Sequential Degradation Research Articles

Sequential structural degradation of red perovskite quantum dots and its prevention by introducing iodide at a stable gradient concentration into the core-shell red perovskite quantum dots.

Perovskite quantum dots (QDs) have been extensively studied as emissive materials for next-generation optoelectronics due to their outstanding optical properties; however, their structural instabilities, specifically those of red perovskite QDs, are critical obstacles in realizing operationally reliable perovskite QD-based optoelectronic devices. Accordingly, herein, we investigated the sequential degradation mechanism of red perovskite QDs upon their exposure to an electric field. Via electrical and chemical characterization, we demonstrated that degradation occurred in the following order: anion-defect-assisted halide migration, cation-defect-assisted migration of I-/Cs+ ions, defective gradient I ion distribution, structural distortion, and ion transport/I2 vaporization with defect proliferation. Among these steps, the defective gradient I ion distribution is the key process in the structural degradation of perovskite QDs. Based on our findings, we designed perovskite/SiO2 core-shell QDs with stable gradient I concentrations. Most notably, the operational stabilities of perovskite QD-light-emitting diodes (PeLEDs) fabricated using the perovskite/SiO2 core-shell QDs were approximately 5000 times those of the PeLEDs constructed using pristine perovskite QDs.

An Interpretable Deep Transfer Learning-Based Remaining Useful Life Prediction Approach for Bearings With Selective Degradation Knowledge Fusion

This article tries to answer the two questions of bearings’ remaining useful life (RUL) prediction with deep transfer learning: what bearing data in the source domain contribute more to transfer learning and how to quantify such contribution? From the perspective of sample-based interpretability, this article proposes a new deep transfer learning approach of RUL prediction. First, a new time series clustering algorithm based on multiscale degradation similarity is proposed. Comprehensively considering the geometry and tendency characteristics of degradation sequences, this algorithm can divide the source domain into multiple subsource domains. Second, a significance metric, named transfer domain validity index (T-DVI), is built to quantify the contribution of each subsource domain to transfer learning in terms of degradation similarity. Furthermore, a new stacked long short-term memory model with selective transfer learning is constructed. Running with the obtained T-DVIs, this model builds two new transfer strategies of weighted initialization and adaptive freezing to improve the transfer effect of degradation knowledge for RUL prediction. Experimental results on the two bearing datasets prove the effectiveness of the proposed approach. More importantly, the proposed approach makes the transfer learning process interpretable via identifying the significance of the bearings data, which helps transfer useful degradation knowledge and improve the RUL prediction performance as well.

The quantity and stability of soil organic carbon following vegetation degradation in a salt-affected region of Northeastern China

Understanding the influence of vegetation conversion induced by land degradation on soil organic carbon (SOC) dynamics provides a basis for the sustainable use of grasslands. While labile carbon fractions often vary with the type of vegetation, little is known about whether and how vegetation degradation affects the recalcitrant carbon fraction that is highly resistant to oxidation. Here, we studied the influence of vegetation degradation on changes in SOC and four oxidizable fractions with different stabilities in Northeastern China. The soil was collected from a vegetation degradation sequence, including Leymus chinensis (LEY, native grassland), Puccinellia tenuiflora(PUC, light degradation), Chloris virgata (CHL, moderate degradation), and Suaeda heteroptera (SUA, severe degradation). Contents of total SOC and four oxidizable SOC fractions extracted under a gradient of oxidation (F1, very labile; F2, labile; F3, less labile; F4, oxidizable resistant) were measured using a modified Walkley-Black method. Results showed that the contents of total SOC and oxidizable SOC fractions were significantly different under different vegetation types and soil depths. Under PUC, CHL, and SUA, contents of total SOC (29.0%, 34.3%, and 55.4%, respectively), F1 (22.5%, 20.8%, and 40.8%, respectively), F2 (28.2%, 53.8%, and 72.1%, respectively), F3 (52.0%, 40.6%, and 66.2%, respectively), and F4 (15.0%, 21.9%, and 42.8%, respectively) were lower than those under LEY. Vegetation degradation had a significant effect on the F4 fraction as well as the F1, F2, and F3 fractions. Regression coefficients of the relationship between oxidizable SOC fractions as a function of total SOC showed that these fractions, as a proportion of total SOC, were 22% for F1 and F2, 26% for F3, and 31% for F4. There were no significant differences in the percentages of active carbon fractions (F1 + F2) in total SOC and the lability of total SOC among the four vegetation types. These findings suggest that the recalcitrant carbon fraction can be affected by land degradation as well as the labile carbon fraction, and that shifts in land use affect the contents of total SOC and its fractions, but have no effect on the stability of SOC in semi-arid areas.

Dynamics of Known Long Non-Coding RNAs during the Maternal-to-Zygotic Transition in Rabbit.

Simple SummaryWe first revealed the expression profile of rabbit known lncRNAs during embryo pre-implantation development and showed minor and major wave of zygotic lncRNAs synthesis. The study then selected the differentially expressed (DE) lncRNAs between consecutive stages and predicted their potential target genes. The GO and KEGG analyses suggested that the lncRNAs participate in the regulation of embryo cleavage and development. Additionally, the sequential degradation of maternal lncRNAs showed that, like maternal mRNAs, maternal lncRNAs degradation occurred via maternal and zygotic pathways and the late-degraded lncRNAs might play a role in the degradation of mRNAs through mRNA surveillance pathway.The control of pre-implantation development in mammals undergoes a maternal-to-zygotic transition (MZT) after fertilization. The transition involves maternal clearance and zygotic genome activation remodeling the terminal differentiated gamete to confer totipotency. In the study, we first determined the profile of long non-coding RNAs (lncRNAs) of mature rabbit oocyte, 2-cell, 4-cell, 8-cell, and morula embryos using RNA-seq. A total of 2673 known rabbit lncRNAs were identified. The lncRNAs exhibited dynamic expression patterns during pre-implantation development. Moreover, 107 differentially expressed lncRNAs (DE lncRNAs) were detected between mature oocyte and 2-cell embryo, while 419 DE lncRNAs were detected between 8-cell embryo and morula, consistent with the occurrence of minor and major zygotic genome activation (ZGA) wave of rabbit pre-implanted embryo. This study then predicted the potential target genes of DE lncRNAs based on the trans-regulation mechanism of lncRNAs. The GO and KEGG analyses showed that lncRNAs with stage-specific expression patterns promoted embryo cleavage and synchronic development by regulating gene transcription and translation, intracellular metabolism and organelle organization, and intercellular signaling transduction. The correlation analysis between mRNAs and lncRNAs identified that lncRNAs ENSOCUG00000034943 and ENSOCUG00000036338 may play a vital role in the late-period pre-implantation development by regulating ILF2 gene. This study also found that the sequential degradation of maternal lncRNAs occurred through maternal and zygotic pathways. Furthermore, the function analysis of the late-degraded lncRNAs suggested that these lncRNAs may play a role in the mRNA degradation in embryos via mRNA surveillance pathway. Therefore, this work provides a global view of known lncRNAs in rabbit pre-implantation development and highlights the role of lncRNAs in embryogenesis regulation.

Electrochemical mineralization of direct blue 71 with boron-doped diamond anodes: Factor analysis and mechanisms study

Electrochemical oxidation with boron-doped diamond (BDD) had been well established as an outstanding technology for wastewater treatment. In this study, BDD technology was initially used to degrade direct blue 71 (DB71) dye under galvanostatic conditions. The main and joint effects of three operating parameters (supporting electrolyte concentration, applied current density and flow rate) on oxidation performance were estimated by Box-Behnken design. Among the variables, sulfate concentration displayed the most unique roles in DB71 degradation. The optimum operating conditions obtained by response surface methodology were: 2.0 mM Na2SO4, applied current density of 7.75 mM cm−2 and flow rate of 600 mL min−1, which gave a decolorization percentage of 100%, a mineralization percentage of 50.2%, as well as an energy consumption of 3845 kWh kg−1 TOC and a mineralization efficiency of 8.7% at 120 min of electrolysis. In addition, based on the quantum chemistry calculation and identified reaction intermediates detected by LC/MS analysis, a plausible degradation sequence of DB71 in BDD anode cells was also proposed. The results obtained were expected to offer useful guidance for the application of BDD technology as powerful and green option for treating DB71 pollutants.

3D zero-thickness interface model for fracture of cement-based materials with chemical degradation

In the framework of the Finite Element Method, zero-thickness interface elements have been widely used to model fracturing processes in quasi-brittle materials in a broad variety of problems. In particular, interface elements equipped with elastoplastic constitutive laws that account for the softening of the material strength parameters due to the fracturing mechanical work has been proved to accurately reproduce observed fracture propagation behaviour in concrete. Along this line, this paper presents the extension of an existing constitutive law of this kind to include the effect of chemical degradation of the material in the formation of fractures. The law is defined in terms of the normal and shear stresses on the average plane of the crack and the corresponding normal and shear relative displacements. A hyperbolic cracking (plastification) surface in the stress state determines the crack initiation. The softening of the cracking surface is governed by two history variables: an internal variable that accounts for the dissipated fracturing (plastic) work, and an external variable to be provided by a chemical degradation model that accounts for the effect of chemical degradation on the strength parameters. After a detailed discussion of the formulation, the main characteristics of the proposed law are illustrated with a number of academic examples for different combinations of mechanical loading and chemical degradation sequences. The model is finally validated against experimental results from the literature consisting of three-point bending tests performed on mortar samples previously exposed to an aggressive solution for different time periods.

Batch effects in population genomic studies with low-coverage whole genome sequencing data: Causes, detection and mitigation.

Over the past few decades, there has been an explosion in the amount of publicly available sequencing data. This opens new opportunities for combining data sets to achieve unprecedented sample sizes, spatial coverage or temporal replication in population genomic studies. However, a common concern is that nonbiological differences between data sets may generate patterns of variation in the data that can confound real biological patterns, a problem known as batch effects. In this paper, we compare two batches of low-coverage whole genome sequencing (lcWGS) data generated from the same populations of Atlantic cod (Gadus morhua). First, we show that with a "batch-effect-naive" bioinformatic pipeline, batch effects systematically biased our genetic diversity estimates, population structure inference and selection scans. We then demonstrate that these batch effects resulted from multiple technical differences between our data sets, including the sequencing chemistry (four-channel vs. two-channel), sequencing run, read type (single-end vs. paired-end), read length (125 vs. 150bp), DNA degradation level (degraded vs. well preserved) and sequencing depth (0.8× vs. 0.3× on average). Lastly, we illustrate that a set of simple bioinformatic strategies (such as different read trimming and single nucleotide polymorphism filtering) can be used to detect batch effects in our data and substantially mitigate their impact. We conclude that combining data sets remains a powerful approach as long as batch effects are explicitly accounted for. We focus on lcWGS data in this paper, which may be particularly vulnerable to certain causes of batch effects, but many of our conclusions also apply to other sequencing strategies.

Bubble dynamics of R-134a/POE and R-123/MO mixture on enhanced surfaces having pores on sub-tunnels

Structured enhanced surfaces are widely used to promote the nucleate boiling heat transfer in a refrigeration system, where a compressor oil circulates. However, there is a significant lack of understanding of the mechanism or predictive models, especially on the boiling of refrigerant/oil mixtures on enhanced surfaces. In this study, as a building block, the bubble dynamic data as well as the heat transfer coefficients were obtained for the refrigerant/oil mixtures on pored surfaces. The test mixtures included R-134a/polylester (POE) and R-123/mineral oil (MO). The results showed that the oil degraded the size of the departing bubbles. The degradation was more severe for R-123/MO than R-134a/POE, and it increased as the saturation temperature increased. The sequence of degradation among samples generally followed the reverse order to the magnitude of the heat transfer coefficient of the pure refrigerant. Similarly, the oil degraded the frequency. The degradation was, in general, in reverse order to the degradation of the bubble departure diameter. The oil also degraded the nucleation site density. As for the heat transfer coefficient, the degradation was more significant at a higher saturation temperature, and for R-134a/POE than for R-123/MO. The changes of bubble dynamic parameters as well as the thermo-physical properties of the refrigerants were shown to be responsible. A heat transfer prediction model was developed based on the bubble dynamic parameters.

Diagenetic fate of glycerol ethers revealed by two novel isoprenoid hydroxyphytanyl glycerol monoethers and non-isoprenoid alkyl glycerol ethers

The diagenesis of isoprenoid glycerol ethers and non-isoprenoid mono- and dialkyl glycerol ethers (MAGEs and DAGEs) is important as they are potential markers of microbes involved in the anaerobic oxidation of methane (AOM) in cold seep ecosystems. Here we studied glycerol ethers and the respective diagenetic products in seep carbonates from the Haima cold seeps using MAGE and DAGE abundances and their carbon isotopic compositions. Two novel sn2-/sn3-O-hydroxyphytanyl glycerol monoethers hydroxylated at C-3 of the phytanyl moieties were identified, both being attributed to anaerobic methane-oxidizing archaea (ANME) of the ANME-2 group according to the high ratios of sn2-hydroxyarchaeol relative to archaeol, the extremely low δ13C values (from −132‰ to −120‰), and the simultaneously abundant crocetane. Based on the sequential degradation pathway of hydroxyarchaeols, sn2-/sn3-O-hydroxyphytanyl glycerol monoethers likely constitute hydrolysis products of di-hydroxyarchaeol since the C-3 hydroxy-phytanyl side chain is preferentially hydrolysed in the presence of H+. By contrast, the isoprenoidal 3,7,11,15-tetramethylhexadecan-1,3-diol was most likely a hydrolysis product of sn2-/sn3-O-hydroxyarchaeols, di-hydroxyarchaeol, and sn2-/sn3-O-hydroxyphytanyl glycerol monoethers, which is supported by structures with the same skeleton and the similar 13C-depletions. Moreover, a similar relationship was found for MAGEs, DAGEs and the corresponding non-isoprenoid short-chain alcohols. Besides the similar δ13C values (from –110‰ to –100‰), the non-isoprenoid short-chain alcohols, MAGEs, and DAGEs, displayed very similar chain lengths and unsaturation patterns, indicating that non-isoprenoid alcohols might be either biosynthetic intermediates or degradation products of MAGEs and DAGEs, dependent on the live status of the lipid-producing microorganisms. Our study highlights the relationship of glycerol ethers and their respective derivatives, which can be used as tracers of ancient microbes preserved in authigenic carbonates and sedimentary rocks.

A regeneration process-matching scaffold with appropriate dynamic mechanical properties and spatial adaptability for ligament reconstruction

Ligament regeneration is a complicated process that requires dynamic mechanical properties and allowable space to regulate collagen remodeling. Poor strength and limited space of currently available grafts hinder tissue regeneration, yielding a disappointing success rate in ligament reconstruction. Matching the scaffold retreat rate with the mechanical and spatial properties of the regeneration process remains challenging. Herein, a scaffold matching the regeneration process was designed via regulating the trajectories of fibers with different degradation rates to provide dynamic mechanical properties and spatial adaptability for collagen infiltration. This core-shell structured scaffold exhibited biomimetic fiber orientation, having tri-phasic mechanical behavior and excellent strength. Besides, by the sequential material degradation, the available space of the scaffold increased from day 6 and remained stable on day 24, consistent with the proliferation and deposition phase of the native ligament regeneration process. Furthermore, mature collagen infiltration and increased bone integration in vivo confirmed the promotion of tissue regeneration by the adaptive space, maintaining an excellent failure load of 67.65% of the native ligament at 16 weeks. This study proved the synergistic effects of dynamic strength and adaptive space. The scaffold matching the regeneration process is expected to open new approaches in ligament reconstruction.

Production of Recombinant Laccase From Coprinopsis cinerea and Its Effect in Mediator Promoted Lignin Oxidation at Neutral pH.

Laccases are multi-copper oxidases that use molecular oxygen as the electron acceptor to oxidize phenolic and indirectly also non-phenolic substrates by mechanisms involving radicals. Due to their eco-friendliness and broad substrate specificity, laccases span a wide range of biotechnological applications. We have heterologously expressed a laccase from the coprophilic basidiomycete Coprinopsis cinerea (CcLcc9) in the methylotrophic yeast Pichia pastoris. The recombinant CcLcc9 (rCcLcc9) oxidized 2,6-dimethoxyphenol in the neutral pH range, and showed thermostability up to 70°C. The rCcLcc9 efficiently oxidized veratryl alcohol to veratraldehyde in the presence of low molecular weight mediators syringyl nitrile, methyl syringate and violuric acid, which are syringyl-type plant phenolics that have shown potential as natural co-oxidants for lignocellulosic materials. In addition, rCcLcc9 is able to depolymerize biorefinery hardwood lignin in the presence of methyl syringate and syringyl nitrile as indicated by gel permeation chromatography, and infrared spectral and nucleic magnetic resonance analyses. Furthermore, we showed that several added-value aromatic compounds, such as vanillin, vanillic acid, syringaldehyde, syringic acid and p-hydroxybenzoic acid, were formed during sequential biocatalytic chemical degradation of biorefinery lignin, indicating that rCcLcc9 harbors a great potential for sustainable processes of circular economy and modern biorefineries.

The safe and effective intraperitoneal chemotherapy with cathepsin B-specific doxorubicin prodrug nanoparticles in ovarian cancer with peritoneal carcinomatosis

Intraperitoneal (IP) chemotherapy has shown promising efficacy in ovarian cancer with peritoneal carcinomatosis (PC), but in vivo rapid clearance and severe toxicity of free anticancer drugs hinder the effective treatment. Herein, we propose the safe and effective IP chemotherapy with cathepsin B-specific doxorubicin prodrug nanoparticles (PNPs) in ovarian cancer with PC. The PNPs are prepared by self-assembling cathepsin B-specific cleavable peptide (FRRG) and doxorubicin (DOX) conjugates, which are further formulated with pluronic F68. The PNPs exhibit stable spherical structure and cytotoxic DOX is specifically released from PNPs via sequential enzymatic degradation by cathepsin B and intracellular proteases. The PNPs induce cytotoxicity in cathepsin B-overexpressing ovarian (SKOV-3 and HeyA8) and colon (MC38 and CT26) cancer cells, but not in cathepsin B-deficient normal cells in cultured condition. With enhanced cancer-specificity and in vivo residence time, IP injected PNPs efficiently accumulate within PC through two targeting mechanisms of direct penetration (circulation independent) and systemic blood vessel-associated accumulation (circulation dependent). As a result, IP chemotherapy with PNPs efficiently inhibit tumor progression with minimal side effects in peritoneal human ovarian tumor-bearing xenograft (POX) and patient derived xenograft (PDX) models. These results demonstrate that PNPs effectively inhibit progression of ovarian cancer with peritoneal carcinomatosis with minimal local and systemic toxicities by high cancer-specificity and favorable in vivo PK/PD profiles enhancing PC accumulation.

Exact analytical solutions with great computational efficiency to three-dimensional multispecies advection-dispersion equations coupled with a sequential first-order reaction network

This study presents novel exact analytical solutions to a set of simultaneous three-dimensional advection-dispersion equations coupled with a sequential first-order degradation reaction network involving distinct retardation factor values among individual species. The analytical solutions to the coupled partial differential equation system subject to both the first - and third -type inlet source boundary conditions are derived by consecutive application of the three integral transformations in combination with sequential substitutions. The correctness of the developed analytical solutions is confirmed through numerical comparisons of three verification examples between our derived exact analytical solutions and a three-dimensional single-species analytical model in a semi-infinite domain, a two-dimensional multispecies exact analytical model in a finite domain and a three-dimensional multispecies semi-analytical model in a semi-infinite domain of the previous studies, respectively. The advantage of the derived analytical solutions is that its computational efficiency is 104 times the computational efficiency of two-dimensional multispecies analytical solutions for a finite domain when two solutions are simultaneously used to solve a two-dimensional multispecies transport problem. The developed analytical solutions are then used to evaluate the performance of the public domain BIOCHLOR model that simulates aquifer remediation by natural attenuation of dissolved multispecies at a chlorinated-solvent contaminated site provided by the Center for Subsurface Modeling Support (CSMoS) of USEPA. Results show that the BIOCHLOR model that was developed based on three-dimensional analytical model assuming a single retardation factor value for all dissolved species would not be suitable for simulating most multispecies plume migration at contaminated sites where each contaminant has its own retardation factor value. The effects of the inlet source boundary conditions on the multispecies plume migration are also investigated. The high computational efficiency of the developed analytical model in this current study renders it a very efficient tool for executing a probabilistic health risk assessment involving a large number of simulations required for problems of multispecies transport of dissolved chlorinated solvent in groundwater at a contaminated site with uncertainties in many different variables.

Pressure propagation and flow restart in a pipeline filled with a gas pocket separated rheomalaxis elasto-viscoplastic waxy gel

A clogged waxy crude oil pipeline, entails a high pressure to de-structure the gelled oil and resume its normal operation. Our earlier work, which utilized generalized Newtonian fluid based model, demonstrated that the presence of a gas pocket in-between the gel plugs, delays pressure propagation in the downstream gel plug [L. Tikariha, L. Kumar, Pressure propagation and flow restart in the multi-plug gelled pipeline, Journal of Fluid Mechanics. 911 (2021)]. This delay in pressure propagation is effectively utilized for sequential gel degradation. In the present work, we consider gel as a rheomalaxis elasto-viscoplastic (REVP) fluid, capable in predicting flow stoppage and pressure signal stoppage. The governing equations for mass, momentum balance, and phase equation are solved together with the REVP rheology model. The propagation of pressure in a REVP gel-filled pipeline is directly related to the gel material's elastic response. For a REVP gel, the flow-restart in a gelled pipeline depends on the conditional statement γ>γs (i.e. mean gel deformation overcoming the yield strain). In the case of a single gel plug, no-pressure propagation is predicted at intermediate compressibility, whereas pressure propagation without flow restart is predicted at low compressibility. In these cases, the presence of a small gas pocket instigates the gel breakage process, resulting in a flow restart. The gas pocket delays the pressure propagation in the second gel plug, resulting in a pressure gradient higher than yield stress across the first gel plug. The first gel plug, which deforms under a high-pressure gradient, compresses the gas pocket. This results in a larger mean deformation in the first gel plug, and it overcomes the threshold yield strain limit (γs). At strain values larger than yield strain the gel structure breaks, resulting in a lower elastic strength in the first gel plug. The lower elastic gel strength ascertains a lower pressure gradient in the first gel plug, allowing a largely unattenuated pressure to propagate in the second plug. The propagation of unattenuated pressure in the second gel plug results in a pressure gradient higher than the yield stress. This causes sequential gel breakage, resulting in a successful flow restart in a pipeline longer than a critical length. The present study also demonstrates that the pressure propagation and initial transient flow depend on the gel properties (i.e. gel strength and compressibility) and the number and size of gas pockets in the gel. The insights gained from the present work provide a cost-effective solution to mitigate the flow restart problem.

RSK Inhibition Induces Metaphase Arrest and Apoptosis in Acute Myeloid Leukemia Cells

The 90 kDa Ribosomal S6 Kinase (RSK) drives cell proliferation and survival in several cancers, although its oncogenic mechanism has not been well characterized. To examine the role of RSK in acute myeloid leukemia (AML), we analyzed apoptosis, DNA-damage, and the cell cycle profile following treatment with BI-D1870, a potent inhibitor of RSK. BI-D1870 treatment (5 µM, 12 h) of HL-60 and KG-1 cells increased the G2/M population and induced apoptosis. Previously, RSK has been shown to activate CDC2 for G2/M progression by dephosphorylating the negative regulatory Tyr14 through activation of CDC25 or inhibition of MYT1. Phosphorylation of CDC2 at Tyr14 was increased transiently during G2 phase following treatment with BI-D1870, while phosphorylation of the positive regulatory Ser198 of CDC25C was inhibited in G2 and mitotic populations. However, BI-D1870 treatment did not decrease CDC2/Cyclin B kinase activity, suggesting that inhibition of CDC2 is not a critical regulatory mechanism in BI-D1870-induced mitotic arrest. The mitotic population was further characterized by evaluation of expression levels of Cyclin A and Cyclin B with flow cytometry. Approximately 70% of mitotic cells accumulated in Cyclin A-negative/Cyclin B-high metaphase at 12 hours after 5 µM BI-D1870 treatment. Metaphase arrest was confirmed using a thymidine/nocodazole block to achieve synchronization at metaphase. Our results show that the metaphase/anaphase transition is significantly stalled by RSK inhibition as assessed by degradation of Cyclin B and Securin following release from mitotic arrest (Metaphase cells in mitotic population (%), control vs. BI-D1870, 0 h post-release: 80.53 ± 0.09% vs. 88.03 ± 0.67%; 2 h post-release: 56.27 ± 1.42% vs. 83.37 ± 0.32%; 4 h post-release: 23.53 ± 0.52% vs. 62.90 ± 0.62%, mean ± SEM, n=3, p< 0.01). We also assessed the efficacy of combination treatment of BI-D1870 with standard AML chemotherapeutic drugs cytarabine and daunorubicin. The combination of BI-D1870 with cytarabine or daunorubicin in HL-60 cells showed an additive effect. Furthermore, BI-D1870 induced apoptosis and metaphase arrest in primary AML cells and significantly suppressed the CD34+ subpopulation containing leukemia stem cells. Mitotic progression is controlled by the sequential degradation of cell cycle regulators including Cyclin A, Cyclin B, and Securin by the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. Since proper association of CDC20 with APC/C is critical to destroy Cyclin B and Securin for metaphase/anaphase progression, we examined the effect of BI-D1870 on the complex formation of CDC20 with APC/C. Co-IP experiments showed that treatment of BI-D1870 impeded the association of activator CDC20 with APC/C, but increased binding of inhibitor MAD2 to APC/C, preventing metaphase/anaphase progression. These data show that BI-D1870 inhibits metaphase/anaphase progression by inactivating APC/C, resulting in apoptosis of AML cells. We are currently studying the effects of RSK knockdown on AML cells. In summary, our study demonstrates that RSK plays an important role in maintaining AML cell survival and proliferation, and RSK inhibitors could be used therapeutically to treat AML by inducing apoptosis and cell cycle arrest through the inhibition of APC/C in AML cells. DisclosuresNo relevant conflicts of interest to declare.

Soil Enzyme Activities and Their Relationships With Soil C, N, and P in Peatlands From Different Types of Permafrost Regions, Northeast China

Peatland is a key component of terrestrial ecosystems in permafrost regions and have important effects on climate warming. Soil enzymes are involved in biogeochemical cycle of soil carbon (C), nitrogen (N) and phosphorus (P), which can be used as early sensitive indicators of soil nutrient changes caused by climate change. To predict the possible effects of permafrost degradation on soil enzymes in peatlands, ten peatlands from three types of permafrost regions along the permafrost degradation sequence (predominantly continuous permafrost region-predominantly continuous and island permafrost region-sparsely island permafrost region) in northeast China were selected to examine the activities of soil invertase, β-glucosidase, urease and acid phosphatase and their relationships with soil physicochemical properties. The results demonstrated that permafrost type had significant effect on soil enzyme activities. Soil enzyme activities in predominantly continuous and island permafrost region were significantly higher than those in sparsely island permafrost region and predominantly continuous permafrost region. The activities of four soil enzymes were higher in 0–15 cm than 15–30 cm soil layer. Soil enzymes activities were positively correlated with soil ammonia nitrogen (NH4+-N), soil moisture content (SMC), total phosphorus (TP) and total nitrogen (TN), but negatively correlated with soil nitrate nitrogen (NO3−-N). Soil inorganic nitrogen and moisture contents were the main factors affecting soil enzyme activities, with NH4+-N accounted for 41.6% of the variance, SMC 29.6%, and NO3−-N 11.0%. These results suggested that permafrost degradation may change soil enzyme activities by changing soil physicochemical properties. In this study, only 0–30 cm peat soil in permafrost regions was collected during the complete thawing period of permafrost active layer, further studies should be placed on the change of soil enzyme activities in active layer and permafrost layer during freezing and thawing process in the southernmost location of northeast China in the Eurasia permafrost body and boreal forest belt.

Metabolism and difference iterative forecasting model based on long-range dependent and grey for gearbox reliability

The reliability prediction of gearbox is a complex and challenging topic. The purpose of this research is to propose a hybrid difference iterative forecasting model to forecast reliability of the gearbox. On this score, a hybrid model based on the fractional Lévy stable motion (fLsm), the Grey Model (GM) and the metabolism method is proposed. To solve the problem of insensitivity to weak faults inside the gearbox, we use feature extraction method to reveal the gearbox degradation. Then, the least square theory is used to separate the degradation sequence in the gearbox into a deterministic term with monotonicity and a stochastic term with Long-Range Dependence (LRD). Next, the fLsm with LRD and non-Gaussian is used to forecast the stochastic term, the deterministic term is simulated by the GM, and the hybrid forecasting model is used to modify the prediction results. The metabolism method is used to update the degradation sequence and to forecast longer-term trend. Finally, a case demonstrated that superiority and generality of the hybrid forecasting model.

Effects of Oversaturated Cathode Humidity Conditions on the Performance Degradation of PEMFCs and Diagnostic Signals of Warburg Impedance under Low Humidity Conditions

A proton exchange membrane fuel cell (PEMFC) inevitably experiences performance degradation during long-term operation under various corrosive conditions. In particular, cell operation under cathode flooding conditions results in severe cell degradation through sequential processes that induce the degradation of each component in the membrane electrode assembly (MEA). Furthermore, an excessive amount of water remaining at the cathode can diffuse into the anode side (back diffusion of water), and repeated instances can cause anode flooding (leading to fuel starvation). Herein, we focus on the collateral anode degradation of a stationary PEMFC operating under cathode flooding conditions with an oversaturated cathode in terms of relative humidity (RH, 150% RH). We suggest low-humidity electrochemical impedance spectroscopy (EIS-RH30) as a fault identification method to detect the degradation of the MEA, including the anode, before severe cell deterioration. Specifically, the EIS-RH30 analysis enables the detection of the malfunctioning anode reaction by limiting the hydrogen oxidation reaction (HOR) and proton conductivity, through which the phase difference between transporting protons from the anode to the cathode can be reflected as the horizontal aspect of the Warburg impedance. A generalized finite-length Warburg is introduced to understand the variation in the Warburg impedance spectra, and its numerical analysis can act as a diagnosable signal to monitor the sequential degradation of an MEA. A feasibility study of EIS-RH30 on actual degradation behavior that occurs under cathode flooding conditions was performed along with a microstructural investigation inside the MEA.

Experimental observation of the sequence of tibial plateau chondrocyte and matrix degeneration in spontaneous osteoarthritis in Guinea pigs

BackgroundTo observe the sequence of chondrocyte degeneration and matrix degradation in the superficial surface cartilage of the tibial plateau in guinea pigs with spontaneous knee osteoarthritis (OA).MethodsSixty guinea pigs were euthanized at the ages of 8 months (n = 20),10 months (n = 20) and 12 months (n = 20) respectively. The degree of degeneration of the tibial plateau cartilage was evaluated by Osteoarthritis Research Society International (OARSI) score. The levels of Aggrecan,CollagenX,MMP-13 and Caspase-3 in the chondrocytes were detected by immunohistochemistry (IHC). The serum concentration of CTX-II was measured and compared. Western blot analysis was used to detect the levels of Aggrecan,CollagenX,MMP-13 and Caspase-3 in the cartilage tissue.ResultsThe OARSI scores both in 8-month-old group and 10-month-old group were lower than that in the 12-month-old group. The levels of Aggrecan in articular chondrocyte were higher both in 8-month-old group and 10-month-old group than that in 12-month-old group. The level of Collagen X increased with the age of guinea pigs. And the levels of MMP-13 and caspase-3 both in 10-month-old group and 12-month-old group were higher than those in 8-month-old group. The concentration of CTX-II in serum increased significantly in 12 months old group.ConclusionThe superficial chondrocytes of the tibial plateau first appeared to be hypertrophic and then apoptotic, and the matrix was further degraded when spontaneous knee osteoarthritis occurred in guinea pigs. Changes in the physiological state of chondrocytes are the initiating factors in the pathogenesis of knee OA.

Baltetin: a new C-type lectin-like isolated from Bothrops alternatus snake venom which act as a platelet aggregation inhibiting

C-type lectin-like proteins found in snake venom, known as snaclecs, have important effects on hemostasis through targeting membrane receptors, coagulation factors and other hemostatic proteins. Here, we present the isolation and functional characterization of a snaclec isolated from Bothrops alternatus venom, designated as Baltetin. We purified the protein in three chromatographic steps (anion-exchange, affinity and reversed-phase chromatography). Baltetin is a dimeric snaclec that is approximately 15 and 25 kDa under reducing and non-reducing conditions, respectively, as estimated by SDS-PAGE. Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry and Edman degradation sequencing revealed that Baltetin is a heterodimer. The first 40 amino acid residues of the N-terminal region of Baltetin subunits share a high degree of sequence identity with other snaclecs. Baltetin had a specific, dose-dependent inhibitory effect on epinephrine-induced platelet aggregation in human platelet-rich plasma, inhibiting up to 69% of platelet aggregation. Analysis of the infrared spectra suggested that the interaction between Baltetin and platelets can be attributed to the formation of hydrogen bonds between the PO32- groups in the protein and PO2- groups in the platelet membrane. This interaction may lead to membrane lipid peroxidation, which prevents epinephrine from binding to its receptor. The present work suggests that Baltetin, a new C-type lectin-like protein isolated from B. alternatus venom, is the first snaclec to inhibit epinephrine-induced platelet aggregation. This could be of medical interest as a new tool for the development of novel therapeutic agents for the prevention and treatment of thrombotic disorders.