Free-breathing time-resolved 4D MRI with improved T1-weighting contrast.

This work proposes MP-Grasp4D (magnetization-prepared golden-angle radial sparse parallel 4D) MRI, a free-breathing, inversion recovery (IR)-prepared, time-resolved 4D MRI technique with improved T1-weighted contrast. MP-Grasp4D MRI acquisition incorporates IR preparation into a radial gradient echo sequence. MP-Grasp4D employs a golden-angle navi-stack-of-stars sampling scheme, where imaging data of rotating radial stacks and navigator stacks (acquired at a consistent rotation angle) are alternately acquired. The navigator stacks are used to estimate a temporal basis for low-rank subspace-constrained reconstruction. This allows for the simultaneous capture of both IR-induced contrast changes and respiratory motion. One temporal frame of the imaging volume in MP-Grasp4D MRI is reconstructed from a single stack and an adjacent navigator stack on average, resulting in a nominal temporal resolution of 0.16 seconds per volume. Images corresponding to the optimal inversion time (TI) can be retrospectively selected for providing the best image contrast. Reader studies were conducted to assess the performance of MP-Grasp4D MRI in liver imaging across 30 subjects in comparison with standard Grasp4D MRI without IR preparation. MP-Grasp4D MRI received significantly higher scores (P < 0.05) than Grasp4D in all assessment categories. There was a moderate to almost perfect agreement (kappa coefficient from 0.42 to 0.9) between the two readers for image quality assessment. When the scan time is reduced, MP-Grasp4D MRI preserves image contrast and quality, demonstrating additional acceleration capability. MP-Grasp4D MRI improves T1-weighted contrast for free-breathing time-resolved 4D MRI and eliminates the need for explicit motion compensation. This method is expected to be valuable in different MRI applications such as MR-guided radiotherapy.

DCE-MRI of the liver with sub-second temporal resolution using GRASP-Pro with navi-stack-of-stars sampling.

Respiratory motion-induced image blurring and artifacts can compromise image quality in dynamic contrast-enhanced MRI (DCE-MRI) of the liver. Despite remarkable advances in respiratory motion detection and compensation in past years, these techniques have not yet seen widespread clinical adoption. The accuracy of image-based motion detection can be especially compromised in the presence of contrast enhancement and/or in situations involving deep and/or irregular breathing patterns. This work proposes a framework that combines GRASP-Pro (Golden-angle RAdial Sparse Parallel MRI with imProved performance) MRI with a new radial sampling scheme called navi-stack-of-stars for free-breathing DCE-MRI of the liver without the need for explicit respiratory motion compensation. A prototype 3D golden-angle radial sequence with a navi-stack-of-stars sampling scheme that intermittently acquires a 2D navigator was implemented. Free-breathing DCE-MRI of the liver was conducted in 24 subjects at 3T including 17 volunteers and 7 patients. GRASP-Pro reconstruction was performed with a temporal resolution of 0.34-0.45 s per volume, whereas standard GRASP reconstruction was performed with a temporal resolution of 15 s per volume. Motion compensation was not performed in all image reconstruction tasks. Liver images in different contrast phases from both GRASP and GRASP-Pro reconstructions were visually scored by two experienced abdominal radiologists for comparison. The nonparametric paired two-tailed Wilcoxon signed-rank test was used to compare image quality scores, and the Cohen's kappa coefficient was calculated to evaluate the inter-reader agreement. GRASP-Pro MRI with sub-second temporal resolution consistently received significantly higher image quality scores (P < 0.05) than standard GRASP MRI throughout all contrast enhancement phases and across all assessment categories. There was a substantial inter-reader agreement for all assessment categories (ranging from 0.67 to 0.89). The proposed technique using GRASP-Pro reconstruction with navi-stack-of-stars sampling holds great promise for free-breathing DCE-MRI of the liver without respiratory motion compensation.

The diamagnetic component map from quantitative susceptibility mapping (QSM) source separation reveals pathological alteration in Alzheimer's disease-driven neurodegeneration.

A sensitive and accurate imaging technique capable of tracking the disease progression of Alzheimer's Disease (AD) driven amnestic dementia would be beneficial. A currently available method for pathology detection in AD with high accuracy is Positron Emission Tomography (PET) imaging, despite certain limitations such as low spatial resolution, off-targeting error, and radiation exposure. Non-invasive MRI scanning with quantitative magnetic susceptibility measurements can be used as a complementary tool. To date, quantitative susceptibility mapping (QSM) has widely been used in tracking deep gray matter iron accumulation in AD. The present work proposes that by compartmentalizing quantitative susceptibility into paramagnetic and diamagnetic components, more holistic information about AD pathogenesis can be acquired. Particularly, diamagnetic component susceptibility (DCS) can be a powerful indicator for tracking protein accumulation in the gray matter (GM), demyelination in the white matter (WM), and relevant changes in the cerebrospinal fluid (CSF). In the current work, voxel-wise group analysis of the WM and the CSF regions show significantly lower |DCS| (the absolute value of DCS) value for amnestic dementia patients compared to healthy controls. Additionally, |DCS| and τ PET standardized uptake value ratio (SUVr) were found to be associated in several GM regions typically affected by τ deposition in AD. Therefore, we propose that the separated diamagnetic susceptibility can be used to track pathological neurodegeneration in different tissue types and regions of the brain. With the initial evidence, we believe the usage of compartmentalized susceptibility demonstrates substantive potential as an MRI-based technique for tracking AD-driven neurodegeneration.

High angular resolution susceptibility imaging and estimation of fiber orientation distribution functions in primate brain.

Uncovering brain-tissue microstructure including axonal characteristics is a major neuroimaging research focus. Within this scope, anisotropic properties of magnetic susceptibility in white matter have been successfully employed to estimate primary axonal trajectories using mono-tensorial models. However, anisotropic susceptibility has not yet been considered for modeling more complex fiber structures within a voxel, such as intersecting bundles, or an estimation of orientation distribution functions (ODFs). This information is routinely obtained by high angular resolution diffusion imaging (HARDI) techniques. In applications to fixed tissue, however, diffusion-weighted imaging suffers from an inherently low signal-to-noise ratio and limited spatial resolution, leading to high demands on the performance of the gradient system in order to mitigate these limitations. In the current work, high angular resolution susceptibility imaging (HARSI) is proposed as a novel, phase-based methodology to estimate ODFs. A multiple gradient-echo dataset was acquired in an entire fixed chimpanzee brain at 61 orientations by reorienting the specimen in the magnetic field. The constant solid angle method was adapted for estimating phase-based ODFs. HARDI data were also acquired for comparison. HARSI yielded information on whole-brain fiber architecture, including identification of peaks of multiple bundles that resembled features of the HARDI results. Distinct differences between both methods suggest that susceptibility properties may offer complementary microstructural information. These proof-of-concept results indicate a potential to study the axonal organization in post-mortem primate and human brain at high resolution.

Rapid Access to 2-Substituted Bicyclo[1.1.1]pentanes.

The replacement of aryl rings with saturated carbocyclic structures has garnered significant interest in drug discovery due to the potential for improved pharmacokinetic properties upon substitution. In particular, 1,3-difunctionalized bicyclo[1.1.1]pentanes (BCPs) have been widely adopted as bioisosteres for parasubstituted arene rings, appearing in a number of lead pharmaceutical candidates. However, despite the pharmaceutical value of 2-substituted BCPs as replacements for ortho- or meta-substituted arene rings, general and rapid syntheses of these scaffolds remain elusive. Current approaches to 2-substituted BCPs rely on installation of the bridge substituent prior to BCP core construction, leading to lengthy step counts and often nonmodular sequences. While challenging, direct functionalization of the strong bridge BCP C-H bonds would offer a more streamlined pathway to diverse 2-substituted BCPs. Here, we report a generalizable synthetic linchpin strategy for bridge functionalization via radical C-H abstraction of the BCP core. Through mild generation of a strong hydrogen atom abstractor, we rapidly synthesize novel 2-substituted BCP synthetic linchpins in one pot. These synthetic linchpins then serve as common precursors to complex 2-substituted BCPs, allowing one-step access to a number of previously inaccessible electrophile and nucleophile fragments at the 2-position via two new metallaphotoredox protocols. Altogether, this platform enables the expedient synthesis of four pharmaceutical analogues, all of which show similar or improved properties compared to their aryl-containing equivalents, demonstrating the potential of these 2-substituted BCPs in drug development.

Using street view imagery to examine the association between urban neighborhood disorder and the long-term recurrence risk of patients discharged with acute myocardial infarction in central Beijing, China.

Background: To examine the association between urban neighborhood disorder and the recurrence risk of patients with acute myocardial infarction (AMI) in central Beijing, China. Methods: Recurrent AMI was identified by the Beijing Monitoring System for Cardiovascular Diseases through the end of 2019 for patients discharged with AMI between 2007 and 2017. Cox proportional hazards models were performed to estimate associations between neighborhood disorder and AMI recurrence. Results: Of 66,238 AMI patients, 11,872 had a recurrent event, and 3117 died from AMI during a median followup of 5.92 years. After covariate adjustment, AMI patients living in the high tertile of neighborhood disorder had a higher recurrence risk (hazard ratio [HR] 1.08, 95 % confidence interval [CI], 1.03-1.14) compared with those in the low tertile. A stronger association was noted for fatal recurrent AMI (HR 1.21, 95 % CI 1.10-1.34). The association was mainly observed in females (HR 1.04, 95 % CI: 1.02 to 1.06). Conclusions: Serious neighborhood disorder may contribute to higher recurrence risk, particularly fatal recurrence, among AMI patients. Policies to eliminate neighborhood disorders may play an important role in the secondary prevention of cardiovascular disease.

Decompose quantitative susceptibility mapping (QSM) to sub-voxel diamagnetic and paramagnetic components based on gradient-echo MRI data.

PURPOSE: A method named DECOMPOSE-QSM is developed to decompose bulk susceptibility measured with QSM into sub-voxel paramagnetic and diamagnetic components based on a three-pool complex signal model. METHODS: Multi-echo gradient echo signal is modeled as a summation of three weighted exponentials corresponding to three types of susceptibility sources: reference susceptibility, diamagnetic and paramagnetic susceptibility relative to the reference. Paramagnetic component susceptibility (PCS) and diamagnetic component susceptibility (DCS) maps are constructed to represent the sub-voxel compartments by solving for linear and nonlinear parameters in the model. RESULTS: Numerical forward simulation and phantom validation confirmed the ability of DECOMPOSE-QSM to separate the mixture of paramagnetic and diamagnetic components. The PCS obtained from temperature-variant brainstem imaging follows the Curie's Law, which further validated the model and the solver. Initial in vivo investigation of human brain images showed the ability to extract sub-voxel PCS and DCS sources that produce visually enhanced contrast between brain structures comparing to threshold QSM.

Enantiomerically Enriched α-Borylzinc Reagents by Nickel-Catalyzed Carbozincation of Vinylboronic Esters.

In this paper is described a synthesis of enantiomerically enriched, configurationally stable organozinc reagents by catalytic enantioselective carbozincation of a vinylboronic ester. This process furnishes enantiomerically enriched α-borylzinc intermediates that are shown to undergo stereospecific reactions, producing enantioenriched secondary boronic ester products. The properties of the intermediate α-borylzinc reagent are probed and the synthetic utility of the products is demonstrated by application to the synthesis of (-)-aphanorphine and (-)-enterolactone.

Asymmetric susceptibility tensor imaging.

PURPOSE: To investigate the symmetry constraint in susceptibility tensor imaging. THEORY: The linear relationship between the MRI frequency shift and the magnetic susceptibility tensor is derived without constraining the tensor to be symmetric. In the asymmetric case, the system matrix is shown to be maximally rank 6. Nonetheless, relaxing the symmetry constraint may still improve tensor estimation because noise and image artifacts do not necessarily follow the constraint. METHODS: Gradient echo phase data are obtained from postmortem mouse brain and kidney samples. Both symmetric and asymmetric tensor reconstructions are applied to the data. The reconstructions are then used for susceptibility tensor imaging fiber tracking. Simulations with ground truth and at various noise levels are also performed. The reconstruction methods are compared qualitatively and quantitatively. RESULTS: Compared to regularized and unregularized symmetric reconstructions, the asymmetric reconstruction shows reduced noise and streaking artifacts, better contrast, and more complete fiber tracking. In simulation, the asymmetric reconstruction achieves better mean squared error and better angular difference in the presence of noise. Decomposing the asymmetric tensor into its symmetric and antisymmetric components confirms that the underlying susceptibility tensor is symmetric and that the main sources of asymmetry are noise and streaking artifacts. CONCLUSION: Whereas the susceptibility tensor is symmetric, asymmetric reconstruction is more effective in suppressing noise and artifacts, resulting in more accurate estimation of the susceptibility tensor.

Aptamer/Graphene Quantum Dots Nanocomposite Capped Fluorescent Mesoporous Silica Nanoparticles for Intracellular Drug Delivery and Real-Time Monitoring of Drug Release.

Great challenges in investigating the release of drug in complex cellular microenvironments necessitate the development of stimuli-responsive drug delivery systems with real-time monitoring capability. In this work, a smart drug nanocarrier based on fluorescence resonance energy transfer (FRET) is fabricated by capping graphene quantum dots (GQDs, the acceptor) onto fluorescent mesoporous silica nanoparticles (FMSNs, the donor) via ATP aptamer for real-time monitoring of ATP-triggered drug release. Under extracellular conditions, the fluorescence of FMSNs remains in the "off" state in the low ATP level which is unable to trigger the release of drug. Once specifically recognized and internalized into the target tumor cells by AS1411 aptamer, in the ATP-rich cytoplasm, the conformation switch of the ATP aptamer causes the shedding of the GQDs from the nanocarriers, leading to the release of the loaded drugs and consequently severe cytotoxicity. Simultaneously, the fluorescence of FMSNs turns "on" along with the dissociation of GQDs, which allows real-time monitoring of the release of drug from the pores. Such a drug delivery system features high specificity of dual-target recognition with AS1411 and ATP aptamer as well as high sensitivity of the FRET-based monitoring strategy. Thus, the proposed multifunctional ATP triggered FRET-nanocarriers will find potential applications for versatile drug-release monitoring, efficient drug transport, and targeted cancer therapeutics.

Highly Sensitive and Selective Photoelectrochemical Biosensor for Hg(2+) Detection Based on Dual Signal Amplification by Exciton Energy Transfer Coupled with Sensitization Effect.

A highly sensitive and selective photoelectrochemical (PEC) biosensor for Hg(2+) detection was developed on the basis of the synergistic effect of exciton energy transfer (EET) between CdS quantum dots (QDs) and Au nanoparticles (NPs) coupled with sensitization of rhodamine 123 (Rh123) for signal amplification. First, the TiO2/CdS hybrid structure obtained by depositing CdS QDs on TiO2 film was employed as a matrix for immobilizing probe DNA (pDNA). Next, Rh123 was introduced into the pDNA terminal, and then Au NP labeled target DNA (Au-tDNA) was hybridized with pDNA to form a rod-like double helix structure. The detection of Hg(2+) was based on a conformational change of the pDNA after incubating with Hg(2+). In the absence of Hg(2+), Rh123 was located away from the electrode surface due to the DNA hybridization, leading to inhibition of the sensitization effect, and meanwhile, the occurrence of EET between CdS QDs and Au NPs resulted in a photocurrent decrease. However, after incubating with Hg(2+), the rod-like double helix was disrupted, and the energy transfer was broken. In this case, the photocurrent recovered, and meanwhile, the folded pDNA made the labeled Rh123 move closer to the electrode surface, leading to the formation of the sensitization structure, which evidently increased the photocurrent intensity. The sensitivity of the biosensor for Hg(2+) detection was greatly enhanced for the dual signal amplification strategy. The linear range was 10 fM to 200 nM, with a detection limit of 3.3 fM. This biosensor provides a promising new platform for detecting various heavy metal ions at ultralow levels.

Unraveling Residual Stress Distribution Characteristics of 6061-T6 Aluminum Alloy Induced by Laser Shock Peening.

Laser shock peening (LSP) is a powerful technique for improving the fatigue performance of metallic components by customizing compressive residual stresses in the desired near-surface regions. In this study, the residual stress distribution characteristics of 6061-T6 aluminum alloy induced by LSP were identified by the X-ray diffraction method, and their dependent factors (i.e., LSP coverage, LSP energy, and scanning path) were evaluated quantitatively by numerical simulations, exploring the formation mechanism of LSP residual stresses and the key role factor of the distribution characteristics. The results show that LSP is capable of creating anisotropic compressive residual stresses on the specimen surface without visible deformation. Compressive residual stresses are positively correlated with LSP coverage. The greater the coverage, the higher the residual stress, but the longer the scanning time required. Raising LSP energy contributes to compressive residual stresses, but excessive energy may lead to a reduction in the surface compressive residual stress. More importantly, the anisotropy of residual stresses was thoroughly explored, identifying the scanning path as the key to causing the anisotropy. The present work provides scientific guidance for efficiently tailoring LSP-induced compressive residual stresses to improve component fatigue life.

Investigation of the Fracture Behaviour of Al-CFRP Cross-Lap Joint Fabricated by Coaxial One-Side Resistance Spot Welding.

In the present research, coaxial one-side resistance spot welding was performed to join Al5052 and CFRP sheets with different welding currents. The mechanical performance of the cross-lap joint was clarified experimentally. The cross-section of the welded joint and the fracture surfaces was subjected to multi-scale characterization. The fracture behaviours and mechanisms of cross-lap joints are discussed in detail. The results showed that the thermal degradation of CFRP was detected on the cross-section under a 6000 A welding current and the O element was enriched in the decomposed area. The joining zone could be divided into four subregions according to their morphology, which were defined, from outside to inside, as the squeezed zone, the adhesion zone, the cohesion zone and the decomposed zone. After welding, the O-C=O bond disappeared on the CFRP surface while the O=C-N bond was detected on the Al5052 surface. The cross-lap joints demonstrated brittle and ductile fracture behaviours in a cross-tension test, which included two sub-modes: brittle-transition mode and ductile-degradation mode. The transformation of failure modes had a relationship with the heat input and corresponding joining zone composition. The maximum cross-tension load was about 1279 ± 40 N with a welding current of 5600 A.

Pulsed selective excitation theory and design in multiphoton MRI.

Excitation in MRI is traditionally done at the Larmor frequency, where the energy of each radiofrequency photon corresponds to the energy difference between two spin states. However, if multiple radiofrequencies are employed, then multiphoton excitation can also occur when the sum or difference of multiple photon frequencies equals the Larmor frequency. Although multiphoton excitation has been known since the early days of NMR, it has been relatively unexplored in MRI. In this work, equations and principles for multiphoton selective RF pulse design in imaging are presented and experimentally demonstrated. In particular, the case where there are radiofrequency fields in both the traditional xy-direction and non-traditional z-direction is considered. To produce the z-direction radiofrequency field, an additional uniform coil was added to a clinical MRI scanner. Using this coil, two-photon slice-selective pulses were designed to be equivalent to traditional pulses, producing similar excitation, slice profiles, and in vivo images. Being the result of a combination of multiple radiofrequency fields instead of just one, two-photon pulses have more flexibility in how their parameters can be changed. Although individual multiphoton excitations are less efficient than their traditional counterparts, when the z-direction radiofrequency field is spatially non-uniform, multiple multiphoton resonances can be simultaneously used at different locations to produce simultaneous multislice excitation with the same pulse duration but less tissue heating than a naive implementation. In particular, non-uniform z-direction radiofrequency fields with negligible added tissue heating provided by oscillating the MRI scanner's gradient fields at kilohertz frequencies were used to excite multiple slices simultaneously with less high-frequency xy-direction radiofrequency power. For an example three-slice excitation, we achieve half the xy-direction radiofrequency power compared to the naïve approach of adding three single-slice pulses. For conventional or unconventional applications, multiphoton excitation may be of interest when designing new MRI systems.

Lipid Oxidation Induced by RF Waves and Mediated by Ferritin Iron Causes Activation of Ferritin-Tagged Ion Channels.

One approach to magnetogenetics uses radiofrequency (RF) waves to activate transient receptor potential channels (TRPV1 and TRPV4) that are coupled to cellular ferritins. The mechanisms underlying this effect are unclear and controversial. Theoretical calculations suggest that the heat produced by RF fields is likely orders of magnitude weaker than needed for channel activation. Using the FeRIC (Ferritin iron Redistribution to Ion Channels) system, we have uncovered a mechanism of activation of ferritin-tagged channels via a biochemical pathway initiated by RF disturbance of ferritin and mediated by ferritin-associated iron. We show that, in cells expressing TRPVFeRIC channels, RF increases the levels of the labile iron pool in a ferritin-dependent manner. Free iron participates in chemical reactions, producing reactive oxygen species and oxidized lipids that ultimately activate the TRPVFeRIC channels. This biochemical pathway predicts a similar RF-induced activation of other lipid-sensitive TRP channels and may guide future magnetogenetic designs.

Generation of Recombinant Mammalian Selenoproteins through Genetic Code Expansion with Photocaged Selenocysteine.

Selenoproteins contain the amino acid selenocysteine (Sec) and are found in all domains of life. The functions of many selenoproteins are poorly understood, partly due to difficulties in producing recombinant selenoproteins for cell-biological evaluation. Endogenous mammalian selenoproteins are produced through a noncanonical translation mechanism requiring suppression of the UGA stop codon and a Sec insertion sequence (SECIS) element in the 3' untranslated region of the mRNA. Here, recombinant selenoproteins are generated in mammalian cells through genetic code expansion, circumventing the requirement for the SECIS element and selenium availability. An engineered orthogonal E. coli leucyl-tRNA synthetase/tRNA pair is used to incorporate a photocaged Sec (DMNB-Sec) at the UAG amber stop codon. DMNB-Sec is successfully incorporated into GFP and uncaged by irradiation of living cells. Furthermore, DMNB-Sec is used to generate the native selenoprotein methionine-R-sulfoxide reductase B1 (MsrB1). Importantly, MsrB1 is shown to be catalytically active after uncaging, constituting the first use of genetic code expansion to generate a functional selenoprotein in mammalian systems. The ability to site-specifically introduce Sec directly in mammalian cells, and temporally modulate selenoprotein activity, will aid in the characterization of mammalian selenoprotein function.

Modulation of dynamic modes by interplay between positive and negative feedback loops in gene regulatory networks.

A positive and a negative feedback loop can induce bistability and oscillation, respectively, in biological networks. Nevertheless, they are frequently interlinked to perform more elaborate functions in many gene regulatory networks. Coupled positive and negative feedback loops may exhibit either oscillation or bistability depending on the intensity of the stimulus in some particular networks. It is less understood how the transition between the two dynamic modes is modulated by the positive and negative feedback loops. We developed an abstract model of such systems, largely based on the core p53 pathway, to explore the mechanism for the transformation of dynamic behaviors. Our results show that enhancing the positive feedback may promote or suppress oscillations depending on the strength of both feedback loops. We found that the system oscillates with low amplitudes in response to a moderate stimulus and switches to the on state upon a strong stimulus. When the positive feedback is activated much later than the negative one in response to a strong stimulus, the system exhibits long-term oscillations before switching to the on state. We explain this intriguing phenomenon using quasistatic approximation. Moreover, early switching to the on state may occur when the system starts from a steady state in the absence of stimuli. The interplay between the positive and negative feedback plays a key role in the transitions between oscillation and bistability. Of note, our conclusions should be applicable only to some specific gene regulatory networks, especially the p53 network, in which both oscillation and bistability exist in response to a certain type of stimulus. Our work also underscores the significance of transient dynamics in determining cellular outcome.

Technical Note: Analysis of motion blurring artifact in fast helical free-breathing thoracic CT scans.

PURPOSE: The aim of this study was to measure and characterize breathing-induced motion artifacts in fast helical free-breathing CT scans. METHODS: Ten lung cancer patients were scanned using fast helical CT during free breathing. In each case, 25 low-dose CT scans were acquired in alternating craniocaudal and caudocranial directions. A bellow-based breathing surrogate was simultaneously acquired. A published breathing motion model was used to estimate the diaphragm craniodaudal velocity at each CT scan. The Hounsfield unit (HU) profiles passing through a small square (7 × 7 mm2 ) portion of the diaphragm were examined and fit to error functions, which were used to characterize the motion blur. The HU profiles that intersected diaphragm-adjacent non-parenchymal tissue were excluded from analysis. The five profiles for each scan that were best isolated from non-parenchymal tissue were used to determine the amount of blurring. A convolution-based blurring model was also employed to compare against the human data. RESULTS: There was a distinct relationship between blurring and diaphragm speed. The convolution model well described the blurring behavior in the patients. Most of the CT scans were acquired at tissue velocities less than 20 mm s-1 , which was the threshold where blurring exceeded 1 mm (corresponding to the slice spacing in this study). CONCLUSIONS: Breathing motion-induced blurring occurs even for relatively fast modern helical CT scans. Measurable motion-induced blurring occurs for velocities greater than 15 mm s-1 and greater than 1 mm for velocities greater than 20 mm s-1 . Methods to manage the residual blurring artifacts will need to be developed to maximize the image quality for free-breathing CT protocols.

Hierarchical Nanocarriers for Precisely Regulating the Therapeutic Process via Dual-Mode Controlled Drug Release in Target Tumor Cells.

A precisely controlled drug release is a great challenge in exploring methodologies of drug administration and fighting drug resistance for successful cancer chemotherapy. Herein, we developed a dual-mode nanocarrier to specifically deliver doxorubicin (Dox) and precisely control the drug release in target tumor cells. This hierarchical nanocarrier consisted of a gold nanorod as the heating core, biodegradable mesoporous silica as the storage chamber, and graphene quantum dot (GQD) as a drug carrier. The Arg-Gly-Asp peptides on the nanocarrier surface facilitated the specific interaction with integrin-overexpressed tumor cells and subsequent uptake via receptor-mediated endocytosis. Once exposed under the near-infrared (NIR) laser, the internalized nanocarrier rapidly heated the surrounding environment, which led to an instantaneous drug release by collapsing the π-π interaction between Dox and GQDs at high temperature and thereby intensified therapeutic efficacy. On the other hand, the silica shells underwent gradual degradation in the cellular matrix environment, along with stepwise liberation of the embedded GQD-Dox composites from the confined porous structure for the Dox release, exerting a long-term lethality to the tumor cells. By virtue of the physicochemical properties and synergistic behavior of the multiple components in this hierarchical nanocarrier, the NIR-triggered prompt release mode and the biodegradation-mediated slow release mode functioned in a precise and collaborative fashion, providing a promising way to manipulate the pharmacokinetics for precise cancer treatment.

Suppressive effect of exogenous carbon monoxide on endotoxin-stimulated platelet over-activation via the glycoprotein-mediated PI3K-Akt-GSK3ß pathway.

Platelet activation is an important event involved in the pathophysiological processes of the coagulation system. Clinical evidence has shown that platelets undergo distinctive pathological processes during sepsis. Unfortunately, how platelets physiologically respond to inflammation or sepsis is not well understood. In this study, we used a lipopolysaccharide (LPS)-stimulated platelet model to systemically investigate alterations in membrane glycoprotein expression, molecular signaling, morphology and critical functions of platelets. We found that platelet adhesion, aggregation, secretion, and spreading on immobilized fibrinogen and the expression of platelet membrane glycoproteins were significantly increased by LPS stimulation, and these changes were accompanied by a significant decrease in cGMP levels and an abnormal distribution of platelet α-granules. Exogenous CO reversed these alterations. Profound morphological changes in LPS-stimulated platelets were observed using atomic force microscopy and phase microscopy. Furthermore, the elevated activities of PI3Ks, AKt and GSK-3ß were effectively suppressed by exogenous CO, leading to the improvement of platelet function. Together, these results provide evidence that platelet over-activation persists under LPS-stimulation and that exogenous CO plays an important role in suppressing platelet activation via the glycoprotein-mediated PI3K-Akt-GSK3ß pathway.