Semiautomated design and soluble expression of a chimeric antigen TbpAB01 from Glaesserella parasuis.

Pathogenic bacterial membrane proteins (MPs) are a class of vaccine and antibiotic development targets with widespread clinical application. However, the inherent hydrophobicity of MPs poses a challenge to fold correctly in living cells. Herein, we present a comprehensive method to improve the soluble form of MP antigen by rationally designing multi-epitope chimeric antigen (ChA) and screening two classes of protein-assisting folding element. The study uses a homologous protein antigen as a functional scaffold to generate a ChA possessing four epitopes from transferrin-binding protein A of Glaesserella parasuis. Our engineered strain, which co-expresses P17 tagged-ChA and endogenous chaperones groEL-ES, yields a 0.346 g/L highly soluble ChA with the property of HPS-positive serum reaction. Moreover, the protein titer of ChA reaches 4.27 g/L with >90% soluble proportion in 5-L bioreactor, which is the highest titer reported so far. The results highlight a timely approach to design and improve the soluble expression of MP antigen in industrially viable applications.

Knockdown of DNMT1 Induces SLCO3A1 to Promote Follicular Growth by Enhancing the Proliferation of Granulosa Cells in Mammals.

In female mammals, the proliferation and apoptosis of granulosa cells (GCs) have been shown to determine the fate of follicles. DNA methyltransferases (DNMTs) and SLCO3A1 have been reported to be involved in the survival of GCs and follicular growth. However, the molecular mechanisms enabling DNMTs to regulate the expression of SLCO3A1 to participate in follicular growth are unclear. In this study, we found that the knockdown of DNMT1 enhanced the mRNA and protein levels of SLCO3A1 by regulating the chromatin accessibility probably. Moreover, SLCO3A1 upregulated the mRNA and protein levels of MCL1, PCNA, and STAR to promote the proliferation of GCs and facilitated cell cycle progression by increasing the mRNA and protein levels of CCNE1, CDK2, and CCND1, but it decreased apoptosis by downregulating the mRNA and protein levels of CASP3 and CASP8. Moreover, SLCO3A1 promoted the growth of porcine follicles and development of mice follicles. In conclusion, the knockdown of DNMT1 upregulated the mRNA and protein levels of SLCO3A1, thereby promoting the proliferation of GCs to facilitate the growth and development of ovarian follicles, and these results provide new insights into investigations of female reproductive diseases.

The relationship of nutritional status with anticancer immunity and its prognostic value for head and neck cancer.

Malnutrition has been reported to be associated with reduced survival and deficient anticancer immunity, and undernourishment is a frequent comorbidity in head and neck cancer (HNC) patients. In this study, we evaluated the relationship between nutritional status and immunologic factors, and its prognostic value for HNC. We retrospectively reviewed 212 HNC patients who had undergone a nutrition evaluation based on the Patient-Generated Subjective Global Assessment (PG-SGA) and curative radiotherapy (RT). The role of nutritional status in the prognosis of HNC and its correlation with anticancer immune response was assessed in HNC patients, and in the 4-nitroquinoline 1-oxide (4NQO)-induced tongue tumor animal model. Our data revealed that malnutrition (high PG-SGA scores) was significantly associated with more advanced disease, lower body mass index, lower RT completion rates, and reduced survival. Patients in the group with high PG-SGA scores had a higher neutrophil-to-lymphocyte ratio, higher proportion of myeloid-derived suppressor cells (MDSCs), and elevated IL-6 levels in the peripheral circulation. Patients with increased PG-SGA scores following treatment were more likely to developing locoregional failure. In the 4NQO-induced tumor model, nutritional supplementation decreased the rate of invasive tumor formation and attenuated the immune-suppressive microenvironment. Following ectopic tumor implantation in an immunocompetent host, nutrition supplements decreased tumor growth in association with attenuated MDSC recruitment and lower IL-6 expression. In conclusion, malnutrition by PG-SGA was associated with poor prognosis in HNC patients. Based on the data of HNC patients and the 4NQO-tumor model, adequate nutritional supplementation might improve the prognosis associated with augmented anticancer immunity.

Role of vitamin D3 in tumor aggressiveness and radiation response for hepatocellular carcinoma.

Locoregional control is a significant prognostic factor for hepatocellular carcinoma (HCC). Historically, the use of radiotherapy (RT) for HCC was limited owing to the low radiotolerance of the liver and the need for high RT doses for disease control. We aimed to examine if 1α,25-dihydroxyvitamin D3 (calcitriol) has a role in the tumor inhibition and the radiation response of HCC in vitro and in vivo, and explore the underlying mechanisms. The human and murine liver cancer cell lines were selected for cellular and animal experiments to investigate the changes in tumor characteristics and the radiation response after calcitriol supplementation. The effects induced by calcitriol supplementation on interleukin-6 (IL-6) signaling and the tumor immune microenvironment following RT were also examined. Our data revealed that calcitriol supplementation attenuated tumor aggressive behavior, decrease IL-6 expression, and augmented radiation-induced tumor inhibition. The biological changes following calcitriol treatment included suppressed epithelial-mesenchymal transition, attenuated cancer stem cell-like properties and increased radiation-induced reactive oxygen species and cell death in vitro. Regarding immune microenvironment, calcitriol attenuated the recruitment of myeloid-derived suppressor cell (MDSC) recruitment and increased the infiltration of cytotoxic T cells in tumor following RT. Furthermore, When the primary liver tumor was irradiated with larger dose per fraction, calcitriol induced a smaller size of synchronous unirradiated tumor in mice, which linked with attenuated IL-6 signaling and MDSC recruitment. In conclusion, calcitriol treatment reduced tumor aggressiveness and enhanced the radiation response. The inhibited IL-6 signaling and subsequently enhanced antitumor immunity might be responsible to augment radiation-induced tumoricidal effect induced by calcitriol. Based on our results, we suggest that calcitriol could exert the antitumor and radiosensitization effects for HCC, especially for multifocal tumors.

Risk of major adverse cardiovascular events among second-line hormonal therapy for metastatic castration-resistant prostate cancer: A real-world evidence study.

BACKGROUND: To evaluate the possible major adverse cardiovascular events (MACE) associated with second-line hormonal therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: We performed a population-based real-world cohort study of 4962 prostate cancer patients between 2014 and 2017 utilizing the Chang Gung Research Database of Taiwan. The second-line hormonal therapies included enzalutamide and abiraterone acetate. The outcomes of interest were MACE, including acute coronary syndrome (ACS), ischemic stroke (IS), and heart failure (HF) events that resulted in hospitalization. Cox proportional-hazards models with inverse probability of treatment weighting (IPTW) with propensity scores were used. RESULTS: After IPTW, 288 patients were prescribed second-line hormonal therapy and 1575 received first-line androgen-deprivation therapy (ADT). Of all patients diagnosed with MACE, the event rates were 2.92% in the second-line hormonal group and 2.22% in the first-line ADT group. The mean follow-up period was 9.52 months for the second-line hormonal group. Patients who received second-line hormonal therapy exhibited a significantly increased risk for MACE (hazard ratio [HR]: 3.15; 95% confidence interval [CI]: 2.03-4.89), ACS (HR: 4.94; 95% CI: 2.36-10.33), and HF (HR: 2.83; 95% CI: 1.53-5.25), compared with the first-line ADT group, but a similar risk for IS was observed in both groups (HR: 1.70; 95% CI: 0.95-3.04). CONCLUSIONS: The real-world evidence study revealed increased risks for MACE in mCRPC patients receiving second-line hormonal therapy.

Prognostic Significance of Neoadjuvant Rectal Scores in Preoperative Short-Course Radiotherapy and Long-Course Concurrent Chemoradiotherapy for Patients with Locally Advanced Rectal Cancer.

BACKGROUND: This study aimed to investigate the prognostic factors and the utility of the neoadjuvant rectal (NAR) score for patients who have locally advanced rectal cancer (LARC) treated with preoperative short-course radiotherapy (SRT) or long-course concurrent chemoradiotherapy (CRT). METHODS: Of 314 consecutive stage 2 or 3 rectal cancer patients enrolled from January 2006 to December 2017, 205 underwent preoperative SRT (2500 cGy/5 fractions), and 109 underwent preoperative CRT (4200-5080 cGy/21-28 fractions) after total mesorectal excision (TME). The study calculated NAR scores using the following equation: [5 pN - 3(cT - pT) + 12]2/9.61. RESULTS: The multivariate analysis showed that age above 65 years, pT4, pN2, NAR scores higher than 16, and distance from anal verges (< 8 cm) were significant prognostic factors for overall survival (OS), whereas, pN2, NAR scores lower than 16, and distance from anal verges (< 8 cm) were significant prognostic factors for disease-free survival (DFS) and distant metastasis (DM). The patients with an NAR score higher than 16, had a 5-year OS rate of 67.6%, a DFS rate of 56.9%, a locoregional recurrence (LRR) rate of 7.7%, and a DM rate of 35% compared with corresponding rates of 87.6%, 76.7%, 5.4%, and 7.2% for the patients with an NAR score of 16 or lower (p < 0.001 for OS, < 0.001 for DFS, 0.25 for LRR, and < 0.001 for DM). CONCLUSIONS: For patients who undergo SRT or CRT for LARC, a higher NAR score is associated with worse OS and DFS and higher DM rates at 5 years. The NAR score could be used as a short-term surrogate end point after neoadjuvant therapy for LARC.

The effect of continuous positive airway pressure on circulating malondialdehyde among obstructive sleep apnea patients: a meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA) has been demonstrated to be associated with an increase of oxidative stress. However, whether circulating malondialdehyde (MDA), a widely used biomarker of oxidative stress, could be reduced by the treatment of OSA by continuous positive airway pressure (CPAP) is debated. The present meta-analysis was performed to determine the effect of CPAP treatment on circulating MDA among patients with OSA. METHODS: A systematic search of PubMed, Embase, and Web of Science was performed for literature covering the period between 1967 and August 2019. Standardized mean difference (SMD) was calculated to estimate the treatment effects of pre- and post-CPAP therapy. RESULTS: A total of 10 studies with 220 patients were included in this meta-analysis. A significant decrease in circulating MDA was observed after CPAP treatment (SMD = 1.164, 95% CI = 0.443 to 1.885, z = 3.16, p = 0.002) in OSA patients. Subgroup analyses revealed that CPAP therapy was associated with a significant decrease of circulating MDA in elder (SMD = 1.629, 95% CI = 0.265 to 2.994, z = 2.34, p = 0.019), more obese patients (SMD = 0.954, 95% CI = 0.435 to 1.473, z = 3.61, p = 0.000), more severe OSA patients (SMD = 0.879, 95% CI = 0.421 to 1.336, z = 3.76, p = 0.000), patients with therapeutic duration ≥ 3 months (SMD = 1.867, 95% CI = 0.563 to 3.172, z = 2.80, p = 0.005), and patients with good compliance (SMD = 1.004, 95% CI = 0.703 to 1.305, z = 6.54, p = 0.000). CONCLUSIONS: This meta-analysis suggested that CPAP therapy exerted significant lowering effects on circulating MDA, especially in elder, more obese, and more severe OSA patients and patients with good compliance as well as longer duration of CPAP application.

The Predictive Value of Pretreatment Neutrophil-To-Lymphocyte Ratio in Esophageal Squamous Cell Carcinoma.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been reported to be both a prognostic biomarker for cancer and associated with inflammation, but its predictive role in tumor immunity is not clear. The present study examined the correlations of the NLR and immune suppression with the prognoses in patients with esophageal squamous cell carcinoma (ESCC). METHODS: We performed a retrospective review of 1168 patients who were newly diagnosed with stage T1N(+) and T2-T4 ESCC at our hospital. The NLR of each ESCC patient prior to treatment was calculated, and the associations of the NLR with various clinicopathological parameters and prognoses were then examined. In addition, correlations of the proportion of myeloid-derived suppressor cells (MDSCs) and level of interleukin (IL)-6 with the NLR were assessed in 242 ESCC patients. RESULTS: An elevated NLR was significantly correlated with advanced-stage disease and reduced overall survival (OS) of ESCC patients. Furthermore, the levels of IL-6 in tumors and MDSCs in the peripheral circulation were significantly correlated with the prognoses of ESCC, and the NLR was positively correlated with MDSC levels in the circulation and IL-6 staining intensity in tumor specimens. Moreover, a high NLR was significantly associated with reduced OS in the 926 patients treated with concomitant chemoradiotherapy, but not in the 242 patients who underwent surgical intervention. CONCLUSION: The NLR may represent a clinically useful biomarker to guide ESCC treatment decisions. Patients with a higher NLR may be an optimal subgroup for IL-6- and MDSC-targeted therapy.

Long-Term Taste Impairment after Intensity-Modulated Radiotherapy to Treat Head-and-Neck Cancer: Correlations with Glossectomy and the Mean Radiation Dose to the Oral Cavity.

We explored the effects of various parameters on taste impairments (TIs) in head-and-neck (H&N) cancer patients receiving intensity-modulated radiotherapy (IMRT). From January 2014 to September 2017, 88 H&N cancer patients subjected to curative or postoperative IMRT were enrolled in this prospective study. All patients underwent at least 1 year of follow-up after IMRT. Quality-of-life assessments in terms of patient-reported gustatory function were measured using the taste-related questions of the European Organization for Research and Treatment of Cancer H&N35 questionnaires. At a median follow-up time of 27 months, 27 of 88 patients (30.7%) reported long-term TIs. In multivariate analyses, glossectomy most significantly predicted TIs (P = 0.04). The percentage of TIs (61.5%) was significantly (P = 0.03) higher in patients who underwent partial or total glossectomy than in patients who did not undergo surgery (28.0%) and those who underwent radical surgery without glossectomy (20.0%). When we excluded surgical patients from analyses, the mean radiation dose to the oral cavity was of borderline significance in terms of TI prediction (P = 0.05). Only 10.5% of patients suffered from TIs when the mean radiation dose was <5000 cGy compared with 38.7% when the mean dose was ≥5000 cGy. In conclusion, glossectomy is the major cause of long-term TIs in H&N cancer patients receiving IMRT. In patients who do not undergo glossectomy, reduction of the mean radiation dose to the oral cavity may reduce TIs after IMRT.

Role of ALDH1 in the prognosis of esophageal cancer and its relationship with tumor microenvironment.

Aldehyde dehydrogenase 1 (ALDH1) is associated with tumorigenesis, and significantly increased in cancer stem-like cells. In the present study, the role of ALDH1 in esophageal squamous cell carcinoma (ESCC) was investigated. We retrospectively analyzed the clinical outcomes of 148 ESCC and examined its correlation with ALDH1 levels. Furthermore, we preformed cellular and animal experiments to investigate the role of ALDH1 in tumor progression and microenvironment. Our data revealed that ALDH1 staining was positively linked to a higher clinical stage, higher loco-regional failure rate, and shorter survival time. Furthermore, there was a positive link between ALDH1 expression and IL-6 signaling according to the data of clinical specimens and cellular experiments. Using animal model, ALDH1-positive tumors were associated with aggressive tumor growth, increased IL-6, augmented epithelial-mesenchymal transition (EMT), and activation of myeloid-derived suppressor cells (MDSCs). Blockade of COX-2 attenuated the aggressive tumor growth of ALDH1-positive cancer cells. In conclusion, our findings suggested that ALDH1 played an important role in tumor aggressiveness and associated with a tumor-promoting microenvironment in esophageal cancer. Directly targeting ALDH1 or using a COX-2 inhibitor could be a promising strategy for the treatment of ESCC.

Predictive Value of CD44 in Muscle-Invasive Bladder Cancer and Its Relationship with IL-6 Signaling.

BACKGROUND: CD44, a cancer stem cell surface marker, is associated with treatment resistance and prognosis in some cancers. In the present study, we examined the predictive value of CD44 in muscle-invasive bladder cancer (MIBC). METHODS: We retrospectively analyzed the clinical outcomes of 105 MIBC patients and correlated these outcomes with the expression of CD44. Furthermore, the bladder cancer cell lines HT1197 and MB49 were selected for cellular and animal experiments to investigate the correlation between CD44 and tumor aggressiveness. RESULTS: Analysis of clinical specimens indicated that CD44 staining was significantly associated with a higher clinical stage, higher locoregional failure rate, and lower disease-specific survival rate for MIBC patients. Using cellular experiments and orthotopic tumor models, we showed that CD44+ bladder cancer cells had a higher invasion ability and augmented epithelial-mesenchymal transition (EMT) compared with CD44 cells. There was a significant correlation between interleukin (IL)-6 and CD44 levels noted by in vitro testing, and clinical samples. Blockade of IL-6 attenuated the expression of CD44, cancer stem-cell-like properties, and aggressive tumor behavior in vitro and in vivo. The related changes included the attenuated STAT3 activation and EMT, and decreased programmed death ligand 1-mediated T-cell suppression. CONCLUSION: Our findings suggest that CD44 expression is positively associated with tumor aggressiveness in bladder cancer, and activated IL-6 signaling provides a suitable microenvironment for the induction of CD44 expression.

Cuffless Blood Pressure Estimation Using Pressure Pulse Wave Signals.

Pulse transit time (PTT) has received considerable attention for noninvasive cuffless blood pressure measurement. However, this approach is inconvenient to deploy in wearable devices because two sensors are required for collecting two-channel physiological signals, such as electrocardiogram and pulse wave signals. In this study, we investigated the pressure pulse wave (PPW) signals collected from one piezoelectric-induced sensor located at a single site for cuffless blood pressure estimation. Twenty-one features were extracted from PPW that collected from the radial artery, and then a linear regression method was used to develop blood pressure estimation models by using the extracted PPW features. Sixty-five middle-aged and elderly participants were recruited to evaluate the performance of the constructed blood pressure estimation models, with oscillometric technique-based blood pressure as a reference. The experimental results indicated that the mean ± standard deviation errors for the estimated systolic blood pressure and diastolic blood pressure were 0.70 ± 7.78 mmHg and 0.83 ± 5.45 mmHg, which achieved a decrease of 1.33 ± 0.37 mmHg in systolic blood pressure and 1.14 ± 0.20 mmHg in diastolic blood pressure, compared with the conventional PTT-based method. The proposed model also demonstrated a high level of robustness in a maximum 60-day follow-up study. These results indicated that PPW obtained from the piezoelectric sensor has great feasibility for cuffless blood pressure estimation, and could serve as a promising method in home healthcare settings.

[New Algorithms to Separate the Contribution of Petroleum Substances and Suspended Particulate Matter on the Scattering Coefficient Spectrum from Mixed Water].

In the water with petroleum pollution, the petroleum will be adsorbed on the surface of suspended particulate matter and form a double-layer structure, which impacts on the spectrum characteristics to the scattering coefficient. It is a key to improve the accuracy of the scattering theory model that the contribution of petroleum substances and suspended particulate matter on the scattering spectrum coefficient is be separated. A backward scattering coefficient spectrum measurement system was being built from linkage observation of three kinds of instruments, including DAWN HELEOS Ⅱ18 angle scattering measuring instrument (Wyatt company, American), LISST-100-xB size instrument(SEQUOIA SCIENTIFIC, INC, American), HydroScat-6 Sprctral Backscattering Sensor (HS6) ( Hobilabs company, American). Many parameters were measured such as voltage value of the scattering intensity, the particle size distribution, particle concentration and backward scattering coefficient in different water samples. Using the Mie scattering theory, a new algorithm to separate the scattering coefficient spectrum and new way of thinking to calculate volume scattering function ß(λ, θ) of the unknown refractive index material were proposed. The matching experiments were done by selecting quartz sand as particles whose refractive index (m) is known and petroleum sewage collected from different oilfield area. On the basis of matching experiments different water samples with different properties were obtained and related data were determinated. Firstly, according to Mie scattering theory the water volume scattering function ß(λ, θ) for each sample is calculated. Secondly, the equation was set up which can convert the scattering intensity corresponding to the voltage value V(θ) measured by DAWN HELEOS Ⅱ 18 Angle laser scattering instrument into volume scattering function ß(λ, θ). Thirdly, according to the method of optimum the equivalent refractive index (mos) of the oil sands mixed and the refractive index (mo) of petroleum sewage were estimated; Finally, using ß(λ, θ) and estimation of mos values and mo values to calculate the backscatter coefficient bb(λ) of all kinds samples, and new algorithms were set up which seperated quartz sand bb, s(λ) and petroleum sewage bb, o(λ) from mixed water with petroleum and sands respectively. The establishment of these separation algorithms improves the accuracy of the scattering theory model of the water petroleum pollution, on the other hand expands the Mie scattering theory in the application of ocean color remote sensing.

The Efficacy of Postoperative Adjuvant Chemotherapy for Patients with pT3N0M0 Upper Tract Urothelial Carcinoma.

PURPOSE: Nephroureterectomy with bladder cuff excision may not be sufficient as monotherapy for patients with pT3N0M0 upper tract urothelial carcinoma. The efficacy of postoperative adjuvant chemotherapy in this setting remains controversial. We evaluated the efficacy of adjuvant chemotherapy for patients with pT3N0M0 upper tract urothelial carcinoma in overall, cancer specific and recurrence-free survival. MATERIALS AND METHODS: We retrospectively reviewed records on 171 consecutive patients with pT3N0M0 upper tract urothelial carcinoma treated with radical nephroureterectomy between 2004 and 2014 at 2 branches of the same institution. Postoperative adjuvant chemotherapy was gemcitabine/cisplatin or cisplatin/fluorouracil/leucovorin. Overall, cancer specific and recurrence-free survival rates were estimated using the Kaplan-Meier method. The values of prognostic factors were evaluated by Cox regression analysis. RESULTS: Postoperative adjuvant chemotherapy was administered in 60 patients vs nonadjuvant therapy in 111 patients. Median followup was 35.8 months. Between the adjuvant and nonadjuvant treatment groups there were statistically significant differences in 5-year cancer specific (80.5% vs 57.6%, p = 0.010) and recurrence-free (74.4% vs 52.9%, p = 0.026) survival rates. Although there was no statistically significant difference in overall survival (71.9% vs 49.0%, p = 0.072), there was a trend of better overall survival in the patients who received postoperative chemotherapy. On multivariable analysis age (p = 0.018), tumor location (p = 0.003) and adjuvant chemotherapy (p = 0.001) were predictors of cancer specific survival. CONCLUSIONS: Adjuvant chemotherapy improves cancer specific and recurrence-free survival in patients with pT3N0M0 upper tract urothelial carcinoma after radical nephroureterectomy.

TGF Beta1 Expression Correlates with Survival and Tumor Aggressiveness of Prostate Cancer.

BACKGROUND: Although biopsy Gleason score and clinical stage can be used to inform treatment decisions for prostate cancer, identifying molecular markers of tumor aggressiveness could lead to a more tailored approaches to therapy. In the present study, we investigated the association of transforming growth factor (TGF)-ß1 levels and various markers of tumor aggressiveness and explore some potential mechanisms underlying the associations. METHODS: We used human and murine prostate cancer cell lines and their respective hormone resistance sub-lines, in vitro and in vivo to examine the changes in tumor aggressiveness, as well as the pathway responsible for these changes. Furthermore, 105 prostate cancer biopsy specimens were analyzed to correlate the level of TGF-ß1 with the clinical characteristics of patients. RESULTS: Our data revealed that activated TGF-ß1 signaling resulted in more aggressive tumor growth and augmented the epithelial-mesenchymal transition. Activated IL-6 signaling was associated with TGF-ß1 levels and the aggressive tumor features noted in TGF-ß1-positive prostate cancers in vitro and in vivo. Furthermore, the TGF-ß1 levels significantly correlated with Tregs accumulation in vivo. The clinical data indicated that TGF-ß1 immunoreactivity had a moderate positive correlation with IL-6 staining, advanced clinical stage, higher Gleason score, and pretreatment PSA in patients with prostate cancer. CONCLUSIONS: TGF-ß1 levels are significantly associated with aggressive prostate features. In vitro and in vivo alternations of TGF-ß1 expression impacts tumor invasiveness, tumor growth rate and recruitment of immunosuppressive Treg cells in the tumor microenvironment. TGF-ß1 expression may represent a clinical useful biomarker to guide prostate cancer treatment decisions.

Identifying typical physical activity on smartphone with varying positions and orientations.

BACKGROUND: Traditional activity recognition solutions are not widely applicable due to a high cost and inconvenience to use with numerous sensors. This paper aims to automatically recognize physical activity with the help of the built-in sensors of the widespread smartphone without any limitation of firm attachment to the human body. METHODS: By introducing a method to judge whether the phone is in a pocket, we investigated the data collected from six positions of seven subjects, chose five signals that are insensitive to orientation for activity classification. Decision trees (J48), Naive Bayes and Sequential minimal optimization (SMO) were employed to recognize five activities: static, walking, running, walking upstairs and walking downstairs. RESULTS: The experimental results based on 8,097 activity data demonstrated that the J48 classifier produced the best performance with an average recognition accuracy of 89.6% during the three classifiers, and thus would serve as the optimal online classifier. CONCLUSIONS: The utilization of the built-in sensors of the smartphone to recognize typical physical activities without any limitation of firm attachment is feasible.

A Wearable Context-Aware ECG Monitoring System Integrated with Built-in Kinematic Sensors of the Smartphone.

Continuously monitoring the ECG signals over hours combined with activity status is very important for preventing cardiovascular diseases. A traditional ECG holter is often inconvenient to carry because it has many electrodes attached to the chest and because it is heavy. This work proposes a wearable, low power context-aware ECG monitoring system integrated built-in kinetic sensors of the smartphone with a self-designed ECG sensor. The wearable ECG sensor is comprised of a fully integrated analog front-end (AFE), a commercial micro control unit (MCU), a secure digital (SD) card, and a Bluetooth module. The whole sensor is very small with a size of only 58 × 50 × 10 mm for wearable monitoring application due to the AFE design, and the total power dissipation in a full round of ECG acquisition is only 12.5 mW. With the help of built-in kinetic sensors of the smartphone, the proposed system can compute and recognize user's physical activity, and thus provide context-aware information for the continuous ECG monitoring. The experimental results demonstrated the performance of proposed system in improving diagnosis accuracy for arrhythmias and identifying the most common abnormal ECG patterns in different activities. In conclusion, we provide a wearable, accurate and energy-efficient system for long-term and context-aware ECG monitoring without any extra cost on kinetic sensor design but with the help of the widespread smartphone.

Glucose-regulated protein 78 mediates hormone-independent prostate cancer progression and metastasis through maspin and COX-2 expression.

Glucose-regulated protein 78 (GRP78) plays an essential role in embryonic development and in the progression and therapeutic resistance of many cancers. However, little is known about the function of GRP78 in hormone-independent prostate cancer. Here, we found that the expression levels of GRP78 were higher in PC-3 cells than in DU-145 cells. When the expression of GRP78 was silenced using a GRP78-specific small interfering RNA in PC-3 cells, the growth rate and adhesive ability were reduced. Cell migration was dramatically decreased in GRP78-depleted cells. Dissection of the involved signal pathways revealed that maspin expression was upregulated after silencing GRP78 expression. The upregulation of maspin and downregulation of COX-2 may cause the decrease in cell proliferation and migration observed after silencing GRP78 expression. Silencing GRP78 expression may suppress the proliferation, adhesion, and migration of prostate cancer cells via maspin and COX-2 regulation.

Thrombomodulin mediates the migratory ability of hormone-independent prostate cancer cells through the regulation of epithelial-to-mesenchymal transition biomarkers.

Thrombomodulin (TM) is highly expressed in endothelial cells and plays the key role in maintaining physical homeostasis. In addition, many pieces of evidence also show that TM contains the diagnostic value for malignant diseases. TM has been found to correlate with metastatic status in multiple cancers, but its role in prostate cancer progression remains unclear. TM expression was determined in prostate cancer cells (DU-145 and PC-3 cells) using real-time PCR and Western blotting. TM expression was manipulated in prostate cancer cells using TM-specific shRNA and an overexpression system. The proliferation, adhesion, and migratory ability of prostate cancer cells expressing various TM levels were determined using the x'Celligence biosensor system and a transwell migration assay. Higher levels of TM transcription and translation were found in DU-145 cells and were negatively correlated with the low migratory ability of DU-145 cells. After silencing TM expression in DU-145 cells, cell growth decreased, but cell adhesion and migration dramatically increased. TM overexpression in PC-3 cells reduced their metastatic ability. We investigated the possible mechanisms of this phenomenon and determined that the enhanced cell migration was mediated through the expression of E-cadherin and vimentin. TM may be a modulator of hormone-independent prostate cancer (HIPC) metastasis. The downregulation of TM expression enhanced the migratory ability of these cells via an increase in vimentin expression and a decrease in E-cadherin expression.

Thrombomodulin expression regulates tumorigenesis in bladder cancer.

BACKGROUND: The identification of potential tumor markers will help improve therapeutic planning and patient management. Thrombomodulin (TM) is a sensitive urothelial marker. TM was reported to be one of the endogenous anti-metastatic factors and has diagnostic and prognostic values for the progression of carcinoma. In the present study, we examine the role of TM in bladder cancer. METHODS: We studied the role of TM in tumor behavior and related signaling pathways in vitro using the human bladder cancer cell lines HT1376, HT1197, J82 and T24, and in vivo using animal models. We also selected clinical specimens from 100 patients with bladder cancer for immunohistochemical staining to evaluate the predictive capacity of TM in tumor invasiveness. RESULTS: The data revealed that positive immunoreactivity for TM was inversely correlated with clinical stage and DNA methyltransferase 1 immunoreactivity. Decreased TM expression could predict the aggressive tumor growth and advanced clinical stage in bladder cancer. When TM was inhibited, tumor growth rate and invasion ability were augmented in vitro and in vivo. The underlying changes included increased cell proliferation, enhanced epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, inhibition of NF-κB activation significantly increased TM expression and attenuated tumor aggressiveness in bladder cancer. CONCLUSIONS: TM plays an important role in bladder cancer tumor aggressiveness in vitro and in vivo and is a clinically significant predictor that may represent a suitable therapeutic target for bladder cancer.