Jinling Jiang

A single-electron-transistor-based analog/digital converter

We propose a novel analog/digital (A/D) converter based on single-electron transistors (SETs) in this paper. In the proposed A/D converter, the core cell is a SET module, composed of capacitive dividers and SET-based universal literal gates. The SET-based universal literal gate is similar to the well-known Tuckers inverter (J.R. Tucker, J. Appl. Phys., vol. 72, no. 9, pp. 4399-4413, 1992), but here it acts as digital conversion and the inputs of upper-SET and lower-SET are two opposite voltages. In the SET-based universal literal gate, by adjusting the some parameters, the output having about 50% duty ratio of square-wave-like and zero-output for zero-input (in contrast, high-voltage output for zero-input in Tuckers inverter) is obtained, where we fully utilize the periodic oscillation of SETs on gate voltage (/spl I.bar/V/sub G/=e/C/sub G/). We demonstrate the basic function of a 4-bit SET-based A/D converter using the MOSES program developed by K.K. Likharevs group, which is based on the so-called orthodox theory and Monte Carlo method. The results may be easily extended to higher-bit A/D converters.

Anti-angiogenesis participates in antitumor effects of metronomic capecitabine on colon cancer

Inhibitory effects and potential mechanisms of capecitabine metronomic chemotherapy on colon cancer were investigated in this study. Metronomic chemotherapy with fluorouracil or capecitabine inhibited proliferation of colon cancer cells both in vitro and in vivo. Capecitabine metronomic chemotherapy demonstrated equal effects as CTX metronomic chemotherapy. Metronomic capecitabine or CTX chemotherapy decreased vascular endothelial growth factor (VEGF) but elevated thrombospondin-1 (TSP-1) expression, reduced CEP levels and decreased microvessel density (MVD). These results indicated anti-angiogenesis may be correlated with the antitumor effects of metronomic capecitabine in colon cancer.

PKM2 promotes cell migration and inhibits autophagy by mediating PI3K/AKT activation and contributes to the malignant development of gastric cancer

Pyruvate kinase M2 (PKM2) is a key kinase of glycolysis and is characteristic of all proliferating cells. The role of PKM2 in gastric cancer (GC) is still ambiguous and yet to be determined. To better understand the role of PKM2 in both the migration and invasion of GC, we measured the expression of PKM2 in GC cell lines using qRT-PCR and western blot. The prognostic value of PKM2 was analyzed by Immunohistochemistry in a cohort containing 88 GC patients. PKM2 was knocked down by the short hairpin RNA plasmid vector in NCI-N87 and BGC-823 cells, and the biological behavior and downstream signaling pathways were also investigated in vitro. Subcutaneous xenografts and pulmonary metastases models were constructed in nude mice to compare the differences in tumorgenesis and metastasis after Knockdown of PKM2. Our results obtained from in vitro cell biological behavior, in vivo tumorigenicity studies, and primary GC samples revealed an oncogenic role for PKM2 in GC. Furthermore, for those GC patients who received radical resection, PKM2 might serve as a novel prognostic biomarker and target which would allow for a brand new treatment strategy for GC in the clinical settings.

Relationship between UGT1A1*6/*28 polymorphisms and severe toxicities in Chinese patients with pancreatic or biliary tract cancer treated with irinotecan-containing regimens

Purpose The aim of this retrospective study was to investigate the relationship between UGT1A1 polymorphisms and toxicities in Chinese patients with pancreatic or biliary tract cancer receiving irinotecan-containing regimens as the second- or third-line chemotherapy. Patients and methods A total of 36 patients with unresectable pancreatic cancer and 12 patients with unresectable biliary tract cancer were included. Approximately 33 patients were treated with FOLFIRI regimen, a chemotherapy regimen, where FOL stands for folinic acid, F for fluorouracil, and IRI for irinotecan (irinotecan 180 mg/m2 at day 1, CF 200 mg/m2 at day 1–2, 5-FU 400 mg/m2 at day 1–2, followed by continuous infusion of 5-FU 600 mg/m2 for 22 hours at day 1–2, every 2 weeks). The other 15 patients were treated with irinotecan monotherapy (180 mg/m2, every 2 weeks). UGT1A1*6/*28 polymorphisms were detected by direct sequencing. Results The frequencies of GG, GA, AA genotypes for UGT1A1*6 were 70.8% (n=34), 25.0% (n=12), and 4.2% (n=2), respectively. And those of TA6/TA6, TA6/TA7, TA7/TA7 for UGT1A1*28 were 79.2% (n=38), 18.8% (n=9), and 2.0% (n=1), respectively. A total of 22 patients (45.8%) had grade III–IV neutropenia, and six patients (12.5%) experienced grade III–IV diarrhea. The incidence of grade III–IV neutropenia in patients with UGT1A1*6 GA or AA genotype was 71.4%, which was significantly higher than that with GG genotype (35.3%, P=0.022). No relationship was found between grade III–IV neutropenia and UGT1A1*28 polymorphism. The statistical analysis between grade III–IV diarrhea and UGT1A1*6/*28 polymorphisms was not conducted in view of the limited number of patients. Conclusion In Chinese patients with pancreatic or biliary tract cancer administered irinotecan-containing regimens, those with UGT1A1*6 variant may have a high risk of severe neutropenia.

A characteristic biosignature for discrimination of gastric cancer from healthy population by high throughput GC-MS analysis

Early diagnosis of gastric cancer is crucial to improve patient′ outcome. A good biomarker will function in early diagnosis for gastric cancer. In order to find practical and cost-effective biomarkers, we used gas chromatography combined mass spectrometer (GC-MS) to profile urinary metabolites on 293 urine samples. Ninety-four samples are taken as training set, others for validating study. Orthogonal partial least squares discriminant analysis (OPLS-DA), significance analysis of microarray (SAM) and Mann-Whitney U test are used for data analysis. The diagnostic value of urinary metabolites was evaluated by ROC curve. As results, Seventeen metabolites are significantly different between patients and healthy controls in training set. Among them, 14 metabolites show diagnostic value better than classic blood biomarkers by quantitative assay on validation set. Ten of them are amino acids and four are organic metabolites. Importantly, proline, p-cresol and 4-hydroxybenzoic acid disclose outcome-prediction value by means of survival analysis. Therefore, the examination of urinary metabolites is a promising noninvasive strategy for gastric cancer screening.

Deubiquitinating enzyme USP20 is a positive regulator of Claspin and suppresses the malignant characteristics of gastric cancer cells

The aim of the present study was to investigate the clinical significance, the biological function and the mechanisms of USP20 in gastric cancer. The expression of USP20 in 89 pairs of primary gastric cancer and peritumoral gastric tissues specimens were measured by immunohistochemistry. The correlation of USP20 expression with the survival and the clinicopathological characteristics of patients were analyzed. Moreover, the underlying mechanisms of ectopic USP20 expression and its impact on GC cells were also investigated. We found that the expression of USP20 is relatively low in GC tissues and negatively correlated with tumor size, tumor invasion and TNM staging. High expression of USP20 in GC predicted longer survival. Experimentally, small interfering RNA-mediated knockdown of USP20 expression significantly promoted cell proliferation, accelerated G1-S phase transition and attenuated the autophagy activity. Overexpression of USP20 led to the inhibition of proliferation, G1-S cell cycle transition delay and autophagy activation. Mechanistically, we confirmed that silencing the expression of USP20 in GC cells could reduce Claspin protein levels without altering Claspin mRNA levels, which is involved in the antitumor activity of USP20. Furthermore, the expression level of Claspin was relatively higher in peritumoral tissue than that of GC tissues and higher expression of Claspin in GC was also correlated with good prognosis of patients. Given its pivotal role in gastric tumorigenesis and progression, USP20 functioned as the tumor suppressor in GC and possessed promising value to be a therapeutic target for GC.

An improved three-state master equation model for capacitively coupled single-electron transistor

In this paper, we develop an improved semi-classical steady-state model for capacitively coupled single-electron transistor (SET). This SET model is based on the three-state steady-state master equation, but has some revision at different device parameters, and is thus called the improved three-state master equation model. We calculate I/sub DS/-U/sub DD/, I/sub DS/-U/sub G/, and G/sub DS/-U/sub DD/ characteristics for different device parameters. We also present corresponding characteristics calculated by the Monte Carlo method and the full master equation method in most cases. The results demonstrate that the new approach is comparable to the Monte Carlo method and the full master equation method in precision, even in the high voltage region of V/sub DS/, and it simplifies the calculation and improves the speed of numerical simulation. This model can easily be embedded in the SPICE program. Of course, the validity of this embedded model depends on whether the SET can be regarded as a separate component in the circuit.

Metronomic chemotherapy remodel cancer‑associated fibroblasts to decrease chemoresistance of gastric cancer in nude mice

The present study aimed to evaluate whether capecitabine or 5-fluorouracil (5-Fu) chemotherapy with the metronomic pattern may cause significant chemoresistance compared with the traditional pattern, and whether CAFs are involved in drug resistance. SGC-7901 cells were subcutaneously injected into the nude mice, and the mice were divided into five groups: The control group, intraperitoneally injected with normal saline; the 5-Fu conventional dose group [5-Fu maximum tolerated dose (MTD) group], intraperitoneally injected with 50 mg/kg, twice per week for 2 weeks, with an 1-week discontinuation for 6 weeks; the capecitabine conventional dose group (capecitabine MTD group), intragastric 500 mg/kg, twice per week for 2 weeks, with a 1-week discontinuation for 6 weeks; the 5-Fu metronomic group [5-Fu low-dose metronomic (LDM) group], intraperitoneally injected with 15 mg/kg, twice a week for 6 weeks; and the capecitabine metronomic group (capecitabine LDM group), intragastric administration at 200 mg/kg, twice a week for 6 weeks. The chemotherapy resistance markers [glutathione transferase Pi (GSTP) and multidrug resistance protein 1 (MDR1)] were detected by immunohistochemical staining (IHC), and the association of the expression of these markers with the chemotherapy administration patterns was analyzed. Vascular endothelial growth factor (VEGF) and the cancer-associated fibroblast (CAF) marker α-smooth muscle actin were also examined by IHC to illustrate the possible mechanism of chemoresistance. The expression of GSTP and MDR1 in the MTD groups was significantly higher compared with those of the LDM groups (P<0.01). Furthermore, the number of CAFs and the level of VEGF in the MTD groups were significantly higher compared with those of the LDM groups (P<0.05). The low dose metronomic chemotherapy did not increase the risk of chemoresistance compared with the conventional dose traditional chemotherapy in terms of capecitabine or 5-Fu, the increasing amount of CAFs in the microenvironment of cancer cell following therapy may protect cell from capecitabine or 5-Fu via producing VEGF to increase vascularization.

Design and analysis of a high speed operational amplifier made by 60 nm gate-length MOSFETs

In this paper, a high speed operational amplifier (op amp) with 60 nm gate length MOSFET (nano-MOSFET) is presented. Cascode input stage is implemented to improve frequency response. After verifying the availability of cascode form in designing high speed op amp via SPICE model, we give simulation results to prove the speed of cascode op amp has no advantage compared with simple two-stage op amp in this ultra-short channel occasion. Our simulation also suggest it is important to choose transistor parameter, as small output resistance can severely deteriorate circuit performance.

HGF derived from cancer‑associated fibroblasts promotes vascularization in gastric cancer via PI3K/AKT and ERK1/2 signaling

Cancer‑associated fibroblasts (CAFs) are predominate cells in tumor stroma and play a key role in tumor progression. Hepatocyte growth factor (HGF) is a cytokine mainly derived from fibroblasts. In the present study, we reported that HGF significantly promoted angiogenesis of human umbilical vein endothelial cells (HUVECs) and vasculogenic mimicry (VM) formation of gastric cancer cells, respectively, by increasing cell proliferation and migration. In addition, mosaic vessels formed by HUVECs and gastric cancer cells were also increased with treatment of recombinant human HGF and conditioned medium from CAFs. The opposite results were achieved in HGF‑neutralized groups. In accordance with these observations, we determined that phosphorylation of AKT and ERK1/2 were upregulated in HUVECs and gastric cancer cells with HGF treatment and co‑culture with CAFs. Both AKT inhibitor LY294002 and ERK1/2 inhibitor U0126 reduced the ability of angiogenesis and VM formation, as well as mosaic vessel formation induced by HGF. Gene Set Enrichment Analysis and correlation analysis were performed to confirm our findings. In conclusion, CAF‑derived HGF promotes angiogenesis, VM and mosaic vessel formation via PI3K/AKT and ERK1/2 signaling in gastric cancer and HGF may serve as a potential therapeutic target for cancer anti‑vascular treatment.