DataSheet_1_Targeting TBK1 Attenuates LPS-Induced NLRP3 Inflammasome Activation by Regulating of mTORC1 Pathways in Trophoblasts.docx

Pathological maternal inflammation and abnormal placentation contribute to several pregnancy-related disorders, including preterm birth, intrauterine growth restriction, and preeclampsia. TANK-binding kinase 1 (TBK1), a serine/threonine kinase, has been implicated in the regulation of various physiological processes, including innate immune response, autophagy, and cell growth. However, the relevance of TBK1 in the placental pro-inflammatory environment has not been investigated. In this study, we assessed the effect of TBK1 inhibition on lipopolysaccharide (LPS)-induced NLRP3 inflammasome activation and its underlying mechanisms in human trophoblast cell lines and mouse placenta. TBK1 phosphorylation was upregulated in the trophoblasts and placenta in response to LPS. Pharmacological and genetic inhibition of TBK1 in trophoblasts ameliorated LPS-induced NLRP3 inflammasome activation, placental inflammation, and subsequent interleukin (IL)-1 production. Moreover, maternal administration of amlexanox, a TBK1 inhibitor, reversed LPS-induced adverse pregnancy outcomes. Notably, TBK1 inhibition prevented LPS-induced NLRP3 inflammasome activation by targeting the mammalian target of rapamycin complex 1 (mTORC1). Thus, this study provides evidence for the biological significance of TBK1 in placental inflammation, suggesting that amlexanox may be a potential therapeutic candidate for treating inflammation-associated pregnancy-related complications.</p

Effect of the Photoinitiator Concentration on the Electro-optical Properties of Thiol–Acrylate-Based PDLC Smart Windows

Polymer-dispersed liquid crystals (PDLCs), an indispensable class of electrically switchable materials, where nano- or microsized liquid crystal (LC) droplets are phase-separated from the polymer matrix, have been widely used in the fabrication of highly efficient and systematic smart windows. In this paper, we explored the effect of the photoinitiator concentration on the morphology and electro-optical properties of PDLC films based on thiol and acrylates. We prepared PDLC films using various concentrations of the photoinitiator, while keeping the concentrations of LC and monomers constant. We observed that the concentration of the photoinitiator directly influences the phase separation process, which in turn determines the morphology and electro-optical characteristics of the PDLC film. Thus, an optimized amount of the photoinitiator is required to prepare PDLC films with high transmittance and low switching time, haze, and power consumption. The optimized photoinitiator concentration can have a transmittance ΔT (difference between on- and off-state transmittances) of >85% at a low driving voltage

A 46-year-old male underwent total thyroidectomy due to thyroid cancer.

<p>A specimen radiograph (a) showed a mass with calcifications in the upper and mid pole of the right thyroid gland and punctate microcalcifications in the lower pole of the right thyroid gland which were not seen on US. There were no discernible calcifications in the left thyroid gland. To verify calcifications on PAI, two thyroid tissues from different lobes were obtained from thyroid specimens, with tissue from the right lobe containing compact punctate calcifications and tissue from the left lobe not containing any calcifications (two square boxes). The tissues were retrieved from the thyroid specimen without disturbing pathologic diagnosis. A specimen radiograph (b) showed punctate microcalcifications (arrows) acquired from the right thyroid gland and no calcifications acquired from the left thyroid gland. The texture analysis was conducted for the selected region-of-interests (ROIs) indicated by the white boxes in PA images (c) at 700-nm lasing wavelength. Note that the clustered hyperreactive PA signals suspected from the blood coagulations (white arrows) were excluded in the texture analysis, which can also be found on the corresponding photographs (d). In visual assessment, the ROI of the right resected tissue with microcalcifications contains more PA signals than that of the left resected tissue without microcalcifications. Correspondingly, the mean values of both US and PA images calculated from the right thyroid gland were higher than that from the left thyroid gland. There were psammoma bodies from a right resected tissue and no psammoma bodies (arrows) (H&E; X100) from a left resected tissue on pathology (e).</p

System configuration for the <i>ex vivo</i> experiments with a 1-dimensional photoacoustic/ultrasound combined probe.

<p>Note that the FB stands for the optical fiber bundle which delivers the laser energy to the thyroid specimen and the <i>x</i>, <i>y</i>, and <i>z</i> direction indicate the elevation, lateral, and axial direction from the PA/US combined probe, respectively.</p

Comparison of textural parameters obtained from specimen photoacoustic images between tissues with punctate microcalcifications on specimen radiology and those without when applying the mean value of the three slices of thyroid specimens.

<p>*Std, standard deviation.</p>†<p>Level, number of level.</p>‡<p>Distance, co-occurrence distance (pixel).</p>§<p>Orthogonal and diagonal, co-occurrence direction with ± (1,0) and ± (1,1), respectively.</p><p>Comparison of textural parameters obtained from specimen photoacoustic images between tissues with punctate microcalcifications on specimen radiology and those without when applying the mean value of the three slices of thyroid specimens.</p

Intracellularly Activatable Nanovasodilators To Enhance Passive Cancer Targeting Regime

Conventional cancer targeting with nanoparticles has been based on the assumed enhanced permeability and retention (EPR) effect. The data obtained in clinical trials to date, however, have rarely supported the presence of such an effect. To address this challenge, we formulated intracellular nitric oxide-generating nanoparticles (NO-NPs) for the tumor site-specific delivery of NO, a well-known vasodilator, with the intention of boosting EPR. These nanoparticles are self-assembled under aqueous conditions from amphiphilic copolymers of poly­(ethylene glycol) and nitrated dextran, which possesses inherent NO release properties in the reductive environment of cancer cells. After systemic administration of the NO-NPs, we quantitatively assessed and visualized increased tumor blood flow as well as enhanced vascular permeability than could be achieved without NO. Additionally, we prepared doxorubicin (DOX)-encapsulated NO-NPs and demonstrated consequential improvement in therapeutic efficacy over the control groups with considerably improved DOX intratumoral accumulation. Overall, this proof of concept study implies a high potency of the NO-NPs as an EPR enhancer to achieve better clinical outcomes

A 43-year-old male underwent total thyroidectomy due to thyroid cancer.

<p>A specimen radiograph (a) showed a mass with diffuse punctate calcifications in the left thyroid gland and no discernable calcifications in the right thyroid gland. To verify calcifications on photoacoustic imaging, two thyroid tissues from different lobes were obtained from thyroid specimens, with tissue from the left lobe containing compact punctate calcifications and tissue from the right lobe not containing any calcifications (two square boxes). The tissues were retrieved from the specimen without disturbing pathologic diagnosis. A specimen radiograph (b) showed punctate microcalcifications (arrows) acquired from the left thyroid gland and no calcifications acquired from the right thyroid gland. The texture analysis was conducted for the selected region-of-interests (ROIs) indicated by the white boxes in PA images (c) at 700-nm lasing wavelength. Note that the clustered hyperreactive PA signals suspected from the blood coagulations (white arrows) were excluded in the texture analysis, which can also be found on the corresponding photographs (d). In visual assessment of PA image, the ROI of the right resected tissue with microcalcifications contains more PA signals than that of the left resected tissue without microcalcifications. Although the mean value of samples from the left thyroid gland was higher than that of those from the right thyroid gland on specimen US, the mean value of samples from the right thyroid gland was higher than that of the left thyroid gland on both photoacoustic images. There were psammoma bodies from a left resected tissue and no psammoma bodies (arrows) (H&E; X100) from a right resected tissue on pathology (e).</p

Comparison of textural parameters obtained from specimen photoacoustic images between tissues with punctate microcalcifications on specimen radiology and those without when applying the value of a thyroid specimen slice which has the highest value of the mean values in the specimen ultrasound.

<p>*Std, standard deviation.</p>†<p>Level, number of level.</p>‡<p>Distance, co-occurrence distance (pixel).</p>§<p>Orthogonal and diagonal, co-occurrence direction with ± (1,0) and ± (1,1), respectively.</p><p>Comparison of textural parameters obtained from specimen photoacoustic images between tissues with punctate microcalcifications on specimen radiology and those without when applying the value of a thyroid specimen slice which has the highest value of the mean values in the specimen ultrasound.</p

Comparison of textural parameters obtained from specimen photoacoustic images between tissues with psammoma bodies on pathology and those without when applying the mean value of the three slices of thyroid specimens.

<p>*Std, standard deviation.</p>†<p>Level, number of level.</p>‡<p>Distance, co-occurrence distance (pixel).</p>§<p>Orthogonal and diagonal, co-occurrence direction with ± (1,0) and ± (1,1), respectively.</p><p>Comparison of textural parameters obtained from specimen photoacoustic images between tissues with psammoma bodies on pathology and those without when applying the mean value of the three slices of thyroid specimens.</p