bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overexpressed cold inducible RNA-binding protein improves cell viability and EGF expression in glial cells
Authors: Liu Aijun , Li Shouchun , Zhang Haitao , Jiao Yongcheng , Kong Haibo , Zhang Zhiwen 
Published: August 2022

Abstract
Background: Cold inducible RNA-binding protein (CIRP) is key protein in the hypothermic therapy. Highly expressed CIRP exerts a neuroprotective effect on neurons. The aim of this study is to provide the evidence of the protective effects of CIRP on the glial cells and try to explore the underlying mechanisms. Results: The results of this study demonstrated that the cell viability of the glial cells with CIRP overexpression was increased significantly compared to the control cells. With CIRP overexpression, the EGF mRNA expression was found increasing significantly and the mRNA expression of BDNF, bcl-2, VEGF and NGF were not upregulated compared to the control. EGF and CIRP co-expression was demonstrated on the glial cells. With CIRP expression, EGF expression on the glial cells was increased statistically compared to the control.Conclusions: CIRP overexpression increases the cell viability of the glial cells, exerting a neuroprotective effect. EGF expression is activated on the glial cells with CIRP overexpression, implying a pathway of CIRP neuroprotection via EGF activation.
Salt-inducible kinase 1-CREB-regulated transcription coactivator 1 signalling in the paraventricular nucleus of the hypothalamus plays a role in depression by regulating the hypothalamic–pituitary–adrenal axis
Authors: Jiang Bo , Wang Yuan , Liu Ling , Gu Jiang-Hong , Wang Cheng-Niu , Guan Wei , Liu Yue , Tang Wen-Qian , Ji Chun-Hui , Chen Yan-Mei , Huang Jie , Li Wei-Yu , Shi Tian-Shun , Chen Wei-Jia , Zhu Bao-Lun 
Published: August 2022

Abstract
Elucidating the molecular mechanism underlying the hyperactivity of the hypothalamic–pituitary–adrenal axis during chronic stress is critical for understanding depression and treating depression. The secretion of corticotropin-releasing hormone (CRH) from neurons in the paraventricular nucleus (PVN) of the hypothalamus is controlled by salt-inducible kinases (SIKs) and CREB-regulated transcription co-activators (CRTCs). We hypothesized that the SIK-CRTC system in the PVN might contribute to the pathogenesis of depression. Thus, the present study employed chronic social defeat stress (CSDS) and chronic unpredictable mild stress (CUMS) models of depression, various behavioral tests, virus-mediated gene transfer, enzyme linked immunosorbent assay, western blotting, co-immunoprecipitation, quantitative real-time reverse transcription polymerase chain reaction, and immunofluorescence to investigate this connection. Our results revealed that both CSDS and CUMS induced significant changes in SIK1-CRTC1 signaling in PVN neurons. Both genetic knockdown of SIK1 and genetic overexpression of CRTC1 in the PVN simulated chronic stress, producing a depression-like phenotype in naïve mice, and the CRTC1-CREB-CRH pathway mediates the pro-depressant actions induced by SIK1 knockdown in the PVN. In contrast, both genetic overexpression of SIK1 and genetic knockdown of CRTC1 in the PVN protected against CSDS and CUMS, leading to antidepressant-like effects in mice. Moreover, stereotactic infusion of TAT-SIK1 into the PVN also produced beneficial effects against chronic stress. Furthermore, the SIK1-CRTC1 system in the PVN played a role in the antidepressant actions of fluoxetine, paroxetine, venlafaxine, and duloxetine. Collectively, SIK1 and CRTC1 in PVN neurons are closely involved in depression neurobiology, and they could be viable targets for novel antidepressants.
Integrin beta1 (ITGB1) as a prognostic marker in esophageal adenocarcinoma
Authors: Damanakis Alexander I. , Wahler Isabell , Fuchs Hans , Löser Heike , Schröder Wolfgang , Zander Thomas , Chon Seung , Bruns Christiane , Quaas Alexander , Gebauer Florian 
Published: August 2022

Abstract
Background: Today, individual prognosis in patients with adenocarcinoma of the esophagus (EAC) is based on post-surgical TNM staging and valid biomarkers are still not implemented. Integrin beta1 (ITGB1) is widely expressed in epithelial cells and promotes cell adhesion and growth. Its impact on tumor progression was described for different tumor entities before, data on its function as biomarker in EAC has not been described. Aim of the study is to evaluate the expression level of ITGB1 in a very large collective of EAC and its impact on individual patients´ prognosis.Methods: 685 patients with esophageal adenocarcinoma were analyzed immunohistochemically for ITGB1. The data was correlated with long term outcome, clinical, pathological and molecular data (TP53, HER2/neu, c-myc, GATA6, PIK3CA and KRAS).Results: Of 640 patients to be analyzed, 127 (19.8%) showed expression of ITGB1. ITGB1 expression was associated with lymph node metastasis, expression of integrin alphaV and KRAS mutation status. Patients with high ITGB1 expression showed impaired overall survival (22.5 months (95%CI: 15.3 – 29.7 months), vs. 34.1 months (95%CI: 25.3 – 42.4 months, P = 0.024). This effect was particularly evident in the group of patients undergoing primary surgery without prior neoadjuvant therapy (10.2 months (95%CI 1.9 – 41.7 months) vs. 31.4 months (95%CI: 21.1 – 144.2 months, p = 0.008). ITGB1 acts here as an independent prognostic marker in multivariable analysis.Conclusion: We demonstrate for the first time the prognostic significance of ITGB1 expression in a large EAC patient population. ITGB1 apparently influences tumor progression in EAC and is associated with a poor prognosis.
Comparative site-specific N-glycoproteome analysis reveals aberrant N-glycosylation and
gives new insights into mannose-6-phosphate pathway in cancer
Authors: Chen Minyong , Assis Diego , Benet Matthieu , McClung Colleen , Gordon Elizabeth , Ghose Shourjo , Dupard Steven , Willetts Matthew , Taron Christopher , Samuelson James 
Published: August 2022

Abstract
N-glycosylation is implicated in cancers and aberrant N-glycosylation is recognized as a hallmark of cancer. Here, we mapped and compared the site-specific N-glycoproteomes of colon cancer HCT116 cells and isogenic non-tumorigenic DNMT1/3b double knockout (DKO1) cells using Fbs1-GYR N-glycopeptide enrichment technology and trapped ion mobility spectrometry. Many significant changes in site-specific N-glycosylation were revealed, providing a molecular basis for further elucidation of the role of N-glycosylation in protein function. HCT116 cells display hypersialylation especially in cell surface membrane proteins. Both HCT116 and DKO1 show an abundance of paucimannose and 80% of paucimannose-rich proteins are annotated to reside in exosomes. The most striking N-glycosylation alteration was the degree of mannose-6-phosphate (M6P) modification. N-glycoproteomic analyses revealed that HCT116 displays hyper-M6P modification, which was orthogonally validated by M6P immunodetection. Significant observed differences in N-glycosylation patterns of the major M6P receptor, CI-MPR in HCT116 and DKO1 may contribute to the hyper-M6P phenotype of HCT116 cells. This comparative site-specific N-glycoproteome analysis provides a pool of potential N-glycosylation-related cancer biomarkers, but also gives new insights into the M6P pathway in cancer.
The effect of cycles of genomic selection on the wheat (T. aestivum) genome
Authors: Blanco Nelly Arguello , Sneller Clay 
Published: August 2022

Abstract
Genomic selection (GS) is widely used in plant breeders to shorten breeding cycles. Our objective was to assess the impact of rapid cycling GS on the wheat genome We used 3927 markers to genotype a training population (YTP) and individuals from five cycles (YC1-YC5) of GS for grain yield. We assessed changes of allele frequency, genetic distance, population structure, and linkage disequilibrium (LD). We found 27.3% of all markers had a significant allele frequency change by YC5, 18% experienced a significant change attributed to selection, and 9.3% had a significant change due to either drift or selection. A total of 725 of 3927 markers were fixed by YC5 with selection fixing 7.3% of the 725 markers. The genetic distance between cycles increased over time. The Fst value of 0.224 between YTP and YC5 indicates their relationship was low. The correlation between LD matrices and the number of LD blocks decreased over time. Overall, we found reduction in genetic diversity, increased genetic differentiation of cycles from the training population, and restructuring of the LD patterns over cycles. The accuracy of GS depends on the genomic similarity of the training population and the prediction populations. Our results show that similarity can decline rapidly over cycles of GS and seriously compromise the predictive ability of the YTP-based model. Our results support implementing a GS scheme where the training and prediction populations co-evolve instead of the use of a static training population.
Subjective Feelings associated with Expectations and Rewards during Risky Decision-making in Impulse Control Disorder
Authors: Liebenow Brittany , Jiang Angela , DiMarco Emily , Sands Lester , Moya-Mendez Mary , Laxton Adrian , Siddiqui Mustafa , Haq Ihtsham , Kishida Kenneth 
Published: August 2022

Abstract
Impulse Control Disorder (ICD) in Parkinson’s disease is a behavioral addiction induced by dopaminergic therapies, but otherwise unclear cognitive etiology. The current study investigates the influence of objective reward processing variables, dopaminergic therapy, and risky decision-making on ‘subjective feelings’ in patients with versus without ICD. Patients with (n = 18) and without (n = 12) a history of ICD secondary to Parkinson’s disease performed a risky decision-making task (on and off standard-of-care dopaminergic therapies). During the task, participants choose a ‘gamble’ or a ‘certain reward’ and report how they feel about decision outcomes. The subjective feeling of ‘pleasure’ is driven by different aspects of reward processing in patients with, versus without, a history of ICD. While off-medication, expectations about risky-decisions have a negative influence on subjective feelings in patients with a history of ICD versus a positive influence in patients without ICD. While on-medication, the influence of reward processing variables and recent experience on modulating subjective feelings in both patient groups are altered; patients with ICD become more emotionally reactive, whereas patients without ICD become less emotionally reactive. Computational modeling of risky decision-making behavior reveals latent factors that drive subjective feelings and risky behaviors in patients with versus without a history of ICD. Group differences are observed in off-medication states. Changes are induced in both groups with medication suggesting ICD-related decision-making may be driven by mechanisms associated with emotion regulation and that heightened dopaminergic processes may induce more reactive, less stable, emotion regulation in patients predisposed to developing ICD.
Geometry in CIELAB color space for protonation of pH indicators
Authors: Suzuki Takayuki , Kitano Karen , Ito Chihiro , Yamaguchi Tomohiro 
Published: August 2022

Abstract
Ultraviolet-visible spectroscopy provides color information on organic compounds during chemical reactions. Absorption spectra of a pH indicator during protonation show absorption bands from electronic transitions based on molecular structure. Information from the bands including the wavelength of maximum absorption and calculated molar extinction coefficient can provide specific parameters for the reactant (the indicator) and the product (the protonated indicator). However, these parameters never directly present what chemical reaction is occurring, which is typically only determined after identification of the compounds with other characterization methods. Here, we show that a geometric object, which was built out of the loci of chromaticity points for a polymer pH-indicator in CIELAB color space, indicates that the reaction is protonation. The object contains information about species, i.e., the pH-indicating portion and its protonated form. Each locus for different initial concentrations was a line segment, which corresponded to the protonation process. The segments for a polymer pH indicator with azobenzene as the pH-indicating dye portion at different initial concentrations created a planar triangle in CIELAB color space. For another polymer pH indicator of nitrophenol, the geometric space was a half line. The corresponding geometric equations may be specific to protonation including information about the chemical species.
C5L2 modulates BDNF production in human dental pulp stem cells via p38α pathway under LPS-induced inflammation
Authors: Irfan Muhammad , Chung Seung 
Published: August 2022

Abstract
Tissue injury affects nerve fibers and triggers an immune response, leading to inflammation. The complement system gets activated during inflammatory conditions and has been reported to be involved in the regeneration process. We have demonstrated that the C5a receptor (C5aR) has crucial roles in regeneration and healing processes including nerve sprouting and hard tissue formation. Another C5a-like 2 receptor (C5L2) has been cloned which is still considered controversial due to limited studies. We previously established that C5L2 regulates BDNF secretion in pulp fibroblasts. However, there is no study available on human dental pulp stem cells (DPSCs), especially in the inflammatory context. Stem cell therapy is an incipient technique to treat and prevent several diseases, while DPSCs are an emerging option to be considered due to their great ability to differentiate into a variety of cells and secrete nerve regeneration factors. Here, we demonstrated that C5L2 modulates brain-derived neurotropic factor (BDNF) secretion in DPSCs. Our results stated that C5L2 silencing through siRNA can increase the BDNF production which could accelerate the nerve regeneration process. Moreover, stimulation with lipopolysaccharide (LPS) enhanced BDNF production in C5L2 silenced DPSCs. Finally, we quantified BDNF secretion in supernatant and cell lysates using ELISA. Our results showed enhanced BDNF production in C5L2 silenced DPSCs and hampered by the p38MAPKα inhibitor. Taken together, our data reveal that C5L2 modulates BDNF production in DPSCs via the p38MAPKα pathway.
Metoprolol Exhibits Discrete Pharmacokinetics Using Various Sites of Sample Collection after Single Oral Dose Administration of Metoprolol Tartrate in SD Rats
Authors: Yesh Yeshwant Singh , Tiwari Sudhir K Tiwari , Prat Pratima Srivastava , Deepti Deepti Sahu , Ravi Ravi A Reddy , giri Giridhar Bilagi , Theertha Theertha Thykandy 
Published: August 2022

Abstract
The aim of the study was to investigate the influences of various routes of sampling on the pharmacokinetics profile metoprolol after single oral dose administration of metoprolol tartrate in rats. For this single dose parallel studies were conducted in SD rats at 5 mg/kg of metoprolol tartrate. In our investigation, significant differences were observed in the plasma PK profile of metoprolol using various routes of sample collection. The mean peak plasma metoprolol concentration obtained from jugular (Cmax; 170.0 ng/mL) and saphenous (Cmax; 113.2 ng/mL) routes were comparable. Similarly, retro-orbital route Cmax (50.0 ng/mL) was comparable with Cmax (76.2 ng/mL) of femoral route. In contrast, the Cmax (39.3 ng/mL) obtained from tail vein sampling route was significantly different (p ≤ 0.05) from all other sampling sites. The Cmax obtained from tail vein sampling site was approximately 2–4 folds less compared to other routes of sampling except for retro-orbital sampling site. Corresponding differences were also observed for other PK parameters. It was concluded that the sampling sites have profound impact on the PK parameters of metoprolol after single dose oral administration in rats.
Molecular surveillance of dihydroartemisinin-piperaquine resistance in northwestern Thailand
Authors: Win Khine Nwe , Manopwisedjaroen Khajohnpong , Phumchuea Kanit , Suansomjit Chayanut , Chotivanich Kesinee , Lawpoolsri Saranath , Cui Liwang , Sattabongkot Jetsumon , Nguitragool Wang 
Published: August 2022

Abstract
Background: Dihydroartemisinin-piperaquine (DHA-PPQ) combination therapy is the current first-line treatment for Plasmodium falciparum malaria in Thailand. Since its introduction in 2015, resistance to this drug combination has emerged in the eastern part of the Greater Mekong Subregion including the eastern part of Thailand near Cambodia. Our aim is to assess whether the resistance genotypes have arisen the western part of country.Methods: Fifty-seven P. falciparum-infected blood samples were collected in Tak province of northwestern Thailand between 2013 and 2019. Resistance to DHA was examined through the single nucleotide polymorphisms (SNPs) of kelch13. PPQ resistance was examined through the copy number plasmepsin-2 and the SNPs of Pfcrt.Results:Among the samples whose kelch13 were successfully sequenced, approximately half (31/55; 56%) had mutation associated with artemisinin resistance, including G533S (23/55; 42%), C580Y (6/55; 11%), and G538V (2/55; 4%). During the study period, G533S mutation appeared and increased from 20% (4/20) in 2014 to 100% (9/9) in 2019. No plasmepsin-2 gene amplification was observed, but one sample (1/54) had the Pfcrt F145I mutation previously implicated in PPQ resistance.Conclusions: Kelch13 mutation was common in Tak Province in 2013-2019. A new mutation G533S emerged in 2014 and rose to dominance, possibly fixation, in 2019. PPQ resistance marker Pfcrt F145I was also detected in 2019. Continued surveillance of treatment efficacy and drug resistance markers is warranted.
Deciphering the involvement of the Hippo pathway co-regulators, YAP/TAZ in invadopodia formation and matrix degradation
Authors: Venghateri Jubina , Dassa Bareket , Morgenstern David , Shreberk-Shaked Michal , Oren Moshe , Geiger Benjamin 
Published: August 2022

Abstract
Invadopodia are adhesive, actin-rich protrusions formed by metastatic cancer cells that degrade the extracellular matrix and facilitate invasion. They support the metastatic cascade by a spatially and temporally coordinated process whereby invading cells bind to the matrix, degrade it by specific metalloproteinases, and mechanically penetrate diverse tissue barriers by forming actin-rich extensions. However, despite the apparent involvement of invadopodia in the metastatic process, the molecular mechanisms that regulate invadopodia formation and function are still largely unclear. In this study, we have explored the involvement of the key Hippo pathway co-regulators, namely YAP, and TAZ, in invadopodia formation and matrix degradation. Towards that goal, we tested the effect of depletion of YAP, TAZ, or both on invadopodia formation and activity in multiple human cancer cell lines. We report that knockdown of YAP and TAZ or their inhibition by verteporfin induces a significant elevation in matrix degradation and invadopodia formation in several cancer cell lines. Conversely, overexpression of these proteins strongly suppresses invadopodia formation and matrix degradation. Proteomic and transcriptomic profiling of MDA-MB-231 cells, following co-knockdown of YAP and TAZ, revealed a significant change in the levels of key invadopodia-associated proteins, including the crucial proteins Tks5 and MT1-MMP (MMP14). Collectively, our findings show that YAP and TAZ act as negative regulators of invadopodia formation in diverse cancer lines, most likely by reducing the levels of essential invadopodia components. Dissecting the molecular mechanisms of invadopodia formation in cancer invasion may eventually reveal novel targets for therapeutic applications against invasive cancer.
Tracing the century-long evolution of microplastics deposited in cold seep
Authors: Feng Jing-Chun , Li Can-Rong , Tang Li , Wu Xiao-Nan , Wang Yi , Yang Zhifeng , Yuan Weiyu , Sun Liwei , Hu Weiqiang , Zhang Si 
Published: August 2022

Abstract
Microplastic (MP) pollution is one of the greatest threats to marine ecosystems. The deep sea is regarded as a hotspot for MP accumulation, but how do deposited MPs evolve from a long-term perspective? In particular, the occurrence features of MPs in cold seeps, which are characterized by methane-rich fluid seepage fueling one of the richest ecosystems on the seafloor, are unclear. Here, we demonstrated how MPs have been deposited in the Haima cold seep since the invention of plastics. We found that the burial rate of MPs exponentially increased since the massive global use of plastics in the 1930s, and this cold seep accommodates more MPs than do coastal areas. Upwelling fluid seepage facilitated the fragmentation and degradation behaviors of MPs. More MP-degrading microorganism populations and functional genes were discovered in methane seepage areas. Our findings illuminated the need to determine fundamental strategies for sustainable marine plastic pollution mitigation in the natural deep-sea environment.
The effect of shame on prosocial behavior toward a stranger
Authors: Li Saiqi , Wang Liusheng 
Published: August 2022

Abstract
Background: This study aimed to examine the effect of different types of shame on prosocial behavior to different help-seekers. Methods: A total of 120 participants were randomly assigned to a neutral mood condition, a public shame or a private shame conditions. Results: All participants rated their willingness to help a benefactor and a stranger in an everyday helping situation and a money-donating situation after emotion-inducement. The study found a higher willingness of participants in public shame group to help strangers than those in neutral mood and private shame groups. Conclusion: These findings support a facilitation effect of public shame on prosocial behavior toward strangers, indicating an effect of restoring motive of shame on social interaction. The results are further discussed in light of functionalism of shame.
Andrographolide exerts anti-respiratory syncytial virus activity by up-regulating heme oxygenase-1 independent of interferon responses in human airway epithelial cells
Authors: Che Siyi , Zhou Na , Liu Ying , Xie Jun , Liu Enmei 
Published: August 2022

Abstract
Background: Respiratory syncytial virus (RSV), the leading cause of mortality and morbidity in children under the age of five, is still lacking in safe and effective vaccines and antiviral agents for clinical use. Andrographolide exerts antiviral functions against a variety of viruses, but whether (and how) it exerts antiviral effects on RSV remains unclear.Methods and results: In vitro RSV infection models using A549 and 16HBE cell lines were established, and the effect of andrographolide on RSV was analyzed via RSV N gene load and proinflammatory levels. The RNA transcriptome was sequenced and data were analyzed by R software. Lentivirus was transfected to knockdown the expression of HO-1. Results showed andrographolide suppressed RSV replication and attenuated subsequent inflammation. RNA sequencing indicated that the hub gene heme oxygenase-1 (HO-1) may play a pivotal role in the anti-RSV effects of andrographolide. Furthermore, results verified that andrographolide exert antiviral effects against RSV partially by inducing HO-1, but did not activate the antiviral interferon response. Conclusion: Our findings demonstrated that andrographolide exerted anti-RSV activity by up-regulating HO-1 in human airway epithelial cells, which may provide novel insights into potential therapeutic targets and drug repurposing in RSV infection.