bluuebunny/crossref_metadata_2025 huggingface dataset:
Ab Initio Molecular Dynamics Simulations of the Interaction between Organic Phosphates and Goethite
Authors: Ganta Prasanth B. , Kühn Oliver , Ahmed Ashour A.
Published: December 2020

Today’s fertilizers rely heavily on mining phosphorus (P) rocks. These rocks are known to become exhausted in near future, and therefore effective P use is crucial to avoid food shortage. A substantial amount of P from fertilizers gets adsorbed onto soil minerals to become unavailable to plants. Understanding P interaction with these minerals would help efforts that improve P efficiency. To this end, we performed a molecular level analysis of the interaction of common organic P compounds (glycerolphosphate (GP) and inositol hexaphosphate (IHP)) with the abundant soil mineral (goethite) in presence of water. Molecular dynamics simulations are performed for goethite–IHP/GP–water complexes using the multiscale quantum mechanics/molecular mechanics method. Results show that GP forms monodentate (M) and bidentate mononuclear (B) motifs with B being more stable than M. IHP interacts through multiple phosphate groups with the 3M motif being most stable. The order of goethite–IHP/GP interaction energies is GP M < GP B < IHP M < IHP 3M. Water is important in these interactions as multiple proton transfers occur and hydrogen bonds are formed between goethite–IHP/GP complexes and water. We also present theoretically calculated infrared spectra which match reasonably well with frequencies reported in literature.
Recent Advances in Nanomicelles Delivery Systems
Authors: Tawfik Salah M. , Azizov Shavkatjon , Elmasry Mohamed R. , Sharipov Mirkomil , Lee Yong-Ill
Published: December 2020

The efficient and selective delivery of therapeutic drugs to the target site remains the main obstacle in the development of new drugs and therapeutic interventions. Up until today, nanomicelles have shown their prospective as nanocarriers for drug delivery owing to their small size, good biocompatibility, and capacity to effectively entrap lipophilic drugs in their core. Nanomicelles are formed via self-assembly in aqueous media of amphiphilic molecules into well-organized supramolecular structures. Molecular weights and structure of the core and corona forming blocks are important properties that will determine the size of nanomicelles and their shape. Selective delivery is achieved via novel design of various stimuli-responsive nanomicelles that release drugs based on endogenous or exogenous stimulations such as pH, temperature, ultrasound, light, redox potential, and others. This review summarizes the emerging micellar nanocarriers developed with various designs, their outstanding properties, and underlying principles that grant targeted and continuous drug delivery. Finally, future perspectives, and challenges for nanomicelles are discussed based on the current achievements and remaining issues.
Color Centers Enabled by Direct Femto-Second Laser Writing in Wide Bandgap Semiconductors
Authors: Castelletto Stefania , Maksimovic Jovan , Katkus Tomas , Ohshima Takeshi , Johnson Brett C. , Juodkazis Saulius
Published: December 2020

Color centers in silicon carbide are relevant for applications in quantum technologies as they can produce single photon sources or can be used as spin qubits and in quantum sensing applications. Here, we have applied femtosecond laser writing in silicon carbide and gallium nitride to generate vacancy-related color centers, giving rise to photoluminescence from the visible to the infrared. Using a 515 nm wavelength 230 fs pulsed laser, we produce large arrays of silicon vacancy defects in silicon carbide with a high localization within the confocal diffraction limit of 500 nm and with minimal material damage. The number of color centers formed exhibited power-law scaling with the laser fabrication energy indicating that the color centers are created by photoinduced ionization. This work highlights the simplicity and flexibility of laser fabrication of color center arrays in relevant materials for quantum applications.
Electrical Excitation Decay Time in Chains of Nanoscale Non-Point Dipoles
Authors: Fateev Evgeny G.
Published: December 2020

On the basis of a previously developed model of disperse systems containing non-point dipole particles self-assembled into chains inside a liquid substrate, the decay time of electrical excitations induced in dipoles by an external field is investigated. It was shown that when the external field is completely turned off (from 10−6 V / m to 106 V / m levels) at biologically significant low frequencies (for example, 13 Hz), the decay time of the excitations of nanoscale dipoles nonlinearly depends on the chain length. It was found that the decay time of excitations increases sharply (by four to five orders of magnitude), with an increase in the chain length more than 19–20 dipoles.
Substrates for Surface-Enhanced Raman Scattering Formed on Nanostructured Non-Metallic Materials: Preparation and Characterization
Authors: Krajczewski Jan , Ambroziak Robert , Kudelski Andrzej
Published: December 2020

The efficiency of the generation of Raman spectra by molecules adsorbed on some substrates (or placed at a very close distance to some substrates) may be many orders of magnitude larger than the efficiency of the generation of Raman spectra by molecules that are not adsorbed. This effect is called surface-enhanced Raman scattering (SERS). In the first SERS experiments, nanostructured plasmonic metals have been used as SERS-active materials. Later, other types of SERS-active materials have also been developed. In this review article, various SERS substrates formed on nanostructured non-metallic materials, including non-metallic nanostructured thin films or non-metallic nanoparticles covered by plasmonic metals and SERS-active nanomaterials that do not contain plasmonic metals, are described. Significant advances for many important applications of SERS spectroscopy of substrates based on nanostructured non-metallic materials allow us to predict a large increase in the significance of such nanomaterials in the near future. Some future perspectives on the application of SERS substrates utilizing nanostructured non-metallic materials are also presented.
Titanium Nitride Nanodonuts Synthesized from Natural Ilmenite Ore as a Novel and Efficient Thermoplasmonic Material
Authors: Thi Le Thanh-Lieu , Nguyen Lam Tan , Nguyen Hoai-Hue , Nghia Nguyen Van , Vuong Nguyen Minh , Hieu Hoang Nhat , Thang Nguyen Van , Le Viet Thong , Nguyen Viet Huong , Lin Pin-Cheng , Yadav Anupam , Madarevic Ivan , Janssens Ewald , Bui Hao Van , Ngoc Loan Le Thi
Published: December 2020

Nanostructures of titanium nitride (TiN) have recently been considered as a new class of plasmonic materials that have been utilized in many solar energy applications. This work presents the synthesis of a novel nanostructure of TiN that has a nanodonut shape from natural ilmenite ore using a low-cost and bulk method. The TiN nanodonuts exhibit strong and spectrally broad localized surface plasmon resonance absorption in the visible region centered at 560 nm, which is well suited for thermoplasmonic applications as a nanoscale heat source. The heat generation is investigated by water evaporation experiments under simulated solar light, demonstrating excellent solar light harvesting performance of the nanodonut structure.
Steviol Glycosides Supplementation Affects Lipid Metabolism in High-Fat Fed STZ-Induced Diabetic Rats
Authors: Kurek Jakub Michał , Król Ewelina , Krejpcio Zbigniew
Published: December 2020

A number of health-promoting properties of Stevia rebaudiana Bertoni and its glycosides, including the antihyperglycemic activity, have been found. The mechanisms of the antidiabetic action of stevia have not been fully understood. The aim of this study was to evaluate the effects of supplementary steviol glycosides on high-fat fed streptozotocin-induced diabetic rats with particular attention to lipid metabolism. The experiment was conducted on 70 male Wistar rats, of which 60 were fed a high-fat diet for 8 weeks followed by intraperitoneal injection of streptozotocin, to induce type 2 diabetes. Afterwards, rats were divided into six groups and fed a high-fat diet supplemented with pure stevioside or rebaudioside A, at two levels (500 or 2500 mg/kg body weight (b.w.)) for 5 weeks. Three additional groups: diabetic untreated, diabetic treated with metformin, and healthy, served as respective controls. Blood and dissected internal organs were collected for hematological, biochemical, and histopathological tests. It was found that dietary supplementation with steviol glycosides did not affect blood glucose, insulin, and insulin resistance indices, antioxidant biomarkers, but normalized hyperlipidemia and affected the appetite, as well as attenuated blood liver and kidney function indices, and reduced tissular damage in diabetic rats. Steviol glycosides normalize lipid metabolism and attenuate internal organs damage in diabetes.
Eight Days of Water-Only Fasting Promotes Favorable Changes in the Functioning of the Urogenital System of Middle-Aged Healthy Men
Authors: Letkiewicz Sławomir , Pilis Karol , Ślęzak Andrzej , Pilis Anna , Pilis Wiesław , Żychowska Małgorzata , Langfort Józef
Published: December 2020

The aim of this study was to determine whether, after 8 days of water-only fasting, there are changes in the efficiency of the lower urinary tract, the concentration of sex hormones, and the symptoms of prostate diseases in a group of middle-aged men (n = 14). For this purpose, before and after 8 days of water-only fasting (subjects drank ad libitum moderately mineralized water), and the following somatic and blood concentration measurements were made: total prostate specific antigen (PSA-T), free prostate specific antigen (PSA-F), follicle stimulating hormone (FSH), luteotropic hormone (LH), prolactin (Pr), total testosterone (T-T), free testosterone (T-F), dehydroepiandrosterone (DHEA), sex hormone globulin binding (SHGB), total cholesterol (Ch-T), β-hydroxybutyrate (β-HB). In addition, prostate volume (PV), volume of each testis (TV), total volume of both testes (TTV), maximal urinary flow rate (Qmax), and International Prostate Symptom Score (IPSS) values were determined. The results showed that after 8 days of water-only fasting, Qmax and IPSS improved but PV and TTV decreased significantly. There was also a decrease in blood levels of PSA-T, FSH, P, T-T, T-F, and DHEA, but SHGB concentration increased significantly. These results indicate that 8 days of water-only fasting improved lower urinary tract functions without negative health effects.
Effects of Nutrient Intake on Diagnostic Measures of Sarcopenia among Arab Men: A Cross-Sectional Study
Authors: Alhussain Maha H. , Alkahtani Shaea , Aljuhani Osama , Habib Syed Shahid
Published: December 2020

Sarcopenia is a major public health condition and is, therefore, of great clinical interest. However, the role of nutrient intake in sarcopenia is unclear. We examined the associations between nutrient intake and diagnostic measures of sarcopenia, including low muscle mass (appendicular lean mass (ALM) divided by height squared, ALM/h2) and strength (hand-grip strength, HGS) among Arab men. This cross-sectional study included 441 men aged 46.8 ± 15.98 years. Habitual nutrient intake was assessed using a food frequency questionnaire (FFQ). Participants were classified according to different ALM/h2 and HGS reference values. Participants with normal muscle mass, defined by an ALM/h2 cutoff of <8.68 kg/m2 (−1 standard deviation (SD) <reference values Arab men), had greater daily energy, protein and fat intake, and percentage of energy from protein and fat (p < 0.01). Conversely, normal muscle mass was associated with a lower percentage of energy from carbohydrates (CHO) (p < 0.001). Regarding muscle strength, participants with HGS above 42 kg (median HGS of Arab men) had higher daily energy and protein and fat intake, but a lower percentage of energy from CHO and a lower intake of total omega-3 fatty acids (p < 0.05). Individuals with normal muscle mass and high HGS have greater daily energy, protein, and fat intake and a lower percentage of energy from CHO compared to sarcopenic individuals.
Associations between Dietary Glycemic Index and Glycemic Load Values and Cardiometabolic Risk Factors in Adults: Findings from the China Health and Nutrition Survey
Authors: Li Minjuan , Cui Zhixin , Meng Shuangli , Li Ting , Kang Tong , Ye Qi , Cao Mengting , Bi Yuxin , Meng Huicui
Published: December 2020

Studies investigating the associations between dietary glycemic index (GI) and glycemic load (GL) values and cardiometabolic risk factors (CMRF) among Chinese populations are strikingly limited. To assess the associations between dietary GI and GL values and CMRF, including dyslipidemia, hyperglycemia, and hyperuricemia in Chinese adults, we extracted data of 7886 apparently healthy adults from the 2009 wave of the China Health and Nutrition Survey. Dietary GI and GL values were calculated using data collected from three consecutive 24 h dietary recalls. Fasting lipid, glucose, and uric acid concentrations were measured and CMRF were defined on the basis of established criteria. There were no significant associations between dietary GI values and CMRF, and analyzing the data by age, sex, body mass index (BMI), and region did not alter these results. Dietary GL values were positively associated with prevalence of hyperuricemia in all participants (Q4 compared with Q1: odds ratio (OR) = 1.46; 95% CI: 1.14, 1.87; p-trend = 0.0030) and prevalence of hypercholesterolemia in participants ≥ 60 years old (Q5 compared with Q1: OR = 1.72; 95% CI: 1.11, 2.68; p-trend < 0.0010). Higher dietary GL but not GI values were associated with increased prevalence of hyperuricemia in apparently healthy Chinese adults and hypercholesterolemia in older Chinese adults. Further studies are required to confirm the public health implication of these findings.
Healthy Eating Index and Nutrition Biomarkers among Army Soldiers and Civilian Control Group Indicate an Intervention Is Necessary to Raise Omega-3 Index and Vitamin D and Improve Diet Quality
Authors: Rittenhouse Melissa , Scott Jonathan , Deuster Patricia
Published: December 2020

Diet quality and nutrition status are important for optimal health and military performance. Few studies have simultaneously evaluated diet quality and biochemical markers of nutritional status of military service members. The Healthy Eating Index (HEI) can be used to assess dietary quality and adherence to federal nutrition guidelines. The aim of this study was to assess soldiers’ diet quality and nutritional status and compare results to a civilian control group. Methods: A cross-sectional study was conducted with 531 soldiers. A food frequency questionnaire was used to calculate HEI scores. A blood sample was collected for analysis of select nutrition biochemical markers. Non-parametric analyses were conducted to compare the diet quality and nutritional status of soldiers and controls. Differences in non-normally distributed variables were determined by using the Wilcoxon signed-rank test. Results: Soldiers had an HEI score of 59.9 out of 100, marginally higher than the control group (55.4). Biochemical markers of interest were within normal reference values for soldiers, except for the omega-3 index and vitamin D. Conclusions: This study identified dietary components that need improvement and deficits in biochemical markers among soldiers. Improving diet quality and nutritional status should lead to better health, performance, and readiness of the force.
Serum 25-Hydroxyvitamin D Is Inversely Associated with Monocyte Percentage to HDL Cholesterol Ratio among Young Healthy Adults in Qatar
Authors: Mousa Hanaa , Islam Nazmul , Ganji Vijay , Zughaier Susu M.
Published: December 2020

Low serum 25-hydroxyvitamin D [25(OH)D] is linked to an altered lipid profile. Monocytes play an important role in inflammation and lipid metabolism. Recently, monocyte percentage to HDL-cholesterol ratio (MHR) has emerged as a novel marker of inflammation. We investigated the association between serum 25(OH)D concentrations and MHR and serum lipids in young healthy adults. Data from the Qatar Biobank were utilized to investigate the relation between serum 25(OH)D and inflammation and serum lipid concentrations in healthy Qatari adults using multivariate regression analysis. Prevalence of serum 25(OH)D concentrations <12 ng/mL (deficiency), 12–20 ng/mL (insufficiency), and ≥20 ng/mL (sufficiency) were 55.8%, 29.9%, and 14.3%, respectively. Serum 25(OH)D was significantly inversely associated with monocyte percentage, MHR, total cholesterol, LDL-cholesterol, and triacylglycerol in multivariable adjusted analysis. MHR could be a potential biomarker to predict cardiometabolic diseases among young healthy Qataris.
Application of a Latent Transition Model to Estimate the Usual Prevalence of Dietary Patterns
Authors: Oliveira Andreia , Lopes Carla , Torres Duarte , Ramos Elisabete , Severo Milton
Published: December 2020

Background: This study aims to derive habitual dietary patterns of the Portuguese adult population by applying two methodological approaches: a latent class model and a latent transition model. The novel application of the latent transition model allows us to determine the day-to-day variability of diet and to calculate the usual prevalence of dietary patterns. Methods: Participants are from the National Food, Nutrition and Physical Activity Survey of the Portuguese population, 2015–2016 (2029 women; 1820 men, aged ≥18 years). Diet was collected by two 24 h dietary recalls (8–15 days apart). Dietary patterns were derived by: (1) a latent class model using the arithmetic mean of food weigh intake, with concomitant variables (age and sex); (2) a latent transition model allowing the transition from one pattern to another, with the same concomitant variables. Results: Six dietary patterns were identified by a latent class model. By using a latent transition model, three dietary patterns were identified: “In-transition to Western” (higher red meat and alcohol intake; followed by middle-aged men), “Western” (higher meats/eggs and energy-dense foods intake; followed by younger men), and “Traditional-Healthier” (higher intake of fruit, vegetables and fish, characteristic of older women). Most individuals followed the same pattern on both days, but around 26% transited between “In-transition to Western” and “Western”. The prevalence of the dietary patterns using a single recall day (40%, 27%, 33%, respectively) is different from the usual prevalence obtained by the latent transition probabilities (48%, 36%, 16%). Conclusion: Three dietary patterns, largely dependent on age and sex, were identified for the Portuguese adult population: “In-transition to Western” (48%), “Western” (36%), and “Traditional-Healthier” (16%), but 26% were transient between patterns. Dietary patterns are, in general, deviating from traditional habits.
Hepatorenal Tyrosinaemia: Impact of a Simplified Diet on Metabolic Control and Clinical Outcome
Authors: Bärhold Friederike , Meyer Uta , Neugebauer Anne-Kathrin , Thimm Eva Maria , Lier Dinah , Rosenbaum-Fabian Stefanie , Och Ulrike , Fekete Anna , Möslinger Dorothea , Rohde Carmen , Beblo Skadi , Hochuli Michel , Bogovic Nina , Korpel Vanessa , vom Dahl Stephan , Mayorandan Sebene , Fischer Aleksandra , Freisinger Peter , Dokoupil Katharina , Heddrich-Ellerbrok Margret , Jörg-Streller Monika , van Teeffelen-Heithoff Agnes , Lahl Janina , Das Anibh Martin
Published: December 2020

Background: Tyrosinaemia type 1 is a rare inherited metabolic disease caused by an enzyme defect in the tyrosine degradation pathway. It is treated using nitisinone and a low-protein diet. In a workshop in 2013, a group of nutritional specialists from Germany, Switzerland and Austria agreed to advocate a simplified low-protein diet and to allow more natural protein intake in patients with tyrosinaemia type 1. This retrospective study evaluates the recommendations made at different treatment centers and their impact on clinical symptoms and metabolic control. Methods: For this multicenter study, questionnaires were sent to nine participating treatment centers to collect data on the general therapeutic approach and data of 47 individual patients treated by those centers. Results: Dietary simplification allocating food to 3 categories led to increased tyrosine and phenylalanine blood concentrations without weighing food. Phenylalanine levels were significantly higher in comparison to a strict dietary regimen whereas tyrosine levels in plasma did not change. Non-inferiority was shown for the simplification and liberalization of the diet. Compliance with dietary recommendations was higher using the simplified diet in comparison to the stricter approach. Age correlates negatively with compliance. Conclusions: Simplification of the diet with increased natural protein intake based on three categories of food may be implemented in the diet of patients with tyrosinaemia type 1 without significantly altering metabolic control. Patient compliance is strongly influencing tyrosine blood concentrations. A subsequent prospective study with a larger sample size is necessary to get a better insight into the effect of dietary recommendations on metabolic control.
NLRP1 Functions Downstream of the MAPK/ERK Signaling via ATF4 and Contributes to Acquired Targeted Therapy Resistance in Human Metastatic Melanoma
Authors: Zhai Zili , Vaddi Prasanna K. , Samson Jenny Mae , Takegami Tomoya , Fujita Mayumi
Published: December 2020

The BRAF V600E mutation leads to constitutive activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway and its downstream effector responses. Uncovering the hidden downstream effectors can aid in understanding melanoma biology and improve targeted therapy efficacy. The inflammasome sensor, NACHT, LRR, and PYD domains-containing protein 1 (NLRP1), is responsible for IL-1β maturation and itself is a melanoma tumor promoter. Here, we report that NLRP1 is a downstream effector of MAPK/ERK signaling through the activating transcription factor 4 (ATF4), creating regulation in metastatic melanoma cells. We confirmed that the NLRP1 gene is a target of ATF4. Interestingly, ATF4/NLRP1 regulation by the MAPK/ERK pathway uses distinct mechanisms in melanoma cells before and after the acquired resistance to targeted therapy. In parental cells, ATF4/NLRP1 is regulated by the MAPK/ERK pathway through the ribosomal S6 kinase 2 (RSK2). However, vemurafenib (VEM) and trametinib (TRA)-resistant cells lose the signaling via RSK2 and activate the cAMP/protein kinase A (PKA) pathway to redirect ATF4/NLRP1. Therefore, NLRP1 expression and IL-1β secretion were downregulated in response to VEM and TRA in parental cells but enhanced in drug-resistant cells. Lastly, silencing NLRP1 in drug-resistant cells reduced their cell growth and inhibited colony formation. In summary, we demonstrated that NLRP1 functions downstream of the MAPK/ERK signaling via ATF4 and is a player of targeted therapy resistance in melanoma. Targeting NLRP1 may improve the therapeutic efficacy of targeted therapy in melanoma.
Copper(II) and Zinc(II) Complexes with the Clinically Used Fluconazole: Comparison of Antifungal Activity and Therapeutic Potential
Authors: Stevanović Nevena Lj. , Aleksic Ivana , Kljun Jakob , Skaro Bogojevic Sanja , Veselinovic Aleksandar , Nikodinovic-Runic Jasmina , Turel Iztok , Djuran Miloš I. , Glišić Biljana Đ.
Published: December 2020

Copper(II) and zinc(II) complexes with clinically used antifungal drug fluconazole (fcz), {[CuCl2(fcz)2].5H2O}n, 1, and {[ZnCl2(fcz)2]·2C2H5OH}n, 2, were prepared and characterized by spectroscopic and crystallographic methods. The polymeric structure of the complexes comprises four fluconazole molecules monodentately coordinated via the triazole nitrogen and two chlorido ligands. With respect to fluconazole, complex 2 showed significantly higher antifungal activity against Candida krusei and Candida parapsilosis. All tested compounds reduced the total amount of ergosterol at subinhibitory concentrations, indicating that the mode of activity of fluconazole was retained within the complexes, which was corroborated via molecular docking with cytochrome P450 sterol 14α-demethylase (CYP51) as a target. Electrostatic, steric and internal energy interactions between the complexes and enzyme showed that 2 has higher binding potency to this target. Both complexes showed strong inhibition of C. albicans filamentation and biofilm formation at subinhibitory concentrations, with 2 being able to reduce the adherence of C. albicans to A549 cells in vitro. Complex 2 was able to reduce pyocyanin production in Pseudomonas aeruginosa between 10% and 25% and to inhibit its biofilm formation by 20% in comparison to the untreated control. These results suggest that complex 2 may be further examined in the mixed Candida-P. aeruginosa infections.
Central Serous Chorioretinopathy Classification
Authors: Vilela Manuel , Mengue Carolina
Published: December 2020

Central serous chorioretinopathy is characterized by an idiopathic neurosensory detachment of the retina. This narrative review aims to discuss the classification system used for central serous chorioretinopathy. Based on our current knowledge, there is no universally adopted classification system. This is the result of the unknown aspects related to pathogenesis and clinical spectrum and evolution. The best option could be to aggregate multimodal pieces of information alongside temporal and phenotypic characteristics.
Flavones, Flavonols, and Glycosylated Derivatives—Impact on Candida albicans Growth and Virulence, Expression of CDR1 and ERG11, Cytotoxicity
Authors: Ivanov Marija , Kannan Abhilash , Stojković Dejan S. , Glamočlija Jasmina , Calhelha Ricardo C. , Ferreira Isabel C. F. R. , Sanglard Dominique , Soković Marina
Published: December 2020

Due to the high incidence of fungal infections worldwide, there is an increasing demand for the development of novel therapeutic approaches. A wide range of natural products has been extensively studied, with considerable focus on flavonoids. The antifungal capacity of selected flavones (luteolin, apigenin), flavonols (quercetin), and their glycosylated derivatives (quercitrin, isoquercitrin, rutin, and apigetrin) along with their impact on genes encoding efflux pumps (CDR1) and ergosterol biosynthesis enzyme (ERG11) has been the subject of this study. Cytotoxicity of flavonoids towards primary liver cells has also been addressed. Luteolin, quercitrin, isoquercitrin, and rutin inhibited growth of Candida albicans with the minimal inhibitory concentration of 37.5 µg/mL. The application of isoquercitrin has reduced C. albicans biofilm establishing capacities for 76%, and hyphal formation by yeast. In vitro treatment with apigenin, apigetrin, and quercitrin has downregulated CDR1. Contrary to rutin and apigenin, isoquercitrin has upregulated ERG11. Except apigetrin and quercitrin (90 µg/mL and 73 µg/mL, respectively inhibited 50% of the net cell growth), the examined flavonoids did not exhibit cytotoxicity. The reduction of both fungal virulence and expression of antifungal resistance-linked genes was the most pronounced for apigenin and apigetrin; these results indicate flavonoids’ indispensable capacity for further development as part of an anticandidal therapy or prevention strategy.
Immunotherapy and Targeted Therapy for Hepatocellular Carcinoma: A Literature Review and Treatment Perspectives
Authors: Girardi Daniel M. , Pacífico Jana Priscila M. , Guedes de Amorim Fernanda P. L. , dos Santos Fernandes Gustavo , Teixeira Marcela C. , Pereira Allan A. L.
Published: December 2020

Advanced hepatocellular carcinoma is a prevalent and potentially aggressive disease. For more than a decade, treatment with sorafenib has been the only approved therapeutic approach. Moreover, no agent has been proven to prolong survival following the progression of disease after sorafenib treatment. However, in recent years, this scenario has changed substantially with several trials being conducted to examine the effects of immunotherapy and novel targeting agents. Several immune checkpoint inhibitors have shown promising results in early-stage clinical trials. Moreover, phase III trials with large cohorts have demonstrated remarkable improvement in survival with the use of new targeted therapies in second-line treatment. Treatment regimens involving the combination of two immune checkpoint inhibitors as well as immune checkpoint inhibitors and anti-angiogenic targeted therapies have shown potential to act synergistically in clinical trials. Recently, the combination of atezolizumab and bevacizumab evaluated in a phase III clinical trial has demonstrated survival superiority in the first-line treatment; it is the new considered standard of care. In this manuscript, we aimed to review the latest advances in the systemic treatment of advanced hepatocellular carcinoma focusing on immunotherapy and targeted therapies.
Gabapentin and Duloxetine Prevent Oxaliplatin- and Paclitaxel-Induced Peripheral Neuropathy by Inhibiting Extracellular Signal-Regulated Kinase 1/2 (ERK1/2) Phosphorylation in Spinal Cords of Mice
Authors: Kato Natsuki , Tateishi Keisuke , Tsubaki Masanobu , Takeda Tomoya , Matsumoto Mikihiro , Tsurushima Katsumasa , Ishizaka Toshihiko , Nishida Shozo
Published: December 2020

Chemotherapy-induced peripheral neuropathy is a common factor in limiting therapy which can result in therapy cessation or dose reduction. Gabapentin, a calcium channel inhibitor, and duloxetine, a serotonin noradrenaline reuptake inhibitor, are used to treat a variety of pain conditions such as chronic low back pain, postherpetic neuralgia, and diabetic neuropathy. It has been reported that administration of gabapentin suppressed oxaliplatin- and paclitaxel-induced mechanical hyperalgesia in rats. Moreover, duloxetine has been shown to suppress oxaliplatin-induced cold allodynia in rats. However, the mechanisms by which these drugs prevent oxaliplatin- and paclitaxel-induced neuropathy remain unknown. Behavioral assays were performed using cold plate and the von Frey test. The expression levels of proteins were examined using western blot analysis. In this study, we investigated the mechanisms by which gabapentin and duloxetine prevent oxaliplatin- and paclitaxel-induced neuropathy in mice. We found that gabapentin and duloxetine prevented the development of oxaliplatin- and paclitaxel-induced cold and mechanical allodynia. In addition, our results revealed that gabapentin and duloxetine suppressed extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation in the spinal cord of mice. Moreover, PD0325901 prevented the development of oxaliplatin- and paclitaxel-induced neuropathic-like pain behavior by inhibiting ERK1/2 activation in the spinal cord of mice. In summary, our findings suggest that gabapentin, duloxetine, and PD0325901 prevent the development of oxaliplatin- and paclitaxel-induced neuropathic-like pain behavior by inhibiting ERK1/2 phosphorylation in mice. Therefore, inhibiting ERK1/2 phosphorylation could be an effective preventive strategy against oxaliplatin- and paclitaxel-induced neuropathy.
The Pharmacological TAILS of Matrix Metalloproteinases and Their Inhibitors
Authors: Das Nabangshu , Benko Colette , Gill Sean E. , Dufour Antoine
Published: December 2020

Matrix metalloproteinases (MMPs) have been demonstrated to have both detrimental and protective functions in inflammatory diseases. Several MMP inhibitors, with the exception of Periostat®, have failed in Phase III clinical trials. As an alternative strategy, recent efforts have been focussed on the development of more selective inhibitors or targeting other domains than their active sites through specific small molecule inhibitors or monoclonal antibodies. Here, we present some examples that aim to better understand the mechanisms of conformational changes/allosteric control of MMPs functions. In addition to MMP inhibitors, we discuss unbiased global approaches, such as proteomics and N-terminomics, to identify new MMP substrates. We present some examples of new MMP substrates and their implications in regulating biological functions. By characterizing the roles and substrates of individual MMP, MMP inhibitors could be utilized more effectively in the optimal disease context or in diseases never tested before where MMP activity is elevated and contributing to disease progression.
Convection Enhanced Delivery of Topotecan for Gliomas: A Single-Center Experience
Authors: Upadhyayula Pavan S. , Spinazzi Eleonora F. , Argenziano Michael G. , Canoll Peter , Bruce Jeffrey N.
Published: December 2020

A key limitation to glioma treatment involves the blood brain barrier (BBB). Convection enhanced delivery (CED) is a technique that uses a catheter placed directly into the brain parenchyma to infuse treatments using a pressure gradient. In this manuscript, we describe the physical principles behind CED along with the common pitfalls and methods for optimizing convection. Finally, we highlight our institutional experience using topotecan CED for the treatment of malignant glioma.
Nanoparticles as Adjuvants and Nanodelivery Systems for mRNA-Based Vaccines
Authors: Alfagih Iman M. , Aldosari Basmah , AlQuadeib Bushra , Almurshedi Alanood , Alfagih Mariyam M.
Published: December 2020

Messenger RNA (mRNA)-based vaccines have shown promise against infectious diseases and several types of cancer in the last two decades. Their promise can be attributed to their safety profiles, high potency, and ability to be rapidly and affordably manufactured. Now, many RNA-based vaccines are being evaluated in clinical trials as prophylactic and therapeutic vaccines. However, until recently, their development has been limited by their instability and inefficient in vivo transfection. The nanodelivery system plays a dual function in RNA-based vaccination by acting as a carrier system and as an adjuvant. That is due to its similarity to microorganisms structurally and size-wise; the nanodelivery system can augment the response by the immune system via simulating the natural infection process. Nanodelivery systems allow non-invasive mucosal administration, targeted immune cell delivery, and controlled delivery, reducing the need for multiple administrations. They also allow co-encapsulating with immunostimulators to improve the overall adjuvant capacity. The aim of this review is to discuss the recent developments and applications of biodegradable nanodelivery systems that improve RNA-based vaccine delivery and enhance the immunological response against targeted diseases.
The Biosimilar Landscape: An Overview of Regulatory Approvals by the EMA and FDA
Authors: Gherghescu Ioana , Delgado-Charro M. Begoña
Published: December 2020

Biosimilar medicines expand the biotherapeutic market and improve patient access. This work looked into the landscape of the European and US biosimilar products, their regulatory authorization, market availability, and clinical evaluation undergone prior to the regulatory approval. European Medicines Agency (EMEA, currently EMA) and Food and Drug Administration (FDA) repositories were searched to identify all biosimilar medicines approved before December 2019. Adalimumab biosimilars, and particularly their clinical evaluations, were used as a case study. In the past 13 years, the EMA has received 65 marketing authorization applications for biosimilar medicines with 55 approved biosimilars available in the EU market. Since the first biosimilar approval in 2015, the FDA has granted 26 approvals for biosimilars with only 11 being currently on the US market. Five adalimumab biosimilars have been approved in the EU and commercialized as eight different medicines through duplicate marketing authorizations. Whilst three of these are FDA-approved, the first adalimumab biosimilar will not be marketed in the US until 2023 due to Humira’s exclusivity period. The EU biosimilar market has developed faster than its US counterpart, as the latter is probably challenged by a series of patents and exclusivity periods protecting the bio-originator medicines, an issue addressed by the US’s latest ‘Biosimilar Action Plan’.
Erratum: Huet, R.; et al. 1,1-Difluoroethane Detection Time in Blood after Inhalation Abuse Estimated by Monte Carlo PBPK Modeling. Pharmaceutics, 2020, 12, 997
Authors: Huet Raul , Johanson Gunnar
Published: December 2020

The authors wish to make the following corrections to this paper [...]
MEMS Scanning Mirrors for Optical Coherence Tomography
Authors: Gorecki Christophe , Bargiel Sylwester
Published: December 2020

This contribution presents an overview of advances in scanning micromirrors based on MEMS (Micro-electro-mechanical systems) technologies to achieve beam scanning for OCT (Optical Coherence Tomography). The use of MEMS scanners for miniaturized OCT probes requires appropriate optical architectures. Their design involves a suitable actuation mechanism and an adapted imaging scheme in terms of achievable scan range, scan speed, low power consumption, and acceptable size of the OCT probe. The electrostatic, electromagnetic, and electrothermal actuation techniques are discussed here as well as the requirements that drive the design and fabrication of functional OCT probes. Each actuation mechanism is illustrated by examples of miniature OCT probes demonstrating the effectiveness of in vivo bioimaging. Finally, the design issues are discussed to permit users to select an OCT scanner that is adapted to their specific imaging needs.
One-Step Synthesis of Eu3+-Modified Cellulose Acetate Film and Light Conversion Mechanism
Authors: Zhang Zhihui , Zhao Zhengdong , Lu Yujia , Wang Di , Wang Chengyu , Li Jian
Published: December 2020

A CA-Eu(III) complex was synthesized by the coordination reaction of cellulose acetate (CA) and Eu3+ to obtain a CA-Eu light conversion film. This product was then doped with Tb(III) to sensitize the luminescence of Eu3+, which could functionalize the CA film. FTIR and XPS showed that the oxygen atoms in C=O, C–O (O=C–O), and O–H were involved in the complexation with Eu3+ and formed a Eu–O bond. SEM revealed that Eu3+ filled in the pores of the CA film. By changing the experimental conditions, the best fluorescence performance was obtained at the CA: Eu3+ ratio of 3:1 with a reaction time of 65 min. The energy transfer between Tb3+–Eu3+ could be realized by doping Tb3+ to enhance the luminescence of Eu3+. The best fluorescence performance of the CA-Eu-Tb light conversion film was at a Eu3+:Tb3+ ratio of 3:1. Compared with the CA film, the light conversion film has high transparency, high tensile strength, and good flexibility. It can convert the ultraviolet light harmful to plants into red light that is beneficial to photosynthesis. This offers high efficiency and environmental protection in the field of agricultural films.
Preparation and Drug Release Properties of a Thermo Sensitive GA Hydrogel
Authors: Duan Jiufang , Huang Yirong , Zong Shiyu , Jiang Jianxin
Published: December 2020

A high-strength galactomannan (GA)-based hydrogel with thermal response and pH response is introduced in this paper. GA, N-isopropylacrylamide (NIPAM), N-[3-dimethylamino)propyl]methylacrylamide (DMAPMA), and montmorillonite were used to form hydrogels through a simple mixed static system. Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) were used to characterize the structure and properties of the hydrogels. The compressive strength of the the hydrogel increased from 23.9 to 105.61 kPa with the increase of GA dosage from 0 to 1.5 wt%. When the NIPAM content in the monomer increased from 75% to 95%, the lower critical solution temperature (LCST) of the hydrogel changed from 36.5 to 45.8 °C. When the monomer content was higher than 10wt%, the swelling kinetics of the sample changed from the second-order equation to the first-order equation. With the increase of the proportion of NIPAM monomer, the release rate of bovine serum album in the early stage was faster, and the cumulative release rate was close to 100%.The release rate of bovine serum albumin at 37 °C was higher than that at 25 °C. The release rate of the hydrogel containing bovine serum albumin was the fastest under the condition of pH 7.4, followed by those at pH 6.6 and pH 5.0. The results showed that this thermal-responsive hydrogel has potential applications as a drug carrier for colon delivery.
Interaction of Proteins with a Planar Poly(acrylic acid) Brush: Analysis by Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D)
Authors: Walkowiak Jacek , Gradzielski Michael , Zauscher Stefan , Ballauff Matthias
Published: December 2020

We describe the preparation of a poly(acrylic acid) (PAA) brush, polymerized by atom transfer radical polymerization (ATRP) of tert-butyl acrylate (tBA) and subsequent acid hydrolysis, on the flat gold surfaces of quartz-crystal microbalance (QCM) crystals. The PAA brushes were characterized by Fourier transform infrared (FT-IR) spectroscopy, ellipsometry and water contact angle analysis. The interaction of the PAA brushes with human serum albumin (HSA) was studied for a range of ionic strengths and pH conditions by quartz-crystal microbalance with dissipation monitoring (QCM-D). The quantitative analysis showed a strong adsorption of protein molecules onto the PAA brush. By increasing the ionic strength, we were able to release a fraction of the initially bound HSA molecules. This finding highlights the importance of counterions in the polyelectrolyte-mediated protein adsorption/desorption. A comparison with recent calorimetric studies related to the binding of HSA to polyelectrolytes allowed us to fully analyze the QCM data based on the results of the thermodynamic analysis of the binding process.
Environment-Friendly and Two-Component Method for Fabrication of Highly Hydrophobic Wood Using Poly(methylhydrogen)siloxane
Authors: Gao Jie , Lin Wensheng , Lin Shumin , Zhang Xinxiang , Yang Wenbin , Li Ran
Published: December 2020

Practical application of wood remains a great challenge because of its highly hydrophilic property. In this work, highly hydrophobic wood was produced using an environment-friendly and two-component package method. Poly(methylhydrogen)siloxane (PMHS) and inhibitor played the key role in the hydrophobicity of wood and the assembly process. The two-component package mechanism was discussed in detail. As a result, the water contact angles of the modified wood surface for the radial and cross sections were 139.5° and 152.9°, respectively, which provided the resultant wood high hydrophobicity and dimensional stability. The two-component package method afforded the wood good anti-fouling property and UV-resistance. In addition, the two-component package method could also be applied in functionalization of filter paper for oil/water separation.
A Kirigami Approach of Patterning Membrane Actuators
Authors: Kiveste Harti , Kiefer Rudolf , Haamer Rain Eric , Anbarjafari Gholamreza , Tamm Tarmo
Published: December 2020

Ionic electroactive polymer actuators are typically implemented as bending trilayer laminates. While showing high displacements, such designs are not straightforward to implement for useful applications. To enable practical uses in actuators with ionic electroactive polymers, membrane-type film designs can be considered. The significantly lower displacement of the membrane actuators due to the lack of freedom of motion has been the main limiting factor for their application, resulting in just a few works considering such devices. However, bioinspired patterning designs have been shown to significantly increase the freedom of motion of such membranes. In this work, we apply computer simulations to design cutting patterns for increasing the performance of membrane actuators based on polypyrrole doped with dodecylbenzenesulfonate (PPy/DBS) in trilayer arrangements with a polyvinylidene fluoride membrane as the separator. A dedicated custom-designed device was built to consistently measure the response of the membrane actuators, demonstrating significant and pattern-specific enhancements of the response in terms of displacement, exchanged charge and force.
Multi-Functional Luminescent Coating for Wood Fabric Based on Silica Sol-Gel Approach
Authors: Li Ming , Huang Rui , Fu Zhengquan , Wang Di , Wang Chengyu , Li Jian
Published: December 2020

Environmentally friendly protection coatings have obtained increasing attention for their use in wooden materials, which can be destroyed easily when exposed to outdoor environments. A series of silane sol coatings coordinated with Eu3+ was prepared by hydrolyzing silane compounds. The obtained luminescent coating with three-dimensional net structure showed excellent optical, anti-ultraviolet aging, and thermal stability. The hybrid silane-modified compound coating was well-distributed on the wood by Si–O bonds to prevent its removal. The compound coating could stave off the decomposition of wood by converting ultraviolet light into red light and a charring action can endow the wood with thermal stability at high temperature, demonstrating the improvement of fire resistance and radiation residence following prolonged exposure to ultraviolet light, proving its excellent anti-ultraviolet aging properties.
Synthesis and Characterization of Partially Renewable Oleic Acid-Based Ionomers for Proton Exchange Membranes
Authors: Corona-García Carlos , Onchi Alejandro , Santiago Arlette A. , Martínez Araceli , Pacheco-Catalán Daniella Esperanza , Alfonso Ismeli , Vargas Joel
Published: December 2020

The future availability of synthetic polymers is compromised due to the continuous depletion of fossil reserves; thus, the quest for sustainable and eco-friendly specialty polymers is of the utmost importance to ensure our lifestyle. In this regard, this study reports on the use of oleic acid as a renewable source to develop new ionomers intended for proton exchange membranes. Firstly, the cross-metathesis of oleic acid was conducted to yield a renewable and unsaturated long-chain aliphatic dicarboxylic acid, which was further subjected to polycondensation reactions with two aromatic diamines, 4,4′-(hexafluoroisopropylidene)bis(p-phenyleneoxy)dianiline and 4,4′-diamino-2,2′-stilbenedisulfonic acid, as comonomers for the synthesis of a series of partially renewable aromatic-aliphatic polyamides with an increasing degree of sulfonation (DS). The polymer chemical structures were confirmed by Fourier transform infrared (FTIR) and nuclear magnetic resonance (1H, 13C, and 19F NMR) spectroscopy, which revealed that the DS was effectively tailored by adjusting the feed molar ratio of the diamines. Next, we performed a study involving the ion exchange capacity, the water uptake, and the proton conductivity in membranes prepared from these partially renewable long-chain polyamides, along with a thorough characterization of the thermomechanical and physical properties. The highest value of the proton conductivity determined by electrochemical impedance spectroscopy (EIS) was found to be 1.55 mS cm−1 at 30 °C after activation of the polymer membrane.