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Before arriving at the intracellular destinations, probes might be trapped in the lysosomes, reducing the amount of cargos, which compromises the therapeutic outcomes. The current methods are based on the fact that probes enter the lysosomes and then escape from them, which do not fundamentally solve the degradation by lysosomal hydrolases. Here, an enzyme-responsive modular peptide probe named PKP that can be divided into two parts, Pal-part and KP-part, by matrix metalloproteinase-2 (MMP-2) overexpressed in tumor microenvironments is designed. Pal-part quickly enters the cells and forms nanofibers in the lysosomes, decreasing protein phosphatase 2A (PP2A), which transforms the endocytic pathway of KP-part from clathrin-mediated endocytosis (CME) into caveolae-mediated endocytosis (CvME) and allows KP-part to directly reach the mitochondria sites without passing through the lysosomes. Finally, through self-regulating intracellular delivery pathways, the mitochondrial delivery efficiency of KP-part is greatly improved, leading to an optimized image-guided therapeutic efficiency. Furthermore, this system also shows great potential for the delivery of siRNA and doxorubicin to achieve precise cancer image-guided therapy, which is expected to significantly expand its application and facilitate the development of personalized therapy.

Cell membrane is a vital barrier to protect the cell from outside damage and involved in many biochemical processes. It is of great significance to label the cell membrane to explore its function. ...

The aims of this study were to determine the prognostic value of primary tumor surgery and identify optimal candidates for such surgery among patients with seminoma and distant metastasis at diagnosis. We identified 521 patients with seminoma and distant metastasis at diagnosis between 2004 and 2014 from the Surveillance, Epidemiology, and End Results database. Among these patients, 434 had undergone surgery, whereas 87 had not. The prognostic value of primary tumor surgery was assessed by Kaplan-Meier methods, log-rank analyses, and multivariate Cox's proportional hazards model. Survival curves and forest plots were also plotted. Survival analysis indicated that patients who underwent surgery had a better 5-year overall survival and cancer-specific survival than those who did not. Multivariate analyses demonstrated that primary tumor surgery is an independent prognostic factor for overall survival and cancer-specific survival, along with age at diagnosis, M stage, and marital status. In addition, primary tumor surgery still had considerable prognostic value in the subgroup of patients with lymph node metastasis. Further, forest plots demonstrated that patients with M1a stage, N1 or N2-3 stage, and a younger age at diagnosis (

Nervous system is critically involved in bone homeostasis and osteogenesis. Dopamine, a pivotal neurotransmitter, plays a crucial role in sympathetic regulation, hormone secretion, immune activation, and blood pressure regulation. However, the role of dopamine on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) remains poorly understood. In this study, we firstly investigated the effect of dopamine on the apoptosis, proliferation, and osteogenic differentiation of rBMSCs. Dopamine did not, however, interfere with the apoptosis and proliferation of rBMSCs. Interestingly, dopamine suppressed the osteogenic differentiation of rBMSCs, as characterized by reduced ALP staining, ALP activity, mineralized nodule formation, and the mRNA and protein levels of osteogenesis-related genes (

Background Displaced aggression is a specific form of attack prompted by rumination on anger experiences and revenge thought which might lead to expression of anger on innocent people. There is sufficient evidence demonstrating the potential role of agreeableness in reducing displaced aggression in theory. However, little is known about the neural basis of displaced aggression and how agreeableness and the underlying neural mechanisms link to displaced aggression. Methods In this investigation, we examined these issues on 123 college students by assessing resting-state brain activity (i.e. amplitude of low-frequency fluctuation, ALFF) and connectivity (i.e. resting-state functional connectivity, RSFC). Results Whole-brain correlation analysis revealed that a higher level of displaced aggression was linked with decreased ALFF in the left dorsomedial prefrontal cortex (dmPFC) and decreased RSFC between the left dmPFC and left ventromedial prefrontal cortex (vmPFC). Mediation analysis further revealed that left dmPFC activity and the left dmPFC–vmPFC connectivity mediated the relationship between agreeableness and displaced aggression, as well as agreeableness mediated the relation between left dmPFC activity and the left dmPFC–vmPFC connectivity and displaced aggression. Limitations Only ALFF and RSFC were used as indicators of brain function in this study. The two mediation models need to be further tested by longitudinal design or experimental methods in further studies. Conclusions This study suggested that dmPFC and vmPFC might be the functional neural markers of displaced aggression and provided two possible mediation models regarding the relationship among the resting-state brain activity and connectivity, agreeableness and displaced aggression.

Denitrification is an important part of the nitrogen cycle and the key step to removal of nitrogen in surface-flow wetlands. In this study, we explored space–time analysis with high-throughput sequencing to elucidate the relationships between denitrifying bacteria community structures and environmental factors during different seasons. Our results showed that along the flow direction of different processing units, there were dynamic changes in physical and chemical indicators. The bacterial abundance indexes (ACEs) in May, August, and October were 686.8, 686.8, and 996.2, respectively, whereas the Shannon-Weiner indexes were 3.718, 4.303, and 4.432, respectively. Along the flow direction, the denitrifying bacterial abundance initially increased and then decreased subsequently during the same months, although diversity tended to increase. The abundance showed similar changes during the different months. Surface flow wetlands mainly contained the following denitrifying bacteria genus: unclassified Bacteria (37.12%), unclassified Proteobacteria (18.16%), Dechloromonas (16.21%), unranked environmental samples (12.51%), unclassified Betaproteobacteria (9.73%), unclassified Rhodocyclaceae (2.14%), and Rhodanobacter (1.51%). During different seasons, the same unit showed alternating changes, and during the same season, bacterial community structures were influenced by the second genus proportion in different processing units. ACEs were strongly correlated with temperature, dissolved oxygen, and pH. Bacterial diversity was strongly correlated with temperature, electrical conductivity, pH, and oxidation reduction potential. Denitrifying bacteria are greatly affected by environmental factors such as temperature and pH.

Enzyme, which exists widely in organisms, has high specificity and high catalytic efficiency for its substrates. The absence, the reduced activity, or the overexpression of enzyme are closely related to the occurrence and development of diseases. Therefore, enzyme is often used as markers for disease detection and treatment. To detect enzyme activity and track drug release, aggregation-induced emission (AIE) bioprobes have been developed because of their excellent photostability and high signal-to-noise ratio (SNR). Among them, peptide-based AIE bioprobes with great biocompatibility and specificity are favored by an increasing number of researchers. Enzymatic hydrolysis of peptide can cause aggregation of AIE molecules and drug release. In this review, enzyme-responsive peptide-based AIE bioprobes used for biomedical application are summarized according to the three aggregation strategies triggered by various reaction between peptide and enzyme, including enzyme-triggered precipitate, enzyme-catalyzed coupling, and enzyme-instructed self-assembly. By giving some representative examples, we discuss how each aggregation strategy detects enzyme activity and treats the diseases under imaging guidance. Finally, we comment on the current problems and future prospects of enzyme-responsive peptide-based AIE bioprobes.

In order to achieve the integration of driver experience and heterogeneous vehicle platform characteristics in the motion planning algorithm, based on the driver-behavior-based transferable motion primitives, a general motion planning framework for offline generation and online selection of motion primitives (MPs) is proposed. The optimal control theory is applied to solve the boundary value problems in the process of generating MPs, where the driver behaviors and the vehicle motion characteristics are integrated into the optimization in the form of constraints. Moreover, this paper proposes a layered, unequal-weighted MPs selection framework and utilizes the combination of environmental constraints, nonholonomic vehicle constraints, trajectory smoothness, and collision risk as the single-step extension evaluation index. The library of MPs generated offline demonstrates that the proposed generation method realizes the effective expansion of the MP types and achieves the diverse generation of MPs with various velocity attributes and platform types. We also present how the MP selection algorithm utilizes the unique MP library to achieve the online extension of MP sequences. The results show that the proposed motion planning framework can not only improve the efficiency and rationality of the algorithm based on driving experience but also can transfer between heterogeneous vehicle platforms and highlight the unique motion characteristics of the platform.

High pressure high temperature technology is an effective route for preparing thermoelectric materials. In this work, a series of multi-doped Mg2.02−xAl x Si1−3yBi2ySb y (x = 0.03, 0.06, y = 0.005, 0.01) compounds have been prepared successfully by high pressure and high temperature method. The effects of post annealing on the microstructure and thermoelectric properties have been investigated. It is found that both electrical conductivity and thermal conductivity are significantly suppressed by annealing. Lower lattice thermal conductivities are observed in Mg1.96Al0.06Si1−3yBi2ySb y compounds, which should be attributed to the increased point-defects phonon scattering of Bi and Sb dopants induced by Al addition. Finally, a maximal figure of merit of 0.9 is achieved by Mg1.96Al0.06Si0.985Bi0.01Sb0.005 at 773 K.

Constructed wetlands (CWs) have been regarded as efficient technologies for both wastewater treatment and reuse of water resources. Most studies on CW treatment efficiency are limited to a short-term perspective, and there are still many unknowns about the long-term performance of CWs. Here we evaluated the performance of an integrated CW that has been in operation for more than ten years. The average removal rates of TN and TP were maintained at 53.6% and 67.3% over 10 years, respectively. The annual mass reductions in TN and TP reached 937.5 kg ha−1 yr−1 and 303.2 kg ha−1 yr−1, respectively. In addition, TN removal rate was significantly higher in summer and autumn than those in spring, yet there was no seasonal difference in TP removal. The bacterial richness and diversity in summer and autumn were higher than those in spring. TN and TOC not only determine the bacterial community structure, but also affect the removal efficiency of CW. Denitrification and dephosphorization microorganisms were enriched and accounted for a considerable proportion (21.14–52.85%) in the bacterial community. In addition, the relative abundance of Pseudomonas was significantly positively related with the rate of TN and TP removal.

Air pollution especially of PM_(2.5) pollution is a serious problem in Beijing. In order to quantify the effect of a festival in which pollution was expected to be reduced, we collected and analyzed PM_(2.5) samples in urban Beijing during the 2015 Spring Festival (from February 9^(th) to March 6^(th) 2015). We divided the sampling period into three phases: non-haze, haze and firework days. The average concentration of PM_(2.5) was highest on firework days at 248.9 μg m^(-3), followed by haze days (199.9 μg m^(-3)) and non-haze days (90.8 μg m^(-3)). The air quality of non-haze days during the holiday was better than that during non-holiday periods. Secondary inorganic ions (SO_4^(2-), NO_3^- and NH_4^+) were enriched on the haze days, while those on firework days contained large amounts of Cl^- and K^+, but small amounts of NO_3^- and NH_4^+. Ratios of NO_3^-/SO_4^(2-), SO_4^(2-)/K^+ and Cl^-/K^+ effectively distinguished the characteristics of PM_(2.5) between firework events and haze days. Ion balance calculations indicated that the acidity of PM_(2.5) from firework days was higher than that from haze and non-haze days. A method using enrichment factors (EF) found that crustal elements (EF ＜ 10 on all three types of days) included Ca, Al, Fe, Na, Co, Ni, P, Ti, and V; firework elements (EF ＞ 10 on firework days, significantly higher than haze days) were made up of Ba, Cr, Cu, Mg, Pb, S, Si, and Zn; common anthropogenic pollution elements (EF ＞ 10 in all three types of days) were As, Cd, Cu, Pb, S, Sb, Zn. Differences in chemical characteristics indicated that holidays such as the Spring Festival can affect air pollution patterns in two ways: a decrease in the population and vehicles but an increase in activities such as firework displays.

In addition to standard TNM N staging, lymph node ratio (LNR) and log odds of metastatic lymph node (LODDS) staging methods have been developed for cancer staging. We compared the prognostic performance of the total number of lymph nodes examined (TNLE), number of metastatic lymph node (NMLN), LNR, and LODDS in prostate cancer. Data from 1400 patients diagnosed with prostate cancer between 2004 and 2009 who underwent lymphadenectomy were extracted from the Surveillance Epidemiology and End Results database. Kaplan–Meier methods and multivariable Cox regression analysis were used to evaluate the prognostic value of different lymph node staging schemes in patients with lymph node metastasis. Univariate analysis showed that age, T stage, radiotherapy history, Gleason score, LNR classification, LODDS classification, and NMLN except TNLE classification were significant prognostic factors for overall survival. In multivariate analysis, LNR classification, LODDS classification, and NMLN but TNLE classification remained significant prognostic factors for overall survival. LNR classification had the highest C-index (0.672; 95% confidence interval [CI]: 0.609–0.734) and the lowest Akaike information criterion (AIC) (4057.018), indicating the best prognostic performance. Scatter plots showed that LODDS increased with increasing LNR, exhibiting a strong overall correlation between these two lymph node staging methods (r2 = 0.9072). LNR and LODDS generally increased with increasing NMLN, although the correlation was relatively low. Our results indicate that LNR and LODDS may be better predictors of overall survival than the AJCC/UICC N category in patients undergoing curative surgery for prostate cancer.

A new biosensor was engineered to visualize Lck kinase preactivation and regulation in live T cells., Lck plays crucial roles in TCR signaling. We developed a new and sensitive FRET biosensor (ZapLck) to visualize Lck kinase activity with high spatiotemporal resolutions in live cells. ZapLck revealed that 62% of Lck signal was preactivated in T-cells. In Lck-deficient JCam T-cells, Lck preactivation was abolished, which can be restored to 51% by reconstitution with wild-type Lck (LckWT) but not a putatively inactive mutant LckY394F. LckWT also showed a stronger basal Lck-Lck interaction and a slower diffusion rate than LckY394F. Interestingly, aggregation of TCR receptors by antibodies in JCam cells led to a strong activation of reconstituted LckY394F similar to LckWT. Both activated LckY394F and LckWT diffused more slowly and displayed increased Lck-Lck interaction at a similar level. Therefore, these results suggest that a phosphorylatable Y394 is necessary for the basal-level interaction and preactivation of LckWT, while antibody-induced TCR aggregation can trigger the full activation of LckY394F.

Supplemental Digital Content is available in the text, Background: The objective of this meta-analysis is to evaluate the association between the presence of Helicobacter pylori (H pylori) and periodontal disease (PD). Methods: PubMed and EMBASE databases were searched to identify eligible articles published from inception up to April 2018. Further articles were retrieved through a manual search of recent reviews. Cross-sectional studies, case–control studies and cohort studies reporting the association between H pylori and PD were included. The pooled odds ratio (OR) and their 95% confidence interval (CI) were calculated. Results: Four case-control studies and nine cross-sectional studies were included. A total of 6800 patients were included in this review. The odds for oral H pylori positivity was 2.31 times (95% CI: 1.99–2.68) greater than those without H pylori. Subgroup analyses involving different study locations, designs, and types of study population showed the similar results. The pooled OR for the gastric disease patients was the largest (3.50, 95% CI: 2.22–5.53, five articles). Stomach H pylori was also significantly associated with PD, with OR 2.90 (95% CI: 1.37–6.14, two articles). Conclusions: This meta-analysis supports an association between H pylori and PD. More well-designed studies, especially prospective cohort studies are necessary to confirm these results.

Tracking-by-detection is an effective approach for regular objects tracking. However, trackers still drift under challenges like fast motion and occlusion in only several frames. In this paper, we propose the challenges driven network (CDNet) for motion and occlusion handling. First, as for proposal, we provide a motion-aware proposal method utilizing cues of optical flow and previous target states. Second, as for classification, a challenges driven feature learning approach is constructed by combining dual multi-domain learning and category prior learning. The dual multi-domain method improves the network responses to both challenge and common targets, and the steady category prior features are utilized to detect and avoid tracking drift. Experiments on the OTB100 [19] and VOT2015 [10] datasets demonstrate that our CDNet can achieve competitive performance against state-of-art trackers.

Tracking-by-detection frameworks have made significant progress in recent years. However, proposal and classification of this framework could still be severely affected by occlusion and motion. In this paper, we propose a tracking algorithm MPLST to improve the accuracy and robustness of proposal and classification under challenges. First, we provide a multi-cue proposal method, which combines Gaussian sampling utilizing previous target state, and motion and appearance selective search making use of the motion and appearance features of the target respectively. Second, we provide a long short-term features learning approach for target classification and network updating. The long-term features are robust to occlusion, and the short-term features can keep up with the fast motion of the target. Experiments on the OTB100 [1] and VOT2015 [2] datasets demonstrate that our MPLST can effectively deal with occlusion and motion, and achieve competitive performance against state-of-the-art trackers.

The calibration of polarization imaging system is the premise to obtain target polarization information accurately, in this paper, we propose a method of calibration based on the radian of distorted curves in the checkboard to solve the problem of losing polarization information in the underwater distorted polarization images. Firstly, we use the radian of distorted curves in the checkboard to calculate the coordinates of distortion center, and calibrate the region near the distortion center. Then we use the calibrated region to reconstruct the whole image. Finally, we combine the distorted image, the reconstructed image and the distortion model to obtain the calibration parameters. With these parameters we can get the calibrated polarization images. The experiments show that our method can calibrate the polarization image accurately, reduce the coupled error and calculate parameters independently.

Objective The aim of this study is to investigate the effects of 17β-Estradiol (E2) at different concentrations combined with cyclical compressive stress on the proliferation and differentiation of mandibular condylar chondrocytes (MCCs). Design MCCs, isolated from female Sprague-Dawley rats, were exposed to E2 at different concentration, cyclical compressive stress or the combination, effects of which on MCCs proliferation and differentiation were detected. Results E2 at physiological concentration (10−9 mol/L) has lower proliferative effects on MCCs, compared with non-physiological concentration (10-12 mol/L or 10-6 mol/L). For MCCs differentiation, effects of E2 at different concentration are totally opposite: E2 at 10−9 mol/L promotes MCCs differentiation, but at 10-12 mol/L or 10-6 mol/L, it inhibits MCCs differentiation. When combined with E2 at 10−9 mol/L, cyclical compressive stress shows synergistic effect on proliferation and differentiation. However, when combined with E2 at 10-12 mol/L or 10-6 mol/L cyclical compressive stress reverses the inhibition in MCCs differentiation provoked by E2 at 10-12 mol/L or 10-6 mol/L. Conclusion Effects of E2 combined with cyclical compressive stress on MCCs proliferation and differentiation are different, which suggests that orthodontist should take fully consideration of the levels of E2 and adopt comprehensive strategies, so as to achieve better orthodontic effect.

As the outfield load spectrum is so complicated that it cannot be used directly for test study in laboratory. This paper presents a method to determine load spectrum for high and low cycle combined fatigue of turbine mortise at elevated temperature through experimental and numerical method. First of all, the low cycle load spectrum with duration time is determined through cumulative damage rule. The rain flow counting method is applied to obtain main cycles and sub cycles, and then the stress cycle is converted into pulsation cycle (stress ratio=0) based on the S-N curve and the Goodman curve; Secondly, three groups of different amplitudes tests are established to determine the high cycle amplitude. Finally, another three groups of the high-low combined cycle fatigue (HLCCF) tests for turbine mortise of a certain type engine are carried out. The results show that the macro and micro failure modes are identical with outfield's, which verifies the accuracy of the conversion method.

The calibration of polarization imaging system is the premise to obtain target polarization information accurately, in this paper, we propose a method of calibration based on the radian of distorted curves in the check board to solve the problem of losing polarization information in the underwater distorted polarization images. Firstly, we use the radian of distorted curves in the check board to calculate the coordinates of distortion center, and calibrate the region near the distortion center. Then we use the calibrated region to reconstruct the whole image. Finally, we combine the distorted image, the reconstructed image and the distortion model to obtain the calibration parameters. With these parameters we can get the calibrated polarization images. The experiments show that our method can calibrate the polarization image accurately, reduce the coupled error and calculate parameters independently.

Wetland plants are important components in constructed wetlands (CWs), and one of their most important functions in CWs is to purify the water. However, wetland plant litter can also increase eutrophication of water via decomposition and nutrient release, and few studies have focused on the interspecific variation in the decomposition rate and nutrient release of multiple plant species in CWs. Here a greenhouse litter-bag experiment was conducted to quantify the decomposition rates and nutrient release of 7 dominant macrophytes (2 floating plants and 5 emergent plants) in three types of water substrate. The results showed that plant litter species and growth forms significantly affected the litter mass losses. The nutrient release was significantly different among plant litter species, but not between floating and emergent plants. Litter traits, such as litter lignin, total nitrogen (TN) and total phosphorus (TP) can well predict the decomposition rates of submerged litter. These results indicated that submerging litter in water did not change the relationships between litter traits and litter decomposition rates, and leaching might play a more important role in the decomposition of submerged litter in CWs than that in other terrestrial ecosystems. These findings can provide suggestions for managers about the maintenance of constructed wetlands.

A new numerical method for the analysis of fatigue crack growth in the multiple load path structure under low-high cycle combined fatigue (L-HCCF) loading is proposed in this paper. Firstly, vibrational stress is obtained through dynamic response analyses considering joint dry friction between the turbine blade and the turbine disc based on equivalent linearization and micro-slip model. Then, the crack growth in the fir-tree attachment is simulated under vibrational stress superimposed with low cycle fatigue loading through fracture mechanics (FM) analysis. Vibrational loading in the fir-tree attachment is redistributed with the crack propagation because of this multiple load path structure. Thus, dynamic response analysis is re-performed on the turbine attachment. At last, the crack growth life of multiple load path structure under L-HCCF loading is predicted based on the linear cumulative damage model. The predicted life agrees well with the experimental data of actual turbine component, which verifies that the new numerical method for the analysis of fatigue crack growth in the multiple load path structure under L-HCCF loading is reasonable and feasible.

We monitored the water quality and hydrological conditions of a horizontal subsurface constructed wetland (HSSF-CW) in Beijing, China, for 2 years. We simulated the area rate constant and the temperature coefficient with the first-order kinetic model. We examined the relationships between the nitrogen (N) removal rate, N load, seasonal variations in the N removal rate, and environmental factors, such as the area rate constant, temperature, and dissolved oxygen (DO). The effluent ammonia (NH4+-N) and nitrate (NO3−-N) concentrations were significantly lower than the influent concentrations (p0.01). The area rate constants of NO3−-N and NH4+-N at 20 °C were 27.01±26.49 and 16.63±10.58 m∙yr−1, respectively. The temperature coefficients for NO3−-N and NH4+-N were estimated at 1.0042 and 0.9604, respectively. The area rate constants for NO3−-N and NH4+-N were not correlated with temperature (p>0.01). The NO3−-N area rate constant was correlated with the corresponding load (R2=0.9625, p

This paper is a study in the application of multi-scale mathematical morphology which is a branch of mathematical morphology in seismic data processing. It mainly research on the seismic signal resolution improving and amplitude compensation. First, Multi-scale mathematical morphology is used in this essay to multi-scale decompose amplitude information of seismic signal, and make an analysis of the morphological characteristics of every scale, and make the choice of multi-scale structural elements. Because of less energy loss and higher resolution of the shallow seismic signal, information of shallow signal is used to simulate information of overall signal, to achieve improving resolution of overall signals.