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High-temperature superconductive (SC) cuprates exhibit not only a SC phase, but also competing orders, suppressing superconductivity. Charge order (CO) has been recognized as an important competing order, but its microscopic spatial interplay with SC phase as well as the interlayer coupling in CO and SC phases remain elusive, despite being essential for understanding the physical mechanisms of competing orders and hence superconductivity. Here we report the achievement of direct real-space imaging with atomic-scale resolution of cryogenically cleaved YBa2Cu3O6.81 using cross-sectional scanning tunneling microscopy/spectroscopy. CO nanodomains are found embedded in the SC phase with a proximity-like boundary region characterized by mutual suppression of CO and superconductivity. Furthermore, SC coherence as well as CO occur on both CuO chain and plane layers, revealing carrier transport and density of states mixing between layers. The CO antiphase correlation along the c direction suggests a dominance of Coulomb repulsion over Josephson tunneling between adjacent layers. Charge ordering and superconductivity are known to compete in layered cuprates; however, precise real-space characterization of their interplay has been lacking. Here, the authors address this using atomically-resolved cross-sectional scanning tunnelling microscopy and spectroscopy on cryogenically cleaved YBa2Cu3O6.81.

Background Cronkhite-Canada syndrome (CCS) is a rare nonhereditary disease characterized by chronic diarrhoea, diffuse gastrointestinal polyposis and ectodermal manifestations. The lethality of CCS can be up to 50% if it is untreated or if treatment is delayed or inadequate. More than 35% of the patients do not achieve long-term clinical remission after corticosteroid administration, with relapse occurring during or after the cessation of glucocorticoid use. The optimal strategy of maintenance therapy of this disease is controversial. Case summary A 47-year-old man presented to the hospital with a 3-mo history of frequent watery diarrhoea, accompanied by macular skin pigmentation that included the palms and soles, and onychodystrophy of the fingernails and toenails. Gastroscopy and colonoscopy revealed numerous polyps in the stomach and colon. After other possibilities were ruled out by a series of examinations, CCS was diagnosed and treated with prednisone. The patient took prednisone for more than 1 year before achieving complete resolution of his symptoms and endoscopic findings. The patient was then given prednisone 5 mg/d for 6 mo of maintenance therapy. With clinical improvement and polyp regression, prednisone was discontinued. Eight mo after the discontinuation of prednisone, the diarrhoea and gastrointestinal polyps relapsed. Therefore, the patient was given the same dose of prednisone, and complete remission was achieved again. Conclusion It is necessary to extend the duration of prednisone maintenance therapy for CCS. Prednisone is still effective when readministered after relapse. Surveillance endoscopy at intervals of 1 year or less is recommended to assess mucosal disease activity.

Different clinical trials for advanced esophageal cancer have investigated diverse immuno-oncology combinational treatment in first-line setting, but the optimal choice has not been identified.We used PubMed, Embase, and Cochrane Library databases for systematic retrieval. The primary endpoint was overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and treatment-related adverse events (AEs) between immune checkpoint inhibitors combined with chemotherapy and chemotherapy.A total of five phase-III randomized controlled trials involving 3,163 patients met the inclusion criteria. Significantly improved OS (HR: 0.69, 95% CI: 0.62-0.76, P＜0.001), PFS (HR: 0.62, 95% CI: 0.55-0.70, P 0.001) and ORR (RR: 1.41, 95% CI: 1.23-1.62, P＜0.001) were observed when programmed death 1 (PD-1) inhibitor was added to chemotherapy. Toripalimab plus chemotherapy achieved the best OS benefit than any other treatment examined (HR: 0.58, 95% CI: 0.43-0.78). The longest PFS was founded in both sintilimab-chemotherapy and camrelizumab-chemotherapy combination (HR: 0.56, 95% CI: 0.46-0.68). Patients treated with nivolumab-chemotherapy got the best ORR improvement as compared to other combinations (RR: 1.73, 95% CI:1.40-2.14). Camrelizumab-chemotherapy and pembrolizumab-chemotherapy caused a relatively lower incidence of grade ≥ 3 AEs than other immunotherapy combination regimens. Subgroup analyses suggested significant OS advantage in programmed death-ligand 1(PD-L1) tumor-positive score (TPS) ≥ 10% groups and obviously longer PFS in PD-L1 combined positive score (CPS) ≥ 10 groups.In advanced esophageal cancer, PD-1 inhibitors combined with chemotherapy as first-line therapy have better survival outcomes than chemotherapy with greater but manageable toxicity. Toripalimab-chemotherapy showed the best OS benefit over chemotherapy, while sintilimab-chemotherapy and camrelizumab-chemotherapy generated the best PFS. The highest ORR improvement was founded in patients receiving nivolumab plus chemotherapy.

ImportanceThe E-cadherin gene, CDH1, and the α-E-catenin gene, CTNNA1, were previously identified as hereditary diffuse gastric cancer (HDGC) susceptibility genes, explaining 25% to 50% of HDGC cases. The genetic basis underlying disease susceptibility in the remaining 50% to 75% of patients with HDGC is still unknown.ObjectiveTo assess the incidence rate of CDH1 germline alterations in HDGC, identify new susceptibility genes that can be used for screening of HDGC, and provide a genetic landscape for HDGC.Design, Setting, and ParticipantsThis cohort study conducted retrospective whole-exome and targeted sequencing of 284 leukocyte samples and 186 paired tumor samples from Chinese patients with HDGC over a long follow-up period (median, 21.7 [range, 0.6-185.9] months). Among 10 431 patients diagnosed with gastric cancer between January 1, 2002, and August 31, 2018, 284 patients who met the criteria for HDGC were included. Data were analyzed from August 1 to 30, 2020.Main Outcomes and MeasuresIncidence rate of CDH1 germline alterations, identification of new HDGC susceptibility genes, and genetic landscape of HDGC.ResultsAmong 284 Chinese patients, 161 (56.7%) were female, and the median age was 35 (range, 20-75) years. The frequency of CDH1 germline alterations was 2.8%, whereas the frequency of CDH1 somatic alterations was 25.3%. The genes with the highest incidence (>10%) of private germline alterations (including insertions and deletions) in the HDGC cohort were MUC4, ABCA13, ZNF469, FCGBP, IGFN1, RNF213, and SSPO, whereas previously reported germline alterations of CTNNA1, BRCA2, STK11, PRSS1, ATM, MSR1, PALB2, BRCA1, and RAD51C were observed at low frequencies (median, 4 [range, 1-12] cases). Furthermore, enrichment of the somatic variant signature of exposure to aflatoxin suggested potential interaction between genetics and environment in HDGC. Double-hit events in genes such as CACNA1D were observed, which suggested that these events might serve as important mechanisms for HDGC tumorigenesis. In addition, germline variants of FSIP2, HSPG2, and NCKAP5 and somatic alterations of FGFR3, ASPSCR1, CIC, DGCR8, and LZTR1 were associated with poor overall survival among patients with HDGC.Conclusions and RelevanceThis study provided a genetic landscape for HDGC. The study’s findings challenged the previously reported high germline alteration rate of CDH1 in HDGC and identified new potential susceptibility genes. Analyses of variant signatures and double-hit events revealed potentially important mechanisms for HDGC tumorigenesis. Findings from the present study may provide helpful information for further investigations of HDGC.

Background: Biomarkers that could predict the beneficial effects of immune checkpoint inhibitors (ICIs) in combination with chemotherapy in treatment-naive advanced or recurrent gastric or gastroesophageal junction (G/GEJ) adenocarcinoma patients are lacking. Methods: We conducted a retrospective analysis of patients with G/GEJ adenocarcinoma who had undergone first-line treatment with programmed death-1 (PD-1) inhibitor plus chemotherapy between October 2017 and July 2021. Comparative analysis of the objective response rate (ORR) was performed using the Chi-square or Fisher’s exact tests. Survival curves were plotted by the Kaplan-Meier analysis and compared for significance with a log-rank test. Univariate and multivariate Cox proportional hazard models were established for evaluating the prognostic value of clinicopathological factors. Results: Of the 172 enrolled patients, 142 showed measurable lesions. The ORR was 52.8%. Higher response rates were observed in patients with age greater than or equal to 60 (p = 0.013), non-diffuse type (p < 0.001), synchronous metastasis (p = 0.029), distant lymph node metastasis (p = 0.002), non-peritoneal metastasis (p= 0.002), HER2 positivity (p = 0.002), and PD-L1 CPS greater than or equal to 5 (p = 0.017). Through univariate analysis, age, histology, number of metastatic sites, and peritoneal metastasis were found to be associated with progression-free survival (PFS). Through multivariate analysis, peritoneal metastasis occurrence was the only identified independent indicator of poor PFS (HR 2.768, 95% CI 1.184-6.472, p = 0.019). Additionally, multi-factor combination results showed that patients with at least one of the following: mismatch repair-deficient (D-MMR)/microsatellite instability-high (MSI-H), HER2 (+), EBV (+), and/or PD-L1 CPS greater than or equal to 5, exhibited higher response rates and longer PFS as compared to those lacking these factors; this benefit was consistent after excluding PD-L1 expression. Among the clinical combinatorial factors, significantly poor ORRs and lower PFS were observed in patients with age < 60, diffuse type, and peritoneal metastasis as compared to those without any of these factors. Conclusions: Peritoneal metastasis was an independent biomarker of poor efficacy to immunotherapy combined with chemotherapy in G/GEJ cancer patients in first-line setting. Some combination factors could be beneficial for efficacy prediction. Citation Format: Yu-Ting Sun, Shi-Xun Lu, Ming-Yu Lai, Xia Yang, Wen-Long Guan, Li-Qiong Yang, Yu-Hong Li, Feng-Hua Wang, Rui-Hua Xu, Miao-Zhen Qiu. Predictive biomarkers for the efficacy of PD-1 inhibitors plus chemotherapy for gastric/gastroesophageal junction cancer in first-line setting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5092.

High-temperature superconductive (SC) cuprates exhibit not only a SC phase, but also competing orders, suppressing superconductivity. Charge order (CO) has been recognized as an important competing order, but its microscopic spatial interplay with SC phase as well as the interlayer coupling in CO and SC phases remain elusive, despite being essential for understanding the physical mechanisms of competing orders and hence superconductivity. Here we report the achievement of direct real-space imaging with atomic-scale resolution of cryogenically cleaved YBa2Cu3O6.81 using cross-sectional scanning tunneling microscopy/spectroscopy. CO nanodomains are found embedded in the SC phase with a proximity-like boundary region characterized by mutual suppression of CO and superconductivity. Furthermore, SC coherence as well as CO occur on both CuO chain and plane layers, revealing carrier transport and density of states mixing between layers. The CO antiphase correlation along the c direction suggests a dominance of Coulomb repulsion over Josephson tunneling between adjacent layers., Charge ordering and superconductivity are known to compete in layered cuprates; however, precise real-space characterization of their interplay has been lacking. Here, the authors address this using atomically-resolved cross-sectional scanning tunnelling microscopy and spectroscopy on cryogenically cleaved YBa2Cu3O6.81.

Recently, specific biomarkers in the surface-enhanced Raman scattering (SERS) spectra of bacteria have been successfully exploited for rapid bacterial antibiotic susceptibility testing (AST) - dubbed SERS-AST. The biomolecules responsible for these bacterial SERS biomarkers have been identified as several purine derivative metabolites involved in bacterial purine salvage pathways (W. R. Premasiri, J. C. Lee, A. Sauer-Budge, R. Theberge, C. E. Costello and L. D. Ziegler, Anal. Bioanal. Chem., 2016, 408, 4631). Here we quantified these metabolites in the SERS spectra of Staphylococcus aureus and Escherichia coli using ultra-performance liquid chromatography/electrospray ionization-mass spectrometry (UPLC/ESI-MS). The time dependences of the concentrations of these molecules were measured using 13C- or 12C-purine derivatives as internal and external standards respectively in UPLC/ESI-MS measurements. Surprisingly, a single S. aureus and an E. coli cell were found to release millions of adenine and hypoxanthine into a water environment in an hour respectively. Furthermore, simulated SERS spectra of bacterial supernatants based on the mixtures of purine derivatives with measured concentrations also show great similarity with those of the corresponding bacterial samples. Our results not only provide a quantitative foundation for the emerging SERS-AST method but also suggest the potential of exploiting SERS for in situ monitoring the changes in bacterial purine salvage processes in response to different physical and chemical challenges.

Kinase suppressor of Ras 1 (KSR1) is a scaffold protein that modulates the activation of the oncogenic mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway. Ginkgo biloba extract (EGb) 761 has been demonstrated to possess antitumor activity that may be related to the KSR1-mediated ERK signaling pathway. However, the roles and its underlying mechanism in gastric cancer are unclear. In the present study, 62 gastric cancer and matched normal tissues were exploited for immunohistochemistry and real-time fluorescent quantitative PCR detection. Results of the immunohistochemistry showed that the expression of ERK1/2 and p-ERK1/2 was correlated to the expression of KSR1 and p-KSR1 in the gastric cancer tissues, and the overexpression of KSR1, p-KSR1, ERK1/2 and p-ERK1/2 was significantly associated with histological grade, TNM stage, lymph node and distant metastasis. Compared with the normal tissues, the relative mRNA copy values of KSR1, ERK1 and ERK2 in the cancer tissues were 2.43 ± 0.49, 2.10 ± 0.44 and 3.65 ± 0.94. In addition, the expression of KSR1, p-KSR1, ERK1/2 and p-ERK1/2 in human gastric cancer multidrug resistant SGC-7901/CDDP cells was higher than that in the SGC-7901 cells as detected by the methods of immunocytochemistry and western blot analysis. EGb 761 not only suppressed expression of these proteins induced by cisplatin (CDDP) and etoposide in SGC-7901 cells, but also inhibited expression of these proteins in the SGC-7901/CDDP cells. Meanwhile, the proliferation-suppressing and apoptosis-inducing capacities of CDDP and etoposide were enhanced following combined treatment with EGb 761. Moreover, EGb 761 reduced the malondialdehyde (MDA) content and elevated the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the tumor cells. These results confirmed that activation of the KSR1-mediated ERK1/2 signaling pathway may contribute to tumorigenesis, metastasis and chemoresistance of human gastric cancer. EGb 761 enhanced the chemotherapy sensitivity and reversed the chemoresistance through suppression of the KSR1-mediated ERK1/2 pathway in gastric cancer cells, and the underlying mechanism may be related to its antioxidative activity.

Systematic chemotherapy is indispensable for gastric cancer patients with advanced stage disease, but the occurrence of chemoresistance drastically limits treatment effectiveness. There is a tremendous need for identifying the underlying mechanism of chemoresistance. NIK‑ and IKKβ‑binding protein (NIBP) (also known as TRAPPC9, trafficking protein particle complex 9) is a regulator of the cytokine‑induced NF‑κB signaling pathway which has been proven to play pivotal roles in the progression of various malignancies. Nevertheless, it is still ambiguous whether NIBP is involved in the chemoresistance of gastric cancer. The aim of the present study was to investigate the effect of NIBP on chemotherapy resistance of gastric cancer (GC) and to research the mechanisms of Ginkgo biloba extract 761 (EGb 761®) on reversing chemoresistence which has been confirmed in our previous study. In the present study, the results of immumohistochemisty revealed that the positive staining rates of NIBP, NF‑κB p65 and NF‑κB p‑p65 in gastric cancer tissues were obviously higher than those in normal tissues. Furthermore, a close correlation was found to exist between the expression of NIBP and NF‑κB p65 (p‑p65) in gastric cancer tissues. Moreover, the overexpression of NIBP was closely related to tumor differentiation, depth of invasion, clinical stage and lymphatic metastasis in gastric cancer. Western blot analysis, real‑time PCR, MTT assay and flow cytometric analysis were performed and the results demonstrated that compared with the gastric cancer SGC‑7901 cells, the expression of NIBP, NF‑κB p65, NF‑κB p‑p65 and mesenchymal marker vimentin were significantly increased in gastric cancer multidrug‑resistant SGC‑7901/CDDP cells, and the epithelial cell marker ZO‑1 was significantly decreased. Meanwhile, it was found that SGC‑7901/CDDP cells were accompanied by spindle‑like mesenchymal appearance and upregulation of stem cell marker CD133 which has been verified to be an upstream regulatory gene of epithelial‑mesenchymal transition (EMT). Further research confirmed that downregulation of NIBP by Ginkgo biloba extract (EGb) 761 EGb 761 suppressed the cis‑diamminedichloroplatinum(II) (CDDP)‑induced NF‑κB signaling pathway, EMT and the expression of CD133 in SGC‑7901 and SGC‑7901/CDDP cells. Altogether, these data indicate that the NIBP‑regulated NF‑κB signaling pathway plays a pivotal role in the chemoresistance of gastric cancer by promoting CD133‑induced EMT.

Sphingosine kinase 1 (SphK1) plays an important role in colorectal carcinoma metastasis. However, whether SphK1 modulates epithelial-mesenchymal transition (EMT)-related marker expression and the underlying mechanisms remain unclear. In this study, in order to clarify this issue, we used various colorectal cancer (CRC) cell lines, Caco2, HT29, RKO and HCT116. Each of the cell lines was divided into 3 groups as follows: the control group, SKI-Ⅱ (SphK1 inhibitor) group and PF-562271 [focal adhesion kinase (FAK) inhibitor] group. The migratory ability of the cells was examined by Transwell chamber assay. The mRNA and protein expression levels of SphK1, FAK (p-FAK), Slug, vimentin, N-cadherin and E-cadherin were detected by PCR and western blot analysis, respectively. The results revealed that the suppression of SphK1 reduced the cell migratory ability, and decreased the expression of Slug, vimentin and N-cadherin; however, the expression of E-cadherin was increased. Moreover, the inhibition of SphK1 reduced the expression of p-FAK. The inhibition of FAK (p-FAK) also decreased the cell migratory ability, and decreased the expression of Slug, vimentin and N-cadherin, whereas the expression of E-cadherin was increased. Thus, our data suggest that SphK1 modulates the expression of EMT-related markers and cell migration by regulating the expression of p-FAK in CRC cells. Thus, SphK1 may play a functional role in mediating the EMT process in CRC.

Hydrolysis of several polysaccharides in neutral and weak acid environment has been shown to exhibit autocatalytic behavior. Because the pH value of the solution decreases during hydrolysis, it has been proposed that proton is the catalyst of the autocatalytic reaction. We monitored the hydrolysis of difructose anhydride III (DFA III) in both strong and weak acid environment using Raman spectroscopy and found that it is also an autocatalytic reaction. Its Raman signatures were analyzed with ab initio method. When the reaction product, fructose, is added in the beginning of the reaction, the speed of hydrolysis increases to a magnitude that cannot be explained by the rate enhancement due to a decrease in the pH value, indicating that proton alone is not an effective catalyst for the reaction. It is the combination of proton and a certain form of reaction product such as monosaccharide or its derivatives that catalyzes the hydrolysis of difructose anhydride III. Similar results are observed in the hydrolysis of cellobiose, suggesting the universality of this autocatalytic reaction. Our findings provide the first clue to a new autocatalytic pathway in the hydrolysis of polysaccharides.

Trypsin (EC 3.4.21.4) hydrolysis of food proteins are done at the optimum pH (7.8) and temperature (37 °C). Little information is available on the effect of sub-optimal conditions on hydrolysis. Bovine β-lactoglobulin (β-Lg) was hydrolysed by trypsin under acidic pH (pH 4–7) between 20 and 60 °C and the substrate concentration from 2.5% to 15% (w/v) and compared with hydrolysis at pH 7.8 and 37 °C. Aliquots were taken at different times ( t = 0 up to 10 min). Samples were analysed using matrix-assisted laser desorption/ionisation time-of-flight tandem mass spectrometry (MALDI–TOF–MS/MS) with α-cyano-4-hydroxycinnamic acid (HCCA) and 2,5-dihydroxyacetophenone (DHAP) matrices. Hydrolysis patterns of β-Lg were generally similar at pH 7.8, 7, 6 and 5 while at pH 4 fewer peptides were detected except a unique fragment f(136–141). The different cleavage sites of β-Lg showed low resistance to trypsin at optimum conditions and pH 7 while being random and simultaneous. At lower pH, some cleavage sites showed increased resistance, while hydrolysis was relatively slow and ordered. Initial attack by trypsin occurred at Arg 40 –Val 41 , Lys 141 –Ala 142 and Arg 148 –Leu 149 resistance was at Lys 60 –Trp 61 , Arg 124 –Thr 125 and Lys 135 –Phe 136 . Five domains were identified based on β-Lg resistance to trypsin in the order f(1–40) f(92–138) > f(139–162). Results suggest that hydrolysis away from trypsin optimum offer better hydrolysis process control and different peptides. This strategy may be used to protect target bioactive or precursor peptides, or avoid the production of unwanted peptides.

Using statistical analysis of the scanning tunneling microscopy images of the 3 × 4-In surface magic cluster (SMC) arrays on Si(100)1 × 2 substrate at low In coverages, the main regularities of the space distribution of the nucleated SMCs have been established. It has been found that a nucleated SMC perturbs the surface potential relief within a limited zone around itself in a way that some of the sites in the zone demonstrate a great preference for nucleating a new cluster, while in the other sites the nucleation is greatly suppressed. Outside the zone, the nucleation probability is close to that of the random nucleation simulated using Monte-Carlo technique. Energetic background of the observed phenomena has been proved using density-functional theory calculations, which clearly demonstrate that the lower the formation energy the higher the occurrence probability of a given cluster-pair configuration.

Xanthogranulomatous pyelonephritis is an uncommon form of chronic bacterial pyelonephritis characterized by the destruction of renal parenchyma and the presence of granulomas, abscesses, and collections of lipid-laden macrophages (foam cells) replacing the renal parenchyma. This case report illustrates the clinical course of bilateral diffuse xanthogranulo-matous pyelonephritis with a subtle manifestation in contrast to those typically presenting with fever, flank pain or urinary tract infection. The patient therefore received supportive treatment for 18 months without hemodialysis, instead of the curative treatment, bilateral nephrectomy, which would have caused immediate loss of residual renal function and dependence on hemodialysis.

Surface magic clusters (SMCs) are clusters exhibiting enhanced stability at certain sizes on a particular surface. Through the formation of SMCs, it is possible to grow an ensemble of nanostructures on a surface with extremely small or essentially zero size dispersion. Such an ensemble of nanostructures with identical size and atomic structure is highly desirable for certain nanotechnologies that rely on the homogeneity in the physical and chemical properties of the constituent nanostructures. This review summarizes current experimental observations and understanding of SMCs and discusses the most recent progress in the formation of a two-dimensional lattice of SMCs, whose constituent clusters have not only identical size and structure but also the same local environment due to the translational symmetry of the system.

Vascular access malfunction, usually presenting with an inadequate access flow (Qa), is the leading cause of morbidity and hospitalization in hemodialysis (HD) patients. Many methods of thermal therapy have been tried for improving Qa but with limited effects. This randomized trial was designed to evaluate the effect of far-infrared (FIR) therapy on access flow and patency of the native arteriovenous fistula (AVF). A total of 145 HD patients were enrolled with 73 in the control group and 72 in the FIR group. A WS TY101 FIR emitter was used for 40 min, and hemodynamic parameters were measured by the Transonic HD(02) monitor during HD. The Qa(1)/Qa(2) and Qa(3)/Qa(4) were defined as the Qa measured at the beginning/at 40 min later in the HD session before the initiation and at the end of the study, respectively. The incremental change of Qa in the single HD session with FIR therapy was significantly higher than that without FIR therapy (13.2 +/- 114.7 versus -33.4 +/- 132.3 ml/min; P = 0.021). In comparison with control subjects, patients who received FIR therapy for 1 yr had (1) a lower incidence (12.5 versus 30.1%; P < 0.01) and relative incidence (one episode per 67.7 versus one episode per 26.7 patient-months; P = 0.03) of AVF malfunction; (2) higher values of the following parameters, including Delta(Qa(4) - Qa(3)) (36.2 +/- 82.4 versus -12.7 +/- 153.6 ml/min; P = 0.027), Delta(Qa(3) - Qa(1)) (36.3 +/- 166.2 versus -51.7 +/- 283.1 ml/min; P = 0.035), Delta(Qa(4) - Qa(2)) (99.2 +/- 144.4 versus -47.5 +/- 244.5 ml/min; P < 0.001), and Delta(Qa(4) - Qa(2)) - Delta(Qa(3) - Qa(1)) (62.9 +/- 111.6 versus 4.1 +/- 184.5 ml/min; P = 0.032); and (3) a better unassisted patency of AVF (85.9 versus 67.6%; P < 0.01). In conclusion, FIR therapy, a noninvasive and convenient therapeutic modality, can improve Qa and survival of the AVF in HD patients through both its thermal and its nonthermal effects.

This paper presents the design and fabrication of a novel piezoelectric actuator for a gas micro pump with check valve having the advantages of miniature size, light weight and low power consumption. The micro pump is designed to have eight major components, namely a stainless steel upper cover layer, a piezoelectric actuator, a stainless steel diaphragm, a PDMS chamber layer, two stainless steel channel layers with two valve seats, a PDMS check valve layer with two cantilever-type check valves and an acrylic substrate. A prototype of the gas micro pump, with a size of 52 mm × 50 mm × 5.0 mm, is fabricated by precise manufacturing. This device is designed to pump gases with the capability of performing the self-priming and bubble-tolerant work mode by maximizing the stroke volume of the membrane as well as the compression ratio via minimization of the dead volume of the micro pump chamber and channel. By experiment apparatus setup, we can get the real-time values of the flow rate of micro pump and the displacement of the piezoelectric actuator, simultaneously. The gas micro pump obtained higher output performance under the sinusoidal waveform of 250 Vpp. The micro pump achieved the maximum pumping rates of 1185 ml/min and back pressure of 7.14 kPa at the corresponding frequency of 120 and 50 Hz., {"references":["H Kim, W H Steinecker, G R Lambertus, A A Astle, K Najafi, E T Zellers,\nL Bernal, P Washabaugh, K D Wise, \"Integrated high-pressure 4-stage\nmicro pump for high speed micro chromatography,\" Proc. 10th Int. Conf.\nMiniaturized Systems for Chemistry and Life Science (uTAS '06),\nTokyo, Japan, pp. 1037–1039, 2006.","P Rodgers, V Eveloy, M Pecht, \"Extending the limits of aircooling in\nmicroelectronic equipment,\" Proc. 6th Int. Conf. Thermal, Mechanical\nand Multiphysics Simulation and Experiment in Micro-electronics and\nMicro-systems, EuroSimE, Berlin, Germany, pp. 695–701, 2005.","Y Wang, G Yuan, Y K Yoon, M G Allen, S A Bidstrup, \"Large eddy\nsimulation (LES) for synthetic jet thermal management,\" Int. J. Heat\nMass Transfer, Vol. 49, pp. 2173–2179, 2006.","L Arana, S Schaevitz, A Franz, M A Schmidt, K F Jensen, \"A\nmicrofabricated suspended-tube chemical reactor for thermally efficient\nfuel processing,\" J. Microelectromech. Syst. Vol. 12, pp. 600–612, 2003.","N T Nguyen, X Huang and T K Chuan, \"MEMS-micro pumps: a review,\"\nASME J. Fluids Eng. Vol. 124, pp. 384-392, 2002.","D J Laser and J G Santiago, \"A review of micro pumps,\" J. Micromech.\nMicroeng. Vol. 14, pp. R35–R64, 2004.","P Woias, \"Micro pumps-past, progress and future prospects,\" Sensors\nActuators B Vol. 105, pp. 28–38, 2005.","H Kim, K Najafi, L P Bernal, \"Gas micro pumps, \" in: Y. Gianchandani,\nO. Tabata, H. Zappe (Eds.), Comprehensive Microsystems, vol. 2,\nElsevier Ltd., The Netherlands, pp. 273-299, 2008.","L Chen, S Lee, J Choo and E K Lee, \"Continuous dynamic flow micro\npumps for microfluid manipulation,\" J. Micromech. Microeng. Vol. 18,\npp. 1–22, 2008.\n[10] F Amirouche, Y Zhou and T Johnson, \"Current micro pump technologies\nand their biomedical applications,\" Microsyst. Technol. Vol. 15 pp.\n647-666, 2009.\n[11] H Andersson, W van der Wijngaart, P Nilsson, P Enoksson and G\nStemme, \"A valve-less diffuser micro pump for microfluidic analytical\nsystems,\" Sensors Actuators B Vol. 72, pp. 259–265, 2001.\n[12] B Fan, G Song and F Hussain, \"Simulation of a piezoelectrically actuated\nvalveless micro pump,\" Smart Mater. Struct. Vol. 14, pp. 400–405, 2005.\n[13] J Kang, J V Mantese and G W Auner, \"A self-priming, high performance,\ncheck valve diaphragm micro pump made from SOI wafers,\" J.\nMicromech. Microeng. Vol. 18, pp. 1-8, 2009.\n[14] R. Rapp, W K Schomburg, D. Maas, J. Schulz and W. Stark, \"LIGA\nmicro pump for gases and liquids,\" Sens. Actuators A Vol. 40, pp. 57–61,\n1994.\n[15] S Boehm, W Olthuis and P Bergveld, \"A plastic micro pump constructed\nwith conventional techniques and materials,\" Sensors Actuators A Vol.\n77, pp. 223–228, 1999.\n[16] S. Santra, P. Holloway, D. Batich, \"Fabrication and testing of a\nmagnetically actuated micro pump,\" Sens. Actuators B Vol. 87, pp. 358–\n364, 2002.\n[17] T Q Truong and N T Nguyen, \"A polymeric piezoelectric micro pump\nbased on lamination technology,\" J. Micromech. Microeng. Vol. 14,\npp.632–638, 2004.\n[18] J H Kim, K T Lau, R Shepherd, Y Wu, G Wallace and D Diamond,\n\"Performance characteristics of a polypyrrole modified\npolydimethylsiloxane (PDMS) membrane based microfluidic pump,\"\nSensors and Actuators A Vol. 148, pp. 239–244, 2008."]}

In this paper, we provide a useful technology to fabricate a long-range ordered nanoparticle array with a feature size under 30 nm. By adjusting the incident angle of Ar + beam milling on a U-shaped barrier layer of anodic alumina oxide, we can create a long-range ordered nanoaperture array with samples prepared by a focused-ion-beam-guided process. Compared to the naturally self-organized alumina nanochannels, the FIB-guided process has increased long-range ordering and uniformity of aperture size, and the aperture size can be varied by changing the grazing angle. The nanoaperture membrane can be used as a contact-mask and its undercut structure has another advantage for nanolithography. This technique could be extensively applied to the manufacturing of advanced nanodevices in large areas and as a catalyst to fabricate one-dimensional nanosized materials. (Some figures in this article are in colour only in the electronic version)

We demonstrate a process to selectively tune the pore size of an individual nanochannel in an array of high-aspect-ratio anodic aluminum oxide (AAO) nanochannels in which the pore sizes were originally uniform. This novel process enables us to fabricate arrays of AAO nanochannels of variable sizes arranged in any custom-designed geometry. The process is based on our ability to selectively close an individual nanochannel in an array by using focused ion beam (FIB) sputtering, which leads to redeposition of the sputtered material and closure of the nanochannel with a capping layer of a thickness depending on the energy of the FIB. When such a partially capped array is etched in acid, the capping layers are dissolved after different time delays due to their different thicknesses, which results in differences in the time required for the following pore-widening etching processes and therefore creates an array of nanochannels with variable pore sizes. The ability to fabricate such AAO templates with high-aspect-ratio nanochannels of tunable sizes arranged in a custom-designed geometry paves the way for the creation of nanophotonic and nanoelectronic devices.

STUDY DESIGN: To investigate the specific mechanisms by which Golgi phosphoprotein 3 (GOLPH3) affects the progression of gastric cancer and to explore its clinical significance. METHODS: Immunohistochemical analysis was used to evaluate the correlations between GOLPH3, phosphorylated mTOR (p-mTOR), phosphorylated Akt (p-Akt), phosphorylated p70S6 (p-p70S6), phosphorylated 4E-BP1 (p-4E-BP1) and the clinicopathological features of gastric cancer. The mRNA expression levels of GOLPH3, mTOR, Akt, p70S6 and 4E-BP1 in gastric cancer, carcinoma-adjacent and paired normal tissue were analyzed using RT-PCR. Western blotting was used to determine the protein expression of GOLPH3, p-mTOR, p-Akt, p-p70S6 and p-4E-BP1 in tissues. RESULTS: High expression protein levels of GOLPH3, p-AKT, p-mTOR, p70S6, p-4E-BP1 were positively associated with histological grade (p

This work is licensed under a Creative Commons Attribution-NonCommercialNoDerivs 3.0 Unported License.-- et al., To exploit Rashba effect in a 2D electron gas on silicon surface for spin transport, it is necessary to have surface reconstruction with spin-split metallic surface-state bands. However, metals with strong spin-orbit coupling (e.g., Bi, Tl, Sb, Pt) induce reconstructions on silicon with almost exclusively spin-split insulating bands. We propose a strategy to create spin-split metallic bands using a dense 2D alloy layer containing a metal with strong spin-orbit coupling and another metal to modify the surface reconstruction. Here we report two examples, i.e., alloying Bi/Si(111) √3 × √3 reconstruction with Na and Tl/Si(111)1 × 1 reconstruction with Pb. The strategy provides a new paradigm for creating metallic surface state bands with various spin textures on silicon and therefore enhances the possibility to integrate fascinating and promising capabilities of spintronics with current semiconductor technology., Part of this work was supported by the Russian Foundation for Basic Research (Grant Nos 12-02-00416, 13-02-00837, 13-02-12110, 14-02-31070) and the NSh-167.2014.2.

The pathogenesis and replication sites of GB virus-C/hepatitis G virus (GBV-C/HGV) in humans remain unclear. The presence of GBV-C/HGV and hepatitis C virus (HCV) RNA sequences in matched serum, peripheral blood mononuclear cells (PBMC) and liver samples in 10 patients with GBV-C/HGV infection, 8 of whom were coinfected with HCV was explored. Positive- and negative-strand GBV-C/HGV and HCV RNA were detected by strand-specific reverse-transcription polymerase chain reaction (RT-PCR), and virus titers were quantified by competitive PCRs. Positive-strand GBV-C/HGV RNA was detected in 7 of 10 PBMC samples of the patients with serum GBV-C/HGV RNA, but negative-strand GBV-C/HGV RNA was not found in these cells. Positive-strand GBV-C/HGV RNA was found in 9 liver samples, and 2 (22%) of them also had negative strand. In contrast, negative-strand HCV RNA was frequently found in PBMC and liver samples. A positive correlation between the titer of viral RNA in liver tissue and that in serum sample was demonstrated in HCV infection, but not in GBV-C/HGV infection. These findings suggest that liver and PBMC are not the major replication sites for GBV-C/HGV and that GBV-C/HGV is not a primary hepatotropic virus.

We found that patients with dual HBV and GBV-C/HGV infection had comparable serum HBV DNA positivity and mean virus concentration compared with age-matched HBV carriers, and those with triple infection had a significantly lower HBV DNA positivity. Serum HCV RNA positivity and mean virus titer were similar between HCV carriers with or without GBV-C/HGV co-infection, and those with GBV-C/HGV co-infection seemed to have a lower serum ALT level. These data suggest that GBV-C/HGV infection exerts no significant suppression on levels of chronic hepatitis B or hepatitis C viremia.

Self-assembly of atoms or molecules on a crystal surface is considered one of the most promising methods to create molecular devices. Here we report a stepwise self-assembly of C₆₀ molecules into islands with unusual shapes and preferred sizes on a gold-indium-covered Si(111) surface. Specifically, 19-mer islands prefer a non-compact boomerang shape, whereas hexagonal 37-mer islands exhibit extraordinarily enhanced stability and abundance. The stepwise self-assembly is mediated by the moire interference between an island with its underlying lattice, which essentially maps out the adsorption-energy landscape of a C₆₀ on different positions of the surface with a lateral magnification factor and dictates the probability for the subsequent attachment of C₆₀ to an island's periphery. Our discovery suggests a new method for exploiting the moire interference to dynamically assist the self-assembly of particles and provides an unexplored tactic of engineering atomic scale moire magnifiers to facilitate the growth of monodispersed mesoscopic structures.

Focused ion beam lithography and a two-step anodization have been combined to fabricate a vertical fan-out platform containing an array of unique probes. Each probe comprises three anodic alumina nanochannels with a fan-out arrangement. The lithography is used to pattern an aluminum sheet with a custom-designed array of triangular ‘cells’ whose apexes are composed of nanoholes. The nanoholes grow into straight nanochannels under proper voltage in the first-step anodization. The second step uses a doubled voltage to induce lateral repulsion among the nanochannels’ growth fronts originating in the same cell. Therefore, the fronts fan out. The repulsion roots in the inter-front distance being shorter than the naturally favoured length, which increases with anodization voltage. The fan-out evolution continues until the growth fronts originating in all the cells evolve into a close-packed two-dimensional hexagonal lattice whose spacing is identical to the favoured one. The chemical and physical mechanisms behind the fan-out fabrication are discussed. This novel fan-out platform facilitates probing and handling of many signals from different areas on a sample’s surface and is therefore promising for applications in detection and manipulation at the nanoscale level.

BACKGROUND & AIMS: In human hepatocellular carcinoma, restriction fragment length polymorphism analysis has shown frequent allelic loss on chromosomes 4q and 16q. To better define the commonly affected region for further positional cloning of the putative tumor-suppressor genes contained in these two chromosome arms, microsatellite polymorphism analysis was conducted to analyze extensively the allelic loss on both chromosome loci. METHODS: DNA from 42 pairs of large hepatocellular carcinoma (> 5 cm) and corresponding nonneoplastic liver tissues were prepared. Allelic loss on chromosome 4q and 16q was investigated by 13 or 12 sets of microsatellite polymorphic markers. RESULTS: The frequency of allelic loss on chromosome 16q was 70%, and the common region was mapped to 16q22-23. An even higher frequency (77%) was found on chromosome 4q with the common region mapped to 4q12- 23. The allelic loss of chromosome 4q was significantly associated with hepatocellular carcinoma of elevated serum alpha-fetoprotein but not with those of normal level (91% vs. 30%; Fisher's Exact Test, two- tailed P=1.12 x 10(-4)). CONCLUSIONS: The results form the basis for further positional cloning of putative tumor-suppressor genes on chromosome 4q and 16q. Moreover, the one on chromosome 4q might shed light on the mechanism of alpha-fetoprotein expression in hepatocellular carcinoma. (Gastroenterology 1996 Jan;110(1):184-92)

Sphingosine kinase (SphK) 1 is an oncogenic enzyme promoting transformation, proliferation, and survival of a number of human tumor cells. However, its effect on colon cancer cell behavior has not been fully clarified.SphK1 plasmid or SphK1 shRNA transfection and N,N-dimethylsphingosine (DMS) was used to regulate the expression and activity of SphK1 in colon cancer line LOVO. Cell proliferation, apoptosis, invasion, and protein expression were detected by MTT, flow cytometry, transwell chambers model, and western blot. The levels of metalloproteinases-2/9 (MMP-2/9) and urokinase plasminogen activator (uPA) were detected by ELISA.Overexpression of SphK1 after plasmid transfection markedly enhanced LOVO cell viability and invasiveness and reduced cell apoptosis. In contrast, inhibition of SphK1 by DMS and shRNA significantly suppressed cell viability and invasiveness but promoted cell apoptosis. SphK1 increased the constitutive expression of extracellular signal-regulated kinase1/2 (ERK1/2) but reduced the constitutive expression of p38 mitogen-activated protein kinase (MAPK). Blocking ERK1/2 pathway inhibited the biological effects induced by overexpression of SphK1. Blocking p38 MAPK pathway reversed the effects of DMS and SphK1 shRNA. Moreover, SphK1 was required for the production of MMP-2/9 and uPA in tumor cells, which was suppressed by ERK1/2 inhibitor U0126, but enhanced by the p38 MAPK inhibitor SB203580.SphK1 enhances colon cancer cell proliferation and invasiveness, meanwhile suppressing cell apoptosis. SphK1 promoting the secretion of MMP-2/9 and uPA via activation of ERK1/2 and suppression of p38 MAPK pathways maybe the molecular mechanisms for its regulation of the malignant behavior of colon cancer cell.

Depositing particles randomly on a 1D lattice is expected to result in an equal number of particle pairs separated by even or odd lattice units. Unexpectedly, the even-odd symmetry is broken in the self-selection of distances between indium magic-number clusters on a Si(100)-2×1 reconstructed surface. Cluster pairs separated by even units are less abundant because they are linked by silicon atomic chains carrying topological solitons, which induce local strain and create localized electronic states with higher energy. Our findings reveal a unique particle-particle interaction mediated by the presence or absence of topological solitons on alternate lattices.

Arrays of nanowires with identical length are fabricated by using ultrasound to remove the length fluctuation among nanowires, which are deliberately grown in burette-shaped nanochannels on an anodic anumina film. The process allows the fabrication of 10 micron Ag-nanowire arrays with length fluctuation as small as 0.09%. By integrating the process with a focused-ion-beam-based lithographic method to grow nanowires into selective nanochannels in an array, we fabricate arrays of uniform-length nanowires that are arranged in a custom-designed lateral geometry. The ability to fabricate such artificial nanomaterials paves the way for the exploitation of their unusual optical, electrical, and thermal properties.

Atomic layer deposition (ALD) has been used to grow zinc oxide (ZnO) into a template of anodic aluminum oxide with quasi-dendritic nanochannels to form quasi-dendritic nanostructures. The characteristic photoluminescence (PL) emission from the inner region of the quasi-dendritic ZnO nanostructure peaks at 397 nm while that from its outer region at 424 nm. In between the two regions, the PL peak shows monotonic shift. In other words, the different layers of the single quasi-dendritic ZnO nanostructure emit PL with graded wavelengths spontaneously. The red shift in the PL peak positions is likely to be caused by the change in local stoichiometry between Zn and O, which are resulted from the limited supply of materials through the quasi-dendritic nanochannels during the ALD. The process to fabricate such quasi-dendritic ZnO nanostructures with spontaneously graded emission could help expand applications of ZnO-based devices.

A 42-year-old woman underwent hemodialysis secondary to diabetic nephropathy. Total parathyroidectomy with forearm autograft was performed due to secondary hyperparathyroidism (HPT) complicated with calciphylaxis. Rapidly progressive enlargement of autograft with unusual "gourd-shape" developed, and then it was removed. Pathologic examination of the autograft disclosed multinodular hyperplasia. Residual parathyroid gland in the retrothyroid region was found later. Rapidly recurrent HPT originating from both the residual parathyroid tissues and the enlarged autograft within such short time after parathyroidectomy is rare in the literature. The multinodular hyperplasia pattern of the parathyroid gland may be a major factor for such rapid recurrence. In addition to good control of calcium and phosphate, regular follow-up of parathyroid hormone level and imaging studies of not only autografted gland at the forearm but also possibly residual parathyroid tissues at the neck are important for monitoring recurrence in maintenance hemodialysis patients after parathyroidectomy with forearm autograft, especially in those with pathologic type of nodular hyperplasia and calciphylaxis.

The structure of a type of surface magic cluster is determined by a combination of scanning tunneling microscopy, density-functional calculations, and dynamical low energy electron diffraction. The diffraction method is applicable because these clusters created through hierarchical self-organization of Ga deposited onto a $\mathrm{S}\mathrm{i}(111)\mathrm{\text{\ensuremath{-}}}7\ifmmode\times\else\texttimes\fi{}7$ surface have identical size and structure and form an ordered array with exact translational symmetry. The unprecedented detailed structure information provided by the diffraction measurement is consistent with direct microscopic imaging and theoretical calculations.

The ability to create an ensemble of mono-dispersed nanostructures is an important step towards the realization nanotechnology. The discovery of surface-magic-clusters (SMC), i. e. clusters exhibiting enhanced stability at certain sizes on a particular surface, has opened up the possibility of exploiting SMC formation for the growth of identical nanostructures on surfaces. Recently, it has been demonstrated that, under a well controlled deposition condition, several group III elements such as gallium can induce almost exclusive formation of SMC on the 7x7-reconstructed Si(111) surface, leading to the complete filling of the 7x7 half unitcells and the creation of unprecedented two-dimensional lattices of SMC. Based on scanning tunneling microscopy imaging studies, structure models for the SMC are proposed. Ab inito calculations of the model clusters are conducted and the results are compared with experiments.

A 64-year-old post-menopausal woman presented with dysuria, weakness and poor appetite that had lasted 3 months. A bilateral percutaneous nephrostomy (PCN) catheter was placed for bilateral hydroureteronephrosis at a local hospital, but malfunctioned due to blood clot formation. Physical examination revealed peritoneal signs. Laboratory test revealed leucocytosis, azotaemia with blood urea nitrogen (BUN) 93mg/dl, creatimine (Cr) 16.3mg/dl, and severe metabolic acidosis. Haemodialysis was initiated for uraemia. Computed tomography of the abdomen demonstrated the presence of ascites with peritoneal thickening in the lower peritoneal cavity, obstruction of the uterine outlet with intra-uterine fluid retention, tissue plane blurring between the uterine cervix and urinary bladder, and obstructive uropathy with the obstruction level at the bilateral uretero-vesical junction (Figures 1 and 2). Cervical cancer with pyometra was suspected and treated with dilation and curettage surgery, during which 150 c.c. of pus was drained out. Empiric antibiotics were given and sepsis resolved thereafter. A bilateral PCN catheter functioned well after repeated revisions. Haemodialysis was discontinued 3 weeks later (BUN 33mg/dl, Cr 2.8mg/dl). A biopsy of the cervix revealed squamous cell carcinoma with stromal invasion and the staging was IVA because of urinary bladder spreading. The patient recalled that she had suffered from intermittent vaginal spotting for the last 4 years, but had ignored it.

AIM: To investigate the effect of high mobility group A2 (HMGA2) gene silencing on gastric cancer MKN-45 cells in vitro. METHODS: HMGA2 short hairpin RNA (shRNA) expression plasmids were constructed, including a pair of random scrambled sequences. Human gastric cancer cell line MKN-45 cells were divided into three groups: blank control group (non-transfected cells), transfected group (cells transfected with HMGA2 shRNA recombinant plasmid) and scrambled sequence group (transfected with random scrambled plasmid). Cells were transfected with HMGA2 shRNA recombinant plasmids and scrambled plasmid in vitro, and the cells transfection efficiency was assayed by fluorescence microscopy. The HMGA2 messenger RNA (mRNA) expression was detected by reverse transcription polymerase chain reaction, gastric cancer cells apoptosis was detected by flow cytometry, cell proliferation was detected by methyl thiazol tetrazolium, and the protein expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), P27, caspase-9 and B-cell leukemia/lymphoma-2 (Bcl-2) were analyzed by Western blotting. RESULTS: Compared with the blank control group and the scrambled sequence group, the levels of HMGA2 mRNA and protein expression in the transfected group were significantly reduced (P < 0.05). The relative HMGA2 mRNA expression levels of the blank control group, transfected group and scrambled sequence group were 0.674 ± 0.129, 0.374 ± 0.048 and 0.689 ± 0.124, respectively. The relative HMGA2 protein expression levels of the blank control group, transfected group and scrambled sequence group were 0.554 ± 0.082, 0.113 ± 0.032 and 0.484 ± 0.123, respectively. Moreover, transfection with the scrambled sequence had no effect on the expression of HMGA2. After being transfected with shRNA for 24, 48 and 72 h, the cell apoptotic rates of the transfected group were 21.65% ± 0.28%, 39.98% ± 1.82% and 24.51% ± 0.93%, respectively, which significantly higher than those of blank control group (4.72% ± 1.34%, 5.83% ± 0.13% and 5.22% ± 1.07%) and scrambled sequence group (4.28% ± 1.33%, 7.87% ± 1.43% and 6.71% ± 0.92%). After 24, 48 and 72 h, the cell proliferation inhibition rates in the transfected group were 31.57% ± 1.17%, 39.45% ± 2.07% and 37.56% ± 2.32%, respectively; the most obvious cell proliferation inhibition appeared at 48 h after transfection. Compared with the blank control group and scrambled sequence group, after transfection of shRNA for 72 h, the protein expression levels of PI3K (0.042 ± 0.005 vs 0.069 ± 0.003, 0.067 ± 0.05), Akt (0.248 ± 0.004 vs 0.489 ± 0.006, 0.496 ± 0.104) and Bcl-2 (0.295 ± 0.084 vs 0.592 ± 0.072, 0.594 ± 0.109) were significantly reduced. The protein expression levels of P27 (0.151 ± 0.010 vs 0.068 ± 0.014, 0.060 ± 0.013) and caspase-9 (0.136 ± 0.042 vs 0.075 ± 0.010, 0.073 ± 0.072) were significantly upregulated. CONCLUSION: HMGA2 shRNA gene silencing induces apoptosis and suppresses proliferation of MKN-45 cells.

Porous anodic aluminum oxide (AAO) membranes have been widely used as templates for growing nanomaterials because of their ordered nanochannel arrays with high aspect ratio and uniform pore diameter. However, the intrinsic growth behavior of an individual AAO nanochannel has never been carefully studied for the lack of a means to fabricate a single isolated anodic alumina nanochannel (SIAAN). In this study, we develop a lithographic method for fabricating a SIAAN, which grows into a porous hemispherical structure with its pores exhibiting fascinating morphological evolution during anodization. We also discover that the mechanical stress affects the growth rate and pore morphology of AAO porous structures. This study helps reveal the growth mechanism of arrayed AAO nanochannels grown on a flat aluminum surface and provides insights to help pave the way to altering the geometry of nanochannels on AAO templates for the fabrication of advanced nanocomposite materials.

AIM: To investigate the effects of aspirin (acetylsalicylic acid) on proliferation and apoptosis of colorectal cancer cell line SW480 and its mechanism. METHODS: Cyclooxygenase (COX)-2 negative colorectal cancer cell line SW480 was treated with aspirin at concentrations of 2.5 mmol/L, 5.0 mmol/L, 10.0 mmol/L for different periods in vitro. Anti-proliferation effect of aspirin on SW480 was detected by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle and apoptosis were observed by flow cytometry (FCM). Transmission electron microscope (TEM) was used for morphological study. Apoptosis-associated genes were detected by immunohistochemical staining and Western blotting. RESULTS: Aspirin inhibited SW480 proliferation and induced apoptosis in a dose- and time-dependent manner. Treatment with different concentrations of aspirin significantly increased the proportions of cells at the G0/G1 phase and decreased the proportions of cells at the S- and G2/M phases in a concentration-dependent manner. Aspirin not only induced apoptosis but also caused cell necrosis at a high concentration as well. After treatment with aspirin, SW480 cells displayed typically morphological features of apoptosis and necrosis under TEM, and increased the Bcl-2 expression in cells, but the expression of Bax was down regulated. CONCLUSION: Aspirin inhibits proliferation and induces apoptosis of SW480 cells. Its anti-tumor mechanism may arrest cell cycle and shift Bax/Bcl-2 balance in cells.