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This paper proposed to use cross wedge rolling (CWR) to manufacture sintered TC4 (S-TC4) titanium alloy blade preform prepared by powder metallurgy technology. The hot uniaxial compression tests, CWR experiments, and numerical simulation were carried out to investigate the influence of forming parameters on microstructure evolution. The results showed that the pattern of stress–strain curve is typical featured of work hardening and dynamic softening, and the Arrhenius equation was determined to describe the high-temperature flow behavior of the studied S-TC4 alloy. In regard to microstructure evolution, the volume fraction of alpha phase f α increases and then decreases radially from inside to outside, and the lamellar alpha phase was equiaxialized by to the shear and torsion stress. And increasing the initial forming temperature T was not conducive to the preservation of the alpha phase, and both the volume fraction of alpha phase fα and average thickness of lamellar alpha phase lα are negatively correlated with the rolling speed n and area reduction φ . Moreover, the maximum initial forming temperature, rolling speed, and area reduction are 940 °C, 10 r/min, and 60%, respectively, in order to achieve the best match between strong plasticity and thermal. [ABSTRACT FROM AUTHOR]

Cross wedge rolling process provides a new way with short production chain and precise control for high-performance blade preforming used in aeroengine, but the issue of central damage needs to be paid attention and investigated. Therefore, this paper aims to understand the formation mechanism of central damage on CWR of GH4169 alloy. The uniaxial hot tensile test and CWR experiments were carried out to explore the high-temperature deformation behavior of GH4169 alloy, as well as the central damage of GH4169 alloy CWR process. Moreover, the finite element model was established and used to analyze the evolution of stress and strain at different position. The results showed that central part of the workpiece is in the state of higher stress triaxiality η, which is easy to cause damage. And the micro-holes in the center of workpiece mainly nucleated around the detached NbC carbide. Meanwhile, the first principal stress σ 1 and the maximum shear stress τ max are the dominant factors which affect the central damage. Therefore, a novel damage criterion suitable for CWR of GH4169 alloy was developed with considering the effect of stress triaxiality η and the sensitivities of deformation temperature and strain rate on the central damage evolution. In addition, initial forming temperature T0 is the most important factor affecting the central damage, and the maximum area reduction φ and rolling speed n are related to the initial deformation temperature T0. And in order to inhibit the damage, the initial forming temperature should be controlled below 1020℃, and the area reduction and rolling speed should not be higher than 55% and 10r/min, respectively. [ABSTRACT FROM AUTHOR]

Blades are important parts of aero-engines, and their manufacturing technology directly affects the preparation level and development speed of aero-engines. In view of the many problems existing in the current blade preforming process, this paper proposes a potential way to prepare blade preforms by using cross wedge rolling (CWR). Furthermore, considering the shape characteristics of the blade, a blade preform with an elliptical section formed by CWR was thoroughly investigated. The roll's profile curve is of significant importance to forming quality, and its equation was deduced based on the plane meshing principle between the roll and the rolling piece and verified by finite element (FE) analysis and CWR experiments on a homemade platform. Meanwhile, the accuracy of the established FE model was quantitatively tested and used to study the forming limit expressed by eccentricity e, and the forming limit was approximately 0.8 (i.e., e ≤ 0.8). Based on this, a blade preform for an aero-engine compressor was designed with two elliptical sections, and it was well formed by the FE model, which verified the feasibility; these research results can also be extended and applied to the preform of other nonrotating parts and other materials. [ABSTRACT FROM AUTHOR]

Background: Patients with brain oligometastases have better prognosis than those with synchronous extracranial metastases in non‐small cell lung cancer (NSCLC). However, studies focusing on intracranial‐only recurrence after curative surgery remained scarce. This study aimed to explore distinct features of patients with exclusive brain relapse after resection of lung adenocarcinoma. Methods: Records were retrospectively reviewed of 2809 patients who had complete resection and pathologically confirmed stage IB‐IIIA NSCLC in our hospital from October 2012 to September 2019. Patients were enrolled if they were adenocarcinoma and developed intracranial recurrence thereafter. They were divided into two groups depending on whether they had synchronous extracranial metastases. Clinical and pathological features of patients enrolled were collected and compared between groups. Results: Ninety‐seven lung adenocarcinoma patients with intracranial recurrences were enrolled. The median follow‐up time was 40 months. Fifty patients (51.5%) had brain oligometastases and 47 patients had synchronous extracranial metastases (ECM). Multivariate logistic regression suggested EGFR‐sensitive mutation and male sex were positively correlated to brain‐only recurrence (OR = 2.59, 95%CI 1.04–6.84 and OR = 2.58, 95% CI 1.05–6.75), while higher clinical stage was associated with synchronous ECM (stage II (OR = 0.33, 95%CI 0.09–1.14) or stage IIIA (OR = 0.54, 95%CI 0.20–1.38) versus stage I). No other pathological feature (lymphovascular invasion, visceral pleural invasion, low tumor differentiation, etc.) or adjuvant chemotherapy was associated with intracranial‐only relapse after complete resection of primary tumor. Conclusion: Among patients with brain relapse after resection of lung adenocarcinoma, patients with EGFR mutations might have intracranial relapse only without synchronous extracranial metastases. Further prospective studies are warranted to verify this. [ABSTRACT FROM AUTHOR]

KDP and ADP crystals doped with different concentrations of Fe3+ ions were grown by the "point seed" technique and some KDP crystal samples were annealed. Positron annihilation lifetime spectroscopy and slow positron beam technique were applied to investigate the types and distributions of the defects with different states of charges for KDP and ADP crystals. It was found that the quality of the prismatic sector was better than that of the pyramidal sector, although Fe3+ was mainly enriched in the prismatic sector. The types and content of defects in the pyramidal sector were relatively larger. ADP crystals showed better structural stability, with fewer defects than KDP crystals. This might be one of the reasons for the higher damage threshold of ADP crystals. The results also indicated that thermal annealing could decompose large-size defects into small-size ones to improve KDP crystal quality. However, it could not reduce the influence of Fe3+, such as causing light absorption at 220–300 nm. In addition, the Raman spectroscopy, Fourier-transformed infrared spectroscopy, and ultraviolet absorption spectroscopy were implemented to illustrate the change in the structure and properties after doping in KDP crystals. Notably, this work focused on the types and distributions of microscopic defects, which would be significant for the crystal growth and quality improvement. [ABSTRACT FROM AUTHOR]

Amino acids (AAs) account for about 15–35% of dissolved organic nitrogen (DON), and are known as the important precursors of nitrogenous disinfection by-products (N-DBPs). Determining the formation potential (FP) of AAs to DBPs is used to reveal the key precursors of DBPs for further control, while the ideal method for N-DBPs FP of AAs during chlorination is not revealed. In this study, the ideal FP test models for five classes of priority DBPs during chlorination of four representative AAs (accounted for about 35% of total AAs) were analyzed. For haloaldehydes (HALs), haloketones (HKs), haloacetonitriles (HANs), haloacetamides (HAMs), and halonitromethanes (HNMs), their FPs during chlorination of four AAs were 0.1–13.0, 0.01–1.1, 0.1–104, not detectable (nd)-173, and nd-0.4 μg/mg, respectively. The FPs of priority DBPs had significant deviations between different FP test models and different tested AAs. For HALs, the model, whose chlorine dosage was determined by 15 × molar concentration of AAs [Cl (mM) = 15 × M](named: model II), was the ideal model. For HKs, model II was also the ideal FP test model for AAs with ≤3 carbons, while for AAs with 4 carbons, the model, whose chlorine dosage was determined by keeping the residual chlorine at 1 ± 0.2 mg/L after 24 h of reaction (named: model 4), was the ideal model. For HANs and HNMs, model 4 was the ideal FP test model for most of the studied AAs. The performance of HAMs during chlorination of amino acids was totally different from other P-DBPs, and model 3 was recommended to be the ideal model, in which chlorine dosage was determined by 3 × mass concentration of AAs [Cl (mg/L) = X × DOC]. This study is a reference that helps researchers select an ideal model for N-DBPs FP study of AAs. [Display omitted] • The ideal FP test models for AAs during chlorination were analyzed. • For P-DBPs, their FPs for four AAs ranged from 0 to 173 μg/mg. • P-DBP FPs had significant deviations between different FP test models. • This study helps researchers to select a ideal model for FP study of AAs. [ABSTRACT FROM AUTHOR]

RGD/GS scaffolds, which were functionalized via the site-specific enzymatic reaction, were used to recruit MSCs from skeletal muscle followed by their engraftment into a bone defect. This strategy can avoid or minimize the complicated and labor-intensive cell isolation, in vitro expansion and cell seeding procedures used in the conventional BTE. [Display omitted] Critical-size bone defects are imposing a substantial biomedical burden. Despite being long regarded as a potential approach to mitigate this burden or an alternative to bone grafts, bone tissue engineering (BTE) has virtually not proceeded to widespread clinical practices. In the BTE field, it is highly required to find a facile method to prepare active scaffolds with tailored biological functions. Here, we immobilized cell adhesive RGD motifs onto gelatin sponge (GS) scaffolds through enzymatic linking. On the basis of the resulting RGD-functionalized GS (RGD/GS) scaffolds, we developed a new and convenient strategy for bone defect repair, in which the scaffolds were first used to recruit mesenchymal stem cells (MSCs) from skeletal muscle, immediately followed by their engraftment into bone defect. We demonstrated significantly enhanced host cells homing into RGD/GS scaffolds as a result of specific RGD-integrin interactions, and the recruited host cells showed a strong osteogenic differentiation potential. After ectopic implantation of cell-laden RGD/GS scaffolds into critical-size mouse bone defects, marked bone tissue regeneration occurred. The presented strategy not only provides an agile route for the preparation of bioactive scaffolds and the construction of osteoinductive bone-graft substitutes, but also avoids or minimizes the complicated and laborious cell isolation, in vitro expansion and cell seeding procedures used in the conventional BTE. [ABSTRACT FROM AUTHOR]

As a representative species of intermediate volatile organic compounds (IVOCs), long-chain alkanes are considered to be important precursors of secondary organic aerosols (SOA) in the atmosphere. This work reviews the previous studies on long-chain alkanes in the atmosphere: (1) the detection methods and filed observations of long-chain alkanes in both gas and particle phases are summarized briefly; (2) the laboratory studies of long chain alkanes are reviewed, the kinetic data, reaction mechanism, SOA yields, and physicochemical properties of SOA are included in detail; (3) the research progress related to model simulations of long-chain alkanes are also discussed. In addition, based on available research results, several perspective contents are proposed that can be used as a guideline for future research plans. [Display omitted] [ABSTRACT FROM AUTHOR]

Let K and L be two convex bodies in R n , n ≥ 3 such that their sections by cones { x ∈ R n : x ⋅ ξ = t | x | } or non-central planes with a fixed distance from the origin are directly congruent. We prove that if their boundaries are of class C 2 , then K and L coincide. [ABSTRACT FROM AUTHOR]

Tobacco black shank (TBS) is a soil-borne fungal disease caused by Phytophthora nicotiana (P. nicotianae), significantly impeding the production of high-quality tobacco. Molybdenum (Mo), a crucial trace element for both plants and animals, plays a vital role in promoting plant growth, enhancing photosynthesis, bolstering antioxidant capacity, and maintaining ultrastructural integrity. However, the positive effect of Mo on plant biotic stress is little understood. This study delves into the inhibitory effects of Mo on P. nicotianae and seeks to unravel the underlying mechanisms. The results showed that 16.32 mg/L of Mo significantly inhibited mycelial growth, altered mycelial morphological structure, damaged mycelial cell membrane, and ultimately led to the leakage of cell inclusions. In addition, 0.6 mg/kg Mo applied in soil significantly reduced the severity of TBS. Mo increased photosynthetic parameters and photosynthetic pigment contents of tobacco leaves, upregulated expression of NtPAL and NtPPO resistance genes, as well as improved activities of SOD, POD, CAT, PPO, and PAL in tobacco plants. Furthermore, Mo could regulate nitrogen metabolism and amino acids metabolism to protect tobacco plants against P. nicotianae infection. These findings not only present an ecologically sound approach to control TBS but also contribute valuable insights to the broader exploration of the role of microelements in plant disease management. [Display omitted] • Molybdenum enhances osmolytes efflux by perturbing the fungal membrane morphology. • Proper concentration of molybdenum can inhibit the growth of Phytophthora nicotiana. • Suitable concentration of molybdenum can reduce the severity of tobacco black shank. • Molybdenum can improve photosynthesis and antioxidant capacity of diseased tobacco. • Molybdenum regulated tobacco nitrogen metabolism and amino acids metabolism to improve disease resistance. [ABSTRACT FROM AUTHOR]

Understanding the formation mechanisms of secondary air pollution is very important for the formulation of air pollution control countermeasures in China. Thus, a large-scale outdoor atmospheric simulation smog chamber was constructed at Chinese Research Academy of Environmental Sciences (the CRAES Chamber), which was designed for simulating the atmospheric photochemical processes under the conditions close to the real atmospheric environment. The chamber consisted of a 56-m3 fluorinated ethylene propylene (FEP) Teflon film reactor, an electrically-driven stainless steel alloy shield, an auxiliary system, and multiple detection instrumentations. By performing a series of characterization experiments, we obtained basic parameters of the CRAES chamber, such as the mixing ability, the background reactivity, and the wall loss rates of gaseous compounds (propene, NO, NO 2 , ozone) and aerosols (ammonium sulfate). Oxidation experiments were also performed to study the formation of ozone and secondary organic aerosol (SOA), including α-pinene ozonolysis, propene and 1,3,5-trimethylbenzene photooxidation. Temperature and seed effects on the vapor wall loss and SOA yields were obtained in this work: higher temperature and the presence of seed could reduce the vapor wall loss; SOA yield was found to depend inversely on temperature, and the presence of seed could increase SOA yield. The seed was suggested to be used in the chamber to reduce the interaction between the gas phase and chamber walls. The results above showed that the CRAES chamber was reliable and could meet the demands for investigating tropospheric chemistry. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to explore the current status of activities of daily living (ADLs), life orientation, and health-related quality of life (HRQoL) among older people in nursing homes and to further examine the mediating role of life orientation in the impact of ADLs on HRQoL. Methods: A national cross-sectional study was conducted among older people aged 60 and above in nursing homes by the randomly stratified cluster sampling method. The status of ADLs, life orientation and HRQoL were measured using an ADL scale, a life orientation scale and the SF-12v2 scale, respectively. Multiple linear regression models were used to identify explanatory factors associated with ADLs, life orientation, and HRQoL. The potential mediating role of life orientation in the relationship between ADL and HRQoL was explored by mediation analysis. Results: The overall prevalence of ADL disability was 52.67%, and 84.37% of older people in nursing homes had a negative life orientation. The mean scores of physical health and mental health among older people in nursing homes were 45.44 ± 6.46 and 42.67 ± 8.48, respectively. Some sociodemographic characteristics were associated with poor physical health and mental health. After adjustments were made for covariates, the life orientation score mediated 13.81% of the total effect of the ADL score on physical component score of HRQoL and mediated 45.33% of the mental component score of HRQoL. Conclusion: A sizeable proportion of older people had ADL disability and negative life orientation, and HRQoL was poor among older Chinese people in nursing homes. Life orientation partially mediates the relationship between ADLs and HRQoL. [ABSTRACT FROM AUTHOR]

Cross wedge rolling (CWR) is one of the most effective plastic deformation methods utilized for the production of shaft parts or non-shaft preforms with refined grains and improved mechanical properties. The main goal of this work was to study the influence of CWR process parameters on the microstructure evolution and mechanical properties of a TC6 alloy and determine the suitable process parameters for a TC6 alloy blade preform fabricated with CWR. The results showed that the volume fraction of the equiaxed α phase ( f α _ e ) decreased from ~ 0.38 to ~ 0.04 by increasing the initial deformation temperature, and the elongation (El) also decreased from ~ 19.6 to ~ 11.8% because dislocation slip first started in the equiaxed grains and then dispersed into the adjacent grains. Thus, additional equiaxed grains contributed to an increased plasticity. Moreover, with an increasing area reduction, the value of f α _ e increased from ~ 0.14 to ~ 0.31, and the grain refinement and microstructure uniformity also increased. In addition, the El was significantly reduced by over 50%, but the ultimate tensile strength (UTS) and yield strength (YS) increased under WC (water cooling) conditions due to the precipitation of the acicular secondary α phase and pinning effect of the small equiaxed α phase. Based on the determined suitable parameters, the TC6 alloy blade preform was successfully manufactured by CWR, the microstructure was evenly distributed, and the UTS, YS and El were 1120.1 MPa, 1020.9 MPa and 15.2%, respectively, which meet the current technical requirements. [ABSTRACT FROM AUTHOR]

Background: Postmenopausal osteoporosis (PMO) is the most common type of primary osteoporosis. ESR1 polymorphism rs2234693 and rs9340799 has been widely studied as a candidate gene associated with PMO, however, the findings were inconclusive. The present study aims to explore the relationship of ESR1 polymorphism rs2234693 and rs9340799 with PMO risk in a Chinese Han population.Methods: PMO patients and healthy controls were recruited from gynecology department. DNA of all participants were extracted from the peripheral blood samples and genotyped by Mass Array method. A meta-analysis of case control studies was also conducted to further elucidate the relationship of polymorphism with PMO.Results: Our results revealed that there were no associations of rs2234693 with PMO. However, GG genotype of rs9340799 was associated with a higher risk of PMO (OR = 1.51, 95%CI:1.08-4.34, p = 0.03), even adjusting for risk factors (OR = 1.83, 95%CI: 1.12-5.04, p = 0.04). Logistic regression analysis showed that dominant model was associated with a higher risk of PMO (OR = 2.07, 95%CI: 1.02-5.16, p = 0.02) after correcting the risk factors (OR = 2.14, 95%CI:1.12-5.64, p = 0.04); In addition, the Meta-analysis results revealed that both two polymorphisms were not associated with PMO.Conclusions: In conclusion, ESR1 polymorphism rs9340799 was associated with PMO. However, well designed studies with larger sample sizes are required to further elucidate the associations. [ABSTRACT FROM AUTHOR]

Titanium alloy blades are significantly important parts for aero-engine, and their special outline and production status requires an efficient and low-cost production process. In this paper, a new sequence for forming the titanium alloy blade using cross-wedge rolling (CWR) and isothermal forging was proposed. A finite element (FE) numerical model which contains the entire sequence, including the transfer process, CWR process, and isothermal forging process, was developed. And the axial displacement, strain-stress state, and temperature variation were analyzed based on its material properties of titanium alloy. The results showed that the billet experiences a smooth flowing in the center along the axial direction, and no large concavity occurs due to the higher viscosity. Moreover, the chilling effect of the dies was effectively counterbalanced by the deformation-heat near the surface, and there is no larger temperature difference. During the isothermal forging, the flash is symmetrically distributed around the fully filled blade and no obvious forming defects occur. Moreover, the novel sequence contributes to improving the deformed microstructure by accelerating the globularization of the long-strip alpha phase and increasing the volume fraction of the primary alpha phase. The technical feasibility of the novel sequence was verified by the corresponding experiments. [ABSTRACT FROM AUTHOR]

Both phosphatidylethanolamine (PE) and phosphatidylserine (PS) can be externalized to the outer cell membrane in apoptosis. Thus the objective was to determine whether PE-targeting 18F-duramycin and PS-targeting 18F-Zn-DPA could be used for imaging apoptosis. Duramycin and Zn-DPA were labeled with either 18F-Al or 18F-SFB. U937 cells were incubated with four different concentrations of camptothecin (CPT). For assessing the effect of incubation time on uptake, 37 MBq of radiotracer was added to cells incubated for 15, 30, 60, and 120 min at 37 °C. For blocking experiments, 150 μg duramycin and 40 μg Zn-DPA were added to cells for 15 min prior to the addition of either duramycin or Zn-DPA labeled with 18F. Apoptosis was measured by flow cytometry using an annexin-V/PI kit. Cells were co-stained with Hoechst, Cy5-duramycin, and PSVue480 (FITC-Zn-DPA) to localize fluorescent dye uptake in cells. Apoptosis in cells increased proportionally with CTP as confirmed by both flow cytometry and fluorescent staining. Both FITC-Zn-DPA and FITC-duramycin localized mainly on the cell membrane during early apoptosis and then translocated to the inside during late apoptosis. Uptake of FITC-duramycin, however, was higher than that of FITC-Zn-DPA. Cellular uptake of four different radiotracers was also proportional to the degree of apoptosis, increasing slightly over time and reaching a plateau at about 1 h. The blocking experiments demonstrated that uptake in all the control groups was predominantly non-specific, whereas the specific uptake in all the treated groups was at least 50% for both 18F labeled duramycin and Zn-DPA. Both PE-targeting 18F-duramycin and PS-targeting 18F-Zn-DPA could be considered as potential radiotracers for imaging cellular apoptosis. Advances in knowledge and implications for patient care: Cellular data support the further development of radiotracers targeting either PE or PS for imaging apoptosis, which can associate with clinical outcome for cancer patients. [ABSTRACT FROM AUTHOR]

In this work, the influences of the initial deformation temperature (T0), area reduction (φ) and rolling speed (n) on the cross wedge rolling (CWR) of TC6 alloy were investigated with a 3D elastic-plastic coupled thermomechanical and microstructural finite element (FE) model based on temperature and strain rate sensitivities. The developed model was suggested to be reliable by comparing the simulated results to those of thermal tests, hot compression tests and CWR experiments. The distribution of the volume fraction of the alpha phase gradually increased from the centre to the outer layer. With increases in the initial deformation temperature (T0), the average volume fraction of the alpha phase (AVF) decreases. Moreover, the standard deviation of the volume fraction of the alpha phase (SDF) was smaller in sections S1 and S2 than that in section S3, which means that the alpha phase is more uniformly distributed in the deformed region. With increases in the area reduction (φ), the AVFs and SDFs decrease, which also indicates the improvement of distribution homogeneity. Additionally, the sensitivity rate of the area reduction (R(φ)AVF) was lowest when the area reduction (φ) was between 51 and 64%. Rolling speed (n) should be controlled to balance the two competitive thermal mechanisms. The max-min permissible rolling speed is related to the initial deformation temperature (T0), and it should be approximately 8 r/min in the present study. [ABSTRACT FROM AUTHOR]

A drone base station (DBS) is a promising technique to extend wireless connections for uncovered users of terrestrial radio access networks (RANs). To improve user fairness and network performance, in this paper, we design three-dimensional (3-D) trajectories of multiple DBSs in the drone-assisted RANs, where DBSs fly over associated areas of interests (AoIs) and relay communications between the base station and users in AoIs. We formulate the multi-DBS 3-D trajectory planning and scheduling as a mixed-integer non-linear programming (MINLP) problem with the objective of minimizing the average DBS-to-user (D2U) pathloss. The 3-D trajectory variations in both horizontal and vertical directions, as well as the state-of-the-art DBS-related channel models, are considered in the formulation. To address the non-convexity and NP-hardness of the MINLP problem, we first decouple it into multiple integer linear programming and quasi-convex sub-problems in which AoI association, D2U communication scheduling, horizontal trajectories, and flying heights of DBSs are, respectively, optimized. Then, we design a multi-DBS 3-D trajectory planning and scheduling algorithm to solve the sub-problems iteratively based on the block coordinate descent method. A k-means-based initial trajectory generation and a search-based start slot scheduling are considered in the proposed algorithm to improve trajectory design performance and ensure the inter-DBS distance constraint, respectively. Extensive simulations are conducted to investigate the impacts of DBS quantity, horizontal speed, and initial trajectory on the trajectory planning results. Compared with the static DBS deployment, the proposed trajectory planning can achieve 10–15 dB reduction on average D2U pathloss and reduce the D2U pathloss standard deviation by 68%, which indicate the improvements of network performance and user fairness. [ABSTRACT FROM AUTHOR]

In this study, [18F]FGA was obtained by a one-step oxidation of [18F]FDG using sodium hypochlorite. The conversion from [18F]FDG to [18F]FGA was confirmed by HPLC to be over 95% using the optimal condition. A549-luciferase NSCLC xenografted mice was used for in vivo PET imaging. Prior to either saline or cisplatin treatment, there was no significant difference on tumor uptake of [18F]FGA in all mice, with an average uptake of (0.21 ± 0.16) %ID/g. After treatment, tumor uptake of [18F]FGA was not changed significantly for saline-treated mice, whereas the tumor uptake of [18F]FGA drastically increased for cisplatin-treated mice, with an average uptake of (1.63 ± 0.16) %ID/g. The ratio of tumor uptake between cisplatin-treated vs. saline-treated mice was 7.8 ± 0.2 within one week of treatment. PET imaging results were consistent with ex vivo biodistribution data. BLI showed significant light intensity suppression after treatment, indicating necrosis. Our data indicate that [18F]FGA uptake was related to tumor necrosis. [18F]FGA PET/CT imaging might be a useful tool to monitor treatment response to chemotherapy by imaging tumor necrosis. • [18F]FGA was obtained by a one-step oxidation of [18F]FDG using sodium hypochlorite. • [18F]FGA PET/CT imaging was performed to monitor treatment response in mice bearing with lung tumor. • Tumor uptake of [18F]FGA was drastically increased after treatment. • [18F]FGA PET is a useful tool to monitor treatment response. [ABSTRACT FROM AUTHOR]

Abstract In this paper, the flow softening and ductile damage of TC6 alloy were investigated using a uniaxial hot tensile test with deformation temperatures of 910 °C∼970 °C and strain rates of 0.01 s−1∼10 s−1. Scanning electron microscopy (SEM) was performed on the deformed specimens to reveal the damage mechanism. The results showed that the flow stress rapidly increases to a peak at a tiny strain, followed by a significant decrease due to flow softening and ductile damage. The ductile damage of the studied TC6 alloy can be ascribe to the nucleation, growth and coalescence of microdefects, and the microvoids preferentially nucleate at the interface of the alpha phase and beta matrix due to the inconsistent strain. Then, a set of unified viscoplastic constitutive equations including flow softening and ductile damage mechanisms was developed and determined, and this set of equations was verified by the experimental flow stress, which indicated the reliability of the prediction. Furthermore, the predicted normalized dislocation density and the adiabatic temperature rise increase with decreasing temperature and increasing strain rate. The predicted damage components show that the microdefects mainly nucleate in the initial stage, but then primarily grow and link together with continuing deformation. Highlights • The flow behaviour and ductile damage mechanism of TC6 alloy were investigated. • A set of physically-based internal-state-variable damage model was developed. • Normalized dislocation density and adiabatic temperature rise were predicted. • The microdefects mainly nucleate in the initial stage. • The microdefects primarily grow and link together with continuing deformation. [ABSTRACT FROM AUTHOR]

Abstract To better characterize the optical properties of atmospheric aerosols, the multi-wavelength cavity ring-down aerosol extinction spectrometer (MCRD-AES) is developed and applied in this study. By using tunable light source and four parallel cavities, the MCRD-AES covers a wide and atmospherically relevant wavelength range from 360 to 663 nm. Four wavelengths (375 nm, 440 nm, 532 nm, and 620 nm) are particularly tested with ammonium sulfate and nigrosine. The refractive index values obtained from this study agree well with literature data. The stability and accuracy of the MCRD-AES are tested, and the minimum detectable extinction coefficient is 0.5 1/Mm. The high sensitivity, high precision, and wavelength changeable of MCRD-AES indicate its great application prospect in comprehensively quantifying the optical properties of atmospheric aerosols. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

MDM2 has been established as a biomarker indicating poor prognosis for individuals undergoing immune checkpoint inhibitor (ICI) treatment for different malignancies by various pancancer studies. Specifically, patients who have MDM2 amplification are vulnerable to the development of hyperprogressive disease (HPD) following anticancer immunotherapy, resulting in marked deleterious effects on survival rates. The mechanism of MDM2 involves its role as an oncogene during the development of malignancy, and MDM2 can promote both metastasis and tumor cell proliferation, which indirectly leads to disease progression. Moreover, MDM2 is vitally involved in modifying the tumor immune microenvironment (TIME) as well as in influencing immune cells, eventually facilitating immune evasion and tolerance. Encouragingly, various MDM2 inhibitors have exhibited efficacy in relieving the TIME suppression caused by MDM2. These results demonstrate the prospects for breakthroughs in combination therapy using MDM2 inhibitors and anticancer immunotherapy. [ABSTRACT FROM AUTHOR]

• Rate constants for reaction of 3-methylhexane and 2-methylheptane with Cl atoms were obtained. • Gas-phase products, particle-phase products, and SOA yield of 3-methylhexane and 2-methylheptane with Cl atoms were analyzed. • The reaction mechanism and atmosphere lifetime of several mono-methyl branched alkanes were deduced. Branched alkanes are ubiquitous in the troposphere and play an important role in the chemical processes. In this work, the rate constants and products for the reaction of Cl atoms with 3-methylhexane and 2-methylheptane were measured at room temperature (298 ± 0.2 K) and atmospheric pressure using a conventional relative rate method. The rate constants of 3-methylhexane and 2-methylheptane in units of cm3/(mol·sec) are (3.09 ± 0.31) × 10−10 and (3.67 ± 0.40) × 10−10, respectively. Furthermore, the corresponding atmospheric lifetime of the studied branched alkanes with Cl was 6.92-89.90 hours and 5.82-75.69 hours, respectively. The estimated atmospheric lifetimes indicated that the reaction with Cl atoms could be the most important atmospheric degradation pathway for 3-methylhexane and 2-methylheptane. Primary gas-phase products of the reactions were identified and quantified, and particle-phase products were also obtained. The atmosphere oxidation mechanism of Cl atoms with 3-methylhexane and 2-methylheptane is proposed. The SOA yields of 3-methylhexane and 2-methylheptane from the reaction of Cl atoms were determined to be 7.96% ± 0.89% and 13.35% ± 1.50% respectively. Overall, the results reveal that the primary loss process of branched alkanes is the reaction with Cl atoms, which impacts its degradation on a regional scale. [Display omitted] [ABSTRACT FROM AUTHOR]

In this paper, the flow behaviour and globularization kinetics of a TC6 alloy were investigated by conducting hot compression tests at different temperatures (910–970 °C), strain rates (0.01–10.0 s-1) and true strains (0.223, 0.511, 0.916). Scanning electron microscopy (SEM) measurements were performed to evaluate the phase transformation and globularization fraction. Based on the experimental results, a set of internal state variable-based unified viscoplastic constitutive equations was developed to model the flow behaviour and the globularization evolution of the TC6 alloy. The model was fully determined by an optimization method based on genetic algorithm (GA). The results show that the predicted beta phase transformation curve fits the experimental data well, and that the predicted flow stress and globularization fraction of the alpha phase are in good agreement with the experimental data, even at strain rates outside the limits of the model. Furthermore, the flow stress begins to decrease at the onset of the softening mechanism, which occurs at a true strain of approximately 0.05. While an analysis of the predicted variations in the strain hardening rate and strain rate of each phase reveals that the softer beta phase accumulates more overall strain, whereas the strain accumulation in the alpha phase decrease. [ABSTRACT FROM AUTHOR]

The application and demand of titanium alloys has been steadily increasing in aviation due to the excellent high-temperature performance. Powder metallurgy (PM) technology has been widely applied in the production of titanium alloy but with more disadvantages. The application of the cross-wedge rolling (CWR) process to manufacture powder sintering titanium alloy has received the least attention but is most significant. This paper presents a numerical and experimental study on the CWR of sintering TC4 alloy blade preforms. The deformation behavior of sintering TC4 alloy was investigated, and a constitutive equation at peak stress was developed and implemented into a finite element (FE) model, by which we analyzed the effect of tool parameters, forming quality, and forming mechanism in the CWR process. We also investigated the effect of the deformation temperature and area reduction on forming quality with CWR experiments. The results show that the deformation behavior of sintering TC4 alloy is sensitive to temperature and strain rate, and the constitutive equation is capable of predicting the flow stress for the CWR process. Among the tool parameters, area reduction is the most significant factor and showed the best performance at less than 65.9%. An applicable range of process parameters for the CWR of sintering TC4 alloy was obtained. After rolling, the relative density improves from 86.21 to 98.2%, and the mechanical properties of the workpiece are significantly enhanced, especially for elongation. Compared with 45# steel, the temperature difference in the radial direction (Δ T) of TC4 alloy is much larger due to a lower thermal conductivity. However, the rolling force and torque of TC4 alloy needed in the CWR process are only half as much as those of 45#. [ABSTRACT FROM AUTHOR]

Ti-6Al-4V alloy is an ideal material for gas turbine blades with high strength and low density. The application of the cross-wedge rolling (CWR) process for manufacturing Ti-6Al-4V alloy blade preforms has great innovative potential. In this study, isothermal hot compression tests with strain rates between 0.01 and 10 s and deformation temperatures between 850 and 1050 °C were carried out. The constitutive equation was established and implemented into a 3D finite element (FE) model to analyze the formability of the CWR of Ti-6Al-4V alloy. Furthermore, CWR experiments were developed to verify the dependability of the FE simulation results and to investigate the influence of the process parameters on the formability of Ti-6Al-4V. The comprehensive results of the FE simulation and CWR experiments show that both the tool parameters and rolling temperature significantly affect the formability of the Ti-6Al-4V alloy. When the forming angle was 30° or 35°, the stretching angle was less than 7°, the area reduction was less than 72.4%, and the rolling temperature was 950 °C, The surface quality during the CWR process can be significantly improved. [ABSTRACT FROM AUTHOR]

Ambient volatile organic compounds (VOCs) at a suburban Beijing site were on-line detected using proton transfer reaction-mass spectrometry (PTR-MS) during autumn of 2014, near the location of the Asia-Pacific Economic Cooperation (APEC) summit. During the APEC summit, the Chinese government enacted strict emission control policies. It was found that VOC concentrations only slightly decreased during the first emission control period (EC I), when control policies were performed in Beijing and 5 cities along the Tai-hang Mountains. However, most of the VOCs (10 out of 12 non-biogenic species) significantly decreased (more than 40%) during the second emission control period (EC II), when control policies were carried out in 16 cities including Beijing, Tianjin, 8 cities of Hebei province and 6 cities of Shandong province. Also the ratio of toluene and benzene decreased during EC II, likely because the emission control policies changed the proportions of different anthropogenic sources. Using the positive matrix factorization (PMF) source apportionment method, five factors are analyzed: (1) vehicle + fuel, (2) solvent, (3) biomass burning, (4) secondary, and (5) background + long-lived. Among them, vehicle + fuel, solvent and biomass burning contribute most of the VOCs concentrations (60%–80%) during the polluted periods and are affected most by emission control policies. During EC II, the reductions of vehicle + fuel, solvent, biomass burning and secondary species were all no less than 50%. Overall, when emission control policies were carried out in many North China Plain (NCP) cities (i.e. EC II), the VOC concentrations of suburban Beijing markedly decreased. This indicates the cross-regional joint-control policies have a large influence on reductions of organic gas species. The findings of this study have vital implications for helping formulate effective emission control policies in China and other countries. [ABSTRACT FROM AUTHOR]

Long-chain alkanes are a type of important intermediate-volatile organic compounds (IVOCs) in the atmosphere, which contribute to a large proportion of secondary organic aerosol (SOA). However, the optical properties of SOA derived from long-chain alkanes remain poorly understood. Here, we investigate the refractive index (RI) of SOA derived from photo-oxidation of dodecane (C12), pentadecane (C15) and heptadecane (C17) under low-NO x and high-NO x conditions with the absence or presence of inorganic aerosol seeds. The RIs of these SOAs are found to be in the range of 1.33 to 1.57 at the wavelength of 532 nm. The results from mass spectroscopy indicate that both reaction mechanisms influenced by NO x level and gas-particle partitioning influenced by seeds have important impact on the chemical compositions of SOAs, which further influence the optical properties like RI. Finally, by comparing the RI values to other literature and model results, we suggest that various RIs of SOAs derived from long-chain alkanes should be applied in atmospheric and climate models. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) mutations are the strongest response predictors to EGFR tyrosine kinase inhibitors (TKI) therapy, but knowledge of the EGFR mutation frequency on lung adenocarcinoma is still limited to retrospective studies. The PIONEER study (NCT01185314) is a prospective molecular epidemiology study in Asian patients with newly diagnosed advanced lung adenocarcinoma, aiming to prospectively analyze EGFR mutation status in IIIB/IV treatment-naïve lung adenocarcinomas in Asia. We report the mainland China subset results. Eligible patients (≥20 yrs old, IIIB/IV adenocarcinoma and treatment-naïve) were registered in 17 hospitals in mainland China. EGFR was tested for mutations by amplification refractory mutation system using biopsy samples. Demographic and clinical characteristics were collected for subgroup analyses. A total of 747 patients were registered. Successful EGFR mutation analysis was performed in 741, with an overall mutation rate of 50.2%. The EGFR active mutation rate is 48.0% (with 1.3% of combined active and resistance mutations). Tobacco use (>30 pack-year vs. 0–10 pack-year, OR 0.27, 95%CI: 0.17–0.42) and regional lymph nodes involvement (N3 vs. N0, OR 0.47, 95%CI: 0.29–0.76) were independent predictors of EGFR mutation in multivariate analysis. However, even in regular smokers, the EGFR mutation frequency was 35.3%. The EGFR mutation frequency was similar between diverse biopsy sites and techniques. The overall EGFR mutation frequency of the mainland China subset was 50.2%, independently associated with the intensity of tobacco use and regional lymph nodes involvement. The relatively high frequency of EGFR mutations in the mainland China subset suggest that any effort to obtain tissue sample for EGFR mutation testing should be encouraged. [ABSTRACT FROM AUTHOR]

Accumulation of misfolded or unfolded proteins in the endoplasmic reticulum (ER) triggers ER stress that initiates unfolded protein response (UPR). XBP1 is a transcription factor that mediates one of the key signaling pathways of UPR to cope with ER stress through regulating gene expression. Activation of XBP1 involves an unconventional mRNA splicing catalyzed by IRE1 endonuclease that removes an internal 26 nucleotides from xbp1 mRNA transcripts in the cytoplasm. Researchers have taken advantage of this unique activation mechanism to monitor XBP1 activation, thereby UPR, in cell culture and transgenic models. Here we report a Tg(ef1α:xbp1δ-gfp) transgenic zebrafish line to monitor XBP1 activation using GFP as a reporter especially in zebrafish oocytes and developing embryos. The Tg(ef1α:xbp1δ-gfp) transgene was constructed using part of the zebrafish xbp1 cDNA containing the splicing element. ER stress induced splicing results in the cDNA encoding a GFP-tagged partial XBP1 without the transactivation activation domain (XBP1Δ-GFP). The results showed that xbp1 transcripts mainly exist as the spliced active isoform in unfertilized oocytes and zebrafish embryos prior to zygotic gene activation at 3 hours post fertilization. A strong GFP expression was observed in unfertilized oocytes, eyes, brain and skeletal muscle in addition to a weak expression in the hatching gland. Incubation of transgenic zebrafish embryos with (dithiothreitol) DTT significantly induced XBP1Δ-GFP expression. Collectively, these studies unveil the presence of maternal xbp1 splicing in zebrafish oocytes, fertilized eggs and early stage embryos. The Tg(ef1α:xbp1δ-gfp) transgenic zebrafish provides a useful model for in vivo monitoring xbp1 splicing during development and under ER stress conditions. [ABSTRACT FROM AUTHOR]

Objective Bis(Zn-dipicolylamine (Zn-DPA)) coordination complexes represent a new class of synthetic small molecules that can target anionic phosphatidylserine (PS) in the apoptotic cells with high affinity and specificity. In this study, we labeled Zn-DPA and Cy7-Zn-DPA with different 18 F-prosthetic groups and characterized their uptake in A549 cells infected with influenza A virus from the 2009 pandemic (H1N1pdm). Methods DPA was labeled with N-succinimidyl 4- 18 F-fluorobenzoate ( 18 F-SFB), 4-nitrophenyl 2- 18 F-fluoropropionate ( 18 F-NFP), 2- 18 F-Fluoroethyl toslyate ( 18 F-FET), and 18 F-aluminum (Al 18 F), respectively. Cy7-DPA was labeled with 18 F-SFB and 18 F-NFP only. The tracers were reconstituted with zinc nitrate before use. Apoptosis in A549 cells was induced by infection with the H1N1pdm virus for 48 h. Three μCi of each tracer was added to each well and incubated at 37 °C. The effect of different prosthetic groups, different MOI, and incubation time on percent cellular uptake was studied. Cell internalization and efflux was evaluated within 2 h of incubation. The competitive binding assay was performed with increasing concentration (10 − 12 -10 − 5 M) of Zn-DPA or Cy7-Zn-DPA prior to the addition of either 18 F-FB-Zn-DPA or 18 F-FB-Cy7-Zn-DPA into each well. IC 50 values for the two Zn-DPA analogues were estimated by GraphPad Prism 6.0. Results Among all the four prosthetic groups, the 18 F-SFB method provided the highest conjugation yield for DPA and the highest uptake ratio between the infection cells and the control when both Zn-DPA and Cy7-Zn-DPA were present in the complex. The uptake ratio was similar for 18 F-FB-Zn-DPA and 18 F-FB-Cy7-Zn-DPA. Uptake of 18 F-FB-Zn-DPA and 18 F-FB-Cy7-Zn-DPA was proportional to the degree of apoptosis with a plateau at MOI 3. Uptake of 18 F-FB-Cy7-Zn-DPA also increased over incubation time and reached a plateau at 1 h, whereas uptake of 18 F-FB-Zn-DPA did not show any significant change over time. Cell internalization studies showed that more than 70% of 18 F-FB-Zn-DPA remained on the cell surface over a time course of 2 hr in the cell media, but over 90% of 18 F-FB-Cy7-Zn-DPA was internalized within 15 min of incubation. IC 50 values were estimated to be 1.5 ± 0.3 nM and 26.2 ± 5.1 nM for Zn-DPA and Cy7-Zn-DPA, respectively. Conclusions 18 F-SFB was the optimal labeling method for Zn-DPA and Cy7-Zn-DPA with respect to radiochemistry and provided complexes with high target-to-background ratios. 18 F-FB-Zn-DPA and 18 F-FB-Cy7-Zn-DPA appeared to have a completely different internalization mechanism, while Zn-DPA showed higher binding affinity than Cy7-Zn-DPA. Based on these favorable characteristics, 18 F-FB-Zn-DPA and 18 F-FB-Cy7-Zn-DPA should be further evaluated as potential imaging agents for viral infection. [ABSTRACT FROM AUTHOR]

Key message: Cell wall polysaccharides' occurrences in two internodes of different development stages in M. lutarioriparius stem were analyzed and three major differences between them were identified by cell wall polysaccharide probes. Abstract: Deposition and modification of cell wall polysaccharides during stem development affect biomass yield of the Miscanthus energy crop. The distribution patterns of cell wall polysaccharides in the 2nd and the 11th internodes of M. lutarioriparius stem were studied using in situ immunofluorescence assay. Crystalline cellulose and xylan were present in most of the stem tissues except phloem, where xyloglucan was the major composition of hemicellulose. The distribution of pectin polysaccharides varied in stem tissues, particularly in vascular bundle elements. Xylogalacturonan, feruloylated-1,4-β- d-galactan and (1,3)(1,4)-β-glucans, however, were insufficient for antibodies binding in both internodes. Furthermore, the distribution of cell wall polysaccharides was differentiated in the two internodes of M. lutarioriparius. The significant differences in the pattern of occurrence of long 1,5-α- l-arabinan chain, homogalacturonan and fucosylated xyloglucans epitope were detected between the two internodes. In addition, the relationships between probable functions of polysaccharides and their distribution patterns in M. lutarioriparius stem cell wall were discussed, which would be helpful to understand the growth characteristics of Miscanthus and identify potential targets for either modification or degradation. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: AS1411 is a 26-base guanine-rich oligonucleotide aptamer shown binding to surface nucleolin, a protein over-expressed in multiple cancer cells, thus AS1411 labeled with a PET isotope can be explored as a potential diagnostic imaging agent. Our objective was to perform preliminary biological characterization of 64Cu-labeled AS1411 in vitro and in vivo. Methods: Four chelators (DOTA, CB-TE2A, DOTA-Bn and NOTA-Bn) were selected to label AS1411 with Cu-64. 185kBq (5μCi) of each tracer was incubated in each well with H460 cells at 37°C for 1, 3, 6, 12, 24 and 48h, respectively (n=4). For microPET/CT imaging, 7.4MBq (200μCi) of AS1411 labeled with either 64Cu-DOTA or 64Cu-CB-TE2A was I.V. injected and multiple scans were obtained at 1, 3, 6 and 24h post injection. Afterward in vivo biodistribution studies were performed. Results: Percent uptake of 64Cu-DOTA-AS1411 and 64Cu-CB-TE2A-AS1411 was significantly higher than that of 64Cu-DOTA-Bn-AS1411 and 64Cu-NOTA-Bn-AS1411. About 90% of uptake for 64Cu-DOTA-AS1411 and 64Cu-CB-TE2A-AS1411 was internalized into cells within 3h and the internalization process was completed before 24h. Both tracers demonstrated reasonable in vivo stability and high binding affinity to the cells. MicroPET imaging with 64Cu-CB-TE2A-AS1411 showed clear tumor uptake at both legs from 1 to 24h post injection, whereas both tumors were undetectable for up to 24h with 64Cu-DOTA-AS1411. In addition, 64Cu-CB-TE2A-AS1411 had faster in vivo pharmacokinetics than 64Cu-DOTA-AS1411 with lower liver uptake and higher tumor to background contrast. Conclusion: CB-TE2A is a preferred chelator with higher tumor-to-background ratio, lower liver uptake and faster clearance than DOTA. Aptamer imaging with 64Cu-CB-TE2A-AS1411 may be feasible for detecting lung cancer, if an appropriate chelator can be identified and further validation can be performed with a known control oligonucleotide. It may also be used as a companion diagnostic imaging agent for AS1411 in the treatment of cancer. [Copyright &y& Elsevier]

Background: Smyd1, the founding member of the Smyd family including Smyd-1, 2, 3, 4 and 5, is a SET and MYND domain containing protein that plays a key role in myofibril assembly in skeletal and cardiac muscles. Bioinformatic analysis revealed that zebrafish genome contains two highly related smyd1 genes, smyd1a and smyd1b. Although Smyd1b function is well characterized in skeletal and cardiac muscles, the function of Smyd1a is, however, unknown. Methodology/Principal Findings: To investigate the function of Smyd1a in muscle development, we isolated smyd1a from zebrafish, and characterized its expression and function during muscle development via gene knockdown and transgenic expression approaches. The results showed that smyd1a was strongly expressed in skeletal muscles of zebrafish embryos. Functional analysis revealed that knockdown of smyd1a alone had no significant effect on myofibril assembly in zebrafish skeletal muscles. However, knockdown of smyd1a and smyd1b together resulted in a complete disruption of myofibril organization in skeletal muscles, a phenotype stronger than knockdown of smyd1a or smyd1b alone. Moreover, ectopic expression of zebrafish smyd1a or mouse Smyd1 transgene could rescue the myofibril defects from the smyd1b knockdown in zebrafish embryos. Conclusion/Significance: Collectively, these data indicate that Smyd1a and Smyd1b share similar biological activity in myofibril assembly in zebrafish embryos. However, Smyd1b appears to play a major role in this process. [ABSTRACT FROM AUTHOR]

Background Epidermal growth factor-tyrosine kinase inhibitors ( EGFR- TKIs) are one of the effective medicines in advanced lung adenocarcinoma leptomeningeal metastasis ( LM) treatment in recent years. Methods This paper reports two cases of advanced lung adenocarcinoma with exon-EGFR19 mutation. LM occurred during gefitinib treatment with an extracranial condition under control. Later, erlotinib was adopted with a recurrent response. Results The progression free survival of both patients was over six months and their LM was under control for six and a half and nine months, respectively. LM may be sensitive on different levels to different EGFR- TKIs. Conclusion Erlotinib can be used to replace gefitinib if intracranial tumor progress occurs during gefitinib treatment. However, our conclusion still needs to be proven by further clinical research. [ABSTRACT FROM AUTHOR]

Abstract: An -point boundary value problem with one-dimensional -Laplacian at resonance on is considered. By establishing a continuation theorem and applying a suitable homotopy, Leray–Schauder degree, a priori estimate, the existence of solutions to the above problem is obtained. [Copyright &y& Elsevier]

Abstract: Polyaniline (PANI) films doped with Ni2+ (PANI/Ni2+) were synthesized by cyclic voltammetry (CV) on stainless steel (SS) substrates in 0.2mol/L aniline (An) and 0.5mol/L sulfuric acid (H2SO4) electrolyte with various concentration of nickel sulfate (NiSO4). The structure and morphology of PANI/Ni2+ films were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), Scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy (XPS) techniques. The electrochemical properties of PANI/Ni2+ films were investigated by cyclic voltammetry, galvanostatic charge–discharge test and electrochemical impedance spectroscopy (EIS) in 0.5mol/L H2SO4 electrolyte in three-electrode system. The results suggest that the growth rate of PANI was greatly increased, which may arise from the interactions between PANI chain and Ni2+. The PANI/Ni2+ films show a larger specific capacitance of 658.3F/g at a current density of 5mA/cm2 and lower resistance compared with the pure PANI film. The results indicate that the PANI/Ni2+ films are promising material for supercapacitors. [Copyright &y& Elsevier]

Abstract: This paper investigates an -point boundary value problem with nonlinear boundary conditions at resonance on infinite intervals. By establishing a general continuation theorem, the existence and uniqueness of unbounded solutions is obtained on the basis of a suitable homotopy, Leray–Schauder degree properties and a priori estimate. This paper provides a new method to solve boundary value problems with nonlinear boundary conditions at resonance on infinite intervals. [Copyright &y& Elsevier]

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible deterioration of the airway wall. Cigarette smoking is the major trigger, and in vitro studies showed that cigarette smoke extract (CSE) induced mitophagy in airway epithelial cells via oxidative stress, but this mechanism was not studied in airway smooth muscle cells (ASMCs). Primary ASMCs isolated from COPD patients or non-disease donors were investigated for CSE-induced remodeling and mitochondria structure. Proteins were assessed by Western blots for remodeling: collagen type-I, α-smooth muscle actin (α-SMA) and fibronectin; autophagy: beclin-1, protein62 (p62), light chain (LC)3A/B; mitochondria activity: mitochondrially encoded cytochrome c oxidase II & -IV (MTCO2, MTCO4), peroxisome proliferator activated receptor gamma coactivator 1α (PGC-1α); lysosomes: early endosome antigen 1, lysosome activated membrane protein 1; and cell signaling: extracellular signal regulated kinase (ERK1/2). Lysotracker and Mitotracker were used to monitor mitochondria morphology and organelle co-localization. Compared with controls, untreated COPD ASMCs showed lower collagen type-I and α-SMA expressions, but increased fibronectin levels. CSE further downregulated collagen type-I and α-SMA expression, but upregulated fibronectin. CSE decreased PGC-1α, MTCO2, and MTCO4, but increased beclin-1, p62, and LC3. CSE upregulated mitophagy and lysosomes activity via ERK1/2 phosphorylation. In vitro, cigarette smoke induced the deterioration of ASMCs, which might explain the tissue loss and structural remodeling in COPD bronchi. The results suggest that preventing exceeded mitophagy in ASMCs might present a novel therapeutic target for COPD. [ABSTRACT FROM AUTHOR]

Abstract: Sulfur dioxide (SO2) is a common gaseous pollutant. It is also, however, endogenously generated from sulfur-containing amino acids. Recent studies have demonstrated that rat blood pressure can be lowered by SO2-exposure in vivo and that vasodilation caused by SO2 at low concentrations (<450μM) is endothelium-dependent in rat aorta. However, effects of SO2 on nitric oxide synthase (NOS) and nitric oxide (NO) production have not been previously studied in rat aorta. The objective of the present study is to assess the effects of acute (10min) and prolonged (2h) stimulation with different concentrations of SO2 on NO/cGMP pathway in isolated rat aorta. The results show that: (1) the acute and prolonged pretreatments with SO2 produced an inhibition of vasoconstrictions induced by norepinephrine. (2) SO2 potentiated activity of endothelial nitric oxide synthase (eNOS), but not of induced NOS (iNOS). (3) SO2 could increase expression of eNOS gene on the transcription and translation levels in rat aorta. (4) SO2 enhanced NO formation in aortic tissue. (5) The level of cGMP in rat aorta was increased by SO2 and no change of cAMP. These findings led to the conclusion: there were acute and prolonged effects of SO2 on the NO/cGMP signalling pathway; and SO2 could upregulate the eNOS–NO–cGMP pathway and at least partly by which the SO2 might cause vasodilation and inhibition to vasoconstriction. [ABSTRACT FROM AUTHOR]

To explore the toxicological and physiological role of gaseous SO2 on vascular contractility and its level in vascular tissues, a vasodilation study of isolated rat thoracic aortic rings by gaseous SO2 was carried out. The level of SO2 in vascular tissue was assayed using a modified high-performance liquid chromatographic method with fluorescence detection (HPLC-FD). The results show that gaseous SO2 (from 1 μ M to 2000 μ M) relaxed rat thoracic aortic rings in a dose-dependent manner. The physiological concentrations of SO2 in thoracic aortic tissues and plasma in rats were 127.76 ± 31.34 μ M and 16.77±8.24 μ M, respectively; The vasorelaxant effect of gaseous SO2 at physiological and low concentrations (<450 μ M) was endothelium dependent, and at high concentrations (>500 μ M) was endothelium independent. The results also show that SO2 could be endogenously generated in vascular tissues, and mainly in vascular endothelial cells; acetylcholine (Ach) increased the SO2 level in vascular tissue, and noradrenaline (NE) decreased the SO2 level. These findings demonstrate that gaseous SO2 is a vasorelaxant substance, and the vasorelaxant effect of gaseous SO2 is much stronger than that of its derivatives sulfite and bisulfite, which result from the inactivation process of SO2 gas transmitter by which SO2 is hydrated to form sulfite, and the latter is enzymatically oxidized to form sulfate. These findings also demonstrate that endogenous SO2 level in vascular tissue may be regulated by Ach and NE. [ABSTRACT FROM AUTHOR]

Abstract: To explore the physiological role of endogenous gaseous sulfur dioxide (SO2) on vascular contractility and its underlying cellular and molecular mechanisms, vasodilation experiment of isolated rat thoracic aortic rings by gaseous SO2 was carried out and the signal transduction pathways involved in the vascular effects of SO2 were investigated. In the present study, SO2 gas and SO2 gas-bubbled solution (SO2 stock solution) were first used to relax vascular tissues. The results show: (1) Gaseous SO2 relaxed rat thoracic aortic rings in a dose-dependent manner (from 1 to 2000μM). The vasorelaxant effect of SO2 at physiological relevant and low concentrations (<450μM) was endothelium-dependent, and at high concentrations (>500μM) was endothelium-independent. (2) The vasorelaxation by addition of SO2 stock solution (final concentrations ⩽2mM) was actually caused by SO2 molecules, not by sulfite or bisulfite, and the characteristic of vasorelaxation by SO2 was different from that of sulfite and bisulfite. (3) The vasorelaxant effect of SO2 was not due to the altered neurotransmitter release from the autonomous or nonadrenergic and noncholinergic (NANC) nerve endings, also not due to superoxide and hydrogen peroxide produced in the vascular tissues, also disapproving the involvement of prostaglandin, PKC, β-adrenoceptor and cAMP pathways. (4) The vasorelaxant effect of SO2 at the physiological relevant and low concentrations was mediated by the cGMP pathway. (5) There was the synergistic effect on smooth muscle relaxation between much lower concentrations of SO2 (3μM) and NO (3 or 5nM). These findings led to the conclusions: endogenous gaseous SO2 was a vasoactive factor, which might regulate vascular smooth muscle tone in synergy with NO. [Copyright &y& Elsevier]

Histone deacetylases (HDACs) are a family of enzymes involved in transcription regulation. HDACs are known to play key roles in the regulation of cell proliferation; consequently, inhibition of HDACs has become an interesting approach for anti-cancer therapy. However, expression of mammalian HDACs has proven to be difficult. All attempts to express these HDACs in E.coli, Pichia and baculovirus systems were unsuccessful. Here we present the stable expression of human recombinant His-tagged HDAC1 and HDAC3 in mammalian cells. Full-length human genes for HDAC1 and HDAC3 were cloned into the pcDNA 3.1 vector containing a N-terminal His-tag with an enterokinase cleavage site. Recombinant HDAC enzyme activity was only detected after nickel affinity purification due to high activity of endogenous HDACs; and removal of the His-tag increased activity 2–4 fold. Western blots demonstrated the nickel affinity purified rhHDAC1 preparation also contained endogenous HDAC2 and HDAC3; likewise, rhHDAC3 preparation contained endogenous HDAC1 and HDAC2. Therefore, the active HDAC preparation is actually a multi-protein and a multi-HDAC containing complex. This provides one explanation for the similar IC50 values exhibited by SAHA and MS-275 against nuclear HDACs and rhHDAC1 and 3 preparations. These results demonstrate that recombinant forms of the HDACs can be over-expressed in mammalian cells, isolated as active multi-protein complexes that contain multiple HDAC enzymes, and caution must be used when determining HDAC inhibitor in vitro selectivity. [Copyright &y& Elsevier]

The role of the individual histone deacetylases (HDACs) in the regulation of cancer cell proliferation was investigated using siRNA-mediated protein knockdown. The siRNA for HDAC3 and HDAC1 demonstrated significant morphological changes in HeLa S3 consistent with those observed with HDAC inhibitors. SiRNA for HDAC 4 or 7 produced no morphological changes in HeLa S3 cells. HDAC1 and 3 siRNA produced a concentration-dependent inhibition of HeLa cell proliferation; whereas, HDAC4 and 7 siRNA showed no effect. HDAC3 siRNA caused histone hyperacetylation and increased the percent of apoptotic cells. These results demonstrate that the Class I HDACs such as HDACs 1 and 3 are important in the regulation of proliferation and survival in cancer cells. These results and the positive preclinical results with non-specific inhibitors of the HDAC enzymes provide further support for the development of Class I selective HDAC inhibitors as cancer therapeutics. [Copyright &y& Elsevier]

Background: In the era of second-generation ALK tyrosine kinase inhibitors (ALK-TKIs), there was a paucity of data regarding the progression patterns, resistant mechanisms, and subsequent therapeutic approaches for ALK-positive (ALK+) non-small cell lung cancer (NSCLC). Methods: Patients with advanced ALK+ NSCLC were retrospectively selected from our center. Cohort 1 consisted of patients who experienced disease progression after receiving first-line alectinib treatment (n = 20), while Cohort 2 included patients who progressed following sequential treatment with crizotinib and second-generation ALK-TKIs (n = 53). Oligo-progression was defined as the occurrence of disease progression in no more than three lesions. Symptomatic progression was determined when patients developed new symptoms or experienced worsening of pre-existing symptoms during radiological progression. Results: The incidence of central nervous system (CNS) progression and symptomatic CNS progression was significantly lower in Cohort 1 compared to patients treated with crizotinib, with rates of 15.0% vs. 56.6% (p = 0.002) and 5.0% vs. 32.1% (p = 0.016), respectively. A total of 60.3% (44/73) patients underwent repeated biopsy and next-generation sequencing subsequent to the second-generation ALK-TKI resistance, with secondary mutation in ALK kinase domain emerging as the predominant mechanism of resistance (56.8%). Local therapy was applied to 50% of oligo-progression cases. Subsequent ALK-TKIs demonstrated significantly prolonged progression-free survival (PFS) (8.6 m vs. 2.7 m, p = 0.021, HR = 0.43, 95%CI: 0.15–0.85) and long-term overall survival (OS) (NA vs. 11.9 m, p = 0.132, HR = 0.50, 95%CI: 0.18–1.25) in patients harboring ALK resistance mutations, compared to those without such mutations. For patients without ALK-resistant mutations following progression on second-generation ALK-TKIs, there was no statistically significant difference in survival outcomes between subsequent chemotherapy or alternative ALK-TKI treatments. Conclusions: First-line alectinib demonstrated superior efficacy in protecting the CNS compared to crizotinib. For patients with ALK-resistant mutations following the resistance to second-generation ALK-TKIs, appropriate sensitive ALK-TKI should be administered; for those without such mutations, the selection of chemotherapy or third-generation ALK-TKI should be based on the patient's overall physical health and personal preferences. [ABSTRACT FROM AUTHOR]

With the development of the economy, anthropogenic emissions in the atmospheric environment increases, and air pollution has caused wide public concern. Vehicle exhaust is an important emission source in the atmosphere, and alkanes are the representative components in it. In this study, the optical properties of secondary organic aerosol (SOA) derived from several C 12 alkanes (2-methylundecane, hexylcyclohexane, and cyclododecane) in the absence of NO X were determined. Absorption (imaginary part of the refractive index (RI), k) at 532 nm was negligible for all the derived SOA, and the scattering (real part of RI, n) of the SOA at 532 nm followed the order of cyclododecane SOA < hexylcyclohexane SOA < 2-methylundecane SOA, at both room- (25 °C) and low- (5 °C) temperature. The chemical compositions of the SOA formed were analyzed with an electrospray ionization time-of-flight mass spectrometer (ESI-TOF-MS). The mass spectra showed that the oligomers were generated in the reactions. It was shown that the different reaction pathways (due to various alkane structures) leaded to the difference in SOA chemical composition, which changed the RI values. The low-temperature condition promoted the progress of the oligomerization reaction so that the final RI values also changed. This work suggested that when estimating the radiative forcing of SOA using regional or global models, the structure of the precursors and reaction conditions should be taken into account. Unlabelled Image • Optical properties of SOA derived from several C 12 alkanes at 25 °C and 5 °C were determined. • SOA RI followed the order: cyclododecane < hexylcyclohexane < 2-methylundecane. • Different alkane structures leaded to different SOA chemical composition, which changed the RI. • Low-temperature promoted the oligomerization reaction progress, final RI values changed. [ABSTRACT FROM AUTHOR]

Rice blast, caused by rice blast fungus (Magnaporthe oryzae), is a global threat to food security, with up to 50% yield losses. Panicle blast is a severe form of rice blast, and disease responses vary between cultivars with different genotypes. Reactive oxygen species (ROS)-mediated signaling reactions and the phenylpropanoid pathway are important defense mechanisms involved in recognizing and resisting against fungal infection. To understand rice-M. oryzae interactions in resistant and susceptible cultivars, we determined dynamic changes in the activities of five defense-related enzymes in resistant cultivar jingsui 18 and susceptible cultivar jinyuan 899 infected with M. oryzae from 4 to 25 days after infection. We then performed untargeted metabolomics analyses to profile the metabolomes of the cultivars under infected and non-infected conditions. Dynamic changes in the activities of five defense-related enzymes were closely related to panicle blast resistance in rice. Metabolome data analysis identified 634 differentially accumulated metabolites (DAMs) between resistant and susceptible cultivars following infection, potentially explaining differences in disease response between varieties. The most enriched DAMs were associated with lipids and lipid-like molecules, phenylpropanoids and polyketides, organoheterocyclic compounds, organic acids and derivatives, and lignans, neolignans, and related compounds. Multiple metabolic pathways are involved in resistance to panicle blast in rice, including biosynthesis of other secondary metabolites, amino acid metabolism, lipid metabolism, phenylpropanoid biosynthesis, arachidonic acid metabolism, arginine biosynthesis, tyrosine metabolism, tryptophan metabolism, tyrosine and tryptophan biosynthesis, lysine biosynthesis, and oxidative phosphorylation. [ABSTRACT FROM AUTHOR]

Liposomes (LPs) are a delivery system for stabilizing pharmaceuticals with limited use due to their propensity to congregate and fuse. A proposed method of addressing these problems is polymer coating. In this study, the potential of octadecylamine (ODA)-coated liposomes and carboxymethyl chitosan (CMCS/ODA-LPs) for enhancing Wacao pentacyclic triterpene saponin (WPTS) transport capacity was investigated. CMCS/ODA-LPs were produced by electrostatic adsorption and thin-film hydration. Response surface methodology (RSM) was employed to enhance the process and encapsulation efficiency (EE) for optimum drug encapsulation efficiency. The synthesized WPTS-CMCS/ODA-LPs were uniformly dispersed in a circular shape, and during 14 days of storage at 4 °C, the particle size and morphology did not significantly change. Vesicle size, zeta potential, polydispersity index (PDI), and entrapment efficiency (%) were 179.1 ± 7.31 nm, −29.6 ± 1.35 mV, 0.188 ± 0.052, and 75.62 ± 0.43, respectively. The hemolysis test revealed that WPTS-CMCS/ODA-LPs were sufficiently biocompatible. Compared to WPTS-LPs, WPTS-CMCS/ODA-LPs consistently showed a much more significant cytotoxic effect on cancer cells. Early and WPTS-CMCS/ODA-LPs-induced apoptosis resulted in almost seven times more cell death than the control. Compared to physiological pH 7.3, the pH-sensitive CMCS coupled LPs increased drug release at acidic pH 6.5. These findings suggest the efficacy of pH-sensitive CMCS/ODA-LPs as a medication delivery method for WPTS. [ABSTRACT FROM AUTHOR]