ARFI破坏微泡增强Fe3O4纳米粒子在大鼠皮下移植瘤靶向递送的实验研究

目的 制备一种具有磁共振显像功能的Fe3O4纳米粒子,通过声脉冲辐射成像(acoustic radiation force impulse,ARFI)辐照脂质微泡(microbubbles,MBs),探讨ARFI辐照微泡对Fe3O4纳米粒子在肿瘤组织分布的影响.方法 采用高温水热法制备Fe3O4纳米粒子,检测其形态、大小、分布等,观察其体外磁共振显像效果.选取60只SD雌性大鼠,体质量为170 ～200 g,制备Walker256皮下移植瘤模型,分为6组(n=10):单纯ARFI辐照组、单纯MBs组、ARFI辐照MBs组、单纯Fe3O4纳米粒子组、ARFI辐照Fe3O4纳米粒子组、ARFI辐照MBs和Fe3O4纳米粒子组.微泡0.2 mL及5 mg/kg Fe3O4纳米粒子经大鼠尾静脉推注,ARFI辐照条件为探头间隔5 s辐照肿瘤部位,累计辐照5 min.将处理后的SD大鼠肿瘤部位行MRI扫描观察肿瘤组织信号变化;处死SD大鼠,取组织标本行病理学分析.结果 制备的Fe3O4纳米粒子形态规则,粒径分布均匀,具有磁共振显像功能.SD大鼠肿瘤组织普鲁士蓝染色结果为单纯Fe3O4纳米粒子组、ARFI辐照Fe3O4纳米粒子组、ARFI辐照MBs和Fe3O4纳米粒子组均可见点状蓝染颗粒.其中ARFI辐照MBs和Fe3O4纳米粒子组蓝染颗粒计数明显多于其余2组(P＜0.05).SD大鼠肿瘤部位磁共振成像结果为单纯Fe3O4纳米粒子组、ARFI辐照Fe3O4纳米粒子组、ARFI辐照MBs和Fe3O4纳米粒子组经相应处理后T2*WI均可见肿瘤内部低信号部分增加.结论 ARFI辐照MBs能够有效地提高Fe3O4纳米粒子在SD大鼠皮下移植瘤组织的分布,增强Fe3O4纳米粒子在活体肿瘤内的靶向递送效果.     

成人内听道底相关结构的多层螺旋CT解剖学观察

目的：应用64层MSCT观测成人内听道底及其相关的解剖结构,为临床应用提供影像解剖学依据。方法筛选2011年4—12月广东省人民医院采用64层MSCT扫描的乳突气化良好、无中耳或内耳病变且无眩晕等平衡功能障碍症状的40例共80耳成人CT资料进行回顾性分析。在MSCT图像上观测：横嵴,横嵴至前庭内侧骨壁的距离（ D1),面神经管迷路段、上前庭神经管、下前庭神经管和后壶腹神经管（单管)各管的长度、宽径,以及后壶腹神经管的内听道开口（单孔)至前庭内侧骨壁的距离（D2)。结果80耳的横嵴、面神经管迷路段、上前庭神经管、下前庭神经管和后壶腹神经管、单孔在横断位、冠状位及矢状位均能显示。其中横嵴局部解剖位置清晰、稳定,位于内听道底的中部,内侧缘自前内向后外走行,D1为（1．56±0．55)mm（0．55~2．67 mm)。面神经管迷路段长度（2．60±0．34)mm（1．54~3．27 mm),宽径（0．91±0．23)mm（0．50~1．58 mm);上前庭神经管长度（3．39±0．52) mm（2．50~5．06 mm),宽径（1．03±0．19)mm（0．74~1．62 mm);下前庭神经管长度（1．35±0．27) mm（0．74~2．17 mm),宽径（1．34±0．25)mm（0．85~2．34 mm);后壶腹神经管长度（3．88±0．84) mm （2．58~6．00 mm),宽径（0．63± 0．12) mm （0．42~0．98 mm)。 D2为（2．50±0．72)mm（1．37~5．01 mm)。结论64层螺旋CT能较好地显示位于内听道底的横嵴以及面神经管迷路段、前庭上神经、前庭下神经、后壶腹神经各骨管和单孔的走行及形态特征,为内耳疾病的诊断、鉴别诊断及术前评估提供有参考价值的信息。     

The acoustic cough monitoring and manometric profile of cough and throat clearing

Cough and throat clearing might be difficult to differentiate when trying to detect them acoustically or manometrically. The aim of this study was to assess the accuracy of acoustic monitoring for detecting cough and throat clearing, and to also determine whether these two symptoms present with different manometric profiles on esophageal pressure topography. Ten asymptomatic volunteers (seven females, mean age 31.1) were trained to simulate cough and throat clearing in a randomized order every 6 minutes during simultaneous acoustic monitoring and high‐resolution manometry. The accuracy of automated acoustic analysis and two blinded reviewers were compared. The pattern of the events and the duration of the pressure changes were assessed using the 30 mmHg isobaric contour. There were 50 cough and 50 throat‐clearing events according to the protocol. The sensitivity and specificity of automated acoustic analysis was 84% and 50% for cough, while the blinded analysis using sound revealed a sensitivity and specificity of 94% and 92%. The manometric profile of both cough and throat clearing was similar in terms of qualitative findings; however, cough was associated with a greater number of repetitive pressurizations and a more vigorous upper esophageal sphincter contraction compared with throat clearing. The acoustic analysis software has a moderate sensitivity and poor specificity to detect cough. The profile of cough and throat clearing in pressure topography revealed a similar qualitative pattern of pressurization with more vigorous pressure changes and a greater rate of repetitive pressurizations in cough.     

Criticality Hidden in Acoustic Emissions and in Changing Electrical Resistance during Fracture of Rocks and Cement-Based Materials

Acoustic emissions (AE) due to microcracking in solid materials permit the monitoring of fracture processes and the study of failure dynamics. As an alternative method of integrity assessment, measurements of electrical resistance can be used as well. In the literature, however, many studies connect the notion of criticality with AE originating from the fracture, but not with the changes in the electrical properties of materials. In order to further investigate the possible critical behavior of fracture processes in rocks and cement-based materials, we apply natural time (NT) analysis to the time series of AE and resistance measurements, recorded during fracture experiments on cement mortar (CM) and Luserna stone (LS) specimens. The NT analysis indicates that criticality in terms of electrical resistance changes systematically precedes AE criticality for all investigated specimens. The observed greater unpredictability of the CM fracture behavior with respect to LS could be ascribed to the different degree of material homogeneity, since LS (heterogeneous material) expectedly offers more abundant and more easily identifiable fracture precursors than CM (homogenous material). Non-uniqueness of the critical point by varying the detection threshold of cracking events is apparently due to finite size effects which introduce deviations from the self-similarity.     

Acoustic Emission Behavior of Early Age Concrete Monitored by Embedded Sensors

Acoustic emission (AE) is capable of monitoring the cracking activities inside materials. In this study, embedded sensors were employed to monitor the AE behavior of early age concrete. Type 1–3 cement-based piezoelectric composites, which had lower mechanical quality factor and acoustic impedance, were fabricated and used to make sensors. Sensors made of the composites illustrated broadband frequency response. In a laboratory, the cracking of early age concrete was monitored to recognize different hydration stages. The sensors were also embedded in a mass concrete foundation to localize the temperature gradient cracks.     

From the Cover: Species interactions and the structure of complex communication networks

A universal challenge faced by animal species is the need to communicate effectively against a backdrop of heterospecific signals. It is often assumed that this need results in signal divergence to minimize interference among community members, yet previous support for this idea is mixed, and few studies have tested the opposing hypothesis that interactions among competing species promote widespread convergence in signaling regimes. Using a null model approach to analyze acoustic signaling in 307 species of Amazonian birds, we show that closely related lineages signal together in time and space and that acoustic signals given in temporal or spatial proximity are more similar in design than expected by chance. These results challenge the view that multispecies choruses are structured by temporal, spatial, or acoustic partitioning and instead suggest that social communication between competing species can fundamentally organize signaling assemblages, leading to the opposite pattern of clustering in signals and signaling behavior.One of the core principles of animal communication is that signals should be detectable and convey an accurate message against a noisy background (1–3). This background can involve direct overlap of sounds, as in the case of masking by simultaneous signals (4, 5), or simply the co-occurrence of different species using confusingly similar signals at the same location (6–8). As most animals communicate within assemblages of related species, the problem of signal interference is widespread and may have far-reaching implications for the evolution of signals and signaling behavior. This concept—variously termed the “noisy neighbors” hypothesis (9) or “cocktail party problem” (10)—has attracted much attention over recent years. However, the extent to which it provides a general explanation for patterns of signaling in animal communities remains contentious (6, 8).The traditional view is that the signaling strategies of animals are shaped by limiting similarity among competitors, much as competition for ecological resources is thought to promote partitioning of niche space (11–13). Partitioning of signal space may occur if species compete for position near overcrowded transmission optima, and, concurrently, if overlap in signal design impairs the detection or discrimination of signals mediating mate choice and resource competition (14). Under these conditions, mechanisms of selection against misdirected aggression (e.g., character displacement) or the production of unfit hybrids (e.g., reinforcement) are predicted to drive phenotypic divergence (9), whereas similar mechanisms may lead to related species signaling at different times or in different locations (13). These pathways theoretically lead to structural, temporal, and spatial partitioning of signals and signalers in animal assemblages, but tests of these patterns have produced mixed results (6, 11, 15).A contrasting possibility is that selection for signal divergence is weak and that co-occurring species instead show the opposite pattern of signal clustering (16). One potential driver of this pattern is that shared habitats can exert convergent selection on signals (17). Another is that signals often have dual function in mate attraction and resource defense (18), potentially mediating competition among closely related species for ecological resources (19). Thus, multispecies choruses may operate to some degree as extended communication networks, not only within species (20) but between species. The effect of such a network would be to increase the likelihood of interspecific communication involving closely related species with similar signals. A pattern of signal clustering caused by communication among similar congeners may be further exaggerated when competitive interactions among species promote signal similarity (16). This process may occur when individuals with convergent agonistic signals have higher fitness because they are better at defending resources against both conspecific and heterospecific competitors, driving convergent evolution (21, 22). Taken together, these alternative views suggest that the most pervasive effect of species interactions on animal communication systems may not be partitioning, as generally proposed, but synchrony and stereotypy among competing species.Progress in resolving these opposing viewpoints has been limited because most studies of signaling assemblages have compiled lists of species co-occurring at particular localities and then compared multiple assemblages across regional scales (6, 15). This approach may be misleading because of spatial biases in phylogenetic relationships and habitat. On the one hand, sympatric species tend to be significantly older than allopatric species, at least within radiations (23, 24), and thus the signals of co-occurring lineages may be more divergent than expected by chance simply because they have had more time to diverge, exaggerating the evidence for partitioning. Conversely, species co-occurring at local scales may be less divergent because they are segregated by habitat across a study site and therefore are unlikely to signal together. Although some studies (7, 11) partially overcome these issues by sampling assemblages from single points in space, none has considered the effects of habitat and the potential role of competitive interactions among related species (16). Moreover, previous studies have generally assessed partitioning in relatively small assemblages (<30 species), reducing both the likelihood of competition over transmission optima and the power of statistical tests.Here, we sample >90 signaling assemblages (Fig. S1) containing a combined total of >300 species (Dataset S1) to assess the role of species interactions in structuring and organizing the dawn chorus of Amazonian rainforest birds. Each assemblage comprised species producing acoustic signals, identified from standardized 120-min sound recordings taken at points distributed across a single study locality. We also restricted analyses to 10-min time blocks and assumed that assemblages of species signaling in these blocks were forced to discriminate among each other (i.e., they were each other’s background noise) and also that they had an increased likelihood of signaling simultaneously (i.e., directly masking each other’s signals). We use the term cosignaling to describe pairs of species signaling during the same 10- or 120-min time block and thus not necessarily signaling simultaneously. We coded all assemblages for habitat and time of day, calculated the acoustic similarity of cosignaling species using spectrographic analyses of voice recordings, and estimated the evolutionary relatedness of cosignaling species using a hierarchical taxonomic framework.Our null hypothesis states that species interactions have no effect on chorus structure and thus that species with similar signals are randomly distributed in space and time (Fig. 1A). The distance between signals in observed choruses should not differ significantly from that expected by chance, accounting for habitat and evolutionary relationships. We envisage two scenarios that may falsify the null. The partitioning hypothesis predicts that signal design is evenly spaced across communities, with a larger distance between co-occurring signals than predicted by chance (Fig. 1B). The network hypothesis predicts that competing species interact using phylogenetically conserved signals and thus that signals are clustered in distribution, with a smaller distance between co-occurring signals than predicted by chance (Fig. 1C). The partitioning and network hypotheses involve different forms of species interaction with opposing effects on chorus structure. Although we do not measure species interactions directly, we follow standard approaches in assuming that such interactions predict patterns in the trait structure of assemblages (25).Open in a separate windowFig. 1.Predictions of three hypotheses proposed to structure multispecies choruses, illustrated using hypothetical seven-species choruses with signal design plotted in multivariate signaling space. The null hypothesis that species interactions have no effect predicts that signal structure is random (A), generating an intermediate mean nearest-neighbor distance d. The partitioning hypothesis predicts an evenly spaced signal structure (B) reflected in larger values for d. The network hypothesis predicts that related species will signal together, causing signals to be clustered around optima (C), and generating small values for d. We test these predictions by assessing whether d, viewed across a sample of communities, is higher or lower than expected by chance. We calculated d in two ways: d₁ (Upper) is the mean nearest neighbor distance [nnd] across all community members; and d₂ (Lower) is the mean nnd across the three pairs of species with most similar signals.Our aims were to (i) quantify acoustic properties of signals transmitted in the dawn chorus; (ii) estimate the degree of signal similarity among cosignaling species; and (iii) compare the observed distribution of signal properties with that expected by chance. We also consider spatial explanations for chorus structure, including the reduced cosignaling of species with similar signals through spatial partitioning. This form of segregation may occur because ecological competition is elevated in tropical bird communities (26), causing parapatric (27) or “checkerboard” distributions (28) among closely related species, thus potentially leading to apparent signal partitioning by competitive exclusion. The network hypothesis predicts the opposite pattern as closely related species should synchronize their signaling activity using shared territorial signals. We test these predictions by comparing 120-min (spatially segregated) and 10-min (nonsegregated) choruses and using taxonomic relatedness to estimate the degree of cosignaling between close relatives.The Amazonian dawn chorus provides one of the world’s most diverse multispecies signaling assemblages and an ideal system for exploring the effects of competition on signaling strategies for three reasons. First, visibility is hampered by dense vegetation, and thus long-distance signaling is forced into one modality (acoustic communication). Second, background noise levels are extremely high as a result of other organisms, including insects, amphibians, and primates, suggesting that selection for partitioning of acoustic signals should be maximized (12). Finally, many tropical species are permanently resident and apparently interspecifically territorial, using acoustic signals to mediate competitive interactions with heterospecifics (18, 26, 29). In combination, these factors imply that large numbers of species compete both for ecological resources and a narrow window of optimal signaling space (7, 30), providing a context in which to test the relative importance of acoustic partitioning and interspecific communication networks.     

Prenatal exposure to PCBs in Cyp1a2 knock‐out mice interferes with F1 fertility,impairs long‐term potentiation,reduces acoustic startle and impairs conditioned freezing contextual memory with minimal transgenerational effects

Polychlorinated biphenyls (PCBs) are toxic environmental pollutants. Humans are exposed to PCB mixtures via contaminated food or water. PCB exposure causes adverse effects in adults and after exposure in utero. PCB toxicity depends on the congener mixture and CYP1A2 gene activity. For coplanar PCBs, toxicity depends on ligand affinity for the aryl hydrocarbon receptor (AHR). Previously, we found that perinatal exposure of mice to a three‐coplanar/five‐noncoplanar PCB mixture induced deficits in novel object recognition and trial failures in the Morris water maze in Cyp1a2^?/?::Ahr^b1 C57BL6/J mice compared with wild‐type mice (Ahr^b1 = high AHR affinity). Here we exposed gravid Cyp1a2^?/?::Ahr^b1 mice to a PCB mixture on embryonic day 10.5 by gavage and examined the F₁ and F₃ offspring (not F₂). PCB‐exposed F₁ mice exhibited increased open‐field central time, reduced acoustic startle, greater conditioned contextual freezing and reduced CA1 hippocampal long‐term potentiation with no change in spatial learning or memory. F₁ mice also had inhibited growth, decreased heart rate and cardiac output, and impaired fertility. F₃ mice showed few effects. Gene expression changes were primarily in F₁ PCB males compared with wild‐type males. There were minimal RNA and DNA methylation changes in the hippocampus from F₁ to F₃ with no clear relevance to the functional effects. F₀ PCB exposure during a period of rapid DNA de‐/remethylation in a susceptible genotype produced clear F₁ effects with little evidence of transgenerational effects in the F₃ generation. While PCBs show clear developmental neurotoxicity, their effects do not persist across generations for effects assessed herein.     

In vitro characterisation of arterial stiffening: From the macro- to the nano-scale

Accurate measurement of the material properties of arterial tissue is important for better characterisation of diseases and the development of reliable computational models. There are a number of in vitro techniques that are applied to study the biomechanical properties of arterial tissue. This review article presents data obtained using tensile testing, nanoindentation, scanning acoustic microscopy (SAM) and atomic force microscopy (AFM). Each of these techniques provides material property information at a different spatial resolution and in many ways are complementary techniques. The lack of consensus in the literature with regard to the appropriate stress and strain definitions that should be used when reporting tensile testing data is also highlighted. The potential of higher spatial resolution techniques, which provide data at micro-scale (nanoindentation and SAM) and nano-scale (AFM) for application to the characterisation of human aortic tissue are discussed. Finally, studies, which have examined age-related changed in the aorta at these different length scales, are highlighted.     

Spatiotemporally controlled single cell sonoporation

This paper presents unique approaches to enable control and quantification of ultrasound-mediated cell membrane disruption, or sonoporation, at the single-cell level. Ultrasound excitation of microbubbles that were targeted to the plasma membrane of HEK-293 cells generated spatially and temporally controlled membrane disruption with high repeatability. Using whole-cell patch clamp recording combined with fluorescence microscopy, we obtained time-resolved measurements of single-cell sonoporation and quantified the size and resealing rate of pores. We measured the intracellular diffusion coefficient of cytoplasmic RNA/DNA from sonoporation-induced transport of an intercalating fluorescent dye into and within single cells. We achieved spatiotemporally controlled delivery with subcellular precision and calcium signaling in targeted cells by selective excitation of microbubbles. Finally, we utilized sonoporation to deliver calcein, a membrane-impermeant substrate of multidrug resistance protein-1 (MRP1), into HEK-MRP1 cells, which overexpress MRP1, and monitored the calcein efflux by MRP1. This approach made it possible to measure the efflux rate in individual cells and to compare it directly to the efflux rate in parental control cells that do not express MRP1.     

Metastasis germinomas of the external acoustic meatus: in a 19-year-boy: a case report

Background: The external acoustic meatus metastasis of germinomas is a rare event. Case presentation: we describe a 19-year-old boy with stuffiness and earplug of the left ear but no other symptoms. The whole body F-18 FDG PET/CT and the brain MRI are performed and demonstrated a germinoma in the pineal gland and vermis cerebellum region and in the right of thalamus. Photomicrograph showing marked infiltration of lymphoplasma cells and macrophages including giant cells. Immunohistochemical analysis results demonstrated the tumor cells are strongly positive for CD117 and PLAP. The final diagnosis was germinoma and all adjuvant therapy was achieved. Conclusion: Although the external acoustic meatus metastasis of germinomas is rare, the diagnosis should be taken into serious consideration in order to improve. In addition, F-18 FDG PET/CT was very useful in diagnosis primary disease and excluding distant metastases. To our knowledge, this is the first published report of this type of case.