bluuebunny/crossref_metadata_2025 huggingface dataset:
Generation and Characterization of a DNA-GCN4 Oligonucleotide-Peptide Conjugate: The Impact DNA/Protein Interactions on the Sensitization of DNA
Authors: Wityk Paweł , Piątek Rafał , Nowak Robert , Kostrzewa-Nowak Dorota
Published: August 2020

Radiotherapy, the most common therapy for the treatment of solid tumors, exerts its effects by inducing DNA damage. To fully understand the extent and nature of this damage, DNA models that mimic the in vivo situation should be utilized. In a cellular context, genomic DNA constantly interacts with proteins and these interactions could influence both the primary radical processes (triggered by ionizing radiation) and secondary reactions, ultimately leading to DNA damage. However, this is seldom addressed in the literature. In this work, we propose a general approach to tackle these shortcomings. We synthesized a protein-DNA complex that more closely represents DNA in the physiological environment than oligonucleotides solution itself, while being sufficiently simple to permit further chemical analyses. Using click chemistry, we obtained an oligonucleotide-peptide conjugate, which, if annealed with the complementary oligonucleotide strand, forms a complex that mimics the specific interactions between the GCN4 protein and DNA. The covalent bond connecting the oligonucleotide and peptide constitutes a part of substituted triazole, which forms due to the click reaction between the short peptide corresponding to the specific amino acid sequence of GCN4 protein (yeast transcription factor) and a DNA fragment that is recognized by the protein. DNAse footprinting demonstrated that the part of the DNA fragment that specifically interacts with the peptide in the complex is protected from DNAse activity. Moreover, the thermodynamic characteristics obtained using differential scanning calorimetry (DSC) are consistent with the interaction energies calculated at the level of metadynamics. Thus, we present an efficient approach to generate a well-defined DNA-peptide conjugate that mimics a real DNA-peptide complex. These complexes can be used to investigate DNA damage under conditions very similar to those present in the cell.
Quinolone and Organophosphorus Insecticide Residues in Bivalves and Their Associated Risks in Taiwan
Authors: Wu Ching-Feng , Chen Ching-Hung , Wu Ching-Yang , Lin Chen-Si , Su Yao-Chi , Wu Ching-Fen , Tsai Hsiao-Pei , Fan Pei-Shan , Yeh Chang-Hui , Yang Wei-Cheng , Chang Geng-Ruei
Published: August 2020

Bivalves, such as freshwater clams (Corbicula fluminea) and hard clams (Meretrix lusoria), are the most extensive and widely grown shellfish in land-based ponds in Taiwan. However, few studies have examined the contamination of bivalves by quinolone and organophosphorus insecticides. Thus, we adapted an established procedure to analyze 8 quinolones and 12 organophosphorus insecticides using liquid and gas chromatography–tandem mass spectrometry. Surveys in Taiwan have not noted high residual levels of these chemicals in bivalve tissues. A total of 58 samples of freshwater or hard clams were obtained from Taiwanese aquafarms. We identified 0.03 mg/kg of enrofloxacin in one freshwater clam, 0.024 mg/kg of flumequine in one freshwater clam, 0.02 mg/kg of flumequine in one hard clam, 0.05 mg/kg of chlorpyrifos in one freshwater clam, 0.03 mg/kg of chlorpyrifos in one hard clam, and 0.02 mg/kg of trichlorfon in one hard clam. The results indicated that 5.17% of the samples had quinolone insecticide residues and 5.17% had organophosphorus residues. However, the estimated daily intake (EDI)/acceptable daily intake quotient (ADI) indicated no significant risk and no immediate health risk from the consumption of bivalves. These results provide a reference for the food-safety screening of veterinary drugs and pesticides in aquatic animals. Aquatic products should be frequently screened for residues of prohibited chemicals to safeguard human health.
State of the Art and Future Perspectives in Advanced CMOS Technology
Authors: Radamson Henry H. , Zhu Huilong , Wu Zhenhua , He Xiaobin , Lin Hongxiao , Liu Jinbiao , Xiang Jinjuan , Kong Zhenzhen , Xiong Wenjuan , Li Junjie , Cui Hushan , Gao Jianfeng , Yang Hong , Du Yong , Xu Buqing , Li Ben , Zhao Xuewei , Yu Jiahan , Dong Yan , Wang Guilei
Published: August 2020

The international technology roadmap of semiconductors (ITRS) is approaching the historical end point and we observe that the semiconductor industry is driving complementary metal oxide semiconductor (CMOS) further towards unknown zones. Today’s transistors with 3D structure and integrated advanced strain engineering differ radically from the original planar 2D ones due to the scaling down of the gate and source/drain regions according to Moore’s law. This article presents a review of new architectures, simulation methods, and process technology for nano-scale transistors on the approach to the end of ITRS technology. The discussions cover innovative methods, challenges and difficulties in device processing, as well as new metrology techniques that may appear in the near future.
Microwave-Assisted Synthesis of Water-Dispersible Humate-Coated Magnetite Nanoparticles: Relation of Coating Process Parameters to the Properties of Nanoparticles
Authors: Kostyukhin Egor M. , Nissenbaum Vera D. , Abkhalimov Evgeny V. , Kustov Alexander L. , Ershov Boris G. , Kustov Leonid M.
Published: August 2020

Nowadays, there is a demand in the production of nontoxic multifunctional magnetic materials possessing both high colloidal stability in water solutions and high magnetization. In this work, a series of water-dispersible natural humate-polyanion coated superparamagnetic magnetite nanoparticles has been synthesized via microwave-assisted synthesis without the use of inert atmosphere. An impact of a biocompatible humate-anion as a coating agent on the structural and physical properties of nanoparticles has been established. The injection of humate-polyanion at various synthesis stages leads to differences in the physical properties of the obtained nanomaterials. Depending on the synthesis protocol, nanoparticles are characterized by improved monodispersity, smaller crystallite and grain size (up to 8.2 nm), a shift in the point of zero charge (6.4 pH), enhanced colloidal stability in model solutions, and enhanced magnetization (80 emu g−1).
Enhancement of Chemical Stability and Dermal Delivery of Cordyceps militaris Extracts by Nanoemulsion
Authors: Marsup Pachabadee , Yeerong Kankanit , Neimkhum Waranya , Sirithunyalug Jakkapan , Anuchapreeda Songyot , To-anun Chaiwat , Chaiyana Wantida
Published: August 2020

This study aimed to develop nanoemulsions for enhancing chemical stability and dermal delivery of Cordyceps militaris extracts. C. militaris was extracted by maceration and infusion. The extracts were investigated for cordycepin, phenolic, and flavonoid content. The antioxidant activity was investigated by in vitro spectrophotometric methods. The irritation profile was investigated by hen’s egg-chorioallantoic membrane test. Nanoemulsions were developed using high-pressure homogenizer. C. militaris extract was incorporated into the nanoemulsion and investigated for safety, release profile, permeation, and skin retention. The results demonstrated that water extract (CW) contained the significantly highest content of cordycepin, phenolics, and flavonoids, which were responsible for antioxidant activity. CW was the most potent antioxidant. CW possessed comparable 2,2′-diphenyl-1-picrylhydrazyl radical scavenging activity and lipid peroxidation inhibition to l-ascorbic acid (96.9 ± 3.1%) and alpha-tocopherol (87.2 ± 1.0%). Consequently, ten mg/mL of CW was incorporated into nanoemulsions composing of sugar squalene, Tween® 85, and deionized water. Nanoemulsion, which had the smallest internal droplet size (157.1 ± 2.6 nm), enhanced the stability of CW, had no cytotoxicity effect and no skin irritation, released the most CW (0.9 ± 0.0% w/w after 24 h), and delivered the highest CW into the skin layer (33.5 ± 0.7% w/w). Therefore, nanoemulsion was suggested for enhancing the stability and dermal delivery of CW.
Optimization of Photogenerated Charge Carrier Lifetimes in ALD Grown TiO2 for Photonic Applications
Authors: Khan Ramsha , Ali-Löytty Harri , Saari Jesse , Valden Mika , Tukiainen Antti , Lahtonen Kimmo , Tkachenko Nikolai V.
Published: August 2020

Titanium dioxide (TiO2) thin films are widely employed for photocatalytic and photovoltaic applications where the long lifetime of charge carriers is a paramount requirement for the device efficiency. To ensure the long lifetime, a high temperature treatment is used which restricts the applicability of TiO2 in devices incorporating organic or polymer components. In this study, we exploited low temperature (100–150 °C) atomic layer deposition (ALD) of 30 nm TiO2 thin films from tetrakis(dimethylamido)titanium. The deposition was followed by a heat treatment in air to find the minimum temperature requirements for the film fabrication without compromising the carrier lifetime. Femto-to nanosecond transient absorption spectroscopy was used to determine the lifetimes, and grazing incidence X-ray diffraction was employed for structural analysis. The optimal result was obtained for the TiO2 thin films grown at 150 °C and heat-treated at as low as 300 °C. The deposited thin films were amorphous and crystallized into anatase phase upon heat treatment at 300–500 °C. The average carrier lifetime for amorphous TiO2 is few picoseconds but increases to >400 ps upon crystallization at 500 °C. The samples deposited at 100 °C were also crystallized as anatase but the carrier lifetime was <100 ps.
Changes in Nutrient Declaration after the Food Labeling and Advertising Law in Chile: A Longitudinal Approach
Authors: Quintiliano Scarpelli Daiana , Pinheiro Fernandes Anna Christina , Rodriguez Osiac Lorena , Pizarro Quevedo Tito
Published: August 2020

Chile has implemented several strategies to decrease the burden of obesity and chronic diseases. The Food Labeling and Advertising Law (Law 20.606) requires a front-of-package “high in” warning label when energy and nutrients of concern (ENC) (total sugar, saturated fats, sodium) exceed established limits. This study aims to evaluate the impact of Law 20.606 on the ENC declaration of packaged foods in Chile, before and after the law implementation. We analyzed food nutritional labeling declarations from 70% of the most consumed packaged foods in Chile. Data collection was conducted in 2013 and 2019 in Santiago. Pictures from all sides of the package were taken from 476 products, classified into 16 food groups. All food groups had changes in the ENC declaration during the study period. Total sugar content showed the highest reduction (−15.0%; p = 0.001). Dairy, confitures and similar and sugary beverages had the greatest reduction in energy and total sugar content (p < 0.01). Energy, total sugar and sodium front of package “high in” simulation was significantly reduced in dairy, sugary beverages, flour-based foods, confitures and similar, fish and seafoods, fats and oils, spices, condiments and sauces and sugars (p < 0.05). We observed that companies reformulated products to adapt to the new regulation.
Heart Rate Variability Behavior during Exercise and Short-Term Recovery Following Energy Drink Consumption in Men and Women
Authors: Clark Nicolas W. , Herring Chad H. , Goldstein Erica R. , Stout Jeffrey R. , Wells Adam J. , Fukuda David H.
Published: August 2020

This study examined the cardiac autonomic responses, as measured by heart rate variability (HRV), during cycling exercise and short-term rest after energy drink consumption. Seventeen participants (seven males and 10 females; age: 22.8 ± 3.5 years; BMI: 24.3 ± 3.3 kg/m2) completed this double-blind, placebo-controlled, counterbalanced crossover design study. Participants received an energy drink formula containing 140 mg of caffeine and a placebo in a randomized order before completing a 10-min steady-state warm up (WUP) and a graded exercise test to exhaustion (GXT) followed by a 15-min short-term rest (STR) period. Heartbeat intervals were recorded using a heart rate monitor. Data were divided into WUP, GXT, and STR phases, and HRV parameters were averaged within each phase. Additionally, root mean square of the standard deviation of R–R intervals (RMSSD) during GXT was analyzed to determine the HRV threshold. Separate two-way (sex (male vs. female) x drink (energy drink vs. placebo)) repeated measures ANOVA were utilized. Significant increases in high frequency (HF) and RMSSD were shown during WUP after energy drink consumption, while interactions between drink and sex were observed for HRV threshold parameters (initial RMSSD and rate of RMSSD decline). No significant differences were noted during STR. Energy drink consumption may influence cardiac autonomic responses during low-intensity exercise, and sex-based differences in response to graded exercise to exhaustion may exist.
Gamma-Polyglutamic Acid-Rich Natto Suppresses Postprandial Blood Glucose Response in the Early Phase after Meals: A Randomized Crossover Study
Authors: Araki Risa , Yamada Takeshi , Maruo Kazushi , Araki Akihiro , Miyakawa Rena , Suzuki Hiroaki , Hashimoto Koichi
Published: August 2020

We evaluated the suppressive effects of high-gamma-polyglutamic acid (γ-PGA) natto on postprandial blood glucose level and insulin response. After confirming the eligibility of candidates using a pre-selective test with packaged white rice, a meal loading test including low- or high-γ-PGA natto (with 57.6 mg (LPGA) and 439.6 mg (HPGA) of γ-PGA, respectively) was conducted in men aged 20 to 70 years (n = 29) and postmenopausal women aged ≤70 years (n = 7). On each examination day, blood samples were obtained after they fasted overnight and for 120 min after test meal loading. The primary outcome of this study was the difference between the measurements of the incremental area under the curve (IAUC) for blood glucose 0 to 30 min after loading of LPGA and HPGA meals. The IAUCs for blood glucose and insulin after the HPGA meal were lower than those after the LPGA meal within 45 min (0 to 15 and 0 to 30 min: p < 0.001, 0 to 45 min: p < 0.01) and 1 h (all p < 0.001) of loading, respectively. The suppressive effects of HPGA natto on postprandial glucose response in the early phase, which possibly relates to the risk of dysglycemia and cardiovascular disease, were clarified.
Disparities in the Healthfulness of School Food Environments and the Nutritional Quality of School Lunches
Authors: Bardin Sarah , Washburn Liana , Gearan Elizabeth
Published: August 2020

The Healthy, Hunger-Free Kids Act (HHFKA), a public law in the United States passed in 2010, sought to improve the healthfulness of the school food environment by requiring updated nutrition standards for school meals and competitive foods. Studies conducted since the passage of the HHFKA indicate improvements in the food environment overall, but few studies have examined whether these improvements varied by the socioeconomic and racial/ethnic composition of students in schools. To better understand the extent of disparities in the school food environment after HHFKA, this paper examined differences in the healthfulness of school food environments and the nutritional quality of school lunches by the school poverty level and racial/ethnic composition of students using data from the School Nutrition and Meal Cost Study. Results from chi-square analyses showed lower proportions of high poverty, majority black, and majority Hispanic schools had access to competitive foods, while higher proportions of these schools had a school wellness policy in addition to a district wellness policy. The overall nutritional quality of school lunches, as measured by total Healthy Eating Index (HEI)-2010 scores, did not vary significantly across school types, although some HEI component scores did. From these findings, we concluded that there were disparities in the school food environment based on the socioeconomic and racial/ethnic composition of students in schools, but no significant disparities in the overall nutritional quality of school lunches were found.
Gestational Dysfunction-Driven Diets and Probiotic Supplementation Correlate with the Profile of Allergen-Specific Antibodies in the Serum of Allergy Sufferers
Authors: Ogrodowczyk Anna Maria , Zakrzewska Magdalena , Romaszko Ewa , Wróblewska Barbara
Published: August 2020

Background: Maternal diet has significant effects on development of childhood atopic disease and hypersensitivity development. However, the gestational dysfunctions demanding special diets are becoming a widespread phenomenon, their immunological implications can be manifested in the profile of antibodies in the offspring’s serum. Methods: 153 allergic and 150 healthy individuals were diagnosed for allergy using specific antibody and cytokine immunoassay tests. The medical history of subjects along with mothers’ course of pregnancy was completed by allergologist’s anamnesis. A self-organizing neural network and multivariate analyses to complex data and pick basic interactions were used. Results: Two significant explanatory modules were determined. The first was formed by gestational diabetic and cholestatic diet, infant formula feeding type, probiotic supplementation and its BMI index, moderate IgE, increased IgG levels of antibodies and single or poly-food allergy type (7 clusters). The second was formed by gestational vegan/vegetarian and elimination diet, maternal probiotic supplementation, sex, high IgE total antibodies and food and mixed poly-allergy to aero- and food-origin allergens (19 clusters). Conclusions: Significant associations were observed between special gestational diet intake underlying foetal programming and the mechanisms of childhood allergy. The novelty is the positive association between diabetic and cholestatic diet intake and IgE/IgG-mediated food hypersensitivity.
Effects of Whey and Pea Protein Supplementation on Post-Eccentric Exercise Muscle Damage: A Randomized Trial
Authors: Nieman David C. , Zwetsloot Kevin A. , Simonson Andrew J. , Hoyle Andrew T. , Wang Xintang , Nelson Heather K. , Lefranc-Millot Catherine , Guérin-Deremaux Laetitia
Published: August 2020

This randomized trial compared pea protein, whey protein, and water-only supplementation on muscle damage, inflammation, delayed onset of muscle soreness (DOMS), and physical fitness test performance during a 5-day period after a 90-min eccentric exercise bout in non-athletic non-obese males (n = 92, ages 18–55 years). The two protein sources (0.9 g protein/kg divided into three doses/day) were administered under double blind procedures. The eccentric exercise protocol induced significant muscle damage and soreness, and reduced bench press and 30-s Wingate performance. Whey protein supplementation significantly attenuated post-exercise blood levels for biomarkers of muscle damage compared to water-only, with large effect sizes for creatine kinase and myoglobin during the fourth and fifth days of recovery (Cohen’s d > 0.80); pea protein versus water supplementation had an intermediate non-significant effect (Cohen’s d < 0.50); and no significant differences between whey and pea protein were found. Whey and pea protein compared to water supplementation had no significant effects on post-exercise DOMS and the fitness tests. In conclusion, high intake of whey protein for 5 days after intensive eccentric exercise mitigated the efflux of muscle damage biomarkers, with the intake of pea protein having an intermediate effect.
Plasma Vitamin C Concentrations Were Negatively Associated with Tingling, Prickling or Pins and Needles Sensation in Patients with Postherpetic Neuralgia
Authors: Wang Li-Kai , Lin Yao-Tsung , Hung Kuo-Chuan , Chang Chia-Yu , Wu Zhi-Fu , Hu Miao-Lin , Chen Jen-Yin
Published: August 2020

Vitamin C deficiency increases the risk of postherpetic neuralgia (PHN). In this cross-sectional study, the relationships among plasma vitamin C concentrations, pain and Leeds assessment of neuropathic symptoms and signs (LANSS) items were investigated during their first pain clinic visit of 120 PHN patients. The factors associated with vitamin C deficiency were determined. Independent predictors of vitamin C deficiency were presented as adjusted odds ratios (AOR) and 95% confidence intervals (CI). The patients had a high prevalence (52.5%) of vitamin C deficiency. Their plasma vitamin C concentrations were negatively associated with spontaneous pain and tingling, prickling or pins and needles sensation according to the LANSS questionnaire. Based on the receiver operator characteristic curve, the cutoffs for plasma vitamin C to predict moderate-to-severe and severe symptoms of sharp sensation were <7.05 and <5.68 mg/L, respectively. By comparison, the patients well-nourished with vitamin C had lower incidences of sharp sensations, sharp pain, and reddish skin. Multivariate analyses revealed that vitamin C deficiency was associated with the low intake of fruit/vegetables (AOR 2.66, 95% CI 1.09–6.48, p = 0.032), peptic ulcer disease (AOR 3.25, 95% CI 1.28–8.28, p = 0.014), and smoking (AOR 3.60, 95% CI 1.33–9.77, p = 0.010). Future studies are needed to substantiate these findings.
Hydroxytyrosol as a Promising Ally in the Treatment of Fibromyalgia
Authors: Ramírez-Tejero Jorge A. , Martínez-Lara Esther , Peinado M Ángeles , del Moral María Luisa , Siles Eva
Published: August 2020

Fibromyalgia (FM) is a chronic and highly disabling syndrome, which is still underdiagnosed, with controversial treatment. Although its aetiology is unknown, a number of studies have pointed to the involvement of altered mitochondrial metabolism, increased oxidative stress and inflammation. The intake of extra virgin olive oil, and particularly of one of its phenolic compounds, hydroxytyrosol (HT), has proven to be protective in terms of redox homeostatic balance and the reduction of inflammation. In this context, using a proteomic approach with nanoscale liquid chromatography coupled to tandem mass spectrometry, the present study analysed: (i) Changes in the proteome of dermal fibroblasts from a patient with FM versus a healthy control, and (ii) the effect of the treatment with a nutritional relevant dose of HT. Our results unveiled that fibroblast from FM show a differential expression in proteins involved in the turnover of extracellular matrix and oxidative metabolism that could explain the inflammatory status of these patients. Moreover, a number of these proteins results normalized by the treatment with HT. In conclusion, our results support that an HT-enriched diet could be highly beneficial in the management of FM.
A Five-Ingredient Nutritional Supplement and Home-Based Resistance Exercise Improve Lean Mass and Strength in Free-Living Elderly
Authors: Nilsson Mats I. , Mikhail Andrew , Lan Lucy , Di Carlo Alessia , Hamilton Bethanie , Barnard Kristin , Hettinga Bart P. , Hatcher Erin , Tarnopolsky Milla G. , Nederveen Joshua P. , Bujak Adam L. , May Linda , Tarnopolsky Mark A.
Published: August 2020

Old age is associated with lower physical activity levels, suboptimal protein intake, and desensitization to anabolic stimuli, predisposing for age-related muscle loss (sarcopenia). Although resistance exercise (RE) and protein supplementation partially protect against sarcopenia under controlled conditions, the efficacy of home-based, unsupervised RE (HBRE) and multi-ingredient supplementation (MIS) is largely unknown. In this randomized, placebo-controlled and double-blind trial, we examined the effects of HBRE/MIS on muscle mass, strength, and function in free-living, older men. Thirty-two sedentary men underwent twelve weeks of home-based resistance band training (3 d/week), in combination with daily intake of a novel five-nutrient supplement (‘Muscle5’; M5, n = 16, 77.4 ± 2.8 y) containing whey, micellar casein, creatine, vitamin D, and omega-3 fatty acids, or an isocaloric/isonitrogenous placebo (PLA; n = 16, 74.4 ± 1.3 y), containing collagen and sunflower oil. Appendicular and total lean mass (ASM; +3%, TLM; +2%), lean mass to fat ratios (ASM/% body fat; +6%, TLM/% body fat; +5%), maximal strength (grip; +8%, leg press; +17%), and function (5-Times Sit-to-Stand time; −9%) were significantly improved in the M5 group following HBRE/MIS therapy (pre vs. post tests; p < 0.05). Fast-twitch muscle fiber cross-sectional areas of the quadriceps muscle were also significantly increased in the M5 group post intervention (Type IIa; +30.9%, Type IIx, +28.5%, p < 0.05). Sub-group analysis indicated even greater gains in total lean mass in sarcopenic individuals following HBRE/MIS therapy (TLM; +1.65 kg/+3.4%, p < 0.05). We conclude that the Muscle5 supplement is a safe, well-tolerated, and effective complement to low-intensity, home-based resistance exercise and improves lean mass, strength, and overall muscle quality in old age.
Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral
Authors: Sandoval Viviana , Sanz-Lamora Hèctor , Arias Giselle , Marrero Pedro F. , Haro Diego , Relat Joana
Published: August 2020

The prevention and treatment of obesity is primary based on the follow-up of a healthy lifestyle, which includes a healthy diet with an important presence of bioactive compounds such as polyphenols. For many years, the health benefits of polyphenols have been attributed to their anti-oxidant capacity as free radical scavengers. More recently it has been described that polyphenols activate other cell-signaling pathways that are not related to ROS production but rather involved in metabolic regulation. In this review, we have summarized the current knowledge in this field by focusing on the metabolic effects of flavonoids. Flavonoids are widely distributed in the plant kingdom where they are used for growing and defensing. They are structurally characterized by two benzene rings and a heterocyclic pyrone ring and based on the oxidation and saturation status of the heterocyclic ring flavonoids are grouped in seven different subclasses. The present work is focused on describing the molecular mechanisms underlying the metabolic impact of flavonoids in obesity and obesity-related diseases. We described the effects of each group of flavonoids in liver, white and brown adipose tissue and central nervous system and the metabolic and signaling pathways involved on them.
Role of Vitamin C in Osteoporosis Development and Treatment—A Literature Review
Authors: Brzezińska Olga , Łukasik Zuzanna , Makowska Joanna , Walczak Konrad
Published: August 2020

Osteoporosis and associated low energy fractures are a significant clinical problem, especially in the elderly population. The occurrence of a hip fracture is associated with significant mortality and a high risk of disability. For this, apart from the treatment of osteoporosis, effective prevention of both the development of the disease and related fractures is extremely important. One aspect of osteoporosis prevention is proper dietary calcium intake and normal vitamin D3 levels. However, there is some evidence for a potential role of vitamin C in osteoporosis and fracture prevention, too. This review aims to summarize the current knowledge about the role of vitamin C in osteoporosis development, prevention and treatment. The PubMed/Medline search on the role of vitamin C in bone metabolism database was performed for articles between 2000 and May 2020. Reports from in vitro and animal studies seem promising. Epidemiological studies also indicate the positive effect of high vitamin C content in the daily diet on bone mineral density. Despite promising observations, there are still few observational and intervention studies and their results do not allow for unequivocal determination of the benefits of high daily intake of vitamin C or its long-term supplementation.
Synthesis, Optimization, Antifungal Activity, Selectivity, and CYP51 Binding of New 2-Aryl-3-azolyl-1-indolyl-propan-2-ols
Authors: Lebouvier Nicolas , Pagniez Fabrice , Na Young Min , Shi Da , Pinson Patricia , Marchivie Mathieu , Guillon Jean , Hakki Tarek , Bernhardt Rita , Yee Sook Wah , Simons Claire , Lézé Marie-Pierre , Hartmann Rolf W. , Mularoni Angélique , Le Baut Guillaume , Krimm Isabelle , Abagyan Ruben , Le Pape Patrice , Le Borgne Marc
Published: August 2020

A series of 2-aryl-3-azolyl-1-indolyl-propan-2-ols was designed as new analogs of fluconazole (FLC) by replacing one of its two triazole moieties by an indole scaffold. Two different chemical approaches were then developed. The first one, in seven steps, involved the synthesis of the key intermediate 1-(1H-benzotriazol-1-yl)methyl-1H-indole and the final opening of oxiranes by imidazole or 1H-1,2,4-triazole. The second route allowed access to the target compounds in only three steps, this time with the ring opening by indole and analogs. Twenty azole derivatives were tested against Candida albicans and other Candida species. The enantiomers of the best anti-Candida compound, 2-(2,4-dichlorophenyl)-3-(1H-indol-1-yl)-1-(1H-1,2,4-triazol-1-yl)-propan-2-ol (8g), were analyzed by X-ray diffraction to determine their absolute configuration. The (−)-8g enantiomer (Minimum inhibitory concentration (MIC) = IC80 = 0.000256 µg/mL on C. albicans CA98001) was found with the S-absolute configuration. In contrast the (+)-8g enantiomer was found with the R-absolute configuration (MIC = 0.023 µg/mL on C. albicans CA98001). By comparison, the MIC value for FLC was determined as 0.020 µg/mL for the same clinical isolate. Additionally, molecular docking calculations and molecular dynamics simulations were carried out using a crystal structure of Candida albicans lanosterol 14α-demethylase (CaCYP51). The (−)-(S)-8g enantiomer aligned with the positioning of posaconazole within both the heme and access channel binding sites, which was consistent with its biological results. All target compounds have been also studied against human fetal lung fibroblast (MRC-5) cells. Finally, the selectivity of four compounds on a panel of human P450-dependent enzymes (CYP19, CYP17, CYP26A1, CYP11B1, and CYP11B2) was investigated.
Emerging Therapeutic Modalities against COVID-19
Authors: Malik Shipra , Gupta Anisha , Zhong Xiaobo , Rasmussen Theodore P. , Manautou Jose E. , Bahal Raman
Published: August 2020

The novel SARS-CoV-2 virus has quickly spread worldwide, bringing the whole world as well as the economy to a standstill. As the world is struggling to minimize the transmission of this devastating disease, several strategies are being actively deployed to develop therapeutic interventions. Pharmaceutical companies and academic researchers are relentlessly working to investigate experimental, repurposed or FDA-approved drugs on a compassionate basis and novel biologics for SARS-CoV-2 prophylaxis and treatment. Presently, a tremendous surge of COVID-19 clinical trials are advancing through different stages. Among currently registered clinical efforts, ~86% are centered on testing small molecules or antibodies either alone or in combination with immunomodulators. The rest ~14% of clinical efforts are aimed at evaluating vaccines and convalescent plasma-based therapies to mitigate the disease's symptoms. This review provides a comprehensive overview of current therapeutic modalities being evaluated against SARS-CoV-2 virus in clinical trials.
Antibacterials in Aquatic Environment and Their Toxicity to Fish
Authors: Bojarski Bartosz , Kot Barbara , Witeska Małgorzata
Published: August 2020

Antibacterial agents are commonly present in aquatic environment at low concentrations. Terrestrial animal farms, human medicine and aquaculture are main sources of water contamination with antibacterials. Antibiotics were proved to be directly toxic to fish causing oxidative stress, general stress response, histopathological lesions, hematological, metabolic, and reproductive disorders, as well as immunosuppressive and genotoxic effects. Environmentally realistic low concentrations of antibiotics also disturb aquatic bacterial communities causing alterations in fish symbiotic microbiota and induce emergence of antibiotic-resistant pathogenic bacteria by exerting selective pressure on spread of antibiotic-resistance genes.
Electroresponsive Silk-Based Biohybrid Composites for Electrochemically Controlled Growth Factor Delivery
Authors: Magaz Adrián , Ashton Mark D. , Hathout Rania M. , Li Xu , Hardy John G. , Blaker Jonny J.
Published: August 2020

Stimuli-responsive materials are very attractive candidates for on-demand drug delivery applications. Precise control over therapeutic agents in a local area is particularly enticing to regulate the biological repair process and promote tissue regeneration. Macromolecular therapeutics are difficult to embed for delivery, and achieving controlled release over long-term periods, which is required for tissue repair and regeneration, is challenging. Biohybrid composites incorporating natural biopolymers and electroconductive/active moieties are emerging as functional materials to be used as coatings, implants or scaffolds in regenerative medicine. Here, we report the development of electroresponsive biohybrid composites based on Bombyx mori silkworm fibroin and reduced graphene oxide that are electrostatically loaded with a high-molecular-weight therapeutic (i.e., 26 kDa nerve growth factor-β (NGF-β)). NGF-β-loaded composite films were shown to control the release of the drug over a 10-day period in a pulsatile fashion upon the on/off application of an electrical stimulus. The results shown here pave the way for personalized and biologically responsive scaffolds, coatings and implantable devices to be used in neural tissue engineering applications, and could be translated to other electrically sensitive tissues as well.
Robustness Optimization of an Existing Tablet Coating Process Applying Retrospective Knowledge (rQbD) and Validation
Authors: Galí Albert , Ascaso Magda , Nardi-Ricart Anna , Suñé-Pou Marc , Pérez-Lozano Pilar , Suñé-Negre Josep M. , García-Montoya Encarna
Published: August 2020

The objective of these studies is to verify and validate the improvement in the inter-tablet coating uniformity for an industrially commercialized coated tablet, without involving changes in the approved registration dossier. Using the CPP (critical process parameters) determined from previous retrospective statistical analysis, the recommended working ranges are identified. Retrospective analysis showed that the design of experiments (DoE) provided an improved process variable configuration. Therefore, it is decided to study two critical parameters: Product temperature and drum speed, with an additional 22 experimental design. The quality results of the samples analyzed show that the aesthetic defects of the batches made with the new working ranges have been reduced. These results have also been corroborated with the 42 industrial batches manufactured with the new ranges. With the optimized parameters, tablets have been coated and the suitability of the model determined. The results demonstrated the overall reliability and effectiveness of the proposed Quality by Design approach and provides a useful tool to help optimize the industrial coating process. This study confirms that it is possible to optimize and validate the manufacturing process of an existing commercial product by means of a DoE with retrospective data. Therefore, no variation in the dossier is required.
Enhancing Oral Bioavailability of Apigenin Using a Bioactive Self-Nanoemulsifying Drug Delivery System (Bio-SNEDDS): In Vitro, In Vivo and Stability Evaluations
Authors: Kazi Mohsin , Alhajri Abdullah , Alshehri Sultan M. , Elzayat Ehab M. , Al Meanazel Osaid T. , Shakeel Faiyaz , Noman Omar , Altamimi Mohammad A. , Alanazi Fars K.
Published: August 2020

Apigenin (APG) is a very well-known flavonoid for its anti-inflammatory and anticancer properties. The purpose of this study is to improve the solubility and bioavailability of APG using a stable bioactive self-nanoemulsifying drug delivery system (Bio-SNEDDS). APG was incorporated in an oil phase comprising coconut oil fatty acid, Imwitor 988, Transcutol P, and HCO30 to form a Bio-SNEDDS. This preparation was characterized for morphology, particle size, and transmission electron microscopy (TEM). The APG performance was investigated in terms of loading, precipitation, release and stability tests from the optimal Bio-SNEDDS. An antimicrobial test was performed to investigate the activity of the Bio-SNEDDS against the selected strains. Bioavailability of the Bio-SNEDDS was evaluated using Wister rats against the commercial oral product and the pure drug. The results demonstrated the formation of an efficient nanosized (57 nm) Bio-SNEDDS with a drug loading of 12.50 mg/gm which is around 500-fold higher than free APG. TEM analysis revealed the formation of spherical and homogeneous nanodroplets of less than 60 nm. The dissolution rate was faster than the commercial product and was able to maintain 90% APG in gastro intestinal solution for more than 4 h. A stability study demonstrated that the Bio-SNEDDS is stable at a harsh condition. The in vivo pharmacokinetics parameters of the Bio-SNEDDS formulation in comparison to the pure drug showed a significant increase in maximum concentration (Cmax) and area under the curve (AUC (0–t)) of 105.05% and 91.32%, respectively. Moreover, the antimicrobial study revealed moderate inhibition in the bacterial growth rate. The APG-Bio-SNEDDS could serve as potential carrier aimed at improving the clinical application of APG.
Superhuman Enhancements via Implants: Beyond the Human Mind
Authors: Warwick Kevin
Published: August 2020

In this article, a practical look is taken at some of the possible enhancements for humans through the use of implants, particularly into the brain or nervous system. Some cognitive enhancements may not turn out to be practically useful, whereas others may turn out to be mere steps on the way to the construction of superhumans. The emphasis here is the focus on enhancements that take such recipients beyond the human norm rather than any implantations employed merely for therapy. This is divided into what we know has already been tried and tested and what remains at this time as more speculative. Five examples from the author’s own experimentation are described. Each case is looked at in detail, from the inside, to give a unique personal experience. The premise is that humans are essentially their brains and that bodies serve as interfaces between brains and the environment. The possibility of building an Interplanetary Creature, having an intelligence and possibly a consciousness of its own, is also considered.
Reflectivity of Cholesteric Liquid Crystals with an Anisotropic Defect Layer Inside
Authors: Grzelczyk Dariusz , Awrejcewicz Jan
Published: August 2020

In this study, first, we numerically investigated the reflectivity of a cholesteric liquid crystal with an anisotropic defect layer inside. To model optical phenomena in the examined system, a 4 × 4 matrix method was employed. The tests were carried out for different thicknesses of the whole system, different thicknesses of the defect layer, as well as different defect layer locations inside the cell. Next, a cholesteric liquid crystal comprising a defect layer and held between two parallel electrical conductors was also considered. In this case, the optical properties of the system could also be adjusted by an external applied electric field. Some interesting simulation results of the reflection coefficient (i.e., the fraction of electromagnetic energy reflected) were obtained, illustrated, and discussed. The simulation results showed a significant influence of both the defect and the external electric field on the selective reflection phenomenon, and the possibility of controlling the shape of the reflection spectrum. Finally, some potential applications of the analyzed optical system were discussed.
Trifolium repens-Associated Bacteria as a Potential Tool to Facilitate Phytostabilization of Zinc and Lead Polluted Waste Heaps
Authors: Oleńska Ewa , Imperato Valeria , Małek Wanda , Włostowski Tadeusz , Wójcik Małgorzata , Swiecicka Izabela , Vangronsveld Jaco , Thijs Sofie
Published: August 2020

Heavy metals in soil, as selective agents, can change the structure of plant-associated bacterial communities and their metabolic properties, leading to the selection of the most-adapted strains, which might be useful in phytoremediation. Trifolium repens, a heavy metal excluder, naturally occurs on metal mine waste heaps in southern Poland characterized by high total metal concentrations. The purpose of the present study was to assess the effects of toxic metals on the diversity and metabolic properties of the microbial communities in rhizospheric soil and vegetative tissues of T. repens growing on three 70–100-years old Zn–Pb mine waste heaps in comparison to Trifolium-associated bacteria from a non-polluted reference site. In total, 113 cultivable strains were isolated and used for 16S rRNA gene Sanger sequencing in order to determine their genetic affiliation and for in vitro testing of their plant growth promotion traits. Taxa richness and phenotypic diversity in communities of metalliferous origin were significantly lower (p < 0.0001) compared to those from the reference site. Two strains, Bacillus megaterium BolR EW3_A03 and Stenotrophomonas maltophilia BolN EW3_B03, isolated from a Zn–Pb mine waste heap which tested positive for all examined plant growth promoting traits and which showed co-tolerance to Zn, Cu, Cd, and Pb can be considered as potential facilitators of phytostabilization.
The Selection of Gamma-Ray Irradiated Higher Yield Rice Mutants by Directed Evolution Method
Authors: Kato Hiroshi , Li Feng , Shimizu Akemi
Published: August 2020

We have succeeded in selecting four higher yield mutants from five gamma-ray irradiated high-yielding Japanese rice varieties using a novel approach. A total of 464 M2 plants which had heavier total panicle weights per plant were first selected from 9801 irradiated M2 plants. Their higher yields were confirmed by yield trials conducted for three years with a six to ten-pairwise replicated plot design. FukuhibikiH6 and FukuhibikiH8 were selected from an irradiated high-yielding variety Fukuhibiki and showed 1.2% to 22.5% higher yield than their original significantly. YamadawaraH3 was selected from an irradiated high-yielding variety Yamadawara and its yield advantages were 2.7% to 3.9%. However, there was no difference in the genotypes of the 96 SNP (single nucleotide polymorphism) markers between the higher yield mutants and their respective original varieties. The differences in the measured phenotypical traits between each mutant and its original variety were not constant and the actual differences were marginal. Therefore, the higher yields of the selected mutants were likely to have been caused by physiological traits rather than phenotypical traits. The selection method used in this study is an application of the directed evolution method which has long been commonly used in the substantial improvements of microorganisms and their proteins.
Substrate and Plant Genotype Strongly Influence the Growth and Gene Expression Response to Trichoderma afroharzianum T22 in Sugar Beet
Authors: Schmidt John , Dotson Bradley R. , Schmiderer Ludwig , van Tour Adriaan , Kumar Banushree , Marttila Salla , Fredlund Kenneth M. , Widell Susanne , Rasmusson Allan G.
Published: August 2020

Many strains of Trichoderma fungi have beneficial effects on plant growth and pathogen control, but little is known about the importance of plant genotype, nor the underlying mechanisms. We aimed to determine the effect of sugar beet genotypic variation on Trichoderma biostimulation. The effect of Trichoderma afroharzianum T22 on sugar beet inbred genotypes were investigated in soil and on sterile agar medium regarding plant growth, and by quantitative reverse transcriptase-linked polymerase chain reaction (qRT-PCR) analysis for gene expression. In soil, T22 application induced up to 30% increase or decrease in biomass, depending on plant genotype. In contrast, T22 treatment of sterile-grown seedlings resulted in a general decrease in fresh weight and root length across all sugar beet genotypes. Root colonization of T22 did not vary between the sugar beet genotypes. Sand- and sterile-grown roots were investigated by qRT-PCR for expression of marker genes for pathogen response pathways. Genotype-dependent effects of T22 on, especially, the jasmonic acid/ethylene expression marker PR3 were observed, and the effects were further dependent on the growth system used. Thus, both growth substrate and sugar beet genotype strongly affect the outcome of inoculation with T. afroharzianum T22.
Effects of Harvest-Aids on Seed Nutrition in Soybean under Midsouth USA Conditions
Authors: Bellaloui Nacer , Bruns H. Arnold , Abbas Hamed K. , Fisher Daniel K. , Mengistu Alemu
Published: August 2020

Interest in using harvest aids (defoliants or crop desiccants) such as paraquat, carfentrazone-ethyl, glyphosate, and sodium chlorate (NaClO3) have become increasingly important to assure harvest efficiency, producer profit, and to maintain seed quality. However, information on the effects of harvest aids on seed nutrition (composition) (protein, oil, fatty acids, sugars, and amino acids) in soybean is very limited. The objective of this research was to investigate the influence of harvest aids on seed protein, oil, fatty acids, sugars, and amino acids in soybean. Our hypothesis was that harvest aid may influence seed nutrition, especially at R6 as at R6 the seeds may still undergo biochemical changes. Field experiments were conducted in 2012 and 2013 under Midsouth USA environmental conditions in which harvest aids were applied at R6 (seed-fill) and R7 (yellow pods) growth stages. Harvest aids applied included an untreated control, 0.28 kg ai ha−1 of paraquat, 0.28 kg ai ha−1 of paraquat, and 1.015 kg ai ha−1 of carfentrazone-ethyl (AIM); 6.72 kg ai ha−1 sodium chlorate, 1.015 kg ai ha−1 carfentrazone-ethyl; and 2.0 kg ae ha−1 glyphosate. Results showed that the application of harvest aids at either R6 or R7 resulted in the alteration of some seed composition such as protein, oil, oleic acid, fructose, and little effects on amino acids. In addition, harvest aids affected seed composition constituents differently depending on year and growth stage. This research demonstrated the possible alteration of some nutrients by harvest aids. This research helps growers and scientists to advance the understanding and management of harvest aids and investigate possible effects of harvest aids on seed nutrition.
Semi-Targeted Metabolomics to Validate Biomarkers of Grape Downy Mildew Infection Under Field Conditions
Authors: Billet Kévin , Malinowska Magdalena Anna , Munsch Thibaut , Unlubayir Marianne , Adler Sophie , Delanoue Guillaume , Lanoue Arnaud
Published: August 2020

Grape downy mildew is a devastating disease worldwide and new molecular phenotyping tools are required to detect metabolic changes associated to plant disease symptoms. In this purpose, we used UPLC-DAD-MS-based semi-targeted metabolomics to screen downy mildew symptomatic leaves that expressed oil spots (6 dpi, days post-infection) and necrotic lesions (15 dpi) under natural infections in the field. Leaf extract analyses enabled the identification of 47 metabolites belonging to the primary metabolism including 6 amino acids and 1 organic acid, as well as an important diversity of specialized metabolites including 9 flavonols, 11 flavan-3-ols, 3 phenolic acids, and stilbenoids with various degree of polymerization (DP) including 4 stilbenoids DP1, 8 stilbenoids DP2, and 4 stilbenoids DP3. Principal component analysis (PCA) was applied as unsupervised multivariate statistical analysis method to reveal metabolic variables that were affected by the infection status. Univariate and multivariate statistics revealed 33 and 27 metabolites as relevant infection biomarkers at 6 and 15 dpi, respectively. Correlation-based networks highlighted a general decrease of flavonoid-related metabolites, whereas stilbenoid DP1 and DP2 concentrations increased upon downy mildew infection. Stilbenoids DP3 were identified only in necrotic lesions representing late biomarkers of downy mildew infection.