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Pancreatic cancer is a malignant disease with poor prognosis. Emerging evidences have showed that miR-597-5p is closely related to tumor development. However, the functional roles of miR-597-5p in pancreatic cancer remain unknown. This study aimed to investigate the expression of miR-597-5p in pancreatic cancer tissues and cells, and explored its regulatory mechanism during pancreatic cancer progression. Pancreatic cancer and adjacent tissues were obtained to detect the expression of miR-597-5p by RT-qPCR. Cell growth, apoptosis, and related protein expression were, respectively, tested by CCK-8 assay, cell formation, wound healing, Transwell assay, flow cytometry, and western blotting. Finally, the pancreatic cancer mice model was constructed. In vitro and in vivo results showed that miR-597-5p expression was down-regulated in pancreatic cancer tissues and cell lines, and increased the overall survival of pancreatic cancer patients. Moreover, miR-597-5p decreased pancreatic cancer cell viability, reduced relative wound width, suppressed colony formation and decreased invasive cell number, as well as reduced the expression of proliferating cell nuclear antigen (PCNA), Ki67, Cyclin D1, N-cad, and Bcl-2. Meanwhile, it increased pancreatic cancer cell apoptosis and the expression of E-cad, cleaved caspase 3, and Bax. The dual-luciferase reporter assay confirmed miR-597-5p could directly target e-twenty six like-1 (ELK1) oncogene. The reduction of cell growth and the induction of cell apoptosis induced by miR-597-5p were reversed by ELK1. In addition, miR-597-5p inhibited the growth of pancreatic cancer in vivo. This study demonstrated that miR-597-5p may be a novel suppressor of pancreatic cancer. It inhibits pancreatic cancer cell growth and promotes apoptosis by the down-regulation of ELK1 in vitro and in vivo.

Thioredoxin (Trx) is a hydrogen acceptor of ribonucleotide reductase and a regulator of some enzymes and receptors. It has been previously shown that significantly elevated levels of Trx expression are associated with the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), but it is not clear how Trx regulates the effects of hydrogen peroxide (H2O2) on myogenic differentiation of BMSCs. Here, we report that rat BMSCs treated with a high dose (150 µm) of H2O2 exhibited a significant reduction in viability, cell cycling, and superoxide dismutase and glutathione peroxidase levels, and an increase in reactive oxygen species and malondialdehyde levels, which was accompanied by reductions in protein kinase B activation and forkhead Box O1, myogenic differentiation 1 and myogenin expression during myogenic differentiation. Furthermore, treatment with recombinant human Trx significantly mitigated the effects of H2O2 on the myogenic differentiation of BMSCs, and this was abrogated by cotreatment with wortmannin [a specific phosphatidylinositol 3‐kinase inhibitor]. In summary, our results suggest that treatment with recombinant human Trx mitigates H2O2‐induced oxidative stress and may promote myogenic differentiation of rat BMSCs by enhancing phosphatidylinositol 3‐kinase/protein kinase B/forkhead Box O1 signaling., Hydrogen peroxide can cause significant peroxidative damage to and inhibit the proliferation and myogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). In this study, we found that recombinant human Trx significantly mitigated hydrogen peroxide‐induced oxidative stress and may promote myogenic differentiation of rat BMSCs by enhancing phosphatidylinositol 3‐kinase/protein kinase B/forkhead Box O1 signaling, which may provide an experimental basis for the BMSC‐based treatment of sarcopenia.

Background Differentiated bone marrow mesenchymal stem cells (BMSCs) may be a therapeutic strategy to treat sarcopenia caused by high glucose. The effects of resveratrol in the myogenic induction of BMSCs under high glucose are unknown. We evaluated the effects and possible mechanisms of high glucose and resveratrol on myogenic induction of rat BMSCs. Methods Primary rat BMSCs were isolated and purified from Sprague-Dawley rats aged between 3 and 4 weeks. Rat BMSCs were differentiated into myogenic cells using conditioned medium and treated with glucose and/or resveratrol along with EX527 (a specific silent information regulator 1 [SIRT1] inhibitor). The expressions of MyoD1 and Myogenin were measured. The reactive oxygen species (ROS) level, superoxide dismutase (SOD) activity, and the expressions of FOXO1 and p-AKT/AKT during myogenic induction were also examined. Results High glucose decreased cell viability, cell proliferation, and SOD activity, increased intracellular ROS levels, and inhibited the AKT/FOXO1. Resveratrol reversed myogenic induction suppression caused by high glucose, partly through restoring cell proliferation and viability, reducing peroxidative damage, and activating the AKT/FOXO1 pathway; this effect was eliminated by EX527. Conclusion Our results indicate that resveratrol promoted myogenic induction and partially reversed the suppression of myogenic induction caused by high glucose through activating the SIRT1/AKT/FOXO1 pathway.

We aimed to detect expression changes of miRNA-203 in the serum of hepatocellular carcinoma (HCC) patients before and after transarterial chemoembolization (TACE), and to explore the clinical significance in influencing the prognosis of HCC.Serum levels of miRNA-203 in HCC patients (n=100) and healthy subjects (n=100) were detected by RT-PCR. The relationship between miRNA-203 level and baseline characteristics of HCC was analyzed by Pearson correlation test. The prognostic potentials of miRNA-203 in HCC were evaluated by Kaplan-Meier method. Changes in miRNA-203 level before and after TACE in HCC patients were determined. Cox regression model was applied for analyzing potential factors that may influence the prognosis in HCC.MiRNA-203 was lowly expressed in the serum of HCC patients than in controls. Its level was closely linked to differentiation, metastasis and TNM stage. Serum level of miRNA-203 in HCC patients was upregulated following TACE. Overall survival was better in HCC patients expressing high level of miRNA-203 at post-TACE. Age (over 60 years), large tumor size (≥ 5 cm), metastasis and stage III-IV were risk factors of HCC death, while highly expressed miRNA-203 was a favorable factor.Serum level of miRNA-203 is downregulated in HCC patients, which is upregulated following TACE. MiRNA-203 can be used to evaluate the prognosis in TACE-treated HCC patients.

Objective: We aimed to investigate the therapeutic effects of Moringa oleifera leaf extracts on osteogenic induction of rat bone marrow mesenchymal stem cells (BMSCs) following peroxidative damage and to explore the underlying mechanisms. Methods: Conditioned medium was used to induce osteogenic differentiation of BMSCs, which were treated with H2O2, Moringa oleifera leaf extracts-containing serum, or the phosphatidyl inositol-3 kinase (PI3K) inhibitor Wortmannin, alone or in combination. Cell viability was measured using the MTT assay. Cell cycle was assayed using flow cytometry. Expression levels of Akt, phosphorylated (p)Akt, Foxo1, and cleaved caspase-3 were analyzed using Western blot analysis. The mRNA levels of osteogenesis-associated genes, including alkaline phosphatase (ALP), collagen І, osteopontin (OPN), and Runx2, were detected using qRT-PCR. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels, as well as superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and ALP activity were detected using commercially available kits. Osteogenic differentiation capability was determined using alizarin red staining. Results: During osteogenic induction of rat BMSCs, H2O2 reduced cell viability and proliferation, inhibited osteogenesis, increased ROS and MDA levels, and decreased SOD and GSH-PX activity. H2O2 significantly reduced pAkt and Foxo1 expression, and increased cleaved caspase-3 levels in BMSCs. Additional treatments with Moringa oleifera leaf extracts partially reversed the H2O2-induced changes. Wortmannin partially attenuated the effects of Moringa oleifera leaf extracts on protein expression of Foxo1, pAkt, and cleaved caspase-3, as well as mRNA levels of osteogenesis-associated genes.Conclusion: Moringa oleifera leaf extracts ameliorate peroxidative damage and enhance osteogenic induction of rat BMSCs by activating the PI3K/Akt/Foxo1 pathway.

The accuracy of time delay estimation (TDE) is primarily determined by the bandwidth of the received signal. For a passive system, however, the emitting signal is non-cooperative so the bandwidth is not controllable. Since a source may radiate or reflect multiple subband signals with different center frequencies but the time delay of each subband is the same, using the subbands together perhaps improves the TDE accuracy. This paper investigates the Cramer-Rao bound (CRB) derivation of multi-subband signals (MSS)-based TDE problem. The new CRB indicates that using multiple subbands should result in a better performance than the classical model. We formulate the MSS-based time delay estimating as a maximizing optimization problem under the least-squares criteria. Simulations illustrate the proposed method of reaching the CRB. And the MSS-based TDE shows notable superiority on the accuracy of both theoretical bound and numerical results.

One of the advantages of differential received signal strength (DRSS)-based localization is eliminating the dependence of the source transmitted signal power. Therefore, DRSS is able to handle the passive localization as time difference of arrival (TDOA) does. The recent work of [1] investigated a new model for DRSS measurements, but the proposed methods are suboptimal. This paper focuses on the study of localization using DRSS measurements. A new formulation for DRSS localization of a 2-D source is proposed, which leads to a closed-form estimator through minimizing a constrained optimization problem. The solution applies weighted least squares technology only, achieving the Cramer Rao Bound (CRB) accuracy if the noise is mild. A brief analysis validates that the mean-square error (MSE) attains the CRB in the small noise region. The performance and theoretical result are verified by simulations.

Gallbladder carcinoma (GBC) commonly occurs in gastrointestinal malignancy and has the fifth highest mortality rate among gastrointestinal malignancy. Recently, miR‐188‐5p, a small noncoding RNA, has been implicated in various types of cancer such as nasopharyngeal carcinoma, oral squamous cell carcinoma, liver cancer, and prostate cancer. However, the effect of miR‐188‐5p on GBC remains unclear. Here, we demonstrated that miR‐188‐5p was downregulated in GBC tissues, and downregulation of miR‐188‐5p correlated with larger tumor size, lymph node metastasis, and extensive metastasis. In addition, the overall survival time of patients with higher miR‐188‐5p expression was significantly longer than that of patients with low‐miR‐188‐5p expression. Moreover, downregulation of miR‐188‐5p promoted the proliferation, migration, and invasion of GBC cells, while its overexpression inhibited cell invasion and induced cell apoptosis, and arrested GBC growth in vivo. Importantly, miR‐188‐5p‐dependent tumorigenesis was correlated with Wnt/β‐catenin signaling and p‐38/JNK signaling. In conclusion, miR‐188‐5p plays a direct role in GBC tumorigenesis. Our study suggests that miR‐188‐5p could serve as a novel diagnosis marker and therapeutic target in GBC.

Background: Long-term high glucose environment can cause muscle tissue atrophy, and then lead to musculoskeletal depression or even disability. Regenerative medicine is an extremely attractive select to solve this problem. Resveratrol is a compound which has various clinical therapeutic effects including regulating the myogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). So, the objective of this study is to observe if resveratrol affect myogenic induction of rat BMSCs under high glucose environment and explore the possible mechanism. Methods: Rat BMSCs were isolated and cultured. The phenotypes were identified when cultured to the third passage cells (P3 cells). Then the P3 cells were used to induce to differentiate into myogenic cells by using the conditioned medium. After grouping, glucose, resveratrol and EX527 (inhibitor of SIRT1) were added. The cell viability was measured by MTT assay. The myogenesis related protein was detected by immunofluorescence. The level of reactive oxygen species (ROS) and superoxide dismutase (SOD) activity were detected by use of assay kits. The cell cycle was assayed with flow cytometry. The expression of FOXO1, AKT, p-AKT, MyoD1 and Myogenin were measured by WB. All above indicators in different groups were quantified and compared. Results: During myogenic induction, after 72h treatment, high glucose (35 mmol/L) reduced cell viability and proliferation of rat BMSCs significantly, increased intracellular ROS levels clearly, decreased SOD activity obviously, and restrained AKT/FOXO1 pathway apparently. Resveratrol (15μmol/L) could regulate the process positively and reverse the suppression caused by high glucose partly through restoring cell proliferation and viability, reducing peroxidative damage and activating AKT/FOXO1 pathway. After pretreated the cells with EX527 (20 μmol/L), this reverse effect of resveratrol was eliminated. Conclusion: Resveratrol not only promoted myogenic induction of rat BMSCs, but also partially reversed myogenic induction supression of rat BMSCs caused by high glucose through activating SIRT1/AKT/FOXO1 pathway. [Key words] resveratrol, bone marrow mesenchymal stem cells, myogenic induction, glucose, SIRT1, AKT, FOXO1

Improper regeneration is associated with lung diseases including lung cancer. Lung cancer is one of the leading causes of death worldwide, with nearly 2 million new cases diagnosed each year. The diagnosis is often too late for successful therapeutic intervention. Lung cancer shows substantial phenotypic and genetic heterogeneity between individuals, making it difficult to model in animals. Organoids, derived from regional stem/progenitor cells in lung epithelia, have attracted extensive interest in both research studies and the clinic, because of their great potential for use in cancer treatment. Various lung cancer organoids have been established to recapitulate the tissue architecture of primary lung tumors and maintain the genomic alterations of the original tumors during long-term expansion in vitro. In this review, we summarize the current data on lung epithelial regeneration by regional endogenous stem/progenitor cells, describe the development of organoid technology, and present its applications in lung cancer research. Furthermore, recent challenges and future directions to improve organoid technologies for lung cancer treatment are discussed.

The expression level of Ubiquitin-conjugating enzyme E2T (UBE2T) is upregulated in various types of human tumors. We explored the correlation and regulatory mechanism of UBE2T in the development of colorectal cancer (CRC).Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to examine the expression of UBE2T in the CRC tissues and cell lines. Immunohistochemical staining, spearman correlation analysis, and Kaplan Meier-survival analysis were used to demonstrate the correlation between UBE2T high expression level and the clinical characteristics of malignant patients and the overall survival. The proliferation, apoptosis, migration and invasion of CRC cells were analyzed by cell transfection, MTT, colony formation, scratch assay, transwell, and flow cytometry. Furthermore, the expression of cell proliferation and apoptosis related proteins and ubiquitination of p53 were detected by western blot.UBE2T was up-regulated in CRC tissues and cell lines, and high expression level of UBE2T was correlated with the clinical characteristics of malignant of CRC patients (P0.05), and patients with high expression level of UBE2T had lower overall survival (P=0.0455). In addition, UBE2T could promote the growth, proliferation, invasion and metastasis of CRC cells and inhibit the apoptosis. At the same time, knockdown of UBE2T inhibited the growth of transplanted tumor in mice of subcutaneous CRC model. Moreover, our experimental results proved that UBE2T regulated the expression of downstream related proteins through ubiquitination of p53 protein to promote the occurrence and development of CRC.Our study elucidated that high expression of UBE2T would enhance the development of CRC, and then further explored its molecular mechanism both in vitro and in vivo. The results indicated that UBE2T facilitated ubiquitination and degradation of p53, which predicts the possibility of UBE2T as one of molecular diagnosis markers, prognostic indicators and therapeutic drug targets of CRC patients.

The aim of the present study was to investigate the indirubin-enhanced effects of arsenic disulfide (As2S2) on the proliferation and apoptosis of diffuse large B-cell lymphoma (DLBCL) cells in order to identify an optimum combination therapy. The human DLBCL cells, LY1 and LY8, were treated with different concentrations of indirubin for 24, 48 and 72 h. Next, the cells were treated with 10 μM As2S2 or a combination of 10 μM As2S2 and 20 μM indirubin for 48 h. Cell proliferation inhibition was detected using cell counting kit-8 and cell apoptosis was determined using flow cytometry. The expression levels of Bcl-2, Bcl-2-associated X protein (Bax) and caspase-3 were analyzed by quantitative polymerase chain reaction (qPCR) and western blotting. The DLBCL cell viability exhibited no significant changes at 24, 48 or 72 h with increasing indirubin concentration. In addition, the apoptotic rates of the LY1 and LY8 cells demonstrated no noticeable effects at 48 h with increasing indirubin concentration. Following treatment with the combination of indirubin and As2S2, the inhibitory and apoptotic rates of the cells were notably increased compared with those of the As2S2-treated group. The qPCR results revealed that indirubin alone had no enhancing effect upon the Bax/Bcl-2 mRNA expression ratio and caspase-3 mRNA expression. Western blot analysis revealed that indirubin alone had an enhancing effect upon the Bax/Bcl-2 protein ratio and procaspase-3 protein expression. In addition, the results demonstrated that the 21-KDa Bax protein was proteolytically cleaved into an 18-KDa Bax in the DLBCL cells treated with the combination of indirubin and As2S2. Indirubin alone did not inhibit proliferation or induce the apoptosis of the LY1 and LY8 cells. However, the combination of indirubin and As2S2 yielded enhancing effects. Therefore, the results of the present study demonstrated that with regard to antitumor activities, As2S2 served as the principal drug, whereas indirubin served as the adjuvant drug. The enhancing effect was due, in part, to the induction of the mitochondrial apoptotic pathway, which involves the cleavage of Bax.

The aim of the present study was to investigate the effect of arsenic disulfide (As2S2) on the proliferation and apoptosis of LY1 and LY8 human diffuse large B cell lymphoma (DLBCL) cells in an attempt to discover a more effective alternative therapy scheme. Human DLBCL cells LY1 and LY8 were treated with various concentrations of As2S2 for different time periods. Cell viability was detected by the CCK-8 assay; cell apoptosis was evaluated by flow cytometric analysis. The expression levels of Bax, Bcl-2 and caspase-3 were examined by quantitative PCR and western blotting. We found that the DLBCL cell viability was significantly decreased following treatment with As2S2 for 24, 48 and 72 h. Along with increasing As2S2 concentrations, the DLBCL cell viability was notably reduced when compared with the control group, and the results were statistically significant. Meanwhile, the apoptotic rates of DLBCL cells were significantly enhanced at 24, 48 and 72 h following treatment with increasing As2S2 concentration, and the results were also statistically significant. The quantitative PCR results showed that at the mRNA level, the Bax/Bcl-2 expression ratio was increased and caspase-3 mRNA expression was upregulated in As2S2-treated DLBCL cells. Western blot analysis revealed that at the protein level, As2S2 increased the Bax/Bcl-2 protein ratio in contrast to decreased pro-caspase-3 expression in the DLBCL cells. Our findings also demonstrated that 21-kDa Bax was proteolytically cleaved into the 18-kDa Bax in the DLBCL cells exposed to As2S2 at a concentration of 10 µM. As2S2 inhibited proliferation and induced apoptosis of LY1 and LY8 cells in a concentration- and time-dependent manner. The effect was partly due to the induction of mitochondrial-dependent apoptosis involving Bax cleavage.

Bergenin, a C-glucoside of 4-O-methyl gallic acid from Bergenia purpurascens, is a naturally antitussive and expectorant agent. A rapid and sensitive liquid chromatography tandem mass spectrometry (LCâMS/MS) method has been developed and validated for the determination of the active componentâbergenin, in rat plasma after oral administration of aqueous B. purpurascens extract. The plasma samples were pretreated by protein precipitation with acetonitrile and chromatographic separation was achieved on a Diamonsil® C18 column (150mmÃ4.6mm, 5μm) with isocratic elution using a mobile phase consisting of waterâmethanol (30:70, v/v) at a flow rate of 0.6mL/min. The detection was accomplished by a triple-quadrupole tandem mass spectrometer in multiple-reaction monitoring (MRM) scanning via an electrospray ionization (ESI) source operating in the negative mode. The optimized mass transition ion-pairs (m/z) for quantitation were 327.3/192.0 for bergenin, and 431.1/311.1 for IS. The time for each analysis run was only 3.5min between injections. The calibration curve exhibited good linearity (r2>0.99) over a range of 1.00â2000ng/mL for bergenin. The lower limit of quantitation (LLOQ) was 1.00ng/mL. The intra- and inter-day precisions were no more than 11.8%, and relative errors (RE) were within the range of 0.0â4.4%. The validated method was successfully applied to investigate the pharmacokinetics of bergenin after oral administration of B. purpurascens extract in rats. Keywords: Bergenin, Bergenia purpurascens, Pharmacokinetics, Rat plasma, LCâMS/MS

The cutwidth problem for a graph G is to embed G into a path such that the maximum number of overlap edges is minimized. This paper presents an approach based on the degree sequence of G for determining the exact value of cutwidth of typical graphs (e.g., n-cube, caterpillars). Relations between the cutwidth and other graph-theoretic parameters are studied as well.

A sensitive and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of corosolic acid (CRA) in rat plasma. The plasma samples were prepared by a simple protein precipitation treatment. Chromatographic separation was performed on an Agela MG-C18 column (50 mm × 4.6 mm; i.d., 5 μm) at 30°C. The mobile phase consisting of methanol-10 mM ammonium acetate-formic acid (80:20:0.1, v/v/v; pH=3.8) was delivered with a flow rate of 0.6 ml/min and a running time of 2.5 min. Quantification was performed with positive electrospray ionization (ESI) in the multiple-reaction monitoring (MRM) mode at m/z 490 → m/z 205 for CRA, and m/z 471 → m/z 203 for TEOA (internal standard, IS), respectively. Linearity was evaluated over the concentration range of 1.00-1000 ng/ml with a lower limit of quantification (LLOQ) of 1.00 ng/ml. The validated method was successfully applied to the pharmacokinetic study of CRA after the drug was orally administered in Sprague-Dawley rats.

Lymphoma is a hematological malignancy that originates from lymph nodes and lymphoid tissues and is divided into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), based on its histopathological characteristics. The aim of this study was to investigate the effects of arsenic sulfide (As2S2), the main ingredient of realgar, on the proliferation and apoptosis of the Raji B-cell lymphoma and Jurkat T-cell lymphoma lines, comparing the sensitivity between the two cell lines and investigating the possible underlying mechanisms. The two lymphoma cell lines were cultured in vitro, using different concentrations of As2S2 for different time periods. The cell proliferation was detected using the Cell Counting kit-8 (CCK-8). Apoptosis was assessed via flow cytometry. Expression levels of the apoptosis-associated genes [Homo sapiens Bcl-2-associated X protein (BAX), Homo sapiens B-cell CLL/lymphoma 2 (Bcl-2), Homo sapiens Bcl-2-like protein 1 (BCL2L1, Bcl-xL), Homo sapiens v-myc myelocytomatosis viral oncogene homolog (avian) (MYC, c-Myc) and Homo sapiens pim-1 oncogene (PIM)] were measured via the reverse transcription polymerase chain reaction (RT-PCR) method. The results demonstrated that As2S2 inhibited proliferation and induced apoptosis in the two lymphoma cell lines in a time- and concentration-dependent manner, with the Raji cells being more sensitive to As2S2 compared to Jurkat cells. As2S2 may also alter the expression levels of different apoptosis-associated genes, with the alterations of the mRNA expression levels being different between Raji and Jurkat cells. These findings indicated that As2S2 may inhibit the proliferation and promote the apoptosis of non-Hodgkin lymphoma (NHL) cell lines and that B-cell lymphoma cell lines are more sensitive compared to T-cell lymphoma cell lines. The possible underlying mechanism is that As2S2 alters the expression levels of the apoptosis-associated genes and activates apoptosis-associated signaling pathways.

The aim of the present study was to investigate the effect of realgar on the viability, proliferation and apoptosis in the human chronic lymphocytic leukemia (CLL) cell line, MEC‑1. Potential mechanisms mediating the effect were also explored in the experiment. Cultured MEC‑1 cells were incubated with various concentrations of realgar for 24, 48 and 72 h. A WST‑8 assay was employed to evaluate the effect on cell viability. Inhibitory effects on cell proliferation were determined using a 5‑bromodeoxyuridine cell proliferation ELISA. The apoptotic effect on MEC‑1 cells was evaluated by annexin V‑fluorescein isothiocyanate/propidium iodide dual staining, followed by flow cytometry. Quantitative polymerase chain reaction was performed to determine the mRNA expression levels of BCL2‑associated X protein (BAX), BCL2‑like 1 (Bcl-xL), v‑myc myelocytomatosis viral oncogene homolog (avian; c‑Myc) and cyclin‑dependent kinase inhibitor 1A (p21). It was found that viability and proliferation were significantly reduced while apoptotic rates increased in MEC‑1 cells following exposure to realgar. Furthermore, mRNA expression of BAX and c‑Myc was upregulated and downregulated, respectively, in realgar‑treated MEC‑1 cells. In conclusion, the results showed that realgar inhibits viability and prolife-ration and induces apoptosis of MEC‑1 cells in a dose‑ and time‑dependent manner. The effect may depend on the mitochondrial apoptosis pathway. The results of the present study may be beneficial in the identification of a new target therapy for CLL.

A simple, sensitive and specific method was developed for simultaneous determination of stachydrine and leonurine in rat plasma using diphenhydramine as an internal standard (IS). The separation was performed on an Agilent ZORBAX Eclipse XDB-C(18) column (150mm×4.6mm, i.d., 5μm) at a flow rate of 0.6mL/min, and the mixture of methanol-water containing 0.1% formic acid was used as the mobile phase. The lower limits of quantitation (LLOQs) in rat plasma were 0.895 and 0.287ng/mL for stachydrine and leonurine, respectively. Intra- and inter-day precisions were within 14.4% and accuracies were not more than 3.0%. After single oral administration of 14.5g/kg Herba Leonuri extract, C(max) of stachydrine and leonurine in rat plasma were respectively 1608±267 and 43.3±8.2ng/mL, while T(max) values were respectively 0.75±0.27 and 0.83±0.26h. The results demonstrated that the present LC-MS/MS method was sensitive enough for pharmacokinetic study of stachydrine and leonurine following oral administration of Herba Leonuri extract.

Bio-mechanism investigations demand single particle tracking with high spatial and temporal resolutions which require single fluorophore 3D localization measurements with matching precision and speed. Although the precision for lateral-localization measurements is well described by an analytical expression, for the axial direction, it is often obtained by repeating location measurements or by estimating a lower bound. Here, we report a precision expression for an axial-localization method that analyzes the standard deviations of single fluorophores' intensity profiles. Like the lateral-localization precision, this expression includes all relevant experimental effects measurable from a Gaussian intensity profile of the fluorophore. This expression completes the precision analysis for single-image 3D localization of individual fluorophores and lifts the temporal resolution to the typical exposure timescales of milliseconds.

The K-means algorithm is among the most popular clustering methods that group observations with similar characteristics or features together. It is widely used in many marketing applications, especially in cluster-based market segmentation. The K-means algorithm is implemented by different commercial software, such as SAS, SPSS and MATLAB, as a standard clustering function/tool. This note compares the performances of K-means algorithm implemented by three software. This note describes the potential shortcomings of the K-means algorithm implementation within the software, and proposes improvement approaches for the K-means algorithms by using silhouette coefficient.

The green phototrophic bacteria contain a unique complement of chlorophyll pigments, which self-assemble efficiently into antenna structures known as chlorosomes with little involvement of protein. The few proteins found in chlorosomes have previously been thought to have a primarily structural function. The biosynthetic pathway of the chlorosome pigments, bacteriochlorophylls c , d , and e , is not well understood. In this report, we used spectroscopic, proteomic, and gene expression approaches to investigate the chlorosome proteins of the green filamentous anoxygenic phototrophic bacterium Chloroflexus aurantiacus . Surprisingly, Mg-protoporphyrin IX monomethyl ester (oxidative) cyclase, AcsF, was identified under anaerobic growth conditions. The AcsF protein was found in the isolated chlorosome fractions, and the proteomics analysis suggested that significant portions of the AcsF proteins are not accessible to protease digestion. Additionally, quantitative real-time PCR studies showed that the transcript level of the acsF gene is not lower in anaerobic growth than in semiaerobic growth. Since the proposed enzymatic activity of AcsF requires molecular oxygen, our studies suggest that the roles of AcsF in C. aurantiacus need to be investigated further.

For the maximum flow f* in the network N, if an arc set B has characteristics: the increase of the capacity of every arc will increase the maximum value v* of the network and meanwhile decrease the total expense Z; then, we call “B” as the “Blocking Set” and the network with blocking set as “ill-conditioned network”. In this paper we first characterize the blocking set and ill-conditioned network and second, present the optimal investment decision for increasing the capacity and removing ill-conditioned network.