bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimization of Hybrid Ink Formulation and IPL Sintering Process for Ink-Jet 3D Printing
Authors: Lee Jae-Young , Choi Cheong-Soo , Hwang Kwang-Taek , Han Kyu-Sung , Kim Jin-Ho , Nahm Sahn , Kim Bum-Seok
Published: May 2021

Ink-jet 3D printing technology facilitates the use of various materials of ink on each ink-jet head and simultaneous printing of multiple materials. It is suitable for manufacturing to process a complex multifunctional structure such as sensors and printed circuit boards. In this study, a complex structure of a SiO2 insulation layer and a conductive Cu layer was fabricated with photo-curable nano SiO2 ink and Intense Pulsed Light (IPL)-sinterable Cu nano ink using multi-material ink-jet 3D printing technology. A precise photo-cured SiO2 insulation layer was designed by optimizing the operating conditions and the ink rheological properties, and the resistance of the insulation layer was 2.43 × 1013 Ω·cm. On the photo-cured SiO2 insulation layer, a Cu conductive layer was printed by controlling droplet distance. The sintering of the IPL-sinterable nano Cu ink was performed using an IPL sintering process, and electrical and mechanical properties were confirmed according to the annealing temperature and applied voltage. Then, Cu conductive layer was annealed at 100 °C to remove the solvent, and IPL sintered at 700 V. The Cu conductive layer of the complex structure had an electrical property of 29 µΩ·cm and an adhesive property with SiO2 insulation layer of 5B.
Catalytic Conversion of n-C7 Asphaltenes and Resins II into Hydrogen Using CeO2-Based Nanocatalysts
Authors: Medina Oscar E. , Gallego Jaime , Acevedo Sócrates , Riazi Masoud , Ocampo-Pérez Raúl , Cortés Farid B. , Franco Camilo A.
Published: May 2021

This study focuses on evaluating the volumetric hydrogen content in the gaseous mixture released from the steam catalytic gasification of n-C7 asphaltenes and resins II at low temperatures (<230 °C). For this purpose, four nanocatalysts were selected: CeO2, CeO2 functionalized with Ni-Pd, Fe-Pd, and Co-Pd. The catalytic capacity was measured by non-isothermal (from 100 to 600 °C) and isothermal (220 °C) thermogravimetric analyses. The samples show the main decomposition peak between 200 and 230 °C for bi-elemental nanocatalysts and 300 °C for the CeO2 support, leading to reductions up to 50% in comparison with the samples in the absence of nanoparticles. At 220 °C, the conversion of both fractions increases in the order CeO2 < Fe-Pd < Co-Pd < Ni-Pd. Hydrogen release was quantified for the isothermal tests. The hydrogen production agrees with each material’s catalytic activity for decomposing both fractions at the evaluated conditions. CeNi1Pd1 showed the highest performance among the other three samples and led to the highest hydrogen production in the effluent gas with values of ~44 vol%. When the samples were heated at higher temperatures (i.e., 230 °C), H2 production increased up to 55 vol% during catalyzed n-C7 asphaltene and resin conversion, indicating an increase of up to 70% in comparison with the non-catalyzed systems at the same temperature conditions.
Graphene Nanoribbon Gap Waveguides for Dispersionless and Low-Loss Propagation with Deep-Subwavelength Confinement
Authors: Wu Zhiyong , Zhang Lei , Ning Tingyin , Su Hong , Li Irene Ling , Ruan Shuangchen , Zeng Yu-Jia , Liang Huawei
Published: May 2021

Surface plasmon polaritons (SPPs) have been attracting considerable attention owing to their unique capabilities of manipulating light. However, the intractable dispersion and high loss are two major obstacles for attaining high-performance plasmonic devices. Here, a graphene nanoribbon gap waveguide (GNRGW) is proposed for guiding dispersionless gap SPPs (GSPPs) with deep-subwavelength confinement and low loss. An analytical model is developed to analyze the GSPPs, in which a reflection phase shift is employed to successfully deal with the influence caused by the boundaries of the graphene nanoribbon (GNR). It is demonstrated that a pulse with a 4 μm bandwidth and a 10 nm mode width can propagate in the linear passive system without waveform distortion, which is very robust against the shape change of the GNR. The decrease in the pulse amplitude is only 10% for a propagation distance of 1 μm. Furthermore, an array consisting of several GNRGWs is employed as a multichannel optical switch. When the separation is larger than 40 nm, each channel can be controlled independently by tuning the chemical potential of the corresponding GNR. The proposed GNRGW may raise great interest in studying dispersionless and low-loss nanophotonic devices, with potential applications in the distortionless transmission of nanoscale signals, electro-optic nanocircuits, and high-density on-chip communications.
Metabolic Response of Triple-Negative Breast Cancer to Folate Restriction
Authors: Coleman Michael F. , O’Flanagan Ciara H. , Pfeil Alexander J. , Chen Xuewen , Pearce Jane B. , Sumner Susan , Krupenko Sergey A. , Hursting Stephen D.
Published: May 2021

Background: Triple-negative breast cancers (TNBCs), accounting for approximately 15% of breast cancers, lack targeted therapy. A hallmark of cancer is metabolic reprogramming, with one-carbon metabolism essential to many processes altered in tumor cells, including nucleotide biosynthesis and antioxidant defenses. We reported that folate deficiency via folic acid (FA) withdrawal in several TNBC cell lines results in heterogenous effects on cell growth, metabolic reprogramming, and mitochondrial impairment. To elucidate underlying drivers of TNBC sensitivity to folate stress, we characterized in vivo and in vitro responses to FA restriction in two TNBC models differing in metastatic potential and innate mitochondrial dysfunction. Methods: Metastatic MDA-MB-231 cells (high mitochondrial dysfunction) and nonmetastatic M-Wnt cells (low mitochondrial dysfunction) were orthotopically injected into mice fed diets with either 2 ppm FA (control), 0 ppm FA, or 12 ppm FA (supplementation; in MDA-MB-231 only). Tumor growth, metabolomics, and metabolic gene expression were assessed. MDA-MB-231 and M-Wnt cells were also grown in media with 0 or 2.2 µM FA; metabolic alterations were assessed by extracellular flux analysis, flow cytometry, and qPCR. Results: Relative to control, dietary FA restriction decreased MDA-MB-231 tumor weight and volume, while FA supplementation minimally increased MDA-MB-231 tumor weight. Metabolic studies in vivo and in vitro using MDA-MB-231 cells showed FA restriction remodeled one-carbon metabolism, nucleotide biosynthesis, and glucose metabolism. In contrast to findings in the MDA-MB-231 model, FA restriction in the M-Wnt model, relative to control, led to accelerated tumor growth, minimal metabolic changes, and modest mitochondrial dysfunction. Increased mitochondrial dysfunction in M-Wnt cells, induced via chloramphenicol, significantly enhanced responsiveness to the cytotoxic effects of FA restriction. Conclusions: Given the lack of targeted treatment options for TNBC, uncovering metabolic vulnerabilities that can be exploited as therapeutic targets is an important goal. Our findings suggest that a major driver of TNBC sensitivity to folate restriction is a high innate level of mitochondrial dysfunction, which can increase dependence on one-carbon metabolism. Thus, folate deprivation or antifolate therapy for TNBCs with metabolic inflexibility due to their elevated levels of mitochondrial dysfunction may represent a novel precision-medicine strategy.
Starchy Vegetables and Metabolic Syndrome in Costa Rica
Authors: Li Zhongyao , Wang Dongqing , Ruiz-Narváez Edward A. , Peterson Karen E. , Campos Hannia , Baylin Ana
Published: May 2021

Only a few studies primarily examined the associations between starchy vegetables (other than potatoes) and metabolic syndrome (MetS). We aimed to evaluate the association between starchy vegetables consumption and MetS in a population-based sample of Costa Rican adults. We hypothesized that a higher overall intake of starchy vegetables would not be associated with higher MetS prevalence. In this cross-sectional study, log-binomial regression models were used to estimate prevalence ratios (PRs) of MetS across quintiles of total, unhealthy, healthy starchy vegetables, and individual starchy vegetables (potatoes, purple sweet potatoes, etc.), among 1881 Costa Rican adults. Least square means and 95% confidence intervals (CIs) from linear regression models were estimated for each MetS component by categories of starchy vegetable variables. Higher intakes of starchy vegetables were associated with a higher prevalence of MetS in crude models, but no significant trends were observed after adjusting for confounders. A significant inverse association was observed between total starchy and healthy starchy vegetables consumption and fasting blood glucose. In this population, starchy vegetables might be part of a healthy dietary pattern.
Dietary Derived Propionate Regulates Pathogenic Fibroblast Function and Ameliorates Experimental Arthritis and Inflammatory Tissue Priming
Authors: Friščić Jasna , Dürholz Kerstin , Chen Xi , Engdahl Cecilia , Möller Lisa , Schett Georg , Zaiss Mario M. , Hoffmann Markus H.
Published: May 2021

Short-chain fatty acids are gut-bacteria-derived metabolites that execute important regulatory functions on adaptive immune responses, yet their influence on inflammation driven by innate immunity remains understudied. Here, we show that propionate treatment in drinking water or upon local application into the joint reduced experimental arthritis and lowered inflammatory tissue priming mediated by synovial fibroblasts. On a cellular level, incubation of synovial fibroblasts with propionate or a physiological mixture of short-chain fatty acids interfered with production of inflammatory mediators and migration and induced immune-regulatory fibroblast senescence. Our study suggests that propionate mediates its alleviating effect on arthritis by direct abrogation of local arthritogenic fibroblast function.
Time-Restricted Feeding and Metabolic Outcomes in a Cohort of Italian Adults
Authors: Currenti Walter , Buscemi Silvio , Cincione Raffaele Ivan , Cernigliaro Achille , Godos Justyna , Grosso Giuseppe , Galvano Fabio
Published: May 2021

Background: research exploring the effects of food timing and frequency on health and disease is currently ongoing. While there is an increasing body of scientific literature showing the potential health benefits of intermittent fasting (IF) in laboratory settings and in animals, studies regarding IF on humans are limited. Therefore, the objective of this research was to evaluate the relationship between the feeding/fasting time window and metabolic outcomes among adult individuals. Methods: dietary and demographic data of 1936 adult subjects living in the south of Italy were examined. Food frequency questionnaires (FFQ) were administered to determine the period of time between the first and the last meal of a typical day. Subjects were then divided into those with a time feeding window lasting more than 10 h, within 8 h (TRF-8) and within 10 h. Results: after adjustment for potential confounding factors related to eating habits (such as adherence to the Mediterranean diet, having breakfast/dinner), TRF-10 was inversely associated with being overweight/obese (OR = 0.05, 95% CI: 0.01, 0.07), hypertension (OR = 0.24, 95% CI: 0.13, 0.45), and dyslipidemias (OR = 0.26, 95% CI: 0.10, 0.63), while TRF-8 only with being overweight/obese (OR = 0.08, 95% CI: 0.04, 0.15) and hypertension (OR = 0.33, 95% CI: 0.17, 0.60). No associations were found with type-2 diabetes. Conclusions: individuals with a restricted feeding time window were less likely to be overweight, obese and hypertensive. Further studies are needed to clearly validate the results of the present study.
Blinded Oral Challenges with Lactose and Placebo Accurately Diagnose Lactose Intolerance: A Real-Life Study
Authors: Rocco Alba , Compare Debora , Sgamato Costantino , Martino Alberto , De Simone Luca , Coccoli Pietro , Melone Maria Laura , Nardone Gerardo
Published: May 2021

Lactose intolerance (LI) is characterized by diarrhea, abdominal pain, or bloating occurring after lactose consumption in patients with lactose malabsorption. The National Institute of Health (NIH) proposed a double-blind placebo testing to identify LI individuals correctly. However, until now, no study used this approach in a real-life setting. We aimed to assess double-blind placebo challenge accuracy in diagnosing LI in patients with self-reported symptoms of LI. 148 patients with self-reported LI were consecutively enrolled and blindly underwent hydrogen breath test (HBT) after 25 g lactose or 1 g glucose (placebo) load. One week later, the subjects were challenged with the alternative substrate. Each subject completed a validated questionnaire, including five symptoms (diarrhea, abdominal pain, vomiting, bowel sounds, and bloating) scored on a 10-cm visual analog scale. Home questionnaire (HQ) referred to symptoms associated with the consumption of dairy products at home, while lactose questionnaire (LQ) and placebo questionnaire (PQ) referred to symptoms perceived throughout the 4-h after the administration of the substrates, respectively. After lactose load, HBT was positive in 81 patients (55%), of whom 60 (74%) reported relevant symptoms at LQ (lactose malabsorbers, LM). After placebo challenge, 45 out of 60 with a positive lactose challenge did not complain of symptoms and therefore were diagnosed as lactose intolerant, according to NIH definition. The blinded oral challenges with lactose and placebo accurately diagnose LI and identify patients who will likely benefit from a lactose-free diet.
Dietary Fibre Modulates the Gut Microbiota
Authors: Cronin Peter , Joyce Susan A. , O’Toole Paul W. , O’Connor Eibhlís M.
Published: May 2021

Dietary fibre has long been established as a nutritionally important, health-promoting food ingredient. Modern dietary practices have seen a significant reduction in fibre consumption compared with ancestral habits. This is related to the emergence of low-fibre “Western diets” associated with industrialised nations, and is linked to an increased prevalence of gut diseases such as inflammatory bowel disease, obesity, type II diabetes mellitus and metabolic syndrome. The characteristic metabolic parameters of these individuals include insulin resistance, high fasting and postprandial glucose, as well as high plasma cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Gut microbial signatures are also altered significantly in these cohorts, suggesting a causative link between diet, microbes and disease. Dietary fibre consumption has been hypothesised to reverse these changes through microbial fermentation and the subsequent production of short-chain fatty acids (SCFA), which improves glucose and lipid parameters in individuals who harbour diseases associated with dysfunctional metabolism. This review article examines how different types of dietary fibre can differentially alter glucose and lipid metabolism through changes in gut microbiota composition and function.
Children’s Health Habits and COVID-19 Lockdown in Catalonia: Implications for Obesity and Non-Communicable Diseases
Authors: Ventura Paula Sol , Ortigoza Ana F. , Castillo Yanira , Bosch Zelmira , Casals Sara , Girbau Cristina , Siurana Jose M. , Arce Amalia , Torres Marisa , Herrero Francisco J.
Published: May 2021

Lockdown during the COVID-19 pandemic imposed changes in children’s daily routine that could lead to changes in behavior patterns. Using a survey targeted at children under 17 years of age, we described dietary (adherence to Mediterranean diet, AMD) and sleeping habits (disorders of initiating and maintaining sleep) after the implementation of lockdown, and examined the probability of the inadequate frequency of physical activity (PA) and use of TV and electronic devices (TV-ED) before and after lockdown through generalized estimating equation models, accounting for age and gender differences. From 3464 children included, 53.2% showed optimal AMD; 79.2% referred to delayed bedtime; and 16.3% were suspected of sleeping disorders after the implementation of lockdown. Delay in bedtime was more frequent among children older than 6 years, and inadequate sleeping hours among those younger than 11 years. There were no gender differences in AMD or sleeping habits. The odds of inadequate frequency of PA and TV-ED use were greater after lockdown, with a greater risk for TV-ED use. Boys were at greater risk of inadequate PA frequency and TV-ED use. Odds ratio of inadequate PA was greater at older ages. Lockdown could influence changes in children’s habits that could lead to risk factors for non-communicable diseases during adulthood if such behaviors are sustained over time.
Markers of Intestinal Permeability Are Rapidly Improved by Alcohol Withdrawal in Patients with Alcohol-Related Liver Disease
Authors: Jung Finn , Burger Katharina , Staltner Raphaela , Brandt Annette , Mueller Sebastian , Bergheim Ina
Published: May 2021

Changes in intestinal microbiome and barrier function are critical in the development of alcohol-related liver disease (ALD). Here, we determined the effects of a one-week alcohol withdrawal on parameters of intestinal barrier function in heavy drinkers with ALD in comparison to healthy non-drinkers (controls). In serum samples of 17 controls (m = 10/f = 7) and 37 age-matched ALD patients (m = 26/f = 11) undergoing a one-week alcohol withdrawal, markers of liver health and intestinal barrier function were assessed. Liver damage, e.g., fibrosis and hepatic steatosis, were assessed using FibroScan. Before alcohol withdrawal, markers of liver damage, lipopolysaccharide binding protein (LBP) and overall TLR4/TLR2 ligands in serum were significantly higher in ALD patients than in controls, whereas intestinal fatty acid binding protein (I-FABP) and zonulin protein concentrations in serum were lower. All parameters, with the exception of LBP, were significantly improved after alcohol withdrawal; however, not to the level of controls. Our data suggest that one-week of abstinence improves markers of intestinal barrier function and liver health in ALD patients.
Influence of Plant and Animal Proteins on Inflammation Markers among Adults with Chronic Kidney Disease: A Systematic Review and Meta-Analysis
Authors: Aycart Danielle Francesca , Acevedo Sofía , Eguiguren-Jimenez Lucía , Andrade Jeanette Mary
Published: May 2021

Proteins, especially plant proteins, may reduce inflammation among adults with chronic kidney disease (CKD). This systematic review and meta-analysis were conducted to evaluate the effect protein types (animal or plant) have on inflammation markers (CRP, IL-6, TNF-α) among adults with varying stages of CKD. The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) was conducted to identify articles from inception until January 2021, utilizing six databases. Controlled trials that compared the effects of different protein types were analyzed using random-effects meta-analysis. Quality assessment and risk of bias of the included articles were assessed by using Cochrane risk of bias instrument and ROBINS-I. Out of the 10 studies that met the criteria, there was a decreasing trend in CRP levels when consuming plant proteins compared to animal proteins among non-dialysis participants. There was a statistically significant decrease when comparing animal proteins to unspecified proteins in CRP levels among dialysis participants [Hedges’ g = 2.11; 95% CI 1.12, 3.11; p ≤ 0.001], favoring unspecified proteins. Furthermore, animal proteins (eggs, red meat) showed increasing trends in CRP levels compared to whey protein isolate. Caution must be considered regarding these results as controlled, non-randomized, trials were included in the analysis, which may have contributed to high risk of bias. Future research should focus on protein types and the impact they have on kidney disease progression and inflammation markers.
Dysregulation of Glycerophosphocholines in the Cutaneous Lesion Caused by Leishmania major in Experimental Murine Models
Authors: Parab Adwaita R. , Thomas Diane , Lostracco-Johnson Sharon , Siqueira-Neto Jair L. , McKerrow James H. , Dorrestein Pieter C. , McCall Laura-Isobel
Published: May 2021

Cutaneous leishmaniasis (CL) is the most common disease form caused by a Leishmania parasite infection and considered a neglected tropical disease (NTD), affecting 700,000 to 1.2 million new cases per year in the world. Leishmania major is one of several different species of the Leishmania genus that can cause CL. Current CL treatments are limited by adverse effects and rising resistance. Studying disease metabolism at the site of infection can provide knowledge of new targets for host-targeted drug development. In this study, tissue samples were collected from mice infected in the ear or footpad with L. major and analyzed by untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS). Significant differences in overall metabolite profiles were noted in the ear at the site of the lesion. Interestingly, lesion-adjacent, macroscopically healthy sites also showed alterations in specific metabolites, including selected glycerophosphocholines (PCs). Host-derived PCs in the lower m/z range (m/z 200–799) showed an increase with infection in the ear at the lesion site, while those in the higher m/z range (m/z 800–899) were decreased with infection at the lesion site. Overall, our results expanded our understanding of the mechanisms of CL pathogenesis through host metabolism and may lead to new curative measures against infection with Leishmania.
Development and Validation of an Up-to-Date Highly Sensitive UHPLC-MS/MS Method for the Simultaneous Quantification of Current Anti-HIV Nucleoside Analogues in Human Plasma
Authors: De Nicolò Amedeo , Manca Alessandra , Ianniello Alice , Palermiti Alice , Calcagno Andrea , Ferrara Micol , Antonucci Miriam , Cusato Jessica , Avataneo Valeria , De Vivo Elisa , Bonora Stefano , De Rosa Francesco Giuseppe , Di Perri Giovanni , D’Avolio Antonio
Published: May 2021

Therapeutic options to treat HIV infection have widened in the past years, improving both effectiveness and tolerability, but nucleoside reverse transcriptase inhibitors (NRTIs) are still considered the standard backbone of the combination regimens. Therapeutic drug monitoring (TDM) can be useful for these drugs, due to concentration–effect relationship, with risk of ineffectiveness, toxicity or adherence concerns: in this scenario, robust and multiplexed methods are needed for an effective TDM activity. In this work, the first validated ultra-high spectrometry liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) method is described for the high-sensitive simultaneous quantification of all the currently used NRTIs in human plasma, including tenofovir alafenamide (TAF), following FDA and EMA guidelines. The automated sample preparation consisted in the addition of an internal standard (IS) working solution, containing stable-isotope-linked drugs, protein precipitation and drying. Dry extracts were reconstituted with water, then, these underwent reversed phase chromatographic separation: compounds were detected through electrospray ionization and multiple reaction monitoring. Accuracy, precision, recovery and IS-normalized matrix effect fulfilled guidelines’ requirements. The application of this method on samples from people living with HIV (PLWH) showed satisfactory performance, being capable of quantifying the very low concentrations of tenofovir (TFV) in patients treated with TAF.
Current Evidence, Challenges, and Opportunities of Physiologically Based Pharmacokinetic Models of Atorvastatin for Decision Making
Authors: Reig-López Javier , García-Arieta Alfredo , Mangas-Sanjuán Víctor , Merino-Sanjuán Matilde
Published: May 2021

Atorvastatin (ATS) is the gold-standard treatment worldwide for the management of hypercholesterolemia and prevention of cardiovascular diseases associated with dyslipidemia. Physiologically based pharmacokinetic (PBPK) models have been positioned as a valuable tool for the characterization of complex pharmacokinetic (PK) processes and its extrapolation in special sub-groups of the population, leading to regulatory recognition. Several PBPK models of ATS have been published in the recent years, addressing different aspects of the PK properties of ATS. Therefore, the aims of this review are (i) to summarize the physicochemical and pharmacokinetic characteristics involved in the time-course of ATS, and (ii) to evaluate the major highlights and limitations of the PBPK models of ATS published so far. The PBPK models incorporate common elements related to the physicochemical aspects of ATS. However, there are important differences in relation to the analyte evaluated, the type and effect of transporters and metabolic enzymes, and the permeability value used. Additionally, this review identifies major processes (lactonization, P-gp contribution, ATS-Ca solubility, simultaneous management of multiple analytes, and experimental evidence in the target population), which would enhance the PBPK model prediction to serve as a valid tool for ATS dose optimization.
Ferri–Liposomes: Preformulation and Selective Cytotoxicity against A549 Lung Cancer Cells
Authors: de Souza Marina Guedes Fonseca , de Jesus Guedes Fabrícia Nunes , Tebaldi Marli Luiza , do Nascimento Alencar Éverton , Amaral-Machado Lucas , do Egito Eryvaldo Sócrates Tabosa , de Barros André Luis Branco , Soares Daniel Crístian Ferreira
Published: May 2021

Liposomes have become successful nanostructured systems used in clinical practices. These vesicles are able to carry important drug loadings with noteworthy stability. The aim of this work was to develop iron oxide-loaded stealth liposomes as a prospective alternative for the treatment of lung cancer. In this study, citric acid iron oxide nanoparticles (IONPs-Ac) were synthesized and encapsulated in stealth liposomes. Their cytotoxicity and selectivity against lung tumor cells were assessed. Stealth liposomal vesicles, with relevant content of IONPs-Ac, named ferri–liposomes (SL-IONPs-Ac), were produced with an average size of 200 nm. They displayed important cytotoxicity in a human lung cancer cells model (A549 cells), even at low concentrations, whereas free IONPs-Ac displayed adequate biocompatibility. Nevertheless, the treatment at the same concentration of ferri–liposomes against HEK-293 cells, a normal human cell lineage, was not significantly cytotoxic, revealing a probable lung tumor selectiveness of the fabricated formulation. Furthermore, from the flow cytometry studies, it was possible to infer that ferri–liposomes were able to induce A549 tumor cells death through apoptosis/ferroptosis processes, evidenced by a significant reduction of the mitochondrial membrane potential.
Comparative Metabolite Profile, Biological Activity and Overall Quality of Three Lettuce (Lactuca sativa L., Asteraceae) Cultivars in Response to Sulfur Nutrition
Authors: Abdalla Muna Ali , Li Fengjie , Wenzel-Storjohann Arlette , Sulieman Saad , Tasdemir Deniz , Mühling Karl H.
Published: May 2021

The main objective of the present study was to assess the effects of sulfur (S) nutrition on plant growth, overall quality, secondary metabolites, and antibacterial and radical scavenging activities of hydroponically grown lettuce cultivars. Three lettuce cultivars, namely, Pazmanea RZ (green butterhead, V1), Hawking RZ (green multi-leaf lettuce, V2), and Barlach RZ (red multi-leaf, V3) were subjected to two S-treatments in the form of magnesium sulfate (+S) or magnesium chloride (−S). Significant differences were observed under −S treatments, especially among V1 and V2 lettuce cultivars. These responses were reflected in the yield, levels of macro- and micro-nutrients, water-soluble sugars, and free inorganic anions. In comparison with the green cultivars (V1 and V2), the red-V3 cultivar revealed a greater acclimation to S starvation, as evidenced by relative higher plant growth. In contrast, the green cultivars showed higher capabilities in production and superior quality attributes under +S condition. As for secondary metabolites, sixteen compounds (e.g., sesquiterpene lactones, caffeoyl derivatives, caffeic acid hexose, 5-caffeoylquinic acid (5-OCQA), quercetin and luteolin glucoside derivatives) were annotated in all three cultivars with the aid of HPLC-DAD-MS-based untargeted metabolomics. Sesquiterpene lactone lactucin and anthocyanin cyanidin 3-O-galactoside were only detected in V1 and V3 cultivars, respectively. Based on the analyses, the V3 cultivar was the most potent radical scavenger, while V1 and V2 cultivars exhibited antibacterial activity against Staphylococcus aureus in response to S provision. Our study emphasizes the critical role of S nutrition in plant growth, acclimation, and nutritional quality. The judicious-S application can be adopted as a promising antimicrobial prototype for medical applications.
The Road to Better Management in Resistant Hypertension—Diagnostic and Therapeutic Insights
Authors: Bădilă Elisabeta , Japie Cristina , Weiss Emma , Balahura Ana-Maria , Bartoș Daniela , Scafa Udriște Alexandru
Published: May 2021

Resistant hypertension (R-HTN) implies a higher mortality and morbidity compared to non-R-HTN due to increased cardiovascular risk and associated adverse outcomes—greater risk of developing chronic kidney disease, heart failure, stroke and myocardial infarction. R-HTN is considered when failing to lower blood pressure below 140/90 mmHg despite adequate lifestyle measures and optimal treatment with at least three medications, including a diuretic, and usually a blocker of the renin-angiotensin system and a calcium channel blocker, at maximally tolerated doses. Hereby, we discuss the diagnostic and therapeutic approach to a better management of R-HTN. Excluding pseudoresistance, secondary hypertension, white-coat hypertension and medication non-adherence is an important step when diagnosing R-HTN. Most recently different phenotypes associated to R-HTN have been described, specifically refractory and controlled R-HTN and masked uncontrolled hypertension. Optimizing the three-drug regimen, including the diuretic treatment, adding a mineralocorticoid receptor antagonist as the fourth drug, a β-blocker as the fifth drug and an α1-blocker or a peripheral vasodilator as a final option when failing to achieve target blood pressure values are current recommendations regarding the correct management of R-HTN.
A Safety and Tolerability Study of Thin Film Freeze-Dried Tacrolimus for Local Pulmonary Drug Delivery in Human Subjects
Authors: Sahakijpijarn Sawittree , Beg Moeezullah , Levine Stephanie M. , Peters Jay I. , Williams Robert O.
Published: May 2021

Due to the low and erratic bioavailability of oral tacrolimus (TAC), the long-term survival rate following lung transplantation remained low compared to other solid organs. TAC was reformulated and developed as inhaled formulations by thin film freezing (TFF). Previous studies reported that inhaled TAC combined with 50% w/w lactose (LAC) was safe and effective for the treatment of lung transplant rejection in rodent models. In this study, we aimed to investigate the safety and tolerability of TFF TAC-LAC in human subjects. The formulation can be delivered to the lung as colloidal dispersions after reconstitution and as a dry powder. Healthy subjects inhaled TAC-LAC colloidal dispersions at 3 mg TAC/dose via a vibrating mesh nebulizer in the first stage of this study and TAC-LAC dry powder at 3 mg TAC/dose via a single dose dry powder inhaler in the second stage. Our results demonstrated that oral inhalation of TAC-LAC colloidal dispersions and dry powder exhibited low systemic absorption. Additionally, they were well-tolerated with no changes in CBC, liver, kidney, and lung functions. Only mild adverse side effects (e.g., cough, throat irritation, distaste) were observed. In summary, pulmonary delivery of TFF TAC-LAC would be a safe and promising therapy for lung transplant recipients.
Citral-Containing Essential Oils as Potential Tyrosinase Inhibitors: A Bio-Guided Fractionation Approach
Authors: Capetti Francesca , Tacchini Massimo , Marengo Arianna , Cagliero Cecilia , Bicchi Carlo , Rubiolo Patrizia , Sgorbini Barbara
Published: May 2021

Excessive melanin production causes serious dermatological conditions as well as minor aesthetic problems (i.e., freckles and solar lentigo). The downregulation of tyrosinase is a widespread approach for the treatment of such disorders, and plant extracts have often proven to be valuable sources of tyrosinase inhibitors. Citral (a mixture of neral and geranial) is an important fragrance ingredient that has shown anti-tyrosinase potential. It is highly concentrated in the essential oils (EOs) of Cymbopogon schoenanthus (L.) Spreng., Litsea cubeba (Lour.) Pers., Melissa officinalis L., and Verbena officinalis L. However, only L. cubeba EO has been investigated for use as a potential skin-whitening agent. This work evaluates the in vitro tyrosinase inhibitory activity of these EOs and studies, using bio-assay oriented fractionation, whether their differing chemical compositions influence the overall EO inhibitory activities via possible synergistic, additive, and/or competitive interactions between EOs components. The inhibitory activity of C. schoenanthus EO and that of M. officinalis EOs, with negligible (+)-citronellal amounts, were in-line with their citral content. On the other hand, L. cubeba and V. officinalis EOs inhibited tyrosinase to considerably greater extents as they contained β-myrcene, which contributed to the overall EO activities. Similar observations were made for M. officinalis EO, which bears high (+)-citronellal content which increased citral activity.
Tissue-Specific RNA-Seq Analysis and Identification of Receptor-Like Proteins Related to Plant Growth in Capsicum annuum
Authors: Kang Won-Hee , Park Boseul , Lee Junesung , Yeom Seon-In
Published: May 2021

Receptor-like proteins (RLPs) are a gene family of cell surface receptors that are involved in plant growth, development, and disease resistance. In a recent study, 438 pepper RLP genes were identified in the Capsicum annuum genome (CaRLPs) and determined to be present in response to multiple biotic stresses. To further understand the role of CaRLPs in plant growth and development, we analyzed expression patterns of all CaRLPs from various pepper tissues and developmental stages using RNA-seq. Ten CaRLP genes were selected for further analysis according to transcript levels with hierarchical clustering. The selected CaRLP genes displayed similarity of motifs within the same groups and structures typical of RLPs. To examine RLP function in growth and development, we performed loss-of-function analysis using a virus-induced gene silencing system. Three of the ten tested CaRLPs (CaRLP238, 253, and 360) in silenced plants exhibited phenotypic alteration with growth retardation compared to controls. All three gene-silenced peppers showed significant differences in root dry weight. Only CaRLP238 had significant differences in both root and shoot dry weight. Our results suggest that CaRLPs may play important roles in regulation of plant growth and development as well as function in defense responses to biotic stresses in the RLP gene family.
Effect of Pisolithus tinctorious on Physiological and Hormonal Traits in Cistus Plants to Water Deficit: Relationships among Water Status, Photosynthetic Activity and Plant Quality
Authors: Lorente Beatriz , Zugasti Inés , Sánchez-Blanco María Jesús , Nicolás Emilio , Ortuño María Fernanda
Published: May 2021

Cistus species can form ectomycorrhizae and arbuscular mycorrhizal fungus that can bring benefits when plants are under water stress conditions. However, the application of some ectomycorrhizae on the water uptake under drought through physiological traits and hormonal regulation is less known. The experiment was performed during three months in a growth chamber with Cistus albidus plants in which the combined effect of the ectomycorrhiza Pisolithus tinctorious inoculation and two irrigation treatments (control and water-stressed plants) were applied. Irrigation absence caused significant decrease in aerial growth and tended to decrease soil water potential at the root surface, leading to a decrease in leaf water potential. Under these conditions, the abscisic acid and salicylic acid content increased while the precursor of ethylene decreased. Although the mycorrhization percentages were not high, the inoculation of P. tinctorious improved the water status and slightly cushioned the rise in leaf temperature of water-stressed plants. The ectomycorrhiza decreased the scopoletin values in leaves of plants subjected to deficit irrigation, indicating that inoculated plants had been able to synthesize defense mechanisms. Therefore, Pisolithus tinctorious alleviated some of the harmful effects of water scarcity in Cistus plants, being its use a sustainable option in gardening or restoration projects.
Transcriptome Analysis of Arabidopsis thaliana Plants Treated with a New Compound Natolen128, Enhancing Salt Stress Tolerance
Authors: Sako Kaori , Van Ha Chien , Matsui Akihiro , Tanaka Maho , Sato Ayato , Seki Motoaki
Published: May 2021

Salinity stress is a major threat to agriculture and global food security. Chemical priming is a promising approach to improving salinity stress tolerance in plants. To identify small molecules with the capacity to enhance salinity stress tolerance in plants, chemical screening was performed using Arabidopsis thaliana. We screened 6400 compounds from the Nagoya University Institute of Transformative Bio-Molecule (ITbM) chemical library and identified one compound, Natolen128, that enhanced salinity-stress tolerance. Furthermore, we isolated a negative compound of Natolen128, namely Necolen124, that did not enhance salinity stress tolerance, though it has a similar chemical structure to Natolen128. We conducted a transcriptomic analysis of Natolen128 and Necolen124 to investigate how Natolen128 enhances high-salinity stress tolerance. Our data indicated that the expression levels of 330 genes were upregulated by Natolen128 treatment compared with that of Necolen124. Treatment with Natolen128 increased expression of hypoxia-responsive genes including ethylene biosynthetic enzymes and PHYTOGLOBIN, which modulate accumulation of nitric oxide (NO) level. NO was slightly increased in plants treated with Natolen128. These results suggest that Natolen128 may regulate NO accumulation and thus, improve salinity stress tolerance in A. thaliana.
Functional Bionanocomposite Fibers of Chitosan Filled with Cellulose Nanofibers Obtained by Gel Spinning
Authors: Marquez-Bravo Sofia , Doench Ingo , Molina Pamela , Bentley Flor Estefany , Tamo Arnaud Kamdem , Passieux Renaud , Lossada Francisco , David Laurent , Osorio-Madrazo Anayancy
Published: May 2021

Extremely high mechanical performance spun bionanocomposite fibers of chitosan (CHI), and cellulose nanofibers (CNFs) were successfully achieved by gel spinning of CHI aqueous viscous formulations filled with CNFs. The microstructural characterization of the fibers by X-ray diffraction revealed the crystallization of the CHI polymer chains into anhydrous chitosan allomorph. The spinning process combining acidic–basic–neutralization–stretching–drying steps allowed obtaining CHI/CNF composite fibers of high crystallinity, with enhanced effect at incorporating the CNFs. Chitosan crystallization seems to be promoted by the presence of cellulose nanofibers, serving as nucleation sites for the growing of CHI crystals. Moreover, the preferential orientation of both CNFs and CHI crystals along the spun fiber direction was revealed in the two-dimensional X-ray diffraction patterns. By increasing the CNF amount up to the optimum concentration of 0.4 wt % in the viscous CHI/CNF collodion, Young’s modulus of the spun fibers significantly increased up to 8 GPa. Similarly, the stress at break and the yield stress drastically increased from 115 to 163 MPa, and from 67 to 119 MPa, respectively, by adding only 0.4 wt % of CNFs into a collodion solution containing 4 wt % of chitosan. The toughness of the CHI-based fibers thereby increased from 5 to 9 MJ.m−3. For higher CNFs contents like 0.5 wt %, the high mechanical performance of the CHI/CNF composite fibers was still observed, but with a slight worsening of the mechanical parameters, which may be related to a minor disruption of the CHI matrix hydrogel network constituting the collodion and gel fiber, as precursor state for the dry fiber formation. Finally, the rheological behavior observed for the different CHI/CNF viscous collodions and the obtained structural, thermal and mechanical properties results revealed an optimum matrix/filler compatibility and interface when adding 0.4 wt % of nanofibrillated cellulose (CNF) into 4 wt % CHI formulations, yielding functional bionanocomposite fibers of outstanding mechanical properties.
The Quinonoid Zwitterion Interlayer for the Improvement of Charge Carrier Mobility in Organic Field-Effect Transistors
Authors: Luczak Adam , Ruiz Angélina Torres , Pascal Simon , Adamski Adrian , Jung Jarosław , Luszczynska Beata , Siri Olivier
Published: May 2021

The interface between the semiconductor and the dielectric layer plays a crucial role in organic field-effect transistors (OFETs) because it is at the interface that charge carriers are accumulated and transported. In this study, four zwitterionic benzoquinonemonoimine dyes featuring alkyl and aryl N-substituents were used to cover the dielectric layers in OFET structures. The best interlayer material, containing aliphatic side groups, increased charge carrier mobility in the measured systems. This improvement can be explained by the reduction in the number of the charge carrier trapping sites at the dielectric active layer interface from 1014 eV−1 cm−2 to 2 × 1013 eV−1 cm−2. The density of the traps was one order of magnitude lower compared to the unmodified transistors. This resulted in an increase in charge carrier mobility in the tested poly [2,5-(2-octyldodecyl)-3,6-diketopyrrolopyrrole-alt-5,5-(2,5-di(thien-2-yl)thieno [3,2-b]thiophene)] (DPPDTT)-based transistors to 5.4 × 10−1 cm2 V−1 s−1.
Biofabrication of a Tubular Model of Human Urothelial Mucosa Using Human Wharton Jelly Mesenchymal Stromal Cells
Authors: Garzón Ingrid , Jaimes-Parra Boris Damián , Pascual-Geler Manrique , Cózar José Manuel , Sánchez-Quevedo María del Carmen , Mosquera-Pacheco María Auxiliadora , Sánchez-Montesinos Indalecio , Fernández-Valadés Ricardo , Campos Fernando , Alaminos Miguel
Published: May 2021

Several models of bioartificial human urothelial mucosa (UM) have been described recently. In this study, we generated novel tubularized UM substitutes using alternative sources of cells. Nanostructured fibrin–agarose biomaterials containing fibroblasts isolated from the human ureter were used as stroma substitutes. Then, human Wharton jelly mesenchymal stromal cells (HWJSC) were used to generate an epithelial-like layer on top. Three differentiation media were used for 7 and 14 days. Results showed that the biofabrication methods used here succeeded in generating a tubular structure consisting of a stromal substitute with a stratified epithelial-like layer on top, especially using a medium containing epithelial growth and differentiation factors (EM), although differentiation was not complete. At the functional level, UM substitutes were able to synthesize collagen fibers, proteoglycans and glycosaminoglycans, although the levels of control UM were not reached ex vivo. Epithelial differentiation was partially achieved, especially with EM after 14 days of development, with expression of keratins 7, 8, and 13 and pancytokeratin, desmoplakin, tight-junction protein-1, and uroplakin 2, although at lower levels than controls. These results confirm the partial urothelial differentiative potential of HWJSC and suggest that the biofabrication methods explored here were able to generate a potential substitute of the human UM for future clinical use.
Constant Temperature Approach for the Assessment of Injection Molding Parameter Influence on the Fatigue Behavior of Short Glass Fiber Reinforced Polyamide 6
Authors: Mrzljak Selim , Delp Alexander , Schlink André , Zarges Jan-Christoph , Hülsbusch Daniel , Heim Hans-Peter , Walther Frank
Published: May 2021

Short glass fiber reinforced plastics (SGFRP) offer superior mechanical properties compared to polymers, while still also enabling almost unlimited geometric variations of components at large-scale production. PA6-GF30 represents one of the most used SGFRP for series components, but the impact of injection molding process parameters on the fatigue properties is still insufficiently investigated. In this study, various injection molding parameter configurations were investigated on PA6-GF30. To take the significant frequency dependency into account, tension–tension fatigue tests were performed using multiple amplitude tests, considering surface temperature-adjusted frequency to limit self-heating. The frequency adjustment leads to shorter testing durations as well as up to 20% higher lifetime under fatigue loading. A higher melt temperature and volume flow rate during injection molding lead to an increase of 16% regarding fatigue life. In situ X-ray microtomography analysis revealed that this result was attributed to a stronger fiber alignment with larger fiber lengths in the flow direction. Using digital volume correlation, differences of up to 100% in local strain values at the same stress level for different injection molding process parameters were identified. The results prove that the injection molding parameters have a high influence on the fatigue properties and thus offer a large optimization potential, e.g., with regard to the component design.
Actuator Behaviour of Tailored Poly(thiourethane) Shape Memory Thermosets
Authors: Gamardella Francesco , Serra Angels , Ramis Xavier , De la Flor Silvia
Published: May 2021

In this work, a new family of poly(thiourethane) shape memory thermosetting actuators was developed and characterized. These materials can be easily prepared from mixtures of two different aliphatic diisocyanates and a trithiol in the presence of a latent catalyst, allowing an easy manipulation of the formulation. Rheological studies of the curing process confirm the latent character of the formulations. The glass transition temperatures and the mechanical properties can be modified by varying the proportion of diisocyanates (hexamethylene diisocyanate, HDI, and isophorone diisocyanate, IPDI) with stoichiometric amounts of trimethylolpropane tris(3-mercaptopropionate). The shape-memory behavior was deeply investigated under three different conditions: unconstrained, partially constrained, and fully constrained. Tests were performed in single cantilever bending mode to simulate conditions closer to real complex mechanics of thermomechanical actuators under flexural performances. The complex recovery process in single cantilever bending mode was compared with that obtained using tensile mode. The results evidenced that the amount of recovery force in fully constrained conditions, or energy released during the recovery process in partially constrained, can be modulated by simply changing the proportion of both diisocyanates. A simple model based on Timoshenko beam theory was used for the prediction of the amount of work performed. The reported results are an important guideline to design shape-memory materials based on poly(thiourethane) networks, establishing criteria for the choice of the material depending on the expected application.