bluuebunny/crossref_metadata_2025 huggingface dataset:
Living with Type 2 Diabetes Mellitus in the Kingdom of Tonga: A Qualitative Investigation of the barriers and enablers to lifestyle management
Authors: Taumoepeau Jennifer , Knight-Agarwal Cathy , Tu'i 'Esiteli , Jani Rati , Osuagwu Levi , Simmons David
Published: April 2021

Background: Despite the increasing prevalence of Type 2 Diabetes Mellitus in the Kingdom of Tonga little is known of the experiences of adults living with this non-communicable disease. This investigation aimed to explore the barriers and enablers to healthy lifestyles in a group of men and women living with type 2 diabetes mellitus residing in this pacific island nation.Methods: This qualitative study consisted of three semi-structured focus groups (n=16) which were conducted at Tonga’s only Public Hospital located in the capital, Nuku’alofa. Discussions were audio recorded, transcribed, cross-checked for consistency, and entered into a word processing document for analysis. Thematic analysis was employed to synthesise results.Results: Four main themes were identified: (1) Knowledge and Support; (2) Fear and Motivation; 3) Physical and Psychological Environment; and (4) Faith and Culture. Conclusion: The qualitative findings from this study may assist the future development and dissemination of culturally appropriate lifestyle-related information for men and women living with Type 2 Diabetes Mellitus in the Kingdom Tonga. The need for collaboration between practitioners at the hospital, the church, family members and local traditional healers is important if the lifestyle-related needs and wants of this group of people are to be met.
Overabundance of Asaia and Serratia bacteria is associated with deltamethrin insecticide susceptibility in Anopheles coluzzii from Agboville, Côte d’Ivoire
Authors: Pelloquin Bethanie , Kristan Mojca , Edi Constant , Meiwald Anne , Clark Emma , Jeffries Claire L. , Walker Thomas , Dada Nsa , Messenger Louisa A
Published: April 2021

Background Insecticide resistance among mosquito species is now a pervasive phenomenon, which threatens to jeopardise global malaria vector control efforts. Evidence of links between the mosquito microbiota and insecticide resistance is emerging, with significant enrichment of insecticide degrading bacteria and enzymes in resistant populations. Using 16S rRNA amplicon sequencing, we characterised and compared the microbiota of Anopheles (An.) coluzzii in relation to their deltamethrin resistance and exposure profiles. Results Comparisons between 2-3 day old deltamethrin resistant and susceptible mosquitoes, demonstrated significant differences in microbiota diversity (PERMANOVA, pseudo-F = 19.44, p=0.0015). Ochrobactrum, Lysinibacillus and Stenotrophomonas genera, each of which comprised insecticide degrading species, were significantly enriched in resistant mosquitoes. Susceptible mosquitoes had a significant reduction in alpha diversity compared to resistant individuals (Shannon index: H=13.91, q=0.0003, Faith’s phylogenetic diversity: H=6.68, q=0.01), with Asaia and Serratia dominating microbial profiles. There was no significant difference in deltamethrin exposed and unexposed 5-6 day old individuals, suggesting that insecticide exposure had minimal impact on microbial composition. Serratia and Asaia were also dominant in 5-6 day old mosquitoes, regardless of exposure or phenotype, and had reduced microbial diversity compared with 2-3 day old mosquitoes. Conclusions Our findings revealed significant alterations of An. coluzzii microbiota associated with deltamethrin resistance, highlighting the potential for identification of novel microbial markers for insecticide resistance surveillance. qPCR detection of Serratia and Asaia was consistent with 16S rRNA sequencing, suggesting that population level field screening of the bacterial microbiota may be feasibly integrated into wider resistance monitoring if reliable and reproducible markers associated with phenotype can be identified.
Ulinastatin Inhibits Nasopharyngeal Carcinoma Metastasis by Suppressing uPA/uPAR Signaling
Authors: Li Chang-Zhi , Qiang Yuan-Yuan , Liu Zhi-Jie , Zheng Li-Sheng , Peng Li-Xia , Mei Yan , Meng Dong-Fang , Wei Wen-Wen , Chen Dong-Wen , Xu Liang , Lang Yan-Hong , Xie Ping , Peng Xing-Si , Wang Ming-Dian , Guo Ling-Ling , Xie De-Huan , Shu Di-Tian , Ding Liu-Yan , Lin Si-Ting , Luo Fei-Fei , Wang Jing , Li Sha-Sha , Huang Bi-Jun , Chen Jin-Dong , Qian Chao-Nan
Published: April 2021

Background: Distant metastasis is the main reason for treatment failure in patients with nasopharyngeal carcinoma (NPC). In this study, we evaluated the effect of ulinastatin (UTI) on NPC metastasis and investigated its underlying mechanism.Methods: Highly-metastatic NPC cell lines S18 and 5-8F were treated with UTI and the effect on cellular growth, migration, and invasion of NPC cells was determined using MTS and transwell assays. The luciferase-expressing S18 cells (S18-1C3) were injected into the left hind footpad of nude mice to establish a spontaneous footpad to popliteal lymph node (LN) metastasis model. The luciferase mRNA was measured by qPCR to calculate the metastatic inhibition rate. The UTI-related uPA, uPAR and the main molecular members of the JAT/STAT3 pathway were detected by qPCR and immunoblotting.Results: UTI inhibited the migration and invasion of S18 and 5-8F cells with no effect on cellular growth in vitro, and suppressed metastasis of S18 cells in vivo. uPAR expression was reduced from 24 to 48 hours after UTI treatment. The anti-metastasis effect of UTI partially relies on the suppression of uPA and uPAR.Conclusion: UTI partially inhibits NPC metastasis via downregulating the expression of uPA and uPAR.
Zoning forest fire risk at a county-level based on geographically weighted logistic regression: a case study of Wuyishan, China
Authors: You Weibin , Liu Wan , Yu Yunqin , He Dongjin
Published: April 2021

Identification of the fire risk area at the county level is the key spatial unit for local forest resource protection and fire prevention. However, current methods and standards focus on the rating of risk level at a national scale which are not necessarily applicable at a local level. Wuyishan is a county-level city in southeastern China, which is rich in forest resources and is important for biodiversity conservation. We used a binary logistic regression (BLR) model and a geographically weighted logistic regression (GWLR) model to examine the indicators of forest fire occurrence and map the forest risk zones in the study area based on historical fire survey data from 1999 to 2013. The results showed that the BLR model simulation found that four indicators (daily average relative humidity, daily sunshine hours, elevation, and distance to the closest railway) had a significant impact on the risk of forest fires in Wuyishan City. Daily sunshine hours had a positive correlation with forest fire risk, and the other three factors were negatively correlated. The GWLR model incorporated the spatial heterogeneity of indicators into the simulation and further demonstrated that only daily average relative humidity was correlated over the entire study area. In contrast, daily sunshine hours, elevation, and distance to the closest railway were effective indicators of fire risk at a local level. The prediction accuracy of the GWLR model (85.3%) was slightly higher than that of the BLR model (84.4%). Around 19.9% of the study area was in a high fire risk zone, 34.0% was in a medium-risk zone, and 46.1% was in a low-risk zone. The high-risk zones were mainly concentrated in the central and southern areas. Our results indicate that, during the fire prevention period, the forest fire management department needs to increase the frequency of daily inspections of the forest edge areas in the high- and medium-risk areas based on the fire risk zoning map. Our approach may improve the identification of forest fire risk and fire prevention and suppression management at a county-level in mountainous and hilly areas.
The Effect of Health Education via Mobile Apps in Promoting Asthma Health Related Quality of Life Among Asthmatic School Children in Urban Malaysia.
Authors: Raimi Abdulaziz Mansoor Al , Chong Chan Mei , Tang Li Yoong , Chua Yan Piaw , Ajeel Latifa Yahya Al
Published: April 2021

Objectives: The objective of study to assess the effect of health education via mobile applications in promoting health-related quality of life among schoolchildren with asthma in urban Malaysia. Methods: A Quasi-experimental with two-group pre- and post-intervention design was used in this study involving a total of 214 students. The students were randomly assigned into two groups (intervention group and control group) in a pre and post intervention approach. The control group received face to face education and the experimental group had health education via mobile apps.Results: The findings showed that the total score of health related quality of life has improvement in the mean total score of health-related quality of life from pre-intervention (5.31±1.27) to post-intervention (5.66±1.28) for the control group, compared with the experimental group with a mean total score of HRQoL at pre-intervention (5.01±1.36) and post-intervention (5.85±1.29). A comparison between the experimental and control groups using an independent t-test showed statistically significant differences in the mean HRQoL scores of asthma between the experimental and control groups. The effect of health education via mobile applications showed statistically significant improvement pre and post intervention in HRQoL score [F (1,288) = 57.46, p = <0.01].Conclusion: The use of mobile technology in health education improved HRQoL as compared of traditional method of face-to-face lecture or handbooks among school children with asthma. Thus, educational module using mobile apps improves HRQoL. Trial registration: This study was registered under the Medical Research Committee, University Malaya Medical Centre, Malaysia under Trial MRECID. NO: 2016112-4501, Also, this study is registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) under Trial ID: ACTRN12614300582550
High expression of RRM2 promotes the pathogenesis of malignant ovarian endometriosis.
Authors: Yang Binkai , Hu Yuanjing , Wang Tian , Li Na , Zhang Wenwen
Published: April 2021

Objective: Our objective was to investigate the upregulated expression of ribonucleotide reductase M2 (RRM2) in the ectopic endometrium (EC) of ovarian endometriosis (OE) patients that may indicate malignant transformation. RRM2 may be used as a marker of OE, which contribute to the research of the mechanism of the malignant transformation of OE.Methods: The gene expression profiles of ovarian cancer and OE were downloaded from Gene Expression Omnibus (GEO), and a common hub gene, RRM2, was identified. The expression of RRM2 was low in OE and high in ovarian cancer. A total of 44 patients with endometriosis-associated ovarian cancers (EAOC) and 44 with OE were enrolled in this study. Immunohistochemistry (IHC) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expression of RRM2, while the relationship between RRM2 and Ki-67 was analyzed by IHC co-localization. Results: There was no significant difference in the expression of RRM2 in the eutopic endometrium (EU), EC, and cancer tissues of EAOC patients. Compared with OE patients, the mRNA and protein expression levels of RRM2 were higher in the EC of EAOC patients (p＜0.01). Moreover, the high expression of RRM2 was consistent with the expression of Ki-67 in EC of EAOC patients.Conclusions: The upregulated expression of RRM2 in the EC of OE patients may indicate malignant transformation. RRM2 may be used as a marker of OE, which allows the investigation of the mechanism of the malignant transformation of OE.
The IRF family can influence tumor immunity and the prognosis of patients with colorectal cancer
Authors: Chen Yan-Jie , Luo Shu-Neng , Dong Ling , Liu Tao-Tao , Shen Xi-Zhong , Zhang Ning-Ping , Liang Li
Published: April 2021

Background: The roles of interferon-regulatory factors (IRFs) in colorectal cancer (CRC) have not been studied through bioinformatics analysis. Methods: We used gene- and microRNA-expression data for patients with somatic mutations and colon adenocarcinoma/rectum adenocarcinoma from The Cancer Genome Atlas Genomic Data Commons as a training dataset. Gene-expression data (accessions GSE17536 and GSE39582) were downloaded from the Gene Expression Omnibus database as the validation dataset. Expressional differences, clinical correlations, disease prognosis, functional enrichment, and immune correlations of IRF genes were analyzed. The results were validated via immunohistochemistry. Results: The mRNA-expression levels of IRF3 and IRF7 differed between tumor and normal tissues and were correlated with patient prognosis. The IRF score was an independent risk factor for overall survival. IRFs recruited inflammatory cells; however, the immune and stromal scores showed inflammatory-cell recruitment only in the tumor stroma; therefore, they did not help eliminate tumor cells. Functional-enrichment analysis and pan-cancer expression analysis revealed that IRFs were differentially expressed in tumor tissues and associated with patient prognosis. Conclusions: IRFs were differentially expressed in tumor tissues and were associated with prognosis in CRC patients. Although IRFs can promote the infiltration of immune cells, the immune and stromal score showed that the infiltrated immune cells mostly stayed in the tumor stroma and cannot directly eliminate the tumor. Our findings can help to improve CRC prognosis and treatment strategies.
The impact of visiting operational departments on improving public health students’ learning about Rabies preventions, coetaneous Leishmaniasis, and serological tests of Brucellosis: a learning trip
Authors: Charkazi Abdurrahman
Published: April 2021

Background: Conventional teaching through lectures cannot be of much use and efficiency for achieving the educational goals of this course. Designing community-based teachings could be influential in students’ learning quality. Hence, the present study was conducted aiming to evaluate the impact of visiting the operational departments of Gonbad-e Kavous county healthcare center on improving public health students’ learning of educational objectives of the national infections disease combat program. Methods: Over a cross-sectional study, 97 students of continues and discontinuous bachelor’s majoring in public health visited the department of rabies prevention and control, coetaneous Leishmaniasis(CL) control, and the central laboratory of Gonbad-e Kavous county healthcare center over the first semester of the 2017-19 academic year. These students were introduced to the methods of treating Leishmaniasis patients and those bitten by animals as well as brucellosis diagnosis tests. The students were provided with the study's questionnaire after the visit so that they could fill it in. collected data entered SPSS v.15 statistical software and were analyzed using descriptive statistics and an independent t-test. Results: 61 (62.9%) of the students were female and 50 (51.5%) people were discontinuous bachelor’s students. The average satisfaction of students with the CL, rabies control and prevention, and Brucellosis test departments was 93.38%, 89.25%, and 82.69%, respectively. Besides, the total satisfaction of the mentioned visits was 92.61%. Discontinuous bachelor's students' satisfaction with rabies control and prevention and Brucellosis departments was significantly higher compared to continuous bachelor's students (P<0.05). Conclusion: results indicated that students’ satisfaction with visiting the operational departments of Gonbad-e Kavous county healthcare center was high. Hence, further such visits are recommended for other public health students.
You Gotta Walk the Walk to Talk the Talk: Happy Older Latino Adults (HOLA) as a pilot health promotion and prevention program for older HIV-positive Latino men
Authors: Jimenez Daniel , Weinstein Elliott R. , Batsis John
Published: April 2021

Background
Older Latinos with HIV have been disproportionately affected by the epidemic and experience compounded health disparities that have deepened over time. These health disparities are largely related to lifestyle and are either preventable or amenable to early detection or intervention. Despite existing resources to deliver an intervention to reduce this compounded health disparity, there is little information on the effects of health promotion interventions on indices of cardiometabolic risk in midlife and older Latinos with HIV. The Happy Older Latinos are Active (HOLA) intervention is an innovative health promotion program that is uniquely tailored to meet the diverse needs and circumstances of older Latinos with HIV. The goal of this pilot study is to evaluate the feasibility and acceptability of HOLA among Latinos aged 50 and older with HIV.
Methods/Design:
HOLA, which is informed by Behavioral Activation and Social Learning theory is a community health worker (CHW)-led, multicomponent, health promotion intervention consisting of: (1) a social and physical activation session; (2) a moderately intense group walk led by a CHW for 45 minutes, 3x/week for 16 weeks; (3) pleasant events scheduling. The proposed pilot study will recruit and enroll 18 community dwelling Latinos with HIV aged 50+. Participants will be assessed at three time points (baseline, post intervention, and 3 months post intervention) on measures of cardiometabolic risk factors (waist circumference, dyslipidemia, hypertension, and glucose), psychosocial functioning, and health-related quality of life.
Conclusions
If HOLA can be delivered successfully by CHWs, then the scalability, accessibility, and potential for dissemination is increased. Additionally, the results of this pilot study have far reaching implications in regard to the health and welfare of other at-risk, under resourced populations. This pilot study will inform feasibility and identify modifications needed in the design of a larger hypothesis testing study.
Combination of dabrafenib with irinotecan might trigger off a higher frequency of adverse events by pharmacokinetic interaction
Authors: Wang Zhe , Wang Xiaoyu , Wang Zhen , Fan Xiaoyu , Yan Mingrui , Jiang Lili , Xia Yangliu , Cao Jun , Liu Yong
Published: April 2021

Dabrafenib and irinotecan are two drugs that can be utilized to treat melanoma. A previous in vivo study has shown that dabrafenib enhances the antitumor activity of irinotecan in a xenograft model with unclear mechanism. This study aims to investigate the inhibition of dabrafenib on SN-38 (the active metabolite of irinotecan) glucuronidation using human liver microsomes (HLMs) and recombinant human UGT1A1, trying to elucidate the possible mechanism underlying the synergistic effect. Our data indicated that dabrafenib noncompetitively inhibited SN-38 glucuronidation in pooled HLMs and recombinant UGT1A1 with a K i,u value was 12.43 ± 0.28 and 2.64 ± 0.27 μM, respectively. Based on the in vitro K i,u value and estimation of kinetic parameters, dabrafenib administered at 150 mg twice daily may result in about 17%-81.9% increase in the area under the curve (AUC) of SN-38 in vivo . Moreover, the ratios of [ I ] gut / K i,u are 0.70 and 3.32 in HLMs and recombinant UGT1A1, respectively, indicating a high risk of drug-drug interactions (DDIs) when dabrafenib was used in combination with irinotecan. Our study provides a basis for further development and optimization of this combination in clinical research.
Techno-Economic and Sensitivity Analysis of Biodiesel Production Using Co-Solvent
Authors: El-Galad M. , El-Khatib kamel , El-Sheltawy Shakinaz
Published: April 2021

Three different continuous homogeneous alkali-catalyzed, heterogeneous alkali-catalyzed and supercritical methanolysis processes with adding tetrahydrofuran as a co-solvent to produce biodiesel from virgin vegetable oil were designed and simulated. An economic assessment was also performed based on the results of the process simulations. Technical assessment of the proposed processes showed that the homogeneous and heterogeneous alkali-catalyzed processes were the simplest with the least amount of process equipment, while for the supercritical methanolysis process; it was more complex with larger sizes of transesterification and separation units. The homogeneous alkali-catalyzed process using tetrahydrofuran was found to have the lowest total capital cost ($2.32 million), the highest aftertax rate of return (513%) and the payback period (0.19 year). However, total manufacturing cost and aftertax net profit, the heterogeneous alkali-catalyzed process using tetrahydrofuran had the lowest operating cost ($82.20 million) and the highest aftertax net profit ($18.20 million). The homogeneous alkali-catalyzed process I is not only technically feasible but also economically viable. Results from the sensitivity analyses indicated that methanol recovery percent, biodiesel purification tower vacuum pressure, price of feedstock oil, price of methanol, price of biodiesel and price of glycerin by-product were the factors that most significantly affected the economic feasibility of biodiesel production.
Investigating degradation metabolites and underlying pathway of azo dye “Reactive Black 5” in bioaugmented floating treatment wetlands
Authors: Tara Nain , Iqbal Mazhar , Habib Fazale , Khan Qaiser Mahmood , Iqbal Samina , Afzal Muhammad , Brix Hans
Published: April 2021

The direct discharge of azo dyes and/or their metabolites into the environment may exert toxic, mutagenic, and carcinogenic effects on exposed fauna and flora. In this study, we analyzed the metabolites produced during the degradation of an azo dye namely Reactive Black 5 (RB5) in the bacterial augmented-floating treatment wetlands (FTWs), followed by the investigation of their underlying toxicity. To this end, a FTWs system was developed by using a common wetland plant Phragmites australis in the presence of three dye-degrading bacteria (Acinetobacter junii strain NT-15, Pseudomonas indoloxydans strain NT-38, and Rhodococcus sp. strain NT-39). We found that the FTW system effectively degraded RB5 into at least 20 different metabolites with the successful removal of color (95.5%) from the water. The fish toxicity assay revealed the non-toxic characteristics of the metabolites produced after dye degradation. Our study suggests that bacterially aided FTWs could be a suitable option for the successful degradation of azo dyes, and the results presented in this study may help improve the overall textile effluent clean-up processes.
Giant Coronary Artery Aneurysms Involving More Than One Coronary Artery
Authors: Khouzam Matthew S , Khouzam Nayer
Published: April 2021

Background: Coronary artery aneurysms are rare findings in patients undergoing coronary angiography. The presence of multiple coronary artery aneurysms located in more than one coronary artery is even more uncommon. The pathophysiology of such aneurysms is unknown, but the majority are often due to atherosclerosis, congenital heart disease, or vasculitis. Case Presentation: We present a rare case of a 78-year-old female patient who presented with unstable angina and non-ST segment elevation myocardial infarction. On coronary angiography she was found to have three separate 1 cm saccular aneurysms involving the proximal left anterior descending coronary artery. The right coronary artery could not be visualized. Computed chest tomography revealed a 6.6 x 6.3 cm saccular aneurysm of the right coronary artery, and a 4.4 cm fusiform aneurysm of the ascending aorta. The patient gave no history of percutaneous coronary intervention or cardiac surgical procedures. She had a previous history of endovascular stenting of an abdominal aortic aneurysm. The sizable right coronary artery aneurysm showed extrinsic compression of both the right atrium and ventricle with right ventricular hypokinesis. Serological studies for vasculitis were all negative. Pathology of the aneurysm wall revealed calcific atherosclerosis without evidence of vasculitis. The patient underwent subtotal resection of the right coronary aneurysm with ligation of the proximal and distal ends of the right coronary artery and double bypass surgery to the left anterior descending and right posterior descending coronary arteries. Conclusion: The presence of multiple, large coronary artery aneurysms is very rare. Treatment can be challenging and should be individualized. Surgical treatment is recommended for giant coronary artery aneurysms to prevent potential complications. Keywords: coronary artery aneurysm, aortic aneurysm, atherosclerosis, non-ST segment 32 elevation myocardial infarction, case report
Fermi blockade of the strong electron-phonon interaction in optimally doped high temperature superconductors
Authors: Mishchenko Andrey , Nagaosa Naoto , Prokof'ev Nikolay , Tupitsyn Igor
Published: April 2021

We study how manifestations of strong electron-phonon interaction (EPI) depend on the carrier concentration by solving the two-dimensional Holstein model for the spin-polarized fermions using an approximation free bold-line diagrammatic Monte Carlo (BDMC) method. We show that the strong EPI, obviously present at very small Fermion concentration, is masked by the Fermi blockade effects and Migdal's theorem to the extent that it manifests itself as moderate one at large carriers densities. Suppression of strong EPI fingerprints is in agreement with experimental observations in doped high temperature superconductors.
Comparative Efficacy of Oral Insulin Sensitizers Metformin, Thiazolidinediones, Inositol, and Berberine in Improving Endocrine and Metabolic Profiles in Women With Pcos: A Network Meta-analysis
Authors: Zhao Han , Xing Chuan , Zhang Jiaqi , He Bing
Published: April 2021

BackgroundMultiple oral insulin-sensitizing agents, such as metformin, thiazolidinediones, inositols, and berberine, have been proven safe and efficacious in improving the endocrine, metabolic, and reproductive abnormalities seen in polycystic ovary syndrome (PCOS), providing more options for healthcare providers and patients. These oral insulin sensitizers are more convenient, practical, and economic than agents that need to be injected. A comparison of the clinical effectiveness of the four different classes of oral insulin sensitizers in PCOS has not been explored, leading to clinical uncertainty about the optimal treatment pathway. The present study aims to compare the effects of oral insulin sensitizers on endocrine and metabolic profiles in women with PCOS.MethodsWe identified randomized controlled trials for PCOS from a variety of databases, published from January 2005 to October 2020. Outcomes included changes in menstrual frequency, improvements in hyperandrogenism and glucolipid metabolism and adverse side effects. A random-effects network meta-analysis was performed.ResultsTwenty-two trials comprising 1079 patients with PCOS were included in this study. Compared with metformin, treatment with Myo-inositol + D-chiro-inositol was associated with a greater improvement in menstrual frequency (odds ratio 14.70 [95% confidence interval (CI) 2.31-93.58]). Myo-inositol + D-chiro-inositol and metformin + thiazolidinediones combination therapies were superior to respective monotherapies in reducing total testosterone levels. Thiazolidinediones, metformin + thiazolidinediones, and myo-inositol + D-chiro-inositol were associated with a lower insulin resistance index (HOMA-IR) compared with that in metformin alone (mean differences: -0.72 [95% CI (-1.11)- (-0.34)] to -0.89 [95% CI (-1.460)- (-0.32)]). Metformin + thiazolidinediones treatment was associated with lower triglyceride levels compared with that in metformin and thiazolidinediones monotherapy, while thiazolidinediones was superior to metformin in increasing high-density lipoprotein cholesterol and decreasing fasting plasma glucose, triglycerides, low-density lipoprotein cholesterol, and gastrointestinal adverse events. ConclusionsOurs is the first study to report that for women with PCOS, Myo-inositol combined with D-chiro-inositol and metformin combined with thiazolidinediones appear superior to metformin alone in improving insulin resistance and decreasing total testosterone. Myo-inositol combined with D-chiro-inositol is particularly efficacious in menstrual recovery. Thiazolidinediones and metformin combined with thiazolidinediones improve lipid metabolism better than metformin alone. Trial registrationPROSPERO CRD42020211524
Nitrogen radical-triggered trifunctionalizing ipso-spirocyclization of unactivated alkenes with vinyl azides towards new spiroaminal frameworks
Authors: Qi Zhongyu , Zhang Zhijie , Yang Li , Zhang Di , Wei Siping , Fu Qiang , Du Xi , Yi Dong
Published: April 2021

Radical-mediated spirocyclization is a powerful and efficient tool to forge complex spirocyclic frameworks. Radical-mediated non-dearomative double-cyclization of linear precursors for the concomitant construction of both rings is more challenging but highly attractive. Herein, we report the first example of non-dearomative trifunctionalizing ipso-spirocyclization of unactivated alkenes through photoredox-catalyzed, nitrogen radical-triggered cyclization-trapping-translocation-cyclization cascade, providing a single-step modular access to architecturally new and fascinating spiroaminal frameworks through simultaneous formation of one C−C bond and two geminal C−N bonds. The developed protocol utilizes not only internal or terminal olefinic oxime esters but also olefinic amides as nitrogen radical precursors, and features broad substrate scope, varied functional group compatibility, easy scalability, and potential for product derivatization and late-stage functionalization of biologically active molecule. Importantly, the mechanistic studies including DFT calculations indicate that such photocatalytic trifunctionalizing ipso-spirocyclization undergoes a radical relay cascade of intramolecular 5-exo-trig cyclization, intermolecular radical trapping, 1,5-hydrogen atom transfer, and sequential 5-endo-trig cyclization, which would open up a new reaction mode of alkenes.
LINC01956 Promotes Metastasis and M2 Polarization of Tumor-Associated Macrophages in Glioblastoma Via The FUS/β-Catenin Signaling Pathway
Authors: lu fengfei , jin fa
Published: April 2021

Background:Long noncoding RNAs (lncRNAs) can drive cancer progression. Here, we studied the role of a novel lncRNA, LINC01956, in glioblastoma (GBM). Methods:RT-PCR assay was used to examine LINC01956 expression levels. Colony-formation, MTT, cell-cycle and in-vivo tumorigenesis assays were used to examine the role of LINC01956 in cell growth in vitro and in vivo. Boyden assay was used to examine cell invasion ability in vitro. RNA immunoprecipitation and RNA-protein pull-down assays were used to examine the interaction between LINC01956 and FUS protein.ChIP assay was used to examine HIF1-binding sites in the LINC01956 promoter.Results:The level of LINC01956 was elevated in GBM cell lines and tissues. LINC01956 downregulation suppressed the migration and proliferation of GBM cells. M2 polarization of macrophages induced by exosomes derived from glioma cells overexpressing LINC01956 further accelerated GBM progression. Mechanistically, we found that FUS interacted with both LINC01956 and β-catenin. LINC01956 bound to FUS and reduced its ubiquitination. LINC01956 evoked nuclear translocation of phosphorylated (p)-β-catenin by recruiting FUS. Furthermore, under hypoxic conditions, LINC01956 was regulated by HIF-1α. Conclusion:Taken together, our data revealed for the first time that LINC01956 exerts protumor effects via FUS-dependent activation of the WNT/β-catenin signaling pathway.
Comparison of mesenchymal stromal cells from peritoneal dialysis effluent with those from umbilical cords: Characteristics and therapeutic effects on chronic peritoneal dialysis in uremic rats
Authors: Du Yangchun , Zong Ming , Guan Qiunong , Huang Zhongli , Zhou Lan , Cai Jing , Roza Gerald da , Wang Hao , Qi Hualin , Lu Yiping , Du Caigan
Published: April 2021

Background: A long-term of peritoneal dialysis (PD) using a hypertonic PD solution (PDS) leads to patient’s peritoneal membrane (PM) injury, resulting in ultrafiltration failure (UFF) and PD drop-out. Our previous study shows that PD effluent-derived mesenchymal stromal cells (pMSCs) prevent the PM injury in normal rats after repeated exposure of the peritoneal cavity to a PDS. This study was designed to compare the cytoprotection between pMSCs and umbilical cord-derived MSCs (UC-MSCs) in the treatment of both PM and kidney injury in uremic rats with chronic PD.Methods: 5/6 nephrectomized (5/6Nx) Sprague Dawley rats were intraperitoneally (IP) injected Dianeal (4.25% dextrose, 10 mL/rat/d), and were treated with pMSCs or umbilical cord (UC)-MSCs (approximately 2×106/rat/wk, IP). Ultrafiltration was determined by IP injection of 30 mL of Dianeal (4.25% dextrose) with 1.5-h dewell time, and kidney failure by serum creatinine (SCr) and blood urea nitrogen (BUN). The structure of the PM and kidneys was assessed using histology. Gene expression was examined using quantitative reverse transcription PCR, and protein levels using flow cytometric and Western blot analyses.Results: We showed a slight difference in the morphology between pMSCs and UC-MSCs in plastic dishes, and significantly higher expression levels of stemness-related genes (NANOG, OCT4, SOX2, CCNA2, RAD21 and EXO1) and MSCs surface markers (CD29, CD44, CD90 and CD105) in UC-MSCs than those in pMSCs, but no difference in the differentiation to chondrocytes, osteocytes or adipocytes. pMSCs treatment was more effective than UC-MSCs in the protection of the MP and remnant kidneys in 5/6Nx rats from PDS-induced injury, which was associated with higher resistance of pMSCs than UC-MSCs to uremic toxins in culture, and more reduction of peritoneal mesothelial cell death by the secretome from pMSCs than from UC-MSCs in response to PDS exposure. The secretome from both pMSCs and UC-MSCs similarly inactivated NOS2 in activated THP1 cells.Conclusions: As compared to UC-MSCs, pMSCs may be more potently prevents PDS-induced PM and remnant kidney injury in this uremic rat model of chronic PD, suggesting that autotransplantation of ex vivo-expanded pMSCs may become a promising therapy for UFF and deterioration of remnant kidney function in PD patients.
Distribution of soil viruses across China and their potential role in phosphorous metabolism
Authors: Han Li-Li , Yu Dan-Ting , Bi Li , Du Shuai , Silveira Cynthia , Güemes Ana Georgina Cobián , Zhang Li-Mei , He Ji-Zheng , Rohwer Forest
Published: April 2021

Background: Viruses are the most abundant biological entities on the planet and drive biogeochemical cycling on a global scale. Our understanding of biogeography of soil viruses and their ecological functions lags significantly behind that of Bacteria and Fungi. Here, a viromic approach was used to investigate the distribution and ecological functions of viruses from 19 soils across China.Results: More than 60% of viral genome fragments could not be classified, representing potential new viruses. Among the 27 viral families identified, 15 families belonged to dsDNA viruses and 12 families belonged to ssDNA viruses. Soil samples clustered more significantly by geographical location than type of soil (agricultural and natural). Three clusters of viral communities were identified from North, Southeast and Southwest regions; these clusters differentiated using taxonomic as well as functional composition and were mainly driven by latitude. Phylogenetic analyses of the phoH gene showed a remarkable diversity and two new viral clades. Notably, five proteins involved in phosphorus (P) metabolism-related nucleotide synthesis functions, including dUTPase, MazG, PhoH, Thy1, and RNR, were mainly identified in agricultural soils. Conclusions: The present work revealed that soil viral communities and their functions were distributed across China according to geographical location, with latitude as the dominant driving factor. In addition, P metabolism genes encoded by these viruses probably drive the synthesis of nucleotides for their own genomes inside bacterial hosts, thereby affecting P cycling in the soil ecosystems.
Physical function and health-related quality of life after surgery for nontuberculous mycobacterium pulmonary disease: a prospective cohort study
Authors: Kuroyama Yuki , Tabusadani Mitsuru , Omatsu Shunya , Yamane Kazumasa , Takao Satoshi , Matsumura Yusuke , Mori Kosuke , Kawahara Kazuma , Ono Kazuki , Hiramatsu Miyako , Shiraishi Yuji , Kimura Hiroshi , Senjyu Hideaki
Published: April 2021

Background: Nontuberculous mycobacterium pulmonary disease (NTM-PD) is a progressive condition characterized by exercise intolerance and impaired health-related quality of life (HRQOL). NTM-PD is sometimes treated with surgery in combination with medication, but little is known about the postoperative physical function and HRQOL. This study aimed to investigate the exercise capacity and HRQOL of patients with NTM-PD preoperatively and 6 months postoperatively.Methods: This prospective observational study included patients with NTM-PD and was conducted at Fukujuji Hospital. The intervention was surgical resection plus perioperative and post-discharge physical therapy. The physical function was assessed preoperatively and 6 months postoperatively using the 6-minute walk test (6MWT). HRQOL was assessed preoperatively and 6 months postoperatively using the Short-Form 36 Health Survey (SF-36) and St. George’s Respiratory Questionnaire. The postoperative HRQOL was compared between patients with and without preoperative clinical symptoms.Results: In total, 35 patients were analyzed. Preoperative clinical symptoms were present in 20 of 35 patients (57%), and the preoperatively symptomatic group had significantly lower preoperative HRQOL than the preoperatively asymptomatic group (p < 0.05). Thirty-two patients completed the 6-month follow-up. Compared with preoperatively, there were significant improvements at 6 months postoperatively in the 6MWT (p < 0.01) and HRQOL, mainly in the SF-36 mental component summary (p < 0.01). The SF-36 mental component summary in the preoperatively symptomatic group was very significantly improved from preoperatively to 6 months postoperatively (p < 0.05).Conclusions: The combination of surgical treatment and physical therapy for NTM-PD contributes to improvements in physical function and HRQOL.
Genetic Analysis of Human Parainfluenza Virus Type 4-Associated with Severe Acute Respiratory Infection Among Children in Luohe City, Henan Province, China, During 2017-2018
Authors: Zhou Shanshan , Mao Naiying , Zhang Yan , Cui Aili , Zhu Zhen , Hu Ruiping , Xu Jin , Xu Wenbo
Published: April 2021

During 2017–2018, Nasopharyngeal aspirates (NPAs) from 627 hospitalized patients with SARI at Luohe Center Hospital were tested by RT-PCR for human parainfluenza virus 4(HPIV-4). 14 (2.2%) of 627 samples were positive for HPIV-4. The complete nucleotide sequence of the HN gene from 9 positive samples was amplified and sequenced successfully. Genetic analysis showed that the HPIV-4 strains circulating in Luohe city are more closely related to HPIV-4A. Our study indicated that there were multiple lineages of HPIV-4 circulating in Henan Province in China during the study period, which will improve our understanding of the epidemiological and clinical characteristics of HPIV-4.
Productivity, nutrient use efficiency, energetics and bio-economics of winter maize in south India
Authors: Salakinkop S R , Hulamani Siddarta
Published: April 2021

Maize area is rapidly spreading in south India in response to rising demand from the poultry and fish feed industries. The planting of maize during winter season is necessary to increase the total area and production of maize. The present investigation encompassing different sowing windows with different fertility levels revealed that significantly higher winter maize productivity was achieved from first and second week of October planting along with application of 200 % RDF(recommended dose of fertilizer) followed by 150 % RDF. Planting of winter maize during first week of October recorded significantly higher grain yield (8786 kg ha-1) and stover yield (1220 kg ha-1) and was found on par with sowing during second week of October. Among fertility levels, significantly higher grain yield (8320 kg ha -1) and stover yield (1195 kg ha-1) were recorded with application of 200 % RDF and was found on par with application of 150 % RDF. Similarly higher dry matter production, more days for physiological maturity, higher accumulation of growing degree days, photo thermal units and heliothermal units were recorded from crop planted during first and second week of October along with application of either 200 % or 150 % RDF. Further higher nutrient use efficiency was recorded from first and second week October planted crop along with lower fertility level (100 % RDF). Similarly significantly higher output energy, net energy and specific energy were higher from crop planted during first week of planting along with application of 200 % RDF. Also it recorded higher net returns and gross returns Whereas, energy use efficiency and energy productivity were higher with planting during first week of October along with application of 100 % RDF.
Improving Selection Efficiency of Crop Breeding with a Genomic Prediction Aided Partial Phenotyping Strategy
Authors: He Sang , Jiang Yong , Thistlethwaite Rebecca , Hayden Matthew , Trethowan Richard , Daetwyler Hans
Published: April 2021

Increasing the number of environments for phenotyping of crop lines in earlier stages of breeding programs can improve selection accuracy. However, this is often not feasible due to cost. In our study, we investigated a partial phenotyping strategy that does not test all entries in all environments, but instead capitalizes on genomic prediction to predict missing phenotypes in additional environments without extra phenotyping expenditure. The breeders’ main interest – response to selection – was directly simulated to evaluate the effectiveness of the partial genomic phenotyping strategy in a wheat dataset. Whether the partial phenotyping strategy resulted in more selection response depended on the correlations of phenotypes between environments. The partial phenotyping strategy consistently showed statistically significant higher simulated responses to selection, compared to complete phenotyping, when the majority of completely phenotyped environments were negatively correlated and any extension environment was highly positively correlated with any of the completely phenotyped environments. Our results indicate that genomics-based partial phenotyping can improve selection response at middle stages of crop breeding programs.
Nitro-oxidized Carboxycellulose Nanofibers From Moringa Plant: Effective Bioadsorbent for Mercury Removal
Authors: CHEN HUI , Sharma Sunil K. , Sharma Priyanka R. , Chi Kai , Fung Eric , Aubrecht Katherine , Keroletswe Ngonye , Chigome Samuel , Hsiao Benjamin S
Published: April 2021

Mercury contamination in drinking water is a worldwide problem due to its severely harming effects on the human body. A nanostructured natural bioadsorbent, carboxycellulose nanofiber extracted from raw moringa plant using the nitro-oxidation method (termed NOCNF), capable of effectively remediating this problem has been demonstrated. Nitro-oxidation is a simple approach that can extract carboxylated nanocellulose directly from raw biomass. In this study, the produced NOCNF contained a large density of carboxylate groups on the cellulose surface (0.97 mmol/g), capable of removing Hg2+ ions by simultaneous electrostatic-interactions and mineralization processes. Using the Langmuir analysis, the adsorption results indicated that the highest Hg2+ removal capacity of this NOCNF was 257.07 mg/g, which is higher than most of the reported values. The interactions between Hg2+ and NOCNF were further characterized by Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy/energy dispersive spectroscopy (SEM/EDS), transmission electron microscopy (TEM) with electron diffraction and wide-angle X-ray diffraction (WAXD) methods, suggesting the existence of two distinct removal mechanisms: predominant adsorption at low Hg2+concentrations (< 250 ppm) and predominant mineralization at high Hg2+ concentrations (> 1000 ppm). The applications of NOCNF were illustrated in both suspension form, as an adsorbent/coagulant, and dry powder form using filtration column. The results indicated that NOCNF in suspension exhibited a higher maximum removal efficiency of 81.6 % as compared to the dry state of 74.3 %. This work demonstrated the feasibility of extracting nanostructured adsorbents from biomass feedstocks to tackle the Hg2+ contamination problem in drinking water.
Dopamine Signaling Modulates Microglial NLRP3 Inflammasome Activation: Implications for Parkinson’s Disease
Authors: Pike Adrianne Frances , Longhena Francesca , Faustini Gaia , Eik Jean-Marc van , Gombert Iris , Herrebout Maaike A.C. , Fayed Mona M.H.E. , Varanita Tatiana , Teunissen Charlotte E. , Hoozemans Jeroen J.M. , Bellucci Arianna , Veerhuis Robert , Bubacco Luigi
Published: April 2021

Background: Parkinson’s disease (PD) is characterized by the loss of nigral dopaminergic neurons leading to impaired striatal dopamine signaling, α-synuclein- (α-syn-) rich inclusions, and neuroinflammation. Degenerating neurons are surrounded by activated microglia with increased secretion of interleukin-1β (IL-1β), driven largely by the NLRP3 inflammasome. A critical role for microglial NLRP3 inflammasome activation in the progression of both dopaminergic neurodegeneration and α-syn pathology has been demonstrated in parkinsonism mouse models. Fibrillar α-syn activates this inflammasome in mouse and human macrophages, and we have shown previously that the same holds true for primary human microglia. Dopamine blocks microglial NLRP3 inflammasome activation in the MPTP model, but its effects in this framework, highly relevant to PD, remain unexplored in primary human microglia and in other in vivo parkinsonism models. Methods: Biochemical techniques including quantification of IL-1β secretion and confocal microscopy were employed to gain insight into dopamine signaling-mediated inhibition of the NLRP3 inflammasome mechanism in primary human microglia and the SYN120 transgenic mouse model. Dopamine and related metabolites were applied to human microglia together with various inflammasome activating stimuli. The involvement of the receptors through which these catecholamines were predicted to act were assessed with agonists in both species. Results: We show in primary human microglia that dopamine, L-DOPA, and high extracellular K+, but not norepinephrine and epinephrine, block canonical, non-canonical, and α-syn-mediated NLRP3 inflammasome-driven IL-1β secretion. This suggests that dopamine acts as an inflammasome inhibitor in human microglia. Accordingly, we provide evidence that dopamine exerts its inhibitory effect through dopamine receptor D1 and D2 (DRD1 and DRD2) signaling. We also show that aged mice transgenic for human C-terminally truncated (1-120) α-syn (SYN120 tg mice) display increased NLRP3 inflammasome activation in comparison to WT mice that is diminished upon DRD1 agonism. Conclusions: Dopamine inhibits canonical, non-canonical, and α-syn-mediated activation of the NLRP3 inflammasome in primary human microglia, as does high extracellular K+. We suggest that dopamine serves as an endogenous repressor of the K+ efflux-dependent microglial NLRP3 inflammasome activation that contributes to dopaminergic neurodegeneration in PD, and that this reciprocation may account for the specific vulnerability of these neurons to disease pathology.