bluuebunny/crossref_metadata_2025 huggingface dataset:
ADAMTS4 or ADAMTS5: Which is the Key Enzyme in the Cartilage Degradation of Osteoarthritis and Kashin-Beck Disease?
Authors: Meng Peilin , Lammi Mikko J. , Yuan Linlin , Tan SiJia , Zhang Feng’e , Li Peilin , Zhang Yanan , Li Wenyu , Wang Sen , Guo Xiong
Published: June 2021

Background: This study aims to investigate the altered expression of a disintegrin and metalloproteinase with thrombospondin motifs 4（ADAMTS4）and a disintegrin and metalloproteinase with thrombospondin motifs 5（ADAMTS5）in the human articular cartilage between osteoarthritis(OA) and Kashin-Beck disease(KBD) and compare their roles in the cartilage injury. Methods: Articular samples were collected from confirmed OA patients and KBD patients then divided into three groups, and the articular cartilages from the normal donors were used as controls. The morphology，location and expression of ADAMTS4 and ADAMTS5 as well as aggrecan were detected by histochemical staining and immunohistochemical staining. Results: Compared to the control, the number of living cells in OA and KBD groups declined at three zones. Meanwhile, the results of toluidine blue staining showed that there was a loss of aggrecan in extracellular matrix of KBD and OA cartilages. The amounts of chondrocytes positively stained for ADAMTS4 were lower in the middle and deep zones of OA and KBD cartilages than those in the control samples. On the contrary, the immunostaining for ADAMTS5 significantly increased in OA and KBD group compared with control group at all three zones. Notably, although there was no statistical significance, the expression of ADAMST5 in KBD was slightly higher than the ones in OA in superficial, middle and deep zones. Conclusions: The role ADAMTS4 acted in aggrecan degradation was seemingly minor. It could be inferred that ADAMTS5 is the key enzyme in the cartilage destruction, particularly in KBD cartilage, which could explain the complex pathogenesis of KBD and provide a potential therapeutic target for KBD patients.
Correlation of In Vivo Imaging To Morphomolecular Pathology In Translational Research – Challenge Accepted
Authors: Ballke Simone , Heid Irina , Mogler Carolin , Braren Rickmer , Schwaiger Markus , Weichert Wilko , Steiger Katja
Published: June 2021

Correlation of in vivo imaging to histomorphological pathology in animal models requires comparative interdisciplinary expertise of different fields of medicine. From the morphological point of view, there is an urgent need to improve histopathological evaluation in animal model based research to expedite translation into clinical applications. While different other fields of translational science were standardized over the last years, little was done to improve the pipeline of experimental pathology to ensure reproducibility based on pathological expertise in experimental animal models with respect to defined guidelines and classifications. Additionally, longitudinal analyses of preclinical models often use a variety of imaging methods and much more attention should be drawn to enable for proper co-registration of in vivo imaging methods with the ex vivo morphological read-outs. Here we present the development of the Comparative Experimental Pathology (CEP) unit embedded in the Institute of Pathology of the Technical University of Munich during the Collaborative Research Center 824 (CRC824) funding period together with selected approaches of histomorphological techniques for correlation of in vivo imaging to morphomolecular pathology.
Parasitological, Serological and Molecular Survey of Camel Trypanosomosis (Surra) in Northern Nigeria
Authors: Mamman Shadrach , Dakul Anthony Danaan , Yohanna Jael Asabe , Dogo Goni Abraham , Reuben Rine Christopher , Ogunleye Oluyomi Oluniyi , Tyem Dinchin A , Peter Joana G , Kamani Joshua
Published: June 2021

Surra, a parasitic disease caused by Trypanosoma evansi and transmitted non-cyclically by biting flies significantly affects the health, productivity and market value of camels thereby constituting a major constraint to food safety, security and economy. This is the first study on the prevalence of surra in Northern Nigeria, using a broad variety of diagnostic tests along the parasitological-serological-molecular continuum hence, emphasizing it as a major enzootic risk for camels in Nigeria. In this cross-sectional study, 600 blood samples were collected from camels at major abattoirs in Northwestern Nigeria and evaluated for the prevalence of surra due to T. evansi using parasitological (Giemsa staining), serological (CATT/T.evansi) and molecular (VSG-PCR and sequencing) methods. The overall prevalence of surra recorded in this study was 5.3%, 11.5% and 22.5% using Giemsa stained blood smears, CATT/T.evansi and VSG-PCR respectively. However, higher prevalence of 6.0%, 13.7% and 26.7% by Giemsa stained blood smears, CATT/T. evansi and VSG-PCR was recorded in Katsina state when compared with Kano state. A significantly (p < 0.05) higher prevalence byVSG-PCR was observed when compared with both parasitological and serological methods used. Although age and body condition scores were associated (p < 0.05) with surra prevalence in sampled camels, no seasonal association (p > 0.05) was however recorded. Sequencing of the VSG region of Trypanosoma spp. Further confirmed the presence of T. evansi as the aetiological agent of surra from the sampled camels. Findings from this study call for the implementation of adequate control measures aimed at reducing the impact of T. evansi infections on camel production in Nigeria.
Analysis of Ionospheric Disturbance Associated With Earth Quakes In Papua New Guinea
Authors: Pereira Felix , Sekere Jessy
Published: June 2021

An analysis of the perturbations in the electron content up to the ionospheric F2 layer peak and F2 layer peak height (hmF2) variations during earthquake time has been done using ionosonde data observed in the equatorial station Vanimo, Papua New Guinea. Two earth quakes occurred, one of magnitude 7.1 in Sissano in 1998 and the other of magnitude 6.7 in Aitape in 2002 in the western province of Papua New Guinea, have been studied. A decrease in electron content was observed in both the cases a few days prior to the earthquakes. An increase in height of hmF2 during night time was also observed during this period. This can be explained in terms of the lithosphere- atmosphere-ionosphere coupling prior to earthquake period.
Identification of Molecular Biomarkers and Pathways for Risk Stratification in Human Papilloma Virus-Associated Cancers
Authors: Kwon Eun Jung , Lee Hye Ran , Lee Ju Ho , Ha Mihyang , Kim Yun Hak , Jang Jeon Yeob
Published: June 2021

Background: Human papillomavirus (HPV) is the major cause of cervical cancer (CC) etiology; its contribution to head and neck cancer (HNC) incidence is steadily increasing. As individual patients’ response to the treatment of HPV-associated cancer is variable, there is a pressing need for the identification of biomarkers for risk stratification that can help determine the intensity of treatment. Methods: We have previously reported a novel prognostic and predictive indicator (HPPI) scoring system in HPV-associated cancers regardless of the anatomical locations by analyzing the TCGA and GEO databases. In this study, we comprehensively investigated the association of group-specific expression patterns of common differentially expressed genes (DEGs) between high-risk and low-risk groups in HPV-associated CC and HNC, identifying a molecular biomarkers and pathways for the risk stratification. Results: Among the identified 174 DEGs, expression of the genes associated with extracellular matrix (ECM)-receptor interaction pathway (ITGA5, ITGB1, LAMB1, LAMC1) were increased in high-risk groups in both HPV-associated CC and HNC while expression of the genes associated with the T-cell immunity (CD3D, CD3E, CD8B, LCK, and ZAP70) were decreased vise versa. The individual genes showed statistically significant prognostic impact on HPV-associated cancers but not on HPV-negative cancers. The expression levels of identified genes were similar between HPV-negative and HPV-associated high-risk groups with distinct expression patterns only in HPV-associated low-risk groups. Each group of genes showed negative correlations, and distinct patterns of immune cell infiltration in tumor microenvironments. Conclusion: These results identify molecular biomarkers and pathways for risk stratification in HPV-associated cancers regardless of anatomical locations. The identified targets are selectively working in only HPV-associated cancers, but not in HPV-negative cancers indicating possibility of the selective targets governing HPV-infective tumor microenvironments.
Dysfunctional Insulin Resistant/mTOR Activation Is Involved In The Formation of Pulmonary Hypertension In Pressure Overload-Induced Heart Failure
Authors: Wu Xiaojing , Dong Bo , Ni Tongxin , Hu Junhao , Zhou Qi
Published: June 2021

Background: Heart failure (HF) usually presents with abnormal changes of metabolisms. Pulmonary hypertension (PH) is a frequent complication of left heart dysfunction. However, the association of serum metabolic changes with PH formation remains unknown. This study analyzed changes of serum metabolomic during the development of PH in a left heart pressure overload model. Methods: Male Sprague-Dawley rats were subjected to transverse aortic constriction (TAC) or sham surgery. Metabolomic analysis was performed on plasma samples of rats at 0 week, 3 weeks and 9 weeks after the surgery. Cardiac remodeling and heart function were determined by echocardiography. Right heart catheterization was performed to assay the mean pulmonary arterial pressure (mPAP). HE staining was performed to observe the remodeling of the myocardium and small pulmonary arteries.Results: The rats developed compensated cardiac hypertrophy with normal mPAP at 3 weeks and PH due to HF (PH-HF) at 9 weeks with distinct metabolic pattern after TAC. Twenty-five metabolites changed in the 9-week group compared with the 3-week group. KEGG analysis suggested abnormal insulin resistance and mTOR activation during the development of PH-HF. Acetylcarnitines related to insulin resistance increased about 3 folds from 4.14 ug/ml at 3 W group to 12.04μg/ml at 9-week group. L-leucine related to mTOR activation increased 1.6-fold with a VIP of 4.08 at 9 W when compared with that of the 3 W group.Conclusions: These results revealed distinct metabolic changes during the development of PH-HF. Dysfunctional insulin resistance and mTOR activation might be involved in the transition from compensated cardiac hypertrophy to PH-HF.
Real-World Study on Upper/Lower Respiratory Tract Microbiome Changes in AECOPD and COPD
Authors: Zhang Yunhui , Xu Yanyan , Liu Nailiang , Yan Dailing , Zhou Shiyi , He Meiyan , Shi Linfeng , Yang Zhiqin , Ma Mengjie , Dai Rufen , Li Xianli , Zhang Zhongyuan , Chen Liping , Wang Lina , Tian Kun , Duan Xingqiu , Yang Xiaohui , Huang Zhenming , Cai Bo , Su Jianyuan , Zhang Jingxin , Qin Jian , Yang Gang , Pan Quan , Yuan Bing
Published: June 2021

Background: Microbiome residing in the respiratory tract has emerged as an important player in the etiology and progression of COPD, but results are conflicting regarding the features of respiratory tract microbiome in COPD and at exacerbations and it is unknown whether these features differ by ethnicity and geography. To address these questions, we enrolled healthy individuals and patients with COPD, including healthy-COPD pairs from same households, from four geographical regions of Yunan province, representative of different ethnicities and/or environmental exposures. Sputum and oropharyngeal swabs were collected from these healthy individuals and from COPD patients at stable state (COPD) or exacerbations (AECOPD) and subjected to 16S amplicon sequencing. Results: We found that both COPD disease status and region had an impact on alpha-diversity of sputum and oropharyngeal microbiomes, with AECOPD having the lowest microbiome diversity. Shifts in the relative abundance (≥ 1.5 fold, adj.p < 0.05) of microbes at healthy, exacerbation and stable COPD. Microbes enriched at exacerbation COPD were primarily Proteobacteria and Firmicutes phylum in upper respiratory tract. In the lower respiratory tract, population-based study did not find any statistical differential abundance of microbe, however, paired-based study showed phylum of Proteobacteria, Chloroflexi, Bacteroidota, Acidobacteriota, Desulfobacterota, Firmicutes and Verrucomicrobiota enriched in exacerbation COPD. Conclusions: This study was the first attempt to combine the population-based and core-family-based to investigate the microbiome profiling in the upper and lower respiratory tract in COPD patients, and specific microbial flora characteristics may inform future study on the pathogenesis or management of COPD patients.
Analysis of Prognostic Factors of Nasopharyngeal Carcinoma and Construction of Risk Nomogram Prediction Model
Authors: zhang xuan hao , Jin LU , Cheng-yi JIANG , Mei-fang FANG , Hai-rong Liu
Published: June 2021

Objective To analyze the factors affecting the prognosis of nasopharyngeal carcinoma (NPC) patients and establish a risk nomogram prediction model for the diagnosis, treatment and prognosis of NPC. Methods A total of 1645 NPC patients (1470 survival) from 1973 to 2015 in the SEER database were included. The clinicopathological data of 180 NPC patients hospitalized in the First Affiliated Hospital of Bengbu Medical College since 2010 were collected. The spearman correlation analysis and COX regression analysis were used to identify the prognostic factors of NPC and establish the risk nomogram prediction model. Receiver operation characteristic (ROC) analysis and area under curves (AUC) were used to evaluate the ability of distinguishing the prognosis of NPC patients. The cross calibration was calculated to evaluate the external validation of established predictive model.Results The survival NPC had higher proportion in female, older age, degree of NPC differentiation, N and M stage (all P<0.05. The study factors including female, older age, and higher degree of differentiation were positively correlated with the prognosis of NPC patients (P<0.05), while N and M stage were negatively correlated with the prognosis of NPC patients (P<0.05). The factors including female (HR=4.92, 95%CI 3.58-6.75), age (HR=, 95%CI=), degree of differentiation (HR=, 95%CI=), N stage (HR=, 95%CI=) were independently associated with prognosis of NPC patients (P<0.05). Comparing with calibration curve, the constructed risk prediction model had good relations between predictive values and actual values (AUC=0.833). Additionally, the external verification results of 96 patients with NPC had a larger AUC in our established predictive model (AUC=0.851). Conclusions Female, degree of differentiation and N stage are independent factors for the prognosis of NPC patients. The risk nomogram prediction model has a good predictive ability for the survival of NPC patients, which can provide important insights into clinical prognosis for NPC patients.
Genome-wide Association Study Reveals Novel Quantitative Trait Loci and Candidate Genes of Lint Percentage in Upland Cotton Based on the CottonSNP80K Array
Authors: Chen Yu , Gao Yang , Chen Pengyun , Zhou Juan , Zhang Chuanyun , Song Zhangqiang , Huo Xuehan , Du Zhaohai , Gong Juwu , Zhao Chengjie , Wang Shengli , Zhang Jingxia , Wang Furong , Zhang Jun
Published: June 2021

Cotton (Gossypium spp.) is an important natural textile fiber and oilseed crop widely cultivated in the world. Lint percentage (LP, %) is one of the important yield factor, thus increasing lint percentage is a core goal of cotton breeding improvement. However, the underlying genetic and molecular mechanisms that control lint percentage in upland cotton remain largely unknown. Here, we performed a Genome-wide association study (GWAS) for LP based on phenotypic tests of 254 upland cotton accessions in four environments and BLUPs using the high-density CottonSNP80K array. A total of 41,413 high-quality single-nucleotide polymorphisms (SNPs) were screened and 34 SNPs within 22 QTLs were identified as significantly associated with lint percentage trait in different environments. In total, 175 candidate genes were identified from two major genomic loci (GR1 and GR2) of upland cotton and 50 hub genes were identified through GO enrichment and WGCNA analysis. Furthermore, two candidate/causal genes, Gh_D01G0162 and Gh_D07G0463, which pleiotropically increased lint percentage were identified and further verified its function through LD blocks, haplotypes and qRT-PCR analysis. Co-expression network analysis showed that the candidate/causal and hub gene, Gh_D07G0463, was significantly related to another candidate gene, Gh_D01G0162, and the simultaneous pyramid of the two genes lays the foundation for a more efficient increase in cotton production. Our study provides crucial insights into the genetic and molecular mechanisms underlying variations of yield traits and serves as an important foundation for lint percentage improvement via marker-assisted breeding.
Underlying IPEX Syndrome in a Patient With Idiopathic Juvenile Arthritis and Vitiligo
Authors: Mendonça Leonardo Oliveira , Chuster Adriana Ptichon dos Reis , Barros Samar Freschi , Alves Janaina Baptista , Gonçalves Victor Lucas , Yang Ariana Campos , Kalil Jorge , Toledo-Barros Myrthes Anna Maragna , Kokron Cristina Maria
Published: June 2021

IPEX syndrome (MIM #304790) also known as immune dysregulation, polyendocrinopathy, enteropathy, X-linked is a monogenic inborn error of immunity due to loss-of-function mutations in the forkhead box 3 (FOXP3) gene. This gene is crucial for the development, maturation and maintenance of CD4+ regulatory T (T-reg) cells. Various phenomenon mainly of autoimmune origin are characteristics of the syndrome such as enteropathy, endocrinopathies, cytopenias, renal disorders and skin manifestations (1).
Association of Patellofemoral Morphology and Alignment With the Radiographic Severity of Patellofemoral Osteoarthritis
Authors: Dai Yike , Yin Heyong , Xu Chongyang , Zhang Hongrui , Guo Ai , Diao Naicheng
Published: June 2021

Background: Risk factors for the progression of patellofemoral osteoarthritis (PFOA) are poorly understood. This research aims to evaluate the association between patellofemoral joint (PFJ) morphology and alignment with the radiographic severity of PFOA.Methods: A retrospective analysis of CT scan and lateral radiograph data were acquired in patients with PFOA. The radiographic severity of PFOA and tibiofemoral OA (TFOA), lateral and medial trochlear inclination angle, sulcus angle and the Wiberg classification of patella morphology, the congruence angle, patellar tilt angle, and lateral patellar angles, and tibial tubercle trochlear groove distance (TT-TG), patella height (i.e., Caton-Deschamps index) were assessed using CT scans and sagittal radiographs of the knee. All the PFJ morphology and alignment data were divided into quarters and the relationship between each measure and the severity of PFOA was investigated.Results: By studying 150 patients with PFOA, we found a U-shaped relationship between the Caton-Deschamps index and the severity of PFOA (P <0.001). A lower value of sulcus angle and lateral patellar angle, a higher value of congruence angle, and type III patella were associated with more severity of lateral PFOA. Compared with the highest quarter of each measure, the adjusted odds ratios (OR) of the severity of PFOA in the lowest quarter of sulcus angle, lateral patellar angle, and congruence angle, and type I patella was 8.80 (p=0.043), 16.51 (P <0.001), 0.04(P <0.001), and 0.18 (p=0.048) respectively.Conclusions: Extreme value of patella height, a higher value of lateral patellar displacement and lateral patellar tilt, lower value of sulcus angle, and type III patella were associated with more severity of PFOA.
Research on Silicone Methacrylates Containing Dental Resins With Anti-adhesion Effect Against S. Mutans and Resistance to Mucin Adsorption
Authors: Tong Hui , Liao Muzi , Huang Xiangya , Liu Fang , Mai Sui , He Jingwei
Published: June 2021

With the purpose of preparing anti-bacterial adhesion dental resin, two silicone methacrylates (SMAs) were synthesized. After being confirmed by the FT-IR and 1H-NMR spectra, SMAs were incorporated into commonly used Bis-GMA/TEGDMA (50/50, wt./wt.) dental resin system with a series of concentration. Physicochemical properties, anti-bacterial adhesion effect, and protein adsorption were tested. The results showed that SMAs had no influence on the double bond conversion of dental resin, and could decrease volumetric shrinkage of dental resin. Because of the increased hydrophobicity and reduced surface free energy, SMAs containing cured resin had resistance to mucin adsorption and anti-adhesion effect against S. mutans. However, flexural properties, water sorption and solubility of dental resin were impaired after introducing SMAs. Therefore, further research should be taken to improve these properties by utilizing appropriate inorganic fillers.
Environmental factors influencing the composition of phyllosphere bacterial communities in bamboo: A staple food source of giant pandas
Authors: Long Juejie , Luo Wei , Xie Jianmei , Yuan Yuan , Wang Jia , Kang Liwen , Li Yi , Zhang Zejun , Hong Mingsheng
Published: June 2021

Background

The giant panda has developed a series of evolutionary strategies to adapt to a bamboo diet. The abundance and diversity of the phyllosphere microbiome change dramatically depending on the season, host species, location etc., which may, in turn, affect the growth and health of host plants. However, few studies have investigated the factors that influence phyllosphere bacteria in bamboo, a staple food source of the giant panda.
Methods

Amplicon sequencing of the 16S rRNA gene of rRNA genomic loci was used to explore the abundance and diversity of phyllosphere bacteria in three bamboo species (Arundinaria spanostachya, Yushania lineolate and Fargesia ferax) over different seasons (spring vs. autumn), elevation, distance from water, etc. in Liziping National Nature Reserve (Liziping NR), China.
Results

The results show that a total of 2,562 operational taxonomic units (OTUs) were obtained from all 101 samples, which belonged to 24 phyla and 608 genera. Proteobacteria was the dominant phyla, followed by Acidobacteria and Actinobacteria. The Sobs index and Shannon index of F. ferax phyllosphere bacteria were greater than that of the other two bamboo species in both seasons. The Sobs index and Shannon index of phyllosphere bacteria in all three bamboo species in autumn were significantly higher than in spring. Season was a stronger driver of community structure of phyllosphere bacteria than host bamboo species based on the (un)weighted UniFrac distance matrix. Many bacteria phyla were negatively correlated with elevation and distance from water, but positively related to mean height of bamboo and mean base diameter of bamboo. Function prediction of PICRUSt revealed the relative abundance of transporters function was highest in all three bamboo species, followed by ABC transporters. There were nine relative abundance pathways with significant differences in the 3-level KEGG pathway. The genes related to membrane transport, signal transduction and porphyrin transport in phyllosphere bacteria of F. ferax were significantly lower than in the other two species.
Conclusions

The composition, diversity and community structure of phyllosphere bacteria in bamboo, a staple food source of giant pandas, were primarily affected by the season, species, altitude, tree layer and shrub layer. The better the growth of bamboo forests, the richer the bacterial phyla in the bamboo phyllosphere. Our study presented a deeper understanding of factors influencing the bacterial community in the bamboo phyllosphere. These findings could provide a reference for the restoration and management of giant panda habitat and food resources in this area, especially for those small isolated populations of giant pandas in Xiaoxiangling mountains.
Development of a Conceptual Framework for Linking mHealth Applications to eRecord Systems in Botswana
Authors: Ndlovu Kagiso , Mars Maurice , Scott Richard E.
Published: June 2021

Background: The proliferation of mHealth solutions and eRecord systems is inevitable in developing countries, and ensuring their bi-directional interoperability is essential. Interoperability has been described as the ability for two or more systems or components to exchange information and use the information that has been exchanged. Given the importance of linking mHealth solutions to eRecord systems in the developing world, a suitable interoperability framework is required to provide an agreed approach to interoperability and specify common elements. Although eHealth interoperability frameworks exist in the literature, none meet all the requirements for linking mHealth solutions to eRecord systems in developing countries. The aim of this study was to describe the design and development of a conceptual framework for linking mHealth solutions to eRecord systems in Botswana, as an exemplar.Methods: An iterative and reflective process was adopted, supported by existing literature and research including consultations with eHealth experts, and guidance from existing frameworks. These collectively identified key elements, concepts, and standards relevant and essential for framework design and development.Results: The mHealth-eRecord Interoperability Framework (mHeRIF) was developed which highlights the need for: governance and regulation of mHealth and eRecord systems, a national health information exchange, and which interoperability levels to achieve. Each of these are supported by integral themes and concepts. It also addresses the need for regular review, accreditation, and alignment of framework concepts and themes with a National eHealth Strategy Interoperability Development Process. To demonstrate the framework’s applicability, a proposed architecture for the Kgonafalo mobile telemedicine programme is presented.Conclusion: Interoperable mHealth solutions and eRecords systems have the potential to strengthen health systems. This study reports the design and development of an evidence-based mHeRIF to align with, build upon, and expand National eHealth Strategies by guiding the linking of mHealth solutions to eRecord systems in Botswana and other developing countries facing similar circumstances.
Beehives Possess Their Own Distinct Microbiomes
Authors: Santorelli Lorenzo , Wilkinson Toby , Abdulmalik Ronke , Rai Yuma , Creevey Christopher J , Huws Sharon , Gutierrez-Merino Jorge
Published: June 2021

Honey bees use plant material to manufacture their own food. These insect pollinators visit flowers repeatedly to collect nectar and pollen, which are shared with other hive bees to produce honey and beebread. While producing these products, beehives accumulate a tremendous amount of microbes, including bacteria that derive from plants and different parts of the honey bees’ body. In this study, we conducted 16S rDNA metataxonomic analysis on honey and beebread samples that were collected from 15 beehives in the southeast of England in order to quantify the bacteria associated with beehives. The results highlighted that honeybee products carry a significant variety of bacterial groups that comprise bee commensals, environmental bacteria and pathogens of plants and animals. Remarkably, this bacterial diversity differs amongst the beehives, suggesting a defined fingerprint that is affected, not only by the nectar and pollen gathered from local plants, but also from other environmental sources. In summary, our results show that every hive possesses their own distinct microbiome, and that honeybee products are valuable indicators of the bacteria present in the beehives and their surrounding environment.
Hyperoside Suppresses Osteoclasts Differentiation and Function through Down-Regulating TRAF6/p38 MAPK Signaling Pathway
Authors: Zhu Jun , Zhang Min , Liu Xiong-Li , Yin Zhi-Gang , Han Xiao-Xue , Wang Hui-Juan , zhou Ying
Published: June 2021

Background: Osteoporosis (OP) is a systemic metabolic bone disease that the bone resorption exceeds the bone formation,resulting in reduced bone mass, degeneration of the microstructure of bone tissue, and then increased bone fragility and fracture risk. Hyperoside (HP), as a natural product, can promote proliferation and differentiation of osteoblasts and presents a protective effect on ovariectomized (OVX) mice. However, the inhibitory effect of HP on osteoclasts (OCs) and the potential mechanism remains to be elucidated.Methods: In this study, RAW264.7 cells were used to generate OCs induced by RANKL, and HP was applied to the cell model. The effect of HP on OCs differentiation by TRAP-positive cell counting and TRAP activity test; Bone resorption assay and actin ring formation assay were used to verify the effect of HP on OCs function; The expression levels of osteoclast-specific genes and proteins were proved by RT-PCR and Western blotting.Results: HP significantly suppressed RANKL-induced OCs differentiation, function and the mRNAs expression levels of the osteoclast-related genes. Western Blotting results demonstrated that HP reduced the expression level of TNF receptor-associated factor 6 (TRAF6) and inhibited the p38 MAPK signing pathway by reducing the phosphorylation level of p38, which subsequently down-regulated the expression level of c-fos and NFATc1, ultimately, led to a decrease of the osteoclast-specific proteins CTSK and TRAP. In addition, TRAP-positive cell counting and TRAP activity test showed that HP could inhibit the differentiation of OCs; Bone resorption assay indicated that HP could restrain the OCs’ bone resorptive activity. Actin ring formation assay showed HP can cause the shrinkage of osteoclasts and disruption of actin ring structure.Conclusion: These results revealed that HP had an inhibitory effect on OCs by down-regulating TRAF6/p38 MAPK signaling pathway. Therefore, HP could be a promising natural compound for lytic bone diseases.
Circular RNA circLOC101928570 Suppress Systemic Lupus Erythematosus Progression Via Targeting the miR-150/c-myb Axis
Authors: Zhao Xingwang , Zhang Longlong , Wang Juan , Song Zhiqiang , Ni Bing , You Yi
Published: June 2021

Background: Accumulating evidence supports the implication of circRNAs in systemic lupus erythematosus (SLE). however, little is known about their the detailed mechanisms and the roles of circRNAs in the pathogenesis of SLE.Methods: Quantitative real time-PCR (qRT-PCR) was used to determine the levels of circLOC101928570 and miR-150 in peripheral blood mononuclear cells (PBMCs) of SLE. Overexpression and knockdown experiments were conducted to assess the effects of circLOC101928570. Fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), luciferase reporter assays, western blot, flow cytometry analysis and enzyme-linked immunosorbent assay (ELISA) were used to investigate the molecular mechanisms underlying the function of circLOC101928570. Results: The results showed that the level of circLOC101928570 was significantly down-regulated in SLE and correlated with systemic lupus erythematosus disease activity index (SLEDAI). Functionally, circLOC101928570 acted as a miR-150 sponge to relieve the repressive effect on its target c-myb, which modulates the activation of immune inflammatory responses. CircLOC101928570 knockdown enhanced apoptosis. Moreover, circLOC101928570 promote the transcriptional level of IL2RA through directly regulate miR-150/c-myb axis. Conclusion: Overall, our findings demonstrated that circLOC101928570 played a critical role in SLE. The down-expression of circLOC101928570 suppressed SLE progression through miR-150/c-myb/IL2RA axis. Our findings identified that circLOC101928570 serve as a potential biomarker for the diagnosis and therapy of SLE.
Randomized Trial of the Feasibility of ED-Initiated School-Based Asthma Medication Supervision (ED-SAMS)
Authors: Gerald Lynn B , Gerald Joe K , VanBuren John , Lowe Ashley , Guthrie Cecilia , Klein Eileen , Morrison Andrea , Startup Emily , Denninghoff Kurt
Published: June 2021

Background: While using an inhaled corticosteroid (ICS) in the weeks after an ED visit reduces repeat visits, few children receive a needed prescription. Because a prescription may not be filled or used, dispensing ICS at discharge and supervising its use at school could overcome both barriers until follow-up care is established. To assess the feasibility of such an intervention, we conducted a pilot study among elementary-age school children with persistent asthma who were discharged from the ED following an asthma exacerbation. Methods: Eligible children were randomly assigned to (a) ED-dispensing of ICS with home supervision or ED-dispensing of ICS with home and school supervision. The primary outcomes were ability to recruit and retain participants, ability to initiate school-supervised medication administration within 5 days of discharge, and participant satisfaction. Results: Despite identifying 437 potentially eligible children, only 13 (3%) were enrolled with 6 being randomized to the intervention group and 7 to the control group. Eleven (85%) randomized participants completed the 90-day interview (primary outcome) and 8 (62%) completed the 120-day interview (safety endpoint). Four (67%) intervention participants started their school regimen within 5 business days and 2 started within 6 business days.Conclusion: While our pilot study did not meet its recruitment goal, it did achieve its primary purpose of assessing feasibility before undertaking a larger, more intensive study. Several major recruitment barriers need to be mitigated before EDs can successfully partner with schools to establish supervised ICS treatment. Clinical Trial Registry: ClinicalTrials.gov, NCT03952286. Registered May 16,2019, https://clinicaltrials.gov/ct2/show/NCT03952286?term=ED+SAMS&draw=2&rank=1
Disease Severity Is an Independent Risk Factor of Mortality and Outcomes in Critically Ill Patients With Carbapenem-resistant Klebsiella Pneumoniae Bloodstream Infections: a 5-year Retrospective Analysis
Authors: Qiu Yuzhen , Xu Wen , Dai Yunqi , Tan Ruoming , Liu Jialin , Gu Feifei , Chen Erzhen , Wang Xiaoli , Qu Hongping
Published: June 2021

Background: Carbapenem-resistant Klebsiella pneumoniae bloodstream infections (CRKP-BSIs) are associated with high morbidity and mortality rates, especially in critically ill patients. Comprehensive mortality risk analyses and therapeutic assessment in real-world practice are beneficial to guide individual treatment.Methods: We retrospectively analyzed 87 patients with CRKP-BSIs (between July 2016 and June 2020) to identify the independent risk factors for 28-day all-cause mortality. The therapeutic efficacies of tigecycline-and polymyxin B-based therapies were analyzed.Results: The 28-day all-cause mortality and in-hospital mortality rates were 52.87% and 67.82%, respectively, arising predominantly from intra-abdominal (56.32%) and respiratory tract infections (21.84%). A multivariate analysis showed that 28-day all-cause mortality was independently associated with the patient’s APACHE II score (p = 0.002) and presence of septic shock at BSI onset (p = 0.006). All-cause mortality was not significantly different between patients receiving tigecycline- or polymyxin B-based therapy (55.81% vs. 53.85%, p = 0.873), and between subgroups mortality rates were also similar. Conclusions: Critical illness indicators (APACHE II scores and presence of septic shock at BSI onset) were independent risk factors for 28-day all-cause mortality. There was no significant difference between tigecycline- and polymyxin B-based therapy outcomes. Prompt and appropriate infection control should be implemented to prevent CRKP infections.
Gene-gene Interaction of AhR With and Within the Wnt Cascade Affects Susceptibility to Lung Cancer
Authors: Rosenberger Albert , Muttray Nils , Hung Rayjean J , Christiani David C , Caporaso Neil E , Liu Geoffrey , Bojesen Stig E , Marchand Loic Le , Albanes Demetrios , Aldrich Melinda C , Tardon Adonina , Fernández-Tardón Guillermo , Rennert Gad , Field John K , Davies Michael P.A. , Liloglou Triantafillos , Kiemeney Lambertus A , Lazarus Philip , Wendel Bernadette , Haugen Aage , Zienolddiny Shanbeh , Lam Stephen , Schabath Matthew B , Andrew Angeline S , Duell Eric J , Arnold Susanne M , Goodman Gary E , Chen Chu , Doherty Jennifer A , Taylor Fiona , Cox Angela , Woll Penella J , Risch Angela , Muley Thomas R , Johansson Mikael , Brennan Paul , Landi Maria Teresa , Shete Sanjay S , Amos Christopher I , Bickeböller Heike
Published: June 2021

Introduction: Aberrant Wnt signalling, regulating cell development and stemness, is observed in many cancer entities. Aryl hydrocarbon receptor (AhR) mediates tumorigenesis of environmental pollutants. Complex interaction patterns of genes assigned to AhR/Wnt-signalling were recently associated to lung cancer susceptibility. Aim: To assess the association and predictive ability of AhR/Wnt-genes with lung cancer in cases and controls of European descent. Methods: Odds ratios (OR) were estimated for genomic variants assigned to the genes DKK2, DKK3, DKK4, FRZB, SFRP4 and Axin2 and other lung cancer-related genes. Logistic regression models with variable selection were trained, validated and tested to predict lung cancer. Further, decision trees were created to investigate variant x variant interaction. All analyses were performed for overall lung cancer and for subgroups. Results: No association with overall lung cancer was observed, but within the subgroups of ever smokers (e.g. maker rs2722278 SFRP4; OR=1.20; 95%-CI: 1.13-1.27; p=5.6 10-10) and never smokers. Although predictability is poor, AhR/Wnt-variants are unexpected overrepresented in optimized prediction scores for overall lung cancer and for small cell lung cancer. Remarkable, the score for never-smokers contained solely two AhR/Wnt-variants. The optimal decision tree for never smokers consists of 7 AhR/Wnt-variants and only two lung cancer variants, no assigned to any CHRN gene. Conclusions: The role of variants belonging to Wnt/AhR-pathways in lung cancer susceptibility may be underrated in main-effects association analysis. Complex interaction patterns in individuals of European descent have moderate predictive capacity for lung cancer or subgroups thereof, especially in never smokers.
Circ_0005232 Promotes the Progression of Oral Squamous Cell Carcinoma by Sponging miR-1299 to Regulate CDK6
Authors: Zhang Xue , Guo Guang-Yu , Wang Zhen-Hua , Zhang Zhong-Ti
Published: June 2021

Objectives: CircRNA may play essential roles and act as biomarkers in tumor development due to their special stable structure. However, the mechanism by which circRNAs affect OSCC progression is still unclear. Methods: qRT-PCR was performed to detect circ_0005232 expression level in oral squamous cell carcinoma (OSCC) tissues and cell lines. Colony formation assays, cell migration and invasion assays, and wound healing assays were performed to verify the effects of overexpression or knockdown of circ_0005232 on the biological function of OSCC cell lines. Western blot was performed to determine the effects of circ_0005232 on epithelial-to-mesenchymal transition (EMT) and expression of MMP2 and MMP9 in OSCC cell lines. Dual luciferase reporter assays, rescue assays, RNA immunoprecipitation assays, and EDU incorporation assays were performed to explore interactions among circ_0005232, miR-1299, and CDK6. Results: qRT-PCR results confirmed that circ_0005232 was expressed significantly higher in OSCC tissue and cell lines. Functional experiments indicated that overexpression of circ_0005232 promoted OSCC cell lines proliferation，migration and invasion ability, while inhibition of circ_0005232 caused opposite results. MiR-1299 knockdown could rescue the changes in cell function caused by circ_0005232 knockdown. The dual luciferase reporter assay verified that circ_0005232 could bind with miR-1299 to affect the proliferation，migration and invasion ability of OSCC cell lines. RNA immunoprecipitation assays indicated that circ_0005232 could increase CDK6 expression by sponging miR-1299.Conclusions: Our results demonstrate that circ_0005232 exerts its tumor-promoting effects by sponging miR-1299 which then affects function of CDK6. Therefore, circ_0005232 may represent a novel potential prognostic biomarker and therapeutic target in OSCC.
Altered Expression of miR-146a-5p and Bcl-2 in Oncocytic Carcinoma of the Breast: A Case Report
Authors: Koi Yumiko , Yamamoto Yuki , Fukunaga Saori , Sasada Tatsunari , Kajitani Keiko , Ohara Masahiro , Daimaru Yutaka , Tahara Hidetoshi , Tamada Ryuichiro
Published: June 2021

Background: Oncocytic carcinoma of the breast is extremely rare, and its molecular profile is poorly understood. The distinctive feature of oncocytic carcinoma of the breast is that the granular eosinophilic cytoplasm contains numerous mitochondria. Recently, microRNA-146a-5p has been identified as a contributor to carcinogenesis and as a mitochondria-related microRNA, which regulates the mitochondrial function affecting Bcl-2. Bcl-2 plays a role in mitochondrial apoptosis.Case presentation: We report the clinical features, histopathological features, and immunohistochemical and molecular findings of oncocytic carcinoma of the breast in a 76-year-old woman. Immunohistochemistry studies revealed that the tumor cells were positive for antimitochondrial antibody but negative for gross cystic disease fluid protein 15, which confirmed the diagnosis. For molecular profiling, expression of microRNA-146a-5p and Bcl-2 messenger RNA (mRNA), which are mitochondria-related small molecules, were evaluated using real-time reverse transcription polymerase chain reaction. We found that the expression of microRNA-146a-5p was significantly lower (p < 0.01) and that of Bcl-2 mRNA was significantly higher (p < 0.01) compared to the control group (with no specific type of breast cancer). Conclusions: The significant changes in the expression of microRNA-146a-5p and Bcl-2 are specific to oncocytic carcinoma of the breast. Therefore, we suggest that the use of microRNA-146a-5p to target Bcl-2 has a potential therapeutic effect on oncocytic carcinoma of the breast.
The Generalized Hamilton Principle and Non-Hermitian Quantum Theory
Authors: Wu Xiang-Yao , Wu Ben-Shan , Liu Xiao-Jing , Ren Ming-Li , Han Meng , Jiang Ming-Qi , Zhu Xiang-Jiu , Liu Han , Wu Qi-Ming
Published: June 2021

The Hamilton principle is a variation principle describing the isolated and conservative systems, its Lagrange function is the difference between kinetic energy and potential energy. By Feynman path integration, we can obtain the Hermitian quantum theory, i.e., the standard Schrodinger equation. In this paper, we have generalized the Hamilton principle to the generalized Hamilton principle, which can describe the open system (mass or energy exchange systems) and nonconservative force systems or dissipative systems, and given the generalized Lagrange function, it has to do with the kinetic energy, potential energy and the work of nonconservative forces to do. With the Feynman path integration, we have given the non-Hermitian quantum theory of the nonconservative force systems. Otherwise, with the generalized Hamilton principle, we have given the generalized Hamiltonian for the particle exchanging heat with the outside world, which is the sum of kinetic energy, potential energy and thermal energy, and further given the equation of quantum thermodynamics. PACS: 03.65.-w, 05.70.Ce, 05.30.Rt
Technical Study of Polychrome Arhat Figures Dated From the Song Dynasty(960-1279 CE) From the Lingyan Temple, Changqing, Shandong, China
Authors: Tong Yongdong , Cai Youzhen , Wang Xuening , Li Zhimin , Nevin Austin , Ma Qinglin
Published: June 2021

Scientific analysis revealed the materials and techniques used in the process of making the polychrome sculptures providing a solid foundation for the protection and restoration of the painted statues. In addition analysis revealed changes in colour schemes applied to the sculptures can provide the basis for the virtual restoration of the painted statues. In order carry out scientifically-informed protection and restoration of the Bodhidharma statue from the Lingyan Temple, Changqinq, Shandong, several analytical methods such as optical microscope (OM), Micro-Raman spectroscopy (μ-RS), scanning electron microscopy coupled with energy dispersive X-ray analysis (SEM-EDS) and Fourier transform infrared spectroscopy (FTIR) were employed. Analysis clearly reveal the information including the stratigraphic structure and the composition of pigment. The use of silver foils and golden yellow pyrophyllite mineral to replace gold foils were found in the gilding paint layer in the later repainting after the Song Dynasty. This work reports the coexistence of emerald green (Cu(C2H3O2)2·3Cu(AsO2)2) and the degradation product lavendulan (NaCaCu5(AsO4)4Cl·5H2O) in large areas of the paint stratigraphy and on the surface confirming that the degradation of emerald green is related to the thickness of the paint layer; in thinner paint layers emerald green is transformed in lavendulan, while thicker layers of contain both lavendulan and emerald green, suggesting an environmental source of chlorides.
Magnitude and determinants of Poor Self-Care Practices and associated factors among Hypertensive Patients attending at Debre Berhan Referral Hospital, Amhara Regional State, Ethiopia
Authors: Getnet Mekasha
Published: June 2021

Background: Hypertension is one of a non-communicable diseases that become public health concern and cause early mortality around the globe. Poor management of hypertension is a very important cause for various cardiovascular problems. Reducing the outcome of the disease through compliance to self-care practices is crucial. However, comprehensive assessment on domains of self-care was not well studied.
Objective: To assess self-care practices and associated factors among hypertensive patient attending in Debre Berhan Referral Hospital.
Method: A hospital based cross-sectional study was conducted. Initially the data were checked manually and entered in to Epi-Data version 3.1. P-value of <0.05 was used as a cut of point to affirm statistical significance. Finally, results were presented in text, tables and graphs.
Result: The prevalence of poor self-care practice was had poor self-care practices with 95% CI (71.7, 80.3%). Multivariate analysis indicated that patients without comorbidities 1.5 (1.3-1.9), being aged 60 and above years 4.2 (1.7-10.3) and unavailability of blood pressure apparatus at home were more likely to have poor self-care practice as compared with their counter parts.
Conclusion: - The level of self-care practice was found to be low and attention is needed for self-care practices.