bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maternal cariprazine exposure inhibits embryonic and postnatal brain cholesterol biosynthesis
Authors: Genaro-Mattos Thiago C. , Anderson Allison , Allen Luke B. , Tallman Keri A. , Porter Ned A. , Korade Zeljka , Mirnics Károly 
Published: June 2020

AbstractCariprazine (CAR) is a strong inhibitor of the Dhcr7 enzyme, the last enzyme in the cholesterol biosynthesis pathway. We assessed the effects of CAR on maternally exposed Dhcr7+/− and wild-type mouse offspring, and tested the biochemical effects of CAR in human serum samples. Dhcr7+/− and wild-type time-pregnant mice were exposed to vehicle or 0.2 mg/kg CAR from E12 to E19. Levels of CAR, CAR metabolites, sterols, and oxysterols were measured in the brain of maternally exposed offspring at various time points using LC-MS/MS. Embryonic exposure to CAR significantly increased levels of 7-DHC in all organs of exposed embryos, with a particularly strong effect in the brain. Detectable levels of CAR and elevated 7-DHC were observed in the brain of newborn pups 14 days after drug exposure. In addition, CAR altered sterol metabolism in all animals analyzed, with the strongest effect on the brain of Dhcr7+/− pups born to Dhcr7+/− dams. Furthermore, CAR elevated toxic oxysterols in the brain of maternally exposed Dhcr7+/− offspring to levels approaching those seen in a mouse model of Smith–Lemli–Opitz syndrome. Finally, we observed that patients taking CAR have elevated 7-DHC in their serum. In summary, maternal DHCR7 heterozygosity, combined with offspring DHCR7 heterozygosity might represent a vulnerability factor to medications that interfere with sterol biosynthesis. Due to the conserved sterol biosynthesis between mice and humans, we suggest that the 1–3% of patient population with single-allele DHCR7 mutations might not be ideal candidates for CAR use, especially if they are nursing, pregnant or plan to become pregnant.
Association of dietary patterns with the newly diagnosed diabetes mellitus and central obesity: a community based cross-sectional study
Authors: Yin Xueyao , Chen Yixin , Lu Weina , Jin Ting , LI Lin 
Published: June 2020

Abstract
Aim
The purpose of this study was to investigate the association of dietary patterns with the risk of insulin resistance (IR), diabetes mellitus (DM), and central obesity in China.

Methods
We performed a cross-sectional study on 1432 participants, aged 40–65 years in Hangzhou, Zhejiang province, China. Dietary intake was assessed using a semi-quantitative food frequency questionnaire.

Results
Factor analysis extracted four major dietary patterns: vegetable-fruits, rice–meat, seafood–eggs, and sweet–fast. The vegetable-fruits pattern was inversely associated with HOMA-IR (p < 0.001 in both genders), while sweet–fast food pattern was significantly associated with higher HOMA-IR (p = 0.002 in male, and p < 0.001 in female). The vegetables–fruits pattern was inversely correlated with visceral fat area (VFA) (p = 0.029 in males, and p = 0.017 in females), while sweet–fast food pattern presented a significant direct association (p < 0.001 in male) with VFA in males. There was no association observed between the rice–meat pattern or the seafood–eggs pattern and HOMA-IR or VFA. After adjustment for potential confounding factors, participants in the highest tertile of vegetable-fruits pattern showed a significantly lower risk of DM in both males and females (OR: 0.30, 95% CI: 0.13–0.70 in male, and OR: 0.28, 95% CI: 0.11–0.72 in female), and lower risk of central obesity was observed in males (OR: 0.50, 95% CI: 0.29–0.86 in male). Conversely, participants in the highest tertile of sweet–fast food pattern had higher risk of DM (OR: 2.58, 95% CI: 1.23–5.88 in male), and central obesity (OR: 2.85, 95% CI: 1.67–4.86 in male) only in male. While neither the rice–meat pattern nor the seafood–eggs pattern showed significant association with DM or central obesity in both genders.

Conclusions
Our findings indicated low risk of IR, DM, and central obesity with vegetable-fruits pattern while inverse relation with sweet–fast food pattern.
BRD4 promotes metastatic potential in oral squamous cell carcinoma through the epigenetic regulation of the MMP2 gene
Authors: Yamamoto Tatsuro , Hirosue Akiyuki , Nakamoto Masafumi , Yoshida Ryoji , Sakata Junki , Matsuoka Yuichiro , Kawahara Kenta , Nagao Yuka , Nagata Masashi , Takahashi Nozomu , Hiraki Akimitsu , Shinohara Masanori , Nakao Mitsuyoshi , Saitoh Noriko , Nakayama Hideki 
Published: June 2020

Abstract
Background
Oral squamous cell carcinoma (OSCC) has increased morbidity, and its high metastatic potential affects patient survival. Bromodomain containing 4 (BRD4) is a chromatin protein that associates with acetylated histone lysines and facilitates transcription. BRD4 has been implicated in cell proliferation, metastasis, and prognosis in several types of cancer. However, the role of BRD4 in OSCC remains to be elucidated.

Methods
We investigated the role of BRD4 and its potential utility as a therapeutic target in OSCC.

Results
JQ1, the BRD4 inhibitor, suppressed the cell proliferation, migration, and invasion in the OSCC cell lines and in vivo. JQ1 reduced the expression levels of 15 metastasis genes in OSCC, including matrix metallopeptidase 2 (MMP2). Our chromatin immunoprecipitation assay showed that JQ1 reduced the BRD4 binding to the histone H3 lysine 27 acetylation-enriched sites in the MMP2 locus. Analyses of biopsy specimens from OSCC patients revealed that the BRD4 and MMP2 expression levels were correlated in the cancerous regions, and both were highly expressed in lymph node metastasis cases, including delayed metastasis.

Conclusions
BRD4 contributes to metastasis in OSCC, through the epigenetic regulation of the MMP2 gene, and thus BRD4 may represent a therapeutic target and a novel prediction indicator for metastasis.
MicroRNA-674-5p induced by HIF-1α targets XBP-1 in intestinal epithelial cell injury during endotoxemia
Authors: Liu Zhihao , Jiang Jie , Dai Weigang , Wei Hongyan , Zhang Xiaofei , Yang Zhen , Xiong Yan 
Published: June 2020

AbstractIntestinal mucosal integrity dysfunction during endotoxemia can contribute to translocation of intestinal bacteria and a persistent systemic inflammatory response, which both fuel the pathophysiological development of sepsis or endotoxemia. The pathogenesis of intestinal damage induced by endotoxemia remains poorly understood. Here, we identified the microRNA (miR)-674-5p/X-box binding protein 1 (XBP-1) axis as a critical regulator and therapeutic target in preventing intestinal crypt cell proliferation during endotoxemia. MiR-674-5p was markedly increased in intestinal epithelial cells (IECs) during endotoxemia and its induction depended on hypoxia-inducible factor-1α (HIF-1α). Intriguingly, gene expression microanalysis revealed that expression of XBP-1 was down-regulated in IECs with over-expression of miR-674-5p. miR-674-5p was found to directly target XBP-1 protein expression. Upon in vitro, anti-miR-674-5p enhanced sXBP-1 expression and facilitated intestinal crypt cell proliferation. Blockade of miR-674-5p promoted XBP-1 activity, attenuated intestinal inflammation, and expedited intestinal regeneration, resulting in protection against endotoxemia-induced intestinal injury in mice. More importantly, the survival in endotoxemia mice was significantly improved by inhibiting intestinal miR-674-5p. Collectively, these data indicate that control of a novel miR-674-5p/XBP-1 signaling axis may mitigate endotoxemia -induced intestinal injury.
Vascularized silk electrospun fiber for promoting oral mucosa regeneration
Authors: Qian Chunyu , Xin Tianwen , Xiao Wanshu , Zhu Huajun , Zhang Qiang , Liu Lili , Cheng Ruoyu , Wang Zhen , Cui Wenguo , Ge Zili 
Published: June 2020

AbstractElectrospun fiber membranes have been extensively researched for tissue repair; however, fiber angiogenesis has been a difficult problem because the biomaterials used to prepare the fiber cannot promote angiogenesis by themselves. To endow the fiber with the function of promoting angiogenesis and oral mucosa regeneration, surface-aminated liposomes (NH2-LIPs) encapsulating leptin, as well as silk fiber (SF) membranes that have been immersed overnight in polydopamine (PDA) solution were synthesized. The NH2-LIPs were then grafted onto the surfaces of SF through reactions between the catechol groups of PDA and the amino groups of NH2-LIPs to induce angiogenesis on the fiber surface and thus promote oral mucosa regeneration. The PDA-modified and NH2-LIP-modified SF retained the original fibrous morphology but increased the SF tensile strength from 1.95 MPa to 2.87 MPa. PDA changed the hydrophilicity of the fibers and improved the adhesion of fibroblasts on the fibrous membranes. Leptin loaded onto SF via PDA had no significant effect on cell proliferation and formed 162.7-node tubes in human umbilical vein endothelial cells (HUVECs) within 10 h, which demonstrated that leptin loaded onto SF can promote angiogenesis. Wound closure of mucosa covered in leptin-loaded fibrous membranes reached 99% at 14 days postsurgery. Histologic analysis showed that leptin-loaded SFs exhibited clear stratification of new mucosa, as well as a strong CD34 signal that indicated the presence of new blood vessels and confirmed the successful loading of leptin on the fiber. Therefore, this work successfully showed that NH2-LIPs grafted onto the surface of SFs via PDA endow the fibers with angiogenic abilities and promote oral mucosa regeneration.
Pericyte FAK negatively regulates Gas6/Axl signalling to suppress tumour angiogenesis and tumour growth
Authors: Lechertier Tanguy , Reynolds Louise E. , Kim Hyojin , Pedrosa Ana Rita , Gómez-Escudero Jesús , Muñoz-Félix José M. , Batista Silvia , Dukinfield Matthew , Demircioglu Fevzi , Wong Ping Pui , Matchett Kylie P. , Henderson Neil C. , D’Amico Gabriela , Parsons Maddy , Harwood Catherine , Meier Pascal , Hodivala-Dilke Kairbaan M. 
Published: June 2020

AbstractThe overexpression of the protein tyrosine kinase, Focal adhesion kinase (FAK), in endothelial cells has implicated its requirement in angiogenesis and tumour growth, but how pericyte FAK regulates tumour angiogenesis is unknown. We show that pericyte FAK regulates tumour growth and angiogenesis in multiple mouse models of melanoma, lung carcinoma and pancreatic B-cell insulinoma and provide evidence that loss of pericyte FAK enhances Gas6-stimulated phosphorylation of the receptor tyrosine kinase, Axl with an upregulation of Cyr61, driving enhanced tumour growth. We further show that pericyte derived Cyr61 instructs tumour cells to elevate expression of the proangiogenic/protumourigenic transmembrane receptor Tissue Factor. Finally, in human melanoma we show that when 50% or more tumour blood vessels are pericyte-FAK negative, melanoma patients are stratified into those with increased tumour size, enhanced blood vessel density and metastasis. Overall our data uncover a previously unknown mechanism of tumour growth by pericytes that is controlled by pericyte FAK.
Highly efficient phosphor-glass composites by pressureless sintering
Authors: Zhang Dao , Xiao Wenge , Liu Chang , Liu Xiaofeng , Ren Jinjun , Xu Beibei , Qiu Jianrong 
Published: June 2020

AbstractThe development of high-power white light-emitting diodes demands highly efficient and stable all-inorganic color converters. In this respect, phosphor-glass/ceramic composites show great promise as they could combine the merits of high quantum efficiency of phosphors and high chemical and thermal stabilities of glass/ceramic matrices. However, strong interfacial reaction between phosphors and matrices at high temperature results in quantum efficiency loss of the embedded phosphors, and traditional solutions rely on high-pressure consolidation techniques. Here we report the intrinsic inhibition of interfacial reaction by using silica glass rather than multicomponent glasses as the matrix. The embedment of phosphors is achieved via a pressureless sintering method, rendering these color-tunable phosphor-glass composites not only accessible to three-dimensional printing technique, but also highly efficient (internal quantum efficiency >90.0%), thermally stable at 1200 °C and hydrothermally stable at 200 °C. Our results provide a facile and general strategy for developing all-inorganic functional composites.
Mechanisms of offline motor learning at a microscale of seconds in large-scale crowdsourced data
Authors: Bönstrup Marlene , Iturrate Iñaki , Hebart Martin N. , Censor Nitzan , Cohen Leonardo G. 
Published: June 2020

AbstractPerformance improvements during early human motor skill learning are suggested to be driven by short periods of rest during practice, at the scale of seconds. To reveal the unknown mechanisms behind these “micro-offline” gains, we leveraged the sampling power offered by online crowdsourcing (cumulative N over all experiments = 951). First, we replicated the original in-lab findings, demonstrating generalizability to subjects learning the task in their daily living environment (N = 389). Second, we show that offline improvements during rest are equivalent when significantly shortening practice period duration, thus confirming that they are not a result of recovery from performance fatigue (N = 118). Third, retroactive interference immediately after each practice period reduced the learning rate relative to interference after passage of time (N = 373), indicating stabilization of the motor memory at a microscale of several seconds. Finally, we show that random termination of practice periods did not impact offline gains, ruling out a contribution of predictive motor slowing (N = 71). Altogether, these results demonstrate that micro-offline gains indicate rapid, within-seconds consolidation accounting for early skill learning.
Hybrid Quantum Protocols for Secure Multiparty Summation and Multiplication
Authors: Sutradhar Kartick , Om Hari 
Published: June 2020

AbstractThe summation and multiplication are two basic operations for secure multiparty quantum computation. The existing secure multiparty quantum summation and multiplication protocols have (n, n) threshold approach and their computation type is bit-by-bit, where n is total number of players. In this paper, we propose two hybrid (t, n) threshold quantum protocols for secure multiparty summation and multiplication based on the Shamir’s secret sharing, SUM gate, quantum fourier transform, and generalized Pauli operator, where t is a threshold number of players that can perform the summation and multiplication. Their computation type is secret-by-secret with modulo d, where d, n ≤ d ≤ 2n, is a prime. The proposed protocols can resist the intercept-resend, entangle-measure, collusion, collective, and coherent quantum attacks. They have better computation as well as communication costs and no player can get other player’s private input.
Neural oscillations and event-related potentials reveal how semantic congruence drives long-term memory in both young and older humans
Authors: Packard Pau A. , Steiger Tineke K. , Fuentemilla Lluís , Bunzeck Nico 
Published: June 2020

AbstractLong-term memory can improve when incoming information is congruent with known semantic information. This so-called congruence effect has widely been shown in younger adults, but age-related changes and neural mechanisms remain unclear. Here, congruence improved recognition memory in younger and older adults (i.e. congruence effect), with only weak evidence for age-related decline in one behavioral study. In an EEG study, however, no significant behavioral differences in the congruence effect could be observed between age-groups. In line with this observation, electroencephalography data show that, in both groups, congruence led to widespread differences in Event-Related Potentials (ERPs), starting at around 400 ms after stimulus onset, and theta, alpha and beta oscillations (4–20 Hz). Importantly, these congruence-related ERPs were associated to increases in memory performance for congruent items, in both age groups. Finally, the described ERPs and neural oscillations in the theta-alpha range (5–13 Hz) were less pronounced in the elderly despite a preserved congruence effect. Together, semantic congruence increases long-term memory across the lifespan, and, at the neural level, this could be linked to neural oscillations in the theta, alpha and beta range, as well as ERPs that were previously associated with semantic processing.
Identification of two aptamers binding to Legionella pneumophila with high affinity and specificity
Authors: Saad Mariam , Chinerman Deanna , Tabrizian Maryam , Faucher Sebastien P. 
Published: June 2020

AbstractLegionella pneumophila (Lp) is a water borne bacterium causing Legionnaires’ Disease (LD) in humans. Rapid detection of Lp in water system is essential to reduce the risk of LD outbreaks. The methods currently available require expert skills and are time intensive, thus delaying intervention. In situ detection of Lp by biosensor would allow rapid implementation of control strategies. To this end, a biorecognition element is required. Aptamers are considered promising biorecognition molecules for biosensing. Aptamers are short oligonucleotide sequence folding into a specific structure and are able to bind to specific molecules. Currently, no aptamer and thus no aptamer-based technology exists for the detection of Lp. In this study, Systemic Evolution of Ligands through EXponential enrichment (SELEX) was used to identify aptamers binding specifically to Lp. Ten rounds of positive selection and two rounds of counter-selection against two Pseudomonas species were performed. Two aptamers binding strongly to Lp were identified with KD of 116 and 135 nM. Binding specificity of these two aptamers to Lp was confirmed by flow cytometry and fluorescence microscopy. Therefore, these two aptamers are promising biorecognition molecules for the detection of Lp in water systems.
Water is a biomarker of changes in the cellular environment in live animals
Authors: Siwach Pratibha , Levy Evgeniya , Livshits Leonid , Feldman Yuri , Kaganovich Daniel 
Published: June 2020

AbstractThe biological processes that are associated with the physiological fitness state of a cell comprise a diverse set of molecular events. Reactive oxygen species (ROS), mitochondrial dysfunction, telomere shortening, genomic instability, epigenetic changes, protein aggregation, and down-regulation of quality control mechanisms are all hallmarks of cellular decline. Stress-related and decline-related changes can be assayed, but usually through means that are highly disruptive to living cells and tissues. Biomarkers for organismal decline and aging are urgently needed for diagnostic and drug development. Our goal in this study is to provide a proof-of-concept for a non-invasive assay of global molecular events in the cytoplasm of living animals. We show that Microwave Dielectric Spectroscopy (MDS) can be used to determine the hydration state of the intracellular environment in live C. elegans worms. MDS spectra were correlative with altered states in the cellular protein folding environment known to be associated with previously described mutations in the C. elegans lifespan and stress-response pathways.
Plastome Structural Conservation and Evolution in the Clusioid Clade of Malpighiales
Authors: Jin Dong-Min , Jin Jian-Jun , Yi Ting-Shuang 
Published: June 2020

AbstractThe clusioid clade of Malpighiales is comprised of five families: Bonnetiaceae, Calophyllaceae, Clusiaceae, Hypericaceae and Podostemaceae. Recent studies have found the plastome structure of Garcinia mangostana L. from Clusiaceae was conserved, while plastomes of five riverweed species from Podostemaceae showed significant structural variations. The diversification pattern of plastome structure of the clusioid clade worth a thorough investigation. Here we determined five complete plastomes representing four families of the clusioid clade. Our results found that the plastomes of the early diverged three families (Clusiaceae, Bonnetiaceae and Calophyllaceae) in the clusioid clade are relatively conserved, while the plastomes of the other two families show significant variations. The Inverted Repeat (IR) regions of Tristicha trifaria and Marathrum foeniculaceum (Podostemaceae) are greatly reduced following the loss of the ycf1 and ycf2 genes. An inversion over 50 kb spanning from trnK-UUU to rbcL in the LSC region is shared by Cratoxylum cochinchinense (Hypericaceae), T. trifaria and Ma. foeniculaceum (Podostemaceae). The large inversed colinear block in Hypericaceae and Podostemaceae contains all the genes in the 50-kb inversed colinear block in a clade of Papilionoideae, with two extra genes (trnK-UUU and matK) at one end. Another endpoint of both inversions in the two clusioids families and Papilionoideae is located between rbcL and accD. This study greatly helped to clarify the plastome evolution in the clusioid clade.
Spontaneous MEG activity of the cerebral cortex during eyes closed and open discriminates Alzheimer’s disease from cognitively normal older adults
Authors: Ikeda Yoshihisa , Kikuchi Mitsuru , Noguchi-Shinohara Moeko , Iwasa Kazuo , Kameya Masafumi , Hirosawa Tetsu , Yoshita Mitsuhiro , Ono Kenjiro , Samuraki-Yokohama Miharu , Yamada Masahito 
Published: June 2020

AbstractThis study aimed to examine whether magnetoencephalography (MEG) is useful to detect early stage Alzheimer’s disease (AD). We analyzed MEG data from the early stage AD group (n = 20; 6 with mild cognitive impairment due to AD and 14 with AD dementia) and cognitively normal control group (NC, n = 27). MEG was recorded during resting eyes closed (EC) and eyes open (EO), and the following 6 values for each of 5 bands (θ1: 4-6, θ2: 6-8, α1: 8-10, α2: 10-13, β: 13-20 Hz) in the cerebral 68 regions were compared between the groups: (1) absolute power during EC and (2) EO, (3) whole cerebral normalization (WCN) power during EC and (4) EO, (5) difference of the absolute powers between the EC and EO conditions (the EC-EO difference), and (6) WCN value of the EC-EO difference. We found significant differences between the groups in the WCN powers during the EO condition, and the EC-EO differences. Using a Support Vector Machine classifier, a discrimination accuracy of 83% was obtained and an AUC in an ROC analysis was 0.91. This study demonstrates that MEG during resting EC and EO is useful in discriminating between early stage AD and NC.
A New Representative Sampling Method for Series Size Rock Joint Surfaces
Authors: Huang Man , Hong Chenjie , Ma Chengrong , Luo Zhanyou , Du Shigui , Yang Fei 
Published: June 2020

AbstractThe greatest variability in both shear strength and roughness exists for joint samples with smaller size, which underscores the necessity of performing representative sampling. This study aims to provide a representative sampling method for series size joint surfaces. The progressive coverage statistical method is introduced to provide the sufficient sample capacity for series sampling sizes by setting different propulsion spaces. The statistical law of the joint surface morphology at different sampling sizes is measured by the 3D roughness parameter with $${{\theta }}_{\max }^{\ast }/({C}+1)$$θmax⁎/(C+1). Through an application in nine natural large-scale rock joints, nine consecutive sampling sizes from 100 mm × 100 mm to 900 mm × 900 mm are selected and 121 samples are successfully acquired from each sampling size. According to the frequency distribution of roughness statistics, a new sampling method combining the layering principle and K-medoids clustering algorithm is proposed to screen representative joint samples for each sampling size. The sampling results that meet the test accuracy requirements suggest the possibility of realizing an intelligent sampling method. In addition, the representative of the interlayer cluster center is validated. Finally, the comparison results with the traditional stratified sampling method prove that the proposed method has better stability.