Search

Aiming at the problem of noise during the operation of the pyrotechnic separation device, this paper uses LS-DYNA software to simulate the separation process of the separation nut. Then uses the LMS Virtual. Lab software to predict and analyse the mechanical impact noise during the separation, and quantitatively decoupling the contribution rate of the mechanical noise generated by the movement of each component. The results indicate that the inner sleeve impact is the main source of mechanical noise during the separation (more than 90 %). [ABSTRACT FROM AUTHOR]

Even though standard treatment options are available for prostate cancer patients, prostate cancer is still a leading cause of death in many Western countries due to drug resistance and recurrence. Immune checkpoint blockade therapy has been proved to be very effective in some melanoma patients, which might dependent on the preconditioned immune system. Here we explored the effect of chemotherapy (oxaliplatin) in combination with immune checkpoint blockade therapy (anti‑PD‑1 treatment) in prostate cancer cell lines and pre‑clinical animal models. We found that oxaliplatin is effective in castration‑resistant cells and enhanced the response of prostate cancer to anti‑PD‑1 antibody treatment. Oxaliplatin stimulated the immunogenic potential and established a pro‑immune microenvironment in prostate cancer. In conclusion, oxaliplatin sensitized anti‑PD‑1 treatment in prostate cancer and this combination may be an option for castration‑resistant prostate cancer patients. [ABSTRACT FROM AUTHOR]

Sirtuin1 (SIRT1) is an NAD+-dependent deacetylase that exhibits multiple biological functions, including cell differentiation inhibition, transcription regulation, cell cycle regulation and anti-apoptosis. Lipopolysaccharides (LPS) are crucial virulence factors produced by Pseudomonas aeruginosa and serve an important role in adjusting the interactions between the host and the pathogen. However, the effect of SIRT1 in the regulation of LPS-induced A459 human alveolar epithelial cells (AECs) oxidative stress remains unclear. The cellular reactive oxygen species (ROS) production was examined in A549 cells that were supplemented with LPS. Relative cell signaling pathway proteins were further investigated by western blot analysis. It was identified that LPS downregulated SIRT1 expression, however, upregulated ROS generation, which was associated with the increase of nuclear factor (NF)-κB and acetyl-NF-κB. Activation of SIRT1 by resveratrol significantly reversed the effects of LPS on A549 cells. By contrast, inhibition of SIRT1 by nicotinamide had the opposite effects that enhance cell ROS production. Thus, the results indicated that SIRT1 serves an important role in the regulation of oxidative stress induced by LPS in human AECs. [ABSTRACT FROM AUTHOR]

Acute brain injury is a critical and emergent condition in clinical settings, which needs to be addressed urgently. Commonly acute brain injuries include traumatic brain injury, ischemic and hemorrhagic strokes. Oxidative stress is a key contributor to the subsequent injuries and impedes the reparative process after acute brain injury; therefore, facilitating an anti-oxidative approach is important in the care of those diseases. Readiness to deliver and permeability to blood brain barrier are essential for the use of this purpose. Inhaled anesthetic gases are a group of such agents. In this article, we discuss the anti-oxidative roles of anesthetic gases against acute brain injury. [ABSTRACT FROM AUTHOR]

Cigarette smoking has been verified to be one of the most important etiological factors causing the development of bronchogenic carcinoma and chronic obstructive pulmonary disease. Azithromycin (AZM) has been demonstrated to have antioxidant capacity. In the present study, whether AZM is able to attenuate cigarette smoke extract (CSE)-induced A549 cell oxidative stress injury was investigated. Cells were incubated with CSE in the presence or absence of AZM. Cell viability was measured using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The expression of vascular endothelial growth factor (VEGF) was analyzed using western blotting and ELISA. The expression of epithelial cell structural proteins, zona occludens (ZO)-1 and occludin was determined using western blotting and immunofluorescence staining. Reactive oxygen species (ROS) production was examined by flow cytometry and fluorescence staining. The results demonstrated that the exposure of A549 cells to CSE decreased cell viability in a dose- and time-dependent manner. AZM significantly attenuated the CSE-induced decreases in the expression of VEGF and epithelial cell structural proteins, including ZO-1 and occludin. CSE also stimulated ROS production in the A549 cell, while AZM significantly reversed the effects of CSE. In addition, the inhibition of ROS by N-acetyl-L-cysteine had similar effects as AZM on the expression of VEGF and epithelial cell structural proteins and also enhanced cell proliferation. In conclusion, AZM attenuated CSE-induced oxidative stress injury in A549 cells and may be a promising therapeutic agent for smoking-associated pulmonary diseases. [ABSTRACT FROM AUTHOR]

Abstract: Eddy current sensors, as one of nondestructive testing and evaluation instruments, have been widely used in displacement measurement as well as defect characterization. However, in eddy current displacement measurement, the test not only depends on the displacement between the coil and samples, but also relates to the electrical and magnetic properties (such as electrical conductivity and magnetic permeability) of samples. So, the eddy current sensor is limited to test one sample after one calibration. In order to make eddy current sensors compatible with more samples after one calibration without testing error, this paper designed a new eddy current displacement instrument extended from the previous theoretical analysis and experiment study investigating the relationship of the coil resistance and inductance. A series of experiments indicate that the designed new eddy current displacement instrument can eliminate the influence of the samples'' electromagnetic properties effectively. [Copyright &y& Elsevier]

The endothelial lining of cerebral microvessels is damaged relatively early after cerebral ischemia/reperfusion (I/R) injury and mediates blood-brain barrier (BBB) disruption, neurovascular injury, and long-term neurological deficits. I/R induces BBB leakage within 1 h due to subtle structural alterations in endothelial cells (ECs), including reorganization of the actin cytoskeleton and subcellular redistribution of junctional proteins. Herein, we show that the protein peroxiredoxin-4 (Prx4) is an endogenous protectant against endothelial dysfunction and BBB damage in a murine I/R model. We observed a transient upregulation of Prx4 in brain ECs 6 h after I/R in wild-type (WT) mice, whereas tamoxifen-induced, selective knockout of Prx4 from endothelial cells (eKO) mice dramatically raised vulnerability to I/R. Specifically, eKO mice displayed more BBB damage than WT mice within 1 to 24 h after I/R and worse long-term neurological deficits and focal brain atrophy by 35 d. Conversely, endothelium-targeted transgenic (eTG) mice overexpressing Prx4 were resistant to I/R-induced early BBB damage and had better long-term functional outcomes. As demonstrated in cultures of human brain endothelial cells and in animal models of I/R, Prx4 suppresses actin polymerization and stress fiber formation in brain ECs, at least in part by inhibiting phosphorylation/ activation of myosin light chain. The latter cascade prevents redistribution of junctional proteins and BBB leakage under conditions of Prx4 repletion. Prx4 also tempers microvascular inflammation and infiltration of destructive neutrophils and proinflammatory macrophages into the brain parenchyma after I/R. Thus, the evidence supports an indispensable role for endothelial Prx4 in safeguarding the BBB and promoting functional recovery after I/R brain injury. [ABSTRACT FROM AUTHOR]

A joint cell range expansion (CRE) and enhanced inter-cell interference coordination (eICIC) scheme is proposed to enhance the capacity of two-tier heterogeneous networks. Optimal CRE bias and almost blank subframe ratio solutions are achieved by considering the fairness of users at the centre and cell edge. Capacity improvement is verified through extended results. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) triggers a plethora of inflammatory events in the brain that aggravate secondary injury and impede tissue repair. Resident microglia (Mi) and blood-borne infiltrating macrophages (MΦ) are major players of inflammatory responses in the post-TBI brain and possess high functional heterogeneity. However, the plasticity of these cells has yet to be exploited to develop therapies that can mitigate brain inflammation and improve the outcome after TBI. This study investigated the transcription factor STAT1 as a key determinant of proinflammatory Mi/MΦ responses and aimed to develop STAT1 as a novel therapeutic target for TBI using a controlled cortical impact model of TBI on adult male mice. TBI induced robust upregulation of STAT1 in the brain at the subacute injury stage, which occurred primarily in Mi/MΦ. Intraperitoneal administration of fludarabine, a selective STAT1 inhibitor, markedly alleviated proinflammatory Mi/MΦ responses and brain inflammation burden after TBI. Such phenotype-modulating effects of fludarabine on post-TBI Mi/MΦ were reproduced by tamoxifen-induced, selective KO of STAT1 in Mi/MΦ (STAT1 mKO). By propelling Mi/MΦ away from a detrimental proinflammatory phenotype, STAT1 mKO was sufficient to reduce long-term neurologic deficits and brain lesion size after TBI. Importantly, short-term fludarabine treatment after TBI elicited long-lasting improvement of TBI outcomes, but this effect was lost on STAT1 mKO mice. Together, our study provided the first line of evidence that STAT1 causatively determines the proinflammatory phenotype of brain Mi/MU after TBI. We also showed promising preclinical data supporting the use of fludarabine as a novel immunomodulating therapy to TBI. [ABSTRACT FROM AUTHOR]

Immunomodulation holds therapeutic promise against brain injuries, but leveraging this approach requires a precise understanding of mechanisms. We report that CD8+CD122+CD49dlo T regulatory-like cells (CD8+ TRLs) are among the earliest lymphocytes to infiltrate mouse brains after ischemic stroke and temper inflammation; they also confer neuroprotection. TRL depletion worsened stroke outcomes, an effect reversed by CD8+ TRL reconstitution. The CXCR3/CXCL10 axis served as the brain-homing mechanism for CD8+ TRLs. Upon brain entry, CD8+ TRLs were reprogrammed to upregulate leukemia inhibitory factor (LIF) receptor, epidermal growth factor-like transforming growth factor (ETGF), and interleukin 10 (IL-10). LIF/LIF receptor interactions induced ETGF and IL-10 production in CD8+ TRLs. While IL-10 induction was important for the antiinflammatory effects of CD8+ TRLs, ETGF provided direct neuroprotection. Poststroke intravenous transfer of CD8+ TRLs reduced infarction, promoting long-term neurological recovery in young males or aged mice of both sexes. Thus, these unique CD8+ TRLs serve as early responders to rally defenses against stroke, offering fresh perspectives for clinical translation. [ABSTRACT FROM AUTHOR]

Anthocyanin production in apple (Malus domestica) fruit and their consequent coloration can be induced by high-light treatment. The hormone ethylene is also essential for this coloration, but the regulatory relationships that link ethylene and light with anthocyanin-associated coloration are not well defined. In this study, we observed that high-light treatment of apple fruit increased anthocyanin accumulation more than moderate-light treatment did and was the main contributor of induced ethylene production and activation of anthocyanin biosynthesis. A transcriptome study of light-treated apple fruit suggested that a long noncoding RNA (lncRNA), MdLNC610, the corresponding gene of which is physically located downstream from the 1-aminocyclopropane-1-carboxylate oxygenase (ACO) ethylene biosynthesis gene MdACO1, likely affects anthocyanin biosynthesis under high-light treatment. Expression and promoter ß-glucuronidase reporter analyses further showed that MdLNC610 upregulates expression of MdACO1 and so likely participates in high-light-induced ethylene biosynthesis. Overexpression of MdACO1 and MdLNC610 in apple fruit and calli indicated that a major increase in MdLNC610 expression activates MdACO1 expression, thereby causing an increase in ethylene production and anthocyanin levels. These results suggest that MdLNC610 participates in the regulation of high-light-induced anthocyanin production by functioning as a positive regulator to promote MdACO1 expression and ethylene biosynthesis. Our study provides insights into the relationship between mRNA and lncRNA networks in the ethylene biosynthetic pathway and anthocyanin accumulation in apple fruit. [ABSTRACT FROM AUTHOR]

In order to study the relationships among national laboratories, universities and industries in U. S., the constitution of American basic research system is analyzed. National laboratories provide a good platform for universities as well as universities provide human resource and logistical support for national laboratories. Industries actively participate in the management of national laboratories, and the technological cooperation between industries and national laboratories is closer. The positions and functions of national laboratories, universities and industries during technology development are studied according to Technology Readiness Levels. Technology Readiness Levels of universities, national laboratories and industries are 1-2, 2-6 and 6-9, respectively. The division of national laboratories, universities and industries is clear-cut. National laboratories, universities and industries form a complete innovative chain, and national laboratories serve as a link. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) contain specific proteins, lipids, and nucleic acids that can be passed to other cells as signal molecules to alter their function. However, there are many problems and challenges in the conversion and clinical application of EVs. Storage and protection of EVs is one of the issues that need further research. To adapt to potential clinical applications, this type of problem must be solved. This review summarizes the storage practices of EVs in recent years, and explains the impact of temperature on the quality and stability of EVs during storage based on current research, and explains the potential mechanisms involved in this effect as much as possible. [ABSTRACT FROM AUTHOR]

In order to improve the recognition performance of the optical correlator for the distortion target, this article makes a complete theoretical analysis of the structure of the lensless integrated micro-optic correlator. Based on this theory, a simulation system for the distortion target of the correlator is established. At the same time, based on the system, an optimal trade-off synthetic discrimination function filter suitable for different distortions situations of the target to be identified was designed. The filter was loaded into the experimental light path of the correlator to verify the recognition effect of correlator on the distortion target. Simulation and experimental results illustrate that our lensless coaxial integrated micro-optical correlator can accurately recognize the targets with rotation distortion in the range of −50° to 50°and scaling distortion in the range of 58%–164%, which has a good distortion invariant recognition performance. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is the most prevalent chronic joint disease in China. The aim of this study was to examine the association between metabolic syndrome (MetS) and knee OA in a population-based Chinese study.Methods: Data included in this analysis is from a cross-sectional study, i.e., the Xiangya Hospital Health Management Center Study. MetS was diagnosed according to the criteria defined by the Chinese Diabetes Society. Radiographic knee OA was defined as changes equivalent to Kellgren-Lawrence (K-L) grade 2 or above at least one side. Associations between MetS and its components with OA were evaluated by conducting multivariable adjusted logistic regression.Results: A total of 5764 participants were included in the present study. The unadjusted OR (1.27, 95%CI: 1.10-1.47, P = 0.001), age-sex adjusted OR (1.17, 95%CI: 1.01-1.36, P = 0.041) and multivariable adjusted OR (1.17, 95%CI: 1.01-1.36, P = 0.043) all suggested a positive association between MetS and knee OA. Besides, its components (e.g., overweight, hypertension and dyslipidemia) were also associated with the prevalence of radiographic knee OA respectively, after adjusting for some confounding factors. In addition, with the accumulation of MetS components, the prevalence of knee OA increased. Furthermore, MetS as a whole was associated with the prevalence of knee osteophyte (OSP) (OR = 1.72, 95%CI: 1.42-2.09, P < 0.001), but not joint space narrowing (JSN) (OR = 1.06, 95%CI: 0.91-1.23, P = 0.449).Conclusions: The findings of the present study indicated that there was a positive association between the prevalence of MetS and knee OA. However, MetS as a whole was associated with the higher prevalence of knee OSP, but not JSN, which should shed light on our understanding the association between MetS and OA. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to examine the associations of dietary magnesium (Mg) intake and serum Mg concentration with the high-sensitivity C-reactive protein (hsCRP) level in early radiographic knee osteoarthritis (OA) patients. Methods: Multivariable logistic regression was used to test the associations of dietary and serum Mg with the serum hsCRP in early radiographic knee OA patients after adjustment of a number of potential confounding factors. Results: A total of 936 early radiographic knee OA patients were included. A significant association between dietary Mg intake and hsCRP was observed. The multivariable-adjusted odds ratio (OR) (95% CI) for elevated hsCRP (3.0 mg/l) in the second, third, fourth, and fifth dietary Mg intake quintile were 0.44 (95% CI: 0.24-0.82), 0.58 (95% CI: 0.31-1.10), 0.34 (95% CI: 0.15-0.77), and 0.19 (95% CI: 0.06-0.57), respectively, compared with the lowest (first) quintile, and p for trend was 0.01. A significant association between serum Mg concentration and hsCRP was observed. The multivariable-adjusted OR (95% CI) for elevated hsCRP in the second, third, fourth, and fifth serum Mg concentration quintile were 0.63 (95% CI: 0.35-1.12), 0.83 (95% CI: 0.50-1.39), 0.53 (95% CI: 0.31-0.91), and 0.46 (95% CI: 0.25-0.85), respectively, compared with the lowest quintile, and p for trend was 0.01. Conclusion: The present study indicated that both dietary and serum Mg were inversely associated with serum hsCRP in early radiographic knee OA patients. [ABSTRACT FROM AUTHOR]

Background: The study aims to investigate the expression of SIRT1 in articular cartilage of patients with primary knee osteoarthritis (OA) and its relationship with disease severity. Methods: Cartilage tissue samples were collected from 38 knee OA patients and 9 normal healthy controls and then ascribed to normal, mild, moderate, and severe groups on the basis of the improved Mankin grading system. The expression of SIRT1 in articular cartilage was detected by immunohistochemistry and western blots. The expression of p53 and acetylated p53 (Ac-p53) was also measured by western blots. Results: The mutual comparisons of the SIRT1 expression levels in all groups have statistical significance except the one between the mild and moderate groups. Moreover, western blot results showed that the SIRT1 was decreased and p53/Ac-p53 were increased in the OA group. The average gray level of SIRT1 increases with the improving grade of the improved Mankin grading system scorers. Conclusions: The expression of SIRT1 in articular cartilage is negatively associated with severity of knee OA, indicating that SIRT1 may act as a monitoring indicator for determining development and progression of knee OA. [ABSTRACT FROM AUTHOR]

Background: Major reports have suggested that bone mineral density (BMD) is higher in patients with osteoarthritis (OA), while other studies do not agree. Our aim was to examine the cross-sectional association between phalangeal BMD and radiographic knee OA.Methods: A total of 2855 participants were included in this study. Radiographic knee OA was defined as Kellgren-Lawrence (K-L) Grade ≥ 2 in at least one leg. BMD scans of the middle phalanges of the second, third and fourth digits of the nondominant hand were performed with a compact radiographic absorptiometry system (Alara MetriScan®). A multivariable logistic analysis model was applied to test the relation between phalangeal BMD with radiographic knee OA, the presence of knee osteophytes (OSTs), and knee joint space narrowing (JSN) after adjusting for a number of potential confounding factors.Results: The multivariable-adjusted odds ratios with 95 % confidence intervals [ORs (95 % CI)] of radiographic knee OA across phalangeal BMDs were 1.08 (95 % CI 0.89-1.32) and 0.62 (95 % CI 0.45-0.86), respectively. The P for trend was 0.09. For the female population, the multivariable-adjusted ORs (95 % CI) of radiographic knee OA across phalangeal BMD were 1.01 (95 % CI 0.73-1.37) and 0.58 (95 % CI 0.38 - 0.87), respectively. The P for trend was 0.02. This positive finding, however, did not exist in the male subgroup. There was a significantly lower prevalence of OST in the osteoporosis (OP) group than in the normal group (OR = 0.59, 95 % CI 0.40-0.88; P for trend was 0.01). In contrast, the prevalence of JSN was significantly higher in the osteopenia group (OR = 1.22, 95 % CI 1.00-1.48) and the OP group (OR = 1.35, 95 % CI 1.00-1.84) than in the normal group. The P for trend was 0.02.Conclusions: This study observed lower odds for the presence of radiographic knee OA and OST in OP patients than in normal subjects. The prevalence of JSN was higher in the osteopenia and OP groups than in normal subjects. [ABSTRACT FROM AUTHOR]

Current first-line artemisinin antimalarials are threatened by the emergence of resistant Plasmodium falciparum. Decreased sensitivity is evident in the initial (early ring) stage of intraerythrocytic development, meaning that it is crucial to understand the action of artemisinins at this stage. Here, we examined the roles of iron (Fe) ions and haem in artemisinin activation in early rings using Fe ion chelators and a specific haemoglobinase inhibitor (E64d). Quantitative modelling of the antagonism accounted for its complex dependence on the chemical features of the artemisinins and on the drug exposure time, and showed that almost all artemisinin activity in early rings (>80%) is due to haem-mediated activation. The surprising implication that haemoglobin uptake and digestion is active in early rings is supported by identification of active haemoglobinases (falcipains) at this stage. Genetic down-modulation of the expression of the two main cysteine protease haemoglobinases, falcipains2and3,renders early ring stage parasites resistant to artemisinins. This confirms the important role of haemoglobin-degrading falcipains in artemisinin activation, and shows that changes in the rate of artemisinin activation could mediate high-level artemisinin resistance. [ABSTRACT FROM AUTHOR]

In this work, a series of binary Ti–Mo alloys with the Mo contents ranging from 3.2 to 12 at.% were prepared using non-consumable arc melting. The microstructures were investigated by X-ray diffraction and transmission electron microscope, and the elastic modulus was evaluated by nanoindentation testing technique. The evolution of the volume fractions of ω phase was investigated using X-ray photoelectron spectroscopy. The results indicated that the phase constitution and elastic modulus of the Ti–Mo alloys are sensitive to the Mo content. Ti–3.2Mo and Ti–8Mo alloys containing only α and β phases, respectively, have a low elastic modulus. In contrast, Ti–4.5Mo, Ti–6Mo, Ti–7Mo alloys, with different contents of ω phase, have a high elastic modulus. A simple micromechanical model was used to calculate the elastic modulus of ω phase ( E ω ), which was determined to be 174.354 GPa. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated that osteopontin (OPN) levels are elevated in the synovial fluid and articular cartilage, and are associated with the severity of knee osteoarthritis (OA). However, the role of OPN in the pathogenesis of OA has yet to be elucidated. The present study aimed to investigate the effects of OPN on the expression of the aggrecanases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)4 and ADAMTS5, in human OA chondrocytes, as they serve a key function in aggrecan degradation. Human OA chondrocytes were obtained from the knees of 16 patients with OA, and subsequently cultured in a monolayer. The chondrocytes were divided into three groups, which included the control (no treatment), N-OPN (treated with 100 ng/ml OPN, the normal circulating OPN concentration) and the H-OPN groups (treated with 1 μg/ml OPN, a high OPN concentration). Reverse transcription-quantitative polymerase chain reaction was performed to quantify the relative mRNA expression levels of ADAMTS4, ADAMTS5 and aggrecan in the chondrocytes. The mRNA expression levels of ADAMTS4 were significantly reduced in the N-OPN and H-OPN groups when compared with the control group (P<0.0001). In addition, the mRNA expression levels of ADAMTS4 were lower in the H-OPN group when compared with the N-OPN group (P<0.001). However, no statistically significant difference was observed in the relative mRNA expression levels of ADAMTS5 among the three groups (P>0.05). Furthermore, the mRNA expression levels of aggrecan were higher in the N-OPN and H-OPN groups when compared with the control group (P<0.0001), and a statistically significant difference was observed between the N-OPN and H-OPN groups with regard to the mRNA expression of aggrecan (P<0.0001). These results demonstrated that OPN may exert a protective effect in human OA chondrocytes against aggrecan degradation by suppressing the expression of ADAMTS4. [ABSTRACT FROM AUTHOR]

A two-marker combination of plastid rbcL and matK has previously been recommended as the core plant barcode, to be supplemented with additional markers such as plastid trnH-psbA and nuclear ribosomal internal transcribed spacer (ITS). To assess the effectiveness and universality of these barcode markers in seed plants, we sampled 6,286 individuals representing 1,757 species in 141 genera of 75 families (42 orders) by using four different methods of data analysis. These analyses indicate that (i) the three plastid markers showed high levels of universality (87.1-92.7%), whereas ITS performed relatively well (79%) in angiosperms but not so well in gymnosperms; (ii) in taxonomic groups for which direct sequencing of the marker is possible, ITS showed the highest discriminatory power of the four markers, and a combination of ITS and any plastid DNA marker was able to discriminate 69.9-79.1% of species, compared with only 49.7% with rbcL + matK; and (iii) where multiple individuals of a single species were tested, ascriptions based on ITS and plastid DNA barcodes were incongruent in some samples for 45.2% of the sampled genera (for genera with more than one species sampled). This finding highlights the importance of both sampling multiple individuals and using markers with different modes of inheritance. In cases where it is difficult to amplify and directly sequence ITS in its entirety, just using ITS2 is a useful backup because it is easier to amplify and sequence this subset of the marker. We therefore propose that ITS/ITS2 should be incorporated into the core barcode for seed plants. [ABSTRACT FROM AUTHOR]