthermore, the in situ interfacial polymerization resulted in the formation of the polyamide selective layer, and the CTA-Fe3O4 membrane's N content was 11.02% to 11.12%. The permeability properties (FO and pressure retarded osmosis modules) were characterized using 1.0M NaCl and 100 mg/L Fe3O4 as draw solutions, respectively. The results indicated that the higher concentration of MNPs supplied more interforce and better FO permeability properties. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44852.

Autophagy-induced cancer cell death has become a novel strategy for the development of cancer therapeutic drugs. Numerous studies have indicated that green tea polyphenols induce both autophagy and apoptosis in a variety of cancer cells. Here, we synthesized a series of green tea polyphenol analogues, among which JP8 was shown to potently activate autophagy. JP8 treatment had a stronger effect on apoptosis in B16-F10 melanoma cells than that in normal AML-12 hepatocytes. JP8 selectively resulted in reactive oxygen species (ROS) accumulation in B16-F10 cells, and this effect was associated with corresponding increases in key components of the ER stress-mediated apoptosis pathway. Pharmacological inhibition of ROS by N-acetyl-L-cysteine (NAC) attenuated JP8-induced autophagy and apoptosis, indicating an upstream role of ROS in JP8-induced autophagy. An in vivo study showed that JP8 had significant antitumor effects in a B16-F10 xenograft mouse model. Our results indicate that JP8 is a novel anticancer candidate with both autophagy and ROS induction activities.