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The wave energy device moves under the drive of waves. During the movement of the device, the damper inside the device is driven to do work and the work done by the damper is converted into energy output.In this paper, the force of the system in the initial equilibrium state of the device is first analyzed, and then according to Newton's second law, the motion state of the float and the oscillator are analyzed separately, and the differential equation motion model of the float and the oscillator is established.When the constraints are damping coefficients, multiple search algorithms are used to solve them, and the negative work done by the linear damping force is obtained, with a period of 40 times as long. After the work is analyzed and discretized, the objective function expression is obtained, and a number of average output powers are obtained and continuously compared, and finally the maximum average output power and its corresponding parameter values are obtained.The optimal damping coefficient and the maximum average power are obtained.

(A) Schematic diagram of Co9S8 nanoparticle-decorated CdS nanoflowers-based photoelectrochemical (PEC) aptasensor for the detection of carcinoembryonic antigen (CEA); and (B) the photocurrent response mechanism of PEC bioanalysis.

Federated learning (FL) is a framework which is used in distributed machine learning to obtain an optimal model from clients' local updates. As an efficient design in model convergence and data communication, cloud-edge-client hierarchical federated learning (HFL) attracts more attention than the typical cloud-client architecture. However, the HFL still poses threats to clients' sensitive data by analyzing the upload and download parameters. In this paper, to address information leakage effectively, we propose a novel privacy-preserving scheme based on the concept of differential privacy (DP), adding Gaussian noises to the shared parameters when uploading them to edge and cloud servers and broadcasting them to clients. Our algorithm can obtain global differential privacy with adjustable noises in the architecture. We evaluate the performance on image classification tasks. In our experiment on the Modified National Institute of Standards and Technology (MNIST) dataset, we get 91% model accuracy-layer HFL-DP, our design is more secure while as being accurate.

The effective remission of acute respiratory distress syndrome- (ARDS-) caused pulmonary fibrosis determines the recovery of lung function. Inositol can relieve lung injuries induced by ARDS. However, the mechanism of myo-inositol in the development of ARDS is unclear, which limits its use in the clinic. We explored the role and mechanism of myo-inositol in the development of ARDS by using an in vitro lipopolysaccharide- (LPS-) established alveolar epithelial cell inflammation model and an in vivo ARDS mouse model. Our results showed that inositol can alleviate the progression of pulmonary fibrosis. More significantly, we found that inositol can induce autophagy to inhibit the progression pulmonary fibrosis caused by ARDS. In order to explore the core regulators of ARDS affected by inositol, mRNA-seq sequencing was performed. Those results showed that transcription factor HIF-1α can regulate the expression of SLUG, which in turn can regulate the key gene E-Cadherin involved in cell epithelial-mesenchymal transition (EMT) as well as N-cadherin expression, and both were regulated by inositol. Our results suggest that inositol activates autophagy to inhibit EMT progression induced by the HIF-1α/SLUG signaling pathway in ARDS, and thereby alleviates pulmonary fibrosis.

With the development of modern browsing, the convenience brought by rich browser features has also produced a large number of features, which are called browser fingerprints. This article surveys the latest research results on browser fingerprinting, hoping to provide a convenient navigation for newcomers to research or apply this technology in the future. This paper first briefly introduces the browser fingerprinting technology itself, then classifies the related research on browsers, and analyzes the development of different research directions of browser fingerprinting in detail. And through the analysis of the existing results, the problems faced by different research directions are pointed out. After that, this paper introduces the application of browser fingerprint technology in detail and discusses the application achievements and technical challenges of this technology. Next, this paper introduces the theoretical tools related to the research of browser fingerprinting technology and introduces the application of different theoretical tools and practical significance. Finally, the research achievements of browser fingerprint recognition are summarized, and the future development trend is pointed out.

The purpose of this study is to analyze the relationships among perceived quality, perceived value, customer satisfaction, and behavioral intention in Turkish fitness centers. The data were collected from 305 fitness customers (149 women and 156 men) using the quantitative method of a questionnaire. The main procedure of this study was to conceptualize fitness clubs’ perceived value as a multidimensional construct of four dimensions. Through a comprehensive review of the literature, a questionnaire was developed to measure perceived quality, perceived value, customer satisfaction, and behavioural intention, which took into consideration the unique characteristics of Turkish fitness centers. After examining the measurement properties by conducting confirmatory factor analysis and structural equation model analysis, the results revealed positive relationships among perceived quality, perceived value, customer satisfaction, and behavioral intention. The findings showed that perceived quality was positively related to social value, functional value, emotional value, and economic value. Likewise, functional value and economic value were positively related to customer satisfaction, and social value and emotional value were not positively related to customer satisfaction. Finally, customer satisfaction was related to behavioral intentions. The implication for management is significant as it shows that quality management is important for the different dimensions of value. Therefore, sports managers must work on quality processes to achieve positive perceived quality and its consequences, such as perceived value or behavioral intentions. This chain of positive perceptions improves consumer loyalty.

In plants, the timely degeneration of tapetal cells is essential for providing nutrients and other substances to support pollen development. Rapid alkalinization factors (RALFs) are small, cysteine-rich peptides known to be involved in various aspects of plant development and growth, as well as defense against biotic and abiotic stresses. However, the functions of most of them remain unknown, while no RALF has been reported to involve tapetum degeneration. In this study, we demonstrated that a novel cysteine-rich peptide, EaF82, isolated from shy-flowering ‘Golden Pothos’ (Epipremnum aureum) plants, is a RALF-like peptide and displays alkalinizing activity. Its heterologous expression in Arabidopsis delayed tapetum degeneration and reduced pollen production and seed yields. RNAseq, RT-qPCR, and biochemical analyses showed that overexpression of EaF82 downregulated a group of genes involved in pH changes, cell wall modifications, tapetum degeneration, and pollen maturation, as well as seven endogenous Arabidopsis RALF genes, and decreased proteasome activity and ATP levels. Yeast two-hybrid screening identified AKIN10, a subunit of energy-sensing SnRK1 kinase, as its interacting partner. Our study reveals a possible regulatory role for RALF peptide in tapetum degeneration and suggests that EaF82 action may be mediated through AKIN10 leading to the alteration of transcriptome and energy metabolism, thereby causing ATP deficiency and impairing pollen development.

Lepton scattering is an established ideal tool for studying inner structure of small particles such as nucleons as well as nuclei. As a future high energy nuclear physics project, an Electron-ion collider in China (EicC) has been proposed. It will be constructed based on an upgraded heavy-ion accelerator, High Intensity heavy-ion Accelerator Facility (HIAF) which is currently under construction, together with a new electron ring. The proposed collider will provide highly polarized electrons (with a polarization of $\sim$80%) and protons (with a polarization of $\sim$70%) with variable center of mass energies from 15 to 20 GeV and the luminosity of (2-3) $\times$ 10$^{33}$ cm$^{-2}$ s$^{-1}$. Polarized deuterons and Helium-3, as well as unpolarized ion beams from Carbon to Uranium, will be also available at the EicC. The main foci of the EicC will be precision measurements of the structure of the nucleon in the sea quark region, including 3D tomography of nucleon; the partonic structure of nuclei and the parton interaction with the nuclear environment; the exotic states, especially those with heavy flavor quark contents. In addition, issues fundamental to understanding the origin of mass could be addressed by measurements of heavy quarkonia near-threshold production at the EicC. In order to achieve the above-mentioned physics goals, a hermetical detector system will be constructed with cutting-edge technologies. This document is the result of collective contributions and valuable inputs from experts across the globe. The EicC physics program complements the ongoing scientific programs at the Jefferson Laboratory and the future EIC project in the United States. The success of this project will also advance both nuclear and particle physics as well as accelerator and detector technology in China., EicC white paper, written by the whole EicC working group

CO2 + O2in situ leaching has been extensively applied in uranium recovery in sandstone-type uranium deposits of China. The geochemical processes impact and constrain the leaching reaction and leaching solution migration; thus, it is necessary to study the CO2 + O2–water–rock geochemical reaction process and its influence on the physical properties of uranium-bearing reservoirs. In this work, a CO2 + O2–water–rock geochemical reaction simulation experiment was carried out, and the mineralogical and multiscale pore characteristics of typical samples before and after this simulation experiment were compared by X-ray diffraction and high-pressure mercury intrusion porosimetry (HPMIP). The results show that the CO2 + O2–water–rock geochemical reaction has complicated effects on the mineral compositions due to the various reaction modes and types. After the CO2 + O2–water–rock geochemical reaction, the femic minerals decrease and the clay minerals in the coarse sandstone, medium sandstone, fine sandstone, and siltstone increase, while the femic minerals and clay minerals in sandy mudstone show a contrary changing trend. The CO2 + O2–water–rock geochemical reaction decreases the total pore volume of uranium-bearing reservoirs and then promotes pore transformation from small scale to large scale. The fractal dimensions of macropores are decreased, and the fractal dimensions of mesopores, transition pores, and micropores are increased. The effects of felsic mineral and carbonate dissolution, secondary mineral precipitate, clay mineral swelling, and mineral particle migration are simultaneously present in the CO2 + O2in situ leaching process, which exhibit the positive transformation and the negative transformation for the uranium-bearing reservoirs. The mineral dissolution may improve reservoir permeability to a certain degree, while the siltation effect will gradually reveal with the extension of CO2 + O2in situ leaching. This research will provide a deep understanding of the physical property response of uranium-bearing reservoirs during CO2 + O2in situ leaching and indicate the direction for the efficient recovery of uranium resources.

Tobacco black shank caused by Phytophthora nicotianae is a devastating disease that causes huge losses to tobacco production across the world. Investigating the regulatory mechanism of tobacco resistance to P. nicotianae is of great importance for tobacco resistance breeding. The jasmonate (JA) signaling pathway plays a pivotal role in modulating plant pathogen resistance, but the mechanism underlying JA-mediated tobacco resistance to P. nicotianae remains largely unclear. This work explored the P. nicotianae responses of common tobacco cultivar TN90 using plants with RNAi-mediated silencing of NtCOI1 (encoding the perception protein of JA signal), and identified genes involved in this process by comparative transcriptome analyses. Interestingly, the majority of the differentially expressed bHLH transcription factor genes, whose homologs are correlated with JA-signaling, encode AtBPE-like regulators and were up-regulated in NtCOI1-RI plants, implying a negative role in regulating tobacco response to P. nicotianae. A subsequent study on NtbHLH49, a member of this group, showed that it’s negatively regulated by JA treatment or P. nicotianae infection, and its protein was localized to the nucleus. Furthermore, overexpression of NtbHLH49 decreased tobacco resistance to P. nicotianae, while knockdown of its expression increased the resistance. Manipulation of NtbHLH49 expression also altered the expression of a set of pathogen resistance genes. This study identified a set of genes correlated with JA-mediated tobacco response to P. nicotianae, and revealed the function of AtBPE-like regulator NtbHLH49 in regulating tobacco resistance to this pathogen, providing insights into the JA-mediated tobacco responses to P. nicotianae.

Introduction To deliver specific antigens in tumor immunotherapy, tumor cell lysates are commonly used to sensitize dendritic cells (DCs). However, the lysates possess low immunogenicity and contain many types of non-tumor-related antigens, which may induce autoimmune diseases. Tumor antigen peptides can provide high specificity but are expensive and their short half-lives limit their clinical application. Methods In this study, we used adenovirus to transfer the carbonic anhydrase IX (CA9) gene into DCs to generate specificity to renal cell carcinoma (RCC) which is the most common space-occupying lesion in humans. Inhibition of antigen presentation attenuators (iAPA) technology was also used to enhance the DC delivery capacity. Finally, DCs were co-cultured with cytotoxic T-lymphocytes (CTLs) and the anti-tumor effects were evaluated. Results The results showed that the CA9-DC-CTLs possessed a high specificity to CA9-positive cells and showed stronger anti-tumor activity than GFP-DC-CTLs both in vitro and in vivo. Discussion These findings may suggest a novel treatment option for RCC.

Mammalian cell-produced recombinant human erythropoietin (rhuEPO(M)) has been shown to be a multimodal neuroprotectant targeting an array of key pathological mechanisms in experimental stroke models. However, the rhuEPO(M) clinical trials were terminated due to increased risk of thrombosis, largely ascribed to its erythropoietic function. We recently took advantage of a plant-based expression system lacking sialylation capacity to produce asialo-rhuEPO(P), a rhuEPO derivative without sialic acid residues. In the present study, we proved that asialo-rhuEPO(P) is non-erythropoietic by repeated intravenous injection (44 μg/kg bw) in mice showing no increase in hemoglobin levels and red blood cell counts, and confirmed that it is non-immunogenic by measuring humoral response after immunizing the mice. We demonstrate that it is neuroprotective in a cerebral ischemia and reperfusion (I/R) mouse model, exhibiting ~ 50% reduction in cerebral infarct volume and edema, and significant improvement in neurological deficits and histopathological outcome. Our studies further revealed that asialo-rhuEPO(P), like rhuEPO(M), displays pleiotropic neuroprotective effects, including restoring I/R-interrupted mitochondrial fission and fusion proteins, preventing I/R injury-induced increase in mitophagy and autophagy markers, and inhibiting apoptosis to benefit nerve cell survival. Most importantly, asialo-rhuEPO(P) lacking erythropoietic activity and immunogenicity holds great translational potential as a multimodal neuroprotectant for stroke treatment.

Toxoplasma gondii is an opportunistic pathogenic protozoan that can infect almost all kinds of warm-blooded animals, including humans. T. gondii can evade the host's immune response, a process known as immune evasion. Our main objective was to evaluate the role played by Sirtuin1 (SIRT1) [one of the sirtuins (SIRTs) that are a family of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases (HDACs)] in the T. gondii infection of RAW264.7 macrophages. In this study, we evaluated and observed alterations in the activity, expression, and localization of SIRT1 and assessed its involvement in the CD154/IFN-γ (CD40 ligand/interferon gamma) killing pathway and in autophagy during T. gondii infection. The inhibition of SIRT1 in host cells effectively reduced the number of intracellular tachyzoites, and the mechanism behind this effect might be the upregulation of IRGM1 [murine ortholog of IRGM (immunity-related GTPase family M)] and the initiation of autophagy. To the best of our knowledge, our study is the first to prove that T. gondii infection upregulates SIRT1 in RAW264.7 cells and that the inhibition of SIRT1 reduces the number of intracellular tachyzoites. Moreover, the upregulation of IRGM1 and the activation of autophagy may contribute to the intracellular inhibition of T. gondii caused by SIRT1 inhibition.

BackgroundImmunotherapy has been widely used to treat Colorectal cancer but has also observe some immune-related adverse effects. With proper treatment, most irAE can be solved and the effect of immunotherapy will not be affected by temporary immunosuppression. However, there are few reports about corneal irAE, and the current understanding of irAE is incomplete. Here we report a metastatic colorectal cancer case of immune-related keratitis caused by nivolumab and to explore the occurrence of immune-related keratitis.Case descriptionHere we report the case of a 49-year-old man with mCRC who had no previous ocular disease but developed immune-related ulcerative keratitis after treatment with nivolumab. We summarize a large amount of literature to discuss the mechanism of immune-related keratitis. In addition, we conclude a method that may be used to detect the occurrence of immune keratitis, by monitoring MMPs and maspin in patients treated with nivolumab. We believe immune-related keratitis may be a rare complication of nivolumab in the treatment of mCRC. The effect of simple anti-infective therapy and repair-promoting drugs was not obvious, but the effect of glucocorticoid combined with autologous serum was significant.ConclusionThe mechanism of immune-related keratitis is that nivolumab destroys the immune microenvironment and ACAID, and affects corneal healing. Patients who use nivolumab can prevent immune keratitis by testing MMPs and maspin. The occurrence of immune keratitis may be a good indicator of the efficacy of ICI, and further study can be done in the follow-up.

BackgroundWith approval of anti-PD-1/PD-L1, metastatic non-small cell lung cancer (NSCLC) has entered the era of immunotherapy. Since immune-related adverse events (irAEs) occur commonly in patients receiving anti-PD-1/PD-L1, the landscape of death causes may have changed in metastatic NSCLC. We aim to compare patterns of death causes in metastatic NSCLC between the pre-immunotherapy and immunotherapy era to identify the consequent landscape transition of death causes.MethodsIn this cohort study, 298,485 patients with metastatic NSCLC diagnosed between 2000 and 2018 were identified from the Surveillance, Epidemiology, and End Results Program. Unsupervised clustering with Bayesian inference method was performed for all patients’ death causes, which separated them into two death patterns: the pre-immunotherapy era group and the immunotherapy era group. Relative risk (RR) of each death cause between two groups was estimated using Poisson regression. Reduced death risk as survival time was calculated with locally weighted scatterplot smooth (Lowess) regression.ResultsTwo patterns of death causes were identified by unsupervised clustering for all patients. Thus, we separated them into two groups, the immunotherapy era (2015-2017, N=40,172) and the pre-immunotherapy era (2000-2011, N=166,321), in consideration of obscure availability to immunotherapy for patients diagnosed in 2012-2014, when the follow-up cutoff was set as three years. Although all-cause death risk had reduced (29.2%, 13.7% and 27.8% for death risks of lung cancer, non-cancer and other cancers), non-cancer deaths in the immunotherapy era (N=2,100, 5.2%; RR=1.155, 95%CI: 1.101-1.211, PConclusionsThe real-world landscape of death causes has changed in metastatic NSCLC when entering the immunotherapy era, and the increased non-cancer diseases may contribute to the changes that may be associated with commonly occurring irAEs.

In this paper, the adsorption of CO on FexCuy (x + y = 3) clusters were studied by BPW91 method, all conceivable geometries and electronic states of carbonyl complexes were explored. The results show that bimetallic clusters tend to have higher stepwise CO adsorption energy than corresponding pure clusters, and the adsorption capacity of FeCu2(CO)3 with CO is substantially larger than that of other carbonyl complexes. Moreover, the frontier molecular orbital theory was used to analyze the effect of the second element in the ligand reactions, which also confirmed that the reactions of CO with bimetallic clusters are easier than that of pure cluster systems. Finally, the energy gaps of HOMO and LUMO were use to explore the reactive activity of carbonyl complexes, it was found that the bimetallic clusters are lower than that of the Fe3 or Cu3, and the Fe2Cu(CO)1 has lower energy gap than that of other carbonyl complexes. This suggests that it may be possible to tune bimetallic cluster to get higher activity carbonyl complexes in the reactions.

Pathophysiology associated with Huntington’s disease (HD) has been studied extensively in various cell and animal models since the 1993 discovery of the mutant huntingtin (mHtt) with abnormally expanded polyglutamine (polyQ) tracts as the causative factor. However, the sequence of early pathophysiological events leading to HD still remains elusive. To gain new insights into the early polyQ-induced pathogenic events, we expressed Htt exon1 (Httex1) with a normal (21), or an extended (42 or 63) number of polyQ in tobacco plants. Here, we show that transgenic plants accumulated Httex1 proteins with corresponding polyQ tracts, and mHttex1 induced protein aggregation and affected plant growth, especially root and root hair development, in a polyQ length-dependent manner. Quantitative proteomic analysis of young roots from severely affected Httex1Q63 and unaffected Httex1Q21 plants showed that the most reduced protein by polyQ63 is a GTP cyclohydrolase I (GTPCH) along with many of its related one-carbon (C1) metabolic pathway enzymes. GTPCH is a key enzyme involved in folate biosynthesis in plants and tetrahydrobiopterin (BH4) biosynthesis in mammals. Validating studies in 4-week-old R6/2 HD mice expressing a mHttex1 showed reduced levels of GTPCH and dihydrofolate reductase (DHFR, a key folate utilization/alternate BH4 biosynthesis enzyme), and impaired C1 and BH4 metabolism. Our findings from mHttex1 plants and mice reveal impaired expressions of GTPCH and DHFR and may contribute to a better understanding of mHtt-altered C1 and BH4 metabolism, and their roles in the pathogenesis of HD.