bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced Immunogenicity of Inactivated Dengue Vaccines by Novel Polysaccharide-Based Adjuvants in Mice
Authors: Wu Shuenn-Jue , Ewing Dan , Sundaram Appavu K. , Chen Hua-Wei , Liang Zhaodong , Cheng Ying , Jani Vihasi , Sun Peifang , Gromowski Gregory D. , De La Barrera Rafael A. , Schilling Megan A. , Petrovsky Nikolai , Porter Kevin R. , Williams Maya
Published: May 2022

Dengue fever, caused by any of four dengue viruses (DENV1-4), is a major global burden. Currently, there is no effective vaccine that prevents infection in dengue naïve populations. We tested the ability of two novel adjuvants (Advax-PEI and Advax-2), using aluminum hydroxide (alum) as control, to enhance the immunogenicity of formalin- or psoralen-inactivated (PIV or PsIV) DENV2 vaccines in mice. Mice were vaccinated on days 0 and 30, and serum samples were collected on days 30, 60, 90, and 101. Neutralizing antibodies were determined by microneutralization (MN) assays, and the geometric mean 50% MN (MN50) titers were calculated. For the PIV groups, after one dose MN50 titers were higher in the novel adjuvant groups compared to the alum control, while MN50 titers were comparable between the adjuvant groups after the second dose. For the PsIV groups, both novel adjuvants induced higher MN50 titers than the alum control after the second dose. Spleen cells were collected on days 45 and 101 for enzyme-linked immunospot (ELISPOT) for IFNγ and IL4. Both PIV and PsIV groups elicited different degrees of IFNγ and IL4 responses. Overall, Advax-2 gave the best responses just ahead of Advax-PEI. Given Advax-2’s extensive human experience in other vaccine applications, it will be pursued for further development.
A Cyanobacteria Enriched Layer of Shark Bay Stromatolites Reveals a New Acaryochloris Strain Living in Near Infrared Light
Authors: Johnson Michael , Burns Brendan , Herdean Andrei , Angeloski Alexander , Ralph Peter , Morris Therese , Kindler Gareth , Wong Hon , Kuzhiumparambil Unnikrishnan , Sedger Lisa , Larkum Anthony
Published: May 2022

The genus Acaryochloris is unique among phototrophic organisms due to the dominance of chlorophyll d in its photosynthetic reaction centres and light-harvesting proteins. This allows Acaryochloris to capture light energy for photosynthesis over an extended spectrum of up to ~760 nm in the near infra-red (NIR) spectrum. Acaryochloris sp. has been reported in a variety of ecological niches, ranging from polar to tropical shallow aquatic sites. Here, we report a new Acarychloris strain isolated from an NIR-enriched stratified microbial layer 4–6 mm under the surface of stromatolite mats located in the Hamelin Pool of Shark Bay, Western Australia. Pigment analysis by spectrometry/fluorometry, flow cytometry and spectral confocal microscopy identifies unique patterns in pigment content that likely reflect niche adaption. For example, unlike the original A. marina species (type strain MBIC11017), this new strain, Acarychloris LARK001, shows little change in the chlorophyll d/a ratio in response to changes in light wavelength, displays a different Fv/Fm response and lacks detectable levels of phycocyanin. Indeed, 16S rRNA analysis supports the identity of the A. marina LARK001 strain as close to but distinct from from the A. marina HICR111A strain first isolated from Heron Island and previously found on the Great Barrier Reef under coral rubble on the reef flat. Taken together, A. marina LARK001 is a new cyanobacterial strain adapted to the stromatolite mats in Shark Bay.
First Case Report of Detection of Multidrug-Resistant Enterobacter hormaechei in Clinical Sample from an Aborted Ruminant
Authors: Zaitsev Sergey S. , Khizhnyakova Mariya A. , Feodorova Valentina A.
Published: May 2022

The emergence of multidrug-resistant (MDR) bacterial strains is one of the significant global challenges with regard to bacterial drug-resistance control. Enterobacter hormaechei organisms belong to the Enterobacter cloacae complex (ECC) and are commonly recognized as causative agents for hospital infections. Recently, a few E. hormaechei MDR strains associated with infection in piglets, calves, and a fox were reported, highlighting the important role of animals and livestock in the emergence and spread of antimicrobial resistance. In this study, the vaginal swab sample from a 5-year-old cow with multiple anamnestic infectious abortions was carefully investigated. The animal was unresponsive to antibiotic therapy recommended by the veterinarian. The MDR bacterial strain isolated from the bovine sample, designated as the Saratov_2019, belonged to Enterobacter hormaechei. The genome-based phylogenetic analysis identified the isolate to be Enterobacter hormaechei subsp. xiangfangensis. The genome of the Saratov_2019 contained a 6364 bp plasmid. Importantly, we revealed the novel sequence type ST1416 and 13 MDR genes correlating with the MDR phenotype in only the chromosome but not the plasmid. These findings indicate that the potential spread of this strain may pose a threat for both animal and human health. The data obtained here support the notion of the important role of livestock in the emergence and spread of antimicrobial resistance, promoting careful investigation of the MDR spectra for livestock-related bacterial isolates. To the best of our knowledge, this is the first report on the association of E. hormaechei subsp. xiangfangensis with the infection of the reproductive system in cattle.
The Notable Achievements and the Prospects of Bacterial Pathogen Genomics
Authors: Amoutzias Grigorios D. , Nikolaidis Marios , Hesketh Andrew
Published: May 2022

Throughout the entirety of human history, bacterial pathogens have played an important role and even shaped the fate of civilizations. The application of genomics within the last 27 years has radically changed the way we understand the biology and evolution of these pathogens. In this review, we discuss how the short- (Illumina) and long-read (PacBio, Oxford Nanopore) sequencing technologies have shaped the discipline of bacterial pathogen genomics, in terms of fundamental research (i.e., evolution of pathogenicity), forensics, food safety, and routine clinical microbiology. We have mined and discuss some of the most prominent data/bioinformatics resources such as NCBI pathogens, PATRIC, and Pathogenwatch. Based on this mining, we present some of the most popular sequencing technologies, hybrid approaches, assemblers, and annotation pipelines. A small number of bacterial pathogens are of very high importance, and we also present the wealth of the genomic data for these species (i.e., which ones they are, the number of antimicrobial resistance genes per genome, the number of virulence factors). Finally, we discuss how this discipline will probably be transformed in the near future, especially by transitioning into metagenome-assembled genomes (MAGs), thanks to long-read sequencing.
The Interactions between Arbuscular Mycorrhizal Fungi and Trichoderma longibrachiatum Enhance Maize Growth and Modulate Root Metabolome under Increasing Soil Salinity
Authors: Yang Rong , Qin Zefeng , Wang Jingjing , Zhang Xiaoxia , Xu Song , Zhao Wei , Huang Zhiyong
Published: May 2022

Trichoderma longibrachiatum sp. are free-living filamentous fungi which are common in agro-ecosystems. However, few studies thus far have examined the interaction between Trichoderma longibrachiatum and arbuscular mycorrhizal (AM) fungi in saline soil and their potential for improving plant stress tolerance. Here, single, dual-inoculated (T. longibrachiatum MF, AM fungal community or Glomus sp.), and non-inoculated maize (Zea may L.) were subjected to different salinity levels (0, 75, 150, and 225 mM NaCl) to test the synergistic effects of dual inoculants on maize plants in different salt stress conditions. Plant performance and metabolic profiles were compared to find the molecular mechanisms underlying plant protection against salt stress. The first experiment revealed that dual inoculation of an AM fungal community and T. longibrachiatum MF improved the biomass and K+/Na+ ratio in maize under non-saline conditions, and generally enhanced AM fungal growth in root and soil under all but the 225 mM NaCl conditions. However, MF inoculant did not influence the structure of AM fungal communities in maize roots. In the second experiment, dual inoculation of Glomus sp. and T. longibrachiatum MF increased maize plant biomass, K+/Na+ ratio, and AM fungal growth in root and soil significantly at both 0 and 75 mM NaCl conditions. We identified metabolic compounds differentially accumulated in dual-inoculated maize that may underline their enhanced maize plant tolerance to increasing soil salinity. Our data suggested that the combination of Glomus sp. and T. longibrachiatum leads to interactions, which may play a potential role in alleviating the stress and improve crop productivity in salt-affected soils.
The Effect of the Concentration of Copper Ions on the Unfrozen Water Content in Bentonites Measured with the Use of DSC Method
Authors: Nartowska Edyta , Kozłowski Tomasz
Published: May 2022

Studies on changes of unfrozen water content in calcium bentonite from Slovakia, with various concentrations of copper ions, were carried out using the method of differential scanning calorimetry (DSC). In this study, the influence of molar concentration of copper(II) chloride solution (1 M, 0.5 M, 0.25 M, 0.1 M), used to saturate clay, was analyzed, as well as the impact of copper ions contained in bentonite and how the copper concentration affects to changes of unfrozen water content versus temperature. The results suggest that new mineral phases originate in bentonite saturated with highly concentrated solutions due to the reaction with copper(II) chloride solutions. These minerals, identified based on XRD and SEM-EDS (X-ray Diffraction and Scanning Electron Microscopy with Energy Dispersive Spectroscopy) studies, are from the atacamite group. ANOVA (Analysis of Variance) has shown a statistically significant relationship between the unfrozen water content and the molar concentration of the solution used to saturate bentonite and between the unfrozen water content and the content of copper ions in the bentonite. The analysis of multiple regression has shown that the change of unfrozen water content in copper bentonites is related to the temperature change, specific surface, and the concentration of copper ions in the clay. An empirical equation was developed to estimate the content of unfrozen water at a given negative temperature in Cu-bentonites, in which the specific surface and copper ions concentration in the bentonite are the main parameters.
A Bi2Te3-Filled Nickel Foam Film with Exceptional Flexibility and Thermoelectric Performance
Authors: Shi Taifeng , Chen Mengran , Liu Zhenguo , Song Qingfeng , Ou Yixiang , Wang Haoqi , Liang Jia , Zhang Qihao , Mao Zhendong , Wang Zhiwen , Zheng Jingyvan , Han Qingchen , Razeeb Kafil M. , Zong Peng-an
Published: May 2022

The past decades have witnessed surging demand for wearable electronics, for which thermoelectrics (TEs) are considered a promising self-charging technology, as they are capable of converting skin heat into electricity directly. Bi2Te3 is the most-used TE material at room temperature, due to a high zT of ~1. However, it is different to integrate Bi2Te3 for wearable TEs owing to its intrinsic rigidity. Bi2Te3 could be flexible when made thin enough, but this implies a small electrical and thermal load, thus severely restricting the power output. Herein, we developed a Bi2Te3/nickel foam (NiFoam) composite film through solvothermal deposition of Bi2Te3 nanoplates into porous NiFoam. Due to the mesh structure and ductility of Ni Foam, the film, with a thickness of 160 μm, exhibited a high figure of merit for flexibility, 0.016, connoting higher output. Moreover, the film also revealed a high tensile strength of 12.7 ± 0.04 MPa and a maximum elongation rate of 28.8%. In addition, due to the film’s high electrical conductivity and enhanced Seebeck coefficient, an outstanding power factor of 850 μW m−1 K−2 was achieved, which is among the highest ever reported. A module fabricated with five such n-type legs integrated electrically in series and thermally in parallel showed an output power of 22.8 nW at a temperature gap of 30 K. This work offered a cost-effective avenue for making highly flexible TE films for power supply of wearable electronics by intercalating TE nanoplates into porous and meshed-structure materials.
Modeling the Radial Growth of Self-Catalyzed III-V Nanowires
Authors: Dubrovskii Vladimir G. , Leshchenko Egor D.
Published: May 2022

A new model for the radial growth of self-catalyzed III-V nanowires on different substrates is presented, which describes the nanowire morphological evolution without any free parameters. The model takes into account the re-emission of group III atoms from a mask surface and the shadowing effect in directional deposition techniques such as molecular beam epitaxy. It is shown that radial growth is faster for larger pitches of regular nanowire arrays or lower surface density, and can be suppressed by increasing the V/III flux ratio or decreasing re-emission. The model describes quite well the data on the morphological evolution of Ga-catalyzed GaP and GaAs nanowires on different substrates, where the nanowire length increases linearly and the radius enlarges sub-linearly with time. The obtained analytical expressions and numerical data should be useful for morphological control over different III-V nanowires in a wide range of growth conditions.
Graphene: Hexagonal Boron Nitride Composite Films with Low-Resistance for Flexible Electronics
Authors: Antonova Irina V. , Shavelkina Marina B. , Ivanov Artem I. , Poteryaev Dmitriy A. , Nebogatikova Nadezhda A. , Buzmakova Anna A. , Soots Regina A. , Katarzhis Vladimir A.
Published: May 2022

The structure and electric properties of hexagonal boron nitride (h-BN):graphene composite with additives of the conductive polymer PEDOT:PSS and ethylene glycol were examined. The graphene and h-BN flakes synthesized in plasma with nanometer sizes were used for experiments. It was found that the addition of more than 10−3 mass% of PEDOT:PSS to the graphene suspension or h-BN:graphene composite in combination with ethylene glycol leads to a strong decrease (4–5 orders of magnitude, in our case) in the resistance of the films created from these suspensions. This is caused by an increase in the conductivity of PEDOT:PSS due to the interaction with ethylene glycol and synergetic effect on the composite properties of h-BN:graphene films. The addition of PEDOT:PSS to the h-BN:graphene composite leads to the correction of the bonds between nanoparticles and a weak change in the resistance under the tensile strain caused by the sample bending. A more pronounced flexibility of the composite films with tree components is demonstrated. The self-organization effects for graphene flakes and polar h-BN flakes lead to the formation of micrometer sized plates in drops and uniform-in-size nanoparticles in inks. The ratio of the components in the composite was found for the observed strong hysteresis and a negative differential resistance. Generally, PEDOT:PSS and ethylene glycol composite films are promising for their application as electrodes or active elements for logic and signal processing.
Near-Infrared Absorption Properties of Neutral Bis(1,2-dithiolene) Platinum(II) Complexes Using Density Functional Theory
Authors: Luong Xuan-Hoang , Pham Nguyet N. T. , An Kyoung-Lyong , Lee Seong Uk , Kim Shi Surk , Park Jong S. , Lee Seung Geol
Published: May 2022

Small metal complexes are highly interesting for bioimaging because of their excellent near-infrared (NIR) absorption properties. In this study, neutral complexes of platinum(II) connected to two monoreduced 1,3-diisopropylimidazoline-2,4,5-trithione ligands—namely, [Pt(iPr2timdt)2]—were investigated. Theoretical studies using the density functional theory (DFT) and GW-BSE approximation verified the effects of the geometry of the isopropyl moieties on the NIR absorption spectra. The calculated absorption spectra showed excellent correspondence with the experimental results. The geometry of the isopropyl groups considerably influenced the electronic structures of the metal complexes, which altered the absorption profiles of the respective geometries, as demonstrated in this research.
Dairy Animal Ownership and Household Milk Production Associated with Better Child and Family Diet in Rural Nepal during the COVID-19 Pandemic
Authors: Miller Laurie C. , Neupane Sumanta , Joshi Neena , Lohani Mahendra , Sah Keshav , Shrestha Bhola
Published: May 2022

The economic and health crises related to the COVID-19 pandemic raised considerable concern about child and family diet, especially among small-holder farming households in low- and middle-income countries (LMIC). In rural Nepal, 309 families (including 368 children aged 6–66 months) were enrolled pre-COVID-19 in a prospective study of a nutrition education intervention and family milk consumption. The intervention could not be implemented due to COVID-19; however, child and family diet was assessed in three household surveys (one before and two during the pandemic). Over time, after adjusting for child and household factors, child and family diet quality declined (reduced diet diversity, consumption of milk and animal-source-foods (ASF)). However, in dairy-animal-owning (vs. non-dairy-animal-owning) households, both children and family were more likely to consume milk (aOR respectively 2.88× (p < 0.05), 5.81× (p < 0.001)). Similarly, in households producing >3.5 L/d milk (vs. ≤3.5 L/d), children and family members were more likely to consume milk (respectively 7.45× and 11.88× (both p < 0.001)). Thus, the overall decline in child and family diet quality, especially related to milk consumption, was buffered independently by household ownership of ≥1 dairy animals (cow or buffalo) and by milk production >3.5 L/day. A better understanding of these protective factors might facilitate the development of interventions to promote resilience in future crises.
Gastro-Protective Effect of Fermented Soybean (Glycine max (L.) Merr.) in a Rat Model of Ethanol/HCl-Induced Gastric Injury
Authors: Lee Minhee , Kim Dakyung , Kim Hyunji , Jo Sukyung , Kim Ok-Kyung , Lee Jeongmin
Published: May 2022

The present research purposed to examine the gastro-protective effect of Glycine max (L.) Merr. fermented using Lactobacillus delbrueckii ssp. delbrueckii Rosell-187 (Gastro-AD®) on ethanol/HCl-induced gastric damage, specifically on gastric acid secretion. After oral supplementation of Gastro-AD® to Sprague–Dawley (SD) rats with ethanol/HCl-induced gastric damage, we determined that Gastro-AD® attenuated the gastric mucosal lesion, hemorrhage and gastric acid secretion induced by ethanol/HCl. In addition, we observed that the Gastro-AD® treatment increased the serum prostaglandin E2 level and decreased the levels of gastric acid secretion-related receptors in both gastric tissues and primary gastric parietal cells. Furthermore, it decreased the levels of inflammatory factors, including serum histamine and expression of p-IκB, p-p65, iNOS and COX-2 and the activity of apoptotic signaling pathways, including those involving p-JNK, Bcl2/Bax, Fas, FADD, caspase-8 and caspase-3, in the stomach of the ethanol/HCl-treated rats. Thus, we suggest that Gastro-AD® supplementation may reduce ethanol/HCl-induced gastric acid secretion and prevent gastric injury.
Short-Term Magnesium Therapy Alleviates Moderate Stress in Patients with Fibromyalgia: A Randomized Double-Blind Clinical Trial
Authors: Macian Nicolas , Dualé Christian , Voute Marion , Leray Vincent , Courrent Marion , Bodé Paula , Giron Fatiha , Sonneville Sylvie , Bernard Lise , Joanny Fabienne , Menard Katell , Ducheix Gilles , Pereira Bruno , Pickering Gisèle
Published: May 2022

Patients suffering from fibromyalgia often report stress and pain, with both often refractory to usual drug treatment. Magnesium supplementation seems to improve fibromyalgia symptoms, but the level of evidence is still poor. This study is a randomized, controlled, double-blind trial in fibromyalgia patients that compared once a day oral magnesium 100 mg (Chronomag®, magnesium chloride technology formula) to placebo, for 1 month. The primary endpoint was the level of stress on the DASS-42 scale, and secondary endpoints were pain, sleep, quality of life, fatigue, catastrophism, social vulnerability, and magnesium blood concentrations. After 1 month of treatment, the DASS-42 score decreased in the magnesium and placebo groups but not significantly (21.8 ± 9.6 vs. 21.6 ± 10.8, respectively, p = 0.930). Magnesium supplementation significantly reduced the mild/moderate stress subgroup (DASS-42 stress score: 22.1 ± 2.8 to 12.3 ± 7.0 in magnesium vs. 21.9 ± 11.9 to 22.9 ± 11.9 in placebo, p = 0.003). Pain severity diminished significantly (p = 0.029) with magnesium while the other parameters were not significantly different between both groups. These findings show, for the first time, that magnesium improves mild/moderate stress and reduces the pain experience in fibromyalgia patients. This suggests that daily magnesium could be a useful treatment to improve the burden of disease of fibromyalgia patients and calls for a larger clinical trial.
Long-Term Effect of Gluten-Free Diets on Nutritional Status, Body Composition, and Associated Factors in Adult Saudi Females with Celiac Disease
Authors: Alhosain Aeshah Ibrahim , Alshammari Ghedeir M. , Almoteri Barakat Lafi , Mohammed Mohammed A. , Binobead Manal Abdulaziz , Yahya Mohammed Abdo
Published: May 2022

This cross-sectional study examines the influence of long-term gluten-free diet (GFD) consumption on nutritional status, body composition, and associated factors in adult Saudi females with celiac diseases (CD). Fifty-one patients who have been diagnosed with CD and have been on GFD for more than 1 year were included in this study where data regarding their dietary pattern, as well as a complete analysis of their anthropometric parameters, vitamins B12 and D levels, and complete blood count (CBC), were collected. Data have shown that all included patients showed a reduced intake in all micro and macro-nutrients, as well as vitamin D, folate, calcium, and iron. However, the vast majority of all measured hematological parameters and blood indices were within the expected reference range. In addition, 51%, 43.1%, and 60.8% of the patients showed low waist/hip ratio (WHR), decreased level of total body fat (BF), and decreased level of visceral fat (VF), respectively, whereas 33.3% were slim. The poor educational level and some psychosocial factors were associated with the poor nutritional status of the patients. In conclusion, the GFD-dependent intake by female patients with CD adversely affects their nutritional intake and anthropometric indices and leads to a deficiency in major nutrients, vitamins, and ions.
House Dust Mite Exposure through Human Milk and Dust: What Matters for Child Allergy Risk?
Authors: Macchiaverni Patricia , Gehring Ulrike , Rekima Akila , Wijga Alet H. , Verhasselt Valerie
Published: May 2022

Allergies are major noncommunicable diseases associated with significant morbidity, reduced quality of life, and high healthcare costs. Despite decades of research, it is still unknown if early-life exposure to indoor allergens plays a role in the development of IgE-mediated allergy and asthma. The objective of this study is to contribute to the identification of early-life risk factors for developing allergy. We addressed whether two different sources of house dust mite Der p 1 allergen exposure during early life, i.e., human milk and dust, have different relationships with IgE levels and asthma outcomes in children. We performed longitudinal analyses in 249 mother–child pairs using data from the PIAMA birth cohort. Asthma symptoms and serum total and specific IgE levels in children were available for the first 16 years of life. Der p 1 levels were measured in human milk and dust samples from infant mattresses. We observed that infant exposure to Der p 1 through human milk was associated with an increased risk of having high levels of serum IgE (top tertile > 150 kU/mL) in childhood as compared to infants exposed to human milk with undetectable Der p 1 [adjusted OR (95% CI) 1.83 (1.05–3.20) p = 0.0294]. The Der p 1 content in infant mattress dust was not associated with increased IgE levels in childhood. The risk of asthma and Der p 1 sensitization was neither associated with Der p 1 in human milk nor with Der p 1 in dust. In conclusion, high levels of IgE in childhood were associated with Der p 1 exposure through human milk but not exposure from mattress dust. This observation suggests that human milk is a source of Der p 1 exposure that is relevant to allergy development and fosters the need for research on the determinants of Der p 1 levels in human milk.
Severe Post-Traumatic Trismus Unresponsive to Drug Therapy in a 12-Year-Old Patient Treated with a Capacitive-Resistive Electrical Transfer Therapy: A Case Report
Authors: Campanella Giuseppe , Artuso Giulia , Murgia Martina Salvatorina , Orrù Germano , Casu Cinzia
Published: May 2022

(1) Background: Trismus clinically manifests as a reduction of the buccal opening and restricted mouth opening due to different etiologies, but it is often associated with traumatic phenomena. Several treatments have been proposed such as physiotherapy exercises, cryotherapy, laser therapy, hyaluronic acid and platelet-rich fibrin infiltration, but the gold standard is represented by drug therapy based on corticosteroids and NSAIDs, currently the most documented in the scientific literature. Capacitive-resistive electric transfer (Cret) therapy is used to treat musculoskeletal injuries. Cret is a non-invasive electrothermal treatment classified as deep thermo-therapy. (2) Patient: We would like to document a case of particularly traumatic trismus in a 12-year-old patient, not responsive to previous pharmacological therapy and treated with a radiofrequency device called Velvet temporomandibular joint (TMJ). Five capacitive and resistive diathermy sessions with the device were performed. The first four sessions were performed every 4 days and the fifth after 5 days. (3) Result: The maximum opening of the mouth was 10 mm at the initial stage and 38 mm at the end of the six sessions. Pain regressed after the second appointment. (4) Conclusions: Clinical studies with a good number of samples need to be conducted to evaluate the effectiveness of this device which has proved to be an excellent treatment for this refractory case to conventional therapies. Finally, it may be useful to define precise and replicable protocols to make this therapy suitable for patients with TMJ disorders.
Scratching the Itch: Updated Perspectives on the Schistosomes Responsible for Swimmer’s Itch around the World
Authors: Loker Eric S. , DeJong Randall J. , Brant Sara V.
Published: May 2022

Although most studies of digenetic trematodes of the family Schistosomatidae dwell on representatives causing human schistosomiasis, the majority of the 130 identified species of schistosomes infect birds or non-human mammals. The cercariae of many of these species can cause swimmer’s itch when they penetrate human skin. Recent years have witnessed a dramatic increase in our understanding of schistosome diversity, now encompassing 17 genera with eight more lineages awaiting description. Collectively, schistosomes exploit 16 families of caenogastropod or heterobranch gastropod intermediate hosts. Basal lineages today are found in marine gastropods and birds, but subsequent diversification has largely taken place in freshwater, with some reversions to marine habitats. It seems increasingly likely that schistosomes have on two separate occasions colonized mammals. Swimmer’s itch is a complex zoonotic disease manifested through several different routes of transmission involving a diversity of different host species. Swimmer’s itch also exemplifies the value of adopting the One Health perspective in understanding disease transmission and abundance because the schistosomes involved have complex life cycles that interface with numerous species and abiotic components of their aquatic environments. Given the progress made in revealing their diversity and biology, and the wealth of questions posed by itch-causing schistosomes, they provide excellent models for implementation of long-term interdisciplinary studies focused on issues pertinent to disease ecology, the One Health paradigm, and the impacts of climate change, biological invasions and other environmental perturbations.
Development and Validation of a Novel LC-MS/MS Method for the Simultaneous Determination of Abemaciclib, Palbociclib, Ribociclib, Anastrozole, Letrozole, and Fulvestrant in Plasma Samples: A Prerequisite for Personalized Breast Cancer Treatment
Authors: Turković Lu , Bočkor Luka , Ekpenyong Oscar , Silovski Tajana , Lovrić Mila , Crnković Slaven , Nigović Biljana , Sertić Miranda
Published: May 2022

Palbociclib, ribociclib and abemaciclib were recently approved as chemotherapeutic agents and are currently in the post-marketing surveillance phase. They are used in combination with aromatase inhibitors anastrozole and letrozole or antiestrogen fulvestrant for HR+, HER2− breast cancer treatment. Here, a novel bioanalytical LC-ESI-MS/MS method was developed for the quantitation of these six drugs in human plasma. The samples were prepared by simple protein precipitation followed by solvent evaporation. A Kinetex biphenyl column (150 × 4.6 mm, 2.6 µm) used for chromatographic analysis adequately resolved even the closely eluting aromatase inhibitors’ peaks. The mobile phase consisted of 0.1% formic acid in water and in ACN, in a linear gradient. An additional gradient step was added to eliminate the observed carry-over. The proposed method was fully validated in the relevant linear ranges covering the expected plasma concentrations of all six drugs (correlation coefficients between 0.9996 and 0.9931). The intra-day method precision (CV) ranged from 3.1% to 15%, while intra-day accuracy (%bias) was between −1.5% and 15.0%. The inter-day precision ranged from 1.6% to 14.9%, with accuracy between −14.3% and 14.6%, which is in accordance with the EMA and ICH guidelines on bioanalytical method validation. The method was successfully applied to samples from patients treated for HR+, HER2− breast cancer.
Inhibition of Human Respiratory Influenza A Virus and Human Betacoronavirus-1 by the Blend of Double-Standardized Extracts of Aronia melanocarpa (Michx.) Elliot and Sambucus nigra L.
Authors: Ochnik Michał , Franz Dominika , Sobczyński Maciej , Naporowski Piotr , Banach Mariusz , Orzechowska Beata , Sochocka Marta
Published: May 2022

Viral and bacterial diseases are among the greatest concerns of humankind since ancient times. Despite tremendous pharmacological progress, there is still a need to search for new drugs that could treat or support the healing processes. A rich source of bioactive compounds with antiviral potency include plants such as black chokeberry and elderberry. The aim of this study was to assess the in vitro antiviral ability of an originally designed double-standardized blend of extracts from Aronia melanocarpa (Michx.) Elliot and Sambucus nigra L. (EAM-ESN) or separated extracts of A. melanocarpa (EAM) or S. nigra (ESN) against four human respiratory tract viruses: influenza A virus (A/H1N1), betacoronavirus-1 (HCoV-OC43) belonging to the same β-coronaviruses as the current pandemic SARS-CoV-2, human herpesvirus type 1 (HHV-1), and human adenovirus type 5 (HAdV-5). Antiviral assays (AVAs) were used to evaluate the antiviral activity of the plant extracts in a cell-present environment with extracts tested before, simultaneously, or after viral infection. The virus replication was assessed using the CPE scale or luminescent assay. The EAM-ESN blend strongly inhibited A/H1N1 replication as well as HCoV-OC43, while having a limited effect against HHV-1 and HAdV-5. This activity likely depends mostly on the presence of the extract of S. nigra. However, the EAM-ESN blend possesses more effective inhibitory activity toward virus replication than its constituent extracts. A post-infection mechanism of action of the EAM-ESN make this blend the most relevant for potential drugs and supportive treatments; thus, the EAM-ESN blend might be considered as a natural remedy in mild, seasonal respiratory viral infections.
Mathematical Modeling of Hydroxyurea Therapy in Individuals with Sickle Cell Disease
Authors: Pandey Akancha , Estepp Jeremie H. , Raja Rubesh , Kang Guolian , Ramkrishna Doraiswami
Published: May 2022

Sickle cell disease (SCD) is a chronic hemolytic anemia affecting millions worldwide with acute and chronic clinical manifestations and early mortality. While hydroxyurea (HU) and other treatment strategies managed to ameliorate disease severity, high inter-individual variability in clinical response and a lack of an ability to predict those variations need to be addressed to maximize the clinical efficacy of HU. We developed pharmacokinetics (PK) and pharmacodynamics (PD) models to study the dosing, efficacy, toxicity, and clinical response of HU treatment in more than eighty children with SCD. The clinical PK parameters were used to model the HU plasma concentration for a 24 h period, and the estimated daily average HU plasma concentration was used as an input to our PD models with approximately 1 to 9 years of data connecting drug exposure with drug response. We modeled the biomarkers mean cell volume and fetal hemoglobin to study treatment efficacy. For myelosuppression, we modeled red blood cells and absolute neutrophil count. Our models provided excellent fits for individuals with known or correctly inferred adherence. Our models can be used to determine the optimal dosing regimens and study the effect of non-adherence on HU-treated individuals.
Extracellular Vesicles from M1-Polarized Macrophages Combined with Hyaluronic Acid and a β-Blocker Potentiate Doxorubicin’s Antitumor Activity by Downregulating Tumor-Associated Macrophages in Breast Cancer
Authors: Jorquera-Cordero Carla , Lara Pablo , Cruz Luis J. , Schomann Timo , van Hofslot Anna , de Carvalho Thaís Gomes , Guedes Paulo Marcos Da Matta , Creemers Laura , Koning Roman I. , Chan Alan B. , de Araujo Junior Raimundo Fernandes
Published: May 2022

One of the main reasons for cancer’s low clinical response to chemotherapeutics is the highly immunosuppressive tumor microenvironment (TME). Tumor-ass ociated M2 macrophages (M2-TAMs) orchestrate the immunosuppression, which favors tumor progression. Extracellular vesicles (EVs) have shown great potential for targeted therapies as, depending on their biological origin, they can present different therapeutic properties, such as enhanced accumulation in the target tissue or modulation of the immune system. In the current study, EVs were isolated from M1-macrophages (M1-EVs) pre-treated with hyaluronic acid (HA) and the β-blocker carvedilol (CV). The resulting modulated-M1 EVs (MM1-EVs) were further loaded with doxorubicin (MM1-DOX) to assess their effect in a mouse model of metastatic tumor growth. The cell death and cell migration profile were evaluated in vitro in 4T1 cells. The polarization of the RAW 264.7 murine macrophage cell line was also analyzed to evaluate the effects on the TME. Tumors were investigated by qRT-PCR and immunohistochemistry. MM1-DOX reduced the primary tumor size and metastases. NF-κB was the major gene downregulated by MM1-DOX. Furthermore, MM1-DOX reduced the expression of M2-TAM (CD-163) in tumors, which resulted in increased apoptosis (FADD) as well as decreased expression of MMP-2 and TGF-β. These results suggest a direct effect in tumors and an upregulation in the TME immunomodulation, which corroborate with our in vitro data that showed increased apoptosis, modulation of macrophage polarization, and reduced cell migration after treatment with M1-EVs combined with HA and CV. Our results indicate that the M1-EVs enhanced the antitumor effects of DOX, especially if combined with HA and CV in an animal model of metastatic cancer.
Construction of Local Drug Delivery System on Titanium-Based Implants to Improve Osseointegration
Authors: Meng Fanying , Yin Zhifeng , Ren Xiaoxiang , Geng Zhen , Su Jiacan
Published: May 2022

Titanium and its alloys are the most widely applied orthopedic and dental implant materials due to their high biocompatibility, superior corrosion resistance, and outstanding mechanical properties. However, the lack of superior osseointegration remains the main obstacle to successful implantation. Previous traditional surface modification methods of titanium-based implants cannot fully meet the clinical needs of osseointegration. The construction of local drug delivery systems (e.g., antimicrobial drug delivery systems, anti-bone resorption drug delivery systems, etc.) on titanium-based implants has been proved to be an effective strategy to improve osseointegration. Meanwhile, these drug delivery systems can also be combined with traditional surface modification methods, such as anodic oxidation, acid etching, surface coating technology, etc., to achieve desirable and enhanced osseointegration. In this paper, we review the research progress of different local drug delivery systems using titanium-based implants and provide a theoretical basis for further research on drug delivery systems to promote bone–implant integration in the future.
Advancements in Skin Delivery of Natural Bioactive Products for Wound Management: A Brief Review of Two Decades
Authors: Ryall Cameron , Duarah Sanjukta , Chen Shuo , Yu Haijun , Wen Jingyuan
Published: May 2022

Application of modern delivery techniques to natural bioactive products improves their permeability, bioavailability, and therapeutic efficacy. Many natural products have desirable biological properties applicable to wound healing but are limited by their inability to cross the stratum corneum to access the wound. Over the past two decades, modern systems such as microneedles, lipid-based vesicles, hydrogels, composite dressings, and responsive formulations have been applied to natural products such as curcumin or aloe vera to improve their delivery and efficacy. This article reviews which natural products and techniques have been formulated together in the past two decades and the success of these applications for wound healing. Many cultures prefer natural-product-based traditional therapies which are often cheaper and more available than their synthetic counterparts. Improving natural products’ effect can provide novel wound-healing therapies for those who trust traditional compounds over synthetic drugs to reduce medical inequalities.
Vehicle-Free Nanotheranostic Self-Assembled from Clinically Approved Dyes for Cancer Fluorescence Imaging and Photothermal/Photodynamic Combinational Therapy
Authors: Huang Mingbin , Xu Chao , Yang Sen , Zhang Ziqian , Wei Zuwu , Wu Ming , Xue Fangqin
Published: May 2022

Phototherapy, including photothermal therapy (PTT) and photodynamic therapy (PDT) has attracted growing attention as a noninvasive option for cancer treatment. At present, researchers have developed various “all-in-one” nanoplatforms for cancer imaging and PTT/PDT combinational therapy. However, the complex structure, tedious preparation procedures, overuse of extra carriers and severe side effects hinder their biomedical applications. In this work, we reported a nanoplatform (designated as ICG-MB) self-assembly from two different FDA-approved dyes of indocyanine green (ICG) and methylene blue (MB) without any additional excipients for cancer fluorescence imaging and combinational PTT/PDT. ICG-MB was found to exhibit good dispersion in the aqueous phase and improve the photostability and cellular uptake of free ICG and MB, thus exhibiting enhanced photothermal conversion and singlet oxygen (1O2) generation abilities to robustly ablate cancer cells under 808 nm and 670 nm laser irradiation. After intravenous injection, ICG-MB effectively accumulated at tumor sites with a near-infrared (NIR) fluorescence signal, which helped to delineate the targeted area for NIR laser-triggered phototoxicity. As a consequence, ICG-MB displayed a combinational PTT/PDT effect to potently inhibit tumor growth without causing any system toxicities in vivo. In conclusion, this minimalist, effective and biocompatible nanotheranostic would provide a promising candidate for cancer phototherapy based on current available dyes in clinic.
Multi-Modal Imaging to Assess the Follicular Delivery of Zinc Pyrithione
Authors: Mangion Sean E. , Sandiford Lydia , Mohammed Yousuf , Roberts Michael S. , Holmes Amy M.
Published: May 2022

Zinc pyrithione (ZnPT) is a widely used antifungal, usually applied as a microparticle suspension to facilitate delivery into the hair follicles, where it then dissociates into a soluble monomeric form that is bioactive against yeast and other microorganisms. In this study, we use multiphoton microscopy (MPM) and fluorescence lifetime imaging microscopy (FLIM) to characterise ZnPT formulations and map the delivery of particles into follicles within human skin. To simulate real-world conditions, it was applied using a massage or no-massage technique, while simultaneously assessing the dissolution using Zinpyr-1, a zinc labile fluorescent probe. ZnPT particles can be detected in a range of shampoo formulations using both MPM and FLIM, though FLIM is optimal for detection as it allows spectral and lifetime discrimination leading to increased selectivity and sensitivity. In aqueous suspensions, the ZnPT 7.2 µm particles could be detected up to 500 µm in the follicle. The ZnPT particles in formulations were finer (1.0–3.3 µm), resulting in rapid dissolution on the skin surface and within follicles, evidenced by a reduced particle signal at 24 h but enhanced Zinpyr-1 intensity in the follicular and surface epithelium. This study shows how MPM-FLIM multimodal imaging can be used as a useful tool to assess ZnPT delivery to skin and its subsequent dissolution.
The First Report on Transgenic Hairy Root Induction from the Stem of Tung Tree (Vernicia fordii)
Authors: Jia Hongyu , Chen Junjie , Zhang Lin , Zhang Lingling
Published: May 2022

Tung tree (Vernicia fordii) is an industrially important oil-bearing woody plant of the Euphorbiaceae family. Functional studies of tung tree at the molecular level are limited by the lack of an efficient transgenic system. The Agrobacterium rhizogenes-mediated hairy root generation system is an alternative to typical plant transformation systems. However, its application in many plants has been blocked due to the inability of existing methods to induce hairy roots. Thus, it is critical to build a method suitable for the hairy induction of the specific plant of interest. In this study, a modified method for tung tree was developed, and it is the first report that hairy roots could be effectively induced in the stem of tung tree. With the method, an average of 10.7 hairy roots per seedling were generated in tung tree, approximately 67% of seedlings produced transgenic hairy roots and approximately 13.96% of the hairy roots of these seedlings were transgenic. This modified method is also suitable for the hairy root induction of two other oil-bearing plants of the Euphorbiaceae family, Ricinus communis and Vernicia montana. This modified method will accelerate functional studies of tung tree at the molecular level and also shed light on plants lacking a transgenic system.
Vegetation Affecting Water Quality in Small Streams: Case Study in Hemiboreal Forests, Latvia
Authors: Saklaurs Mārcis , Dubra Stefānija , Liepa Līga , Jansone Diāna , Jansons Āris
Published: May 2022

Riparian forests are important ecosystems located along the margins of freshwaters. Riparian zones provide many ecosystem services, such as nutrient modification, erosion and temperature control, leading to improvements in water quality in adjacent water ecosystems. In many areas, riparian forest management is restricted to improve adjacent water quality. The potential influence of forest management on water quality of small streams was assessed by analysing species composition and structural diversity in riparian forests. We collected data in riparian forests along 15 streams in the eastern Baltics (Latvia) with different water quality classes. We used detrended correspondence analysis and indicator species’ analysis to determine relationships between woody plants and understory vegetation. We also used ADONIS and ANOSIM analysis to determine possible factors that affect species composition. Our results suggested that water quality is affected by ground vegetation, which in turn was altered by stand density and total yield. Site-specific decision making in management is required in riparian forests to ensure the required conditions in the streams, because species composition differs between sites, dominant tree species and stand parameters (density, total yield, stand age). Introduction of Betula pubescens Ehrh. in coniferous stands is favourable to ensure litter fall quality and provide shade for streams during summer.
Phenotypic and Genotypic Characterization and Correlation Analysis of Pea (Pisum sativum L.) Diversity Panel
Authors: Uhlarik Ana , Ćeran Marina , Živanov Dalibor , Grumeza Radu , Skøt Leif , Sizer-Coverdale Ellen , Lloyd David
Published: May 2022

Phenotypic and genotypic characterization were performed to assess heritability, variability, and seed yield stability of pea genotypes used in breeding to increase the pea production area. A European pea diversity panel, including genotypes from North America, Asia, and Australia consisting of varieties, breeding lines, pea, and landraces was examined in 2019 and 2020 in Serbia and Belgium using augmented block design. The highest heritability was for thousand seed weight; the highest coefficient of variation was for seed yield. The highest positive correlation was between number of seeds per plant and number of pods per plant; the highest negative correlation was between seed yield and protein content. Hierarchical clustering separated pea germplasm based on use and type. Different Principal component analysis grouping of landraces, breeding lines, and varieties, as well as forage types and garden and dry peas, confirms that there was an apparent decrease in similarity between the genotypes, which can be explained by their different purposes. Pea breeding should be focused on traits with consistent heritability and a positive effect on seed yield when selecting high-yielding genotypes, and on allowing for more widespread use of pea in various agricultural production systems.
Ascorbic Acid Preconditioning Effect on Broccoli Seedling Growth and Photosynthesis under Drought Stress
Authors: MacDonald Mason T. , Kannan Rajeswari , Jayaseelan Renuga
Published: May 2022

Drought is an abiotic stress that decreases crop photosynthesis, growth, and yield. Ascorbic acid has been used as a seed preconditioning agent to help mitigate drought in some species, but not yet in broccoli (Brassica oleracea var. italica). The objective was to investigate the effect of ascorbic acid on growth, photosynthesis, and related parameters in watered and drought-stressed broccoli seedlings. A 2 × 4 factorial experiment was designed where stress (watered or drought) was the first factor and ascorbic acid preconditioning (untreated, 0 ppm, 1 ppm, or 10 ppm) was the second factor. Positioning within the greenhouse was included as a blocking factor and the experiment was replicated three times. All seedlings were watered for 8 weeks and then half had water withheld for 7 days to impose drought while the other half continued to be watered. Ascorbic acid preconditioning increased shoot dry mass, root dry mass, water use efficiency, and photosynthesis in all seedlings while also increasing chlorophyll, relative water content, and leaf area in droughted seedlings. Ascorbic acid preconditioning also decreased membrane injury in droughted seedlings to the point that membrane injury was not significantly different than the watered control. There was strong evidence to support ascorbic acid as a successful seed preconditioning agent in watered and droughted broccoli.