bluuebunny/crossref_metadata_2025 huggingface dataset:
Insomnia in Relation to Academic Performance, Self-Reported Health, Physical Activity, and Substance Use Among Adolescents
Authors: Hedin Gita , Norell-Clarke Annika , Hagell Peter , Tønnesen Hanne , Westergren Albert , Garmy Pernilla
Published: September 2020

Purpose: Insomnia affects up to one in four adolescents and has been shown to have a negative impact on their mental and physical health. This study aimed to investigate the association between insomnia, academic performance, self-reported health, physical activity, school start time, and substance use among adolescents. Methods: A survey with a cross-sectional design was completed by adolescents (15–17 years old; n = 1504) in southern Sweden. The Minimal Insomnia Symptoms Scale (MISS) was used to operationalize insomnia. A multiple logistic regression analysis was used to analyze the relationship between insomnia and self-reported health, failed school courses, substance use, school start time, family financial situation, screen time, and gender. Results: Insomnia (MISS ≥ 6) was associated with poor self-reported health (OR: 4.35), failed school courses (OR: 1.47), and use of alcohol and/or cigarettes (OR: 1.43). When the combined effect of self-reported health and physical activity were investigated, a combination of low physical activity (≤1 time/week) and poor self-reported health was strongly associated with insomnia (OR: 18.87). Conclusions: Insomnia was associated with other problems that in themselves are risk factors for poor health. This highlights the need for a holistic health-promoting approach to prevent insomnia, such as efforts to promote physical activity, school success, and the reduction of alcohol/cigarette use.
Physical Performance, Anthropometrics and Functional Characteristics Influence the Intensity of Nonspecific Chronic Low Back Pain in Military Police Officers
Authors: Tavares Janny M. A. , Rodacki André L. F. , Hoflinger Francielle , dos Santos Cabral Alexandre , Paulo Anderson C. , Rodacki Cintia L. N.
Published: September 2020

Background: Chronic low back pain (CLBP) is a serious problem in Military Police Officers (MPO), which accounts for up to 45% of the sick leave rates. It has been assumed that the strength and the endurance of trunk flexor and extensor muscles are CLPB key factors, but it is not known whether these attributes are related to pain intensity. It was aimed to determine whether the strength and endurance of trunk flexor and extensor muscles differ in MPO with no pain (CON; n = 24), moderate (MOD; n = 42), and severe (SEV; n = 37) nonspecific chronic low back pain (CLBP). Methods: The peak torque and endurance test of trunk flexor (PTF.BM−1) and extensor (PTE.BM−1) muscles were compared. A multiple regression analysis was used to identify pain intensity predictors in all groups (PAIN) and according to pain intensity (MOD and SEV). Results: The PTF.BM−1 was negatively related to pain and was a significant predictor, irrespective of pain intensity (PAIN). Conclusion: When pain intensity was considered the PTF.BM−1 and PTE.BM−1 explained the pain in the MOD, while the PTE.BM−1 and service time explained pain intensity in the SEV. Endurance of the flexor and extensor muscles was not related to pain intensity. These results indicated that training protocols must emphasize specific strengthening routines.
Circulating Exosomal miRNAs Signal Circadian Misalignment to Peripheral Metabolic Tissues
Authors: Khalyfa Abdelnaby , Gaddameedhi Shobhan , Crooks Elena , Zhang Chunling , Li Yan , Qiao Zhuanhong , Trzepizur Wojciech , Kay Steve A. , Andrade Jorge , Satterfield Brieann C. , Hansen Devon A. , Kheirandish-Gozal Leila , Van Dongen Hans P. A. , Gozal David
Published: September 2020

Night shift work increases risk of metabolic disorders, particularly obesity and insulin resistance. While the underlying mechanisms are unknown, evidence points to misalignment of peripheral oscillators causing metabolic disturbances. A pathway conveying such misalignment may involve exosome-based intercellular communication. Fourteen volunteers were assigned to a simulated day shift (DS) or night shift (NS) condition. After 3 days on the simulated shift schedule, blood samples were collected during a 24-h constant routine protocol. Exosomes were isolated from the plasma samples from each of the blood draws. Exosomes were added to naïve differentiated adipocytes, and insulin-induced pAkt/Akt expression changes were assessed. ChIP-Seq analyses for BMAL1 protein, mRNA microarrays and exosomal miRNA arrays combined with bioinformatics and functional effects of agomirs and antagomirs targeting miRNAs in NS and DS exosomal cargo were examined. Human adipocytes treated with exosomes from the NS condition showed altered Akt phosphorylation responses to insulin in comparison to those treated with exosomes from the DS condition. BMAL1 ChIP-Seq of exosome-treated adipocytes showed 42,037 binding sites in the DS condition and 5538 sites in the NS condition, with a large proportion of BMAL1 targets including genes encoding for metabolic regulators. A significant and restricted miRNA exosomal signature emerged after exposure to the NS condition. Among the exosomal miRNAs regulated differentially after 3 days of simulated NS versus DS, proof-of-concept validation of circadian misalignment signaling was demonstrated with hsa-mir-3614-5p. Exosomes from the NS condition markedly altered expression of key genes related to circadian rhythm in several cultured cell types, including adipocytes, myocytes, and hepatocytes, along with significant changes in 29 genes and downstream gene network interactions. Our results indicate that a simulated NS schedule leads to changes in exosomal cargo in the circulation. These changes promote reduction of insulin sensitivity of adipocytes in vitro and alter the expression of core clock genes in peripheral tissues. Circulating exosomal miRNAs may play an important role in metabolic dysfunction in NS workers by serving as messengers of circadian misalignment to peripheral tissues.
Impact of Human Cytomegalovirus and Human Herpesvirus 6 Infection on the Expression of Factors Associated with Cell Fibrosis and Apoptosis: Clues for Implication in Systemic Sclerosis Development
Authors: Arcangeletti Maria-Cristina , D’Accolti Maria , Maccari Clara , Soffritti Irene , Conto Flora De , Chezzi Carlo , Calderaro Adriana , Ferri Clodoveo , Caselli Elisabetta
Published: September 2020

Systemic sclerosis (SSc) is a severe autoimmune disorder characterized by vasculopathy and multi-organ fibrosis; its etiology and pathogenesis are still largely unknown. Herpesvirus infections, particularly by human cytomegalovirus (HCMV) and human herpesvirus 6 (HHV-6), have been suggested among triggers of the disease based on virological and immunological observations. However, the direct impact of HCMV and/or HHV-6 infection on cell fibrosis and apoptosis at the cell microenvironment level has not yet been clarified. Thus, this study aimed to investigate the effects of HCMV and HHV-6 infection on the induction of pro-fibrosis or pro-apoptosis conditions in primary human dermal fibroblasts, one of the relevant SSc target cells. The analysis, performed by microarray in in vitro HCMV- or HHV-6-infected vs. uninfected cells, using specific panels for the detection of the main cellular factors associated with fibrosis or apoptosis, showed that both viruses significantly modified the expression of at least 30 pro-fibrotic and 20 pro-apoptotic factors. Notably, several recognized pro-fibrotic factors were highly induced, and most of them were reported to be involved in vivo in the multifactorial and multistep pathogenic process of SSc, thus suggesting a potential role of both HCMV and HHV-6.
Progression-Free Survival and Overall Survival of CDK 4/6 Inhibitors Plus Endocrine Therapy in Metastatic Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Piezzo Michela , Chiodini Paolo , Riemma Maria , Cocco Stefania , Caputo Roberta , Cianniello Daniela , Di Gioia Germira , Di Lauro Vincenzo , Rella Francesca Di , Fusco Giuseppina , Iodice Giovanni , Nuzzo Francesco , Pacilio Carmen , Pensabene Matilde , Laurentiis Michelino De
Published: September 2020

The introduction of CDK4/6 inhibitors in combination with endocrine therapy (ET) represents the most relevant advance in the management of hormone receptor (HR) positive, HER2-negative metastatic breast cancer over the last few years. This meta-analysis of randomized controlled trials (RCTs) is aimed to better characterize the efficacy of CDK4/6 inhibitors in some relevant subgroups and to test heterogeneity between different compounds with a particular focus on their ability to improve overall survival (OS). Pooled estimates of hazard ratios (HRs) were computed for progression-free survival (PFS), OS, and objective response rate (ORR) analysis in predefined subgroups to better understand treatment effect concerning specific patients’ characteristics. To estimate the absolute benefit in terms of PFS, pooled survival curves were generated by pooling the data of all trials. A total of eight RCTs were included. Adding a CDK4/6 inhibitor to ET is beneficial in terms of PFS, irrespective of the presence or not of visceral metastases, the number of metastatic sites, and the length of the treatment-free interval (TFI). The addition of CDK4/6 inhibitors produces a significant OS improvement, both in aromatase inhibitor (AI)-sensitive (HR 0.75, 95% CI) and AI-resistant patients (HR 0.77, 95% CI [0.67–0.89]). Pooled data from each single drug show that palbociclib remains the only class member not showing a statistically significant HR for OS (HR 0.83, 95% CI [0.68–1.02]).
The Role of the IL-23/IL-17 Pathway in the Pathogenesis of Spondyloarthritis
Authors: Tsukazaki Hiroyuki , Kaito Takashi
Published: September 2020

Spondyloarthritis (SpA) is a subset of seronegative rheumatic-related autoimmune diseases that consist of ankylosing spondylitis (AS), psoriatic spondylitis (PsA), reactive spondylitis (re-SpA), inflammatory bowel disease (IBD)-associated spondylitis, and unclassifiable spondylitis. These subsets share clinical phenotypes such as joint inflammation and extra-articular manifestations (uveitis, IBD, and psoriasis [Ps]). Inflammation at the enthesis, where ligaments and tendons attach to bones, characterizes and distinguishes SpA from other types of arthritis. Over the past several years, genetic, experimental, and clinical studies have accumulated evidence showing that the IL-23/IL-17 axis plays a critical role in the pathogenesis of SpA. These discoveries include genetic association and the identification of IL-23- and IL-17-producing cells in the tissue of mouse models and human patients. In this review, we summarize the current knowledge of the pathomechanism by focusing on the IL-23/IL-17 pathway and examine the recent clinical studies of biological agents targeting IL-23 and IL-17 in the treatment of SpA.
Phenolic-Enriched Collagen Fibrillar Coatings on Titanium Alloy to Promote Osteogenic Differentiation and Reduce Inflammation
Authors: Mieszkowska Anna , Beaumont Harrison , Martocq Laurine , Koptyug Andrey , Surmeneva Maria A. , Surmenev Roman A. , Naderi Javad , Douglas Timothy E.L. , Gurzawska-Comis Katarzyna A.
Published: September 2020

The adsorption of biomolecules on biomaterial surfaces can promote their integration with surrounding tissue without changing their bulk properties. For biomaterials in bone reconstruction, the promotion of osteogenic differentiation and reduction of inflammation are desirable. Fibrillar coatings are interesting because of fibrils’ high surface area-volume ratio, aiding adsorption and adhesion. Fibrils also serve as a matrix for the immobilization of biomolecules with biological activity, such as the phenolic compound phloroglucinol (PG), the subunit of marine polyphenols. The aim of this work was to investigate the influence of PG coatings on fibroblast- and osteoblast-like cells to increase the osseointegration of titanium implants. Collagen fibril coatings, containing PG at low and high concentrations, were produced on titanium alloy (Ti6Al4V) scaffolds generated by additive manufacturing (AM). These coatings, especially PG-enriched coatings, reduced hydrophobicity and modulated the behavior of human osteosarcoma SaOS-2 and mouse embryonic fibroblast 3T3 cell lines. Both osteoblastic and fibroblastic cells spread and adhered well on PG-enriched coatings. Coatings significantly reduced the inflammatory response. Moreover, osteogenic differentiation was promoted by collagen coatings with a high PG concentration. Thus, the enrichment of collagen fibril coatings with PG is a promising strategy to improve Ti6Al4V implants for bone contact in orthopedics and dentistry and is worthy of further investigation.
The Phenomenon of Clopidogrel High On-Treatment Platelet Reactivity in Ischemic Stroke Subjects: A Comprehensive Review
Authors: Wiśniewski Adam , Filipska Karolina
Published: September 2020

Clopidogrel is increasingly being used for the secondary prevention of ischemic stroke according to the updated guidelines on acute stroke management. Failure to achieve a drug response is referred to as clopidogrel resistance. Similarly, a higher activation of platelets during clopidogrel therapy—high on-treatment platelet reactivity—is equivalent to a reduced effectiveness of a therapy. Clopidogrel resistance is considered to be a common and multifactorial phenomenon that significantly limits the efficacy of antiplatelet agents. The aim of the current study is to review the latest literature data to identify the prevalance and predictors of clopidogrel high on-treatment platelet reactivity among stroke subjects and to establish the potential impact on clinical outcomes and prognosis. Clinical databases were searched by two independent researchers to select relevant papers on the topic, including all types of articles. Several important predictors contributing to clopidogrel resistance were identified, including genetic polymorphisms, the concomitant use of other drugs, or vascular risk factors, in particular nonsmoking and diabetes. Clopidogrel high on-treatment platelet reactivity has a negative impact on the clinical course of stroke, worsens the early- and long-term prognoses, and increases the risk of recurrent vascular events. Platelet function testing should be considered in selected stroke individuals, especially those predisposed to clopidogrel resistance, for whom an improvement in the efficacy of antiplatelet therapy is essential. This particular group may become the greatest beneficiaries of the modification of existing therapy based on platelet function monitoring.
GANT61 and Lithium Chloride Inhibit the Growth of Head and Neck Cancer Cell Lines Through the Regulation of GLI3 Processing by GSK3β
Authors: Zubčić Vedran , Rinčić Nikolina , Kurtović Matea , Trnski Diana , Musani Vesna , Ozretić Petar , Levanat Sonja , Leović Dinko , Sabol Maja
Published: September 2020

Several signaling pathways are aberrantly activated in head and neck squamous cell carcinoma (HNSCC), including the Hedgehog-Gli (HH-GLI), WNT, EGFR, and NOTCH pathways. The HH-GLI pathway has mostly been investigated in the context of canonical signal transduction and the inhibition of the membrane components of the pathway. In this work we investigated the role of downstream inhibitors GANT61 and lithium chloride (LiCl) on cell viability, wound closure, and colony forming ability of HNSCC cell lines. Five HNSCC cell lines were treated with HH-GLI pathway inhibitors affecting different levels of signal transduction. GANT61 and LiCl reduce the proliferation and colony formation capabilities of HNSCC cell lines, and LiCl has an additional effect on wound closure. The major effector of the HH-GLI signaling pathway in HNSCC is the GLI3 protein, which is expressed in its full-length form and is functionally regulated by GSK3β. LiCl treatment increases the inhibitory Ser9 phosphorylation of the GSK3β protein, leading to increased processing of GLI3 from full-length to repressor form, thus inhibiting HH-GLI pathway activity. Therefore, downstream inhibition of HH-GLI signaling may be a promising therapeutic strategy for HNSCC.
The HMOX1 Pathway as a Promising Target for the Treatment and Prevention of SARS-CoV-2 of 2019 (COVID-19)
Authors: Batra Neelu , De Souza Cristabelle , Batra Jyoti , Raetz Alan G. , Yu Ai-Ming
Published: September 2020

The coronavirus disease of 2019 (COVID-19) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global pandemic with increasing incidence and mortality rates. Recent evidence based on the cytokine profiles of severe COVID-19 cases suggests an overstimulation of macrophages and monocytes associated with reduced T-cell abundance (lymphopenia) in patients infected with SARS-CoV-2. The SARS-CoV-2 open reading frame 3 a (ORF3a) protein was found to bind to the human HMOX1 protein at a high confidence through high-throughput screening experiments. The HMOX1 pathway can inhibit platelet aggregation, and can have anti-thrombotic and anti-inflammatory properties, amongst others, all of which are critical medical conditions observed in COVID-19 patients. Here, we review the potential of modulating the HMOX1-ORF3a nexus to regulate the innate immune response for therapeutic benefits in COVID-19 patients. We also review other potential treatment strategies and suggest novel synthetic and natural compounds that may have the potential for future development in clinic.
Dual Oxidase Maturation Factor 1 Positively Regulates RANKL-Induced Osteoclastogenesis via Activating Reactive Oxygen Species and TRAF6-Mediated Signaling
Authors: Cheon Yoon-Hee , Lee Chang Hoon , Jeong Da Hye , Kwak Sung Chul , Kim Soojin , Lee Myeung Su , Kim Ju-Young
Published: September 2020

Receptor activator of NF-κB ligand (RANKL) induces generation of intracellular reactive oxygen species (ROS), which act as second messengers in RANKL-mediated osteoclastogenesis. Dual oxidase maturation factor 1 (Duoxa1) has been associated with the maturation of ROS-generating enzymes including dual oxidases (Duox1 and Duox2). In the progression of osteoclast differentiation, we identified that only Duoxa1 showed an effective change upon RANKL stimulation, but not Duox1, Duox2, and Duoxa2. Therefore, we hypothesized that Duoxa1 could independently act as a second messenger for RANKL stimulation and regulate ROS production during osteoclastogenesis. Duoxa1 gradually increased during RANKL-induced osteoclastogenesis. Using siRNA or retrovirus transduction, we found that Duoxa1 regulated RANKL-stimulated osteoclast formation and bone resorption positively. Furthermore, knockdown of Duoxa1 decreased the RANKL-induced ROS production. During Duoxa1-related control of osteoclastogenesis, activation of tumor necrosis factor receptor-associated factor 6 (TRAF6)-mediated early signaling molecules including MAPKs, Akt, IκB, Btk, Src and PLCγ2 was affected, which sequentially modified the mRNA or protein expression levels of key transcription factors in osteoclast differentiation, such as c-Fos and NFATc1, as well as mRNA expression of osteoclast-specific markers. Overall, our data indicate that Duoxa1 plays a crucial role in osteoclastogenesis via regulating RANKL-induced intracellular ROS production and activating TRAF6-mediated signaling.
Prodigiosin Modulates the Immune Response and Could Promote a Stable Atherosclerotic Lession in C57bl/6 Ldlr-/- Mice
Authors: Cuevas Alejandro , Saavedra Nicolás , Salazar Luis A. , Cavalcante Marcela F. , Silva Jacqueline C. , Abdalla Dulcineia S. P.
Published: September 2020

Atherosclerosis is a chronic inflammatory disease, whose progression and stability are modulated, among other factors, by an innate and adaptive immune response. Prodiginines are bacterial secondary metabolites with antiproliferative and immunomodulatory activities; however, their effect on the progression or vulnerability of atheromatous plaque has not been evaluated. This study assessed the therapeutic potential of prodigiosin and undecylprodigiosin on inflammatory marker expression and atherosclerosis. An in vitro and in vivo study was carried out. Migration, low-density lipoprotein (LDL) uptake and angiogenesis assays were performed on cell types involved in the pathophysiology of atherosclerosis. In addition, male LDL receptor null (Ldlr-/-) C57BL/6J mice were treated with prodigiosin or undecylprodigiosin for 28 days. Morphometric analysis of atherosclerotic plaques, gene expression of atherogenic factors in the aortic sinus and serum cytokine quantification were performed. The treatments applied had slight effects on the in vitro tests performed, highlighting the inhibitory effect on the migration of SMCs (smooth muscle cells). On the other hand, although no significant difference in atherosclerotic plaque progression was observed, gene expression of IL-4 and chemokine (C-C motif) ligand 2 (Ccl2) was downregulated. In addition, 50 µg/Kg/day of both treatments was sufficient to inhibit circulating tumor necrosis factor alpha (TNF-α), interleukin-2 (IL-2) and interferon-gamma (IFN-γ) in serum. These results suggested that prodigiosin and undecylprodigiosin modulated inflammatory markers and could have an impact in reducing atherosclerotic plaque vulnerability.
Adiponectin: The Potential Regulator and Therapeutic Target of Obesity and Alzheimer’s Disease
Authors: Kim Jong Youl , Barua Sumit , Jeong Ye Jun , Lee Jong Eun
Published: September 2020

Animal and human mechanistic studies have consistently shown an association between obesity and Alzheimer’s disease (AD). AD, a degenerative brain disease, is the most common cause of dementia and is characterized by the presence of extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles disposition. Some studies have recently demonstrated that Aβ and tau cannot fully explain the pathophysiological development of AD and that metabolic disease factors, such as insulin, adiponectin, and antioxidants, are important for the sporadic onset of nongenetic AD. Obesity prevention and treatment can be an efficacious and safe approach to AD prevention. Adiponectin is a benign adipokine that sensitizes the insulin receptor signaling pathway and suppresses inflammation. It has been shown to be inversely correlated with adipose tissue dysfunction and may enhance the risk of AD because a range of neuroprotection adiponectin mechanisms is related to AD pathology alleviation. In this study, we summarize the recent progress that addresses the beneficial effects and potential mechanisms of adiponectin in AD. Furthermore, we review recent studies on the diverse medications of adiponectin that could possibly be related to AD treatment, with a focus on their association with adiponectin. A better understanding of the neuroprotection roles of adiponectin will help clarify the precise underlying mechanism of AD development and progression.
The Molecular Floodgates of Stress-Induced Senescence Reveal Translation, Signalling and Protein Activity Central to the Post-Mortem Proteome
Authors: Wasinger Valerie C. , Curnoe Darren , Boel Ceridwen , Machin Naomi , Goh Hsiao Mei
Published: September 2020

The transitioning of cells during the systemic demise of an organism is poorly understood. Here, we present evidence that organismal death is accompanied by a common and sequential molecular flood of stress-induced events that propagate the senescence phenotype, and this phenotype is preserved in the proteome after death. We demonstrate activation of “death” pathways involvement in diseases of ageing, with biochemical mechanisms mapping onto neurological damage, embryonic development, the inflammatory response, cardiac disease and ultimately cancer with increased significance. There is sufficient bioavailability of the building blocks required to support the continued translation, energy, and functional catalytic activity of proteins. Significant abundance changes occur in 1258 proteins across 1 to 720 h post-mortem of the 12-week-old mouse mandible. Protein abundance increases concord with enzyme activity, while mitochondrial dysfunction is evident with metabolic reprogramming. This study reveals differences in protein abundances which are akin to states of stress-induced premature senescence (SIPS). The control of these pathways is significant for a large number of biological scenarios. Understanding how these pathways function during the process of cellular death holds promise in generating novel solutions capable of overcoming disease complications, maintaining organ transplant viability and could influence the findings of proteomics through “deep-time” of individuals with no historically recorded cause of death.
Antibiotic Treatment Prior to Injury Improves Post-Traumatic Osteoarthritis Outcomes in Mice
Authors: Mendez Melanie E. , Murugesh Deepa K. , Sebastian Aimy , Hum Nicholas R. , McCloy Summer A. , Kuhn Edward A. , Christiansen Blaine A. , Loots Gabriela G.
Published: September 2020

Osteoarthritis (OA) is a painful and debilitating disease characterized by the chronic and progressive degradation of articular cartilage. Post-traumatic OA (PTOA) is a secondary form of OA that develops in ~50% of cases of severe articular injury. Inflammation and re-occurring injury have been implicated as contributing to the progression of PTOA after the initial injury. However, there is very little known about external factors prior to injury that could affect the risk of PTOA development. To examine how the gut microbiome affects PTOA development we used a chronic antibiotic treatment regimen starting at weaning for six weeks prior to ACL rupture, in mice. A six-weeks post-injury histological examination showed more robust cartilage staining on the antibiotic (AB)-treated mice than the untreated controls (VEH), suggesting slower disease progression in AB cohorts. Injured joints also showed an increase in the presence of anti-inflammatory M2 macrophages in the AB group. Molecularly, the phenotype correlated with a significantly lower expression of inflammatory genes Tlr5, Ccl8, Cxcl13, and Foxo6 in the injured joints of AB-treated animals. Our results indicate that a reduced state of inflammation at the time of injury and a lower expression of Wnt signaling modulatory protein, Rspo1, caused by AB treatment can slow down or improve PTOA outcomes.
Collagen/Chitosan Functionalization of Complex 3D Structures Fabricated by Laser Direct Writing via Two-Photon Polymerization for Enhanced Osteogenesis
Authors: Păun Irina Alexandra , Mustăciosu Cosmin Cătălin , Popescu Roxana Cristina , Călin Bogdan Ştefăniţă , Mihăilescu Mona
Published: September 2020

The fabrication of 3D microstructures is under continuous development for engineering bone substitutes. Collagen/chitosan (Col/CT) blends emerge as biomaterials that meet the mechanical and biological requirements associated with bone tissue. In this work, we optimize the osteogenic effect of 3D microstructures by their functionalization with Col/CT blends with different blending ratios. The structures were fabricated by laser direct writing via two-photons polymerization of IP-L780 photopolymer. They comprised of hexagonal and ellipsoidal units 80 µm in length, 40 µm in width and 14 µm height, separated by 20 µm pillars. Structures’ functionalization was achieved via dip coating in Col/CT blends with specific blending ratios. The osteogenic role of Col/CT functionalization of the 3D structures was confirmed by biological assays concerning the expression of alkaline phosphatase (ALP) and osteocalcin secretion as osteogenic markers and Alizarin Red (AR) as dye for mineral deposits in osteoblast-like cells seeded on the structures. The structures having ellipsoidal units showed the best results, but the trends were similar for both ellipsoidal and hexagonal units. The strongest osteogenic effect was obtained for Col/CT blending ratio of 20/80, as demonstrated by the highest ALP activity, osteocalcin secretion and AR staining intensity in the seeded cells compared to all the other samples.
BcMF30a and BcMF30c, Two Novel Non-Tandem CCCH Zinc-Finger Proteins, Function in Pollen Development and Pollen Germination in Brassica campestris ssp. chinensis
Authors: Xu Liai , Xiong Xingpeng , Liu Weimiao , Liu Tingting , Yu Youjian , Cao Jiashu
Published: September 2020

Chinese cabbage (Brassica campestris) is an economically important leaf vegetable crop worldwide. Mounting studies have shown that cysteine-cysteine-cysteine-histidine (CCCH) zinc-finger protein genes are involved in various plant growth and development processes. However, research on the involvement of these genes in male reproductive development is still in its infancy. Here, we identified 11 male fertility-related CCCH genes in Chinese cabbage. Among them, a pair of paralogs encoding novel non-tandem CCCH zinc-finger proteins, Brassica campestris Male Fertility 30a (BcMF30a) and BcMF30c, were further characterized. They were highly expressed in pollen during microgametogenesis and continued to express in germinated pollen. Further analyses demonstrated that both BcMF30a and BcMF30c may play a dual role as transcription factors and RNA-binding proteins in plant cells. Functional analysis showed that partial bcmf30a bcmf30c pollen grains were aborted due to the degradation of pollen inclusion at the microgametogenesis phase, and the germination rate of viable pollen was also greatly reduced, indicating that BcMF30a and BcMF30c are required for both pollen development and pollen germination. This research provided insights into the function of CCCH proteins in regulating male reproductive development and laid a theoretical basis for hybrid breeding of Chinese cabbage.
State of the Art Review of Cell Therapy in the Treatment of Lung Disease, and the Potential for Aerosol Delivery
Authors: Brave Hosanna , MacLoughlin Ronan
Published: September 2020

Respiratory and pulmonary diseases are among the leading causes of death globally. Despite tremendous advancements, there are no effective pharmacological therapies capable of curing diseases such as COPD (chronic obstructive pulmonary disease), ARDS (acute respiratory distress syndrome), and COVID-19. Novel and innovative therapies such as advanced therapy medicinal products (ATMPs) are still in early development. However, they have exhibited significant potential preclinically and clinically. There are several longitudinal studies published, primarily focusing on the use of cell therapies for respiratory diseases due to their anti-inflammatory and reparative properties, thereby hinting that they have the capability of reducing mortality and improving the quality of life for patients. The primary objective of this paper is to set out a state of the art review on the use of aerosolized MSCs and their potential to treat these incurable diseases. This review will examine selected respiratory and pulmonary diseases, present an overview of the therapeutic potential of cell therapy and finally provide insight into potential routes of administration, with a focus on aerosol-mediated ATMP delivery.
Comparative Proteomic Analysis Identifies EphA2 as a Specific Cell Surface Marker for Wharton’s Jelly-Derived Mesenchymal Stem Cells
Authors: Al Madhoun Ashraf , Marafie Sulaiman K. , Haddad Dania , Melhem Motasem , Abu-Farha Mohamed , Ali Hamad , Sindhu Sardar , Atari Maher , Al-Mulla Fahd
Published: September 2020

Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) are a valuable tool in stem cell research due to their high proliferation rate, multi-lineage differentiation potential, and immunotolerance properties. However, fibroblast impurity during WJ-MSCs isolation is unavoidable because of morphological similarities and shared surface markers. Here, a proteomic approach was employed to identify specific proteins differentially expressed by WJ-MSCs in comparison to those by neonatal foreskin and adult skin fibroblasts (NFFs and ASFs, respectively). Mass spectrometry analysis identified 454 proteins with a transmembrane domain. These proteins were then compared across the different cell-lines and categorized based on their cellular localizations, biological processes, and molecular functions. The expression patterns of a selected set of proteins were further confirmed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence assays. As anticipated, most of the studied proteins had common expression patterns. However, EphA2, SLC25A4, and SOD2 were predominantly expressed by WJ-MSCs, while CDH2 and Talin2 were specific to NFFs and ASFs, respectively. Here, EphA2 was established as a potential surface-specific marker to distinguish WJ-MSCs from fibroblasts and for prospective use to prepare pure primary cultures of WJ-MSCs. Additionally, CDH2 could be used for a negative-selection isolation/depletion method to remove neonatal fibroblasts contaminating preparations of WJ-MSCs.
Plasma-Derived miRNA-222 as a Candidate Marker for Papillary Thyroid Cancer
Authors: Kondrotienė Aistė , Daukša Albertas , Pamedytytė Daina , Kazokaitė Mintautė , Žvirblienė Aurelija , Daukšienė Dalia , Simanavičienė Vaida , Klimaitė Raimonda , Golubickaitė Ieva , Stakaitis Rytis , Šarauskas Valdas , Verkauskienė Rasa , Žilaitienė Birutė
Published: September 2020

We analyzed five miRNA molecules (miR-221; miR-222; miR-146b; miR-21; miR-181b) in the plasma of patients with papillary thyroid cancer (PTC), nodular goiter (NG) and healthy controls (HC) and evaluated their diagnostic value for differentiation of PTC from NG and HC. Preoperative PTC plasma miRNA expression (n = 49) was compared with plasma miRNA in the HC group (n = 57) and patients with NG (n = 23). It was demonstrated that miR-221; miR-222; miR-146b; miR-21 and miR-181b were overexpressed in preoperative PTC plasma samples compared to HC (p < 0.0001; p < 0.0001; p < 0.0001; p < 0.0001; p < 0.002; respectively). The upregulation in tumor tissue of these miRNAs was consistent with The Cancer Genome Atlas Thyroid Carcinoma dataset. A significant decrease in miR-21; miR-221; miR-146b and miR-181b expression was observed in the plasma of PTC patients after total thyroidectomy (p = 0.004; p = 0.001; p = 0.03; p = 0.036; respectively). The levels of miR-222 were significantly higher in the preoperative PTC compared to the NG group (p = 0.004). ROC curve (receiver operating characteristic curve) analysis revealed miR-222 as a potential marker in distinguishing PTC from NG (AUC 0.711; p = 0.004). In conclusion; circulating miR-222 profiles might be useful in discriminating PTC from NG.
Temporal Dynamics of ‘Ca. Phytoplasma mali’ Load in the Insect Vector Cacopsylla melanoneura
Authors: Candian Valentina , Monti Monia , Tedeschi Rosemarie
Published: September 2020

The transmission of phytoplasmas is the result of an intricate interplay involving pathogens, insect vectors and host plants. Knowledge of the vector’s competence during its lifespan allows us to define more sustainable well-timed control strategies targeted towards the most worrisome life stages. We investigated the temporal dynamics of ‘Candidatus Phytoplasma mali’ load in Cacopsylla melanoneura in the different developmental stages in Northwest Italy. The phytoplasma load in the vector was evaluated in overwintering adults, nymphs and newly emerged adults after different acquisition access periods. Moreover, we followed the multiplication of the phytoplasma during the aestivation and the overwintering period on conifers. Our results confirmed the ability of remigrants to retain the phytoplasma until the end of winter. We also highlighted the high acquisition efficiency and vector competence, based on phytoplasma load, of nymphs and newly emerged adults. Therefore, particular attention should be paid to the management of overwintered C. melanoneura as soon as they return to the orchards, but also to newly emerged adults, particularly in orchards with a high infection rate and when the migration to conifers is delayed.
Electrosprayed Chitin Nanofibril/Electrospun Polyhydroxyalkanoate Fiber Mesh as Functional Nonwoven for Skin Application
Authors: Azimi Bahareh , Thomas Lily , Fusco Alessandra , Kalaoglu-Altan Ozlem Ipek , Basnett Pooja , Cinelli Patrizia , De Clerck Karen , Roy Ipsita , Donnarumma Giovanna , Coltelli Maria-Beatrice , Danti Serena , Lazzeri Andrea
Published: September 2020

Polyhydroxyalkanoates (PHAs) are a family of bio-based polyesters that have found different biomedical applications. Chitin and lignin, byproducts of fishery and plant biomass, show antimicrobial and anti-inflammatory activity on the nanoscale. Due to their polarities, chitin nanofibril (CN) and nanolignin (NL) can be assembled into micro-complexes, which can be loaded with bioactive factors, such as the glycyrrhetinic acid (GA) and CN-NL/GA (CLA) complexes, and can be used to decorate polymer surfaces. This study aims to develop completely bio-based and bioactive meshes intended for wound healing. Poly(3-hydroxybutyrate)/Poly(3-hydroxyoctanoate-co-3-hydroxydecanoate), P(3HB)/P(3HO-co-3HD) was used to produce films and fiber meshes, to be surface-modified via electrospraying of CN or CLA to reach a uniform distribution. P(3HB)/P(3HO-co-3HD) fibers with desirable size and morphology were successfully prepared and functionalized with CN and CLA using electrospinning and tested in vitro with human keratinocytes. The presence of CN and CLA improved the indirect antimicrobial and anti-inflammatory activity of the electrospun fiber meshes by downregulating the expression of the most important pro-inflammatory cytokines and upregulating human defensin 2 expression. This natural and eco-sustainable mesh is promising in wound healing applications.
Effect of the Layer Sequence on the Ballistic Performance and Failure Mechanism of Ti6Al4V/CP-Ti Laminated Composite Armor
Authors: Yu Hong , Fan Qunbo , Zhu Xinjie
Published: September 2020

The effect of the layer sequence on the ballistic performance of Ti6Al4V (35 mm)/CP-Ti (5 mm) laminated composite armor, against a 12.7 mm armor piercing projectile, was systematically investigated, both experimentally and computationally. By introducing the Johnson–Cook constitutive model and fracture criterion, the penetrating process of the composite plate was well-simulated. Furthermore, the influence of the layer sequence on the ballistic performance and failure mechanism of the composite plate was evaluated from the perspective of energy absorption and the stress distribution. Numerical simulation results of the macro morphology and penetration depth agreed well with the experimental results. The results showed that the energy absorption histories of each layer and stress distribution of the composite plate were found to be significantly affected by the arrangement sequence. The ballistic performance of Ti6Al4V/CP-Ti was far superior to that of CP-Ti/Ti6Al4V because more energy was absorbed in the early stage of the penetration process, thereby reducing the damage to the rear face. Further studies showed that the first principal stress in both structures was radially distributed in space, but was mainly concentrated at the rear face when the CP-Ti was placed at the front. Therefore, this stress induced cracking and failure in that region and, consequently, lowered the overall ballistic performance.
Study on Hydrogen Diffusion Behavior during Welding of Heavy Plate
Authors: Yang Jianguo , Liu Guohao , Zheng Wenjian
Published: September 2020

For the multi-layer and multi-pass welding process of the heavy plate, the hydrogen diffusion behavior was numerically simulated to study the effect of solid-state phase transition (SSPT) on the hydrogen diffusion in the thickness direction, and the influence of the residual stress-induced diffusion after SSPT. The calculation results were compared with the experimental results. The comparison shows that the distribution of hydrogen concentration in the direction of thickness was in good agreement. The position with the most severe cold cracking sensitivity was located at a 20–30 mm depth from the top surface in this article. After welding, the hydrogen concentration in this position was kept at a high level for a long time under the effect of the size-constraint effect of the heavy plate and the existence of welding residual stress gradient. In addition, the SSPT reduced the residual stress level of weld metal (WM) significantly, increased that of the heat affected zone (HAZ), and the hydrogen was redistributed under the influence of stress. In the process of phase transformation, the parameters of hydrogen diffusion property of the material changed dramatically in a short time, the hydrogen diffusion coefficient increased in order of magnitude, and the solubility decreased in order of magnitude. This directly led to the upward diffusion of hydrogen in WM, and produced a self-gathering effect. For a welded joint of heavy plate, the self-gathering effect between passes was effective in the short-range and ineffective in the long-range.
Plasticity of Bead-on-Plate Welds Made with the Use of Stored Flux-Cored Wires for Offshore Applications
Authors: Świerczyńska Aleksandra , Landowski Michał
Published: September 2020

Extreme atmospheric conditions in the marine and offshore industry are harmful to engineering materials, especially to welded joints, and may cause degradation of their properties. This article presents the results of research on the plasticity of bead-on-plate welds made using two types of seamless, copper plated flux-cored wires. Before welding, spools with wire were stored for 1 month in two distinct locations with different geographical and industrial conditions in Poland, and then subjected to visual examination. Bead-on-plate welds were subjected to a static tensile test and on this basis plasticity indexes showing the effect of storage on plasticity were determined. The fractures after tensile tests and the surfaces of the wires were examined on an electron scanning microscope. Additionally, diffusible hydrogen content in deposited metal measurements for each condition were carried out. The highest degradation level was found for wire stored in an agricultural building in north-eastern Poland—there was an almost fourfold decrease in the plasticity index value and the highest diffusible hydrogen content. For the same wire and the same location, the largest difference was also observed in fracture morphology after the tensile test—ductile fracture was obtained for wire at delivery condition while an almost full cleavage fracture was found after relatively short (1 month) storage of wire.
Tribological Performance of Environmentally Friendly Bio-Degradable Lubricants Based on a Combination of Boric Acid and Bio-Based Oils
Authors: Trzepieciński Tomasz
Published: September 2020

Finding effective and environmentally friendly lubrication to use in sheet metal forming operations presents a substantial environmental and economic challenge to the automotive industry. This paper examines the effectiveness of different lubricants in the reduction of the coefficient of friction (COF) in the process of sheet metal forming of the low carbon steel sheets. These lubricants are based on a combination of boric acid (H3BO3) and edible vegetable oils, both of which are natural and environmentally friendly. To evaluate the friction characteristics of the lubricants in a forming operation, a strip drawing friction test is used. This test consisted in drawing a specimen in the form of a sheet metal strip between two non-rotating counter-samples with radii of 200 and 10 mm. The effectiveness of environmentally friendly lubricants in reducing the COF was compared to the traditional petroleum-based lubricants which are used in sheet metal-forming operations. The effect of lubricant conditions and tool surface roughness on the value of COFs is studied. It was found that palm oil in both configurations of countersample radius, both as pure oil and with the addition of 5 wt.% of H3BO3, was the most effective in lowering the coefficient of friction. In most of the conditions analysed, the addition of boric acid into vegetable oils leads to an increase in the lubrication efficiency by up to 15% compared to pure oils. The effectiveness of lubrication by olive and rapeseed oils in decreasing the frictional resistances clearly depends on the nominal pressure applied.
An Overview of Additive Manufacturing Technologies—A Review to Technical Synthesis in Numerical Study of Selective Laser Melting
Authors: Razavykia Abbas , Brusa Eugenio , Delprete Cristiana , Yavari Reza
Published: September 2020

Additive Manufacturing (AM) processes enable their deployment in broad applications from aerospace to art, design, and architecture. Part quality and performance are the main concerns during AM processes execution that the achievement of adequate characteristics can be guaranteed, considering a wide range of influencing factors, such as process parameters, material, environment, measurement, and operators training. Investigating the effects of not only the influential AM processes variables but also their interactions and coupled impacts are essential to process optimization which requires huge efforts to be made. Therefore, numerical simulation can be an effective tool that facilities the evaluation of the AM processes principles. Selective Laser Melting (SLM) is a widespread Powder Bed Fusion (PBF) AM process that due to its superior advantages, such as capability to print complex and highly customized components, which leads to an increasing attention paid by industries and academia. Temperature distribution and melt pool dynamics have paramount importance to be well simulated and correlated by part quality in terms of surface finish, induced residual stress and microstructure evolution during SLM. Summarizing numerical simulations of SLM in this survey is pointed out as one important research perspective as well as exploring the contribution of adopted approaches and practices. This review survey has been organized to give an overview of AM processes such as extrusion, photopolymerization, material jetting, laminated object manufacturing, and powder bed fusion. And in particular is targeted to discuss the conducted numerical simulation of SLM to illustrate a uniform picture of existing nonproprietary approaches to predict the heat transfer, melt pool behavior, microstructure and residual stresses analysis.
Effect of Different Hydration Time on Carbonation Degree and Strength of Steel Slag Specimens Containing Zeolite
Authors: Zhang Xiong , Chang Jun
Published: September 2020

Steel slag partially substituted by zeolite (SZ) was beneficial for improving the compressive strength and carbonation degree of SZ specimens after a combined curing (hydration and then carbonation) process due to pozzolanic reaction between them. By previous work results, the zeolitic substitution ratios of 5 wt.% and 15 wt.% in steel slag specimens (SZ5 and SZ15) gained the optimum compressive strength and carbonation degree, respectively, after 1 day hydration and then 2 h carbonation. This study investigated the effect of previous hydration time (1, 3, 7, 14, and 196 days) on carbonation degree and strength of SZ specimens after subsequent carbonation curing. Two zeolitic substitution ratios (5 wt.% and 15 wt.%) were selected and pure steel slag specimens were also prepared as controls. Compressive strength results revealed that the optimum hydration curing time was 1 day and the optimum zeolitic substitution ratio was 5 wt.%. The pozzolanic reaction happened in SZ specimens was divided into early and late pozzolanic reaction. In the late hydration, a new mineral, monocarboaluminate (AFmc) was produced in SZ15 specimens, modifying the carbonation degree and strength further. And the mechanism of pozzolanic reaction in early and late hydration in SZ specimens was explained by several microscopic test methods.