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The purpose of this study is to develop MRI methods to measure the solid fraction in granular flows quantitatively. It is increasingly recognised that solid fraction plays a key role in granular rheology, but experimental characterisation of it during flow is challenging. Here centric sectoral-SPRITE imaging is applied to image mustard seeds discharging from a 3D-printed hopper. Quantitative images are obtained after considering and correcting artefacts that may arise from flow and relaxation. The image intensity is then further corrected for spatial variations in the B1 field. Various maps of nominally homogeneous samples were tested to correct for variations in the B1 field. The B1 field was found to be sensitive to the geometry of the sample and the material in the sample. Hence, here static images of the seeds in the hopper were used to correct for B1 field variations. Moreover, small signal variations were observed from measurements performed on different days owing to subtle differences in the spectrometer operation. Here an internal standard was used to scale the signal intensity and correct for these variations. Following these corrections, a linear correlation (R2 = 0.999) was observed between the scaled image intensities and the known solid fractions of packed samples with solid fractions between 0.55 and 0.64. This correlation was used as a calibration of the 3D image of the hopper to extract quantitative time-averaged spatial maps of solid fraction during steady flow. The measurements were confirmed to be quantitative by also measuring the velocity of the particles. Together these measurements were used to calculate a mass flow rate in the hopper, which was consistent with the mass flow measured gravimetrically.Manganese(III) porphyrins (MnIIIPs) as MRI contrast agents (CAs) have drawn particular attention due to their high longitudinal relaxivity (r1) and unique biodistribution. In this work, two MnIIIP-based oligomers, MnPD and MnPT, were designed to further improve the relaxivity with ease of synthesis. The two compounds were fully characterized and their nuclear magnetic relaxation dispersion (NMRD) profiles were acquired with a fast field cycling NMR relaxometer. Both of the compounds exhibited extended high molar r1 at high fields, higher than that of Gd-DTPA, the first clinical gadolinium(III)-based MRI CA. The r1 value of per manganese atom increased with the increasing number of MnIIIP building blocks, suggesting rotational correlation time (τR) played dominant role in the r1 dispersion. The toxicity of the two MnIIIPs and the imaging effectiveness were estimated in vitro and in vivo. With good biocompatibility, significant contrast enhancement, and complete excretion in 24 h, MnPD and MnPT are both promising for high field clinical applications. The applied strategy also potentially provided a facile approach for creation of more MnIIIP oligomer as efficient T1 MRI CAs.

Emerging evidence indicates the important role of herbal medicine for neuroinflammation, which is closely associated with neurodegenerative diseases.

To clarify the characteristics and primary mechanisms of action of the traditional herbal medicine Daphne kiusiana var. atrocaulis (Rehd.) F. Maekawa in neuroinflammation by phytochemistry and bioassays using both in vitro and in vivo assays.

The chemical composition of D. kiusiana var. atrocaulis was clarified using multiple chromatography technologies and spectroscopic analysis. The anti-neuroinflammatory effects of the identified components were evaluated in LPS-induced BV-2 cells by monitoring the production of nitric oxide. C57BL/6 mice were used to construct a neuroinflammatory model by injecting LPS into the lateral ventricle of the brain. The most promising component was evaluated in vivo by measuring the number of Iba-1 cells and expression of inflammatory factors. Furthermore, the anti-neuroinflammatory mechanism involved in the activation of theand decreasing the mRNA expression of iNOs, TNF-α, IL-1β, and IL-6 in the cortex.

We found that D. kiusiana var. atrocaulis had an inhibitory activity on neuroinflammation. In addition, the main active component (-)-acutissimalignan B (13) showed anti-neuroinflammatory effects in both in vivo and in vitro assays. Its mechanism of action may be associated with the inhibition of the NF-κB signaling pathway. Our current findings provide new information on D. kiusiana var. atrocaulis in the treatment of neuroinflammation.

We found that D. kiusiana var. atrocaulis had an inhibitory activity on neuroinflammation. In addition, the main active component (-)-acutissimalignan B (13) showed anti-neuroinflammatory effects in both in vivo and in vitro assays. Its mechanism of action may be associated with the inhibition of the NF-κB signaling pathway. Our current findings provide new information on D. kiusiana var. atrocaulis in the treatment of neuroinflammation.

Oxidative stress and frequently unwanted alterations in mitochondrial structure and function are key aspects of the pathological cascade in transient focal cerebral ischemia. Chikusetsu saponin V (CHS V), a major component of saponins from Panax japonicas, can attenuate H

O

-induced oxidative stress in SH-SY5Y cells.

The aim of the present study was to investigate the neuroprotective effects and the possible underlying mechanism of CHS V on transient focal cerebral ischemia/reperfusion.

Mice with middle cerebral artery occlusion (MCAO) and cultured cortical neurons exposed to oxygen glucose deprivation (OGD) were used as in vivo and in vitro models of cerebral ischemia, respectively. The neurobehavioral scores, infarction volumes, H&E staining and some antioxidant levels in the brain were evaluated. The occurrence of neuronal death was estimated. Total and mitochondrial reactive oxygen species (ROS) levels, as well as mitochondrial potential were measured using flow cytometry analysis. Mitochondrial structure and respiratory activity were also examined. Protein levels were investigated by western blotting and immunohistochemistry.

CHS V effectively attenuated cerebral ischemia/reperfusion (CI/R) injury, including improving neurological deficits, shrinking infarct volume and reducing the number of apoptotic cells. Furthermore, CHS V treatment remarkably increased antioxidant levels and reduced ROS levels and mitochondrial damage by enhancing the expression and deacetylation of peroxisome proliferator-activated receptor γcoactivator-1α(PGC-1α) by activating AMPK and SIRT-1, respectively.

Our data demonstrated that CHS V prevented CI/R injury by suppressing oxidative stress and mitochondrial damage through the modulation of PGC-1αwith AMPK and SIRT-1.

Our data demonstrated that CHS V prevented CI/R injury by suppressing oxidative stress and mitochondrial damage through the modulation of PGC-1α with AMPK and SIRT-1.

Host-directed therapeutics for Mycobacterium tuberculosis (Mtb) offer potential strategies for combatting antibiotic resistance and for killing non-replicating bacilli. Phenylbutyrate, a partially selective histone-deacetylase (HDAC) inhibitor, was previously shown to control Mtb growth and alter macrophage inflammatory pathways at 2-4mM concentrations.

To identify a more potent and selective HDAC inhibitor that modulates macrophage responses to mycobacteria and has direct antibacterial effects against Mtb.

We used cellular approaches to characterize the role of pharmacologic inhibition of HDAC3 on Mtb growth and Mtb-induced peripheral and alveolar macrophage immune functions.

RGFP966, an HDAC3 inhibitor, controlled Mtb, BCG and M. avium growth directly in broth culture and in human peripheral blood monocyte-derived and alveolar macrophages with an MIC50 of approximately 5-10μM. In contrast, RGFP966 did not inhibit growth of several other intracellular and extracellular bacteria. We also found that RGFP966 modulated macrophage pro-inflammatory cytokine secretion in response to Mtb infection with decreased IL6 and TNF secretion.

We identified a potent and selective small molecule inhibitor of HDAC3 with direct antimicrobial activity against Mtb and modulation of macrophage signaling pathways.

We identified a potent and selective small molecule inhibitor of HDAC3 with direct antimicrobial activity against Mtb and modulation of macrophage signaling pathways.Glucosinolates, an important class of secondary metabolites in cruciferous vegetables, play a crucial role in protecting plants from stress-related damage. The mechanism of glucosinolate synthesis under short-term high temperature stress has not been sufficiently studied. In this work, we investigated the changes in transcription factors, synthetic genes, and related metabolites involved in glucosinolate synthesis by pakchoi seedlings under short-term high temperature stress (40 °C for 8 h). Short-term high temperature stress inhibited the primary sulfur assimilation and the contents of methionine, cysteine and glutathione. The contents of aliphatic and indolic glucosinolates were increased by short-term high temperature stress, whereas the content of 4-methoxy-glucobrassicin increased significantly. During the stress period, the transcript level of glucosinolate related MYB transcription factors had been basically significantly up-regulated, whereas the transcript level of aliphatic and indolic glucosinolate synthetic genes were predominantly up-regulated and down-regulated respectively. In the early recovery period, primary sulfur assimilation up-regulated rapidly, and decreased during the late recovery process. The glucosinolate content and synthesis gene expression act similar to the primary sulfur assimilation, a short up-regulated in early recovery, then all go down at 40 and 48 h after short-term high temperature treatment.ABA signaling plays a central role in regulating plants respond to drought. Although much progress has been made in understanding the functions of ABA signaling in drought response, very little information is available regarding woody plants. In this study, the components of ABA signaling pathway were identified in mulberry which has excellent adaptation to drought, including three PYLs, two PP2Cs, two SnRK2s, four ABFs, and an ABA responsive gene MaRD29B. The gene expression of ABA signaling components exhibited significant response to ABA and drought, and their roles in drought response were revealed using a transient transformation system in mulberry seedlings. We discovered the ABA signaling components, MaABI1/2 and MaSnRK2.1/2.4, could directly interact with G-protein γ subunits, MaGγ1 and MaGγ2, which indicated that G-protein γ subunits may mediate the signal crosstalk between G-proteins and ABA signaling. Transient activation assay in tobacco and RNAi silencing assay in mulberry further demonstrated that MaGγ1 and MaGγ2 regulated drought response by enhancing ABA signaling. This study expands the repertoire of ABA signaling controlling drought responses in plants and provides the direct evidence about the crosstalk between ABA signaling and G-proteins for the first time.

The human epidermal growth factor receptor (HER/ErbB) family-targeted therapies result in a significant improvement in cancer immunotherapy. Monoclonal antibodies (MAb) against HER2 demonstrated a survival benefit for patients; however, drug resistance unavoidably occurs due to the overexpression of HER3, which leads to treatment failure. Effective inhibition of HER3 besides HER2 is thought to be required to overcome resistance and enhance therapeutic efficacy.

The present study describes the production and characterization of a novel MAb, designated 1G5D2, which acts as a natural bispecific antibody targeting extracellular domains (ECD) of both HER2 and HER3.

In this study, 1G5D2 was produced by hybridoma technology against HER3-ECD, and its structural and functional characteristics were studied by various methodologies, including enzyme linked-immunosorbent assays, flow cytometry, immunoblotting, cell signaling, and cell proliferation assays.

1G5D2 specifically binds to both HER2 (subdomain III + IV) and HER3 (subdomain I + II) expressed on tumor cells, and these receptors compete with each other for binding to this MAb.