bluuebunny/crossref_metadata_2025_split huggingface dataset:
MicroRNA-550a-3-5p controls the brain metastasis of lung cancer by directly targeting YAP1
Authors: Wei Liang , Wang Guangxue , Yang Cheng , Zhang Yanfei , Chen Yiming , Zhong Chunlong , Li Qinchuan 
Published: September 2021

AbstractBackgroundThis study aimed to explore the potential regulatory mechanisms of brain metastasis and to identify novel underlying targets of lung cancer with brain metastasis.MethodsExosomes were isolated from the plasma of lung cancer patients with or without brain metastasis and low or high metastatic lung cancer cells, and small RNA from plasma-derived exosomes were sequenced. Differentially expressed miRNAs (DE-miRNAs) were identified. Human brain microvascular endothelial cells (HBMECs) were transfected with miR-550a-3-5p mimics or inhibitors and exosomes. Cell viability, migration, and apoptosis/cycle were determined using Cell Counting Kit-8 (CCK-8), Transwell, and flow cytometry, respectively. Western blotting was used to measure the expression of the associated proteins. Finally, a dual-luciferase reporter gene assay was performed to confirm the miR-550a-3-5p target.ResultsTransmission electron microscopy, NanoSight, and western blotting showed that exosomes were successfully isolated and cell-derived exosomes could be taken up by HBMECs. Sequencing identified 22 DE-miRNAs which were enriched in the MAPK, chemokine, PPAR, and Wnt signaling pathways. MiR-550a-3-5p was significantly enriched in brain metastatic exosomes. Cellular experiments showed that miR-550a-3-5p and exosome enrichment significantly inhibited cell viability and migration, promoted apoptosis, and regulated the cell cycle of HBMECs compared with the controls (P  <  0.05). Compared with the controls, high levels of both miR-550a-3-5p and exosomes markedly upregulated cleaved-PARP expression, but downregulated the expression of pRB, CDK6, YAP1, CTGF, and CYR61 (P  <  0.05). Finally, YAP1 was confirmed to bind directly to miR-550a-3-5p.ConclusionOur results indicate that miR-550a-3-5p and YAP1 may be novel potential targets for controlling brain metastasis.
Nanoceria seed priming enhanced salt tolerance in rapeseed through modulating ROS homeostasis and α-amylase activities
Authors: Khan Mohammad Nauman , Li Yanhui , Khan Zaid , Chen Linlin , Liu Jiahao , Hu Jin , Wu Honghong , Li Zhaohu 
Published: September 2021

Abstract
Background
Salinity is a big threat to agriculture by limiting crop production. Nanopriming (seed priming with nanomaterials) is an emerged approach to improve plant stress tolerance; however, our knowledge about the underlying mechanisms is limited.

Results
Herein, we used cerium oxide nanoparticles (nanoceria) to prime rapeseeds and investigated the possible mechanisms behind nanoceria improved rapeseed salt tolerance. We synthesized and characterized polyacrylic acid coated nanoceria (PNC, 8.5 ± 0.2 nm, −43.3 ± 6.3 mV) and monitored its distribution in different tissues of the seed during the imbibition period (1, 3, 8 h priming). Our results showed that compared with the no nanoparticle control, PNC nanopriming improved germination rate (12%) and biomass (41%) in rapeseeds (Brassica napus) under salt stress (200 mM NaCl). During the priming hours, PNC were located mostly in the seed coat, nevertheless the intensity of PNC in cotyledon and radicle was increased alongside with the increase of priming hours. During the priming hours, the amount of the absorbed water (52%, 14%, 12% increase at 1, 3, 8 h priming, respectively) and the activities of α-amylase were significantly higher (175%, 309%, 295% increase at 1, 3, 8 h priming, respectively) in PNC treatment than the control. PNC primed rapeseeds showed significantly lower content of MDA, H2O2, and •O2− in both shoot and root than the control under salt stress. Also, under salt stress, PNC nanopriming enabled significantly higher K+ retention (29%) and significantly lower Na+ accumulation (18.5%) and Na+/K+ ratio (37%) than the control.

Conclusions
Our results suggested that besides the more absorbed water and higher α-amylase activities, PNC nanopriming improves salt tolerance in rapeseeds through alleviating oxidative damage and maintaining Na+/K+ ratio. It adds more knowledge regarding the mechanisms underlying nanopriming improved plant salt tolerance.

Graphical abstract
“It is the One Thing that has Worked”: facilitators and barriers to switching to nicotine salt pod system e-cigarettes among African American and Latinx people who smoke: a content analysis
Authors: Pulvers Kim , Rice Myra , Ahluwalia Jasjit S. , Arnold Michael J. , Marez Crystal , Nollen Nicole L. 
Published: September 2021

Abstract
Background
Electronic cigarettes are a harm reduction strategy for individuals who smoke cigarettes who cannot or do not want to quit using FDA-approved cessation methods. Identifying perceived facilitators and barriers to switching among people who smoke cigarettes is critical to optimizing health impact. This is particularly important for the most dominant e-cigarette device, nicotine salt pod electronic cigarettes. We investigate the experience using pod electronic cigarettes among African American and Latinx individuals who smoke, the two largest racial/ethnic minority groups who experience significant health disparities.

Methods
From July 2018 to May 2019, adults who smoked cigarettes, age 21 + (N = 114; M age = 44.6, 59.6% male, 52.6% African American from Kansas City, 47.4% Latinx from San Diego) received JUUL-brand electronic cigarettes (referred to hereafter as JUUL) for 6 weeks and answered interview questions at week six. We inquired what they liked and disliked about using JUUL, what helped with switching and made switching difficult, future intentions for continued JUUL use, and how JUUL compared to past smoking reduction methods. Responses were coded into themes by independent raters. Theme frequencies were analyzed separately by race/ethnicity and week 6 use trajectory (exclusive JUUL use, dual JUUL and cigarette use, exclusive cigarette use).

Results
Clean/smell was the aspect of using JUUL most commonly liked (23%), followed by convenience (19%). Coughing/harshness was a more common barrier to switching for African American (44%) than Latinx (9%), and for continuing cigarette use (56%) than for those who exclusively switched or dually used JUUL and combustible cigarettes (15–21%). Most (78% African American; 90% Latinx) reported that the benefits of using JUUL outweighed barriers, and this varied by JUUL use trajectory: 94% exclusive switch, 86% dual use, and 42% continued cigarette use. The majority said they would continue using JUUL to replace cigarettes (83% African American; 94% Latinx) and that JUUL worked better than other methods to reduce cigarettes (72%).

Conclusion
African American and Latinx individuals who smoked experience using pod electronic cigarettes was generally positive. Understanding facilitators and impediments to switching to electronic cigarettes among racial/ethnic minority people who smoke can inform harm reduction interventions and reduce tobacco-related health disparities.
Trial Registration ClinicalTrials.gov Identifier: NCT03511001 posted April 27, 2018.
Effects of differential measurement error in self-reported diet in longitudinal lifestyle intervention studies
Authors: Aaby David , Siddique Juned 
Published: September 2021

Abstract
Background
Lifestyle intervention studies often use self-reported measures of diet as an outcome variable to measure changes in dietary intake. The presence of measurement error in self-reported diet due to participant failure to accurately report their diet is well known. Less familiar to researchers is differential measurement error, where the nature of measurement error differs by treatment group and/or time. Differential measurement error is often present in intervention studies and can result in biased estimates of the treatment effect and reduced power to detect treatment effects. Investigators need to be aware of the impact of differential measurement error when designing intervention studies that use self-reported measures.

Methods
We use simulation to assess the consequences of differential measurement error on the ability to estimate treatment effects in a two-arm randomized trial with two time points. We simulate data under a variety of scenarios, focusing on how different factors affect power to detect a treatment effect, bias of the treatment effect, and coverage of the 95% confidence interval of the treatment effect. Simulations use realistic scenarios based on data from the Trials of Hypertension Prevention Study. Simulated sample sizes ranged from 110-380 per group.

Results
Realistic differential measurement error seen in lifestyle intervention studies can require an increased sample size to achieve 80% power to detect a treatment effect and may result in a biased estimate of the treatment effect.

Conclusions
Investigators designing intervention studies that use self-reported measures should take differential measurement error into account by increasing their sample size, incorporating an internal validation study, and/or identifying statistical methods to correct for differential measurement error.
Physical activity in out of school hours care: an observational study
Authors: Crowe Ruth K. , Probst Yasmine C. , Stanley Rebecca M. , Ryan Sarah T. , Weaver R. Glenn , Beets Michael W. , Norman Jennifer A. , Furber Susan E. , Vuong Cecilia , Hammersley Megan L. , Wardle Karen , Franco Lisa , Davies Marc , Innes-Hughes Christine , Okely Anthony D. 
Published: September 2021

Abstract
Background
Opportunities for physical activity within out of school
hours care (OSHC) are not well documented in Australia. This study explored factors associated with children (5–12 years) meeting 30 min of moderate to vigorous physical activity (MVPA) while attending OSHC in the afternoon period.

Methods
A cross-sectional study, conducted in 89 OSHC services in New South Wales, Australia, serving 4,408 children. Each service was visited twice between 2018–2019. Physical activity promotion practices were captured via short interviews and System for Observing Staff Promotion of Physical Activity and Nutrition (SOSPAN). Physical activity spaces was measured (m2) and physical activity of 3,614 child days (42% girls), were collected using Acti-Graph accelerometers. Association between program practices and children accumulation of MVPA was tested using mixed effects logistic regression, adjusted by OSHC service and child.

Results
Twenty-six percent of children (n = 925) accumulated 30 min or more of MVPA. Factors associated with children reaching MVPA recommendations included: services scheduling greater amounts of child-led free play, both 30–59 min (OR 2.6, 95%CI 1.70, 3.98) and ≥ 60 min (OR 6.4, 95%CI 3.90, 10.49); opportunities for staff-led organised play of ≥ 30 min (OR 2.3, 95%CI 1.47, 3.83); and active games that engaged the majority of children (OR 1.7, 95%CI 1.11, 2.61). Children were less likely to meet MVPA recommendations if services played games with elimination components (OR 0.56, 95%CI 0.37, 0.86).

Conclusion
Improvements to service-level physical activity promotion practices, specifically the type of physical activity scheduled and the structure of games, may be an effective strategy to increase MVPA of children attending OSHC afterschool in NSW, Australia.
IL-18 binding protein suppresses IL-17-induced osteoclastogenesis and rectifies type 17 helper T cell / regulatory T cell imbalance in rheumatoid arthritis
Authors: Min Hong Ki , Kim Sehee , Lee Ji-Yeon , Kim Kyoung-Woon , Lee Sang-Heon , Kim Hae-Rim 
Published: September 2021

Abstract
Background
Patients with rheumatoid arthritis (RA) have increased levels of interleukin-18 (IL-18) and decreased levels of IL-18 binding protein (IL-18BP) in the serum and synovial fluid (SF) compared to those in patients with osteoarthritis (OA) or in healthy controls. In this study, we evaluated the effects of IL-18BP on osteoclastogenesis and T cell differentiation in RA in vitro.

Methods
Serum and SF of patients with RA and OA were collected to compare IL-18 and IL-18BP levels by the enzyme-linked immunosorbent assay. Peripheral blood mononuclear cells (PBMCs) and SF mononuclear cells (SFMCs) of RA patients were cultured under type 17 helper T cell (Th17) polarisation conditions with or without IL-18BP. In addition, PBMCs were cultured in the presence of receptor activator of nuclear factor kappa-Β ligand (RANKL) or IL-17A with or without IL-18BP, and tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative polymerase chain reaction for expression levels of osteoclast-related genes were performed.

Results
IL-18 levels were higher in the serum and SF of patients with RA, whereas IL-18BP was lower in the SF of patients with RA than in the control group. Treatment of patients’ PBMCs with IL-18BP decreased the differentiation of CD4+ IL-17A+ and CD4+ RANKL+ T cells, whereas the differentiation of CD4+CD25highFOXP3+ T cell population increased in a dose-dependent manner. These changes in CD4+ T cell differentiation were also observed in the SFMCs of patients with RA. The levels IL-17A and soluble RANKL in the culture medium were significantly decreased by IL-18BP. IL-18BP administration decreased TRAP+ cell counts in a dose-dependent manner on the background of stimulation with RANKL-and IL-17A. In addition, expression levels of TRAP, NFATC1, CTSK, and TNFRSF11A (RANK) genes were lower in the IL-18BP treated cells.

Conclusion
We showed that IL-18BP can rectify the Th17/Treg imbalance and decrease IL-17-induced osteoclastogenesis in PBMCs from patients with RA. Therefore, IL-18BP may have therapeutic potential for RA treatment.
Infections and antibiotics during fetal life and childhood and their relationship to juvenile idiopathic arthritis: a prospective cohort study
Authors: Kindgren Erik , Ludvigsson Johnny 
Published: September 2021

Abstract
Background
The aetiology of juvenile idiopathic arthritis (JIA) is poorly understood. It has been shown that use of antibiotics is associated with JIA. However, whether the association is due to increased occurrence of infection in these individuals is unknown. The purpose of this investigation was to measure the association between number of infections and use of antibiotics during childhood with development of JIA.

Methods
In ABIS (All Babies in Southeast Sweden) a population-based prospective birth cohort of 17,055 children, data were collected on infections and antibiotic exposure during pregnancy and childhood. 102 individuals with JIA were identified. Multivariable logistic regression analyses were performed, adjusting for confounding factors.

Results
Exposure to antibiotics during the periods 1–12 months, 1–3 years and 5–8 years was significantly associated with increased risk for JIA. The odds of developing JIA were three times higher in those exposed to antibiotics during the first 3 years of life compared with those not exposed (aOR 3.17; 95% CI 1.11–9.03, p = 0.031), and more than twice as high in those exposed to antibiotics during the first 5 years of life compared with those not exposed (aOR 2.18; 95% CI 1.36–3.50, p = 0.001). The odds of developing JIA were 78% higher in those exposed to antibiotics during the first 8 years of life compared with those not exposed (aOR 1.78; 95% CI 1.15–2.73, p = 0.009). Occurrence of infection during fetal life or childhood showed no significant association with the risk of developing JIA, after confounder adjustment.
The cumulative number of courses of antibiotics was significantly higher during childhood for the individuals who developed JIA (p < 0.001). Penicillins were more frequently used than non-penicillins, but both had an equal effect on the risk of developing JIA.

Conclusions
Exposure to antibiotics early in life is associated with later onset of JIA in a large birth cohort from the general population. The relationship was dose dependent. These results suggest that further, more restrictive, antibiotic policies during the first years of life would be advisable.
MD2 contributes to the pathogenesis of perioperative neurocognitive disorder via the regulation of α5GABAA receptors in aged mice
Authors: Zuo Wenqiang , Zhao Jianshuai , Zhang Jinming , Fang Zongping , Deng Jiao , Fan Ze , Guo Yaru , Han Jing , Hou Wugang , Dong Hailong , Xu Feifei , Xiong Lize 
Published: September 2021

Abstract
Background
Perioperative neurocognitive disorder (PND) is a long-term postoperative complication in elderly surgical patients. The underlying mechanism of PND is unclear, and no effective therapies are currently available. It is believed that neuroinflammation plays an important role in triggering PND. The secreted glycoprotein myeloid differentiation factor 2 (MD2) functions as an activator of the Toll-like receptor 4 (TLR4) inflammatory pathway, and α5GABAA receptors (α5GABAARs) are known to play a key role in regulating inflammation-induced cognitive deficits. Thus, in this study, we aimed to investigate the role of MD2 in PND and determine whether α5GABAARs are involved in the function of MD2.

Methods
Eighteen-month-old C57BL/6J mice were subjected to laparotomy under isoflurane anesthesia to induce PND. The Barnes maze was used to assess spatial reference learning and memory, and the expression of hippocampal MD2 was assayed by western blotting. MD2 expression was downregulated by bilateral injection of AAV-shMD2 into the hippocampus or tail vein injection of the synthetic MD2 degrading peptide Tat-CIRP-CMA (TCM) to evaluate the effect of MD2. Primary cultured neurons from brain tissue block containing cortices and hippocampus were treated with Tat-CIRP-CMA to investigate whether downregulating MD2 expression affected the expression of α5GABAARs. Electrophysiology was employed to measure tonic currents. For α5GABAARs intervention experiments, L-655,708 and L-838,417 were used to inhibit or activate α5GABAARs, respectively.

Results
Surgery under inhaled isoflurane anesthesia induced cognitive impairments and elevated the expression of MD2 in the hippocampus. Downregulation of MD2 expression by AAV-shMD2 or Tat-CIRP-CMA improved the spatial reference learning and memory in animals subjected to anesthesia and surgery. Furthermore, Tat-CIRP-CMA treatment decreased the expression of membrane α5GABAARs and tonic currents in CA1 pyramidal neurons in the hippocampus. Inhibition of α5GABAARs by L-655,708 alleviated cognitive impairments after anesthesia and surgery. More importantly, activation of α5GABAARs by L-838,417 abrogated the protective effects of Tat-CIRP-CMA against anesthesia and surgery-induced spatial reference learning and memory deficits.

Conclusions
MD2 contributes to the occurrence of PND by regulating α5GABAARs in aged mice, and Tat-CIRP-CMA is a promising neuroprotectant against PND.
1α,25-dihydroxyvitamin D3 protects retinal ganglion cells in glaucomatous mice
Authors: Lazzara Francesca , Amato Rosario , Platania Chiara Bianca Maria , Conti Federica , Chou Tsung-Han , Porciatti Vittorio , Drago Filippo , Bucolo Claudio 
Published: September 2021

Abstract
Background
Glaucoma is an optic neuropathy characterized by loss of function and death of retinal ganglion cells (RGCs), leading to irreversible vision loss. Neuroinflammation is recognized as one of the causes of glaucoma, and currently no treatment is addressing this mechanism. We aimed to investigate the anti-inflammatory and neuroprotective effects of 1,25(OH)2D3 (1α,25-dihydroxyvitamin D3, calcitriol), in a genetic model of age-related glaucomatous neurodegeneration (DBA/2J mice).

Methods
DBA/2J mice were randomized to 1,25(OH)2D3 or vehicle treatment groups. Pattern electroretinogram, flash electroretinogram, and intraocular pressure were recorded weekly. Immunostaining for RBPMS, Iba-1, and GFAP was carried out on retinal flat mounts to assess retinal ganglion cell density and quantify microglial and astrocyte activation, respectively. Molecular biology analyses were carried out to evaluate retinal expression of pro-inflammatory cytokines, pNFκB-p65, and neuroprotective factors. Investigators that analysed the data were blind to experimental groups, which were unveiled after graph design and statistical analysis, that were carried out with GraphPad Prism. Several statistical tests and approaches were used: the generalized estimated equations (GEE) analysis, t-test, and one-way ANOVA.

Results
DBA/2J mice treated with 1,25(OH)2D3 for 5 weeks showed improved PERG and FERG amplitudes and reduced RGCs death, compared to vehicle-treated age-matched controls. 1,25(OH)2D3 treatment decreased microglial and astrocyte activation, as well as expression of inflammatory cytokines and pNF-κB-p65 (p < 0.05). Moreover, 1,25(OH)2D3-treated DBA/2J mice displayed increased mRNA levels of neuroprotective factors (p < 0.05), such as BDNF.

Conclusions
1,25(OH)2D3 protected RGCs preserving retinal function, reducing inflammatory cytokines, and increasing expression of neuroprotective factors. Therefore, 1,25(OH)2D3 could attenuate the retinal damage in glaucomatous patients and warrants further clinical evaluation for the treatment of optic neuropathies.
TLR7 is expressed by support cells, but not sensory neurons, in ganglia
Authors: Proskocil Becky J. , Wai Karol , Lebold Katherine M. , Norgard Mason A. , Michaelis Katherine A. , De La Torre Ubaldo , Cook Madeline , Marks Daniel L. , Fryer Allison D. , Jacoby David B. , Drake Matthew G. 
Published: September 2021

Abstract
Background
Toll-like receptor 7 (TLR7) is an innate immune receptor that detects viral single-stranded RNA and triggers the production of proinflammatory cytokines and type 1 interferons in immune cells. TLR7 agonists also modulate sensory nerve function by increasing neuronal excitability, although studies are conflicting whether sensory neurons specifically express TLR7. This uncertainty has confounded the development of a mechanistic understanding of TLR7 function in nervous tissues.

Methods
TLR7 expression was tested using in situ hybridization with species-specific RNA probes in vagal and dorsal root sensory ganglia in wild-type and TLR7 knockout (KO) mice and in guinea pigs. Since TLR7 KO mice were generated by inserting an Escherichia coli lacZ gene in exon 3 of the mouse TLR7 gene, wild-type and TLR7 (KO) mouse vagal ganglia were also labeled for lacZ. In situ labeling was compared to immunohistochemistry using TLR7 antibody probes. The effects of influenza A infection on TLR7 expression in sensory ganglia and in the spleen were also assessed.

Results
In situ probes detected TLR7 in the spleen and in small support cells adjacent to sensory neurons in the dorsal root and vagal ganglia in wild-type mice and guinea pigs, but not in TLR7 KO mice. TLR7 was co-expressed with the macrophage marker Iba1 and the satellite glial cell marker GFAP, but not with the neuronal marker PGP9.5, indicating that TLR7 is not expressed by sensory nerves in either vagal or dorsal root ganglia in mice or guinea pigs. In contrast, TLR7 antibodies labeled small- and medium-sized neurons in wild-type and TLR7 KO mice in a TLR7-independent manner. Influenza A infection caused significant weight loss and upregulation of TLR7 in the spleens, but not in vagal ganglia, in mice.

Conclusion
TLR7 is expressed by macrophages and satellite glial cells, but not neurons in sensory ganglia suggesting TLR7’s neuromodulatory effects are mediated indirectly via activation of neuronally-associated support cells, not through activation of neurons directly. Our data also suggest TLR7’s primary role in neuronal tissues is not related to antiviral immunity.