bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deletion of pgi gene in E. coli increases tolerance to furfural and 5-hydroxymethyl furfural in media containing glucose–xylose mixture
Authors: Jilani Syed Bilal , Dev Chandra , Eqbal Danish , Jawed Kamran , Prasad Rajendra , Yazdani Syed Shams 
Published: July 2020

Abstract
Background
Furfural and 5-hydroxymethyl furfural (5-HMF) are key furan inhibitors that are generated due to breakdown of lignocellulosic sugars at high temperature and acidic treatment conditions. Both furfural and 5-HMF act in a synergistic manner to inhibit microbial metabolism and resistance to both is a desirable characteristic for efficient conversion of lignocellulosic carbon to ethanol. Genetic manipulations targeted toward increasing cellular NADPH pools have successfully imparted tolerance against furfural and 5-HMF. In present study, deletion of pgi gene as a strategy to augment carbon flow through pentose phosphate pathway (PPP) was studied in ethanologenic Escherichia coli strain SSK101 to impart tolerance towards either furfural or 5-HMFor both inhibitors together.

Results
A key gene of EMP pathway, pgi, was deleted in an ethanologenic E. coli strain SSK42 to yield strain SSK101. In presence of 1 g/L furfural in minimal AM1 media, the rate of biomass formation for strain SSK101 was up to 1.9-fold higher as compared to parent SSK42 strain, and it was able to clear furfural in half the time. Tolerance to inhibitor was associated with glucose as carbon source and not xylose, and the tolerance advantage of SSK101 was neutralized in LB media. Bioreactor studies were performed under binary stress of furfural and 5-HMF (1 g/L each) and different glucose concentrations in a glucose–xylose mixture with final sugar concentration of 5.5%, mimicking major components of dilute acid treated biomass hydrolysate. In the mixture having 6 g/L and 12 g/L glucose, SSK101 strain produced ~ 18 g/L and 20 g/L ethanol, respectively. Interestingly, the maximum ethanol productivity was better at lower glucose load with 0.46 g/(L.h) between 96 and 120 h, as compared to higher glucose load where it was 0.33 g/(L.h) between 144 and 168 h. Importantly, parent strain SSK42 did not exhibit significant metabolic activity under similar conditions of inhibitor load and sugar concentration.

Conclusions
E. coli strain SSK101 with pgi deletion had enhanced tolerance against both furfural and 5-HMF, which was associated with presence of glucose in media. Strain SSK101 also had improved fermentation characteristics under both hyperosmotic as well as binary stress of furfural and 5-HMF in media containing glucose–xylose mixture.
Colon metastasis from hepatocellular carcinoma: a case report and literature review
Authors: Yu Yong-Ming , Cao Yi-Sheng , Wu Zhou , Huang Rong , Shen Zhong-Lei 
Published: July 2020

AbstractBackgroundHepatocellular carcinoma (HCC) is a malignant tumor with frequent intrahepatic metastases; extrahepatic metastases are not rare but less frequent compared to intrahepatic ones. The most frequent sites of extrahepatic metastases are the lungs, followed by the lymph nodes, bones, and adrenal glands. Case report covering gastrointestinal (GI) tract involvement from HCC is limited.Case presentationA 60-year-old man was referred to us in May 2019 with a diagnosis of sigmoid colon tumor. The patient had a history of HCC and had received two stages of open resections for the primary and the abdominal metastasis successively and many times of transcatheter arterial chemoembolization (TACE). The sigmoid colon tumor received Hartmann procedure after abdominal enhanced computerized tomography (CT) scan and colonoscopy, while postoperative pathology and immunohistochemistry identified it as extrahepatic colonic metastasis from HCC.ConclusionsThe ratio of extrahepatic metastasis to the digestive tract was very low, and the majority was upper gastrointestinal involvement because of direct invasion or intraperitoneal implantation. TACE may be the risk factor of retrograde hematogenous metastasis to the downstream colon.KeywordsHepatocellular carcinoma; Extrahepatic metastases; Colon metastasis; Transcatheter arterial chemoembolization
Comprehensive analysis and establishment of a prediction model of alternative splicing events reveal the prognostic predictor and immune microenvironment signatures in triple negative breast cancer
Authors: Yu Shanshan , Hu Chuan , Liu Lixiao , Cai Luya , Du Xuedan , Yu Qiongjie , Lin Fan , Zhao Jinduo , Zhao Ye , Zhang Cheng , Liu Xuan , Li Wenfeng 
Published: July 2020

Abstract
Background
Triple-negative breast cancer (TNBC) is widely concerning because of high malignancy and poor prognosis. There is increasing evidence that alternative splicing (AS) plays an important role in the development of cancer and the formation of the tumour microenvironment. However, comprehensive analysis of AS signalling in TNBC is still lacking and urgently needed.

Methods
Transcriptome and clinical data of 169 TNBC tissues and 15 normal tissues were obtained and integrated from the cancer genome atlas (TCGA), and an overview of AS events was downloaded from the SpliceSeq database. Then, differential comparative analysis was performed to obtain cancer-associated AS events (CAAS). Metascape was used to perform parent gene enrichment analysis based on CAAS. Unsupervised cluster analysis was performed to analyse the characteristics of immune infiltration in the microenvironment. A splicing network was established based on the correlation between CAAS events and splicing factors (SFs). We then constructed prediction models and assessed the accuracy of these models by receiver operating characteristic (ROC) curve and Kaplan–Meier survival analyses. Furthermore, a nomogram was adopted to predict the individualized survival rate of TNBC patients.

Results
We identified 1194 cancer-associated AS events (CAAS) and evaluated the enrichment of 981 parent genes. The top 20 parent genes with significant differences were mostly related to cell adhesion, cell component connection and other pathways. Furthermore, immune-related pathways were also enriched. Unsupervised clustering analysis revealed the heterogeneity of the immune microenvironment in TNBC. The splicing network also suggested an obvious correlation between SFs expression and CAAS events in TNBC patients. Univariate and multivariate Cox regression analyses showed that the survival-related AS events were detected, including some significant participants in the carcinogenic process. A nomogram incorporating risk, AJCC and radiotherapy showed good calibration and moderate discrimination.

Conclusion
Our study revealed AS events related to tumorigenesis and the immune microenvironment, elaborated the potential correlation between SFs and CAAS, established a prognostic model based on survival-related AS events, and created a nomogram to better predict the individual survival rate of TNBC patients, which improved our understanding of the relationship between AS events and TNBC.
NF-κB p65-dependent transcriptional regulation of histone deacetylase 2 contributes to the chronic constriction injury-induced neuropathic pain via the microRNA-183/TXNIP/NLRP3 axis
Authors: Miao Jiamin , Zhou Xuelong , Ji Tianjiao , Chen Gang 
Published: July 2020

Abstract
Background
Neuropathic pain is related to the sustained activation of neuroglial cells and the production of proinflammatory cytokines in the spinal dorsal horn. However, the clinical efficacy of currently available treatments is very limited. The transcription factor nuclear factor κB (NF-κB) is a ubiquitously expressed protein family and considered to be crucial in autoimmunity. Thus, our study aimed to examine the influence of NF-κB p65 in chronic constriction injury (CCI)-induced neuropathic pain as well as its underlying mechanism.

Methods
A rat model of neuropathic pain was established by CCI induction followed by isolation of microglial cells. The binding of NF-κB p65 to HDAC2, of miR-183 to TXNIP, and of TXNIP to NLRP3 was investigated. Expression of miR-183, NF-κB p65, HDAC2, TXNIP, and NLRP3 was determined with their functions in CCI rats and microglial cells analyzed by gain- and loss-of-function experiments.

Results
NF-κB p65 and HDAC2 were upregulated while miR-183 was downregulated in the dorsal horn of the CCI rat spinal cord. NF-κB p65 was bound to the HDAC2 promoter and then increased its expression. HDAC2 reduced miR-183 expression by deacetylation of histone H4. Additionally, miR-183 negatively regulated TXNIP. Mechanistically, NF-κB p65 downregulated the miR-183 expression via the upregulation of HDAC2 and further induced inflammatory response by activating the TXNIP-NLRP3 inflammasome axis, thus aggravating the neuropathic pain in CCI rats and microglial cells.

Conclusion
These results revealed a novel transcriptional mechanism of interplay between NF-κB and HDAC2 focusing on neuropathic pain via the miR-183/TXNIP/NLRP3 axis.
Microscale thermophoresis as a powerful tool for screening glycosyltransferases involved in cell wall biosynthesis
Authors: Shao Wanchen , Sharma Rita , Clausen Mads H. , Scheller Henrik V. 
Published: July 2020

Abstract
Background
Identification and characterization of key enzymes associated with cell wall biosynthesis and modification is fundamental to gain insights into cell wall dynamics. However, it is a challenge that activity assays of glycosyltransferases are very low throughput and acceptor substrates are generally not available.

Results
We optimized and validated microscale thermophoresis (MST) to achieve high throughput screening for glycosyltransferase substrates. MST is a powerful method for the quantitative analysis of protein–ligand interactions with low sample consumption. The technique is based on the motion of molecules along local temperature gradients, measured by fluorescence changes. We expressed glycosyltransferases as YFP-fusion proteins in tobacco and optimized the MST method to allow the determination of substrate binding affinity without purification of the target protein from the cell lysate. The application of this MST method to the β-1,4-galactosyltransferase AtGALS1 validated the capability to screen both nucleotide-sugar donor substrates and acceptor substrates. We also expanded the application to members of glycosyltransferase family GT61 in sorghum for substrate screening and function prediction.

Conclusions
This method is rapid and sensitive to allow determination of both donor and acceptor substrates of glycosyltransferases. MST enables high throughput screening of glycosyltransferases for likely substrates, which will narrow down their in vivo function and help to select candidates for further studies. Additionally, this method gives insight into biochemical mechanism of glycosyltransferase function.
Contribution of central sensitization to stress-induced spreading hyperalgesia in rats with orofacial inflammation
Authors: Li Jia-Heng , Yang Jia-Le , Wei Si-Qi , Li Zhuo-Lin , Collins Anna A. , Zou Min , Wei Feng , Cao Dong-Yuan 
Published: July 2020

AbstractTemporomandibular disorder (TMD) is commonly comorbid with fibromyalgia syndrome (FMS). The incidence of these pain conditions is prevalent in women and prone to mental stress. Chronic pain symptoms in patients with FMS and myofascial TMD (mTMD) are severe and debilitating. In the present study, we developed a new animal model to mimic the comorbidity of TMD and FMS. In ovariectomized female rats, repeated forced swim (FS) stress induced mechanical allodynia and thermal hyperalgesia in the hindpaws of the 17β-estradiol (E2) treated rats with orofacial inflammation. Subcutaneous injection of E2, injection of complete Freund’s adjuvant (CFA) into masseter muscles or FS alone did not induce somatic hyperalgesia. We also found that the somatic hyperalgesia was accompanied by upregulation of GluN1 receptor and serotonin (5-hydroxytryptamine, 5-HT)3A receptor expression in the dorsal horn of spinal cord at L4-L5 segments. Intrathecal injection of N-methyl-D-aspartic acid receptor (NMDAR) antagonist 2-amino-5-phosphonovaleric acid (APV) or 5-HT3 receptor antagonist Y-25130 blocked stress-induced wide-spreading hyperalgesia. These results suggest that NMDAR-dependent central sensitization in the spinal dorsal horn and 5-HT-dependent descending facilitation contribute to the development of wide-spreading hyperalgesia in this comorbid pain model.
Cortico-amygdala interaction determines the insular cortical neurons involved in taste memory retrieval
Authors: Abe Konami , Kuroda Marin , Narumi Yosuke , Kobayashi Yuki , Itohara Shigeyoshi , Furuichi Teiichi , Sano Yoshitake 
Published: July 2020

AbstractThe insular cortex (IC) is the primary gustatory cortex, and it is a critical structure for encoding and retrieving the conditioned taste aversion (CTA) memory. In the CTA, consumption of an appetitive tastant is associated with aversive experience such as visceral malaise, which results in avoidance of consuming a learned tastant. Previously, we showed that levels of the cyclic-AMP-response-element-binding protein (CREB) determine the insular cortical neurons that proceed to encode a conditioned taste memory. In the amygdala and hippocampus, it is shown that CREB and neuronal activity regulate memory allocation and the neuronal mechanism that determines the specific neurons in a neural network that will store a given memory. However, cellular mechanism of memory allocation in the insular cortex is not fully understood. In the current study, we manipulated the neuronal activity in a subset of insular cortical and/or basolateral amygdala (BLA) neurons in mice, at the time of learning; for this purpose, we used an hM3Dq designer receptor exclusively activated by a designer drug system (DREADD). Subsequently, we examined whether the neuronal population whose activity is increased during learning, is reactivated by memory retrieval, using the expression of immediate early gene c-fos. When an hM3Dq receptor was activated only in a subset of IC neurons, c-fos expression following memory retrieval was not significantly observed in hM3Dq-positive neurons. Interestingly, the probability of c-fos expression in hM3Dq-positive IC neurons after retrieval was significantly increased when the IC and BLA were co-activated during conditioning. Our findings suggest that functional interactions between the IC and BLA regulates CTA memory allocation in the insular cortex, which shed light on understanding the mechanism of memory allocation regulated by interaction between relevant brain areas.
Characterisation of the transcriptome and proteome of SARS-CoV-2 reveals a cell passage induced in-frame deletion of the furin-like cleavage site from the spike glycoprotein
Authors: Davidson Andrew D. , Williamson Maia Kavanagh , Lewis Sebastian , Shoemark Deborah , Carroll Miles W. , Heesom Kate J. , Zambon Maria , Ellis Joanna , Lewis Philip A. , Hiscox Julian A. , Matthews David A. 
Published: July 2020

Abstract
Background
SARS-CoV-2 is a recently emerged respiratory pathogen that has significantly impacted global human health. We wanted to rapidly characterise the transcriptomic, proteomic and phosphoproteomic landscape of this novel coronavirus to provide a fundamental description of the virus’s genomic and proteomic potential.

Methods
We used direct RNA sequencing to determine the transcriptome of SARS-CoV-2 grown in Vero E6 cells which is widely used to propagate the novel coronavirus. The viral transcriptome was analysed using a recently developed ORF-centric pipeline. Allied to this, we used tandem mass spectrometry to investigate the proteome and phosphoproteome of the same virally infected cells.

Results
Our integrated analysis revealed that the viral transcripts (i.e. subgenomic mRNAs) generally fitted the expected transcription model for coronaviruses. Importantly, a 24 nt in-frame deletion was detected in over half of the subgenomic mRNAs encoding the spike (S) glycoprotein and was predicted to remove a proposed furin cleavage site from the S glycoprotein. Tandem mass spectrometry identified over 500 viral peptides and 44 phosphopeptides in virus-infected cells, covering almost all proteins predicted to be encoded by the SARS-CoV-2 genome, including peptides unique to the deleted variant of the S glycoprotein.

Conclusions
Detection of an apparently viable deletion in the furin cleavage site of the S glycoprotein, a leading vaccine target, shows that this and other regions of SARS-CoV-2 proteins may readily mutate. The furin site directs cleavage of the S glycoprotein into functional subunits during virus entry or exit and likely contributes strongly to the pathogenesis and zoonosis of this virus. Our data emphasises that the viral genome sequence should be carefully monitored during the growth of viral stocks for research, animal challenge models and, potentially, in clinical samples. Such variations may result in different levels of virulence, morbidity and mortality.
Capparis spinosa improves the high fat diet-induced non-alcoholic steatohepatitis in rats: the possible role of FGF21
Authors: Akbari Rasoul , Yaghooti Hamid , Jalali Mohammad Taha , Khorsandi Laya Sadat , Mohammadtaghvaei Narges 
Published: July 2020

Abstract
Objectives
This study focused on the beneficial effects of Capparis spinosa (CS) treatment on the steatohepatitis induced by the administration of a high-fat emulsion in rats. Changes of hepatic expression and secretion of fibroblast growth factor 21 (FGF21) were also evaluated as a probable mechanism of the CS effects on fatty liver. Male Wistar rats were allocated in different groups to receive a normal diet (NC group), a high-fat diet (HF group), or the high-fat emulsion plus CS extract at a dose of 20 mg/kg (HF+CS group). Body and liver weight, liver index, serum biochemical factors, histopathological examination, and serum level and hepatic gene expression of FGF21 were determined.

Results
CS administration markedly reduced liver weight and index, serum levels of glucose, lipids, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) and improved histological features of nonalcoholic steatohepatitis (NASH) which were induced by HF feeding in this model. CS supplementation also restored the decreased hepatic and serum FGF21 levels in the fatty liver rats. We propose that the FGF21 up-regulation may partly account for the favorable effects of CS in this steatohepatitis model.
Recovery and maintenance of NESTIN expression in umbilical cord-MSC using a novel culture medium
Authors: Liu Yuncheng , Xiao Feidi , Hu Xiang , Tang Zan , Fu Zeqin , Liang Xiao , Zeng Guifang , Zeng Weijie , Liao Yan , Ren Yuan , Liu Zhiyu , Peng Hao , Mei Qiuhong , Liu Muyun 
Published: July 2020

AbstractMesenchymal stem cells (MSC) are a popular candidate in cellular therapy for many diseases. MSCs are well known by their feature of self-renewal and their differentiation potential. NESTIN is a cytoskeletal protein expressed in MSC that functions directly in cell proliferation and differentiation. Here, we demonstrated that adding UltraGRO, a medium supplement, could maintain and partially recover the expression of NESTIN in human umbilical cord derived MSCs (UC-MSCs). Furthermore, the UC-MSCs cultured with UltraGRO showed a better immunomodulation ability in a colitis mouse model compared with those cultured in other types of media. This indicates that the use of novel culture medium benefits the maintenance of NESTIN expression and NESTIN may be one of the vital factors that regulates the performance of MSCs.
Correntropy-based DOA estimation algorithm under impulsive noise environments
Authors: Chen Jin , Guan Sheng 
Published: July 2020

AbstractIn this paper, the direction of arrival (DOA) estimation of signals in the presence of impulsive noise environment is studied. Complex isotropic symmetric alpha-stable (SαS) random variables are modeled as impulsive noise, then a novel second-order statistic method that correntropy-based covariance matrix (CBCM) is defined, based on the combination of the CBCM of the array sensor outputs with the signal subspace technique (e.g., multiple signal classification (MUSIC)), which can be achieved source localization under impulsive noise environments. The Monte-Carlo simulation results illustrate the improved performance of CBCM-MUSIC for DOA estimation under a wide range of impulsive noise conditions.
Medical cannabis for the reduction of opioid dosage in the treatment of non-cancer chronic pain: a systematic review
Authors: Okusanya Babasola O. , Asaolu Ibitola O. , Ehiri John E. , Kimaru Linda Jepkoech , Okechukwu Abidemi , Rosales Cecilia 
Published: July 2020

Abstract
Background
Medical cannabis (MC) is currently being used as an adjunct to opiates given its analgesic effects and potential to reduce opiate addiction. This review assessed if MC used in combination with opioids to treat non-cancer chronic pain would reduce opioid dosage.

Methods
Four databases—Ovid (Medline), Psyc-INFO, PubMed, Web of Science, and grey literature—were searched to identify original research that assessed the effects of MC on non-cancer chronic pain in humans. Study eligibility included randomized controlled trials, controlled before-and-after studies, cohort studies, cross-sectional studies, and case reports. All databases were searched for articles published from inception to October 31, 2019. Cochrane’s ROBINS-I tool and the AXIS tool were used for risk of bias assessment. PRISMA guidelines were followed in reporting the systematic review.

Results
Nine studies involving 7222 participants were included. There was a 64–75% reduction in opioid dosage when used in combination with MC. Use of MC for opioid substitution was reported by 32–59.3% of patients with non-cancer chronic pain. One study reported a slight decrease in mean hospital admissions in the past calendar year (P = .53) and decreased mean emergency department visits in the past calendar year (P = .39) for patients who received MC as an adjunct to opioids in the treatment of non-cancer chronic pain compared to those who did not receive MC. All included studies had high risk of bias, which was mainly due to their methods.

Conclusions
While this review indicated the likelihood of reducing opioid dosage when used in combination with MC, we cannot make a causal inference. Although medical cannabis’ recognized analgesic properties make it a viable option to achieve opioid dosage reduction, the evidence from this review cannot be relied upon to promote MC as an adjunct to opioids in treating non-cancer chronic pain. More so, the optimal MC dosage to achieve opioid dosage reduction remains unknown. Therefore, more research is needed to elucidate whether MC used in combination with opioids in the treatment of non-cancer chronic pain is associated with health consequences that are yet unknown.

Systematic review registration
This systematic review was not registered.
Two sequential fractional hybrid differential inclusions
Authors: Mohammadi Hakimeh , Rezapour Shahram , Etemad Sina , Baleanu Dumitru 
Published: July 2020

AbstractThe main objective of this paper is to concern with a new category of the sequential hybrid inclusion boundary value problem with three-point integro-derivative boundary conditions. In this direction, we employ various novel analytical techniques based on α-ψ-contractive mappings, endpoints, and the fixed points of the product operators to obtain the main results. Finally, we provide two examples to illustrate our main results.