Search

Abstract Nasopharyngeal carcinoma (NPC), a malignancy highly prevalent in East and Southeast Asia, is primarily treated with radiotherapy (RT). However, hypoxia-induced radioresistance presents a significant challenge. Nanozymes, nanomaterials with catalase-like activity, have emerged as a promising strategy for radiosensitization by converting elevated hydrogen peroxide in the tumor microenvironment into oxygen. Despite their potential, effectively targeting hypoxic lesions has been difficult. Here, we identify transferrin receptor 1 (TfR1) as an upregulated target in NPC, with its expression levels positively correlated with hypoxia. Human heavy-chain ferritin, a specific ligand of TfR1, selectively recognizes hypoxic NPC lesions in preclinical models. Based on these findings, we design a hypoxia-targeted nanozyme by loading platinum nanoparticles into ferritin. This nanozyme exhibits enhanced catalase-like activity and effectively alleviates tumor hypoxia in NPC xenografts. When combined with RT, a single injection of the nanozyme significantly inhibits tumor growth and prolongs mouse survival, outperforming sodium glycididazole, a clinically used radiosensitizer. In summary, our findings highlight TfR1 as an accessible cell surface target in hypoxic NPC lesions. The nanozyme targeting TfR1 holds promise for enhancing the therapeutic effectiveness of RT in NPC through an in situ oxygen-generation mechanism.

Abstract This study aimed to evaluate [18F]GSK1482160 Positron emission tomography imaging for targeting P2X7R, a biomarker for neuroinflammation. Studies of acute neuroinflammation in rodents and transgenic mice with Alzheimer's disease (AD), as well as wild‐type (WT) controls, were conducted via PET‐CT‐MRI scans after tail vein injection of [18F]GSK1482160. Imaging was quantified based on the time‐activity curve, the standardized uptake value ratio, and the binding kinetics distribution volume ratio (DVR) to assess the expression of P2X7R. Tissues were collected post‐PET for immunofluorescence staining. Correlation analysis was performed between DVR and Morris water maze test results. Finally, dynamic Positron Emission Tomography‐Magnetic Resonance Imaging (PET‐MRI) scans were performed in healthy non‐human primates (NHPs). Our study demonstrated that AD mice had a significantly higher DVR than WT mice in the hippocampus (0.92 ± 0.06 vs. 0.79 ± 0.02, p

PURPOSETo investigate the feasibility and usefulness of 2-deoxy-2-(18F)-fluoro-D-glucose positron emission tomography/computed tomography [(18F)-FDG PET/CT] as a novel examination in the surveillance of abnormal myocardial energy metabolism and cardiac dysfunction after cardiopulmonary resuscitation (CPR).METHODSThirteen male Sprague–Dawley rats were randomly divided into a sham group (n = 4), CPR group (n = 4), and trimetazidine (TMZ) + CPR group (n = 5). The expression levels of the myocardial injury marker cardiac troponin I (CTNI) in serum were tested at 6 hours after CPR or TMZ + CPR. The ejection fraction and fraction shortening were evaluated by echocardiography. (18F)-FDG PET/CT was used to measure the FDG uptake and the standardized uptake value (SUV) after CPR or TMZ + CPR for 6 hours. The intermediary carbohydrate metabolites of glycolysis including phosphoenolpyruvate, 3-phospho-D-glycerate, and the lactate/pyruvate ratio were detected through the multiple reaction monitoring approach. Simultaneously, the authors also tested the expression levels of the total adenosine triphosphate (ATP) and the key intermediate products of glucose ovidation as alpha ketoglutarate, citrate, and succinate in the myocardium.RESULTSThe authors found that the aerobic oxidation of glucose was reduced, and the anaerobic glycolysis was significantly enhanced in the myocardium in the early stage of CPR. Meanwhile, the myocardial injury marker CTNI was upregulated considerably (P = 0.014, P = 0.021), and the left ventricular function of the animal heart also markedly deteriorated with the downregulation of ATP after CPR. In contrast, myocardial injury and cardiac function were greatly improved with the increase of ATP in the CPR + TMZ group. In addition, aerobic glucose oxidation metabolites were significantly increased (P < 0.05) and anaerobic glycolysis metabolites were significantly decreased (P < 0.05) after CPR in the myocardium. Surprisingly, (18F)-FDG PET/CT could track the above changes by detecting the FDG uptake value and the SUV.CONCLUSIONGlucose metabolism is an essential factor for myocardial self-repair after CPR. (18F) FDG PET/CT, as a non-invasive technology, can monitor myocardial energy metabolism and cardiac function by tracking changes in glucose metabolism after CPR.

Organic cluster-triggered emission (CTE) displays promising application in bioimaging, chemical sensing, and multicolor luminescence but circular polarize luminescence derived from CTE remains less studied. Here, the authors demonstrate CTE based CPL emission from a supramolecular film derived from solid phase molecular self-assembly.

Stress in life is ubiquitous and unavoidable. Prolonged exposure to severe stress can lead to physical intolerance and impair cognitive function. Non-human primates are considered to be the best animal model for studying cognitive function, especially memory and attention. The finger maze test, with the advantages of short training time and lower cost, is recommended to evaluate learning and memory in non-human primates. In this study, we modified the finger maze test method to evaluate the cognitive function of single-housed cynomolgus monkeys. The flexibility and attention of cynomolgus monkeys were assessed by performing the complex task test and the stranger intrusion interference test, respectively, which increased the difficulty of obtaining rewards, and the ability of long-term memory was also evaluated by the memory test. Furthermore, the changes in cognitive function of the cynomolgus monkeys were tested by using the finger maze test after audio-visual stimulation, and the changes in the cortisol levels during stimulation were also analyzed. We found that, after completing the learning test, there was no significant decrease in their success rate when monkeys processed multitasks at the same time. In the stranger intrusion interference test, all subjects were distracted, but the accuracy did not decrease. The monkeys completed the memory tests in the 1st and 2nd months after the learning tests, with a high success rate. However, the success rate decreased significantly at the end of the 4th month. During audio-visual stimulation, the plasma cortisol level significantly increased in the first 2 months and was maintained at a high level thereafter. One month after audio-visual stimulation, the accuracy of the memory test was significantly reduced, and the total time of distraction was significantly prolonged. In conclusion, chronic audio-visual stimulation can increase blood cortisol levels and impair cognitive function. The modified finger maze test can evaluate many aspects of cognitive function and assess the changes in the cognitive function of adult cynomolgus monkeys under stress.

Abstract Human skin moisture is closely related to health and personal care issues. Many creams were developed to claim capable of skin moisturizing. However, people can hardly check their skin moisture status and the moisturizing effect of various creams conveniently, since currently all the skin moisturizing detection rely on large equipment requiring power supply. Herein, we report a power‐supply independent supramolecular film that is able to directly report the moisturizing status of the skin. With the strategy of solid‐phase molecular self‐assembly (SPMSA), the aqueous precipitates formed by commercially available polyelectrolyte and oppositely charged surfactant would transform into a supramolecular film under a mild mechanical pressure, where the hydrophobic surfactant domains bridged by polyelectrolyte merge into hydrophobic mesophases to reduce interfacial energy. The hydrophobic mesophase will greatly retard water diffusion inside the film, so that a humidity gradient is generated as the film is exposed to a humid environment. The film will bend upward automatically in touch with moisture skin, and the bending degree is proportional to the skin moisture status. Therefore, the film can be used as portable smart power‐free skin moisture sensor.

It has been a big challenge to distinguish synchronous multiple primary lung cancer (sMPLC) from primary lung cancer with intrapulmonary metastases (IPM). We aimed to assess the clinical application of dynamic 18F-FDG PET/CT in patients with multiple lung cancer nodules. We enrolled patients with multiple pulmonary nodules who had undergone dynamic 18F-FDG PET/CT and divided them into sMPLC and IPM groups based on comprehensive features. The SUVmax, fitted Ki value based on dynamic scanning, and corresponding maximum diameter (Dmax) from the two largest tumors were determined in each patient. We determined the absolute between-tumor difference of SUVmax/Dmax and Ki/Dmax (ΔSUVmax/Dmax; ΔKi/Dmax) and assessed the between-group differences. Further, the diagnostic accuracy was evaluated by ROC analysis and the correlation between ΔSUVmax/Dmax and ΔKi/Dmax from all groups was determined. There was no significant difference for ΔSUVmax/Dmax between the IPM and sMPLC groups, while the IPM group had a significantly higher ΔKi/Dmax than the sMPLC group. The AUC of ΔKi/Dmax for differentiating sMPLC from IPM was 0.80 (cut-off value of Ki=0.0059, sensitivity 79%, specificity 75%, p0.05). Dynamic 18F-FDG PET/CT could be a useful tool for distinguishing sMPLC from IPM. Ki calculation based on Patlak graphic analysis could be more sensitive than SUVmax in discriminating IPM from sMPLC in patients with multiple lung cancer nodules.

Abstract Rapid progress has been made to identify and study the causative agent leading to coronavirus disease 2019 (COVID‐19) but many questions including who is most susceptible and what determines severity remain unanswered. Angiotensin‐converting enzyme 2 (ACE2) is a key factor in the infection process of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). In this study, molecularly specific positron emission tomography imaging agents for targeting ACE2 are first developed, and these novel agents are evaluated in vitro, in preclinical model systems, and in a first‐in‐human translational ACE2 imaging of healthy volunteers and a SARS‐CoV‐2 recovered patient (NCT04422457). ACE2 expression levels in different organs in live subjects are quantitatively delineated and observable differences are measured in the patient recovered from COVID‐19. Surprising sites of uptake in the breast, reproductive system and very low uptake in pulmonary tissues are reported. This novel method can add a unique tool to facilitate SARS‐CoV‐2 related research and improve understanding of this enigmatic disease. Molecular imaging provides quantitative annotation of ACE2, the SARS‐CoV‐2 entry receptor, to noninvasively monitor organs impacted by the COVID‐19.

There is an incontestable need for improved treatment modality for glioblastoma due to its extraordinary resistance to traditional chemoradiation therapy. Boron neutron capture therapy (BNCT) may play a role in the future. We designed and synthesized a 10B-boronated derivative of temozolomide, TMZB. BNCT was carried out with a total neutron radiation fluence of 2.4 ± 0.3 × 1011 n/cm2. The effects of TMZB in BNCT were measured with a clonogenic cell survival assay in vitro and PET/CT imaging in vivo. Then, 10B-boronated phenylalanine (BPA) was tested in parallel with TMZB for comparison. The IC50 of TMZB for the cytotoxicity of clonogenic cells in HS683 was 0.208 mM, which is comparable to the IC50 of temozolomide at 0.213 mM. In BNCT treatment, 0.243 mM TMZB caused 91.2% ± 6.4% of clonogenic cell death, while 0.239 mM BPA eliminated 63.7% ± 6.3% of clonogenic cells. TMZB had a tumor-to-normal brain ratio of 2.9 ± 1.1 and a tumor-to-blood ratio of 3.8 ± 0.2 in a mouse glioblastoma model. BNCT with TMZB in this model caused 58.2% tumor shrinkage at 31 days after neutron irradiation, while the number for BPA was 35.2%. Therefore, by combining the effects of chemotherapy from temozolomide and radiotherapy with heavy charged particles from BNCT, TMZB-based BNCT exhibited promising potential for therapeutic applications in glioblastoma treatment.

Abstract Background Acute myeloid leukemia (AML) with mutated nucleophosmin (NPM1) has been recognized as a distinct leukemia entity in the 2016 World Health Organization (WHO) classification. The genetic events underlying oncogenesis in NPM1-mutated AML that is characterized by a normal karyotype remain unclear. Inositol polyphosphate 4-phosphatase type II (INPP4B), a new factor in the phosphoinositide-3 kinase (PI3K) pathway-associated cancers, has been recently found a clinically relevant role in AML. However, little is known about the specific mechanistic function of INPP4B in NPM1-mutated AML. Methods The INPP4B expression levels in NPM1-mutated AML primary blasts and AML OCI-AML3 cell lines were determined by qRT-PCR and western blotting. The effect of INPP4B knockdown on OCI-AML3 leukemia cell proliferation was evaluated, using the Cell Counting Kit-8 and colony formation assay. After INPP4B overexpression or knockdown, the activation of serum and glucocorticoid-regulated kinase 3 (SGK3) and AKT was assessed. The effects of PI3K signaling pathway inhibitors on the levels of p-SGK3 in OCI-AML3 cells were tested. The mass of PI (3,4) P2 and PI (3) P was analyzed by ELISA upon INPP4B overexpression. Knockdown of SGK3 by RNA interference and a rescue assay were performed to confirm the critical role of SGK3 in INPP4B-mediated cell survival. In addition, the molecular mechanism underlying INPP4B expression in NPM1-mutated leukemia cells was explored. Finally, Kaplan–Meier survival analysis was conducted on the NPM1-mutated AML cohort stratified into quartiles for INPP4B expression in The Cancer Genome Atlas (TCGA) dataset. Results High expression of INPP4B was observed in NPM1-mutated AML. Knockdown of INPP4B repressed cell proliferation in OCI-AML3 cells, whereas recovered INPP4B rescued this inhibitory effect in vitro. Mechanically, INPP4B enhanced phosphorylated SGK3 (p-SGK3) status, but did not affect AKT activation. SGK3 was required for INPP4B-induced cell proliferation in OCI-AML3 cells. High levels of INPP4B were at least partially caused by the NPM1 mutant via ERK/Ets-1 signaling. Finally, high expression of INPP4B showed a trend towards lower overall survival and event-free survival in NPM1-mutated AML patients. Conclusions Our results indicate that INPP4B promotes leukemia cell survival via SGK3 activation, and INPP4B might be a potential target in the treatment of NPM1-mutated AML.

How does the visual system realize dynamic tracking? This topic has become popular within cognitive science in recent years. The classical theory argues that multiple object tracking is accomplished via pre-attention visual indexes as part of a cognitively impenetrable low-level visual system. The present research aimed to investigate whether and how tracking processes are influenced by facial expressions that convey abundant social information about one’s mental state and situated environment. The results showed that participants tracked fearful faces more effectively than neutral faces. However, this advantage was only present under the low-attentional load condition, and distractor face emotion did not impact tracking performance. These findings imply that visual tracking is not driven entirely by low-level vision and encapsulated by high-level representations; rather, that facial expressions, a kind of social information, are able to influence dynamic tracking. Furthermore, the effect of fearful expressions on multiple face tracking is mediated by the availability of attentional resources.

Two α-synuclein ligands, 3-methoxy-7-nitro-10H-phenothiazine (2a, Ki = 32.1 ± 1.3 nM) and 3-(2-fluoroethoxy)-7-nitro-10H-phenothiazine (2b, Ki = 49.0 ± 4.9 nM), were radiolabeled as potential PET imaging agents by respectively introducing 11C and 18F. The syntheses of [11C]2a and [18F]2b were accomplished in a good yield with high specific activity. Ex vivo biodistribution studies in rats revealed that both [11C]2a and [18F]2b crossed the blood-brain barrier (BBB) and demonstrated good brain uptake 5 min post-injection. MicroPET imaging of [11C]2a in a non-human primate (NHP) confirmed that the tracer was able to cross the BBB with rapid washout kinetics from brain regions of a healthy macaque. The initial studies suggested that further structural optimization of [11C]2a and [18F]2b is necessary in order to identify a highly specific positron emission tomography (PET) radioligand for in vivo imaging of α-synuclein aggregation in the central nervous system (CNS).

Sphingosine-1-phosphate receptor (S1PR) activation plays a key role in vascular inflammatory response. Here, we report in vivo validation of [ 11 C]TZ3321, a potent S1PR1 radioligand, for imaging vascular inflammation in a rat model of carotid injury. The right common carotid artery of male adult Sprague-Dawley rats was injured by balloon overinflation that denuded the endothelium and distended the vessel wall. Animals received a 60-minute micro-positron emission tomography (micro PET) scan with [ 11 C]TZ3321 at 72 hours after injury. Ex vivo autoradiography was also conducted. The expression and cellular location of S1PR1 were examined by immunohistological analysis. Three-dimensional (3D) reconstruction of the first 100-second microPET/computed tomography (CT) image indicated the location of bilateral common carotid arteries. [ 11 C]TZ3321 displayed significantly higher accumulation (standardized uptake values: 0.93 ± 0.07 vs 0.78 ± 0.09, n = 6, P = .001) in the injured carotid artery than in the contralateral side. Increased tracer uptake in the injured artery was confirmed by autoradiography (photostimulated luminescence measures: 85.5 ± 0.93 vs 71.48 ± 6.22, n = 2). Concordantly, high S1PR1expression was observed in infiltrated inflammatory cells in the injured artery. Our studies demonstrate [ 11 C]TZ3321 microPET is able to detect the acute upregulation of S1PR1 expression in inflamed carotid artery. Therefore, [ 11 C]TZ3321 has potential to be a PET radiotracer for detecting early inflammatory response and monitoring therapeutic efficacy of vascular inflammation.

A variety of post-translational protein modifications (PTMs) are known to be altered as a result of cancer development. Thus, these PTMs are potentially useful biomarkers for breast cancer. Mass spectrometry, antibody microarrays and immunohistochemistry techniques have shown promise for identifying changes in PTMs. In this review, we summarize the current literature on PTMs identified in the plasma and tumor tissue of breast-cancer patients or in breast cell lines. We also discuss some of the analytical techniques currently being used to evaluate PTMs.

Environmental protection through biological mechanisms that aid in the reductive immobilization of toxic metals (e.g., chromate and uranyl) has been identified to involve specific NADH-dependent flavoproteins that promote cell viability. To understand the enzyme mechanisms responsible for metal reduction, the enzyme kinetics of a putative chromate reductase from Gluconacetobacter hansenii (Gh-ChrR) was measured and the crystal structure of the protein determined at 2.25 Å resolution. Gh-ChrR catalyzes the NADH-dependent reduction of chromate, ferricyanide, and uranyl anions under aerobic conditions. Kinetic measurements indicate that NADH acts as a substrate inhibitor; catalysis requires chromate binding prior to NADH association. The crystal structure of Gh-ChrR shows the protein is a homotetramer with one bound flavin mononucleotide (FMN) per subunit. A bound anion is visualized proximal to the FMN at the interface between adjacent subunits within a cationic pocket, which is positioned at an optimal distance for hydride transfer. Site-directed substitutions of residues proposed to involve in both NADH and metal anion binding (N85A or R101A) result in 90-95% reductions in enzyme efficiencies for NADH-dependent chromate reduction. In comparison site-directed substitution of a residue (S118A) participating in the coordination of FMN in the active site results in only modest (50%) reductions in catalytic efficiencies, consistent with the presence of a multitude of side chains that position the FMN in the active site. The proposed proximity relationships between metal anion binding site and enzyme cofactors is discussed in terms of rational design principles for the use of enzymes in chromate and uranyl bioremediation.

Recent studies revealed that micro RNA-10b (mir-10b) is highly expressed in metastatic breast cancer cells and positively regulates breast cancer cell migration and invasion through inhibition of HOXD10 target synthesis. In this study we designed anti-mir-10b molecules and combined them with poly L-lysine (PLL) to test the delivery effectiveness. An RNA molecule sequence exactly matching the mature mir-10b minor antisense showed strong inhibition when mixed with PLL in a wound-healing assay with human breast cell line MDA-MB-231. The resulting PLL-RNA nanoparticles delivered the anti-microRNA molecules into cytoplasm of breast cancer cells in a concentration-dependent manner that displayed sustainable effectiveness.

Space travel causes rapid weight loss of astronauts, but the underlying reasons are still obscure. Brown adipose tissue (BAT) is a well-known thermogenesis tissue that is innervated by sympathetic nerves, and norepinephrine stimulation can promote the thermogenesis and angiogenesis of BAT. Herein, the structural and physiological changes of BAT as well as serological indicators were investigated in mice under hindlimb unloading (HU) to simulate a weightless environment in space. The results showed that long-term HU could induced the thermogenic activation of BAT by upregulating the mitochondrial uncoupling protein. Further, peptide-conjugated indocyanine green was developed to target the vascular endothelial cells of BAT. Noninvasive fluorescence-photoacoustic imaging presented the neovascularization of BAT on the micron scale in the HU group, accompanying by the increase of vessel density. Downward trend of serum triglyceride and glucose level of mice treated with HU proved the more heat production and energy consumption in BAT compared with the control group. This study suggested that HU may be an effective strategy to curb the occurrence of obesity, whereas fluorescence-photoacoustic dual-modal imaging showed capability of assessing BAT activity. NEW & NOTEWORTHY We found that the mechanism of weight loss of astronauts in space flight may be that hindlimb unloading (HU) promotes the activation of brown adipose tissue (BAT) and the increase of uncoupling protein (UCP1) expression, which accelerates the body’s heat production. Meanwhile, the activation of BAT is accompanied by the proliferation of blood vessels. With the help of peptide CPATAERPC conjugated indocyanine green targeting to vascular endothelial cells, fluorescence-photoacoustic imaging has selectively tracked the vascular structure of BAT on the micron scale, which provided noninvasive imaging tools to in situ measure the changes of BAT. [ABSTRACT FROM AUTHOR]

This study innovatively utilized coffee grounds oil (CGO) extracted from waste coffee grounds to modify base asphalt, aiming to promote sustainable reuse of coffee waste. The effects of modifier dosage, type, and aging conditions on the rheological properties of asphalt were investigated. After determining the extraction protocol, coffee grounds oil-modified asphalt (CGOA) and waste cooking oil-modified asphalt (WCOA) were prepared and subjected to short-term aging. Fourier transform infrared spectroscopy (FTIR) analyzed the modification mechanism, while temperature sweep, frequency sweep, bending beam rheometer, and multiple stress creep recovery (MSCR) tests assessed the rheological properties at high and low temperatures. Results showed that before aging, CGO improved thermal stability at medium to high temperatures and enhanced deformation and stress relaxation at low temperatures, though it reduced rutting resistance at high temperatures. After aging, CGOA with a dosage limited to 4 % exhibited rheological properties approaching base asphalt and improved the viscoelasticity of aged asphalt. In comparison, WCOA demonstrated significantly weaker performance, particularly after aging. This study provides practical insights into the novel application of CGO in pavement engineering.

PURPOSE To investigate the feasibility and usefulness of 2-deoxy-2-(18F)-fluoro-D-glucose positron emission tomography/computed tomography [(18F)-FDG PET/CT] as a novel examination in the surveillance of abnormal myocardial energy metabolism and cardiac dysfunction after cardiopulmonary resuscitation (CPR). METHODS Thirteen male Sprague-Dawley rats were randomly divided into a sham group (n = 4), CPR group (n = 4), and trimetazidine (TMZ) + CPR group (n = 5). The expression levels of the myocardial injury marker cardiac troponin I (CTNI) in serum were tested at 6 hours after CPR or TMZ + CPR. The ejection fraction and fraction shortening were evaluated by echocardiography. (18F)-FDG PET/CT was used to measure the FDG uptake and the standardized uptake value (SUV) after CPR or TMZ + CPR for 6 hours. The intermediary carbohydrate metabolites of glycolysis including phosphoenolpyruvate, 3-phospho-D-glycerate, and the lactate/pyruvate ratio were detected through the multiple reaction monitoring approach. Simultaneously, the authors also tested the expression levels of the total adenosine triphosphate (ATP) and the key intermediate products of glucose ovidation as alpha ketoglutarate, citrate, and succinate in the myocardium. RESULTS The authors found that the aerobic oxidation of glucose was reduced, and the anaerobic glycolysis was significantly enhanced in the myocardium in the early stage of CPR. Meanwhile, the myocardial injury marker CTNI was upregulated considerably (P = 0.014, P = 0.021), and the left ventricular function of the animal heart also markedly deteriorated with the downregulation of ATP after CPR. In contrast, myocardial injury and cardiac function were greatly improved with the increase of ATP in the CPR + TMZ group. In addition, aerobic glucose oxidation metabolites were significantly increased (P < 0.05) and anaerobic glycolysis metabolites were significantly decreased (P < 0.05) after CPR in the myocardium. Surprisingly, (18F)-FDG PET/CT could track the above changes by detecting the FDG uptake value and the SUV. CONCLUSION Glucose metabolism is an essential factor for myocardial self-repair after CPR. (18F) FDG PET/CT, as a non-invasive technology, can monitor myocardial energy metabolism and cardiac function by tracking changes in glucose metabolism after CPR. [ABSTRACT FROM AUTHOR]

A new statistically validated computational method is developed and employed to identify the unfavorable sequence motifs that contribute to the chemokine quaternary state. The conservation of these motifs is shown to highly affect the quaternary structure of the chemokine family.

The pavement bending deformation resistance of the existing macadam base structure is poor. The geogrid-reinforced macadam base can effectively strengthen the bending resistance of the pavement, but no international consensus has been reached at present over bending failure laws of reinforced macadam base structure. Discrete element models of semi-rigid base pavement structure, macadam base pavement structure, and geogrid-reinforced macadam base pavement structure were built based on MATDEM discrete element simulation program; loading calculation of the three models was conducted by taking their centers as loading positions; and model displacement nephogram, strain nephogram, and effects of different spans on their bending deformation were analyzed to reveal bending failure laws of reinforced macadam base and improvement effect of the geogrid on the anti-bending performance of the macadam structural layer. Finally, bending deformation laws of the three pavement structures and improvement effect of geogrid reinforcement on bending properties of the macadam base structure were established. The results show that under bending deformation of semi-rigid base, the vertical strain at the contract surface between the baseplate and soil base and horizontal strain at midspan position reach the maximum, which can easily lead to fracture and shear failure, and the macadam base layer can effectively isolate the tensile strain transmitted from bottom up. Through their own deformation, grids can transform surface pressure load into frictional resistance at the geogrid/soil interface and partial kinetic energy in the system into their own elastic potential energy to reduce the kinetic energy at the subbase layer. Geogrid reinforcement can improve the nonlinearity of macadam materials, reduce the fluctuation amplitude of the strain curve and displacement curve, lengthen the service life of the macadam base pavement structure, and improve its structural soundness under bending deformation. This study can provide a theoretical reference for numerical simulation of bending failure of geogrid-reinforced macadam base.

Existing macadam base structures have poor resistance to bending deformation of pavement. The structural layer is challenged with serious cracking due to the long-term dynamic loads. Despite these issues, however, studies on reinforcement techniques for macadam base structure have been scarce. No reasonable and feasible method on how to improve the bending resistance of flexible base structures (e.g. macadam base structure) and prolong their bending fatigue life has yet been reported. Thus, this study proposed a method for reinforcing macadam base structures with geogrids to strengthen bending performance, anti-fatigue performance and dynamic stability of flexible base structures under different loading levels. The reinforced macadam base structure was investigated through a laboratory test of flexural-tensile strength and a three-point fatigue bending test. A cyclic loading test of reinforced and non-reinforced girder specimens was carried out under five stress levels. The effect of such a new reinforcement method in improving the bending fatigue properties of macadam base structures was analyzed by comparing the yield curves and fatigue lives of reinforced and non-reinforced specimens under different loading levels. Results demonstrate that the non-reinforced macadam base has poor bending resistance. The yield curve and fatigue life of non-reinforced specimens attenuated quickly as it approached the ultimate loading level. Non-reinforced specimens have low-cycle fatigue failures when the loads reach the 0.8 stress level and the ultimate displacement at failure is relatively small, accompanied by obvious failure surface. After geogrids are added, the fatigue life of specimens improved significantly. The yield curve shows no significant attenuation at a high loading level. The reinforced specimens can still maintain high-cycle fatigue failure under the 0.8 stress level and avoid the occurrence of low-cycle fatigue failures. Moreover, reinforced specimens can inhibit transmission of reflection cracks at midspan of cement-stabilized macadam base, delay the propagation of oblique shearing fractures close to the support, and strengthen the dynamic stability and durability of pavement structure with a macadam base. The conclusions of this study provide theoretical references to practical engineering applications of such new reinforcement technology for macadam bases.

Pavement pothole repair, as one of the commonest methods used in routine road maintenance works, is effective to extend the pavement service life and increase its transport capacity. However, there are significant color differences between the old and new pavements after pothole repair, and there are few studies about the impact of color differences on driving safety. Thus, using multiple typical pavements with the pothole repair, we aim to reveal the impact of the color differences between the old and new materials on the driving safety, and to improve the safety and comfort of drivers. Tobii eye tracker and the ErgoLAB physiological recorder were used to test the driver's visual parameters when the vehicles run under the pothole repair environment, including drivers' gaze frequency, gaze duration, saccade range and heart rate variability. Results show that the color differences of the road after pothole repair have a significant influence on the drivers' vision and psychology, resulting in reduced driving safety and stability. Compared with the unrepaired road section, the gaze frequency and duration of drivers on pothole sections are significantly increased. The speed of saccade is also increased, and the saccade range is reduced. Meanwhile, the average heart rate of drivers on the pothole sections is increased by 10-20%, indicating that drivers' attention and heart rate fluctuate greatly when passing through potholes, which can easily cause emotional tension and misjudgment, and thereby reduce the safety of driving. The obtained conclusions provide a significant reference for subsequent research.

The parameters of rockfill materials are important factors that influence the stability of high rockfill embankment. However, the influencing laws of parameter changes on the deformation of high rockfill embankments still remain unknown. To deepen understanding on the influencing laws of parameters of rockfill materials on the stability of high rockfill embankment, a case study using an orthogonal test and numerical simulation was conducted on the high rockfill embankment with 50.6 m banking in the secondary road reconstruction project of the national highway 316 from Xunyang to Ankang in the Shaanxi Province of China. The influences of elasticity modulus, dry density, Poisson's ratio, frictional angle, and cohesion on the stability of high rockfill embankment were analyzed. A three-dimensional numerical model of high rockfill embankment was constructed using FLAC3D, and a numerical simulation of the embankment deformation was performed using the maximum settlement of embankment as the evaluation index. The influences of different factors on the deformation of high rockfill embankment were evaluated through a numerical simulation based on the orthogonal test to verify the accuracy of the orthogonal test. In addition, the deformation law of high rockfill embankment was examined. Research results demonstrate that dry density predominantly influences the stability of high rockfill embankment, followed by elasticity modulus, Poisson's ratio, cohesion, and frictional angle. The optimal combination of parameters of rockfill materials was concluded from further analysis. The numerical simulation and orthogonal test results are consistent. The top surface of the high rockfill embankment develops settlement deformation during the construction period, accompanied by outward lateral squeezing trend at the foot of slope. The vertical deformation consists of settlement first and then upheaval. Research conclusions can provide some references for the reasonable selection of rockfill materials for embankment and the stability analysis of high rockfill embankment.

In the Loess Plateau, seasonal freeze and thaw cause great damage to the mechanical behavior and microstructure of soil, which leads to frequent geological disasters during winter and spring. To investigate the influence of freeze-thaw (FT) cycling (FTC) on the shear strength and microstructure of intact loess, triaxial shear, nuclear magnetic resonance, and scanning electron microscope tests were carried out on soil samples after target FT cycles. The results indicate that the FTC has limited changes to the soil stress-strain curve, but has a significant attenuation effect on the peak deviatoric stress. The peak deviatoric stress was attenuated by FTC but changed insignificantly after ten cycles. The cohesive force decays exponentially with the number of FT cycles, while the internal friction angle increases slightly. Moreover, under FTC, the T2 hydrogen spectra of soil samples showed a multimodal distribution, with the main peak appearing to have two obvious upward shifts that occurred at 6 and 10 FT cycles. Indeed, a depolarization phenomenon related to the directional frequency of soil particles was observed, and the mass fractal dimension of the pore network increased slightly. In an FT environment, the shear strength declines due to accumulated internal microstructural damage. These findings contribute to a better understanding of the response of loess to FTC and provide novel ideas for the prevention of frost damage in loess areas.

To investigate the microstructure of paleosol and its expansion characteristics, the paleosol of the Zaosheng #3 tunnel of the Yinxi high-speed railway was studied. Based on X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDX), nuclear magnetic resonance (NMR), and scanning electron microscopy techniques (SEM), the microstructure of the paleosol was analyzed in terms of the mineral composition, formation elements, pore structure, and particle morphology. Five groups of undisturbed and remolded soils with different moisture contents were tested for the unloaded expansion rate and loaded expansion rate. The results show that the mineral components of the paleosol are mainly quartz, potash feldspar, calcite, and hematite, with the highest-content-component quartz accounting for 45.4% of the total content; the clay mineral composition of the paleosol has the highest content of montmorillonite at 12.3%. The elemental composition of the paleosol is dominated by Al, Si, Ca, and Fe, which form expansive mineral components such as quartz and montmorillonite, creating inherent conditions for expansibility of the paleosol. The T2 distribution curves of the undisturbed and remolded paleosol are composed of three peaks. The pore distribution of paleosol mainly includes medium pores, followed by large pores, and the contents of small pores and superlarge pores are very small. In terms of particle contact, the undisturbed soil is mostly in the form of “surface-surface” and “surface-edge” contact, and the remolded soil is mainly in the form of “point-surface” and “point-point” contact. The unloaded expansion rate of remolded soil is approximately twice that of undisturbed soil. The rate of loaded expansion of both soils decreases with increasing moisture content.

Commonly used in biotechnology applications, filamentous M13 phage are non-lytic viruses that infect E. coli and other bacteria, with the potential to promote horizontal gene transfer in natural populations with synthetic biology implications for engineering community systems. Using the E. coli strain TG1, we have investigated how a selective pressure involving elevated levels of toxic chromate, mimicking that found in some superfund sites, alters population dynamics following infection with either wildtype M13 phage or an M13-phage encoding a chromate reductase (Gh-ChrR) capable of the reductive immobilization of chromate (ie, M13-phageGh-ChrR). In the absence of a selective pressure, M13-phage infection results in a reduction in bacterial growth rate; in comparison, in the presence of chromate there are substantial increases in both cellular killing and biomass formation following infection of E. coli strain TG1with M13-phageGh-ChrR that is dependent on chromate-reductase activity. These results are discussed in terms of community structures that facilitate lateral gene transfer of beneficial traits that enhance phage replication, infectivity, and stability against environmental change. [ABSTRACT FROM AUTHOR]

Background: Nitric oxide is a physiological regulator of endothelial function and hemodynamics. Oxidized products of nitric oxide can form nitrotyrosine, which is a marker of nitrative stress. Cigarette smoking decreases exhaled nitric oxide, and the underlying mechanism may be important in the cardiovascular toxicity of smoking. Even so, it is unclear if this effect results from decreased nitric oxide production or increased oxidative degradation of nitric oxide to reactive nitrating species. These two processes would be expected to have opposite effects on nitrotyrosine levels, a marker of nitrative stress. Objective: In this study, we evaluated associations of cigarette smoking and chronic obstructive pulmonary disease (COPD) with nitrotyrosine modifications of specific plasma proteins to gain insight into the processes regulating nitrotyrosine formation. Methods: A custom antibody microarray platform was developed to analyze the levels of 3-nitrotyrosine modifications on 24 proteins in plasma. In a cross-sectional study, plasma samples from 458 individuals were analyzed. Results: Average nitrotyrosine levels in plasma proteins were consistently lower in smokers and former smokers than in never smokers but increased in smokers with COPD compared with smokers who had normal lung-function tests. Conclusions: Smoking is associated with a broad decrease in 3-nitrotyrosine levels of plasma proteins, consistent with an inhibitory effect of cigarette smoke on endothelial nitric oxide production. In contrast, we observed higher nitrotyrosine levels in smokers with COPD than in smokers without COPD. This finding is consistent with increased nitration associated with inflammatory processes. This study provides insight into a mechanism through which smoking could induce endothelial dysfunction and increase the risk of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Chemokine dimerization has been the subject of much interest in recent years as evidence has accumulated that different quaternary states of chemokines play different biological roles; the monomer is believed to be the receptor-binding unit, whereas the dimer has been implicated in binding cell surface glycosaminoglycans. However, although several studies have provided evidence for this paradigm by making monomeric chemokine variants or dimer-impaired chemokines, few have provided direct evidence of the receptor function of a chemokine dimer. We have produced a covalent dimer of the CC chemokine macrophage inflammatory protein-1β (MIP-1β) by placing a disulfide bond at the center of its dimer interface through a single amino acid substitution (MIP-1β-A10C). This variant was shown to be a nondissociating dimer by SDS-PAGE and analytical ultracentrifugation. NMR reveals a structure largely the same as the wild type protein. In studies of glycosaminoglycan binding, MIP-1β-A10C binds to a heparin-Sepharose column as tightly as the wild type protein and more tightly than monomeric variants. However, MIP-1β-A10C neither binds nor activates the MIP-1β receptor CCR5. It was found that the ability to activate CCR5 was recovered upon reduction of the intermolecular disulfide cross-link by incubation with 1 mM dithiothreitol. This work provides the first definitive evidence that the CC chemokine MIP-1β dimer is not able to bind or activate its receptor and implicates the CC chemokine monomer as the sole receptor-interacting unit. [ABSTRACT FROM AUTHOR]

Presents a study on the freshwater quality criteria of acetonitrile on the basis of the features of the aquatic biota in China, and with reference to the guidelines of the U.S. Environmental Protection Agency. Background on acetonitrile; Analysis of the acute toxicity of acetonitrile to 13 aquatic species; Implications for the aquatic life in China.