bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel tumour suppressor protein encoded by circMAPK14 inhibits progression and metastasis of colorectal cancer by competitively binding to MKK6
Authors: Wang Lu , Zhou Jiahui , Zhang Chuan , Chen Ranran , Sun Qingyang , Yang Peng , Peng Chaofan , Tan Yuqian , Jin Chi , Wang Tuo , Ji Jiangzhou , Sun Yueming 
Published: October 2021

AbstractBackgroundThe mitogen‐activated protein kinase (MAPK) pathway is highly associated with the progression and metastasis of various solid tumours. MAPK14, a core molecule of the MAPK pathway, plays vital roles in the colorectal cancer (CRC). Recent studies have shown that circRNAs can affect tumour progression by encoding peptides. However, little is known regarding the potential protein translated from circMAPK14 and whether it plays a role in the carcinogenesis of colorectal cancer.MethodsThe RNA level and translatable potential of circMAPK14 in CRC was verified using qRT‐PCR and public databases. RNase R digestion assay, qRT‐PCR, sanger sequencing and FISH assays were utilised to verify the circular characteristics and subcellular localisation of circMAPK14. The suppressive role of circMAPK14 on the progression and metastasis of CRC was verified in vivo and in vitro. LC/MS analysis combined with western blotting demonstrated the presence and relative expression of circMAPK14‐175aa. The underlying mechanism of circMAPK14‐175aa action to inhibit CRC was identified by co‐IP analysis. The binding of U2AF2 within the flanking introns of circMAPK14 was evaluated by RNA pull‐down assay and RIP assay. Ultimately, luciferase reporter gene assays and ChIP assays confirmed that FOXC1 suppressed transcription of U2AF2 by binding to the U2AF2 promoter in the –400 bp to –100 bp region.　ResultsWe identified that hsa_circ_0131663 (termed circMAPK14) showed significantly decreased expression level in cells and tissue samples of CRC, and was primarily localised in the cytoplasm. A series of function experiments demonstrated that circMAPK14 influenced CRC progression and metastasis by encoding a peptide of 175 amino acids (termed circMAPK14‐175aa). We also found that circMAPK14‐175aa reduced nuclear translocation of MAPK14 by competitively binding to MKK6, thus facilitating ubiquitin‐mediated degradation of FOXC1. Moreover, we described a positive feedback loop in CRC in which elevated FOXC1 expression was caused by reduced circMAPK14‐175aa expression. This, in turn, decreased circMAPK14 biogenesis by suppressing U2AF2 transcription.ConclusionIn summary, we reported for the first time that circMAPK14 functioned as a tumour‐suppressor by encoding circMAPK14‐175aa, which blocked the progression and metastasis of colorectal cancer.
Paeonol inhibits human lung cancer cell viability and metastasis in vitro via miR‐126‐5p/ZEB2 axis
Authors: Lv Jing , Zhu Shibing , Chen Huiping , Xu Ying , Su Qingyu , Yu Guofen , Ma Wei 
Published: October 2021

AbstractPaeonol exerted an effect in lung cancer, but the underlying mechanism remained vague. In this research, we assessed the effects of Paeonol and microRNA (miR)‐126‐5p on the viability, migration, invasion, and epithelial‐mesenchymal transition (EMT) of lung cancer cells. Lung cancer cells and BEAS‐2B cells were treated with Paeonol, and viability was detected by 3‐(4,5)‐dimethylthiahiazo (‐z‐y1)‐3,5‐di‐ phenytetrazoliumromide (MTT) assay. The migration and invasion of lung cancer cells after treatment with Paeonol at 40 μg/mL or 80 μg/mL were detected by wound healing assay and Transwell assay, respectively. The effects of Paeonol on transforming growth factor‐β1 (TGF‐β1)‐induced EMT and relative expressions of EMT‐related proteins were determined using Western blot. The target gene of miR‐126‐5p and the binding sites between them were predicted by TargetScan, and confirmed using dual‐luciferase reporter assay. Relative expressions of miR‐126‐5p, its target gene and EMT‐related proteins were determined by quantitative real‐time polymerase chain reaction (qRT‐PCR) and Western blot. Rescue assay was performed to analyze the relation between Paeonol and miR‐126‐5p. Paeonol down‐regulated cell viability and inhibited migration, invasion and TGF‐β1‐induced EMT while up‐regulating miR‐126‐5p expression in lung cancer cells as the dose increased. However, miR‐126‐5p inhibitor could reverse the effect of Paeonol. ZEB2 was the target gene of miR‐126‐5p, and silencing ZEB2 expression reversed the effects of miR‐126‐5p downregulation. Paeonol also regulated the expression of ZEB2 in lung cancer cells, and this regulation depends on the regulation of miR‐126‐5p. Paeonol inhibits human lung cancer cell viability and metastasis via the miR‐126‐5p/ZEB2 axis, and could be adopted as a potential agent for lung cancer treatment.
Actinic keratoses: The latest in therapy
Authors: Berman Brian , Berman Daniela K. 
Published: October 2021

AbstractThe following is a review of the pathogenesis and natural history of actinic keratoses, their progression to squamous cell carcinoma, and recent findings and insights into the mechanisms of action of chemopreventative and field therapeutic agents for actinic keratoses are highlighted. Oral nicotinamide appears to be a safe and tolerable chemopreventative agent although its effectiveness requires continued use. Tirbanibulin ointment 1% is novel in its proposed mechanism of action and requires the shortest period of treatment of currently US Food and Drug Administration‐approved, topically applied field therapies for actinic keratoses.
Similarities and differences between multiple sclerosis and type 1 diabetes
Authors: Pozzilli Valeria , Grasso Eleonora Agata , Tomassini Valentina 
Published: October 2021

AbstractMultiple sclerosis (MS) and type 1 diabetes (T1D) are chronic conditions that result from dysfunction of the immune system. Their common root in autoimmunity stimulates interest in the exploration of similarities and differences between the two diseases. Genetic susceptibility is relevant, creating a substrate, on which environmental factors act as a trigger of an aberrant immune response. Despite being both T‐cell mediated disorders with a strong involvement of the humoral arm, immunomodulation is a mainstay of MS management, whereas hormone replacement therapy remains the principal approach for T1D. T1D is usually diagnosed in children and adolescents, while MS is typical of young adults. This difference has implications for disease progression and treatment. The SARS‐CoV‐2 pandemic and its effect on immunity may affect the prevalence of these conditions, as well as their clinical manifestation.
Natural history of a bighorn sheep pneumonia epizootic: Source of infection, course of disease, and pathogen clearance
Authors: Besser Thomas E. , Cassirer E. Frances , Lisk Amy , Nelson Danielle , Manlove Kezia R. , Cross Paul C. , Hogg John T. 
Published: October 2021

AbstractA respiratory disease epizootic at the National Bison Range (NBR) in Montana in 2016–2017 caused an 85% decline in the bighorn sheep population, documented by observations of its unmarked but individually identifiable members, the subjects of an ongoing long‐term study. The index case was likely one of a small group of young bighorn sheep on a short‐term exploratory foray in early summer of 2016. Disease subsequently spread through the population, with peak mortality in September and October and continuing signs of respiratory disease and sporadic mortality of all age classes through early July 2017. Body condition scores and clinical signs suggested that the disease affected ewe groups before rams, although by the end of the epizootic, ram mortality (90% of 71) exceeded ewe mortality (79% of 84). Microbiological sampling 10 years to 3 months prior to the epizootic had documented no evidence of infection or exposure to Mycoplasma ovipneumoniae at NBR, but during the epizootic, a single genetic strain of M. ovipneumoniae was detected in affected animals. Retrospective screening of domestic sheep flocks near the NBR identified the same genetic strain in one flock, presumptively the source of the epizootic infection. Evidence of fatal lamb pneumonia was observed during the first two lambing seasons following the epizootic but was absent during the third season following the death of the last identified M. ovipneumoniae carrier ewe. Monitoring of life‐history traits prior to the epizootic provided no evidence that environmentally and/or demographically induced nutritional or other stress contributed to the epizootic. Furthermore, the epizootic occurred despite proactive management actions undertaken to reduce risk of disease and increase resilience in this population. This closely observed bighorn sheep epizootic uniquely illustrates the natural history of the disease including the (presumptive) source of spillover, course, severity, and eventual pathogen clearance.
Nitrogen and phosphorus addition differentially enhance seed production of dominant species in a temperate steppe
Authors: Su Lei , Liu Mengzhou , You Chengming , Guo Qun , Hu Zhongmin , Yang Zhongling , Li Guoyong 
Published: October 2021

AbstractPrevious studies have demonstrated changes in plant growth and reproduction in response to nutrient availability, but responses of plant growth and reproduction to multiple levels of nutrient enrichment remain unclear. In this study, a factorial field experiment was performed with manipulation of nitrogen (N) and phosphorus (P) availability to examine seed production of the dominant species, Stipa krylovii, in response to N and P addition in a temperate steppe. There were three levels of N and P addition in this experiment, including no N addition (0 g N m−2 year−1), low N addition (10 g N m−2 year−1), and high N addition (40 g N m−2 year−1) for N addition treatment, and no P addition (0 g P m−2 year−1), low P addition (5 g P m−2 year−1), and high P addition (10 g P m−2 year−1) for P addition treatment. Low N addition enhanced seed production by 814%, 1371%, and 1321% under ambient, low, and high P addition levels, respectively. High N addition increased seed production by 2136%, 3560%, and 3550% under ambient, low, and high P addition levels, respectively. However, P addition did not affect seed production in the absence of N addition, but enhanced it under N addition. N addition enhanced seed production mainly by increasing the tiller number and inflorescence abundance per plant, whereas P addition stimulated it by decreasing the plant density yet stimulating height of plants and their seed number per inflorescence. Our results indicate seed production is not limited by P availability but rather by N availability in the temperate steppe, whereas seed production will be increased by P addition when N availability is improved. These findings enable a better understanding of plant reproduction dynamics in the temperate steppe under intensified nutrient enrichment and can inform their improved management in the future.
Population assignment tests uncover rare long‐distance marine larval dispersal events
Authors: D’Aloia C. C. , Bogdanowicz S. M. , Andrés J. A. , Buston P. M. 
Published: October 2021

AbstractLong‐distance dispersal (LDD) is consequential to metapopulation ecology and evolution. In systems where dispersal is undertaken by small propagules, such as larvae in the ocean, documenting LDD is especially challenging. Genetic parentage analysis has gained traction as a method for measuring larval dispersal, but such studies are generally spatially limited, leaving LDD understudied in marine species. We addressed this knowledge gap by uncovering LDD with population assignment tests in the coral reef fish Elacatinus lori, a species whose short‐distance dispersal has been well‐characterized by parentage analysis. When adults (n = 931) collected throughout the species’ range were categorized into three source populations, assignment accuracy exceeded 99%, demonstrating low rates of gene flow between populations in the adult generation. After establishing high assignment confidence, we assigned settlers (n = 3,828) to source populations. Within the settler cohort, <0.1% of individuals were identified as long‐distance dispersers from other populations. These results demonstrate an exceptionally low level of connectivity between E. lori populations, despite the potential for ocean currents to facilitate LDD. More broadly, these findings illustrate the value of combining genetic parentage analysis and population assignment tests to uncover short‐ and long‐distance dispersal, respectively.
Neosilyllithium‐Catalyzed Hydroboration of Alkynes and Alkenes in the Presence of Pinacolborane (HBpin)
Authors: Kumar Gobbilla Sai , Moorthy Shruti , Karmakar Himadri , Singh Saurabh Kumar , Panda Tarun K. 
Published: October 2021

AbstractWe report here a novel protocol for the hydroboration of alkynes and alkenes, which in the presence of neosilyllithium (LiCH2SiMe3) (5 mol %) and pinacolborane efficiently results in the formation of corresponding alkenyl and alkyl boronate ester products in good yields. The electron‐donating and electron‐withdrawing substituents on the aromatic rings of alkynes and alkenes converted smoothly to the desired products. When we extended the scope of reactivity to various aliphatic alkynes and styrenes using similar conditions, the alkenyl and alkyl boronate ester products were again formed in good yields. We also performed intramolecular and intermolecular reactions to check the reactivity of different functional groups on the phenyl ring. Experimental investigations and DLPNO‐CCSD(T) calculations reveal mechanistic insights from the LiCH2SiMe3‐catalyzed alkyne hydroboration.
Facile Synthesis of Gold/Graphene Nanocomposites for Simultaneous Determination of Sunset Yellow and Tartrazine in Soft Drinks
Authors: Wu Tingxuan , Wang Qi , Peng XiuYing , Guo Yujing 
Published: October 2021

AbstractHerein, poly (diallyldimethylammonium chloride) (PDDA) functionalized gold nanoparticles/graphene (AuNPs/Gr) composites were prepared by the one‐pot method under simple, rapid and mild conditions. The prepared nanocomposites combined the excellent conductivity and electrocatalytic performance of Gr and AuNPs. Based on the above advantages, an outstanding electrochemical sensor was constructed to detect sunset yellow (SY) and tartrazine (TZ) simultaneously. Under the optimum conditions, the linear response ranges for SY and TZ were 0.006–5.0 and 0.008–3.0 μmol/L, with low detection limits of 2.0 and 2.5 nmol/L, respectively. The as‐proposed sensor displayed long‐term stability, anti‐interference performance and reproducibility, revealing its promising method for practical monitoring.
MiRNome analysis identifying miR‐205 and miR‐449a as biomarkers of disease progression in intestinal‐type sinonasal adenocarcinoma
Authors: Re Massimo , Tomasetti Marco , Monaco Federica , Amati Monica , Rubini Corrado , Sollini Giacomo , Bajraktari Arisa , Gioacchini Federico Maria , Santarelli Lory , Pasquini Ernesto 
Published: October 2021

AbstractBackgroundPatients with intestinal‐type sinonasal adenocarcinoma (ITAC) have an unfavorable prognosis, and new diagnostic and therapeutic approaches are needed to improve clinical management.MethodsNext‐generation sequencing‐based miRNome analysis was performed on 43 ITAC patients who underwent surgical resection, and microRNA (miRNA) data were obtained from 35 cases. Four miRNAs were identified, and their expression levels were detected by reverse‐transcription quantitative polymerase chain reaction and related to the relevant patient outcome. Overall survival and disease‐free survival rates were evaluated through the Kaplan–Meier method and log‐rank test, and multivariate analysis was performed by means of Cox proportional hazard analysis.ResultsHigh levels of miR‐205 and miR‐34c/miR‐449 cluster expression were associated with an increased recurrence risk and, therefore, a worse prognosis. Multivariate analysis confirmed that miR‐205 and miR‐449 were significant prognostic predictors.ConclusionsA high expression of miR‐205 and miR‐449 is independent predictors of poor survival for ITAC patients.
Synthesis of Stereochemically Flexible Cyclic Biphenylbisphosphinite Ligands: Control of the Dynamics and Selectivity
Authors: Menke Jan‐Michael , Scholz Katharina , Trapp Oliver 
Published: October 2021

AbstractNovel l‐tartaric acid based stereodynamic biphenylbisphosphinite ligands with anilino linkers were prepared as cyclic diamide compounds. The influence of the constitutional substitution pattern of the amino group at the aniline moiety on the diastereoselective formation of the ligand was investigated. While the meta‐anilino bridged ligands showed a highly dynamic behavior and no discrimination between (Rax) and (Sax) configuration, l‐tartaric acid substitution on ortho‐anilino bridged ligands leads to diastereoselective self‐alignment of the central biphenol axis, which controls the stereoselectivity of the ligand and catalyst. The experimental findings were corroborated by theoretical calculations. In the rhodium‐catalyzed enantioselective hydrogenation of methyl 2‐acetamidoacrylate (MAA), an enantiomeric ratio of 75 : 25 (R/S) was obtained for the ortho‐substituted ligand.
Aligning priorities in Ethiopian health finance: How do the essential health services package and health benefit plans compare?
Authors: Koon Adam D. , Wright Jenna , Ageze Leulseged , Charles Jodi , Holtz Jeanna 
Published: October 2021

AbstractPriority setting is a key function of health systems in low‐ and middle‐income countries that seek to achieve universal health coverage. Essential health services packages (EHSPs) and health benefit plans are two types of instruments used in setting health care priorities. Both instruments exist in Ethiopia, but little is known about how they are aligned. To gain insights into the evolution, purpose, policy objectives, and governance of the EHSP, community‐based health insurance (CBHI), and social health insurance (SHI) in Ethiopia, we conducted a case study. This included a desk review of relevant documents as well as qualitative analysis of key informant interviews conducted with 15 leading health finance experts in Addis Ababa. Interviewees understood the EHSP to be a key priority‐setting instrument in the country by coordinating the activities of health system stakeholders, and guaranteeing the right of citizens to a basic level of care. Community‐based health insurance and SHI were described as mechanisms for the government to expand health coverage and provide financial protection. Interviewees acknowledged that Ethiopia had drawn on the experience of other countries when designing health benefit plans, but contrasted Ethiopia's experience with that of other countries. We found that in Ethiopia, the EHSP, CBHI, and SHI are not explicitly aligned. We propose that EHSPs play an important role in early stages of health systems development. However, as governments develop health benefit plans with expansive packages of services, the importance of EHSPs becomes less clear.
Islet amyloid toxicity: From genesis to counteracting mechanisms
Authors: Marmentini Carine , Branco Renato C. S. , Boschero Antonio C. , Kurauti Mirian A. 
Published: October 2021

AbstractIslet amyloid polypeptide (IAPP or amylin) is a hormone co‐secreted with insulin by pancreatic β‐cells and is the major component of islet amyloid. Islet amyloid is found in the pancreas of patients with type 2 diabetes (T2D) and may be involved in β‐cell dysfunction and death, observed in this disease. Thus, investigating the aspects related to amyloid formation is relevant to the development of strategies towards β‐cell protection. In this sense, IAPP misprocessing, IAPP overproduction, and disturbances in intra‐ and extracellular environments seem to be decisive for IAPP to form islet amyloid. Islet amyloid toxicity in β‐cells may be triggered in intra‐ and/or extracellular sites by membrane damage, endoplasmic reticulum stress, autophagy disruption, mitochondrial dysfunction, inflammation, and apoptosis. Importantly, different approaches have been suggested to prevent islet amyloid cytotoxicity, from inhibition of IAPP aggregation to attenuation of cell death mechanisms. Such approaches have improved β‐cell function and prevented the development of hyperglycemia in animals. Therefore, counteracting islet amyloid may be a promising therapy for T2D treatment.
MAP kinase/ERK kinase 1 (MEK1) phosphorylates regulator of calcineurin 1 (RCAN1) to regulate neuronal differentiation
Authors: Kim Seon Sook , Lee Eun Hye , Shin Jin Hak , Seo Su Ryeon 
Published: October 2021

AbstractRegulator of calcineurin 1 (RCAN1) is located close to the Down syndrome critical region (DSCR) on human chromosome 21 and is related to the Down syndrome (DS) phenotype. To identify a novel binding partner of RCAN1, we performed yeast two‐hybrid screening and identified mitogen‐activated protein (MAP) kinase/extracellular signal‐regulated kinase (ERK) kinase 1 (MEK1) as a partner. MEK1 was able to bind and phosphorylate RCAN1 in vitro and in vivo. MEK1‐dependent RCAN1 phosphorylation caused an increase in RCAN1 expression by increasing the protein half‐life. Nerve growth factor (NGF)‐dependent activation of the MEK1 pathway consistently induced RCAN1 expression. Moreover, we found that RCAN1 overexpression inhibited NGF‐induced neurite outgrowth and expression of neuronal marker genes, such as growth cone‐associated protein 43 (GAP43) and synapsin I, via inhibition of MEK1‐ERK1/2 pathways. Our findings provide evidence that MEK1‐dependent RCAN1 phosphorylation acts as an important molecular mechanism in the control of neuronal differentiation.
Blood cyst of the pulmonary valve causing right ventricular outflow tract obstruction: A case report
Authors: Wang Xiaoyan , Yang Yanfeng , Zhang Yong , Fan Lingxia , Wang Shushui 
Published: October 2021

AbstractBlood cysts are rare cardiac tumors, often involve the atrioventricular valves. Blood cysts are usually small and tend to be clinically silent. Here, we report a case of blood cyst adhered to the junction of the pulmonary valve and the right ventricular outflow, causing severe outflow obstruction. This case was initially misdiagnosed as pulmonary valve stenosis by transthoracic echocardiography (TTE) and even underwent percutaneous balloon pulmonary valvuloplasty (PBPV). As the right ventricle‐to‐pulmonary artery peak gradient did not decrease after PBPV procedure, the boy underwent TTE again and the diagnosis was corrected as blood cyst. The cystic mass was successfully resected subsequently, and the boy recovered well.