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The amplitude of spectral analysis of the tip timing data from individual blade observations is significant to turbomachinery health monitoring and aeroelastic researches. The accuracy of non-uniform discrete Fourier transform (NUDFT), extended discrete Fourier transform (EDFT), and compressed sensing (CS) is studied systematically. The benchmark data is obtained on a novel test bench where blade tip displacement can be acquired by laser displacement sensor directly. In the experiment, all three methods can successfully recognize the dominant 1F vibration but fail to discover the underlying 1T component. The accuracy of NUDFT to estimate the transient amplitude is approximately 69%. For EDFT and CS, the values are 30% and 84%, respectively. The number of cycles included in an analysis batch is found to influence the results. The robustness of the methods is discussed. The three methods are applied to a single-rotor rig and NSV is discovered in a field test. All of them could capture the frequency feature. It is determined that the blade is vibrating in the first flex mode. The difference between the measured frequency and the simulation is only 2.7%. Regarding the amplitude, CS yields the most convincing estimations.

Connected and Automated Vehicles (CAV) have been rapidly developed, which, inevitably, renders that human-driven and autonomous vehicles share the road. Thus, trajectory prediction is an important research topic, which helps each CAV to efficiently follow a Human-Driven Vehicle (HV). In a wider scope, trajectory prediction, also, helps to improve the throughput of traffic flow and enhance its stability. To realize the trajectory prediction of Connected and Automated Vehicles to Human-Driven Vehicles, a car-following model, which is based on trajectory data, was established. Adding deep neural networks and an Attention mechanism, this paper established a data-driven car-following model, based on CNN-BiLSTM-Attention for CAV, to predict trajectory, by referring to the modeling idea of the traditional car-following model. The trajectory data in the next-generation-simulation (NGSIM) datasets that match the car-following characteristics were selected. In addition, noise-reduction pre-processing of the trajectory data was performed, to make it match the actual car-following situation. Experiments, for selecting the optimal structure of the model and the method of trajectory prediction, were carried out. The data-driven car-following models, such as LSTM, GRU, and CNN-BiLSTM, were selected for comparative analysis of trajectory prediction. The results show that the CNN-BiLSTM-Attention model has the smallest MAE and MSE as well as the largest R2. The CNN-BiLSTM-Attention model has the highest accuracy in vehicle-trajectory prediction. The model can, effectively, realize vehicle-trajectory prediction and provide a theoretical basis for vehicle-trajectory-based velocity guidance of Human-Driven Vehicles. In the future, the model can, also, provide the theoretical basis for Connected and Automated Vehicles, to make car-following decisions in mixed traffic flow.

Due to the inherent molecular heterogeneity of metastatic tumours and the dynamic evolution ability of tumour genomes, tumour tissues obtained through biopsy and other methods cannot capture all of the features of tumour genomes. A new diagnostic concept called “liquid biopsy” has received widespread attention in recent years. Liquid biopsy has changed the clinical practice of oncology and is widely used to guide targeted drug utilization, monitor disease progression and track drug resistance. The latest research subject in liquid biopsy is platelets. Platelets originate from multifunctional haematopoietic stem cells in the bone marrow haematopoietic system. They are small cells from the cytoplasm of bone marrow megakaryocytes. Their main physiological functions are to participate in the processes of physiological haemostasis and coagulation. Tumour cells transfer biomolecules (such as RNA) to platelets through direct contact and release of exosomes, which changes the platelet precursor RNA. Under the stimulation of tumour cells and the tumour microenvironment, platelet precursor mRNA is spliced into mature RNA and converted into functional protein to respond to external stimuli, forming tumour-educated platelets (TEPs). The detection of TEPs in the peripheral blood of patients is expected to be used in clinical tumour diagnosis. This emerging liquid biopsy method can replace and supplement the current tumour detection methods. Further research on the role of platelets in tumour diagnosis will help provide a novel theoretical basis for clinical tumour diagnosis.

Background: Ovarian cancer is the second most common cancer to cause large death among gynecological tumors. Paclitaxel is important to the standard treatment for epithelial ovarian cancer. Due to its low solubility and permeability, nano-paclitaxel came into public view. Objective: To evaluate the effect of nano-paclitaxel in ovarian cancer. Methods: Considering the importance of bevacizumab in clinical treatment, we set four groups for research: control, paclitaxel, paclitaxel + bevacizumab, and nano-paclitaxel + bevacizumab. CCK-8, apoptosis, and cell cycle assays were used to detect the cell survival condition. qRT-PCR and western blot were used to detect the gene mRNA and protein expression level. Tumor xenograft in nude mice was used to detect the effect in vivo. Results: The nano-paclitaxel combined with bevacizumab had the best curative effect. Moreover, the downstream indicators, such as caspases, BAX, FAS, OGFr, PD-L1 and VEGF, changed in four groups, which suggested that the therapy worked by affecting the cell apoptosis, cell cycle, angiogenesis, and immune reaction. Conclusion: In conclusion, the study helped us better commandof nano-paclitaxel for ovarian cancer treatment and thus could play a role in OC therapy.

Immunotherapy for cervical carcinoma is becoming increasingly important recently. In these studies methionine enkephalin (menk) is shown to inhibit cervical tumor cell proliferation in vitro in association with an increase in the expression of apoptosis markers and mediators, including an increase in fas, caspase 8, and caspase 3 expression and intrinsic expression of the signaling pathway mediator bax. In vivo, tumor growth was restrained in mice xenotransplant model with typical pathological features of apoptosis. Furthermore, myeloid derived suppressor cells (MDSCs) had a significant decrease in circulation and in tumor site. In brief, these findings showed menk could inhibit tumor growth in vitro and in vivo, providing direction of further research and clinical application prospect.

Tin-based materials have been considered as promising anode materials due to their advantages including high specific capacity, abundant resources, and low toxicity. Unfortunately, it has remained ...

The benefits of the arbuscular mycorrhizal (AM) symbiosis between plants and fungi are modulated by the functional characteristics of both partners. However, it is unknown to what extent functionally distinct groups of plants naturally associate with different AM fungi. We reanalysed 14 high-throughput sequencing data sets describing AM fungal communities associating with plant individuals (2427) belonging to 297 species. We examined how root-associating AM fungal communities varied between plants with different growth forms, photosynthetic pathways, CSR (competitor, stress-tolerator, ruderal) strategies, mycorrhizal statuses and N-fixing statuses. AM fungal community composition differed in relation to all studied plant functional groups. Grasses, C4 and nonruderal plants were characterised by high AM fungal alpha diversity, while C4 , ruderal and obligately mycorrhizal plants were characterised by high beta diversity. The phylogenetic diversity of AM fungi, a potential surrogate for functional diversity, was higher among forbs than other plant growth forms. Putatively ruderal (previously cultured) AM fungi were disproportionately associated with forbs and ruderal plants. There was phylogenetic correlation among AM fungi in the degree of association with different plant growth forms and photosynthetic pathways. Associated AM fungal communities constitute an important component of plant ecological strategies. Functionally different plants associate with distinct AM fungal communities, linking mycorrhizal associations with functional diversity in ecosystems.

The enlarged interlayer spacing in NaNi0.5Mn0.5O by doping with Sn4+ prevents TMO2 slips and eliminates irreversible multiphase transitions during cycling, achieving a high capacity of 191 mA h g-1 at 0.1C for half cells, as well as 1000 long cycles at 1C and high power ability at 50C for the full cell.

Herein, an effective technique of curing reaction-induced phase separation (CRIPS) was used to construct a reduced graphene oxide (RGO) network in the immiscible diglycidyl ether of the bisphenol A/polyetherimide (DGEBA/PEI) polyblend system. The unique chemical reduction of RGO facilitated the reduction of oxygenated groups and simultaneously appended amino groups that stimulate the curing process. The selective interfacial localization of RGO was predicted numerically by the harmonic and geometric mean technique and further confirmed by field emission transmission electron microscopy (FETEM) analysis. Due to interfacial localization, the electrical conductivity was increased to 366 S/m with 3 wt.% RGO reinforcement. The thermomechanical properties of nanocomposites were determined by dynamic mechanical analysis (DMA). The storage modulus of 3 wt.% RGO-reinforced polyblend exhibited an improvement of ~15%, and glass transition temperature (Tg) was 10.1 °C higher over neat DGEBA. Furthermore, the total shielding effectiveness (SET) was increased to 25.8 dB in the X-band region, with only 3 wt.% RGO, which represents ~99.9% shielding efficiency. These phase separation-controlled nanocomposites with selective localization of electrically conductive nanofiller at a low concentration will extend the applicability of polyblends to multifunctional structural nanocomposite applications.

Radiomics is a novel concept that relies on obtaining image data from examinations such as computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET). With the appropriate algorithm, the extracted results have broad applicability and potential for a massive positive impact in radiology. For example, clinicians can verify treatment efficiency, predict the location of tumor metastasis, correlate results with a histopathological examination, or more accurately define the type of cancer. Combining radiomics with other testing techniques allows every patient to have a personalized treatment plan that is essential for advanced examination and treatment. This article explains the process of radiomics, including data collection mechanisms, combined use with genomics, and artificial intelligence and immunology techniques, which may solve many of the challenges faced by doctors in diagnosing and treating their patients.

The new coronavirus (2019-nCoV) is an emerging pathogen that can cause severe respiratory infections in humans. It is worth noting that many of the affected COVID-19 patients have malignant tumors. In addition, cancer has been identified as a personal risk factor for COVID-19. Transmembrane proteaseserine-2 (TMPRSS2) is a crucial host protease that mediates S protein activation and initially promotes virus entry into host cells. Moreover, it is abnormally expressed in a variety of tumors. However, the systematic analysis of TMPRSS2 aberrations in human cancer remains to be elucidated. Here, we analyzed the genetic changes, RNA expression, and DNA methylation of TMPRSS2 in more than 30 tumors. It has been reported that TMPRSS2 is overexpressed in tumors such as prostate adenocarcinoma (PRAD), and in contrast, the expression of TMPRSS2 is decreased in tumors such as head and neck cancer (HNSC). In addition, TMPRSS2 low DNA methylation was also found in most of these TMPRSS2 high-expressing tumors in this study. Clinical studies have found that there is a significant correlation between the expression of TMPRSS2 and the prognosis of some tumor patients. The expression of TMPRSS2 is also related to the infiltration of cancer-related fibroblasts, and the potential pathways and functional mechanisms were analyzed through KEGG/GO enrichment. In the end, our study planned the genetic and epigenetic variation of TMPRSS2 in human malignant tumors for the first time and provided a relatively comprehensive understanding of the carcinogenic effects of TMPRSS2.

Accumulating evidence has implicated members of the procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) gene family, PLOD1, PLOD2, and PLOD3, in cancer progression and metastasis. However, their expression, prognostic value, and mechanisms underlying their roles in lung adenocarcinoma (LUAD) have not yet been reported. We downloaded PLOD data for LUAD and normal tissues from The Cancer Genome Atlas (TCGA). PLOD1-3 protein expression was evaluated using the Clinical Proteomics Tumor Analysis Consortium and Human Protein Atlas. Survival analysis was performed using the Kaplan-Meier method. A protein-protein interaction network was constructed using STRING software. The "ClusterProfiler" package was used for functional-enrichment analysis. The relationship between PLOD mRNA expression and immune infiltration was analyzed using the Tumor Immunity Assessment Resource and Tumor Immune System Interaction Database. The expression of PLODs in LUAD tissues was significantly upregulated compared with that in adjacent normal tissues. PLOD mRNA overexpression is associated with lymph node metastasis and high TNM staging. Receiver operating characteristic curve analysis showed that when the cut-off level was 6.073, the accuracy, sensitivity, and specificity of PLOD1 in distinguishing LUAD from adjacent controls were 84.4, 79.7, and 82.6%, respectively. The accuracy, sensitivity, and specificity of PLOD2 in distinguishing LUAD from adjacent controls were 81.0, 98.3, and 68.0%, respectively, at a cut-off value of 4.360. The accuracy, sensitivity, and specificity of PLOD3 in distinguishing LUAD from adjacent controls were 69.0, 86.4, and 52.0%, respectively, with a cut-off value of 5.499. Kaplan-Meier survival analysis demonstrated that LUAD patients with high PLODs had a worse prognosis than those with low PLODs. Correlation analysis showed that PLOD mRNA expression was related to immune infiltration and tumor purity. Upregulation of PLOD expression was significantly associated with poor survival and immune cell infiltration in LUAD. Our research shows that PLOD family members have potential as novel biomarkers for poor prognosis and as potential immunotherapy targets for LUAD.

Mycorrhizal symbiosis is an ancient association of plants and mycorrhizal fungi central to woody plant evolution and expansion. This symbiosis has established a complex exchange of services between plants and mycorrhizal fungi that ultimately helps plants thrive in extreme abiotic conditions and build resistance against lack of nutrients and water, pathogens, herbivores, or pollutants. Here, we briefly comment on the roles of mycorrhizal symbiosis as modulators of the responses of woody plants to multiple abiotic stress factors typical to ongoing global change. We comment on the most studied factors, i.e. drought, extreme temperatures, nutrient and light deficiency. There is a general lack of understanding of the interaction among stress factors and their combined effects on woody plants, their symbiotic interaction with mycorrhizal fungi and their impact on ecosystem processes. As a first step, identifying and ranking the severity of stress factors and situations/locations where multiple stress factors co-occur could guide initial expectations and hypotheses to comprehend the mycorrhizal benefits to woody species tolerance under multifactorial stress combinations. We finally highlight topical areas that require more information and research. CGB and YM have been funded by the Estonian Ministry of Education and Research (PRG1065) and an ERC incentive grant from the University of Tartu to CGB (PLTOMARENG70).

One of the keys to the cycling stability of electrode materials is the formation of a stable interface film on cathode materials, which is called a cathode electrolyte interphase (CEI). For a Li/Mn-rich cathode, especially, the high working voltage will cause an extremely unstable electrolyte environment, becoming a challenge for the stable interface film formation. In this work, an operando-attenuated total reflection-Fourier transform infrared (ATR-FTIR) technique is developed to monitor in real time the dynamic mechanism of CEI formation in a carbonate-based electrolyte with or without the moderate additive tris(trimethylsilyl)borate (TMSB), which could promote the formation and stability of high-quality CEI films when it charges to 4.8 V. It is interesting that the components of CEI are basically generated in the first cycle owing to ethylene carbonate (EC) priority decomposition. Besides, the presence of TMSB can suppress the decomposition of EC in part and modify the stability of the CEI film. This is because TMSB containing an electron-deficient boron atom can easily combine with an electron-rich F- and PF6- forming a polyanion group initially, which will weaken the electrostatic force between the anionic groups and EC to reduce the concentration of EC on the cathode surface and prevent the continuous decomposition of EC at a high voltage. X-ray photoelectron spectroscopy also verifies the presence of polyanion groups and their further participation in CEI formation. This work highlights the dynamical stability of CEI modified by moderate TMSB and the formation mechanism of this dynamical change during cycling characterized by the operando ATR-FTIR technique, which paves the way for a better understanding of the complex and hard-characterized cathode interface reactions.

Cobalt-free Li and Mn-rich layered cathode materials are promising for next generation lithium ion batteries due to their high specific capacity and low cost. However, these materials are facing serious issues, such as structural collapse due to volume shrinkage during Ni2+ oxidation to Ni4+ and oxygen vacancy generation over 4.5V. In this work, we report a strategy to address the issue of volume shrinkage caused by structural deformation via constructing a large-size rigid frame by simultaneously doping inactive and large radius atoms of Cd and S. This strategy significantly reduces the volume shrinkage when fully delithiated relative to the pristine material. The Cd- and S-doped cathode materials present a highly reversible structure, which were determined by using HAADF-STEM and in-situ XRD characterization. The doped Cd and S atoms act as supporting atoms and synergistically enlarge the layer spacing of crystalline from 0.455 to 0.483 nm. The in-situ XRD monitors the structural changes in real time during charging and discharging processes, further verifying structural stability during cycling. Due to the unique structural properites, an initial capacity of 268.5 mAh g−1 at 0.1 C along with a good rate capacity of 153.8 mAh g−1 at 5 C were achieved. Also, a capacity of 243.4 mAh g-1 at 0.1 C over 80 cycles indicate good cyclic stability of the co-doped Li- and Mn-rich layered cathode.

Promoting the antitumor effects of cell-based immunotherapy for clinical application remains a difficult challenge. Nocardia rubra cell-wall skeleton (N-CWS) is an immunotherapeutic agent for cancers that have been proven to possess the ability to activate immune response without showing toxicity. However, its effects on immune cells that are derived from tumor patients and cultured in vitro remain unclear. As expected, N-CWS can enhance the proliferation and viability of cytokine-induced killer (CIK) cells, dendritic cells (DCs), and natural killer (NK) cells. The maturation of DCs and specific cytotoxicity against NK cells and CIK cells were consistently promoted. The TUNEL-staining and the Annexin V/propidium iodide assay revealed that after treatment with N-CWS, the stimulated CIK/NK cells could induce DNA breaks in tumor cells. Furthermore, quantitative real-time polymerase chain reaction and western blot analysis showed upregulation of proapoptotic biomarkers (caspase-3 and caspase-9) and a downregulation of the antiapoptotic biomarker Bcl-2 in the tumor cells of the N-CWS-treated group, indicating that N-CWS could induce hepatocellular carcinoma cell apoptosis via CIK/NK cells. Finally, CIK/NK cells could notably suppress the invasion and migration of tumor cells in the presence of N-CWS. Our study provides evidence that N-CWS could significantly increase the growth of CIK cells, DCs, and NK cells, particularly due to its robust antitumor activities by inducing apoptosis, and attenuate the invasion and migration of tumor cells.

The study of control synthesis for reach-avoid-stay objectives for nonlinear systems has received considerable interest in recent years. Such objectives can be naturally treated as a formal specification and effectively handled by formal methods. While formal methods often rely on constructing a finite-state approximation and developing algorithms to capture the winning set (a set of initial states from which a controller exists to realize the given task), Lyapunov methods can characterize stability and safety properties without having to discretize the state space. Inspired by recent work on converse Lyapunov-barrier theorems, we propose control Lyapunov-barrier functions to provide sufficient conditions for control synthesis with reach-avoid-stay specifications. A comparison between the proposed Lyapunov method and formal methods based on a fixed-point algorithm is illustrated by an application to enhancing the performance of jet engine compressors, which is based on a reduced Moore-Greitzer nonlinear ODE model. We apply a quadratic programming (QP) framework to reactively synthesize controllers in the case study.

The progressively increased motivation for cocaine during abstinence is closely associated with the dysfunction of dopamine (DA) system. As DA receptors also dynamically regulate L-type calcium channels (LTCCs), in this study we examined how DA receptors (D1R or D2R) and LTCCs (Cav 1.2 or Cav 1.3) exert their influences on cocaine-seeking in a tree shrew (Tupaia belangeri chinensis) model. First, we demonstrated the 'incubation' effect by showing tree shrews exhibited a significantly higher seeking behaviour on withdrawal day (WD) 45 than on WD1. Then, we confirmed that longer abstinence period induced higher D1R expression in the nucleus accumbens (NAc). Next, we showed that LTCCs in the NAc participated in drug seeking. Moreover, Cav 1.2 expression in the NAc was increased on WD45, and disruption of the Cav 1.2 inhibited drug seeking. Finally, we found that D1R antagonist blocked the increase of Cav 1.2 on drug-seeking test. Collectively, these findings suggest that D1R-mediated upregulation of Cav 1.2 is involved in the incubation of cocaine craving.

The progressively increased motivation for cocaine during abstinence is closely associated with the dysfunction of dopamine (DA) system. As DA receptors also dynamically regulate L-type calcium channels (LTCCs), in this study we examined how DA receptors (D1R or D2R) and LTCCs (Ca

Hepatocellular carcinoma (HCC) is the most common visceral neoplasms with its heterogeneity and high rate of recurrence. HCC is characterized to be delayed diagnosis and the development of resistant disease. However, the molecular mechanism for HCC pathogenesis and progression remains largely unknown. Here, we demonstrated that ubiquitin-specific protease14 (USP14) is highly expressed in HCC samples, and the higher expression of USP14 is positively correlated with poor prognosis. Interestingly, USP14 is involved in the maintenance of HIF1-α stability to activate HIF1-α-induced transactivation via its deubiquitinase activity. USP14 depletion or its specific inhibitor IU1 treatment decreased cell proliferation, invasion, migration, and Vascular Mimicry (VM) formation even under hypoxia conditions in HCC cell lines. Moreover, we provided the evidence to show that knockdown of USP14 or USP14 inhibitor (IU1) treatment inhibited tumor growth in tumor-bearing nude mice. Our findings suggest that USP14 maintains HIF1-α stability through its deubiquitination activity, providing a potential biomarker for the early diagnosis and therapy of HCC.

Deserts cover a significant proportion of the Earth’s surface and continue to expand as a consequence of climate change. Mutualistic arbuscular mycorrhizal (AM) fungi are functionally important plant root symbionts, and may be particularly important in drought stressed systems such as deserts. Here we provide a first molecular characterization of the AM fungi occurring in several desert ecosystems worldwide. We sequenced AM fungal DNA from soil samples collected from deserts in six different regions of the globe using the primer pair WANDA-AML2 with Illumina MiSeq. We recorded altogether 50 AM fungal phylotypes. Glomeraceae was the most common family, while Claroideoglomeraceae, Diversisporaceae and Acaulosporaceae were represented with lower frequency and abundance. The most diverse site, with 35 virtual taxa (VT), was in the Israeli Negev desert. Sites representing harsh conditions yielded relatively few reads and low richness estimates, for example, a Saudi Arabian desert site where only three Diversispora VT were recorded. The AM fungal taxa recorded in the desert soils are mostly geographically and ecologically widespread. However, in four sites out of six, communities comprised more desert-affiliated taxa (according to the MaarjAM database) than expected at random. AM fungal VT present in samples were phylogenetically clustered compared with the global taxon pool, suggesting that nonrandom assembly processes, notably habitat filtering, may have shaped desert fungal assemblages.

Herein, a feasible and effective approach is developed to build an electrically conductive and double percolation network-like structure via the incorporation of highly reduced graphene oxide (HRGO) into a polymer blend of diglycidyl ether of bisphenol A/polyetherimide (DGEBA/PEI). With the assistance of the curing reaction-induced phase separation (CRIPS) technique, an interconnected network of HRGO is formed in the phase-separated structure of the DGEBA/PEI polymer blend due to selective localization behavior. In this study, HRGO was prepared from a unique chemical reduction technique. The DGEBA/PEI/HRGO nanocomposite was analyzed in terms of phase structure by content of PEI and low weight fractions of HRGO (0.5 wt.%). The HRGO delivered a high electrical conductivity in DGEBA/PEI polyblends, wherein the value increased from 5.03 &times, 10&minus, 16 S/m to 5.88 S/m at a low content of HRGO (0.5 wt.%). Furthermore, the HRGO accelerated the curing reaction process of CRIPS due to its amino group. Finally, dynamic mechanical analyses (DMA) were performed to understand the CRIPS phenomenon and selective localization of HRGO reinforcement. The storage modulus increased monotonically from 1536 MPa to 1660 MPa for the 25 phr (parts per hundred in the DGEBA) PEI polyblend and reached 1915 MPa with 0.5 wt.% HRGO reinforcement. These simultaneous improvements in electrical conductivity and dynamic mechanical properties clearly demonstrate the potential of this conductive polyblend for various engineering applications.

Control barrier functions have shown great success in addressing control problems with safety guarantees. These methods usually find the next safe control input by solving an online quadratic programming problem. However, model uncertainty is a big challenge in synthesizing controllers. This may lead to the generation of unsafe control actions, resulting in severe consequences. In this paper, we develop a learning framework to deal with system uncertainty. Our method mainly focuses on learning the dynamics of the control barrier function, especially for high relative degree with respect to a system. We show that for each order, the time derivative of the control barrier function can be separated into the time derivative of the nominal control barrier function and a remainder. This implies that we can use a neural network to learn the remainder so that we can approximate the dynamics of the real control barrier function. We show by simulation that our method can generate safe trajectories under parametric uncertainty using a differential drive robot model.

The enlarged interlayer spacing in NaNi

Background Due to the difficulties in acquiring large numbers of megakaryocytes, the impact of inflammatory responses on these cells and their ability to produce fully functional platelets under various pathological conditions has not been investigated in detail. Objectives The primary objective of this study is to develop and functionally characterise a novel megakaryocyte NF-κB reporter cell line in order to determine the effects of various inflammatory molecules on megakaryocytes and their signalling pathways. Methods A Meg-01-NF-κB-GFP-Luc (Meg-01R) cell line was developed by inserting a reporter NF-κB-GFP-Luc cassette into normal Meg-01 cells to produce luciferase following activation of NF-κB to enable easy detection of pro-inflammatory and reparative signalling. Results and conclusions Meg-01 and Meg-01R cells have comparable characteristics including the expression of both GPIb and integrin β3. Meg-01R cells responded to various inflammatory molecules as measured by NF-κB-dependent bioluminescence. For example, inflammatory molecules such as TNFα and Pam3CSK4 increased NF-κB activity, whereas an antimicrobial peptide, LL37, reduced its activity. Meg-01R cells were also found to be sensitive to inhibitors (IMD0354 and C87) of inflammatory pathways. Notably, Meg-01R cells were able to respond to LPS (non-ultrapure) although it was not able to react to ultrapure LPS due to the lack of sufficient TLR4 molecules on their surface. For the first time, we report the development and characterisation of a novel megakaryocyte NF-κB reporter cell line (Meg-01R) as a robust tool to study the inflammatory responses/signalling of megakaryocytes upon stimulation with a broad range of inflammatory molecules that can affect NF-κB activity.

There are some problems in the thermal system of Huabei Oilfield, such as high energy consumption, high operation cost and poor production safety. With more stringent requirements for energy conservation and emission reduction, it is particularly important to replace fuel oil projects and improve the efficiency of heating system.The utilization of waste heat and waste heat resources in Huabei Oilfield and the application conditions of various heat pump technologies were investigated, according to the characteristics of large amount of sewage and high temperature produced by crude oil dehydration in Huabei Oilfield. Aiming at the characteristics of large amount of sewage and high temperature produced by crude oil dehydration in Huabei Oilfield, Pilot Application of Optimized Extracted Water Source Heat Pump Technology, the research results are applied to the the He Yi Station in the third oil production plant, estimating the scale and benefit of saving, finally, the purpose of reducing cost and increasing efficiency is achieved, and the data basis and technical guidance for energy saving renovation of thermal system in the future are improved.

Stability and safety are two important aspects in safety-critical control of dynamical systems. It has been a well established fact in control theory that stability properties can be characterized by Lyapunov functions. Reachability properties can also be naturally captured by Lyapunov functions for finite-time stability. Motivated by safety-critical control applications, such as in autonomous systems and robotics, there has been a recent surge of interests in characterizing safety properties using barrier functions. Lyapunov and barrier functions conditions, however, are sometimes viewed as competing objectives. In this paper, we provide a unified theoretical treatment of Lyapunov and barrier functions in terms of converse theorems for stability properties with safety guarantees and reach-avoid-stay type specifications. We show that if a system (modeled as a dynamical system with measurable perturbations) possesses a stability with safety property, then there exists a smooth Lyapunov function to certify such a property. This Lyapunov function is shown to be defined on the entire set of initial conditions from which solutions satisfy this property. A similar but slightly weaker statement is made for reach-avoid-stay specifications. We show by a simple example that the latter statement cannot be strengthened without additional assumptions. We further extend the results for systems with control inputs and prove existence of converse Lyapunov-barrier functions for reach-and-avoid specifications. While the converse Lyapunov-barrier theorems are not constructive, as with classical converse Lyapunov theorems, we believe that the unified necessary and sufficient conditions with a single Lyapunov-barrier function are of theoretical interest and can hopefully shed some light on computational approaches., Comment: Preprint submitted for publication, 13 pages, 2 figures

Naltrexone (NTX) is a nonspecific opioid antagonist that exerts pharmacological effects on the opioid axis by blocking opioid receptors distributed in cytoplastic and nuclear regions. NTX has been used in opioid use disorder (OUD), immune-associated diseases, alcoholism, obesity, and chronic pain for decades. However, low-dose naltrexone (LDN) also exhibits remarkable inhibition of DNA synthesis, viability, and other functions in numerous cancers and is involved in immune remodeling against tumor invasion and chemical toxicity. The potential anticancer activity of LDN is a focus of basic research. Herein, we summarize the associated studies on LDN oncotherapy to highlight the potential mechanisms and prospective clinical applications.

Cell-based immunotherapy holds promise in the quest for the treatment of cancer, having potential synergy with surgery, chemotherapy and radiotherapy. As a novel approach for adoptive cell-based immunotherapy, cytokine-induced killer (CIK) cells have moved from the 'bench to bedside'. CIK cells are a heterogeneous subset of ex-vitro expanded, polyclonal T-effector cells with both natural killer (NK) and T-cell properties, which present potent non-major histocompatibility complex-restricted cytotoxicity against a variety of tumor target cells. Initial clinical studies on CIK cell therapy have provided encouraging results and revealed synergistic antitumor effects when combined with standard therapeutic procedures. At the same time, issues such as inadequate quality control and quantity of CIK cells as well as exaggerated propaganda were continuously emerging. Thus, the Ministry of Health in China stopped CIK cell therapy in May 2016, which was a major setback for the innovation of CIK cell-based immunotherapy. Thus, it is very important to modify technical criteria to develop a standardized operation procedure (SOP) and standardized system for evaluating antitumor efficacy in a safe way.

MENK, an endogenous opioid peptide has been reported to have many immunological and antitumor activities. So far the detailed mechanisms of antitumor through regulating DCs by MENK have not been elucidated yet. The aim of this work was to investigate the antitumor mechanisms of MENK via regulating DC. The monitoring methods, such as ELISA, MTS assay, CFSE, Real-time PCR and Western blot were included in our research. We found bone marrow derived dendritic cells (BMDCs) in 36 female C57BL/6 mice treated with MENK enhanced expression of key surface molecules, increased production of critical cytokines reduced endocytosis of FITC-dextran, upregulated TLR4 through MyD88/NF-κB signaling pathway and mounted higher antitumor activity. These observations were further supported by an enhancement of nuclear translocation of the p65NF-κB subunit involved in this process. Surprisingly, mu-opioid receptors were the main participants of this kind of activation, not delta-opioid receptors nor kappa-opioid receptors, and these interactions could be partly blocked by Naltrexone (a kind of opioid antagonist). In vivo study the activated CD4 + , CD8 + T cells and decreased ability to induce differentiation of Foxp3 + regulatory T cells were detected post treatment of MENK. Thus, it is concluded that MENK could exert antitumor effect through precisely regulating opioid receptor mediated functions of DCs. In addition, MENK treated DCs may serve as a new immunotherapy approach against tumor.

Cancer immunotherapy, due to its high anti-tumor efficacy, has attracted considerable attention globally from experts in various fields. However, immunotherapy could be severely toxic; not all patients may respond, thus requiring combination therapy. Therefore, a reasonable selection strategy for early treatment is urgently needed. It is vital to capture the dynamic, heterogeneous, and complex tumor behavior considering the absence of ideal companion biomarkers. Since tumor immune response involves tumor cells, several other cell types, and molecules in the tumor microenvironment, detection is very complex and variable. However, molecular imaging technology, namely the non-invasive whole-body molecular imaging by positron emission tomography and single-photon emission computed tomography, has shown considerable promise in tumor detection and cancer immunotherapy response. Identification of potential novel imaging biomarkers will allow a personalized treatment plan for every patient. Future imaging strategies for these molecules used alone or in combination or continuously, might help stratify patients before or during the early stages of immunotherapy, and might address the immunotherapy challenges encountered by the oncologists.

One of the keys to the cycling stability of electrode materials is the formation of a stable interface film on cathode materials, which is called a cathode electrolyte interphase (CEI). For a Li/Mn-rich cathode, especially, the high working voltage will cause an extremely unstable electrolyte environment, becoming a challenge for the stable interface film formation. In this work, an operando-attenuated total reflection-Fourier transform infrared (ATR-FTIR) technique is developed to monitor in real time the dynamic mechanism of CEI formation in a carbonate-based electrolyte with or without the moderate additive tris(trimethylsilyl)borate (TMSB), which could promote the formation and stability of high-quality CEI films when it charges to 4.8 V. It is interesting that the components of CEI are basically generated in the first cycle owing to ethylene carbonate (EC) priority decomposition. Besides, the presence of TMSB can suppress the decomposition of EC in part and modify the stability of the CEI film. This is because TMSB containing an electron-deficient boron atom can easily combine with an electron-rich F

The standard treatments for neoplasia include surgery, chemotherapy, hormone antagonists and radiotherapy, which can prolong survival, but rarely cure the tumors of gynecological cancer patients. OGF - OGFr expression, in various gynecologic cells and tissues, is an intersection point between cell development, neuroendocrine function and immune modulation. It has been identified that OGF and OGFr expression differs between gynecological tumor and normal cells. Further, exogenous or endogenous OGF and OGFr antagonists have been known to have a role in regulating cell viability and apoptosis. Moreover, the expression of proteins in the OGF - OGFr axis modulate differentiation and membrane expression of immune cells, which can enhance the immune response. In vivo and in vitro assays have shown that OGF and OGFr antagonists inhibit mitosis as well as induce apoptosis in gynecologic cancer cells. Although immune augmentation combination therapies can intensify cytotoxic activity, OGF or OGFr antagonists do not increase toxicities associated with dual-immune regulation. In conclusion, the OGF - OGFr axis provides significant strategies for antitumor efficiency in gynecological cancer.

Revegetation accelerates the recovery of degraded lands. Different microbial trophic groups underpin this acceleration from the aspects of soil structure stabilization, nutrient accumulation, and ecosystem functions. However, little is known about how revegetation influences the community and biodiversity of different soil microbial trophic groups. Here, six revegetation treatments with different plantings of plant species were established at an excavation pit in the Qinghai-Tibetan Plateau. Communities of plant, bacteria, and several key soil fungal groups were investigated after 12 years of revegetation. Plant and all microbial trophic group compositions were markedly influenced by revegetation treatments. Total fungal and pathogenic fungal compositions were not significantly predicted by any factor of plant and soil, but arbuscular mycorrhizal fungal composition could be mainly predicted by plant composition and plant P content. Bacterial composition was mainly determined by soil total N, organic carbon concentration, and moisture content; and saprotrophic fungal composition was mainly determined by soil organic carbon. Soil pH was the strongest factor to predict bacterial metabolic functions. Our findings highlight that even the differences of microbial compositions were because of different revegetation treatments, but each trophic microbial composition had different relations with plant and/or soil; especially, the bacterial community and metabolic functions and saprotrophic fungal community were more correlated with soil properties rather than plant community or characteristics per se.

Revegetation is widely used to enhance degraded topsoil recovery with the enhancements of soil nutrient accumulation and soil structure stabilization. Arbuscular mycorrhizal fungi (AMF) are important for the allocation of carbon into the soil and the formation of soil aggregates. Thus, we hypothesized that AMF could construct more niches for other microbes during revegetation, making AMF keystone taxa of soil. Soil fungal and bacterial communities were investigated under a revegetation experiment and correlation networks between soil fungi and bacteria were constructed. Simultaneously, the plant growth level, soil properties and structure, and soil microbial carbon decomposition abilities were measured. The results revealed that AMF were the most central fungi at the phylum (degree = 3), class (degree = 11), and family (degree = 15) levels. The reads number of AMF were positively correlated with both fungal (R2 = 0.431, P

Energy-related investment decisions in the buildings sector are heterogeneous in that the outcome for each individual varies according to budget, values, and perception of a technology, even if an apparently identical decision task is faced. In particular, the rate of adoption of new energy-efficient technologies is often hard to model and underlines the need for an advanced approach to capture diversity in decision-making, and enable the inclusion of economic, comfort, environmental and social aspects. This paper presents an enhanced agent-based model that captures several characteristics of consumer behaviour that influence investment decisions. Multiple agents with different objectives, search strategies, and decision methods are implemented. A case study is presented which illustrates the benefits of the approach for the residential sector in the UK. The agent-based method shows diversity in investment decisions, without requiring the constraints on uptake needed in many models. This leads to a range of technologies in the market during a transition phase, continuous investment in low capital cost technologies, and eventually the emergence of a low carbon system based on new mass market technologies. The system that emerges is vastly different from one observed when economically rational investment is assumed and uptake constraints are applied.

Negligible solubility of curcumin in water combined with rapid degradation have limited its medical applications. In this contribution, eutectic mixture of curcumin with one of its degradation products (ferulic acid) was encapsulated into long and medium chain triglycerides oils and stabilised by the non-ionic surfactant polyoxyethylene oleyl ether Brij® O10 (C18:1E10) and bile acid derivative (sodium deoxycholate). Thermal and spectroscopic analysis confirmed the presence of curcumin as solid nanocrystals embedded within the microemulsion droplets. UV-spectroscopy and LC-MS studies of formed microemulsions revealed that degradation of curcumin in water was significantly reduced with more than 83% of curcumin remained intact after 24 h 1H NMR results showed that curcumin remained stable upon heating in the range between 297K and 327 K with no signs of degradation to ferulic acid. The results showed solubility enhancement of curcumin with a range of 3–5 mg/mL. NF-κB reporter cell assay revealed low cytotoxicity and three folds stronger anti-inflammatory potential compared to curcumin. Microemulsions remained stable for over 12 months with extended stability of formulations that contained curcumin/ferulic acid in glyceryl tricaprate based microemulsions. Overall these results suggest novel role for particle engineering via using ferulic acid as stability and activity enhancer for curcumin through free radicals scavenging mechanism.

To fully utilize deoiled end-cut (DOE) from selective asphaltene extraction process, Venezuela n-pentane DOE was subjected to hydroconversion in an autoclave reactor using tetralin as hydrogen donor. Venezuela DOE and its hydroconversion products were separated into gas, n-heptane maltenes (HM), n-heptane asphaltenes (HAs), and coke. The effects of reaction conditions including reaction temperature, solvent-to-feedstock (S/F) weight ratio, and reaction time on product distribution were investigated. High temperature, large S/F ratio, and long time benefited the generation of gas, HM, and coke to some extent. Under optimal conditions, over 50 wt % HAs in DOE was converted into HM fraction, with less than 3 wt % coke yield. The elemental compositions and molecular weights of HAs and HM, along with reaction time, were also analyzed. The hydrogen-to-carbon (H/C) ratio of HAs declined from 1.115 to 0.871, indicating that HAs underwent dehydrogenation and dealkylation reactions. However, the H/C ratio of HM ini...

This study was to explore the effect and mechanisms of anti- human gastric cancer by MENK in vitro and in vivo. The results showed in MENK-treated xenograft tissue, the percentage of M2-type macrophages decreased while M1-type macrophages increased. MENK increased the expression of M1-related cytokine TNF-α and attenuated the expression of M2-related cytokine IL-10 expression. MENK upregulated the expression of opioid receptor (OGFr), while it inhibited HGC27 and SGC7901 cells through blocking PI3K/AKT/mTOR signal pathway in vitro and in vivo. These effects of MENK could be cancelled when OGFr was knockdown. This indicates that binding to OGFr by MENK appears to be essential for the anti- GC cells. Therefore, it is concluded that MENK might skew macrophage toward M2 phenotype from M1 phenotype within tumor and induce cells apoptosis though blocking OGFr/PI3K/AKT/mTOR signaling pathway.

Cell-based immunotherapy using natural killer (NK) cells, cytokine-induced killer (CIK) cells and dendritic cells (DCs) is emerging as a potential novel approach in the auxiliary treatment of a tumor. However, non-standard operation procedure, small-scale cell number, or human error may limit the clinical development of cell-based immunotherapy. To simplify clinical scale NK cells, CIK cells and DCs expansions, we investigated the use of the WAVE bioreactor, a closed system bioreactor that utilizes active perfusion to generate high cell numbers in minimal volumes. We developed an optimized rapid expansion protocol for the WAVE bioreactor that produces clinically relevant number of cells for our adoptive cell transfer clinical protocols. The high proliferative rate, surface phenotypes, and cytotoxicity of these immune cells, as well as the safety of cultivation were analyzed to illuminate the effect of WAVE bioreactor. The results demonstrated that the benefit of utilizing modern WAVE bioreactors in cancer immunotherapy was simple, safe, and flexible production.

To characterize different tissue MSCs as sources of cell immunomodulatory therapy. Examined the effects of IFN-γ on WJ-MSC and their immunomodulatory function characteristics. We compared human fetal bone marrow (F-BM), adipose tissue (AT), and Warton's Jelly-derived MSCs (WJ-MSCs) for surface antigen expression, differentiation ability, proliferation capacity, clonality, tolerance for aging, gene expression, and whether IFN-γ affected WJ-MSC gene expression, as determined by real time quantitative PCR. Fifteen geneswere examined. We further assess WJ-MSCs-mediated immunomodulatory on peripheral blood mononuclear, stimulated by PHA, IL-2 and CD3Ab after 5 days of co-cultured in a 5:1 ratio (PBMC:MSCs). Examined the effect of WJ-MSCs on the Th1, Th2, Th17 cytokines production and Treg augument. MSCs from different tissues have similar levels of cell surface antigen expression and differentiation ability, while F-BM-MSCs and WJ-MSC had higher rates of cell proliferation and clonality than AD-MSCs. All 15 genes were expressed at similar levels in WJ-MSCs and AD-MSCs (P > 0.05). 9 genes were upregulated in WJ-MSCFor F-MSC, including IL-6, CXCL9, CXCL10, CXCL11, ICAM-1, IDO1, HLA-G5, SDF1A, and NOTCH were down expression, but VCAM-1 was lower expressionin WJ-MSCS. After IFN-γ treatment, 7 genes were upregulated in WJ-MSC, including chemokine ligands CXCL9, CXCL10 and CXCL11, and the adhesion protein VCAM1and ICAM1. Additionally, immunosuppressive factors, such as HLA-G and IDO were both increased. When cocultured with peripheral blood mononuclear, WJ-MSCs showed an immunosuppressive function by inhibit the proliferative response of Th1 and Th17 but augment Th2 and Treg. Primed WJ-MSCs by IFNγ caused a greater reduction in IFNγ and TNFα than untreated WJ-MSCs, also the effect on augument in Treg and inhibit Th17 (P < 0.01). Our results demonstrate that primitive F-BM-MSCs and WJ-MSCs have biological advantages as compared to adult cells, WJ-MSCs have a gene expression pattern similar to AT-MSCs but not F-BM MSCs, and that inflammatory stimuli regulate gene expression in WJ-MSCs. WJ-MSC showed the immunosuppressive function in co-cultured system with PBMC, and IFNγ can promoted the immunosuppressive function.

Various components of mulberry leaves, such as iminosugars, flavonoids and polysaccharides, have been reported to exert anti-diabetic activity. The purpose of our present study was to examine the modulating effect of mulberry leaf polysaccharides (MLPs) on murine bone-marrow-derived dendritic cells (BMDCs). The ultrastructure, phenotype and functional maturation of BMDCs were studied using transmission electron microscopy (TEM), flow cytometry (FCM), and tested for phagocytosis, acid phosphatase (ACP) activity using an enzyme linked immunosorbent assay (ELISA). Our results demonstrated that MLPs could markedly induce BMDC maturation by up-regulating the expression of membrane phenotypic markers, such as CD80, CD86, CD83,CD40, and MHC II, down-regulating phagocytosis and ACP activity, and by enhancing the production of interleukin 12 (IL-12) and tumor necrosis factor α (TNF-α) secreted by BMDCs. We therefore concluded that MLPs can positively modulate BMDCs.

Our understanding of the mechanisms of effect of Ginkgo Seed Polysaccharides (GSPs) on the immune system remains unclear. The aim of this work was to investigate the effect of GSPs on the maturation and function of bone-marrow-derived dendritic cells (BMDCs). The results demonstrate that GSP could exert positive immune modulation on the maturation and functions of BMDCs. This effect was evidenced by decreased changes of phagosome number inside BMDCs, decreased activity of acidic phosphatase (ACP), decreased phagocytosis of BMDCs, and increased changes of key membrane molecules on BMDCs. Upregulated production of cytokines IL-12 and TNF-α also was confirmed. Therefore, it can be concluded that GSPs can efficiently induce the maturation of BMDCs. Our exploration provides direct data and a rationale for potential application of GSPs as an immune enhancer in improving immunity and as a potent adjuvant in the design of DC-based vaccines.