Unique Advantages of Dendrimers-Structured Mesoporous Silica Nanoparticles over Traditional Hollow ones in Delivering Bcl2-Functional Converting Peptide for Multidrug Resistant Cancer Treatment.

Innovative silica nanomaterials have made the significant advancements in curative therapy against cancers with multidrug resistance (MDR). The study on different-nanostructured mesoporous silica nanoparticles (MSNs) with discrepant pore sizes affecting biomacromolecules in resisting cancer MDR hasn't been reported yet. In this study, a systematic comparison of 6 nm-pore sized hollow-structured MSNs (HMSNs) and 10 nm-pore sized dendrimers-structured MSNs (LMSNs) for delivering Bcl-2-functional converting peptide (N9) or doxorubicin (DOX) to overcome cancer MDR was comprehensively carried out both in in vitro and in vivo resistant tumor models. Our results showed that both LMSNs and HMSNs exerted no significant difference in delivering DOX to treat drug-resistant cancers. However, compared with N9@HMSNs, N9@LMSNs displayed the increased loading efficiency, the improved cell-penetrative capability, the higher cancer cell apoptosis effect, the enhanced tumor accumulation and retention efficiency, and the final elevated tumor inhibition efficiency. Unexpectedly, naked LMSNs without surface modification especially at high dosage produced relatively more serious toxicity than HMSNs whatever in cells, zebrafish embryo or mice models. Collectively, our data provided the sufficient theoretical evidence that LMSNs might be a better choice for delivering biomacromolecules to treat resistant cancers after appropriate surface functionalization such as with PEGylation to weaken its intrinsic toxicity. This article is protected by copyright. All rights reserved.

Integrin α5 regulates motility of human monocyte-derived Langerhans cells during immune response.

Langerhans cells (LCs) are mainly present in the epidermis and mucosa, and have important roles during skin infection. Migration of LCs to lymph nodes is essential for antigen presentation. However, due to the difficulties in isolating and culturing human LCs, it is not fully understood how LCs move and interact with the extracellular matrix (ECM) through their adhesion molecules such as integrin, during the immune responses. In this study, we aimed to investigate LC motility, cell shape and the role of integrin under inflammatory conditions using monocyte-derived Langerhans cells (moLCs) as a model. As a result, lipopolysaccharide (LPS) stimulation increased adhesion on fibronectin coated substrate and integrin α5 expression in moLCs. Time-lapse imaging of moLCs revealed that stimulation with LPS elongated cell shape, whilst decreasing their motility. Additionally, this decrease in motility was not observed when pre-treated with a neutralising antibody targeting integrin α5. Together, our data suggested that activation of LCs decreases their motility by promoting integrin α5 expression to enhance their affinity to the fibronectin, which may contribute to their migration during inflammation.

Effect of curvature on sound propagation in the ear canal.

In this paper, we investigate the effect of the curvature and torsion of the ear canal on its resonance through a comparison between several ear canal models. Utilizing Stinson's ear canal geometries as a reference, we build and analyze several ear canal models using both transmission matrix and numerical methods for the purpose of comparative assessment. A conical transmission unit, which considers visco-thermal effects, is employed for the modeling of the human ear canal. While the transfer matrix and numerical method agree well for a straight axis model, this simplification results in up to 20% deviation from a curved canal. We propose the curve twist ratio as a metric to quantify the influence of curvature on the ear canal and find that our proposed metric can effectively express the error introduced by the simplified straight axis model. Upon this metric, an empirical equation is proposed for incorporating the curvature effect in the transmission matrix method, enabling it to generate comparable results to those of the numerical method, which considers the effect of the curvature and torsion, thus dramatically accelerating computation.

Alpha peak activity in resting-state EEG is associated with depressive score.

Introduction: Depression is a serious psychiatric disorder characterized by prolonged sadness, loss of interest or pleasure. The dominant alpha peak activity in resting-state EEG is suggested to be an intrinsic neural marker for diagnosis of mental disorders. Methods: To investigate an association between alpha peak activity and depression severity, the present study recorded resting-state EEG (EGI 128 channels, off-line average reference, source reconstruction by a distributed inverse method with the sLORETA normalization, parcellation of 68 Desikan-Killiany regions) from 155 patients with depression (42 males, mean age 35 years) and acquired patients' scores of Self-Rating Depression Scales. We measured both the alpha peak amplitude that is more related to synchronous neural discharging and the alpha peak frequency that is more associated with brain metabolism. Results: The results showed that over widely distributed brain regions, individual patients' alpha peak amplitudes were negatively correlated with their depressive scores, and individual patients' alpha peak frequencies were positively correlated with their depressive scores. Discussion: These results reveal that alpha peak amplitude and frequency are associated with self-rating depressive score in different manners, and the finding suggests the potential of alpha peak activity in resting-state EEG acting as an important neural factor in evaluation of depression severity in supplement to diagnosis.

Roles of TRPM4 in immune responses in keratinocytes and identification of a novel TRPM4-activating agent.

The skin is a protective interface between the internal organs and environment and functions not only as a physical barrier but also as an immune organ. However, the immune system in the skin is not fully understood. A member of the thermo-sensitive transient receptor potential (TRP) channel family, TRPM4, which acts as a regulatory receptor in immune cells, was recently reported to be expressed in human skin and keratinocytes. However, the function of TRPM4 in immune responses in keratinocytes has not been investigated. In this study, we found that treatment with BTP2, a known TRPM4 agonist, reduced cytokine production induced by tumor necrosis factor (TNF) α in normal human epidermal keratinocytes and in immortalized human epidermal keratinocytes (HaCaT cells). This cytokine-reducing effect was not observed in TRPM4-deficient HaCaT cells, indicating that TRPM4 contributed to the control of cytokine production in keratinocytes. Furthermore, we identified aluminum potassium sulfate, as a new TRPM4 activating agent. Aluminum potassium sulfate reduced Ca2+ influx by store-operated Ca2+ entry in human TRPM4-expressing HEK293T cells. We further confirmed that aluminum potassium sulfate evoked TRPM4-mediated currents, showing direct evidence for TRPM4 activation. Moreover, treatment with aluminum potassium sulfate reduced cytokine expression induced by TNFα in HaCaT cells. Taken together, our data suggested that TRPM4 may serve as a new target for the treatment of skin inflammatory reactions by suppressing the cytokine production in keratinocytes, and aluminum potassium sulfate is a useful ingredient to prevent undesirable skin inflammation through TRPM4 activation.

Visual over auditory superiority in sensorimotor timing under optimized condition.

Auditory over visual advantage in temporal processing is generally appreciated, such as the well-established auditory superiority in sensorimotor timing. To test for a possible visual superiority in temporal processing, here, we present a data set composed of a large 60 subjects sample and a data set including eight smaller samples of approximately 15 subjects, showing that synchronization to a temporally regular sequence was more stable for a visual bouncing ball (VB) than for auditory tones (ATs). The results demonstrate that vision can be superior over audition in sensorimotor timing under optimized conditions, challenging the generally believed auditory superiority in temporal processing. In contrast to the auditory-specific biological substrates of timing in sensorimotor interaction, the present finding points to tight visual-motor cortical coupling in sensorimotor timing.

Responses of soil N2 O emissions and their abiotic and biotic drivers to altered rainfall regimes and co-occurring wet N deposition in a semi-arid grassland.

Global change factors such as changed rainfall regimes and nitrogen (N) deposition contribute to increases in the emission of the greenhouse gas nitrous oxide (N2 O) from the soil. In previous research, N deposition has often been simulated by using a single or a series of N addition events over the course of a year, but wet N deposition actually co-occurs with rainfall. How soil N2 O emissions respond to altered rainfall amount and frequency, wet N deposition, and their interactions is still not fully understood. We designed a three-factor, fully factorial experiment with factors of rainfall amounts (ambient, -30%) rainfall frequency (ambient, ±50%) and wet N deposition (with/without) co-occurring with rainfall in semi-arid grassland mesocosms, and measured N2 O emissions and their possible biotic and abiotic drivers. Across all treatments, reduced rainfall amount and N deposition increased soil N2 O emissions by 35% and 28%, respectively. A significant interactive effect was observed between rainfall amount and N deposition, and to a lesser extent between rainfall frequency and N deposition. Without N deposition, reduced rainfall amount and altered rainfall frequency indirectly affected soil N2 O emissions by changing the abundance of nirK and soil net N mineralization, and the changes in nirK abundance were indirectly driven by soil N availability rather than directly by soil moisture. With N deposition, both the abundance of nirK and the level of soil water-filled pore space contributed to changes in N2 O emissions in response to altered rainfall regimes, and the changes in the abundance of nirK were indirectly driven by plant N uptake and nitrifier (ammonia-oxidizing bacteria) abundance. Our results imply that unlike wetter grassland ecosystems, reduced precipitation may increase N2 O emissions, and N deposition may only slightly increase N2 O emissions in arid and semi-arid N-limited ecosystems that are dominated by grasses with high soil N uptake capacity.

Impact of macroporous silica nanoparticles at sub-50nm on bio-behaviors and biosafety in drug-resistant cancer models.

The in vivo bio-behaviors and biosafety of nanoparticles were demonstrated to be closely correlated with particle sizes, which illustrated whether they could be used as the effective drug delivery carriers. Though tumor penetration capabilities of the small pore sized-mesoporous silica nanoparticles (MSNs) were reported to be in a particle size-dependent manner, the size effects of large pore sized-MSNs on the safe and effective cancer resistance treatment, especially at sub-50 nm, were not explicitly evaluated. In this study, we fabricate the 20 nm and 50 nm MSNs, and aim at investigating their difference in tumor accumulation, penetration, retention and toxicity both in vitro and in vivo. Our results showed that these two particle sized-MSNs possessed the excellent tumor penetration capabilities both in resistant human hepatocellular carcinoma cells-cultured spheroids and in the corresponding xenograft mice models, but the 50 nm MSNs seemed to have the better tumor accumulation and retention effects than the 20 nm MSNs. Moreover, the 50 nm MSNs displayed the lower toxicities than the 20 nm MSNs whatever on resistant cancer cell lines or on zebrafish embryos, indicating the greater systematic biosafety. In a word, our data provide the evidence that selection of the large pore-sized MSNs at the appropriate particle size (not the smaller the better) as bio-macromolecule nanocarriers will play a key role in the safe and effective treatment against cancer resistance.

Target familiarity and visual working memory do not influence familiarity effect in visual search.

Familiarity effect refers to the phenomenon that searching for a novel target among familiar distractors is more efficient than that searching for a familiar target among novel distractors. While the familiarity of distractors is considered as a key role on familiarity effect, the familiarity of targets contribute to this asymmetric visual search is unclear. The present study investigated how target familiarity influences visual search efficiency from the perspective of perceptual load. Experiment 1 using two similar Chinese characters ("" and "") suggested that searching for a familiar target from familiar distractors is an inefficient search process in Chinese context. Experiment 2 adopted a dual-task paradigm with a visual working memory task to increase the perceptual load and attempt to affect the efficiency of searching a novel target (mirrored "") from familiar distractors (""). Results demonstrated no difference in the search efficiency between single and dual-task conditions. The present study suggests that the familiarity of target does not influence the search efficiency with familiar distractors when involving semantic processing of Chinese characters. Additionally, the interference of extra working memory load would not impair the efficiency of searching target among familiar distractors, supporting the critical effect of distractor familiarity on the efficiency of visual search.

A partially confirmatory approach to scale development with the Bayesian Lasso.

The exploratory and confirmatory approaches of factor analysis lie on two ends of a continuum of substantive input for scale development. Recent advancements in Bayesian regularization methods enable more flexibility in covering a wide range of the substantive continuum. Based on the Bayesian Lasso (least absolute shrinkage and selection operator) methods for the regression model and covariance matrix, this research proposes a partially confirmatory approach to address the loading and residual structures at the same time. With at least one specified loading per item, a one-step procedure can be applied to figure out both structures simultaneously. With a few specified loadings per factor, a two-step procedure is preferred to capture the model configuration correctly. In both cases, the Bayesian hierarchical formulation is implemented using Markov Chain Monte Carlo estimation with different Lasso or regular priors. Both simulated and real data sets were analyzed to evaluate the validity, robustness, and practical usefulness of the proposed approach across different situations. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Gel properties and flavor characteristics of blended anchovy (Engraulis japonicus) mince and silver carp (Hypophthalmichthys molitrix) surimi.

This paper aims to research the gel properties and flavor characteristics of anchovy mince and silver carp surimi blended in different ratios (0/100, 10/90, 20/80, 30/70, 40/60 and 100/0). When the ratios of anchovy mince to silver carp surimi were 10/90 and 20/80, the gel strength of the blended systems increased significantly from 4629.17 g mm to 7568.01 g mm and 6804.22 g mm, respectively. Under these two ratios, the water-holding capacity of the blended systems increased significantly from 56.43% to 71.82% and 69.36%, respectively. In addition, the blended systems formed a highly uniform and dense network structure. At ratios of 0/100, 10/90 and 20/80, the myosin heavy chain was cross-linked, resulting in the formation of macromolecular aggregates. With the increase in anchovy mince content, the brightness and whiteness of the blended systems decreased gradually. When the ratio of anchovy mince to silver carp surimi was 10/90, the sensory evaluation score of the blended system was the highest and the bitterness score the lowest. Under this ratio, the relative contents of esters and aldehydes were the highest, while those of alcohols and ketones were the lowest. In conclusion, the optimum sample formulation contained a 10/90 ratio of anchovy mince to silver carp surimi.