Plasma microRNA-16-5p, -17-5p and -20a-5p are potential diagnostic biomarkers in GDM.

Astrocytes are critical for ischemic stroke, and understanding their role in mesenchymal stem cell (MSC)-mediated protection against ischemic injury is important. The paracrine capacity of MSCs has been proposed as the principal mechanism contributing to the protection and repair of brain tissue. In the present study, an in vitro oxygen-glucose deprivation (OGD) model was used to mimic ischemic injury. OGD-induced astrocytes were reperfused with MSC-conditioned medium (MSC-CM) or co-cultured with MSCs for 24 h to create an environment abundant in paracrine factors. The results indicated that both situations could protect astrocytes from apoptosis, increase cell metabolic activity, and reduce glial fibrillary acidic protein (GFAP) overexpression; however, the effects of co-culturing with MSCs were more positive. Paracrine factors suppressed the activation of p38 MAPK, JNK, and their downstream targets p53 and STAT1. Inhibition of p38 MAPK, JNK, p53, and STAT1 attenuated astrocyte injury and/or GFAP upregulation. Activation of p38 MAPK and JNK suppressed the beneficial effects of paracrine factors, resulting in decreased survival and GFAP overexpression. These results suggest that paracrine factors inhibit p38 MAPK and JNK, and most likely by regulating their downstream targets, p53 and STAT1, to promote astrocyte survival associated with GFAP downregulation after ischemic stroke in vitro.

Ultrasound-targeted delivery of nanobubbles (NBs) has become a promising strategy for noninvasive drug delivery. The biosafety and drug-transporting ability of NBs have been a research hotspot, especially regarding chitosan NBs due to their biocompatibility and high biosafety. Since the drug-carrying capacity of chitosan NBs and the performance of ultrasound-assisted drug delivery remain unclear, the aim of this study was to synthesize doxorubicin hydrochloride (DOX)-loaded biocompatible chitosan NBs and assess their drug delivery capacity. In this study, the size distribution of chitosan NBs was measured by dynamic light scattering, while their drug-loading capacity and ultrasound-mediated DOX release were determined by a UV spectrophotometer. In addition, a clinical ultrasound imaging system was used to evaluate the ability of chitosan NBs to achieve imaging enhancement, while the biosafety profile of free chitosan NBs was evaluated by a cytotoxicity assay in MCF-7 cells. Furthermore, NB-mediated DOX uptake and the apoptosis of Michigan Cancer Foundation-7 (MCF-7) cells were measured by flow cytometry. The results showed that the DOX-loaded NBs (DOX-NBs) exhibited excellent drug-loading ability as well as the ability to achieve ultrasound enhancement. Ultrasound (US) irradiation promoted the release of DOX from DOX-NBs in vitro. Furthermore, DOX-NBs effectively delivered DOX into mammalian cancer cells. In conclusion, biocompatible chitosan NBs are suitable for ultrasound-targeted DOX delivery and are thus a promising strategy for noninvasive and targeted drug delivery worthy of further investigation.

The past decades have witnessed the rapid development of organic and polymeric semiconductors with high charge mobilities, [1][2][3][4] thanks to the design and synthesis of various conjugated molecules and macromolecules along with the manipulation of self-assembly and interfacial structures. Performances for both p-channel and n-channel field-effect transistors (FETs) are now comparable to and even higher than those of traditional amorphous silicon FETs. Moreover, the promising applications of organic and polymeric semiconductors in low-cost logic circuits (e.g., radio frequency identification tags) and flexible electronics have been successfully demonstrated. [5] New conjugated molecules and macromolecules are being continuously explored for boosting the performances of FETs. Meanwhile, stimuli-responsive organic semiconducting materials, for which the semiconducting properties can be tuned by external stimuli other than electrical fields such as light irradiation and heating, have received increasing attentions in recent years. [6][7][8][9][10][11] This is because multifunctional devices can be constructed with such stimuli-responsive organic semiconducting materials. For instances, Samori and co-workers reported the reversible modulation of device currents for FETs with photoresponsive semiconducting layers by blending of photochromic diarylethenes with organic semiconductors. [8a-c] Photochromic molecules were also inserted into the dielectric layer and the electrode-semiconductor interface to fabricate FETs with photoregulation functions. [10] We have just devised a new approach to photoresponsive polymeric semiconductor by incorporating azobenzene units into the side chains. [11a] Furthermore, these photoresponsive FETs were successfully utilized to fabricate memory devices for which the programming, reading and erasing signals are different without mutual interferences. [10b] It is noted that FETs with organic and polymeric semiconductors have also been investigated for nonvolatile memory It is shown that the semiconducting performance of field-effect transistors (FETs) with PDPP4T (poly(diketopyrrolopyrrolequaterthiophene)) can be reversibly tuned by UV light irradiation and thermal heating after blending with the photochromic hexaarylbiimidazole compound (p-NO 2 -HABI). A photo-/thermal-responsive FET with a blend thin film of PDPP4T and p-NO2 -HABI is successfully fabricated. The transfer characteristics are altered significantly with current enhanced up to 10 6 -fold at V G = 0 V after UV light irradiation. However, further heating results in the recovery of the transfer curve. This approach can be extended to other semiconducting polymers such as P3HT (poly(3-hexyl thiophene)), PBTTT (poly(2,5-bis(3-tetradecylthiophen-2-yl)thieno[3,2-b] thiophene)) and PDPPDTT (poly(diketopyrrolopyrrole-dithienothiophene)). It is hypothesized that TPIRs (2,4,5-triphenylimidazolyl radicals) formed from p-NO 2 -HABI after UV light irradiation can interact with charge defects at the gate dielectric-semiconducto...

Muscle cells could serve as antigen-presenting cells, and participate in the activation of immune response. Immunological characteristics of muscle cells, and their capacities to equip themselves with immunorelevant molecules, remain to be elucidated. In this study, we investigated the immunological properties of myoblasts and differentiated myotubes in vitro and in vivo, under the IFN-γ induced inflammatory condition. We found that the fused C C myotubes are more sensitive to inflammatory stimulation, and significantly upregulated the expression levels of MHC-I/II and TLR3/7 molecules, than that of proliferated myoblasts. As well, some co-stimulatory/-inhibitory molecules, including CD40, CD86, ICAM-I, ICOS-L, and PD-L1, were prominently upregulated in IFN-γ induced myotubes. Notably, we detected the protein levels of ASC, NLRP3, and Caspase-1 increased in stimulated myotubes, and IL-1β in cell culture supernatant, implying the activation of NLRP3 inflammasomes in IFN-γ treated myotubes. The pro-inflammatory cytokines and chemokines mRNA levels in IFN-γ induced C C myotubes and myoblasts, involving IL-1, IL-6, and MCP-1, increased markedly. T cell activation test further verified IFN-γ induced C C myotubes prompt to the proliferation of the splenic CD4 and CD8 T cells. In Cardiotoxin-damaged tibialis anterior (TA) muscle, some regenerated myofibers expressed both MHC class I and class II molecules under IFN-γ enhanced inflammatory condition. Thus, our work demonstrates that muscle cells are active participants of local immune reactions. Anat Rec, 301:1551-1563, 2018. © 2018 Wiley Periodicals, Inc.

IntroductionConjugated donor-acceptor (D-A) polymers have attracted increasing attention due to their easily modified structures, good solution rheology, semiconducting properties, and A novel building block, denoted as half-fused diketopyrrolopyrrole (DPP) (9-(3-octadecylhenicosyl)-8-(thiophen-2-yl)-7H-pyrrolo[3,4-a]thieno[3,2-g] indolizine-7,10(9H)-dione), in which one of the flanking thiophene units is fused to one of the DPP rings via a carbon-carbon double bond at the N-position is reported. The half-fused DPP is successfully utilized as an electron acceptor to prepare the conjugated donor-acceptor polymer PTFDFT, which exhibits ambipolar semiconducting behavior in ambient air. Theoretical calculations and absorption spectral studies show that the backbone of PTFDFT is more planar compared to the reference polymer with conventional DPP units. As a result, PTFDFT shows a narrow bandgap and low lowest unoccupied molecular orbital level. The more planar backbone with fewer side chains favors the dense packing of the polymer chains of PTFDFT with a short π-π stacking distance (3.49 Å). Grazing-incidence wide-angle X-ray scattering data further confirm the predominant edge-on packing mode of the PTFDFT polymer chains on the substrate. As expected, the PTFDFT thin film shows excellent ambipolar semiconducting properties under ambient conditions, reaching 2.23 and 1.08 cm 2 V −1 s −1 for the n-and p-channels, respectively. In addition, complementary-like inverter with gain value as high as 141 is successfully constructed using the PTFDFT thin film. mechanical properties. [1][2][3] Accordingly, they show promising applications in largearea, lightweight, and flexible electronic devices. [4,5] Among them, ambipolar conjugated D-A polymers, which are capable of transporting both electron and hole carriers, have drawn interest due to the fact that they facilitate the fabrication of complementary-like logic circuits using singlecomponent solution processing instead of selective deposition of p-and n-channel materials, which demand advanced patterning techniques. [6] In the pursuit of high ambipolar performance polymeric field-effect transistors (FETs), various conjugated D-A polymers have been developed and investigated. Different electron acceptors, including diketopyrrolopyrrole (DPP), [2e,7,8] isoindigo, [9] and naphthalene diimide, [10] have been introduced into conjugated D-A polymers to obtain ambipolar semiconductors. [2e,6-11] Among them, DPP-based polymers have been intensively investigated as semiconducting materials for FETs. [2e,6b,7,8,12,13] However, a large number of DPP-based polymers mainly show hole mobilities. This is because of the hindrance of electron injection due to the large gaps between lowest unoccupied molecular orbitals (LUMOs) (−3.2 to −3.6 eV) of DPP-based polymers and the electrode (normally gold) W F (work function ≈ 5.1 eV), while their highest occupied molecular orbitals (HOMOs) (−5.0 to −5.5 eV) were close to the W F of gold. [12] Therefore, lowering the LUMOs of DPP-based conjuga...

Excessive inflammatory response may delay the regeneration and damage the normal muscle fibers upon myoinjury. It would be important to be able to attenuate the inflammatory response and decrease inflammatory cells infiltration in order to improve muscle regeneration formation, resulting in better muscle functional recovery after myoinjury. This study was undertaken to explore the role of Nitric oxide (NO) during skeletal muscle inflammatory process, using a mouse model of Notexin induced myoinjury. Intramuscular injection (tibialis anterior, TA) of Notexin was performed for preparing mice myoinjury. NO synthase inhibitor (L-NAME) or NO donor (SNP) was intraperitoneally injected into model mice. On day 4 and 7 post-injury, expression of muscle-autoantigens and toll-like receptors (TLRs) was evaluated from muscle tissue by qRT-PCR and Western Blot; the intramuscular infiltration of monocytes/macrophage (CD11b+ or F4/80+ cells), CD8+ T cell (CD3ε+CD8α+), apoptotic cell (CD11b+caspase3+), and MHC-I molecule H-2Kb-expressing myofibers in damaged muscle were assessed by imunoflourecence analysis; the mRNAs expression of cytokines and chemokines associated with the preferential biological role during the muscle damage-induced inflammation response, were assessed by qRT-PCR. We detected the reduced monocytes/macrophages infiltration, and increased apoptotic cells in the damaged muscle treated with SNP comparing to untreatment. As well, SNP treatment down-regulated mRNA and protein levels of muscle autoantigens, TLR3, and mRNA levels of TNF-α, IL-6, MCP-1, MCP-3, and MIP-1α in damaged muscle. On the contrary, L-NAME induced more severe intramuscular infiltration of inflammatory cells, and mRNA level elevation of the above inflammatory mediators. Notably, we observed an increased number of MHC-I (H2-Kb) positive new myofibers, and of the infiltrated CD8+ T cells in damaged muscle at the day 7 after L-NAME treatment. The result herein shows that, NO can act as an endogenous anti-inflammatory molecule during the ongoing muscle inflammation. Our finding may provide new insight to optimize NO-based therapies for improving muscle regeneration after myoinjury.

he twinkling artifact was first described by Rahmouni et al 1 as a rapidly changing mixture of red and blue behind a strongly reflective structure. It has been extensively studied, and its methodological aspects and concrete applications continue to be investigated. Acoustic shadowing as the main principle for diagnosing renal stones has been well known for many years; however, some recent studies reported sensitivity for stone detection as low as 24%. 2 Since the twinkling artifact has been adopted as an additional sonographic feature of urinary stones, the sensitivity of sonography has improved substantially, and use of the twinkling artifact in the diagnosis of renal and ureter stones has been proven in many studies. [3][4][5][6] Lee et al 7 suggested that more than 80% of urinary stones had the twinkling artifact, and no false-positive findings were observed during the scanning of 36 stones in their study. An Optimized InvestigationMeng Wang, MD, Jie Li, MD, Jing Xiao, MD, Dandan Shi, MD, Kaining Zhang, MD Received March 28, 2011, from Methods-An in vitro phantom made of sandpaper was designed to mimic rough physiologic surfaces prone to generating the twinkling artifact. Sandpaper strips embedded in a plastic box were scanned through a water path under different machine settings with only 1 parameter varied each time. After choosing the best settings for displaying the twinkling artifact, 4 types of sandpaper with different roughness were scanned. The resulting images were recorded at random, and the number of color pixels in the color box of each image was calculated by a custom-designed program developed using commercially available software. All data were then evaluated by regression analysis, a paired 2-tailed Student t test, and single-factor analysis of variance.Results-The highest color write priority and color gain, which were just below the threshold for color noise, a focus depth setting below the sandpaper, a maximum wall filter under a higher pulse repetition frequency, and a color box adjusted properly in the fundamental imaging mode (P < .001) were found to most readily improve the twinkling artifact intensity. The roughness of the sandpaper was shown to be highly correlated with the twinkling artifact intensity (R 2 = 0.832; P < .001).Conclusions-The twinkling artifact was influenced by some machine parameters and the roughness of the sandpaper. By adjusting some ultrasound machine parameters, a better image reflecting the twinkling artifact can be shown in clinical practice and research.