bluuebunny/crossref_metadata_2025 huggingface dataset:
The equine gastrointestinal microbiome: Impacts of weight-loss
Authors: Morrison Philippa , Newbold Charles J. , Jones Eleanor , Worgan Hilary J. , Grove-White Dai H. , Dugdale Alexandra H. , Barfoot Clare , Harris Patricia A. , Argo Caroline McG.
Published: February 2020

Background Obesity is an important equine welfare issue. Whilst dietary restriction is the most effective weight-loss tool, individual animals range in their weight-loss propensity. Gastrointestinal-derived bacteria play a fundamental role in host-health and have been associated with obesity and weight-loss in other species. This study evaluated the faecal microbiome (next-generation sequencing of 16S rRNA genes) of 15 obese Welsh Mountain pony mares, in the same 11-week period across 2 years (n = 8 Year 1; n = 7 Year 2). Following a 4-week acclimation period (pre-diet phase) during which time individuals were fed the same hay to maintenance (2% body mass (BM) as daily dry matter (DM) intake), animals underwent a 7-week period of dietary restriction (1% BM hay as daily DM intake). Faeces were sampled on the final 3 days of the pre-diet phase and the final 3 days of the dietary restriction phase. Bacterial communities were determined using Next Generation Sequencing of amplified V1-V2 hypervariable regions of bacterial 16S rRNA. Results Losses in body mass ranged from 7.11% to 11.59%. Changes in the faecal microbiome composition following weight-loss included a reduction in the relative abundance of Firmicutes and Tenericutes and a reduction in indices of bacterial diversity. Pre-diet diversity was negatively associated with weight-loss. Pre-diet faecal acetate concentration was a strong predictor of subsequent weight-loss and negatively associated with Sphaerochaeta (Spirochaetes phylum) abundance. When animals were divided into 3 groups (high, mid, low) based overall weight loss, pre-diet bacterial community structure was found to have the greatest divergence between the high and low weight-loss groups (R = 0.67, p < 0.01), following PERMANOVA and ANOSIM analysis. Conclusions Weight-loss in this group of ponies was associated with lower pre-diet faecal bacterial diversity and greater pre-diet acetate concentration. Overall, these data support a role for the faecal microbiome in weight-loss propensity in ponies and provide a baseline for research evaluating elements of the faecal microbiome in predicting weight-loss success in larger cohorts.
Views of health care professionals and policy-makers on the use of surveillance data to combat antimicrobial resistance
Authors: Al-Haboubi Mustafa , Trathen Andrew , Black Nick , Eastmure Elizabeth , Mays Nicholas
Published: February 2020

Background Providing healthcare professionals with health surveillance data aims to support professional and organisational behaviour change. The UK Five Year Antimicrobial Resistance (AMR) Strategy 2013 to 2018 identified better access to and use of surveillance data as a key component. Our aim was to determine the extent to which data on antimicrobial use and resistance met the perceived needs of health care professionals and policy-makers at national, regional and local levels, and how provision could be improved. Methods We conducted 41 semi-structured interviews with national policy makers in the four Devolved Administrations and 71 interviews with health care professionals in six locations across the United Kingdom selected to achieve maximum variation in terms of population and health system characteristics. Transcripts were analysed thematically using a mix of a priori reasoning guided by the main topics in the interview guide together with themes emerging inductively from the data. Views were considered at three levels - primary care, secondary care and national - and in terms of availability of data, current uses, benefits, gaps and potential improvements. Results Respondents described a range of uses for prescribing and resistance data. The principal gaps identified were prescribing in private practice, internet prescribing and secondary care (where some hospitals did not have electronic prescribing systems). Some respondents under-estimated the range of data available. There was a perception that the responsibility for collecting and analysing data often rests with a few individuals who may lack sufficient time and appropriate skills. Conclusions There is a need to raise awareness of data availability and the potential value of these data, and to ensure that data systems are more accessible. Any skills gap at local level in how to process and use data needs to be addressed. This requires an identification of the best methods to improve support and education relating to AMR data systems.
Transcriptomic analysis of brain tissues identifies a role for CCAAT enhancer binding protein β in HIV-associated neurocognitive disorders
Authors: Canchi Saranya , Swinton Mary K. , Rissman Robert A. , Fields Jerel Adam
Published: February 2020

Background: HIV-associated neurocognitive disorders (HAND) persist in the era of combined antiretroviral therapy (ART) despite reductions in viral load (VL) and overall disease severity. The mechanisms underlying HAND in ART era are not well understood but are likely multifactorial, involving alterations in common pathways such as inflammation, autophagy, neurogenesis, and mitochondrial function. Newly developed omics approaches hold potential to identify mechanisms driving neuropathogenesis of HIV in the ART era. Methods: In this study, using 33 postmortem frontal cortex (FC) tissues, neuropathological, molecular, and biochemical analyses were used to determine cellular localization and validate expression levels of the prolific transcription factor (TF), CCAAT enhancer binding protein (C/EBP) ß, in brain tissues from HIV+ cognitively normal and HAND cases. RNA sequencing (seq) and transcriptomics analyses were performed on FC tissues including 24 specimens from well-characterized people with HIV that had undergone neurocognitive assessments. In vitro models for brain cells were used to investigate the role of C/EBPß in mediating gene expression. Results: The most robust signal for TF dysregulation was observed in cases diagnosed with Minor Neurocognitive Disorders (MND) compared to cognitive normal (CN) cases. Of particular interest, due to its role in inflammation, autophagy and neurogenesis, C/EBPß was significantly upregulated in MND compared to CN brains. C/EBPß was increased at the protein level in HAND brains. C/EBPß levels were significantly reduced in neurons and increased in astroglia in HAND brains compared to CN. Transfection of human astroglial cells with a plasmid expressing C/EBPß induced expression of multiple targets identified in the transcriptomic analysis of HAND brains, including dynamin-1-like protein (DNM1L) and interleukin-1 receptor-associated kinase 1. Recombinant HIV-Tat reduced and increased C/EBPß levels in neuronal and astroglial cells, respectively. Conclusions: These findings are the first to present RNAseq-based transcriptomic analyses of HIV+ brain tissues, providing further evidence of altered neuroinflammation, neurogenesis, mitochondrial function, and autophagy in HAND. Interestingly, these studies confirm a role for CEBPß in regulating inflammation, metabolism, and autophagy in astroglia. Therapeutic strategies aimed at transcriptional regulation of astroglia or downstream pathways may provide relief to HIV+ patients at risk for HAND and other neurological disorders.
Burden of Fatigue among Adults Living with HIV/AIDS Attending Antiretroviral Therapy in Ethiopia
Authors: Gebreyesus Tsiwaye , Belay Addisalem , Berhe Gebretsadik , Haile Gebremedhin
Published: February 2020

Background: Fatigue is one of the most common and devastating HIV-related symptoms, with a varying prevalence in different study areas. In Ethiopia, there is a paucity of information on the magnitude and factors associated with fatigue among HIV/AIDS patients. This may lead to under-diagnosis and eventually under-management of the symptom.Objectives: This study assessed the prevalence and factors associated with fatigue among adults living with HIV/AIDS attending antiretroviral therapy at health facilities of Mekelle city, Tigray, North Ethiopia, 2019. Methods: Institution based cross-sectional study design was conducted among 609 HIV/AIDS patients who were selected by using a systematic random sampling method. Data were collected by using interviewer administered structured questionnaire. Level of fatigue was measured by Fatigue Severity Scale.Results: The prevalence of fatigue was found to be 51.7%. The factors associated with fatigue were: Parity [AOR= 2.01; 95% CI: 1.09-3.71], CD4 count 200-499 cells/mm3 [AOR= 2.81; 95% CI: 1.58-4.99], anemia [AOR= 4.90 95% CI: 2.40-9.97], co-morbidities [AOR= 3.65; 95% CI: 1.71-7.78], depression [AOR= 3.68 95% CI: 1.99-6.79], not being physically active [AOR= 3.20 95% CI: 1.50-6.81], clinical stage II or IV HIV [AOR= 3.11; 95% CI: 1.51-6.40] and [AOR= 4.08; 95% CI: 1.37-12.14], respectively.Conclusion: The finding of this study revealed that fatigue is a common health problem among adult PLHIV. Factors associated with fatigue included: Parity, CD4 count 200-499 cells/mm3, Clinical Stage II or IV HIV, anemia, co-morbidities, depression, and not being physically active. The health care service needs to address the predisposing factors by provision optimum care so that PLHIV can be encouraged in physical activity in order to relieve the impact of fatigue.
Performance, metabolic and hormonal responses of grazing Nellore cows to an energy-protein supplementation during the pre-partum phase
Authors: Ferreira Matheus Fellipe de Lana , Rennó Luciana Navajas , Detmann Edenio , Paulino Mário Fonseca , Filho Sebastião de Campos Valadares , Moreira Samira Silveira , Martins Hudson Caio , de Oliveira Bruno Inácio Correa , Marquez Julia Avansi , Cidrine Isabela de Paula
Published: February 2020

Background: Supplementation programs for prepartum beef cows are usually adopted because the nutritional status of the cows upon calving is a main factor impacting reproductive performance of the next production cycle. This study evaluated the effects of 60-d pre-partum energy-protein supplementation on performance, metabolic and hormonal responses during the peripartum phase of grazing beef cows. Thirty-eight pregnant multiparous Nellore cows were assigned to a completely randomized design with two treatments: control (no supplement) and supplementation (1.5 kg of energy-protein per d with 30% crude protein, dry matter basis) Results: The supplemented cows had higher ADG pre-partum (P<0.10), but postpartum ADG did not differ between treatments. Supplementation did not affect BCS and calf BW upon calving, on days 45 and 90, milk yield and composition (P>0.10). No differences were found for forage intake and neutral detergent fiber digestibility (P>0.10). The intake and digestibility of CP and OM increased in response to supplementation (P<0.10). An interaction occurred between supplementation and peripartum days for BUN, βHB, T3 and T4, which had higher concentrations for supplemented cows at pre-partum period (P<0.10). Concentration of others blood parameters significantly changed along peripartum days (P<0.10). There was no difference in pregnancy rates and days from calving to conception between treatments (P>0.10). Conclusions: Providing an energy and protein supplement to grazing Nellore cows over the last 60 d of gestation improved their pre-partum energy balance. However, no post-partum carryover effects were detected. Keywords: nutrition, metabolism, parturition, Zebu
Betaine attenuates LPS-induced downregulation of Occludin and Claudin-1 and restores intestinal barrier function
Authors: Wu Jingtao , He Caimei , Bu Jie , Luo Yue , Yang Shuyuan , Ye Chengyan , Yu Silei , He Binsheng , Yin Yulong , Yang Xiaoping
Published: February 2020

Background ： The intestinal epithelial barrier, which works as the first line of defense between the luminal environment and the host, once destroyed, it will cause serious inflammation or other intestinal diseases. Tight junctions (TJs) play a vital role to maintain the integrity of the epithelial barrier. Lipopolysaccharide (LPS), one of the most important inflammatory factors will downregulate specific TJ proteins including Occludin and Claudin-1 and impair integrity of the epithelial barrier. Betaine has excellent anti-inflammatory activity but whether betaine has any effect on TJ proteins, particularly on LPS-induced dysfunction of epithelial barriers remains unknown. The purpose of this study is to explore the pharmacological effect of betaine on improving intestinal barrier function represented by TJ proteins. Intestinal porcine epithelial cells (IPEC-J2) were used as an in vitro model.
Results: The results demonstrated that betaine enhanced the expression of TJ proteins while LPS (1µg/mL) downregulates the expression of these proteins. Furthermore, betaine attenuates LPS-induced decreases of TJ proteins both shown by Western blot (WB) and Reverse transcription-
polymerase chain reaction (RT-PCR). The immunofluorescent images consistently revealed that LPS induced the disruption of TJ protein Claudin-1 and reduced its expression while betaine could reverse these alterations. Similar protective role of betaine on intestinal barrier function was observed by transepithelial electrical resistance (TEER) approach.
Conclusion: In conclusion, our research demonstrated that betaine attenuated LPS-induced downregulation of Occludin and Claudin-1 and restored the intestinal barrier function.
Ankle Joint Pressure Change in Varus Malalignment of the Tibia
Authors: Zhu Yuan , Li Xingchen , Xu Xiangyang
Published: February 2020

Background : Varus malalignment of the tibia could alter ankle biomechanics, and might lead to degenerative changes of the ankle joint. However, previous studies failed to report the detailed changes of ankle biomechanics in varus malalignment of the tibia. The aim of this biomechanical study was to evaluate how the ankle joint pressure would change in response to the incremental increases in varus malalignment of the tibia.

Methods
8 fresh-frozen human cadaver legs were tested in this study. Varus malalignment of the tibia and a total of 600N compressive force was simulated using a custom made fixture. Intra-articular sensors (TeckScan) were inserted in the ankle joint to collect the ankle joint pressure data. The testing sequence was 0°, 2°,4°,6°,8°,10°,12°,14°,16°,18°,20° of tibial varus.

Results
As the tibial varus progressed, the center of force (COF) shifted laterally both for the medial and lateral aspect of the ankle joint. For the medial aspect of the ankle joint, the lateral shift reached its maximum at 8º [2.76 (1.62) mm, p=0.002] of tibial varus, while for the lateral aspect of the ankle joint, the lateral shift reached its maximum at 12º [2.11 (1.19) mm, p=0.002] of tibial varus. Thereafter, the COF shifted medially as the tibial varus progressed. For the lateral aspect of the ankle joint, The P mean increased from 2103.8 (625.1) kPa at 0º to 2295.3 (589.7) kPa at 8º of tibial varus (p=0.047) , significant difference was found between the P mean at 0º and 8º (p=0.047) of tibial varus. Then as the tibial varus progressed, the P mean decreased to 1748.9 (467.2) kPa at 20º of tibial varus (p=0.002) . The lateral joint pressure ratio also increased from 0.481 (0.125) at 0º to 0.548 (0.108) at 10º of tibial varus (p=0.002) , then decreased to 0.517 (0.101) at 20º of tibial varus (p=0.002) .

Conclusions
For mild tibial varus deformities, there was a lateral shift of COF and lateral stress concentration within the ankle joint. However, as the tibial varus progressed, the COF shifted medially and the lateral stress concentration decreased.
The association between recreational sedentary behaviour and cancer risk: Findings from the UK Biobank, a large prospective cohort study
Authors: Hunter Ruth , Murray Jennifer M. , Coleman Helen G.
Published: February 2020

Background Evidence is suggestive of sedentary behaviour being associated with an increased risk of endometrial cancer, but the evidence base is too limited to draw any conclusions for other cancers. The aim of the study was to investigate the association between recreational sedentary behaviour and site-specific, and total, cancer incidence. Methods We analysed data from the prospective UK Biobank cohort study. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) between recreational sedentary behaviour (including television (TV) viewing time, computer use time and daily total screen time) and cancer risk. Partition models and isotemporal substitution models investigated the impact of substituting recreational sedentary behaviour with physical activity. Results During a mean follow-up of 7.6 years, 28,992 incident cancers were identified among 470,578 adults. A 1-hour increase in daily TV viewing time was associated with higher risks of oropharyngeal, oesophago-gastric and colon cancer in fully adjusted models. Participants who reported ≤1, compared with 1-≤3, hours/day of TV viewing time had lower risks of lung, breast, and oesophago-gastric cancer. Findings were inconsistent for computer use and daily total screen time. The majority of observed associations were small, and were attenuated after excluding cancers diagnosed within the first two years of follow-up, except for oesophago-gastric and colon cancers (HR 1.05, 95% CI: 1.01-1.10; and HR 1.04, 95% CI: 1.01-1.07 per 1-hour increase in daily TV viewing time, respectively). However, isotemporal substitution models showed reduced risk of total cancer (HR 0.97, 95% CI: 0.95, 0.99) and some site-specific (oropharyngeal, lung, breast and colorectal) cancers when replacing 1-hour/day of TV viewing with 1-hour of moderate-intensity physical activity or walking. Conclusions Our findings show that recreational sedentary behaviours, particularly TV viewing, were associated with small increased risks of oesophago-gastric and colon cancer. Replacing 1-hour per day of TV viewing with 1-hour of moderate-intensity physical activity or walking was associated with lower risk of total cancer and oropharyngeal, lung, breast and colorectal cancers. Further research from other large prospective cohort studies is required, while mechanistic research is warranted to enhance the biological plausibility of these findings.
What are sociodemographic and gender determinants of non-fatal self-harm in older adults users and non-users of antidepressants? A national population-based study
Authors: Hedna Khedidja , Fastbom Johan , Skoog Ingmar , Hensing Gunnel , Waern Margda
Published: February 2020

Background Late-life self-harm (SH) is often linked to depression. However, very few studies have explored the role of other factors and their interaction with depression in the occurrence of late-life SH. The objective of this research was to examine sociodemographic and gender factors associated with non-fatal SH, in older adults with and without antidepressant therapy. Methods We used national longitudinal register data from a total cohort of all Swedish residents aged ≥75 years between 2006-2014 (N=1,413,806). Using personal identity numbers, we linked individuals' data from numerous national registers. We identified all those with at least one episode of non-fatal self-harm (regardless of level of intent to die) and matched 50 controls to each case. A nested case–control design was used to investigate the sociodemographic factors associated with non-fatal SH in the total cohort and among antidepressant users and non-users. Risk factors were analysed in adjusted conditional logistic regression models for the entire cohort and by gender. Results In all, 2242 individuals had at least one episode of a non-fatal SH (980 men and 1262 women). In the total cohort, being married was a protective factor for non-fatal SH in men but not in women. A higher non-fatal SH risk was found in antidepressant users from outside Nordic countries (IRR: 1.44; 95% CI: 1.11-1.86), and in non-users of antidepressants from other Nordic countries (IRR: 1.58; 95% CI: 1.08-2.29). Antidepressant users with higher education had an increased risk of non-fatal SH (IRR: 1.34; 95% CI: 1.12-1.61), in both men and women. Conclusions Being married did not mitigate risk of self-harm in older women. Foreign country of birth and higher education were associated with increased risk of non-fatal SH. Healthcare professionals and social workers must be informed about high-risk groups for suicidal behaviour, and ensure they are adequately monitored both in term of antidepressant therapy and access to psychosocial support.
Oral manifestations in premature infants. A systematic review
Authors: Couto Lara Vivero , Pozo Elena Planells del , Escobar José Ignacio Salmerón , López Jorge Molina , Ruiz-Extremera Ángela , Pozo Paloma Planells del
Published: February 2020

Background

Preterm delivery, defined as delivery occurring before 37 completed weeks of pregnancy, represents 6-10% of all births in developed countries. Preterm infants are characterized by a short prenatal development period and are at an increased risk of systemic disorders as a result of their immaturity. Few studies have analyzed oral alterations among preterm infants. This systematic review examines the orofacial characteristics most commonly found among preterm infants versus infants born at term, and evaluates their repercussions upon oral health and quality of life.

Methods

The search was limited to articles published in English or Spanish and that studied the prevalence of oral sequelae and alterations in preterm children. Their methodological quality was assessed based on the guidelines of the Joanna Briggs Institute (JBI).

Results

Most of the studies found the prevalence of structural enamel defects of the primary dentition to be greater among preterm infants. Other disorders such as structural enamel defects of the permanent dentition, caries, malocclusions or alterations in dental composition, size and development also appeared to be more frequent among preterm infants, though the supporting evidence was weak.

Conclusions

Further studies are needed, analyzing the association between preterm delivery and certain orofacial disorders such as caries, malocclusions and dental anomalies.
Phytohormone up-regulates the biochemical constituent, exopolysaccharide and nitrogen metabolism in paddy-field cyanobacteria exposed to chromium stress
Authors: Tiwari Sanjesh , Patel Anuradha , Prasad Sheo Mohan
Published: February 2020

The authors have withdrawn the journal submission associated with this preprint and requested that the preprint also be withdrawn.
Image-and-text health warning labels on alcohol and food: potential effectiveness and acceptability
Authors: Pechey Emily , Clarke Natasha , Mantzari Eleni , Blackwell Anna , De-loyde Katie , Morris Richard , Marteau Theresa , Hollands Gareth
Published: February 2020

Background

Health warning labels (HWLs) using images and text to depict the negative health consequences of tobacco consumption are effective and acceptable for changing smoking-related outcomes. There is currently limited evidence concerning their potential use for reducing consumption of alcoholic drinks and energy-dense foods. The aim of this research was to describe the potential effectiveness and acceptability of image-and-text (also known as pictorial or graphic) HWLs applied to : i. alcoholic drinks and ii. energy-dense snack foods.

Methods

Two online studies were conducted using between-subjects designs with general population samples. Participants rated one of 21 image-and-text HWLs on alcoholic drinks (n=5528), or one of 18 image-and-text HWLs on energy-dense snacks (n=4618). HWLs comprised a graphic image with explanatory text, depicting, respectively, seven diseases linked to excess alcohol consumption, and six diseases linked to excess energy intake. Diseases included heart disease and various cancers. Outcomes were negative emotional arousal, desire to consume the labelled product, and acceptability of the label. Free-text comments relating to HWLs were content analysed.

Results

For both alcoholic drinks and energy-dense snacks, HWLs depicting bowel cancer generated the highest levels of negative emotional arousal and lowest desire to consume the product, but were the least acceptable. Acceptability was generally low for HWLs applied to alcohol, with 3 of 21 rated as acceptable, and was generally high for snacks, with 13 of 18 rated as acceptable. The majority of free-text comments expressed negative reactions to HWLs on alcohol or energy-dense snacks.

Conclusions

Image-and-text health warning labels depicting bowel cancer showed greatest potential for reducing selection and consumption of alcoholic drinks and energy-dense snacks, although they were the least acceptable. Laboratory and field studies are needed to assess their impact on selection and consumption.
RETRACTED: An Exploratory Case study of the effect of Ecology on Malaria Risk Factors in Northern Pakistan.
Authors: JAMAL QAISAR , Rasheed Syed Basit , KHAN NAZMA HABIB , ZAIDI FARRAH , NAZ NAZIA , ILTAF SUMBAL , ADNAN MUHAMMAD , Tanzila Gule , . Israil , ZAHID MUHAMMAD , ZAMAN QAISAR
Published: February 2020

The authors have requested that this preprint be removed from Research Square.
MiR-30a-5p regulates GLT-1 function via a PKCα-mediated ubiquitin degradation pathway in a mouse model of Parkinson’s disease
Authors: Meng Xingjun , Zhong Jianping , Zeng Chong , Yung Ken Kin Lam , Zhang Xiuping , Wu Xiaojuan , Qu Shaogang
Published: February 2020

Background:Glutamate excitotoxicity caused by dysfunctional glutamate transporters plays an important role in the pathogenesis of Parkinson’s disease (PD); however, the mechanisms that underlie the regulation of glutamate transporters in PD are still not fully elucidated. MicroRNAs have been reported to play key roles in regulating the translation of glutamate-transporter mRNA. Methods: We established model of PD 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice in vivo and 1-methyl-4-phenylpyridinium (MPP+) treated astrocyte in vitro. Stereotaxic injection of shRNA in mouse, and miRNA inhibitor/mimic, or antagonist/agonist treated the cell model, Behavioral experiments, glutamic acid uptake, transport activity of synaptosomes, underlying mechanisms and the impact on neuronal survival were assessed.Results We demonstrated that short-hairpin RNA-mediated knockdown of miR-30a-5p ameliorated motor deficits and pathological changes like astrogliosis and reactive microgliosis in a mouse model of PD. Western blotting and immunofluorescent labeling revealed that miR-30a-5p suppressed the expression and function of GLT-1 in MPTP-treated mice and specifically in astrocytes treated with (cell model of PD). Conclusion Both in vitro and in vivo, we found that miR-30a-5p knockdown promoted glutamate uptake and increased GLT-1 expression by hindering GLT-1 ubiquitination and subsequent degradation in a PKCα-dependent manner. Therefore, miR-30a-5p represents a potential therapeutic target for the treatment of PD.
FGF21 alleviates neuroinflammation following ischemic stroke by modulating the temporal and spatial dynamics of microglia/macrophages
Authors: Wang Dongxue , Liu Fei , Zhu Liyun , Lin Ping , Han Fanyi , Wang Xue , Tan Xianxi , Xiong Ye , Lin Li
Published: February 2020

Background: Resident microglia and macrophages are the predominant contributors to neuroinflammation and immune reactions, which play a critical role in the pathogenesis of ischemic brain injury. Controlling inflammatory responses is considered a promising therapeutic approach for stroke. Recombinant human fibroblast growth factor 21 (rhFGF21) has anti-inflammatory properties by modulating microglia and macrophages, but our knowledge of the inflammatory modulation of rhFGF21 in focal cerebral ischemia is lacking. Therefore, we investigated whether rhFGF21 improves ischemic outcomes in experimental stroke by targeting microglia and macrophages. Methods: C57BL/6 mice were subjected to transient middle cerebral artery occlusion (tMCAO) and randomly divided into groups that received intraperitoneal rhFGF21 or vehicle daily starting at 6 h after reperfusion. Behavior assessments were monitored for 14 d after tMACO and the gene expression levels of inflammatory cytokines were analyzed with qPCR. The phenotypic variation of microglia/macrophages and the presence of infiltrated immune cells were examined by flow cytometry and immunostaining. Additionally, magnetic cell sorting (MACS) in combination with fluorescence-activated cell sorting (FACS) was used to purify microglia and macrophages. Results: rhFGF21 administration ameliorated neurological deficits in behavioral tests by regulating the secretion of pro-inflammatory and anti-inflammatory cytokines. rhFGF21 also attenuated the polarization of microglia/macrophages toward the M1 phenotype and the accumulation of peripheral immune cells after stroke, accompanied by a temporal evolution of the phenotype of microglia/macrophages and infiltration of peripheral immune cells. Furthermore, rhFGF21 treatment through its actions on FGF receptor 1(FGFR1) inhibited M1 polarization of microglia and pro-inflammatory cytokine expression by suppressing nuclear factor-kappa B (NF-κB ) and upregulating peroxisome proliferator-activated receptor PPAR-γ. conclusion：In summary, rhFGF21 treatment promoted functional recovery in experimental stroke by modulating microglia/macrophage-mediated neuroinflammation via the NF-κB and PPAR-γ signaling pathways, making it a potential anti-inflammatory agent for stroke treatment. Keywords : rhFGF21, stroke, neuroinflammation, microglia/macrophage, NF-κB, PPAR-γ
Resveratrol Ameliorates Atherosclerosis Induced by High-fat Diet and LPS in ApoE-/- Mice and Inhibits the Activation of CD4+ T Cells by Regulating the Expression of Dnmt
Authors: Zhou Liyu , Long Jun , Sun Yuting , Chen Weikai , Qiu Runze , Yuan Dongping
Published: February 2020

Background Atherosclerosis (AS), which characterized with the accumulation of lipids on the vessel wall, is the pathological basis of many cardiovascular diseases (CVD) and seriously threatens human health. Resveratrol (RES) has been reported to be benefit for AS treatment. This research aimed to observe the effects of RES on AS induced by high-fat diet (HFD) and LPS in ApoE -/- mice and investigate the underlying mechanism. Methods ApoE -/- mice were fed with HFD companied with LPS to induce AS and RES was administrated for 20 weeks. Splenic CD4 + T cells were cultured and treated with anti-CD3/CD28 together with LPS, and RES was added. Serum lipids and the atherosclerotic areas of aortas were detected. The activation of CD4 + T cells were investigated both in vivo and in vitro and the expression of DNA methyltransferases (Dnmt) in CD4 + T cells were measured. Results In vivo, administration of RES prevented HFD and LPS induced dysfunction of serum lipids including TC (total cholesterol), TG (triglyceride), LDL-C (low density lipoprotein cholesterol) and HDL-C (high density lipoprotein cholesterol), ameliorated the thickened coronary artery wall and decreased the areas of atherosclerotic lesion on aortas. Besides, RES decreased the number of CD4 + T cells in peripheral blood, decreased the expression of CD25 and CD44, but not affected the expression of L-selectin (CD62L). In vitro, RES decreased the expression of Ki67, CD25 and CD44 in CD4 + T cells. Moreover, RES increased the secretion of IL-2, IL-10 and TGF-β1, decreased IL-6. In addition, RES decreased both the mRNA and protein level of Dnmt1 and Dnmt3b in CD4 + T cells. Conclusion These results indicated that RES ameliorated AS induced by HFD companied with LPS in ApoE -/- mice and inhibited the proliferation and activation of CD4 + T cells by regulating the expression of Dnmt1 and Dnmt3b.
Withdrawing treatment of Children in the pediatric intensive care unit of a China Children’s Hospital: A Single Center Years Retrospective Analysis
Authors: Liu Huaqing , Su Dongni , Guo Xubei , Dai Yunhong , Dong Xingqiang , Zhu Qiujiao , Bai Zhengjiang , Li Ying , Wu Shuiyan
Published: February 2020

Background: Published data and practice recommendations on end-of-life generally reflect Western practice frameworks, there are few reports that refer to withdrawing treatment of children in China. Methods: Withdrawing treatment and reasons of children in the pediatric intensive care unit (PICU) of a regional children's hospital in eastern China from 2006 to 2017 was studied retrospectively. Withdrawing treatment was divided into medical withdrawing and premature withdrawing as defined. Results: The incidence of withdrawing treatment among children in the PICU decreased significantly, for premature withdrawing from a 3-year average of 15.1% in 2006–2008 to 1.9% in 2015–2017 (87.4% reduction). The decrease in cases of premature withdrawing contributed most of the decrease in total withdrawing. The median age of children in whom treatment was withdrawn increased from 14.5 (interquartile range: 4.0–72.0) months in 2006 to 40.5 (interquartile range: 8.0– 99.0) months in 2017. Reasons given by guardians of children whose treatments were withdrawn in 2011–2017, “illness is too severe” ranked first, accounting for 66.3%, followed by “condition has been improved” (20.9%). Only a few of the guardians ascribed withdrawing treatment to economic reasons. Conclusions: The decreasing in incidence of withdrawing treatment and an increase in the age of children whose treatment was withdrawn show that guardians are more willing to actively treat their children in this children’s hospital during the last years. Chinese children's guardians have their own unique ways of expression when self-reported reasons for withdrawing treatment.
The Association between Ambient Temperature and Sperm Quality in Wuhan, China
Authors: Wang Xiaochen , Tian Xiaojia , Ye Bo , Zhang Yi , Zhang Xiaotong , Huang Shichun , Li Cunlu , Wu Simin , Li Rui , Zou Yuliang , Liao Jingling , Yang Jing , Ma Lu
Published: February 2020

Background Few epidemiological investigations have focused on the influence of environmental temperature on human sperm quality. Here, we evaluated the potential association between ambient temperature and human sperm quality in Wuhan, China, and examined the interactive effect of particulate matter (PM 2.5 ) and temperature. Methods 1780 males who had been living in Wuhan for no less than three months and received semen analysis at the Department of Reproductive Medicine in Renmin Hospital of Wuhan University between April 8, 2013 and June 30, 2015 were recruited. Daily mean meteorological data and air pollution data (PM 2.5 , O 3 and NO 2 ) in Wuhan between 2013 and 2015 were collected. A generalized linear model was used to explore the associations between ambient temperature and sperm quality (including sperm concentration, percentage of normal sperm morphology, and progressive motility) at 0–9, 10–14, 15–69, 70–90, and 0–90 days before semen examination, and the interaction between temperature and PM 2.5 . Results The associations between ambient temperature and sperm quality were an inverted U-shape at five exposure windows, except for a lag of 0–9 days for sperm concentration. A 1 °C increase in ambient temperature above the thresholds was associated with a 2.038 (1.292~2.783), 1.814 (1.217~2.411), 1.458 (1.138~1.777), 0.934(0.617~1.251) and 1.604 (1.258~1.951) decrease in the percentage of normal sperm morphology at lag 0–9, lag 10–14, lag 15–69, lag 70–90, and lag 0–90 days, respectively. The interaction p- values of PM 2.5 and temperature were mostly less than 0.05 at five exposure windows. When ambient temperature exposure levels were above the thresholds, a 0.979 (0.659-1.299) and 3.559 (0.251~6.867) decrease in percentage of normal sperm morphology per 1 °C increase in temperature at lag 0-90 days was observed in the PM 2.5 ≤ P 50 group and PM 2.5 > P 50 group, respectively. Conclusions Our results indicate that exposure to ambient temperature has a threshold effect on sperm quality, and PM 2.5 enhances the effect of temperature on sperm quality when temperatures are above the threshold.
QTL Mapping of Web Blotch Resistance in Peanut by High-throughput Genome-wide Sequencing
Authors: Liu Hua , Sun Ziqi , Zhang Xinyou , Qin Li , Qi Feiyan , Wang Zhenyu , Du Pei , Xu Jing , Zhang Zhongxin , Han Suoyi , Li Shaojian , Gao Meng , Zhang Lina , Cheng Yujie , Zheng Zheng , Huang Bingyan , Dong Wenzhao
Published: February 2020

Background: Web blotch is one of the most important foliar diseases worldwide in peanut (Arachis hypogaea L.). The identification of quantitative trait loci (QTLs) for peanut web blotch resistance represents the basis for gene mining and the application of molecular breeding technologies.Results: In this study, a peanut recombinant inbred line (RIL) population was used to map QTLs for web blotch resistance by high-throughput genome-wide sequencing. Frequency distribution of disease grade and disease index in five environments indicated wide phenotypic variation in response to web blotch among RILs. A high-density genetic map was constructed, containing 3,634 bin markers distributed on 20 peanut linkage groups (LGs) with an average genetic distance of 0.5 cM. In total, eight QTLs were detected for peanut web blotch resistance in at least three environments, explaining from 2.8 to 15.1% of phenotypic variance. The two major QTLs qWBRA04 and qWBRA14 were detected in all five environments and were linked to 41 candidate genes encoding nucleotide-binding site leucine-rich repeat (NBS-LRR) or other proteins related to disease resistances. Conclusions: The results of this study provide a basis for breeding peanut cultivars with web blotch resistance.
Integrated sRNAome and RNA-Seq Analysis Reveals miRNA Effects on Betalain Biosynthesis in Pitaya
Authors: Chen Canbin , Xie Fangfang , Hua Qingzhu , Zur Noemi Tel , Zhang Lulu , Zhang Zhike , Zhang Rong , Zhao Jietang , Hu Guibing , Qin Yonghua
Published: February 2020

Background: MicroRNAs (miRNAs) and their regulatory functions in anthocyanin, carotenoid, and chlorophyll accumulation have been extensively characterized in many plant species. However, the miRNA regulatory mechanism in betalain biosynthesis remains mostly unknown. Results: In this study, 126 conserved miRNAs and 41 novel miRNAs were first isolated from Hylocereus monacanthus, among which 95 conserved miRNAs belonged to 53 miRNA families. 34 candidate miRNAs related to betalain biosynthesis were found to be differentially expressed. The expression patterns of those differential expressed miRNAs were analyzed in various tissues of the pitaya by RT-qPCR. A significantly negative correlation was detected between the expression levels of half those miRNAs and corresponding target genes. Target genes of miRNAs i.e. aly-miR157d-5p_L+1_1ss4AC-comp25631_c0, aau-miR160_L-4R+ 1-comp36993_c0_seq3, nta-miR6020b-comp234190_c0, PC-5p-192_7269-comp29967_c0, PC-5p-23845_39-comp28219_c0, mdm-miR828a_1ss22AT-comp24967_c0, mdm-miR858- comp15143_c0, mdm-miR858-comp24362_c0 and mdm-miR858-comp403340_c0 were verified by 5′RACE and transient expression system in tobacco.Conclusions: aly-miR157d-5p_L+1_1ss4AC, aau-miR160_L-4R+1, nta-miR6020b PC-5p-192_7269, PC-5p-23845_39, mdm-miR828a_1ss22AT and mdm-miR858 may play important roles in pitaya fruit coloration and betalain accumulation. Our findings provide insights into the roles of miRNAs and their target genes of regulatory functions involved in betalain biosynthesis of pitaya.
Integrated Single-Molecule Long-Read Sequencing and Illumina sequencing reveals the resistance mechanism in response to barley yellow dwarf virus-GAV in Psathyrostachys huashanica
Authors: Shen Chuan , Wei Caiyan , Li Jingyuan , Zhang Xudong , Wu Yunfeng
Published: February 2020

Background: Even though Psathyrostachys huashanica has great potential and promising prospects for resistance gene mining and molecular genetic breeding and a significant germplasm resource value, there is not yet a reference genome available. To date, most of the studies of P. huashanica have focused on the creation of translocation lines and addition lines as well as the development of molecular markers. Therefore, there is a great lack of research at the transcriptional level.Results: The full-length transcriptome of P. huashanica was sequenced using PacBio isoform sequencing (Iso-Seq) of a pooled RNA sample derived from roots, stems, buds and leaves in equal amounts to explore potential full-length transcript isoforms. A total of 112,596 unique transcript isoforms were obtained, with a total length of 114,957,868 base pairs (bp). Illumina sequencing reads were used to correct and trim PacBio isoforms. In total, 103,875 unigenes were annotated with at least one functional database. In addition, a mass of DEGs involved in BYDV-GAV defence were identified; most of these resistance related genes showed gene ontology (GO), and KEGG enrichment analysis showed that these DEGs were mostly involved in the response to plant-pathogen interaction, plant hormone signal transduction and the MAPK signalling pathway. Then, twenty resistance-related upregulated genes, including MAPKs, CRPKs, CDPKs, PR proteins, WRKYs and disease resistance proteins were selected for RNA-seq data validation using quantitative real-time PCR, which showed consistencies between these two sets of data. Besides, the results also indicated that a series of defense-related genes were induced during BYDV-GAV infection at different stages.Conclusions: The full-length transcriptome dataset should contribute to improved P. huashanica stress resistance gene utilisation, and will serve as a reference database for the analysis of transcript expression in P. huashanica. In addition, we identified genes in our transcriptome dataset involved in the regulation of the BYDV-GAV infection response in P. huashanica.
High-performance AlGaN double channel HEMTs with improved drain current density and high breakdown voltage
Authors: Zhang Yachao , Wang Zhizhe , Xu Shengrui , Zhang Jincheng , Hao Yue
Published: February 2020

In this work, for the first time, AlGaN double channel heterostructure is proposed and grown by metal organic chemical vapor deposition (MOCVD), and high-performance AlGaN double channel high electron mobility transistors (HEMTs) are fabricated and investigated. The implementation of double channel feature effectively improves the transport properties of AlGaN channel heterostructures. On one hand, the total two dimensional electron gas (2DEG) density is promoted due to the double potential wells along the vertical direction and the enhanced carrier confinement. On the other hand, the average 2DEG density in each channel is reduced, and the mobility is elevated resulted from the suppression of carrier-carrier scattering effect. As a result, the maximum drain current density (Imax) of AlGaN double channel HEMTs reaches 473 mA/mm with gate voltage of 0V. Moreover, the superior breakdown performance of the AlGaN double channel HEMTs is also demonstrated. These results not only show the great application potential of AlGaN double channel HEMTs in microwave power electronics, but also develops a new thinking for the studies of group III nitride based electronic devices.
Prevalence of anemia and iron deficiency anemia in Chinese pregnant women (IRON WOMEN): a national cross-sectional survey
Authors: Tan Jing , He Guolin , Qi Yana , Yang Hongmei , Xiong Yiquan , Liu Chunrong , Wang Wen , Zou Kang , Lee Andy H. , Liu Xinghui , Sun Xin
Published: February 2020

Background: The current evidence about anemia and iron deficiency anemia (IDA) during pregnancy remains elusive in China. The purpose of this study is to investigate the prevalence of anemia and IDA and their risk factors in Chinese pregnant women. Methods: A nationwide cross-sectional survey of pregnant women was conducted during their antenatal visits. Using a multi-stage sampling method, 24 hospitals from 16 provinces across China were selected. Structured questionnaires were administered to collect information from participants and to extract clinical data from electronic medical records. Mixed-effects logistic regression models were performed to determine the risk factors associated with anemia and IDA. Results: In total, 12,403 pregnant women were enrolled, including 1,018 (8.2%) at the first trimester, 3,487 (28.1%) at the second, and 7,898 (63.7%) at the third. Overall, 19.8% of women were diagnosed with anemia and 13.9% were diagnosed with IDA. The prevalence of anemia and IDA varied between regions and increased by gestational month, peaking at the eighth gestational month (24.0% for anemia and 17.8% for IDA). Pregnant women at advanced stage of gestation, non-local residents, multiple gestations, multiparity, pre-pregnancy underweight, and those experiencing severe nausea or vomiting during pregnancy, were associated with higher risks of anemia and IDA. Conclusions: The prevalence of anemia and IDA during pregnancy is high and varies across regions in China, particularly for women at their second and third trimesters. Interventions are needed to improve the condition during pregnancy. Keywords : anemia, iron deficiency anemia, prevalence, risk factors, cross-sectional survey
Communication of advance care planning decisions: a retrospective cohort study of documents in general practice
Authors: Panozzo Laura , Harvey Pam , Adams Meagan-Jane , O'Connor Dennis , Ward Bernadette
Published: February 2020

Background Doctors, particularly general practitioners, play a significant role in assisting patients to create advance care plans. These documents are important tools to ensure that the end-of-life care a patient receives is in alignment with their personal preferences. Despite this, little is known regarding the availability of these documents in hospitals. The aim of this study was to identify the proportion of people who died in hospital without an advance care plan and how many of these had advance care planning (ACP) documents in their general practice records. Methods A retrospective cohort study was conducted of patient hospital records in a large regional Australian hospital with a catchment population in excess of 300,000. The study sample was patients aged 75 years and over who died in the hospital between 1 January 2016 and 31 December 2017. The hospital records of these patients were examined to identify those which did not have a system alert for ACP documents on the file. Alerted ACP documents were limited to those legislated in the state of Victoria: advance care plan, Enduring Power of Attorney (Medical Treatment) or Enduring Power of Guardianship. Where no ACP document system alert was found in the hospital record, the corresponding general practice file was examined. Data were tested for normality and analysed using descriptive statistics. Results Of the 406 patients who died in hospital, 76.1% (309) did not have a system alert for any ACP document. 144 corresponding general practice records of the 309 hospital files without a system alert were examined. Of these, 14.6% included at least one ACP document, and four patients had an advance care plan that was not available in hospital. Conclusions Unless ACP documents are consistently communicated from general practice, advance care plans may go unreferenced during end-of-life care. It is important that both doctors and patients are supported to use connected electronic health records to ensure that documents are readily available to healthcare staff when they are required.