Search

Enhancement of malignant cell immunogenicity to relieve immunosuppression of lung cancer microenvironment is essential in lung cancer treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind of phytopharmaceutical, is effective in inhibiting lung cancer cells and boosting their immunogenicity, while the initial target of DHA's intracellular action is poorly understood. The present in‐depth analysis aims to reveal the influence of DHA on the highly expressed TOM70 in the mitochondrial membrane of lung cancer. The affinity of DHA and TOM70 was analyzed by microscale thermophoresis (MST), pronase stability, and thermal stability. The functions and underlying mechanism were investigated using western blots, qRT‐PCR, flow cytometry, and rescue experiments. TOM70 inhibition resulted in mtDNA damage and translocation to the cytoplasm from mitochondria due to the disruption of mitochondrial homeostasis. Further ex and in vivo findings also showed that the cGAS/STING/NLRP3 signaling pathway was activated by mtDNA and thereby malignant cells underwent pyroptosis, leading to enhanced immunogenicity of lung cancer cells in the presence of DHA. Nevertheless, DHA‐induced mtDNA translocation and cGAS/STING/NLRP3 mobilization were synchronously attenuated when TOM70 was replenished. Finally, DHA was demonstrated to possess potent anti‐lung cancer efficacy in vitro and in vivo. Taken together, these data confirm that TOM70 is an important target for DHA to disturb mitochondria homeostasis, which further activates STING and arouses pyroptosis to strengthen immunogenicity against lung cancer thereupon. The present study provides vital clues for phytomedicine‐mediated anti‐tumor therapy. [ABSTRACT FROM AUTHOR]

Palatal expansion has been widely used for the treatment of transverse discrepancy or maxillae hypoplasia, but the biological mechanism of bone formation during this procedure is largely unknown. Osteoclasts, which could be regulated by T cells and other components of the immune system, play a crucial role in force‐induced bone remodeling. However, whether T cells participate in the palatal expansion process remains to be determined. In this study, we conducted the tooth borne rapid palatal expansion model on the mouse, and detect whether the helper T cells (Th) and regulatory T cells (Treg) could affect osteoclasts and further bone formation. After bonding open spring palatal expanders for 3‐day, 5‐day, 7‐day, and retention for 28‐day, micro‐computed tomography scanning, histologic, and immunofluorescence staining were conducted to evaluate how osteoclasts were regulated by T cells during the bone remodeling process. We revealed that the increased osteoclast number was downregulated at the end of the early stage of rapid palatal expansion. Type 1 helper T (Th1) cells and Type 17 helper T (Th17) cells increased initially and promoted osteoclastogenesis. Thereafter, the regulatory T (Treg) cells emerged and maintained a relatively high level at the late stage of the experiment to downregulate the osteoclast number by inhibiting Th1 and Th17 cells, which governed the new bone formation. In conclusion, orchestrated T cells are able to regulate osteoclasts at the early stage of rapid palatal expansion and further facilitate bone formation during retention. This study identifies that T cells participate in the palatal expansion procedure by regulating osteoclasts and implies the potential possibility for clinically modulating T cells to improve the palatal expansion efficacy. [ABSTRACT FROM AUTHOR]

Skull optical clearing window permits us to perform in vivo cortical imaging without craniotomy, but mainly limits to visible (vis)‐near infrared (NIR)‐I light imaging. If the skull optical clearing window is available for NIR‐II, the imaging depth will be further enhanced. Herein, we developed a vis‐NIR‐II skull optical clearing agents with deuterium oxide instead of water, which could make the skull transparent in the range of visible to NIR‐II. Using a NIR‐II excited third harmonic generation microscope, the cortical vasculature of mice could be clearly distinguished even at the depth of 650 μm through the vis‐NIR‐II skull clearing window. The imaging depth after clearing is close to that without skull, and increases by three times through turbid skull. Furthermore, the new skull optical clearing window promises to realize NIR‐II laser‐induced targeted injury of cortical single vessel. This work enhances the ability of NIR‐II excited nonlinear imaging techniques for accessing to cortical neurovasculature in deep tissue. [ABSTRACT FROM AUTHOR]

Aims This study was to investigate whether cell proliferation and adult neurogenesis are affected at early neurodegenerative stage when neuron loss has not begun to display. Methods and Results Forebrain-specific nicastrin ( NCT) conditional knockout ( cKO) mice were generated by crossing NCT f/f with Ca MKIIα -Cre Tg mice. BrdU was used as a lineage tracer to label proliferating neural progenitor cells ( NPCs). Immunohistochemistry ( IHC) on BrdU indicated that the total number of BrdU positive (+) cells was increased in NCT cKO mice. IHC on doublecortin ( DCX) showed that the total number of DCX+ cells was also increased in NCT cKO mice. NCT cKO mice displayed significant astrogliosis as well. However, NCT cKO mice at 3 months did not show significant neuronal death or synaptic loss. Conclusions NCT-dependent γ-secretase activity plays an important role in cell proliferation and immature neuron generation. Enhanced neurogenesis and astrogliosis may be early cellular events prior to the occurrence of neuronal death in neurodegenerative disease. [ABSTRACT FROM AUTHOR]

BACKGROUND A good knowledge in wetting behavior of pesticide spray liquid on plant surface is crucial to spray applications. Difference in leaf surface wettability would result in obvious changes in spray wetting behavior. The aim of this paper is to obtain the changes of wettability during different growth periods. RESULTS The contact angle ( CA) of rice leaf for each liquid increased with rice growth. No significant difference was found between cultivars. The CA was found to be correlated with the polar component of liquid surface tension. The square of the polar component was also found to be highly significant indicating that the relationship between these two properties was not a simple linear one. The surface energy of each plant surface decreased as the plants aged. This was also true of each part of the surface energy. However, no obvious difference on the proportion of the components was found among different cultivars and stages. CONCLUSIONS The changes in value of CA and surface free energy ( SFE) both reflect the changes of the leaf surface wettability, while the SFE value shows better in wettability characterizing. Obvious rice leaf wettability changes were found on different development stages, which may be beneficial for researches in agrochemical sprays wetting and spreading behavior. Factors influencing these alterations were discussed. © 2013 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Highlights: [•] We identified 18 differentially expressed miRNAs in ESCC compared with normal esophageal tissues. [•] miR-195 was downregulated in ESCC. [•] Loss of miR-195 expression contributed to ESCC progression through cell cycle arrest and inhibition of Cdc42 expression. [ABSTRACT FROM AUTHOR]

Growing experimental and clinical data highlights the important roles of increased reactive oxygen species production in cardiovascular remodeling (CR). Oligomeric grape seed proanthocyanidins (GSPs) have been shown to be potent antioxidants and free radical scavengers. Mice were treated with DOCA-salt to induce CR and were given distilled water or oligomeric GSPs for 4 weeks. The heart weight (HW) index and kidney weight (KW) index were expressed as heart weight/body weight (HW/BW) and kidney weight/body weight (KW/BW); the histological changes were investigated by hematoxylin and eosin and Van Gieson staining.The endothelial-dependent vasodilation function induced by acetylcholine was investigated in isolated thoracic aorta ring. Colorimetric analysis was used to assay superoxide dismutase (SOD) activity, malondialdehyde (MDA) content and nitric oxide (NO) content in serum and hydroxyproline content in cardiac tissue. Administration of GSPs markedly alleviated the elevation of HW/BW ratio, KW/BW ratio and cross-sectional area of cardiomyocytes, decreased collagen deposition in heart and attenuated histopathology injury, and improves endothelial-dependent aorta ring relaxation in vitro accompany by increasing of NO content in serum. Meanwhile, treatment with GSPs significantly ameliorated oxidative stress via increasing SOD activities and decreasing MDA formation. These findings suggest that administration of GSPs has the potential to attenuate DOCA-salt induced CR and KH and preserve NO activity and endothelial function, which mechanism may contribute to its antioxidant characteristic, at least in part. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Optical clearing skull window is a novel technique compared to the traditional surgery based cranial window, which could reduce the scattering of skull and make it transparent to visible light. Here, the NIR‐II optimized skull clearing window was established. In the application of NIR‐II excited THG microscopy, the imaging depth was more than 3 times as it without optical clearing, and close to it with the open‐skull window. In addition, the established skull optical clearing window promises to realize NIR‐II laser induced targeted injury of cortical singlevessel. Further details can be found in the article by Dong‐Yu Li, Zheng Zheng, Ting‐Ting Yu, Ben‐Zhong Tang, Peng Fei, Jun Qian, Dan Zhu (e202000142). [ABSTRACT FROM AUTHOR]

N-Sulfonylpyrrolidines (III) and (Va,b), piperidine derivative (Vc), and N-alkyl sulfonamides (VII) are synthesized under mild conditions in good yields using a new general and practical one-step protocol. [ABSTRACT FROM AUTHOR]