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MethodsIn this study, we developed a strategy for the prevention and therapy of melanoma using a whole-cell vaccine combined with a CpG/αOX40/cGAMP triple adjuvant. The CpG/αOX40/cGAMP triple adjuvant was used to co-culture melanoma cells in vitro to induce immunogenic death of tumor cells. The mixture of inactivated tumor cells and the triple drug was an optimized tumor whole-cell vaccine, which was injected subcutaneously into mice for tumor prevention and therapy. Furthermore, we analyzed the changes of immune cells in spleen and tumor by flow cytometry and immunohistochemistry, and detected the changes of cytokines after vaccine application by cytometric bead array to explore the specific mechanism of vaccine.ResultsIn vaccine prevention and therapy experiments, it was observed that the tumor growth was significantly inhibited in the whole-cell vaccine group, and the survival time of mice was significantly prolonged. Flow cytometry results showed that the proportion of CD4+ T cells and CD8+ T cells in tumor of mice in vaccine group was higher than that in control group, especially the CD4+ T cells.ConclusionThe optimized vaccine has the unique ability to amplify tumor-specific CD4+ T cells, which improves antitumor sensitivity, and has a significant effect on the prevention and therapy of melanoma mice.

Microplastics (MPs) pervade the environment and increasingly threaten both natural ecosystems and human health. In this study, we investigated MP particle concentrations in sediment samples collected from 54 sites along the banks of the Yangtze River and its major tributaries and on lakeshores. The main polymer types found in the samples were polypropylene (PP), polystyrene (PS) and polyethylene (PE). MP particle abundance in the various types of locations was 35-51,968 particles/kg dry weight (d.w.) on the banks of the main river, 52-1463 particles/kg (d.w.) on the banks of tributaries and 2574-23,685 particles/kg (d.w.) on lakeshores. Correlation between MP abundance and mean annual runoff of each upstream tributary was significant, which suggests that increased runoff brings more microplastic waste to streambank sediments. The most common shape of MP particles in all upstream samples was flake, and in downstream samples it was foam. Small microplastic particles ( 0.50 mm) were predominant at all sites in this study, and the minimum particle size in samples from the Yangtze river banks was 0.065 mm. Average abundance of MP particles on the shores of the source lake was 9069 particles/kg around the inlet but only 866 particles/kg around the outlet; the difference was due to interception associated with sedimentation and precipitation in the lake. Our study represents the large-scale study of MPs contamination in sediment along the Yangtze River and provides important data regarding the accumulation and distribution of MPs in shoreline sediments of the upper, middle and lower reaches of the Yangtze River, main tributaries and lakes in China.

Fluid flow in fractures has the potential to drastically change the economic, environmental, and safety risks associated with a subsurface operation. This work focuses on the analysis of experimental shear fracturing and subsequent shear displacement of a shale specimen that contains multiple pre-existing natural fractures. A triaxial direct shear apparatus with concurrent µCT imaging allowed continuous monitoring of sample permeability and changes in fracture geometry during fracture creation, displacement, and changes in stress. Steady-state, low Reynolds number fluid flow simulations were used to determine the changes of each individual fracture’s hydraulic aperture due to displacement and effective stress. The development of anisotropy in the hydraulic aperture of a generated shear fracture was determined for shear displacements of 0.38, 0.74, and 2.04 mm. At high confining stress (30 MPa), shear displacement significantly reduced the hydraulic aperture of the shear fracture to below flow detectable limits and X-ray imaging resolution (23 × 23 × 23 µm3). The shear generated fracture was found to be more sensitive to changes in effective stress compared to the pre-existing natural fractures. Existing models derived from fluid flow equations accounting for stochastic fracture roughness were able to partially fit the simulated flow properties of the pre-existing fractures, but no model was found to fit the flow properties of the newly formed shear fracture. These results are the first report of simultaneous changes in the geometry and flow properties of surrounding, parallel natural fractures as a shear fracture is generated with varying stress and shear displacement conditions.

Purpose Mutation-specific T-cell response to epithelial cancers and T-cell-based immunotherapy has been successfully used to treat several human solid cancers. We aimed to investigate the anti-tumour effect of neo-antigen-reactive T(NRT) cells induced by RNA mutanome vaccine, which may serve as a feasible and effective therapeutic approach for lung cancer. Methods We predicted candidate neo-antigens according to the mutant gene analysis by sequencing the mouse Lewis cells and C57BL/6 mouse tail tissue. RNA vaccine was prepared with the neo-antigens as the template. We assessed antitumor efficacy, cytokine secretion and pathological changes after adoptive transfer of NRT cells in vitro and vivo experiments. Results We identified 10 non-synonymous somatic mutations and successfully generated NRT cells. The percentage of T-cell activation proportion was increased from 0.072% in conventional T cells to 9.96% in NRT cells. Interferon-γ secretion augmented from 17.8 to 24.2% as well. As an in vivo model, adoptive NRT cell infusion could promote active T-cell infiltration into the tumour tissue and could delay tumour progression. Conclusion NRT cells induced by RNA mutanome vaccine exert a significant anti-tumour effect in mouse lung cancer, and adoptive NRT cell therapy might be considered a feasible, effective therapeutic approach for lung cancer.

Plant SnRK1 kinases have been reported to participate in regulating many aspects of plant biology including resistance to biotic and abiotic stresses. Wild soybean (Glycine soja) has strong adaptation abilities to extreme environmental conditions and has four GsSnRK1 genes in its genome. However, the functions of GsSnRK1 are still largely unknown. In this work, we employed yeast two-hybrid and co-immunoprecipitation to determine the physical interactions of GsSnRK1 and three unknown proteins (GsKIP1, GsKIP2, and GsKIP3). To further characterize these proteins, we expressed and purified them in E. coli system. Biochemical analyses indicated that Thr176 of GsSnRK1 could be directly phosphorylated by its upstream kinase GsGRIK1 and the activated GsSnRK1 could phosphorylate its interactors GsKIP1, GsKIP2, GsKIP3, and ABF2 revealed by PhosTag-based approaches and specific phospho-antibodies. Intriguingly, a constituted ABA receptor complex consisting of GsPYL, GsPP2C, could perceive exogenous ABA, and subsequently, the ABA-bound receptor could activate GsSnRK1 to phosphorylate ABF2, suggesting that GsSnRK1 is an essential and bona fide component of ABA signaling pathway. This study is the first time to comprehensively characterize the in vitro functions of wild soybean GsSnRK1 kinase, providing the clues to unveil the novel molecular roles of SnRK1 kinase in cell signaling.

In this research, a multi-objective frequency domain-constrained static output feedback control is developed for the delayed active suspension system with wheelbase preview information. Firstly, the model of the half-vehicle active suspension system with wheelbase preview information and time delay is constructed by employing the augmented method. Secondly, in vertical vibration, the human body senses are more intense when the frequency of the external disturbance is in the range of 4–8 Hz. Therefore, a finite frequency control method is proposed for the controller design with robust $$ H_{\infty } $$ and generalized $$ H_{2} $$ performance. Thirdly, considering that a full online knowledge of states is not available in practical suspension systems, a static output feedback strategy is proposed to guarantee the feasibility of the controller by using a two-stage method. Finally, simulation study is given to explain the effectiveness and superiority of the presented controller.

The Co3O4 decorated TiO2 nanotube arrays(NTAs) coatings are fabricated by the combination of anodization and impregnating methods. It is found that the introduction of Co3O4 can reduce the diffraction intensity of (101) plane of the TiO2 and accelerate the separation of photogenerated electron/hole pairs. In addition, the open circuit potential(OCP) and the corrosion potential of 304 stainless steel(304SS) with or without Co3O4 decorated TiO2 NTAs were measured under visible light, which indicated the 304SS coupled with Co3O4 decorated TiO2 NTAs had better anticorrosion performance than that of the 304SS or the 304SS coupled with pure TiO2 NTAs. The enhancement of the cathodic protection performance of the Co3O4 decorated TiO2 NTAs can be ascribed to the matched energy levels and strong interaction between Co3O4 and TiO2 NTAs, and the improvement of light absorption.

Water falling film dielectric barrier discharge (WFFDBD) has been widely studied for water treatment, due to its good performance on production of active species, mass transfer of active species from gas phase into liquid phase, and therefore the degradation of pollutants. However, few studies have focused on the production characteristics of active species of WFFDBD. In this paper, the formation characteristics of hydrogen peroxide, ozone and nitrate ions in a WFFDBD reactor powered by bipolar pulsed generator were studied under different electric discharge time, peak pulse voltage, power–frequency, air flow rate, water circulation flow rate, pH value and conductivity. The results show that the concentrations of hydrogen peroxide, ozone and nitrate ions increased with the peak pulse voltage, power supply frequency and water circulation flow rate, but the inputted air flow rate presented different effect on the production of active species. Moreover, the increase in pH value and conductivity led to a decrease in the concentration of hydrogen peroxide, while nitrate ion increased with the water pH value and conductivity. The p-nitrophenol degradation result indicates that both ozone and hydrogen peroxide contribute to its degradation possibly via their reaction into hydroxyl radical.

Reasonable hydrophobic anode is deemed to be a promising electrode for photoelectrocatalytic degradation of wastewater. In this study, the C3N4-modified Ti/PbO2 electrode with tunable hydrophobic characteristics is fabricated by a facile electrodeposition process. It is found that the introduction of C3N4 into the PbO2 films changed the morphology, surface hydrophilicity, and hydrophobicity of the electrode, which promotes the photoelectrochemical active areas, generating efficiency of hydroxyl radicals. In addition, introducing C3N4 into PbO2 coating can enhance oxygen evolution potential and carrier density of PbO2. Photoelectrocatalytic degradation experiments show that the addition of C3N4 can further improve the catalytic performance of PbO2 and there exists a significant photoelectric synergism in photoelectrocatalytic process. These results demonstrate that the combination of reasonable surface hydrophobic characteristics and photoelectrocatalytic is a prospective approach for wastewater treatment.

Filamin A is the most widely expressed isoform of filamin in mammalian tissues. It can be hydrolyzed by Calpain, producing a 90-kDa carboxyl-terminal fragment (ABP90). Calpeptin is a chemical inhibitor of Calpain, which can inhibit this effect. It has been shown that ABP90 acts as a transcription factor which is involved in mediating cell signaling. However, the significance of ABP90 and its clinical signature with underlying mechanisms have not been well studied in glioblastoma multiforme (GBM). ABP90 protein was measured in 36 glioma patients by Western blot. Human GBM cell lines U87 and A172 were used to clarify the precise role of ABP90. CCK-8 assay was used to analyze the cell viability. Transwell invasion assay and wound healing assay were used to analyze the migration and invasion. Expression of matrix metalloproteinase 2/tissue inhibitors of metalloproteinase 2 (MMP2/TIMP2) protein was analyzed by Western blot. ABP90 protein expression was lower in GBM tissues. The patients with low ABP90 protein expression had a shorter OS time (p = 0.046). After being treated with Calpain, the expression of ABP90 was upregulated, which led to a decline of cell viability, enhanced the efficacy of temozolomide and restrained the cell invasion. Calpeptin could inhibit the effect. The mechanism might be involved in the balance of MMP2/TIMP2. Our present data suggest that ABP90 expression is a significant prognostic factor and may play an important role in cell viability, chemotherapeutic sensitivity and invasion of GBM.

The aim of this study was to compare the phenolic compound profiles and antioxidant capacities of eight varieties of longan (Dimocarpus longan Lour.) planted in the middle and upper Yangtze River area. The total polyphenols content (TPC) and total flavonoids content (TFC) of dried longan pulp ranged from 1.07 ± 0.05 to 1.22 ± 0.05 mg gallic acid equivalents/g and 0.25 ± 0.07 to 0.87 ± 0.14 mg rutin equivalents/g. UHPLC-QqQ-MS/MS analysis revealed 12 individual polyphenol compounds in longan. The Fuwan8, Dongliang and FD97 varieties showed the strongest DPPH scavenging activity (IC50 of 1.03 g/mL). The highest ABTS+ scavenging activity was found in the Dongliang. In the enzyme assays, the Fuwan8 and Dongliang varieties demonstrated maximum α-amylase and α-glucosidase inhibition activities, with values of 97.56 and 88.58%, respectively. The principal component analysis indicated that the Rongyu8 and Songfengben cultivars have nearly analogous polyphenol compounds.

Multicolor-tunable materials have attracted extensive interest due to their unique advantages in applications of lighting and displays. In this paper, energy transfer from Ce3+ to Tb3+ occurred and the effective energy transfer efficiency (ηETE) of Ce3+-Tb3+ has been calculated to be as high as 36%. To obtain multicolor-tunable emissions, Eu3+ ions were successfully introduced into Ce3+–Tb3+ codoped Sr3La6(SiO4)6 samples. Furthermore, an energy transfer process from Ce3+ to Eu3+ ions has also been demonstrated by an energy transfer bridge of Tb3+. Meanwhile, we achieved the precise adjustment of purple, green, orange and red emissions of Sr3La6(SiO4)6: Ce3+, Tb3+, and Sr3La6(SiO4)6: Ce3+, Tb3+, Eu3+. In addition, Sr3La6(SiO4)6: Ce3+, Tb3+, Eu3+ phosphors exhibited a good thermal stability: their integrated emission intensities at 450 K still kept more than 90% of their initial intensity at room temperature. Therefore, these results might provide a novel multicolor-tunable phosphor for lighting and display application.

The aim of this study was to investigate the effects of three different drying methods, freeze drying (FD), vacuum drying (VD) and oven drying (OD) on phenolic contents and antioxidant activities of litchi fruits. 20 polyphenols were exactly identified in the litchi fruits by UPLC-QqQ/MS. Significant losses were observed in the contents of total polyphenols and antioxidant activities in the dried litchi when compared with the fresh litchi. Principle component analysis indicated that there was significant difference of phenolic component between the use of thermal drying (VD and OD) and FD. Our results suggest that FD is the optimum drying method for litchi fruits considering the content of total polyphenols and antioxidant activities.

BackgroundSmall-cell lung cancer (SCLC) remains an aggressive cancer with short-term survival due to limited therapeutic options. Apatinib is a small-molecule tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor-2. This study aimed to investigate the efficacy and safety of apatinib in patients with extensive-stage (EC) SCLC who had progressed after two or three previous therapies.MethodsEligible patients were histologically confirmed ES-SCLC after two or three previous treatments, including a platinum-based regimen. Patients received apatinib at an initial dose of 500 mg once daily. The primary endpoint was the objective response rate.ResultsForty patients were enrolled. At the data cut-off time (November 15, 2018), the median follow-up was 7.4 months; no patients remained on treatment, and five were still in follow-up. An objective response was achieved in 7 of 40 patients (17.5%) in the intention-to-treat population, and 7 of 38 patients (18.4%) in the per-protocol population. The median progression-free survival and overall survival were 3.0 months and 5·8 months, respectively. The most commonly observed grade 3 or greater treatment-related adverse events were hypertension, hand–foot syndrome, increased L-gamma-glutamyltransferase.ConclusionsApatinib exhibited efficacy and an acceptable safety profile in previously heavily-treated ES-SCLC patients. Further exploration of apatinib in phase III trials is warranted.Trial registrationNCT02945852.

The development of high drug loading and sustained release nanoparticles by simple and economical methods is significant for the treatment of diseases. Amorphous calcium carbonate (ACC) is an ideal drug delivery system because of its excellent pH responsiveness, biocompatibility and biodegradability. In this work, ACC nanoparticles were successfully precipitated in ethanol–calcium solutions using ammonium carbonate as the internal source of CO2, which exhibited a relatively narrow size distribution in range of 10–200 nm. The microscopic morphology, amorphous characters, porous structure and thermal behavior of resultants were investigated by electron microscopy, Fourier-transform infrared spectroscopy, Brunauer–Emmett–Teller and thermogravimetric analysis, respectively. In vitro drug release assay showed that ACC nanoparticles had high loading capacity of curcumin (Cur) and favorable drug release properties. Furthermore, ACC-Cur showed excellent abilities to scavenge free radicals, protect Cur stability and damage A549 cells, providing a broadened space for the applications of this material in the fields of biomedical or food.

The static anisotropic elastic properties of shales can be measured by performing uniaxial compression on core specimens with bedding planes of different inclination angles (or anisotropy angles). However, these measurements differ when different numbers of specimens are tested, mainly because of the heterogeneity of shales. This study aimed to quantify the uncertainties of the anisotropic elastic properties of a shale when testing different numbers of specimens with distinct anisotropic angles. Three sets of room-dried core samples were prepared, and each set consisted of seven specimens with incremental anisotropic angles of 15°. Uniaxial compression measurements were used to determine the anisotropic elastic properties for a given number (2–7) of specimens in each set. The results indicated that the uncertainties of the determined anisotropic elastic properties decreased monotonically as the number of measurements was increased. The results also suggested that at least five specimens with different anisotropic angles should be tested in order to obtain accurate elastic properties (uncertainty

Osteoarthritis (OA) is a degenerative joint disease, in which low-grade inflammation plays an important role at the initiating step. Low-doses of LPS-induced inflammation in the plasma activate chondrocytes and promote the secretion proinflammatory cytokines, leading to secondary inflammation. Blocking OA-associated TLR activation is a promising strategy for the development of suitable therapies. Here, we want to find some bacteria-derived peptides that can block TLR signaling in chondrocytes more efficiently. Based on previous studies, we screened 12 TIR domain-derived peptides for their effects on NF-кB activation induced by LPS, IL-1β or TNF-α in murine ATDC-5 cells. We evaluated their effects on LPS-induced cytokine expression and secretion. Among them, two bacteria-derived peptides, TcpC-DD and TcpB-DD, showed the most potent inhibitory activities. In comparison with TcpB-DD, TcpC-DD exhibited broader TLR-inhibitory specificity during inflammation in chondrocytes. Furthermore, both TcpC-DD and TcpB-DD displayed strong inhibition of LPS- and IL-1β-induced catabolic reactions in chondrocytes. However, only TcpC-DD exhibited obvious suppression of TNF-α-induced catabolism. In conclusion, we identified two novel inhibitory peptides that modulate catabolism in chondrocytes and innate immune responses, and these peptides could be used to develop novel therapeutic strategies for OA.

Forgotten ureteral stents (FUS) is a great threat to both patients and doctors. Applications on smartphones can significantly reduce the incidence of FUS. But existing applications do not have instant notification and consultation functions. To implement those function, we developed a ureteral stent tracking system embedded in a social networking service application, WeChat. "Ureteral Stent Tracking System" was developed on WeChat, a social media application using by 1.4 million active users. The study consecutively enrolled patients who underwent ureteral stent installation from April 2018 to July 2018. Each patient's information was recorded on the smartphone by the urologists to create a document immediately after the surgery. The system sends notifications twice a week to both patients and clinicians via the message function of WeChat. A total of 183 patients were enrolled. The most senior patient enrolled was 73 years old. 156 (85.2%) patients underwent stent extraction before the scheduled time. 22 did not undergo stent extraction before the scheduled time because of urinary tract infection or stone residue. They underwent stent extraction within 1 month after the scheduled time. Two patients did not come to the hospital until we had made a phone call to them, though they had received notification from the online system. During the study, no patient was lost-to-follow up. In bilateral stents cases, no stent was forgotten after extraction surgery. A total of 85 (46.4%) patients consulted 132 issues in the system. 52 (39.4%) patients complained about hematuria. 36 (27.3%) patients reported lower urinary tract symptoms. All the consultations were answered within 24 h. "Ureteral Stent Tracking System" implement instant notification and consultation functions via WeChat. It helps urologists to manage indwelling ureteral stents and to reduce the incidence of FUS efficiently.

BackgroundThe proline-rich protein 11 (PRR11) is a newly identified oncogene associated with a poor prognosis in several human cancers. Nonetheless, research on its role in ovarian cancer (OC) remains largely understudied. Therefore, this study aims to evaluate the expression levels of PRR11 protein and its role in human ovarian cancer.MethodsImmunohistochemistry analysis was used to evaluate the expression levels of PRR11 protein in human samples obtained from 49 patients diagnosed with OC and subjected to curative surgery in the First Affiliated Hospital of Wenzhou Medical University between 2007 and 2015.ResultsIn total, 57.1% of the primary OC tumor tissue evaluated demonstrated overexpression of PRR11. Meanwhile, the survival analysis showed that the overall survival (OS) of patients presenting overexpression of PRR11 was significantly lower than the OS of the patients with negative PRR11. In subsequent experiments, it was found that silencing the expression of PRR11 expression inhibited the proliferation of tumor cells and the migration of cells in vitro. Further, cells subjected to PRR11 knockdown exhibited a decrease in tumor growth in vivo. The downregulation of PRR11 was coupled with a decrease in N-cadherin and downregulation in the expression of early growth response protein 1 (EGR1).ConclusionsThe findings suggest that PRR11 might be considered as a potential target for prognostic assessment and gene therapy strategies for patients diagnosed with OC.

Background Empirical evidence that demonstrates the relationship between pelvic asymmetry and non-specific chronic low back pain (NCLBP) is currently lacking. Objective To establish the reliability of the Global Postural System (GPS) in assessing pelvic asymmetry and identify the association between pelvic asymmetry parameters and the occurrence of NCLBP in young adults. Design A cross-sectional, regression study. Methods People who were aged between 18 and 30 and were diagnosed with NCLBP were recruited. Healthy individuals who were matched for age, sex, and education level were recruited as controls. Global Postural System (GPS) was employed to assess pelvic asymmetry. Prior to exploring the association, the reliability of GPS was assessed by the ICC (2, k) for interrater reliability, ICC (3, k) for intra-rater reliability, standard error and minimal detectable difference. Bivariate correlation analysis and logistic regression analysis were used to determine the relationship between pelvic asymmetry and the occurrence of NCLBP. Results Twenty-eight healthy participants and 28 people with NCLBP were recruited. Moderate to excellent ICCs were observed for the inter-rater and intra-rater reliability of most postural parameters. The bivariate correlation analysis indicated that age, body mass index and pelvic asymmetry parameters were related to the occurrence of NCLBP. Pelvic angle asymmetry (odds ratio = 1.17), and asymmetry of the distance between the posterior superior iliac spine and the floor (odds ratio = 1.21) were associated with NCLBP. Limitations This study did not explore the causal relationship between pelvic asymmetry in the sagittal plane/pelvic asymmetry in the transverse plane and the occurrence of NCLBP. The interpretation of the results may not be generalized beyond the sample population. Conclusions The GPS is a reliable method to assess pelvic asymmetry in a clinical setting. Two pelvic parameters were associated with the presence of NLBP. Measurement of pelvic asymmetry may assist in the early identification of potential occurrence of NCLBP but further work is required.

Background We describe the clinical benefit of immune checkpoint inhibitors using the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) and ASCO VF. Methods We identify all approved indications of immune checkpoint inhibitors based on RCTs between January 1, 2011 and September 30, 2018 by FDA. Information including medians and HR of OS (PFS or DFS) and 95% CI, grade 3 or 4 toxicities in each arm, QOL data, survival probability at fixed time were extracted. Results Immune checkpoint inhibitors were approved for 18 indications based on RCTs. All the indications meet the ESMO-MCBS 1.1 threshold for meaningful benefit. By the updated ASCO-VF, the median Net Health Benefit (NHB) of these agents was 55.3 (range 17.4–77.1). Two third of the indication gained the bonus points for durable survival benefits by updated ASCO VF. When updated results were incorporated in the assessment, clinical benefit of most approved immune checkpoint inhibitors increased with a median improvement of NHB of 10 (range 2–20). Conclusions Approved immune checkpoint inhibitors provided clinical meaningful benefit by ESMO-MCBS 1.1, and most of these agents reach the threshold for bonus points for durable survival in the updated ASCO VF.

Background Triple-negative breast cancer (TNBC) is widely concerning because of high malignancy and poor prognosis. There is increasing evidence that alternative splicing (AS) plays an important role in the development of cancer and the formation of the tumour microenvironment. However, comprehensive analysis of AS signalling in TNBC is still lacking and urgently needed. Methods Transcriptome and clinical data of 169 TNBC tissues and 15 normal tissues were obtained and integrated from the cancer genome atlas (TCGA), and an overview of AS events was downloaded from the SpliceSeq database. Then, differential comparative analysis was performed to obtain cancer-associated AS events (CAAS). Metascape was used to perform parent gene enrichment analysis based on CAAS. Unsupervised cluster analysis was performed to analyse the characteristics of immune infiltration in the microenvironment. A splicing network was established based on the correlation between CAAS events and splicing factors (SFs). We then constructed prediction models and assessed the accuracy of these models by receiver operating characteristic (ROC) curve and Kaplan–Meier survival analyses. Furthermore, a nomogram was adopted to predict the individualized survival rate of TNBC patients. Results We identified 1194 cancer-associated AS events (CAAS) and evaluated the enrichment of 981 parent genes. The top 20 parent genes with significant differences were mostly related to cell adhesion, cell component connection and other pathways. Furthermore, immune-related pathways were also enriched. Unsupervised clustering analysis revealed the heterogeneity of the immune microenvironment in TNBC. The splicing network also suggested an obvious correlation between SFs expression and CAAS events in TNBC patients. Univariate and multivariate Cox regression analyses showed that the survival-related AS events were detected, including some significant participants in the carcinogenic process. A nomogram incorporating risk, AJCC and radiotherapy showed good calibration and moderate discrimination. Conclusion Our study revealed AS events related to tumorigenesis and the immune microenvironment, elaborated the potential correlation between SFs and CAAS, established a prognostic model based on survival-related AS events, and created a nomogram to better predict the individual survival rate of TNBC patients, which improved our understanding of the relationship between AS events and TNBC.

The geomechanical characterization of a carbonate reservoir is required for formation stimulation and hydrocarbon recovery. The pertinent core- or block-scale (large-scale) characterizations are time consuming and expensive, and more importantly, cannot be used for drill cuttings. The present study proposes a two-scale model based on microscale (small-scale) measurements to predict the geomechanical properties of a carbonate formation at the core scale. At the small scale, we develop a physically representative element by accounting for the effective stiffness of a constitutive mineral and of voids. At the large scale, we account for the volume fraction of each mineral, the porosity, and the pore structure of the void space. The elastic deformation of a large-scale model is simulated using a finite element method (FEM), whose results are tested against independent lab measurements. The proposed two-scale model has applications for geomechanical characterization of a formation at the core scale from drill cuttings.

As one of the most important convergence layer (CL) protocol for delay/disruption-tolerant networking (DTN), Licklider transmission protocol (LTP) is designed for deep space communications, but it has rarely been considered for near earth applications. In this paper, LTP is proposed instead of TCP as CL with Bundle protocol (BP) for future application in GEO-relayed space networks (GRSN). Analytical models are built to estimate the file delivery time of LTP in GRSN. Experiments are also conducted on our computer based testbed in emulation of the basic scenarios during data transmission from LEO satellite to a ground station in GRSN. The results show that in transmission efficiency BP with LTPCL outperforms other protocols, such as BP with TCPCL, direct terrestrial TCP (TCP Cubic) and TCP variants (TCP Hybla) for space segments in most scenarios. It could be envisioned that DTN with LTPCL for space segment is currently the best choice for future GEO-relayed space internetworking. Moreover, performance of two different networking schemes,i.e. the on-board DTN routers and the bent-pipe relays are compared. It is observed that bent-pipe relays outperform the on-board DTN routers scheme when the channel condition is good, while the on-board DTN routers scheme performs better with high data loss ratio.

Nosema ceranae causes widespread infection in adult workers of European honey bees, Apis mellifera, and has often been linked to honey bee colony losses worldwide. Previous investigations of honey bee immune response to N. ceranae infection were largely based on laboratory experiment, however, little is known about the immune response of honey bees that are naturally infected by N. ceranae. Here, we compared the infection levels of N. ceranae in three different categories of adult bees (emergent bees, nurses, and foragers) and detected the host immune response to the N. ceranae infection under natural conditions. Our studies showed that the Nosema spore load and infection prevalence varied among the different types of adult workers, and both of them increased as honey bees aged: No infection was detected in emergent bees, nurses had a medium spore load and prevalence, while foragers were with the highest Nosema infection level and prevalence. Quantification of the mRNA levels of antimicrobial peptides (abaecin, apidaecin, defensin-1, defensin-2, and hymenoptaecin) and microbial recognition proteins (PGRP-S1, PGRP-S2, PGRP-S3, PGRP-LC, GNBP1-1, and GNBP1-2) confirmed the involvement of the Toll and/or Imd immune pathways in the host response to N. ceranae infection, and revealed an activation of host immune response by N. ceranae infection under natural conditions. Additionally, the levels of immune response were positively correlated with the Nosema spore loads in the infected bees. The information gained from this study will be relevant to the predictive modeling of honey bee disease dynamics for Nosema disease prevention and management.

A retrofitting technology using precast steel reinforced concrete (PSRC) panels is developed to improve the seismic performance of old masonry buildings. The PSRC panels are built up as an external PSRC wall system surrounding the existing masonry building. The PSRC walls are well connected to the existing masonry building, which provides enough confinement to effectively improve the ductility, strength, and stiffenss of old masonry structures. The PSRC panels are prefabricated in a factory, significantly reducing the situ work and associated construction time. To demonstrate the feasibility and mechanical effectivenss of the proposed retrofitting system, a full-scale five-story specimen was constructed. The retrofitting process was completed within five weeks with very limited indoor operation. The specimen was then tested in the lateral direction, which could potentially suffer sigifnicant damage in a large earthquake. The technical feasibility, construction workability, and seismic performance were thoroughly demonstrated by a full-scale specimen construction and pseudo-dynamic tests.

Background The prevalence of low back pain is rising among the young adult population. Altered lumbar muscle tone was suggested to be associated with underlying pathologies and symptoms. To date, there is minimum information available on the repeatability of lumbar spine muscle mechanical properties in the young adults who experienced low back pain. This study aimed to assess the reproducibility of mechanical properties of lumbar spinal muscle in young adults with spinal pain by myotonometer and explored the difference in reproducibility when different number of indentations was used. Methods Participants who aged between 18 to 25 and reported chronic LBP were recruited. Lumbar muscle tone (Hz) and stiffness (N/m) were assessed by myotonometer on one occasion by two assessors. Parameters were recorded by triple scans and 5-scans mode. Intraclass correlation coefficient (ICC), standard error of measurement (SEM), smallest real difference (SRD), Bland and Altman analysis were used to assess agreement between two measurements. The relationship between muscle mechanical properties and pain score and disability level were assessed by Spearman’s rank correlation coefficient. Results The results of ICCs indicated excellent repeatability in triple scans and 5-scans mode for each lumbar level bilaterally (ICC > 0.75). SEM and SRD were smaller in triple scans than 5-scans mode for most levels. Bland and Altman analysis revealed no systematic bias. Spearman’s rank correlation analysis indicated significant high correlations between muscle tone and disability level (r = 0.80, p r = 0.81, p Conclusions This study found that lumbar spinal muscle tone and stiffness were repeatable parameters when measured by myotonometer. The reproducibility of muscle mechanical parameters did not appear to differ between the two scanning modes with different number of indentations. Muscle tone and stiffness measured by myotonometer may therefore be reliable as outcome measures to assess intervention induced changes. The lack of significant association between intensity of pain and mechanical properties of paraspinal muscles may suggest that muscle properties measured at rest might not be related to pain level at rest but more related to pain elicited during movement.

The synthesis of new carbonaceous electrode materials for supercapacitors and the discovery of efficient techniques for the CaC2 activation are meaningful subjects. In this study, unique alkynyl carbon materials (ACMs) were effectively synthesized through solvent-free mechanochemical reactions of CaC2 with C2Cl6 or C6Br6. Their components and structure were comprehensively characterized, and their supercapacitor performances were examined in detail. The mechanochemistry has proved to be an efficient and targeted technique for the reactive activation of CaC2. The sp-C dominated ACMs feature interconnected framework with hierarchical pores, tunable structures, and low cost of raw materials. As electrodes for supercapacitors, the ACMs exhibit high specific capacitances in the range of 48.4–132.4 F g−1 with excellent electrical conductivities and outstanding cycling stabilities. This work provides an efficient, green, and cost-effective strategy for the synthesis of ACMs from wildly available precursors, and a significant assistance for the renaissance of CaC2 chemistry.

Large deformation of tunnels in longwall coal mines creates massive cracks in the surrounding rocks, which may cause groundwater loss and threaten the coal mine safety. Rock mechanical characterization is crucial for understanding the large deformation of underground openings. Based on the theoretical analysis and laboratory triaxial tests, this study aims to propose a strength degradation model of the rocks for a deep understanding on the large deformation of underground openings. The proposed model captures the non-linear post-peak rock strength degradation which is dependent on the plastic strains accumulated under the decreasing confining pressures. The stress-dependent elastic properties were not considered in this study. The proposed model was incorporated in a finite difference package (FLAC3D) for engineering application. The simulated surface convergence of the underground opening matches the in-mine measurements, which supports the proposed model. More importantly, the simulated crack zone after tunnel excavation agrees with the observations from borehole images. Therefore, the proposed model provides a helpful tool to evaluate the safe margin of an underground tunnel if it is close to a subsurface water-bearing formation. It also sheds lights on the underground tunnel design to prevent the adjacent groundwater from inrush.

Active friction drag reduction by spanwise transversal traveling surface waves is investigated experimentally in a fully developed zero-pressure gradient (ZPG) turbulent boundary layer (TBL). The spanwise transversal traveling wave of an aluminum surface is generated by an electromagnetic actuator system. A parametric study focusing on the influence of the wave amplitude (A+) and wave period (T+) is performed to analyze the impact of the wave parameters on drag reduction. Within the range of the parameters investigated, the maximum local drag reduction of 4.5% is found at A+ = 11.8 and T+ = 110. Furthermore, the TBL flows above the wave crest and trough are investigated by phase-locked PIV and µ-PTV measurements. The results evidence that the drag reduction effect is not only enhanced by increasing the amplitude, but also by reducing the period in the range of the current parameters. The turbulence statistics show that the velocity fluctuations and the Reynolds shear stresses in the streamwise and in the wall-normal direction are damped by the traveling surface wave motion in the near-wall region. The outer velocity distribution deviates from the inner scaling based on the actuated friction velocity, i.e., it possesses a slight tendency of a varying slope in the log region. The phase-locked measurements of the velocity profiles above the crest and the trough show that only above the crest the inner scaling property is valid. Above the moving surface a non-zero spanwise secondary flow is induced. The quadrant decomposition of the turbulent productions shows that the sweep and ejection events are weakened.

Cancer is still a clinical challenge, with many efforts invested in order to achieve timely detection. Unexplained elevated blood carcinoembryonic antigen levels are occasionally observed in an asymptomatic population and considered as a risk factor of cancers. The purpose of this study was to determine the validity of 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography (F-18 FDG-PET/CT) for detecting cancer in an asymptomatic population with an unexplained elevation in blood carcinoembryonic antigen (CEA) levels.This retrospective study included a total of 1920 asymptomatic examinees conducted from August 2011 through September 2013. The participants underwent CEA assay and conventional medical imaging (CEA-conventional), or CEA assay and F-18 FDG-PET/CT (CEA-PET/CT). The validity of conventional medical imaging and CEA-PET/CT scanning for detecting cancer and early-stage cancer in an asymptomatic population with an unexplained elevation in blood CEA levels were evaluated.Sensitivity, specificity, cancer detection rate, missed cancer detection rate, early-stage cancer detection rate, and early-stage cancer ratio using the CEA-PET/CT scanning were 96.6 %, 100 %, 10.4 %, 0.4 %, 3.7 %, and 34.5 %, respectively. In contrast, the corresponding values obtained using the conventional medical imaging were 50.6 % (P 0.0001), 100 % (P 0.9999), 50.6 % (P 0.0001), 99.9 % (P = 0.055), 2.6 % (P 0.0001), 2.5 % (P = 0.04), 0.7 % (P = 0.0004), and 14.5 % (P = 0.002), respectively.The F-18 FDG-PET/CT scanning significantly improved the validity of the cancer detection program in the asymptomatic population with an unexplained elevation in CEA levels.

The influence of a spanwise traveling transversal surface wave on the near-wall flow field of turbulent boundary layers is investigated by particle-image velocimetry (PIV) and micro-particle tracking velocimetry (μ-PTV). The experimental setup consists of a flat plate equipped with an insert to generate a transversal spanwise traveling wave of an aluminum surface. PIV and μ-PTV measurements are conducted for three Reynolds numbers based on the freestream velocity and momentum thickness immediately downstream of the actuated surface Re θ = 1200, 1660, and 2080. The transversal traveling wave is generated by a newly developed electromagnetic actuator system underneath the aluminum surface. Three amplitudes A = 0.25, 0.30, and 0.375 mm at a wave length of $$\lambda \, = \,160\,{\text{mm}}$$ and a frequency of f = 81 Hz are investigated. The detailed analysis of the velocity profile shows the transversal traveling surface motion to redistribute the velocity in the viscous sublayer and in the logarithmic region of the turbulent boundary layer. The streamwise and wall-normal velocity fluctuations in the outer boundary layer are increased and the streamwise momentum in the near-wall regime is lowered. The drag reduction ratio (DR) due to the actuation is determined by the velocity gradient in the viscous sublayer. At the lowest Reynolds number the drag-reducing impact is proportional to the amplitude of the wave. That is, the higher the amplitude, the more pronounced the drag reduction resulting in a friction drag reduction up to 3.4 % compared to the non-actuated configuration.

Gob-side entry (GSE) is defined as caving that is developed along the gob with a yield pillar. Compared to other entry layouts, GSE has many advantages, such as the advantageous stress environment, high recovery rate, and prevention of coal bumps. Recently, many Chinese coal mines have reached deep mining depths. As a result of the high stress in deep mining conditions, severe bulk and dilatant deformation has occurred in deep GSE (DGSE). The direct problems in this situation, such as interruptions to production, increasing rehabilitation cost, and high labor consumption, affect the safety and mining efficiency of deep coal seams. In this paper, based on analysis of the deformation characteristics of a typical DGSE, numerical modeling was used to study the causes and mechanism of DGSE failure. In addition, a series of strategies are proposed for DGSE deformation control. The case study presented indicates that the proposed control strategies can prevent severe deformation of the DGSE. Thus, the results of this research can be used as a reference for DGSE control in other deep mining settings.

Cigarette smoking might lead to lung cancer. However, the related signaling pathways at molecular level remained unknown until now. In this study, we studied the signaling processes associated between tobacco exposure and lung cancer. First, we detected and validated pathway-specific gene expression at bronchial epithelium. These proteins reflected the activation of signaling pathways relevant to tobacco exposure, including ATM, BCL2, GPX1, K-Ras, IKBKB, and SIRT1. Tobacco smoking was simulated via reactive oxygen species (ROS) pathway. ROS not only arrested cell cycle at G1/S stage but also increased expressions of Sirt1 and p27. Further studies showed that the expression of p27 was dependent on ERK1/2 activation, and p27 itself could halt cell cycle by inhibiting the activation of CDKs. Moreover, activation of K-Ras, the key regulator of Ras/ERK pathway, was tightly regulated by enzyme activity of Sirt1. Deacetylation of K-Ras by Sirt1 increased the transformation of Ras-GTP to Ras-GDP, promoting the activation of downstream of ERK1/2. In reverse, Ras/ERK pathway could also regulate Sirt1 transcription. In conclusion, inhibition of Sirt1 may be an effective strategy for the prevention of tumor progression in high-risk patients or as a therapeutic strategy in established tumors.

Since no cell line from shrimp has been established up till now, an optimization of the primary cell culture protocol is necessary. In this context, the effect of extracts (supernatant of a 1:50 (w/v) suspension) from different shrimp organs (muscle, brain, ganglia, eyestalk, ovary, and eye) on the performance of primary lymphoid cell cultures was evaluated. Ten percent of eye extract and 3% of ovary extract enhanced maximally the migration and survival of cells of the lymphoid organ of Litopenaeus vannamei significantly at 48, 96, and 144 h post seeding. Extracts from the eyestalk (10%), muscle (10%), and brain (1%) significantly promoted the migration and survival of cells at 48 and 96 h post seeding but not anymore at 144 h post seeding. In conclusion, it may be advised to add 10% of eye extract or 3% of ovary extract to cells for the maximal health of primary cell cultures from the lymphoid organ of L. vannamei.

Hydrophobins are a large group of low-molecular weight proteins. These proteins are highly surface-active and can form amphipathic membranes by self-assembling at hydrophobic-hydrophilic interfaces. Based on physical properties and hydropathy profiles, hydrophobins are divided into two classes. Upon the analysis of amino acid sequences and higher structures, some models suggest that the Cys3-Cys4 loop regions in class I and II hydrophobins can exhibit remarkable difference in their alignment and conformation, and have a critical role in the rodlets structure formation. To examine the requirement for the Cys3-Cys4 loop in class I hydrophobins, we used protein fusion technology to obtain a mutant protein HGFI-AR by replacing the amino acids between Cys3 and Cys4 of the class I hydrophobin HGFI from Grifola frondosa with those ones between Cys3 and Cys4 of the class II hydrophobin HFBI from Trichoderma reesei. The gene of the mutant protein HGFI-AR was successfully expressed in Pichia pastoris. Water contact angle (WCA) and X-ray photoelectron spectroscopy (XPS) measurements demonstrated that the purified HGFI-AR could form amphipathic membranes by self-assembling at mica and hydrophobic polystyrene surfaces. This property enabled them to alter the surface wettabilities of polystyrene and mica and change the elemental composition of siliconized glass. In comparison to recombinant class I hydrophobin HGFI (rHGFI), the membranes formed on hydrophobic surfaces by HGFI-AR were not robust enough to resist 1 % hot SDS washing. Atomic force microscopy (AFM) measurements indicated that unlike rHGFI, no rodlet structure was observed on the mutant protein HGFI-AR coated mica surface. In addition, when compared to rHGFI, no secondary structural change was detected by Circular Dichroism (CD) spectroscopy after HGFI-AR self-assembled at the water-air interface. HGFI-AR could not either be deemed responsible for the fluorescence intensity increase of Thioflavin T (THT) and the Congo Red (CR) absorption spectra shift (after the THT(CR)/HGFI-AR mixed aqueous solution was drastically vortexed). Remarkably, replacement of the Cys3-Cys4 loop could impair the rodlet formation of the class I hydrophobin HGFI. So, it could be speculated that the Cys3-Cys4 loop plays an important role in conformation and functionality, when the class I hydrophobin HGFI self-assembles at hydrophobic-hydrophilic interfaces.

The KIV model approximates the operation of the basic vertebrate forebrain together with the basal ganglia and motor systems. In KIV model, the hypothalamus and the basal ganglia which are two important parts in the midline forebrain are closely associated with the locomotion. The CPG model with time delay is established in this paper and the stability of this CPG model is discussed. The CPG output is treated as the proprioception and fed back to the basal ganglia. We focus on the effects on the hypothalamus and the basal ganglia when the time delay parameter a d , the CPG amplitude parameter e and the CPG frequency parameter T r are changed. Through analysis, we find that there exists optimum value of the parameters a d or T r which can make the synchronization of the hypothalamus optimum when the CPG is added into the basal ganglia. The results could have important implications for biological processes which are about interaction between the neural network and the CPG.

Particle swarm optimization (PSO) is an effective method for solving a wide range of problems. However, the most existing PSO algorithms easily trap into local optima when solving complex multimodal function optimization problems. This paper presents a variation, called adaptive PSO based on clustering (APSO-C), by considering the population topology and individual behavior control together to balance local and global search in an optimization process. APSO-C has two steps. First, via a K-means clustering operation, it divides the swarm dynamically in the whole process to construct variable subpopulation clusters and after that adopts a ring neighborhood topology for information sharing among these clusters. Then, an adaption mechanism is proposed to adjust the inertia weight of all individuals based on the evaluation results of the states of clusters and the swarm, thereby giving the individual suitable search power. The experimental results of fourteen benchmark functions show that APSO-C has better performance in the terms of convergence speed, solution accuracy and algorithm reliability than several other PSO algorithms.

There have been many researches and semantics in answering top-k queries on uncertain data in various applications. However, most of these semantics must consume much of their time in computing position probability. Our approach to support various top-k queries is based on position probability distribution (PPD) sharing. In this paper, a PPD-tree structure and several basic operations on it are proposed to support various top-k queries. In addition, we proposed an approximation method to improve the efficiency of PPD generation. We also verify the effectiveness and efficiency of our approach by both theoretical analysis and experiments.

The paper investigates the dynamics of a new multiple bipolar multiple Dielectric Barrier Discharges (DBD) actuator using in large-scale flow control. Particle image velocimetry experiments are performed to characteristic the effectiveness of the multiple bipolar DBD plasma actuator. The results show that the mutual interaction between the electrodes, one major disadvantage of traditional DBD characterized by reverse discharge can be entirely avoided, and a constantly accelerating electric wind velocity can be obtained by using the new multiple bipolar DBD plasma actuator.

Two single-entry gateroad systems employing a yield pillar for bump control in a Chinese coal mine were introduced. The overburden depth of the longwall panels was approximately 390 m. When the width/height (W/H) ratio of the yield pillar was 2.67, coal bumps in the tailgate occurred in front of the longwall retreating face. However, in another panel, the coal bump was eliminated because the W/H ratio was reduced to 1.67. Under this condition, instrumentation results indicated that the roof-to-floor and rib-to-rib convergences reached 1,050 and 790 mm, respectively, during longwall retreat. The numerical model was used to back-analyze the two cases of yield pillar application in the hope to find the principle for yield pillar design. In order to improve the reliability of the numerical model, the strain-hardening gob and strain-softening pillar materials were meticulously calibrated, and the coal/rock interface strength was determined by laboratory direct shear tests. The results of the validated model indicate that if the W/H ratio of the yield pillar equals 1.67, the peak vertical stress in the panel rib (37.7 MPa) is much larger than that in the yield pillar (21.1 MPa); however, the peak vertical stress in the panel rib (30.87 MPa) is smaller than that in the yield pillar (36 MPa) when the W/H ratio of yield pillar is 2.67. These findings may be helpful to the design of yield pillars for bump control.

We investigated the electronic structures and thermoelectric properties of CuMTe2 (M = Al Ga, In) copper chalcopyrites based on first-principles calculations using the Tran-Blaha-modified Becke-Johnson potential, which yielded accurate band gaps for the semiconductors. The band structures show both light and heavy bands near the valence band maximum. Light bands improve mobility, and heavy bands often increase the Seebeck coefficient, so our results suggest that the chalcopyrites should have larger power factors. To calculate the thermoelectric properties of CuMTe2 (M = Al, Ga, In), we used semi-classical Boltzmann transport theory. The results show relatively high Seebeck coefficients and Z e T for low carrier concentrations at a given temperature, and n-type CuAlTe2 appears to be a particularly promising thermoelectric material.