bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Osmotic Stress to Stabilize Mannitol Production in Synechocystis sp. PCC6803
Authors: Wu Wenyang , Du Wei , Gallego Ruth Perez , Hellingwerf Klaas J. , Woude Aniek D. van der , Santos Filipe Branco dos 
Published: March 2020

Abstract
Background Mannitol is a C(6) polyol that is used in the food and medical sector as a sweetener and antioxidant, respectively. The sustainable production of mannitol, especially via the direct conversion of CO 2 by photosynthetic cyanobacteria, has become increasingly appealing. However, previous work aiming to achieve mannitol production in the marine Synechococcus sp. PCC 7002 via heterologous expression of mannitol-1-phosphate-5-dehydrogenase ( mtlD ) and mannitol-1-phosphatase ( m1p , in short: a ‘mannitol cassette’), proved to be genetically unstable. Results Here, we explore the stabilizing effect that mannitol production may have on cells faced with osmotic stress, in the freshwater cyanobacterium Synechocystis sp. PCC 6803. We first validated that mannitol can function as a compatible solute in Synechocystis sp. PCC 6803, and in derivative strains in which the ability to produce one or both of the native compatible solutes was impaired. Wild type Synechocystis , complemented with a mannitol cassette, indeed showed increased salt tolerance, which was even more evident in Synechocystis strains in which the ability to synthesize the endogenous compatible solutes was impaired. Next we tested the genetic stability of all these strains with respect to their mannitol productivity, with and without salt stress, during prolonged turbidostat cultivations. The obtained results show that mannitol production under salt stress conditions in the Synechocystis strain that cannot synthesize its endogenous compatible solutes is remarkably stable, while the control strain completely loses this ability in only 6 days. DNA sequencing results of the control groups that lost the ability to synthesize mannitol revealed that multiple types of mutation occurred in the mtlD gene that can explain the disruption of mannitol production. Conclusions Mannitol production in freshwater Synechocsytis sp. PCC6803 confers it with increased salt tolerance. Under this strategy, genetically instability which was the major challenge for mannitol production in cyanobacteria is tackled. This paper marks the first report of both stable mannitol production directly from CO 2 in cyanobacteria, and of the utilization of the response to salt stress as a factor that can stabilize production in a cyanobacterial cell factory.
LINC00152 promotes Ovarian tumor progression and Predicts Poor Prognosis by inhibiting the ubiquitination of BCL6
Authors: Wang Shunni , Weng Weiwei , Chen Tingting , Xu Midie , Wei Ping , Li Jing , Lu Linghui , Wang Yiqin 
Published: March 2020

Abstract
Background : Long non-coding RNA 00152 (LINC00152) has been found oncogenic in multiple somatic malignancies. But its roles in the ovarian cancer remain elusive. We aim to investigate its functions and mechanism in the ovarian tumor progression. Methods: We used RNAscope and RT-qPCR assays to detect the LINC00152 levels in 152 pairs of ovarian tumor and paratumorous tissues, conducted in vitro and in vivo experiments to evaluate its biological functions, and performed RNA immunoprecipitation, RNA-pulldown, MS/LS analysis, mutant construction and ubiquitination assays to explore the LINC00152-BCL6 binding and regulation. Results: LINC00152 was abnormally increased in the ovarian tumor tissues and its high expression predicted poorer survivals of patients; overexpression of LINC00152 promoted ovarian tumor proliferation and metastasis both in vitro and in vivo ; LINC00152 bond to Serine333 and Serine343 of BCL6 and then suppressed its ubiquitination; Finally, LINC00152 facilitated its oncogenic functions in a BCL6-mediated manner in ovarian cancer. Conclusions: LINC00152 is the independent prognostic predictor of ovarian cancer; and the abnormal expression of LINC00152 facilitates ovarian tumor proliferation and invasion by suppress the ubiquitination of BCL6. Our data might be helpful in exploring the molecular mechanisms of lncRNA-protein interactions, and might provide the potential target for the tumor pharmacology of ovarian cancer.
in silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy
Authors: Wei Tianzi , Wang Hao , Wu Xueqing , Lu Yi , Guan Shenghui , Dong Fengquan , Dong Chenle , Zhu Guli , Bao Yuzhou , Zhang Jian , Wang Guanyu , Li Haiying 
Published: March 2020

Abstract
COVID-19 has globally spread and has become a new pandemic, but there is still no effective drugs or vaccines to treat or prevent this disease. SARS-Cov-2 invades human cells through its spike proteins interacting with human ACE2 receptors. One strategy to prevent the virus from entering cells is the interruption of the viral spike protein interacting with ACE2. In such an emergent situation, drug repurposing is a promising method for rapid drug development. Here, we selected around 15000 molecular candidates including FDA-approved drugs from DrugBank and natural compounds from TCMSP to perform virtual screening for potential molecules that can target viral spike protein based on its crystal structure. In this article, we present the top 20 molecules with high binding affinity with spike protein, of which, digitoxin, a cardiac glycoside in DrugBank and bisindigotin in TCMSP, extracted from indigo naturalis and polygoni tinctorii foliu, have the highest docking scores. In addition, we also found that raltegravir, an HIV integrase inhibitor, has a relatively high binding score. Those molecules with high binding capacity to spike glycoprotein might be used by other researchers for further anti-COVID-19 drug development.
Altered fractional amplitude of low frequency fluctuation in Women with Premenstrual Syndrome Via Acupuncture at Sanyinjiao(SP6)
Authors: Duan Gaoxiong , Chen Ya , Pang Yong , Feng Zhuo , Liao Hai , Liu Huimei , Zou Zhuocheng , Li Min , Tao Jien , He Xin , Li Shasha , Liu Peng , Deng Demao 
Published: March 2020

Abstract
Background: Premenstrual Syndrome(PMS) is a prevalent gynecological disease and is significantly associated with abnormal neural activity. Acupuncture is an effective treatment on PMS in clinical practice. However, few studies have been performed to investigate whether acupuncture might modulate the abnormal neural activity in patients with PMS. Thereby, the aim of the study was to assess alterations of the brain activity induced by acupuncture stimulation in PMS patients. Methods: 20 PMS patients were enrolled in this study. All patients received a 6-min resting-state functional magnetic resonance imaging(rs-fMRI) scan before and after electro-acupuncturing stimulation (EAS) at Sanyinjiao (SP6) acupoint in the late luteal phase of menstrual. Applied the fractional amplitude of low frequency fluctuation(fALFF) method to examine EAS-related brain changes in PMS patients. Results: Compared with pre-EAS at SP6, increased fALFF value in several brain regions induced by SP6, including brainstem, right thalamus, bilateral insula, right paracentral lobule, bilateral cerebellum, meanwhile, decreased fALFF in the left cuneus, right precuneus, left inferior temporal cortex. Conclusions: Our findings provide imaging evidence to support that SP6-related acupuncture stimulation may modulate the neural activity in patients with PMS. This study may partly interpret the neural mechanisms of acupuncture at SP6 which is used to treat PMS patients in clinical. Trial registration:The study was registered on http://www.chictr.org.cn, the Clinical Trial Registration Number is ChiCTR-OPC-15005918, registry in 29/01/2015.
Radiobiological effects of the interruption time in radiation therapy with photon beams based on the microdosimetric kinetic model
Authors: Nakano Hisashi , Kawahara Daisuke , Tanabe Satoshi , Utsunomiya Satoru , Takizawa Takeshi , Aoyama Hidefumi 
Published: March 2020

Abstract
Background: We investigated the effect of the interruption time on the radiobiological effectiveness with photon beams based on a modified microdosimetric kinetic model. Background: The interruption time is used is that irradiation interruption occurs at sites and operations such as the gantry, collimator, couch rotation, and patient set-up in radiotherapy. However, the effect of interruption time on photon beams for tumor cells is little evaluated.Methods: The dose-mean lineal energy yD (keV/µm) of 6 MV photon beams was calculated by the particle and heavy ion transport system (PHITS). We set the absorbed dose to 2 or 8 Gy, and the interruption time (τ) was set to 1, 3, 5, or 10 min. The biological parameters values were acquired from a human non-small cell lung cancer cell line (NCI-H460) for the mMK model. We used two-field and four-field irradiation with a constant dose rate (3 Gy/min); the photon beams were paused for interruption time τ. We calculated the relative biological effectiveness (RBE) to evaluate the interruption time's effect compared with photon beams that were not interrupted as a reference. Results: The RBE with four-field irradiation for 8 Gy was decreased to 0.997, 0.992, 0.987, and 0.975 for τ = 1, 3, 5, and 10 min, respectively. The decrease in the RBE was within 3% compared with the non-interrupted photon beams. Conclusions: The effect of RBE was decreased by increasing the interruption time, indicating that an escalation of the prescribed dose might be necessary when the interruption time was large.
Self-perceived Workplace Discrimination And Mental Health Among Immigrant Workers In Italy: A Cross-sectional Study
Authors: Napoli Anteo Di , Rossi Alessandra , Baralla Francesca , Ventura Martna , Gatta Rosaria , Perez Minica , Sarchiapone Marco , Mirisola Concetta , Petrelli Alessio 
Published: March 2020

Abstract
Background: Immigration process is associated with poor mental and physical health. The workplace represents an important context of social integration, and previous studies, that evaluated the effect of discrimination experienced at workplace, found worse mental health status among immigrants. The aim of this study investigated the association between self-perceived workplace discrimination and other personal experiences, like self-perceived loneliness, level of life satisfaction, and physical health and mental well-being among immigrants in Italy.Methods: A cross-sectional study was conducted on a sample of 12,408 immigrants (aged 15-64) living and working in Italy. Data derived from the first national survey on immigrants carried out by the Italian National Institute of Statistics (Istat). Mental health status was measured through the mental component summary (MCS) of the SF-12 questionnaire. A linear multivariate regression was carried out to evaluate the association between mental health status, self-perceived workplace discrimination, and sociodemographic factors; a structural equation model was used to test hypothesized relationships shown in a conceptual path analysis model.Results: Worse mental health status was independently (p<0.001) associated with self-perceived workplace discrimination (β:-1.873), self-perceived loneliness (β:-3.021), level of life satisfaction (β:-2.775), and physical health status (β:-0.088). As confirmed by structural equation model, the self-perceived workplace discrimination effect on MCS was mediated by the other factors considered: self-perceived loneliness (13.6%), level of life satisfaction (13.6%), and physical health status (3.9%).Conclusions: Our study suggest that self-perceived workplace discrimination is associated with worse mental health status in immigrant workers. These results support the hypothesis that self-perceived workplace discrimination may affect mental health status through personal experiences in the workplace and explain the effect of the exposure to workplace discrimination on immigrants’ psychological well-being. Our findings suggest that an overall public health response to facilitate the social integration of immigrants and their access to health services, in particular those dedicated to addressing mental health issues.
Factors Influencing Resilience of Medical Workers from Other Provinces to Wuhan Fighting Against 2019 Novel Coronavirus Pneumonia
Authors: Lin Jing , Ren Yunhong , Gan Haijie , Chen Ying , Huang Yingfan , You Xuemei 
Published: March 2020

Abstract
Objective: To investigate the resilience of medical workers from other provinces to Wuhan to support fighting against 2019 novel coronavirus pneumonia (COVID-19). Methods : In February 2020, medical works supporting Wuhan in the fighting against COVID-19 were eligible to complete an online survey made up of Connor Davidson Resilience Scale (CD-RISC), Hospital Anxiety Depression Scale (HADS) and Simplified Coping Style Questionnaire (SCSQ). Results : A total of 114 medical workers were investigated. The CD-RISC scores of medical workers were at a high level (67.03±13.22). The resilience level was highest for physicians (73.48±11.49), followed by supporting staff, including health care assistants, technicians (67.78±12.43) and nurses (64.86±13.46). There were also significant differences in education, training and support from hospital, adequate preparation and confidence to complete support tasks (P<0. 05). Resilience was negatively correlated with anxiety (r=-.498, P<0.01) and depression (r=-.471, P<0.01), but positively correlated with active coping styles (r=.733, P<0.01). Multiple regression analysis showed that active coping (β=1.314, p<0.05), depression (β= -.806, p<0.05), anxiety (β= -1.091, p<0.05) and training and support from hospital (β= -3.510, p<0.05) were significant influence factors of resilience. Conclusion : The manager of the health management system should be aware that active coping, depression, anxiety and training, and support from hospitals are the influential factor of resilience. In addition, it is necessary to need to take these preferences into account and develop psychosocial interventions to help reinforce the resilience of medical works fighting emerging contagious diseases such as COVID-19.
Calculating the Most Likely Intron Splicing Orders in S. pombe, Fruit Fly, Zebrafish, and Humans
Authors: Li Meng 
Published: March 2020

Abstract
Background Introns have been shown to be spliced in a defined order, and this order influences both alternative splicing regulation and splicing fidelity, but previous studies have only considered neighbouring introns. The detailed intron splicing order remains unknown. Results In this work, I developed a method that can calculate the intron splicing orders of all introns in each transcript. A simulation study showed that this method can accurately calculate intron splicing orders. I further applied this method to real pombe, fruit fly, zebrafish and human sequencing datasets and found that intron splicing orders change from gene to gene and that humans contain more not in-order spliced transcripts than S. pombe, fruit fly and zebrafish. In addition, I reconfirmed that the first introns in humans are spliced slower than those in S. pombe, fruit fly and zebrafish genome-widely. Both the calculated most likely orders and the method developed here are available on the web. Conclusions I developed a novel computational method to calculate the intron splicing orders and applied the method to real sequencing datasets. I obtained intron splicing orders for hundreds or thousands of genes in four organisms. I found humans contain more number of not in-order spliced transcripts. Keywords : Splicing; Intron splicing order; Most likely order; Bayesian network
Echographic analysis of the alterations musculoskeletal associated with endothelial dysfunction and obesity
Authors: Coria Alejandra Martínez , Estrada-Cruz Norma Angélica , Ordoñez María Inés Pérez , Montes-Cortes Daniel , Apolinar Leticia Manuel 
Published: March 2020

Abstract
Background: Modern imaging plays a central role in the care of obese patients, with an integral focus on its use and accessibility in individuals with this condition with alterations of various organs. Objective. To perform an echographical analysis of musculoskeletal system disorders, endothelial dysfunction and the left ventricle in obese rats. Methods. Sprague Dawley rats (250±5 g) were used and divided into two groups: control group (C) fed a standard diet and the obese group (Ob), fed with a hyper caloric diet of high fructose-fat for 4 mounts. Body weight, cholesterol, triglycerides, glucose, inflammatory cytokines and adhesion molecules (ICAM-1, VCAM-1) were measured. Additionally, two-dimensional echocardiography and abdominal ultrasound and musculoskeletal system studies in the lower extremities were performed. Results . Body weight in the Ob group was increased compared to the control group, (p <0.001); in addition, increased glucose, cholesterol and triglycerides of were found in the Ob group vs the C group, (p <0.05), and as well as increased adhesion molecules ICAM-1 and, VCAM-1 (p <0.01). On ultrasound, 75% of the Ob group presented showed 75% fatty liver and distal joint abnormalities. Conclusion . Endothelial dysfunction and changes at the level of the musculoskeletal system with the presence of joint cysts in the posterior region of the distal joint of the lower extremities were observed in obese rodents.
The characteristics of lumbar paraspinal muscle degeneration based on the Roussouly classification: a retrospective study
Authors: Yang Shuo , Xu Guangyu , Zou Fei , Jiang Jianyuan , Lu Feizhou , Xia Xinlei , Ma Xiaosheng 
Published: March 2020

Abstract
Background: To analyse the characteristics of lumbar paraspinal muscle degeneration in individuals with different Roussouly types.Methods: Eighty patients (20 patients for each Roussouly type) with degenerative lumbar disease were retrospectively enrolled from January 2017 to February 2018. The cross-sectional area (CSA) and percentage of fat infiltration (FI) of the paraspinal muscles at the L1-S1 levels were measured using T2-weighted axial MRI and ImageJ software. The measured data were analysed with independent samples t-tests.Results: Degeneration of the paraspinal muscles of the upper lumbar region was significantly severer in Type 1 than in Type 3, the degrees of paraspinal muscle degeneration of Type 2 appeared to be more evenly distributed in all segments than Type 3, and Type 4 showed severer degeneration in L5-S1 than Type 3.Conclusion: The degree of paraspinal muscle degeneration in each segment was different across the four Roussouly types, but the degrees of degeneration were consistent with the characteristics of degenerative disease within each type.
Assessment of the possibility of vertical transmission of COVID-19: A systematic review and meta-analysis protocol
Authors: Dashti Sareh , Najafi Tahereh Fathi , Tohidinik Hamid Reza , Bahri Narjes 
Published: March 2020

Abstract
BackgroundThe novel coronavirus 2019 (COVID-19) outbreak has put a great burden on global health and healthcare systems. One of the vulnerable groups to COVID-19 infection and complications is the pregnant women. There is controversy regarding the possibility of vertical transmission of COVID-19 from mother to infant. The aim of this systematic review and meta-analysis was to assess the possibility of vertical transmission of COVID-19 based on currently published literature including observational studies. All published articles including case reports, case series,MethodsThis study will be conducted on all published observational studies, including cross-sectional studies, cohort, case-control, case reports, and case series, in peer reviewed journals in any language until the end of March 2020. Editorials, commentaries and letter to editors will be excluded from the review. Search will be conducted in international bibliographic databases including PubMed, Embase, and Web of Science based on preferred reporting items for systematic reviews and meta-analysis (PRISMA) checklist. Primary search will be performed in PubMed and Embase using the Coronavirus 2019 and vertical transmission keywords based on medical subject heading (MeSH) terms along with free text searching in combination with Boolean operations. The search strategy will be improved and finalized based on the results of the primary search. The World Health Organization (WHO) and google scholar websites will be searched as grey literature. Articles will be reviewed by two authors independently for the relevance of titles and abstracts. Data extraction of the included articles will be performed by two researchers using the Zotero and review manager (revMan) software. Heterogeneity of the articles will be assessed using DerSimonian & Laird Q test and I 2 statistic. The pooled estimated prevalence of vertical transmission of COVID-19 will be performed using the Metaprop command. Publication bias will be assessed using the Begg's rank correlation and the Egger weighted regression methods.DiscussionThe findings of this systematic review and meta-analysis will help practitioners and health care providers in decision making for the care and management of COVID-19 infected pregnant women. Systematic review registration In process
Characterization of novel dual tandem CD19/BCMA chimeric antigen receptor T cells to potentially treat multiple myeloma
Authors: Kang Liqing , Zhang Jian , Li Minghao , Xu Nan , Qi Wei , Tan Jingwen , Lou Xiaoyan , Yu Zhou , Sun Juanjuan , Wang Zhenkun , Fu Chengcheng , Tang Xiaowen , Dai Haiping , Chen Jia , Wu Depei , Yu Lei 
Published: March 2020

Abstract
Background: Chimeric antigen receptor (CAR) engineered T cells directed B cell maturation antigen (BCMA) showed transient recovery to multiple myeloma (MM). However, the expression of CD19 on immature plasma cell may escape the recognition by BCMA-CAR T, which restrict the efficacy and facilitate to relapse. The purpose of this study is to characterize a novel CAR structure with a tandem orientation of scFv-BCMA and scFv-CD19, tandem CAR (tan-CAR), to provide an effective solution for killing both BCMA and/or CD19 expression MM cells.Method: Single-chain variable fragment (scFv) sequences from the anti-CD19 antibody FMC63 and the anti-BCMA antibody C11D5.3 were ligated in tandem with transmembrane and T cell signaling domains to achieve tan-CAR construct. The therapeutic specificity and efficiency were analyzed for tan-CAR T cells activation, proliferation, cytokine release and cytolytic toxicity in vitro. Also, in vivo efficacy evaluation conducted in xenograft mouse models with the combination of two corresponding target tumor cells, in comparison with conventional CAR.Results: The in vitro studies demonstrated specific activation of tan-CAR T cells to the K562 tumor cell overexpressing CD19, BCMA, or both. Besides, it also elicits the comparable immunoreactivities, in terms of proliferation, cytokine release and cytolytic activity compared to single scFv modified CAR T cells. Importantly, the in vivo studies of tan-CAR-transduced T cells results specific inhibition of tumor growth in xenograft model that express combined tumor antigen i.e. CD19 and BCMA. Moreover, systemic administration of tan-CAR resulted in complete tumor remission, whilst neither BCMA-CAR T nor CD19-CAR-T could. Conclusion: A novel tan-CAR T was successfully designed and showed the significant antitumor efficacy for combined antigen-positive tumor cells in vitro and in vivo. However, the single CAR T cells with targeting one antigen didn’t achieve similar potency. The data from this study suggest a novel strategy to help reduce relapse due to existing CD19-expressing multiple myeloma cells or downregulation of the BCMA antigen after CAR-based treatment of multiple myeloma.