bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustainable Recovery of Valuable Nanoporous Materials from High-Chlorine MSWI Fly Ash by Ultrasound with Organic Acids
Authors: Nguyen Tam Thanh , Tsai Cheng-Kuo , Horng Jao-Jia
Published: April 2022

The new technology development for municipal solid waste incineration fly ash treatment and reuse is urgent due to landfill shortage and environmental effect of leached hazardous substances. Chlorine (Cl) is worth considering due to its high levels in fly ash. In this study, a treatment process of ultrasound combined with organic acid was used to eliminate Cl from fly ash to enhance its properties for reuse. Taguchi methodology was implemented to design the experiments by controlling four impact factors and the contribution of each factor was evaluated by the ANOVA analysis of variance. Following two treatment steps within 5 min with a solid/liquid ratio of 1:10 at 165 kHz, 98.8% of Cl was eliminated. Solid/liquid ratio was the most prominent factor that contributed to the Cl removal with more than 90%, according to the ANOVA analysis of variance. Tert-butyl alcohol (tBuOH), an •OH radical scavenger, was utilized to examine different effects of ultrasonic cavitation on Cl removal efficiency. A 20 kHz ultrasound was used to explore the influence of multi-frequency ultrasound with different mechanical and sonochemical effects on the fly ash dechlorination. This ultrasonic-assisted organic acid treatment was found to be a time and cost-effective pathway for fly ash Cl removal.
Laser-Induced Plasmonic Nanobubbles and Microbubbles in Gold Nanorod Colloidal Solution
Authors: Yu Shang-Yang , Tu Chang-Hsuan , Liaw Jiunn-Woei , Kuo Mao-Kuen
Published: April 2022

In this work, we studied the initiated plasmonic nanobubbles and the follow-up microbubble in gold nanorod (GNR) colloidal solution induced by a pulsed laser. Owing to the surface plasmon resonance (SPR)-enhanced photothermal effect of GNR, several nanobubbles are initiated at the beginning of illumination and then to trigger the optical breakdown of water at the focal spot of a laser beam. Consequently, microbubble generation is facilitated; the threshold of pulsed laser energy is significantly reduced for the generation of microbubbles in water with the aid of GNRs. We used a probing He-Ne laser with a photodetector and an ultrasonic transducer to measure and investigate the dynamic formations of nanobubbles and the follow-up microbubble in GNR colloids. Two wavelengths (700 nm and 980 nm) of pulsed laser beams are used to irradiate two kinds of dilute GNR colloids with different longitudinal SPRs (718 nm and 966 nm). By characterizing the optical and photoacoustic signals, three types of microbubbles are identified: a single microbubble, a coalesced microbubble of multiple microbubbles, and a splitting microbubble. The former is caused by a single breakdown, whereas the latter two are caused by discrete and series-connected multiple breakdowns, respectively. We found that the thresholds of pulsed energy to induce different types of microbubbles are reduced as the concentration of GNRs increases, particularly when the wavelength of the laser is in the near-infrared (NIR) region and close to the SPR of GNRs. This advantage of a dilute GNR colloid facilitating the laser-induced microbubble in the NIR range of the bio-optical window could make biomedical applications available. Our study may provide an insight into the relationship between plasmonic nanobubbles and the triggered microbubbles.
Synthesis of BiOI/Mordenite Composites for Photocatalytic Treatment of Organic Pollutants Present in Agro-Industrial Wastewater
Authors: Gallegos-Alcaíno Alejandra , Robles-Araya Nathaly , Avalos Camila , Alfonso-Alvarez Alexander , Rodríguez Carlos A. , Valdés Héctor , Sánchez-Flores Norma A. , Durán-Alvarez Juan C. , Bizarro Monserrat , Romero-Salguero Francisco J. , Mera Adriana C.
Published: April 2022

Recently, bismuth oxyiodide (BiOI) is an attractive semiconductor to use in heterogeneous photocatalysis processes. Unfortunately, BiOI individually shows limited photocatalytic efficiency, instability, and a quick recombination of electron/holes. Considering the practical application of this semiconductor, some studies show that synthetic zeolites provide good support for this photocatalyst. This support material permits a better photocatalytic efficiency because it prevents the quick recombination of photogenerated pairs. However, the optimal conditions (time and temperature) to obtain composites (BiOI/ synthetic zeolite) with high photocatalytic efficiency using a coprecipitation-solvothermal growth method have not yet been reported. In this study, a response surface methodology (RSM) based on a central composite design (CCD) was applied to optimize the synthesis conditions of BiOI/mordenite composites. For this purpose, eleven BiOI/mordenite composites were synthesized using a combined coprecipitation-solvothermal method under different time and temperature conditions. The photocatalytic activities of the synthesized composites were evaluated after 20 min of photocatalytic oxidation of caffeic acid, a typical organic pollutant found in agro-industrial wastewater. Moreover, BiOI/mordenite composites with the highest and lowest photocatalytic activity were physically and chemically characterized using nitrogen adsorption isotherms, scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and diffuse reflectance spectroscopy (DRS). The optimal synthesis conditions prove to be 187 °C and 9 h. In addition, the changes applied to the experimental conditions led to surface property modifications that influenced the photocatalytic degradation efficiency of the BiOI/mordenite composite toward caffeic acid photodegradation.
Manufacturing a TiO2-Based Semiconductor Film with Nanofluid Pool Boiling and Sintering Processes toward Solar-Cell Applications
Authors: Vafaei Saeid , Holmes Ian , Errion Benjamin , Thukka Zigmey , Narita Ryoki , Sugiura Takashi , Manseki Kazuhiro
Published: April 2022

For the first time, nanofluid boiling was applied as a process for the creation of a semiconductor TiO2 nanoparticle film that can be deposited onto a conductive substrate (F-doped SnO2 glass: FTO). A steel-base device designed for pool boiling was used to deposit a TiO2-based nanofluid consisting of nanoparticles with an average size of about 20 nm. The boiling of the nanofluid directly on the FTO glass substrate allowed for the deposition of the nanoparticles onto the FTO surface. In principle, the surface responsible for transferring heat to the fluid can be covered with these nanoparticles when the nanofluid boils. Using the as-deposited films, crystal growth of the TiO2 nanoparticle was controlled by varying the strategies of the post-sintering profile. The maximum temperatures, periods, and ramping rates for the obtained samples were systematically changed. Scanning electron microscopy (SEM) revealed that a densely packed TiO2-nanoparticle layer was obtained for the as-deposited substrate via pool boiling. For the maximum temperature at 550 °C, the TiO2 grain sizes became larger (~50 nm) and more round-shaped TiO2 nanostructures were identified. Notably, we have demonstrated for the first time how the sintering of TiO2 nanoparticles proceeds for the nanoporous TiO2 films using high-resolution transmission electron microscopy (TEM) measurements. We found that the TiO2 nanoparticles fused with each other and crystal growth occurred through neighboring 2–4 nanoparticles for the 550 °C sample, which was proved by the TEM analysis that continuous lattice fringes corresponding to the (101) anatase phase were clearly observed through the entire area of some nanoparticles aligned horizontally. In addition, the loss of the TiO2 nanofluid (precursor solution) was completely avoided in our TiO2 deposition. Unlike the commonly used spin-coating method, nanofluid pool boiling would provide an alternative cost-effective approach to manufacture semiconductor layers for various applications, such as solar cells.
A Non-Resonant Piezoelectric–Electromagnetic–Triboelectric Hybrid Energy Harvester for Low-Frequency Human Motions
Authors: Tang Gang , Wang Zhen , Hu Xin , Wu Shaojie , Xu Bin , Li Zhibiao , Yan Xiaoxiao , Xu Fang , Yuan Dandan , Li Peisheng , Shi Qiongfeng , Lee Chengkuo
Published: April 2022

With the rapid development of wireless communication and micro-power technologies, smart wearable devices with various functionalities appear more and more in our daily lives. Nevertheless, they normally possess short battery life and need to be recharged with external power sources with a long charging time, which seriously affects the user experience. To help extend the battery life or even replace it, a non-resonant piezoelectric–electromagnetic–triboelectric hybrid energy harvester is presented to effectively harvest energy from low-frequency human motions. In the designed structure, a moving magnet is used to simultaneously excite the three integrated energy collection units (i.e., piezoelectric, electromagnetic, and triboelectric) with a synergistic effect, such that the overall output power and energy-harvesting efficiency of the hybrid device can be greatly improved under various excitations. The experimental results show that with a vibration frequency of 4 Hz and a displacement of 200 mm, the hybrid energy harvester obtains a maximum output power of 26.17 mW at 70 kΩ for one piezoelectric generator (PEG) unit, 87.1 mW at 500 Ω for one electromagnetic generator (EMG) unit, and 63 μW at 140 MΩ for one triboelectric nanogenerator (TENG) unit, respectively. Then, the generated outputs are adopted for capacitor charging, which reveals that the performance of the three-unit integration is remarkably stronger than that of individual units. Finally, the practical energy-harvesting experiments conducted on various body parts such as wrist, calf, hand, and waist indicate that the proposed hybrid energy harvester has promising application potential in constructing a self-powered wearable system as the sustainable power source.
Diallyl Trisulfide Induces Apoptosis in Breast Ductal Carcinoma In Situ Derived and Minimally Invasive Breast Cancer Cells
Authors: Stan Silvia D. , Abtahi Minna
Published: April 2022

Breast ductal carcinoma in situ (DCIS) is a localized form of breast cancer that can progress to invasive breast cancer. Diallyl trisulfide (DATS) is a bioactive compound from Allium vegetables reported to induce anticancer effects in several cancer models. The objective of this study was to characterize DATS-induced apoptosis in breast DCIS and minimally invasive breast cancer cells. Breast DCIS cells SUM 102PT (ductal carcinoma in situ with areas of micro-invasion) and SUM 225CWN (chest wall recurrence of ductal carcinoma in situ) were used in this study. DATS induced a dose-dependent reduction in the colony formation ability of breast DCIS cells. DATS inhibited DCIS cell growth by inducing apoptosis as shown by a dose-dependent increase in cytoplasmic histone-associated DNA fragmentation. Induction of apoptosis was more pronounced in SUM 102PT cells than in SUM 225CWN cells at similar concentrations of DATS. DATS-induced apoptosis was characterized by a dose-dependent increase in cleaved poly-ADP ribose polymerase (PARP). DATS treatment resulted in an increase in the cytochrome c levels and cleavage of caspases 3, 7, and 9. This study shows that DATS inhibits cell proliferation and induces apoptosis in breast DCIS derived and minimally invasive breast cancer cells, and supports further investigation of DATS as a potential chemopreventive agent for DCIS.
Estimation of Vitamin C Intake Requirements Based on Body Weight: Implications for Obesity
Authors: Carr Anitra C. , Block Gladys , Lykkesfeldt Jens
Published: April 2022

Higher body weight is known to negatively impact plasma vitamin C status. However, despite this well-documented inverse association, recommendations on daily vitamin C intakes by health authorities worldwide do not include particular reference values for people of higher body weight. This suggests that people of higher body weight and people with obesity may be receiving insufficient vitamin C in spite of ingesting the amounts recommended by their health authorities. The current preliminary investigation sought to estimate how much additional vitamin C people with higher body weights would need to consume in order to attain a comparable vitamin C status to that of a lower weight person consuming an average Western vitamin C intake. Data from two published vitamin C dose-concentration studies were used to generate the relationship: a detailed pharmacokinetic study with seven healthy non-smoking men and a multiple depletion–repletion study with 68 healthy non-smoking men of varying body weights. Our estimates suggest that an additional intake of 10 mg vitamin C/day is required for every 10 kg increase in body weight to attain a comparable plasma concentration to a 60 kg individual with a vitamin C intake of ~110 mg/day, which is the daily intake recommended by the European Food Safety Authority (EFSA). Thus, individuals weighing e.g., 80 and 90 kg will need to consume ~130 and 140 mg vitamin C/day, respectively. People with obesity will likely need even higher vitamin C intakes. As poor vitamin C status is associated with increased risk of several chronic diseases including cardiovascular disease, these findings may have important public health implications. As such, dose-finding studies are required to determine optimal vitamin C intakes for overweight and obese people.
Gastrointestinal Tolerance of Short-Chain Fructo-Oligosaccharides from Sugar Beet: An Observational, Connected, Dose-Ranging Study in Healthy Volunteers
Authors: Le Bourgot Cindy , Rigaudier Florian , Juhel Christine , Herpin Florent , Meunier Claire
Published: April 2022

Dietary fibres are important in the human diet with multiple health benefits. This study aimed to determine the gastrointestinal tolerance of short-chain fructo-oligosaccharides (scFOS), well-known prebiotic fibres, at doses up to 40 g/d. An observational, connected, dose-ranging trial was conducted in 116 healthy volunteers. During the first week, the participants were instructed to consume their usual diet. During the second week, half of the subjects consumed 15 g scFOS per day, and the other half consumed 20 g scFOS per day. For the third week, the scFOS dose was doubled for all subjects. Gastrointestinal symptom severity was reported daily, as well as stool consistency and frequency. The results show that scFOS are well tolerated up to 40 g/d; all reported symptoms remained very mild from a clinical perspective. Stool consistency stayed normal, between 3 and 5 on the Bristol stool scale, confirming that no diarrhoea appeared after scFOS intake. Stool frequency also remained within the normal range. In conclusion, scFOS intake is well tolerated up to 40 g/d in healthy subjects. Thanks to their short chains and unique composition, scFOS prebiotic fibres are much better tolerated than other types of inulin-type fructans with longer chains. The digestive tolerance of fibres should be considered when added to foods and beverages.
Food Insecurity across the Life-Course and Cognitive Function among Older Mexican Adults
Authors: Saenz Joseph L. , Kessler Jamie , Nelson Ehlana
Published: April 2022

Background: Food insecurity remains a global public health problem. Experiencing food insecurity is related to poorer cognitive function among older adults. However, few studies have examined how food insecurity, experienced over the life-course, relates to cognitive function among older adults in Mexico. Methods: Data came from the 2015 Mexican Health and Aging Study (n = 11,507 adults aged 50 and over). Early- and late-life food insecurity were ascertained by self-report. We evaluated how both measures of food insecurity related to the performance of multiple cognitive tasks (Verbal Learning, Verbal Recall, Visual Scanning, and Verbal Fluency), while controlling for key health and sociodemographic confounders using linear regression. Results: In descriptive analyses, respondents who experienced food insecurity in either early or late life performed significantly worse on all cognitive tasks when compared to the food secure. In models adjusted for health and sociodemographic confounders, early-life food insecurity predicted worse Verbal Learning performance and late-life food insecurity was associated with poorer Visual Scanning performance. Conclusions: Food insecurity was related to poorer cognitive function in a nationally representative sample of older adults in Mexico. However, results suggested that the significance of effects depended on cognitive task and when in the life-course food insecurity was experienced.
Higher Dietary Intake of Advanced Glycation End Products Is Associated with Faster Cognitive Decline in Community-Dwelling Older Adults
Authors: Schnaider Beeri Michal , Lotan Roni , Uribarri Jaime , Leurgans Sue , Bennett David A. , Buchman Aron S.
Published: April 2022

Objective: Dietary-derived advanced glycation end products (AGEs) vary for different food types and the methods employed during their preparation may contribute to diverse chronic health conditions. The goal of this study was to investigate the associations of dietary AGEs (dAGEs) with cognitive decline in older adults. Methods: Non-demented older adults (n = 684) underwent annual testing with 19 cognitive tests summarized as a global cognitive score based on five cognitive domains. We modified a previously validated food frequency questionnaire designed to assess dAGE. The modified questionnaire assessed portion size and frequency of consumption of six food groups (meat, poultry, fish, cheese, spreads, and processed foods), as well as the method of their preparation (e.g., grilling, boiling). dAGE was the sum of the scores of the six food groups. Linear mixed-effect models were used to examine the association of baseline dAGE with cognitive decline. All models controlled for age, sex, education, race, and body mass index (BMI). Results: Average follow-up was 3.0 years. Higher baseline dAGEs was associated with a faster rate of global cognitive decline (Estimate = −0.003 (standard error = 0.001, p-value = 0.015). This association was driven by declines in episodic memory (−0.004 (0.002, 0.013)) and perceptual speed (−0.003 (0.001, 0.049)) but not by semantic memory, working memory, and visuospatial domains. These associations were not attenuated by controlling for cardiovascular risk factors and diseases, including diabetes. Levels of dAGE of the specific food groups were not associated with cognitive decline. Conclusions: Higher levels of dietary AGE levels in older adults are associated with faster cognitive decline. These data lend further support for the importance of diet and that its modification may slow or prevent late-life cognitive impairment. Further clinical studies will be needed and the molecular mechanisms underlying these associations will need to be identified.
Lung Diffusing Capacity in Dutch Special Operations Forces Divers Exposed to Oxygen Rebreathers over 18 Years
Authors: den Ouden Tom H.B. , Wingelaar Thijs T. , Endert Edwin L. , van Ooij Pieter-Jan A.M.
Published: April 2022

Exposure to hyperoxic conditions can induce pulmonary oxygen toxicity (POT). Divers of the Special Operations Forces (SOF) use oxygen rebreather systems during dives, and therefore are frequently exposed to hyperoxic conditions. Few studies have reported on POT in this population. This study reports on long-term pulmonary function tests (PFTs) and diffusing capacity in SOF divers to test the hypothesis that these measures of pulmonary function do not change clinically significantly during their career. The Royal Netherlands Navy performs yearly medical assessments of its military divers. All PFT and diffusing capacity data of SOF divers between the years 2000 and 2020 were analyzed using generalized estimating equations. The study included 257 SOF divers (median age, 27; interquartile range, 24–32), with 1612 dive medical assessments and a maximum follow-up time of 18.8 years. Alveolar volume (VA) and the diffusing capacity of carbon monoxide (TLCO) were significantly lower at baseline in smokers. Although these parameters were within the normal range, they declined over time and were significantly associated with age and years of diving. Smoking additionally affected TLCO and the transfer coefficient for carbon monoxide (KCO). TLCO and KCO were reduced by years of diving with oxygen rebreathers, albeit over clinically insignificant ranges, but smoking increased these changes by factors of 10 and 15, respectively.
Impact of Vaccination on Rotavirus Genotype Diversity: A Nearly Two-Decade-Long Epidemiological Study before and after Rotavirus Vaccine Introduction in Sicily, Italy
Authors: Bonura Floriana , Mangiaracina Leonardo , Filizzolo Chiara , Bonura Celestino , Martella Vito , Ciarlet Max , Giammanco Giovanni M. , De Grazia Simona
Published: April 2022

Sicily was the first Italian region to introduce rotavirus (RV) vaccination with the monovalent G1P[8] vaccine Rotarix® in May 2012. In this study, the seasonal distribution and molecular characterization of RV strains detected over 19 years were compared to understand the effect of Rotarix® on the evolutionary dynamics of human RVs. A total of 7846 stool samples collected from children < 5 years of age, hospitalized with acute gastroenteritis, were tested for RV detection and genotyping. Since 2013, vaccine coverage has progressively increased, while the RV prevalence decreased from 36.1% to 13.3% with a loss of seasonality. The local distribution of RV genotypes changed over the time possibly due to vaccine introduction, with a drastic reduction in G1P[8] strains replaced by common and novel emerging RV strains, such as equine-like G3P[8] in the 2018–2019 season. Comparison of VP7 and VP4 amino acid (aa) sequences with the cognate genes of Rotarix® and RotaTeq® vaccine strains showed specific aa changes in the antigenic epitopes of VP7 and of the VP8* portion of VP4 of the Italian RV strains. Molecular epidemiological surveillance data are required to monitor the emergence of novel RV strains and ascertain if these strains may affect the efficacy of RV vaccines.
Evaluation of Staphylococcus aureus Colonization in Adult Patients Undergoing Tonsillectomy for Recurrent Tonsillitis
Authors: Klagisa Renata , Racenis Karlis , Broks Renars , Kise Ligija , Kroiča Juta
Published: April 2022

Background and objectives: Staphylococcus aureus (S. aureus) is often recovered from the pharynx. However, the role of this pathogen in the etiology of tonsillar inflammation is still unclear and complicated due to frequent carriage of S. aureus. The aim of the study was to evaluate the frequency and the clinical importance of S. aureus colonization and biofilm production ability in patients with recurrent tonsillitis (RT) using patient samples from tonsillar crypts during tonsillectomy, and from the throat, nasal cavity, and armpits after tonsillectomy. Materials and Methods: A case series study was carried out at a tertiary referral center among 16 patients diagnosed with RT who were undergoing tonsillectomy. Samples from tonsillar crypts were obtained during tonsillectomy, and samples from the throat, nasal cavity, and armpit were obtained a year after surgery. An evaluation of S. aureus incidence, biofilm formation, and antibacterial susceptibility was performed. Results: During tonsillectomy, 16 strains of S. aureus were isolated from 16 patients, while 15/16 S. aureus strains were biofilm producers. A year after tonsillectomy, 8 S. aureus strains were isolated from 6 out of 16 patients, while 6/8 S. aureus strains were biofilm producers. After tonsillectomy, 3 patients showed S. aureus in throat culture. Conclusions: In 10/16 cases S. aureus was the causative agent of RT, in 4/16 cases patients had a predisposition to colonization of S. aureus, and in 2/16 cases S. aureus was a part of the patients` oral microbiome. Tonsillectomy results in less frequent isolation of S. aureus strains.
Assessing Differences between Clinical Isolates of Aspergillus fumigatus from Cases of Proven Invasive Aspergillosis and Colonizing Isolates with Respect to Phenotype (Virulence in Tenebrio molitor Larvae) and Genotype
Authors: El-Kamand Sam , Steiner Martina , Ramirez Carl , Halliday Catriona , Chen Sharon C.-A. , Papanicolaou Alexie , Morton Charles Oliver
Published: April 2022

The fungus Aspergillus fumigatus, the cause of invasive aspergillosis (IA), is a serious risk to transplant patients and those with respiratory diseases. Host immune suppression is considered the most important factor for the development of IA. Less is known about the importance of fungal virulence in the development of IA including the significance of variation between isolates. In this study, isolates of A. fumigatus from cases diagnosed as having proven IA or colonisation (no evidence of IA) were compared in assays to measure isolate virulence. These assays included the measurement of radial growth and protease production on agar, sensitivity to UV light and oxidative stressors, and virulence in Tenebrio molitor (mealworm) larvae. These assays did not reveal obvious differences in virulence between the two groups of isolates; this provided the impetus to conduct genomic analysis. Whole genome sequencing and analysis did not allow grouping into coloniser or IA isolates. However, focused analysis of single nucleotide polymorphisms revealed variation in three putative genes: AFUA_5G09420 (ccg-8), AFUA_4G00330, and AFUA_4G00350. These are known to be responsive to azole exposure, and ccg-8 deletion leads to azole hypersensitivity in other fungi. A. fumigatus virulence is challenging, but the findings of this study indicate that further research into the response to oxidative stress and azole exposure are required to understand the development of IA.
Fucoidan Is Not Completely Dependent on Degradation to Fucose to Relieve Ulcerative Colitis
Authors: Wei Qiang , Xing Maochen , Wang Ke , Yang Qiong , Zhao Jiarui , Wang Yuan , Li Xia , Ji Kai , Song Shuliang
Published: April 2022

Recently, fucoidan has been proposed for use as a potential anti-inflammatory drug. The purpose of this study was to investigate the mechanism of fucoidan in the treatment of ulcerative colitis. We compared the anti-inflammatory effects of fucoidan and fucose induced by dextran sulfate sodium, and the effects of fucoidan and fucose on the gut microbiota of mice. Our results showed that low-dose fucoidan significantly improved weight loss, disease activity index scores, colonic shortening, colonic histopathological damage, intestinal fatty acid binding protein 2 levels, and the expression of Occludin, Claudin-4, and Claudin-1. However, both high-dose fucoidan and fucose did not perform as well as low-dose fucoidan as described above. In addition, 16S rDNA high-throughput sequencing showed that low-dose fucoidan significantly increased the abundance of Alloprevotella, and fucose significantly increased Ruminococcaceae, but neither significantly reversed the imbalance in the gut microbiota. Therefore, we inferred that the regulation of fucoidan on colitis has a unique and complex mechanism, and it is not completely dependent on degradation to fucose to relieve ulcerative colitis, nor is it achieved only by regulating the gut microbiota. The mechanism by which fucoidan treats colitis may also include reducing inflammatory cell infiltration and increasing intestinal barrier function.
Development of Advanced 3D-Printed Solid Dosage Pediatric Formulations for HIV Treatment
Authors: Malebari Azizah M. , Kara Aytug , Khayyat Ahdab N. , Mohammad Khadijah A. , Serrano Dolores R.
Published: April 2022

The combination of lopinavir/ritonavir remains one of the first-line therapies for the initial antiretroviral regimen in pediatric HIV-infected children. However, the implementation of this recommendation has faced many challenges due to cold-chain requirements, high alcohol content, and unpalatability for ritonavir-boosted lopinavir syrup. In addition, the administration of crushed tablets has shown a detriment for the oral bioavailability of both drugs. Therefore, there is a clinical need to develop safer and better formulations adapted to children’s needs. This work has demonstrated, for the first time, the feasibility of using direct powder extrusion 3D printing to manufacture personalized pediatric HIV dosage forms based on 6 mm spherical tablets. H-bonding between drugs and excipients (hydroxypropyl methylcellulose and polyethylene glycol) resulted in the formation of amorphous solid dispersions with a zero-order sustained release profile, opposite to the commercially available formulation Kaletra, which exhibited marked drug precipitation at the intestinal pH.
Peptides vs. Polymers: Searching for the Most Efficient Delivery System for Mitochondrial Gene Therapy
Authors: Faria Rúben , Paul Milan , Biswas Swati , Vivès Eric , Boisguérin Prisca , Sousa Ângela , Costa Diana
Published: April 2022

Together with the nucleus, the mitochondrion has its own genome. Mutations in mitochondrial DNA are responsible for a variety of disorders, including neurodegenerative diseases and cancer. Current therapeutic approaches are not effective. In this sense, mitochondrial gene therapy emerges as a valuable and promising therapeutic tool. To accomplish this goal, the design/development of a mitochondrial-specific gene delivery system is imperative. In this work, we explored the ability of novel polymer- and peptide-based systems for mitochondrial targeting, gene delivery, and protein expression, performing a comparison between them to reveal the most adequate system for mitochondrial gene therapy. Therefore, we synthesized a novel mitochondria-targeting polymer (polyethylenimine–dequalinium) to load and complex a mitochondrial-gene-based plasmid. The polymeric complexes exhibited physicochemical properties and cytotoxic profiles dependent on the nitrogen-to-phosphate-group ratio (N/P). A fluorescence confocal microscopy study revealed the mitochondrial targeting specificity of polymeric complexes. Moreover, transfection mediated by polymer and peptide delivery systems led to gene expression in mitochondria. Additionally, the mitochondrial protein was produced. A comparative study between polymeric and peptide/plasmid DNA complexes showed the great capacity of peptides to complex pDNA at lower N/P ratios, forming smaller particles bearing a positive charge, with repercussions on their capacity for cellular transfection, mitochondria targeting and, ultimately, gene delivery and protein expression. This report is a significant contribution to the implementation of mitochondrial gene therapy, instigating further research on the development of peptide-based delivery systems towards clinical translation.
Radiolabeling Method for Lyophilizate for Dry Powder Inhalation Formulations
Authors: Miyamoto Kahori , Akita Tomomi , Yamashita Chikamasa
Published: April 2022

Human lung deposition data is non-mandatory for drug approval but very useful for the development of orally inhaled drug products. Lung deposition of inhaled drugs can be quantified by radionuclide imaging, for which one of the first considerations is the method used to radiolabel formulations. In this study, we report the development of a radiolabeling method for lyophilizate for dry powder inhalation (LDPI) formulations. TechneCoatTM is one method that can radiolabel drug particles without using solvents. In this method, particles are radiolabeled with a dispersion of 99mTc-labeled nanoparticles called TechnegasTM. Because a LDPI formulation is not comprised of particles but is a lyophilized cake aerosolized by air impact, the TechneCoat method cannot be used for the radiolabeling of LDPI formulations. We therefore modified the TechneCoat apparatus so that LDPI formulations were not aerosolized by the Technegas flow. Radiolabeling using a modified TechneCoat apparatus was validated with model LDPI formulations of interferon alpha (IFN). IFN of 99mTc-unlabeled, IFN of 99mTc-labeled, and 99mTc of 99mTc-labeled LDPI formulations showed similar behavior, and differences from IFN of 99mTc-unlabeled LDPI formulations were within ±15% in aerodynamic particle size distribution measurement. Our radiolabeling method for LDPI formulations may be useful for the quantification of drug deposition in human lungs.
Polymer-Stabilized Elemental Boron Nanoparticles for Boron Neutron Capture Therapy: Initial Irradiation Experiments
Authors: Zaboronok Alexander , Khaptakhanova Polina , Uspenskii Sergey , Bekarevich Raman , Mechetina Ludmila , Volkova Olga , Mathis Bryan J. , Kanygin Vladimir , Ishikawa Eiichi , Kasatova Anna , Kasatov Dmitrii , Shchudlo Ivan , Sycheva Tatiana , Taskaev Sergey , Matsumura Akira
Published: April 2022

Sufficient boron-10 isotope (10B) accumulation by tumor cells is one of the main requirements for successful boron neutron capture therapy (BNCT). The inability of the clinically registered 10B-containing borophenylalanine (BPA) to maintain a high boron tumor concentration during neutron irradiation after a single injection has been partially solved by its continuous infusion; however, its lack of persistence has driven the development of new compounds that overcome the imperfections of BPA. We propose using elemental boron nanoparticles (eBNPs) synthesized by cascade ultrasonic dispersion and destruction of elemental boron microparticles and stabilized with hydroxyethylcellulose (HEC) as a core component of a novel boron drug for BNCT. These HEC particles are stable in aqueous media and show no apparent influence on U251, U87, and T98G human glioma cell proliferation without neutron beam irradiation. In BNCT experiments, cells incubated with eBNPs or BPA at an equivalent concentration of 40 µg 10B/mL for 24 h or control cells without boron were irradiated at an accelerator-based neutron source with a total fluence of thermal and epithermal neutrons of 2.685, 5.370, or 8.055 × 1012/cm2. The eBNPs significantly reduced colony-forming capacity in all studied cells during BNCT compared to BPA, verified by cell-survival curves fit to the linear-quadratic model and calculated radiobiological parameters, though the effect of both compounds differed depending on the cell line. The results of our study warrant further tumor targeting-oriented modifications of synthesized nanoparticles and subsequent in vivo BNCT experiments.
Fabricating High-Resolution and High-Dimensional Microneedle Mold through the Resolution Improvement of Stereolithography 3D Printing
Authors: Choo Sangmin , Jin SungGiu , Jung JaeHwan
Published: April 2022

Microneedles are transdermal drug delivery tools that can be fabricated simply, economically, and rapidly using SLA 3D printing. However, SLA 3D printing has a limitation in that the resolution is slightly lowered when the microneedle is precisely printed. To solve this issue, we optimized the SLA 3D printing conditions such as printing angle, needle height, aspect ratio, and spacing between the microneedles for high-resolution microneedle fabrication. The sharpest microneedle tip was obtained when the printing angle was adjusted to 60° in both the x and y axes. The aspect ratio and the spacing between the microneedles did not affect the output of the sharp tip. Under optimal conditions, the microneedles with 1180 ± 20 µm height, 490 ± 20 µm base, and 30.2 ± 3.4 µm tip diameter were obtained. The dissolving microneedle patch, prepared using the 3D printed microneedle as a mold, penetrated the porcine skin ex vivo. When the printing angle was 60° in the x and y axes, the area of the single stacking layer, including the microneedle tip, increased, and thus the sharp tip could be printed. A high-dimensional, side-notched arrowhead (SNA) microneedle was fabricated by applying the SLA 3D printing condition. Moreover, a letter-type microneedle patch was fabricated using the customized characteristics of 3D printing. Consequently, high-resolution and high-dimensional microneedles were successfully fabricated by adjusting the printing angle using a general SLA 3D printer, and this technology will be applied to the manufacture of drug delivery tools and various microstructures.
Dual-Functional Polymeric Micelles Co-Loaded with Antineoplastic Drugs and Tyrosine Kinase Inhibitor for Combination Therapy in Colorectal Cancer
Authors: Shih Ying-Hsia , Peng Cheng-Liang , Chiang Ping-Fang , Shieh Ming-Jium
Published: April 2022

The aim of this research was to evaluate the receptor tyrosine kinase inhibitor Sunitinib combined with SN-38 in polymeric micelles for antitumor efficacy in colorectal cancer. First, SN-38 and Sunitinib co-loaded micelles were developed and characterized. We studied cell viability and cellular uptake in HCT-116 cells. Then, subcutaneous HCT-116 xenograft tumors were used for ex vivo biodistribution, antitumor efficacy, and histochemical analysis studies. Results of cellular uptake and ex vivo biodistribution of SN-38/Sunitinib micelles showed the highest accumulation in tumors compared with other normal organs. In the antitumor effect studies, mice bearing HCT-116 tumors were smallest at day 28 after injection of SN-38/Sunitinib micelles, compared with other experiment groups (p < 0.01). As demonstrated by the results of inhibition on multi-receptors by Sunitinib, we confirmed that SN-38/Sunitinib co-loaded micelles to be a treatment modality that could inhibit VEGF and PDGF receptors and enhance the antitumor effect of SN-38 (p < 0.05). In summary, we consider that this micelle is a potential formulation for the combination of SN-38 and Sunitinib in the treatment of colorectal cancer.
Genetic Characteristics and Metabolic Interactions between Pseudocercospora fijiensis and Banana: Progress toward Controlling Black Sigatoka
Authors: Noar Roslyn D. , Thomas Elizabeth , Daub Margaret E.
Published: April 2022

The international importance of banana and severity of black Sigatoka disease have led to extensive investigations into the genetic characteristics and metabolic interactions between the Dothideomycete Pseudocercospora fijiensis and its banana host. P. fijiensis was shown to have a greatly expanded genome compared to other Dothideomycetes, due to the proliferation of retrotransposons. Genome analysis suggests the presence of dispensable chromosomes that may aid in fungal adaptation as well as pathogenicity. Genomic research has led to the characterization of genes and metabolic pathways involved in pathogenicity, including: secondary metabolism genes such as PKS10-2, genes for mitogen-activated protein kinases such as Fus3 and Slt2, and genes for cell wall proteins such as glucosyl phosphatidylinositol (GPI) and glycophospholipid surface (Gas) proteins. Studies conducted on resistance mechanisms in banana have documented the role of jasmonic acid and ethylene pathways. With the development of banana transformation protocols, strategies for engineering resistance include transgenes expressing antimicrobial peptides or hydrolytic enzymes as well as host-induced gene silencing (HIGS) targeting pathogenicity genes. Pseudocercospora fijiensis has been identified as having high evolutionary potential, given its large genome size, ability to reproduce both sexually and asexually, and long-distance spore dispersal. Thus, multiple control measures are needed for the sustainable control of black Sigatoka disease.
Expression of a Cytochrome P450 Gene from Bermuda Grass Cynodon dactylon in Soybean Confers Tolerance to Multiple Herbicides
Authors: Zheng Ting , Yu Xiaoxing , Sun Yongzheng , Zhang Qing , Zhang Xianwen , Tang Mengzhen , Lin Chaoyang , Shen Zhicheng
Published: April 2022

Bermuda grass (Cynodon dactylon) is notoriously difficult to control with some commonly used herbicides. We cloned a cytochrome P450 gene from Bermuda grass, named P450-N-Z1, which was found to confer tolerance to multiple herbicides in transgenic Arabidopsis. These herbicides include: (1) acetolactate synthase (ALS) inhibitor herbicides nicosulfuron and penoxsulam; (2) p-hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting herbicide mesotrione; (3) synthetic auxin herbicide dicamba; (4) photosynthesis inhibitor bentazon. We further generated transgenic soybean plants expressing P450-N-Z1, and found that these transgenic soybean plants gained robust tolerance to nicosulfuron, flazasulfuron, and 2,4-dichlorophenoxyacetic acid (2,4-D) in greenhouse assays. A field trial demonstrated that transgenic soybean is tolerant to flazasulfuron and 2,4-D at 4-fold and 2-fold the recommended rates, respectively. Furthermore, we also demonstrated that flazasulfuron and dicamba are much more rapidly degraded in vivo in the transgenic soybean than in non-transgenic soybean. Therefore, P450-N-Z1 may be utilized for engineering transgenic crops for herbicide tolerance.
Entanglement of Arabidopsis Seedlings to a Mesh Substrate under Microgravity Conditions in KIBO on the ISS
Authors: Nakano Masataka , Furuichi Takuya , Sokabe Masahiro , Iida Hidetoshi , Yano Sachiko , Tatsumi Hitoshi
Published: April 2022

The International Space Station (ISS) provides a precious opportunity to study plant growth and development under microgravity (micro-G) conditions. In this study, four lines of Arabidopsis seeds (wild type, wild-type MCA1-GFP, mca1-knockout, and MCA1-overexpressed) were cultured on a nylon lace mesh placed on Gelrite-solidified MS-medium in the Japanese experiment module KIBO on the ISS, and the entanglement of roots with the mesh was examined under micro-G and 1-G conditions. We found that root entanglement with the mesh was enhanced, and root coiling was induced under the micro-G condition. This behavior was less pronounced in mca1-knockout seedlings, although MCA1-GFP distribution at the root tip of the seedlings was nearly the same in micro-G-grown seedlings and the ground control seedlings. Possible involvement of MCA1 in the root entanglement is discussed.
Enhanced Lateral Photovoltaic Effects in n-Si/SiO2/PEDOT:PSS Structures
Authors: Zhang Jingying , Meng Kang , Ni Gang
Published: April 2022

Organic/silicon hybrid structures have been extensively studied for the application of solar cells due to their high photoelectric conversion efficiency and simple fabrication process. However, studies of lateral photovoltaic effects (LPEs) in the devices are still scarce. Herein, the Si/SiO2/PEDOT:PSS devices were prepared by spin-coating, and showing the lateral photovoltage (LPV) sensitivity of 14.0 mV/mm at room temperature, which is higher than the control samples of Si/SiO2 (0.1 mV/mm) and Si/PEDOT:PSS (9.0 mV/mm) structures. With the decrease in temperature, the lateral photovoltage increases initially, and reaches a peak at around 210 K, then drops accordingly. The enhancement of LPE can be mainly ascribed to the formation of the p-n junction and the native oxide layer at the organic/inorganic interface.
Antimicrobial Properties of Bacterial Cellulose Films Enriched with Bioactive Herbal Extracts Obtained by Microwave-Assisted Extraction
Authors: Bodea Ioana M. , Cătunescu Giorgiana M. , Pop Carmen R. , Fiț Nicodim I. , David Adriana P. , Dudescu Mircea C. , Stănilă Andreea , Rotar Ancuța M. , Beteg Florin I.
Published: April 2022

The use of bacterial cellulose (BC) as scaffold for active biofilms is one of the most interesting applications, especially for the biomedical and food industries. However, there are currently few studies evaluating the potential of incorporating herbal extracts into various biomaterials, including BC. Thus, the aim of this study is to report a screening of the total phenolic content and antioxidant and antimicrobial activity of ethanolic extracts of oregano, rosemary, parsley, and lovage. At the same time, the bioactive potential of BC enriched with the four ethanolic extracts is described. Microwave-assisted extraction was used to extract bioactive compounds from the four selected herbs. The physical, mechanical, structural, and chemical properties of BC were also assessed. Next, BC was enriched with the extracts, and their effect against Escherichia coli, Staphylococcus aureus, and Candida albicans was evaluated. The results showed that the bioactivity of the herbs varied significantly, with rosemary extract being the most bioactive. The BC films possessed good mechanical properties, and a three-dimensional network fibrillar structure appropriate for ethanolic-extract incorporation. The BC samples enriched with rosemary extracts had the highest antibacterial activity against S. aureus, while E. coli. and C. albicans seemed to be resistant to all extracts, regardless of herbs.
First Lidar Campaign in the Industrial Sites of Volta Redonda-RJ and Lorena-SP, Brazil
Authors: Lopes Fábio Juliano da Silva , Carvalho Silvânia A. , Catalani Fernando , da Silva Jonatan João , de Almeida Rogério M. , Ribeiro Fábio de Jesus , Fellows Carlos Eduardo , Landulfo Eduardo , Menegatti Carlos Renato , Peixoto Carlos José Todero
Published: April 2022

We report on the first aerosol profiling campaign in the Paraíba valley, a hub connecting the region between the two largest Brazilian metropolitan areas, São Paulo and Rio de Janeiro. São Paulo Sanitation Technology Company (CETESB) air quality and Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) data show homogeneous behavior of the atmosphere throughout the region. A more detailed description of the particulate material in the local atmosphere, including its temporal dependence, can be obtained by using ground-based lidars. Measurements were carried out with a backscatter lidar system in two industrial cities, Volta Redonda and Lorena. The aerosol backscatter profiles present several peaks at different altitudes, indicating the presence of aerosol in several atmospheric layers. In addition, The Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) air-mass back-trajectories indicate a possible detection of long-range aerosol transported from biomass burning areas of South America. The present study emphasizes the importance of investigating and monitoring the emission of particulate matter at this important hub connection between two dense populated regions of Brazil.
A Fusion Method for Multisource Land Cover Products Based on Superpixels and Statistical Extraction for Enhancing Resolution and Improving Accuracy
Authors: Jin Qi , Xu Erqi , Zhang Xuqing
Published: April 2022

The discrepancies in existing land cover data are relatively high, indicating low local precision and application limitations. Multisource data fusion is an effective way to solve this problem; however, the fusion procedure often requires resampling to unify the spatial resolution, causing a lower spatial resolution. To solve this problem, this study proposes a multisource product fusion mapping method of filtering training samples and product correction at a fine resolution. Based on the Superpixel algorithm, principal component analysis (PCA), and statistical extraction techniques, combined with the Google Earth Engine (GEE) platform, reliable land cover data were acquired. GEE and machine-learning algorithms correct the unreliable information of multiple products into a new land cover fusion result. Compared to the common method of extracting consistent pixels from existing products, our proposed method effectively removes nearly 38.75% of them, with a high probability of classification error. The overall accuracy of fusion in this study reached 85.80%, and the kappa coefficient reached 0.82, with an overall accuracy improvement of 11.75–24.17% and a kappa coefficient improvement of 0.16 to 0.3 compared to other products. For existing single-category products, we corrected the phenomenon of overinterpretation in inconsistent areas; the overall accuracy improvement ranged from 2.99% to 20.71%, while the kappa coefficient improvement ranged from 0.22 to 0.56. Thus, our proposed method can combine information from multiple products and serve as an effective method for large areas and even as a global land cover fusion product.