bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin-like growth factor 2 hypermethylation in peripheral blood leukocytes and colorectal cancer risk and prognosis: a propensity score analysis
Authors: Sun HongRu , Liu YanLong , Zhang YuXue , Wang Yibaina , Zhao YaShuang , Liu YuPeng 
Published: May 2023

BackgroundTo comprehensively assess and validate the associations between insulin-like growth factor 2 (IGF2) gene methylation in peripheral blood leukocytes (PBLs) and colorectal cancer (CRC) risk and prognosis.MethodsThe association between IGF2 methylation in PBLs and CRC risk was initially evaluated in a case-control study and then validated in a nested case-control study and a twins’ case-control study, respectively. Meanwhile, an initial CRC patient cohort was used to assess the effect of IGF2 methylation on CRC prognosis and then the finding was validated in the EPIC-Italy CRC cohort and TCGA datasets. A propensity score (PS) analysis was performed to control for confounders, and extensive sensitivity analyses were performed to assess the robustness of our findings.ResultsPBL IGF2 hypermethylation was associated with an increased risk of CRC in the initial study (ORPS-adjusted, 2.57, 95% CI: 1.65 to 4.03, P&lt;0.0001), and this association was validated using two independent external datasets (ORPS-adjusted, 2.21, 95% CI: 1.28 to 3.81, P=0.0042 and ORPS-adjusted, 10.65, 95% CI: 1.26 to 89.71, P=0.0295, respectively). CRC patients with IGF2 hypermethylation in PBLs had significantly improved overall survival compared to those patients with IGF2 hypomethylation (HRPS-adjusted, 0.47, 95% CI: 0.29 to 0.76, P=0.0019). The prognostic signature was also observed in the EPIC-Italy CRC cohort, although the HR did not reach statistical significance (HRPS-adjusted, 0.69, 95% CI: 0.37 to 1.27, P=0.2359).ConclusionsIGF2 hypermethylation may serve as a potential blood-based predictive biomarker for the identification of individuals at high risk of developing CRC and for CRC prognosis.
Analysis and comparisons of gene expression changes in patient- derived neurons from ROHHAD, CCHS, and PWS
Authors: Victor A. Kaitlyn , Hedgecock Tayler , Donaldson Martin , Johnson Daniel , Rand Casey M. , Weese-Mayer Debra E. , Reiter Lawrence T. 
Published: May 2023

BackgroundRapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is an ultra-rare neurocristopathy with no known genetic or environmental etiology. Rapid-onset obesity over a 3–12 month period with onset between ages 1.5–7 years of age is followed by an unfolding constellation of symptoms including severe hypoventilation that can lead to cardiorespiratory arrest in previously healthy children if not identified early and intervention provided. Congenital Central Hypoventilation syndrome (CCHS) and Prader-Willi syndrome (PWS) have overlapping clinical features with ROHHAD and known genetic etiologies. Here we compare patient neurons from three pediatric syndromes (ROHHAD, CCHS, and PWS) and neurotypical control subjects to identify molecular overlap that may explain the clinical similarities.MethodsDental pulp stem cells (DPSC) from neurotypical control, ROHHAD, and CCHS subjects were differentiated into neuronal cultures for RNA sequencing (RNAseq). Differential expression analysis identified transcripts variably regulated in ROHHAD and CCHS vs. neurotypical control neurons. In addition, we used previously published PWS transcript data to compare both groups to PWS patient-derived DPSC neurons. Enrichment analysis was performed on RNAseq data and downstream protein expression analysis was performed using immunoblotting.ResultsWe identified three transcripts differentially regulated in all three syndromes vs. neurotypical control subjects. Gene ontology analysis on the ROHHAD dataset revealed enrichments in several molecular pathways that may contribute to disease pathology. Importantly, we found 58 transcripts differentially expressed in both ROHHAD and CCHS patient neurons vs. control neurons. Finally, we validated transcript level changes in expression of ADORA2A, a gene encoding for an adenosine receptor, at the protein level in CCHS neurons and found variable, although significant, changes in ROHHAD neurons.ConclusionsThe molecular overlap between CCHS and ROHHAD neurons suggests that the clinical phenotypes in these syndromes likely arise from or affect similar transcriptional pathways. Further, gene ontology analysis identified enrichments in ATPase transmembrane transporters, acetylglucosaminyltransferases, and phagocytic vesicle membrane proteins that may contribute to the ROHHAD phenotype. Finally, our data imply that the rapid-onset obesity seen in both ROHHAD and PWS likely arise from different molecular mechanisms. The data presented here describes important preliminary findings that warrant further validation.
In vitro evaluation of the neuroprotective potential of Olea dioica against Aβ peptide-induced toxicity in human neuroblastoma SH-SY5Y cells
Authors: Kenchappa Pratap G. , Karthik Yalpi , Vijendra Poornima D. , Hallur Raghavendra L. S. , Khandagale Ajay S. , Pandurangan Ashok K. , Jayanna Sathisha G. , Alshehri Mohammed Ali , Alasmari Abdulrahman , Sayed Samy , Shantaram Manjula , Mushtaq Muntazir 
Published: May 2023

Alzheimer’s disease (AD) is a type of neurodegenerative disease, associated with the hastening of ROS, acetylcholinesterase (AChE) activity, and amyloid β peptides plaques in the brain. The limitations and side effects of existing synthetic drugs incline toward natural sources. In the present communication active principles of methanolic extract of Olea dioica Roxb, leaves are explored as an antioxidant, AChE inhibitor, and anti-amyloidogenic. Furthermore, neuroprotection against the amyloid beta-peptide has been studied. The bioactive principles were identified by GC-MS and LC-MS and further subjected to antioxidant (DPPH and FRAP) and neuroprotection (AChE inhibition, ThT binding, and MTT assay, DCFH-DA and lipid peroxidation (LPO) assay using neuroblastoma (SHSY-5Y) cell lines) assays. Methanolic extract of O. dioica Roxb, leaves was found to contain polyphenols and flavonoids. In vitro assays exhibited potential antioxidant and anti-AChE (˃50%) activities. ThT binding assay indicated protection against amyloid-beta aggregation. MTT assay, Aβ1-40 (10 µM) with extract increase the cell viability (˃50%) and showed significant cytotoxicity to SHSY-5Y cells. ROS level (˃25%) significantly decreased in the Aβ1-40 (10 µM) + extract (15 and 20 μM/mL) and LPO assay (˃50%) suggesting prevention of cell damage. Results advocate that O. dioica leaves are a good source of antioxidants, anti-AChE, and anti-amyloidogenic compounds which may be further evaluated as a natural medicine for the treatment of AD.
Antidepressant-like activity of a brain penetrant HCN channel inhibitor in mice
Authors: Pinares-Garcia Paulo , Spyrou James , McKenzie Chaseley E. , Forster Ian C. , Soh Ming S. , Mohamed Syazwan Erlina , Atif Mohammed , Reid Christopher A. 
Published: May 2023

Changes in Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) channel function have been linked to depressive-like traits, making them potential drug targets. However, there is currently no peer-reviewed data supporting the use of a small molecule modulator of HCN channels in depression treatment. Org 34167, a benzisoxazole derivative, has been patented for the treatment of depression and progressed to Phase I trials. In the current study, we analysed the biophysical effects of Org 34167 on HCN channels in stably transfected human embryonic kidney 293 (HEK293) cells and mouse layer V neurons using patch-clamp electrophysiology, and we utilised three high-throughput screens for depressive-like behaviour to assess the activity of Org 34167 in mice. The impact of Org 34167 on locomotion and coordination were measured by performing rotarod and ledged beam tests. Org 34167 is a broad-spectrum inhibitor of HCN channels, slowing activation and causing a hyperpolarising shift in voltage-dependence of activation. It also reduced Ih-mediated sag in mouse neurons. Org 34167 (0.5 mg/kg) reduced marble burying and increased the time spent mobile in the Porsolt swim and tail suspension tests in both male and female BALB/c mice, suggesting reduced depressive-like behaviour. Although no adverse effects were seen at 0.5 mg/kg, an increase in dose to 1 mg/kg resulted in visible tremors and impaired locomotion and coordination. These data support the premise that HCN channels are valid targets for anti-depressive drugs albeit with a narrow therapeutic index. Drugs with higher HCN subtype selectivity are needed to establish if a wider therapeutic window can be obtained.
Modeling semiconducting silicene nanostrips: electronics and THz plasmons
Authors: Tene Talia , Guevara Marco , Borja Myrian , Mendoza Salazar María José , Palacios Robalino María de Lourdes , Vacacela Gomez Cristian , Bellucci Stefano 
Published: May 2023

Silicene nanostrips (SiNSs) have garnered significant attention due to their remarkable physical properties, making them an ideal candidate for numerous electronics and plasmonics applications. Their compatibility with current semiconductor technology further enhances their potential. This study aims to investigate the electronic and plasmonic properties of SiNSs with a minimum width of 100 nm using a semi-analytical model that utilizes the carrier velocity of silicene. The carrier velocity was calculated using density functional computations and refined through the GW approximation. Our results reveal that SiNSs with widths ranging from 100 to 500 nm exhibit small bandgaps within the range of a few meV, specifically ranging from 30 to 6 meV, respectively. Furthermore, all the nanostrips analyzed in this study exhibit a q-like plasmon dispersion within the THz regime (≤ 35 THz). By varying the experimental setup or the geometric factors of the nanostrips, the associated plasmon THz frequency can be manipulated, resulting in an increase or decrease in frequency or a shift to larger momentum values. Our study serves as a fundamental starting point and a source of inspiration for future experiments, providing a foundation for confirming the results presented in this study.
Understanding development of jugular bulb stenosis in vein of galen malformations: identifying metrics of complex flow dynamics in the cerebral venous vasculature of infants
Authors: Hadad Sara , Rangwala Shivani D. , Stout Jeffrey N. , Mut Fernando , Orbach Darren B. , Cebral Juan R. , See Alfred P. 
Published: May 2023

Introduction: Computational fluid dynamics (CFD) assess biological systems based on specific boundary conditions. We propose modeling more advanced hemodynamic metrics, such as core line length (CL) and critical points which characterize complexity of flow in the context of cerebral vasculature, and specifically cerebral veins during the physiologically evolving early neonatal state of vein of Galen malformations (VOGM). CFD has not been applied to the study of arteriovenous shunting in Vein of Galen Malformations but could help illustrate the pathophysiology of this malformation.Methods: Three neonatal patients with VOGM at Boston Children’s Hospital met inclusion criteria for this study. Structural MRI data was segmented to generate a mesh of the VOGM and venous outflow. Boundary condition flow velocity was derived from PC-MR sequences with arterial and venous dual velocity encoding. The mesh and boundary conditions were applied to model the cerebral venous flow. We computed flow variables including mean wall shear stress (WSSmean), mean OSI, CL, and the mean number of critical points (nCrPointsmean) for each patient specific model. A critical point is defined as the location where the shear stress vector field is zero (stationary point) and can be used to describe complexity of flow.Results: The division of flow into the left and right venous outflow was comparable between PC-MR and CFD modeling. A high complexity recirculating flow pattern observed on PC-MR was also identified on CFD modeling. Regions of similar WSSmean and OSImean (&lt;1.3 fold) in the left and right venous outflow channels of a single patient have several-fold magnitude difference in higher order hemodynamic metrics (&gt; 3.3 fold CL, &gt; 1.7 fold nCrPointsmean). Specifically, the side which developed JBS in each model had greater nCrPointsmean compared to the jugular bulb with no stenosis (VOGM1: 4.49 vs. 2.53, VOGM2: 1.94 vs. 0, VOGM3: 1 vs. 0). Biologically, these regions had subsequently divergent development, with increased complexity of flow associating with venous stenosis. Discussion: Advanced metrics of flow complexity identified in computational models may reflect observed flow phenomena not fully characterized by primary or secondary hemodynamic parameters. These advanced metrics may indicate physiological states that impact development of jugular bulb stenosis in VOGM.
Ultrasonic evaluation of metoclopramide’s effect on gastric motility in emergency trauma patients
Authors: Lin Huan , He Jing-Jing , Cai Zhi-Shi , Lu Zhi-Wei , Lin Zhi-Jian , Lin Xian-Zhong , Huang Qiao-Wen 
Published: May 2023

Objective: The present study aimed to use bedside ultrasound to evaluate the effects of metoclopramide on gastric motility in patients being treated for trauma in the emergency department.Methods: Fifty patients underwent an ultrasound immediately after attending the emergency department of Zhang Zhou Hospital due to trauma. The patients were randomly divided into two groups: a metoclopramide group (group M, n = 25) and a normal saline group (group S, n = 25). The cross-sectional area (CSA) of the gastric antrum was measured at 0, 30, 60, 90, and 120 min (T = time). The gastric emptying rate (GER, GER=−AareaTn/AareaTn−30−1×100), GER/min (GER divided by the corresponding interval time), gastric content properties, Perlas grade at different time points, T120 gastric volume (GV), and GV per unit of body weight (GV/W) were evaluated. The risk of vomiting, reflux/aspiration, and type of anesthetic treatment were also evaluated.Results: The differences between the two groups in the CSA of the gastric antrum at each time point were statistically significant (p &lt; 0.001). The CSAs of the gastric antrum in group M were lower than those in group S, and the greatest difference between the two groups occurred at T30 (p &lt; 0.001). The differences between the two groups in GER and GER/min were also statistically significant (p &lt; 0.001); those differences in group M were higher than those in group S, and the greatest differences between the two groups occurred at T30 (p &lt; 0.001). There were no obvious change trends in the properties of the gastric contents and the Perlas grades in either group, and the differences between the two groups were not statistically significant (p = 0.97). The differences between the two groups in the GV and GV/W at T120 were statistically significant (p &lt; 0.001), as was the risk of reflux and aspiration at T120 (p &lt; 0.001).Conclusion: When metoclopramide was used in satiated emergency trauma patients, it accelerated gastric emptying within 30 min and reduced the risk of accidental reflux. However, a normal gastric emptying level was not achieved, which can be attributed to the delaying effect of trauma on gastric emptying.
Transcriptional regulations of pollen tube reception are associated with the fertility of the ginger species Zingiber zerumbet and Zingiber corallinum
Authors: Liang Shan , Hu Ming-li , Lin Hao-chuan , He Han-jun , Ning Xi-ping , Peng Pei-pei , Lu Guo-hui , Sun Shu-lan , Wang Xiao-jing , Wang Ying-qiang , Wu Hong 
Published: May 2023

Zingiber zerumbet and Zingiber corallinum are economically valuable species in the genus Zingiber. While Z. corallinum is sexually active, Z. zerumbet adopts clonal propagation, although it has the potential for sexual reproduction. It is unclear so far at which step during the sexual reproduction of Z. zerumbet inhibition occurs, and what are the regulatory mechanisms underlying this inhibition. Here, by comparing with the fertile species Z. corallinum using microscopy-based methods, we show that rare differences were observed in Z. zerumbet up to the point when the pollen tubes invaded the ovules. However, a significantly higher percentage of ovules still contained intact pollen tubes 24 h after pollination, suggesting pollen tube rupture was impaired in this species. Further RNA-seq analysis generated accordant results, showing that the transcription of ANX and FER, as well as genes for the partners in the same complexes (e.g., BUPS and LRE, respectively), and those putative peptide signals (e.g., RALF34), were timely activated in Z. corallinum, which ensured the pollen tubes being able to grow, reorient to ovules, and receipt by embryo sacs. In Z. zerumbet, genes for these complexes were cooperatively suppressed, which would result in the maintenance of PT integrity due to the disruption of RALF34-ANX/BUPS signaling in PT and the failure of PT reception by an active synergid due to the insufficiency of the synergid-harbored FER/LRE complex. Taking the results from the cytological and RNA-seq studies together, a model is proposed to illustrate the possible regulation mechanisms in Z. zerumbet and Z. corallinum, in which the regulations for pollen tube rupture and reception are proposed as the barrier for sexual reproduction in Z. zerumbet.
Exploring genetic diversity and population structure of a large grapevine (Vitis vinifera L.) germplasm collection in Türkiye
Authors: Kaya Hilal Betul , Dilli Yıldız , Oncu-Oner Tulay , Ünal Akay 
Published: May 2023

Grapevine (Vitis Vinifera L.) has been one of the significant perennial crops in widespread temperate climate regions since its domestication around 6000 years ago. Grapevine and its products, particularly wine, table grapes, and raisins, have significant economic importance not only in grapevine-growing countries but also worldwide. Grapevine cultivation in Türkiye dates back to ancient times, and Anatolia is considered one of the main grapevine migration routes around the Mediterranean basin. Turkish germplasm collection, conserved at the Turkish Viticulture Research Institutes, includes cultivars and wild relatives mainly collected in Türkiye, breeding lines, rootstock varieties, and mutants, but also cultivars of international origin. Genotyping with high-throughput markers enables the investigation of genetic diversity, population structure, and linkage disequilibrium, which are crucial for applying genomic-assisted breeding. Here, we present the results of a high-throughput genotyping-by-sequencing (GBS) study of 341 genotypes from grapevine germplasm collection at Manisa Viticulture Research Institute. A total of 272,962 high-quality single nucleotide polymorphisms (SNP) markers on the nineteen chromosomes were identified using genotyping-by-sequencing (GBS) technology. The high‐density coverage of SNPs resulted in an average of 14,366 markers per chromosome, an average polymorphism information content (PIC) value of 0.23 and an expected heterozygosity (He) value of 0.28 indicating the genetic diversity within 341 genotypes. LD decayed very fast when r2 was between 0.45 and 0.2 and became flat when r2 was 0.05. The average LD decay for the entire genome was 30 kb when r2 = 0.2. The PCA and structure analysis did not distinguish the grapevine genotypes based on different origins, highlighting the occurrence of gene flow and a high amount of admixture. Analysis of molecular variance (AMOVA) results indicated a high level of genetic differentiation within populations, while variation among populations was extremely low. This study provides comprehensive information on the genetic diversity and population structure of Turkish grapevine genotypes.
The MADS-box gene EjAGL15 positively regulates lignin deposition in the flesh of loquat fruit during its storage
Authors: Ge Hang , Xu Hongxia , Li Xiaoying , Chen Junwei 
Published: May 2023

IntroductionLignification of fruit flesh is a common physiological disorder that occurs during post-harvest storage, resulting in the deterioration of fruit quality. Lignin deposition in loquat fruit flesh occurs due to chilling injury or senescence, at temperatures around 0°C or 20°C, respectively. Despite extensive research on the molecular mechanisms underlying chilling-induced lignification, the key genes responsible for the lignification process during senescence in loquat fruit remain unknown. MADS-box genes, an evolutionarily conserved transcription factor family, have been suggested to play a role in regulating senescence. However, it is still unclear whether MADS-box genes can regulate the lignin deposition that arises from fruit senescence.MethodsBoth senescence- and chilling-induced flesh lignification were simulated by applying temperature treatments on loquat fruits. The flesh lignin content during the storage was measured. Transcriptomic, quantitative reverse transcription PCR and correlation analysis were employed to identify key MADS-box genes that may be involved in flesh lignification. The Dual-luciferase assay was utilized to identify the potential interactions between MADS-box members and genes in phenylpropanoid pathway. Results and DiscussionThe lignin content of the flesh samples treated at 20°C or 0°C increased during storage, but at different rates. Results from transcriptome analysis, quantitative reverse transcription PCR, and correlation analysis led us to identify a senescence-specific MADS-box gene, EjAGL15, which correlated positively with the variation in lignin content of loquat fruit. Luciferase assay results confirmed that EjAGL15 activated multiple lignin biosynthesis-related genes. Our findings suggest that EjAGL15 functions as a positive regulator of senescence-induced flesh lignification in loquat fruit.
The spatiotemporal profile of Dendrobium huoshanense and functional identification of bHLH genes under exogenous MeJA using comparative transcriptomics and genomics
Authors: He Xiaomei , Zhang Wenwu , Sabir Irfan Ali , Jiao Chunyan , Li Guohui , Wang Yan , Zhu Fucheng , Dai Jun , Liu Longyun , Chen Cunwu , Zhang Yingyu , Song Cheng 
Published: May 2023

IntroductionAlkaloids are one of the main medicinal components of Dendrobium species. Dendrobium alkaloids are mainly composed of terpene alkaloids. Jasmonic acid (JA) induce the biosynthesis of such alkaloids, mainly by enhancing the expression of JA-responsive genes to increase plant resistance and increase the content of alkaloids. Many JA-responsive genes are the target genes of bHLH transcription factors (TFs), especially the MYC2 transcription factor.MethodsIn this study, the differentially expressed genes involved in the JA signaling pathway were screened out from Dendrobium huoshanense using comparative transcriptomics approaches, revealing the critical roles of basic helix-loop-helix (bHLH) family, particularly the MYC2 subfamily.Results and discussionMicrosynteny-based comparative genomics demonstrated that whole genome duplication (WGD) and segmental duplication events drove bHLH genes expansion and functional divergence. Tandem duplication accelerated the generation of bHLH paralogs. Multiple sequence alignments showed that all bHLH proteins included bHLH-zip and ACT-like conserved domains. The MYC2 subfamily had a typical bHLH-MYC_N domain. The phylogenetic tree revealed the classification and putative roles of bHLHs. The analysis of cis-acting elements revealed that promoter of the majority of bHLH genes contain multiple regulatory elements relevant to light response, hormone responses, and abiotic stresses, and the bHLH genes could be activated by binding these elements. The expression profiling and qRT-PCR results indicated that bHLH subgroups IIIe and IIId may have an antagonistic role in JA-mediated expression of stress-related genes. DhbHLH20 and DhbHLH21 were considered to be the positive regulators in the early response of JA signaling, while DhbHLH24 and DhbHLH25 might be the negative regulators. Our findings may provide a practical reference for the functional study of DhbHLH genes and the regulation of secondary metabolites.