bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-145 attenuates TNF-α-driven cartilage matrix degradation in osteoarthritis via direct suppression of MKK4
Authors: Hu Guoli , Zhao Xiaoying , Wang Chuandong , Geng Yiyun , Zhao Jingyu , Xu Jiajia , Zuo Bin , Zhao Chen , Wang Chenglong , Zhang Xiaoling 
Published: October 2017

AbstractCartilage dyshomeostasis contributes to osteoarthritis (OA) pathogenesis, and tumor necrosis factor (TNF)-α has critical role in this process by driving inflammatory cascades and cartilage degradation. However, the negative regulation of TNF-α-mediated signaling remains undefined. Here we demonstrate the crucial role of miR-145 in the modulation of TNF-α-mediated signaling and cartilage matrix degradation. MicroRNA (miRNA) expression profiles of TNF-α-stimulated chondrocytes showed that miR-145 expression was rapidly downregulated by TNF-α. Moreover, miR-145 was directly repressed by p65 and was negatively correlated with TNF-α secretion during OA progression. Further, we found that miR-145 directly targeted mitogen-activated protein kinase kinase 4 (MKK4) and broadly restrained the production of several TNF-α-triggered matrix-degrading enzymes (MMP-3, MMP-13, and Adamts-5). Mechanistic studies unveiled that miR-145 negatively regulated TNF-α-mediated JNK and p38 activation, as well as the nuclear accumulation of p-c-Jun and p-ATF2, by inhibiting MKK4 phosphorylation, eventually resulting in the alteration of catabolic genes transcription. Indeed, p-ATF2 interacted with the promoter of Mmp-13, whereas p-c-Jun bound to promoters of Mmp-3 and Adamts-5. MKK4 was significantly elevated in OA cartilage. Eliminating MKK4 by short hairpin RNA resulted in obviously decreased matrix-degrading enzymes production, JNK and p38 inactivation, and an inhibition of cartilage degradation. On the contrary, MKK4 overexpression enhanced TNF-α-mediated signaling activation and transcription of downstream catabolic genes, and consequently worsened cartilage degradation. Moreover, intra-articular (IA) injection of miR-145 agonist to rat with surgery-induced OA alleviated cartilage destruction. Altogether, we elucidate a novel regulatory mechanism underlying TNF-α-triggered cartilage degradation and demonstrate the potential utility of miR-145 and MKK4 as therapy targets for OA.
Guanylate-binding protein 2 regulates Drp1-mediated mitochondrial fission to suppress breast cancer cell invasion
Authors: Zhang Juan , Zhang Yu , Wu Wenshuang , Wang Fang , Liu Xinyu , Shui Guanghou , Nie Chunlai 
Published: October 2017

AbstractGuanylate-binding protein 2 (GBP2) is a member of the large GTPase superfamily that is strongly induced by interferon-γ (IFN-γ). Although the biochemical characteristics of GBP2 have been reported in detail, its biological function has not been thoroughly elucidated to date. To the best of our knowledge, this study presents the first demonstration that GBP2 inhibits mitochondrial fission and cell metastasis in breast cancer cells both in vitro and in vivo. Our previous work demonstrated that dynamin-related protein 1 (Drp1)-dependent mitochondrial fission has a key role in breast cancer cell invasion. In this study, we demonstrate that GBP2 binds directly to Drp1. Elimination of Drp1 by shRNA or Mdivi-1 (a Drp1-specific inhibitor) suppressed GBP2’s regulatory function. Furthermore, GBP2 blocks Drp1 translocation from the cytosol to mitochondria, thereby attenuating Drp1-dependent mitochondrial fission and breast cancer cell invasion. In summary, our data provide new insights into the function and molecular mechanisms underlying GBP2’s regulation of breast cancer cell invasion.
C-X-C motif chemokine ligand 10 produced by mouse Sertoli cells in response to mumps virus infection induces male germ cell apoptosis
Authors: Jiang Qian , Wang Fei , Shi Lili , Zhao Xiang , Gong Maolei , Liu Weihua , Song Chengyi , Li Qihan , Chen Yongmei , Wu Han , Han Daishu 
Published: October 2017

AbstractMumps virus (MuV) infection usually results in germ cell degeneration in the testis, which is an etiological factor for male infertility. However, the mechanisms by which MuV infection damages male germ cells remain unclear. The present study showed that C-X-C motif chemokine ligand 10 (CXCL10) is produced by mouse Sertoli cells in response to MuV infection, which induces germ cell apoptosis through the activation of caspase-3. CXC chemokine receptor 3 (CXCR3), a functional receptor of CXCL10, is constitutively expressed in male germ cells. Neutralizing antibodies against CXCR3 and an inhibitor of caspase-3 activation significantly inhibited CXCL10-induced male germ cell apoptosis. Furthermore, the tumor necrosis factor-α(TNF-α) upregulated CXCL10 production in Sertoli cells after MuV infection. The knockout of either CXCL10 or TNF-αreduced germ cell apoptosis in the co-cultures of germ cells and Sertoli cells in response to MuV infection. Local injection of MuV into the testes of mice confirmed the involvement of CXCL10 in germ cell apoptosisin vivo. These results provide novel insights into MuV-induced germ cell apoptosis in the testis.
The spontaneous differentiation and chromosome loss in iPSCs of human trisomy 18 syndrome
Authors: Li Ting , Zhao Hanzhi , Han Xu , Yao Jiaying , Zhang Lingling , Guo Ying , Shao Zhen , Jin Ying , Lai Dongmei 
Published: October 2017

AbstractAneuploidy including trisomy results in developmental disabilities and is the leading cause of miscarriages in humans. Unlike trisomy 21, pathogenic mechanisms of trisomy 18 remain unclear. Here, we successfully generated induced pluripotent stem cells (iPSCs) from human amniotic fluid cells (AFCs) with trisomy 18 pregnancies. We found that trisomy 18 iPSCs (18T-iPSCs) were prone to differentiate spontaneously. Intriguingly, 18T-iPSCs lost their extra 18 chromosomes and converted to diploid cells after 10 generations. fluorescence in situ hybridization analysis showed chromosome loss was a random event that might happen in any trisomic cells. Selection undifferentiated cells for passage accelerated the recovery of euploid cells. Overall, our findings indicate the genomic instability of trisomy 18 iPSCs bearing an extra chromosome 18.
Optical Controlled Terahertz Modulator Based on Tungsten Disulfide Nanosheet
Authors: Fan Zhiyuan , Geng Zhaoxin , Lv Xiaoqin , Su Yue , Yang Yuping , Liu Jian , Chen Hongda 
Published: October 2017

AbstractThe terahertz (THz) modulator, which will be applied in next-generation wireless communication, is a key device in a THz communication system. Current THz modulators based on traditional semiconductors and metamaterials have limited modulation depth or modulation range. Therefore, a THz modulator based on annealed tungsten disulfide (WS2, p-type) and high-resistivity silicon (n-type) is demonstrated. Pumped by a laser, the modulator presents a laser power-dependent modulation effect. Ranging from 0.25 to 2 THz, the modulation depth reaches 99% when the pumping laser is 2.59 W/cm2. The modulator works because the p-n heterojunction can separate and limit carriers to change the conductivity of the device, which results in a modulation of the THz wave. The wide band gap of WS2 can promote the separation and limitation of carriers to obtain a larger modulation depth, which provides a new direction for choosing new materials and new structures to fabricate a better THz modulator.
Antithrombotic properties of JJ1, a potent and novel thrombin inhibitor
Authors: Lee Wonhwa , Lee Suyeon , Choi Joonhyeok , Park Jun-Hyeong , Kim Kyung-Min , Jee Jun-Goo , Bae Jong-Sup 
Published: October 2017

AbstractThe development of new anticoagulants is an important goal for the improvement of thrombosis treatment. Recent studies have suggested the importance of thrombin inhibitors in the modulation of thromboembolic disorders. The aim of this study was to discover a new small-molecule thrombin inhibitor. In this study, the compoundJJ1, which has a novel scaffold, was selected by structure-based docking simulation to determine its potential inhibitory activity against thrombin.JJ1was shown to inhibit the catalytic activity of human α-thrombin with aKiof 0.019 μM by direct binding to the active site and with at least 10,000-fold selectivity relative to that reported for the inhibition of other biologically important serine proteases.JJ1prolonged clotting times (activated partial thromboplastin time and prothrombin time) and inhibited the activity and production of thrombin. Furthermore, it inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. Similar to itsin vitroantithrombotic activities,JJ1showed enhanced antithrombotic effects in anin vivopulmonary embolism and arterial thrombosis model. It also exhibited anticoagulant effects in mice. Collectively, these results demonstrated thatJJ1was a potent, direct, and selective thrombin inhibitor that may be useful in the management of various thrombotic disorders.
Dosimetric comparison of the helical tomotherapy, volumetric-modulated arc therapy and fixed-field intensity-modulated radiotherapy for stage IIB-IIIB non-small cell lung cancer
Authors: Xu Yujin , Deng Weiye , Yang Shuangyan , Li Pu , Kong Yue , Tian Ye , Liao Zhongxing , Chen Ming 
Published: October 2017

AbstractThe study aimed to compare the dosimetric parameters to target dose coverage and the critical structures in the treatment planning of helical tomotherapy (TOMO), volumetric-modulated arc therapy (VMAT), and fixed-field intensity-modulated radiotherapy (IMRT) for NSCLC delivering conventionally fractionated radiotherapy. Thirty patients with pathologically confirmed NSCLC were included. Three radiation treatment plans were designed for each patient. All patients received the uniform prescription dose of 60 Gy to the planning target volume. The conformity index (CI), heterogeneity index (HI), and parameters of critical structures were calculated. A significantly superior mean CI was observed in VMAT than in TOMO or IMRT (P = 0.013, 0.001). Mean HI was also better using VAMT or IMRT than TOMO (P = 0.002, 0.003). Mean lung V20 and V30 were significantly reduced by TOMO compared to IMRT (P = 0.019, 0.029). The heart was spared by IMRT compared to TOMO in terms of mean heart dose, V5, V10, and V20 (P < 0.05). In larger tumor, VMAT provided the optimal dose distribution and sparing to heart. Compared to TOMO and IMRT, VMAT achieved better target dose distribution and similar sparing of critical structures. VMAT seemed to be the optimal technique for NSCLC.
A Lithium-ion Battery Using Partially Lithiated Graphite Anode and Amphi-redox LiMn2O4 Cathode
Authors: Jeon Yuju , Noh Hyun Kuk , Song Hyun-Kon 
Published: October 2017

AbstractDelithiation followed by lithiation of Li+-occupied (n-type) tetrahedral sites of cubic LiMn2O4 spinel (LMO) at ~4 $${{\bf{V}}}_{{{\bf{Li}}{\boldsymbol{/}}{\bf{Li}}}^{{\boldsymbol{+}}}}$$

V

Li
/
Li

+

(delivering ~100 mAh gLMO−1) has been used for energy storage by lithium ion batteries (LIBs). In this work, we utilized unoccupied (p-type) octahedral sites of LMO available for lithiation at ~3 $${{\bf{V}}}_{{{\bf{Li}}{\boldsymbol{/}}{\bf{Li}}}^{{\boldsymbol{+}}}}$$

V

Li
/
Li

+

(delivering additional ~100 mAh gLMO−1) that have never been used for LIBs in full-cell configuration. The whole capacity of amphi-redox LMO, including both oxidizable n-type and reducible p-type redox sites, at ~200 mAh gLMO−1 was realized by using the reactions both at 4 $${{\bf{V}}}_{{{\bf{Li}}{\boldsymbol{/}}{\bf{Li}}}^{{\boldsymbol{+}}}}$$

V

Li
/
Li

+

and 3 $${{\bf{V}}}_{{{\bf{Li}}{\boldsymbol{/}}{\bf{Li}}}^{{\boldsymbol{+}}}}$$

V

Li
/
Li

+

. Durable reversibility of the 3 V reaction was achieved by graphene-wrapping LMO nanoparticles (LMO@Gn). Prelithiated graphite (LinC6, n < 1) was used as anodes to lithiate the unoccupied octahedral sites of LMO for the 3 V reaction.
Retinoic acid signaling maintains epithelial and mesenchymal progenitors in the developing mouse ureter
Authors: Bohnenpoll Tobias , Weiss Anna-Carina , Labuhn Maurice , Lüdtke Timo H. , Trowe M.-O. , Kispert Andreas 
Published: October 2017

AbstractThe differentiated cell types of the mature ureter arise from the distal ureteric bud epithelium and its surrounding mesenchyme. Uncommitted epithelial cells first become intermediate cells from which both basal and superficial cells develop. Mesenchymal progenitors give rise to separated layers of adventitial fibrocytes, smooth muscle cells and lamina propria fibrocytes. How progenitor expansion and differentiation are balanced is poorly understood. Here, we addressed the role of retinoic acid (RA) signaling in these programs. Using expression analysis of components and target genes, we show that pathway activity is restricted to the mesenchymal and epithelial progenitor pools. Inhibition of RA signaling in ureter explant cultures resulted in tissue hypoplasia with a relative expansion of smooth muscle cells at the expense of lamina propria fibroblasts in the mesenchyme, and of superficial cells at the expense of intermediate cells in the ureteric epithelium. Administration of RA led to a slight reduction of smooth muscle cells, and almost completely prevented differentiation of intermediate cells into basal and superficial cells. We identified cellular programs and transcriptional targets of RA signaling that may account for this activity. We conclude that RA signaling is required and sufficient to maintain mesenchymal and epithelial progenitors in early ureter development.
Therapeutic siRNA targeting endothelial KDR decreases portosystemic collateralization in portal hypertension
Authors: Gallego Javier , Garcia-Pras Ester , Mejias Marc , Pell Nuria , Schaeper Ute , Fernandez Mercedes 
Published: October 2017

AbstractDevelopment of portosystemic collateral vessels and gastroesophageal varices is responsible for the most serious clinical consequences of portal hypertension, but effective clinical therapies are limited. Here we developed and investigated the therapeutic potential of an innovative liposomally-formulated short-interfering RNA (siRNA) technology based on clinical stage components, capable to attenuate production of the endothelial kinase insert domain receptor (KDR), which controls portosystemic collateralization and contributes to disease progression and aggravation. These siRNAs were first validated in vitro, and then, their therapeutic potential on portosystemic collateralization and pathological angiogenesis was tested in vivo in mouse models of portal hypertension (portal vein-ligation). siRNAKDR-lipoplexes efficiently transported siRNAKDR to vascular endothelial cells in mesenteric microvenules and portal vein of portal hypertensive mice, where collaterogenesis and angiogenesis take place. This systemic treatment significantly downregulated pathological KDR overexpression, without causing complete KDR knockout, preserving homeostatic baseline KDR levels and thus limiting adverse effects. siRNAKDR-lipoplex-induced endothelial-specific KDR knockdown drastically reduced by 73% the portosystemic collateralization, and impaired the pathologic angiogenic potential of vascular endothelial cells at different levels (cell proliferation, sprouting and remodeling). Targeting endothelial KDR with therapeutic siRNAKDR-lipoplexes could be a promising and plausible treatment modality for attenuating the formation of portosystemic collaterals in a clinical setting.
Sporadic Hirschsprung Disease: Mutational Spectrum and Novel Candidate Genes Revealed by Next-generation Sequencing
Authors: Zhang Zhen , Li Qi , Diao Mei , Liu Na , Cheng Wei , Xiao Ping , Zou Jizhen , Su Lin , Yu Kaihui , Wu Jian , Li Long , Jiang Qian 
Published: October 2017

AbstractHirschsprung disease (HSCR) is a common cause of functional colonic obstruction in children. The currently available genetic testing is often inadequate as it mainly focuses on RET and several other genes, accounting for only 15–20% of cases. To identify novel, potentially pathogenic variants, we isolated a panel of genes from a whole-exome sequencing study and from the published mouse aganglionosis phenotypes, enteric nervous system development, and a literature review. The coding exons of 172 genes were analyzed in 83 sporadic patients using next-generation sequencing. Rare stop-gain, splice-site variants, frameshift and in-frame insertions/deletions and non-synonymous variants (conserved and predicted to be deleterious) were prioritized as the most promising variants to have an effect on HSCR and subjected to burden analysis. GeneMANIA interaction database was used to identify protein–protein interaction-based networks. In addition, 6 genes (PTPN13, PHKB, AGL, ZFHX3, LAMA1, and AP3B2) were prioritized for follow-up studies: both their time-space expression patterns in mouse and human colon showed that they are good candidates for predicting pathogenicity. The results of this study broaden the mutational spectrum of HSCR candidate genes, and they provide an insight into the relative contributions of individual genes to this highly heterogeneous disorder.
Intraoperative Assessment of Parathyroid Viability using Laser Speckle Contrast Imaging
Authors: Mannoh E. A. , Thomas G. , Solórzano C. C. , Mahadevan-Jansen A. 
Published: October 2017

AbstractPost-surgical hypoparathyroidism and hypocalcemia are known to occur after nearly 50% of all thyroid surgeries as a result of accidental disruption of blood supply to healthy parathyroid glands, which are responsible for regulating calcium. However, there are currently no clinical methods for accurately identifying compromised glands and the surgeon relies on visual assessment alone to determine if any gland(s) should be excised and auto-transplanted. Here, we present Laser Speckle Contrast Imaging (LSCI) for real-time assessment of parathyroid viability. Taking an experienced surgeon’s visual assessment as the gold standard, LSCI can be used to distinguish between well vascularized (n = 32) and compromised (n = 27) parathyroid glands during thyroid surgery with an accuracy of 91.5%. Ability to detect vascular compromise with LSCI was validated in parathyroidectomies. Results showed that this technique is able to detect parathyroid gland devascularization before it is visually apparent to the surgeon. Measurements can be performed in real-time and without the need to turn off operating room lights. LSCI shows promise as a real-time, contrast-free, objective method for helping reduce hypoparathyroidism after thyroid surgery.
Influence of Altered Auditory Feedback on Oral–Nasal Balance in Speech
Authors: de Boer Gillian , Bressmann Tim 
Published: October 2017

Purpose
This study explored the role of auditory feedback in the regulation of oral–nasal balance in speech.

Method
Twenty typical female speakers wore a Nasometer 6450 (KayPentax) headset and headphones while continuously repeating a sentence with oral and nasal sounds. Oral–nasal balance was quantified with nasalance scores. The signals from 2 additional oral and nasal microphones were played back to the participants through the headphones. The relative loudness of the nasal channel in the mix was gradually changed so that the speakers heard themselves as more or less nasal. An additional amplitude control group of 9 female speakers completed the same task while hearing themselves louder or softer in the headphones.

Results
A repeated-measures analysis of variance of the mean nasalance scores of the stimulus sentence at baseline, minimum, and maximum nasal feedback conditions demonstrated a significant effect of the nasal feedback condition. Post hoc analyses found that the mean nasalance scores were lowest for the maximum nasal feedback condition. The scores of the minimum nasal feedback condition were significantly higher than 2 of the 3 baseline feedback conditions. The amplitude control group did not show any effects of volume changes on nasalance scores.

Conclusions
Increased nasal feedback led to a compensatory adjustment in the opposite direction, confirming that oral–nasal balance is regulated by auditory feedback. However, a lack of nasal feedback did not lead to a consistent compensatory response of similar magnitude.
SOLAR-ISS: A new reference spectrum based on SOLAR/SOLSPEC observations
Authors: Meftah M. , Damé L. , Bolsée D. , Hauchecorne A. , Pereira N. , Sluse D. , Cessateur G. , Irbah A. , Bureau J. , Weber M. , Bramstedt K. , Hilbig T. , Thiéblemont R. , Marchand M. , Lefèvre F. , Sarkissian A. , Bekki S. 
Published: October 2017

Context. Since April 5, 2008 and up to February 15, 2017, the SOLar SPECtrometer (SOLSPEC) instrument of the SOLAR payload on board the International Space Station (ISS) has performed accurate measurements of solar spectral irradiance (SSI) from the middle ultraviolet to the infrared (165 to 3088 nm). These measurements are of primary importance for a better understanding of solar physics and the impact of solar variability on climate. In particular, a new reference solar spectrum (SOLAR-ISS) is established in April 2008 during the solar minima of cycles 23–24 thanks to revised engineering corrections, improved calibrations, and advanced procedures to account for thermal and aging corrections of the SOLAR/SOLSPEC instrument.
Aims. The main objective of this article is to present a new high-resolution solar spectrum with a mean absolute uncertainty of 1.26% at 1σ from 165 to 3000 nm. This solar spectrum is based on solar observations of the SOLAR/SOLSPEC space-based instrument.Methods. The SOLAR/SOLSPEC instrument consists of three separate double monochromators that use concave holographic gratings to cover the middle ultraviolet (UV), visible (VIS), and infrared (IR) domains. Our best ultraviolet, visible, and infrared spectra are merged into a single absolute solar spectrum covering the 165–3000 nm domain. The resulting solar spectrum has a spectral resolution varying between 0.6 and 9.5 nm in the 165–3000 nm wavelength range. We build a new solar reference spectrum (SOLAR-ISS) by constraining existing high-resolution spectra to SOLAR/SOLSPEC observed spectrum. For that purpose, we account for the difference of resolution between the two spectra using the SOLAR/SOLSPEC instrumental slit functions.Results. Using SOLAR/SOLSPEC data, a new solar spectrum covering the 165–3000 nm wavelength range is built and is representative of the 2008 solar minimum. It has a resolution better than 0.1 nm below 1000 nm and 1 nm in the 1000–3000 nm wavelength range. The new solar spectrum (SOLAR-ISS) highlights significant differences with previous solar reference spectra and with solar spectra based on models. The integral of the SOLAR-ISS solar spectrum yields a total solar irradiance of 1372.3 ± 16.9 Wm−2 at 1σ, that is yet 11 Wm−2 over the value recommended by the International Astronomical Union in 2015.