bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Ultrafine Single-Nanometer Oxygen Bubbles on Radiation Sensitivity in a Tumor-Bearing Mouse Model
Authors: Gombodorj Navchaa , Yokobori Takehiko , Mutsuki Nobutoshi , Erkhem-Ochir Bilguun , Okami Haruka , Asao Takayuki , Saeki Hiroshi , Shirabe Ken , Yamanouchi Dai
Published: June 2022

Radiation therapy against cancer cells often causes radiation resistance via accumulation of hypoxia-inducible factor 1 subunit alpha (HIF-1α) under hypoxic conditions and severe side effects. Radiation sensitizers without side effects are required to overcome hypoxia-induced radiation resistance and decrease radiation-related side effects in patients with refractory cancer. We previously developed oxygen nanobubble water (NBO2 water) and demonstrated that it suppresses hypoxia-induced radiation resistance in cancer cell lines within the single-nanometer range. This study aimed to elucidate whether NBO2 water could act as a radiosensitizer via regulation of HIF-1α in a tumor-bearing mouse model. Six-week-old female BALB/c mice subcutaneously injected with tumor cells received control water or NBO2 water for 28 days, after which biochemical examinations and radiation treatment were performed. Hypoxic tumor regions were detected immunohistochemically. We found that NBO2 water sensitized radiation reactivity in the xenografted tumors. Notably, NBO2 water administration downregulated the accumulation of HIF-1α in xenografted tumors and did not affect the vital organs of healthy mice. The combination of radiation and single-nanometer NBO2 water without severe side effects may be a promising therapeutic option to improve radiation sensitivity in cancer patients without tolerance to invasive treatments.
Arabidopsis ERF012 Is a Versatile Regulator of Plant Growth, Development and Abiotic Stress Responses
Authors: Huang Yupu , Liu Ling , Hu Haitao , Tang Ning , Shi Lei , Xu Fangsen , Wang Sheliang
Published: June 2022

The AP2/ERF transcription factors are widely involved in the regulation of plant growth, development and stress responses. Arabidopsis ERF012 is differentially responsive to various stresses; however, its potential regulatory role remains elusive. Here, we show that ERF012 is predominantly expressed in the vascular bundles, lateral root primordium and vein branch points. ERF012 overexpression inhibits root growth, whereas it promotes root hair development and leaf senescence. In particular, ERF012 may downregulate its target genes AtC4H and At4CL1, key players in phenylpropanoid metabolism and cell wall formation, to hinder auxin accumulation and thereby impacting root growth and leaf senescence. Consistent with this, exogenous IAA application effectively relieves the effect of ERF012 overexpression on root growth and leaf senescence. Meanwhile, ERF012 presumably activates ethylene biosynthesis to promote root hair development, considering that the ERF012-mediated root hair development can be suppressed by the ethylene biosynthetic inhibitor. In addition, ERF012 overexpression displays positive and negative effects on low- and high-temperature responses, respectively, while conferring plant resistance to drought, salinity and heavy metal stresses. Taken together, this study provides a comprehensive evaluation of the functional versatility of ERF012 in plant growth, development and abiotic stress responses.
Genome-Wide Identification of Binding Sites for SmTCP7a Transcription Factors of Eggplant during Bacterial Wilt Resistance by ChIP-Seq
Authors: Xiao Xi’ou , Lin Wenqiu , Feng Enyou , Wu Caiyu , Ou Xiongchang
Published: June 2022

Teosinte branched 1/cycloidea/proliferating cell factor (TCP) transcription factors play a key role in the regulation of plant biotic and abiotic stresses. In this study, our results show that SmTCP7a positively regulated bacterial wilt that was caused by Ralstonia solanacearum. ChIP-seq was conducted to analyze the transcriptional regulation mechanism of SmTCP7a before (R0 h) and 48 h after infection (R48 h). SmTCP7a regulated a total of 92 and 91 peak-associated genes in R0 h and R48 h, respectively. A KEGG (Kyoto encyclopedia of genes and genomes) pathway analysis showed that phenylpropanoid biosynthesis, MAPK (mitogen-activated protein kinas) signaling pathway, plant hormone signal transduction and plant-pathogen interactions were involved. The difference in peaks between R0 h and R48 h showed that there were three peak-associated genes that were modulated by infection. A better understanding of the potential target genes of SmTCP7a in response to R. solanacearum will provide a comprehensive understanding of the SmTCP7a regulatory mechanism during the eggplant defense response to bacterial wilt.
Molecular Research on Mitochondrial Dysfunction
Authors: Viscomi Carlo , Soriano Maria Eugenia
Published: June 2022

This Special Issue collects current knowledge on the molecular mechanisms underlying mitochondrial dysfunction and its related diseases, as well as therapies and perspectives pertaining to their treatment [...]
Safety of Special Waveform of Transcranial Electrical Stimulation (TES): In Vivo Assessment
Authors: Adeel Muhammad , Chen Chun-Ching , Lin Bor-Shing , Chen Hung-Chou , Liou Jian-Chiun , Li Yu-Ting , Peng Chih-Wei
Published: June 2022

Intermittent theta burst (iTBS) powered by direct current stimulation (DCS) can safely be applied transcranially to induce neuroplasticity in the human and animal brain cortex. tDCS-iTBS is a special waveform that is used by very few studies, and its safety needs to be confirmed. Therefore, we aimed to evaluate the safety of tDCS-iTBS in an animal model after brain stimulations for 1 h and 4 weeks. Thirty-one Sprague Dawley rats were divided into two groups: (1) short-term stimulation for 1 h/session (sham, low, and high) and (2) long-term for 30 min, 3 sessions/week for 4 weeks (sham and high). The anodal stimulation applied over the primary motor cortex ranged from 2.5 to 4.5 mA/cm2. The brain biomarkers and scalp tissues were assessed using ELISA and histological analysis (H&E staining) after stimulations. The caspase-3 activity, cortical myelin basic protein (MBP) expression, and cortical interleukin (IL-6) levels increased slightly in both groups compared to sham. The serum MBP, cortical neuron-specific enolase (NSE), and serum IL-6 slightly changed from sham after stimulations. There was no obvious edema or cell necrosis seen in cortical histology after the intervention. The short- and long-term stimulations did not induce significant adverse effects on brain and scalp tissues upon assessing biomarkers and conducting histological analysis.
A Dual-Acting Nitric Oxide Donor and Phosphodiesterase 5 Inhibitor Activates Autophagy in Primary Skin Fibroblasts
Authors: Martínez-Martínez Esther , Atzei Paola , Vionnet Christine , Roubaty Carole , Kaeser-Pebernard Stephanie , Naef Reto , Dengjel Jörn
Published: June 2022

Wound healing pathologies are an increasing problem in ageing societies. Chronic, non-healing wounds, which cause high morbidity and severely reduce the quality of life of affected individuals, are frequently observed in aged individuals and people suffering from diseases affected by the Western lifestyle, such as diabetes. Causal treatments that support proper wound healing are still scarce. Here, we performed expression proteomics to study the effects of the small molecule TOP-N53 on primary human skin fibroblasts and keratinocytes. TOP-N53 is a dual-acting nitric oxide donor and phosphodiesterase-5 inhibitor increasing cGMP levels to support proper wound healing. In contrast to keratinocytes, which did not exhibit global proteome alterations, TOP-N53 had profound effects on the proteome of skin fibroblasts. In fibroblasts, TOP-N53 activated the cytoprotective, lysosomal degradation pathway autophagy and induced the expression of the selective autophagy receptor p62/SQSTM1. Thus, activation of autophagy might in part be responsible for beneficial effects of TOP-N53.
Determination of Moisture and Protein Content in Living Mealworm Larvae (Tenebrio molitor L.) Using Near-Infrared Reflectance Spectroscopy (NIRS)
Authors: Kröncke Nina , Benning Rainer
Published: June 2022

Yellow mealworm larvae (Tenebrio molitor L.) are a sustainable source of protein for food and feed. This study represents a new approach in analyzing changes in the nutritional composition of mealworm larvae using near-infrared reflectance spectroscopy (NIRS) combined with multivariate analysis. The moisture and protein content of living larvae were scanned with a near-infrared spectrometer using wavelengths from 1100 to 2100 nm. Different feeding groups with varying moisture sources and amount and the difference between low (50%) and high (75%) humidity were tested, and the influence on larval moisture and protein content was measured. A calibration was developed, with modified partial least squares as the regression method. The NIR spectra were influenced by the moisture and protein content of the larvae, because the absorbance values of the larval groups differed greatly. The coefficient of the determination of calibration (R2c) and prediction (R2p) were over 0.98 for moisture and over 0.94 for protein content. The moisture source and content also had a significant influence on the weight gain of the larvae. Consequently, significant differences in protein content could be determined, depending on the water supply available. With respect to wet weight, the larvae moisture content varied from 60 to 74% and protein content from 16 to 24%. This investigation revealed that with non-invasive NIRS online monitoring, the composition of insects can be continuously recorded and evaluated so that specific feeding can be carried out in the course of larval development and composition.
Identification of Pathogenicity-Related Effector Proteins and the Role of Piwsc1 in the Virulence of Penicillium italicum on Citrus Fruits
Authors: Li Xiaoying , Yang Shuzhen , Zhang Meihong , Yang Yanting , Peng Litao
Published: June 2022

Blue mold caused by Penicillium italicum is one of the two major postharvest diseases of citrus fruits. The interactions of pathogens with their hosts are complicated, and virulence factors that mediate pathogenicity have not yet been identified. In present study, a prediction pipeline approach based on bioinformatics and transcriptomic data is designed to determine the effector proteins of P. italicum. Three hundred and seventy-five secreted proteins of P. italicum were identified, many of which (29.07%) were enzymes for carbohydrate utilization. Twenty-nine candidates were further analyzed and the expression patterns of 12 randomly selected candidate effector genes were monitored during the early stages of growth on PDA and infection of Navel oranges for validation. Functional analysis of a cell wall integrity-related gene Piwsc1, a core candidate, was performed by gene knockout. The deletion of Piwsc1 resulted in reduced virulence on citrus fruits, as presented by an approximate 57% reduction in the diameter of lesions. In addition, the mycelial growth rate, spore germination rate, and sporulation of ΔPiwsc1 decreased. The findings provide us with new insights to understand the pathogenesis of P. italicum and develop an effective and sustainable control method for blue mold.
Development of an Oriented Co-Culture System Using 3D Scaffolds Fabricated via Non-Linear Lithography
Authors: Kordas Antonis , Manganas Phanee , Selimis Alexandros , Barmparis Georgios D. , Farsari Maria , Ranella Anthi
Published: June 2022

Damage in the Peripheral Nervous System (PNS) is related to numerous neurodegenerative diseases and has consequently drawn the attention of Tissue Engineering (TE), which is considered a promising alternative to already established methods such as surgery and autografts. TE focuses on the design, optimization, and use of scaffolds in vitro and in vivo. In this work, the authors used a novel scaffold geometry fabricated via Multiphoton Lithography (MPL), a commonly used fabrication method, for the mono- and co-cultures of glial Schwann (SW10) and neuronal Neuro-2a (N2a) cells. Both cell types have already been used for the study of various neurodegenerative diseases. However, their focus has been on only one of the cell types at a time, with studies regarding their co-culture only recently documented. Here, the suitability of the fabricated scaffolds has been explored and the effects of topography on SW10 and N2a behavior have been investigated. Our findings demonstrate that scaffold co-culture systems favor the presence of neurites compared to mono-cultures at 21 days (31.4 ± 5.5% and 15.4 ± 5.4%, respectively), while there is also a significant decrease in long neurites in the mono-culture over time (45.3 ± 15.9% at 7 days versus 15.4 ± 5.4% at 21 days). It has been shown that the scaffolds can successfully manipulate cell growth, elongation, and morphology, and these results can form a basis for the development of an experimental model for the study of PNS-related diseases and understanding of key cell functions such as myelination.
Experimental Analysis of Steel Circular Hollow Section under Bending Loads: Comprehensive Study of Mechanical Performance
Authors: Khalaf Manahel Shahath , Ibrahim Amer M. , Najm Hadee Mohammed , Sabri Mohanad Muayad Sabri , Morkhade Samadhan , Agarwal Ashish , Alamir Mohammed A. , Alarifi Ibrahim M.
Published: June 2022

The present study aimed at evaluating the mechanical performance under bending loads of circular hollow sections of steel. Different bending tests have been carried out by applying two-point loads, to determine and examine the effects of the diameter, the thickness of the section, and the span of the beam on the performance of the steel tube. The effects of square opening and variation in the number of openings on the performance of these sections have also been examined. Ten samples of hollow circular beams of varying thickness (2 mm, 3 mm, and 6 mm), varying diameter (76.2 mm, 101.6 mm, and 219 mm), and varying span (1000 mm, 1500 mm, and 2000 mm) were fabricated and tested for pre-failure and post-failure stages. The dimensions of the reference specimen considered were 3 mm in thickness, 101.6 mm in diameter, and 1500 mm in span. The results have shown that on increasing the section thickness by 200%, ductility and bearing strength were enhanced by 58.04% and 81.75%, respectively. Meanwhile, decreasing the section thickness by 67%, ductility and bearing strength were reduced by 64.86% and 38.87%, respectively. Moreover, on increasing the specimen diameter and on decreasing span, a significant increase in bearing strength and stiffness was observed; however, ductility was reduced. Meanwhile, on increasing the span of the specimen, all the parameters observed, i.e., bearing strength, stiffness, and ductility, decreased. On observing the ultimate strength of each specimen with square opening, the ultimate strength was reduced by 17.88%, 19.71%, and 14.23% for one, two-, and three-square openings, respectively. Moreover, the ductility was significantly reduced by 72.40%, 67.71%, and 60.88% for one, two-, and three-square openings/apertures, respectively, and led to the sudden failure of these specimens. The local buckling failure dominated for specimens having a D/t ratio more than 50 and showed very negligible levels of ovalization of the cross-section. Local buckling failure was observed to be prevented after providing the circular rings in the specimen, since bearing strength increased compared with the specimen without rings.
Microstructure and Phase Evolution of Ti-Al-C-Nb Composites Prepared by In Situ Selective Laser Forming
Authors: Zhang Kai , Li Shurui , Yan Zhilong , Xiong Zhiwei , Bakoutas Desti Dorion Likoundayenda , Liu Tingting , Liao Wenhe
Published: June 2022

In the present work, a novel Ti-Al-C-Nb composite was prepared using in situ selective laser forming (ISLF). The formation mechanism of the Ti-Al-C-Nb bulks, which were synthesized using elemental titanium, aluminum, and carbon (graphite) powders via ISLF techniques, was investigated. The results showed that the Ti3Al and TiC phases were the dominant synthesis products during the chemical reactions, and these occurred during the ISLF process. The size of the fine nanoscale crystal TiC grains could reach 157 nm at an energy level of 60 J/mm3. The porous structure of the ISLF specimens was disclosed, and an open porosity of 20–44% was determined via the scanning speed and the laser power. Both the high dynamic viscosity and the reactions of the raw powders led to the generation of a considerable number of pores, whereas the specimen processed using 45 W and 100 mm/s possessed the lowest degree of open porosity.
Machine Learning Approaches for Monitoring of Tool Wear during Grey Cast-Iron Turning
Authors: Tabaszewski Maciej , Twardowski Paweł , Wiciak-Pikuła Martyna , Znojkiewicz Natalia , Felusiak-Czyryca Agata , Czyżycki Jakub
Published: June 2022

The dynamic development of new technologies enables the optimal computer technique choice to improve the required quality in today’s manufacturing industries. One of the methods of improving the determining process is machine learning. This paper compares different intelligent system methods to identify the tool wear during the turning of gray cast-iron EN-GJL-250 using carbide cutting inserts. During these studies, the experimental investigation was conducted with three various cutting speeds vc (216, 314, and 433 m/min) and the exact value of depth of cut ap and federate f. Furthermore, based on the vibration acceleration signals, appropriate measures were developed that were correlated with the tool condition. In this work, machine learning methods were used to predict tool condition; therefore, two tool classes were proposed, namely usable and unsuitable, and tool corner wear VBc = 0.3 mm was assumed as a wear criterium. The diagnostic measures based on acceleration vibration signals were selected as input to the models. Additionally, the assessment of significant features in the division into usable and unsuitable class was caried out. Finally, this study evaluated chosen methods (classification and regression tree, induced fuzzy rules, and artificial neural network) and selected the most effective model.
Treatment of As(III)-Laden Contaminated Water Using Iron-Coated Carbon Fiber
Authors: Fu Dun , Kurniawan Tonni Agustiono , Gui Herong , Feng Songbao , Li Qian , Othman Mohd Hafiz Dzarfan
Published: June 2022

This work presents the fabrication, characterization, and application of iron-coated carbon fiber (Fe@CF), synthesized in a facile in situ iron reduction, for As(III) removal from an aqueous solution. The physico-chemical properties of the composite were characterized using Brunauer–Emmett–Teller (BET) surface area, scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared (FTIR) spectroscopy. Adsorption studies were evaluated in batch experiments with respect to reaction time, the dose of adsorbent, As(III) initial concentration, pH, and co-existing ions. The results showed that the BET surface area and pore volume of Fe@CF slightly decreased after Fe coating, while its pore size remained, while the SEM and XRD analyses demonstrated that the Fe was successfully anchored on the CF. A maximum As(III) adsorption of 95% was achieved with an initial As concentration of 1.5 mg/L at optimum conditions (30 min of reaction time, 1 g/L of dose, 1 mg/L of As(III) concentration, and pH 3.5). Since the treated effluents could not meet the strict discharge standard of ≤10 μg/L set by the World Health Organization (WHO), a longer reaction time is required to complete the removal of remaining As(III) in the wastewater effluents. As compared to the other adsorbents reported previously, the Fe@CF composite has the highest As(III) removal. Overall, the findings suggested that the use of Fe@CF as an adsorbent is promising for effective remediation in the aquatic environment.
Federated Learning-Inspired Technique for Attack Classification in IoT Networks
Authors: Ahanger Tariq Ahamed , Aldaej Abdulaziz , Atiquzzaman Mohammed , Ullah Imdad , Yousufudin Muhammad
Published: June 2022

More than 10-billion physical items are being linked to the internet to conduct activities more independently and with less human involvement owing to the Internet of Things (IoT) technology. IoT networks are considered a source of identifiable data for vicious attackers to carry out criminal actions using automated processes. Machine learning (ML)-assisted methods for IoT security have gained much attention in recent years. However, the ML-training procedure incorporates large data which is transferable to the central server since data are created continually by IoT devices at the edge. In other words, conventional ML relies on a single server to store all of its data, which makes it a less desirable option for domains concerned about user privacy. The Federated Learning (FL)-based anomaly detection technique, which utilizes decentralized on-device data to identify IoT network intrusions, represents the proposed solution to the aforementioned problem. By exchanging updated weights with the centralized FL-server, the data are kept on local IoT devices while federating training cycles over GRUs (Gated Recurrent Units) models. The ensemble module of the technique assesses updates from several sources for improving the accuracy of the global ML technique. Experiments have shown that the proposed method surpasses the state-of-the-art techniques in protecting user data by registering enhanced performance measures of Statistical Analysis, Energy Efficiency, Memory Utilization, Attack Classification, and Client Accuracy Analysis for the identification of attacks.
Innovative Digital Stochastic Methods for Multidimensional Sensitivity Analysis in Air Pollution Modelling
Authors: Todorov Venelin , Dimov Ivan
Published: June 2022

Nowadays, much of the world has a regional air pollution strategy to limit and decrease the pollution levels across governmental borders and control their impact on human health and ecological systems. Environmental protection is among the leading priorities worldwide. Many challenges in this research area exist since it is a painful subject for society and a fundamental topic for the healthcare system. Sensitivity analysis has a fundamental role during the process of validating a large-scale air pollution computational models to ensure their accuracy and reliability. We apply the best available stochastic algorithms for multidimensional sensitivity analysis of the UNI-DEM model, which plays a key role in the management of the many self-governed systems and data that form the basis for forecasting and analyzing the consequences of possible climate change. We develop two new highly convergent digital sequences with special generating matrices, which show significant improvement over the best available existing stochastic methods for measuring the sensitivity indices of the digital ecosystem. The results obtained through sensitivity analysis will play an extremely important multi-sided role.
FADS Polymorphisms Affect the Clinical and Biochemical Phenotypes of Metabolic Syndrome
Authors: Žák Aleš , Jáchymová Marie , Burda Michal , Staňková Barbora , Zeman Miroslav , Slabý Adolf , Vecka Marek , Šeda Ondřej
Published: June 2022

Long-chain polyunsaturated fatty acids (LC-PUFAs) play important roles in human health, from controlling inflammation to lipid and glucose homeostasis. In our previous study, which employed a cluster analysis of a plasma fatty acid (FA) pattern, we identified two clusters of metabolic syndrome (MetS) independent of clinical and biochemical parameters within the whole study group (controls together with metabolic syndrome (MetS) patients). FA desaturase (FADS) genes are the key regulators of LC-PUFA metabolism. The aim of this study was to analyze associations between FADS polymorphisms and clusters of MetS. The study group consisted of 188 controls and 166 patients with MetS. The first cluster contained 71 controls (CON1) and 109 MetS patients (MetS1). The second cluster consisted of 117 controls (CON2) and 57 MetS patients (MetS2). In comparison with MetS2, cluster MetS1 displayed a more adverse risk profile. Cluster CON1 had, in comparison with CON2, higher body weight and increased triacylglycerol levels (p < 0.05). We found that the FADS rs174537 (p < 0.001), rs174570 (p < 0.01), and rs174602 (p < 0.05) polymorphisms along with two inferred haplotypes had statistically significant genotype associations with the splitting of MetS into MetS1 and MetS2. Conversely, we observed no significant differences in the distribution of FADS polymorphisms between MetS and CON subjects, or between CON1 and CON2. These associations between FADS polymorphisms and two clusters of MetS (differing in waist circumference, HOMA-IR, lipolysis, and oxidative stress) implicate the important influence of genetic factors on the phenotypic manifestation of MetS.
A Bibliometric Analysis of Low-Cost Piezoelectric Micro-Energy Harvesting Systems from Ambient Energy Sources: Current Trends, Issues and Suggestions
Authors: Sarker Mahidur R. , Saad Mohamad Hanif Md , Riaz Amna , Lipu M. S. Hossain , Olazagoitia José Luis , Arshad Haslina
Published: June 2022

The scientific interest in piezoelectric micro-energy harvesting (PMEH) has been fast-growing, demonstrating that the field has made a major improvement in the long-term evolution of alternative energy sources. Although various research works have been performed and published over the years, only a few attempts have been made to examine the research’s influence in this field. Therefore, this paper presents a bibliometric study into low-cost PMEH from ambient energy sources within the years 2010–2021, outlining current research trends, analytical assessment, novel insights, impacts, challenges and recommendations. The major goal of this paper is to provide a bibliometric evaluation that is based on the top-cited 100 articles employing the Scopus databases, information and refined keyword searches. This study analyses various key aspects, including PMEH emerging applications, authors’ contributions, collaboration, research classification, keywords analysis, country’s networks and state-of-the-art research areas. Moreover, several issues and concerns regarding PMEH are identified to determine the existing constraints and research gaps, such as technical, modeling, economics, power quality and environment. The paper also provides guidelines and suggestions for the development and enhancement of future PMEH towards improving energy efficiency, topologies, design, operational performance and capabilities. The in-depth information, critical discussion and analysis of this bibliometric study are expected to contribute to the advancement of the sustainable pathway for PMEH research.
Considerations for the Maximum Heat Load and Its Influence on Temperature Variation of the Evaporator in Flat MHPs in Transient Regimes
Authors: Mihai Ioan , Suciu Cornel , Picus Claudiu Marian
Published: June 2022

The present paper describes a series of considerations for the occurrence of capillary boundaries in flat micro heat pipes (flat MHPs) and the conditions required for their stable operation in relation to the working circumstances and to the type of liquids inside the pipes. Particularities of heat transfer in a flat MHP are analyzed for situations of either excessive or deficient working liquid. Depending on the physical properties of the working liquids (acetone, methanol and distilled water), the maximum rate of heat flow that can be applied to a flat MHP is determined analytically. The calculus is made with the assumption that constant vaporization of the liquid is ensured in the flat MHP’s evaporator, with no overheating. The considered analytical models allow for the evaluation of the liquid film thickness and the mass flow corresponding to the vaporization region. The temperature difference between the inner and outer walls of a flat MHP is found in the case of a transient regime and a variable thermal flow is applied in the evaporation region. The interior of flat MHPs was modeled in MATLAB using an FTCS (Forward-Time Central-Space) method, which is a finite difference method used for numerically solving the heat equation.
Diatom Biosilica in Targeted Drug Delivery and Biosensing Applications: Recent Studies
Authors: Zobi Fabio
Published: June 2022

Diatoms are single-cell algae encased in a cell wall (named frustule) composed of transparent, biogenic (or opaline) silica with intricate and strikingly regular patterns. Over the past 30 years, these microorganisms have proven to be a valuable replacement for synthetic silica that satisfies numerous pharmaceutical requirements for the realization of drug delivery vectors, biosensing supports and photonic crystals. It is not only the structural features of the diatoms, but also the possibility of chemically modifying the frustule that permits the relatively straightforward transformation of the biosilica into potential devices for biomedical applications. In this short review, we explore the applications of diatoms-derived biosilica in the drug delivery and biosensing fields. Specifically, we consider the use of diatoms for the targeted delivery of anticancer and antibiotic drugs and how the same microalgae are employed in the fabrications of biosensors whose analyte signal response is evaluated via fluorescence and surface-enhanced Raman scattering techniques. We limit our discussion to studies published in the last seven years, with the intention of minimizing possible redundancy with respect to previously published contributions.
Biological Activities of Organic Extracts of the Genus Aristolochia: A Review from 2005 to 2021
Authors: Lerma-Herrera Martín A. , Beiza-Granados Lidia , Ochoa-Zarzosa Alejandra , López-Meza Joel E. , Navarro-Santos Pedro , Herrera-Bucio Rafael , Aviña-Verduzco Judit , García-Gutiérrez Hugo A.
Published: June 2022

Different ethnomedicinal studies have investigated the relationship between various phytochemicals as well as organic extracts and their bioactive aspects. Studies on biological effects are attributed to secondary metabolites such as alkaloids, phenolic compounds, and terpenes. Since there have been no reviews in the literature on the traditional, phytochemical, and ethnomedicinal uses of the genus Aristolochia so far, this article systematically reviews 141 published studies that analyze the associations between secondary metabolites present in organic extracts and their beneficial effects. Most studies found associations between individual secondary metabolites and beneficial effects such as anticancer activity, antibacterial, antioxidant activity, snake anti-venom and anti-inflammatory activity. The aim of this review was to analyze studies carried out in the period 2005–2021 to update the existing knowledge on different species of the genus Aristolochia for ethnomedicinal uses, as well as pharmacological aspects and therapeutic uses.
Benzamides Substituted with Quinoline-Linked 1,2,4-Oxadiazole: Synthesis, Biological Activity and Toxicity to Zebrafish Embryo
Authors: Sun Bin-Long , Wang Ying-Ying , Yang Sen , Tu Min-Ting , Shao Ying-Ying , Hua Yi , Zhou Yi , Tan Cheng-Xia
Published: June 2022

To develop new compounds with high activity, broad spectrum and low-toxicity, 17 benzamides substituted with quinoline-linked 1,2,4-oxadiazole were designed using the splicing principle of active substructures and were synthesized. The biological activities were evaluated against 10 fungi, indicating that some of the synthetic compounds showed excellent fungicidal activities. For example, at 50 mg/L, the inhibitory activity of 13p (3-Cl-4-Cl substituted, 86.1%) against Sclerotinia sclerotiorum was superior to that of quinoxyfen (77.8%), and the inhibitory activity of 13f (3-CF3 substituted, 77.8%) was comparable to that of quinoxyfen. The fungicidal activities of 13f and 13p to Sclerotinia sclerotiorum were better than that of quinoxyfen (14.19 mg/L), with EC50 of 6.67 mg/L and 5.17 mg/L, respectively. Furthermore, the acute toxicity of 13p was 19.42 mg/L, classifying it as a low-toxic compound.
Fluoride Content of Matcha Tea Depending on Leaf Harvest Time and Brewing Conditions
Authors: Jakubczyk Karolina , Ligenza Alicja , Gutowska Izabela , Janda-Milczarek Katarzyna
Published: June 2022

Matcha, or powdered green tea (Camellia sinensis) of the Tencha type, is popular all around the world, and its consumption continues to rise. Because of its unique cultivation method, it is rich in phytochemicals and has many health-promoting properties; it contains high concentrations of polyphenols, theanine and chlorophyll. Tea, and by extension matcha, contains numerous minerals, one of which is fluorine. Under physiological conditions, this mineral plays a significant role in hard tissue mineralisation processes. However, even in low concentrations, with prolonged exposure, fluoride can accumulate in the body, leading to a number of harmful effects. The aim of this study was to evaluate, for the first time, the fluoride content of the matcha infusions from different harvests, brewed using water at different temperatures (25 °C, 70 °C, 80 °C and 90 °C). The content of fluoride ions was measured by the potentiometric method. The fluoride content ranged from 3.36 to 4.03 mg/L and was dependent on both the leaf harvest time and brewing temperature. The concentration of this mineral in the dry powder ranged from 118.39 to 121.65 mg/kg. Irrespective of the water temperature or harvest time, matcha was found to have a high fluoride content, with particularly high concentrations being noted in the powder itself.
Eriodictyol Attenuates H2O2-Induced Oxidative Damage in Human Dermal Fibroblasts through Enhanced Capacity of Antioxidant Machinery
Authors: Buranasudja Visarut , Muangnoi Chawanphat , Sanookpan Kittipong , Halim Hasseri , Sritularak Boonchoo , Rojsitthisak Pornchai
Published: June 2022

Oxidative stress in dermal fibroblasts is strongly correlated with the aging process of the skin. The application of natural compounds that can increase the ability of dermal fibroblasts to counteract oxidative stress is a promising approach to promote skin health and beauty. Eriodictyol is a flavonoid that exerts several pharmacological actions through its antioxidant properties. However, its protective effects on dermal fibroblasts have not yet been investigated. In this study, we investigated whether eriodictyol protects human dermal fibroblasts (BJ fibroblasts) from the harmful effects of hydrogen peroxide (H2O2). Eriodictyol pretreatment significantly prevented necrotic cell death caused by H2O2 exposure. In addition, the level of 2′,7′-dichloro-dihydro-fluorescein oxidation was decreased, and that of glutathione was maintained, indicating that the beneficial effects of eriodictyol against H2O2 were closely associated with oxidative-stress attenuation. Eriodictyol mediates its antioxidant effects on dermal fibroblasts against H2O2 through (i) the direct neutralization of reactive oxygen species; (ii) the enhancement of the activities of H2O2-detoxifying enzymes, including catalase and glutathione peroxidase; and (iii) the induction of the expressions of catalase and glutathione peroxidase 1 via the activation of the Nrf2 signaling system. These results support the potential application of eriodictyol as an ingredient in skincare products for cosmeceutical and pharmaceutical purposes.
Relation of Dietary Patterns and Nutritional Profile to Hepatic Fibrosis in a Sample of Lebanese Non-Alcoholic Fatty Liver Disease Patients
Authors: Sayegh Nicole Fakhoury , Heraoui Gessica N. H. A. , Younes Hassan , Sayegh Lea Nicole , Boulos Christa , Sayegh Raymond
Published: June 2022

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver injury worldwide. NAFLD can evolve into non-alcoholic steatohepatitis (NASH) with or without fibrosis. The objectives of this study were to determine the nutritional profile and dietary patterns of NAFLD Lebanese patients and to report the type of diet-related to the presence of hepatic fibrosis. We hypothesized that the traditional pattern was related to a low risk of fibrosis. This cross-sectional study included 320 eligible Lebanese NAFLD patients. Three dietary patterns were identified: the Traditional diet, the High Fruit diet, and the Westernized diet. Multivariate analysis showed a significant relationship between high adherence to the traditional diet and absence of hepatic fibrosis with a decreased risk of 82%, p = 0.031 after adjusting for its covariables. Fruits were absent from this dietary pattern. Although our results pointed to a possible relationship between fibrosis in NAFLD patients and fruit intake, experimental studies are needed to show whether this is a causal relationship. However, the results obtained in this study may contribute to the planning of dietary interventions and recommendations and enable a better follow-up for NAFLD patients with fibrosis.
Turning a Targeting β-Catenin/Bcl9 Peptide Inhibitor into a GdOF@Au Core/Shell Nanoflower for Enhancing Immune Response to Cancer Therapy in Combination with Immune Checkpoint Inhibitors
Authors: You Weiming , Ma Fang , Zhang Zhang , Yan Jin
Published: June 2022

Combination administration is becoming a popular strategy in current cancer immunotherapy to enhance tumor response to ICIs. Recently, a peptide drug, a protein–protein interaction inhibitor (PPI), that disrupts the β-catenin/Bcl9 interaction in the tumoral Wnt/β-catenin pathway has become a promising candidate drug for immune enhancement and tumor growth inhibition. However, the peptide usually suffers from poor cell membrane permeability and proteolytic degradation, limiting its adequate accumulation in tumors and ultimately leading to side effects. Herein, a gadolinium–gold-based core/shell nanostructure drug delivery system was established, where Bcl9 was incorporated into a gadolinium–gold core–shell nanostructure and formed GdOFBAu via mercaptogenic self-assembly. After construction, GdOFBAu, when combined with anti-PD1 antibodies, could effectively inhibit tumor growth and enhance the response to immune therapy in MC38 tumor-bearing mice; it not only induced the apoptosis of cancer cells, but also promoted the tumor infiltration of Teff cells (CD8+) and decreased Treg cells (CD25+). More importantly, GdOFBAu maintained good biosafety and biocompatibility during treatment. Taken together, this study may offer a promising opportunity for sensitizing cancer immunotherapy via metal–peptide self-assembling nanostructured material with high effectiveness and safety.
Electrospun Scaffolds as Cell Culture Substrates for the Cultivation of an In Vitro Blood–Brain Barrier Model Using Human Induced Pluripotent Stem Cells
Authors: Rohde Felix , Danz Karin , Jung Nathalie , Wagner Sylvia , Windbergs Maike
Published: June 2022

The human blood–brain barrier (BBB) represents the interface of microvasculature and the central nervous system, regulating the transport of nutrients and protecting the brain from external threats. To gain a deeper understanding of (patho)physiological processes affecting the BBB, sophisticated models mimicking the in vivo situation are required. Currently, most in vitro models are cultivated on stiff, semipermeable, and non-biodegradable Transwell® membrane inserts, not adequately mimicking the complexity of the extracellular environment of the native human BBB. To overcome these disadvantages, we developed three-dimensional electrospun scaffolds resembling the natural structure of the human extracellular matrix. The polymer fibers of the scaffold imitate collagen fibrils of the human basement membrane, exhibiting excellent wettability and biomechanical properties, thus facilitating cell adhesion, proliferation, and migration. Cultivation of human induced pluripotent stem cells (hiPSCs) on these scaffolds enabled the development of a physiological BBB phenotype monitored via the formation of tight junctions and validated by the paracellular permeability of sodium fluorescein, further accentuating the non-linearity of TEER and barrier permeability. The novel in vitro model of the BBB forms a tight endothelial barrier, offering a platform to study barrier functions in a (patho)physiologically relevant context.
Kidney Function Assessment in African American Patients: A Narrative Review for Pharmacists
Authors: Rungkitwattanakul Dhakrit , Chaijamorn Weerachai , Han Eunice , Aldhaeefi Mohammed
Published: June 2022

Recent recognitions of longstanding societal inequity in kidney function assessments have prompted the call to eliminate race as part of the algorithm to assess estimated glomerular filtration rate (eGFR). Previous equations for eGFR estimation adopted race as part of the calculation. Incorporating race within eGFR equations results in overestimating and underestimating Black and nonblack patients, respectively. The inclusion of race is controversial. In September 2021, the National Kidney Foundation (NKF) and the American Society of Nephrology (ASN) combined task force recommended estimating the kidney function without using a race variable. The task force endorsed race-free creatinine-cystatin C equations to be more accurate than the creatinine-only equations. Before the application of NKF-ASN revised recommendations, major healthcare disparities influenced daily clinical practice. Those disparities include the delay in initiating medications that have reanl or cardio-protective effects, such as sodium-glucose cotransporter–2 inhibitors (SGLT-2i) and angiotensin-converting enzyme inhibitors (ACEIs). Clinical judgment should be employed when dose adjusting medications. Combining the eGFR with other clinical assessment tools such as urinary output, the expanded use of confirmatory tests, and the eGFR trend is suggested for a better kidney function assessment. Additionally, creatinine-cystatin C is recommended when feasible, and when institutions have the laboratory abilities.
Callus-Mediated High-Frequency Plant Regeneration, Phytochemical Profiling, Antioxidant Activity and Genetic Stability in Ruta chalepensis L.
Authors: Qahtan Ahmed A. , Faisal Mohammad , Alatar Abdulrahman A. , Abdel-Salam Eslam M.
Published: June 2022

Efficient methods for callus induction and the high-frequency plant regeneration of Ruta chalepensis L. were established, and the phytochemical potential and antioxidant activity of a donor plant, ex-vitro-established micropropagated plants, and callus were also studied. Yellowish-green callus was induced with a frequency of 97.8% from internode shoot segments of the donor plant growing in soil in the botanical garden cultured on Murashige and Skoog (MS) medium containing 10 μM 2,4-D (2,4-dichlorophenoxyacetic acid) and 1 μM BA (6-benzyladenine). Adventitious shoots were regenerated from the yellowish-green callus on MS medium containing 5.0 μM (BA) and 1.0 μM 1-naphthaleneacetic acid (NAA), with a regeneration frequency of 98.4% and a maximum of 54.6 shoots with an average length of 4.5 cm after 8 weeks. The regenerated shoots were rooted in a medium containing 1.0 μM IBA (indole-3-butyric acid) and successfully transferred to ex vitro conditions in pots containing normal garden soil, with a 95% survival rate. The amounts of alkaloids, phenolics, flavonoids, tannins, and antioxidant activity of the ex-vitro-established micropropagated plants were higher than in the donor plant and callus. The highest contents of hesperidin and rutin (93.3 and 55.9 µg/mg, respectively) were found in the ex-vitro-established micropropagated plants compared to those obtained from the donor plant (91.4 and 31.0 µg/mg, respectively) and callus (59.1 and 21.6 µg/mg, respectively). The genetic uniformity of the ex-vitro-established micropropagated plants was appraised by the ISSR markers and compared with the donor plant. This is the first report describing the callus-mediated plant regeneration, as well as the production of phenolic compounds and antioxidant activities in R. chalepensis, which might be a potential alternative technique for the mass propagation and synthesis of bioactive compounds such as hesperidin and rutin.
Compost Addition Attenuates the Negative Impacts of High Soil Mineral Nitrogen Levels on Rhizosphere Microbial Characteristics and Enhances Cucumber Growth in Monoculture Systems
Authors: Cao Yune , Gao Yanming , Tian Yongqiang , Li Jianshe
Published: June 2022

Due to the increase in the human population, it is necessary to seek efficient methods of increasing crop productivity and, simultaneously, sustaining the soil. One way is to grow high demand crops continuously without rotating with other crops. This practice is often accompanied by increased rates of fertilizer application that can affect efficient nitrogen (N) cycling in the plant rhizosphere soil which, in turn, affects both plant growth and environmental pollution. In the present study, twelve various cucumber soils were selected from monoculture systems presenting different cropping years and divided into two groups including soils with relatively high mineral N (HMN) content (N > 100 mg kg−1 soil) and those with a lower mineral N (LMN) content (N < 100 mg kg−1 soil). All soils were amended with the addition of compost alone or in combination with bacterial inoculation to evaluate their effects on plant growth, microbial numbers, N mineralization, and N cycling genes. In general, the HMN soils increased (p < 0.05) net N mineralization (NNM) but did not statistically (p > 0.05) affect plant biomass compared to the LMN soils; however, compost addition increased both NNM and plant biomass in the HMN soils. In addition, the HMN soils had higher fungal pathogen numbers (FPNs) but lower total microbial biomass (TMB) and bacterial numbers (BNs) compared to the LMN soils; however, compost addition decreased FPNs but increased TMB and BNs in the HMN soils (all p < 0.05). Plant biomass was positively related to TMB, BN and NNM but was negatively related to FPN (all p < 0.05). In summary, compost addition reduced the high mineral N levels’ adverse effects on the rhizosphere soil and plant growth.
Enhancing the UV-Light Barrier, Thermal Stability, Tensile Strength, and Antimicrobial Properties of Rice Starch–Gelatin Composite Films through the Incorporation of Zinc Oxide Nanoparticles
Authors: Homthawornchoo Wantida , Kaewprachu Pimonpan , Pinijsuwan Suttiporn , Romruen Orapan , Rawdkuen Saroat
Published: June 2022

The effects of zinc oxide nanoparticles (ZnONPs) on the properties of rice starch–gelatin (RS–G) films were investigated. ZnONPs were synthesized by a green method utilizing Asiatic pennywort (Centella asiatica L.) extract. The ZnONPs were rod-shaped, with sizes ranging from 100–300 nm. An increase in the concentration of ZnONPs significantly (p < 0.05) increased the thickness (0.050–0.070 mm), tensile strength (3.49–4.63 MPa), water vapor permeability (5.52–7.45 × 10−11 g m/m2 s Pa), and thermal stability of the RS–G–ZnONPs nanocomposite films. On the other hand, elongation at break (92.20–37.68%) and film solubility (67.84–30.36%) were significantly lower (p < 0.05) than that of the control RS–G film (0% ZnONPs). Moreover, the addition of ZnONPs strongly affected the film appearance, color, transmission, and transparency. The ZnONPs had a profound effect on the UV-light barrier improvement of the RS–G film. The crystalline structure of the ZnONPs was observed in the fabricated nanocomposite films using X-ray diffraction analysis. Furthermore, the RS–G–ZnONPs nanocomposite films exhibited strong antimicrobial activity against all tested bacterial strains (Staphylococcus aureus TISTR 746, Bacillus cereus TISTR 687, Escherichia coli TISTR 527, Salmonella Typhimurium TISTR 1470) and antifungal activity toward Aspergillus niger. According to these findings, RS–G–ZnONPs nanocomposite film possesses a potential application as an active packaging: antimicrobial or UV protective.