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To increase the understanding of how the external environment impact the local industrial development, this study builds a conceptual framework of industrial evolutionary development by integrating evolutionary and developmental theories from the perspective of evolutionary economic geography. This study emphasised the combination of two mechanisms. The first evolutionary mechanism consisting of variation, selection and retention, and the diversity within and between enterprise clusters serves as the starting point for evolution. The external environment selects and retains the most competitive enterprises under the mechanism of selection. The second developmental mechanism is the influence of the external environment on enterprises. The external environment screens and affects the development of firms at and across multiple levels, same level and across levels. Based on the case studies of the e‐sports industry in China, this study finds that technological development has driven the transformation of the e‐sports industry. Additionally, location cost, spatial proximity, local policy, urban strategy and national planning have been identified as crucial factors that influence the location choice of the e‐sports industry. This study highlights the importance of paying more attention to environmental dynamics in the research and practice of industrial evolution. [ABSTRACT FROM AUTHOR]

Flash sintering (FS) is a potentially rapid and low‐cost manufacturing technique for advanced ceramics. There are still many unknowns about ceramic FS, especially for highly conductive high‐temperature ceramics (HTC), which often display decreased bulk conductivity with increasing temperature. This study qualitatively characterizes the flash behavior of highly conductive HTC materials using zirconium nitride (ZrN) as an example. The effects of processing parameters (e.g., DC voltage/electrical field strength, voltage ramp rate, post‐flash holding time, mechanical pressure, sample milling, and choice of electrode materials) on ZrN flash behavior are also qualitatively studied and linked to samples microstructure and hardness. It is observed that best densification was achieved using 5 min Spex‐milled ZrN powder under 25 MPa of applied pressure and constant 8 V DC. The potential mechanism for ZrN FS and the similarity and difference from FS of conventional oxides like YSZ have been proposed based on experimental observations, and the directions for future research are also pointed out. [ABSTRACT FROM AUTHOR]

Traditional polarization converters suffer from drawbacks such as significant thickness and high losses, which limit their practical applications. This study introduces a novel metamaterial structure that combines electromagnetically induced transparency (EIT) with linear polarization conversion to overcome these limitations. By harnessing the properties of EIT, this structure achieves low‐loss polarization conversion. The mechanism behind this is the generation of an EIT effect through the coupling of the light and dark modes. Additionally, this study focuses on introducing a slight vertical polarization symmetry disruption and inducing the excitation of small components within the dipole of the EIT structure to achieve close‐to‐complete cross‐polarization conversion. The effect of asymmetry on the polarization conversion rate is also explored. This study offers an innovative approach to designing low‐loss polarization converters utilizing EIT technology. [ABSTRACT FROM AUTHOR]

Objective: This network meta‐analysis evaluates the efficacy and safety of tirzepatide compared to glucagon‐like peptide‐1 receptor agonists (GLP‐1 RA) and other weight loss drugs in the treatment of overweight and obesity. Methods: MEDLINE, Embase, and Cochrane CENTRAL were searched for randomized controlled trials on tirzepatide, GLP‐1 RA, and weight loss drugs approved by the US Food and Drug Administration. A network meta‐analysis was performed, drawing direct and indirect comparisons between treatment groups. Network diagrams and surface under the cumulative ranking curve analysis were performed for primary (≥5%, ≥10%, ≥15%, absolute weight loss) and secondary outcomes and adverse effects. Results: Thirty‐one randomized controlled trials, involving more than 35,000 patients, were included in this study. Tirzepatide 15 mg ranked in the top three across weight‐related parameters, glycemic profile (glycated hemoglobin), lipid parameters (total cholesterol, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, triglycerides), and blood pressure. Tirzepatide 15 mg had the highest efficacy compared with placebo for achieving ≥15% weight loss (risk ratio 10.24, 95% CI: 6.42–16.34). As compared to placebo, tirzepatide and GLP‐1 RA across all doses had significant increases in gastrointestinal adverse effects. Conclusions: The superiority of tirzepatide and GLP‐1 RA in inducing weight loss and their ability to target multiple metabolic parameters render them promising candidates in the treatment of patients with overweight and obesity. [ABSTRACT FROM AUTHOR]

Alveolar echinococcosis (AE) is a zoonotic parasitic disease, resulting from being infected with the metacestode larvae of the tapeworm Echinococcus multilocularis (E. multilocularis). Novel prophylactic and therapeutic interventions are urgently needed since the current chemotherapy displays limited efficiency in AE treatment. Bioengineered nano cellular membrane vesicles are widely used for displaying the native conformational epitope peptides because of their unique structure and biocompatibility. In this study, four T‐cells and four B‐cells dominant epitope peptides of E. multilocularis with high immunogenicity were engineered into the Vero cell surface to construct a membrane vesicle nanovaccine for the treatment of AE. The results showed that the nanovesicle vaccine can efficiently activate dendritic cells, induce specific T/B cells to form a mutually activated circuit, and inhibit E. multilocularis infection. This study presents for the first time a nanovaccine strategy that can completely eliminate the burden of E. multilocularis. [ABSTRACT FROM AUTHOR]

The lattice thermal conductivity (κph) of metals and semimetals is limited by phonon‐phonon scattering at high temperatures and by electron‐phonon scattering at low temperatures or in some systems with weak phonon‐phonon scattering. Following the demonstration of a phonon band engineering approach to achieve an unusually high κph in semiconducting cubic‐boron arsenide (c‐BAs), recent theories have predicted ultrahigh κph of the semimetal tantalum nitride in the θ‐phase (θ‐TaN) with hexagonal tungsten carbide (WC) structure due to the combination of a small electron density of states near the Fermi level and a large phonon band gap, which suppress electron‐phonon and three‐phonon scattering, respectively. Here, measurements on the thermal and electrical transport properties of polycrystalline θ‐TaN converted from the ε phase via high‐pressure synthesis are reported. The measured thermal conductivity of the θ‐TaN samples shows weak temperature dependence above 200 K and reaches up to 90 Wm−1K−1, one order of magnitude higher than values reported for polycrystalline ε‐TaN and δ‐TaN thin films. These results agree with theoretical calculations that account for phonon scattering by 100 nm‐level grains and suggest κph increase above the 249 Wm−1 K−1 value predicted for single‐crystal WC when the grain size of θ‐TaN is increased above 400 nm. [ABSTRACT FROM AUTHOR]

In this paper, we consider the estimation algorithm of tensor response on vector covariate regression model. Based on projection theory of tensor and the idea of randomized algorithm for tensor decomposition, three new algorithms named SHOLRR, RHOLRR and RSHOLRR are proposed under the low‐rank Tucker decomposition and some theoretical analyses for two randomized algorithms are also provided. To explore the nonlinear relationship between tensor response and vector covariate, we develop the KRSHOLRR algorithm based on kernel trick and RSHOLRR algorithm. Our proposed algorithms can not only guarantee high estimation accuracy but also have the advantage of fast computing speed, especially for higher‐order tensor response. Through extensive synthesized data analyses and applications to two real datasets, we demonstrate the outperformance of our proposed algorithms over the stat‐of‐art. [ABSTRACT FROM AUTHOR]

Rationale: Anlotinib is a multi‐target tyrosine kinase inhibitor, approved in China for treating several cancer types. Dose individualization based on therapeutic drug monitoring (TDM) is a useful tool to reduce toxicity. However, it is not convenient for patients to go to hospital for routine TDM via venous blood sampling at a certain time. Methods: An ultra‐performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method was developed and validated for determination of anlotinib in human plasma and dried blood spot (DBS), characterized by simple sample preparation, high sensitivity, and short analysis time. The assay was validated in the concentration range of 0.2–200 ng/mL in plasma and 5–1000 ng/mL in DBS. This method was applied to monitor anlotinib exposure levels in patients with advanced biliary tract cancer (BTC) and non‐small cell lung cancer (NSCLC). Results: The trough plasma concentration (Ctrough) of anlotinib was highly variable among BTC patients with coefficients of variation (CV) of 47.5%. DBS and venous blood samples were also collected from NSCLC patients to determine whether DBS sampling is a viable alternative sampling approach. Pearson correlation coefficient (R) between DBS and plasma concentration was 0.985. Bland–Altman plot demonstrated that the difference between estimated and measured plasma concentration was −2.9%. And 87% of sample pairs had a maximal deviation of ±20%. Conclusions: Anlotinib exhibits a high inter‐individual variability in plasma exposure, and DBS sampling could be a promising tool for TDM of anlotinib. [ABSTRACT FROM AUTHOR]

Virtual 3D modeling is widely implemented in urban planning and design. To evaluate urban planning modeling, based on existing computer vision models, this article aims to improve performance in the field of human perception analysis for urban street views. In this study, the PSP module extracts detailed features from recognized objects of different sizes, an attention mechanism is applied to solve the problem of large information differences in pictures, and transfer learning technology is used to expand the model to the field of virtual 3D modeling to extract more representative and universal features, similar to how humans perceive street view information. Finally, we obtain a more objective, stable, and accurate neural network model that imitates human perception. This evaluation model converges within the correct interval on the training and validation datasets compared with an evaluation of virtual modeling by a large number of people. [ABSTRACT FROM AUTHOR]

How to satisfactorily implement the public–private partnership (PPP) network is the most important target for infrastructure and public services policymakers. In this article, we elaborate on how project‐ and process‐management styles can combine to deliver a satisfactory PPP. This paper uses a fuzzy‐set qualitative comparative analysis to investigate the relationship between management styles and PPP network outcomes. Specifically, we examine the management tools (i.e. results orientation, control, communication and flexibility) and their joint effects on PPP network outcome. Results show that three combinations of sufficient conditions yield satisfactory PPP network outcomes consisting of project‐ and process‐management styles. We elaborate on how project‐ and process‐management styles can combine to deliver a satisfactory PPP. [ABSTRACT FROM AUTHOR]

Carbon nanogels (CNGs) with dual ability of reactive oxygen species (ROS) imaging and photodynamic therapy have been designed with self‐assembled chemiluminescent carbonized polymer dots (CPDs). With efficient deep‐red/near‐infrared chemiluminescence (CL) emission and distinctive photodynamic capacity, the H2O2‐driven chemiluminescent CNGs are further designed by assembling the polymeric conjugate and CL donors, enabling an in vitro and in vivo ROS bioimaging capability in animal inflammation models and a high‐performance therapy for xenograft tumors. Mechanistically, ROS generated in inflammatory sites or tumor microenvironment can trigger the chemically initiated electron exchange luminescence in the chemical reaction of peroxalate and H2O2, enabling in vivo CL imaging. Meanwhile, part of the excited‐state electrons will transfer to the ambient H2O or dissolved oxygen and in turn lead to the type I and type II photochemical ROS production of hydroxyl radicals or singlet oxygen, endowing the apoptosis of tumor cells and thus enabling cancer therapy. These results open up a new avenue for the design of multifunctional nanomaterials for bioimaging and antienoplastic agents. [ABSTRACT FROM AUTHOR]

Zirconium nitride (ZrN) is a transition metal nitride of great interest due to its excellent physical and chemical properties. This study aims to synthesize ZrN fine powders by a facile and low‐cost urea route that avoids the use of any solvent. ZrCl4 and urea mixtures were heat‐treated at up to 1600˚C in nitrogen gas. The products were characterized by X‐ray diffraction, scanning electron microscopy, transmission electron microscopy, energy‐dispersive X‐ray spectroscopy, and thermogravimetric analysis. The effects of different processing parameters such as metal to urea molar ratio, heat treatment temperature, and dwelling time on the product phase and stoichiometry were studied to understand the synthesis method. In addition, synthesized ZrN powder was consolidated into near fully dense single‐phase bulk ceramic with a homemade flash sintering setup. A constant DC electrical field of ∼80 V/cm and pressure of ∼14 MPa at room temperature triggered flash sintering without pre‐heating, and the entire process finished in 200 s. The composition, microstructure, density, hardness, and oxidation properties of the sintered pellet were also characterized. [ABSTRACT FROM AUTHOR]

Rapid underwater self‐healing elastomers with high mechanical strength at ambient temperature are highly desirable for dangerous underwater operations. However, current room temperature self‐healing materials have shortcomings, such as low healing strength (below megapascal), long healing time (hours), and decay of healing functions in harsh environments (salty, acidic, and basic solutions), limiting their practical applications. Herein, it is introduced water‐stable Debye forces and high‐density nano‐sized physical crosslinking into one network to achieve a stiff yet rapid self‐healing elastomer that can work in harsh aqueous environments. The obtained elastomer possesses a high Young's modulus of 48 MPa (24 times than that of natural elastomer), and it can achieve 90% of maximum mechanical strength healing for 10 s at ambient temperature in all types of harsh aqueous conditions, outperforming three orders of magnitudes in healing speed of reported room‐temperature self‐healing elastomers with Young's modulus over 10 MPa. The new stiff yet rapidly healable elastomers have great potential in emergent repair in urgent and dangerous cases. [ABSTRACT FROM AUTHOR]

Silicon carbide/silicon carbide (SiC/SiC) composites are often used in oxidizing environments at high temperatures. Measurements of the thermal conductance of the oxide layer provide a way to better understand the oxidation process with high spatial resolution. We use time‐domain thermoreflectance (TDTR) to map the thermal conductance of the oxide layer and the thermal conductivity of the SiC/SiC composite with a spatial resolution of 3 μm. Heterodyne detection using a 50‐kHz‐modulated probe beam and a 10‐MHz‐modulated pump suppresses the coherent pick‐up and enables faster data acquisition than what has previously been possible using sequential demodulation. By analyzing the noise of the measured signals, we find that in the limit of small integration time constants or low laser powers, the dominant source of noise is the input noise of the preamplifier. The thermal conductance of the oxide that forms on the fiber region is lower than the oxide on the matrix due to small differences in thickness and thermal conductivity. [ABSTRACT FROM AUTHOR]

Endothelial nitric oxide synthase (eNOS)‐derived nitric oxide (NO) plays a crucial role in maintaining vascular homeostasis. As a hallmark of eNOS activation, phosphorylation of eNOS at Ser1177 induced by activated protein kinase B (PKB/Akt) is pivotal for NO production. The complete activation of Akt requires its phosphorylation of both Thr308 and Ser473. However, which site plays the main role in regulating phosphorylation of eNOS Ser1177 is still controversial. The purpose of the present study is to explore the specific regulatory mechanism of phosphorylated Akt in eNOS activation. Inhibition of Akt Thr308 phosphorylation by a specific inhibitor or by siRNA in vitro led to a decrease in eNOS phosphorylation at Ser1177 and to lower NO concentration in the cell culture medium of HUVECs. However, inhibiting p‐Akt Ser473 had no effect on eNOS phosphorylation at Ser1177. Next, we administered mice with inhibitors to downregulate p‐Akt Ser473 or Thr308 activity. Along with the inhibition of p‐Akt Thr308, vascular p‐eNOS Ser1177 protein was simultaneously downregulated in parallel with a decrease in plasma NO concentration. Additionally, we cultured HUVECs at various temperature conditions (37, 22, and 4 °C). The results showed that p‐Akt Ser473 was gradually decreased in line with the reduction in temperature, accompanied by increased levels of p‐Akt Thr308 and p‐eNOS Ser1177. Taken together, our study indicates that the phosphorylation of Akt at Thr308, but not at Ser473, plays a more significant role in regulating p‐eNOS Ser1177 levels under physiological conditions. [ABSTRACT FROM AUTHOR]

Cell death is an important physiological and pathological phenomenon in multicellular animals and occurs widely in various body's systems. In recent years, researchers have gained a deeper understanding of the mechanisms of necrosis and apoptosis in mammals. In addition, many new forms of lytic regulated cell death (RCD), such as pyroptosis, necroptosis and ferroptosis, have been discovered, thus enhancing our understanding of the molecular mechanisms of programmed cell death (PCD) and the associated signalling pathways as well as their relationship with diseases. However, our understanding of lytic RCD in fish is limited. Recently, some progress has been made regarding the induction conditions, expression of related genes and regulation of lytic RCD in fish. Furthermore, research on the roles of lytic RCD in tissue development, against pathogenic microorganism, inflammatory disease and neurological disease, has also been advanced. Understanding lytic RCD in fish will enable the regulation of its occurrence through human intervention to inhibit disease processes, improve fish health and explore possible countermeasures based on these basic theoretical studies. [ABSTRACT FROM AUTHOR]

In this research, near fully dense single phase bulk multicomponent transition metal nitride (Nb1/3Ta1/3Ti1/3)N1−δ has been successfully synthesized from mixed commercial powders of NbN, TaN and TiN via reaction flash sintering technique. This was performed with an applied pressure of ~ 35 MPa at 25°C under a constant DC electric field (~24‐32 V/cm). The flash event, which is the abrupt increase in current (up to ~ 25.2 A/mm2) and temperature, occurred without preheating. The threshold power dissipation on the sample right before the flash is ~ 0.7 W/mm3. The formation of single phase (Nb1/3Ta1/3Ti1/3)N1−δ random solid solution and its compositional uniformity were confirmed by XRD and EDS, respectively. The effects of ball milling duration and limiting current density on phase formation were studied. Simulation based on Joule heating provides an estimate of the ultimate sample temperature of ~ 1850°C. Vickers hardness of the obtained (Nb1/3Ta1/3Ti1/3)N1−δ is 17.6 ± 0.6 GPa, which is comparable to similarly flash sintered ingredient binary nitrides of TaN and NbN. TGA in air shows that the oxidation resistance of (Nb1/3Ta1/3Ti1/3)N1−δ is better than that of TaN and NbN but inferior to TiN. The study demonstrates that reaction flash sintering can be a highly efficient technique for synthesizing bulk multicomponent ceramics for both material fundamental investigations and application development. [ABSTRACT FROM AUTHOR]

When attacked by herbivores, plants emit volatiles to attract parasitoids and predators of herbivores. However, our understanding of the effect of plant volatiles on the subsequent behaviour of conspecific parasitoids when herbivores on plants are parasitized is limited. In this study, rice plants were infested with gravid females of the brown planthopper (BPH) Nilaparvata lugens for 24 hr followed by another 24 hr in which the BPH eggs on plants were permitted to be parasitized by their egg parasitoid, Anagrus nilaparvatae; volatiles from rice plants that underwent such treatment were less attractive to subsequent conspecific parasitoids compared to the volatiles from plants infested with gravid BPH females alone. Chemical analysis revealed that levels of JA and JA‐Ile as well as of four volatile compounds—linalool, MeSA, α‐zingiberene and an unknown compound—from plants infested with BPH and parasitized by wasps were significantly higher than levels of these compounds from BPH‐infested plants. Laboratory and field bioassays revealed that one of the four increased chemicals—α‐zingiberene—reduced the plant's attractiveness to the parasitoid. These results suggest that host plants can fine‐tune their volatiles to help egg parasitoids distinguish host habitats with parasitized hosts from those without. We demonstrate that the parasitism of the brown planthopper (BPH) eggs by Anagrus nilaparvatae increased levels of four volatile chemicals emitted from BPH gravid female‐infested rice plants, and these increased volatiles decreased the attractiveness of the host plant to the conspecific parasitoid. Our results suggest that host plants can alter their volatiles to help egg parasitoids discriminate host habitats with parasitized hosts from those without parasitized hosts. [ABSTRACT FROM AUTHOR]

Objective: To investigate the molecular mechanism of Progranulin (PGRN) in promoting osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in inflammatory environment. Background: Progranulin is an antagonist of tumor necrosis factor (TNF) receptors (TNFRs) and is known to promote inflammatory periodontal bone defect regeneration. Methods: TNFR1‐ and TNFR2‐silenced hPDLSCs designed as hPDLSCs‐sh‐TNFR1 and hPDLSCs‐sh‐TNFR2 were cultured with osteoinductive medium containing TNF‐α and (or) PGRN. Immunofluorescence, quantitative real‐time PCR, and western blot were used to, respectively, detect expressions of TNFR1\TNFR2 and osteogenic differentiation markers as well as phosphorylation level in NF‐κB\MAPK‐related pathways. Results: Immunofluorescence and real‐time PCR showed that TNFR1 and TNFR2 positively expressed in hPDLSCs. TNF‐α stimulation could significantly decrease the expressions of ALP and RUNX2 in hPDLSCs, whereas PGRN treatment could significantly enhance their expressions, and reverse TNF‐α‐mediated expression suppression of ALP and RUNX2 in hPDLSCs. In hPDLSCs‐sh‐TNFR1, TNF‐α mediated osteogenic inhibition decreased, but both TNF‐α + PGRN and alone PGRN significantly promoted expression of ALP and RUNX2. PGRN significantly enhanced expression of P‐ERK1/2 and P‐JNK, while corresponding inhibitors eliminated PGRN‐stimulated osteogenic differentiation. In hPDLSCs‐sh‐TNFR2, no significant difference existed in osteogenic markers and P‐JNK expression between the PGRN group and the control group. However, PGRN still activated P‐ERK1/2 expression. Besides, PGRN antagonized TNF‐α‐enhanced NF‐κB P65 expression. Conclusion: Progranulin promotes osteogenic differentiation of hPDLSCs via TNFR1 to inhibit TNF‐α‐sensitized NF‐κB and via TNFR2 to activate JNK signaling. The mechanism by which PGRN activates ERK signaling remains to be explored. [ABSTRACT FROM AUTHOR]

To solve the negative sequence (NS) problem and enhance the regenerative braking energy (RBE) utilisation in an electrified railway, a novel energy storage traction power supply system (ESTPSS) is proposed in this study. In the new system, a power flow controller is adopted to compensate for the NS, and a super‐capacitor energy storage system is applied to absorb and release the RBE. In addition, through the cooperation of each part, the proposed power supply system can provide continuous power without neutral sections. The NS compensation principle of the new system is illustrated. Depending on the operational state of the traction load, the control model is presented for different working patterns, including a regenerative braking pattern, a peak clipping pattern and a valley filling pattern. Moreover, a hierarchical control strategy including upper energy management and low‐layer converter control is proposed, which effectively coordinate switches between the different working patterns. Finally, the validity of the control method and the excellent performance of the system are demonstrated by a case study. The results indicate that compared to a conventional TPSS, the ESTPSS increases the RBE utilisation of the system by 83%. [ABSTRACT FROM AUTHOR]

The aggregation‐induced electrochemiluminescence (AIECL) of carboranyl carbazoles in aqueous media was investigated for the first time. Quantum yields, morphologies, and particle sizes were observed to determine the electrochemiluminescence (ECL) performance of these aggregated organic dots (ODs). All compounds exhibit much higher ECL stability and intensity than the carborane‐free compound, demonstrating the essential role of the carboranyl motif. Moreover, the results of cyclic voltammetry (CV) suggest that oxidation/reduction reactions take place at the carboranyl motif. The excited states of ODs were proposed to be generated by the mechanism of surface state transitions. More importantly, these compounds show a reductive–oxidative mechanism in contrast to other organic materials that show oxidative–reductive mechanisms. Our experiments and data have established the relation between AIE organic structures and ECL properties that has a strong potential for biological and diagnostic applications. Carborane‐based AIEgens: The reductive–oxidative aggregation‐induced electrochemiluminescence (AIECL) of carboranyl carbazoles in air‐saturated aqueous media was investigated. Mechanistic studies indicate that the carboranyl motif plays vital role in the high ECL intensity and stability of the aggregates. [ABSTRACT FROM AUTHOR]

Abstract: Fine ultrahigh‐temperature ceramic (UHTC) powders have found very important applications in many fields. In this work, a facile high‐temperature spray pyrolysis (HTSP) approach is implemented for the synthesis of HfC and TaC UHTC nanopowders starting from organic solvent (e.g., ethanol or 1‐pentanol) solutions of metal precursors (HfCl4 or TaCl5). It is proposed that, during HTSP, the precursor solution droplets would continuously undergo rapid drying, thermolysis (i.e., removal of low molecular weight species such as H2, H2O, and CO), and finally in situ carbothermal reduction (CTR) process to give rise to metal carbide nanopowders. The as‐obtained materials are shown by SEM as uniform and separated nanoparticles (~90 nm), whereas TEM reveals the carbide (e.g., HfC) nanoparticles are actually even smaller (~10‐20 nm) and embedded in amorphous carbon from excess solvent decomposition. It is found that among different processing parameters, the organic solvent used and the metal precursor concentration could largely influence the formation of metal carbide. In addition, lower HTSP temperatures (≤~1500°C for HfC) only lead to oxide‐carbon mixtures while higher temperatures (≥~1650°C) promote carbide formation. The HTSP method developed in this work is simple, low‐cost and efficient, and could potentially be optimized further for future large‐scale manufacturing of ultrafine UHTC nanopowders. [ABSTRACT FROM AUTHOR]

Abstract: Ta1−xHfxB2 material is attractive for various aerospace applications. In this study, 2 low‐cost approaches were adopted to synthesize nanocrystalline Ta0.5Hf0.5B2 solid solution and related composite powders. The first was based on carbothermal reduction reaction (CTR) of intimately mixed tantalum‐hafnium‐boron oxide(s) and carbon obtained from aqueous solution processing of TaCl5, HfCl4, B2O3, and sucrose as precursors. It was found that when using this method, due to the low solubility of each other for Ta2O5 and HfO2 and the difference in reactivity of those 2 oxides with carbon (as well as B2O3), individual TaB2 (‐rich) and HfB2 phases always form separately. Those borides tend to remain phase separated due to the slow inter‐diffusion between them. However, it was observed that addition of copper “catalyst” noticeably accelerates the inter‐diffusion and the solid solution formation. The second approach was based on alkali metal reduction reaction, in which TaCl5 and HfCl4 are directly reacted with sodium borohydride (NaBH4). This method yields a single phase Ta0.5Hf0.5B2 solid solution nanopowders in one step at much lower temperatures (e.g., 700°C) by avoiding the oxides formation and the associated phase separation of individual borides as observed in the CTR‐based process. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the incidence of pulmonary thromboembolism (PTE) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD),and to evaluate the efficacy and safety of low-dose urokinase (UK) thrombolysis therapy when treating hemodynamically stable AECOPD patients with acute PTE (AECOPD-PTE). Methods: A total of 419 AECOPD patients, including 96 AECOPD-PTE, were enrolled. A total of 30 AECOPD-PTE patients were collected retrospectively, and 66 AECOPD-PTE patients were prospectively divided into anticoagulation-only, lowdose UK and standard-dose UK groups. Follow-up 1 year, we evaluated the efficacy and safety of low-dose UK therapy for hemodynamically stable AECOPD-PTE patients. Results: The incidence of PTE in AECOPD patients was 22.9% (96/419), which increased with COPD severity degree ranging from 3.5% (2/57) in mild, 13.6% (19/ 140) in moderate and 33.8% (75/222) in severe subgroups (P < .05). In the prospective study, the total effective rate of low-dose UK group 97.2% (35/36) was higher than that in anticoagulation 75.0% (12/16) and standard-dose UK group 78.6% (11/ 14) respectively (P < .05). In the follow-up, the adverse events rate in low-dose UK group 8.3% (3/36) was significantly lower than that in anticoagulation group 25.0% (4/16) and standard-dose UK group 71.4% (10/14) respectively (P < .05). In addition, the mean PTE recurrence time of low-dose UK group (9.0 ± 0) months was longer than anticoagulation group (2.0 ± 1.41) months (P < .05). AECOPD relapse time in anticoagulation, low-dose UK and standard-dose UK groups corresponding to (8.5 ± 2.12), (9.0 ± 0) and (8.8 ± 3.40) months were compared with no significant difference (P > .05). Conclusions: The incidence of PTE in AECOPD patients was 22.9%, especially with higher occurrence rate in severe COPD. Compared with anticoagulation-only therapy, low-dose UK treatment (500 000 IU/day for 5-7 days) could obtain a better efficacy and safety in hemodynamically stable AECOPD patients with acute PTE, corresponding with a higher effective rate (97.2%) and lower adverse events rate (8.3%) respectively. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To explore the diagnostic value of joint detection of soluble B7‐H4 (sB7‐H4) and carcinoembryonic antigen (CEA) in identifying malignant pleural effusion (MPE) from benign pleural effusion (BPE). Methods: A total of 97 patients with pleural effusion specimens were enrolled from The First Affiliated Hospital of Zhengzhou University between June 2014 and December 2015. All cases were categorized into malignant pleural effusion group (n = 55) and benign pleural effusion group (n = 42) according to etiologies. Enzyme‐linked immunosorbent assay was applied to examine the levels of sB7‐H4 in pleural effusion and meanwhile CEA concentrations were detected by electro‐chemiluminescence immunoassays. Receiver operating characteristic (ROC) curve was established to assess the diagnostic value of sB7‐H4 and CEA in pleural effusion. The correlation between sB7‐H4 and CEA levels was analyzed by Pearson's product‐moment. Results: The concentrations of sB7‐H4 and CEA in MPE exhibited obviously higher than those of BPE ([60.08 ± 35.04] vs. [27.26 ± 9.55] ng/ml, P = .000; [41.49 ± 37.16] vs. [2.41 ± 0.94] ng/ml, P = .000). The AUC area under ROC curve of sB7‐H4 and CEA was 0.884 and 0.954, respectively. Two cutoff values by ROC curve analysis of sB7‐H4 36.5 ng/ml and CEA 4.18 ng/ml were obtained, with a corresponding sensitivity (81.82%, 87.28%), specificity (90.48%, 95.24%), accuracy (85.57%, 90.72%), positive predictive value (PPV) (91.84%, 96.0%), negative predictive value (NPV) (79.17%, 85.11%), positive likelihood ratio (PLR) (8.614, 18.327), and negative likelihood ratio (NLR) (0.201, 0.134). When sB7‐H4 and CEA were combined to detect pleural effusion, it obtained a higher sensitivity 90.91% and specificity 97.62%. Furthermore, correlation analysis result showed that the level of sB7‐H4 was correlated with CEA level (r = .770, P = .000). Conclusions: sB7‐H4 was a potentially valuable tumor marker in the differentiation between BPE and MPE. The combined detection of sB7‐H4 and CEA could improve the diagnostic sensitivity and specificity for MPE. [ABSTRACT FROM AUTHOR]

Synthesis of single-phase tantalum hafnium carbide (Ta xHf1− xC, 0< x<1) solid solution nanopowders via carbothermal reduction ( CTR) reaction is complicated due to the difference in reactivity of parent oxides with carbon and presence of a miscibility gap in TaC-HfC phase diagram below ~887°C. These can lead to phase separation, ie, formation of two distinct carbides instead of a single-phase solid solution. In this study, nanocrystalline Ta xHf1− xC powders were synthesized via CTR of finely mixed amorphous tantalum-hafnium oxide(s) and carbon obtained from a low-cost aqueous solution processing of tantalum pentachloride, hafnium tetrachloride, and sucrose. Particular emphasis was given to investigate the influences of starting compositions and processing conditions on phase separation during the formation of carbide phase(s). It was found that due to the immiscibility of Ta-Hf oxides and relatively fast CTR reaction, individual nano-HfC and TaC phases form quickly (within minutes at 1600°C), then go through interdiffusion forming carbide solid solution phase. Moreover, the presence of excess carbon in the CTR product slows down the interdiffusion of Ta and Hf dramatically and delays the solid solution formation, whereas DC electrical field (applied through the use of a spark plasma sintering system) accelerates interdiffusion significantly but leads to more grain growth. [ABSTRACT FROM AUTHOR]

The relative importance of regulation at the mRNA versus protein level is subject to ongoing debate. To address this question in a dynamic system, we mapped proteomic and transcriptomic changes in mammalian cells responding to stress induced by dithiothreitol over 30 h. Specifically, we estimated the kinetic parameters for the synthesis and degradation of RNA and proteins, and deconvoluted the response patterns into common and unique to each regulatory level using a new statistical tool. Overall, the two regulatory levels were equally important, but differed in their impact on molecule concentrations. Both mRNA and protein changes peaked between two and eight hours, but mRNA expression fold changes were much smaller than those of the proteins. mRNA concentrations shifted in a transient, pulse-like pattern and returned to values close to pre-treatment levels by the end of the experiment. In contrast, protein concentrations switched only once and established a new steady state, consistent with the dominant role of protein regulation during misfolding stress. Finally, we generated hypotheses on specific regulatory modes for some genes. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the feasibility of creating extracellular matrix (ECM) scaffolds from mesenchymal stem cells. Bone marrow mesenchymal stem cell (BMSC)-derived ECM (BMSC-dECM) scaffolds were fabricated by lyophilization after crosslinking, without using a decellularization process. Acellular porcine chondrocyte-derived ECM (AC-dECM) scaffolds were used as a control. The surface morphology, internal structure, water uptake ratio, mechanical properties, and biocompatibility of the scaffolds, as well as the in vitro behavior of cells grown on the scaffolds were examined and compared between the two scaffold types. For the BMSC-dECM scaffolds, the average pore size was 304.4 ± 108.2 μm, average porosity was 93.3% ± 4.5%, average compressive modulus was 6.8 ± 1.5 kPa, and average water uptake ratio exceeded 20. The BMSC-dECM scaffolds supported the in vitro attachment and proliferation of cells, with these aspects likely being comparable to those of the AC-dECM scaffolds. The findings of this preliminary study highlight the potential utility of BMSC-derived ECM scaffolds for future cartilage tissue-engineering applications. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 670-678, 2015. [ABSTRACT FROM AUTHOR]

ABSTRACT Phoxim ( O, O-diethyl O-(alpha-cyanobenzylideneamino) phosphorothioate) is a powerful organophosphorus pesticide with high potential for Bombyx mori larvae of silkworm exposure. However, it is possible that during the phoxim metabolism, there is generation of reactive oxygen species (ROS) and phoxim may produce oxidative stress and neurotoxicity in an intoxicated silkworm. Titanium dioxide nanoparticles (TiO2 NPs) pretreatment has been demonstrated to increase antioxidant capacity and acetylcholinesterase (AChE) activity in organisms. This study was, therefore, undertaken to determine phoxim-induced oxidative stress and neurotoxicity to determine whether phoxim intoxication alters the antioxidant system and AChE activity in the B. mori larval midgut, and to determine whether TiO2 NPs pretreatment attenuates phoxim-induced toxicity. The findings suggested that phoxim exposure decreased survival of B. mori larvae, increased malondialdehyde (MDA), carbonyl and 8-OHdG levels, and ROS accumulation in the midgut. Furthermore, phoxim significantly decreased the activities of AChE, superoxide dismutase (SOD), ascorbate peroxidase (APX), glutathione reductase (GR), glutathione- S-transferase (GST), and levels of ascorbic acid (AsA), reduced glutathione (GSH), and thiol in the midgut. TiO2 pretreatment, however, could increase AChE activity, and remove ROS via activating SOD, CAT, APX, GR, and GST, and accelerating AsA-GSH cycle, thus attenuated lipid, protein, and DNA peroxidation and improve B. mori larval survival under phoxim-induced toxicity. Moreover, this experimental system would help nanomaterials to be applied in the sericulture. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1355-1366, 2014. [ABSTRACT FROM AUTHOR]

Numerous studies have demonstrated lanthanide (Ln) accumulation in the liver, and the corresponding damage; however, very little work has been done to evaluate the relationship between Ln-induced liver injury and its gene expression profile in mice. In this study, liver injury and gene-expressed profiles in male mice induced by oral administration of CeCl3 (2 mg/kg) via gavage for 90 consecutive days were investigated. The results showed that cerium accumulation, liver inflammation, and hepatocyte necrosis were observed. CeCl3 exposure significantly decreased the counts of white blood cells, lymphocyte, and platelet, the reticulocyte count (Ret) and neutrophilic granulocyte percentages as well as A/G ratio, whereas markedly increased the activities of alkaline phosphatase, lactate dehydrogenase, and cholinesterase, and the concentrations of triglycerides and total cholesterol. Furthermore, microarray results of liver showed that the differential expression of 675 known function genes involved in immune/inflammation response, apoptosis, metabolic process, cell cycle, cell proliferation, cytoskeleton, oxidative stress, signal transduction, transcription, translation, and transportation in CeCl3 exposed livers, respectively. Specifically, the significant downregulation of Nt5e led to inflammation, overexpressed Cyp4a12a and great suppression of Cdkn1a resulted in hepatocyte apoptosis, marked elevation of Cel, and Cyp7b1 expression caused the metabolic disorders in mouse liver after long-term CeCl3 exposure. Therefore, these genes may be in great relation to liver damages induced by exposure to CeCl3. © 2012 Wiley Periodicals, Inc. Environ Toxicol 29: 837-846, 2014. [ABSTRACT FROM AUTHOR]

Background Although molecular mechanism of growth differentiation factor 15 ( GDF15) in tumorigenesis of oral squamous cell carcinoma ( OSCC) is not clear, the diagnostic and prognostic value of serum GDF15 detection has been noticed. However, serum GDF15 levels in patients with oral leukoplakia and GDF15 as a potential predictive biomarker for response to induction chemotherapy in patients with OSCC have not been reported. Methods Pretreatment serum GDF15 concentration was detected using an enzyme-linked immunosorbent assay in 30 healthy persons, 24 patients with oral leukoplakia, and 60 patients with OSCC. Results Serum GDF15 concentration was significantly higher in patients with oral leukoplakia and OSCC, compared with healthy controls ( F = 13.701, df = 2, P < 0.001). From a diagnostic standpoint, a cutoff value of 346.9 ng/l of serum GDF15 concentration was calculated using receiver operating characteristic curve, with a sensitivity of 0.750, specificity of 0.867, Youden's Index of 0.617, and area under curve of 0.863. From a prognostic standpoint, patients with serum GDF15 concentration <346.9 ng/l had an improved 3-year disease-free survival rate (64.3% vs 56.5%) compared with those above 346.9 ng/l, but the difference was not statistically significant. A decreased concentration of GDF15 (<346.9 ng/l) showed a predictive trend toward an improved response to induction chemotherapy compared with elevated concentration with clinical response rates of 100% and 71.4%, respectively, but the difference was not significant. Conclusion Elevated GDF15 level may be not only a diagnostic biomarker for oral leukoplakia, but also a prognostic/predictive biomarker associated with decreased survival and diminished response to induction chemotherapy for patients with OSCC. [ABSTRACT FROM AUTHOR]

In an effort to investigate the effects of exposure to lanthanoids (Ln) on the immune response and liver function, mice were orally exposed to LaCl3, CeCl3, and NdCl3 at 2, 10, and 20 mg/kg doses for 30 days, respectively; lymphocyte counts, serum IgM level, hematological indices, biochemical parameters of liver functions, and histopathological changes in Ln3+-treated mice were assessed. Indeed, 20 mg/kg Ln3+ significantly inhibited mice growth and reduced the counts of white blood cells, platelets, and reticulocyte in mice blood. Specifically, in these Ln3+-treated mice, CD3+, CD4+, CD8+, CD19+ and NK cells, and CD4+/CD8+ ratio as well as serum IgM level were decreased. Furthermore, liver function was disrupted, as evidenced by the increased alanine aminotransferase, total bilirubin, total bile acid and triglycerides, and the decreased glucose and ratio of albumin to globulin. The cytoarchitecture damage and fatty degeneration in liver caused by Ln3+ at 20 mg/kg dose were also observed. Our findings showed that exposure to Ln affected the cell and humoral immunity and disturbed liver function in mice. In addition, Ce3+ was found to exhibit higher toxicity than La3+ and Nd3+. © 2011 Wiley Periodicals, Inc. Environ Toxicol 29: 64-73, 2014. [ABSTRACT FROM AUTHOR]

Nanoparticulate titanium dioxide (nano-TiO2) is a widely used powerful nanoparticulate material with high stability, anticorrosion, and photocatalytic property. However, it is possible that during nano-TiO2 exposure, there may be negative effects on cardiovascular system in intoxicated mice. The present study was therefore undertaken to determine nano-TiO2-induced oxidative stress and to determine whether nano-TiO2 intoxication alters the antioxidant system in the mouse heart exposed to 2.5, 5, and 10 mg/kg body weight nano-TiO2 for 90 consecutive days. The findings showed that long-term exposure to nano-TiO2 resulted in obvious titanium accumulation in heart, in turn led to sparse cardiac muscle fibers, inflammatory response, cell necrosis, and cardiac biochemical dysfunction. Nano-TiO2 exposure promoted remarkably reactive oxygen species production such as superoxide radicals, hydrogen peroxide, and increased malondialdehyde, carbonyl and 8-OHdG levels as degradation products of lipid, protein, and DNA peroxidation in heart. Furthermore, nano-TiO2 exposure attenuated the activities of antioxidative enzymes, such as superoxide dismutase, ascorbate peroxidase, glutathione reductase, glutathione-S-transferase, and levels of antioxidants including ascorbic acid, glutathione, and thiol in heart. Therefore, TiO2 NPs exposure may impair cardiovascular system in mice, and attention should be aroused on the application of nano-TiO2 and their potential long-term exposure effects especially on human beings. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 3238-3246, 2013. [ABSTRACT FROM AUTHOR]

To investigate the molecular mechanism of inflammatory response in the mouse liver caused by exposure to CeCl3, we measured the liver indices, and cerium content, evaluated the liver histopathological section, detected serum biochemical parameters of liver function, and the immunoglobulin M (IgM) content, analyzed the liver mRNA and protein expression levels of Toll-like receptor 2, 4 (TLR2, TLR4), and inflammatory cytokines in liver using real-time quantitative reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay. The results showed that exposure to CeCl3 decreased body weight and caused cerium accumulation in the mouse liver and histopathological changes of liver (such as inflammatory cell infiltration). Furthermore, biochemical assays suggested that CeCl3 could promote the activities of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, lactate dehydrogenase, pseudocholinesterase, and leucine aminopeptidase, decrease serum IgM, upregulate the levels of TLR2, TLR4, nuclear factor-κB (NF-κB), NF-κBp52, NF-κBp65, NF-κB-inducing kinase (NIK), IκB kinase α (IKK-α), IκB kinase β (IKK-β), and tumor necrosis factor-α (TNF-α) expression, and suppress NF-κB-inhibiting factor (IκB) and interleukin-2 (IL-2) expression in liver. Taken together, the inflammation of mice liver caused by exposure to CeCl3 might be closely associated with the alteration of inflammatory cytokine expressions in the mouse liver, the signal-transducing events happening in CeCl3-induced macrophages of liver sequentially might occur via activation of TLRs→TNF-α→NIK→IκB kinase (including IKK1, IKK2)→NF-κB (including NF-κBP52, NF-κBP65)→ inflammation. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013. [ABSTRACT FROM AUTHOR]

Experimental studies have demonstrated that lanthanides could impair cognitive functions of children and animals, but very little is known about the hippocampal apoptosis and its molecular mechanism. The study investigated the signal pathway of hippocampal apoptosis induced by intragastric administration of CeCl3 for 60 consecutive days. It showed that cerium had been significantly accumulated in the mouse hippocampus, and CeCl3 caused hippocampal apoptosis and impairment of spatial recognition memory of mice. CeCl3 effectively activated caspase-3 and -9, inhibited Bcl-2, and increased the levels of Bax and cytochrome c, promoted accumulation of reactive oxygen species in the mouse hippocampus. It implied that CeCl3-induced apoptosis in the mouse hippocampus could be triggered via mitochondrion-mediated pathway. Our findings suggest the need for great caution to handle the lanthanides for workers and consumers. © 2011 Wiley Periodicals, Inc. Environ Toxicol 2012. [ABSTRACT FROM AUTHOR]

Exposure to titanium dioxide nanoparticles (TiO2 NPs) elicits an adverse response such as oxidative damage. The molecular targets of TiO2 NPs remain largely unidentified. In the present study, the function and signal pathway of nuclear factor erythroid 2 related factor 2 (Nrf2) in protection against TiO2 NPs-induced oxidative stress in the mouse lung were investigated. Mice were exposed to 10 mg/kg body weight by an intratracheal administration for 15-90 days. With increasing exposed terms, TiO2 NPs were significantly accumulated and increased the reactive oxygen species (ROS) production in lung, which resulted in severe pulmonary edema, inflammatory response and pneumonocyte apoptosis for 90 days. Furthermore, TiO2 NPs exposure could greatly induce expression of Nrf2, heme oxygenase 1 (HO-1), and glutamate-cysteine ligase catalytic subunit (GCLC) from 15-day to 75-day exposure, whereas 90-day exposure caused significant decreases of three factors expression levels in lung. Our findings imply that the induction of Nrf2 expression is an adaptive intracellular response to TiO2 NPs-induced oxidative stress in the mouse lung, and that Nrf2 is protective against TiO2 NPs-induced pulmonary damages during certain exposure terms. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 100A:2554-2562, 2012. [ABSTRACT FROM AUTHOR]

J. Neurochem. (2012) 121, 135-145. Abstract Although the pathological role of presenilin-1 mutation in early onset familial Alzheimer's disease has been widely studied, few focused on how the presenilin-1 mutations result in memory impairment and tau hyperphosphorylation. In the present study, we expressed human Val97Leu mutant presenilin-1, which is reported in Chinese pedigrees by our group, in transgenic mice and found that the mutant presenilin-1 induced spatial memory deficit and tau hyperphosphorylation at PHF-1, pS199/202, pT231 and pS396 epitopes, but not at pS214 and pS422 epitopes. Pearson analysis showed that the memory deficit was only significantly correlated with tau phosphorylation level at PHF-1, pS199/202, pT231 and pS396 epitopes. Additionally, the hyperphosphorylated tau and tangle-like argentophilic structures were detected at CA3 and CA4, but not CA1, region of hippocampus, and we also found tangle-like structure and wizened degenerative neurons in frontal cortex. We demonstrated the tau hyperphosphorylation at the same epitopes in N2a cells expressing the mutant presenilin-1, which is caused by inhibition of phosphoinositol-3 kinase/Akt and activation of glycogen synthase kinase-3 specifically. Our data demonstrated that human Val97Leu mutant presenilin-1 causes spatial memory deficit in mice and increases tau phosphorylation level in glycogen synthase kinase-3-dependent manner. [ABSTRACT FROM AUTHOR]

To understand the chronic spleen injury induced by intragastric administrations with 2.5, 5, and 10 mg kg−1 body weight titanium dioxide nanoparticles (TiO2 NPs) for 90 consecutive days, histopathological and ultrastructure changes, hematological parameters, lymphocyte subsets, the inflammatory, and apoptotic cytokines in the mouse spleen were investigated. Our findings indicate that TiO2 NPs exposure results in the significant increase in the spleen indices, histopathological changes, and splenocyte apoptosis in spleen. Especially, in these TiO2 NPs-treated mice, immunoglobulin, blood cells, platelets, hemoglobin, lymphocyte subsets (such as CD3, CD4, CD8, B cell, natural killer cell) of mice were significantly decreased. Furthermore, TiO2 NPs exposure can significantly increase the levels of nucleic factor-κB, tumor necrosis factor-α, macrophage migration inhibitory factor, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, interleukin-18, interleukin-1β, cross-reaction protein, transforming growth factor-β, interferon-γ, Bax, and CYP1A1 expression, whereas decrease the levels of Bcl-2 and heat shock protein 70 expression. These findings suggest that long-term exposure to low dose TiO2 NPs may result in spleen injury and reduction of immune capacity, TiO2 NP-induced injury in spleen may result from alteration of inflammatory and apoptotic cytokines expression, and workers and consumers should take great caution when handling nanomaterials. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2012. [ABSTRACT FROM AUTHOR]

Summary [ABSTRACT FROM AUTHOR]

The protein phosphatase 1 catalytic subunit (PP1c) and the protein phosphatase 2B (PP2B or calcineurin) catalytic subunit (CNA) contain nonconserved N-terminal regions followed by conserved phosphatase cores. To examine the role of the N-termini of these two phosphatases, we substituted the residues 1–8 of PP1c with residues 1–42 of CNA, which is designated CNA(1-42)-PP1(9-330). The activities of CNA(1-42)-PP1(9-330) were similar to those of PP2B and different from those of PP1. The chimera was at least fourfold less sensitive to inhibition by okadaic acid, but was stimulated by nickel ions and chlorogenic acid, characteristics of PP2B not of PP1. These observations suggest that the N-terminus of CNA shifts the properties of PP1 toward those of PP2B. Our findings provide evidence that the nonconserved N-terminus of PP2B not only functions as important regulatory domain but also confers itself particular characteristics. This region may be targeted for regulation of PP2B activities in vivo. © 2008 IUBMB IUBMB Life, 61(2): 178–183, 2009 [ABSTRACT FROM AUTHOR]