Search

Abstract Background PTEN (phosphatase and tensin homolog gene on chromosome 10), a well-characterized tumor suppressor, is a key regulator of the phosphatidylinositol-3-kinase (PI3K)/AKT pathway involved in cell survival, metastasis and cell renewal. PTEN expression is closely related to the phenotype, prognosis and drug selection in breast cancer. It is mainly regulated by transcriptional and post-transcriptional modifications. RNA binding motif protein 38 (RBM38), an RNA-binding protein (RBP) and a target of P53 family, plays a crucial role in the regulation of cellular processing, especially in post-transcription regulation and gene transcription. In this study, we investigated a new post-transcription regulation mechanism of PTEN expression by RBM38 in breast cancer. Methods Immunohistochemistry, lentivirus transfections, Western blotting analysis, qRT-PCR and ELISA were used to conduct the relation between RBM38 and PTEN. RNA immunoprecipitation, RNA electrophoretic mobility shift and dual-luciferase reporter assays were employed to identify the direct binding sites of RBM38 with PTEN transcript. Colony formation assay was conducted to confirm the function of PTEN in RBM38-induced growth suppression. Results PTEN expression was positively associated with the expression of RBM38 in breast cancer tissues and breast cancer cells. Moreover, RBM38 stabilized PTEN transcript to enhance PTEN expression via binding to multiple AU/U- rich elements (AREs) in 3′-untranslated region (3′-UTR) of PTEN transcript. Additionally, specific inhibitors of PTEN activity and small interfering (siRNA) of PTEN expression inhibited RBM38-mediated suppression of proliferation, which implied that RBM38 acted as a tumor suppressor partly by enhancing PTEN expression. Conclusion The present study revealed a new PTEN regulating mechanism that PTEN was positively regulated by RBM38 via stabilizing its transcript stability, which in turn alleviated RBM38-mediated growth suppression.

Two new types of sandbars are found in distributary channels of the modern Ganjiang Delta, Poyang Lake, China, respectively named as branching-point bar (BPB) and merging-point bar (MPB). BPB is defined as sandbar formed at the branching point of a channel where one channel branches into two. MPB is defined as sandbar formed at the merging point of two channels. BPB results from current velocity decrease at the branching point. BPB, arrowhead-shaped and growing towards upstream through upstream accretion, can be divided into bar head, middle and tail. Bar head refers to the lower part of the bar below average low water level, submerges under water whether in rainy seasons or dry seasons, and no plants grow on it. Bar middle refers to the middle part of the bar between average low and average high water levels, and sparse plants grow on it. Bar tail refers to the upper part of the bar above average high water level, and plants grow densely on it. From bar head to bar tail, sediment becomes finer and sorting degree becomes poorer; plant fossils increase in number, and silting-mud layers increase both in number and thickness. Vertically BPB shows a fining-upward sequence. BPB can be classified into 3 types: baby BPB with only bar head, child BPB with bar head and middle, and adult BPB with bar head, middle and tail. Generally from the lower delta plain to upper delta plain, BPB becomes more and more mature. If a channel is suddenly abandoned, BPB at different stages may be preserved. MPB is very similar to BPB in depositional characteristics, and main differences lie in its origin and growth direction. Discovery of BPB and MPB has important implications in finding remaining oil in oilfields. Previously, geologists considered point bars on convex bank of meandering channels or longitudinal bars and transverse bars in the middle of braided channels as favorable locations for finding remaining oil. Our study shows such locations as branching points and merging points of channels are also significant because BPB and MPB develop at these locations. Remaining oil has been found at branching points of channels in Pubei Oilfield, Songliao Basin, Northeast China.

Abstract Background RNA-binding protein 38 (RBM38) is a member of the RNA recognition motif (RRM) family of RNA-binding proteins (RBPs). RBM38 often exerts its function by forming regulatory loops with relevant genes. c-Myc is an oncogenic transcription factor that is upregulated in one-third of breast cancers and involved in many cellular processes in this malignancy. In our previous study, RBM38 was identified as a tumor suppressor in breast cancer. In the present study, we investigated the mechanisms underlying the regulation of this tumor suppressor. Methods Lentivirus transfections, Western blotting analysis, qRT-PCR and immunohistochemistry were employed to study the expression of c-Myc and RBM38. Chromatin immunoprecipitation and dual-luciferase reporter assays were performed to investigate the direct relationship between c-Myc protein and the RBM38 gene. RNA immunoprecipitation combined with dual-luciferase reporter assays was conducted to confirm the direct relationship between the RBM38 protein and the c-Myc transcript. Results Knockdown of c-Myc increased RBM38 expression by binding directly to specific DNA sequences (5′-CACGTG-3′), known as the E-box motif, in the promoter region of RBM38 gene. Additionally, RBM38 destabilized the c-Myc transcript by directly targeting AU-rich elements (AREs) in the 3′-untranslated region (3′-UTR) of c-Myc mRNA to suppress c-Myc expression. Moreover, specific inhibitors of c-Myc transcriptional activity inhibited RBM38-induced suppression of growth, implying that RBM38 acts as a tumor suppressor via a mechanism that depends, at least partially, on the reduction of c-Myc expression in breast cancer. Conclusions RBM38 and c-Myc form a unique mutually antagonistic RBM38-c-Myc loop in breast cancer.

Background/Aims: It is known that the activation of hepatic stellate cells (HSCs) is a pivotal step in the initiation and progression of liver fibrosis. Aberrant activated Wnt/β-catenin pathway is known to accelerate the development of liver fibrosis. microRNAs (miRNAs)-mediated Wnt/β-catenin pathway has been reported to be involved in HSC activation during liver fibrosis. However, whether long noncoding RNAs (lncRNAs) regulate Wnt/β-catenin pathway during HSC activation still remains unclear. Methods: Long intergenic noncoding RNA-p21 (lincRNA-p21) expression was detected in Salvianolic acid B (Sal B)-treated cells. Effects of lincRNA-p21 knockdown on HSC activation and Wnt/β-catenin pathway activity were analyzed in Sal B-treated cells. In lincRNA-p21-overexpressing cells, effects of miR-17-5p on HSC activation and Wnt/β-catenin pathway activity were examined. Results: LincRNA-p21 expression was up-regulated in HSCs after Sal B treatment. In primary HSCs, lincRNA-p21 expression was down-regulated at Day 5 relative to Day 2. Sal B-inhibited HSC activation including the reduction of cell proliferation, α-smooth muscle actin (α-SMA) and type I collagen was inhibited by lincRNA-p21 knockdown. Sal B-induced Wnt/β-catenin pathway inactivation was blocked down by loss of lincRNA-p21. Notably, lincRNA-p21, confirmed as a target of miR-17-5p, suppresses miR-17-5p level. Lack of the miR-17-5p binding site in lincRNA-p21 prevents the suppression of miR-17-5p expression. In addition, the suppression of HSC activation and Wnt/β-catenin pathway induced by lincRNA-p21 overexpression was almost inhibited by miR-17-5p. Conclusion: We demonstrate that lincRNA-p21-inhibited Wnt/β-catenin pathway is involved in the effects of Sal B on HSC activation and lincRNA-p21 suppresses HSC activation, at least in part, via miR-17-5p-mediated-Wnt/β-catenin pathway.

Direct interspecies electron transfer has been shown in methane-producing communities, but it is unknown how widespread this mechanism is. Here, Haet al. show that anoxygenic photosynthesis can be driven by direct electron transfer from a heterotrophic partner bacterium.

Purpose. Pancreatitis can lead to systemic inflammatory response, but the relationship between lymphocyte changes and patients with pancreatitis remains unclear. In this study, we evaluated the feedback function of changes in peripheral lymphocyte subsets on the condition of patients with pancreatitis. Materials and Methods. 131 acute pancreatitis (AP) patients and 11 chronic pancreatitis (CP) patients constituted the patients’ group; 20 healthy individuals were enrolled as healthy controls (HC). Serum concentration of C-reactive protein (CRP), amylase, and lipase and the frequency and absolute number of many types of peripheral lymphocytes (including T, B, NK, CD16+/CD56+ T, CD4+ T, CD8+ T, CD4+CD8+ T, and CD4−CD8− T cells) were detected on admission and the seventh day of standard treatment. Besides, the length of hospital stay was recorded. Results. The absolute number of all lymphocytes we studied decreased in patients with CP and in patients with almost all types of AP. The frequency change of lymphocytes varies among the different types of AP. During disease onset, B cell frequency correlated positively with CRP concentration and NK cell frequency correlated positively with amylase and lipase concentration. B cell frequency and CD4+ T cell absolute number were recovering towards normal after short-term treatment. The frequency of B cells and NK cells correlated positively with the length of hospital stay. Conclusions. B cells and NK cells closely correlate with patients’ condition and may help to diagnose AP more accurately and reflect treatment effect of AP in time, affecting the recovery speed of patients with M-AP, which may help physicians to better understand the pathophysiology of pancreatitis.

Mind wandering is a phenomenon that involves thoughts shifting away from a primary task to the process of dealing with other personal goals. A large number of studies have found that mind wandering can predict negative emotions, but researchers have seldom focused on the positive role of mind wandering. The current study aimed to explore the relationships among mind wandering, emotions and thought control ability, which is the ability to inhibit one’s own unpleasant or unwanted intrusive thoughts. Here, we collected resting-state functional magnetic resonance imaging (rsfMRI) data from 368 participants who completed a set of questionnaires involving mind wandering, thought control ability and positive or negative emotions. The results revealed that (1) rsfMRI connectivity features related to thought control ability and mind wandering could divide individuals into two groups: HMW (high mind-wandering) group and LMW (low mind-wandering) group. The HMW group scored lower in thought control ability (TCA), higher in negative emotion (NE) and lower in positive emotion (PE) than the LMW group. (2) TCA moderated the association between MW and positive affect (PA). (3) Two groups exhibited different segregation within key nodes (SWKN) of the frontoparietal control network (FPCN), and the subsequent analysis showed that the SWKN of the FPCN was negatively correlated with PA. These findings indicate that TCA moderates the effect of mind wandering on affect via the FPCN, which may have important implications for our understanding of the positive role of mind wandering.

Background. In patients with persistent atrial fibrillation (AF), the procedural and clinical outcomes of ablation combined with infusion of antiarrhythmic drug are unknown. Objectives. To determine the impact of low-dose ibutilide after circumferential pulmonary vein isolation (CPVI) and/or left atrial (LA) substrate modification on acute procedural and clinical outcome of persistent AF. Methods. In a prospective cohort of 135 consecutive patients with persistent AF, intravenous 0.25 mg ibutilide was administered 3 days before the procedure and intraprocedurally, if required, after CPVI and/or additional LA substrate modification of sites with continuous, rapid or fractionated, and low-voltage (0.05–0.3 mv) atrial activity. Results. Persistent AF was terminated by CPVI alone (n=15) or CPVI + ibutilide (n=32) in 47 (34.8%) patients (CPVI responders). Additional LA substrate modification without (n=33) or with subsequent administration of 0.25 mg ibutilide (n=19) terminated AF in another 52 (38.5%) patients (substrate modification responders). Sinus rhythm was restored by electrical cardioversion in the remaining 36 (26.7%) patients (nonresponders). The mean LA substrate ablation time was 14 ± 6 minutes. At follow-up of 24 ± 10 months, the rates of freedom from atrial tachyarrhythmias among the responders in CPVI and substrate modification groups were mutually comparable (66.0% and 69.2%) and higher than among the nonresponders (36.1%; P

To exchange electrons with extracellular substrates, some microorganisms employ extracellular electron transfer (EET) pathways that physically connect extracellular redox reactions to intracellular metabolic activity. These pathways are made of redox and structural proteins that work cooperatively to transfer electrons between extracellular substrates and the cytoplasmic membrane. Crucial to the bacterial and archaeal EET pathways are the quinol oxidases and/or quinone reductases in the cytoplasmic membrane where they recycle the quinone/quinol pool in the cytoplasmic membrane during EET reaction. Up to date, three different families of quinol oxidases and/or quinone reductases involved in bacterial EET have been discovered. They are the CymA, CbcL/MtrH/MtoC, and ImcH families of quinol oxidases and/or quinone reductases that are all multiheme c-type cytochromes (c-Cyts). To investigate to what extent they are distributed among microorganisms, we search the bacterial as well as archaeal genomes for the homologs of these c-Cyts. Search results reveal that the homologs of these c-Cyts are only found in the Domain Bacteria. Moreover, the CymA homologs are only found in the phylum of Proteobacteria and most of them are in the Shewanella genus. In addition to Shewanella sp., CymA homologs are also found in other Fe(III)-reducing bacteria, such as of Vibrio parahaemolyticus. In contrast to CymA, CbcL/MtrH/MtoC, and ImcH homologs are much more widespread. CbcL/MtrH/MtoC homologs are found in 15 phyla, while ImcH homologs are found in 12 phyla. Furthermore, the heme-binding motifs of CbcL/MtrH/MtoC and ImcH homologs vary greatly, ranging from 3 to 23 and 6 to 10 heme-binding motifs for CbcL/MtrH/MtoC and ImcH homologs, respectively. Moreover, CymA and CbcL/MtrH/MtoC homologs are found in both Fe(III)-reducing and Fe(II)-oxidizing bacteria, suggesting that these families of c-Cyts catalyze both quinol-oxidizing and quinone-reducing reactions. ImcH homologs are only found in the Fe(III)-reducing bacteria, implying that they are only the quinol oxidases. Finally, some bacteria have the homologs of two different families of c-Cyts, which may improve the bacterial capability to exchange electrons with extracellular substrates.

The androgen receptor (AR) was found to suppress hepatocellular carcinoma (HCC) metastasis at late stages. Due to this discovery, we searched for some AR enhancers to increase the efficacy of Sorafenib chemotherapy, and identified the microRNA (miR)-367-3p, whose expression is positively correlated with AR expression in advanced HCC, as an HCC metastasis suppressor. Combining miR-367-3p with Sorafenib showed better efficacy to suppress HCC cell invasion in vitro and in vivo. Mechanism dissection revealed that miR-367-3p could increase AR expression via directly targeting the 3′UTR of MDM2 to decrease MDM2 protein expression. The resultant increase of AR expression might then promote the expression of FKBP5 and PHLPP, thus dephosphorylating and inactivating AKT and ERK, to suppress the HCC cell invasion. Interestingly, the suppression of pAKT by miR-367-3p could subsequently attenuate the phosphorylation of AR and MDM2, giving rise to additional enhancement of AR protein expression, effectively forming a positive feedback loop. Together, these results suggest that miR-367-3p may function as an AR enhancer to increase Sorafenib chemotherapy efficacy via altering the MDM2/AR/FKBP5/PHLPP/(pAKT and pERK) signals to better suppress HCC metastasis. Successful development of this newly combined chemotherapy in the future may help us to better suppress the HCC metastasis at late stages.

In this paper, TiO2 photoanodes were doped with yttrium under different doping concentrations via hydrothermal method and further employed to assemble dye-sensitized solar cells (DSSCs). XRD, XPS, SEM, TEM, UV–Vis DRS and PL measurements were carried out to investigate the yttrium doping effects on crystal structure, chemical status, optical properties and dye loading capacity of the photoanodes. The photovoltaic performance of the photoanodes with various yttrium doping concentration was measured by recording the photocurrent-photovoltaic curves, and the result indicated that TiO2:0.006 Y exhibited the best power conversion efficiency with high short circuit current density (Jsc) and open circuit voltage (Voc). This improvement may be due to the enhanced visible light harvesting, increased dye loading capacity and reduced photoelectron recombination. Keywords: Dye sensitized solar cells, TiO2 photoanode, Rare earth doping, Yttrium

Droughts are a recurrent phenomenon in the semiarid forest-steppe ecotone of Mongolia with negative consequences for tree growth and agricultural management. In order to better cope with the uncertainty of a changing climate, the study of historical drought and its effects on forests could provide useful insights into ecosystem responses to climate variability. Siberian larch (Larix sibirica) is a dominant tree species in Western Mongolia that provides a valuable source of proxy data in the form of annual rings. We used dendrochronological techniques to establish a standard master chronology and analyze the relationship between annual ring widths and climatic factors. Correlation analyses revealed that the strongest associations of tree-ring index (TRI) values for the master chronology to direct climate variables were June temperature (r = −0.36, p < 0.01) and precipitation (r = 0.39, p < 0.01). The master chronology was strongly correlated to Palmer Drought Severity Index (PDSI) for June (r = 0.606, p < 0.001), and this variable (PDSIJun) was chosen for reconstruction. A simple linear regression of PDSIJun based on TRI explained 35.4% of the total variance for the period 1965–2016 and based on this model the PDSIJun changes from 1731–2016 were reconstructed. Split–sample calibration–verification tests were conducted to evaluate the quality of the model used for climate reconstruction. In the past 286 years, the number of non-drought years (PDSI > 0) was low, with a frequency of only 14.1% of the total reconstruction years. Extreme drought (PDSIJun < −2.70) occurred frequently in the 19th and early and late 20th centuries. Multi-taper method (MTM) spectra and wavelet analysis showed that the reconstructed PDSI series had high and low frequency periods (2.4–3.3 and 85–92 years). Our findings provide an understanding of the drought history of the semiarid forest-steppe ecotone of western Mongolia.

The rise of edge computing has promoted the development of the industrial internet of things (IIoT). Supported by edge computing technology, data acquisition can also support more complex and perfect application requirements in industrial field. Most of traditional sampling methods use constant sampling frequency and ignore the impact of changes of sampling objects during the data acquisition. For the problem of sampling distortion, edge data redundancy and energy consumption caused by constant sampling frequency of sensors in the IIoT, a data-driven adaptive sampling method based on edge computing is proposed in this paper. The method uses the latest data collected by the sensors at the edge node for linear fitting and adjusts the next sampling frequency according to the linear median jitter sum and adaptive sampling strategy. An edge data acquisition platform is established to verify the validity of the method. According to the experimental results, the proposed method is more effective than other adaptive sampling methods. Compared with constant sampling frequency, the proposed method can reduce the edge data redundancy and energy consumption by more than 13.92% and 12.86%, respectively.

Visible-light-driven Cr-doped SrTiO _3 nanocubes were successfully synthesized by hydrothermal method in alkaline KOH conditions. X-ray diffraction spectroscopy (XRD), Raman spectra, x-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to characterize the samples, and the Cr-doped SrTiO _3 possess cubic morphology with about 30–50 nm in size, and single-crystal feature. In addition, the Cr-doped SrTiO _3 extended light-harvesting properties to visible-light region which was testified by UV–vis absorption spectra, and excellent charge transfer and separation efficiency were approved by photo fluorescence spectra (PL), electrochemical impedance spectroscopy (EIS) and photocurrent response measurements. Among the synthesized photocatalysts, SrTiO _3 nanocubes doped with 2% Cr by molar ratio exhibits the highest photocatalytic activity, achieving 11.66 μ mol of H _2 evolution during 5 h visible-light irradiation. This study provides a facile and effective way to enhance the performance of SrTiO _3 -based photocatalysts.

As a new type of heterogeneous social network, Event-Based Social Network (EBSN) has experienced rapid development after its appearance. In EBSN, the interaction data between users and events is relatively sparse because of the short life cycle of events, which brings great challenges to event recommendation. In this paper, a multiple features based event recommendation method is proposed, which makes full use of various information in the network to mine users’ preference for event recommendation. Firstly, a heterogeneous information network model is constructed based on the intrinsic structure characteristics. Then multiple features about topology, temporal, spatial and semantic are extracted to measure the user’s event preference, and a linear scoring model is designed to acquire user’s preference score on events. At last, the bayesian personalized ranking method is used to learn the feature weights by using user-event pairs in scoring model and events are recommended to users according to the descending score order. Experiments are carried out on two real EBSN data sets, the results show that our approach can effectively alleviate the data sparseness problem and achieve better recommendation results.

Hybrid ablation, an emerging therapy that combines surgical intervention and catheter ablation, has become a viable option for the treatment of persistent atrial fibrillation. In this analysis, we aimed to evaluate the safety and efficacy of hybrid ablation, as well as compare the outcomes of one-step and staged approaches.We conducted a search in major online databases and selected the studies that met the inclusion criteria. The primary endpoint was defined as no episode of atrial fibrillation or atrial tachycardia lasting longer than 30 seconds without administration of antiarrhythmic drugs.Sixteen studies including 785 patients (paroxysmal atrial fibrillation, n = 83; persistent atrial fibrillation, n = 214; long-standing persistent atrial fibrillation, n = 488) were selected. Average history of atrial fibrillation was (5.0±1.6) years. The pooled proportion of patients who were arrhythmia-free at the primary endpoint was 73% (95% CI, 64%-81%, Cochran's Q, P

Based on data from core analysis and thin section, the influence of overpressure on the compaction and cementation of the Paleogene Dongying Formation reservoir is studied quantitatively in the northwestern subsag of the Bozhong sag, Bohai Bay Basin. Reservoir compaction is inhibited obviously by overpressure because the compaction strength of sandstones in overpressure setting is weaker than that of its overlying sandstones in normal setting. The primary porosity of sandstones is preserved about 1.1% as pore pressure is above hydrostatic pressure every 4 MPa in overpressure setting. Moreover, reservoir cementation is affected by overpressure: cementation strength is strong in overpressure setting and the adjacent inner-pressure setting, while it declines rapidly in outer-pressure setting far away from the overpressure. The thickness of zone with strong carbonate strength is thinner than that with strong authigenic clay strength. Differential carbonate cementation presents “build-up effect in fine grain”, which means that carbonate is prior to generate in sandstones of fine size, and causes that physical properties of sandy reservoir are different in the same overpressure setting. The results show that outer-pressure setting is the most favorable zone for preserving primary porosity, overpressure setting is the secondary, and iner-pressure setting is relatively poor. Key words: overpressure, compaction strength, cementation strength, differential carbonate cementation, Bozhong sag

Background: Hepatocellular carcinoma (HCC) is one of the most lethal malignancies worldwide. A major cause for the failure of cancer therapy is the development of chemoresistance. Although progress has been made in the study of the mechanisms underlying cancer cells resistance, little is known about the role of microRNAs (miRNAs) in cancer therapy resistance. Methods and Results: Fifteen miRNAs, including 6 up-regulated miRNAs (> 2.0-fold) and 9 down-regulated miRNAs (Conclusion: Our study showed that miR-141 plays a key role in 5-FU resistance by down-regulating Keap1 expression, thereby reactivating the Nrf2-dependent antioxidant pathway, which may serve as a potential target for overcoming 5-FU resistance in hepatocellular carcinoma cells.

The most common cause of gastric cancer is infection with helicobacter pylori (HP), but the associated molecular mechanism is not well understood. In the present study, we found a marked increase in the expression of B7-H1, a member of the B7 co-stimulatory family of molecules that bind to programmed death-1 (PD-1) and play a critical immunoregulatory role in the cell-mediated immune response, in HP-positive gastric cancer tissue. Infection of cultured gastric cancer cells with HP promoted B7-H1 expression and inhibited miR-152 and miR-200b expression. We further demonstrated that these two miRNAs targeted B7-H1 mRNA and suppressed B7-H1 expression in gastric cancer cells. Finally, B7-H1 expression was found to correlate with miR-152 and miR-200b levels in gastric tumor tissues from human patients. Our findings suggest a novel mechanism by which HP infection promotes gastric cancer and also suggest potential targets, i.e., miR-152 and miR-200b, for the prevention and treatment of gastric cancer.

Five provinces in central People’s Republic of China (P.R. China) have successfully reduced the burden of malaria due to Plasmodium vivax in the last 7 years. The results of the Action Plan of China Malaria Elimination (APCME) that com- menced in 2010 are analysed against the background of the progress reached by the national malaria control programme (NMEP) that was launched in 2006. We examined the epidemiological changes in the number of autochthonous cases over time and discuss the feasibility of achieving the goal of malaria elimination by 2020. There was a total decline of 34,320 malaria cases between 2006 and 2012 arriving at an average annual incidence of 0.04 per 10,000 people by 2012. At the same time, the number of counties reporting autochthonous cases declined from 290 to 19. Spatial autocorrelation and Bayesian modelling were used to evaluate the datasets and predict the spatio-temporal pattern in the near future. The former approach showed that spatial clusters of P. vivax malaria existed in the study region during the study period, while the risk prediction map generated by the Bayesian model indicates that only sporadic malaria cases will appear during in the future. The results suggest that the initial NMEP approach and the follow-up APCME strategy have played a key role in reducing the threat of malaria in central P.R. China. However, to achieve the goal of malaria elimination by the end of the current decade, interven- tion plans must be adjusted with attention paid to those endemic counties still at risk according to the prediction map.

Background and objective Afatinib is an irreversible ErbB-family blocker with a clinical activity in non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations. The aim of this study is to assess the safety of afatinib in patients with advanced lung adenocarcinoma. Methods Patients with lung adenocarcinoma (stage IIIb or IV) with EGFR mutations were first-line treated with an oral administration of afatinib (40 mg/d) until disease progression. Adverse events, effects, and survival condition were observed. Results The most common adverse events were diarrhea (n=5, 100%), skin rash (n=4, 80%), and mucositis/stomatitis (n=4, 80%). Moderate toxicities not exceeding grade 3 were observed. Relatively, the most serious adverse reaction was mucositis/stomatitis. Mild diarrhea occurred in all patients. Three patients experienced temporary drug withdrawal and dose reduction because of adverse reaction. Among the four patients who were evaluated, partial response was observed in two patients (50%), one with stable disease (25%) and one with progressive disease (25%). Median progression-free survival was 9.7 months, whereas median overall survival was 18.4 months. Conclusion Afatinib was approved as first-line treatment for patients with advanced lung adenocarcinoma. The most common adverse events were diarrhea and skin rash. However, mucositis/stomatitis related to afatinib should also be considered. Considering the small number of cases, the conclusion requires more trials for confirmation.

Treadmills are widely used to recover walking function in the rehabilitation field for those patients with gait disorders. Nevertheless, the ultimate goal of walking function recovery is to walk on the ground rather than on the treadmill. This study aims to determine the effect of treadmill walking on gait and upper trunk movement characteristics using wearable sensors. Eight healthy male subjects are recruited to perform 420-m straight overground walking (OW) and 5 min treadmill walking (TW), wearing 3 inertial measurement units and a pair of insole sensors. In addition to common linear features, nonlinear features, which contains sample entropy, maximal Lyapunov exponent and fractal dynamic of stride intervals (detrended fluctuation analysis), are used to compare the difference between TW and OW condition. Canonical correlation analysis is also used to indicate the correlation between upper trunk movement characteristics and gait features in the aspects of spatiotemporal parameters and gait dynamic features. The experimental results show that the treadmill can cause a shorter stride length, less stride time and worsen long-range correlation of stride intervals. And the treadmill can significantly increase the stability for both gait and upper trunk, while it can significantly reduce gait regularity during swing phase. Canonical correlation analysis results show that treadmill can reduce the correlation between gait and upper trunk features. One possible interpretation of these results is that people tend to walk more cautiously to prevent the risk of falling and neglect the coordination between gait and upper trunk when walking on the treadmill. This study can provide fundamental insightful information about the effect of treadmill walking on gait and upper trunk to support future similar studies.

Traditional Collaborative Representation-based Classification algorithms for face recognition (CRC) usually suffer from data uncertainty, especially if it includes various poses and illuminations. To address this issue, in this paper, we design a new CRC method using histogram statistical measurement (H-CRC) combined with a 3D morphable model (3DMM) for pose-invariant face classification. First, we fit a 3DMM to raw images in the dictionary to reconstruct the 3D shapes and textures. The fitting results are used to render numerous virtual samples of 2D images that are frontalized from arbitrary poses. In contrast to other distance-based evaluation algorithms for collaborative (or sparse) representation-based methods, the histogram information of all the generated 2D face images is subsequently exploited. Second, we use a histogram-based metric learning to evaluate the most similar neighbours of the test sample, which aims to obtain ideal result for pose-invariant face recognition using the designed histogram-based 3DMM model and online pruning strategy, forming a unified 3D-aided CRC framework. The proposed method achieves desirable classification results that are conducted on a set of well-known face databases, including ORL, Georgia Tech, FERET, FRGC, PIE and LFW.

This study concerns an integrated strategy of schistosomiasis control, focusing on the management and elimination of the main transmission cycles and reservoirs along Yangtze river, Jiangsu Province (China), instituted in 2004. Our analysis, including mapping, spatial autocorrelation and spatio-temporal scanning, was implemented between 2001 and 2013 to explore the changes in the distribution of Oncomelania hupensis, the intermediate host of Schistosoma japonicum. Two high-density snail locations in the upper and middle reaches of the river were observed along with one high-risk area due to infected snails in the upper reaches at the beginning of the study period. The number of high-density snail habitats declined sharply after 2004 and infected snails disappeared completely by 2010. Global spatial autocorrelation showed spatial clustering of snails in general, as well as of infected ones when snail densities were relatively high, while local spatial autocorrelation showed the number of specific clusters declining and switching spatially from the upper to the middle reaches of the Yangtze river in Jiangsu Province during the study period. The integrated snail control strategy was found to be effective, but the middle reaches of the river will require continued strong control resources.

The present study used event-related potentials (ERPs) to investigate the function of signals induced by cognitive conflict during the detection stage and the resolution stage of perceptual processing. The study used a combination of the Stroop task and an affective priming task to examine the conflict priming effect when the stimulus onset asynchrony (SOA) was 200 ms or 800 ms. Behavioral results showed that the RTs were shorter for positive targets following congruent primes relative to incongruent primes, and for negative targets following incongruent primes relative to congruent primes when the SOA was 200 ms. ERP results showed that the N2 amplitudes (200-300 ms) for incongruent stimuli were significantly larger than for congruent stimuli in the Stroop task, which indicated a significant conflict effect. Moreover, the N400 amplitudes (500-700 ms) for positive targets after congruent primes were significantly lower than those after incongruent primes when the SOA was 200 ms, which showed a significant negative priming effect. While the SOA was 800 ms, behavioral results showed that the RTs were shorter for positive targets following incongruent primes relative to congruent primes. ERP results showed that the N2 amplitudes (200-300 ms) for incongruent stimuli were significantly larger than for congruent stimuli in the Stroop task, which indicated a significant conflict effect. The N400 amplitudes (1100-1300 ms) for the negative targets after congruent primes were significantly lower than those after incongruent primes when the SOA was 800 ms, which showed a significant positive priming effect. The results demonstrated that the functions of signals induced by cognitive conflict were reversed in two different cognitive processing stages.

Recently, numerous studies have reported that hexokinase-2 (HK2) is aberrantly expressed in cancer, indicating that HK2 plays a pivotal role in the development and progression of cancer. However, its prognostic significance in solid tumor remains unclear. Accordingly, we performed a meta-analysis to assess the prognostic value of HK2 in solid tumor.Eligible studies were identified using PubMed, Embase, and Web of Science databases. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS) or progression-free survival (PFS)/disease-free survival (DFS)/relapse-free survival (RFS) were estimated with random effects or fixed effects models, respectively. Subgroup analysis was also performed according to patients' ethnicities, tumor types, detection methods, and analysis types.Data from 21 included studies with 2532 patients were summarized. HK2 overexpression was significantly associated with worse OS (pooled HR = 1.90, 95% CI = 1.51-2.38, p < 0.001) and PFS (pooled HR = 2.91, 95% CI = 2.02-4.22, p < 0.001) in solid tumor. As to a specific form of cancer, the negative effect of HK2 on OS was observed in hepatocellular carcinoma (pooled HR = 2.06, 95% CI = 1.67-2.54, p < 0.001), gastric cancer (pooled HR = 1.72, 95% CI = 1.09-2.71, p = 0.020), colorectal cancer (pooled HR = 2.89, 95% CI = 1.62-5.16, p < 0.001), but not in pancreatic cancer (pooled HR = 1.13, 95% CI = 0.28-4.66, p = 0.864). No publication bias was found in the included studies for OS (Begg's test, p = 0.325; Egger's test, p = 0.441).In this meta-analysis, we identified that elevated HK2 expression was significantly associated with shorter OS and PFS in patients with solid tumor, but the association varies according to cancer type.

Specific isotopic labeling of hemes provides a unique opportunity to characterize the structure and function of heme-proteins. Unfortunately, current methods do not allow efficient labeling in high yields of multiheme cytochromes c, which are of great biotechnological interest. Here, a method for production of recombinant multiheme cytochromes c in Escherichia coli with isotopically labeled hemes is reported. A small tetraheme cytochrome of 12 kDa from Shewanella oneidensis MR-1 was used to demonstrate the method, achieving a production of 4 mg pure protein per liter. This method achieves, in a single step, efficient expression and incorporation of hemes isotopically labeled in specific atom positions adequate for spectroscopic characterization of these complex heme proteins. It is, furthermore, of general application to heme proteins, opening new possibilities for the characterization of this important class of proteins.