bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement of a Genetic Transformation System and Preliminary Study on the Function of LpABCB21 and LpPILS7 Based on Somatic Embryogenesis in Lilium pumilum DC. Fisch
Authors: Song Shengli , Yan Rui , Wang Chunxia , Wang Jinxia , Sun Hongmei
Published: September 2020

Auxin transport mediates the asymmetric distribution of auxin that determines the fate of cell development. Agrobacterium-mediated genetic transformation is an important technical means to study gene function. Our previous study showed that the expression levels of LpABCB21 and LpPILS7 are significantly up-regulated in the somatic embryogenesis (SE) of Lilium pumilum DC. Fisch. (L. pumilum), but the functions of both genes remain unclear. Here, the genetic transformation technology previously developed by our team based on the L.pumilum system was improved, and the genetic transformation efficiency increased by 5.7–13.0%. Use of overexpression and CRISPR/Cas9 technology produced three overexpression and seven mutant lines of LpABCB21, and seven overexpression and six mutant lines of LpPILS7. Analysis of the differences in somatic embryo induction of transgenic lines confirmed that LpABCB21 regulates the early formation of the somatic embryo; however, excessive expression level of LpABCB21 inhibits somatic embryo induction efficiency. LpPILS7 mainly regulates somatic embryo induction efficiency. This study provides a more efficient method of genetic transformation of L. pumilum. LpABCB21 and LpPILS7 are confirmed to have important regulatory roles in L. pumilum SE thus laying the foundation for subsequent studies of the molecular mechanism of Lilium SE.
Diclofenac Degradation—Enzymes, Genetic Background and Cellular Alterations Triggered in Diclofenac-Metabolizing Strain Pseudomonas moorei KB4
Authors: Żur Joanna , Piński Artur , Wojcieszyńska Danuta , Smułek Wojciech , Guzik Urszula
Published: September 2020

Diclofenac (DCF) constitutes one of the most significant ecopollutants detected in various environmental matrices. Biological clean-up technologies that rely on xenobiotics-degrading microorganisms are considered as a valuable alternative for chemical oxidation methods. Up to now, the knowledge about DCF multi-level influence on bacterial cells is fragmentary. In this study, we evaluate the degradation potential and impact of DCF on Pseudomonas moorei KB4 strain. In mono-substrate culture KB4 metabolized 0.5 mg L−1 of DCF, but supplementation with glucose (Glc) and sodium acetate (SA) increased degraded doses up to 1 mg L−1 within 12 days. For all established conditions, 4′-OH-DCF and DCF-lactam were identified. Gene expression analysis revealed the up-regulation of selected genes encoding biotransformation enzymes in the presence of DCF, in both mono-substrate and co-metabolic conditions. The multifactorial analysis of KB4 cell exposure to DCF showed a decrease in the zeta-potential with a simultaneous increase in the cell wall hydrophobicity. Magnified membrane permeability was coupled with the significant increase in the branched (19:0 anteiso) and cyclopropane (17:0 cyclo) fatty acid accompanied with reduced amounts of unsaturated ones. DCF injures the cells which is expressed by raised activities of acid and alkaline phosphatases as well as formation of lipids peroxidation products (LPX). The elevated activity of superoxide dismutase (SOD) and catalase (CAT) testified that DCF induced oxidative stress.
Design, Synthesis and Biological Evaluation of Biphenylglyoxamide-Based Small Molecular Antimicrobial Peptide Mimics as Antibacterial Agents
Authors: Yu Tsz Tin , Kuppusamy Rajesh , Yasir Muhammad , Hassan Md. Musfizur , Alghalayini Amani , Gadde Satyanarayana , Deplazes Evelyne , Cranfield Charles , Willcox Mark D.P. , Black David StC , Kumar Naresh
Published: September 2020

There has been an increasing interest in the development of antimicrobial peptides (AMPs) and their synthetic mimics as a novel class of antibiotics to overcome the rapid emergence of antibiotic resistance. Recently, phenylglyoxamide-based small molecular AMP mimics have been identified as potential leads to treat bacterial infections. In this study, a new series of biphenylglyoxamide-based small molecular AMP mimics were synthesised from the ring-opening reaction of N-sulfonylisatin bearing a biphenyl backbone with a diamine, followed by the conversion into tertiary ammonium chloride, quaternary ammonium iodide and guanidinium hydrochloride salts. Structure–activity relationship studies of the analogues identified the octanesulfonyl group as being essential for both Gram-positive and Gram-negative antibacterial activity, while the biphenyl backbone was important for Gram-negative antibacterial activity. The most potent analogue was identified to be chloro-substituted quaternary ammonium iodide salt 15c, which possesses antibacterial activity against both Gram-positive (MIC against Staphylococcus aureus = 8 μM) and Gram-negative bacteria (MIC against Escherichia coli = 16 μM, Pseudomonas aeruginosa = 63 μM) and disrupted 35% of pre-established S. aureus biofilms at 32 μM. Cytoplasmic membrane permeability and tethered bilayer lipid membranes (tBLMs) studies suggested that 15c acts as a bacterial membrane disruptor. In addition, in vitro toxicity studies showed that the potent compounds are non-toxic against human cells at therapeutic dosages.
Anticancer Properties of Platinum Nanoparticles and Retinoic Acid: Combination Therapy for the Treatment of Human Neuroblastoma Cancer
Authors: Gurunathan Sangiliyandi , Jeyaraj Muniyandi , Kang Min-Hee , Kim Jin-Hoi
Published: September 2020

Neuroblastoma is the most common extracranial solid tumor in childhood. The different treatments available for neuroblastoma are challenged by high rates of resistance, recurrence, and progression, most notably in advanced cases and highly malignant tumors. Therefore, the development of more targeted therapies, which are biocompatible and without undesired side effects, is highly desirable. The mechanisms of actions of platinum nanoparticles (PtNPs) and retinoic acid (RA) in neuroblastoma have remained unclear. In this study, the anticancer effects of PtNPs and RA on neuroblastoma were assessed. We demonstrated that treatment of SH-SY5Y cells with the combination of PtNPs and RA resulted in improved anticancer effects. The anticancer effects of the two compounds were mediated by cytotoxicity, oxidative stress (OS), mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and apoptosis-associated networks. Cytotoxicity was confirmed by leakage of lactate dehydrogenase (LDH) and intracellular protease, and oxidative stress increased the level of reactive oxygen species (ROS), 4-hydroxynonenal (HNE), malondialdehyde (MDA), and nitric oxide (NO), and protein carbonyl content (PCC). The combination of PtNPs and RA caused mitochondrial dysfunction by decreasing the mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) content, number of mitochondria, and expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Endoplasmic reticulum-mediated stress and apoptosis were confirmed by upregulation of protein kinase RNA-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), activating transcription factor 4 (ATF4), p53, Bax, and caspase-3 and down regulation of B-cell lymphoma 2 (BCl-2). PtNPs and RA induced apoptosis, and oxidative DNA damage was evident by the accumulation of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-hydroxyguanosine (8-OHG). Finally, PtNPs and RA increased the differentiation and expression of differentiation markers. Differentiated SH-SY5Y cells pre-treated with PtNPs or RA or the combination of both were more sensitive to the cytotoxic effect of cisplatin than undifferentiated cells. To our knowledge, this is the first study to demonstrate the effect of the combination of PtNPs and RA in neuroblastoma cells. PtNPs may be a potential preconditioning or adjuvant compound in chemotherapeutic treatment. The results of this study provide a rationale for clinical evaluation of the combination of PtNPs and RA for the treatment of children suffering from high-risk neuroblastoma.
New Era of Diacylglycerol Kinase, Phosphatidic Acid and Phosphatidic Acid-Binding Protein
Authors: Sakane Fumio , Hoshino Fumi , Murakami Chiaki
Published: September 2020

Diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DG) to generate phosphatidic acid (PA). Mammalian DGK consists of ten isozymes (α–κ) and governs a wide range of physiological and pathological events, including immune responses, neuronal networking, bipolar disorder, obsessive-compulsive disorder, fragile X syndrome, cancer, and type 2 diabetes. DG and PA comprise diverse molecular species that have different acyl chains at the sn-1 and sn-2 positions. Because the DGK activity is essential for phosphatidylinositol turnover, which exclusively produces 1-stearoyl-2-arachidonoyl-DG, it has been generally thought that all DGK isozymes utilize the DG species derived from the turnover. However, it was recently revealed that DGK isozymes, except for DGKε, phosphorylate diverse DG species, which are not derived from phosphatidylinositol turnover. In addition, various PA-binding proteins (PABPs), which have different selectivities for PA species, were recently found. These results suggest that DGK–PA–PABP axes can potentially construct a large and complex signaling network and play physiologically and pathologically important roles in addition to DGK-dependent attenuation of DG–DG-binding protein axes. For example, 1-stearoyl-2-docosahexaenoyl-PA produced by DGKδ interacts with and activates Praja-1, the E3 ubiquitin ligase acting on the serotonin transporter, which is a target of drugs for obsessive-compulsive and major depressive disorders, in the brain. This article reviews recent research progress on PA species produced by DGK isozymes, the selective binding of PABPs to PA species and a phosphatidylinositol turnover-independent DG supply pathway.
Cannabidiol Modifies the Formation of NETs in Neutrophils of Psoriatic Patients
Authors: Wójcik Piotr , Garley Marzena , Wroński Adam , Jabłońska Ewa , Skrzydlewska Elżbieta
Published: September 2020

Psoriasis is associated with increased production of reactive oxygen species which leads to oxidative stress. As antioxidants can provide protection, the aim of this study was to evaluate the effects of cannabidiol (CBD) on neutrophil extracellular trap (NET) formation in psoriatic and healthy neutrophils. Important markers of NETosis were measured in healthy and psoriatic neutrophils after incubation with CBD, lipopolysaccharide (LPS), and LPS + CBD). The percentage of neutrophils undergoing NETosis and the level of NETosis markers (cfDNA, MPO, elastase) were higher in the neutrophils and blood plasma of psoriatic patients, compared to controls. After LPS treatment, all of the markers of NETosis, except elastase, and p47 and citrullinated histones, were increased in samples from healthy subjects and psoriasis patients. CBD reduced the concentrations of NETosis markers. This led to a reduction in NETosis, which was more pronounced in psoriatic neutrophils and neutrophils treated with LPS in both psoriatic and healthy participants. These results suggest that psoriatic patients neutrophils are at a higher risk of NETosis both in vitro and in vivo. CBD reduces NETosis, mainly in psoriatic neutrophils, possibly due to its antioxidant properties. The anti-NET properties of CBD suggest the positive effect of CBD in the treatment of autoimmune diseases.
Decreased Expression of Canstatin in Rat Model of Monocrotaline-Induced Pulmonary Arterial Hypertension: Protective Effect of Canstatin on Right Ventricular Remodeling
Authors: Sugiyama Akira , Kaisho Maina , Okada Muneyoshi , Otani Kosuke , Yamawaki Hideyuki
Published: September 2020

Pulmonary arterial hypertension (PAH) is a progressive disease which causes right ventricular (RV) failure. Canstatin, a C-terminal fragment of type IV collagen α2 chain, is expressed in various rat organs. However, the expression level of canstatin in plasma and organs during PAH is still unclear. We aimed to clarify it and further investigated the protective effects of canstatin in a rat model of monocrotaline-induced PAH. Cardiac functions were assessed by echocardiography. Expression levels of canstatin in plasma and organs were evaluated by enzyme-linked immunosorbent assay and Western blotting, respectively. PAH was evaluated by catheterization. RV remodeling was evaluated by histological analyses. Real-time polymerase chain reaction was performed to evaluate RV remodeling-related genes. The plasma concentration of canstatin in PAH rats was decreased, which was correlated with a reduction in acceleration time/ejection time ratio and an increase in RV weight/body weight ratio. The protein expression of canstatin in RV, lung and kidney was decreased in PAH rats. While recombinant canstatin had no effect on PAH, it significantly improved RV remodeling, including hypertrophy and fibrosis, and prevented the increase in RV remodeling-related genes. We demonstrated that plasma canstatin is decreased in PAH rats and that administration of canstatin exerts cardioprotective effects.
The First Record of Monochamus saltuarius (Coleoptera; Cerambycidae) as Vector of Bursaphelenchus xylophilus and Its New Potential Hosts in China
Authors: Li Min , Li Huan , Sheng Ruo-Cheng , Sun Hui , Sun Shou-Hui , Chen Feng-Mao
Published: September 2020

Pine wilt disease was first discovered in Dongtang town, Liaoning Province, China, in 2017. However, no record of Monochamus alteratus existed in Fengcheng, where M. saltuarius is an indigenous insect, and no experimental evidence has thus far indicated that M. saltuarius can transport the Bursaphelenchus xylophilus in China. In this study, we investigated whether M. saltuarius is a vector of B. xylophilus in China. On the sixth day after eclosion, beetles began to transmit nematodes into the twigs. The transmission period of nematodes is known to be able to last for 48 days after beetle emergence. In laboratory experiments, M. saltuarius fed and transmitted B. xylophilus not only on pines but also on other non-Pinus conifers. The non-Pinus conifers preferred by M. saltuarius for feeding are Picea pungens, Picea asperata, and Abies fabri. The experimental results show that M. saltuarius functions as a vector of B. xylophilus in northeast China.
The Use of Vasoactive Drugs in the Treatment of Male Erectile Dysfunction: Current Concepts
Authors: Kedia George T. , Ückert Stefan , Tsikas Dimitrios , Becker Armin J. , Kuczyk Markus A. , Bannowsky Andreas
Published: September 2020

It is widely accepted that disorders of the male (uro)genital tract, such as erectile dysfunction (ED) and benign diseases of the prostate (lower urinary tract symptomatology or benign prostatic hyperplasia), can be approached therapeutically by influencing the function of both the vascular and non-vascular smooth muscle of the penile erectile tissue or the transition zone/periurethral region of the prostate, respectively. As a result of the discovery of nitric oxide (NO) and cyclic guanosine monophosphate (GMP) as central mediators of penile smooth muscle relaxation, the use of drugs known to increase the local production of NO and/or elevate the intracellular level of the second messenger cyclic GMP have attracted broad attention in the treatment of ED of various etiologies. Specifically, the introduction of vasoactive drugs, including orally active inhibitors of the cyclic GMP-specific phosphodiesterase (PDE) 5, has offered great advantage in the pharmacotherapy of ED and other diseases of the genitourinary tract. These drugs have been proven efficacious with a fast on-set of action and an improved profile of side-effects. This review summarizes current strategies for the treatment of ED utilizing the application of vasoactive drugs via the oral, transurethral, topical, or self-injection route.
What Is the Ideal Blood Pressure Threshold for the Prevention of Atrial Fibrillation in Elderly General Population?
Authors: Park Yoon Jung , Yang Pil-Sung , Yu Hee Tae , Kim Tae-Hoon , Jang Eunsun , Uhm Jae-Sun , Pak Hui-Nam , Lee Moon-Hyoung , Lip Gregory Y.H. , Joung Boyoung
Published: September 2020

Intensive blood pressure (BP) lowering in patients with hypertension at increased risk of cardiovascular disease has been associated with a lowered risk of incident atrial fibrillation (AF). It is uncertain whether maintaining the optimal BP levels can prevent AF in the general elderly population. We included 115,866 participants without AF in the Korea National Health Insurance Service-Senior (≥60 years) cohort from 2002 to 2013. We compared the influence of BP on the occurrence of new-onset AF between octogenarians (≥80 years) and non-octogenarians (<80 years) subjects. With up to 6.7 ± 1.7 years of follow-up, 4393 incident AF cases occurred. After multivariable adjustment for potentially confounding clinical covariates, the risk of AF in non-octogenarians was significantly higher in subjects with BP levels of <120/<80 and ≥140/90 mm Hg, with hazard ratios of 1.15 (95% confidence interval (CI), 1.03–1.28; p < 0.001) and 1.14 (95% CI, 1.04–1.26; p < 0.001), compared to the optimal BP levels (120–129/<80 mm Hg). In octogenarians, the optimal BP range was 130–139/80–89 mm Hg, higher than in non-octogenarians. A U-shaped relationship for the development of incident AF was evident in non-octogenarians, and BP levels of 120–129/<80 mm Hg were associated the lowest risk of incident AF. Compared to non-octogenarians, the lowest risk of AF was associated with higher BP levels of 130–139/80–89 mm Hg amongst octogenarians.
Impact of Anticholinergic Medication Burden on Mobility and Falls in the Lifestyle Interventions for Elders (LIFE) Study
Authors: Squires Patrick , Pahor Marco , Manini Todd M. , Vouri Scott , Brown Joshua D.
Published: September 2020

Anticholinergic cognitive burden (ACB) may be associated with detrimental effects on mobility and physical independence in older adults. We evaluated the incidence of major mobility disability (MMD), persistent major mobility disability (PMMD), and injurious falls among participants within the Lifestyle Interventions for Elders (LIFE) trial according to varied anticholinergic burden levels. Participants aged 70–89 years were randomized to a physical activity (PA) or successful aging (SA) intervention and evaluated by ACB medication use as a summed score of a previously developed ACB scale. Confounders included demographic characteristics, physical function, cognitive function, and fall history. Average participant follow-up was 2.6 years and included outcome assessment for MMD, PMMD, and injurious falls every six months. Adjusted proportional hazards models evaluated the independent effects of ACB scores as well as interaction effects with the intervention. Of the 1635 participants, 986 (60%) used ≥1 anticholinergic medication. Compared to those with no burden, participants with an ACB score of 1 demonstrated increased MMD (HR = 1.42 [1.13–1.78]), PMMD (HR = 1.53 [1.12–2.09]), and injurious falls (HR = 1.60 [1.10–2.32]). Results similar in magnitude were observed for all other ACB levels versus the no burden group. Stepwise dose–response comparisons between ACB groupings did not demonstrate significant differences in outcomes. Stratification by PA or SA interventions demonstrated few differences from the combined overall trial results. Compared to those not taking anticholinergic medications, participants taking anticholinergic medications generally demonstrated increased risk of MMD, PMMD, and injurious falls. Total anticholinergic burden was not associated with a stepwise dose–response relationship in mobility disability and may lack sensitivity to capture varied responses.
Unimanual Intensive Therapy with or without Unaffected Hand Containment in Children with Hemiplegia. A Randomized Controlled Pilot Study
Authors: Palomo-Carrión Rocío , Pinero-Pinto Elena , Ando-LaFuente Sara , Ferri-Morales Asunción , Bravo-Esteban Elisabeth , Romay-Barrero Helena
Published: September 2020

Children with hemiplegia have lower spontaneous use and quality of movement in the affected upper limb. The modified constraint-induced movement therapy (mCIMT) is applied to improve the affected upper limb function. The objective of this study was to study the efficacy of unaffected hand containment to obtain changes in the function of the affected upper limb after applying two unimanual therapies. A randomized controlled pilot study was performed with 16 children diagnosed with congenital infantile hemiplegia, with eight children randomized in each group (average age: 5.54 years; SD: 1.55). mCIMT and unimanual therapy without containment (UTWC) were applied, with a total of 50 h distributed in five weeks (two h/per day). Two assessments were performed (pre- and post-treatment) to evaluate the affected upper limb spontaneous use, measured with the Shiners Hospital Upper Extremity Evaluation (SHUEE), and the quality of movement, measured with the Quality of Upper Extremity Skills Test (QUEST scale). The progression of the variables was different in both groups. The results are expressed in the median of the improvement percent and interquartile range (IQR). The spontaneous use analysis showed an improvement percent of 31.65 (IQR: 2.33, 110.42) in the mCIMT group with respect to 0.00 (IQR: 0.00, 0.00) in the UTWC group. The quality of movement increased in the mCIMT and UTWC groups, 24.21 (IQR: 13.44, 50.39), 1.34 (IQR: 0.00, 4.75), respectively and the greatest increase was obtained in the grasp variable for both groups. The use of unaffected hand containment in mCIMT would produce improvements in the affected upper limb functionality in children with hemiplegia (4–8 years old) compared to the same protocol without containment (UTWC).
ROC Analysis Identifies Baseline and Dynamic NLR and dNLR Cut-Offs to Predict ICI Outcome in 402 Advanced NSCLC Patients
Authors: Carnio Simona , Mariniello Annapaola , Pizzutilo Pamela , Numico Gianmauro , Borra Gloria , Lunghi Alice , Soto Parra Hector , Buosi Roberta , Vavalà Tiziana , Stura Ilaria , Genestroni Silvia , Alemanni Alessandra , Arizio Francesca , Catino Annamaria , Montrone Michele , Tabbò Fabrizio , Galetta Domenico , Migliaretti Giuseppe , Novello Silvia
Published: September 2020

Background: Neutrophil-to-Lymphocyte Ratio (NLR) and derived Neutrophils-to-(Leukocytes minus neutrophils) Ratio (dNLR) have been proposed as possible biomarkers of response to immune checkpoint inhibitors (ICI). However, in non-small cell lung cancer (NSCLC) studies, various NLR and/or dNLR cut-offs have been used, manly based on previous reports on melanoma. Methods: In this Italian multicenter retrospective study, NLR, dNLR, platelet-to-lymphocyte ratio, albumin, and lactate dehydrogenase (LDH) were longitudinally assessed in patients with stage IV non-small cell lung cancer (NSCLC) treated with ICI. The primary objective was to evaluate if baseline parameters predicted response to ICI, using Receiver Operating Characteristic (ROC) curves. Secondary endpoint was to evaluate if dynamic changing of NLR and dNLR also predicted response. Results: Data of 402 patients were collected and analyzed. Among the baseline parameters considered, NLR and dNLR were the most appropriate biomarkers according to the ROC analyses, which also identified meaningful cut-offs (NLR = 2.46; dNLR = 1.61). Patients with low ratios reported a significantly improved outcome, in terms of overall survival (p = 0.0003 for NLR; p = 0.0002 for dNLR) and progression free survival (p = 0.0004 for NLR; p = 0.005 for dNLR). The role of NLR and dNLR as independent biomarkers of response was confirmed in the Cox regression model. When assessing NLR and dNLR dynamics from baseline to cycle 3, a decrease ≥1.04 for NLR and ≥0.41 for dNLR also predicted response. Conclusions in our cohort, we confirmed that NLR and dNLR, easily assessable on peripheral blood, can predict response at baseline and early after ICI initiation. For both baseline and dynamic assessment, we identified clinically meaningful cut-offs, using ROC curves.
Bioinformatics Data Mining Repurposes the JAK2 (Janus Kinase 2) Inhibitor Fedratinib for Treating Pancreatic Ductal Adenocarcinoma by Reversing the KRAS (Kirsten Rat Sarcoma 2 Viral Oncogene Homolog)-Driven Gene Signature
Authors: Liu Li-Wei , Hsieh Yao-Yu , Yang Pei-Ming
Published: September 2020

Pancreatic ductal adenocarcinoma (PDAC) is still one of the most aggressive and lethal cancer types due to the late diagnosis, high metastatic potential, and drug resistance. The development of novel therapeutic strategies is urgently needed. KRAS (Kirsten rat sarcoma 2 viral oncogene homolog) is the major driver mutation gene for PDAC tumorigenesis. In this study, we mined cancer genomics data and identified a common KRAS-driven gene signature in PDAC, which is related to cell–cell and cell–extracellular matrix (ECM) interactions. Higher expression of this gene signature was associated with poorer overall survival of PDAC patients. Connectivity Map (CMap) analysis and drug sensitivity profiling predicted that a clinically approved JAK2 (Janus kinase 2)-selective inhibitor, fedratinib (also known as TG-101348), could reverse the KRAS-driven gene signature and exhibit KRAS-dependent anticancer activity in PDAC cells. As an approved treatment for myelofibrosis, the pharmacological and toxicological profiles of fedratinib have been well characterized. It may be repurposed for treating KRAS-driven PDAC in the future.
Liquid lncRNA Biopsy for the Evaluation of Locally Advanced and Metastatic Squamous Cell Carcinomas of the Head and Neck
Authors: Łasińska Izabela , Kolenda Tomasz , Guglas Kacper , Kopczyńska Magda , Sobocińska Joanna , Teresiak Anna , Strzelecki Norbert Oksza , Lamperska Katarzyna , Mackiewicz Andrzej , Mackiewicz Jacek
Published: September 2020

Background: Long non-coding RNA (lncRNA) are RNA molecules that are more than 200 nucleotides long and have the ability to modify the activity of genes. They can be found in both healthy and cancer tissues, as well as in plasma, saliva and other bodily fluids. They can also be used as biomarkers of early detection, prognosis and chemotherapy resistance in several cancer types. Treatment of head and neck squamous cell carcinoma (HNSCC) patients with locally advanced disease is still difficult, and choice of treatment should be based on more precise and available biomarkers, such as those obtained from a liquid biopsy. For improvement of treatment efficacy, identification and clinical implementation of new biomarkers are of the utmost importance. Methods: Plasma samples drawn before (p1) and three cycles post (p2) (TPF: docetaxel, cisplatin, 5-fluorouracil/PF: cisplatin, 5-fluorouracil) chemotherapy from 53 HNSCC patients (17 with locally advanced and 36 with metastatic disease) and 14 healthy volunteers were studied. Expression levels of 90 lncRNA expression were analyzed using the qRT-PCR method, and the obtained results were compared between proper groups. Statistical analyses were carried out using Jupyter Notebooks (5.7.2), Python (ver. 3.6) and GraphPad Prism 8. Results: The study demonstrated the differences between the expressions of several lncRNA in cancer patients’ and healthy volunteers’ plasma, as well as between locally advanced and metastatic patients’ groups. A correlation between the response to systemic therapy and lncRNA expression levels was observed. Patients with a (high/low) expression of Alpha 250 and Emx2os showed statistically significant differences in progression free survival (PFS), as well as for overall survival (OS) depending on the level of Alpha 250, snaR, SNHG1. The univariate and multivariate Cox regression model showed Alpha 250 as the best prognostic factor for HNSCC patients. Conclusions: Liquid biopsies based on lncRNAs are promising diagnostic tools that can be used to differentiate between those with cancer and healthy individuals. Additionally, they can also serve as biomarkers for chemotherapy resistance. An identified, circulating lncRNA Alpha 250 seems to prove the best prognostic biomarker, associated with extended PFS and OS, and should be validated in a larger cohort in the future.
Dairy Joint Ventures in South Africa’s Land and Agrarian Reform Programme: Who Benefits?
Authors: Bunce Brittany
Published: September 2020

Joint Ventures (JVs) between ‘agribusiness’ investors and ‘small farmers’ or ‘customary landowners’ are being promoted in South Africa’s land and agrarian reform programme as a way to include land reform beneficiaries in the country’s competitive agricultural sector. This paper undertakes an in-depth comparative analysis of two JV dairy farms located on irrigation schemes in the former ‘homeland’ of the Ciskei, in South Africa’s Eastern Cape Province. The community, through government investment, brings the fixed assets to the business: land, irrigation infrastructure and milking parlours. The agribusiness partner or ‘sharemilker’ contributes the dairy cows and other movable assets. The paper explores what incentivizes agribusiness partners to enter into these types of ‘sharemilking’ JVs. The research reveals that investing in ‘moveable assets’ is more profitable for agribusiness and is also viewed as a more politically pragmatic way to arrange production in the context of land reform. These arrangements have led to further opportunities for investment in other parts of the dairy value chain. The social relations of production involved in sharemilking JVs also obscure class and race relations in ways that benefit agribusiness partners. Although beneficiaries are receiving benefits in the form of jobs and dividends, which in certain cases make notable contributions to household incomes, the structuring of sharemilking contracts is not a fair return on investment for the customary landowners. It is also argued that the JV model is at risk of equating ‘black emerging farmers’ with a group of ‘beneficiaries’ who are in reality workers and passive recipients of dividends and land rents.
Effects of Different Fertilizer Treatments on Rhizosphere Soil Microbiome Composition and Functions
Authors: Li Yanan , Wang Chengyu , Wang Tianye , Liu Yutao , Jia Shuxia , Gao Yunhang , Liu Shuxia
Published: September 2020

Fertilization influences the soil microbiome. However, little is known about the effects of long-term fertilization on soil microbial metabolic pathways. In this study, we investigated the soil microbiome composition and function and microbial participation in the N cycle according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) functional annotation of different genes in a metagenomic analysis after long-term fertilization. Fertilizer application significantly changed the soil C/N ratio. Chemical fertilizer (NPK) treatment decreased soil pH, and chemical fertilizer combined with straw (NPK+S0.5) treatment increased ammonium nitrogen (NH4+-N) but decreased nitrate nitrogen (NO3−-N). NPK, NPK+S0.5 and S0.5 applications did not change the soil microbiome composition or dominant phylum but changed the relative abundances of microbiome components. Moreover, fertilizer significantly influenced metabolic processes, cellular processes and single-organism processes. Compared with a no-fertilizer treatment (CK), the NPK treatment resulted in more differentially expressed gene (DEG) pathways than the NPK+S0.5 and S0.5 treatments, and these pathways significantly correlated with soil nitrate nitrogen (NO3−-N), available phosphorus (AP) and the moisture content of soil (MC). KEGG analysis found that fertilizer application mainly affected the ribosome, photosynthesis and oxidative phosphorylation pathways. S0.5 and NPK+S0.5 increased microbial nitrogen fixation, and NPK and NPK+S0.5 decreased amoA and amoB and accelerated denitrification. Thus, organic fertilizer increased N fixation and nitrification, and inorganic N fertilizer accelerated denitrification. We found that the function of the soil microbiome under different fertilizer applications could be important for the rational application of fertilizer and for environmental and sustainable development.
Age Hardening Characteristics of an Ultra-Low Carbon Cu Bearing Steel
Authors: Sun Mingxue , Xu Yang
Published: September 2020

We studied the influence of aging temperature on microstructure and mechanical properties in an ultra-low carbon Cu bearing steel in the present study. During the aging process, a continuous recovery of matrix associated with formation and growth of Cu precipitates could be observed during aging processes, exerting significant effects on the mechanical properties of the steel. At aging temperature below 600 °C, the mechanical properties were dominated by the precipitation strengthening effect, leading to excessive matrix strengthening and poor low-temperature toughness. Conversely, steel aged at temperatures above 650 °C exhibited an extraordinary improvement in toughness at the expense of strength, which can be attributed to the synergistic effects of softening matrix, coarsened Cu precipitates and formation of reverted austenite. After aging at 650 °C, reverted austenite formed at the lath boundaries. Increasing the aging temperature to 700 °C lowered the thermal stability of reverted austenite, consequently, the reverted austenite was partially transformed to fresh martensite. After aging at 650 °C for 0.5 h, the mechanical properties were optimized as follows—yield strength = 854 MPa, tensile strength = 990 MPa, elongation = 19.8% and Charpy impact energy = 132 J at −80 °C.
Effects of Adding Neutralized Red Mud on the Hydration Properties of Cement Paste
Authors: Kang Sukpyo , Kang Hyeju , Lee Byoungky
Published: September 2020

Red mud is a highly alkaline waste by-product of the aluminum industry. Although recycling of red mud is being actively researched, a feasible technological solution has not been found yet. In this study, we propose that neutralization of red mud alkalinity could assist in its use as a construction material. Neutralized red mud (LRM + S; pH 6–8) was prepared by adding sulfuric acid to liquefied red mud (LRM; pH 10–12). After adding LRM and LRM + S to cement paste, the heat of hydration, compressive strength, and hydration products were examined. The experiments revealed that the calorific value of the cement paste with LRM was low, and its peak was delayed, when compared with that of plain cement paste (referred to as Plain), whereas the calorific value of the cement paste with LRM + S was similar to that of Plain. At the age of 28 d, the compressive strength of the cement paste with 10% LRM + S was 99% whereas that with 20% LRM was only 55% of the strength of Plain. Thus, our results help to resolve the issue of strength degradation of cementitious materials observed upon the addition of red mud and enable its reuse as a construction material.
Review of Plastic Surgery Biomaterials and Current Progress in Their 3D Manufacturing Technology
Authors: Peng Wei , Peng Zhiyu , Tang Pei , Sun Huan , Lei Haoyuan , Li Zhengyong , Hui Didi , Du Colin , Zhou Changchun , Wang Yongwei
Published: September 2020

Plastic surgery is a broad field, including maxillofacial surgery, skin flaps and grafts, liposuction and body contouring, breast surgery, and facial cosmetic procedures. Due to the requirements of plastic surgery for the biological safety of materials, biomaterials are widely used because of its superior biocompatibility and biodegradability. Currently, there are many kinds of biomaterials clinically used in plastic surgery and their applications are diverse. Moreover, with the rise of three-dimensional printing technology in recent years, the macroscopically more precise and personalized bio-scaffolding materials with microporous structure have made good progress, which is thought to bring new development to biomaterials. Therefore, in this paper, we reviewed the plastic surgery biomaterials and current progress in their 3D manufacturing technology.
Intuitionistic Fuzzy Normed Subrings and Intuitionistic Fuzzy Normed Ideals
Authors: Abed Alhaleem Nour , Ahmad Abd Ghafur
Published: September 2020

The main goal of this paper is to introduce the notion of intuitionistic fuzzy normed rings and to establish basic properties related to it. We extend normed rings by incorporating the idea of intuitionistic fuzzy to normed rings, we develop a new structure of fuzzy rings which will be called an intuitionistic fuzzy normed ring. As an extension of intuitionistic fuzzy normed rings, we define the concept of intuitionistic fuzzy normed subrings and intuitionistic fuzzy normed ideals. Some essential operations specially subset, complement, union, intersection and several properties relating to the notion of generalized intuitionistic fuzzy normed rings are identified. Homomorphism and isomorphism of intuitionistic fuzzy normed subrings are characterized. We identify the image and the inverse image of intuitionistic fuzzy normed subrings under ring homomorphism and study their elementary properties. Some properties of intuitionistic fuzzy normed rings and relevant examples are presented.
Optimising the Preparedness Capacity of Enterprise Resilience Using Mathematical Programming
Authors: Sanchis Raquel , Duran-Heras Alfonso , Poler Raul
Published: September 2020

In today’s volatile business arena, companies need to be resilient to deal with the unexpected. One of the main pillars of enterprise resilience is the capacity to anticipate, prevent and prepare in advance for disruptions. From this perspective, the paper proposes a mixed-integer linear programming (MILP) model for optimising preparedness capacity. Based on the proposed reference framework for enterprise resilience enhancement, the MILP optimises the activation of preventive actions to reduce proneness to disruption. To do so, the objective function minimizes the sum of the annual expected cost of disruptive events after implementing preventive actions and the annual cost of such actions. Moreover, the algorithm includes a constraint capping the investment in preventive actions and an attenuation formula to deal with the joint savings produced by the activation of two or more preventive actions on the same disruptive event. The management and business rationale for proposing the MILP approach is to keep it as simple and comprehensible as possible so that it does not require highly mathematically skilled personnel, thus allowing top managers at enterprises of any size to apply it effortlessly. Finally, a real pilot case study was performed to validate the mathematical formulation.
MHD Radiative Blood Flow Embracing Gold Particles via a Slippery Sheet through an Erratic Heat Sink/Source
Authors: Khan Umair , Shafiq Anum , Zaib Aurang , Sherif El-Sayed M. , Baleanu Dumitru
Published: September 2020

Cancer remains one of the world’s leading healthcare issues, and attempts continue not only to find new medicines but also to find better ways of distributing medications. It is harmful and lethal to most of its patients. The need to selectively deliver cytotoxic agents to cancer cells, to enhance protection and efficacy, has prompted the implementation of nanotechnology in medicine. The latest findings have found that gold nanomaterials can heal and conquer it because the material is studied such as gold (atomic number 79) which produces a large amount of heat and contribute to the therapy of malignant tumors. The purpose of the present study is to research the consequence of heat transport through blood flow (Casson model) that contains gold particles in a slippery shrinking/stretching curved surface. The mathematical modeling of Casson nanofluid containing gold nanomaterials towards the slippery curved shrinking/stretching surface is simplified by utilizing suitable transformation. Numerical dual solutions for the temperature and velocity fields are calculated by using bvp4c methodology in MATLAB. Impacts of related parameters are investigated in the temperature and velocity distribution. The results indicate that the suction parameter accelerates the velocity in the upper branch solution and decelerates it in the lower branch solution, while the temperature diminishes in both solutions. In addition, the Casson parameter shrinks the thickness of the velocity boundary-layer owing to rapid enhancement in the plastic dynamics’ viscosity. Moreover, the nanoparticle volume fraction accelerates the viscosity of blood as well as the thermal conductivity. Thus, findings suggested that gold nanomaterials are useful for drug moving and delivery mechanisms since the velocity boundary is regulated by the volume fraction parameter. Gold nanomaterials also raise the temperature field, so that cancer cells can be destroyed.
Biochemical Characterization of a Novel Endo-1,3-β-Glucanase from the Scallop Chlamys farreri
Authors: Li Zhijian , Liu Weizhi , Lyu Qianqian
Published: September 2020

Endo-1,3-β-glucanases derived from marine mollusks have attracted much attention in recent years because of their unique transglycosylation activity. In this study, a novel endo-1,3-β-glucanase from the scallop Chlamys farreri, named Lcf, was biochemically characterized. Unlike in earlier studies on marine mollusk endo-1,3-β-glucanases, Lcf was expressed in vitro first. Enzymatic analysis demonstrated that Lcf preferred to hydrolyze laminarihexaose than to hydrolyze laminarin. Furthermore, Lcf was capable of catalyzing transglycosylation reactions with different kinds of glycosyl acceptors. More interestingly, the transglycosylation specificity of Lcf was different from that of other marine mollusk endo-1,3-β-glucanases, although they share a high sequence identity. This study enhanced our understanding of the diverse enzymatic specificities of marine mollusk endo-1,3-β-glucanases, which facilitated development of a unique endo-1,3-β-glucanase tool in the synthesis of novel glycosides.
Antifouling Property of Oppositely Charged Titania Nanosheet Assembled on Thin Film Composite Reverse Osmosis Membrane for Highly Concentrated Oily Saline Water Treatment
Authors: Ahmad Nor Akalili , Goh Pei Sean , Zulhairun Abdul Karim , Ismail Ahmad Fauzi
Published: September 2020

With the blooming of oil and gas industries, oily saline wastewater treatment becomes a viable option to resolve the oily water disposal issue and to provide a source of water for beneficial use. Reverse osmosis (RO) has been touted as a promising technology for oily saline wastewater treatment. However, one great challenge of RO membrane is fouling phenomena, which is caused by the presence of hydrocarbon contents in the oily saline wastewater. This study focuses on the fabrication of antifouling RO membrane for accomplishing simultaneous separation of salt and oil. Thin film nanocomposite (TFN) RO membrane was formed by the layer by layer (LbL) assembly of positively charged TNS (pTNS) and negatively charged TNS (nTNS) on the surface of thin film composite (TFC) membrane. The unique features, rendered by hydrophilic TNS bilayer assembled on TFC membrane in the formation of a hydration layer to enhance the fouling resistance by high concentration oily saline water while maintaining the salt rejection, were discussed in this study. The characterization findings revealed that the surface properties of membrane were improved in terms of surface hydrophilicity, surface roughness, and polyamide(PA) cross-linking. The TFC RO membrane coated with 2-bilayer of TNS achieved >99% and >98% for oil and salt rejection, respectively. During the long-term study, the 2TNS-PA TFN membrane outperformed the pristine TFC membrane by exhibiting high permeability and much lower fouling propensity for low to high concentration of oily saline water concentration (1000 ppm, 5000 ppm and 10,000 ppm) over a 960 min operation. Meanwhile, the average permeability of uncoated TFC membrane could only be recovered by 95.7%, 89.1% and 82.9% for 1000 ppm, 5000 ppm and 10,000 ppm of the oily saline feedwater, respectively. The 2TNS-PA TFN membrane achieved almost 100% flux recovery for three cycles by hydraulic washing.
Scale Formation on HSLA Steel during Continuous Casting Part II: The Effect of Surface Conditions
Authors: Pineda Huitron Rosa Maria , Ramírez López Pavel Ernesto , Vuorinen Esa , Nazen Jalali Pooria , Pelcastre Leonardo , Kärkkäinen Maija
Published: September 2020

The present research addresses the effect of surface condition on oxide scale formation at high temperatures such as those experienced during secondary cooling in Continuous Casting. Tests were carried out in clean, as-cast and surfaces covered with casting powder to replicate the oxidation/re-oxidation after the mould. Specimens oxidized at 1000, 1100 and 1200 °C under dry air and water-vapour conditions revealed that the oxide scale formation is strongly influenced by temperature, environmental and surface conditions. The oxide scale thickness increases with temperature alterations in the surface (e.g., as-cast and covered with powder) where oxides and carbonates from the casting powder accelerate oxidation kinetics leading to thick and unstable scales. A high amount of carbon is present on surfaces covered with casting powder where it diffuses through the oxide scale forming CO and CO2 which lead to stress accumulation that makes scales prone to defects such as pores, voids and micro-cracks. Ultimately, if wüstite remains attached to the steel surface or inside oscillation marks, it may disturb heat transfer during secondary cooling which has deep industrial implications for crack formation and overall casting yield. Therefore, accurate insights on scale type and growth mechanisms could lead to accurate control of its formation during casting.
TRIM Proteins and Their Roles in the Influenza Virus Life Cycle
Authors: Lee Hye-Ra , Lee Myoung Kyu , Kim Chan Woo , Kim Meehyein
Published: September 2020

The ubiquitin-proteasome system (UPS) has been recognized for regulating fundamental cellular processes, followed by induction of proteasomal degradation of target proteins, and triggers multiple signaling pathways that are crucial for numerous aspects of cellular physiology. Especially tripartite motif (TRIM) proteins, well-known E3 ubiquitin ligases, emerge as having critical roles in several antiviral signaling pathways against varying viral infections. Here we highlight recent advances in the study of antiviral roles of TRIM proteins toward influenza virus infection in terms of the modulation of pathogen recognition receptor (PRR)-mediated innate immune sensing, direct obstruction of influenza viral propagation, and participation in virus-induced autophagy.