bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of cembratriene-ol and cembratriene-diol in yeast via the MVA pathway
Authors: Zhang Yu , Bian Shiquan , Liu Xiaofeng , Fang Ning , Wang Chunkai , Liu Yanhua , Du Yongmei , Timko Michael P. , Zhang Zhongfeng , Zhang Hongbo 
Published: February 2021

Abstract
Background
Cembranoids are one kind of diterpenoids with multiple biological activities. The tobacco cembratriene-ol (CBT-ol) and cembratriene-diol (CBT-diol) have high anti-insect and anti-fungal activities, which is attracting great attentions for their potential usage in sustainable agriculture. Cembranoids were supposed to be formed through the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway, yet the involvement of mevalonate (MVA) pathway in their synthesis remains unclear. Exploring the roles of MVA pathway in cembranoid synthesis could contribute not only to the technical approach but also to the molecular mechanism for cembranoid biosynthesis.

Results
We constructed vectors to express cembratriene-ol synthase (CBTS1) and its fusion protein (AD-CBTS1) containing an N-terminal GAL4 AD domain as a translation leader in yeast. Eventually, the modified enzyme AD-CBTS1 was successfully expressed, which further resulted in the production of CBT-ol in the yeast strain BY-T20 with enhanced MVA pathway for geranylgeranyl diphosphate (GGPP) production but not in other yeast strains with low GGPP supply. Subsequently, CBT-diol was also synthesized by co-expression of the modified enzyme AD-CBTS1 and BD-CYP450 in the yeast strain BY-T20.

Conclusions
We demonstrated that yeast is insensitive to the tobacco anti-fungal compound CBT-ol or CBT-diol and could be applied to their biosynthesis. This study further established a feasibility for cembranoid production via the MVA pathway and provided an alternative bio-approach for cembranoid biosynthesis in microbes.
Within‐household clustering of genetically related Plasmodium falciparum infections in a moderate transmission area of Uganda
Authors: Briggs Jessica , Kuchta Alison , Murphy Max , Tessema Sofonias , Arinaitwe Emmanuel , Rek John , Chen Anna , Nankabirwa Joaniter I. , Drakeley Chris , Smith David , Bousema Teun , Kamya Moses , Rodriguez-Barraquer Isabel , Staedke Sarah , Dorsey Grant , Rosenthal Philip J. , Greenhouse Bryan 
Published: February 2021

Abstract
Background
Evaluation of genetic relatedness of malaria parasites is a useful tool for understanding transmission patterns, but patterns are not easily detectable in areas with moderate to high malaria transmission. To evaluate the feasibility of detecting genetic relatedness in a moderate malaria transmission setting, relatedness of Plasmodium falciparum infections was measured in cohort participants from randomly selected households in the Kihihi sub-county of Uganda (annual entomological inoculation rate of 27 infectious bites per person).

Methods
All infections detected via microscopy or Plasmodium-specific loop mediated isothermal amplification from passive and active case detection during August 2011-March 2012 were genotyped at 26 microsatellite loci, providing data for 349 samples from 230 participants living in 80 households. Pairwise genetic relatedness was calculated using identity by state (IBS).

Results
As expected, genetic diversity was high (mean heterozygosity [He] = 0.73), and the majority (76.5 %) of samples were polyclonal. Despite the high genetic diversity, fine-scale population structure was detectable, with significant spatiotemporal clustering of highly related infections. Although the difference in malaria incidence between households at higher (mean 1127 metres) versus lower elevation (mean 1015 metres) was modest (1.4 malaria cases per person-year vs. 1.9 per person-year, respectively), there was a significant difference in multiplicity of infection (2.2 vs. 2.6, p = 0.008) and, more strikingly, a higher proportion of highly related infections within households (6.3 % vs. 0.9 %, p = 0.0005) at higher elevation compared to lower elevation.

Conclusions
Genetic data from a relatively small number of diverse, multiallelic loci reflected fine scale patterns of malaria transmission. Given the increasing interest in applying genetic data to augment malaria surveillance, this study provides evidence that genetic data can be used to inform transmission patterns at local spatial scales even in moderate transmission areas.
Dietary fiber intake from fresh and preserved food and risk of nasopharyngeal carcinoma: observational evidence from a Chinese population
Authors: MAI Zhi-Ming , NGAN Roger Kai-Cheong , KWONG Dora Lai-Wan , NG Wai-Tong , Yuen Kam-Tong , Ip Dennis Kai-Ming , CHAN Yap-Hang , LEE Anne Wing-Mui , HO Sai-Yin , LUNG Maria Li , LAM Tai-Hing 
Published: February 2021

Abstract
Background
The role of dietary fiber intake on risk of nasopharyngeal carcinoma (NPC) remains unclear. We examined the associations of dietary fiber intake on the risk of NPC adjusting for a comprehensive list of potential confounders.

Methods
Using data from a multicenter case-control study, we included 815 histologically confirmed NPC incident cases and 1502 controls in Hong Kong, China recruited in 2014–2017. Odds ratios (ORs) of NPC (cases vs controls) for dietary fiber intake from different sources at different life periods (age 13–18, age 19–30, and 10 years before recruitment) were evaluated using unconditional logistic regression, adjusting for sex, age, socioeconomic status, smoking and drinking status, occupational hazards, family history of cancer, salted fish, and total energy intake in Model 1, Epstein-Barr virus viral capsid antigen serological status in Model 2, and duration of sun exposure and circulating 25-hydroxyvitamin D in Model 3.

Results
Higher intake of total dietary fiber 10 years before recruitment was significantly associated with decreased NPC risk, with demonstrable dose-response relationship (P-values for trend = 0.001, 0.020 and 0.024 in Models 1–3, respectively). The adjusted ORs (95% CI) in the highest versus the lowest quartile were 0.51 (0.38–0.69) in Model 1, 0.48 (0.33–0.69) in Model 2, and 0.48 (0.33–0.70) in Model 3. However, the association was less clear after adjustment of other potential confounders (e.g. EBV) in the two younger periods (age of 13–18 and 19–30 years). Risks of NPC were significantly lower for dietary fiber intake from fresh vegetables and fruits and soybean products over all three periods, with dose-response relationships observed in all Models (P-values for trend for age 13–18, age 19–30 and 10 years before recruitment were, respectively, 0.002, 0.009 and 0.001 for Model1; 0.020, 0.031 and 0.003 for Model 2; and 0.022, 0.037 and 0.004 for Model 3). No clear association of NPC risk with dietary fiber intake from preserved vegetables, fruits and condiments was observed.

Conclusion
Our study has shown the protective role of dietary fiber from fresh food items in NPC risk, but no association for total dietary fiber intake was observed, probably because total intake also included intake of preserved food. Further studies with detailed dietary information and in prospective settings are needed to confirm this finding, and to explore the possible underlying biological mechanisms.
Evaluation of efflux pump activity and biofilm formation in multidrug resistant clinical isolates of Pseudomonas aeruginosa isolated from a Federal Medical Center in Nigeria
Authors: Ugwuanyi Florence Chijindu , Ajayi Abraham , Ojo David Ajiboye , Adeleye Adeyemi Isaac , Smith Stella Ifeanyi 
Published: February 2021

Abstract
Background
Pseudomonas aeruginosa an opportunistic pathogen, is widely associated with nosocomial infections and exhibits resistance to multiple classes of antibiotics. The aim of this study was to determine the antibiotic resistance profile, biofilm formation and efflux pump activity of Pseudomonas strains isolated from clinical samples in Abeokuta Ogun state Nigeria.

Methods
Fifty suspected Pseudomonas isolates were characterized by standard biochemical tests and PCR using Pseudomonas species -specific primers. Antibiotic susceptibility testing was done by the disc diffusion method. Efflux pump activity screening was done by the ethidium bromide method and biofilm formation assay by the tissue plate method. Genes encoding biofilm formation (pslA & plsD) and efflux pump activity (mexA, mexB and oprM) were assayed by PCR.

Results
Thirty-nine Pseudomonas spp. were identified of which 35 were Pseudomonas aeruginosa and 4 Pseudomonas spp. All 39 (100%) Pseudomonas isolates were resistant to ceftazidime, cefuroxime and amoxicillin-clavulanate. Thirty-six (92%), 10(25.6%), 20 (51.2%), 11(28%) and 9(23%) of the isolates were resistant to nitrofurantoin, imipenem, gentamicin, cefepime and aztreonam respectively. All the isolates had the ability to form biofilm and 11 (28%) of them were strong biofilm formers. They all (100%) harboured the pslA and pslD biofilm encoding genes. Varied relationships between biofilm formation and resistance to ciprofloxacin, ofloxacin, cefixime, gentamicin, imipenem, and aztreonam were observed. Only 23(59%) of the Pseudomonas isolates phenotypically exhibited efflux pump activity but mexA gene was detected in all 39 (100%) isolates while mexB and oprM genes were detected in 91%, 92%, and 88% of strong, moderate and weak biofilm formers respectively.

Conclusion
Multidrug resistance, biofilm and efflux pump capabilities in Pseudomonas aeruginosa have serious public health implications in the management of infections caused by this organism.
CircNR3C2 promotes HRD1-mediated tumor-suppressive effect via sponging miR-513a-3p in triple-negative breast cancer
Authors: Fan Ya , Wang Jia , Jin Wen , Sun Yifei , Xu Yuemei , Wang Yipin , Liang Xiubin , Su Dongming 
Published: February 2021

Abstract
Background
E3 ubiquitin ligase HRD1 (HMG-CoA reductase degradation protein 1, alias synoviolin with SYVN1 as the official gene symbol) was found downregulated and acting as a tumor suppressor in breast cancer, while the exact expression profile of HRD1 in different breast cancer subtypes remains unknown. Recent studies characterized circular RNAs (circRNAs) playing an regulatory role as miRNA sponge in tumor progression, presenting a new viewpoint for the post-transcriptional regulation of cancer-related genes.

Methods
Examination of the expression of HRD1 protein and mRNA was implemented using public microarray/RNA-sequencing datasets and breast cancer tissues/cell lines. Based on public RNA-sequencing results, online databases and enrichment/clustering analyses were used to predict the specific combinations of circRNA/miRNA that potentially govern HRD1 expression. Gain-of-function and rescue experiments in vitro and in vivo were executed to evaluate the suppressive effects of circNR3C2 on breast cancer progression through HRD1-mediated proteasomal degradation of Vimentin, which was identified using immunoblotting, immunoprecipitation, and in vitro ubiquitination assays.

Results
HRD1 is significantly underexpressed in triple-negative breast cancer (TNBC) against other subtypes and has an inverse correlation with Vimentin, inhibiting the proliferation, migration, invasion and EMT (epithelial-mesenchymal transition) process of breast cancer cells via inducing polyubiquitination-mediated proteasomal degradation of Vimentin. CircNR3C2 (hsa_circ_0071127) is also remarkably downregulated in TNBC, negatively correlated with the distant metastasis and lethality of invasive breast carcinoma. Overexpressing circNR3C2 in vitro and in vivo leads to a crucial enhancement of the tumor-suppressive effects of HRD1 through sponging miR-513a-3p.

Conclusions
Collectively, we elucidated a bona fide circNR3C2/miR-513a-3p/HRD1/Vimentin axis that negatively regulates the metastasis of TNBC, suggesting that circNR3C2 and HRD1 can act as potential prognostic biomarkers. Our study may facilitate the development of therapeutic agents targeting circNR3C2 and HRD1 for patients with aggressive breast cancer.
TGR5 activation attenuates neuroinflammation via Pellino3 inhibition of caspase-8/NLRP3 after middle cerebral artery occlusion in rats
Authors: Liang Hui , Matei Nathanael , McBride Devin W. , Xu Yang , Zhou Zhenhua , Tang Jiping , Luo Benyan , Zhang John H. 
Published: February 2021

Abstract
Background
Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) plays an important role in mediating inflammatory responses during ischemic stroke. Bile acid receptor Takeda-G-protein-receptor-5 (TGR5) has been identified as an important component in regulating brain inflammatory responses. In this study, we investigated the mechanism of TGR5 in alleviating neuroinflammation after middle cerebral artery occlusion (MCAO).

Methods
Sprague-Dawley rats were subjected to MCAO and TGR5 agonist INT777 was administered intranasally 1 h after MCAO. Small interfering RNAs (siRNA) targeting TGR5 and Pellino3 were administered through intracerebroventricular injection 48 h before MCAO. Infarct volumes and neurologic scores were evaluated, and ELISA, flow cytometry, immunofluorescence staining, immunoblotting, and co-immunoprecipitation were used for the evaluations.

Results
Endogenous TGR5 and Pellino3 levels increased after MCAO. TGR5 activation by INT777 significantly decreased pro-inflammatory cytokine, cleaved caspase-8, and NLRP3 levels, thereby reducing brain infarctions; both short- and long-term neurobehavioral assessments showed improvements. Ischemic damage induced the interaction of TGR5 with Pellino3. Knockdown of either TGR5 or Pellino3 increased the accumulation of cleaved caspase-8 and NLRP3, aggravated cerebral impairments, and abolished the anti-inflammatory effects of INT777 after MCAO.

Conclusions
TGR5 activation attenuated brain injury by inhibiting neuroinflammation after MCAO, which could be mediated by Pellino3 inhibition of caspase-8/NLRP3.
Heat production in a feeding matrix formed on carrion by communally breeding beetles
Authors: Matuszewski Szymon , Mądra-Bielewicz Anna 
Published: February 2021

AbstractInsects regulate their body temperature mostly behaviourally, by changing posture or microhabitat. Usually they use heat that is already present in the environment. Sometimes, however, they may manipulate the environment to affect, focus or benefit from thermogenesis. Carrion beetles create a feeding matrix by applying to cadaver surface anal or oral exudates. We tested the hypothesis that the matrix, which is formed on carrion by communally breeding beetle Necrodes littoralis L. (Silphidae), produces heat that enhances insect fitness. Using thermal imaging we demonstrate that heat produced in the matrix formed on meat by adult or larval beetles is larger than in meat decomposing without insects. Larval beetles regularly warmed up in the matrix. Moreover, by comparing matrix temperature and larval fitness in colonies with and without preparation of meat by adult beetles, we provide evidence that formation of the matrix by adult beetles has deferred thermal effects for larval microhabitat. We found an increase in heat production of the matrix and a decrease in development time and mortality of larvae after adult beetles applied their exudates on meat in the pre-larval phase. Our findings indicate that spreading of exudates over carrion by Necrodes larvae, apart from other likely functions (e.g. digesting carrion or promoting growth of beneficial microbes), facilitates thermoregulation. In case of adult beetles, this behaviour brings distinct thermal benefits for their offspring and therefore may be viewed as a new form of indirect parental care with an important thermal component.
A meta-analysis of the efficacy and safety of accelerated partial breast irradiation versus whole-breast irradiation for early-stage breast cancer
Authors: Xiang Xiaoyong , Ding Zhen , Feng Lingling , Li Ning 
Published: February 2021

Abstract
Objective
This meta-analysis evaluated the efficacy and safety of accelerated partial breast irradiation versus whole-breast irradiation for early-stage breast cancer after breast-conserving surgery.

Materials and methods
A systematic search of PubMed, Embase, and the Cochrane libraries was performed according to the PRISMA statement the last 10 years to April 7, 2020 to identify the randomized controlled trials of APBI versus WBI for treating patients with early-stage breast cancer. Two independent observers evaluated the identified studies. The obtained data were analyzed using the RevMan 5.3 software.

Results
A total of 10 randomized controlled trials involving 15,500 patients with early-stage breast cancer were selected according to the inclusion and exclusion criteria and included in this meta-analysis. In this meta-analysis, we included ten studies that reported local recurrence and found significant differences in local recurrence rates (HR = 1.46; 95% CI 1.20–1.79, P = 0.0002). Further analysis showed that this difference may be related to the choice of treatment methods. No differences in distant metastasis, breast cancer deaths, contralateral breast cancer, disease-free survival, and overall survival rates were observed between WBI and APBI groups. There was no significant difference in late toxicity, cosmetic outcomes and quality of life between the two groups, the compliance and tolerance of the patients were well. Compared to whole breast irradiation, accelerated partial breast irradiation significantly reduced serious (≥ grade 2) early toxicities, especially regarding acute skin toxicity.

Conclusions
The analysis showed that patients receiving APBI had a higher local recurrence rate, but no differences in distant metastasis, breast cancer deaths, contralateral breast cancer, disease-free survival, and overall survival rates.
MiR-140-3p inhibits the cell viability and promotes apoptosis of synovial fibroblasts in rheumatoid arthritis through targeting sirtuin 3
Authors: Zu Beibei , Liu Lin , Wang Jingya , Li Meirong , Yang Junxia 
Published: February 2021

Abstract
Background
Synovial fibroblasts (SFs) with the abnormal expressions of miRNAs are the key regulator in rheumatoid arthritis (RA). Low-expressed miR-140-3p was found in RA tissues. Therefore, we attempted to investigate the effect of miR-140-3p on SFs of RA.

Methods
RA and normal synovial fibrous tissue were gathered. The targets of miR-140-3p were found by bioinformatics and luciferase analysis. Correlation between the expressions of miR-140-3p with sirtuin 3 (SIRT3) was analyzed by Pearson correlation analysis. After transfection, cell viability and apoptosis were detected by cell counting kit-8 and flow cytometry. The expressions of miR-140-3p, SIRT3, Ki67, Bcl-2, Bax, and cleaved Caspase-3 were detected by RT-qPCR or western blot.

Results
Low expression of miR-140-3p and high expression of SIRT3 were found in RA synovial fibrous tissues. SIRT3 was a target of miR-140-3p. SIRT3 expression was negatively correlated to the expression of miR-140-3p. MiR-140-3p mimic inhibited the MH7A cell viability and the expressions of SIRT3, Ki67, and Bcl-2 and promoted the cell apoptosis and the expressions of Bax and cleaved Caspase-3; miR-140-3p inhibitor showed an opposite effect to miR-140-3p mimic on MH7A cells. SIRT3 overexpression not only promoted the cell viability and inhibited cell apoptosis of MH7A cells but also reversed the effect of miR-140-3p mimic had on MH7A cells.

Conclusions
The results in this study revealed that miR-140-3p could inhibit cell viability and promote apoptosis of SFs in RA through targeting SIRT3.
Correlation between weight-bearing asymmetry and bone mineral density in patients with bilateral knee osteoarthritis
Authors: Nishizawa Kohei , Harato Kengo , Morishige Yutaro , Kobayashi Shu , Niki Yasuo , Nagura Takeo 
Published: February 2021

Abstract
Background
Although unloading of the joint is related to reduction of the local bone mineral density (BMD), little attention had been paid to the relationship between loading asymmetry and side-to-side difference of BMD in patients with bilateral knee osteoarthritis (OA). The aim of the present study was to evaluate and clarify the relationship between gait parameters and bone mineral density in those patients.

Methods
A total of 36 knees in eighteen patients (mean age = 73.7 ± 6.3 years, mean body mass index = 26.7 ± 3.8 kg/m2) with bilateral medial knee OA were enrolled in the present study. All subjects performed relaxed standing and level walking at our gait laboratory after informed consent was obtained. First, ground reaction force was calculated on bilateral knees during standing. The knees in each patient were divided into higher and lower force side for the definition of dominant side limb. Second, gait parameters in each subject were obtained. To analyze the factors that affect the weight-bearing distribution in both limbs, clinical data and biomechanical parameters were compared between knees. Clinical data included radiographic OA grade, femorotibial angle, and BMD at the bilateral femoral neck.

Results
Knees on higher force side were significantly more extended than on lower force side in standing (P = 0.012) and knee excursion during weight acceptance phase in gait was significantly larger in higher side than in lower side (P = 0.006), while the other parameters were not significantly different. As to the clinical data, higher force side had greater BMD, compared to lower force side. In terms of Kellgren–Lawrence scale and femorotibial angle on plain radiographs, there were no significant differences between higher and lower force side.

Conclusions
Based on loading asymmetry in the present study, lower BMD was observed on Lower force side in patients with knee OA. Therefore, it is helpful for orthopedic surgeons to examine side-to-side differences of bone mineral density or extension limitation during standing for evaluation of the loading condition in patients with bilateral knee OA.
Survey of HCMV in allogenic and autologous stem cell transplantation by real-time PCR in Kermanshah, west of Iran
Authors: Payandeh Mehrdad , Zamanian Mohammad Hossein , Nomanpour Bizhan , Farhadi Mohammad Soroush , Janbakhsh Alireza , Rostamian Mosayeb , Elahi Azam , Jafari Somayeh , Dehghannejad Mohammad 
Published: February 2021

Abstract
Introduction
Human Cytomegalovirus (HCMV) is the most important viral pathogen in people undergoing bone marrow transplantation (BMT). HCMV detection in the early stages makes is possible to save the patients’ lives through immediate and timely treatment. The aim of this study was to investigate the status of HCMV using the real-time PCR method in BMT patients in Kermanshah, west of Iran.

Methods
HCMV monitoring was done in 120 patients who underwent BMT, 38 allogeneic cases and 82 autologous cases, using the ELISA serology test before transplantation. The participants were followed up 100 days after transplantation for HCMV detection in blood samples using real-time PCR. Preemptive therapy started with Ganciclovir and Foscarnet when the viral load was > 200 HCMV DNA copies/ml.

Results
Despite preemptive therapy, infection recurred in less than 1 month. HCMV recurred more frequently in patients undergoing allogenic transplation versus those receiving autologous transplantation. Recurrence was seen in 5 patients receiving allogenic transplantation. HCMV recurrence occurred in five patients with allogeneic transplantation. Twelve patients undergoing allogeneic or autologous transplantation (83%) and a virus load of > 1000 copies/ml showed HCMV-related symptoms. Three patients died, two due to HCMV-related pneumonia and the other one due to a fungal infection.

Conclusion
Real-time PCR may be a useful method for quantification and monitoring of HCMV recurrence and may be helpful in choosing more efficient HCMV preemptive treatment in BMT recipients.