bluuebunny/crossref_metadata_2025_split huggingface dataset:
CRISPR interference-guided modulation of glucose pathways to boost aconitic acid production in Escherichia coli
Authors: Li Qingyang , Zhao Peng , Yin Hang , Liu Zhaonan , Zhao Haifeng , Tian Pingfang 
Published: September 2020

Abstract
Background
One major mission of microbial breeding is high-level production of desired metabolites. Overproduction of intermediate metabolites in core pathways is challenging as it may impair cell growth and viability.

Results
Here we report that aconitic acid, an intermediate metabolite in tricarboxylic acid (TCA) cycle, can be overproduced by an engineered CRISPR interference (CRISPRi) system in Escherichia coli. This CRISPRi system was designed to simultaneously target pyruvate kinase (PK) and isocitrate dehydrogenase (IDH), two enzymes in glycolytic pathway and TCA cycle, respectively. Reverse transcription and quantitative PCR and enzyme activity assays showed that this engineered CRISPRi system significantly repressed the genes encoding IDH and PK, resulting in simultaneous reduction in the activities of IDH and PK. In shake-flask and fed-batch cultivation, this CRISPRi strain produced 60-fold (362.80 ± 22.05 mg/L) and 15-fold (623.80 ± 20.05 mg/L) of aconitic acid relative to the control strain, respectively. In addition, this two-target CRISPRi strain maintained low levels of acetate and lactate, two problematic byproducts.

Conclusions
This work demonstrates that CRISPRi system can improve aconitic acid production by coordinating glycolysis and TCA cycle. This study provides insights for high-level production of the intermediate metabolites in central pathways.
Bacillus subtilis: a universal cell factory for industry, agriculture, biomaterials and medicine
Authors: Su Yuan , Liu Chuan , Fang Huan , Zhang Dawei 
Published: September 2020

AbstractDue to its clear inherited backgrounds as well as simple and diverse genetic manipulation systems, Bacillus subtilis is the key Gram-positive model bacterium for studies on physiology and metabolism. Furthermore, due to its highly efficient protein secretion system and adaptable metabolism, it has been widely used as a cell factory for microbial production of chemicals, enzymes, and antimicrobial materials for industry, agriculture, and medicine. In this mini-review, we first summarize the basic genetic manipulation tools and expression systems for this bacterium, including traditional methods and novel engineering systems. Secondly, we briefly introduce its applications in the production of chemicals and enzymes, and summarize its advantages, mainly focusing on some noteworthy products and recent progress in the engineering of B. subtilis. Finally, this review also covers applications such as microbial additives and antimicrobials, as well as biofilm systems and spore formation. We hope to provide an overview for novice researchers in this area, offering them a better understanding of B. subtilis and its applications.
EIF3J-AS1 promotes glioma cell growth via up-regulating ANXA11 through sponging miR-1343-3p
Authors: Qi Jianguo , Wang Zhengrui , Zhao Zhensheng , Liu Lijun 
Published: September 2020

AbstractBackgroundGlioma is one prevalent malignant tumor originates from the central nervous system. Dysregulation of long non-coding RNAs (lncRNAs) has been found to be a molecular signature behind the pathology of a variety of cancers, including glioma. EIF3J antisense RNA 1 (EIF3J-AS1) is a novel lncRNA, whose performance in carcinogenesis has been unfolded. Nevertheless, the role of EIF3J-AS1 has never been investigated in glioma.MethodsqRT-PCR analysis was adopted to evaluate the relative levels of RNAs. In vitro functional assays, including colony formation, EdU, TUNEL and caspase-3/8/9 activity assays were conducted to study the impacts of EIF3J-AS1 on glioma. Dual-luciferase activity assays, RNA pull down assay and RIP assay were performed to elucidate molecular interplay among genes.ResultsEIF3J-AS1 was overexpressed in glioma cell lines. Knockdown of EIF3J-AS1 hampered glioma malignant phenotypes. MiR-1343-3p could bind to EIF3J-AS1. Moreover, miR-1343-3p targeted Annexin A11 (ANXA11) in its 3′UTR region. Mechanistically, EIF3J-AS1 relieved ANXA11 from miR-1343-3p silencing in the EIF3J-AS1/miR-1343-3p/ANXA11 RNA induced silencing complex (RISC), thus eliciting promoting effects on glioma progression. MiR-1343-3p inhibitor and ANXA11 overexpression offset the inhibitory impacts of EIF3J-AS1 silencing on glioma development.ConclusionEIF3J-AS1/miR-1343-3p/ANXA11 axis significantly affected biological behaviors in glioma, suggesting new therapeutic target for glioma treatment.
Establishment of a 5-gene risk model related to regulatory T cells for predicting gastric cancer prognosis
Authors: Hu Gang , Sun Ningjie , Jiang Jiansong , Chen Xiansheng 
Published: September 2020

Abstract
Background
Gastric cancer (GC) is one of the high-risk cancers that lacks effective methods for prognosis prediction. Therefore, we searched for immune cells related to the prognosis of GC and studied the role of related genes in GC prognosis.

Methods
In this study, we collected the mRNA data of GC from The Cancer Genome Atlas (TCGA) database and studied the immune cells that were closely related to the prognosis of GC. Spearman correlation analysis was performed to show the association between immune cell-related genes and the differentially expressed genes (DEGs) of GC. Univariate and multivariate Cox regression analyses were conducted on the immune cell-related genes with a high correlation with GC. A prognostic risk score model was constructed and the most significant feature genes were identified. Kaplan–Meier method was then used to compare the overall survival (OS) of patients with high-risk and low-risk, and receiver operating characteristic (ROC) analysis was used to assess the accuracy of the risk model. In addition, GC patients were grouped according to the median expression of the features genes, and survival analysis was further carried out.

Results
It was noted that regulatory T cells (Tregs) were significantly correlated with the prognosis of GC, and 172 genes related to Tregs were found to be closely associated with GC. An optimal prognostic risk model was constructed, and a 5-gene (including LRFN4, ADAMTS12, MCEMP1, HP and MUC15) signature-based risk score was established. Survival analysis showed significant difference in OS between low-risk and high-risk samples. ROC analysis results indicated that the risk model had a high accuracy for the prognosis prediction of samples (AUC = 0.717). The results of survival analysis on each feature gene based on expression levels were consistent with the results of multivariate Cox analysis for predicting the risk rate of the 5 genes.

Conclusion
These results proved that the 5-gene signature-based risk score could be used to predict the survival of GC patients, and these 5 genes were closely related to Tregs. These findings are of great significance for studying the role of immune cells and related immune factors in regulating the prognosis of GC.
The relationship between TRAF6 and tumors
Authors: Li Jiaoduan , Liu Nian , Tang Ling , Yan Bei , Chen Xiang , Zhang Jianglin , Peng Cong 
Published: September 2020

AbstractTumor necrosis factor receptor (TNFR)-related factors (TRAFs) are important linker molecules in the tumor necrosis factor superfamily (TNFSF) and the Toll-like/interleukin-1 receptor (TLR/ILR) superfamily. There are seven members: TRAF1-TRAF7, among those members, tumor necrosis factor receptor-associated factor 6 (TRAF6) is upregulated in various tumors, which has been related to tumorigenesis and development. With the in-depth study of the relationship between TRAF6 and different types of tumors,TRAF6has oncogenic characteristics involved in tumorigenesis, tumor development, invasion, and metastasis through various signaling pathways, therefore, targeting TRAF6 has provided a novel strategy for tumor treatment. This review summarizes and analyzes the role of TRAF6 in tumorigenesis and tumor development in combination with the current research on TRAF6 and tumors.
circRAE1 promotes colorectal cancer cell migration and invasion by modulating miR-338-3p/TYRO3 axis
Authors: Du Jiabin , Xu Jianhua , Chen Junxing , Liu Weinan , Wang Pengcheng , Ye Kai 
Published: September 2020

AbstractBackgroundGrowing evidence has revealed the involvement of circular RNAs (circRNAs) in numerous carcinogenesis. However, the role of circRNAs in the cancer biology of colorectal cancer (CRC) remains vague.MethodsQuantitative RT-PCR was used to detect the expression level of circRAE1 in CRC tissues and CRC cell lines. Cell proliferation, migration, and invasion were detected using CCK8 assay, Colony formation assay, wound-healing and Transwell assays. The interaction between circRAE1 and miR-338-3p and TRYO3 was confirmed using dual-luciferase reporter assays.ResultsWe uncovered a novel circRNA Hsa_circ_0060967 (also known as circRAE1) that was remarkably increased in CRC tissues. The high circRAE1 level was positively associated with advanced tumor stage, lymph node metastasis, and tumor size. The loss-of-function assay showed that circRAE1 accelerated cell proliferation, migration, and invasion. Besides, miR-338-3p was lowly expressed in the CRC tissues and CRC cell lines. The dual-luciferase reporter assays showed that circRAE1 could sponge miR-338-3p, which targeted TRYO3 in CRC cells. Furthermore, the overexpression of circRAE1 could rescue the impaired migration and invasion triggered by miR-338-3p mimics or si-TYRO3 in CRC cells and vice versa.ConclusionWe identified the network of circRAE1, miR-338-3p, and TYRO3 in CRC cells and determined that the increase in circRAE1 could serve as an oncogene by sponging miR-338-3p, which resulted in an upregulated TYRO3 expression. The finding suggests that circRAE1 is a potential therapeutic target and diagnostic marker for CRC treatment.
CircRNA_104889 promotes lung adenocarcinoma cell invasion via sponging miR4458
Authors: Yan Yongyong , Yang Jiantian , Pathak Janak L. , Wang Haiyan , Zha Jun , Wei Yongxiang , Tang Haibo , Ge Linhu 
Published: September 2020

Abstract
Background
Lung adenocarcinoma is metastatic cancer with a high mortality rate. Circular RNAs (circRNAs) are a type of noncoding RNA and play a vital role in cancer progression. However, the expression and function of circRNAs in lung adenocarcinoma are still mostly unknown.

Methods
In this study, we screened the differential expression of circRNAs in human bronchial epithelial cells (HBE) and A549 human lung adenocarcinoma cell line (A549) by human circRNA microarray and RT-qPCR. The role of overexpressed circRNA_104889 in A549 cell proliferation, apoptosis, migration, and invasion was studied extensively. Intracellular localization of circRNA_104889 was visualized by FISH assay. MiRNA sponging, ERK1/2 signaling, and caspase-3 expression were analyzed in siRNA-mediated circRNA_104889 knockdowned A549 cells.

Results
CircRNA microarray showed overexpression of circRNA_104889 (> 13-fold) in A459 cells compared to HBE. This finding was further corroborated by the RT-qPCR result. CircRNA_104889 was mainly localized in the cytoplasm of A549 cells. The knockdown of circRNA_104889 in A549 cells by si-RNA mediated RNA interference did not affect cell proliferation and apoptosis but significantly inhibited cell migration and invasion in vitro. Furthermore, knockdown of circRNA_104889 led to an increase of miR4458 expression. Overexpression of miR4458 inhibited A549 cell migration. Both the knockdown of circRNA_104889 and overexpression of miR4458 inhibited the caspase-3 expression and ERK1/2 phosphorylation in A549 cells.

Conclusions
CircRNA_104889 promotes lung adenocarcinoma cell migration and invasion by sponging miR4458 and targeting ERK1/2 signaling and caspase-3 expression.
Molecular epidemiological surveillance of Africa and Asia imported malaria in Wuhan, Central China: comparison of diagnostic tools during 2011–2018
Authors: Xie Yiting , Wu Kai , Cheng Weijia , Jiang Tingting , Yao Yi , Xu Mingxing , Yang Yan , Tan Huabing , Li Jian 
Published: September 2020

Abstract
Background
Malaria remains a serious public health problem globally. As the elimination of indigenous malaria continues in China, imported malaria has gradually become a major health hazard. Well-timed and accurate diagnoses could support the timely implementation of therapeutic schedules, reveal the prevalence of imported malaria and avoid transmission of the disease.

Methods
Blood samples were collected in Wuhan, China, from August 2011 to December 2018. All patients accepted microscopy and rapid diagnosis test (RDT) examinations. Subsequently, each of the positive or suspected positive cases was tested for four human-infectious Plasmodium species by using 18S rRNA-based nested PCR and Taqman probe-based real-time PCR. The results of the microscopy and the two molecular diagnostic methods were analysed. Importation origins were traced by country, and the prevalence of Plasmodium species was analysed by year.

Results
A total of 296 blood samples, including 288 that were microscopy and RDT positive, 7 RDT and Plasmodium falciparum positive, and 1 suspected case, were collected and reanalysed. After application of the two molecular methods and sequencing, 291 cases including 245 P. falciparum, 15 Plasmodium vivax, 20 Plasmodium ovale, 6 Plasmodium malariae and 5 mixed infections (3 P. falciparum + P. ovale, 2 P. vivax + P. ovale) were confirmed. These patients had returned from Africa (95.53%) and Asia (4.47%). Although the prevalence displayed a small-scale fluctuation, the overall trend of the imported cases increased yearly.

Conclusions
These results emphasize the necessity of combined utilization of the four tools for malaria diagnosis in clinic and in field surveys of potential risk regions worldwide including Wuhan.
The clinical spectrum of severe childhood malaria in Eastern Uganda
Authors: Olupot-Olupot Peter , Engoru Charles , Nteziyaremye Julius , Chebet Martin , Ssenyondo Tonny , Muhindo Rita , Nyutu Gideon , Macharia Alexander W. , Uyoga Sophie , Ndila Carolyne M. , Karamagi Charles , Maitland Kathryn , Williams Thomas N. 
Published: September 2020

Abstract
Background
Few recent descriptions of severe childhood malaria have been published from high-transmission regions. In the current study, the clinical epidemiology of severe malaria in Mbale, Eastern Uganda, is described, where the entomological inoculation rate exceeds 100 infective bites per year.

Methods
A prospective descriptive study was conducted to determine the prevalence, clinical spectrum and outcome of severe Plasmodium falciparum malaria at Mbale Regional Referral Hospital in Eastern Uganda. All children aged 2 months–12 years who presented on Mondays to Fridays between 8.00 am and 5.00 pm from 5th May 2011 until 30th April 2012 were screened for parasitaemia. Clinical and laboratory data were then collected from all P. falciparum positive children with features of WHO-defined severe malaria by use of a standardized proforma.

Results
A total of 10 208 children were screened of which 6582 (64%) had a positive blood film. Of these children, 662 (10%) had clinical features of severe malaria and were consented for the current study. Respiratory distress was the most common severity feature (554; 83.7%), while 365/585 (62.4%) had hyperparasitaemia, 177/662 (26.7%) had clinical jaundice, 169 (25.5%) had severe anaemia, 134/660 (20.2%) had hyperlactataemia (lactate ≥ 5 mmol/L), 93 (14.0%) had passed dark red or black urine, 52 (7.9%) had impaired consciousness and 49/662 (7.4%) had hypoxaemia (oxygen saturations < 90%). In-hospital mortality was 63/662 (9.5%) overall but was higher in children with either cerebral malaria (33.3%) or severe anaemia (19.5%). Factors that were independently associated with mortality on multivariate analysis included severe anaemia [odds ratio (OR) 5.36; 2.16–1.32; P = 0.0002], hyperlactataemia (OR 3.66; 1.72–7.80; P = 0.001), hypoxaemia (OR) 3.64 (95% CI 1.39–9.52; P = 0.008), and hepatomegaly (OR 2.29; 1.29–4.06; P = 0.004). No independent association was found between mortality and either coma or hyperparasitaemia.

Conclusions
Severe childhood malaria remains common in Eastern Uganda where it continues to be associated with high mortality. An unusually high proportion of children with severe malaria had jaundice or gave a history of having recently passed dark red or black urine, an issue worthy of further investigation.
Tranexamic acid adverse reactions: a brief summary for internists and emergency doctors
Authors: Murdaca Giuseppe , Greco Monica , Vassallo Chiara , Gangemi Sebastiano 
Published: September 2020

AbstractTranexamic acid (TXA) is a synthetic lysine analogue that is well known as antifibrinolytic agent. It can reduce blood loss in clinical use, especially in conditions where fibrinolysis or hyperfibrinolysis are involved, such as trauma or surgery. Moreover, TXA has been approved as second-line prophylactic therapy for hereditary angioedema and further data have been published about a possible use of TXA as maintenance treatment for nonhistaminergic angioedema and treatment for episodes of bradykinin-mediated angioedema induced by ACE inhibitors. TXA can be administered through several routes: orally, topically, or intravenously. Although, it is a drug with a very high safety profile, in few cases hypersensitivity reactions have been described occurring with different clinical manifestations. Ethamsylate can be an alternative in TXA sensitized patients. In this brief article we describe TXA adverse reactions and current protocols which have been proposed to help clinicians to diagnose TXA hypersensitivity.
Gender differences in quality of life among patients with myasthenia gravis in China
Authors: Dong Dong , Chong Marc Ka-chun , Wu Yushan , Kaminski Henry , Cutter Gary , Xu Xianhao , Li Haifeng , Zhao Chongbo , Yin Jian , Yu Siyue , Zhu Jianfeng 
Published: September 2020

Abstract
Background
Myasthenia gravis (MG), a chronic neuromuscular disorder, can adversely affect patients’ health-related quality of life (HRQoL), especially in women. The study aimed to evaluate the difference in HRQoL of women and men MG patients and explore the factors that mediate the relationship between gender and HRQoL.

Methods
A cross-sectional study was conducted among 1815 patients with MG in China. The revised 15-item MG quality of life scale (MG-QOL15r) was used to access patients’ HRQoL in overall, physical, social and emotional domains. Socio-demographic information, diagnosis and treatment history, comorbidities, social support, active lifestyle and the MG activities of daily living scale (MG-ADL) were recorded and compared between women and men using the Student’s t-test and Pearson’s Chi-square test. Multivariable regression analyses were conducted to identify independent contributors to HRQoL, especially those affecting different gender.

Results
On average, female patients with MG reported a lower MG-QOL15r score than the males (44.49 ± 29.10 vs 49.32 ± 29.18). The association between gender and patients’ HRQoL interacted with the number of comorbidities across the overall, physical and social domains of patients. As the number of comorbidities increased, the scores of HRQoL decreased and it was faster among females than the males (p < 0.05). Moreover, unemployment, exacerbation of the disease, and active lifestyle contributed to the patients’ HRQoL across all domains. Unemployment (β = − 4.99 [95%CI, − 7.80 to − 2.18], p < 0.001) and exacerbations (β = − 8.49 [95%CI, − 11.43 to − 5.54], p < 0.001) were correlated with poorer HRQoL; while an active lifestyle had a positive impact on HRQoL (β = 0.28 [95%CI, 0.16 to 0.40], p < 0.001).

Conclusions
The results indicate that the HRQoL of women MG patients was lower than that of men. The relationship between gender and HRQoL is modulated by the number of comorbidities. Thus, to improve the HRQoL of women MG patients, symptomatic treatments might not be enough, their comorbid conditions should be considered as well. Additionally, employment status, MG exacerbations, and an active lifestyle have been found as determining factors of the patients’ HRQoL, which suggests future interventions should cope with these factors to improve their quality of life.
Immune infiltrating cells in duodenal cancers
Authors: Donisi G. , Capretti G. , Cortese N. , Rigamonti A. , Gavazzi F. , Nappo G. , Pulvirenti A. , Sollai M. , Spaggiari P. , Zerbi A. , Marchesi F. 
Published: September 2020

Abstract
Background
Duodenal adenocarcinoma (DA) is a rare yet aggressive malignancy, with increasing incidence in the last decades. Its low frequency has hampered a thorough understanding of the pathogenesis of the disease and of its biology, limiting the identification of tailored therapeutic options. A large body of evidence has clearly shown the clinical relevance of immune cells in solid tumors, correlating immune features with post-surgical prognosis. The aim of this study was to analyze the immune contexture in a cohort of duodenal adenocarcinomas surgically resected at our Institution and define its correlation with clinical variables.

Methods
Tissue slides from paraffin-embedded tumor specimens of 15 consecutive DA and 3 adenomas that underwent a pancreaticoduodenectomy in our center between 2010 to 2018 were immunohistochemically stained. The density (percentage of immune reactive area, IRA%) of immune markers CD45RO, CD8, CD20, IL-17, PD-1, CD68 was quantified by computer-assisted image analysis. Demographic, clinical, histopathological data were collected.

Results
In our population, median IRA % (IQR) of immune subsets was respectively CD45RO-TILs 2.19 (2.14), CD8-TIL 0.42 (0.81), CD20-TILs 0.22 (0.51), CD20-TLT 2.84 (4.64), CD68-TAM 2.19 (1.56), IL17+ cells 0.39 (0.39), PD1-TILs 0.19 (0.41). The median follow-up was 47.5 (22.4–63.3) months. At statistical analysis, the density of CD8-TILs inversely correlated with lymph node ratio (p = 0.013), number of metastatic lymph nodes (p = 0.019), and was lower in N+ adenocarcinomas compared to N0 (1.07 vs 0.29; p = 0.093), albeit not significantly. Stratifying patients for the N status, the density of CD8-TILs decreased with the increasing of the N stage (p = 0.065) and was lower in patients who experienced recurrence and died for the disease (0.276 vs 0.641; p = 0.044). Notably, also CD68-TAM distribution was different in patients who had recurrence versus patients who did not (1.028 vs 2.276; p = 0.036).

Conclusions
Immune cells showed variable expression in correlation with common prognostic factors, suggesting T cell infiltration may play a protective role towards lymphatic spread of disease and nodal metastatization. Furthermore, T cell density and macrophage infiltration were associated to a lower risk of recurrence and disease related death. A multicentric approach may be indicated to allow analysis of larger cohorts of patients, potentially increasing the power of our observations.