Search

Radiodynamic therapy (RDT) has emerged as a promising modality for cancer treatment, offering notable advantages such as deep tissue penetration and radiocatalytic generation of oxygen free radicals. However, the oxygen-dependent nature of RDT imposes limitations on its efficacy in hypoxic conditions, particularly in modulating and eliminating radioresistant immune suppression cells. A novel approach involving the creation of a “super” tetrahedron polyoxometalate (POM) cluster, Fe12-POM, has been developed for radiation boosted chemodynamic catalysis to enable oxygen-independent RDT in hypoxic conditions. This nanoscale cluster comprises four P2W15units functioning as energy antennas, while the Fe3core serves as an electron receptor and catalytic center. Under X-ray radiation, a metal-to-metal charge transfer phenomenon occurs between P2W15and the Fe3core, resulting in the valence transition of Fe3+to Fe2+and a remarkable 139-fold increase in hydroxyl radical generation compared to Fe12-POM alone. The rapid generation of hydroxyl radicals, in combination with PD-1 therapy, induces a reprogramming of the immune environment within tumors. This reprogramming is characterized by upregulation of CD80/86, downregulation of CD163 and FAP, as well as the release of interferon-? and tumor necrosis factor-a. Consequently, the occurrence of abscopal effects is facilitated, leading to significant regression of both local and distant tumors in mice. The development of oxygen-independent RDT represents a promising approach to address cancer recurrence and improve treatment outcomes.

The image classification task of porcelain fragments is of great significance for the digital preservation of cultural heritage. However, common issues are encountered in the image processing of porcelain fragments, including the low computation speed, decreased accuracy due to the uneven distribution of sample categories, and model instability. This study proposes a novel Capsule Network model, referred to as LBCapsNet, which is suitable for the extraction of features from images of porcelain artifacts fragments. A bottleneck-like channel transformation module denoted by ChannelTrans, which resides between the convolutional layer and the PrimaryCaps layer, was first designed. This module is used to reduce the computational complexity and enhance the processing speed when dealing with intricate porcelain images. The MF-R loss function was then proposed by incorporating focal loss into the original loss function. This allows to address the issue of imbalanced distribution of ceramic shard samples and reduce the classification errors, which leads to faster convergence with smoother trend. Finally, an adaptive dynamic routing mechanism is designed with a dynamic learning rate to enhance the overall stability of the classification process. The experimental results obtained on public datasets, such as MNIST, Fashion- MNIST, CIFAR10, FMD and DTD as well as porcelain fragments dataset, demonstrate that LBCapsNet achieves high classification accuracy with faster and more stable computation compared with existing methods. Furthermore, the ability of LBCapsNet to process special textures can provide technical support for the digital preservation and restoration of cultural heritage.

A highly amorphous Fe70Ti2Y6B22bulk alloy, with a diameter of 3 mm and a height of 2 mm, was synthesized by applying isothermal compression from 10 to 15 GPa at 1473 K using mixed metal powder. The structural analyses by performing X-ray diffraction and transmission electron microscopy revealed that the alloy was composed of a glassy structure. According to the differential scanning calorimetry analysis, a large supercooled liquid region (ΔTx) of approximately 550 K was obtained, which is caused by the highly densely packed structures of a highly amorphous Fe70Ti2Y6B22bulk alloy. The value was six times the value obtained by rapid cooling. Also, the Vickers hardness of the sample was approximately 8.5 GPa at a loading force of 29.4 N. These results indicated that isothermal compression under high pressure is a feasible method for fabricating bulk metallic glasses satisfying large-size requirements.

Sodium zirconium cyclosilicate (SZC) is an effective potassium binder for patients with hyperkalemia. This single‐center, open‐label, phase I study (NCT03283267) characterized the pharmacodynamics and safety of SZC in Chinese individuals. Twenty‐two healthy Chinese adults (mean age, 33.5 years) randomized 1:1 received daily oral SZC 5 or 10 g for 4 days, following 4 days on a low‐sodium, high‐potassium diet (continued throughout the study). End points were mean change from baseline in 24‐hour urinary potassium (primary) and sodium excretion, and serum potassium concentration. Urinary potassium excretion significantly decreased with SZC 5 g (mean change [mmol], –13.0; P< .001) and 10 g (–15.4; P< .001). Although urinary sodium excretion decreased significantly with SZC 5 g (–11.5; P= .030), there was no significant change with SZC 10 g (–5.1; P= .299). Serum potassium concentrations decreased significantly with SZC 5 g (–0.14; P= .031) and 10 g (–0.20; P= .002). All treatment‐emergent adverse events were mild, and none were considered causally related to SZC. Over 4 days, the pharmacodynamics and safety of SZC were consistent in healthy Chinese adults with global studies and patients of Japanese ethnicity.

abstractCandida albicansis a polymorphic fungus which is the predominant cause of superficial and deep tissue fungal infections. This microorganism has developed efficient strategies to invade the host and evade host defense systems. However, the host immune system will be prepared for defense against the microbe by recognition of receptors, activation of signal transduction pathways and cooperation of immune cells. As a consequence, C. albicanscould either be eliminated by immune cells rapidly or disseminate hematogenously, leading to life-threatening systemic infections. The interplay between Candida albicansand the host is complex, requiring recognition of the invaded pathogens, activation of intricate pathways and collaboration of various immune cells. In this review, we will focus on the effects of innate immunity that emphasize the first line protection of host defense against invaded C. albicansincluding the basis of receptor-mediated recognition and the mechanisms of cell-mediated immunity.

Based on the daily reanalysis data released by NCEP/NCAR and the daily precipitation of 753 Chinese stations from May to August during the period of 1960 to 2012, the statistical characteristics of the cold vortex in northeastern China were analyzed. In addition, the strength index, which described the characteristics of the vortex consistently and frequently, and the geographical distribution were given by continuous anomalies of circulation. Based on this index, the activity routines of the cold vortex, characteristics of atmospheric circulation, and their effects on precipitation in northeastern China were analyzed. The results show that: the activities of the cold vortex exhibit remarkable features of annual and interdecadal oscillation, and the vortex high frequency and its characteristics of atmospheric circulation are described more accurately by the strength index of the cold vortex, which shows a high correspondence with the vortex precipitation during early summer and midsummer in the northeast. In strong (weak) vortex years, the general circulation in the middle and high latitudes of Eurasia is to the advantage (disadvantage) of the formation, development and maintenance of the cold vortex, thus it is easy (difficult) to form the circulation which is beneficial to transmit vapor from south to north during the period of July to August. Blocking over the Ural Mountains prevails (does not prevail) in early summer, and blocking over the Sea of Okhotsk prevails (does not prevail) in midsummer. Areas where the subtropical high is too small (large) and moves toward the north too late (early) are better (worse) for the maintenance of the cold vortex in northeastern China.

Although much has been known about how humans psychologically perform data-driven scientific discovery, less has been known about its brain mechanism. The number series completion is a typical data-driven scientific discovery task, and has been demonstrated to possess the priming effect, which is attributed to the regularity identification and its subsequent extrapolation. In order to reduce the heterogeneities and make the experimental task proper for a brain imaging study, the number magnitude and arithmetic operation involved in number series completion tasks are further restricted. Behavioral performance in Experiment 1 shows the reliable priming effect for targets as expected. Then, a factorial design (the priming effect: prime vs. target; the period length: simple vs. complex) of event-related functional magnetic resonance imaging (fMRI) is used in Experiment 2 to examine the neural basis of data-driven scientific discovery. The fMRI results reveal a double dissociation of the left DLPFC (dorsolateral prefrontal cortex) and the left APFC (anterior prefrontal cortex) between the simple (period length=1) and the complex (period length=2) number series completion task. The priming effect in the left DLPFC is more significant for the simple task than for the complex task, while the priming effect in the left APFC is more significant for the complex task than for the simple task. The reliable double dissociation may suggest the different roles of the left DLPFC and left APFC in data-driven scientific discovery. The left DLPFC (BA 46) may play a crucial role in rule identification, while the left APFC (BA 10) may be related to mental set maintenance needed during rule identification and extrapolation.

Lysosomal acid lipase (LAL) hydrolyzes cholesteryl esters and triglycerides to generate free fatty acids and cholesterol in the cell. The downstream metabolites of these compounds serve as hormonal ligands for nuclear receptors and transcription factors. Genetic ablation of the lal gene in the mouse caused malformation of macrophages and inflammation-triggered multiple pathogenic phenotypes in multiple organs. To assess the relationship between macrophages and lal−/−pathogenic phenotypes, a macrophage-specific doxycycline-inducible transgenic system was generated to induce human LAL (hLAL) expression in the lal−/−genetic background under control of the 7.2-kb c-fms promoter/intron2 regulatory sequence. Doxycycline-induced hLAL expression in macrophages significantly ameliorated aberrant gene expression, inflammatory cell (neutrophil) influx, and pathogenesis in multiple organs. These studies strongly support that neutral lipid metabolism in macrophages contributes to organ inflammation and pathogenesis.

The functional roles of neutral lipids in the lung are poorly understood. However, blocking cholesteryl ester and triglyceride metabolism in lysosomal acid lipase gene knockout mice (lal−/−) results in severe pathogenic phenotypes in the lung, including massive neutrophil infiltration, foamy macrophage accumulation, unwanted cell growth, and emphysema. To elucidate the mechanism underlining these pathologies, we performed Affymetrix GeneChip microarray analysis of 1-, 3-, and 6-month-old mice and identified aberrant gene expression that progressed with age. Among changed genes, matrix metalloproteinase (MMP)-12, apoptosis inhibitor 6 (Api-6), erythroblast transformation-specific domain (Ets) transcription factor family member Spi-C, and oncogene MafB were increased 100-, 70-, 40-, and 10-fold, respectively, in lal−/− lungs versus the wild-type lungs. The pathogenic increases of these molecules occurred primarily in alveolar type II epithelial cells. Transcriptional activities of the MMP-12 and Api-6 promoters were stimulated by Spi-C or MafB in respiratory epithelial cells. Treatment with 9-hydroxyoctadecanoic acids and ciglitazone significantly rescued lal−/− pulmonary inflammation and aberrant gene expression. In addition, both compounds as well as peroxisome proliferator-activated receptor gamma inhibited MMP-12 and Api-6 promoter activities. These data suggest that inflammation-triggered cell growth and emphysema during lysosomal acid lipase deficiency are partially caused by peroxisome proliferator-activated receptor-γ inactivation.

Abstract: Two imaging experiments were performed—one involving an algebraic transformation task studied by Anderson, Reder, and Lebiere (1996) and the other an abstraction symbol manipulation task studied by Blessing and Anderson (1996). ACT-R models exist that predict the latency patterns in these tasks. These models require activity in an imaginal buffer to represent changes to the problem representation, in a retrieval buffer to hold information from declarative memory, and in a manual buffer to hold information about motor behavior. A general theory is described about how to map activity in these buffers onto the fMRI blood oxygen level dependent (BOLD) response. This theory claims that the BOLD response is integrated over the duration that a buffer is active and can be used to predict the observed BOLD function. Activity in the imaginal buffer is shown to predict the BOLD response in a left posterior parietal region; activity in the retrieval buffer is shown to predict the BOLD response in a left prefrontal region; and activity in the manual buffer is shown to predict activity in a motor region. More generally, this article shows how to map a large class of information-processing theories (not just ACT-R) onto the BOLD response and provides a precise interpretation of the cognitive significance of the BOLD response.

Gaucher disease (GD) is an autosomal recessive lipid storage disorder, caused by deficient activity of the lysosomal enzyme β-glucocerebrosidase, resulting in accumulation of glucocerebroside in tissue macrophages. HGT-GCB-068 was an open-label study designed to explore the efficacy and safety of velaglucerase alfa in children and adolescents with type 3 GD, a neuronopathic form of the disease. Six treatment-naive patients received infusions of velaglucerase alfa every other week at 60 U/kg over 12 months. Velaglucerase alfa demonstrated a favorable tolerability profile, and 1 infusion-related reaction (headache) was the only drug-related adverse event reported. Numerical increases from baseline in hematological parameters and decreases in visceral parameters were seen at 12 months. http://ClinicalTrials.govidentifier NCT01685216.