bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic analysis of the basic/helix-loop-helix (bHLH) transcription factor family in pummelo (Citrus grandis) and identification of the key members involved in the response to iron deficiency
Authors: Zhang Xiao-Yong , Qiu Jie-Ya , Hui Qiu-Ling , Xu Yuan-Yuan , He Yi-Zhong , Peng Liang-Zhi , fu xing-zheng 
Published: March 2020

Abstract
Background

Iron (Fe) deficiency is a common problem in citrus production. As the second largest superfamily of transcription factors (TFs), the basic/helix-loop-helix (bHLH) proteins have been shown to participate in the regulation of Fe homeostasis and a series of other biological and developmental processes in plants. However, this family of members in citrus and their functions in citrus Fe deficiency are still largely unknown.

Results

In this study, we identified a total of 128 CgbHLHs from pummelo ( Citrus grandis ) genome that were classified into 18 subfamilies by phylogenetic comparison with Arabidopsis thaliana bHLH proteins. All of these CgbHLHs were randomly distributed on nine known (125 genes) and one unknown (3 genes) chromosomes, and 12 and 47 of them were identified to be tandem and segmental duplicated genes, respectively. Sequence analysis showed detailed characteristics of their intron-exon structures, bHLH domain and conserved motifs. Gene ontology (GO) analysis suggested that most of CgbHLHs were annotated to the nucleus, DNA-binding transcription factor activity, response to abiotic stimulus, reproduction, post-embryonic development, flower development and photosynthesis. In addition, 27 CgbHLH proteins were predicted to have direct or indirect protein-protein interactions. Based on GO annotation, RNA sequencing data in public database and qRT-PCR results, several of CgbHLHs were identified as the key candidates that respond to iron deficiency.

Conclusions

In total, 128 CgbHLH proteins were identified from pummelo, and their detailed sequence and structure characteristics and putative functions were analyzed. This study provides comprehensive information for further functional elucidation of CgbHLH genes in citrus.
Ubiquitin-specific protease-44 inhibits the proliferation and migration of cells via inhibition of JNK pathway in clear cell renal cell carcinoma
Authors: Zhou Jiangqiao , Wang Tianyu , Qiu Tao , Chen Zhongbao , Ma Xiaoxiong , Zhang Long , Zou Jilin 
Published: March 2020

Abstract
Background: Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer. Ubiquitin-specific protease (USP)44 has been reported to be involved in various cancers. We investigated the function, role and molecular mechanism of USP44 in ccRCC. Methods: Data obtained from the Cancer Genome Atlas Data Portal and Gene Expression Omnibus database were analyzed to uncover the clinical relevance of USP44 expression and tumor development. USP44 function in the proliferation and migration of tumor cells was assessed by cellular and molecular analyses using ccRCC lines (786-O cells and Caki-1 cells).Results: USP44 showed low expression in ccRCC cancer tissues compared with that in normal tissue. USP44 expression was negatively correlated with tumor stage, tumor grade, and patient survival. USP44 overexpression inhibited the proliferation and migration of 786-O cells and Caki-1 cells significantly. USP44 overexpression also prohibited cell proliferation by upregulating expression of P21, downregulating cyclin-D1 expression, and inhibiting cell migration by upregulating expression of matrix metalloproteinase (MMP)2 and MMP9. USP44 knockdown enhanced the proliferation and migration of 786-O cells and Caki-1 cells. USP44 function in inhibiting the proliferation and migration of 786-O cells and Caki-1 cells was associated with phosphorylation of Jun N-terminal kinase (JNK).Conclusion: USP44 may be a marker in predicting ccRCC progression. Inhibition by USP44 of the proliferation and migration of 786-O cells and Caki-1 cells is dependent upon the JNK pathway.
Offspring sex affects the susceptibility to maternal smoking-induced lung inflammation and the effect of maternal antioxidant supplementation in mice
Authors: Wang Baoming , Chan Yik Lung , Zhou Shengyu , Saad Sonia , Chen Hui , Oliver Brian G 
Published: March 2020

Abstract
Background: Cigarette smoke exposure ( SE ) during pregnancy is the largest modifiable risk factor for the development of lung disorders in offspring. We have previously shown that maternal L-Carnitine treatment can reduce the adverse impacts of maternal SE on renal and brain disorders in offspring. Here, we investigated the effect of maternal L-Carnitine supplementation on lung inflammatory pathways, autophagy, and mitophagy markers in the offspring in response to maternal SE. Female Balb/c mice (8 weeks) were exposed to cigarette smoke for 6 weeks prior to mating, during gestation and lactation. Half of the SE mothers were given L-Carnitine supplementation (1.5mM in drinking water, SE+LC) during gestation and lactation. Lungs from the offspring were studied at birth and adulthood (13 weeks) in both genders. Results: At birth, in male offspring, there were increased lev inflammatory markers (phosphorylated(p)-ERK1,2, p-P38 MAPK, p-NF-kB), and inflammasome marker (NLRP3), as well as mitophagy fission marker Drp-1 and autophagosome marker (LC3A/B-II) in the lung. Maternal L-Carnitine supplementation significantly reduced NLRP3 level. In contrast, maternal SE only increased IL1-β in female offspring, which was reversed by maternal L-Carnitine supplementation. At 13 weeks, there was an increase in LC3A/B-II and p-NF-kB in the male SE offspring with reduced p-JNK1,2, which were partially normalised by maternal L-Carnitine treatment. Female offspring were not affected by maternal SE at this age. Conclusion : Maternal SE had adverse impacts on the male offspring’s lung, which were partially alleviated by maternal L-Carnitine supplementation. Females seem to be protected from the adverse effects of maternal SE.
Clinicopathological and Prognostic Value of SNHG6 in Cancers: a Systematic Review and a Meta-analysis
Authors: Zhang Shuo , Qiu Dandan , Xie Xiaohong , Shen Yong 
Published: March 2020

Abstract
Background The long non-coding RNA small nucleolar RNA host gene 16 (lncRNA SNHG6) is dysregulated in various malignant tumor. However, a definite conclusion on the clinical value of lncRNA SNHG6 expression in human cancers has not been determined. The purpose of the present meta-analysis was to comprehensively elucidate the association between SNHG6 expression and clinical outcomes in cancers. Methods A systematic search was performed through the PubMed, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wangfang databases for relevant studies. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were collected to estimate the prognostic value, and the odds ratios (ORs) with 95% CIs were used to evaluate the relationship between lncRNA SNHG6 expression and clinicopathological features, including tumor invasion depth, lymph node metastasis (LNM), distance metastasis (DM), and TNM stage. Results A total of 914 patients from 13 studies were included in this meta-analysis. The pooled results suggested that evaluated SNHG6 expression could predict an unfavorable overall survival (OS) (HR = 2.04, 95% CI:1.56~2.52) with no heterogeneity ( I 2 = 0.0%, p = 0.996). Subgroup analysis indicated a significant association between high SNHG6 expression and shorter OS in studies with digestive system cancers (HR = 2.05, 95%CI: 1.47-2.62), sample size < 70 (HR = 2.70, 95%CI: 1.29-4.11), and univariate and multivariate analysis (HR = 2.04, 95%CI: 1.44-2.64). Moreover, high SNHG6 expression was positively correlated with tumor invasion depth (OR = 1.76, 95%CI: 1.18-2.63), LNM (OR = 1.60, 95%CI: 1.18-2.17), DM (OR = 1.90, 95%CI: 1.37-2.64) and advanced TNM stage (OR = 1.88, 95%CI: 1.36-2.60) in patients with cancers. Conclusions High lncRNA SNHG6 expression was correlated with tumor invasion depth, LNM, DM, and advanced TNM stage, suggesting that SNHG6 may serve as a promising prognostic biomarker of human cancers.
Sex difference in synaptic plasticity in the anterior cingulate cortex of adult mice
Authors: Liu Ren-Hao , Xue Man , Li Xu-Hui , Zhuo Min 
Published: March 2020

Abstract
Sex differences in certain types of pain sensitivity and emotional responses have been previously reported. Synaptic plasticity is a key cellular mechanism for pain perception and emotional regulation, including long-term potentiation (LTP) and long-term depression (LTD). However, it is unclear whether there is a sex difference at synaptic level. Recent studies indicate that excitatory transmission and plasticity in the anterior cingulate cortex (ACC) are critical in chronic pain and pain related emotional responses. In the present study, we used 64-channel multielectrode (MED64) system to record synaptic plasticity in the ACC of male and female adult mice. We found that there was no significant difference in theta-burst stimulation (TBS)-induced LTP between female and male mice. Furthermore, the recruitment of inactive channels was also not different. For LTD, we found that LTD was greater in slices of ACC in male mice than female mice. Our results demonstrate that LTP in the ACC does not show any sex-related difference.
Serum concentrations of asprosin in new-onset type 2 diabetes
Authors: Naiemian Shakiba , naeemipour Mohsen , Zarei Mehdi , Gohari Ali , Behroozikhah Mohammad Reza , Heydari Hafez , Miri Mohammad 
Published: March 2020

Abstract
Background: Asprosin, a newly identified adipokine, is pathologically increased in individuals with insulin resistance. However, the available evidence on the association of asprosin and type 2 diabetes mellitus (T2DM) status is still scarce. Therefore, this study aimed to determine the relationship between serum concentrations of asprosin and T2DM status . Methods: This observational study was performed based on 194 adults (97 newly diagnosed T2DM and 97 healthy individuals). Anthropometric and biochemical variables were determined in all participants . Serum concentrations of asprosin were measured using enzyme-linked immunosorbent assay (ELISA). Results: In patients with T2DM, the serum concentrations of asprosin were significantly higher than the healthy controls (4.18 [IQR: 4.4] vs. 3.5 [IQR: 1.85], P< 0.001). The concentrations of asprosin were significantly correlated with body mass index (BMI) and fasting blood glucose (FBG) in healthy subjects and with BMI, FBG, hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), and quantitative insulin check index (QUICKI), triacylglycerol (TAG) and total cholesterol/ high-density lipoprotein cholesterol (TC/HDL-C) ratio in the T2DM group. In fully adjusted model, the odds ratio (OR) of T2DM with serum concentrations of asprosin was approximately 1.547 (95% CI 1.293-1.850, P< 0.001) compared to the control group . Multiple stepwise regression analysis indicated that FBG and HOMA-IR were independently associated with asprosin in T2DM. Conclusion : Our findings indicated that serum concentrations of asprosin are increased in patients with T2DM. Also, asprosin is correlated with insulin resistance and TC/HDL-C ratio (atherosclerotic risk factor of cardiovascular diseases) in patients with T2DM.
The considerations, experiences and support needs of family members making treatment decisions for patients admitted with major stroke: a qualitative study.
Authors: Visvanathan Akila , Mead Gillian , Dennis Martin , Whiteley William , Doubal Fergus , Lawton Julia 
Published: March 2020

Abstract
Background Treatment decision-making by family members on behalf of patients with major stroke can be challenging because of the shock of the diagnosis and lack of knowledge of the patient’s treatment preferences. We aimed to understand how, and why, family members made certain treatment decisions, and explored their information and support needs. Method Semi-structured interviews with family members (n=24) of patients with major stroke, within two weeks of hospital admission. Data were analysed thematically. Results Families’ approach to treatment decision-making lay on a spectrum according to the patient’s state of health pre-stroke (i.e. patient’s prior experience of illness and functional status) and any views expressed about treatment preferences in the event of life-threatening illness. Support and information needs varied according to where they were on this spectrum. At one extreme, family members described deciding not to initiate life-extending treatments from the outset because of the patients’ deteriorating health and preferences expressed pre-stroke. Information from doctors about poor prognosis was merely used to confirm this decision. In the middle of the spectrum were family members of patients who had been moderately independent pre-stroke. They described the initial shock of the diagnosis and how they had initially wanted all treatments to continue. However, once they overcame their shock, and had gathered relevant information, including information about poor prognosis from doctors, they decided that life-extending treatments were no longer appropriate. Many reported this process to be upsetting and expressed a need for psychological support. At the other end of the spectrum were family members of previously independent patients whose preferences pre-stroke had not been known. Family members described feeling extremely distressed at such an unexpected situation and wanting all treatments to continue. They described needing psychological support and hope that the patient would survive. Conclusion The knowledge that family members’ treatment decision-making approaches lay on a spectrum depending on the patient’s state of health and stated preferences pre-stroke may allow doctors to better prepare for discussions regarding the patient’s prognosis. This may enable doctors to provide information and support that is tailored towards family members’ needs.
Adenovirus infection promotes the formation of glioma stem cells by glioblastoma cells through the TLR9/NEAT1/STAT3 pathway
Authors: Zang Jian , Zheng Min-hua , Cao Xiu-li , Zhang Yi-zhe , Zhang Yu-fei , Gao Xiang-yu , Cao Yuan , Shi Mei , Han Hua , Liang Liang 
Published: March 2020

Abstract
BackgroundGlioma stem cells (GSCs) are glioma cells with stemness and are responsible for a variety of malignant behaviors of glioma. Evidence has shown that signals from tumor microenvironment (TME) enhance stemness of glioma cells, but the identity of the signaling molecules and underlying mechanisms have been incompletely elucidated.MethodsHuman samples and glioma cell lines were cultured in vitro to determine the effects of viral infection by sphere formation, qRT-PCR, Western blot, FACS and immunofluorescence; for in vivo analysis, mice subcutaneous tumor model was carried; while bioinformatics analysis and qRT-PCR were applied for further mechanistic studies.ResultsIn this study, we show that infection of patient-derived glioma cells with adenovirus (ADV) increases the formation of tumor spheres. ADV infection upregulated stem cell markers, and the resultant tumor spheres held the capacities of self-renewal and multi-lineage differentiation, and had stronger potential to form xenograft tumors in immune-compromised mice. ADV promoted GSC formation likely via TLR9, because TLR9 was upregulated after ADV infection, and knockdown of TLR9 reduced ADV-induced GSCs. Consistently, MYD88, as well as total STAT3 and phosphorylated (p-)STAT3, were also upregulated in ADV-induced GSCs. Knockdown of MYD88 or pharmaceutical inhibition of STAT3 attenuated stemness of ADV-induced GSCs. Moreover, we found that ADV infection upregulated lncRNA NEAT1, which is downstream to TLRs and play important roles in cancer stem cells via multiple mechanisms including strengthening STAT3 signaling. Indeed, knockdown of NEAT1 impaired stemness of ADV-induced GSCs. Lastly, we show that HMGB1, a damage associated molecular pattern (DAMP) that also triggers TLR signaling, upregulated stemness markers in glioma cells.ConclusionsIn summary, our data indicate that ADV, which has been developed as vectors for gene therapy and oncolytic virus, promotes the formation of GSCs via TLR9/NEAT1/STAT3 signaling.
TMEM147 promotes hepatocellular carcinoma progress by inducing EGFR/MAPK activity
Authors: Sun Chengyi , Xu Jing , Tian She , Liu Yanqing , Zhu Changhao , Yu Chao 
Published: March 2020

Abstract
Backgroud: Hepatocellular carcinoma (HCC) is characterized by rapid early proliferation and distant metastasis and is extremely difficult to treat. Aerobic glycolysis is a hallmark of abnormal glucose metabolism in cancer cells as has been shown to be associated with tumor proliferation and metastasis; however, the mechanisms underlying aerobic glycolysis remain unclear. Methods: Immunohistochemistry (IHC) and qRT-PCR was performed to investigate the association between TMEM147 expression and the clinicopathological characteristics and prognosis of patients with HCC. Loss- and gain-of function assays were performed to investigate the role of TMEM147 in proliferation, metastasis and glycolysis in vitro and vivo. Bioinformatic analysis and rescue assay were used to demonstrated the TMEM147 interacted with EGFR and promoted its retromer-mediated recycling back to the plasma membrane.Results: we identified TMEM147 as a protein that was highly expressed and associated with poor survival in patients with HCC. Both gain- and loss-of-function studies revealed that TMEM147 acted as a key oncoprotein by promoting HCC growth, metastasis, and glycolysis via the EGFR/ MAPK signaling pathway. Mechanistically, TMEM147 interacted with EGFR and promoted its retromer-mediated recycling back to the plasma membrane, thus increasing the stability of EGFR and prolonging activation of the downstream MAPK pathway.Conclusion: Collectively, these results demonstrated the role and functional mechanism of TMEM147 in HCC, and indicated that TMEM147 may represent a prognostic biomarker and potential therapeutic target for HCC.
Spouse and parent differences in caregiving experiences of people living with schizophrenia in rural China
Authors: Yu Yu , Li Tong-xin , Li Yi-lu , Qiu Dan , Xi Shi-jun , Xiao Shuiyuan , Tebes Jacob 
Published: March 2020

Abstract
Background: To comprehensively examine and carefully compare caregiving experiences and impacts between spouse and parent caregivers for people living with schizophrenia in China. Methods: A cross-sectional study was conducted in a sample of 264 community-dwelling primary family caregivers of people living with schizophrenia. Face-to-face interviews were conducted to collect information on caregiving activities, both objective and subjective burden, caregiver psychological distress including depression and anxiety, positive caregiving impact including caregiving rewarding feelings and family functioning between spouse and parent caregivers. Results: Both types of caregivers report engaging in similar caregiving activities and report comparable levels of objective burden. However, parent caregivers report significantly higher subjective burden than spouse caregivers (β=7.93, 95%CI:2.13, 13.73), which is also reflected in significantly higher depression (β =3.60, 95%CI:1.09, 6.12) and anxiety scores (β=2.37, 95%CI: 0.08, 4.65), and reports of lower family functioning (β =-1.61, 95%CI: -2.73, -0.49). Despite these differences, both groups of caregivers report comparable rewarding feelings about caregiving. Conclusions: The findings may be explained by the difference between subjective burden and objective burden, as well as the unique cultural and social characteristics of family caregivers in China. The study discusses implications for future intervention, particularly for parents as family caregivers. Keywords: Schizophrenia; family caregivers; caregiver burden; caregiving, parent, spouse
Intraoperative intrathoracic chemotherapy and debulking surgery for pulmonary adenocarcinoma with pleural dissemination and no lymph node metastasis
Authors: Ye Yiwang , Wu Da 
Published: March 2020

Abstract
Objective: assess the feasibility of intraoperative intrathoracic chemotherapy and debulking surgery for pulmonary adenocarcinoma patients with pleural dissemination and no lymph node metastasis. Methods: We retrospectively reviewed medical records of 23 pulmonary adenocarcinoma patients with pleural dissemination and no lymph node metastasis underwent debulking surgery. They were divided into intraoperative intrathoracic chemotherapy (IC) group comprising patients who not intraoperative intrathoracic chemotherapy (NIC) group. Result: There was no significant difference in the adverse reactions of chemotherapy between the two groups. The median progression-free survival (PFS) was 38.0 months (95% CI: 25.6-50.4) in IC group and 24.0months (95% CI: 6.3-41.7) in NIC group, respectively. There was statistical significance between two group (IC vs NIC, p=0.016).The median overall survival (OS) was42.0 months (95% CI: 37.4-46.6) in IC group and was 36.0months (95% CI: 28.4-43.6) in NIC group, respectively. But there were no statistical significance between two groups (p=0.082). Conclusions: Intraoperative intrathoracic chemotherapy might improve PFS for unexpected pulmonary adenocarcinoma with pleural dissemination and no lymph node metastasis in primary tumor resected patients and with less adverse reactions.
WEARCON: Wearable home monitoring in children with asthma reveals a strong association with hospital based assessment of asthma control.
Authors: Kamp Mattienne R van der , Klaver Emilie C , Thio Bernard J , Driessen Jean MM , de Jongh Franciscus HC , Tabak Monique , Palen Job AM van der , Hermens Hermie J 
Published: March 2020

Abstract
Asthma is one of the most common chronic diseases in childhood. Regular follow-up of physiological parameters in the home setting, in relation to asthma symptoms, can provide complementary quantitative insights into the dynamics of the asthma status. Despite considerable interest in asthma home-monitoring in children, there is a paucity of scientific evidence, especially on multi-parameter monitoring approaches. Therefore, the aim of this study is to investigate whether asthma control can be correctly assessed in the home situation by combining parameters from respiratory physiology sensors.
Sixty asthmatic and 30 healthy children were enrolled in the observational WEARCON-study. The paediatrician assessed asthma control according to GINA guidelines. All children were also evaluated during a 2-week home-monitoring period with wearable devices; a physical activity tracker, a handheld spirometer, smart inhalers, and an ambulatory electrocardiography device to monitor heart and respiratory rate. Multiple logistic regression analysis was used to determine which diagnostic measures were associated asthma control.
All 27 of the 27 uncontrolled asthmatic children and 31 of the 32 controlled asthmatic children could correctly be identified with this model. The final model showed that a larger variation in pre-exercise lung function (OR=1.36 95%-CI 1.06-1.75), an earlier wake-up-time (OR=1.06 95%-CI 1.01-1.11), more reliever use (OR=1.14 95%-CI 1.05-1.24) and a longer respiratory rate recovery time (OR=1.18 95%-CI 1.04-1.34) were significant contributors to the probability of having uncontrolled asthma.
Home-monitoring of physiological parameters is associated with paediatrician assessed asthma control. The constructed multivariate model identifies 100% of all uncontrolled asthmatic children, indicating a high potential for monitoring of asthma control. This may allow healthcare professionals to assess asthma control at home.
Trial registration: Netherlands Trail Register, NL6087. Registered 14 February 2017, https://www.trialregister.nl/trial/6087