bluuebunny/crossref_metadata_2025 huggingface dataset:
Anticancer Activities of Marine-Derived Phenolic Compounds and Their Derivatives
Authors: Matulja Dario , Vranješević Filip , Kolympadi Markovic Maria , Pavelić Sandra Kraljević , Marković Dean
Published: February 2022

Since the middle of the last century, marine organisms have been identified as producers of chemically and biologically diverse secondary metabolites which have exerted various biological activities including anticancer, anti-inflammatory, antioxidant, antimicrobial, antifouling and others. This review primarily focuses on the marine phenolic compounds and their derivatives with potent anticancer activity, isolated and/or modified in the last decade. Reports on the elucidation of their structures as well as biosynthetic studies and total synthesis are also covered. Presented phenolic compounds inhibited cancer cells proliferation or migration, at sub-micromolar or nanomolar concentrations (lamellarins D (37), M (38), K (39), aspergiolide B (41), fradimycin B (62), makulavamine J (66), mayamycin (69), N-acetyl-N-demethylmayamycin (70) or norhierridin B (75)). In addition, they exhibited anticancer properties by a diverse biological mechanism including induction of apoptosis or inhibition of cell migration and invasive potential. Finally, phlorotannins 1–7 and bromophenols 12–29 represent the most researched phenolic compounds, of which the former are recognized as protective agents against UVB or gamma radiation-induced skin damages. Finally, phenolic metabolites were assorted into six main classes: phlorotannins, bromophenols, flavonoids, coumarins, terpenophenolics, quinones and hydroquinones. The derivatives that could not be attributed to any of the above-mentioned classes were grouped in a separate class named miscellaneous compounds.
Advanced Nanomechanical Characterization of Biopolymer Films Containing GNPs and MWCNTs in Hybrid Composite Structure
Authors: Batakliev Todor , Ivanov Evgeni , Angelov Verislav , Spinelli Giovanni , Kotsilkova Rumiana
Published: February 2022

Nanomechanical definition of the properties of composite specimens based on polylactic acid (PLA) was made in the present study. Research activities with accent on biodegradable polymer nanocomposites have fundamental significance originated from the worldwide plastic waste pollution. To receive hybrid nanocomposites with high level of homogeneity, the low cost and environmentally friendly melt extrusion method has been applied. The role of graphene nanoplatelets (GNPs) and multiwall carbon nanotubes (MWCNTs) as reinforcing nanoparticles dispersed in the polymer matrix was thoroughly investigated. Quasi-static nanoindentation analysis was enriched by performance of accelerated property mapping and nanodynamic mechanical testing in order to fully describe the nanoscale surface homogeneity and stress relaxation behavior of the nanocomposite specimens. That novelty of the research approach had a well-marked contribution over the detection of the new samples’ nanomechanical features as a function of the type of carbon nanofiller. Refined nanoscratch experiments uncovered the resistance of the materials against notches by means of measurement of the coefficient of friction and accurate estimation of the residual penetration depth.
Highly Unidirectional Radiation Enhancement Based on a Hybrid Multilayer Dimer
Authors: Huang Dengchao , Liu Shilin , Yang Kang
Published: February 2022

Dimers made of plasmonic particles support strong field enhancements but suffer from large absorption losses, while low-loss dielectric dimers are limited by relatively weak optical confinement. Hybrid dimers could utilize the advantages of both worlds. Here, we propose a hybrid nanoantenna that contains a dimer of core-dual shell nanoparticles known as the metal–dielectric–metal (MDM) structure. We discovered that the hybrid dimer sustained unidirectional forward scattering, which resulted in a nearly ideal Kerker condition in the frequency close to the resonance peak of the dimer due to enhancing the amplitude of the induced high-order electric multiples in the gap and effectively superimposing them with magnetic ones, which respond to the excitation of the plane wave in the dielectric layer of the dimer. Furthermore, when an electric quantum emitter is coupled to the dimer, our study shows that the optimal hybrid dimer simultaneously possesses high radiation directivity and low-loss features, which illustrates a back-to-front ratio of radiation 53 times higher than that of the pure dielectric dimer and an average radiation efficiency 80% higher than that of the pure metallic dimer. In addition, the unique structures of the hybrid hexamer direct almost decrease 75% of the radiation beamwidth, hence heightening the directivity of the nanoantenna based on a hybrid dimer.
A Micro Electrochemical Sensor for Multi-Analyte Detection Based on Oxygenated Graphene Modified Screen-Printed Electrode
Authors: Yuan Baiqing , Gan Liju , Li Gang , Xu Chunying , Liu Gang
Published: February 2022

Electrode interfaces with both antibiofouling properties and electrocatalytic activity can promote the practical application of nonenzymatic electrochemical sensors in biological fluids. Compared with graphene, graphene oxide (GO) possesses unique properties such as superior solubility (hydrophilicity) in water, negative charge, and abundant oxygenated groups (oxo functionalities) in the plane and edge sites, which play an essential role in electrocatalysis and functionalization. In this work, a micro electrochemical sensor consisting of GO-modified screen-printed electrode and PDMS micro-cell was designed to achieve multi-analyte detection with excellent selectivity and anti-biofouling properties by electrochemically tuning the oxygen-containing functional species, hydrophilicity/hydrophobicity, and electrical conductivity. In particular, the presented electrodes demonstrated the potential in the analysis of biological samples in which electrodes often suffer from serious biofouling. The interaction of proteins with electrodes as well as uric acid was investigated and discussed.
Photodetection Tuning with High Absorptivity Using Stacked 2D Heterostructure Films
Authors: Farooq Umar , Min-Dianey Kossi A. A. , Rajagopalan Pandey , Malik Muhammad , Kongnine Damgou Mani , Choi Jeong Ryeol , Pham Phuong V.
Published: February 2022

Graphene-based photodetection (PD) devices have been broadly studied for their broadband absorption, high carrier mobility, and mechanical flexibility. Owing to graphene’s low optical absorption, the research on graphene-based PD devices so far has relied on hybrid heterostructure devices to enhance photo-absorption. Designing a new generation of PD devices supported by silicon (Si) film is considered as an innovative technique for PD devices; Si film-based devices are typically utilized in optical communication and image sensing owing to the remarkable features of Si, e.g., high absorption, high carrier mobility, outstanding CMOS integration. Here, we integrate (i) Si film via a splitting/printing transfer with (ii) graphite film grown by a pyrolysis method. Consequently, p-type Si film/graphite film/n-type Si-stacked PD devices exhibited a broadband detection of 0.4–4 μm (in computation) and obtained good experimental results such as the responsivity of 100 mA/W, specific detectivity of 3.44 × 106 Jones, noise-equivalent power of 14.53 × 10−10 W/(Hz)1/2, external quantum efficiency of 0.2, and rise/fall time of 38 μs/1 μs under 532 nm laser illumination. Additionally, our computational results also confirmed an enhanced light absorption of the above stacked 2D heterostructure film-based PD device compatible with the experimental results.
High Curie Temperature Achieved in the Ferromagnetic MnxGe1−x/Si Quantum Dots Grown by Ion Beam Co-Sputtering
Authors: Duan Xiaoxiao , Ye Shuming , Yang Jing , Li Chen , Lu Chunjiang , He Xinpeng , Zhang Luran , Wang Rongfei , Qiu Feng , Yang Jie , Cui Haoyang , Wang Chong
Published: February 2022

Ferromagnetic semiconductors (FMSs) exhibit great potential in spintronic applications. It is believed that a revolution of microelectronic techniques can take off, once the challenges of FMSs in both the room-temperature stability of the ferromagnetic phase and the compatibility with Si-based technology are overcome. In this article, the MnxGe1−x/Si quantum dots (QDs) with the Curie temperature (TC) higher than the room temperature were grown by ion beam co-sputtering (IBCS). With the Mn doping level increasing, the ripening growth of MnGe QDs occurs due to self-assembly via the Stranski–Krastanov (SK) growth mode. The surface-enhanced Raman scattering effect of Mn sites observed in MnGe QDs are used to reveal the distribution behavior of Mn atoms in QDs and the Si buffer layer. The Curie temperature of MnxGe1−x QDs increases, then slightly decreases with increasing the Mn doping level, and reaches its maximum value of 321 K at the doping level of 0.068. After a low-temperature and short-time annealing, the TC value of Mn0.068Ge0.932 QDs increases from 321 K to 383 K. The higher Ge composition and residual strain in the IBCS grown MnxGe1−x QDs are proposed to be responsible for maintaining the ferromagnetic phase above room temperature.
A Molecular Communication Platform Based on Body Area Nanonetwork
Authors: Pan Wenxin , Chen Xiaokang , Yang Xiaodong , Zhao Nan , Meng Lingguo , Shah Fiaz Hussain
Published: February 2022

With the development of nanotechnology and biotechnology, the nanomachine can be applied to the interior of the human body. In order to achieve the goal of completing complex tasks, measures to connect multiple nanomachines that can complete more simple tasks are taken. This can expand the ability of a single nanomachine to cooperate and share information to complete more complex tasks—namely, the emergence of the Body Area Network (BAN). In response to the requirements of building a BAN, we must first need to solve the communication problem between two nanomachines. Communication networks based on molecular communication (MC), known as “natural body area networks”, are widely used in biomedical fields. With the considerable development of MC theory, it is urgent to set up an experimental platform to verify and guide theoretical modeling. In this paper, a nanomaterial-based MC platform is designed and built to simulate the cardiovascular system. The platform uses the diffusion of nanoscale pigment particles in water solution in silicone tube to achieve communication process and modulates binary sequence information to messenger molecules by on-off keying (OOK). The platform successfully transmits and receives a 17-bit binary sequence to prove its communication possibilities. To assess the platform capabilities, this paper tests the effects of different solution concentrations, pipeline flow rates, and pressure on platform communications. These factors can be used to expand the modulation schemes that the platform can implement. In future work, some nanomaterials that can be used for molecular communication can be applied to the platform to characterize their channel characteristics.
Flexible Piezoresistive Pressure Sensor Based on Electrospun Rough Polyurethane Nanofibers Film for Human Motion Monitoring
Authors: Xue Bin , Xie Haiyi , Zhao Jinxu , Zheng Jianming , Xu Chunye
Published: February 2022

Flexible piezoresistive pressure sensors have been attracted a lot of attention due to their simple mechanism, easy fabrication, and convenient signal acquisition and analysis. Herein, a new flexible piezoresistive sensor based on microstructured electrospun rough polyurethane (PU) nanofibers film is assembled. The microstructured PU film with tiny bumps is prepared in one step via electrospinning technology, which imparts a microstructured rough upper surface and a smooth lower surface. With this unique microstructure, we have made it possible for PU/Ag films to serve as sensing layers for piezoresistive sensors by introducing a silver conductive layer on the surface of electrospun PU film. The fabricated piezoresistive pressure sensor delivers high sensitivity (10.53 kPa−1 in the range of 0–5 kPa and 0.97 kPa−1 in the range of 6–15 kPa), fast response time (60 ms), fast recovery time (30 ms), and long-time stability (over 10,000 cycles). This study presents a fabrication strategy to prepare the microstructured PU nanofiber film using electrospinning technology directly, and the as-developed sensor shows promise in applications such as wrist pulse measurement, finger movement monitoring, etc., proving its great potential for monitoring human activities.
Determination of the Transport Efficiency in spICP-MS Analysis Using Conventional Sample Introduction Systems: An Interlaboratory Comparison Study
Authors: Geiss Otmar , Bianchi Ivana , Bucher Guillaume , Verleysen Eveline , Brassinne Frédéric , Mast Jan , Loeschner Katrin , Givelet Lucas , Cubadda Francesco , Ferraris Francesca , Raggi Andrea , Iacoponi Francesca , Peters Ruud , Undas Anna , Müller Alexandra , Meinhardt Ann-Katrin , Hetzer Birgit , Gräf Volker , Montoro Bustos Antonio R. , Barrero-Moreno Josefa
Published: February 2022

In single particle inductively coupled plasma mass spectrometry (spICP-MS), the transport efficiency is fundamental for the correct determination of both particle number concentration and size. In the present study, transport efficiency was systematically determined on three different days with six carefully characterised gold nanoparticle (AuNP) suspensions and in seven European and US expert laboratories using different ICP-MS instruments and spICP-MS software. Both particle size—(TES)—and particle frequency—(TEF)—methods were applied. The resulting transport efficiencies did not deviate much under ideal conditions. The TEF method however systematically resulted in lower transport efficiencies. The extent of this difference (0–300% rel. difference) depended largely on the choice and storage conditions of the nanoparticle suspensions used for the determination. The TES method is recommended when the principal measurement objective is particle size. If the main aim of the measurement is the determination of the particle number concentration, the TEF approach could be preferred as it might better account for particle losses in the sample introduction system.
Iodine Status of 6–12-Year-Old Children in Russia over the Past 10 Years: A Scoping Review
Authors: Korobitsyna Rimma , Aksenov Andrey , Sorokina Tatiana , Trofimova Anna , Grjibovski Andrej M.
Published: February 2022

Iodine is an essential element for growth and development of children. Ensuring adequate iodine intake and monitoring iodine intake are important public health concerns. According to the World Health Organization, a population-based assessment of iodine status is often done by measuring urine iodine concentration (UIC) in children aged 6–12 years. National data for large countries may hide regional differences in the UIC. Currently, there is limited data on the iodine status of children in Russia. We summarized the evidence on the iodine status of children in Russia using both international and local literature in accordance with the PRISMA guidelines. A total of 2164 studies were identified, 12 of which met the selection criteria and covered 10 of 85 federal subjects. For most of the Russian regions there was no information on UIC. A range of methodologies were used to determine UIC. The median UIC ranged from 46 μg/L in the mountainous areas in the Republic of Kabardino-Balkaria, which corresponds to a moderate iodine deficiency (ID), to 719 μg/L in the town of Turinsk (Sverdlovsk region) indicating excessive of iodine intake. Nationwide monitoring should be implemented in Russia and public health measures should be adjusted to regional and local conditions to ensure adequate iodine nutrition for all citizens.
Why and How the Indo-Mediterranean Diet May Be Superior to Other Diets: The Role of Antioxidants in the Diet
Authors: Singh Ram B. , Fedacko Jan , Fatima Ghizal , Magomedova Aminat , Watanabe Shaw , Elkilany Galal
Published: February 2022

The Seven Countries Study showed that traditional Japanese and Mediterranean diets are protective against cardiovascular diseases (CVDs). The Japanese diet is considered the healthiest because it provides Japanese populations with the highest longevity and health. DASH and Mediterranean-style diets are also considered healthy diets, although the Indo-Mediterranean-style diet may provide better protective effects among patients with CVDs compared to other diets. The concept of the Indo-Mediterranean type of diet was developed after examining its role in the prevention of CVDs in India, the value of which was confirmed by a landmark study from France: the Lyon Heart Study. These workers found that consuming an alpha-linolenic acid-rich Mediterranean-style diet can cause a significant decline in CVDs and all-cause mortality. Later in 2018, the PREDIMED study from Spain also reported that a modified Mediterranean-style diet can cause a significant decline in CVDs, type 2 diabetes mellitus (T2DM), and cancer. The Indo-Mediterranean diet may be superior to DASH and Mediterranean diets because it contains millets, porridge, and beans, as well as spices such as turmeric, cumin, fenugreek, and coriander, which may have better anti-inflammatory and cardioprotective effects. These foods are rich sources of nutrients, flavonoids, calcium, and iron, as well as proteins, which are useful in the prevention of under- and overnutrition and related diseases. It is known that DASH and Mediterranean-style diets have a similar influence on CVDs. However, the Indo-Mediterranean-style diet may be as good as the Japanese diet due to improved food diversity and the high content of antioxidants.
The Association between Postpartum Practice and Chinese Postpartum Depression: Identification of a Postpartum Depression-Related Dietary Pattern
Authors: Zhao Ai , Huo Shanshan , Tan Yuefeng , Yang Yucheng , Szeto Ignatius Man-Yau , Zhang Yumei , Lan Hanglian
Published: February 2022

Conflicting results of Chinese traditional postpartum practices have aroused concerns over their health effects. The role of postpartum practices in postpartum depression (PPD) is still a matter of discussion, especially from a dietary practice point of view. The current study was designed to (1) explore the association between postpartum practices and PPD, (2) to identify the dietary pattern related to PPD, and (3) to identify the possible pathways among postpartum practices and PPD. This study is part of the YI Study, which was a cross-sectional study conducted in 10 cities in China. Data for 955 postpartum women were used in the current analysis. The Edinburgh Postnatal Depression Scale (EPDS-10) was used to evaluate PPD with a cutoff value of 9. Postpartum practice was based on the participants’ self-reported practices. Individual practices were recorded and categorized as dietary and non-dietary practices. The dietary pattern was identified based on the food intake frequencies of 25 food groups using the method of reduced rank regression. Structural equation modeling was used to explore the potential pathways between postpartum practices and PPD. The current study observed significant associations between postpartum practices and PPD (Adjusted OR = 1.41, 95% CI: 1.04–1.90). A similar trend was also found between dietary postpartum practices and PPD (Adjusted OR = 1.39, 95%CI: 1.03–1.88) but not for non-dietary practices and PPD (Adjusted OR = 1.26, 95%CI: 0.92–1.75). A PPD-related dietary pattern was identified with the characteristics of a high intake of meat and eggs and a lower intake of vegetables, mushrooms, and nuts. This dietary pattern was significantly associated with a higher chance of adhering to postpartum practice (Adjusted OR = 1.26, 95% CI: 1.10–1.44). Based on the pathway analysis, this study also observed the association between postpartum practices and PPD, and the association between dietary practices and PPD were both mediated by sleep quality. In conclusion, this study demonstrated that a substantial proportion of women in modern China experience traditional postpartum Chinese practices and that either overall or dietary-related postpartum practices are associated with a higher risk of PPD. The current dietary practices in postpartum rituals may play an important role in developing PPD. A culturally embedded, science-based dietary guideline is required to help women to achieve both physical and psychological health in the postpartum period.
Antihypertensive Mechanism of Orally Administered Acetylcholine in Spontaneously Hypertensive Rats
Authors: Yamaguchi Shohei , Hayasaka Yuzumi , Suzuki Miho , Wang Wenhao , Koyama Masahiro , Nagasaka Yasuko , Nakamura Kozo
Published: February 2022

Acetylcholine (ACh) acts as a neurotransmitter and neuromodulator. A small dose of eggplant powder rich in ACh (equivalent to 22 g fresh eggplant/d) has been shown to reduce blood pressure (BP) in individuals with higher BP. Here, we investigated the mechanisms underlying the antihypertensive effects of low-dose orally administered ACh in spontaneously hypertensive rats (SHRs). The effects of ACh on BP and sympathetic nervous activity (SNA), including lumbar SNA (LSNA) and renal SNA (RSNA), were evaluated by subjecting conscious SHRs to a telemetry method. Single oral administration of ACh decreased LSNA and lowered BP. Repeated oral administration of ACh for 30 d decreased RSNA and suppressed the elevated BP. Noradrenaline levels in the urine also decreased. However, vagotomy and co-administration of M3 muscarinic ACh receptor antagonist reversed the BP-lowering effect; the dynamics of non-absorbable orally administered ACh was revealed using stable isotope-labeled ACh. In conclusion, ACh acts on the gastrointestinal M3 muscarinic ACh receptor to increase afferent vagal nerve activity, which decreases SNA by autonomic reflex, suppressing noradrenaline release and lowering BP. This study suggests the use of exogenous ACh as an antihypertensive food supplement for controlling the autonomic nervous system, without absorption into the blood.
Olive Oil Improves While Trans Fatty Acids Further Aggravate the Hypomethylation of LINE-1 Retrotransposon DNA in an Environmental Carcinogen Model
Authors: Szabo Laszlo , Molnar Richard , Tomesz Andras , Deutsch Arpad , Darago Richard , Varjas Timea , Ritter Zsombor , Szentpeteri Jozsef L. , Andreidesz Kitti , Mathe Domokos , Hegedüs Imre , Sik Attila , Budan Ferenc , Kiss Istvan
Published: February 2022

DNA methylation is an epigenetic mechanism that is crucial for mammalian development and genomic stability. Aberrant DNA methylation changes have been detected not only in malignant tumor tissues; the decrease of global DNA methylation levels is also characteristic for aging. The consumption of extra virgin olive oil (EVOO) as part of a balanced diet shows preventive effects against age-related diseases and cancer. On the other hand, consuming trans fatty acids (TFA) increases the risk of cardiovascular diseases as well as cancer. The aim of the study was to investigate the LINE-1 retrotransposon (L1-RTP) DNA methylation pattern in liver, kidney, and spleen of mice as a marker of genetic instability. For that, mice were fed with EVOO or TFA and were pretreated with environmental carcinogen 7,12-dimethylbenz[a]anthracene (DMBA)—a harmful substance known to cause L1-RTP DNA hypomethylation. Our results show that DMBA and its combination with TFA caused significant L1-RTP DNA hypomethylation compared to the control group via inhibition of DNA methyltransferase (DNMT) enzymes. EVOO had the opposite effect by significantly decreasing DMBA and DMBA + TFA-induced hypomethylation, thereby counteracting their effects.
Populations in Low-Magnesium Areas Were Associated with Higher Risk of Infection in COVID-19’s Early Transmission: A Nationwide Retrospective Cohort Study in the United States
Authors: Tian Jing , Tang Liwei , Liu Xinwei , Li Yulan , Chen Jinghong , Huang Weiren , Liu Min
Published: February 2022

Many studies have confirmed the important roles of nutritional status and micronutrients in the COVID-19 pandemic. Magnesium is a vital essential trace element that is involved in oxidative stress, inflammation, and many other immunological functions and has been shown to be associated with the outcome of COVID-19 infection. Here, we conducted a nationwide retrospective cohort study in the United States involving 1150 counties, 287,326,503 individuals, and 5,401,483 COVID-19 confirmed cases as of 30 September 2020 to reveal the infection risk of the populations distributed in low-magnesium areas in the early transmission of COVID-19. Our results indicate that the average county-level COVID-19 cumulative incidence in low-magnesium areas was significantly higher than in the control areas. Additionally, a significant negative nonlinear association was found between environmental magnesium concentration and the county-level COVID-19 cumulative incidence. Furthermore, the populations distributed in low environmental magnesium areas faced a higher COVID-19 infection risk (RR: 1.066; CI: 1.063–1.068), among which females (RR: 1.07; CI: 1.067–1.073), the 0–17 years subgroup (RR: 1.125; CI: 1.117–1.134), the 65+ years subgroup (RR: 1.093; CI: 1.087–1.098), black people (RR: 1.975; CI: 1.963–1.986), populations outside metro areas, and counties with a smaller population experienced higher risk of infection by COVID-19 than other subgroups. Considering that the magnesium intake of about half the population of the United States is below the daily required dose, our study will contribute to the creation of long-term public health strategies to help protect against COVID-19.
Associations between Plasma Folate and Vitamin B12, Blood Lead, and Bone Mineral Density among Adults and Elderly Who Received a Health Examination
Authors: Hsieh Ru-Lan , Huang Ya-Li , Chen Wei-Jen , Chen Hsi-Hsien , Shiue Horng-Sheng , Lin Ying-Chin , Hsueh Yu-Mei
Published: February 2022

This study hypothesized that plasma folate and vitamin B12 levels modified the association between blood lead and cadmium and total urinary arsenic levels and bone loss. A total of 447 study subjects who received a physical examination at the Wanfang Hospital Medical Center were recruited. Bone loss was defined as a calcaneus bone mineral density T-score less than −1. Blood cadmium and lead concentrations were measured by ICP-MS. Urinary arsenic species were determined using HPLC-HG-AAS. A SimulTRAC-SNB radioassay was used to measure plasma folate, vitamin B12, and homocysteine levels. Total urinary arsenic and blood lead concentration were positively correlated with the odds ratio (OR) for bone loss in a dose–response manner. The OR and 95% confidence interval (CI) for bone loss in participants with blood lead concentrations > 56.14 versus ≤33.82 μg/dL were 1.82 and 1.10–3.01. No correlation between plasma folate and vitamin B12 levels alone and bone loss was observed. However, this study is the first observational study to find that blood lead concentrations tend to increase the OR of bone loss in a low plasma folate and plasma vitamin B12 group with multivariate ORs (95% CI) of 2.44 (0.85–6.96).
Cold Enrichment Methods for the Detection of Foodborne Yersiniosis: Friend or Foe?
Authors: Zhang Yuwei , On Stephen L. W.
Published: February 2022

Yersinia enterocolitica and Y. pseudotuberculosis are important causes of enteric illness worldwide. Rapid response to suspected foodborne outbreaks is hampered by the widespread use of cold enrichment methods that require incubation periods of 10–21 days. Although these species grow faster at elevated temperatures, part of the rationale for cold enrichment is that a key pathogenicity marker (pYV virulence plasmid) is said to be lost at elevated temperatures. Experimental data on this claim seems scarce. We previously described an approach involving an enrichment step at 37 °C for Yersinia detection, applied this approach to additional strains, and examined the presence of plasmids in reisolates, as well as those recovered in our original study. Plasmids were recovered from every reisolate examined; the presence of marker genes yadA and virF denoted the virulence plasmid in 10 of the 11 strains examined. Use of an enrichment step at 37 °C does not appear to promote loss of the pYV or other plasmids harboured by foodborne pathogenic Y. enterocolitica and Y. pseudotuberculosis; wider adoption of this approach may assist the development of more rapid detection methods.
A High-Throughput Phenotypic Screen of the ‘Pandemic Response Box’ Identifies a Quinoline Derivative with Significant Anthelmintic Activity
Authors: Shanley Harrison T. , Taki Aya C. , Byrne Joseph J. , Jabbar Abdul , Wells Tim N. C. , Samby Kirandeep , Boag Peter R. , Nguyen Nghi , Sleebs Brad E. , Gasser Robin B.
Published: February 2022

Parasitic nematodes cause diseases in livestock animals and major economic losses to the agricultural industry worldwide. Nematodes of the order Strongylida, including Haemonchus contortus, are particularly important. The excessive use of anthelmintic compounds to treat infections and disease has led to widespread resistance to these compounds in nematodes, such that there is a need for new anthelmintics with distinctive mechanisms of action. With a focus on discovering new anthelmintic entities, we screened 400 chemically diverse compounds within the ‘Pandemic Response Box’ (from Medicines for Malaria Venture, MMV) for activity against H. contortus and its free-living relative, Caenorhabditis elegans—a model organism. Using established phenotypic assays, test compounds were evaluated in vitro for their ability to inhibit the motility and/or development of H. contortus and C. elegans. Dose-response evaluations identified a compound, MMV1581032, that significantly the motility of H. contortus larvae (IC50 = 3.4 ± 1.1 μM) and young adults of C. elegans (IC50 = 7.1 ± 4.6 μM), and the development of H. contortus larvae (IC50 = 2.2 ± 0.7 μM). The favourable characteristics of MMV1581032, such as suitable physicochemical properties and an efficient, cost-effective pathway to analogue synthesis, indicates a promising candidate for further evaluation as a nematocide. Future work will focus on a structure-activity relationship investigation of this chemical scaffold, a toxicity assessment of potent analogues and a mechanism/mode of action investigation.
Potential Anti-SARS-CoV-2 Activity of Pentosan Polysulfate and Mucopolysaccharide Polysulfate
Authors: Zhang Fuming , He Peng , Rodrigues Andre L. , Jeske Walter , Tandon Ritesh , Bates John T. , Bierdeman Michael A. , Fareed Jawed , Dordick Jonathan , Linhardt Robert J.
Published: February 2022

With the increased prevalence of new SARS-CoV-2 variants of concern, such as Delta and Omicron, the COVID-19 pandemic has become an ongoing human health disaster, killing millions worldwide. SARS-CoV-2 invades its host through the interaction of its spike (S) protein with a host cell receptor, angiotensin-converting enzyme 2 (ACE2). In addition, heparan sulfate (HS) on the surface of host cells plays an important role as a co-receptor for this viral pathogen–host cell interaction. Our previous studies demonstrated that many sulfated glycans, such as heparin, fucoidans, and rhamnan sulfate have anti-SARS-CoV-2 activities. In the current study, a small library of sulfated glycans and highly negatively charged compounds, including pentosan polysulfate (PPS), mucopolysaccharide polysulfate (MPS), sulfated lactobionic acid, sulodexide, and defibrotide, was assembled and evaluated for binding to the S-proteins and inhibition of viral infectivity in vitro. These compounds inhibited the interaction of the S-protein receptor-binding domain (RBD) (wild type and different variants) with immobilized heparin, a highly sulfated HS, as determined using surface plasmon resonance (SPR). PPS and MPS showed the strongest inhibition of interaction of heparin and S-protein RBD. The competitive binding studies showed that the IC50 of PPS and MPS against the S-protein RBD binding to immobilized heparin was ~35 nM and ~9 nM, respectively, much lower than the IC50 for soluble heparin (IC50 = 56 nM). Both PPS and MPS showed stronger inhibition than heparin on the S-protein RBD or spike pseudotyped lentiviral particles binding to immobilized heparin. Finally, in an in vitro cell-based assay, PPS and MPS exhibited strong antiviral activities against pseudotyped viral particles of SARS-CoV-2 containing wild-type or Delta S-proteins.
Synthesis, Characterization and Host-Guest Complexation of Asplatin: Improved In Vitro Cytotoxicity and Biocompatibility as Compared to Cisplatin
Authors: Fahmy Sherif Ashraf , Ponte Fortuna , Grande Giulia , Fawzy Iten M. , Mandour Asmaa A. , Sicilia Emilia , Azzazy Hassan Mohamed El-Said
Published: February 2022

Para-sulfocalix[n]arenes are promising host molecules that can accommodate various chemotherapeutic drugs. Pt(IV)-based complexes, including satraplatin and asplatin, are promising alternatives that overcome the shortcomings of Pt(II) complexes. In this study, asplatin has been synthesized by fusing acetylsalicylic acid (aspirin) and cisplatin. Furthermore, it has been characterized using 1H NMR, mass spectrometry, elemental analysis, and UHPLC. A host-guest complex of asplatin and p-sulfocalix[4]arene (PSC4) has been developed and characterized using UV, Job’s plot analysis, HPLC, and density functional theory (DFT) calculations. The experimental and computational investigations propose that a 1:1 complex between asplatin and PSC4 is formed. The stability constant of the designed complex has been determined using Job’s plot and UHPLC and computed to be 9.1 × 104 M–1 and 8.7 × 104 M−1, which corresponds to a free energy of complexation of −6.8 kcal mol–1, while the calculated value for the inclusion free energy is −13.2 kcal mol−1. Both experimentally and theoretically estimated complexation free energy show that a stable host-guest complex can be formed in solution. The in vitro drug release study displayed the ability of the complex to release its cargo at a cancerous pH (pH of 5.5). Additionally, the asplatin/PSC4 complex is shown to be biocompatible when tested on human skin fibroblast noncancerous cells, demonstrating the highest in vitro cytotoxic activity against (MCF-7), cervical (HeLa), and lung cancer cells (A-549), with IC50 values of 0.75, 2.15, and 3.60 µg/mL, respectively. This is as compared to either cisplatin (IC50 of 5.47, 5.94 and 9.61 µg/mL, respectively) or asplatin (IC50 of 1.54, 5.05 and 3.91 µg/mL, respectively). On the other hand, the free asplatin exhibited higher cytotoxicity on cancerous cells and lower toxicity on noncancerous cells. The outcomes of the present joint theoretical and experimental investigation reinforce the interest in platinum-based anticancer therapeutics when they are protected from undesired interactions and suggest the use of the PSC4 macromolecule as a promising carrier for Pt(IV) anticancer drugs. The formed asplatin/PSC4 inclusion complex may represent an effective chemotherapeutic agent.
Native RNA Purification Method for Small RNA Molecules Based on Asymmetrical Flow Field-Flow Fractionation
Authors: Levanova Alesia A. , Lampi Mirka , Kalke Kiira , Hukkanen Veijo , Poranen Minna M. , Eskelin Katri
Published: February 2022

RNA molecules provide promising new possibilities for the prevention and treatment of viral infections and diseases. The rapid development of RNA biology and medicine requires advanced methods for the purification of RNA molecules, which allow fast and efficient RNA processing, preferably under non-denaturing conditions. Asymmetrical flow field-flow fractionation (AF4) enables gentle separation and purification of macromolecules based on their diffusion coefficients. The aim of the study was to develop an AF4 method for efficient purification of enzymatically produced antiviral small interfering (si)RNA molecules and to evaluate the overall potential of AF4 in the separation of short single-stranded (ss) and double-stranded (ds) RNA molecules. We show that AF4 separates monomeric ssRNA from dsRNA molecules of the same size and monomeric ssRNA from multimeric forms of the same ssRNA. The developed AF4 method enabled the separation of enzymatically produced 27-nt siRNAs from partially digested substrate dsRNA, which is potentially toxic for mammalian cells. The recovery of AF4-purified enzymatically produced siRNA molecules was about 70%, which is about 20% higher than obtained using anion-exchange chromatography. The AF4-purified siRNAs were not toxic for mammalian cells and fully retained their biological activity as confirmed by efficient inhibition of herpes simplex virus 1 replication in cell culture. Our work is the first to develop AF4 methods for the separation of short RNA molecules.
Increased Targeting Area in Tumors by Dual-Ligand Modification of Liposomes with RGD and TAT Peptides
Authors: Amin Mohamadreza , Mansourian Mercedeh , Burgers Peter C. , Amin Bahareh , Jaafari Mahmoud Reza , ten Hagen Timo L. M.
Published: February 2022

Modification with polyethylene glycol (PEGylation) and the use of rigid phospholipids drastically improve the pharmacokinetics of chemotherapeutics and result in more manageable or reduced side-effects. A major drawback is retarded cellular delivery of content, which, along with tumor heterogeneity, are the two main obstacles against tumor targeting. To enhance cellular delivery and reach a bigger area of a tumor, we designed liposomes decorated with two ligands: one for targeting tumor vasculature via a cyclic-pentapeptide containing arginine-glycine-aspartic acid (RGD), which impacts tumor independent of passive accumulation inside tumors, and one for extravascular targeting of tumor cells via a cell-penetrating peptide derived from human immunodeficiency virus type 1 transactivator of transcription (TAT). Liposomes with different ligand combinations were prepared and compared with respect to performance in targeting. Intravital imaging illustrates the heterogeneous behavior of RGD-liposomes in both intravascular and extravascular distribution, whereas TAT-liposomes exhibit a predictable extravascular localization but no intravascular targeting. Dual-ligand modification results in enhanced vascular targeting and a predictable extravascular behavior that improves the therapeutic efficacy of doxorubicin-loaded liposomes but also an augmented clearance rate of liposomes. However, the dual-modified liposome could be a great candidate for targeted delivery of non-toxic payloads or contrast agents for therapeutic or diagnostic purposes. Here we show that the combination of vascular-specific and tumor cell-specific ligands in a liposomal system is beneficial in bypassing the heterogeneous expression of tumor-specific markers.
Drug Properties Prediction Based on Deep Learning
Authors: Yoo Soyoung , Kim Junghyun , Choi Guang J.
Published: February 2022

In recent research on the formulation prediction of oral dissolving drugs, deep learning models with significantly improved performance compared to machine learning models were proposed. However, the performance degradation due to limitations of an imbalanced dataset with a small size and inefficient neural network structure has still not been resolved. Therefore, we propose new deep learning-based prediction models that maximize the prediction performance for disintegration time of oral fast disintegrating films (OFDF) and cumulative dissolution profiles of sustained-release matrix tablets (SRMT). In the case of OFDF, we use principal component analysis (PCA) to reduce the dimensionality of the dataset, thereby improving the prediction performance and reducing the training time. In the case of SRMT, the Wasserstein generative adversarial network (WGAN), a neural network-based generative model, is used to overcome the limitation of performance improvement due to the lack of experimental data. To the best of our knowledge, this is the first work that utilizes WGAN for pharmaceutical formulation prediction. Experimental results show that the proposed methods have superior performance than the existing methods for all the performance metrics considered.
An On-Demand Drug Delivery System for Control of Epileptiform Seizures
Authors: Nakano Takashi , Rizwan Shakila B. , Myint David M. A. , Gray Jason , Mackay Sean M. , Harris Paul , Perk Christopher G. , Hyland Brian I. , Empson Ruth , Tan Eng Wui , Dani Keshav M. , Reynolds John NJ , Wickens Jeffery R.
Published: February 2022

Drug delivery systems have the potential to deliver high concentrations of drug to target areas on demand, while elsewhere and at other times encapsulating the drug, to limit unwanted actions. Here we show proof of concept in vivo and ex vivo tests of a novel drug delivery system based on hollow-gold nanoparticles tethered to liposomes (HGN-liposomes), which become transiently permeable when activated by optical or acoustic stimulation. We show that laser or ultrasound simulation of HGN-liposomes loaded with the GABAA receptor agonist, muscimol, triggers rapid and repeatable release in a sufficient concentration to inhibit neurons and suppress seizure activity. In particular, laser-stimulated release of muscimol from previously injected HGN-liposomes caused subsecond hyperpolarizations of the membrane potential of hippocampal pyramidal neurons, measured by whole cell intracellular recordings with patch electrodes. In hippocampal slices and hippocampal–entorhinal cortical wedges, seizure activity was immediately suppressed by muscimol release from HGN-liposomes triggered by laser or ultrasound pulses. After intravenous injection of HGN-liposomes in whole anesthetized rats, ultrasound stimulation applied to the brain through the dura attenuated the seizure activity induced by pentylenetetrazol. Ultrasound alone, or HGN-liposomes without ultrasound stimulation, had no effect. Intracerebrally-injected HGN-liposomes containing kainic acid retained their contents for at least one week, without damage to surrounding tissue. Thus, we demonstrate the feasibility of precise temporal control over exposure of neurons to the drug, potentially enabling therapeutic effects without continuous exposure. For future application, studies on the pharmacokinetics, pharmacodynamics, and toxicity of HGN-liposomes and their constituents, together with improved methods of targeting, are needed, to determine the utility and safety of the technology in humans.
Carboxyl-Functionalized Carbon Nanotubes Loaded with Cisplatin Promote the Inhibition of PI3K/Akt Pathway and Suppress the Migration of Breast Cancer Cells
Authors: Badea Madalina Andreea , Balas Mihaela , Prodana Mariana , Cojocaru Florentina Gina , Ionita Daniela , Dinischiotu Anca
Published: February 2022

PI3K/Akt signaling is one of the most frequently dysregulated pathways in cancer, including triple-negative breast cancer. With considerable roles in tumor growth and proliferation, this pathway is studied as one of the main targets in controlling the therapies’ efficiency. Nowadays, the development of nanoparticle–drug conjugates attracts a great deal of attention due to the advantages they provide in cancer treatment. Hence, the main purpose of this study was to design a nanoconjugate based on single-walled carbon nanotubes functionalized with carboxyl groups (SWCNT-COOH) and cisplatin (CDDP) and to explore the potential of inhibiting the PI3K/Akt signaling pathway. MDA-MB-231 cells were exposed to various doses (0.01–2 µg/mL SWCNT-COOH and 0.00632–1.26 µg/mL CDDP) of SWCNT-COOH-CDDP and free components for 24 and 48 h. In vitro biological tests revealed that SWCNT-COOH-CDDP had a high cytotoxic effect, as shown by a time-dependent decrease in cell viability and the presence of a significant number of dead cells in MDA-MB-231 cultures at higher doses. Moreover, the nanoconjugates induced the downregulation of PI3K/Akt signaling, as revealed by the decreased expression of PI3K and p-Akt in parallel with PTEN activation, the promotion of Akt protein degradation, and inhibition of tumor cell migration.
Fast Estimation of the Spectral Optical Properties of Rabbit Pancreas and Pigment Content Analysis
Authors: Martins Inês Soraia , Silva Hugo Filipe , Tuchin Valery Victorovich , Oliveira Luís Manuel
Published: February 2022

The pancreas is a highly important organ, since it produces insulin and prevents the occurrence of diabetes. Although rare, pancreatic cancer is highly lethal, with a small life expectancy after being diagnosed. The pancreas is one of the organs less studied in the field of biophotonics. With the objective of acquiring information that can be used in the development of future applications to diagnose and treat pancreas diseases, the spectral optical properties of the rabbit pancreas were evaluated in a broad-spectral range, between 200 and 1000 nm. The method used to obtain such optical properties is simple, based almost on direct calculations from spectral measurements. The optical properties obtained show similar wavelength dependencies to the ones obtained for other tissues, but a further analysis on the spectral absorption coefficient showed that the pancreas tissues contain pigments, namely melanin, and lipofuscin. Using a simple calculation, it was possible to retrieve similar contents of these pigments from the absorption spectrum of the pancreas, which indicates that they accumulate in the same proportion as a result of the aging process. Such pigment accumulation was camouflaging the real contents of DNA, hemoglobin, and water, which were precisely evaluated after subtracting the pigment absorption.
Examining the Interaction between Phytophthora sojae and Soybean Cyst Nematode on Soybean (Glycine max)
Authors: Chowdhury Rawnaq N. , Okello Paul N. , Byamukama Emmanuel
Published: February 2022

Phytophthora sojae and soybean cyst nematode (SCN) are important pathogens of soybean. Although these pathogens infect soybean roots, there is limited evidence of any interaction between them. The objective of this study was to examine the interaction between SCN and P. sojae on soybean in the greenhouse. Seeds of four soybean cultivars (Jack, Surge, Williams 82, Williams) were pre-germinated and placed in cone-tainers (Stuewe and Sons Inc., Tangent, OR, USA), containing a steam pasteurized sand-clay mixture. The experiment was set up in a completely randomized design with five replications and performed twice. Two P. sojae isolates were used in this study that represented two different virulence pathotypes (simple and complex pathotypes). For each isolate, soybean plants were not inoculated, inoculated with one of the treatments—SCN, P. sojae, and combination of P. sojae and SCN. After 35 DOI, stem length, root length, plant weight, root weight, lesion length, and SCN population were recorded. On all soybean cultivars with different types of incomplete resistance, the complex pathotype (PS-15-TF3) influenced the lesion length (mm) in the presence of SCN. However, the SCN population was reduced by both complex and simple pathotypes of P. sojae. This suggests that use both SCN and P. sojae resistance cultivars, can manage the disease complex and reduce soybean yield loss.