bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Gold in Inflammation and Tristetraprolin Activity
Authors: Ok Kiwon , Li Wenjing , Neu Heather M. , Batelu Sharon , Stemmler Timothy L. , Kane Maureen A. , Michel Sarah L. J. 
Published: October 2019

AbstractThe zinc finger protein tristetraprolin (TTP) regulates inflammation by downregulating cytokine mRNAs. Misregulation results in arthritis, sepsis and cancer, and there is an interest in modulating TTP activity with exogenous agents. Gold has anti‐inflammatory properties and has recently been shown to modulate the signaling pathway that produces TTP, suggesting that TTP may be a target of gold. The reactivity of [AuIII(terpy)Cl]Cl2 with TTP was investigated by UV/Vis spectroscopy, spin‐filter inductively coupled plasma mass spectrometry, X‐ray absorption spectroscopy and native electrospray ionization mass spectrometry. AuIII was found to replace zinc in the protein active site in the reduced AuI form, with the AuI ion coordinated to two cysteine residues in a linear geometry. The replacement of ZnII with AuI results in loss of both secondary structure and RNA binding function. In contrast, when ZnIITTP is bound to its RNA target, no replacement of ZnII with AuI is observed, even in the presence of excess AuIIIterpy. This discovery of differential reactivity of gold with TTP versus TTP/RNA offers a potential strategy for selective targeting with gold complexes to control inflammation.
Mono‐Heteroatom Substitution for Harnessing Excited‐State Structural Planarization of Dihydrodibenzo[a,c]phenazines
Authors: Chen Yi , Chen Deng‐Gao , Chen Yi‐An , Wu Cheng‐Ham , Chang Kai‐Hsin , Meng Fan‐Yi , Chen Meng‐Chi , Lin Jia‐An , Huang Chun‐Ying , Su Jianhua , Tian He , Chou Pi‐Tai 
Published: October 2019

AbstractWith the aim of generalizing the structure–properties relationship of bending heterocyclic molecules that undergo prominent photoinduced structural planarization (PISP), a series of new dihydrodibenzo[ac]phenazine derivatives in which one nitrogen atom is replaced by oxygen (PNO), sulfur (PNS), selenium (PNSe), or dimethylmethanediyl (PNC) was strategically designed and synthesized. Compounds PNO, PNS, and PNSe have significantly nonplanar geometries in the ground state, which undergo PISP to give a planarlike conformer and hence a large emission Stokes shift. A combination of femtosecond early relaxation dynamics and computational approaches established an R*→I* (intermediate)→P* sequential kinetic pattern for PNS and PNSe, whereas PNO undergoes R*→P* one‐step kinetics. The polarization ability of the substituted heteroatoms, which is in the order O<S<Se, correlates with their increase in π conjugation, and hence the Stokes shift of the emission is in the order PNO<PNS<PNSe. Compound PNSe with the largest PISP barrier was shown to be a highly sensitive viscosity probe. Further evidence for heteroatom‐harnessing PISP is given by PNC, in which the dimethylmethanediyl substituent lacks lone pair electrons for π extension, showing the normal emission of the bent structure. The results led to the conclusion that PISP is ubiquitous in dihydrodibenzo[ac]phenazines, for which the driving force is elongation of the π delocalization to gain stabilization in the excited state.
Competition and succession among coral endosymbionts
Authors: McIlroy Shelby E. , Cunning Ross , Baker Andrew C. , Coffroth Mary Alice 
Published: October 2019

AbstractHost species often support a genetically diverse guild of symbionts, the identity and performance of which can determine holobiont fitness under particular environmental conditions. These symbiont communities are structured by a complex set of potential interactions, both positive and negative, between the host and symbionts and among symbionts. In reef‐building corals, stable associations with specific symbiont species are common, and we hypothesize that this is partly due to ecological mechanisms, such as succession and competition, which drive patterns of symbiont winnowing in the initial colonization of new generations of coral recruits. We tested this hypothesis using the experimental framework of the de Wit replacement series and found that competitive interactions occurred among symbionts which were characterized by unique ecological strategies. Aposymbiotic octocoral recruits within high‐ and low‐light environments were inoculated with one of three Symbiodiniaceae species as monocultures or with cross‐paired mixtures, and we tracked symbiont uptake using quantitative genetic assays. Priority effects, in which early colonizers excluded competitive dominants, were evidenced under low light, but these early opportunistic species were later succeeded by competitive dominants. Under high light, a more consistent competitive hierarchy was established in which competitive dominants outgrew and limited the abundance of others. These findings provide insight into mechanisms of microbial community organization and symbiosis breakdown and recovery. Furthermore, transitions in competitive outcomes across spatial and temporal environmental variation may improve lifetime host fitness.
Fabrication of the Enzyme‐less Voltammetric Bilirubin Sensor Based on Sol‐gel Imprinted Polymer
Authors: Akhoundian Maedeh , Alizadeh Taher , Pan Guoqing 
Published: October 2019

AbstractMeasuring the serum bilirubin (BR) level is part of the common test for newborns, since high concentrations of bilirubin in the blood can cause brain damage and even death for them. Therefore, achieving a fast, accurate and cost effective method for bilirubin assay in medical diagnosis and Medical management of patients with jaundice, especially neonates, is very important. In this study, an electrochemical sensor was developed to detect low amounts of bilirubin in serum samples. The basis of the work is the BR imprinted polymer synthesis and the use of this polymer as a recognition element in the production of the bilirubin voltammetric sensor. For this purpose, bilirubin imprinted polymer was synthesized using the simple sol gel method and the prepared polymer is characterized by SEM and FT‐IR. In the next step, this polymer was applied to modify the carbon paste electrode and provide a sensitive and selective sensor for the BR molecule. The proposed sensor was able to measure the bilirubin in the concentration range of 1 to 100 μM after optimizing the operating conditions. The limit of detection (LOD) and limit of quantification (LOQ) was calculated 0.75 μM and 2.5 μM respectively. It is also applicable to bilirubin assay in serum samples.
Liver kinase B1 depletion from astrocytes worsens disease in a mouse model of multiple sclerosis
Authors: Kalinin Sergey , Meares Gordon P. , Lin Shao Xia , Pietruczyk Elizabeth A. , Saher Gesine , Spieth Lena , Nave Klaus‐Armin , Boullerne Anne I. , Lutz Sarah E. , Benveniste Etty N. , Feinstein Douglas L. 
Published: October 2019

AbstractLiver kinase B1 (LKB1) is a ubiquitously expressed kinase involved in the regulation of cell metabolism, growth, and inflammatory activation. We previously reported that a single nucleotide polymorphism in the gene encoding LKB1 is a risk factor for multiple sclerosis (MS). Since astrocyte activation and metabolic function have important roles in regulating neuroinflammation and neuropathology, we examined the serine/threonine kinase LKB1 in astrocytes in a chronic experimental autoimmune encephalomyelitis mouse model of MS. To reduce LKB1, a heterozygous astrocyte‐selective conditional knockout (het‐cKO) model was used. While disease incidence was similar, disease severity was worsened in het‐cKO mice. RNAseq analysis identified Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched in het‐cKO mice relating to mitochondrial function, confirmed by alterations in mitochondrial complex proteins and reductions in mRNAs related to astrocyte metabolism. Enriched pathways included major histocompatibility class II genes, confirmed by increases in MHCII protein in spinal cord and cerebellum of het‐cKO mice. We observed increased numbers of CD4+ Th17 cells and increased neuronal damage in spinal cords of het‐cKO mice, associated with reduced expression of choline acetyltransferase, accumulation of immunoglobulin‐γ, and reduced expression of factors involved in motor neuron survival. In vitro, LKB1‐deficient astrocytes showed reduced metabolic function and increased inflammatory activation. These data suggest that metabolic dysfunction in astrocytes, in this case due to LKB1 deficiency, can exacerbate demyelinating disease by loss of metabolic support and increase in the inflammatory environment.
Role of implants surface modification in osseointegration: A systematic review
Authors: Liu Yu , Rath Björn , Tingart Markus , Eschweiler Jörg 
Published: October 2019

AbstractLong‐term and stable fixation of implants is one of the most important points for a successful orthopedic surgery in the field of endoprosthesis. Osseointegration (OI), functional connection between bone and implants, is considered as a pivotal process of cementless implant fixation and integration, respectively. OI is affected by various factors of which the property of implants is of high significance. The modification of implants surface for better OI has raised increasing attention in modern orthopedic medicine. Here, the process of OI and the interactions between implants and ambient bone tissues were emblazed. The knowledge regarding the contemporary surface modification strategies was systematically analyzed and reviewed, including materials used for the fabrication of implants, advanced modification techniques, and key factors in the design of porous implants structure. We discussed the superiority of current surface modification programs and concluded that the problems remain to be solved. The primary intention of this systematic review is to provide comprehensive reference information and an extensive overview for better fabrication and design of orthopedic implants.
miR‐22‐3p enhances the intrinsic regenerative abilities of primary sensory neurons via the CBL/p‐EGFR/p‐STAT3/GAP43/p‐GAP43 axis
Authors: Li Bo , Wang Zhijie , Yu Mei , Wang Xu , Wang Xin , Chen Chuanjie , Zhang Zheng , Zhang Meiling , Sun Chao , Zhao Chenxi , Li Qiang , Wang Wei , Wang Tianyi , Zhang Liang , Ning Guangzhi , Feng Shiqing 
Published: October 2019

AbstractSpinal cord injury (SCI) is a devastating disease. Strategies that enhance the intrinsic regenerative ability are very important for the recovery of SCI to radically prevent the occurrence of sensory disorders. Epidermal growth factor (EGF) showed a limited effect on the growth of primary sensory neuron neurites due to the degradation of phosphorylated‐epidermal growth factor receptor (p‐EGFR) in a manner dependent on Casitas B‐lineage lymphoma (CBL) (an E3 ubiquitin‐protein ligase). MiR‐22‐3p predicted from four databases could target CBL to inhibit the expression of CBL, increase p‐EGFR levels and neurites length via STAT3/GAP43 pathway rather than Erk1/2 axis. EGF, EGFR, and miR‐22‐3p were downregulated sharply after injury. In vivo miR‐22‐3p Agomir application could regulate CBL/p‐EGFR/p‐STAT3/GAP43/p‐GAP43 axis, and restore spinal cord sensory conductive function. This study clarified the mechanism of the limited promotion effect of EGF on adult primary sensory neuron neurite and targeting miR‐22‐3p could be a novel strategy to treat sensory dysfunction after SCI.
A prognostic eight‐lncRNA expression signature in predicting recurrence of ER‐positive breast cancer receiving endocrine therapy
Authors: Tang Jianing , Cui Qiuxia , Zhang Dan , Kong Deguang , Liao Xing , Ren Jiangbo , Gong Yan , Wu Gaosong 
Published: October 2019

AbstractLong noncoding RNAs (lncRNAs) have the main role in the tumorigenesis of breast cancer. In the present study, lncRNA expression profiling was collected to identify a lncRNA expression signature from the Gene Expression Omnibus database. An eight‐lncRNA signature was established to predict the survival of patients with estrogen receptor (ER)‐positive breast cancer receiving endocrine therapy. Patients were separated into a low‐risk group and a high‐risk group based on this signature. Patients in high‐risk group have worse survival compared to those in low‐risk group using Kaplan–Meier curve analysis with log‐rank test. Receiver operating characteristic analysis suggested good diagnostic efficiency of the eight‐lncRNA signature. When adjusting the clinical features, including age, grade, lymph node status, and tumor size, this signature was independently associated with the relapse‐free survival. The prognostic value of the lncRNA prognostic model was then validated in validation sets. When validated in a cohort of patients treated with neoadjuvant chemotherapy and endocrine therapy, this signature demonstrated good performance as well. Besides, we have built a nomogram that integrated the conventional clinicopathological features and the eight‐lncRNA‐based signature. To sum up, our results indicated that the eight‐lncRNA prognostic model was a reliable tool to group patients at high and low risk of disease relapse. This signature may have possible implication in prognostic evaluations of patients with ER‐positive breast cancer receiving endocrine therapy.
Combined effects of avasimibe immunotherapy, doxorubicin chemotherapy, and metal–organic frameworks nanoparticles on breast cancer
Authors: Lei Jun , Wang Hongjian , Zhu Daoming , Wan Yibin , Yin Lei 
Published: October 2019

AbstractCD8+ T cells play a vital role in cancer immunotherapy and can be shaped by metabolism. Avasimibe is an acyl coenzyme A‐cholesterol acyltransferase (ACAT) inhibitor, which has been clinically verified safe in other phase Ⅲ clinical trials. It can potentiate the killing function of CD8+ T cells by modulating cholesterol metabolism. Doxorubicin (DOX) is an anticancer drug widely used in many cancers to induce tumor cell apoptosis. Unfortunately, DOX also can induce toxic and side effects in many organs, compromising its usage and efficacy. Herein, we report the combinational usage of avasimibe and a safe pH sensitive nano‐drug delivery system composing of DOX and metal–organic frameworks nanoparticles (MNPs). Our findings demonstrated that DOX–MNPs treatment inhibited tumor growth with good safety profile and avasimibe treatment combined DOX–MNPs treatment exhibited a better efficacy than monotherapies in 4T1 breast cancer therapy.
Outer membrane vesicles enhance tau phosphorylation and contribute to cognitive impairment
Authors: Wei Shouchao , Peng Wanjuan , Mai Yingren , Li Kanglan , Wei Wei , Hu Li , Zhu Shaoping , Zhou Haihong , Jie Wanxin , Wei Zhuangsheng , Kang Chenyao , Li Ruikai , Liu Zhou , Zhao Bin , Cai Zhiyou 
Published: October 2019

AbstractOuter membrane vesicles (OMVs) are nanosized vesicles produced by the gut microbiota (GM). The GM is well‐known to be involved in the pathological process of Alzheimer's disease (AD). However, the mechanism of OMVs is not clear. In the present study, we demonstrated the involvement of OMVs in the development of cognitive (learning and memory) dysfunction induced by blood–brain barrier (BBB) disruption. More important, further study showed that OMVs induced tau phosphorylation by activating glycogen synthase kinase 3β (GSK‐3β) in the hippocampus. OMVs activated astrocytes and microglia, increased secretion of inflammatory cytokines (nuclear factor κB, interleukin‐1β, and tumour necrosis factor‐α) in the hippocampus. Therefore, OMVs increase the permeability of the BBB and promote the activation of astrocytes and microglia, inducing an inflammatory response and tau hyperphosphorylation by activating the GSK‐3β pathway and finally leading to cognitive impairment.
MiR‐34a inhibits the proliferation, migration, and invasion of oral squamous cell carcinoma by directly targeting SATB2
Authors: Ge Xin , Gao Jie , Sun Qiu‐Wangyue , Wang Chen‐Xing , Deng Wei , Mao Guang‐Yan , Li Huai‐Qi , Guo Song‐Song , Cheng Jie , Wu Yu‐Nong , Ye Jin‐Hai 
Published: October 2019

AbstractIn various kinds of carcinomas, the special AT‐rich sequence‐binding protein 2 (SATB2) with its atypical expression promotes the metastasis and progression of the tumor, though in the oral squamous cell carcinoma (OSCC) its inherent mechanism and the status of SATB2 remain unclear. The role played by the SATB2 expression in the OSCC cell lines and tissue samples in the target of miR‐34a downstream is the intended endeavor of this study. In te OSCCs the miR‐34a expression was determined by quantitative real‐time polymerase chain reaction (q‐PCR), while the SATB2 expression in the cell lines and tissue samples in OSCC was analyzed with the q‐PCR and the western blot. Studies in both in vitro and in vivo of the effects of miR‐34a on the initiation of OSCC were conducted. As a direct target of the miR‐34a the SATB2 was verified with the luciferase reporter assay. In cases where the miR‐34a levels were low, the SATB2 in OSCCs seemed to be overexpressed. Besides, both in the in vitro and in vivo a suppression of migration, invasion, and cell growth was caused by miR‐34a by down regulating the SATB2 expression. The SATB2 being a direct target of miR‐34a was confirmed by the cotransfection of miR‐34a mimics specifically the decrease in the expression of luciferase of SATB2–3′UTR‐wt reporter. As a whole, our study confirmed the inhibition of miR‐34a in the invasion, proliferation, and migration of the OSCCs, playing a potential tumor suppressor role with SATB2 as its downstream target.
Focal adhesion kinase promotes BMP2‐induced osteogenic differentiation of human urinary stem cells via AMPK and Wnt signaling pathways
Authors: Sun Xingwei , Zheng Weiwei , Qian Chen , Wu Qin , Hao Yuefeng , Lu Guohai 
Published: October 2019

AbstractHuman urine‐derived stem cells (hUSCs) serve as favorable candidates for bone transplants due to their efficient proliferative and multipotent differentiation abilities, as well as the capacity to secrete a variety of vasoactive agents to facilitate tissue engineering. The present study aimed to explore the role of focal adhesion kinase (FAK) in bone morphogenetic protein 2 (BMP2)‐induced osteogenic differentiation of hUSCs and to investigate the underlying mechanism. The degree of osteogenic differentiation and the correlated signals, following BMP2 overexpression and siRNA‐mediated silencing of FAK, were determined in vitro. Moreover, hUSCs induced bone formation in a rat model with cranial defects, in vivo. Our findings revealed that alkaline phosphatase production, calcium deposits, osteocalcin and osteopontin expression, and bone formation were upregulated in vitro and in vivo following BMP2‐induced osteogenic differentiation, and AMPK and Wnt signaling pathway activation by FAK could effectively regulate BMP2‐enhanced osteogenic differentiation of hUSCs. Taken together, these findings indicated that FAK could mediate BMP2‐enhanced osteogenic differentiation of hUSCs through activating adenosine 5’‐monophosphate‐activated protein kinase and Wnt signaling pathways.
Comparison of pan‐ethnic and ethnic‐based carrier screening panels for individuals of Ashkenazi Jewish descent
Authors: Rosenblum Lynne S. , Zhu Hui , Zhou Zhaoqing , Teicher Jennifer , Heim Ruth A. , Leach Natalia T. 
Published: October 2019

AbstractThe intent of carrier screening is to identify individuals at risk for having a child with a genetic disorder. American College of Medical Genetics and Genomics (ACMG) guidelines currently recommend that individuals of Ashkenazi Jewish (AJ) descent be screened for carrier status for nine disorders. However, a joint statement from five professional organizations acknowledges benefits of expanded carrier screening and this is becoming common practice. To better understand the impact of expanded carrier screening for the AJ population, we performed a retrospective analysis comparing detection rates for AJ individuals screened by two targeted panels: a pan‐ethnic panel comprising 87 disorders and an AJ panel comprising an 18‐disorder subset of the pan‐ethnic panel. We also extrapolated the detection rates for the 18 AJ disorders from the pan‐ethnic panel data and for the nine ACMG‐recommended disorders using data from both panels. We found that with the pan‐ethnic panel 431/1150 (37.5%) individuals were carriers of at least one disorder, compared to 319/1248 (25.6%) individuals with the AJ panel. If the pan‐ethnic panel cohort were tested in the AJ panel or for the nine ACMG‐recommended disorders, the detection rates would have been 280/1150 (24.3%) and 207/1150 (18.0%) respectively. Therefore, the pan‐ethnic expanded carrier screening panel of 87 disorders increased the carrier detection rate in AJ individuals by approximately 50% and 100%, respectively, compared with a panel of 18 disorders considered relevant to the AJ population and the ACMG‐recommended disorders. Twenty disorders accounted for the difference in carrier detection rates between the pan‐ethnic and AJ panels. Of these, three were among the 10 most commonly identified disorders. Our findings reinforce published data that targeted AJ panels are less effective than a pan‐ethnic panel in carrier detection among AJ individuals and provide metrics to address the impact of expanded carrier screening in this population.
Does Gadoterate Meglumine Cause Gadolinium Retention in the Brain of Children? A Case–Control Study
Authors: Topcuoglu Elif Dilara , Topcuoglu Osman Melih , Semiz Oysu Aslihan , Bukte Yasar 
Published: October 2019

BackgroundAccumulation of macrocyclic gadolinium agents in children's brains remain to be determined.PurposeTo demonstrate whether there is an intracranial macrocyclic gadolinium deposition after multiple contrast‐enhanced MRI with gadoterate meglumine in a pediatric population.Study TypeRetrospective case–control.PopulationIn all, 45 children (age range: 5–17 years; mean, 13.7 ± 3.4 years) for the study group and 45 healthy children (age range: 5–17 years; mean, 13.7 ± 3.4 years) for the control group.Field Strength/SequenceT1‐ and T2‐weighted axial images on a 1.5T scanner.AssessmentChildren with at least three enhanced brain MRIs and an age‐ and sex‐matched control group with an unenhanced brain MRIs were compared in terms of T1 signal intensity (SI). All patients in the study group received gadoterate meglumine intravenously (0.1 mmol/kg). SI measurements were made by drawing six regions of interest (ROIs): dentate nuclei (DN), pons, globus pallidi (GP), frontal white matter (FWM), thalamus (T), clivus, and cerebrospinal fluid (CSF) for both groups on unenhanced T1‐weighted images.Statistical TestsStudent's t‐test was used for comparison of SI. The Pearson correlation was calculated for the correlation between the SI and the number of gadolinium administrations.ResultsA significant difference was detected between two groups for DN/CSF, pons/CSF, GP/CSF, thalamus/CSF, and FWM/CSF (P < 0.001, P < 0.001, P = 0.002, P = 0.002, P = 0.024, respectively). There was no significant difference between the two groups for clivus/CSF (P = 0.15). A good correlation between the number of gadoterate meglumine administrations and the SI for DN/CSF, pons/CSF, GP/CSF, and T/CSF (r = 0.80, r = 0.73, r = 0.91, and r = 0.90, respectively) was found.Data ConclusionA significant T1 SI increase reflecting gadolinium retention in the brain was detected for children with at least three gadoterate meglumine administrations in this series. The number of administrations correlated well with the increased SI.Level of Evidence: 3Technical Efficacy Stage: 5J. Magn. Reson. Imaging 2020;51:1471–1477.