bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR-4448 is involved in deltamethrin resistance by targeting CYP4H31 in Culex pipiens pallens
Authors: Li Xixi , Hu Shengli , Yin Haitao , Zhang Hongbo , Zhou Dan , Sun Yan , Ma Lei , Shen Bo , Zhu Changliang 
Published: March 2021

Abstract
Background
Culex pipiens (Cx. pipiens) complex, which acts as a vector of viruses and is widespread and abundant worldwide, including West Nile virus, Japanese encephalitis virus, and Sindbis virus, can cause serious vector-borne diseases affecting human health. Unfortunately, mosquitoes have developed deltamethrin resistance because of its long-term overuse, representing a major challenge to mosquito control. Understanding the molecular regulatory mechanisms of resistance is vital to control mosquitoes. MicroRNAs (miRNAs) are short non-coding RNAs that have been demonstrated to be important regulators of gene expression across a wide variety of organisms, which might function in mosquito deltamethrin resistance. In the present study, we aimed to investigate the regulatory functions of miR-4448 and CYP4H31 in the formation of insecticidal resistance in mosquito Culex pipiens pallens.

Methods
We used quantitative real-time reverse transcription PCR to measure miR-4448 and CYP4H31 (encoding a cytochrome P450) expression levels. The regulatory functions of miR-4448 and CYP4H31 were assessed using dual-luciferase reporter assays. Then, oral feeding, RNA interference, and the American Centers for Disease Control and Prevention bottle bioassay were used to determine miR-4448’s association with deltamethrin resistance by targeting CYP4H31in vivo. Cell Counting Kit-8 (CCK-8) was also used to detect the viability of pIB/V5-His-CYP4H31-transfected C6/36 cells after deltamethrin treatment in vitro.

Results
MiR-4448 was downregulated in the deltamethrin-resistant strain (DR strain), whereas CYP4H31 was downregulated in deltamethrin-susceptible strain. CYP4H31 expression was downregulated by miR-4448 recognizing and binding to its 3′ untranslated region. Functional verification experiments showed that miR-4448 overexpression resulted in lower expression of CYP4H31. The mortality of miR-4448 mimic-injected DR strain mosquitoes was higher than that of the controls. CCK-8 assays showed that CYP4H31 decreased cellular resistance to deltamethrin in vitro and the mortality of the DR strain increased when CYP4H31 was knocked down in vivo.

Conclusions
In mosquitoes, miR-4448 participates in deltamethrin resistance by targeting CYP4H31. The results of the present study increase our understanding of deltamethrin resistance mechanisms.

Graphical Abstract
Positive feedback regulation between USP15 and ERK2 inhibits osteoarthritis progression through TGF-β/SMAD2 signaling
Authors: Wang Wenjuan , Zhu Yanhui , Sun Zhenyu , Jin Chen , Wang Xiang 
Published: March 2021

Abstract
Background
The transforming growth factor-β (TGF-β) signaling pathway plays an essential role in maintaining homeostasis in joints affected by osteoarthritis (OA). However, the specific mechanism of non-SMAD and classical SMAD signaling interactions is still unclear, which needs to be further explored.

Methods
In ATDC5 cells, USP15 overexpression and knockout were performed using the transfected lentivirus USP15 and Crispr/Cas9. Western blotting and immunofluorescence staining were used to test p-SMAD2 and cartilage phenotype-related molecular markers. In rat OA models, immunohistochemistry, hematoxylin and eosin (HE)/Safranin-O fast green staining, and histology were used to examine the regulatory activity of USP15 in TGF-β/SMAD2 signaling and the cartilage phenotype. Then, ERK2 overexpression and knockout were performed. The expressions of USP15, p-SMAD2, and the cartilage phenotype were evaluated in vitro and in vivo. To address whether USP15 is required for ERK2 and TGF-β/SMAD2 signaling, we performed rescue experiments in vitro and in vivo. Immunoprecipitation and deubiquitination assays were used to examine whether USP15 could bind to ERK2 and affect the deubiquitination of ERK2. Finally, whether USP15 regulates the level of p-ERK1/2 was evaluated by western blotting, immunofluorescence staining, and immunohistochemistry in vitro and in vivo.

Results
Our results indicated that USP15 stimulated TGF-β/SMAD2 signaling and the cartilage phenotype. Moreover, ERK2 required USP15 to influence TGF-β/SMAD2 signaling for regulating the cartilage phenotype in vivo and in vitro. And USP15 can form a complex with ERK2 to regulate ubiquitination of ERK2. Interestingly, USP15 did not regulate the stability of ERK2 but increased the level of p-ERK1/2 to further enhance the TGF-β/SMAD2 signaling pathway.

Conclusions
Taken together, our study revealed positive feedback regulation between USP15 and ERK2, which played a critical role in TGF-β/SMAD2 signaling to inhibit OA progression. Therefore, this specific mechanism can guide the clinical treatment of OA.
Prevalence of thinness and its effect on height velocity in schoolchildren
Authors: Narchi Hassib , Alblooshi Afaf , Altunaiji Maisoon , Alali Nawal , Alshehhi Latifa , Alshehhi Huda , Almazrouei Asma , Alsuwaidi Ahmed R. , Souid Abdul-Kader 
Published: March 2021

AbstractObjectiveIn contrast to childhood obesity, studies involving thin children are much fewer, especially in developed countries. Furthermore, most reports do not address the impact of childhood thinness on height velocity. This study investigated the prevalence of thinness and its effect on height velocity in schoolchildren in the United Arab Emirates (UAE). Weight and height were measured in 29,410 schoolchildren (50.5% females), as part of the health assessment (academic year 2014–2015). The body mass index (BMI) was classified as normal, thinness, overweight, or obese using cutoffs established by the International Obesity Task Force (IOTF), World Health Organization, and Centers for Disease Control.ResultsThe median age was 10.2 years (range, 3–19). Using the IOTF scale, one-quarter of the children aged 4–6 years and one-third of the children aged 7–9 years were thin (BMI ≤ 18.5 kg/m2). Thinness was less prevalent (8–10%) in adolescents. Group peak height velocity was delayed 1–3 years in thin children and was higher in children with excess body fat. In conclusion thinness was the highest (25–33%) in children aged 4–9 years of age and their peak height velocity was delayed 1–3 years when compared to the other children.
Epigenetic age acceleration is associated with cardiometabolic risk factors and clinical cardiovascular disease risk scores in African Americans
Authors: Ammous Farah , Zhao Wei , Ratliff Scott M. , Mosley Thomas H. , Bielak Lawrence F. , Zhou Xiang , Peyser Patricia A. , Kardia Sharon L. R. , Smith Jennifer A. 
Published: March 2021

AbstractBackgroundCardiovascular disease (CVD) is the leading cause of mortality among US adults. African Americans have higher burden of CVD morbidity and mortality compared to any other racial group. Identifying biomarkers for clinical risk prediction of CVD offers an opportunity for precision prevention and earlier intervention.ResultsUsing linear mixed models, we investigated the cross-sectional association between four measures of epigenetic age acceleration (intrinsic (IEAA), extrinsic (EEAA), PhenoAge (PhenoAA), and GrimAge (GrimAA)) and ten cardiometabolic markers of hypertension, insulin resistance, and dyslipidemia in 1,100 primarily hypertensive African Americans from sibships in the Genetic Epidemiology Network of Arteriopathy (GENOA). We then assessed the association between epigenetic age acceleration and time to self-reported incident CVD using frailty hazard models and investigated CVD risk prediction improvement compared to models with clinical risk scores (Framingham risk score (FRS) and the atherosclerotic cardiovascular disease (ASCVD) risk equation). After adjusting for sex and chronological age, increased epigenetic age acceleration was associated with higher systolic blood pressure (IEAA), higher pulse pressure (EEAA and GrimAA), higher fasting glucose (PhenoAA and GrimAA), higher fasting insulin (EEAA), lower low density cholesterol (GrimAA), and higher triglycerides (GrimAA). A five-year increase in GrimAA was associated with CVD incidence with a hazard ratio of 1.54 (95% CI 1.22–2.01) and remained significant after adjusting for CVD risk factors. The addition of GrimAA to risk score models improved model fit using likelihood ratio tests (P = 0.013 for FRS andP = 0.008 for ASCVD), but did not improve C statistics (P > 0.05). Net reclassification index (NRI) showed small but significant improvement in reassignment of risk categories with the addition of GrimAA to FRS (NRI: 0.055, 95% CI 0.040–0.071) and the ASCVD equation (NRI: 0.029, 95% CI 0.006–0.064).ConclusionsEpigenetic age acceleration measures are associated with traditional CVD risk factors in an African-American cohort with a high prevalence of hypertension. GrimAA was associated with CVD incidence and slightly improved prediction of CVD events over clinical risk scores.
Additive interaction of mid- to late-life depression and cerebrovascular disease on the risk of dementia: a nationwide population-based cohort study
Authors: Jang Yoo Jin , Kang Cinoo , Myung Woojae , Lim Shinn-Won , Moon Young Kyung , Kim Ho , Kim Doh Kwan 
Published: March 2021

Abstract
Background
Dementia is a progressive neurocognitive disease with a substantial social burden. No apparent breakthroughs in treatment options have emerged so far; thus, disease prevention is essential for at-risk populations. Depression and cerebrovascular disease (CVD) are independent risk factors for dementia, but no studies have examined their interaction effect on dementia risk. This study aimed to identify the association of depression and CVD with the risk of dementia and evaluate whether dementia risk among patients with comorbid depression and CVD is higher than the sum of the individual risk due to each condition.

Methods
A population-based cohort study was conducted to analyze the Korean National Health Insurance Service-National Sample Cohort data of all individuals over 50 years of age. Individuals who had not been diagnosed with dementia at baseline were included and followed up from January 1, 2005, to December 31, 2013. A time-varying Cox proportional hazard regression model adjusted for potential confounding factors was used for the analysis. The interaction between depression and CVD was estimated based on the attributable proportion (AP), relative excess risk due to interaction (RERI), synergy index (SI), and multiplicative-scale interaction.

Results
A total of 242,237 participants were included in the analytical sample, of which 12,735 (5.3%) developed dementia. Compared to that for participants without depression or CVD, the adjusted hazard ratio for the incidence of dementia for those with depression alone was 2.35 (95% confidence interval [CI] 2.21–2.49), CVD alone was 3.25 (95% CI 3.11–3.39), and comorbid depression and CVD was 5.02 (95% CI 4.66–5.42). The additive interaction between depression and CVD was statistically significant (AP—0.08, 95% CI 0.01–0.16; RERI—0.42, 95% CI 0.03–0.82; SI—1.12, 95% CI 1.01–1.24). The multiplicative interaction was significant too, but the effect was negative (0.66, 95% CI 0.60–0.73).

Conclusions
In this population-based nationwide cohort with long-term follow-up, depression and CVD were associated with an increased risk of dementia, and their coexistence additively increased dementia risk more than the sum of the individual risks.
Fibrolamellar hepatocellular carcinoma treated with atezolizumab and bevacizumab: two case reports
Authors: AL Zahrani Ali , Alfakeeh Ali 
Published: March 2021

Abstract
Background
Fibrolamellar hepatocellular carcinoma is a unique tumor of the liver that differs from the classical hepatocellular carcinoma in diagnosis, behavior, and possibly treatment. There is usually absent underlying liver disease, and it usually occurs in young patients. The survival outcomes in localized fibrolamellar hepatocellular carcinoma are perhaps better than in classical hepatocellular carcinoma if treated early and radically. On the other hand, the prognosis remains poor for locally advanced and metastatic fibrolamellar hepatocellular carcinoma. Many reports suggested a limited benefit from systemic chemotherapy. Sorafenib also did not show major effects on fibrolamellar hepatocellular carcinoma. Given the rarity of fibrolamellar hepatocellular carcinoma, lack of large studies, and absence of standard treatment, the treatment decisions rely on case reports, previously reported cases series, and expert opinions. Recent studies have shown promising effects of immunotherapy with checkpoint inhibitors in the first- and second-line therapy of hepatocellular carcinoma. Atezolizumab with bevacizumab regimen has been approved recently as a first-line treatment for classical hepatocellular carcinoma. Currently, there are no reports yet on the use of atezolizumab with bevacizumab for fibrolamellar hepatocellular carcinoma.

Case report
In this article, we present two Arabic patients with advanced fibrolamellar hepatocellular carcinoma who received atezolizumab and bevacizumab combinations but did not show any clinical benefits.

Conclusion
While atezolizumab and bevacizumab combinations had shown benefits in classical hepatocellular carcinoma, the current data showed a lack of benefit and tumor response in fibrolamellar hepatocellular carcinoma.
Gene engineered mesenchymal stem cells: greater transgene expression and efficacy with minicircle vs. plasmid DNA vectors in a mouse model of acute lung injury
Authors: Florian Maria , Wang Jia-Pey , Deng Yupu , Souza-Moreira Luciana , Stewart Duncan J. , Mei Shirley H. J. 
Published: March 2021

Abstract
Background
Acute lung injury (ALI) and in its severe form, acute respiratory distress syndrome (ARDS), results in increased pulmonary vascular inflammation and permeability and is a major cause of mortality in many critically ill patients. Although cell-based therapies have shown promise in experimental ALI, strategies are needed to enhance the potency of mesenchymal stem cells (MSCs) to develop more effective treatments. Genetic modification of MSCs has been demonstrated to significantly improve the therapeutic benefits of these cells; however, the optimal vector for gene transfer is not clear. Given the acute nature of ARDS, transient transfection is desirable to avoid off-target effects of long-term transgene expression, as well as the potential adverse consequences of genomic integration.

Methods
Here, we explored whether a minicircle DNA (MC) vector containing human angiopoietin 1 (MC-ANGPT1) can provide a more effective platform for gene-enhanced MSC therapy of ALI/ARDS.

Results
At 24 h after transfection, nuclear-targeted electroporation using an MC-ANGPT1 vector resulted in a 3.7-fold greater increase in human ANGPT1 protein in MSC conditioned media compared to the use of a plasmid ANGPT1 (pANGPT1) vector (2048 ± 567 pg/mL vs. 552.1 ± 33.5 pg/mL). In the lipopolysaccharide (LPS)-induced ALI model, administration of pANGPT1 transfected MSCs significantly reduced bronchoalveolar lavage (BAL) neutrophil counts by 57%, while MC-ANGPT1 transfected MSCs reduced it by 71% (p < 0.001) by Holm-Sidak’s multiple comparison test. Moreover, compared to pANGPT1, the MC-ANGPT1 transfected MSCs significantly reduced pulmonary inflammation, as observed in decreased levels of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-2 (MIP-2). pANGPT1-transfected MSCs significantly reduced BAL albumin levels by 71%, while MC-ANGPT1-transfected MSCs reduced it by 85%.

Conclusions
Overall, using a minicircle vector, we demonstrated an efficient and sustained expression of the ANGPT1 transgene in MSCs and enhanced the therapeutic effect on the ALI model compared to plasmid. These results support the potential benefits of MC-ANGPT1 gene enhancement of MSC therapy to treat ARDS.
Chronic ethanol vapor exposure potentiates cardiovascular responses to acute stress in male but not in female rats
Authors: Bianchi Paula C. , Gomes-de-Souza Lucas , Costa-Ferreira Willian , Palombo Paola , Carneiro de Oliveira Paulo E. , Engi Sheila A. , Leão Rodrigo M. , Planeta Cleopatra S. , Crestani Carlos C. , Cruz Fabio C. 
Published: March 2021

Abstract
Background
Ethanol use is related to a wide variety of negative health outcomes, including cardiovascular diseases. Stress is also involved in numerous pathologies, such as cardiovascular diseases and psychiatric disorders. Sexual dimorphism is an important factor affecting cardiovascular response and has been proposed as a potential risk factor for sex-specific health problems in humans. Here, we evaluated the effect of prolonged ethanol vapor inhalation on arterial pressure, heart rate, and tail skin temperature responses to acute restraint stress, investigating differences between male and female rats.

Methods
We exposed male and female Long-Evans rats to ethanol vapor for 14 h, followed by ethanol withdrawal for 10 h, for 30 consecutive days, or to room air (control groups). The animals underwent surgical implantation of a cannula into the femoral artery for assessment of arterial pressure and heart rate values. The tail skin temperature was measured as an indirect measurement of sympathetic vasomotor response.

Results
Chronic ethanol vapor inhalation reduced basal heart rate in both female and male rats. Sex-related difference was observed in the decrease of tail cutaneous temperature evoked by stress, but not in the pressor and tachycardiac responses. Furthermore, prolonged ethanol inhalation enhanced the blood pressure and heart rate increase caused by acute restraint stress in male, but not in female rats. However, no effect of chronic ethanol vapor was observed in the tail cutaneous temperature response to restraint in either sex.

Conclusion
Chronic ethanol vapor exposure increased the cardiovascular reactivity to stress in male, but not in female rats.
Exploration and validation of related hub gene expression during SARS-CoV-2 infection of human bronchial organoids
Authors: Fang Ke-Ying , Cao Wen-Chao , Xie Tian-Ao , Lv Jie , Chen Jia-Xin , Cao Xun-Jie , Li Zhong-Wei , Deng Shu-Ting , Guo Xu-Guang 
Published: March 2021

Abstract
Background
In the novel coronavirus pandemic, the high infection rate and high mortality have seriously affected people’s health and social order. To better explore the infection mechanism and treatment, the three-dimensional structure of human bronchus has been employed in a better in-depth study on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods
We downloaded a separate microarray from the Integrated Gene Expression System (GEO) on a human bronchial organoids sample to identify differentially expressed genes (DEGS) and analyzed it with R software. After processing with R software, Gene Ontology (GO) and Kyoto PBMCs of Genes and Genomes (KEGG) were analyzed, while a protein–protein interaction (PPI) network was constructed to show the interactions and influence relationships between these differential genes. Finally, the selected highly connected genes, which are called hub genes, were verified in CytoHubba plug-in.

Results
In this study, a total of 966 differentially expressed genes, including 490 upregulated genes and 476 downregulated genes were used. Analysis of GO and KEGG revealed that these differentially expressed genes were significantly enriched in pathways related to immune response and cytokines. We construct protein-protein interaction network and identify 10 hub genes, including IL6, MMP9, IL1B, CXCL8, ICAM1, FGF2, EGF, CXCL10, CCL2, CCL5, CXCL1, and FN1. Finally, with the help of GSE150728, we verified that CXCl1, CXCL8, CXCL10, CCL5, EGF differently expressed before and after SARS-CoV-2 infection in clinical patients.

Conclusions
In this study, we used mRNA expression data from GSE150819 to preliminarily confirm the feasibility of hBO as an in vitro model to further study the pathogenesis and potential treatment of COVID-19. Moreover, based on the mRNA differentiated expression of this model, we found that CXCL8, CXCL10, and EGF are hub genes in the process of SARS-COV-2 infection, and we emphasized their key roles in SARS-CoV-2 infection. And we also suggested that further study of these hub genes may be beneficial to treatment, prognostic prediction of COVID-19.
Improving oxidation stability of 2D MXenes: synthesis, storage media, and conditions
Authors: Iqbal Aamir , Hong Junpyo , Ko Tae Yun , Koo Chong Min 
Published: March 2021

AbstractUnderstanding and preventing oxidative degradation of MXene suspensions is essential for fostering fundamental academic studies and facilitating widespread industrial applications. Owing to their outstanding electrical, electrochemical, optoelectronic, and mechanical properties, MXenes, an emerging class of two-dimensional (2D) nanomaterials, show promising state-of-the-art performances in various applications including electromagnetic interference (EMI) shielding, terahertz shielding, electrochemical energy storage, triboelectric nanogenerators, thermal heaters, light-emitting diodes (LEDs), optoelectronics, and sensors. However, MXene synthesis using harsh chemical etching causes many defects or vacancies on the surface of the synthesized MXene flakes. Defective sites are vulnerable to oxidative degradation reactions with water and/or oxygen, which deteriorate the intrinsic properties of MXenes. In this review, we demonstrate the nature of oxidative degradation of MXenes and highlight the recent advancements in controlling the oxidation kinetics of MXenes with several promising strategic approaches, including careful control of the quality of the parent MAX phase, chemical etching conditions, defect passivation, dispersion medium, storage conditions, and polymer composites.
Immediate and legacy effects of snow exclusion on soil fungal diversity and community composition
Authors: Zhang Li , Ren Yuzhi , Yang Kaijun , Li Zhijie , Tan Bo , Liu Yang , Li Han , You Chengming , Liu Sining , Wang Lixia , Yin Rui , Zhang Jian , Xu Zhenfeng 
Published: March 2021

Abstract
Background
Soil fungi play crucial roles in ecosystem functions. However, how snow cover change associated with winter warming affects soil fungal communities remains unclear in the Tibetan forest.

Methods
We conducted a snow manipulation experiment to explore immediate and legacy effects of snow exclusion on soil fungal community diversity and composition in a spruce forest on the eastern Tibetan Plateau. Soil fungal communities were performed by the high throughput sequencing of gene-fragments.

Results
Ascomycota and Basidiomycota were the two dominant fungal phyla and Archaeorhizomyces, Aspergillus and Amanita were the three most common genera across seasons and snow manipulations. Snow exclusion did not affect the diversity and structure of soil fungal community in both snow-covered and snow-free seasons. However, the relative abundance of some fungal communities was different among seasons. Soil fungal groups were correlated with environmental factors (i.e., temperature and moisture) and soil biochemical variables (i.e., ammonium and enzyme).

Conclusions
These results suggest that the season-driven variations had stronger impacts on soil fungal community than short-term snow cover change. Such findings may have important implications for soil microbial processes in Tibetan forests experiencing significant decreases in snowfall.