bluuebunny/crossref_metadata_2025_split huggingface dataset:
RND2 attenuates apoptosis and autophagy in glioblastoma cells by targeting the p38 MAPK signalling pathway
Authors: Xu Yang , Sun Qian , Yuan Fan’en , Dong Huimin , Zhang Huikai , Geng Rongxin , Qi Yangzhi , Xiong Xiaoxing , Chen Qianxue , Liu Baohui 
Published: August 2020

Abstract
Background
Inhibition of p38 MAPK signalling leads to glioblastoma multiform (GBM) tumourigenesis. Nevertheless, the molecular mechanism that induces p38 MAPK signalling pathway silencing during GBM genesis has yet to be determined. Identifying new factors that can regulate p38 MAPK signalling is important for tumour treatment.

Methods
Flow cytometry, TUNEL assays, immunofluorescence, JC-1 assays, and western blot analyses were used to detect the apoptosis of GBM cells. The specific methods used to detect autophagy levels in GBM cells were western blot analysis, LC3B protein immunofluorescence, LC3B puncta assays and transmission electron microscopy. The functions of these critical molecules were further confirmed in vivo by intracranial xenografts in nude mice. Tumour tissue samples and clinical information were used to identify the correlation between RND2 and p62 and LC3B expression, survival time of patients, and tumour volumes in clinical patients.

Results
By summarizing data from the TCGA database, we found that expression of the small GTPase RND2 was significantly increased in human glioblastomas. Our study demonstrated that RND2 functions as an endogenous repressor of the p38 MAPK phosphorylation complex. RND2 physically interacted with p38 and decreased p38 phosphorylation, thereby inhibiting p38 MAPK signalling activities. The forced expression of RND2 repressed p38 MAPK signalling, which inhibited glioblastoma cell autophagy and apoptosis in vitro and induced tumour growth in the xenografted mice in vivo. By contrast, the downregulation of RND2 enhanced p38 MAPK signalling activities and promoted glioma cell autophagy and apoptosis. The inhibition of p38 phosphorylation abolished RND2 deficiency-mediated GBM cell autophagy and apoptosis. Most importantly, our study found that RND2 expression was inversely correlated with patient survival time and was positively correlated with tumour size.

Conclusions
Our findings revealed a new function for RND2 in GBM cell death and offered mechanistic insights into the inhibitory effects of RND2 with regard to the regulation of p38 MAPK activation.
EIF3H promotes aggressiveness of esophageal squamous cell carcinoma by modulating Snail stability
Authors: Guo Xiaobin , Zhu Rui , Luo Aiping , Zhou Honghong , Ding Fang , Yang Hongxin , Liu Zhihua 
Published: August 2020

Abstract
Background
Overexpression of eukaryotic translation initiation factor 3H (EIF3H) predicts cancer progression and poor prognosis, but the mechanism underlying EIF3H as an oncogene remains unclear in esophageal squamous cell carcinoma (ESCC).

Methods
TCGA database and the immunohistochemistry (IHC) staining of ESCC samples were used and determined the upregulation of EIF3H in ESCC. CCK8 assay, colony formation assay and transwell assay were performed to examine the ability of cell proliferation and mobility in KYSE150 and KYSE510 cell lines with EIF3H overexpression or knockdown. Xenograft and tail-vein lung metastatic mouse models of KYSE150 cells with or without EIF3H knockdown were also used to confirm the function of EIF3H on tumor growth and metastasis in vivo. A potential substrate of EIF3H was screened by co-immunoprecipitation assay (co-IP) combined with mass spectrometry in HEK293T cells. Their interaction and co-localization were confirmed using reciprocal co-IP and immunofluorescence staining assay. The function of EIF3H on Snail ubiquitination and stability was demonstrated by the cycloheximide (CHX) pulse-chase assay and ubiquitination assay. The correlation of EIF3H and Snail in clinical ESCC samples was verified by IHC.

Results
We found that EIF3H is significantly upregulated in esophageal cancer and ectopic expression of EIF3H in ESCC cell lines promotes cell proliferation, colony formation, migration and invasion. Conversely, genetic inhibition of EIF3H represses ESCC tumor growth and metastasis in vitro and in vivo. Moreover, we identified EIF3H as a novel deubiquitinating enzyme of Snail. We demonstrated that EIF3H interacts with and stabilizes Snail through deubiquitination. Therefore, EIF3H could promote Snail-mediated EMT process in ESCC. In clinical ESCC samples, there is also a positive correlation between EIF3H and Snail expression.

Conclusions
Our study reveals a critical EIF3H-Snail signaling axis in tumor aggressiveness in ESCC and provides EIF3H as a promising biomarker for ESCC treatment.
Body-mass index and long-term risk of sepsis-related mortality: a population-based cohort study of 0.5 million Chinese adults
Authors: Weng Li , Fan Junning , Yu Canqing , Guo Yu , Bian Zheng , Wei Yuxia , Yang Ling , Chen Yiping , Du Huaidong , Chang Liang , Gong Weiwei , Chen Junshi , Chen Zhengming , Du Bin , Lv Jun , Li Liming 
Published: August 2020

Abstract
Background
Sepsis represents a major worldwide healthcare burden. However, how body-mass index (BMI) is related to the long-term risk of sepsis-related mortality in low- and middle-income countries remains uncertain.

Methods
We examined the associations of sepsis-related mortality with both baseline BMI and waist circumference (WC) using data from China Kadoorie Biobank, a prospective cohort recruited during 2004–2008 and followed up to December 2016. After excluding participants with chronic obstructive pulmonary disease, tuberculosis, cancer, heart disease, and stroke, and omitting the first 3 years of follow-up, 440,763 participants remained for analysis.

Results
During a median follow-up of 10.0 years, 1957 sepsis-related deaths (3,134,870 person-years) were included for analysis. Compared with reference BMI of 22.5 to < 25.0 kg/m2, the multivariable-adjusted hazard ratios (HRs) for sepsis-related mortality were 2.42 (95% CIs 2.07–2.84) for BMI of < 18.5, 1.59 (1.36–1.85) for 18.5 to < 20.0, 1.21 (1.06–1.38) for 20.0 to < 22.5, 0.97 (0.83–1.13) for 25.0 to < 27.5, 0.98 (0.80–1.21) for 27.5 to < 30.0, and 1.22 (0.93–1.60) for ≥ 30.0 kg/m2. Further adjustment for WC led to slightly augmentation of the effect size for the lower BMI groups and null association in the obese group. In the association analysis between WC and sepsis-related mortality, compared with the middle quintile group, only the highest quintile group showed an increased risk of sepsis-related mortality after adjusted for BMI (HR = 1.54; 95% CI 1.28–1.84).

Conclusions
Underweight, lower normal weight, and abdominal obesity are associated with increased future risk of sepsis-related mortality over 10 years in the Chinese population. The double burden of underweight and obesity indicates a heavy sepsis burden faced by low- and middle-income countries.
CSS: cluster similarity spectrum integration of single-cell genomics data
Authors: He Zhisong , Brazovskaja Agnieska , Ebert Sebastian , Camp J. Gray , Treutlein Barbara 
Published: August 2020

AbstractIt is a major challenge to integrate single-cell sequencing data across experiments, conditions, batches, time points, and other technical considerations. New computational methods are required that can integrate samples while simultaneously preserving biological information. Here, we propose an unsupervised reference-free data representation, cluster similarity spectrum (CSS), where each cell is represented by its similarities to clusters independently identified across samples. We show that CSS can be used to assess cellular heterogeneity and enable reconstruction of differentiation trajectories from cerebral organoid and other single-cell transcriptomic data, and to integrate data across experimental conditions and human individuals.
Inhibition of glucose assimilation in Auxenochlorella protothecoides by light
Authors: Xiao Yibo , Guo Jianying , Zhu Huachang , Muhammad Anwar , Deng Haiteng , Hu Zhangli , Wu Qingyu 
Published: August 2020

AbstractBackgroundThe yield of microalgae biomass is the key to affect the accumulation of fatty acids. A few microalgae can assimilate organic carbon to improve biomass yield. In mixotrophic cultivation, microalgae can use organic carbon source and light energy simultaneously. The preference of the main energy source by microalgae determines the biomass yield.Auxenochlorella protothecoidesis an oleaginous mixotrophic microalga that can efficiently assimilate glucose and accumulate a large amount of biomass and fatty acids. The current study focused on the effect of light on the growth and glucose assimilation ofA. protothecoides.ResultsIn this study, we found that the uptake and metabolism of glucose inA. protothecoidescould be inhibited by light, resulting in a reduction of biomass growth and lipid accumulation. We employed comparative proteomics to study the influence of light on the regulation of glucose assimilation inA. protothecoides. Proteomics revealed that proteins involving in gene translation and photosynthesis system were up-regulated in the light, such as ribulose-phosphate 3-epimerase and phosphoribulokinase. Calvin cycle-related proteins were also up-regulated, suggesting that light may inhibit glucose metabolism by enhancing the production of glyceraldehyde-3-phosphate (G3P) in the Calvin cycle. In addition, the redox homeostasis-related proteins such as thioredoxin reductase were up-regulated in the light, indicating that light may regulate glucose uptake by changing the redox balance. Moreover, the increase of NADH levels and redox potential of the medium under illumination might inhibit the activity of the glucose transport system and subsequently reduce glucose uptake.ConclusionsA theoretical model of how glucose assimilation inA. protothecoidesis negatively influenced by light was proposed, which will facilitate further studies on the complex mechanisms underlying the transition from autotrophy to heterotrophy for improving biomass accumulation.
PUFA-synthase-specific PPTase enhanced the polyunsaturated fatty acid biosynthesis via the polyketide synthase pathway in Aurantiochytrium
Authors: Wang Sen , Lan Chuanzeng , Wang Zhuojun , Wan Weijian , Cui Qiu , Song Xiaojin 
Published: August 2020

Abstract
Background
Phosphopantetheinyl transferase (PPTase) can change the acyl-carrier protein (ACP) from an inactive apo-ACP to an active holo-ACP that plays a key role in fatty acids biosynthesis. Currently, the PPTase has been proved to be involved in the biosynthesis of polyunsaturated fatty acids (PUFAs) via a polyketide synthase (PKS) pathway in Thraustochytrids, while its characteristics are not clarified.

Results
Here, the heterologous PPTase gene (pfaE) from bacteria was first co-expressed with the PKS system (orfA–orfC) from Thraustochytrid Aurantiochytrium. Then, a new endogenous PPTase (ppt_a) in Aurantiochytrium was identified by homologous alignment and its function was verified in E. coli. Moreover, the endogenous ppt_a was then overexpressed in Aurantiochytrium, and results showed that the production and proportion of PUFAs, especially docosahexaenoic acid (DHA), in the transformant SD116::PPT_A were increased by 35.5% and 17.6%, respectively. Finally, higher DHA and PUFA proportion (53.9% and 64.5% of TFA, respectively) were obtained in SD116::PPT_A using a cerulenin feeding strategy.

Conclusions
This study has illustrated a PUFAs-synthase-specific PPTase in PKS system and provided a new strategy to improve the PUFA production in Thraustochytrids.
Vertical stratification of sand fly diversity in relation to natural infections of Leishmania sp. and blood-meal sources in Jamari National Forest, Rondônia State, Brazil
Authors: Leão Paula de Oliveira , Pereira Júnior Antonio Marques , de Paulo Paula Frassinetti Medeiros , Carvalho Luis Paulo Costa , Souza Ana Beatriz Nascimento , da Silva Michelli Santos , Castro Thaís Santos , Freitas Moisés Thiago de Souza , Rodrigues Moreno Magalhães de Souza , Ferreira Gabriel Eduardo Melim , Medeiros Jansen Fernandes 
Published: August 2020

Abstract
Background
Almost 1000 cases of American cutaneous leishmaniasis have been registered yearly in Rondônia State, Brazil. Little is known about the Leishmania transmission cycle (vectors and reservoirs) in the state. This study aimed to evaluate sand fly fauna from two vertical stratification layers in order to identify potential vectors and their blood-meal sources.

Methods
The study was conducted in Jamari National Forest. Sand flies were collected in the canopy (15 m) and at ground level (1 m) using HP light traps during four months, February, April, August and October, 2018. Insects were identified to the species level, and females were subjected to DNA extraction and PCR targeting minicircle kDNA and hsp70 (for Leishmania detection and species identification), and cytb (to identify blood-meal sources). Exploratory data analysis was used to determine mean of abundance and species richness between stratifications. The hsp70 and cytb sequences were analyzed and compared with sequences from GenBank.

Results
Overall, 68 species were identified from 15,457 individuals. On the Potosi trail, 7531 individuals of 49 species were collected; canopy captures totaled 6463 individuals of 46 species, while ground captures totaled 1068 individuals of 38 species. On the Santa Maria trail, 7926 individuals of 61 species were collected; canopy captures totaled 6136 individuals of 51 species, while ground captures totaled 1790 individuals of 53 species. A total of 23 pools were positive for kDNA (canopy n = 21, ground n = 2). Only two samples were sequenced for hsp70 (both in canopy); one sequence exhibited similarity with Leishmania braziliensis (Lutzomyia davisi pool) and another with L. naiffi (Lu. antunesi pool). The cytb fragment was amplified in 11 of 86 samples. Sample sequencing identified cytb DNA from 5 blood-meal sources: Micrastur gilvicollis, Psophia viridis, Tamandua tetradactyla, Homo sapiens and Choloepus didactylus.

Conclusions
Sand fly fauna is more diverse in the canopy than at ground level. Factors such as blood-meal sources, resting sites, and abiotic components probably contribute to high abundance in the canopy. Our results reinforce the possibility that Lu. antunesi and Lu. davisi participate in Leishmania transmission in forest environments and may play an important role in transmission from sylvatic to human hosts.
Mental health in the era of COVID-19: prevalence of psychiatric disorders in a cohort of patients with type 1 and type 2 diabetes during the social distancing
Authors: Alessi Janine , de Oliveira Giovana Berger , Franco Debora Wilke , Brino do Amaral Bibiana , Becker Alice Scalzilli , Knijnik Carolina Padilla , Kobe Gabriel Luiz , de Carvalho Taíse Rosa , Telo Guilherme Heiden , Schaan Beatriz D. , Telo Gabriela Heiden 
Published: August 2020

Abstract
Background
In patients with diabetes, the prevalence of depression and anxiety symptoms is about two to four times greater than in the general population. The association between diabetes and mental health disorders could be exacerbated in a stressful environment, and psychological distress could increase depressive symptoms and cause adverse diabetes outcomes.

Objectives
To assess the prevalence of mental health disorders in patients with diabetes during the social distancing period due to COVID-19 pandemic.

Methods
This is a cross-sectional study developed to assess the impact of social distancing on a cohort of adults with type 1 (n = 52) and type 2 diabetes (n = 68) in Brazil. Inclusion criteria involved having an HbA1c test collected in the past 3 months and having a valid telephone number in electronic medical records. The primary outcome was the prevalence of minor psychiatric disorders, assessed by survey (SRQ-20). Secondary outcomes included the prevalence of diabetes related emotional distress, eating and sleeping disorders, all assessed by validated surveys at the moment of the study. Statistical analyses included unpaired t-test for continuous variables and χ2 test for categorical variables.

Results
Overall (n = 120), participants had a mean age of 54.8 ± 14.4 years-old, and HbA1c of 9.0 ± 1.6% (75 ± 17.5 mmol/mol); 93% of patients showed signs of current mental suffering based on the surveys measured. Almost 43% of patients showed evidence of significant psychological distress, with a significant greater tendency in patients with type 2 diabetes. The presence of diabetes related emotional distress was found in 29.2% of patients; eating disorders in 75.8%; and moderate/severe sleeping disorders in 77.5%.

Conclusions
We found a high prevalence of evidence of psychological distress among patients with diabetes during the COVID-19 pandemic and this highlights the need for mental health access and support for patients with type 1 and type 2 diabetes.
Eye care utilization among diabetics in the South African National Health and Nutrition Examination Survey (SANHANES-1): a cross-sectional study
Authors: Akuffo Kwadwo Owusu , Asare Akosua Kesewah , Sewpaul Ronel , Dukhi Natisha , Kumah David Ben , Agyei-Manu Eldad , Addo Emmanuel Kofi , Reddy Priscilla 
Published: August 2020

AbstractObjectiveDiabetes is a chronic disease of uncontrolled blood sugar levels. People with diabetes are at an increased risk of developing visual impairment and other diabetes-related visual complications. The study aims to determine the eyecare utilization pattern and its associated determinants among diabetics in the South African National Health and Nutrition Examination Survey (SANHANES-1).ResultsThe mean age of participants was 56.2 years and 66.6% were females. The prevalence of eyecare utilization among participants was 49.0% and this differed significantly by age groups (p = 0.024) and the number of years since diabetes diagnosis (p < 0.001). After statistical adjustments, older age (55–64 years OR = 4.18, p = 0.003 and ≥ 65 years OR = 4.78, p = 0.002), having health insurance (OR = 6.32, p = 0.002), and having had diabetes for 6–10 years (OR = 4.23, p = 0.005) were significantly associated with eye care utilization. About half of people diagnosed with diabetes in South Africa have had an eye examination since diabetes diagnosis, which is disturbingly low given the impact of diabetes complications on eye health. Government policies must be directed at ensuring access to affordable health insurance and eye health education on diabetes.
HGF and IL-10 expressing ALB::GFP reporter cells generated from iPSCs show robust anti-fibrotic property in acute fibrotic liver model
Authors: Choi Ja Sung , Jeong In Sil , Park Young-Jin , Kim Sung-Whan 
Published: August 2020

Abstract
Background
Cell therapy using hepatocytes derived from stem cells has been regarded as a promising alternate to liver transplantation. However, the heterogeneity of these hepatocytes makes them unsuitable for therapeutic use. To overcome this limitation, we generated homogenous hepatocyte like induced hepatocyte-like (iHep) cells.

Methods
iHep cells were generated from induced pluripotent stem cells (iPSCs) integrated with the albumin (ALB) reporter gene. The therapeutic properties of these iHep cells were investigated after transplantation in fibrotic liver tissues of a mouse model.

Results
The iHep cells expressed hepatocyte specific genes and proteins, and exhibited high levels of hepatocyte growth factor (HGF) and interleukin (IL)-10 expressions. Transplantation of iHep cells significantly decreased thioacetamide (TAA)-induced liver fibrosis, apoptotic cells in the liver, and ameliorated abnormal liver function. Liver tissues engrafted with iHep cells exhibited decreased expression of pro-inflammatory factors such as transforming growth factor (TGF)-β, IL-6, and monocyte chemo attractant protein (MCP)-1. Furthermore, an increased number of proliferating hepatocytes and human albumin-expressing iHep cells were detected in mice liver.

Conclusions
This study has investigated and proven the liver regeneration potential of genome-edited iHep cells and promises to be a strong foundation for further studies exploring cell therapy as an alternative therapeutic option for the treatment of liver fibrosis.
Neural machine translation of chemical nomenclature between English and Chinese
Authors: Xu Tingjun , Chen Weiming , Zhou Junhong , Dai Jingfang , Li Yingyong , Zhao Yingli 
Published: August 2020

AbstractMachine translation of chemical nomenclature has considerable application prospect in chemical text data processing between languages. However, rule based machine translation tools have to face significant complication in rule sets building, especially in translation of chemical names between English and Chinese, which are the two most used languages of chemical nomenclature in the world. We applied two types of neural networks in the task of chemical nomenclature translation between English and Chinese, and made a comparison with an existing rule based machine translation tool. The result shows that deep learning based approaches have a great chance to precede rule based translation tools in machine translation of chemical nomenclature between English and Chinese.
177Lu radiolabeling and preclinical theranostic study of 1C1m-Fc: an anti-TEM-1 scFv-Fc fusion protein in soft tissue sarcoma
Authors: Delage J. A. , Faivre-Chauvet A. , Fierle J. K. , Gnesin S. , Schaefer N. , Coukos G. , Dunn S. M. , Viertl D. , Prior J. O. 
Published: August 2020

Abstract
Purpose
TEM-1 (tumor endothelial marker-1) is a single-pass transmembrane cell surface glycoprotein expressed at high levels by tumor vasculature and malignant cells. We aimed to perform a preclinical investigation of a novel anti-TEM-1 scFv-Fc fusion antibody, 1C1m-Fc, which was radiolabeled with 177Lu for use in soft tissue sarcomas models.

Methods
1C1m-Fc was first conjugated to p-SCN-Bn-DOTA using different excess molar ratios and labeled with 177Lu. To determine radiolabeled antibody immunoreactivity, Lindmo assays were performed.
The in vivo behavior of [177Lu]Lu-1C1m-Fc was characterized in mice bearing TEM-1 positive (SK-N-AS) and negative (HT-1080) tumors by biodistribution and single-photon emission SPECT/CT imaging studies. Estimated organ absorbed doses were obtained based on biodistribution results.

Results
The DOTA conjugation and the labeling with 177Lu were successful with a radiochemical purity of up to 95%. Immunoreactivity after radiolabeling was 86% ± 4%. Biodistribution showed a specific uptake in TEM-1 positive tumor versus liver as critical non-specific healthy organ, and this specificity is correlated to the number of chelates per antibody. A 1.9-fold higher signal at 72 h was observed in SPECT/CT imaging in TEM-1 positive tumors versus control tumors.

Conclusion
TEM-1 is a promising target that could allow a theranostic approach to soft-tissue sarcoma, and 1C1m-Fc appears to be a suitable targeting candidate. In this study, we observed the influence of the ratio DOTA/antibody on the biodistribution. The next step will be to investigate the best conjugation to achieve an optimal tumor-to-organ radioactivity ratio and to perform therapy in murine xenograft models as a prelude to future translation in patients.