2-Hydroxy-5-nitro-3-(trifluoromethyl)pyridine as a Novel Matrix for Enhanced MALDI Imaging of Tissue Metabolites.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which is a label-free imaging technique, determines the spatial distribution and relative abundance of versatile endogenous metabolites in tissues. Meanwhile, matrix selection is generally regarded as a pivotal step in MALDI tissue imaging. This study presents the first report of a novel MALDI matrix, 2-hydroxy-5-nitro-3-(trifluoromethyl)pyridine (HNTP), for the in situ detection and imaging of endogenous metabolites in rat liver and brain tissues by MALDI-MS in positive-ion mode. The HNTP matrix exhibits excellent characteristics, including strong ultraviolet absorption, µm-scale matrix crystals, high chemical stability, low background ion interference, and high metabolite ionization efficiency. Notably, the HNTP matrix also shows superior detection capabilities, successfully showing 185 detectable metabolites in rat liver tissue sections. This outperforms the commonly used matrices of 2,5-dihydroxybenzoic acid and 2-mercaptobenzothiazole, which detect 145 and 120 metabolites from the rat liver, respectively. Furthermore, a total of 152 metabolites are effectively detected and imaged in rat brain tissue using the HNTP matrix, and the spatial distribution of these compounds clearly shows the heterogeneity of the rat brain. The results demonstrate that HNTP is a new and powerful positive-ion mode matrix to enhance the analysis of metabolites in biological tissues by MALDI-MSI.

Peripheral vision and crowding in mental maze-solving.

Solving a maze effectively relies on both perception and cognition. Studying maze-solving behavior contributes to our knowledge about these important processes. Through psychophysical experiments and modeling simulations, we examine the role of peripheral vision, specifically visual crowding in the periphery, in mental maze-solving. Experiment 1 measured gaze patterns while varying maze complexity, revealing a direct relationship between visual complexity and maze-solving efficiency. Simulations of the maze-solving task using a peripheral vision model confirmed the observed crowding effects while making an intriguing prediction that saccades provide a conservative measure of how far ahead observers can perceive the path. Experiment 2 confirms that observers can judge whether a point lies on the path at considerably greater distances than their average saccade. Taken together, our findings demonstrate that peripheral vision plays a key role in mental maze-solving.

Hemorrhage risk prediction after computed tomography-guided lung biopsy: Clinical parameters and quantitative pulmonary vascular analysis.

BACKGROUND/PURPOSE: We evaluated the utility of combining quantitative pulmonary vasculature measures with clinical factors for predicting pulmonary hemorrhage after computed tomography (CT)-guided lung biopsy. METHODS: Patients who underwent CT-guided lung biopsy were retrospectively included in this study. Clinical and radiographic vasculature variables were evaluated as predictors of pulmonary hemorrhage. The radiographic pulmonary vascular analysis included vessel count, density, diameter, and area, and also blood volume in small vessels with a cross-sectional area ≤5 mm2 (BV5) and total blood vessel volume (TBV) in the lungs. Univariate and multivariate logistic regressions were used to identify the independent risk factors of higher-grade pulmonary hemorrhage and establish the prediction model presented as a nomogram. RESULTS: The study included 126 patients; discovery cohort n = 103, and validation cohort n = 23. All pulmonary hemorrhage, higher-grade (grade ≥2) pulmonary hemorrhage, and hemoptysis occurred in 42.9%, 15.9%, and 3.2% of patients who underwent CT-guided lung biopsies. In the discovery cohort, patients with larger lesion depth (p = 0.013), higher vessel density (p = 0.033), and higher BV5 (p = 0.039) were more likely to experience higher-grade hemorrhage. The nomogram prediction model for higher-grade hemorrhage built by the discovery cohort showed similar performance in the validation cohort. CONCLUSIONS: Higher-grade pulmonary hemorrhage may occur after CT-guided lung biopsy. Lesion depth, vessel density, and BV5 are independent risk factors for higher-grade pulmonary hemorrhage. Nomograms integrating clinical parameters and radiographic pulmonary vasculature measures offer enhanced capability for assessing hemorrhage risk following CT-guided lung biopsy, thereby facilitating improved patient clinical care.

Development of mixed pitch grating for the optical addressing of trapped Sr+ ion with data analysis techniques.

Mixed pitch gratings are developed for the optical addressing of trapped 88Sr+ ion by means of simulation and experimental measurement approaches. Meanwhile, Python-based data analysis techniques were developed to analyze simulated and measured beam profiles. A fixed pitch grating with a pitch of 1.2 µm was used as a reference, and a mixed pitch grating with pitches of 1.1/1.2 µm of various ratios are investigated. The Python-based data analysis codes demonstrates highly automated capability in processing both simulated and measured beam profile data to compute key parameters, including beam waist and Gaussian fitting. Mixed pitch grating delivers light beam with smaller beam waist (17.4 µm) compared to the fixed pitch grating (26.4 µm), exhibiting ∼34% beam waist reduction.

[Effects of all-trans retinoic acid on the macrophage function of prostatic stromal cells].

Objective: To investigate the effects of all-trans retinoic acid (ATRA) on prostatic stromal cells during wound repair after prostatectomy in vitro. METHODS: Each of the M1 and M2 types of monocytic macrophage (THP-1) cells were divided into an experimental, a control and a non-activated group, the M1 macrophages of the former two groups activated by PMA and IFNγ, and the M2 macrophages by PMA and IL-4, respectively. The cells in the two experimental groups were treated with all-trans retinoic acid (ATRA) at 100 nmol/L, followed by detection of the expressions of IL-10, IL-12, IL-6, TNF-α and TGF-ß in the supernatant by ELISA. The supernatant was co-cultured with primarily cultured prostatic stromal cells or vascular endothelial cells in different groups. The expressions of RARα, RARß, RARγ, Arg1, Mmp9 and Soat1 in the macrophages were determined by PCR. The influence of the macrophages on the function of the stromal cells was analyzed by gel shrinkage test, scratch test and vascular endothelial cell tubular vascular formation test. The expression levels of Arg1 mRNA were reexamined under the action of RAR receptor subtype inhibitors. RESULTS: Compared with the control, the M2 macrophages treated with ATRA showed dramatically up-regulated expressions of IL-10 (ï¼»213.38 ± 2.02ï¼½ vs ï¼»298.22 ± 1.70ï¼½ pg/ml, P < 0.01) and TGF-ß (ï¼»185.37 ± 1.33ï¼½ vs ï¼»246.00 ± 2.14ï¼½ pg/ml, P < 0.01). The ATRA-treated macrophage supernatant enhanced the contraction and migration of the prostatic stromal cells and tubular formation of the vascular endothelial cells. The mRNA levels of Arg1 and RARß were significantly increased in the experimental group, and RARß was further confirmed to be the key receptor subtype in this process. CONCLUSIONS: ATRA activates prostatic stromal cells and enhances their migration and angiogenesis by acting on macrophages via RARß.

Specific antigen-guiding exosomes inhibit food allergies by inducing regulatory T cells.

The therapies for food allergy (FA) need to be improved. The generation of inducible regulatory T cells (Tregs) can support immune tolerance in the body. This study aims to suppress experimental FA by inducing Tregs through the employment of modified exosomes (mExosomes). In this study, mExosomes were prepared by incubating dendritic cells with interleukin (IL)-2 and ovalbumin (OVA, used as a specific antigen) in the culture. Exosomes were purified from culture supernatant and used as the mExosomes. A murine FA model was developed to test the effects of mExosomes on the generation of Tregs in the mouse intestinal tissues and inhibiting FA. The results showed that mExosomes, which carried IL-2 and a complex of OVA peptide-major histocompatibility complex class II on the surface of exosomes, bound to OVA-specific CD4+ T cells and induced CD4+ T cells to differentiate into Tregs. In the FA mouse intestinal tissues, we found low IL-2 levels that were positively correlated with the number of Tregs. Depletion of IL-2 in mice prevented the generation of Tregs. The levels of peroxisome proliferator-activated receptor-γ were increased in the FA intestinal tissues with inhibited IL-2 production. Administration of mExosomes induced Tregs in the intestinal tissues and efficiently suppressed FA in mice. We conclude that the mExosomes can suppress FA in mice through inducing Tregs. The data suggest that the mExosomes have translational potential in the treatment of FA and other allergic disorders.

Chimeric specific antigen epitope-carrying dendritic cells induce interleukin-17(+) regulatory T cells to suppress food allergy.

BACKGROUND: The on-purpose-modulated dendritic cells (DCs) have shown charming effects on restoring immune regulatory functions in subjects with immune diseases. OBJECTIVE: This study aims to construct DCs carrying chimerical antigen (Ag) peptides (CAP-DCs) to induce interleukin (IL)-17+ inducible Tregs (iTregs) to alleviate food allergy (FA) in a murine model. METHODS: In this study, we constructed CAP-DCs. The CAP is a fusion protein, consisting of a segment of recombinant scFv of anti-DEC205 antibody and an ovalbumin (OVA) epitope (IC). A murine OVA-FA model was developed to test the effects of CAP-DCs on suppressing the allergic response in the intestine. RESULTS: The CAP-DCs are characterized as that a complex of scFv-IC is presented on the surface of the cells, moderately express CD80 and CD86 as well as IL-6, IL-23, transforming growth factor (TGF)-ß and CCR9. After being passively transferred with CAP-DCs or injection of scFv-IC, Ag-specific IL-17+ Foxp3+ iTregs were induced in the intestinal lamina propria of FA mice. The iTregs showed immune suppressive effects on Ag-specific Th2 response. FA mice were adoptively transferred with the CAP-DCs or scFv-IC injection, which resulted in a significant decrease in the number of Ag-specific Th2 cells and suppression of FA response in an Ag-specific manner. CONCLUSIONS AND CLINICAL RELEVANCE: CAP-DCs can ameliorate FA response by inducing Ag-specific IL-17+ Foxp3+ iTregs and suppressing Ag-specific Th2 response. To generate CAP-DCs has the translational potential in the treatment of FA.

Cold stress promotes IL-33 expression in intestinal epithelial cells to facilitate food allergy development.

BACKGROUND: The causative factors and pathogenesis of food allergy (FA) is not fully understood yet. Cold stress (CS) occurs frequently in human life that influences physiological activities in the body. In this study, we aimed to investigate the chronic CS (CS) effects on promoting the expression of IL-33 in intestinal epithelial cells. METHODS: CS was carried out by placing mice at 4 °C for 1 h daily for 7 consecutive days. We developed a mouse model used to test the effects of CS on the FA development. RESULTS: We found that, similar to conventional FA mouse model, CS induced the core body temperature to drop markedly in mice, increased intestinal epithelial barrier permeability and facilitated FA development. CS promoted interleukin (IL)-33 expression in intestinal epithelial cells through the adrenocorticotropic hormone (ACTH)/cortisol axis and via inducing the Il33 promoter methylation. CS facilitated the FA development in mice, that could be blocked by depletion of IL-33 expression in intestinal epithelial cells. CONCLUSIONS: CS induces IL-33 expression in intestinal epithelial cells to promote Th2 polarization in the intestinal tissues and facilitates FA development.

Exosomes carry IL-10 and antigen/MHC II complexes to induce antigen-specific oral tolerance.

BACKGROUND: It is known that the immune tolerance can be naturally established in the intestine, while the mechanism by which the immune tolerance development in the intestine is not fully understood yet. Vasoactive intestinal peptides (VIP) has the immune regulatory functions. This study aims to investigate the role of VIP in the immune tolerance development in the intestine. METHODS: Intestinal epithelial cell (IEC)-derived exosomes were prepared. The exosomes carried IL-10 and antigen/MHC II complexes. VIP-deficient (VIPd) mice and wild type mice were employed to test the role of VIP in the development of immune tolerance in the intestine. RESULTS: VIPd mice failed to induce type 1 regulatory T cells (Tr1 cells) in the intestine and retarded the establishment of antigen (Ag)-specific immune tolerance. Exposure to VIP in the culture induced IL-10 expression in intestinal epithelial cells (IECs). Exosomes derived from ovalbumin (OVA, used as a specific Ag)/VIP-primed IECs carried IL-10 and OVA/MHC II complexes; these exosomes were designated IL10CARs (IL-10/chimeric antigen receptor-carrying exosomes). IL10CARs could recognize OVA-specific CD4+ T cells and converted OVA-specific CD4± T cells to OVA-specific Tr1 cells. Administration of IL10CARs suppressed experimental food allergy. CONCLUSIONS: The data show that IL10CARs are capable of suppressing experimental FA by inducing antigen-specific Tr1 cells, which has the translation potential for FA treatment.

Ti3C2 (MXene) based field electron emitters.

As a novel class of two-dimensional materials, MXene has provoked tremendous progress for various applications in functional devices. Here, we pioneer a preliminary understanding on the field emission behavior of MXene for the first time. Ti3C2 paper is fabricated by using facile filtration method, and multiple vertical sheets appear on the surface of MXene paper with high electrical conductivity (2.93 × 105 S m-1) and low work function (3.77 eV). The field electron emission performance and electric field distribution on MXene emitters are measured and simulated under planar and standing conditions. Both emitter conditions exhibit stable, uniform electron emission pattern, and the standing emitter achieves high emission current density of 59 mA cm-2 under 7.5 V µm-1. This work demonstrates the feasibility of MXene as cold electron source, establishing a preliminary foundation for its applications in field emission-based devices.

Severe Poverty and Growth in Behavioral Self-Regulation: The Mediating Role of Parenting.

This study examined how exposure to severe poverty related to behavioral self-regulation growth during early childhood as mediated by parenting practices. Ethnic differences were tested. Data were collected across 4 waves from 359 low-income African American and Latino families. The frequency of exposure to severe poverty was indicated by how many times family income fell below 50% of the federal poverty line across 4 waves. Behavioral self-regulation was assessed when children were 3½, 6, and 7 years old (Wave 2-4), and parenting was observed when children were age 2½ years old (Wave 1). More frequent exposure to severe poverty was associated with slower behavioral self-regulation growth, and the effect was partially mediated through less sensitive and supportive parenting practices for Latino families. The mediation was not observed for African American families. Targeting the promotion of sensitive and supportive parenting practices may be an effective strategy for accelerating self-regulation development.

Similarity Grouping as Feature-Based Selection.

Across the natural world as well as the artificial worlds of maps, diagrams, and data visualizations, feature similarity (e.g., color and shape) links spatially separate areas into sets. Despite a century of study, it is yet unclear what mechanism underlies this gestalt similarity grouping. One recent proposal is that similarity grouping-for example, seeing a red, vertical, or square group-is just global selection of those features. Although parsimonious, this account makes the counterintuitive prediction that similarity grouping is strictly serial: A green group cannot be constructed at the same time as a red group. We tested this prediction with a novel measure-a grouping illusion within number-estimation tasks that should work only if participants simultaneously construct groups-and found the strongest evidence yet in favor of serial feature-based attention ( Ns = 14, 12, and 12 for Experiment 1, Experiment 2, and Experiment 3, respectively).

Challenges to pooling models of crowding: Implications for visual mechanisms.

A set of phenomena known as crowding reveal peripheral vision's vulnerability in the face of clutter. Crowding is important both because of its ubiquity, making it relevant for many real-world tasks and stimuli, and because of the window it provides onto mechanisms of visual processing. Here we focus on models of the underlying mechanisms. This review centers on a popular class of models known as pooling models, as well as the phenomenology that appears to challenge a pooling account. Using a candidate high-dimensional pooling model, we gain intuitions about whether a pooling model suffices and reexamine the logic behind the pooling challenges. We show that pooling mechanisms can yield substitution phenomena and therefore predict better performance judging the properties of a set versus a particular item. Pooling models can also exhibit some similarity effects without requiring mechanisms that pool at multiple levels of processing, and without constraining pooling to a particular perceptual group. Moreover, we argue that other similarity effects may in part be due to noncrowding influences like cuing. Unlike low-dimensional straw-man pooling models, high-dimensional pooling preserves rich information about the stimulus, which may be sufficient to support high-level processing. To gain insights into the implications for pooling mechanisms, one needs a candidate high-dimensional pooling model and cannot rely on intuitions from low-dimensional models. Furthermore, to uncover the mechanisms of crowding, experiments need to separate encoding from decision effects. While future work must quantitatively examine all of the challenges to a high-dimensional pooling account, insights from a candidate model allow us to conclude that a high-dimensional pooling mechanism remains viable as a model of the loss of information leading to crowding.

One-Step Synthesis of Tunable-Size Gold Nanoplates on Graphene Multilayers.

Au nanoplates (quasi-two-dimensional single crystals) are most commonly synthesized using a mixture of Au precursors via approaches involving multiple processing steps and the use of seed crystals. Here, we report the synthesis of truncated-hexagonal {111}-oriented micrometer-scale Au nanoplates on graphene multilayers using only potassium tetrabromoaurate (KAuBr4) as the precursor. We demonstrate that the nanoplate sizes can be controllably varied from tens of nanometers up to a few micrometers by introducing desired concentrations of chloroauric acid (HAuCl4) to KAuBr4 and their thicknesses from ∼13 to ∼46 nm with the synthesis time. Through a series of experiments carried out as a function of synthesis time and precursor composition [mixtures of HAuCl4 and KAuBr4, KBr, or ionic liquid 1-butyl-3-methylimidazolium bromide ([Bmim]Br)], we identify the optimal HAuCl4 and KAuBr4 concentrations and synthesis times that yield the largest and the thinnest size nanoplates. We show that the nanoplates are kinetically limited morphologies resulting from preferential growth of {111} facets facilitated by bromide ions in KAuBr4 solutions; we suggest that the presence of chloride ions enhances the rate of Au deposition and the relative concentration of chloride and bromide ions determines the shape anisotropy of resulting crystals. Our results provide new insights into the kinetics of nanoplate formation and show that a single precursor containing both Au and Br is sufficient to crystallize nanoplates on graphitic layers, which serve as reducing agent while enabling the nucleation and growth of Au nanoplates. We suggest that a similar approach may be used for the synthesis of nanoplates of other metals on weakly interacting van der Waals layers for, potentially, a variety of new applications.

TRAF6 regulates proliferation of stromal cells in the transition and peripheral zones of benign prostatic hyperplasia via Akt/mTOR signaling.

BACKGROUND: Increased prostatic smooth muscle tone and hyperplastic growth contribute to urethral obstruction and voiding symptoms in benign prostatic hyperplasia (BPH). It has been suggested that different proliferative potential of stromal cells between transition zone (TZ) and adjoining regions of the prostate plays a significant role in the development of BPH. However, the molecular mechanisms of this hyperplastic process remain unclear. We found tumor necrosis factor receptor-associated factor 6 (TRAF6) highly expressed in TZ stromal cells compared to peripheral zone (PZ) stromal cells by gene array analyzes. Therefore, we aim to study the potential mechanisms of stromal TRAF6 in promoting BPH progression. METHODS: Stromal cells obtained from BPH-derived primary cultures. The TRAF6-siRNA vector were constructed and transfected into cultured human BPH primary TZ stromal cells, and TRAF6-overexpressing vector were constructed and transfected into cultured human BPH primary PZ stromal cells. Stromal cells were recombined with BPH-1 cells then subcutaneously inoculated into the kidney capsule of male nude mice. Cell proliferation was evaluated by CCK-8 assay. Multiple proteins in the Akt/mTOR pathway were assessed using western blot. RESULTS: TRAF6 levels were increased in TZ stroma compared with PZ stroma of BPH. The in vitro cell culture and in vivo cell recombination revealed that selective downregulation of TRAF6 in TZ stromal cells led to suppression of the proliferation, while upregulation of TRAF6 in PZ stromal cells enhanced the proliferation. We found that the Phosphorylation and Ubiquitination of Akt as well as the Phosphorylation of mTOR, P70S6K were decreased when TRAF6 was downregulated in primary cultured TZ stromal cells of BPH. CONCLUSIONS: TRAF6 can promote the proliferation of stromal cells of BPH via Akt/mTOR signaling. Our results may make stromal TRAF6 responsible for zonal characteristic of BPH and as a promising therapeutic strategy for BPH treatment.

Bcl2L12 mediates effects of protease-activated receptor-2 on the pathogenesis of Th2-dominated responses of patients with ulcerative colitis.

The immune dysregulation plays an important role in the pathogenesis of ulcerative colitis (UC). Bcl2 like protein-12 (Bcl2L12) and mast cells are involved in immune dysregulation of UC. This study aims to elucidate the role of Bcl2L12 in the contribution to the pathogenesis of T helper (Th)2-biased inflammation in UC patients. The results showed that Bcl2L12 was expressed by peripheral CD4+ T cells that was associated with Th2 polarization in UC patients. Bcl2L12 mediated the protease-activated receptor-2 (PAR2)-induced IL-4 expression in CD4+ cells. Activation of PAR2 increased expression of Bcl2L12 in CD4+ T cells. Bcl2L12 mRNA decayed spontaneously in CD4+ T cells after separated from UC patients which was prevented by activating PAR2. Bcl2L12 mediated the binding between GATA3 and the Il4 promoter in CD4+ T cells. Mice with Bcl2L12 deficiency failed to induce Th2-biased inflammation in the colon mucosa. We conclude that CD4+ T cells from UC patients expressed high levels of Bcl2L12; the latter plays an important role in the development of Th2-biased inflammation in the intestine. Bcl2L12 may be a novel therapeutic target in the treatment of Th2-biased inflammation.

Field emission properties of SiO2-wrapped CNT field emitter.

Carbon nanotubes (CNTs) exhibit unstable field emission (FE) behavior with low reliability due to uneven heights of as-grown CNTs. It has been reported that a mechanically polished SiO2-wrapped CNT field emitter gives consistent FE performance due to its uniform CNT heights. However, there are still a lack of studies on the comparison between the FE properties of freestanding and SiO2-wrapped CNTs. In this study, we have performed a comparative study on the FE properties of freestanding and SiO2-wrapped CNT field emitters. From the FE measurements, freestanding CNT field emitter requires lower applied voltage of 5.5 V µm-1 to achieve FE current density of 22 mA cm-2; whereas SiO2-wrapped field emitter requires 8.5 V µm-1 to achieve the same current density. This can be attributed to the lower CNT tip electric field of CNTs embedded in SiO2, as obtained from the electric field simulation. Nevertheless, SiO2-wrapped CNTs show higher consistency in FE current than freestanding CNTs. Under repeated FE measurement, SiO2-wrapped CNT field emitter achieves consistent FE behavior from the 1st voltage sweep, whereas freestanding field emitter only achieved consistent FE performance after 3rd voltage sweep. At the same time, SiO2-wrapped CNTs exhibit better emission stability than freestanding CNTs over 4000 s continuous emission.

Enhanced field emission properties of carbon nanotube bundles confined in SiO2 pits.

It has been widely reported that carbon nanotubes (CNTs) exhibit superior field emission (FE) properties due to their high aspect ratios and unique structural properties. Among the various types of CNTs, random growth CNTs exhibit promising FE properties due to their reduced inter-tube screening effect. However, growing random growth CNTs on individual catalyst islands often results in spread out CNT bundles, which reduces overall field enhancement. In this study, significant improvement in FE properties in CNT bundles is demonstrated by confining them in microfabricated SiO2 pits. Growing CNT bundles in narrow (0.5 µm diameter and 2 µm height) SiO2 pits achieves FE current density of 1-1.4 A cm-2, which is much higher than for freestanding CNT bundles (76.9 mA cm-2). From the Fowler Nordheim plots, confined CNT bundles show a higher field enhancement factor. This improvement can be attributed to the reduced bundle diameter by SiO2 pit confinement, which yields bundles with higher aspect ratios. Combining the obtained outcomes, it can be conclusively summarized that confining CNTs in SiO2 pits yields higher FE current density due to the higher field enhancement of confined CNTs.