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Summary: Avatrombopag (AVA) is a novel thrombopoietin receptor agonist (TPO‐RA) that has been recently approved as a second‐line therapy for immune thrombocytopenia (ITP) in adults; however, its safety and efficacy data in children are lacking. Here, we demonstrated the efficacy and safety of AVA as second‐line therapy in children with ITP. A multicentre, retrospective, observational study was conducted in children with persistent or chronic ITP who did not respond to or relapsed from previous treatment and were treated with AVA for at least 12 weeks between August 2020 and December 2022. The outcomes were the responses (defined as achieving a platelet count ≥30 × 109/L, twofold increase in platelet count from baseline and absence of bleeding), including rapid response within 4 weeks, sustained response at weeks 12 and 24, bleeding control and adverse events (AEs). Thirty‐four (18 males) patients with a mean age of 6.3 (range: 1.9–15.3) years were enrolled. The median number of previous treatment types was four (range: 1–6), and 41.2% patients switched from other TPO‐RAs. Within 4 weeks, overall response (OR) was achieved in 79.4% patients and complete response (CR, defined as a platelet count ≥100 × 109/L and the absence of bleeding) in 67.7% patients with a median response time of 7 (range: 1–27) days. At 12 weeks, OR was achieved in 88.2%, CR in 76.5% and sustained response in 44% of patients. At 24 weeks, 22/34 (64.7%) patients who achieved a response and were followed up for 24 weeks were evaluated; 12/22 (54.55%) achieved a sustained response. During AVA therapy, median platelet counts increased by week 1 and were maintained throughout the treatment period. The proportion of patients with grade 1–3 bleeding decreased from 52.95% at baseline to 2.94% at 12 weeks, while concomitant ITP medications decreased from 36.47% at baseline to 8.82% at 12 weeks, with only 9 (26.47%) patients receiving rescue therapy 23 times within 12 weeks. There were 61.8% patients with 59 AEs: 29.8% with Common Terminology Criteria for Adverse Events grade 1 and the rest with grade 2. These findings show that AVA could achieve a rapid and sustained response in children with persistent or chronic ITP as a second‐line treatment, with good clinical bleeding control and reduction of concomitant ITP therapy, without significant AEs. [ABSTRACT FROM AUTHOR]

Nitrous oxide (N2O) and ammonia (NH3) volatilization (AV) are the major pathways of nitrogen (N) loss in soil, and recently, N2O and NH3 mitigation has become urgently needed in agricultural systems worldwide. However, the influence of straw incorporation (SI) and biochar addition (BC) on N2O and NH3 emissions are still unclear. To fill this knowledge gap, a soil column experiment was conducted with two management strategies using straw ‐ straw incorporation (S1) and straw removal (S0) ‐ and four biochar application rates (0 (C0), 15 (C1), 30 (C2), and 45 t ha−1 (C3)) to evaluate the impacts of their interactions on N2O and NH3 emissions. The results showed that NO3−−N concentration and pH was the major contributors to affect the N2O and NH3 losses. Without biochar addition, N2O emissions was decreased by 59.6% (P<0.05) but AV was increased by 97.3% (P<0.05) under SI when compared to SR. Biochar was beneficial for N2O mitigation when straw was removed, but increased N2O emission by 39.4%−83.8% when straw was incorporated. Additionally, biochar stimulated AV by 27.9%−60.4% under S0 and 78.6%−170.3% under S1. Consequently, SI was found to significantly interact with BC in terms of affecting N2O (P<0.001) and NH3 (P<0.001) emissions; co-application of SI and BC promoted N2O emissions and offset the mitigation potential by SI or BC alone. The indirect N2O emissions caused by AV, however, might offset the reduction of direct N2O caused by SI or BC, thus leading to an increase in overall N2O emission. This paper recommended that SI combined BC at the amount of 8.2 t ha−1 for maintaining a lower overall N2O emission for future agriculture practices, but the long-term impacts of straw incorporation and biochar addition on the trade-off between N2O and NH3 emissions and reactive N losses should be further examined and assessed. [ABSTRACT FROM AUTHOR]

Water retention is an important soil property affecting the hydro-mechanical behavior of unsaturated soils. This study investigated the water retention property and the microstructure of lime-treated Ili loess from Xinjiang in China. Such material is a typical central Asian loess characterized by high salt content and strong collapsibility. The matric suction and total suction were measured by the filter paper method and saturated salt solution method. The microstructure characteristics of untreated and lime-treated loess were analyzed by scanning electron microscopy and mercury intrusion porosimetry, and the influence of the microstructure variation on the macroscopic water retention property was analyzed by introducing the parameter of fractal dimension, which is commonly used to describe the characteristic of pore shape and size. Results showed that, along the curing time, the lime treatment induced a change of the soil microstructure in terms of pore distribution with a consequent increase of the matric suction and overall water retention capacity. However, the osmotic suction decreased during curing. During curing, the lime treatment reduced the percentage of macro-pores and increased the nano-pores. Then, the soil microstructure was characterized by the fractal dimension, which increased with the curing times. Finally, the proposed fitting model of water retention consisting in introducing the fractal dimension into the Van-Genuchten model appeared adequate with good accuracy. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) is the treatment of choice for colorectal neoplasms in Japan. ESD can completely peel off the lesion and is associated with a significantly lower recurrence rate of colorectal cancers than EMR and is widely used to treat gastrointestinal tumors. This study aimed to evaluate in vivo traction in endoscopic submucosal dissection (ESD) of proximal colon lesions. Methods: This retrospective study included patients with lesions in the proximal colon who received ESD treatment at Qilu Hospital of Shandong University from June 2018 to December 2020. Patients were divided into two groups according to the in vivo traction method (orthodontic ring or elastic ring) during operation. The operation time, dissection time, proportion of complete resection of lesions, and complications were compared between the two groups. Results: There were 28 patients in this study. In the orthodontic ring group (n = 10), the average lesion diameter was 2.0–2.5 cm, and the average operation and dissection times were 26.5 ± 7.47 and 21.5 ± 7.47 min, respectively. In the elastic ring group (n = 18), the average lesion diameter was 2.5–5.5 cm, and the average operation and dissection times were 27.39 ± 11.83 and 22.39 ± 11.83 min, respectively. All lesions were completely resected in a single operation, and no wound perforation and delayed bleeding occurred. Conclusion: In vivo traction-assisted ESD can be used to resect proximal colon lesions in selected patients (precancerous lesions and early colon cancer limited to the mucosa or with a submucosa infiltration depth of < 1000 µm). [ABSTRACT FROM AUTHOR]

The transformation of prostatic epithelial cells to prostate cancer (PCa) has been characterized as a transition from citrate secretion to citrate oxidation, from which one would anticipate enhanced mitochondrial complex I (CI) respiratory flux. Molecular mechanisms for this transformation are attributed to declining mitochondrial zinc concentrations. The unique metabolic properties of PCa cells have become a hot research area. Several publications have provided indirect evidence based on investigations using pre-clinical models, established cell lines, and fixed or frozen tissue bank samples. However, confirmatory respiratory analysis on fresh human tissue has been hampered by multiple difficulties. Thus, few mitochondrial respiratory assessments of freshly procured human PCa tissue have been published on this question. Our objective is to document relative mitochondrial CI and complex II (CII) convergent electron flow to the Q-junction and to identify electron transport system (ETS) alterations in fresh PCa tissue. The results document a CII succinate: quinone oxidoreductase (SQR) dominant succinate oxidative flux model in the fresh non-malignant prostate tissue, which is enhanced in malignant tissue. CI NADH: ubiquinone oxidoreductase activity is impaired rather than predominant in high-grade malignant fresh prostate tissue. Given these novel findings, succinate and CII are promising targets for treating and preventing PCa. [ABSTRACT FROM AUTHOR]

This study investigates the influence of Zr on the microstructural evolution, mechanical and tribological properties of CoFeNi 1.5 VZr x (x = 0–0.6) eutectic high entropy alloys (EHEAs). The main composition evolutes from single FCC to FCC and Laves phase with increasing Zr content. Simultaneously, the microstructure changed from hypoeutectic to eutectic and then to hypereutectic with decreasing in grain size. The increase in Zr content improves the wear resistance of EHEAs at 25–800 °C. The rise in strength and hardness is the main reason for improved room-temperature wear resistance of EHEAs. The formation of gradient nano-tribo-layer and the transformation of the wear subsurface layer components from the FCC phase to the highly wear-resistant Laves phase help to enhance the high-temperature wear resistance of the EHEAs. [ABSTRACT FROM AUTHOR]

Objective. Inactivation of NLRP3 inflammasome plays a role in reducing the permeability of endothelial cells and improving blood-brain barrier (BBB) dysfunction following traumatic brain injury (TBI). However, the mechanism controlling NLRP3 inflammasome activation remains unclear. This study is aimed at defining the role of miR-29a-5p in NLRP3 inflammasome activation and permeability of endothelial cells under TBI. Methods. The scratch injury model on brain bEnd.3 microvascular endothelial cells was used as in vitro TBI model cells. Effects of miR-29a mimics and inhibitors on TBI model cells were observed by examining their action on FITC, TEER, and protein contents of ZO-1 and occludin, and cell permeability-associated protein. Luciferase reporter assay evaluated miR-29a-5p targeting to NLRP3. ELISA examined of IL-1β and IL-18 levels. miR-29a-5p mimic was injected into TBI mouse and its effect on BBB, indicated by Evans blue (EB) staining assay and cerebral water content, and NLRP3 activation was examined. Results. miR-29a-3p and miR-29a-5p mimics decrease the concentration of FITC, and increase TEER and the protein contents of ZO-1 and occludin in TBI model cells. miR-29a-5p silencing disrupted the permeability of mouse bEnd.3 cells. miR-29a-5p targets to NLRP3 through the binding on its 3 ′ UTR and negatively regulates its expression in TBI model cells. NLRP3 inhibition and miR-29a-5p silencing together caused significantly decreased FITC concentration and increased TEER value and release of IL-1β and IL-18. miR-29a-5p mimic alleviated the BBB and cerebral water content and inactivates NLRP3 in the mouse TBI model. Conclusions. miR-29a-5p mimics protect TBI-induced increased endothelial cell permeability and BBB dysfunction via suppressing NLRP3 expression and activation. [ABSTRACT FROM AUTHOR]

The study was aimed to determine the effect of wheat straw incorporation and nitrogen (N) fertilization on soil fertility and enzyme activity, as well as sweetpoato yield and quality. Field experiment was conducted in the summer seasons of 2017 and 2018, and four treatments were set: zero straw +50 kg·ha−1N (S0N50), 50% straw return +50 kg ha−1N (S1N50), 100% straw return +50 kg·ha−1N (S2N50), 100% straw return+150 kg ha−1N (S2N150). The aboveground yield, storage roots yield and single root fresh weight increased with the increase of straw returning quantity(S2N50> S1N50> S0N50). The storage root yield ofS2N150in 2017 was higher than that ofS2N50,but lower than that ofS2N50in 2018. Two years of nitrogen/straw incorporation also increased the starch content of sweetpotato, but decreased the reducing sugar, soluble sugar and protein content. The available N, total N, available P, available K and organic matter content, as well as catalase, alkaline phosphorylase, urease and invertase activity in soil were enhanced by nitrogen/straw incorporation. The results indicated that the conjoint application of full amount of straw and appropriate amount of N had the best effect on increasing the yield and starch content of sweetpotato. [ABSTRACT FROM AUTHOR]

The squash bug, Anasa tristis (De Geer) is a serious pest of cucurbit crops. The egg parasitoid, Gryon pennsylvanicum (Ashmead), is the primary parasitoid of the squash bug and has been considered as a biological control agent. In the present study, we conducted both laboratory and greenhouse bioassays to determine the effects of kairomones emitted by A. tristis on the host searching behaviour of G. pennsylvanicum. Chemicals were extracted from A. tristis eggs, unmated females and males, and mated females and males. The percentage of females responding to extracts was significantly higher for egg extracts than the other extracts tested. In greenhouse tests, percent parasitism of egg masses baited with extract-treated lures was significantly higher than for those treated with solvent-treated control lures for all six extracts tested: ethanol and hexane extracts of eggs, mated females and mated males. Further research on kairomones of A. tristis may result in the development of synthetic lures that could be used in squash fields to increase parasitism by G. pennsylvanicum. The promising results from this study highlights the potential application of kairomones in enhancing the efficacy and effectiveness of biological control programmes and should be of interest to growers and pest control professionals. [ABSTRACT FROM AUTHOR]

Subsampling plays a crucial role in tackling problems associated with the storage and statistical learning of massive datasets. However, most existing subsampling methods are model-based, which means their performances can drop significantly when the underlying model is misspecified. Such an issue calls for model-free subsampling methods that are robust under diverse model specifications. Recently, several model-free subsampling methods have been developed. However, the computing time of these methods grows explosively with the sample size, making them impractical for handling massive data. In this article, an efficient model-free subsampling method is proposed, which segments the original data into some regular data blocks and obtains subsamples from each data block by the data-driven subsampling method. Compared with existing model-free subsampling methods, the proposed method has a significant speed advantage and performs more robustly for datasets with complex underlying distributions. As demonstrated in simulation experiments, the proposed method is an order of magnitude faster than other commonly used model-free subsampling methods when the sample size of the original dataset reaches the order of 107. Moreover, simulation experiments and case studies show that the proposed method is more robust than other model-free subsampling methods under diverse model specifications and subsample sizes. [ABSTRACT FROM AUTHOR]

Refractory high entropy alloys (RHEAs) have attracted a great deal of attention for the competitive properties at elevated temperatures, whereas the ambient-temperature brittleness has been still a bottleneck for practical applications. Herein, we report on a newly-designed Ti 30 Hf 20 Nb 20 Ta 10 V 10 Mo 7 W 3 RHEA which exhibits an excellent combination of mechanical properties and wear resistance in a wide temperature range. The present RHEA possesses a yield strength of 1225 ± 17 MPa together with a fracture strain of > 45 % at room temperature, showing an excellent strength-ductility synergy. The alloy also maintains considerable yield strength and ductility at elevated temperatures, outperforming numerous ductile RHEAs. In addition, the coefficient of friction and wear rate decrease with increasing temperature from room temperature to 800 ℃. Interestingly, the alloy exhibits a wear rate as low as (5.50 ± 0.11) × 10−6 mm3 N−1 m−1 at 800 ℃, which is related to the formation of continues and dense oxide layer. • A novel Ti 30 Hf 20 Nb 20 Ta 10 V 10 Mo 7 W 3 RHEA with a single BCC phase was designed and fabricated. • Mechanical and tribological behaviors at various temperatures were investigated. • The RHEA presents an excellent strength-ductility trade-off at room temperature, while it maintains considerable yield strength even up to 1000 ℃. • At 800 ℃, the RHEA possesses the lowest wear rate on the order of 10−6 mm3 N−1 m−1, which is related to the formation of continues and dense oxide layer. [ABSTRACT FROM AUTHOR]

Investigating soil organic carbon balance characteristics is important for a better understanding of the stabilization and fertility mechanism of soil organic carbon. We analyzed the dynamics of soil organic carbon (SOC) and crop yield in a long-term fertilization experiment initiated in 1980. We observed that balanced fertilization treatments regardless of manure application increased the carbon input in 36 years. Higher SOC sequestration rates were observed after manure application. A significantly positive correlation was observed between the annual SOC sequestration rate and annual carbon input (R2 = 0.94); while the minimum amount of annual carbon input to maintain the SOC equilibrium amount was 0.24 t C ha−1. In particular, balanced fertilization had positive effects on the crop yields regardless of manure application. Meanwhile, a significant positive correlation was observed between SOC content and crop yields in wheat (R2 = 0.29), maize (R2 = 0.38), and sweet potato (R2 = 0.13). These results indicated that a balanced application of manure was beneficial for crop yield and SOC sequestration. [ABSTRACT FROM AUTHOR]

In the navigation of unmanned underwater vehicle (UUV), a filtering algorithm suitable for the working conditions is required. Due to the disturbance from the environment and maneuverability, outliers and noise with time-varying statistical properties always exist, which greatly affect the positioning accuracy and stability of the navigation system. In this paper, we present a novel nonlinear state estimation algorithm named AH∞CKF based on the combination of H∞CKF and Sage-Husa estimator. The recently developed H∞CKF provides nonlinear filtering good robustness, and Sage-Husa estimator could timely modify the statistical properties of noise. The novel algorithm is superior to H∞CKF in accuracy by combining Sage-Husa estimator with the H∞CKF while ensuring robustness. The effectiveness of the novel AH∞CKF is verified by lake experiment and simulation. [ABSTRACT FROM AUTHOR]

(VNbTaMoW)C high entropy carbide was fabricated by reaction synthesis using the constituent metal and graphite powders as raw materials. Phase formation and composition uniformity are analyzed using XRD, EDS and SEM. The phase composition for samples sintered at 1600℃ includes TaC, NbC, WC, MoC and VC according to XRD peak fitting and deconvolution. Samples sintered at 1850℃ form a single phase high entropy carbides, which exhibit high microhardness and relatively lower thermal conductivity of 9.2 W/m.K-1 at room temperature compared with binary carbides. Severe lattice distortion and high concentration of point defects are responsible for the low thermal conductivity of the high entropy (VNbTaMoW)C. [ABSTRACT FROM AUTHOR]

The present study investigated the roles of exogenous hormones in mitigating the loss caused by potassium (K+) deficiency stress in terms of plant growth and physiology in sweet potato (Ipomoea batatas L. [Lam.]). Two cultivars, Xushu 32 (tolerant to K+ deficiency) and Ningzishu 1 (sensitive to K+ deficiency) were used for the study. Exogenous hormones (indole-3-acetic acid, IAA; gibberellin 3, GA3; abscisic acid, ABA) were applied foliarly on the 14th day of K+ deficiency stress (–K). After 5 days of application, the exogenous hormones significantly increased the chlorophyll content (Chl) and net photosynthetic rate (Pn), as well as the activities of antioxidant enzymes (superoxide dismutase, SOD; peroxidase, POD; catalase, CAT) in leaves, while reduced the lipid peroxidation levels (hydrogen peroxide, H2O2 and malondialdehyde, MDA). Application of hormones also significantly increased the root activity and alleviated the root tip cell damage. All these changes led to the enhancement of the plant dry weight, K+ content and K+ accumulation under – K condition, indicating that exogenous hormones can be used as potential tools to improve the K+ deficiency tolerance of sweet potato. However, exogenous IAA has a better effect on Xushu 32 than GA3 and ABA, while ABA is the best for Ningzishu 1. [ABSTRACT FROM AUTHOR]

The critical properties of polycrystalline Pr1−xBaxMnO3 (x = 0.13 and 0.23) samples prepared by using a standard ceramic fabrication method were investigated. Pr1−xBaxMnO3 exhibited a second-order magnetic transition. As per the modified Arrott plot method and double logarithmic M-μ0H curve, the critical exponents (CE) were calculated as β = 0.459 ± 0.03, γ = 1.346 ± 0.02, δ = 4.32 ± 0.04, and TC ≈ 130 K, for x = 0.13, and β = 0.424 ± 0.03, γ = 1.362 ± 0.02, δ = 4.19. ± 0.03, and TC ≈ 163 K, for x = 0.23. To confirm the reliability of such CE values, the M (H) data of Pr1−xBaxMnO3 were checked by the scaling equation M(H, t) = |t|βf±(H/|t|β + γ), where t = T T C − 1 refers to the reduced temperature, f± is the scaling function above (+)/below (−) TC. The β values for Pr1−xBaxMnO3 (x = 0.13 and 0.23) are between β = 0.365 (3D Heisenberg exponent) and β = 0.5 (mean-field exponent), whereas γ values are fairly close to γ = 1.386. This reveals long- and short-range order coexisting in Pr1−xBaxMnO3. [ABSTRACT FROM AUTHOR]

To improve the high-temperature strength and decrease the density of NbTaWMo alloys, addition of light element Si producing the second-phase silicide is employed. Refractory NbTaWMoSix (x = 0, 0.25, 0.5, 0.75) high-entropy alloys are produced by spark plasma sintering. The phase evolution, microstructure, compressive mechanical properties, and high-temperature hardness are investigated in this study. It reveals that there is only a disordered body-centered cubic (BCC) phase in the matrix NbTaWMo alloy. After adding the Si element, NbTaWMoSix alloys demonstrate the presence of multiphase structure: disordered BCC phase and silicide phase. As the content of Si is increased, the proportion of silicide is increased, which improves the hardness and strength. The addition of Si at certain concentration (x = 0.25 and 0.5) has positive effect on ductility of the alloys. The alloys all demonstrate brittle fracture due to the brittle phase of BCC and silicide phase. The high-temperature hardness of NbTaWMoSix alloys is increased with the addition of Si, but the same alloy presents a slightly decreasing phenomenon as the temperature improves. [ABSTRACT FROM AUTHOR]

Abstract Liver cancer has been considered as one of the major leading causes of cancer-related mortality. The incidence of liver cancer tends to increase in less developed regions. Increasing evidences have demonstrated that mircoRNAs (miRNAs) play crucial roles in the modulation of tumor growth and progression. Whereas, the functional role of miR-539 in hepatocellular carcinoma (HCC) is not well established. In our present study, we sought to explore biological role of miR-539 in HCC progression. qRT-PCR was utilized to evaluate the expression level of miR-539. Immunoblotting analysis, qRT-PCR and luciferase reporter assays were used for the identification of the potential target of miR-539. Proliferation, migration and invasion assays and flow cytometric were performed to assess the biological functional role of miR-539. The molecular signaling pathways related to the integration of miR-539 were also evaluated. MiR-539 was reduced in human HCC. Mitogen-activated protein kinase 1, also known as MAP2K1 was verified as the target of miR-539. Overexpression of miR-539 inhibited migration, invasion and cell proliferation, while apoptosis rate was increased. Knockdown or overexpression of MAP2K1 in HCC cell transfected with ag-miR-539 or in-miR-539 indicated that miR-539 suppresses the progression of HCC by directly targeting and regulating MAP2K1. Our results reveal that miR-539 might be a tumor suppressor in HCC, supporting a potential target for advanced therapeutic strategy for this disease. [ABSTRACT FROM AUTHOR]

The ℓ 0 trend filtering ( ℓ 0 -TF) is a new effective tool for nonparametric regression with the power of automatic knot detection in function values or derivatives. It overcomes the drawback of ℓ 1 -TF that is known to have bias issues. To solve the ℓ 0 -TF problem, we propose an alternating minimization induced active set (AMIAS) search method based on the necessary optimality conditions derived from an augmented Lagrangian framework. The proposed method takes full advantage of the primal and dual variables with complementary supports, and decouples the high-dimensional problem into two subsystems on the active and inactive sets, respectively. A sequential AMIAS algorithm with warm start initialization is developed for efficient determination of the cardinality parameter, along with the output of solution paths. Theoretically, the oracle estimator of ℓ 0 -TF is justified to behave like regression splines under the continuous time setting with mild conditions. Our numerical experiments include simulation studies for comparing ℓ 0 -TF to ℓ 1 -TF and free-knot splines on several synthetic examples, and a real data application of time series segmentation on Hong Kong PM2.5 indexes. History: Accepted by Antonio Frangioni, Area Editor for Design & Analysis of Algorithms – Continuous. Funding: This work was supported in part by Hong Kong General Research Fund [No. 17306519]. C. Wen's research is partially supported by National Science Foundation of China [12171449] and Fundamental Research Funds for the Central Universities [WK3470000027, YD2040002019]. X. Wang's research is partially supported by National Natural Science Foundation of China [Grants 72171216, 12231017, 71921001, and 71991474], and the National Key R&D Program of China [No. 2022YFA1003803]. Supplemental Material: The e-companion is available at https://doi.org/10.1287/ijoc.2021.0313. The software that supports the findings of this study is available within the paper and its Supplemental Information (https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2021.0313) as well as from the IJOC GitHub software repository (https://github.com/INFORMSJoC/2021.0313). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/. [ABSTRACT FROM AUTHOR]

In this study, a novel CoCrFeNiS 0.5 high entropy alloy (HEA) containing sulfur which simultaneously possesses good mechanical properties and excellent tribological performances is reported for the first time. The CoCrFeNiS 0.5 self-lubricating HEA was successfully prepared by spark plasma sintering (SPS) via powder mixture of Co, Cr, Fe, Ni and FeS. The SPSed HEA was composed of a face-centered cubic (FCC) phase and a Cr x S y phase, and these phases were formed by in-situ reaction of powder mixture during SPS. The FCC phase connected with each other to form the matrix of the HEA, and the Cr x S y phase distributed uniformly in the FCC phase matrix. The FCC phase matrix was mainly responsible for good ductility and fracture toughness of the HEA, and the Cr x S y phase enabled the HEA to have good strength. The combination of the Cr x S y phase and various metal oxides formed on the worn surfaces at high temperatures made the CoCrFeNiS 0.5 HEA have good tribological properties over a wide range of temperatures. [ABSTRACT FROM AUTHOR]

Abstract: Aberrant mitochondrial energy transfer underlies prevalent chronic health conditions, including cancer, cardiovascular, and neurodegenerative diseases. Mitochondrial transplantation represents an innovative strategy aimed at restoring favorable metabolic phenotypes in cells with dysfunctional energy metabolism. While promising, significant barriers to in vivo translation of this approach abound, including limited cellular uptake and recognition of mitochondria as foreign. The objective is to functionalize isolated mitochondria with a biocompatible polymer to enhance cellular transplantation and eventual in vivo applications. Herein, it is demonstrated that grafting of a polymer conjugate composed of dextran with triphenylphosphonium onto isolated mitochondria protects the organelles and facilitates cellular internalization compared with uncoated mitochondria. Importantly, mitochondrial transplantation into cancer and cardiovascular cells has profound effects on respiration, mediating a shift toward improved oxidative phosphorylation, and reduced glycolysis. These findings represent the first demonstration of polymer functionalization of isolated mitochondria, highlighting a viable strategy for enabling clinical applications of mitochondrial transplantation. [ABSTRACT FROM AUTHOR]

T-cell acute lymphoblastic leukemia (T-ALL) has a poor prognosis as a result of severe immunosuppression and rapid tumor progression with resistance to conventional chemotherapy. Excessive IgD may play a role in T cell activation via IgD Fc receptor (FcδR). Here we aimed to investigate the effects of IgD in T-ALL and demonstrated the potential benefit by targeting IgD/FcδR in T-ALL patients with IgD-Fc-Ig fusion protein. In T-ALL patients' blood samples and cell lines, the level of IgD, the percentage of FcδR expressing cells and the binding affinity were determined by flow cytometry. T cell viability, proliferation and apoptosis were analyzed. A mouse xenograft model was used to evaluate the in vivo effect of IgD-Fc-Ig, an IgD-FcδR blocker. The levels of serum IgD and FcδR were abnormally increased in part of T-ALL patients and IgD could induce over-proliferation and inhibit apoptosis of T-ALL cells in vitro. FcδR was constitutively expressed on T-ALL cells. IgD-Fc-Ig showed similar binding affinity to FcδR and selectively blocked the stimulation effect of IgD on T-ALL cells in vitro. In vivo study exhibited that IgD-Fc-Ig may also have therapeutic benefit. IgD-Fc-Ig administration inhibited human T-ALL growth and extended survival in xenograft T-ALL mice. In conclusion, this work supports the idea of targeting IgD/FcδR in T-ALL patients with excessive IgD. IgD-Fc-Ig fusion protein might be a potential biological drug with high selectivity for T-ALL treatment. [Display omitted] • IgD and FcδR expression may be functional biomarkers of T-ALL cells and play crucial roles in T-ALL pathogenesis. • IgD induced over-proliferation in T-ALL cells. • IgD-Fc-Ig inhibited the over-proliferation induced by IgD in T-ALL cells. • IgD-Fc-Ig fusion protein targeting FcδR might be a potential biological drug with high selectivity for T-ALL treatment. [ABSTRACT FROM AUTHOR]

A CoCrFeNi high entropy alloy matrix self-lubricating composite was prepared by spark plasma sintering using a mixture of CoCrFeNi high entropy alloy powder, nickel-coated graphite powder and nickel-coated MoS 2 powder. The composite consisted of four phases: face-centered cubic phase of the high entropy alloy, graphite, MoS 2 and nickel. Graphite and MoS 2 existed in the composite were mainly due to the nickel coatings onto the lubricants and the unique advantage of spark plasma sintering. The hardness, yield strength, compressive strength and fracture toughness of the composite were 271 HV, 610 MPa, 921 MPa and 14.3 MPa·m 0.5 , respectively. The good mechanical properties of the composite were mainly derived from the CoCrFeNi high entropy alloy matrix. The composite exhibited excellent tribological properties from room temperature to 800 °C. From room temperature to medium temperatures, the reduction of friction coefficients and wear rates of the composite was attributed to the synergistic lubricating effect of graphite and MoS 2 . At high temperatures, it was found that various metal oxides formed on the composite surfaces played a key role in improving the tribological properties. [ABSTRACT FROM AUTHOR]

A rapid method using spark plasma sintering (SPS) to prepare the AlCoCrFeNi high entropy alloy (HEA) from elemental powder mixture is firstly presented. The SPSed AlCoCrFeNi HEA consists of a face-centered cubic (FCC) phase and a duplex body-centered cubic (BCC) structure (composed of spinodally modulated disordered and ordered BCC phases). The microhardness, yield strength, compressive strength, ultimate plasticity strain and fracture toughness of the HEA are 518 HV, 1262 MPa, 3228 MPa, 29.1% and 25.2 MPa m 1/2 , respectively. The good mechanical properties are mainly contributed to the effective combination of the BCC and the FCC phases. This method has great potential for preparing HEAs in future. [ABSTRACT FROM AUTHOR]

A novel Hf 30 Nb 25 Ta 25 Ti 15 Mo 5 refractory high entropy alloy (RHEA) with BCC structure has been proposed. The compressive yield strength, fracture strain and fracture toughness at room temperature are 964 ± 16 MPa, > 50% and 94.7 ± 1.4 MPa m1/2, respectively. Compared with most BCC-type RHEAs, this alloy exhibits the superior combination of strength, ductility and fracture toughness. [ABSTRACT FROM AUTHOR]

Indirubin, a traditional Chinese medicine, is used to treat autoimmune diseases in clinics. However, the effects of indirubin on the immunosuppressive CD4+CD25+Foxp3+ regulatory T cells (Treg) have not been addressed. Thus, we aimed to investigate the effects of indirubin on CD4+CD25+Treg cells in immune thrombocytopenia (ITP) CBA mice, which were established by immunization with Wistar rat platelets. 50 mg/kg indirubin treatment daily for 4 weeks significantly decreased anti-platelet antibody production and prevented the decrease of platelets caused by immunization in ITP mice. Consistently, indirubin significantly enhanced the percentage and cell number of CD4+CD25+Foxp3+Treg cells in the peripheral blood, spleen and lymph nodes. We also observed a significant increase of the frequency and cell number of CD4+CD25+Foxp3+Treg cells in the thymus upon indirubin treatment. Furthermore, CD4+CD25+Treg cells from indirubin-treated mice showed similar immunosuppression on T effector cells as compared to those from control mice. Altogether, indirubin ameliorates ITP by enhancing CD4+CD25+Foxp3+Treg cell level with preserving immunosuppressive function. [ABSTRACT FROM AUTHOR]

This paper presents a multi-objective robust optimization method for a drive system consisting of a permanent magnet transverse flux machine with soft magnetic composite cores and a field-oriented controller. Unlike existing research work, the torque ripple is considered an optimization objective. Several machine uncertainties caused by manufacturing tolerances are investigated in the robust optimization model under the framework of the design for six-sigma. Since this is a system-level optimization problem, two approximation models are employed to decrease the computational cost. First, a Kriging model is used to approximate the steady-state electromagnetic performances of the motor, such as the output power and efficiency. Second, a Taylor series approximation is employed to estimate the dynamic performances of the control system, such as the speed overshoot and settling time. Furthermore, a sampling selection method is proposed to reduce the computational cost of the Monte Carlo analysis in robust optimization. To show the effectiveness of the proposed method, both deterministic and robust Pareto solutions are presented and discussed. It can be seen that the system-level multi-objective design optimization based on robust approach can produce optimal Pareto solutions with a high manufacturing quality for the whole drive system. This is valuable for the batch production of electrical drive systems. [ABSTRACT FROM AUTHOR]

In this paper, an active contours model using neighborhood average fitting with thresholding is proposed for noisy images segmentation. Energy of the proposed model is formulated according to the difference between the local average and global region information. For images corrupted by noise, the neighborhood average method is capable of denoising at the expense of blurring images to some extent. However, problems that appear with average method can be settled by thresholding in this work. Minimization of the energy associated with the active contour model is then implemented in a variational level set framework. Moreover, to eliminate the need for costly re-initialization procedure, a reaction-diffusion method is adopted to regularize the level set function for stability. Experimental results on synthetic and real images validate the effectiveness of the proposed approach. [ABSTRACT FROM AUTHOR]

This paper is devoted to the study of spatial propagation dynamics of species in locally spatially inhomogeneous patchy environments or media. For a lattice differential equation with monostable nonlinearity in a discrete homogeneous media, it is well-known that there exists a minimal wave speed such that a traveling front exists if and only if the wave speed is not slower than this minimal wave speed. We shall show that strongly localized spatial inhomogeneous patchy environments may prevent the existence of transition fronts (generalized traveling fronts). Transition fronts may exist in weakly localized spatial inhomogeneous patchy environments but only in a finite range of speeds, which implies that it is plausible to obtain a maximal wave speed of existence of transition fronts. [ABSTRACT FROM AUTHOR]

• A series of boron doped Al 0.2 Co 1.5 CrFeNi 1.5 Ti 0.5 B x HEA was firstly reported. • Boron doping induces the transformation of microstructure from dendrite to eutectic. • The eutectic structure with lamellar morphology composed by FCC and Laves phase. • Boron doping improves mechanical properties of the HEAs significantly. [Display omitted] High entropy alloys (HEAs) have attracted considerable attention due to their excellent mechanical properties, which provides new insights for designing next generation structural materials. A series of Al 0.2 Co 1.5 CrFeNi 1.5 Ti 0.5 B x (x = 0, 0.15, 0.3, 0.45, 0.6, 0.75 and 0.9, in molar ratio) HEAs was prepared by vacuum arc melting to investigate the effect of boron doping on the phase evolution, microstructure transformation and mechanical properties. The results indicated that the HEAs with trace boron doping (x = 0.15) maintained single FCC phase, while it evolved to FCC phase, in-situ borides (TiB 2 and Cr 2 B) and Laves phase when the boron molar ratio higher than 0.3. With the boron molar content increased from 0 to 0.9, the microstructures of the HEAs transformed from complete dendrite to dendrites, irregularly shaped TiB 2 , needle-shaped Cr 2 B and lamellar eutectic structure which composed by alternate layers of FCC phase and Laves phase. B doping improved the strength and hardness of the HEAs. The enhanced mechanical properties of the boron doped HEAs was attributed to the synergistic strengthening effect among interstitial solid solution strengthening, second phase strengthening, dislocation strengthening, fine grain strengthening and heterostructure strengthening. [ABSTRACT FROM AUTHOR]

Background: Combinations of drugs are becoming increasingly common in oncology treatment. In some cases, patients can benefit from the interaction between two drugs, although there is usually a higher risk of developing toxicity. Due to drug–drug interactions, multidrug combinations often exhibit different toxicity profiles than those of single drugs, leading to a complex trial scenario. Numerous methods have been proposed for the design of phase I drug combination trials. For example, the two-dimensional Bayesian optimal interval design for combination drug (BOINcomb) is simple to implement and has desirable performance. However, in scenarios where the lowest and starting dose is close to being toxic, the BOINcomb design may tend to allocate more patients to overly toxic doses, and select an overly toxic dose combination as the maximum tolerated dose combination. Method: To improve the performance of BOINcomb in the above extreme scenarios, we widen the range of variation of the boundaries by setting the self-shrinking dose escalation and de-escalation boundaries. We refer to the new design as adaptive shrinking Bayesian optimal interval design for combination drug (asBOINcomb). We conduct a simulation study to evaluate the performance of the proposed design using a real clinical trial example. Results: Our simulation results show that asBOINcomb is more accurate and stable than BOINcomb, especially in some extreme scenarios. Specifically, in all ten scenarios, the percentage of correct selection is higher than the BOINcomb design within 30 to 60 patients. Conclusion: The proposed asBOINcomb design is transparent and simple to implement and can reduce the trial sample size while maintaining accuracy compared with the BOINcomb design. [ABSTRACT FROM AUTHOR]

Enantiopurecaffeic acid esters were successfully synthesized fromcaffeic acid and corresponding (R,S)-alcohol catalyzed by an immobilized lipase (Novozym435) from Candida antarctica. Effects of the alcoholcarbon chain length and the type of organic solvents were first investigated,and anhydrous isooctane was finally selected as the most suitablereaction medium. The optimal synthesis parameters for caffeic acidester synthesis were evaluated using response surface methodology.The actual experimental conversions of 33.8 ± 1.8% and an Evalue of >100 for (R)-1-methylbutylcaffeate,achieved under optimized reaction conditions, indicated a good fitto the predictive model. Kinetic and thermodynamic analyses were conductedto determine the main factors affecting enantiomeric discrimination.Results from the batch reuse stability study show that the immobilizedenzyme could be effectively reused. The present study is the firstto use lipase as the chiral catalyst to prepare optically pure caffeicacid ester compounds. [ABSTRACT FROM AUTHOR]

Highlights: [•] SDF-1 pretreating increased the levels of CXCR4, CXCR7 in ADSCs. [•] SDF-1 improved cells paracrine migration and proliferation abilities. [•] CXCR4 and CXCR7 could function in ADSCs paracrine, migration and proliferation. [Copyright &y& Elsevier]

• A novel explainable neural network is proposed for modeling main effects and structured interactions. • The GAMI-Net is a disentangled feedforward network with multiple additive subnetworks. • GAMI-Net takes into account three interpretability constraints: sparsity, heredity, marginal clarity. • An adaptive training algorithm is developed for training GAMI-Net efficiently. • GAMI-Net enjoys superior interpretability and outperforms benchmark methods. The lack of interpretability is an inevitable problem when using neural network models in real applications. In this paper, an explainable neural network based on generalized additive models with structured interactions (GAMI-Net) is proposed to pursue a good balance between prediction accuracy and model interpretability. GAMI-Net is a disentangled feedforward network with multiple additive subnetworks; each subnetwork consists of multiple hidden layers and is designed for capturing one main effect or one pairwise interaction. Three interpretability aspects are further considered, including a) sparsity, to select the most significant effects for parsimonious representations; b) heredity, a pairwise interaction could only be included when at least one of its parent main effects exists; and c) marginal clarity, to make main effects and pairwise interactions mutually distinguishable. An adaptive training algorithm is developed, where main effects are first trained and then pairwise interactions are fitted to the residuals. Numerical experiments on both synthetic functions and real-world datasets show that the proposed model enjoys superior interpretability and it maintains competitive prediction accuracy in comparison to the explainable boosting machine and other classic machine learning models. [ABSTRACT FROM AUTHOR]

High entropy alloys (HEAs) are expected to be applied at elevated temperatures. However, the tribological properties of the HEAs in a wide temperature range have not been studied systemically, especially at high temperatures. In this paper, the micro-hardness as well as the tribological properties of Al 0.2 Co 1.5 CrFeNi 1.5 Ti 0.5+x C x (x = 0, 1.0 and 2.0) HEAs from 25°C to 800°C was investigated and compared with Inconel 718 superalloy. The results showed that the solid solution strengthening effect of the HEAs and the dispersion strengthening effect of in situ generated TiC resulted in a significantly higher high temperature microhardness of the carbon-doped HEAs than that of the Inconel 718. The friction coefficient of the HEAs increased with increasing carbon content at same temperature, but it decreased as the temperature increased. The wear resistance of carbon doped HEAs were superior than that of Inconel 718 and carbon-free HEAs from 25 to 800 °C. Below 600 °C, the wear rate of the HEAs which decreased monotonously with increasing carbon content was in the range of (0.31-12.56) × 10-5 mm3 N-1∙m-1, but above 600 °C, the wear rate of the HEAs was proportion to carbon content within (2.64-23.90) × 10-6 mm3 N-1∙m-1. The excellent high-temperature wear resistance of the HEAs was attributed to the synergistic effect of the good high temperature softening resistance and a nano-oxidized glaze layer with superior mechanical properties on the worn surface. • The wear behavior of Al 0.2 Co 1.5 CrFeNi 1.5 Ti 0.5+x C x HEAs up to 800 °C was studied. • Excellent high temperature softening resistance was positive for wear resistance. • Wear resistance was proportional to the carbon content below 600 °C. • The sliding-induced the nano-oxide glaze layer were characterized. • The nano-oxide glaze layer improved the high temperature tribological properties. [ABSTRACT FROM AUTHOR]

Abstract: Activated platelet-specific autoreactive T cells play a key role in the pathophysiology of immune thrombocytopenia (ITP). Tolerogenic dendritic cells (tDCs) that induce T cells tolerance to platelet autoantigens are a promising strategy for specific cellular therapy in autoimmunity. In this study, we generated three kinds of GPIIb -specific tDCs stimulated by IL-10 (10-DCs), TGFβ1 (T-DCs), or a combination of IL-10 and TGFβ1 (10T-DCs), respectively, and compared their phenotypes and biological function. Our data demonstrate that GPIIb-specific 10T-DCs induced the weakest memory lymphocytes responses and exhibited stronger tolerogenic potential than others, making them suitable for tolerance inducing therapies. Furthermore, in ITP mice model we found that 10T-DCs abrogated the decrease in platelet counts and the increase in serum IFN-γlevel, confirming the in vivo tolerogenic potential of 10T-DCs. Our study provides a promising strategy for ITP intervention in the clinic by the induction of platelet-specific immune tolerance. [Copyright &y& Elsevier]

Using a ternary sex pheromone blend [86:6:6 v:v:v ( Z, Z)-3,13-octadecadienyl acetate: ( E, Z)-2,13-octadecadienyl acetate: ( Z, E)-3,13-octadecadienyl acetate], we tested the effect of dispenser type and trap design for capture of dogwood borer (DWB), Synanthedon scitula Harris (Lepidoptera: Sesiidae) in apple orchards in West Virginia, Virginia, and North Carolina. Wing-style sticky traps baited with polyethylene vial pheromone dispensers captured more male DWB over the first 2 months than traps baited with rubber septum pheromone dispensers. However, catches in vial-baited traps decreased considerably after the first 2 months, possibly due to the antagonistic effect of 3,5-di- tert-butyl-4-hydroxy acetophenone that diffused from the polyethylene vials. By contrast, traps baited with rubber septum dispensers captured DWB males for at least 6 months; over the last four months of the flight season, catches in traps baited with a rubber septum were greater than those in traps baited with a vial dispenser. Therefore, the rubber septum dispenser is recommended for season-long monitoring of DWB. A release-rate study, using laboratory and field-aged dispensers, demonstrated that desorption of DWB sex pheromone from polyethylene vial or rubber septum dispensers followed first order kinetics, with half-lives of 1.6 and 10.7 months, respectively. Several trap designs, including wing-and delta-style sticky traps, and white and green 'bucket-style' traps, baited with rubber septum dispensers were compared in commercial apple orchards for catch of DWB. Bucket traps caught more moths when moth populations were high, because the sticky surfaces of the 1C and delta traps likely became saturated. However, among the commercially available traps tested, no particular design gave consistently higher catches. Further work is needed to explore capture mechanisms and maintenance needs of different trap types. [ABSTRACT FROM AUTHOR]

Objective: To investigate the distribution patterns of H3K4me3 and H3K27me3 in human oocytes and preimplantation embryos. Design: Experimental study. Setting: University reproductive medical center. Patient(s): Patients undergoing IVF cycles. Intervention(s): Oocytes and embryos were collected from patients undergoing IVF cycles. Main Outcome Measure(s): The distribution patterns of H3K4me3 and H3K27me3 in oocytes and embryos were analyzed by indirect immunofluorescent staining and scanning confocal microscopy. Result(s): H3K4me3 and H3K27me3 signals were detectable at each stage of oocyte and embryonic development. However, only one of the pronuclei showed signal for H3K27me3 in each of the zygotes, whereas H3K4me3 staining was always uniform in all zygotes. The level of H3K4me3 decreased steadily from germinal vesicle to metaphase II stage, obviously increased from zygote stage to four-cell stage, and reached the lowest at eight-cell stage. A sharp increase was then observed at blastocyst stage. The level of H3K27me3 slightly changed from germinal vesicle stage to zygote stage, then decreased steadily and reached the lowest at eight-cell stage, followed by a significant increase at blastocyst stage. Conclusion(s): The levels of H3K4me3 and H3K27me3 show dynamic changes during human oocyte maturation and preimplantation embryonic development. Asymmetric distribution of H3K27me3 exists in human zygote pronuclei, whereas H3K4me3 is always uniform in all of the pronuclei. [ABSTRACT FROM AUTHOR]

Accumulating evidence indicates that the APOA1 binding protein (AIBP)—a secreted protein—plays a profound role in lipid metabolism. Interestingly, AIBP also functions as an NAD(P)H-hydrate epimerase to catalyze the interconversion of NAD(P)H hydrate [NAD(P)HX] epimers and is renamed as NAXE. Thus, we call it NAXE hereafter. We investigated its role in NAD(P)H-involved metabolism in murine cardiomyocytes, focusing on the metabolism of hexose, lipids, and amino acids as well as mitochondrial redox function. Unbiased metabolite profiling of cardiac tissue shows that NAXE knockout markedly upregulates the ketone body 3-hydroxybutyric acid (3-HB) and increases or trends increasing lipid-associated metabolites cholesterol, α-linolenic acid and deoxycholic acid. Paralleling greater ketone levels, ChemRICH analysis of the NAXE-regulated metabolites shows reduced abundance of hexose despite similar glucose levels in control and NAXE-deficient blood. NAXE knockout reduces cardiac lactic acid but has no effect on the content of other NAD(P)H-regulated metabolites, including those associated with glucose metabolism, the pentose phosphate pathway, or Krebs cycle flux. Although NAXE is present in mitochondria, it has no apparent effect on mitochondrial oxidative phosphorylation. Instead, we detected more metabolites that can potentially improve cardiac function (3-HB, adenosine, and α-linolenic acid) in the Naxe−/− heart; these mice also perform better in aerobic exercise. Our data reveal a new role of NAXE in cardiac ketone and lipid metabolism. [ABSTRACT FROM AUTHOR]

Objective: To investigate the anti-inflammatory effects of Sirt1 and its roles in steroidogenesis in Leydig cells. Design: In vitro cell culture study. Setting: Reproductive medical center. Animal(s): C57BL/6 male mice. Intervention(s): TM3 Leydig cells were treated with proinflammatory cytokines including tumor necrosis factor-α, interleukin-6, or interleukin-1β. Main Outcomes Measure(s): Sirt1 mRNA and protein levels were measured by real-time polymerase chain reaction and Western blotting in TM3 Leydig cells treated with proinflammatory cytokines. The cell viability was determined using MTT and BrdU incorporation assays. The effect of Sirt1 on the coactivation of steroidogenic factor 1 (SF-1) was characterized by coimmunoprecipitation and luciferase reporter assays. Result(s): Sirt1 mRNA and protein levels were significantly down-regulated by proinflammatory cytokines treatment in TM3 Leydig cells. Sirt1 agonist or overexpression could efficiently protect cytotoxicity induced by proinflammatory cytokines. Sirt1 promoted steroidogenesis through its coactivation of SF-1. Conclusion(s): Sirt1 plays protective roles and promotes steroidogenesis in Leydig cells through its anti-inflammatory actions and coactivation of SF-1. [ABSTRACT FROM AUTHOR]

This paper deals with positive stationary solutions and spreading speeds of monostable equations with nonlocal dispersal in spatially periodic habitats. The existence and uniqueness of positive stationary solutions and the existence and characterization of spreading speeds of such equations with symmetric convolution kernels are established in the authors' earlier work for the following cases: the nonlocal dispersal is nearly local; the periodic habitat is nearly globally homogeneous or it is nearly homogeneous in a region where it is most conducive to population growth. The above conditions guarantee the existence of principal eigenvalues of nonlocal dispersal operators associated to linearized equations at the trivial solution. In general, a nonlocal dispersal operator may not have a principal eigenvalue. In this paper, we extend our earlier results to general spatially periodic nonlocal monostable equations. As a consequence, it is seen that the spatial spreading feature is generic for monostable equations with nonlocal dispersal. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of human cumulus cells on the maturation and developmental potential of immature oocytes in ICSI cycles. Methods: Immature oocytes were randomly divided into two groups: the cumulus-denuded oocyte group (group A) and the cumulus-intact oocyte group (group B). Only oocytes that reached metaphase II (MII) stage after in vitro maturation were used in the ICSI procedure. In vivo mature sibling MII oocytes served as the control group. Maturation rate, fertilization rate, embryo quality and developmental potential were examined. Results: There was no significant difference in maturation rate between group A (68.16%) and group B (70.49%; P > 0.05). The total fertilization rate among the three groups was comparable ( P > 0.05), while the zygotes with two pronuclei in group A (74.59%) or group B (75.97%) were significantly lower than those in control group (84.29%; P < 0.05). The available embryo rate in group A (11.49%) was markedly lower than that in group B (27.66%; P < 0.05), and both of them were significantly lower than that in control group (62.38%; P < 0.05). The proportion of ≥6-cell embryos in group B (45.74%) was notably higher than in group A (26.44%; P < 0.05), and both were markedly lower than in control group (65.92%; P < 0.05). The proportion of embryos with <10% fragmentation in group A (13.79%) was significantly lower than in group B (29.79%; P < 0.05), and both were notably lower than in control group (42.98%; P < 0.05). Conclusions: The presence of cumulus cells surrounding the immature oocytes during IVM before ICSI had no influence on nuclear maturation and fertilization, but leads to better subsequent embryonic development. This is perhaps mediated by an improvement in cytoplasmic maturation. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the influxation of synovia and synovial compartments with immune cells including dendritic cells (DCs). DCs that induce autoimmune tolerance are called tolerogenic DCs (tolDCs). As a promising immunotherapeutic strategy for RA, tolDCs have received increasing attention. In this review, we first introduce the significant role of tolDCs in autoimmune regulation and then describe the manipulation strategies to generate tolDCs; next, we summarize recent progress in the experimental application of tolDCs for RA therapy, and finally we discuss the perspectives of tolerogenic vaccination for the treatment for RA in clinic. [ABSTRACT FROM AUTHOR]

Abstract: The objective of the study was to investigate the effects of recombinant human erythropoietin (rhEPO) in a rat model of cervical sub-acute spinal cord compression. 80 Wistar rats were randomly divided into 4 groups. Rats in the sham group (Group A, n =5) underwent surgical procedures without cervical spinal cord compression; while rats in other groups were subjected to the spinal compression process. In the control group (Group B, n =25), rats received an i.v. injection of 1mL saline at day 7 post-surgery. Rats in the low-dose group (Group C, n =25) and the high-dose group (Group D, n =25) were treated with rhEPO at 500units/kg body-weight and 5000units/kg, respectively, via intravenous injection at day 7 post surgery. Limb motor function was scored by Basso–Beattie–Bresnahan (BBB) standards at 3, 7, 14, 21 and 28 days post-surgery. The distribution and quantities of EPO and its receptor (EPO-R) in the compressed segment of the spinal cord were detected by immunohistochemistry. Motor neuron apoptosis in the spinal cord was evaluated using TUNEL staining and flow cytometry at the indicated time points. Finally, IL-8, TNF-α, IL-6, and IL-1β levels in the compressed cervical spinal cord were determined by ELISA within the lesion epicenter at each time point post-surgery. The data suggest that expression of EPO-R was significantly increased following sub-acute cervical spinal cord compression; Groups C and D exhibited better BBB scores at all observed time points compared with the control group (p <0.01). Using TUNEL staining and FCM, we observed that rhEPO profoundly inhibited motor neuron apoptosis in the spinal cord at day 21 (p <0.01). Additionally, treatment with rhEPO halted the elevation of inflammatory cytokines. rhEPO administration decreased motor neuron apoptosis in the cervical spinal cord, improved motor functions and reduced the inflammatory response in a sub-acute cervical spinal cord compression model. Moreover, sustained treatment with low doses of rhEPO revealed a positive therapeutic effect. [Copyright &y& Elsevier]

Abstract: The current paper is devoted to the study of spatial spreading dynamics of monostable equations with nonlocal dispersal in spatially periodic habitats. In particular, the existence and characterization of spreading speeds is considered. First, a principal eigenvalue theory for nonlocal dispersal operators with space periodic dependence is developed, which plays an important role in the study of spreading speeds of nonlocal periodic monostable equations and is also of independent interest. In terms of the principal eigenvalue theory it is then shown that the monostable equation with nonlocal dispersal has a spreading speed in every direction in the following cases: the nonlocal dispersal is nearly local; the periodic habitat is nearly globally homogeneous or it is nearly homogeneous in a region where it is most conducive to population growth in the zero-limit population. Moreover, a variational principle for the spreading speeds is established. [Copyright &y& Elsevier]

Abstract: A novel lipase gene from an organic solvent degradable strain Pseudomonas fluorescens JCM5963 was cloned, sequenced, and overexpressed as an N-terminus His-tag fusion protein in E. coli. The alignment of amino acid sequences revealed that the protein contained a lipase motif and shared a medium or high similarity with lipases from other Pseudomonas strains. It could be defined as a member of subfamily I.1 lipase. Most of the recombinant proteins expressed as enzymatically active aggregates soluble in 20mM Tris–HCl buffer (pH 8.0) containing sodium deoxycholate are remarkably different from most subfamily I.1 and I.2 members of Pseudomonas lipases expressed as inactive inclusion body formerly described in E. coli. The recombinant lipase (rPFL) was purified to homogeneity by Ni-NTA affinity chromatography and Sephacryl S-200 gel filtration chromatography. The purified lipase was stable in broad ranges of temperatures and pH values, with the optimal temperature and pH value being 55°C and 9.0, respectively. Its activity was found to increase in the presence of metal ions such as Ca2+, Sn2+ and some non-ionic surfactants. In addition, rPFL was activated by and remained stable in a series of water-miscible organic solvents solutions and highly tolerant to some water-immiscible organic solvents. These features render this novel lipase attraction for biotechnological applications in the field of organic synthesis and detergent additives. [Copyright &y& Elsevier]

Abstract: Allografts are currently short for clinical potential recipients. Organs and tissues from pigs could be a potential alternative source for clinical transplantation because of their high similarity in anatomical and physiological aspects. Thrombosis could be a consequence of the immunological response or the physiological incompatibilities in cell and molecular levels across species. Platelets play an essential role in haemostasis and the incompatibility of platelets between pigs and humans could be related to rejection and dysfunction of xenografts. Pig blood components, including plasma, leukocytes, red blood cells and platelets, could induce aggregation of human platelets directly, which then resulted in severe thrombosis after xenotransplantation. On the other hand, the existence of potential incompatibilities in coagulation and fibrinolytic system between pigs and humans in the context of xenotransplantation is an important consideration. Here we reviewed platelet incompatibility between pigs and humans related to thrombosis after xenotransplantation, and contribution of immunosuppressive agents to minimizing thrombosis and rejection. [Copyright &y& Elsevier]

Abstract: Fractional factorial designs are popular and widely used for industrial experiments. Generalized minimum aberration is an important criterion recently proposed for both regular and non-regular designs. This paper provides a formal optimization treatment on optimal designs with generalized minimum aberration. New lower bounds and optimality results are developed for resolution-III designs. Based on these results, an effective computer search algorithm is provided for sub-design selection, and new optimal designs are reported. [Copyright &y& Elsevier]

Our previous field studies suggested that the two chiral centers in the sex pheromone of pink hibiscus mealybug, Maconellicoccus hirsutus, could elicit different male responses. The chiral center in the acid moiety of the pheromone seemed to be more critical than the alcohol portion of the pheromone molecule for attractiveness. The objective of the current study was to test this hypothesis by deploying stereoisomeric blends in pheromone traps. Captures of male M. hirsutus showed that pheromone with the naturally occurring (R)-maconelliyl (S)-2-methylbutanoate and (R)-lavandulyl (S)-2-methylbutanoate [R-S configuration] was most attractive and that pheromone with the unnatural S-S configuration was less attractive. In addition, the RS-R blend (containing R-R and S-R stereoisomers) yielded captures of male M. hirsutus that were comparable to blank controls, and an inhibitory effect was observed when R-R and S-R were combined with naturally occurring R-S blend. These results suggest a unique chirality recognition mechanism; olfactory discrimination among different pheromone stereoisomers depends upon both asymmetric centers. The S configuration on the acid moiety elicits attraction, whereas the R configuration induces inhibition. However, the attractive activity shows some degree of tolerance toward chirality change in the alcohol portion of the pheromone molecules. [ABSTRACT FROM AUTHOR]